Influenza - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

INFLUENZA A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R EFERENCES J AMES N. P...

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INFLUENZA A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R EFERENCES

J AMES N. P ARKER , M.D. AND P HILIP M. P ARKER , P H .D., E DITORS

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ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright ©2004 by ICON Group International, Inc. Copyright ©2004 by ICON Group International, Inc. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without written permission from the publisher. Printed in the United States of America. Last digit indicates print number: 10 9 8 7 6 4 5 3 2 1

Publisher, Health Care: Philip Parker, Ph.D. Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher's note: The ideas, procedures, and suggestions contained in this book are not intended for the diagnosis or treatment of a health problem. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960Influenza: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References / James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary, and index. ISBN: 0-597-83991-3 1. Influenza-Popular works. I. Title.

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Disclaimer This publication is not intended to be used for the diagnosis or treatment of a health problem. It is sold with the understanding that the publisher, editors, and authors are not engaging in the rendering of medical, psychological, financial, legal, or other professional services. References to any entity, product, service, or source of information that may be contained in this publication should not be considered an endorsement, either direct or implied, by the publisher, editors, or authors. ICON Group International, Inc., the editors, and the authors are not responsible for the content of any Web pages or publications referenced in this publication.

Copyright Notice If a physician wishes to copy limited passages from this book for patient use, this right is automatically granted without written permission from ICON Group International, Inc. (ICON Group). However, all of ICON Group publications have copyrights. With exception to the above, copying our publications in whole or in part, for whatever reason, is a violation of copyright laws and can lead to penalties and fines. Should you want to copy tables, graphs, or other materials, please contact us to request permission (E-mail: [email protected]). ICON Group often grants permission for very limited reproduction of our publications for internal use, press releases, and academic research. Such reproduction requires confirmed permission from ICON Group International Inc. The disclaimer above must accompany all reproductions, in whole or in part, of this book.

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Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this book which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which produce publications on influenza. Books in this series draw from various agencies and institutions associated with the United States Department of Health and Human Services, and in particular, the Office of the Secretary of Health and Human Services (OS), the Administration for Children and Families (ACF), the Administration on Aging (AOA), the Agency for Healthcare Research and Quality (AHRQ), the Agency for Toxic Substances and Disease Registry (ATSDR), the Centers for Disease Control and Prevention (CDC), the Food and Drug Administration (FDA), the Healthcare Financing Administration (HCFA), the Health Resources and Services Administration (HRSA), the Indian Health Service (IHS), the institutions of the National Institutes of Health (NIH), the Program Support Center (PSC), and the Substance Abuse and Mental Health Services Administration (SAMHSA). In addition to these sources, information gathered from the National Library of Medicine, the United States Patent Office, the European Union, and their related organizations has been invaluable in the creation of this book. Some of the work represented was financially supported by the Research and Development Committee at INSEAD. This support is gratefully acknowledged. Finally, special thanks are owed to Tiffany Freeman for her excellent editorial support.

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About the Editors James N. Parker, M.D. Dr. James N. Parker received his Bachelor of Science degree in Psychobiology from the University of California, Riverside and his M.D. from the University of California, San Diego. In addition to authoring numerous research publications, he has lectured at various academic institutions. Dr. Parker is the medical editor for health books by ICON Health Publications. Philip M. Parker, Ph.D. Philip M. Parker is the Eli Lilly Chair Professor of Innovation, Business and Society at INSEAD (Fontainebleau, France and Singapore). Dr. Parker has also been Professor at the University of California, San Diego and has taught courses at Harvard University, the Hong Kong University of Science and Technology, the Massachusetts Institute of Technology, Stanford University, and UCLA. Dr. Parker is the associate editor for ICON Health Publications.

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About ICON Health Publications To discover more about ICON Health Publications, simply check with your preferred online booksellers, including Barnes&Noble.com and Amazon.com which currently carry all of our titles. Or, feel free to contact us directly for bulk purchases or institutional discounts: ICON Group International, Inc. 4370 La Jolla Village Drive, Fourth Floor San Diego, CA 92122 USA Fax: 858-546-4341 Web site: www.icongrouponline.com/health

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Table of Contents FORWARD .......................................................................................................................................... 1 CHAPTER 1. STUDIES ON INFLUENZA ............................................................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Influenza ....................................................................................... 6 E-Journals: PubMed Central ....................................................................................................... 59 The National Library of Medicine: PubMed ................................................................................ 97 CHAPTER 2. NUTRITION AND INFLUENZA ................................................................................... 143 Overview.................................................................................................................................... 143 Finding Nutrition Studies on Influenza .................................................................................... 143 Federal Resources on Nutrition ................................................................................................. 151 Additional Web Resources ......................................................................................................... 152 CHAPTER 3. ALTERNATIVE MEDICINE AND INFLUENZA ............................................................. 153 Overview.................................................................................................................................... 153 National Center for Complementary and Alternative Medicine................................................ 153 Additional Web Resources ......................................................................................................... 170 General References ..................................................................................................................... 177 CHAPTER 4. DISSERTATIONS ON INFLUENZA ............................................................................... 179 Overview.................................................................................................................................... 179 Dissertations on Influenza ......................................................................................................... 179 Keeping Current ........................................................................................................................ 182 CHAPTER 5. CLINICAL TRIALS AND INFLUENZA .......................................................................... 183 Overview.................................................................................................................................... 183 Recent Trials on Influenza ......................................................................................................... 183 Keeping Current on Clinical Trials ........................................................................................... 186 CHAPTER 6. PATENTS ON INFLUENZA .......................................................................................... 189 Overview.................................................................................................................................... 189 Patents on Influenza .................................................................................................................. 189 Patent Applications on Influenza .............................................................................................. 218 Keeping Current ........................................................................................................................ 251 CHAPTER 7. BOOKS ON INFLUENZA ............................................................................................. 253 Overview.................................................................................................................................... 253 Book Summaries: Federal Agencies............................................................................................ 253 Book Summaries: Online Booksellers......................................................................................... 255 The National Library of Medicine Book Index ........................................................................... 260 Chapters on Influenza ................................................................................................................ 261 CHAPTER 8. MULTIMEDIA ON INFLUENZA ................................................................................... 265 Overview.................................................................................................................................... 265 Video Recordings ....................................................................................................................... 265 Audio Recordings....................................................................................................................... 266 Bibliography: Multimedia on Influenza..................................................................................... 266 CHAPTER 9. PERIODICALS AND NEWS ON INFLUENZA ................................................................ 269 Overview.................................................................................................................................... 269 News Services and Press Releases.............................................................................................. 269 Newsletters on Influenza ........................................................................................................... 272 Newsletter Articles .................................................................................................................... 272 Academic Periodicals covering Influenza................................................................................... 273 CHAPTER 10. RESEARCHING MEDICATIONS................................................................................. 275 Overview.................................................................................................................................... 275 U.S. Pharmacopeia..................................................................................................................... 275 Commercial Databases ............................................................................................................... 277

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APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 281 Overview.................................................................................................................................... 281 NIH Guidelines.......................................................................................................................... 281 NIH Databases........................................................................................................................... 283 Other Commercial Databases..................................................................................................... 286 APPENDIX B. PATIENT RESOURCES ............................................................................................... 287 Overview.................................................................................................................................... 287 Patient Guideline Sources.......................................................................................................... 287 Finding Associations.................................................................................................................. 298 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 301 Overview.................................................................................................................................... 301 Preparation................................................................................................................................. 301 Finding a Local Medical Library................................................................................................ 301 Medical Libraries in the U.S. and Canada ................................................................................. 301 ONLINE GLOSSARIES................................................................................................................ 307 Online Dictionary Directories ................................................................................................... 310 INFLUENZA DICTIONARY ....................................................................................................... 311 INDEX .............................................................................................................................................. 395

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FORWARD In March 2001, the National Institutes of Health issued the following warning: "The number of Web sites offering health-related resources grows every day. Many sites provide valuable information, while others may have information that is unreliable or misleading."1 Furthermore, because of the rapid increase in Internet-based information, many hours can be wasted searching, selecting, and printing. Since only the smallest fraction of information dealing with influenza is indexed in search engines, such as www.google.com or others, a non-systematic approach to Internet research can be not only time consuming, but also incomplete. This book was created for medical professionals, students, and members of the general public who want to know as much as possible about influenza, using the most advanced research tools available and spending the least amount of time doing so. In addition to offering a structured and comprehensive bibliography, the pages that follow will tell you where and how to find reliable information covering virtually all topics related to influenza, from the essentials to the most advanced areas of research. Public, academic, government, and peer-reviewed research studies are emphasized. Various abstracts are reproduced to give you some of the latest official information available to date on influenza. Abundant guidance is given on how to obtain free-of-charge primary research results via the Internet. While this book focuses on the field of medicine, when some sources provide access to non-medical information relating to influenza, these are noted in the text. E-book and electronic versions of this book are fully interactive with each of the Internet sites mentioned (clicking on a hyperlink automatically opens your browser to the site indicated). If you are using the hard copy version of this book, you can access a cited Web site by typing the provided Web address directly into your Internet browser. You may find it useful to refer to synonyms or related terms when accessing these Internet databases. NOTE: At the time of publication, the Web addresses were functional. However, some links may fail due to URL address changes, which is a common occurrence on the Internet. For readers unfamiliar with the Internet, detailed instructions are offered on how to access electronic resources. For readers unfamiliar with medical terminology, a comprehensive glossary is provided. For readers without access to Internet resources, a directory of medical libraries, that have or can locate references cited here, is given. We hope these resources will prove useful to the widest possible audience seeking information on influenza. The Editors

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From the NIH, National Cancer Institute (NCI): http://www.cancer.gov/cancerinfo/ten-things-to-know.

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CHAPTER 1. STUDIES ON INFLUENZA Overview In this chapter, we will show you how to locate peer-reviewed references and studies on influenza.

The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and influenza, you will need to use the advanced search options. First, go to http://chid.nih.gov/index.html. From there, select the “Detailed Search” option (or go directly to that page with the following hyperlink: http://chid.nih.gov/detail/detail.html). The trick in extracting studies is found in the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Journal Article.” At the top of the search form, select the number of records you would like to see (we recommend 100) and check the box to display “whole records.” We recommend that you type “influenza” (or synonyms) into the “For these words:” box. Consider using the option “anywhere in record” to make your search as broad as possible. If you want to limit the search to only a particular field, such as the title of the journal, then select this option in the “Search in these fields” drop box. The following is what you can expect from this type of search: •

Influenza Infection and Diabetes Mellitus: Case for Annual Vaccination Source: Diabetes Care. 13(8): 876-882. August 1990. Summary: In this article, epidemiological data on influenza pneuomonia and mortality, results of clinical studies, and the outcome of influenza vaccination trials in the diabetes patient population are reviewed. All excess mortality studies that specify for underlying disease list diabetes as one of the major risk factors. The authors note that the extent to which cardiovascular disease and old age contribute to the increased influenza mortality and morbidity in patients with diabetes remains unclear. The influence of epidemic influenza on the incidence of diabetic acidosis in combination with an impaired immune response suggests that diabetes mellitus itself is the main risk factor. It is concluded that all patients with diabetes mellitus should receive annual vaccinations and that, in

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official recommendations, patients with diabetes mellitus should be mentioned as a separate risk group. 1 table. 62 references. (AA-M). •

Vaccination Update: Hib, Hepatitis, Polio, Varicella, Influenza, Pneumococcal and Meningococcal Disease Source: Postgraduate Medicine. 98(5): 141-144, 146, 149-150. November 1995. Summary: Inadequate immunization of infants, children, and persons at high risk for certain infectious diseases continues to result in excess deaths every year in the United States. This article focuses on current immunization guidelines and recent developments in the fight against seven vaccine-preventable diseases: Hib disease, hepatitis B, poliomyelitis, varicella (chicken-pox), influenza, pneumococcal disease, and meningococcal disease. The authors conclude that immunization of infants and children is the most effective strategy for decreasing the incidence of some infectious diseases. Readers can qualify for continuing medical education credits by completing the posttest after the article. 2 tables. 28 references. (AA-M).

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Immunization and the Prevention of Influenza and Pneumococcal Disease in People with Diabetes Source: Diabetes Care. 25(Supplement 1): S117. January 2002. Contact: Available from American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 232-3472. Website: www.diabetes.org. Summary: This article presents the American Diabetes Association position statement on immunization and the prevention of influenza and pneumococcal disease in people with diabetes. The article first reviews the rationale for immunization, primarily that the effective implementation of immunization can reduce the cost of human suffering and health care expenditures in people with diabetes. The recommendations offered in the position statement are based in large part on observational studies with high potential for bias. The narrative review supports expert opinion that immunization intervention is low risk, is low cost, and may have a moderate to substantial impact on the care of people with diabetes. The statement reviews patient selection and other considerations for influenza vaccination and for vaccination against pneumococcal disease in people with diabetes.

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Association Between Type 1 Diabetes and Haemophilus Influenza Type B Vaccination: Birth Cohort Study Source: BMJ. 318(7192): 1169-1172. May 1, 1999. Contact: Available from BMA House. BMJ Fulfillment Department, Tavistock Square, London WC1H 9TD. 44(0)171 383 6270. E-mail: [email protected]. Summary: This article reports on a study undertaken to determine the effect of Haemophilus influenzae type b (Hib) vaccination and its timing on the risk of type 1 diabetes in children in Finland. Cumulative incidence and relative risk of type 1 diabetes was compared among three birth cohorts of Finnish children: those born during the 24 months before the Hib vaccination trial, those in the trial cohort who were vaccinated at 3 months of age and later with a booster vaccine, and those in the trial cohort who were vaccinated at 24 months of age only. The probability of type 1 diabetes was estimated using regression analysis, assuming that there were no losses to 10 year follow up and no competing risks. The study included 128,936 children born from October 1983 to September 1985 and 116,352 children born from October 1985 through August 1987. No

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statistically significant difference was found at any time during the 10 year follow up in the risk of type 1 diabetes between the children born before the vaccination period and those vaccinated at the age of 24 months only. The difference in the risk between the cohort vaccinated first at the age of 3 months and the cohort vaccinated at the age of 24 months only was not statistically significant. The authors conclude that it is unlikely that Hib vaccination or its timing cause type 1 diabetes in children. 2 figures. 3 tables. 22 references. •

Use of Influenza and Pneumococcal Vaccines in People with Diabetes Source: Diabetes Care. 23(1): 95-108. January 2000. Contact: Available from American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 232-3472. Website: www.diabetes.org. Summary: This review article focuses on the use of influenza and pneumococcal vaccines in people who have diabetes. The article reviews the evidence for the risks of infection in diabetes as it relates to antibody response, cell-mediated immunity, leukocyte function, colonization rates, epidemiologic evidence for infections, immune response to immunization, and efficacy of vaccination. Another topic is the immune response to viral and bacterial illness in people who have diabetes. In addition, the article systemically reviews the clinical reports of infection, vaccine immunogenicity, and vaccine effectiveness for influenza and pneumococcus in people who have diabetes. Data suggest that people who have diabetes and its complications are at increased risk for the morbidity, mortality, and health care costs resulting from influenza infection. Many studies have reported a sufficient immune response in more than 70 percent of patients who have diabetes. Although there is a lack of definitive proof of the efficacy of influenza vaccination specifically in people who have diabetes, studies including diabetes as one of the at risk patient groups support immunization in this patient group. Published studies support the fact that people who have diabetes are at least as likely to be susceptible to pneumococcal infection as other patients who have chronic disease. Although the efficacy of the pneumococcal vaccine is uncertain in nonbacteremic illness, many studies have shown that the vaccine is effective in reducing pneumococcal bacteremia in people who have diabetes. The article concludes with a review of general vaccine implementation strategies. 4 tables. 141 references.

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Chronic Stress in Elderly Carers of Dementia Patients and Antibody Response to Influenza Vaccination Source: Lancet. 353(9153): 627-631. February 20, 1999. Summary: This study investigated whether antibody responses to influenza vaccination differed between spousal carers of patients with dementia and a control group, and the relation of the antibody response to the hypothalamic-pituitary-adrenal (HPA) axis. Fifty spousal carers, median age 73 years, and 67 controls, aged 66 to 71 years, of similar socioeconomic status were enrolled. Anxiety and depression were measured using the Savage Aged Personality Screening scale and stress by the Global Measure of Perceived Stress scale. Salivary cortisol concentrations were measured repeatedly over one day. Participants received a trivalent influenza vaccine. IgG antibody titres to each strain were measured on days 0, 7, 14, and 28. Data show mean emotional distress was significantly higher in carers at each measurement than in controls. Salivary cortisol concentrations were higher in carers than controls. At all three times, 8 of 50 carers and 26 of 67 controls had a four-fold increase in at least one of the IgG titres. An inverse relation showed the Nanchang strain of vaccine between the area under the curve of

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cortisol and IgG antibody titre. Results suggest elderly carers and their spouses with dementia have increased activation of the HPA axis and a poor antibody response to influenza vaccine. 2 figures, 3 tables, 23 references. (AA-M).

Federally Funded Research on Influenza The U.S. Government supports a variety of research studies relating to influenza. These studies are tracked by the Office of Extramural Research at the National Institutes of Health.2 CRISP (Computerized Retrieval of Information on Scientific Projects) is a searchable database of federally funded biomedical research projects conducted at universities, hospitals, and other institutions. Search the CRISP Web site at http://crisp.cit.nih.gov/crisp/crisp_query.generate_screen. You will have the option to perform targeted searches by various criteria, including geography, date, and topics related to influenza. For most of the studies, the agencies reporting into CRISP provide summaries or abstracts. As opposed to clinical trial research using patients, many federally funded studies use animals or simulated models to explore influenza. The following is typical of the type of information found when searching the CRISP database for influenza: •

Project Title: (HVTN) HIV VACCINE TRIAL UNITS Principal Investigator & Institution: Burke, Donald S.; Professor; International Health; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2001; Project Start 01-JUN-2000; Project End 31-MAY-2005 Summary: This proposal describes a plan for an HIV Vaccine Trial Unit (HVTU) at Johns Hopkins University. The HVTU will be a consortium with its core at the Johns Hopkins Center for Immunization Research (CIR) in Baltimore, Maryland. There will be a local urban sub-site at Morgan State University and international sub-sites in China, India, and Thailand. The HVTU will contribute to the scientific research agenda of the NIH HIV Vaccine Trials Network, will enroll 60 volunteers into Phase I trials per year and 40 volunteers into Phase II per year, and will prepare to rapidly enroll 1000 volunteers into a Phase III efficacy trial. The HVTU also will increase participation of minorities in HIV vaccine research, establish international HIV vaccine trial sites, and provide training opportunities to affiliated researchers. The experienced Hopkins CIR team is already proven to be highly proficient in vaccine trials. As an NIH AIDS Vaccine Evaluation Unit, the Johns Hopkins CIR has conducted 35 HIV vaccine trials, administered 1,817 immunizations of investigational HIV vaccines, and collected over 13,000 clinical specimens for research analyses. 95% of volunteers in Johns Hopkins CIR HIV vaccine Phase I and II trials, and 100% of volunteers in Phase III HIV vaccine trials, have completed all scheduled vaccinations. In the past 5 years the Hopkins CIR has also conducted successful Phase I/Il trials of investigational vaccines for hepatitis B, hepatitis C, papillomavirus, influenza, parainfluenza, respiratory syncytial virus, and rotavirus, involving over 1600 volunteer subjects and 20,000 study visits. The planned HVTU will build on this extensive experience. A new collaboration with Morgan State University, a

2 Healthcare projects are funded by the National Institutes of Health (NIH), Substance Abuse and Mental Health Services (SAMHSA), Health Resources and Services Administration (HRSA), Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDCP), Agency for Healthcare Research and Quality (AHRQ), and Office of Assistant Secretary of Health (OASH).

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historically black university, will explore methods to improve community understanding about HIV and vaccines among urban African-Americans. International collaborations will examine the effects of differing viral strains, human immunogenetics, routes of infection, cultural practices, and other factors on HIV vaccine safety and immunogenicity. All of the scientific expertise at Johns Hopkins on HIV/AIDS, vaccinology, ethics, and other relevant disciplines will be coordinated through the proposed HVTU. Training opportunities will be available to HVTU-affiliated researchers through the Fogarty AIDS program at Johns Hopkins and through internetbased courses. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: A MICROFABRICATED DEVICE FOR RAPID VIRAL GENOME ANALYSIS Principal Investigator & Institution: Larson, Ronald G.; G.G. Brown Professor; Chemical Engineering; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2001; Project Start 01-APR-2001; Project End 31-MAR-2004 Summary: (Applicant's abstract): We propose to develop a portable, self-contained, microfabricated device for extraction of genomic information from RNA or DNA viruses. Initially, we choose as a model system and as an important target the hemagglutinin HA1 of influenza A virus. Influenza is a prevalent human pathogen with an RNA genome. Mutations in the hemagglutinin (HA1) domains of influenza regularly produce new virulent forms that are responsible for 6 percent of annual mortalities in the U.S.A. Seasonal changes in influenza HA1 have a major impact on influenza epidemics and public health, and pose an on-going threat of world-wide pandemic. From analyses of influenza virus evolution, 18 of the most dangerous mutation sites have been identified. A present need is a reliable means to rapidly survey domestic and foreign populations for the emergence of new mutations. A self-contained, inexpensive, microfabricated device that can rapidly detect viral mutations using a small amount of sample would address this need. To expedite development of such a device we will perform research to achieve the following specific aims: Aim 1 - Determine the Influenza-A RNA purity requirements for Aims 2-4 by preparing samples of three levels: (a) cultured viral-infected cells, (b) purified whole viral particles, and (c) purified viral RNA. Aim 2 - On a microfabricated device, reverse transcribe and amplify the HA1 hemagglutinin domain of Influenza A using reverse-transcription PCR to produce double-stranded complementary DNA. Aim 3 - On a microfabricated device, perform fluorescent primer extension reactions on double-stranded DNA produced in Aim 2 to detect variations in bases in codons from the HA1 domain of hemagglutinin that have been involved in past viral mutations. Aim 4 - On a microfabricated device, separate primer-extended DNA products by gel electrophoresis and identify the locations of the base variations. Aim 5 - Integrate RNA separation, RT-PCR, primer extension reactions, electrophoretic separation, and (if necessary) RNA purification on a single microfabricated device. Aim 6 - Develop a silica gel RNA-adsorption column for purification of RNA on a microfabricated device. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: AGING--ANTIBODY RESPONSE TO BACTERIAL AND VIRAL AGS Principal Investigator & Institution: Casali, Paolo; Professor; Pathology and Laboratory Medicine; Weill Medical College of Cornell Univ New York, Ny 10021

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Timing: Fiscal Year 2001; Project Start 15-AUG-1997; Project End 31-JUL-2003 Summary: The overall scope of this proposal is to uncover the mechanisms underlying the generation of antibodies (Abs) to exogenous antigens (Ags) as they change with aging. Aged people display abnormal Ab responses to exogenous Ags, particularly those on bacteria and viruses, including Streptococcus pneumoniae (Pneumococcus) and influenza virus, and they are affected with significant rates of morbidity and mortality following infection with these and other microbial pathogens. Similarly abnormal Ab responses to microbial Ags have been found in aged mice and have been related to alterations of the clonal composition of the B cell repertoire. We hypothesize that in aged humans the-abnormal responses to microbial pathogens are due to the recruitment of clonotypes different from those recruited in young adults in response to the same exogenous Ags, and may reflect alterations of the composition of the steadystate B cell repertoire. We also hypothesize that, in addition to an altered B cell clonotypic recruitment, the mechanisms of somatic B cell diversification, i.e., Ig V(D)J gene hypermutation and selection by Ag, are ineffective, thereby leading to imperfect affinity maturation of Ag-induced Abs in aged subjects. Such ineffective somatic selection mechanisms may reflect a defect inherent to the B cell mutational machinery, perhaps compounded by a defective T cell help, as documented in the elderly, and would result in abnormal responses to T cell-independent as well as T cell-dependent Ags. To test our hypotheses, we propose to vaccinate with Pneumococcus polysaccharide and influenza virus vaccines aged subjects (65 years of age and older) and, for comparison, young adults (20 to 45 years of age), and to: (i) analyze the phenotypic and clonotypic composition of the B cell repertoire as a whole, and those of some of its subsets, as well as the phenotype, the frequency, and the clonotypic assortment of the precursors of cells producing IgM, IgG, and IgA Abs to Pneumococcus and influenza virus Ags; under maximal activating conditions and absence of activating stimuli; (ii) generate monoclonal antibodies (mAbs) to Pneumococcus and to influenza virus Ags, analyze the mAb Ag-binding properties, the primary structure of their VHDJH and VLJL segments, and their status with respect to somatic point-mutations; and, finally, (iii) validate the data provided by the structural and functional analyses of selected B cell clones to Pneumococcus and influenza virus, and extend them to multiple elements of individual clonotypes to measure the extent of intraclonal diversification by Ig gene "repertoire cloning" in combinatorial phage display libraries. The cellular and molecular features of the Ab response to Pneumococcus and influenza virus in aged subjects will be compared not only to those of the corresponding responses in young adults, but also to those of the natural and Ad-induced Ab responses to other microbial Ags in aged subjects, and may, therefore, help design specific means of therapeutic intervention. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ANTIGEN PRESENTATION AND T CELL POLARIZATION IN UTERO Principal Investigator & Institution: Miller, Rachel L.; Columbia University Health Sciences New York, Ny 10032 Timing: Fiscal Year 2001; Project Start 27-AUG-2001; Project End 31-JUL-2006 Description (provided by applicant): Substantial increases in asthma have occurred among children age 0-4 years and urban ethnic minorities. Exposures to allergens critical to the onset of asthma may occur at a very young age, as suggested by the finding that children with elevated immunoglobulin E (IgE) levels at age 9 months are predisposed to recurrent wheezing and positive allergy skin tests by age 6 years. In

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addition, cord blood mononuclear cells (CBMC) have been shown to proliferate following in vitro stimulation to multiple antigens. Dust mite and ovalbumin - specific neonatal T cells clones have been derived and genotyped, confirming their fetal origin. These results suggest that sensitization may even occur prenatally. However, acceptance of CBMC antigen-induced proliferative responses as signifying in utero sensitization has been questioned, in part because the mechanism of T cell priming has not been demonstrated and specificity of these in vitro responses has not been proven. We hypothesize that in utero sensitization occurs. To demonstrate in utero sensitization, we will determine whether neonatal T cell priming occurs to influenza antigens administered prenatally by vaccination of the pregnant mother. Influenza-specific T cells will be measured by applying tetramer technology. We also hypothesize that increased asthma severity and/or increased T helper 2 (Th2) polarization during pregnancy may influence Th polarization in the newborn and young child. To study these prenatal events, we will recruit pregnant women with atopic asthma and compare the Th2 status and asthma severity of the mother during pregnancy with the Th2 status of the newborn. Th2 status will be evaluated by multiple biomarkers, including IgE levels, intracytoplasmic cytokines, and chemokine levels. To determine the impact of molecular biomarkers for Th2 immune responses at birth on the risk for atopy during early childhood, newborns will be followed prospectively through age 5 years. Both clinical (i.e., history of recurrent wheezing, physician diagnosis of asthma) and immunological (i.e., total and allergen-specific IgE, cytokine levels) endpoints will be evaluated. Identifying critical biomarkers at birth or at the earliest possible time would in turn provide the greatest opportunity for early identification of children at increased risk for allergies, including asthma. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: B CELL IMMUNITY TO INFLUENZA Principal Investigator & Institution: Greenberg, Harry; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-AUG-2008 Summary: There is no text on file for this abstract. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: BIOPHYSICS OF INFLUENZA HEMAGGLUTININ-MEDIATED FUSION Principal Investigator & Institution: Cohen, Fredric S.; Professor; Rush-Presbyterian-St Lukes Medical Ctr Chicago, Il 60612 Timing: Fiscal Year 2001; Project Start 30-SEP-1996; Project End 31-JUL-2003 Summary: Membrane fusion is a ubiquitous cellular process, but the proteins responsible for fusion have been unambiguously identified only in the case of enveloped virus. For enveloped virus, infection of cells is initiated by membrane fusion. A fusion pore forms and enlarges and the viral genome passes through the pore and into cytosol. The biophysical mechanism of fusion has been more extensively studied for hemagglutinin (HA) of influenza virus than for any other fusion protein. As HA and many other viral fusion proteins, including that of HIV-1, have the same core structure, and all viral fusion proteins initiate their action by insertion of fusion peptides into membranes, the overall mechanism by which HA induces fusion is probably similar for many, if not all, viral fusion proteins. Fusion, including pore behavior, has been most extensively studied by expressing HA on cell surfaces and fusing these cells to target

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membranes. However, cellular proteins could alter the fusion process and affect the pores. Individual influenza virions will therefore be fused to phospholipid bilayer membranes, which are free of protein, and the steps leading up to the formation of the fusion pore, the pore itself, and its subsequent enlargement will be characterized by electrical capacitance measurements. Whether full lipid continuity between membranes is established immediately upon fusion of a virus will be assessed by determining if fluorescent lipid dye can pass through the small fusion pore that initially forms. The density of HA in the viral envelope will be systematically reduced by proteolytically removing it and kinetics will be measured so that the number of HA molecules that associate in the creation of a pore can be estimated. Intermediate states of protein conformation and lipid monolayer arrangement from the bound state to fusion have been inferred for cellular systems that express HA. Whether these intermediate states do in fact precede fusion in the viral system will be established. An experimentally testable theoretical model will be constructed that relates the structural changes HA is known to undergo when fusion is triggered to the configurations through which membrane monolayers are thought to proceed. Whether a given change in HA can cause a corresponding change in monolayer configuration will be established by explicit calculation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BRAIN FUNCTION AND AFFECTIVE STYLE IN MIDUS II Principal Investigator & Institution: Davidson, Richard J.; Vilas Professor; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2002; Project Start 01-JAN-2003; Project End 31-DEC-2008 Summary: This project builds upon previous work by the PI and others indicating that asymmetrical prefrontal activation derivedfrom brain electrical activity recordings is associated with both psychological and biological indices that reflect affective style. We have found that subjects with greater left prefrontal activation report more dispositional positive affect, have lower levels of basal cortisol, recover more quickly from a laboratory stressor and show higher levels of antibody titer following vaccination with influenza vaccine. During this grant period, we propose to test 400 MIDUS respondents on measuresof brain electrical activity under both baseline conditions and in response to affective stimuli. In addition, using emotion-modulated startle, we will assess startle modulation before, during and after the presentation of positive, negative and neutral pictures to derive indices of affective chronometry, or the time course of emotional responding. Brain electrical activity measures will be analyzed using both conventional spectral power estimates as well as source localization procedures. We predict that subjects with greater left prefrontal activation will show faster recovery following negative challenge. These individuals are also predicted to have lower cortisol (both basal and in response to challenge), lower levels of IL-6 and higher levels of psychological well-being. Analyses will also be conducted to ascertain the impact of cumulative adversity on these biological indices and to determine the extent to which measures of adversity account for variance in brain function and emotionmodulatedstartle over and beyond variance accounted for by contemporary measures of mood and well-being. The data from this project will provide significant clues to understanding the central mechanisms through which cumulative adversity and psychological well-being are instantiated in the brain and affect peripheral biology in ways that may be consequential for health. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CD4 T CELL IMMUNITY TO INFLUENZA Principal Investigator & Institution: Lewis, David A.; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-AUG-2008 Summary: There is no text on file for this abstract. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CD40L IN ALLOGRAFT TOLERANCE AND VIRAL IMMUNITY Principal Investigator & Institution: Pierson, Richard N.; Associate Professor of Surgery; Surgery; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2001; Project Start 01-FEB-1999; Project End 31-JAN-2003 Summary: (adapted from applicant's abstract): The long term goal of this work is to develop a clinical strategy for modulating donor- recipient interactions to promote allograft tolerance, while preserving host responses to infectious challenges. CD40L is a T-cell molecule central to several important pathways driving allograft rejection. Blockade of CD40L (CD154) has shown considerable promise as a foundation upon which to build a tolerogenic strategy. In this application, studies are proposed to 1) establish whether CD40L blockade, alone or in combination with other agents, induces tolerance in nonhuman primates, and 2) to assess the impact of anti-CD40L-based therapy on responses to human influenza virus, an important infectious agent. Based on current understanding of CD40L's role in allograft rejection, more intense perioperative therapy or a higher cumulative dose of anti- CD40L antibody may result in long-term prevalent graft acceptance. An alternate strategy is to add CD40L blockade to a conventional immunosuppressive regimen. A third approach, adding blockade of the costimulatory CD28/B7 pathway to CD40L inhibition, is associated with prevalent rejection-free graft survival in several models. These three candidate strategies will be tested in a primate cardiac allograft model. By examining correlations between graft outcomes and in vitro indices of specific anti-donor immune responses, this proposal addresses important questions regarding how CD40L-dependent interactions modulate allograft rejection. The experiments outlined will also directly assess whether host defenses to influenza virus, an important infectious agent, are regulated by CD40L. Finally, this study will investigate the potential of CD40L inhibition to induce prolonged acceptance of a transplanted organ, and may contribute to development of clinically relevant approaches to the induction of tolerance. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CELL MEDIATED IMMUNITY IN INFLUENZA Principal Investigator & Institution: Doherty, Peter C.; Chairman; St. Jude Children's Research Hospital Memphis, Tn 381052794 Timing: Fiscal Year 2001; Project Start 01-APR-1990; Project End 31-MAR-2005 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CELLULAR IMMUNITY TO INFLUENZA VIRUS INFECTIONS Principal Investigator & Institution: Crowe, Sherry R.; Trudeau Institute, Inc. Saranac Lake, Ny 12983 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2006

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Influenza

Summary: (provided by the applicant): Influenza virus infections are a significant clinical problem and there is particular concern that highly virulent strains may emerge, either through natural mechanism, or through terrorist actions. Despite the impact of influenza viruses on human health, satisfactory vaccines have not been developed. It has been established that cytotoxic CD8+ T cells play a critical role in the control of influenza virus infections. However, the mechanisms controlling the specificity and magnitude of CD8+ T cell responses are poorly understood. This proposal investigates the regulation of T cell responses to two T cell epitopes in C57BL/6 mice (NP[366374]/Db and PA[224-233]/Db). Whereas equivalent T cell responses are generated to these epitopes during a primary response, NP[366-374]/Db-specific T cells dominate the secondary response. Interestingly, these epitopes are differentially expressed in cell lines infected with influenza virus in vitro. Thus, the PA[224-233]/Db epitope appears to be exclusively expressed in dendritic cells whereas the NP[366- 374]/Db epitope is expressed in all cell lines tested. Based on these observations, we hypothesize that differences in antigen presentation in macrophages and dendritic cells regulate the immunodominance of the T cell response in vivo. This hypothesis will be tested in aim 1 by analyzing the expression of the NP[366-374]/Db and PA[224-233]/Db epitopes in different cell types in vivo. The relationship between epitope expression and the capacity to drive T cell responses will also be investigated. The impact of vaccination on the immunodominance patterns and efficacy of NP[366-374]/Db and PA[224-233]/Db specific T cells will be analyzed in aim 2. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CELLULAR PROTEIN INTERACTIONS WITH VIRAL INHIBITORS Principal Investigator & Institution: Chua, Mark A.; Microbiology; Mount Sinai School of Medicine of Nyu of New York University New York, Ny 10029 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2006 Summary: (provided by applicant): For a virus to grow in a host, it must find a way around the immune response that it causes. One of the first lines of immune defense against viral infection is the interferon (IFN) response. The IFN response is used to signal an antiviral state in the cell that is infected and to neighboring cells. Many viruses that block the IFN response can proliferate in the host cell. Viruses can do this by producing certain products that block specific parts of the interferon pathway. Two viruses that have this function are ebola and influenza viruses. Ebola virus has viral protein 35 (VP35) which can block the IFN pathway. In preliminary data, VP35 is found to block the phosphorylation of interferon regulatory factor 3 (IRF-3) which is known to transcriptionally induce IFN genes. It is then hypothesized that VP35 interacts with a cellular protein. Similarly it has also been shown that the nonstructural protein 1 (NS 1) of influenza virus can block IRF-3 activation. Also there is a host specie-specificity for NS 1, implying that there should be an interaction with a cellular protein. This proposal outlines the identification and characterization of the cellular proteins that VP35 and NS 1 interacts with. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CLONING AND EXPRESSION OF INFLUENZA VIRAL RNA SEGMENTS Principal Investigator & Institution: Nayak, Debi P.; Professor; Microbiology and Immunology; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024

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Timing: Fiscal Year 2001; Project Start 01-MAY-1980; Project End 31-JAN-2006 Summary: (Adapted from the Investigator's abstract): Influenza viruses, a group of major human pathogens, are responsible for 10,000-20,000 deaths and economic loss of $10-20 billions/yr. Influenza viruses asemble and bud from the plasma membrane, specifically from the apical side of polarized epithelial cells. Long term goal of this project is to elucidate the processes involved in polarized transport of viral proteins and assembly and budding of virus particles. Specific objectives are to: (i) define the apical determinants of HA and NA, the envelope viral proteins, (ii) define the interactions of HA and NA with M1, (iii) define the role of envelope proteins, HA and NA determining the apical vs. basolateral budding. We shall use chimeric constructions, site-specific mutations as well as reverse genetics to define the function of these proteins in virus assembly and budding. We have discovered a novel apical signal in the transmembrane domain (TMD) of apical NA and HA proteins. We will dissect and define the sequences and requirements of apical signal in the TMD of HA and NA. Using the floatation gradient analysis of Triton X-100 detergent-treated membranes, we will dissect the sequences in the TMD and cytoplasmic tail of HA and NA required for specific interaction with M1. Using reverse genetics, we will determine the role TMD and cytoplasmic tail of HA and NA in virus biology. Finally, using basolaterally targeted HA and NA in transfectant viruses we will examine if HA and NA determine the budding site (apical vs. basolatral) of influenza viruses in polarized MDCK cells. Assembly and budding of influenza viruses are critical for growth, replication and consequently in pathogenesis of influenza viruses. A detailed understanding of these processes will facilitate the rational development of antiviral agents which could interfere with one or more steps in virus assembly. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: COMPLETE CHARACTERIZATION OF THE 1918 INFLUENZA VIRUS Principal Investigator & Institution: Taubenberger, Jeffery K.; Chief; American Registry of Pathology, Inc. Armed Forces Institute/Pathology, Bldg 54 Washington, Dc 20306 Timing: Fiscal Year 2002; Project Start 10-JAN-2002; Project End 31-DEC-2006 Summary: (provided by applicant): The 'Spanish' influenza pandemic of 1918-1919 was the worst influenza pandemic in history, killing 40 million people worldwide in about one year. The agent responsible was not isolated in 1918. Pandemic influenza viruses have emerged twice since 1918, in 1957 and 1968. Future influenza pandemics will undoubtedly arise. An understanding of the genetic make-up of the most virulent influenza strain in history will facilitate prevention of such future pandemics. Using archival autopsy material from the 1918 pandemic, small fragments of influenza virus RNA can be isolated and sequenced. Assembling overlapping fragments, the complete genomic sequence of each gene of the 1918 strain can be deduced. In preliminary work, the hemagglutinin, neuraminidase, matrix, and non-structural gene segments have been sequenced. This application proposes to extend these findings by sequencing the remaining four gene segments: nucleoprotein and the three polymerase genes, PA, PB1, and PB2. Complete characterization of the viral genome is likely to yield insights into the origin and lethality of the 1918 virus, and is essential for an understanding of the molecular basis of the emergence of pandemic influenza viruses. Hypotheses on the virulence of the 1918 virus can only be tested once the complete genomic sequence of the virus is known. The second goal of the proposal is to place the 1918 virus in context by performing an initial characterization of the viruses that preceded and followed it. By identifying pre-1918 influenza viruses it can be determined which gene segments were replaced in the pandemic strain. The 1918 pandemic occurred in waves, with the first

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wave being significantly less virulent than the second. Identification of a spring wave ease would allow direct genetic comparison of the two strains and any differences would help elucidate the genetic basis of virulence of the fall wave strain. Further, by identifying influenza RNA positive cases from the post-pandemic period, 1920-1940, a comparison of the drift rate of early HINI viruses with modern ones can be made and it can be ascertained whether the unusual features of the extant 1930's influenza viruses were artifacts of culture or primary features of these viruses. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DETERMINING/UNDERSTANDING IMMUNIZATION

BARRIERS

TO

ADULT

Principal Investigator & Institution: Zimmerman, Richard K.; Family Med/Clin Epidemiology; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2001; Project Start 01-APR-1999; Project End 31-MAR-2003 Summary: Each year, an estimated 65,000 deaths occur in the US due to vaccinepreventable diseases of which more than 30,000 are preventable by immunization. In 1995 only 58% and 36% of persons 65 years of age or older reported receiving influenza and pneumococcal vaccines, respectively and rates were even lower for certain influenza immunization levels to at least 60% is unlikely to be achieved. Why are immunization rates for adults so low? Why are pro-active systems used so little, given that the literature shows that they are effective in raising rates? In the first phase of this study, the primary barriers to influenza and pneumococcal vaccination and to use of pro-active systems will be identified by an in depth study in a diverse group of settings including Veterans Administration clinics (one of which uses pro-active systems), inner city neighborhood clinics, and a set of primary care practices. To do this, a multidisciplinary team with qualitative expertise will conduct chart audits and clinician staff, and patient interviews. Provider knowledge, attitudes, and practices will be quantified about 1) vaccine indications, missed opportunities, and invalid contra- indications, 2) disease severity, vaccine efficacy, and adverse reactions, 3) vaccine reimbursement, 4) influence of peers, experts, and patients, 5) vaccine litigation, 6) use of systems that enhance immunization, such as reminder/tracking systems, 7) barriers to office systems, 8) office operations, core values and openness to change, and 9) personal vaccination status. Patient attitudes and beliefs will be quantified using the theory of reasoned action. The relative contributions of patient beliefs, provider beliefs and office systems will be quantified and used to develop a validated questionnaire for the second phase. In the second phase, a more generalizable, national sample of primary care physician (family physicians, general practitioners, general internists, and geriatricians) will be interviewed by telephone about barriers to immunizations and to proactive systems, over-sampling those practicing in areas with high proportions of minorities. This project will furnish relevant, up-to-date to enhance policy planning, practice management and medical education. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DEVELOPMENT OF NOVEL ANTI-INFLUENZA AGENTS Principal Investigator & Institution: Lallos, Lisa A.; Aphios Corporation 3-E Gill St Woburn, Ma 01801 Timing: Fiscal Year 2003; Project Start 01-JAN-2003; Project End 31-DEC-2003

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Summary: (provided by applicant): Influenza is a common and serious respiratory illness affecting tens of thousands each year and causing 20,000 - 40,000 deaths. This significantly contributes to the loss of manpower hours and revenue each year. Annual vaccine programs are in place to protect individuals at high risk, but participation is far from complete. The influenza strains used in the vaccine are predicted from prevalent strains during the previous flu season; emerging strains not present in the vaccine will be able to infect vaccinated individuals. In addition, several manufacturing problems have led to a shortage of vaccine early during the flu season. Antiviral therapy is an important adjunct to the vaccine; currently, only four anti-influenza drugs are on the market in the United States. The need exists, therefore, for additional anti-influenza drugs. The applicants propose to screen their unique library of extracts, derived from SuperFluids extraction of marine microorganisms, for activity against influenza A and B. Extracts will be identified as "hits" based on a selective index (SI) for either influenza A or B, or both. Confirmatory assays followed by preliminary target identification will be done to confirm activity and prioritize the active extracts for fractionation and purification of the active compound(s). To date, the investigators have identified two extracts that are effective against influenza B in preliminary screening assays. The proposed screening of the unique marine molecules library may result in the development of a novel anti-influenza drug. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: INFECTION

EFFECTS

OF

MORPHINE

ON

PULMONARY

INFLUENZA

Principal Investigator & Institution: Coussons-Read, Mary E.; Psychology; University of Colorado at Denver Campus Box 129 Denver, Co 802173364 Timing: Fiscal Year 2000; Project Start 01-APR-2000; Project End 31-MAR-2004 Summary: (Adapted from the Applicant's Abstract): Respiratory illness is a leading cause of death among HIV-positive intravenous opioid users. It is critical to understand the effects of opioid use on respiratory immunity and how such effects may impact HIV disease. The proposed AREA project uses an animal model to address this issue by characterizing the effects of morphine on pulmonary immunity and influenza virus infection in rats. The project will be conducted at the University of Colorado at Denver (UCD), which is an urban university that serves many nontraditional students, trains significant numbers of graduates who pursue careers in the biomedical sciences, and is not a major recipient of NIH support. This AREA project utilizes a Rat-Adapted Influenza Virus (RAIV) model, and preliminary data show that morphine treatment impairs both resting pulmonary immunity and the innate pulmonary immune response to RAIV. Specific Aim 1 extends these findings by examining dose-effect relationships in the impact of sub-chronic and chronic morphine treatment on resting pulmonary immunity. Lymphocyte proliferation to mitogen and superantigen, natural killer cell activity, and phenotypic distribution of lymphocytes will be used to assess resting pulmonary immune status. Specific Aim 2 will assess the dose-dependency and mechanism of morphine's effects on the innate pulmonary immune response to RAIV infection. Viral replication, pulmonary inflammation, and characterization of pulmonary cell types after infection will be used to measure the response to RAIV. Specific Aim 3 will test the hypothesis that morphine treatment will cause dose-dependent reductions in RAIV-specific acquired immunity, and that activation of opioid receptors is responsible for these effects. Measurements of anti-RAIV antibodies, RAIV-specific lymphocyte proliferation, and RAIV-specific CTL activity in the lungs and peripheral blood will be used to assess acquired immunity. Future studies will utilize RAIV and

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bacterial infection to increase understanding of how interactions between infection, drug use, and the immune system may adversely affect HIV infection in humans. Importantly, this project will establish a new and meritorious research program that will provide increased research opportunities for UCD students. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ENDOCYTOSIS OF INFLUENZA VIRUSES Principal Investigator & Institution: Whittaker, Gary R.; Microbiology and Immunology; Cornell University Ithaca Office of Sponsored Programs Ithaca, Ny 14853 Timing: Fiscal Year 2001; Project Start 01-JUL-2001; Project End 31-MAY-2006 Summary: (provided by applicant): The entry mechanisms of viruses into cells are critical for infection and subsequent pathogenesis. For -influenza virus, many of the aspects of the entry pathway under viral control are well understood, but how the virus interacts with the cellular trafficking machinery for internalization and endocytosis remains unclear. The virus is known to bind to a sialic acid-containing receptor and to fuse out of a low-pH intracellular compartment, but how the virus traverses the cell between these two events, and which cellular control mechanisms regulate these events are unknown. Transit through the cellular endocytic pathway is regulated by GTPases such as dynamin and specific Rab proteins. The effects on virus entry of specific inhibition of these molecules will be studied in this proposal. Experiments will be performed both by light microscopy and at the ultra-structural level by electron microscopy. GTPase function will be inhibited by use of dominant-negative mutants and by microinjection of inhibitory antibodies. We have shown that influenza virus entry into cells is inhibited by a specific inhibitor of cellular protein kinase C (PKC). This may represent a key control point for the virus in its route of entry into a host cell. The mechansim of action of the inhibitor and the role of PKC in virus endocytosis will be examined, in relation to the various endocytic pathways of the cell. Influenza virus is known to occur in nature as both a large filamentous form (100 nm by up to 2pm) and a small spherical form (100 nrn diameter). It is the filamentous forms that are thought to be important for infection in the human lung, but a study of the entry mechanism for this morphological form of the virus has never been carried out. Whereas entry of tissue culture-adapted spherical virus occurs via clathrin-coated pits, this would appear to be an inefficient route of entry for large filamentous viruses. Both filamentous and spherical viruses will be isolated and compared for their route of entry, to determine the entry mechanism for the clinically-important filamentous viruses. Influenza remains a major threat to human health. These studies will lead to a more complete understanding of the entry mechanism of the virus and may lead to the development of more effective anti-viral drugs. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: EXERCISE & INFLUENZA IMMUNITY:PSYCHONEUROENDOCRINE MODEL Principal Investigator & Institution: Kohut, Marian L.; Assistant Professor; Health and Human Performance; Iowa State University of Science & Tech Ames, Ia 500112207 Timing: Fiscal Year 2002; Project Start 01-JUN-2002; Project End 31-MAY-2005 Summary: (provided by applicant): The purpose of the proposed study is to investigate the effects of a regular, moderate exercise program on the immune response to influenza immunization in older adults; and to determine whether the mechanisms of the exercise-induced immunomodulation involve psychosocial and/or neuroendocrine

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adaptations. Older adults experience a greater incidence and severity of influenza infection, as well as reduced vaccine efficacy. We hypothesize that exercise will enhance immune response to the vaccine and improve psychosocial state. A total of 72 men and women > age 65 will be assigned to an exercise (EX), n=36, or control (CON) group, n=36. An additional 32 subjects (n= 16 EX, n=16 CON) currently treated with nonselective beta-adrenergic receptor antagonists will be recruited to test the hypothesis that the immunomodulatory effects of exercise are mediated via catecholamine activation of beta-adrenergic receptors. Subjects will be immunized with influenza vaccine and will be randomly assigned to participate in either a regular vigorous aerobic exercise program (EX) or a flexibility program (CON) for one year. Blood samples will be taken pre and post-immunization. At the end of one year, subjects will be immunized again and blood samples will be taken pre-immunization and up to 6 months postimmunization. Psychosocial measures of depression, perceived stress, social support, positive/negative affect, and daily hassles/uplifts will be assessed numerous times throughout the study. The primary immune outcome measures are: anti-influenza IgG and IgG1, influenza specific peripheral blood mononuclear cell proliferation and cytokine (interleukin (lL)-2, IL-10, interferon (IFN)-gamma) production, cytotoxic T lymphocyte (CTL) function, and intracellular influenza-specific IL-2, IL-b 0, IFN-gamma, in CD4+, CD8+, CD45RA+ and CD45RO+ cells. Growth curve modeling will be used to analyze the relationship between treatment condition and changes in the measures of immunocompetence over time. The findings from this study may have relevance from both a clinical and basic research perspective, if moderate exercise is associated with enhanced anti-influenza immunity and improved protection from infection. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: FLOW CYTOMETRIC ANALYSIS FOR T CELL PROLIFERATION Principal Investigator & Institution: Ghanekar, Smita; University of Washington Seattle, Wa 98195 Timing: Fiscal Year 2001; Project Start 30-JUL-2001; Project End 31-DEC-2006 Summary: (provided by applicant) T cell proliferation and the calculation of a stimulation index are one of the mostly widely used methods in both mouse and man to demonstrate antigen specific immunity. We propose to define a "second generation" assay to replace traditional lymphocyte proliferation assays using [3H]thymidine uptake. Multiparameter flow cytometry will be used to assess antigen-specific T cell proliferation by measuring incorporation of BrdU, a thymidine analog. In addition to proliferating T cells, surface markers associated with proliferating cells will be examined. Surface markers to be examined will include CO27, CD45RO/RA, and CO95. These are all markers that can be used, singly or in combination, to distinguish naive from memory cells. Antigen-specific BrdU incorporation will be used to identify proliferating antigen-responsive cells, so that analysis of other markers can be perfoffi1ed by gating on these cells. In a preliminary study using SEB as a stimulus, positive correlation was observed between flow cytometric measurement of proliferating CD4+ T cells by BrdU incorporation and a standard proliferation assay measuring [3H]thymidine uptake by PBMC. We propose to extend the use of BrdU proliferation assay using flow cytometry in assessing T cell proliferative responses to CMV, flu, and tumor antigens. The aim of this pilot project will be to correlate lymphocyte proliferation assay using non-radioactive BrdU incorporation measured by multiparametric flow cytometry and a standard radioactive [3H]thymidine incorporation assay in the following systems: CMV, influenza, and at least one of the

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Influenza

candidate cancer antigens to be evaluated by the consortium (MAGE-3, HER2, CEA, or gp100). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HETEROGENEOUS SUBSETS OF MEMORY CD4 T CELLS Principal Investigator & Institution: Farber, Donna L.; Associate Professor; Surgery; University of Maryland Balt Prof School Baltimore, Md 21201 Timing: Fiscal Year 2003; Project Start 01-FEB-2003; Project End 31-JAN-2008 Summary: (provided by applicant): A successful bio-defense strategy involves the largescale immunization of individuals to provide protective immunity against deadly pathogens from anthrax to influenza. Such vaccines depend entirely on the generation of immunological memory mediated by long-lived memory T cells that coordinate efficacious clearance of the pathogen. Understanding the precise mechanisms for the generation, long-term maintenance and superior functional properties of memory T cells is therefore of paramount importance for the design of effective vaccines as part of a preemptive bio-defense plan. My laboratory has been studying the memory immune response directed against the hemagglutinin (HA) protein of influenza. HA-specific immunity protects an individual from subsequent infection with influenza virus and is targeted in many influenza vaccine preparations. We have identified novel and profound heterogeneity within influenza HAspecific memory CD4 T cells. In particular, we have found that HA-specific memory T cells are heterogeneous for expression of a homing receptor that directs T cells to lymphoid compartments. This phenotypic heterogeneity, in turn, delineates functional subsets of HA-specific memory T cells. Here, we propose experiments to dissect the mechanisms for the generation, maintenance, in vivo homing properties, and gene expression profiles of these memory subsets. We have also identified heterogeneity in the ability of HA-specific memory T cells to produce different types of effector cytokines according to the nature of the recall stimulus. These findings reveal remarkable functional plasticity of memory T cells that has direct implications for vaccine design aimed at maintaining protective immunity, and we propose to examine mechanisms underlying this functional flexibility, including determining how bacterial superantigens such as Staphylococcal Enterotoxin B (SEB) may alter HA- specific memory T cell function. Our results suggest that pathogenspecific memory immune responses are mediated by memory T cells with diverse functional and phenotypic properties, and that the very success of vaccines to generate a long-lived anamnestic response depends on generating heterogeneous memory T cells. This research proposal will therefore address the basic mechanisms underlying memory T cell heterogeneity, using novel cellular immunologic and molecular approaches. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: HIGH SPEED AUTOMATED INFLUENZA VACCINE HARVESTER Principal Investigator & Institution: Phelps, Patricia V.; Embrex, Inc. 1035 Swabia Crt Research Triangle Park, Nc 27709 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 31-MAR-2002 Summary: (Provided by Applicant): The Influenza vaccine manufacturing process is far from optimal and this results in delay and shortage of flu vaccine available to the US population. The inefficient and time consuming production of vaccine in chicken eggs is a key problem in manufacturing. The key bottleneck in the manufacturing process is the harvesting of allantoic fluid (vaccine) from embryonated eggs. This proposal discloses adapting automated egg handling technology developed for use in the poultry industry

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to improve egg handling technology and automation in human influenza vaccine production processes. Improved automation and implementation of advanced technology in the influenza vaccine manufacturing process should increase vaccine production efficiency, reduce labor needs, shorten vaccine manufacturing time, reduce costs and decrease problems associated with production of vaccines in eggs. The resulting technology will benefit influenza vaccine manufacturers by reducing costs and simplification of the manufacturing process. The resulting technology will benefit the people of the United States by improving time to market and availability of influenza vaccines. The resulting technology will enhance ability to meet Healthy People 2010 goals for Influenza vaccination and complement influenza vaccination programs recommended by the Center for Disease Control (CDC), National Immunization Program (NIP), Advisory Committee on Immunization Practices (ACIP) and World Health Organization (WHO). The proposed influenza vaccine-harvesting device will increase the production rate by 25 percent and improve efficiency of harvesting by at least 5 percent. PROPOSED COMMERCIAL APPLICATION: Improved automation of current Influenza vaccine harvesting processes can potentially increase the amount of vaccine produced per egg and production cycle thus reducing vaccine cost, improving time to market and easing manufacturing burdens. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HOST RESPONSE TO POST-OPERATIVE PNEUMONIA Principal Investigator & Institution: Knight, Paul R.; Professor and Vice Chairman; Anesthesiology; State University of New York at Buffalo Suite 211 Ub Commons Amherst, Ny 14228 Timing: Fiscal Year 2001; Project Start 01-JUL-2001; Project End 31-MAY-2006 Summary: (Verbatim from the Applicant's Abstract): Anesthesia/surgery predisposes the patient to develop nosocomial pneumonia by mechanisms that are not completely defined. The presence of a viral respiratory tract infection (RTI) during anesthesia/surgery further complicates the host antibacterial response. Evidence from our laboratory has demonstrated anesthesia/surgery induces changes in cytokine response (e.g., TNFalpha, MIP-2, IFNgamma), leukocyte recruitment, and lung injury to influenza RTI. These responses are also critical to innate host defenses against bacterial pathogens. Our focus is to examine cellular mechanisms during a viral RTI that predispose the host to a post-surgical bacterial pneumonia. We hypothesize that anesthesia/surgery will change host responses differently during distinct periods in the course of a viral RTI by altering expression of pro- and antiinflammatory cytokines, thereby decreasing antibacterial defenses. Aim #1 will assess the effects of anesthesia/surgery during influenza on bacterial clearance, inflammatory cell influx, and cytokine expression an Escherichia coli challenge. We predict that laparotomy during influenza will promote the relative expression of MCP-1 and IL-10 over TNFalpha, MIP-2, and IFNgamma. Aim #2: will assess ex vivo the combined effect of laparotomy and influenza on a) LPS stimulated aMphi cytokine expression and phagocytic activity, and b) the ability of in vitro antiMCP-1, antiIL-10, or IFNgamma administration to improve M dysfunction. We postulate that laparotomy during influenza will alter aMphi regulatory functions and decrease effector functions as a result of selective enhancement of expression anti-compared to proinflammatory cytokines. Finally, in Aim #3, we will examine the contribution of endogenous cytokines in the suppression of antibacterial defenses following laparotomy during influenza by selective cytokine manipulations. Bacterial clearance, inflammatory cell influx, and cytokine levels will be assessed. We anticipate that neutralization of IL-10 or MCP-1,

20

Influenza

administration of IFNgamma, or increased TNFalphaexpression will improve antibacterial host defenses following laparotomy during physical signs of influenza. These studies will examine mechanisms that lead to alterations in bacterial clearance post-surgically following a viral RTI, assess the pathogenesis of post-surgical pneumonia in general, and suggest immune adjuvant strategies to prevent this complication. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HUMAN AND MOUSE ANTIBODIES AGAINST INFLUENZA VIRUS Principal Investigator & Institution: Air, Gillian M.; Professor; Biochem and Molecular Biology; University of Oklahoma Hlth Sciences Ctr Health Sciences Center Oklahoma City, Ok 73126 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JAN-2007 Summary: (provided by applicant): Influenza vaccines have variable efficacy and protection is often low in the elderly. One hypothesis is that low effectiveness of vaccine in the elderly may be due to a preponderance of influenza-specific but non-neutralizing antibodies. These non-neutralizing antibodies may be against earlier influenza viruses, against denatured or internal viral proteins, or of low avidity. The long-term goal of this research is to develop more effective influenza vaccines by maximizing induction of neutralizing antibodies against the vaccine strain and minimizing the response to denatured glycoproteins, internal proteins, and earlier viruses. Qualitative and quantitative studies of neutralizing and non-neutralizing antibodies in sera of multiplyvaccinated or infected subjects will be undertaken in three Specific Aims. Aim 1: What antibody specificities are present in serum after repeated flu vaccination or infection? Measurement of serum antibodies in vaccinees and infected subjects against the major antigenic drift variants of H3N2 viruses, and in competition assays against monoclonal antibodies specific to those viruses will provide quantitative information on neutralizing versus non-neutralizing, cross-reactive versus strain-specific antibodies, and if the nonneutralizing antibody response is primarily directed against older viruses or against denatured virions. Aim 2: Do the major antigenic regions change in dominance during antigenic drift? The major antigenic sites on the hemagglutinin (HA) have changed in relative dominance over the years. The relative immunodominance of epitopes on the HA and the relative avidity of antibodies will be measured by competition assays, and the results refined by constructing recombinant HA genes engineered to express only one of the major antigenic sites. Aim 3: Devise a vaccine strategy to optimize production of neutralizing antibodies. The results of Aims 1 and 2 will provide a measure of the origins of non-neutralizing antibodies in serum, and allow development of a vaccine strategy to maximize neutralizing antibodies. These experiments are designed to fill a large gap in knowledge of the breadth of human antibody response to influenza vaccines, and to apply this knowledge to vaccine production to improve the ratio of protective, neutralizing antibodies. This may be of particular help in protecting the elderly from influenza. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: HUMAN VACCINE POTENCY IN MICE WITH A HUMAN IMMUNE SYSTEM Principal Investigator & Institution: Palucka, a Karolina.; Investigator; Baylor Research Institute 3434 Live Oak St, Ste 125 Dallas, Tx 75204 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-AUG-2008

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Summary: Project 1: Vaccines are the most accessible and probably most effective means of protecting humans from infectious agents. While a wealth of vaccines has been developed, natural evolution and engineering for bioterrorism purposes create novel biothreats for which novel vaccines may represent the most potent countermeasures. Vaccines need to be tested in vivo but studies in mice often cannot be directly extrapolated to humans because of differences in their immune systems. Hence, the need for pre-clinical models of the human immune system for testing vaccine potency. With this in mind, we have constructed mice with a human immune system (Humouse). There, NOD/SCID mice transplanted with human CD34+ HPCs develop naive B cells and all subsets of human dendritic cells (DCs) including myeloid DCs and plasmacytoid DCs in the bone marrow/blood, Langerhans cells in the skin and interstitial DCs in other tissues including lung. In our current, first generation model, naive/memory T cells are adoptively transferred. The Technical Development Component is expected to construct a second generation model with a complete human immune system. This project is designed to demonstrate the validity of the Humouse (first and second generations) for testing vaccine potency. We will evaluate the induction of specific cellular and humoral immune responses using Influenza virus as a model pathogen and Influenza vaccine as a model vaccine. The ultimate parameter will be the protection of mice from virus rechallenge. AIM 1 will establish how subsets of human DC in Humouse interact with Influenza virus in vivo. AIM 2 will establish the capacity of Humouse to mount protective Influenza-specific recall T cell immunity. AIM 3 will establish the capacity of Humouse to mount protective Influenza-specific primary T cell immunity. AIM 4 will establish the capacity of Humouse to mount protective humoral immune responses. This project will validate the use of mice with a full human immune system (Humouse) for in vivo testing of human vaccine potency. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: IMMUNE DETERMINANTS TO BACTERIAL AND VIRAL COINFECTION Principal Investigator & Institution: Montaner, Luis J.; Associate Professor of Immunology; Wistar Institute Philadelphia, Pa 191044268 Timing: Fiscal Year 2003; Project Start 01-JAN-2003; Project End 31-DEC-2004 Summary: (provided by applicant): The long-range goal of this application is to determine the factors that predict the manner in which pathogenesis develops during poly-microbial infections. The short-term goal of this project will be to determine the manner in which BCG-associated inflammation and its modulation of antigen presenting cells affects a new immune response to a vaccine antigen delivered as and inactivated organism. Our preliminary studies support our goals and application by establishing a link between innate DC dysfunction and lower adaptive responses to vaccine antigens delivered as an inactivated organism during an ongoing bacterial infection. Based on our preliminary observations, we hypothesize that a decreased potential to develop protective immune responses during Mycobacterial infection is due to a cyclic period of down-regulation of accessory cell function and a decrease of CD11c cell subsets. We will test this hypothesis by defining immune correlates and gene expression patterns within CD11c+ and CD11b+ accessory cell subsets during BCG infection through [1] longitudinal analysis of the changes in B-cell proliferation, T -cell activation, DC cell subsets, DC activation (CD86, CD80, CD40, CD95, MHC-II) and function (MLR, endocytosis, TLR-4 induced IL-12p70, IL-I0, TNF-a secretion), and RNA gene expression of sorted CD11c+CD11b+ or CD 11c+CD 11 b+ DC subsets from longitudinal time points by cDNA microarrays of un-stimulated and in vitro stimulated

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cultures; and [2] establishing the biological impact of accessory cell changes due to primary BCG infection on the development of secondary anti-flu responses by analysis of the development and recruitment of antiviral humoral and cell-mediated immune memory responses acquired through UV inactivated Influenza A/PR8 vaccination of naive or BCG-infected animals at weekly intervals throughout BCG infection. We apply a vaccine approach within an on-going bacterial infection as a surrogate method to elicit a primary immune response and its associated memory pools with minimal pathology or additional pathogen co-factors. We will compare morbidity and mortality outcomes to developing antiviral immune responses following live challenge of animals having received vaccination against Influenza A/PR8 at different periods of BCG infection and clearance. Completion of this application will provide identify innovative targets for increased susceptibility to bacterial/viral co-infections by addressing understudied areas of innate immunity and chronic inflammation as central factors to decreased adaptive responses and protective immunity. This application represents a collaborative effort by The Wistar Institute and the Department of Dermatology, and the Center for Clinical Epidemiology and Biostatistics from the University of Pennsylvania. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: IN INFLAMMATION

VITRO

/IN

VIVO

APPROACH

TO

ARTERY

WALL

Principal Investigator & Institution: Fogelman, Alan M.; Professor of Medicine & Chief; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2008 Summary: During the current grant period normal HDL was shown to inhibit three steps in the formation of mildly oxidized LDL (MM-LDL). The function of HDL (its ability to prevent LDL oxidation and inactivate oxidized phospholipids (Ox-PAPC) in MM-LDL) was found to better predict atherosclerosis in some patients than HDLcholesterol. MKP-1 was required for Ox-PAPC to induce endothelial cells to produce MCP-1. Paraoxonase (PON)-2 was found to be an intracellular enzyme capable of inactivating Ox-PAPC while PON-3 was shown to be an HDL associated enzyme that like PON-1 inactivates Ox-PAPC, but unlike PON-1 is not regulated by Ox-PAPC. OxPAPC regulated hepatic PON-1 and apoJ, but not MCP-1, via IL-6. Following influenza A infection in mice, HDL lost PON activity and lost the ability to protect LDL against oxidation. When an apoA-I mimetic peptide synthesized from all D-amino acids (D-4F) was given orally to LDL receptor null mice on a Western diet or apoE null mice on a chow diet, there was a dramatic improvement in HDL's ability to inhibit LDL oxidation accompanied by a dramatic decrease in atherosclerotic lesions independent of total plasma or HDL-cholesterol. When D-4F was given to LDL receptor null mice after a Western diet and influenza A infection there was a dramatic reduction in macrophage traffic into the aortic arch and innominate arteries. In the next grant period the mechanisms by which MKP-1 mediates the inflammatory response induced by OxPAPC will be determined in genetically engineered mice. A link between reverse cholesterol transport and LDL oxidation will be explored in mice. The mechanisms of action of D-4F will be determined in mouse models of atherosclerosis. The ability of D4F to promote the formation and cycling of pre-beta HDL-like particles through the reverse cholesterol transport pathway will also be studied. The mechanism by which D4F inhibits macrophage traffic into arteries after influenza infection will be determined. The mechanisms by which oral administration of a synthetic phospholipid raises HDL and PON levels, and decreases atherosclerosis in mouse models will be determined.

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Finally we will determine if HDL function is a sensitive indicator of the presence or absence of atherosclerosis in mice and humans. This proposal will identify potential diagnostic and therapeutic targets by elucidating the molecular and genetic mechanisms that enhance or inhibit the inflammatory response to oxidized phospholipids. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: IN VIVO TARGETING OF HUMAN DENDRITIC CELL SUBSETS Principal Investigator & Institution: Banchereau, Jacques F.; Director; Baylor Research Institute 3434 Live Oak St, Ste 125 Dallas, Tx 75204 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-AUG-2008 Summary: Project 4: Vaccines and antibiotics help prevent or ameliorate many infectious diseases. Yet, natural evolution and engineering for bioterrorism purposes create novel biothreats for which novel countermeasures are necessary including i) development of novel chemotherapeutic agents, and ii) utilization of natural defense mechanisms, i.e., the immune system. The latter one may include non-specific activation of the innate immune system and manipulation of the adaptive immunity through vaccines. We now know that vaccines act through dendritic cells (DCs), the initiators and controllers of immune effectors (T and B lymphocytes) differentiation. Just as lymphocytes are composed of different subsets, DCs comprise several subsets that differentially control lymphocyte function. It is therefore important to understand how distinct DC subsets modulate vaccine immunity in vivo. Such knowledge will permit us to design targeted vaccines that will induce a desired type of immunity. This project is designed to i) construct novel human vaccines comprised of antibodies targeting distinct subsets of human DCs coupled to an antigen of choice, either as chemical conjugates or as antibody-antigen fusion proteins, and ii) determine the quality and magnitude of antigen-specific immune responses elicited in vitro and in vivo by targeting distinct subsets of human DCs. We will evaluate, in the mice with a human immune system (Humouse), the induction of specific cellular and humoral immune responses using Influenza virus as a model pathogen. AIM 1 will determine whether anti-DC mAb/Flu conjugates can induce Flu-specific secondary responses in vitro. AIM 2 will determine whether anti-DC mAb/Flu conjugates that target different DC subsets prime immune responses in vitro. AIM 3 will determine the in vivo targeting of human DC subsets by selected anti-DC mAb/Flu conjugates. AIM 4 will determine whether specific anti-DC mAb/Flu conjugates targeted to distinct human DC subsets in vivo permit the priming of Flu-specific protective immune responses. The ultimate parameter of vaccine potency will be the protection of Humouse from virus rechallenge. This study will lead to generation of novel vaccines targeted to human DC subsets in vivo. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: INFLUENZA DNA VACCINE FOR BIODEFENSE/PANDEMIC READINESS Principal Investigator & Institution: Haynes, Joel R.; Powderject Vaccines, Inc. 585 Science Dr Madison, Wi 53711 Timing: Fiscal Year 2003; Project Start 15-AUG-2003; Project End 31-JAN-2008 Summary: (provided by applicant): DNA vaccines encoding influenza hemagglutinin (HA) antigens offer an important advantage toward influenza pandemic and biodefense readiness in terms of the speed with which new influenza DNA vaccine vectors can be formulated and manufactured following identification of a new threat virus. Importantly, large scale manufacturing of influenza DNA vaccines specific for

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highly pathogenic viruses can be accomplished in the absence of biological containment requirements. The use of particle-mediated epidermal delivery (PMED) technology offers further advantages in the low DNA dosage requirement, the ability to deliver such vaccines with a reusable, mass vaccination device, and the proven ability of PMEDbased DNA vaccines to induce protective level humoral and cellular responses in humans. In this application, we intend to conduct three clinical research trials to establish proof-of-concept for the protective efficacy of PMED influenza DNA vaccines encoding HA. These trials will evaluate the ability of a trivalent PMED DNA vaccine formulation to induce HA-specific humoral and cellular responses to three separate antigens. Evidence for the protective efficacy of these responses will be demonstrated in a human challenge trial. In addition, evaluation of the potential of this approach for pandemic protection will be accomplished by examining the ability of this technology to elicit significant humoral and cellular responses to an H9 pandemic threat virus. Finally, we will focus PMED device development efforts toward a proof-of-concept prototype reusable device that will serve as the basis for a future mass vaccination PMED device. This reusable device will discharge a measured dose of pressurized helium through disposable unit-dose nozzles. These nozzles will be designed to facilitate manufacturing scale-up and to deliver increased DNA/gold payloads to larger skin target areas as a means of increasing the effective vaccine dose. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: INTERMEDIATES AND TRANSBILAYER PEPTIDES Principal Investigator & Institution: Caffrey, Martin D.; Professor; Chemistry; Ohio State University 1960 Kenny Road Columbus, Oh 43210 Timing: Fiscal Year 2001; Project Start 01-JAN-1998; Project End 31-DEC-2001 Summary: Membrane fusion is a critical and ubiquitous phenomenon in biology. However, the mechanism of biomembrane fusion remains one of the central mysteries of membrane biology. The "stalk" theory is widely cited as the basis for biological membrane fusion, yet there is no direct evidence that even pure lipid membrane fusion occurs via this mechanism. There is evidence that both lipid bilayer fusion and bilayer/inverted phase transitions proceed via closely-related mechanisms, involving the same intermediate structures. Dr. Caffrey will use this correspondence to test two aspects of the stalk theory as a basis for biomembrane fusion, and also test a hypothesis about the role of transmembrane domains of fusion-inducing proteins. First, he will use a unique experimental system to attempt direct determination of fusion intermediate structure, using time-resolved x-ray diffraction. Recent time-resolved cryoelectron microscopy results show that transient, ordered arrays of fusion intermediates exist under special circumstances in systems undergoing the bilayer/inverted hexagonal phase transition. In this study Dr. Caffrey will establish conditions that increase the size of and order in these arrays, and will attempt to determin directly the intermediate structure using time-resolved x-ray diffraction. This would be the first direct demonistration of a fusion mechanism. Second, the stalk theory predicts that the membrane fusion and the rate of the bilayer/inverted cubic phase transition in bulk lipid/water systems are controlled by the rate of decay of the same intermediate structure. If the stalk theory is correct, reducing the bilayer rupture tension should increase both rates in parallel. Transmembrabe peptides have been shown to substantially reduce this rupture tension at low concentrations in lipid membranes. Therefore, Dr. Caffrey and collegues will add traces of carefully characterized transbilayer peptides to lipid systems, measure their effect on the membrane tensions, and measure the rates of both the phase transition and the rate of membrane fusion in

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unilmaellar liposomes containing these peptides. The latter experiment will also test the hypothesis that the transmembrane domains of fusion-catalyzing proteins in viruses are imoportant to fusion activity because they serve to destabilize the same sort of fusion itermediate. In influenza virus hemagglutinin (HA), the transmembrane domain is crtical for fusion activity: substituting a lipid anchor for this domaim destroys HA fusion activity, but the lipid mixing activity inact. Such activity is consistent with Dr. Caffrey's hypothesis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: INTERPLAY BETWEEN THE HA AND NA OF INFLUENZA VIRUSES Principal Investigator & Institution: Gubareva, Larisa V.; Internal Medicine; University of Virginia Charlottesville Box 400195 Charlottesville, Va 22904 Timing: Fiscal Year 2001; Project Start 01-AUG-1999; Project End 31-JUL-2004 Summary: Influenza virus infection continues to be the most important respiratory disease both in terms of morbidity and mortality. The two major surface glycoproteins, hemagglutinin (HA) and neuraminidase (NA), play important roles in tissue and organ tropism, spread, and pathogenicity of influenza viruses. Our long term goals are to understand the molecular mechanisms underlying the balance between the receptorbinding and receptor-destroying functions of the HA and NA and how changes in this balance affect the pathogenicity of influenza viruses in humans. The antiviral effect of a new NA inhibitor, zanamivir, has been demonstrated in clinical trials. However, there is a major gap in our knowledge of the effects of NA inhibitors on properties of the HA and NA of human influenza viruses when replication occurs in a human host. Previous studies on the effect of NA inhibitors on the properties of influenza viruses utilized in vitro cell culture systems without regard to the specificity of the cellular receptors, neglecting the fact that the efficiency of the HA and NA functions strongly depends on the specificity of these receptors (Siaalpha2,3Gal or Siaalpha2,6Gal). Therefore, in Specific Aim 1 we will identify the mechanism(s) that allow human influenza viruses to replicate in the presence of an NA inhibitor in human respiratory tract epithelium containing Siaalpha2,6Gal-receptors. In specific Aim 2 we will test the hypothesis that a decrease in NA activity promotes the replication of zanamivir-resistant viruses with reduced affinity for HA receptors, while in Specific Aim 3 we will determine the effect of HA and NA mutations on the development of zanamivir resistance in vivo, utilizing a ferret model that possesses receptor specificity similar to that of human respiratory epithelium. Finally, in Specific Aim 4, we will determine how changes in the HA and/or NA of zanamivir-resistant mutants affect the virulence of such viruses in ferrets. The major strength of this application is (i) availability of well-characterized zanamivirresistant mutants isolated from human respiratory tract and (ii) experimental systems with adequate receptor specificity, primary tissue culture of the human respiratory tract epithelium (in vitro) and a ferret model (in vivo). Overall, the proposed studies will provide fundamental information on the interdependence of the two major surface glycoproteins of influenza viruses, focussing on adaptive mechanisms allowing replication under pressure from an NA inhibitor. Improved understanding of HA-NA interactions will undoubtedly aid in counteracting resistance to antiviral agents that specifically target the NA glycoprotein and in elucidating the impact on virulence of such adaptive strategies in human influenza viruses. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ISS-LINKED NP VACCINE TO CONTROL PANDEMIC FLU OUTBREAK Principal Investigator & Institution: Van Nest, Gary A.; Senior Director of Preclinical Research; Dynavax Technologies Corporation 717 Potter St, Ste 100 Berkeley, Ca 94710 Timing: Fiscal Year 2003; Project Start 11-AUG-2003; Project End 31-JAN-2007 Summary: (provided by applicant): The goal of this proposal is to develop and evaluate a novel influenza vaccine that incorporates conserved internal components of influenza virus such as the nucleoprotein (NP) with a potential to induce protective immunity against divergent and potentially pandemic influenza strains. The hypothesis of this proposal is that the nucleoprotein (NP) of influenza virus linked to an immunostimulatory oligonucleotide (ISS) will induce strong Th1 and CTL responses that will cross-react with widely divergent influenza A strains due to the conserved nature of the nucleoprotein molecule. The immune response induced by the NP-ISS linked material may additionally provide cross-help to enhance the response to other viral antigens such as HA, when co-administered in a vaccine, or when subsequently encountered in association with NP during viral infection. The Specific Aims of the program are: 1. Produce a nucleoprotein immunostimulatory oligonucleotide conjugate (NP-ISS) and demonstrate potent induction of Th1 and CTL responses by the NP-ISS vaccine in naive and previously infected mice. 2. Evaluate the protective immunity provided by the NP-ISS vaccine, or NP-ISS mixed with monovalent inactivated whole virus vaccine against homologous and divergent influenza strains in mice. 3. Test the immunogenicity of NP-ISS, and NP-ISS combined with standard split vaccine in primates compared to standard split vaccine alone. 4. Perform GMP scale-up manufacture and IND-enabling toxicology with NP-ISS. Assuming success in each Specific Aim, this program is intended to produce an IND-ready product that could rapidly move into clinical testing. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: LETHAL PNEUMOCOCCUS

SYNERGISM

BETWEEN

INFLUENZA

AND

Principal Investigator & Institution: Mccullers, Jonathan A.; Assistant Member; St. Jude Children's Research Hospital Memphis, Tn 381052794 Timing: Fiscal Year 2001; Project Start 01-APR-2001; Project End 31-MAR-2004 Summary: (provided by applicant): The K08 Award will provide an opportunity for the applicant to extend his virology training in the area of viral-bacterial interactions and to develop new expertise in pneumococcal pathogenesis in the setting of prior viral infection. These skills will enable the applicant to achieve his long term career goals by becoming a fully independent research scientist who can translate observations made at the bench into therapeutics and interventions at the bedside. Epidemiologic evidence suggests that there is a lethal synergism between influenza A virus and Streptococcus pneumonias accounting for excess mortality (average 20,000 influenza-related deaths per year in the US) during influenza epidemics. However, the pathogenic mechanisms underlying this interaction are poorly understood, and the lack of a suitable animal model of pneumonia following infection with both organisms has hampered study. The goal of the proposed research plan is to determine the role of receptor alterations engendered by influenza virus infection in the pathogenesis of pneumococcal pneumonia. A newly developed murine model of dual infection will be used to examine the relationships of timing and of infectious doses of influenza virus and pneumococcus to morbidity and mortality. Influenza viruses with different pathogenic features in the

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mouse will be utilized to determine how cytokine expression varies with different viruses. Expression of receptors permissive for pneumococcal adherence and invasion will be examined in the context of cytokine expression following influenza virus infection, and a correlation to development of pneumonia and in the murine model of dual infection will be made. Identification of specific pneumococcal proteins involved in this synergistic interaction will provide drug and vaccine targets for future intervention in human disease and death caused by pneumococcal superinfection following influenza. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: M2-BASED INFLUENZA TYPE A VIRUS VACCINE Principal Investigator & Institution: Gerhard, Walter; Professor; Wistar Institute Philadelphia, Pa 191044268 Timing: Fiscal Year 2001; Project Start 15-SEP-2000; Project End 31-AUG-2005 Summary: (Adapted from Applicant's Abstract) Influenza virus infection remains a serious threat to human health, particularly in the elderly, in whom it tends to cause severe morbidity associated with high mortality. Unfortunately, current influenza virus vaccines are less than 50 percent effective in preventing serious disease and hospitalization in the elderly. This could be due to the declining ability of aging immune systems to generate effective antibody (Ab) responses to antigens encountered for the first time. The latter is the basis of current vaccines, which attempt to induce Ab responses that are largely specific for determinants of the hemagglutinin and neuraminidase of newly emerging epidemic virus strains. By contrast, since established memory Ab responses can often be sustained for decades, a protective cross-reactive Ab response may provide increased protection in elderly people. This proposal aims to explore the protective efficacy of such a cross-reactive Ab response that is directed to the ektodomain of the M2 protein, a highly conserved influenza virus transmembrane protein. The specific aims are: 1) to construct a multiple antigenic peptide vaccine that comprises several M2 ektodomains and helper T cell determinants; 2) to identify, in a murine model, a vaccination protocol that induces a strong M2-specific Ab response and protection against influenza virus induced morbidity; 3) to test the ability of virus to escape this Ab-mediated protection through mutation; 4) to test whether a sustained M2-specific memory response provides enhanced protection in old mice; and 5) to determine how the M2-specific protection is modified by infections occurring prior or subsequent to vaccination. The proposed research will tell whether a cross-reactive M2specific Ab-mediated immunity has the potential of providing improved protection in the elderly. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MALARIA VACCINE--ATTENUATED INFLUENZA & VACCINIA VECTORS Principal Investigator & Institution: Nussenzweig, Ruth S.; Professor; Medical/Molecular Parasitology; New York University School of Medicine 550 1St Ave New York, Ny 10016 Timing: Fiscal Year 2001; Project Start 01-SEP-1994; Project End 31-MAY-2004 Summary: During the course of the previous grant the PI characterized the humoral and cellular anti-malaria immune responses induced by recombinant influenza and vaccinia viruses expressing selected sequences or the entire CS protein or malaria parasites. She characterized the immune responses of mice resulting from their successive vaccination

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with these two recombinant viruses, expressing the CS protein of rodent (P. yoelii) and human (P. falciparum) malaria parasites. These studies demonstrated that in the case of Py, the combined immunization with these two viruses induces protecting, mediated by malaria-specific antibodies and T cells which confer extensive resistance to challenge with viable parasites. In the case of Pf, the presence of in vivo activated circulating, protective CS-specific T cells was shown indirectly by the increased resistance of immunized mice to the intracerebral replication of recombinant vaccinia virus expressing the same CS-specific epitope. Considering the possibility of applying this approach to the development of a human malaria vaccine, we currently propose to pursue the following aims: Determine the optimal conditions for the engineering of highly immunogenic recombinant influenza viruses expressing a) a unique B cell epitope which has been shown to induce effective antibody responses against the native parasite protein, and b) a universal CD4+ T cell epitope which can be recognized by individuals bearing different class II MHC molecules. With the purpose of developing safe and effective malaria vaccines, she will generate highly attenuated recombinant viruses expressing an optimal set of CS epitopes. She will use cold adapted influenza viruses and the MVA strain of vaccinia viruses, both of which have been used to immunize large numbers of humans, without severe side effects. These attenuated vectors will be evaluated with regard to their safety and immunogenicity to induce antibodies and CD4+ and CD8+ T cell responses against malaria epitopes/antigens. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MECHANISM OF AUTOANTIBODY FORMATION IN HUMAN AGING Principal Investigator & Institution: Stollar, Bernard D.; Professor and Chairman; Biochemistry; Tufts University Boston Boston, Ma 02111 Timing: Fiscal Year 2001; Project Start 15-AUG-1996; Project End 31-JUL-2004 Summary: The long term goal of the proposed research is to understand agingassociated changes in autoantibody formation and humoral responses to vaccination. In the current period of this grant support, we have confirmed the increased frequency of autoantibody production, identified changes in the expressed Ig gene repertoire in human aging, and found a high degree of variability among elderly humans in frequency of Ig gene mutations and in the memory B cell numbers. We will pursue the implications of these findings, both in continuing studies on the origins of agingassociated autoantibodies and in tests of the functional significance of variations in memory B cell numbers. Specific Aim 1. We will continue to test alternate hypotheses for mechanisms underlying autoantibody formation, to distinguish between unmasked expression of natural autoantibodies and autoantigen-stimulated selection. Specific Aim 2: We will test the hypothesis that marked deviations from normal numbers of CD27+ memory B cells predict a poor response of nursing home residents to influenza vaccination and that their memory B cell changes are related to underlying changes in T cell functions. We will determine: a. whether CD19+CD27+ cells correspond to memory B cells, with mutated V region genes, in elderly people as in young adults; b. whether the size of the CD27+ memory B cell population is a fixed characteristic for individuals, or a labile parameter that may reflect disease or diminished regulation; c. whether influenza-specific memory B cells are present among the CD27+ B cells of vaccinated subjects; d. Whether unusually low or high levels of CD27+ B cells are correlated with unusual levels of T cell subset populations and/or low T cell function, which might underlie B cell dysregulation; and e. whether nursing home residents with either very

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low or very high numbers of memory B cells generate a low humoral response to influenza vaccine. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MECHANISMS OF ALLOGRAFT TOLERANCE Principal Investigator & Institution: Orosz, Charles G.; Professor; Surgery; Ohio State University 1960 Kenny Road Columbus, Oh 43210 Timing: Fiscal Year 2001; Project Start 01-JAN-1999; Project End 31-DEC-2002 Summary: Long-term allograft survival is readily achieved in murine cardiac allograft recipients, but very little is known about the mechanisms by which this allograft acceptance is induced or maintained. We have developed a testable, working paradigm of cardiac allograft acceptance. This paradigm holds that allograft acceptance involves immune processes that actively protect allografts. We believe that one manifestation of this alloprotective process, the phenomenon of linked antigen non-responsiveness, holds the key to understanding allograft acceptance. The proposed studies will investigate important aspects of the alloprotective responses that develop in allograft recipients. Specific Aim 1: To evaluate the contributions of three intriguing cell types to the initiation of allograft acceptance responses. These are addressed as the "memory hypothesis", the "gamma/delta hypothesis", and the "NKT hypothesis". In general, we will use cell transfer studies with SCID mice to determine the role of memory T cells, gammadeltaT cells or NKT cells in the generation of alloprotective activity, ie., linked DTH non-responsiveness or cardiac allograft acceptance. Specific Aim 2: To evaluate two non-competing mechanisms by which allograft acceptance is maintained. These are addressed as the "cytokine synergy hypothesis" and the "protected compartment hypothesis". In general, we will use cytokine knock-out mice and anti-cytokine antibodies to dissect the roles of TGFbeta, IL10 and IL4 in the expression of alloprotective activity (linked DTH non-responsiveness and cardiac allograft acceptance). We will also determine whether new alloprotective mechanisms independent of these cytokines are installed in accepted allografts over time. Specific Aim 3: To identify the cytokine environment necessary for the in vitro generation of alloprotective T cells that can be transferred into allograft recipients to promote cardiac allograft acceptance. Initially, these studies will use IL10 to drive alloantigen- stimulated splenic T cells towards alloprotective behavior. Specific Aim 4: To evaluate and optimize the experimental system in which tolerization to BSA, a foreign protein unrelated to an allograft, can be used to promote linked non-responsiveness to graft alloantigens, and thus educate an allograft recipient toward allograft acceptance. This represents a novel therapeutic approach that uses BSA as a "vaccine" for transplant recipients. Routine molecular genetic methods would allow us to explore the potential of this vaccine strategy for use as a potential gene therapy in transplant recipients. Finally, we will evaluate the effects of concurrent infection with murine influenza virus on he survival of the graft and recipient in mice that are being educated with BSA for allograft acceptance. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MECHANISMS OF ENZYME CATALYSIS Principal Investigator & Institution: Dunaway-Mariano, Debra; Associate Professor; Chemistry; University of New Mexico Albuquerque Controller's Office Albuquerque, Nm 87131 Timing: Fiscal Year 2002; Project Start 01-FEB-1996; Project End 31-MAY-2006

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Summary: (provided by applicant): The goal of this project is to determine structure, function, and mechanism of action of selected members of the PEP mutase/isocitrate lyase and 4-hydroxybenzoyl-CoA thioesterase enzyme families. This information will be used to relate active site structure to catalysis, and thereby identify markers, which can be applied in the assignment of function to all unknown proteins within each enzyme family. The novel protein functions and metabolic pathways that are anticipated to emerge from these efforts will, along with the active site structure determinations, serve as the foundation for drug discovery. Finally, from the proposed studies the principal investigator and her group will gain insight into the catalytic mechanisms of the enzymes mediating the diverse chemistries represented by the two enzyme families, and into how these catalytic mechanisms evolved from ancestral active site templates. Specific Aims 1-4 will address structure, function and catalytic mechanism in four members of the PEP mutase/ isocitrate lyase enzyme family: phosphonopyruvate hydrolase of Burkholderia cepacia, 5, 1 0-methylenetetrahydrofolate: 3-methyl-2oxobutanoate hydroxymethyl transferase of Pseudomonas aeruginosa, a protein associated with petal death in carnation, and a protein of unknown function present in Mycobacterium tuberculosis (Rv1998c). Specific Aims 5-9 will address structure, function and catalytic mechanism in five members of the 4-hydroxybenzoyl-CoA thioesterase enzyme family: 4-hydroxybenzoyl-CoA thioesterase, the YgbC enzyme of the Haemophilus influenza Tol-pal Pathway, the P76084 unknown protein of the E.coli Phenylacetate Catabolic Pathway, the BH1 997 unknown protein of the Bacillus halodurans Upper Gentisate Pathway and the Pseudomonas aeruginosa PA551 9 homologue to the Human Long Chain Acyl-CoA Thioesterase Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MECHANISMS OF SLEEP RESPONSES TO VIRAL INFECTIONS Principal Investigator & Institution: Krueger, James M.; Professor of Neurobiology; Vet & Comp Anat/Pharm/Physiol; Washington State University 423 Neill Hall Pullman, Wa 99164 Timing: Fiscal Year 2001; Project Start 30-SEP-1997; Project End 31-AUG-2006 Summary: (applicant's abstract): Fatigue, excessive sleepiness, excess sleep, and sleep disturbances are presenting symptoms in nearly all infectious diseases. The broad objective of this proposal is to characterize the molecular mechanisms responsible for changes in sleep induced by influenza virus. We hypothesize that viral double-stranded (ds) RNA is produced in infected cells and it, in turn, induces an upregulation of cytokines including interferons (IFN). The cytokines then induce growth hormone releasing hormone (GHRH) release and it, via nitric oxide (NO), enhances sleep. Substantial preliminary data support this hypothesis. The model used in the proposed studies is A/PR/8/34-HIN1 influenza virus infection in the mouse. PR8 causes a pneumonitis accompanied by early onset of sleep responses. In Specific Aim #1, a comparison will be made using gene arrays of the time courses of cytokines induced by pure influenza virus and dsRNA in lung and brain. We expect a similar cytokine profile after both stimuli. In Specific Aim #2 the role of the GHRH receptor in viral-induced sleep responses will be determined. Preliminary data indicate that mice lacking a functional GHRH receptor sleep less, rather than more, after viral challenge. We anticipate that that finding will be confirmed and that GH replacement therapy will not alter the virus-induced sleep responses, but may reduce mortality. In Specific Aim #3, nitric oxide synthase knockout mice will be used to investigate the role of NO in viralinduced sleep. Preliminary data indicate an attenuated sleep response after host challenge in NOS-2 (inducible NOS) knockout mice. In Specific Aim #4, IFN receptor

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(types I and II) knockout mice will be used to investigate the role of IFNs in viralinduced sleep. In Specific Aims 2, 3, and 4 we anticipate that the cytokine gene profiles induced by virus in the mutant strain will be different from controls and will reflect the different sleep responses induced by virus in these mutant strains of mice. In Specific Aim #5, we will investigate, in vitro, the role of virus-associated dsRNA in cytokine induction by influenza. Since we hypothesize that dsRNA upregulates cytokines via nuclear factor kappa B (NFKB) we will determine what other activators of NFKB, e.g., free radicals, do to NFKB activation in murine macrophages and how pharmacological blockers affect viral-induced activation of NFKB and the cytokine cascade. The anticipated results will greatly aid our understanding of the molecular mechanisms involved in viral-induced sleep responses and other facets of the acute phase response. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MEMORY T CELL RECRUITMENT AND RESPONSES IN THE LUNG Principal Investigator & Institution: Bradley, Linda M.; Associate Professor; Trudeau Institute, Inc. Saranac Lake, Ny 12983 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-AUG-2008 Summary: A key feature of the immune system is its ability to respond quickly and specifically to previously encountered pathogens by mobilization of memory cells that were generated by an initial exposure to Ag. With the threat of bioterrorism using viral and bacterial pathogens, the critical importance of exploiting the memory response for protection of the human population against disease through vaccines has renewed immediacy. A major route of infection for agents likely to be used for bioterrorism is inhalation. Two pathogens that will be studied as part of this program that are typically transmitted by aerosol infection are influenza (flu), and tuberculosis (Tb). Both agents cause inflammation of the lung and are associated with T cell recruitment into the site to clear (flu), or limit (Tb) disease. Vaccine development to such organisms will depend upon greater understanding of the requirements for generating effector and memory cells with the capacity to migrate, respond, and persist in target tissues. We have developed adoptive transfer models with TCR transgenic CD4 and CD8 cells in which we can induce memory cells with a known history of Ag exposure and study factors that affect their function in vivo. We will study mechanisms that regulate T cell recruitment into the lungs in flu infections using genetically engineered viruses carrying epitopes for which these T cells are specific. We will collaborate with projects 1 and 2 to extend our studies to flu-specific CD4 and CD8 effector and memory subsets to investigate means to optimally induce and maintain persisting memory in the lung. We will study normal animals to validate our findings to flu and to investigate molecular pathways that regulate recruitment of CD4 cells into the lung in Tb with project 4. The goals of this proposal are to determine the adhesion pathways that regulate T cell migration into the lung, to assess the contribution of the inflammation to migration, to define memory T cell subsets that confer protection in the lung, and to evaluate the importance of memory T cells that persist in the lung for long term immunity. For this project, we will take advantage of established experimental strategies as well as novel tools that will facilitate basic studies of mechanisms that promote and modulate T cell memory to inhaled pathogens. Such information will be valuable for development of vaccination protocols that enhance efficacy through immunotherapeutic approaches to optimize protective T cell responses in the lung. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: METHODS FOR EVALUATING VACCINE EFFICACY Principal Investigator & Institution: Halloran, M Elizabeth.; Professor; Biostatistics; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2001; Project Start 01-JAN-1992; Project End 31-MAR-2003 Summary: The overall objective of this research is to develop methods for estimating efficacy and effectiveness in the field and for characterizing complex and long-term properties of vaccines in individuals and populations. The specific aims are: (1) To develop methods for community trials of vaccines that estimate the indirect, total, and overall effects of vaccination strategies as well as the direct protective effects of vaccination, VE/S. (2) To continue development of methods for evaluating the vaccine efficacy for infectiousness, VE/1. In particular, we will develop the augmented vaccine trial design for acute and directly transmitted infectious diseases. (3) To develop methods for using exposure to infection data that may available on some individuals to improve estimation of vaccine efficacy for susceptibility, VE/5. (4) To develop designs and methods of analysis for using validation samples to correct for misclassified outcomes in vaccine studies. The goal is improved estimates of vaccine efficacy and of indirect, total, and overall effectiveness of vaccination strategies as well as designs for efficient, cost-effective studies. (5) To explore interpretation of the protective effects of vaccination, VE/5, when combining results across studies in different populations, taking into account different levels of baseline transmission and pre- existing immunity. Statistical approaches include likelihood inference, generalized estimating equations, semi-parametric methods for missing and mismeasured data, hierarchical models, and survival methods. The methods are motivated by studies of vaccines against influenza, cholera, rotavirus and tuberculosis, as well as other acute and childhood diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MHC AND GAMMA/DELTA T-CELL RECOGNITION Principal Investigator & Institution: Chien, Yueh-Hsiu; Professor; Microbiology and Immunology; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2003; Project Start 01-JAN-1993; Project End 31-MAR-2008 Summary: (provided by the applicant): gamma/deltaT cells contribute to host immune competence distinctly, but their function remains undefined. Our last granting period yielded the first description of a gamma/deltaT cell population that could potentially mediate immune regulation through cross-talk between lymphocytes and immune protection through clearing infected cells with an activated phenotype. For these studies, we generated a monoclonal antibody specific for the non-classical MHC class I molecule T10, and a related molecule T22, as well as a tetrameric T10/T22 specific gamma/deltaT cell staining reagent. We showed that the expression of T10/T22 is activation induced and that they are ligands for a sizable population (about 0.1-2%) of gamma/delta T cells in unimmunized mice. Our goal is to use this system to study (i) the molecular basis of gamma/delta TCR-T10/T22 interactions; (ii) how this selfreactive TCR repertoire is regulated by ligand expression; and (iii) how T10/T22 specific gamma/delta T cells fit into the context of an immune response to Influenza virus infection. A clear understanding of how a useful gamma/delta TCR repertoire is regulated and how the T10/T22 specificity fits into the context of an immune response will shed new light on the role of these cells in the immune system. Moreover, as the T10/T22 specificity has many of the features expected of regulatory T cells, elucidation of the molecular mechanisms governing their activities should prove relevant to immunity in the contexts of tumor surveillance, autoaggression, and infection.

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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MICROCARRIER CULTURE SYSTEM FOR HUMAN INFLUENZA VACCINE Principal Investigator & Institution: Hillegas, William J.; Solohill Engineering, Inc. 4220 Varsity Dr Ann Arbor, Mi 48108 Timing: Fiscal Year 2003; Project Start 01-SEP-2001; Project End 31-JUL-2005 Summary: (provided by applicant): The goal of the proposed research is to develop an optimized microcarrier-bioreactor cell culture system that enables the rapid, efficient, large scale, low cost production of human influenza vaccine. Most human influenza virus vaccine is produced in embryonated eggs. The Federal government and other worldwide organizations are seeking alternative cell-culture approaches to influenza vaccine production since there are inherent difficulties with the egg-derived vaccines. Under normal conditions there are long lead times between (a) the identification of particular virus strains likely in each flu season and (b) the availability of appropriate vaccines against these virus strains. Microcarrier-bioreactor cell-culture technology has the potential to lower production costs and reduce the time required to produce 93 million doses of monovalent vaccine to a few months. This potential to rapidly achieve large scale, would be invaluable in case of an influenza pandemic and possibly could counter a pandemic or bioterrorist acts. To achieve the research goals, five specific aims will optimize microcarrier-bioreactor culture process parameters that affect viral yield with Vero and MDCK cells and develop protocols applicable to economic commercial use. We will (i) license manufacturing protocols to large producers of flu vaccine and (ii) sell Hillex microcarriers for those protocols. Specific Aim I. To identify and integrate critical cell culture and viral growth parameters for optimal production of human influenza virus in Vero cells grown in Hillex microcarrier-suspension culture. Specific Aim II. To extend the range of viral growth parameters (as identified in Specific Aim I) to include six additional strains of influenza virus and to compare the virus production in direct "head-to-head" competition between embryonated eggs and Vero cells grown in Hillex microcarrier-suspension culture. Specific Aim III. To assess production of human influenza virus in Vero cells grown in a microcarrier-bioreactor culture at the one liter scale. Specific Aim IV: To develop a process to expand and scale-up Vero cells from a working seed ampoule to a five liter culture and to demonstrate that the passaged cells will support high influenza virus concentrations at a larger scale. Specific Aim V: To identify and integrate critical cell culture parameters for optimal production of human influenza virus (A/Wuhan/395/95) in MDCK cells grown in Hillex microcarrier-bioreactor culture. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MICROSTRUCTURAL HETEROGENEITY IN MEMBRANES Principal Investigator & Institution: Lentz, Barry R.; Professor; Biochemistry and Biophysics; University of North Carolina Chapel Hill Office of Sponsored Research Chapel Hill, Nc 27599 Timing: Fiscal Year 2001; Project Start 01-DEC-1983; Project End 31-MAR-2002 Summary: (Adapted from applicant's abstract): The long term goal of this project is to define the lipid molecule arrangements necessary for cell membrane fusion. The focus is on understanding the molecular details of the fusion of model lipid membranes with as mediated by poly(ethylene glycol) [PEG]. The information obtained will advance PEGmediated cell fusion technologies and provide insight into how proteins mediate fusion

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of cell membranes. PEG acts to bring model membranes into close contact by removing the water between them. Biomolecular leaflets of lipids organized into closed vesicular structures serve as models for cell membranes. The Lentz group has shown that disrupted molecular packing in the contacting monolayers of lipid bilayers will induce membrane fusion. The time course of the ensuing fusion process has also been defined and shown to bear remarkable similarity to the sequence of events observed in viral membrane fusion and secretory granule fusion, except that many more molecular details can be defined in the model membrane experiments carried out by the Lentz group. Dr. Lentz plans now to define molecular details as they occur in fusion of PEGaggregated model membranes and to compare the model membrane process with what is known about biomembrane fusion in order to test the hypothesis that these two processes share molecular mechanisms. This will involve three specific aims: 1] define and compare the kinetics of model and biomembrane fusion; 2] define the lipid structural rearrangements that occur during fusion; and 3] determine how membrane structural perturbations might alter the fusion process. In addition, Dr. Lentz will test whether peptide fragments from the fusion proteins of lipid-sheathed viruses (in this case, influenza; others include human and simian immunodeficiency virus) will disrupt bilayers in ways that enhance membrane fusion. Three specific aims will also be addressed here: 1] define the effects of viral fusion peptide on model membranes and on their PEG-mediated fusion; 2] test whether lipid packing disruption is critical to allow peptide to bind to membranes in a fusion-inducing conformation; and 3] determine how the influenza viral fusion peptide might alter membrane structure so as to encourage one of more steps in the fusion process. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MODULATION OF IMMUNE RESPONSES DURING PREGNANCY Principal Investigator & Institution: Caton, Andrew J.; Associate Professor; Wistar Institute Philadelphia, Pa 191044268 Timing: Fiscal Year 2001; Project Start 01-APR-1999; Project End 31-MAR-2004 Summary: Pregnancy is associated with changes in immune function which may protect the fetus from harmful maternal immune responses, but which also increase maternal susceptibility to infections and can exacerbate or alleviate particular autoimmune diseases. This proposal will use the influenza virus A/PR/8/34 hemagglutinin (PR8 HA) as a well characterized model antigen with which to determine factors modulating the immune responses to viral, maternal and fetal antigens during murine pregnancy. The following specific questions will be addressed: 1) How do pregnancy-associated changes in immune function modulate maternal immune responses to influenza virus? The specific aspects of anti-viral immunity that are suppressed or enhanced during pregnancy will be determined by comparing pregnant and non-pregnant BALB/c mice for their abilities to generate influenza virus-specific immune responses. How pregnancy affects the capacity of influenza virus-specific T helper (Th) cells to differentiate into distinct phenotypes (e.g. Th1 versus Th2 cells) will be examined using transgenic (Tg) mice expressing HA-specific T cell receptors (TCR Tg mice). 2) Does pregnancy affect autoreactivity to influenza HA as a maternal self antigen? Whether pregnancy influences the magnitude of autoreactive HA-specific T and/or B cell responses will be examined in mice that express the HA as a neo-self antigen (HA Tg mice). In addition, the extent to which maternal anti-HA (self) Th responses in HA Tg mice are suppressed or modified (either systemically, or in lymph nodes draining the uterus) during pregnancy will be determined. 3) How does the maternal immune system perceive the HA as a fetal antigen? Female BALB/c mice will be mated with

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male HA Tg mice, and the ability of the fetal HA either to activate or to induce antigenspecific tolerance among maternal HA-specific T and/or B cells will be analyzed. Whether expression in different fetal cell types affects how the HA is perceived by the maternal immune system will be evaluated. How the induction of anti-viral immune responses can be harmful to fetal development will also be assessed. By defining mechanisms by which the maternal immune system accommodates the fetal allograft, these studies may provide clinical benefits in the areas of transplantation and autoimmunity. Determining the effects of pregnancy on immune responses to viral and self antigens, and the effects of maternal immunity on fetal development, may similarly benefit women's health and child development. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOLECULAR MECHANISMS OF INFLUENZA PANDEMICS Principal Investigator & Institution: Kawaoka, Yoshihiro; Professor; Pathobiological Sciences; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2001; Project Start 01-JAN-1999; Project End 31-DEC-2003 Summary: The long-term goal of this study is to understand the emergence of pandemic strains of influenza virus at the molecular level. New viral hemagglutinin (HA) and/or neuraminidase (NA) genes that entered the human viral gene pool in 1957 and 1968 were associated with a substantial number of influenza deaths. Moreover, epidemiologic studies on the 1918-1919 influenza pandemic suggest that generation of catastrophic pandemic viruses may involve the acquisition of enhanced virulence during replication in humans. A recent episode of human infection by an HSN1 avian influenza virus in Hong Kong underscores the possibility that avian virus can be transmitted directly to humans during the emergence of a pandemic strain. Although well-described in birds, molecular mechanisms that would account for the increased pathogenicity of influenza viruses in human hosts are lacking. Thus, the current research proposal seeks (1) to establish the phylogenetic relationships of the recently isolated HSN1 Hong Kong influenza virus and identify the properties (e.g., receptor specificity and HA cleavability) that might account for its replication and pathogenicity in humans, (2) to elucidate the role of HA-NA interplay in influenza virus replication in a new host, and (3) to identify the NA and HA structural changes that contribute to plasminogen-mediated HA cleavage, leading to enhanced virulence of influenza viruses. Over the past three decades, a number of several new viral pathogens have appeared in humans (including human immunodeficiency virus, influenza A virus, Hanta virus, Ebola virus, monkeypox virus, and Borna virus), after being maintained in small isolated human populations or in other animal hosts. Understanding the mechanism(s) by which these viruses emerge is essential for predicting the likelihood of a new pandemic and for developing effective counter-measures. Influenza A viruses provide an unparalled model of a pathogen that rapidly mutates to a form capable of global devastation. Studies addressing the specific aims will further understanding of the processes that give rise to global outbreaks of viral disease and, therefore, may stimulate efforts to devise preventative strategies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MOLECULAR MECHANISMS OF VIRAL MEMBRANE FUSION Principal Investigator & Institution: Tamm, Lukas K.; Professor; Mol Physiol/Biological Physics; University of Virginia Charlottesville Box 400195 Charlottesville, Va 22904 Timing: Fiscal Year 2001; Project Start 01-SEP-1991; Project End 31-MAR-2002

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Summary: Membrane fusion, mediated by viral spike glycoproteins, is a key process in the infection cycle of all enveloped human and animal viruses. Even though influenza hemagglutinin (HA) is the structurally best studied of all viral (or cellular) fusion proteins, the molecular mechanisms by which this proteins catalyzes membrane fusion are only poorly understood. Therefore, the overall goal of this research is to help elucidate these mechanisms and, particularly, the structural transformations that take place during influenza HA-mediated membrane fusion. A combined biochemical and biophysical approach will be taken to pursue three specific aims, namely: (1) to develop improved fluorescence and infrared spectroscopic methods for studying the structure and dynamics of membrane components as they relate to the mechanism of viral membrane fusion; (2) to determine the dynamic structure of fusion intermediates using strain X31HA as the model protein; and (3) to investigate the structure, dynamics, and interactions of wild-type and mutant fusion and transmembrane peptides and their effect on membrane structure by vibrational and electron paramagnetic resonance spectroscopy. The general methodology to achieve these goals will be the following: Influenza HA will be functionally reconstituted into planar supported phospholipid bilayers. Surface-sensitive techniques such as total internal reflection fluorescence microscopy (TIRFM) and attenuated total reflection Fourier transform infrared (ATRFTIR) spectroscopy will be used to structurally investigate the reconstituted fusion complexes. Membrane structures and lipid bilayer distances will be determined by TIRFM at various stages of membrane fusion. Protein conformational changes, including molecular orientations and secondary structure changes of putative fusion intermediates will be studied by ATR-FTIR spectroscopy in situ as a function of pH, lipid composition, temperature and time. Proteolytic fragmentation of HA and spectroscopic studies of synthetic wild-type and mutant fusion and transmembrane peptide will be used to establish detailed structure-function relationships for several segments of the HA molecule. Taken together, these studies will provide a structural and functional basis for understanding the molecular mechanisms of viral spike glyoprotein-mediated membrane fusion. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOLECULAR MECHANISMS OF VIRAL MEMBRANE FUSION PROTEINS Principal Investigator & Institution: White, Judith M.; Professor; Cell Biology; University of Virginia Charlottesville Box 400195 Charlottesville, Va 22904 Timing: Fiscal Year 2001; Project Start 01-JUL-1985; Project End 31-JAN-2005 Summary: (Adapted from Applicant's Summary): The long term objectives of this research are to elucidate the mechanisms of viral membrane fusion proteins and to use this information in the rational design of novel anti-viral agents. There are two types of viral fusion proteins. One, typified by the influenza hemagglutinin (HA), functions at low pH for endosomal virus entry. The other, typified by the envelope (env) glycoprotein of HIV, functions at neutral pH for cell surface virus entry. When exposed to low pH, HA undergoes conformational changes, exposes its fusion peptide, binds to target membranes, induces hemifusion, and then opens a fusion pore. For retroviral env proteins (which function at neutral pH) interactions between env and host cell receptor(s) trigger fusion-inducing conformational changes. The first hypothesis of this proposal is that conformational intermediates between the native fusion protein and its final form mediate distinct steps of the fusion cascade. The second hypothesis is that after activation, all viral fusion proteins use a common mechanism. A third hypothesis is that small molecular weight anti-viral agents can be designed that block distinct steps in

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the fusion process. The major goal of this proposal is to test these hypotheses for a viral fusion protein that functions at low pH, the influenza HA, and for one that functions at neutral pH, the env glycoprotein of a model avian retrovirus. The specific aims are to: 1) test a new model for HA-mediated membrane fusion, 2) elucidate the fusion mechanism of the avian retroviral env protein, and 3) use a structure-based approach to identify small molecules that prevent the fusion-inducing conformational change in the influenza HA. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MURINE SLEEP PHENOTYPE DURING MICROBIAL INFECTIONS Principal Investigator & Institution: Toth, Linda A.; Professor; Pharmacology; Southern Illinois University Carbondale 900 S. Normal Carbondale, Il 629014709 Timing: Fiscal Year 2001; Project Start 30-SEP-1999; Project End 31-JUL-2003 Summary: Work conducted in my laboratory has demonstrated that microbial infections induced by numerous pathogenic agents cause alterations in normal sleep patterns, and that facets of the immune response to microbial challenge are likely to mediate these behavioral effects. Identifying the factors that cause fatigue and excessive or disturbed sleep during microbial infections and developing effective interventions for these disabling symptoms could improve the economic well-being and quality of life of many individuals. My long-term goal is to define the genetic and inflammatory mechanisms that mediate fatigue and altered sleep propensity during infectious disease. To that end, I recently completed an analysis of genetic contributions to altered sleep patterns in influenza-infected mice. My preliminary data indicate that a discrete subset of genes is likely to account for large and consistent differences in influenza-induced sleep in different strains of inbred mice. This application proposes to build on that work by identifying the genetic and pathologic mechanisms that mediate sleep responses to other types of microbial challenges and by integrating the new data with our previous findings. A genome-wide approach to identifying candidate genes will be applied in the proposed aims. As the critical first step in identifying genes that regulate infectioninduced alterations in sleep, we will characterize the sleep patterns of prototypic strains of mice after specific microbial challenges. We will use those data to select the most efficient strategies for mapping quantitative trait loci for infection-related sleep phenotypes using recombinant inbred mice. Identifying the genes that modulate infection-induced sleep is an important step toward discovering gene products that influence disease susceptibility and symptomatology. Studying the mechanisms by which genes and their products modulate sleep will ultimately improve our understanding of processes that control normal sleep and contribute to sleep disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: NK CELL IMMUNITY TO INFLUENZA Principal Investigator & Institution: Parham, Peter R.; Professor; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-AUG-2008 Summary: There is no text on file for this abstract. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PATHOBIOLOGY OF THE OSTEOCLAST IN PAGETS DISEASE Principal Investigator & Institution: Roodman, G David.; Professor; Medicine; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2002; Project Start 01-SEP-1998; Project End 31-AUG-2007 Summary: (provided by applicant): Understanding the pathogenesis of Paget's Disease and the role that paramyxovirus may play is severely hampered by the lack of an in vivo model. Recently, we cloned and sequence-analyzed a full-length Measles Virus Nucleocapsid (MVNP) cDNA from bone marrow cells from a Paget's patient. The MVNP gene contained several sense mutations, which constituted 1% of the nucleotide sequence. Interestingly, partial sequence analysis of MVNP cDNAs isolated from three other patients from different geographic locales revealed similar mutations. However, the pathologic significance of these mutations, in terms of persistence of the virus or induction of abnormal osteoclast (OCL) formation and activity in Paget's disease is unknown. It is our hypothesis that the mutated MVNP expressed in OCL from Paget's patients participates in protein interactions and induces gene expression that result in pagetic OCL development. These effects cannot be mimicked by nucleocapsids from other paramyxovirus or non-paramyxovirus. Furthermore, specific structural motifs present within the MVNP gene are responsible for development of pagetic OCL. Thus, expression of the MVNP gene in OCL in the setting of increased OCL activity is sufficient for development of Paget's disease. Therefore, to test this hypothesis we will: (1.A) determine the effects of mutant MVNP expression on normal OCL formation and activity. If differences are noted, the mutations present in the pagetic MVNP will be sequentially introduce into the Edmonston strain MVNP gene to identify which mutations or structural motifs may be responsible for these differences; (1.B) determine the effects of nucleocapsid proteins derived from other paramyxoviruses, such as Canine Distemper Virus (CDV), or Respiratory Syncytial Virus (RSV) and the nonparamyxovirus Influenza on osteoclastogenesis; (1.C) determine if IL-6 is induced by the various nucleocapsid proteins (MVN, CDV, RS influenza) and if IL-6 is in part responsible for development of the pagetic OCL; (2) identify the OCL-specific gene products that interact with MVNP. As part of these studies, the expression of candidate genes identified above will be confirmed in pagetic bone marrow cells by RT-PCR. These candidate genes will then be over-expressed in normal OCL precursors to determine their capacity to induce the pagetic phenotype in OCL; (3) determine if constitutive expression of the MVNP gene from a patient with Paget's disease in cells of the OCL lineage in transgenic mice (TRAP-MVNP) is sufficient to induce pagetic-like bone lesions; (3.A) determine if treatment of these mice chronically for 5 days per month with parathyroid hormone-related protein (PTHrP) or RANK ligand (RANKL) to enhance OCL formation is required to develop pagetic lesions in these animals; (3.B) determine if local overproduction of RANK ligand by marrow stromal cells in these mice results in development of localized Paget's disease; (3.C) determine if marrow cells from TRAP-MVNP mice can form OCLs in vitro, which have features of pagetic OCLs, and if IL-6 expression is critical to this process; and (4) determine if chronic overproduction of IL-6 is in part responsible for development of the pagetic lesions, by breeding TRAP-MVNP mice either to transgenic mice in which IL-6 expression is targeted to cells in the OCL lineage (TRAP-IL-6) or to IL-6 knock-out mice. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PILOT--CAUSES OF RACIAL DISPARITIES IN INFLUENZA VACCINATIONS Principal Investigator & Institution: Hebert, Paul C.; Mount Sinai School of Medicine of Nyu of New York University New York, Ny 10029 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2007 Summary: Several studies have documented the persistent under-use of influenza vaccination among elderly African American and Hispanic populations. However, little is known about the causes of this under-use, and consequently, it is unclear whether clinic-based strategies to improve vaccination rates will be effective in African American and Hispanic communities. The purpose of this pilot study is to provide preliminary data for an investigation into the causes of racial differences in influenza vaccination rates in the elderly. We propose to: 1. Assess perceived barriers to influenza vaccination use by holding focus groups with African American and Hispanic elderly patients, 2. Develop and pilot a survey based on information gained in these focus groups, and 3. Conduct a brief chart review to assess racial discrimination in the offering of influenza vaccination by physicians. The setting for this study is the Geriatrics Clinic at Mount Sinai Medical Center, which serves an ethnically diverse panel of elderly patients. The results of this analysis will be used as preliminary data for a more comprehensive study of the causes of racial disparities in influenza vaccination use, and of effective strategies to improve vaccination rates in African American and Hispanic communities. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: POINT OF CARE INSTRUMENT FOR VIRAL RESPIRATORY DIAGNOSIS Principal Investigator & Institution: Ives, Jeffrey T.; Scientist; Xtrana, Inc. 717 Yosemite Cir Denver, Co 80220 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-JUL-2005 Summary: (provided by applicant): The common respiratory viruses (influenza, parainfluenza, respiratory syncytial virus or RSV, and rhinovirus) cause millions of cases of upper and lower respiratory tract disease every year. The spectrum of illness induced directly by the viruses is very broad, ranging from mild colds and simple ear infections to more serious and sometimes life-threatening diseases such as bronchiolitis, pneumonia, and asthma. In spite of the importance of diagnosing and treating these viral infections, current diagnostic methods of physical exam or rapid immunoassays or culture in reference laboratories do not provide the accuracy, sensitivity, or timely information that the primary care physician needs for treatment. Antiviral therapeutics are becoming increasingly viable, but they require accurate identification of the infectious virus(es). While sensitive, newer assays and instrumentation based on nucleic acid technologies are not cost effective or practical for point of care in a physician's office. To provide a cost effective, point of care system for diagnosing respiratory viruses, this application describes an integrated and unique device that will begin with a nasal wash sample and use nucleic acid-based technologies to accurately identify eight respiratory viruses: RSV A and B; parainfluenza 1, 2, and 3; influenza A and B; and rhinovirus. After loading the sample, proprietary steps of sample preparation, RNA extraction, multiplexed amplification, and detection by lateral flow strips will be automatically performed. These processing steps will be directed on a disposable, microfluidic card that both minimizes the reagent costs and provides an enclosed container for convenient, biosafe disposal. To develop this diagnostic device, a series of technical milestones will be accomplished. First, a novel method of multiplexed target

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amplification will be optimized on respiratory viral targets. Second, nasal wash samples will be directly prepared for multiplexed amplification by flow through extraction and unique solid phase analysis. Sample preparation and amplification will be managed by developing disposable, laminated microfluidics cards with channels, reagents, and valves. Using a protoype workstation, the described system will be tested with patient samples and spiked samples to verify the utility, specificity, sensitivity, and reproducibility of the system. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: POPULATION BIOLOGY AND EVOLUTION OF INFLUENZA A Principal Investigator & Institution: Levin, Simon A.; Professor; Ecology and Evolutionary Biol; Princeton University 4 New South Building Princeton, Nj 085440036 Timing: Fiscal Year 2001; Project Start 01-JAN-2000; Project End 31-DEC-2003 Summary: The goals of this proposal are to improve our understanding of both the evolution and management of influenza by developing a unified modeling framework. In particular, the questions we will address are (1) How do given strain and subtype structures, and the associated patterns of cross-reactivity, affect disease dynamics? (2) How does cross-reactivity affect pathogen evolution? (3) How do strain structure and patterns of cross-reactivity self-organize over evolutionary time, for example into quasispecies, and how does this organization feed back to affect dynamics? (4) What are the implications of these issues for vaccination strategies, and what are the reciprocal effects of vaccination programs upon the organization of the viral population? Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PREDICTING THE EVOLUTION OF HUMAN INFLUENZA Principal Investigator & Institution: Bush, Robin M.; Assistant Professor; Ecology and Evolutionary Biol; University of California Irvine Irvine, Ca 926977600 Timing: Fiscal Year 2002; Project Start 01-JUL-1999; Project End 31-JAN-2007 Summary: (provided by applicant): The goal of the proposed research is to understand the molecular basis of antigenic variation in the human influenza virus, and to apply this knowledge to improving influenza surveillance and vaccine strain selection. Antibodies directed against the surface protein hemagglutinin (HA) provide the major defense against influenza infection. Surveillance using genetic analysis of the quickly evolving HA provides a much finer scaled view of evolutionary change in circulating viral strains than traditional antigenic analysis. However, the relationship between genetic and antigenic variation is often unclear, and this relationship may vary over evolutionary time. Towards a better understanding of influenza evolution four specific aims are proposed: 1) A small number of codons in the HA of influenza A subtype H3N2 appear to have been under positive selection by the human immune system to repeatedly change the amino acid they encode. A model for predicting evolution has been developed which assumes a selective advantage for newly emerging viruses with additional changes at these codons. This model performed successfully in retrospective tests. In Aim 1 viruses predicted to be "most fit" at the end of each influenza season are tested to determine whether they caused the next epidemic. 2) This prediction model assumes that codons identified as having been positively selected in the past will continue to be positively selected in the future. This assumption is tested in Aim 2 using datasets drawn from different influenza seasons. 3) Hypotheses about the types and amounts of genetic change needed to produce an antigenically distinct HA will be developed through observations of past epidemics. Reverse genetics will be used to test

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these hypotheses: the HAs of transfectant viruses will be mutated at selected codons and then contrasted for differences in antigenicity. Genetic change that alters antigenicity will be characterized using homology models of the HA. One potential outcome will be the incorporation of homology modeling into current techniques of influenza surveillance. 4) The generality of the results from study of H3N2 will be tested by contrasting them with similar studies of influenza A subtype H1N1 and influenza B. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PROSTATE CANCER IMMUNOTHERAPY Principal Investigator & Institution: Darnell, Robert B.; Profssor; Lab/Molecular Neurooncology; Rockefeller University New York, Ny 100216399 Timing: Fiscal Year 2003; Project Start 05-JUN-2003; Project End 31-MAY-2008 Summary: (provided by applicant): Prostate cancers that have spread beyond the confines of the gland regress following the withdrawal or blockade of androgens, and at relapse, following chemotherapy. In both settings the outcomes are similar: most cells undergo growth arrest, but only few undergo apoptotic death. We hypothesize that an immune based approach can eliminate the non-proliferating yet viable cells, particularly after tumor mass has been de-bulked. Prostate cancer offers several advantages in testing new tumor immunotherapies. Serum prostate specific antigen (PSA) levels provide a simple, yet excellent marker of response to therapy. Patients with rising PSA, who have a poor prognosis, can be identified while they are still functionally healthy. As elimination of growth-arrested cells is essential in such patients, they are ideally suited for tumor immunotherapy. Our objective is to demonstrate that immunization of prostate cancer patients with autologous dendritic cells (DC's) cross-presenting apoptotic prostate tumor cells safely induces cytolytic T cell responses to tumor antigens. We will establish a system for the detection of tumor-specific T cell responses in prostate cancer patients that parallels methods established in our laboratory for influenza-specific T cell responses in normal individuals. Apoptotic prostate tumor cells will be co-cultured with DC's, allowing uptake and presentation of multiple tumor antigens on all MHC I molecules. These DC's will then be used to immunize patients. We will monitor patients for acute toxicity and T cell responses to established (e.g. prostate-specific membrane antigen) and new marker antigens present in the apoptotic prostate tumor cells to determine activity of our immunization. Our immunization method and key assays for antigen-specific T cell response are independent of patient HLA haplotype, allowing patients of all haplotype to enter the study. Our strategy is distinct in the breadth of antigen presented and potency resulting from use of the crosspriming pathway--up to 10,000 times more efficient than peptide pulsed DCs. Our results should indicate whether this new approach to DC based, immunotherapy has a potential role in the treatment of prostatic cancer as well as other malignancies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PROTECTIVE MECHANISMS AGAINST PANDEMIC RESPIRATORY VIRUS Principal Investigator & Institution: Arvin, Ann M.; Professor of Microbiology and Immunology; Pediatrics; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-MAR-2008 Summary: (provided by applicant): This Cooperative Center for Translational Research on Human Immunology and Biodefense is entitled 'Influenza Immunity: Protective Mechanisms against a Pandemic Respiratory Virus'. Our objective is to use vaccine-

42

Influenza

induced and naturally acquired influenza A immunity as a model for comprehensive, integrated analyses of adaptive and innate immune mechanisms and antimicrobial protection of the respiratory tract in children and adults. Influenza immunology is relevant to biodefense because influenza A has significant potential to be modified genetically to create a bioterrorist agent. Further, influenza A causes natural pandemics, which can incapacitate a large fraction of the population, endangering preparedness. Influenza A has many characteristics of microbial pathogens that could become agents of civilian bioterrorism. Among these are: capacity to cause illness with high morbidity and mortality, highly efficient person-to-person transmission, high infectivity by aerosol, resulting in the capacity to cause large outbreaks, potential to cause anxiety in the public, and potential to be weaponized. While influenza vaccines exist, the immunologic mechanisms by which protection is induced in the respiratory tact are poorly understood in the human host. Genetically altered influenza A viruses that express unique hemagglutinin (HA) and neuraminidase (NA) proteins have the capacity to infect all age groups. In a biodefense context, the rapidity with which protection can be elicited in a non-immune population is critical. The influenza A model is expected to allow a better definition of specialized adaptive B cell and T cell immune mechanisms that control infections of the respiratory system. Our investigative approach also encompasses the study of innate, natural killer cell responses to influenza, in parallel with acquisition of adaptive immunity in children and adults. Comparing influenza vaccines will identify differences when the host responds to parenterally administered, inactivated antigens, versus live attenuated virus delivered via the respiratory route. At our Center, investigators leading the Research Resource Technical Development component and the Research Projects will undertake rapid translation of basic immunology methods into applications for analyzing innate and acquired influenza A immunity. These innovations will have broad relevance for for understanding human immunity against microbial pathogens of concern for biodefense. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: REGULATION OF HUMORAL IMMUNITY TO INFLUENZA VIRUS Principal Investigator & Institution: Baumgarth, Nicole; Ctr for Comparative Medicine; University of California Davis Sponsored Programs, 118 Everson Hall Davis, Ca 95616 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-MAR-2006 Summary: (provided by applicant): High morbidity and >20,000 deaths per year in the US alone are caused by infection with influenza virus. Neutralizing antibodies are one immune mechanism that provides effective protection against this virus. Natural virusbinding antibodies secreted prior to infection and virus-induced antibodies generated in the absence of T cell help, are both crucial for survival from this infection. The underlying basis of their induction however, is poorly understood. This proposal aims to define the basic principles that underlie the induction of these antibodies. Thus, providing a first step for identification of the precise molecular mechanisms that regulate their induction. The central hypothesis that will be tested is that intrinsic differences in B cell subsets contribute significantly to the regulation of antiviral humoral responses and that B-1 cells are one B cell subset participating early in immune defense. The first aim is to characterize distinct virus-specific B cell populations induced to influenza virus A/PR8 in mice and to determine their in vivo function. This will include the analysis of two distinct idiotype-expressing B cells, differing in the kinetics of their responses, and of the B-1 cell subset, which secretes virus-binding natural antibodies. These studies will test the hypothesis that virus-specific B cell subpopulations differ in lifespan, ability to proliferate and to differentiate to antibody-

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secreting cells. Virus-responding B cell subsets will be characterized by 10-color flow cytometry. Proliferative responses will be assessed by in vivo labeling of dividing cells. Antibody secretion will be measured by ELISA and ELISPOT of FACS-purified B cell subsets. Immunohistochemistry will determine the precise tissue location of idiotypeexpressing B cells. The second aim is to test whether the function and fate of virusspecific B cells is determined by their intrinsic regulatory properties. For this, B cell subset responses will be characterized in T cell-deficient mice, as for aim #1. B cell receptor-affinity will be assessed to determine its influence on antibody-kinetics. Phenotypic studies are expected to identify new molecules involved in the regulation of early virus-specific B cell responses. The third aim is to test whether B cell differentiation into short-lived antibody-secreting cells causes the rapid disappearance of the early expressed idiotypes. Molecular outcomes of B cell subset activation will be assessed by real-time RT-PCR and Western-blot analysis of genes known to regulate B cell differentiation. This study challenges the current paradigm of B cell activation. Successful outcome of this study would provide a new framework that explains better how protective antiviral B cell responses are induced. It would also form the basis for defining the precise molecular mechanisms of early virus-specific B cell activation, thus for identifying possible new targets for rationale vaccine design. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: REPERTOIRE OF CD8+ T CELLS IN AGED MICE Principal Investigator & Institution: Judice, Stephen A.; Trudeau Institute, Inc. Saranac Lake, Ny 12983 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2006 Summary: (provided by the applicant): Aged individuals suffer from infectious disease with increased frequency and severity. In particular, influenza viruses represent a major cause of illness among elderly individuals. Given that the protective efficacy of vaccination is greatly reduced in the elderly, it is critical that effective vaccination strategies for the elderly be developed for not only protection from natural yearly influenza infection epidemics, but also from potential bioterrorism attacks. An agerelated defect in the activation of naive CD4+ T-cells as well a diminished primary CD8+ T-cell response to influenza virus infection has been described, although there is less evidence of a functional defect in the aged CD8+ T-cells. It has been suggested that the defective cellular immune response in the aged is in part due to a loss of diversity in the CD8+ T-cell repertoire. The current research proposal will investigate the CD8+ Tcell deficit in a two pronged approach. First, we will compare the overall and functional diversity of the naive CD8+ repertoire in young aged mice via DNA spectratye analysis. Second, we will examine the diversity in the CD8+ cellular immune response of aged mice as compared to young mice in response to a primary influenza virus vaccination by DNA spectratype analysis. Together, these studies will determine whether an age associated loss of naive T-cell diversity affects immune function in the elderly. These results have relevance in determining the feasibility of some vaccination strategies for the elderly in which defined viral proteins or epitopes may be used as immunogens. Given that a significantly reduced repertoire diversity may result in 'holes' in the T-cell repertoire, these vaccination strategies may prove ineffective in an elderly population requiring alternate approaches. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Influenza

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Project Title: REPLICATION OF INFLUENZA VIRUS Principal Investigator & Institution: Krug, Robert M.; Professor and Chairman; Inst for Cell & Mol Biology; University of Texas Austin 101 E. 27Th/Po Box 7726 Austin, Tx 78712 Timing: Fiscal Year 2002; Project Start 01-JUL-1977; Project End 31-JUL-2007 Summary: (provided by applicant): The biological activities of the NS1 protein of influenza A virus (NS1A protein) differ markedly from those of the NS1 protein of influenza B virus (NS1B protein). The NS1 proteins of these two genera of influenza viruses, which cause widespread human disease, likely mediate many of the viral countermeasures that combat cellular antiviral responses. Our overall aim is to identify all the activities of the NS1A and NS1B proteins and to elucidate how these different activities counter the cellular antiviral response and/or have other functions during virus replication. At early times after infection with either influenza A or B virus the transcription of cellular genes controlled by IFN (interferon)-stimulated response elements (ISREs) is activated without the involvement of IFNalpha/beta. Mature cellular mRNAs are produced in influenza B-, but not in influenza A-, infected cells. Our aims are to determine: (1) whether the absence of mature cellular mRNAs in influenza A virus-infected cells is caused by the block in 3' end processing of cellular pre-mRNA that is mediated by the NS1A protein, a function lacked by the NS1B protein; and (2) the mechanism by which ISREs of these cellular genes are activated in influenza A and B virus-infected cells. The NS1A protein contains a nuclear export signal (NES) which is activated between 2 and 4 hours post-infection. Our aim is to determine the mechanism of activation of this NES and its role during influenza A virus infection. The NS1B protein, but not the NS1A protein, binds ISG15, a human ubiquitinlike protein that is induced by either IFNalpha/beta or virus infection, and inhibits the conjugation of ISG15 to its target proteins. Because these protein targets have not yet been identified, it is not known why ISG15 conjugation would be detrimental to influenza B virus infection. Our goals are: (i) to establish how the conjugation of ISG15 to its target protein affects influenza B virus replication; and (ii) to identify the protein targets of ISG15 conjugation and to determine how this conjugation affects the activities of these target proteins. Other cellular proteins also likely bind to the NS1A and/or NS1B protein, e.g., the SRp54 protein that binds to NS1A, but not to NS1B, and our aim is to determine whether the binding of these other proteins has a functional role in influenza virus-infected cells. These functional analyzes of the NS1A and NS1B proteins will be complemented by structural studies using both nuclear magnetic resonance and X-ray crystallography. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: RESPIRATORY VIRUS ION CHANNELS Principal Investigator & Institution: Pinto, Lawrence H.; Neurobiology and Physiology; Northwestern University 633 Clark St Evanston, Il 60208 Timing: Fiscal Year 2003; Project Start 01-APR-1993; Project End 31-MAR-2008 Summary: (provided by applicant): Influenza contributes substantially to worldwide morbidity and mortality, and it has been estimated that the next influenza pandemic will result in over 80,000 deaths, 300,000 hospitalizations and 18 million outpatient visits in the United States. The M2 ion channel protein of influenza A virus is the target of the antiviral drug rimantadine, but its usefulness is limited by the formation of rimantadineresistant escape mutations within a few days of treatment. In order to develop more effective antiviral drugs, more information is needed about the M2 protein, especially

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the structure of its transmembrane pore and cytoplasmic domains and the mechanism by which it is activated. The following individual aims are designed to elucidate important features of the structure and function of the M2 protein. 1. Tryptophan 41 in the transmembrane pore is essential for activation of the M2 ion channel protein; we will perform functional and structural experiments to ascertain the role of tryptophan 41 in activation of the M2 protein. 2. The function of the M2 protein depends on the integrity of its cytoplasmic tail. Fluorescence and electroparamagnetic resonance (EPR) spectroscopy experiments will be performed to determine whether the cytoplasmic tail of the M2 protein forms a rosette lying on the membrane surface or forms a helix extending into the cytoplasm. 3. Key features of the structure of the pore and the cytoplasmic tail of the M2 ion channel will be determined using (EPR) spectroscopy. 4. In order to understand better the mechanism for resistance and to identify which functional properties of the channel are essential for its role in the virus life cycle, the functional properties of amantadine-resistant mutant M2 proteins will be characterized. 5. In a separate set of experiments we will use a sensitive method to test the NB protein of influenza B virus for ion channel activity. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: RNA INTERFERENCE OF INFLUENZA VIRUS INFECTION Principal Investigator & Institution: Chen, Jianzhu; Associate Profesor; Center for Cancer Research; Massachusetts Institute of Technology Cambridge, Ma 02139 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-JAN-2007 Summary: (provided by applicant): Influenza A virus causes one of the most widespread infections in humans. In a typical year, it infects 10-20% of the population in the U.S., causing up to 40,000 deaths. During the 1918 influenza virus pandemic, over 20 million people died worldwide. The threat of another pandemic continues even now because, despite intensive efforts, there is still no effective therapy for influenza infection and prevention is haphazard. Existing vaccines are of limited value because the influenza viruses they target are determined by "best guess," based upon recently prevalent strains. The virulence of influenza A virus results from i) its easy spread by aerosol, ii) its ability to escape from protective immunity, and iii) the periodic emergence of new, virulent strains of the virus. For these reasons, the National Institutes of Health has designated influenza infection as a top priority area for biodefense. RNA interference (RNAi) is a process by which double-stranded RNA directs sequencespecific degradation of messenger RNA in animal and plant cells. Studies have shown that RNAi can be triggered by synthetic 21-nucleotide duplexes of small interfering RNA (siRNA) molecules. This project proposes to investigate siRNAs in both preventing and treating influenza virus infection. Specifically, we propose to i) identify siRNAs that potently inhibit influenza virus production in cultured cells, ii) develop systems for efficient delivery of siRNAs into cells of the upper respiratory tract and the lung, where influenza infection normally occurs, iii) investigate the in vivo efficacy of siRNA inhibition of influenza infection in mice, and iv) elucidate the mechanisms by which siRNAs inhibit influenza virus production. Results obtained from the proposed studies may provide a basis for further development of siRNAs as prophylaxis and therapy of influenza virus infection in humans. Theoretically, an siRNA-based treatment should remain effective even with the emergence of new strains of the virus. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Influenza

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Project Title: 'ROLE LYMPHOCYTES

OF

SELF-PEPTIDES

IN

THE

SELECTION

OF

T

Principal Investigator & Institution: Ashton-Rickardt, Philip G.; Assistant Professor; Pathology; University of Chicago 5801 S Ellis Ave Chicago, Il 60637 Timing: Fiscal Year 2001; Project Start 01-JUL-1997; Project End 31-OCT-2005 Summary: Pathogenic viruses pose a world-wide public health problem of great importance. The immune system has evolved strategies to combat viral infections, an important one being the detection and illimination of virally infected host-cells by cytotoxic T lymphocytes (CTLs). The T lymphocytes antigen receptor (TCR) recognizes virally infected cells by detecting peptide fragments of virus, expressed on the surface of cells in complexes with self-MHC (Major Histocompatibility Complex) molecules. How T cells distinguish between viral-peptide and self- peptides is unclear. However, the impairment of this ability can lead to the development of autoimmunity. The TCR repertoire displayed by CTLs is determined through the development of T cells in the thymus. Within the thymus, T cell development selects for cells that recognize peptide antigen presented by self-MHC, but are not reactive to MHC/self-peptide complexes. However, we have shown that the recognition of self-peptide/self-MHC complexes, expressed on the surface of thymic stromal cells, is required to trigger the development of cells destined to become CTLs. We aim to determine how thymic self-peptides shape the antigenic repertoire of CTLs. Using a combination of chromatographic and massspectroscopic techniques, we will purify and sequence self-peptides for thymic-MHC molecules, which are recognized by CTLs specific for two different pathogenic viruses, Influenza (IF) and Lymphocytic Choriomeningitis virus (LCMV). By adding synthetic self-peptides to a fetal thymic organ culture (FTOC) system utilizing TAP1- mice, we will examine how self-peptides specific for a given TCR (anti-IF peptide or anti-LCMV peptide) trigger the differentiation of CTLs with the same TCR. Using a similar FTOC system, we will also study how the recognition of the thymic self-peptides gives rise to the development of the diverse array of antigenic specificity~s displayed by CTLs. Analysis of mice, with impaired peptidase activity and impaired thymic selection of CTLs, will allow us to identify which thymic self-peptides trigger the development of CTLs. This proposal seeks to understand how the recognition of self during development gives rise to an immune system which can respond specifically to non-self pathogens. It is hoped that this study lead to a better understanding of how autoimmune disease can be prevented as well as facilitate our understanding of how antiviral immunity develops. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SECONDARY INFECTIONS DURING MYCOBACTERIAL DISEASE Principal Investigator & Institution: Sandor, Matyas; Pathology and Lab Medicine; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-AUG-2005 Summary: (provided by applicant): Approximately 30% of the world's population has been infected with Mycobacterium tuberculosis, and tuberculosis has been estimated to be the leading cause of death worldwide. A significant fraction of that mortality is from weakened cellular immunity due to co-infection with other endemic infections. Antimycobacterial immunity is mediated primarily by CD4+ T cells, which regulate the formation of protective granulomatous inflammation to restrict pathogen dissemination and protect surrounding healthy tissue. We propose to use a mouse model of chronic tuberculosis, M. bovis strain bacille Calmette Gu rin (BCG), to examine the effect of

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super-infection with influenza virus and the fungus Histoplasma capsulatum. We will genetically mark both the BCG and secondary pathogen with different wellcharacterized T cell epitopes. Using epitope specific class ll tetramer staining reagents, we can follow the localization and phenotype of TCR-populations specific for either BCG or the secondary pathogen by flow cytometric analysis of granuloma cells. This model will also be used to examine the effect of super-infection upon organ load, the capacity of different TCR-specific T cell populations to produce protective cytokines, and gene-expression changes associated with local antigenic specificity. T cell interactions (help, suppression, competition) have been described with nominal antigens, and our studies will focus on how T cell responses for two infectious agents interfere with each other. We intend to make our observations by infecting animals with a full spectrum of T cells (B10.BR), infecting B10.BR animals into which TCR transgenic T cell populations specific for both epitopes have been adoptively transferred as sentinels, and infecting immunodeficient Rag2-/- after adoptive transfer of TCR transgenic T cells that are specific for the epitope tags expressed by the infectious agents to construct a small T-cell network. Thus we can very precisely study the recruitment and functional qualities of granuloma cells having mycobacterial specificity and those with specificity for other infections. The goal of this research is to understand the interaction of T cell responses controlling different infections. Hopefully, this will lead to better treatments of mycobacterial disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SELF-REGULATION DEPRESSIVE/ANXIOUS SYMPTOMS AND URIS Principal Investigator & Institution: Strauman, Timothy J.; Professor and Chair; Psychology; Duke University Durham, Nc 27706 Timing: Fiscal Year 2001; Project Start 20-SEP-1999; Project End 31-MAY-2003 Summary: We propose a program of research consisting of four studies demonstrating how the emotional and physiological consequences of self-regulation can influence susceptibility to upper respiratory illness (URIs) in women with menstrual dysfunction. The proposed research will test a model in which perceived failure in self-regulation (operationalized as high self-discrepancy) is hypothesized to increase susceptibility to URIs via the mediating influences of negative affect, menstrual dysfunction, and changes in stress hormones (cortisol) and immune function (natural killer cell cytotoxicity). Study 1 will examine the acute emotional, hormonal, and immunological consequences of self-regulatory cognition via a within-subject priming manipulation in high vs. low self-discrepant women with vs. without menstrual dysfunction. Study 2 is a prospective investigation of the incidence and severity of colds and flu as a function of self-regulation, conducted over a 6-month period of the academic year that includes two naturalistic challenges (the onset of the flu season and final exams). Study 3 will replicate and extend the self-report outcome measures of Study 2 by measuring antibodies to influenza virus in high-risk (high self-discrepancy plus menstrual dysfunction) vs. low-risk (low self-discrepancy without menstrual dysfunction) women randomized to receive or not receive flu vaccine and then followed through the two naturalistic challenges. Study 4, again following high-risk and low-risk women through naturalistic challenges, will test a brief intervention based on Pennebaker's studies of the health impact of disclosure. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Influenza

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Project Title: CHELATES

SENSITIVE,

RAPID

BIOASSAY

USING

UPCONVERTING

Principal Investigator & Institution: Faris, Gregory W.; Senior Physicist; Sri International 333 Ravenswood Ave Menlo Park, Ca 94025 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2005 Summary: (provided by applicant): The long-term objective of this project is to develop appropriate diagnostic assays for bioterrorism attacks. A well coordinated and executed attack could kill hundreds of thousands to millions. Effective diagnostics will be crucial to minimizing morbidity and mortality from such an attack, as well as maintaining social order. These diagnostics must be rapid, easy to use, inexpensive, very sensitive, and very specific. Multiplexed tests (i.e., those that test for multiple targets) and low waste generation are also attractive capabilities for these diagnostics. Our near-term objective is to test the feasibility of a new diagnostic approach that should significantly outperform existing diagnostics in terms of speed, sensitivity, and simplicity of use. This assay is based on upconverting chelates in a homogeneous assay format. Upconverting chelates are a novel reporter SRI International (SRI) has invented that comprises a lanthanide (rare earth) ion in a chelating ligand. When excited with near infrared light, they upconvert, emitting light at visible wavelengths. These reporters have no autofluorescent background, do not photobleach, and have good properties for multiplexing. Because the assay is homogeneous, very little sample preparation is required, enabling rapid analysis. We propose a 2-year R21 project to prove the feasibility of this assay. As a test target we will use influenza virus strain PR8. Our specific aims in this work are to: (1) build a simple optical apparatus for detecting surface-enhanced upconverting chelate signals; (2) prove and optimize the homogeneous assay concept; (3) prove and optimize the assay for hemagglutinin protein; and (4) prove and optimize the assay for influenza virus. This work will combine the efforts of optical physicists, chemists, immunologists, and a virologist. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SES DIFFERENCES IN HMO UTILIZATION BY OLDER AMERICANS Principal Investigator & Institution: Escarce, Jose J.; Rand Corporation 1700 Main St Santa Monica, Ca 90401 Timing: Fiscal Year 2001; Project Start 01-APR-1999; Project End 31-MAR-2003 Summary: The number of elderly Medicare beneficiaries enrolled in managed care plans has grown rapidly in the past few years, and recent changes in Medicare are likely accelerate this trend. Because managed cre plans use financial incentives and nonfinancial mechanisms to curb utilization, there is concern that the elderly in these plans may face barriers to receiving appropriate medical care. This concern is especially acute with respect to elderly persons of low socioeconomic status. Despite widespread interest in the impact of managed care on the use of medical services by vulnerable elderly populations, there is currently little research on this issue. The propose project is a 3year observation study of the influence of socioeconomic status (SES) on the medical care utilization of elderly Medicare beneficiaries enrolled in HMOs, and represent a collaborative effort between investigators at RAND and the Center for Health Care Policy and Evaluation at United Health Care, a leading managed care organization. The goals of the project are to evaluate the impact of SES on: 1. total physician visits, visits to primary care physicians, and visits to specialists; 2. visits to non-physician providers; 3. hospitalization rates and hospital length of stay; 4. use of the emergency room as a source of care; 5. rates of mammography and influenza vaccination; 6. total charges for

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medical care. A secondary goal of the project is to provide information on the pathways by which SES affects utilization among elders in managed care plans. This project will assess the utilization experience of enrollees in 3 geographically dispersed Medicare HMOs that are affiliated with UHC. Data sources will include a telephone survey of enrollees and administrative data from the study HMOs. To identify the effect of SES on utilization, we will estimate multi-variate regression models that control for comprehensive measures of health status and other factors that may affect the demand for medical care. The results of this project will provide important new information to policy makers and directors of health care plans on how well elderly persons of low SES fare in managed health care systems designed to control utilization. These understudied questions are particularly important to address given the increasing numbers of Medicare beneficiaries who will receive their medical care in managed care settings. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SHIKIMATE PATHWAY VARIANTS Principal Investigator & Institution: Frost, John W.; Professor; Chemistry; Michigan State University 301 Administration Bldg East Lansing, Mi 48824 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2006 Summary: (provided by applicant): Some of the more interesting aspects of natural product biosynthesis are the variations on common themes. A case in point is the shikimate pathway. Starting with the condensation of phosphoenolpyruvate with Derythrose 4-phosphate, the shikimate pathway has been the focus of intense scrutiny. One variant of the shikimate pathway is found in Amycolatopsis mediterranei where 1imino-1-deoxy-D-erythrose 4-phosphate replaces D-erythrose 4-phosphate as the likely starting point of what has been named the aminoshikimate pathway. The hypothesis that 3-amino-3-deoxy-D-fructose 6-phosphate is the source of 1-imino-1-deoxy-Derythrose 4-phosphate will be explored. In turn, the biosynthesis of 3-amino-3-deoxy-Dfructose 6-phosphate is to be elaborated. Beyond answering fundamental biosynthetic questions associated with the source of the nitrogen atom utilized by the aminoshikimate pathway, proposed research could ultimately lead to a biocatalytic route to aminoshikimic acid suitable for use in the synthesis of anti-influenza agents. A second variant of the shikimate pathway is to be created in Escherichia coli where phosphoenolpyruvate will be replaced by pyruvate as the three-carbon metabolite condensed with D-erythrose 4-phosphate. This will require recruitment of native and evolved 2-keto-3-deoxy-6-phosphogalactonate aldolase to catalyze the condensation of pyruvate with D-erythrose 4-phosphate. Initiating the shikimate pathway with the condensation of pyruvate with D-erythrose 4-phosphate could substantially improve the yields of pharmaceutically important molecules microbially synthesized by way of this pathway and may serve as a paradigm of shikimate pathway variants employed by microbes under anaerobic growth conditions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: STREPTOCOCCUS PNEUMONIAE ADHERENCE AND OTITIS MEDIA PATH Principal Investigator & Institution: Demaria, Thomas F.; Otolaryngology; Ohio State University 1960 Kenny Road Columbus, Oh 43210 Timing: Fiscal Year 2001; Project Start 01-AUG-1996; Project End 31-JUL-2005 Summary: (Adapted from the Investigator's Abstract) Otitis media (middle ear inflammation) ranks first among the most common diagnoses requiring a physician's

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office visit and recent estimates indicate that virtually all children (99%) will experience a least one episode of otitis media (OM) by age 2. The disease progresses in many children to recurrent infections and chronic inflammation, often with complications and sequalae that include persistent hearing loss nd communication disorders. Streptococcus pneumoniae (Spn), is one of the foremost human pathogens and is the primary nasopharynx, the initial event in the induction of OM and the mechanisms which effect the transition for a colonized state to invasion of the middle ear and the induction of the disease state by Spn are not known. The long term objectives of this proposal are to delineate the pathogenic mechanisms involved in Spn adherence, colonization, and invasion of the middle ear and to develop a scientific rationale for the design of novel diagnostic and prevention strategies. The specific aims of this proposal are: 1) To continue to define the role of Spn neuraminidase in the pathogenesis of OM and to assess whether it is a protective antigen and a potential protein-based vaccine candidate, and whether neuraminidase inhibitors are effective in the prevention of Spn nasopharyngeal colonization of OM. 2) To assess the efficacy of lacto-N-neotetraose, a Spn carbohydrate receptor analog, as an anti-infective for nasopharyngeal colonization. 3) To continue to define the mechanisms whereby influenza A virus affects Spn adherence, colonization, and OM. These aims are designed to delineate the initial interaction, adherence, and colonization which represents the first in a series of steps that culminates in otitis media. These studies may suggest avenues for blocking interaction of Spn with host cells either by immunization or direct intervention blockade with isolated receptor moieties or bacterial adhesin components. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: STRUCTURAL STUDIES OF BACTERIAL COMPETENCE PROTEINS Principal Investigator & Institution: Cavanagh, John; Professor; Biochemistry; North Carolina State University Raleigh 2230 Stinson Drive Raleigh, Nc 27695 Timing: Fiscal Year 2003; Project Start 01-FEB-2003; Project End 31-JAN-2007 Summary: (provided by applicant): Bacteria have obtained a significant portion of their genetic diversity, metabolic fitness and lethality through the acquisition of nucleotide sequences from both closely and distantly related organisms. Horizontal gene transfer produces extremely dynamic genomes, in which substantial amounts of DNA are transferred between the chromosomes of different bacterial strains. Without question, such transfers have changed the ecological and pathogenic character of bacterial species. Transformation represents one of the main mechanisms by which DNA is incorporated into the recipients genome. It involves the uptake of naked DNA from the environment and has the potential to transmit DNA between distantly related organisms. For bacteria to be transformable, they must develop the physiological state referred to as competence. Genetic competence is defined as the ability of a cell to take up free DNA from the surrounding medium. If the cell is not competent, it cannot be transformed and its growth, survival and evolution are compromised. Research into the very nature of competence addresses both very fundamental and very practical questions and concerns. What mechanisms allow bacteria to incorporate new genes to develop novel, more sophisticated mechanisms for survival? By what means is genetic diversity provided, such that a microorganism can enlarge its own genomic complement? From a health related perspective, genetic transfer via competence is becoming more implicated in the development of the pathogenic character of bacteria. There is mounting evidence that virulent attributes and antibiotic resistance can be introduced and/or enhanced in this manner. The studies proposed here will focus on mechanistic characteristics of a set of interacting proteins that form the critical regulatory network initiating competence

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development in Bacillus subtilis. The goals of the research are to provide structural, dynamic and interaction information, in order to understand the regulatory effects of the proteins MecA, ComS, ClpP/C and ComK (and their complexes). This will be achieved by a combination of high-resolution NMR spectroscopy, electrospray mass spectrometry, surface plasmon resonance and other bioanalytical techniques, along with mutagenesis and protease foot-printing investigations. The results from these studies will provide a basis for the development of models to describe the mechanism of activation of competence, not only in B. subtilis, but also in other important grampositive (e.g. Streptococcus pneumoniae) and gram-negative (e.g. Neisseria gonorrhoeae and Haemophihts influenza) bacteria. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: STRUCTURE OF M2 PROTON CHANNEL FROM INFLUENZA A VIRUS Principal Investigator & Institution: Degrado, William F.; Professor; Biochemistry and Biophysics; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2001; Project Start 01-AUG-1997; Project End 31-JUL-2005 Summary: Membrane proteins are of critical importance to nearly every aspect of cell physiology, comprising one quarter to one third of all proteins encoded by eubacterial, archaean, and eukaryotic organisms. Nevertheless, our understanding of their folding and structures is at a very primitive state when compared to that of water-soluble proteins. The M2 proton channel from influenza A virus provides an attractive system for understanding the folding and function of membrane proteins. This proton channel is essential to the survival of the virus, and is the target of the anti-influenza drugs, amantadine and rimantadine. The M2 proton channel is formed by the intermolecular association of four identical transmembrane helices, and a peptide (tmM2) spanning only the transmembrane helix of M2 forms amantadine- dependent channels in bilayers. In the past period, we have studied the thermodynamics of assembly of tmM2 and the full- length protein. Diffraction-quality crystals of tmM2 have also been obtained at low pH, where the channel is maximally active, as well as at pH 8.0, near the pH optimum for inhibition by the drug amantadine. Our specific aims for the current period are to: 1. Determine the structure of functional fragments of M2 using NMR, IR, and X-ray crystallography. 2. Determine what features in the sequence of M2 contribute to its thermodynamic stability. 3. Determine the mechanism of proton conductance by M2, and its inhibition by amantadine. 4. Design and structurally characterize a water-soluble version of M2, which retains the tertiary structure of M2 as well as its ability to bind amantadine. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: STRUCTURE/FUNCTION OF THE INFLUENZA VIRUS GENOMEN Principal Investigator & Institution: Lamb, Robert A.; Investigator; Basic Science & Oral Biology; Northwestern University Office of Sponsored Programs Chicago, Il 60611 Timing: Fiscal Year 2001; Project Start 01-JAN-1983; Project End 31-DEC-2001 Summary: The structure and function of the genes of influenza virus will be investigated. Influenza continues to be a regular epidemic, and occasionally pandemic, disease which ranks among the leading causes of morbidity and mortality throughout the world, particularly in the elderly and in individuals with heart and lung disease. The design of better vaccines and chemotherapeutic approaches is dependent on a greater understanding of the genome of the virus, how it is expressed during replication and the

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mechanism by which it damages cells. We have identified two previously unrecognized integral membrane proteins of influenza viruses: M2 of influenza A virus and the NB glycoprotein of influenza B virus. The structure, mode of synthesis, expression and function of these proteins forms the focus of our work. We will investigate if the NB glycoprotein is expressed on the infected cell surface and determine its orientation in membranes. We will analyze the precise glycosylation sites used and measure the effect of glycosylation on transport of NB in the cell. We shall learn about the nucleotide sequences important for initiating two proteins (NB and NA) on a functionally active bicistronic mRNA. We will examine the mode of synthesis of M2 to investigatie how it initially becomes inserted into membrane vesicles and analyze the amino acids that are necessary for anchoring M2 in membranes. The geographic distribution of M2 on the infected cell surface will be investigated by immune electron microscopy using sitespecific antisera. The effect of amantadine hydrochloride on inhibiting viral replication and its specific effect on the amino acids in the M2 membrane anchorage domain will be investigated particularly with respect to the involvement of M2 with HA in forming virus particles. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: T CELL FUNCTION IN PULMONARY VIRAL INFECTION AND INJURY Principal Investigator & Institution: Braciale, Thomas J.; Director and Professor; Beirne Carter Center for Immunology Research; University of Virginia Charlottesville Box 400195 Charlottesville, Va 22904 Timing: Fiscal Year 2003; Project Start 18-SEP-1991; Project End 31-DEC-2007 Summary: (provided by applicant): This proposal is designed to investigate the murine CD8+ T cell response in the lungs and draining lymph nodes after lethal and sub lethal type A influenza virus infection and to define the mechanism for the impaired CD8+ T cell response after lethal infection. It is predicated upon our recent observations implicating the response of airway dendritic cells (ADC) early in the course of pulmonary virus infection (i.e. either the first 24 hours of infection) as a critical regulator of the subsequent development of an effective anti-viral CD8+ T cell response. The underlying hypothesis is that high-level exposure (infection) of ADC in the lungs early in pulmonary influenza infection, alters the maturation/activation or function of ADC resulting in defective induction of a protective anti-viral CD8+ T cell response by responding ADC. Our experimental approach will be to examine the response of DC to influenza infection at different multiplicities (MOI) in vitro and the response of ADC to lethal/sub lethal infection in vivo for maturation/activation (i.e. DC activation marker expression), function (i.e. cytokine synthesis) and for the tempo and magnitude of viral gene expression (i.e. HA, NP, and NS1 proteins). These studies will be coupled with an analysis of the CD8+ T response in the lungs and draining nodes after lethal/sub lethal infection in vivo. Companion studies will examine the activation/differentiation of CD8+ T cells responding in vitro to DC infected at different MOI to elucidate the mechanism of underlying the defective CD8+ T cell response to lethal pulmonary infection. Our ongoing studies in this area will be directed to the following Specific Aims: 1. To characterize the in vivo response to airway dendritic cells to sub lethal type A influenza virus infection; 2. To determine the effect of infectious influenza virus dose on DC phenotype and function in vivo and in vitro; 3. To determine the impact of infecting virus dose on the CD8+ T cell response to influenza virus infection in vivo and in vitro. A thorough understanding of the interplay between CD8+ T cells and DC in the induction of an effective adaptive immune response is essential for understanding the

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process of recovery from pulmonary virus infection. Furthermore, detailed information on the impact of infecting virus dose on DC and T cell function will likely provide new insight into the effect of virus inoculum at mucosal surfaces on the subsequent host immune response to a variety of pathogenic human viruses. Finally, this analysis may have important implications for the development of strategies to counteract the use of potentially lethal pulmonary viruses like influenza as biological weapons. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: T CELL MEMORY TO PATHOGENS: GENERATION AND FUNCTION Principal Investigator & Institution: Swain, Susan L.; Director; Trudeau Institute, Inc. Saranac Lake, Ny 12983 Timing: Fiscal Year 2003; Project Start 30-SEP-1999; Project End 31-MAR-2008 Summary: (provided by applicant): Our collaborative effort will be aimed at combining cellular and molecular approaches to study the factors that are required for the optimum development of long-lasting T cell memory to influenza virus and M. tuberculosis. Induction of such memory is the key goal of vaccination, but the pathways leading to and factors regulating memory development are poorly understood. Knowledge of the basic processes involved will yield important insights that can be exploited therapeutically and used to increase the efficacy of immunization. Disease from influenza infection ranges from mild to lethal, depending on the level of strainspecific antibody protection afforded by prior exposure to virus. Devastating epidemics have occurred when new viral strains have emerged carrying new hemagglutinin proteins distinct from those to which the population has been exposed. Such strains could also be produced by genetic engineering. Fortunately, T cell responses are not restricted to the variable epitopes and a vaccine strategy focusing on T cell immunity might provide protection to all or most potential strains and/or augment host responses sufficiently to prevent the worst consequences of a pandemic. Tuberculosis is one of the leading causes of morbidity and mortality in the world and is the leading cause of death as a result of an infectious agent. Although drug treatment is available its long duration leads to non-compliance and the subsequent generation of drug resistant strains. For the past 80 years an attenuated vaccine strain has been available however it is of variable efficacy and its use within a population fails to result in eradication of disease. Our studies will identify the kinds of memory CD4 and CD8 T cells immunity required for protection and determine factors that regulate the generation and persistence of those cells. Projects: 1. Regulation of CD4 Memory Cell Development and Persistence (Swain) will identify memory CD4 subsets in response to influenza, determine which are protective, how protective memory is generated and what regulates persistence. 2. Characterization of Influenza-Specific CD8 Memory (Dutton) will ask similar question for protective CD8 memory in influenza. Together Projects 1 and 2 will compare CD4 Vs CD8 immunity to influenza. 3. Regulation of Memory T Cell Recruitment and Responses in the Lung. (Bradley) will determine the mechanisms, which determine the recruitment of CD4 and CD8 T cells to the lung following influenza infection and will determine the responses of these cells in the lung. 4. Expression of T cell memory in the TB infected lung. (Cooper) will determine how memory responses to TB are induced, how they are recruited to the lung and whether they provide long-term protection against pulmonary TB. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: T-CELL RESPONSES PREDICT INFLUENZA RISK IN OLDER ADULTS Principal Investigator & Institution: Mcelhaney, Janet E.; Associate Professor; None; Eastern Virginia Medical School Norfolk, Va 23507 Timing: Fiscal Year 2002; Project Start 15-APR-2002; Project End 31-MAR-2005 Summary: (Provided by Applicant) This proposal addresses the NIA Program (PA-97097), "The Impact of Immune Senescence and Maturation on Vaccine Responsiveness in the Elderly" and describes a strategy to advance the basic science of influenza learned from studies in the aged mouse model which will be applied to a very high-risk population of older adults with congestive heart failure (CHF). The innovation in this proposal has been the development of a simple laboratory measure of cytotoxic Tlymphocyte (CTL) activity using an ex vivo assay of granzyme B (Grz B). This translational research will characterize the protective immunologic response to influenza vaccination, define the defective T-cell mechanism that increases risk for influenza in older adults, and determine individual risk based on clinical markers of disease severity in CHF. CHF provides a model for studying the significant added risk of serious influenza illness to that related to advancing age. In the process, important clinical indicators and laboratory measures of influenza risk will identify older people with a high risk for serious influenza illness. The general hypothesis is that Iow levels of Grz B predict high risk for influenza illness and are associated with a dysregulation of cytokine production in older adults. To explore this hypothesis, vaccinated healthy older adults and older adults with CHF will be studied to determine the: 1) association between antibody, cytokine and Grz B levels and the development of influenza illness, 2) mechanism underlying poor Grz B responses to influenza vaccination with advancing age and CHF, and 3) relationship between functional performance and antibody, cytokine and Grz B levels Aim (1) will be accomplished by measuring antibody, cytokine and Grz B levels before and after influenza vaccination in different risk groups for influenza. From these results, the principal investigator will test a threshold level of Grz B for its ability to predict risk for influenza-related illness in older people with CHF. The components of a "protective" T-cell response to vaccination will be defined. Aim (2) will be accomplished by measuring age and CHF-related changes in cytokine and Grz B levels and the number virus-specific T-cells in different T-cell subsets. Aim (3) will be accomplished by comparing cytokine and Grz B levels in virusstimulated PBMC, to clinical indicators of CHF severity as a potential marker of "immunologic frailty" for complications of influenza. By comparing these immune responses to influenza vaccination in healthy young and older adults and older adults with CHF, the mechanism that leads to decreased efficacy of current influenza vaccines will be identified. The goal is to define an immunologic test that measures influenza risk, a measure critical to future vaccine development and targeted prophylaxis in older adults. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: TGFB1 ALLOGRAFTS

GENE

TRANSFER

IN

VASCULARIZED

CARDIAC

Principal Investigator & Institution: Bishop, D. Keith.; Associate Professor; Surgery; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2001; Project Start 01-JUL-1995; Project End 31-JUL-2004

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Summary: (adapted from applicants's abstract) Immunosuppressive gene therapy holds promise as an inductive therapy in transplantation. However, many fundamental aspects of this technology must be addressed before it may be applied to clinical transplantation. These include questions regarding the use of viral vs. non-viral vectors, underlying mechanisms of action, effects on systemic immunity, and the duration of transgene expression. The investigators have developed a model of TGFbeta1 gene transfer into mouse vascularized cardiac allografts to address these issues. Donor hearts are perfused with either DNA-liposome complexes or adenoviral vectors which encode the active form of TGFbeta1. Interestingly, CD4+ cells are readily suppressed by this modality, while CD8+ cells are not. This differential sensitivity is most pronounced when adenoviral vectors are used. The overall hypothesis to be tested is that transient depletion of CD8+ cells will enhance the efficacy of immunosuppressive gene therapy. Hence, the Specific Aims will: 1) Define mechanisms by which TGFbeta1 gene transfer mediates immunosuppressive activities. T cell functional assays will identify critical immune functions which are either turned off or turned on by TGFbeta1 gene transfer, and adoptive transfer studies will determine if regulatory cells are induced by TGFbeta1 gene transfer. 2) Elucidate mechanisms by which adenoviral mediated TGFbeta1 gene transfer stimulates CD8+ cells. The investigators will test the hypothesis that adenoviral vectors, but not DNA-liposome complexes, stimulate production of inflammatory cytokines which over-ride TGFbeta1 suppression of CD8+ cells. 3) Determine the impact of TGFbeta1 gene transfer on systemic immune surveillance. They will assess the effects of TGFbeta1 gene transfer on primary and memory responses to Listeria and on antibody responses to influenza immunization. 4) Determine if TGFbeta1 gene expression may be silenced following initial inductive immunosuppression. Tetracycline regulated promoters will be used to limit the duration of TGFbeta1 expression, and gene transfer of decorin, which binds and neutralizes TGFbeta1, will be employed to neutralize the transgene product. This study will provide insight for optimizing immunosuppressive gene therapy in clinical transplantation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: TH1 CYTOKINES AND IMPAIRED CD8* CTLS IN ELDERLY Principal Investigator & Institution: Mbawuike, Innocent N.; Microbiology and Immunology; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2001; Project Start 01-JUN-1997; Project End 31-MAY-2003 Summary: (Adapted from the Applicant's Abstract): The objectives of this proposal are to determine the mechanisms of deficient cytotoxic T lymphocytes (CD8+ CTL) activity against influenza virus among elderly persons and how this deficiency can be corrected. Elderly persons represent a high risk group for severe influenza disease, pneumonia and death. The Centers for Disease Control estimates that up to 40,000 influenzaassociated deaths occur during each yearly influenza epidemic; more then 90% of these deaths occur among persons >65 years of age (Morbidity and Mortality Weekly Report, Vol. 3, No. RR-3, April 21, 1995). It is now clear that CD8+ CTL activity plays a major role in the recovery from severe influenza virus infection and disease. Unfortunately, elderly persons generally exhibit significantly lower CD8+ CTL responses to influenza virus relative to the young, providing a basis for occurrence of prolonged and more severe infections. However, the cause of this age-related CD8+ CTL deficiency is not known. Cell-medicated immunity is controlled by two major categories of cytokines. The Th1 cytokines, such as interferon gamma (IFN-g), interleukin 2 (IL-2) and interleukin 12 (IL-12), favor the induction of CD8+ CTLs while Th2 cytokines, such as interleukin 4 (IL-4) and interleukin 10 (IL-10) inhibit them. Preliminary results show that

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T lymphocytes from elderly persons produce relatively less IFN-gamma and more IL-4 when stimulated with influenza virus in vitro. Similar results have been demonstrated in old mice, suggesting that these cytokines play a pivotal role in determining the activity of CD8+ CTL in the elderly. The investigators propose that the mechanism underlying the deficient CD8+ CTL activity among the elderly is an age-related switch from producing predominantly Th1 cytokines to Th2 cytokines. This loss of Th1 cytokines results in reduced numbers of CD8+ CTLs expressing CD28, an essential costimulatory molecule and also in reduced perforin-granzyme-medicated lytic activity and accumulation of anergic memory CD8+ T (CD45RO+/CD28) cells. Using our well characterized in vitro influenza CTL model, plans are to test for induction of CD8+ CTL activity specific for influenza virus to identify a cohort of elderly persons with reduced CTL responses. It will then be determined if CD8+ CTL from these also express decreased IFN-g (Th1) and increased IL-4 and IL-10 (Th2) production, lower frequency of CD8+ cells expressing CD28 and reduced perforin and granzyme synthesis, IL-12 stimulates IFN-g production and enhances CD8+ CTL activity. Therefore, if treatment of T cells from elderly persons with deficient CTL activity with IL-12 results in increased IFN-g production, and in the restoration of CD8+ CTL activity (as suggested from results in limited studies), then the hypothesis that deficient Th1 cytokine production is the cause of CTL deficiency in the elderly would be correct. Alternatively, elderly CD8+ CTL deficiency may be due to defective Th1 cytokine-mediated signal transduction (JAK/STAT tyrosine phosphorylation) pathways in the CD8+ T cells. If the Th1 cytokine switch is shown to be the mechanism underlying the CD8+ CTL deficiency in elderly persons, then cytokine immunotherapy or formulation of cytokines with standard influenza vaccines may be designed for the development of more effective immunoprophylaxis against influenza and other respiratory infections for high risk elderly persons. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: TRANSLATIONAL CONTROL IN INFLUENZA VIRUS INFECTED CELLS Principal Investigator & Institution: Katze, Michael G.; Professor; Microbiology; University of Washington Seattle, Wa 98195 Timing: Fiscal Year 2001; Project Start 01-JAN-1987; Project End 31-MAR-2004 Summary: Influenza virus is a major public health problem in the United States and worldwide. To better understand the cellular events that occur during influenza virus infection, we have been studying the shut-off of host cell protein synthesis and the selective translation of viral mRNAs in influenza virus-infected cells. We have accumulated evidence that the molecular strategies employed by influenza virus to accomplish these goals are intimately intermeshed with the host cell defense and stressresponse pathways. In Specific Aim 1, we will further define the mechanisms of selective translation. We have identified a cellular RNA-binding protein, GRSF-1, that binds to the 5' untranslated region (UTR) of influenza virus mRNAs. This is significant, since we earlier demonstrated that the 5' UTR was both necessary and sufficient to redirect the host cell protein synthesizing machinery to translate only viral mRNAs. We hypothesize that GRSF-1 interacts with the 5' UTR of influenza virus mRNAs to upregulate viral protein synthesis. To test this hypothesis, we will perform separate in vitro functional assays and in vivo experiments with wild-type and transdominant mutant GRSF-1. Specific Aim 2 focuses on the stress-response pathway activated by influenza virus to ensure efficient viral mRNA translation. Influenza virus recruits the cellular TPR protein, P58IPK, PK, to down-regulate the interferon-induced PKR protein

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kinase, thereby keeping protein synthetic activity high in a virus-infected cell. In the absence of this regulation, activation of PKR by viral RNAs results in the phosphorylation of the eukaryotic initiation factor, eIF-2alpha and inhibition of protein synthesis initiation. In this aim, we will dissect the P58IPK/PKR pathway and examine the roles played by the P58IPK regulators, hsp40, P52rIPK, and the molecular chaperone hsp70, which we now hypothesize plays a key role in the downregulation of PKR. Finally, in Aim 3, we propose to construct a knockout mouse with a deletion of the P58IPK gene. We will examine the effects of deleting P58IPK on viral and cellular mRNA translation and gene expression, both in the null mice and in fibroblasts prepared from these mice. Together, the studies outlined will contribute to a better understanding of eukaryotic protein synthesis regulation, which may ultimately provide insights into novel antiviral therapeutics. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: TRANSMISSIBILITY OF INFLUENZA A VIRUSES Principal Investigator & Institution: Perez, Daniel R.; University of Maryland College Pk Campus College Park, Md 20742 Timing: Fiscal Year 2003; Project Start 15-SEP-2003; Project End 31-DEC-2006 Summary: (provided by applicant): The long-term objective of this proposal is to generate knowledge that may be used to prepare for or prevent pandemic influenza. The interspecies transmission of influenza viruses is a key element in the generation of a pandemic influenza strain. Although little is known about the molecular steps required to create a potential human pandemic strain, intermediate hosts are considered necessary. Aquatic birds are the natural reservoir of influenza A viruses, but the influenza A viruses isolated from humans in Hong Kong (H5N1 in 1997 and H9N2 in1999) contained genes that had circulated and adapted in land-based birds, particularly quail, which are widely farmed in Southern China. Epidemiological evidence and our preliminary results strongly suggest that quail could play a unique role among land-based birds in the emergence of novel influenza A viruses that can cross the species barrier. The proposed research will use molecular, classical virologic, and reverse genetics methods to define 1) the role of land-based birds, particularly quail, as intermediate hosts in interspecies transmission and spread of influenza A viruses; and 2) the molecular basis of the transmissibility of influenza A viruses in land-based avian intermediate hosts. With poultry production increasing worldwide (more than 200% since the 1960's), the mechanisms underlying interspecies transmission of influenza viruses must be elucidated if the emergence of a pandemic influenza strain is to be forestalled or adequately prepared for. The techniques needed to obtain this information are now available, and the results will lay the groundwork for important changes in agricultural policies and pandemic planning. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: UNIVERSAL INFLUENZA A VACCINE Principal Investigator & Institution: Birkett, Ashley J.; Director of Research; Apovia, Inc. 11125 Flintkote Ave, Ste A-E San Diego, Ca 92121 Timing: Fiscal Year 2003; Project Start 15-SEP-2003; Project End 31-AUG-2005 Summary: (provided by applicant): In the last century there were three major outbreaks of pandemic influenza, and the possibility of future outbreaks remains very high. According to the CDC, the next pandemic will likely result in up to 200 million infections, resulting in 88,000 to 300,000 deaths. In addition to natural transmission,

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recent years have seen the emergence of bioterrorism as an additional threat. Pandemic influenza is listed as a category C pathogen by the Government's biodefense taskforce. Vaccination represents the most effective mechanism for combating the threat of pandemic influenza; however, current influenza vaccines are not likely to provide adequate protection. We are developing a vaccine candidate based on the highly conserved extracellular domain of the M2 protein, which has the potential to elicit protective immune responses against all influenza A strains. The specific aims of this proposal focus on advancing our understanding of the mechanism and universality of this approach and engineering the vaccine candidate to exhibit increase potency. Specifically, we intend to elucidate the mechanism of anti-M2e antibody associated protection, which we have shown thus far to be antibody mediated, using both in vitro and in vivo techniques. A clearer understanding of the mechanism of protection will be valuable for selecting optimal adjuvant formulations, designing human clinical studies, and establishing correlates of protection for use in human Phase UII studies. While M2 is highly conserved, strains have been identified that contain mutations that could potentially compromise the universality of the vaccine. We intend to investigate the effects of known, naturally occurring M2 mutations on protection using both in vitro and in vivo techniques. Further, we will attempt to improve the potency of the vaccine by incorporating a conserved, broadly HLA-reactive human Th epitope from the nucleoprotein of influenza A. Once a lead candidate vaccine has been identified, we will initiate process development work. This will begin with the manufacture of GMP master and working cell banks, followed by fermentation and purification optimization. This work is expected to yield a manufacturing process that can be transferred to our GMP manufacturing facility to provide high quality protein for formulation, stability, and animal safety toxicology studies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: VIRAL MEMBRANE AND GLYCOPROTEIN STRUCTURE Principal Investigator & Institution: Harrison, Stephen C.; Professor; Molecular and Cellular Biology; Harvard University Holyoke Center 727 Cambridge, Ma 02138 Timing: Fiscal Year 2001; Project Start 01-JAN-1977; Project End 31-JUL-2005 Summary: (Verbatim from the applicant's abstract) Emerging Infections: To study the mechanism by which influenza virus strains can emerge as infectious to humans, we plan to examine the X-ray structure and function of hemagglutinins from viral strains apparently limited to infecting animal reservoirs and for comparison human infectious strains from the major pandemics. Preferences for different sialoside linkages on cellular receptors correlate with the spread of infection in animals versus humans. One goal is to help explain observations like why outbreaks in the past two years in Hong Kong of avian virus infections in humans did not spread into the human population. Viral Entry Mechanisms: To investigate membrane fusion by influenza virus, we plan crystal structure studies of protein/detergent complexes of intact HA and HA2 and mechanistic studies of the interaction of HA with membranes and of intermediates in the fusion reaction. The hypothesis that HA2 in the low pH conformation observed by crystallography is membrane fusion active will also be tested with intact recombinant HA2 molecules transfected in cells suitable for membrane fusion assays. The hypothesis that the N- and C-terminal segments of HA1 plus all of HA2 (BHA's stem) was an ancestral membrane fusion protein will be tested by engineering such a protein, testing whether it can be proteolytically primed and activated by low pH, and whether the HA1 segments have a role, such as in the assembly of a putative multi-trimer containing pore. M2 Ion Channel: To generate structural information about the ion channel protein M2 of

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influenza virus we propose crystallization in detergent of bacterially expressed and refolded M2 tetramers that we have produced; and/or a tetramer of a channel-active synthetic transmembrane helix. Complexes with the inhibitory drug, amantadine, will also be studied. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

E-Journals: PubMed Central3 PubMed Central (PMC) is a digital archive of life sciences journal literature developed and managed by the National Center for Biotechnology Information (NCBI) at the U.S. National Library of Medicine (NLM).4 Access to this growing archive of e-journals is free and unrestricted.5 To search, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Pmc, and type “influenza” (or synonyms) into the search box. This search gives you access to fulltext articles. The following is a sample of items found for influenza in the PubMed Central database: •

[Delta]12-Prostaglandin J2 Is a Potent Inhibitor of Influenza A Virus Replication. by Pica F, Palamara AT, Rossi A, De Marco A, Amici C, Santoro MG.; 2000 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=89655

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1917 Avian Influenza Virus Sequences Suggest that the 1918 Pandemic Virus Did Not Acquire Its Hemagglutinin Directly from Birds. by Fanning TG, Slemons RD, Reid AH, Janczewski TA, Dean J, Taubenberger JK.; 2002 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=136362

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1918 Spanish influenza: The secrets remain elusive. by Webster RG.; 1999 Feb 16; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=33548

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A Chimeric Influenza Virus Expressing an Epitope of Outer Membrane Protein F of Pseudomonas aeruginosa Affords Protection against Challenge with P. aeruginosa in a Murine Model of Chronic Pulmonary Infection. by Staczek J, Gilleland HE Jr, Gilleland LB, Harty RN, Garcia-Sastre A, Engelhardt OG, Palese P.; 1998 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=108472

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A DNA transfection system for generation of influenza A virus from eight plasmids. by Hoffmann E, Neumann G, Kawaoka Y, Hobom G, Webster RG.; 2000 May 23; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=18566

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A Hairpin Loop at the 5[prime prime or minute] End of Influenza A Virus Virion RNA Is Required for Synthesis of Poly(A) + mRNA In Vitro. by Pritlove DC, Poon LL, Devenish LJ, Leahy MB, Brownlee GG.; 1999 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=104455

3 4

Adapted from the National Library of Medicine: http://www.pubmedcentral.nih.gov/about/intro.html.

With PubMed Central, NCBI is taking the lead in preservation and maintenance of open access to electronic literature, just as NLM has done for decades with printed biomedical literature. PubMed Central aims to become a world-class library of the digital age. 5 The value of PubMed Central, in addition to its role as an archive, lies in the availability of data from diverse sources stored in a common format in a single repository. Many journals already have online publishing operations, and there is a growing tendency to publish material online only, to the exclusion of print.

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A Mouse Model for the Evaluation of Pathogenesis and Immunity to Influenza A (H5N1) Viruses Isolated from Humans. by Lu X, Tumpey TM, Morken T, Zaki SR, Cox NJ, Katz JM.; 1999 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=112651

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A novel antiviral agent which inhibits the endonuclease of influenza viruses. by Tomassini JE, Davies ME, Hastings JC, Lingham R, Mojena M, Raghoobar SL, Singh SB, Tkacz JS, Goetz MA.; 1996 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=163289

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A novel mechanism for the acquisition of virulence by a human influenza A virus. by Goto H, Kawaoka Y.; 1998 Aug 18; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=21489

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A Point Mutation in the Transmembrane Domain of the Hemagglutinin of Influenza Virus Stabilizes a Hemifusion Intermediate That Can Transit to Fusion. by Melikyan GB, Markosyan RM, Roth MG, Cohen FS.; 2000 Nov 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=15035

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A Potential Peptide Vaccine Against Two Different Strains of Influenza Virus Isolated at Intervals of about 10 Years. by Naruse H, Ogasawara K, Kaneda R, Hatakeyama S, Itoh T, Kida H, Miyazaki T, Good RA, Onoe K.; 1994 Sep 27; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=44858

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A practical approach to genetic screening for influenza virus variants. by Zou S.; 1997 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=230022

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A Previously Unrecognized H-2Db-Restricted Peptide Prominent in the Primary Influenza A Virus-Specific CD8 + T-Cell Response Is Much Less Apparent following Secondary Challenge. by Belz GT, Xie W, Altman JD, Doherty PC.; 2000 Apr 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=111856

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A pulmonary influenza virus infection in SCID mice can be cured by treatment with hemagglutinin-specific antibodies that display very low virus-neutralizing activity in vitro. by Mozdzanowska K, Furchner M, Washko G, Mozdzanowski J, Gerhard W.; 1997 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=191651

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A Reverse Genetics Approach for Recovery of Recombinant Influenza B Viruses Entirely from cDNA. by Jackson D, Cadman A, Zurcher T, Barclay WS.; 2002 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=136801

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A sensitive, single-tube assay to measure the enzymatic activities of influenza RNA polymerase and other poly(A) polymerases: application to kinetic and inhibitor analysis. by Hooker L, Strong R, Adams R, Handa B, Merrett JH, Martin JA, Klumpp K.; 2001 Jul 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=55778

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A Simple Restriction Fragment Length Polymorphism-Based Strategy That Can Distinguish the Internal Genes of Human H1N1, H3N2, and H5N1 Influenza A Viruses. by Cooper LA, Subbarao K.; 2000 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=86974

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A Single Amino Acid Alteration in the Human Parainfluenza Virus Type 3 Hemagglutinin-Neuraminidase Glycoprotein Confers Resistance to the Inhibitory Effects of Zanamivir on Receptor Binding and Neuraminidase Activity. by Murrell MT, Porotto M, Greengard O, Poltoratskaia N, Moscona A.; 2001 Jul 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=114353

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A Single Amino Acid Mutation in the PA Subunit of the Influenza Virus RNA Polymerase Inhibits Endonucleolytic Cleavage of Capped RNAs. by Fodor E, Crow M, Mingay LJ, Deng T, Sharps J, Fechter P, Brownlee GG.; 2002 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=136441

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A Single Amino Acid Mutation in the PA Subunit of the Influenza Virus RNA Polymerase Promotes the Generation of Defective Interfering RNAs. by Fodor E, Mingay LJ, Crow M, Deng T, Brownlee GG.; 2003 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=152145

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A single-nucleotide natural variation (U4 to C4) in an influenza A virus promoter exhibits a large structural change: implications for differential viral RNA synthesis by RNA-dependent RNA polymerase. by Lee MK, Bae SH, Park CJ, Cheong HK, Cheong C, Choi BS.; 2003 Feb 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=150232

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A Specific Point Mutant at Position 1 of the Influenza Hemagglutinin Fusion Peptide Displays a Hemifusion Phenotype. by Qiao H, Armstrong RT, Melikyan GB, Cohen FS, White JM.; 1999 Aug 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=25511

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Activation of influenza virus RNA polymerase by the 5[prime prime or minute] and 3[prime prime or minute] terminal duplex of genomic RNA. by Lee MT, Klumpp K, Digard P, Tiley L.; 2003 Mar 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=152857

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Activation of Interferon Regulatory Factor 3 Is Inhibited by the Influenza A Virus NS1 Protein. by Talon J, Horvath CM, Polley R, Basler CF, Muster T, Palese P, GarciaSastre A.; 2000 Sep 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=112330

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Adaptation of Influenza A Viruses to Cells Expressing Low Levels of Sialic Acid Leads to Loss of Neuraminidase Activity. by Hughes MT, McGregor M, Suzuki T, Suzuki Y, Kawaoka Y.; 2001 Apr 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=114867

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African green monkey kidney (Vero) cells provide an alternative host cell system for influenza A and B viruses. by Govorkova EA, Murti G, Meignier B, de Taisne C, Webster RG.; 1996 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=190510

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Alveolar macrophages regulate the induction of primary cytotoxic T-lymphocyte responses during influenza virus infection. by Wijburg OL, DiNatale S, Vadolas J, van Rooijen N, Strugnell RA.; 1997 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=230250

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Amantadine Selection of a Mutant Influenza Virus Containing an Acid-Stable Hemagglutinin Glycoprotein: Evidence for Virus-Specific Regulation of the pH of Glycoprotein Transport Vesicles. by Steinhauer DA, Wharton SA, Skehel JJ, Wiley DC, Hay AJ.; 1991 Dec 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=53168

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Amino Acid Residues Contributing to the Substrate Specificity of the Influenza A Virus Neuraminidase. by Kobasa D, Kodihalli S, Luo M, Castrucci MR, Donatelli I, Suzuki Y, Suzuki T, Kawaoka Y.; 1999 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=112759

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Amino Acid Sequence Requirements of the Transmembrane and Cytoplasmic Domains of Influenza Virus Hemagglutinin for Viable Membrane Fusion. by Melikyan GB, Lin S, Roth MG, Cohen FS.; 1999 Jun 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=25377

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Amino Acids Responsible for the Absolute Sialidase Activity of the Influenza A Virus Neuraminidase: Relationship to Growth in the Duck Intestine. by Kobasa D, Wells K, Kawaoka Y.; 2001 Dec 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=114763

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An Influenza A Virus Containing Influenza B Virus 5' and 3' Noncoding Regions on the Neuraminidase Gene is Attenuated in Mice. by Muster T, Subbarao EK, Enami M, Murphy BR, Palese P.; 1991 Jun 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=51835

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An Intact Dilysine-like Motif in the Carboxyl Terminus of MAL Is Required for Normal Apical Transport of the Influenza Virus Hemagglutinin Cargo Protein in Epithelial Madin-Darby Canine Kidney Cells. by Puertollano R, Martinez-Menarguez JA, Batista A, Ballesta J, Alonso MA.; 2001 Jun 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=37348

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Analysis of the Pore Structure of the Influenza A Virus M2 Ion Channel by the Substituted-Cysteine Accessibility Method. by Shuck K, Lamb RA, Pinto LH.; 2000 Sep 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=112304

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Analysis of the Transmembrane Domain of Influenza Virus Neuraminidase, a Type II Transmembrane Glycoprotein, for Apical Sorting and Raft Association. by Barman S, Nayak DP.; 2000 Jul 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=112163

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Antigenic and Genetic Characterization of Influenza C Viruses Which Caused Two Outbreaks in Yamagata City, Japan, in 1996 and 1998. by Matsuzaki Y, Sugawara K, Mizuta K, Tsuchiya E, Muraki Y, Hongo S, Suzuki H, Nakamura K.; 2002 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=153379

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Antigenic Drift in the Influenza A Virus (H3N2) Nucleoprotein and Escape from Recognition by Cytotoxic T Lymphocytes. by Voeten JT, Bestebroer TM, Nieuwkoop NJ, Fouchier RA, Osterhaus AD, Rimmelzwaan GF.; 2000 Aug 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=112197

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Antiviral activity of influenza virus M1 zinc finger peptides. by Nasser EH, Judd AK, Sanchez A, Anastasiou D, Bucher DJ.; 1996 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=190957

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Apical Budding of a Recombinant Influenza A Virus Expressing a Hemagglutinin Protein with a Basolateral Localization Signal. by Mora R, Rodriguez-Boulan E, Palese P, Garcia-Sastre A.; 2002 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=136015

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Application of a Fluorogenic PCR Assay for Typing and Subtyping of Influenza Viruses in Respiratory Samples. by Schweiger B, Zadow I, Heckler R, Timm H, Pauli G.; 2000 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=86487

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Application of Subtype-Specific Monoclonal Antibodies for Rapid Detection and Identification of Influenza A and B Viruses. by Ueda M, Maeda A, Nakagawa N, Kase T, Kubota R, Takakura H, Ohshima A, Okuno Y.; 1998 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=104539

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Assessment of Markers of the Cell-Mediated Immune Response after Influenza Virus Infection in Frail Older Adults. by McElhaney JE, Gravenstein S, Krause P, Hooton JW, Upshaw CM, Drinka P.; 1998 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=96213

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Association of Influenza Virus Matrix Protein with Ribonucleoproteins. by Ye Z, Liu T, Offringa DP, McInnis J, Levandowski RA.; 1999 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=104273

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Attenuation of Influenza A Virus mRNA Levels by Promoter Mutations. by Fodor E, Palese P, Brownlee GG, Garcia-Sastre A.; 1998 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=109764

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Augmentation of Cellular Immunity and Reduction of Influenza Virus Titer in Aged Mice Fed Lactobacillus casei Strain Shirota. by Hori T, Kiyoshima J, Shida K, Yasui H.; 2002 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=119906

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Avian-to-human transmission of H9N2 subtype influenza A viruses: Relationship between H9N2 and H5N1 human isolates. by Lin YP, Shaw M, Gregory V, Cameron K, Lim W, Klimov A, Subbarao K, Guan Y, Krauss S, Shortridge K, Webster R, Cox N, Hay A.; 2000 Aug 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=16920

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Avirulent Avian Influenza Virus as a Vaccine Strain against a Potential Human Pandemic. by Takada A, Kuboki N, Okazaki K, Ninomiya A, Tanaka H, Ozaki H, Itamura S, Nishimura H, Enami M, Tashiro M, Shortridge KF, Kida H.; 1999 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=112847

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Bacterial Superantigen Exposure after Resolution of Influenza Virus Infection Perturbs the Virus-Specific Memory CD8 +-T-Cell Repertoire. by Huang CC, Shah S, Nguyen P, Altman JD, Blackman MA.; 2002 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=136287

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Balanced Hemagglutinin and Neuraminidase Activities Are Critical for Efficient Replication of Influenza A Virus. by Mitnaul LJ, Matrosovich MN, Castrucci MR, Tuzikov AB, Bovin NV, Kobasa D, Kawaoka Y.; 2000 Jul 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=112098

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Biological Heterogeneity, Including Systemic Replication in Mice, of H5N1 Influenza A Virus Isolates from Humans in Hong Kong. by Gao P, Watanabe S, Ito T, Goto H, Wells K, McGregor M, Cooley AJ, Kawaoka Y.; 1999 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=104081

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Caspase-Dependent N-Terminal Cleavage of Influenza Virus Nucleocapsid Protein in Infected Cells. by Zhirnov OP, Konakova TE, Garten W, Klenk HD.; 1999 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=113068

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Cell Surface Expression of Biologically Active Influenza C Virus HEF Glycoprotein Expressed from cDNA. by Pekosz A, Lamb RA.; 1999 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=112902

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Cellular mechanisms involved in protection and recovery from influenza virus infection in immunodeficient mice. by Bot A, Reichlin A, Isobe H, Bot S, Schulman J, Yokoyama WM, Bona CA.; 1996 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=190532

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Cellular Splicing Factor RAF-2p48/NPI-5/BAT1/UAP56 Interacts with the Influenza Virus Nucleoprotein and Enhances Viral RNA Synthesis. by Momose F, Basler CF, O'Neill RE, Iwamatsu A, Palese P, Nagata K.; 2001 Feb 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=115136

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Cellular transcriptional profiling in influenza A virus-infected lung epithelial cells: The role of the nonstructural NS1 protein in the evasion of the host innate defense and its potential contribution to pandemic influenza. by Geiss GK, Salvatore M, Tumpey TM, Carter VS, Wang X, Basler CF, Taubenberger JK, Bumgarner RE, Palese P, Katze MG, Garcia-Sastre A.; 2002 Aug 6; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=125029

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Characteristics of virus-specific CD8 + T cells in the liver during the control and resolution phases of influenza pneumonia. by Belz GT, Altman JD, Doherty PC.; 1998 Nov 10; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=24906

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Characterization of a Highly Pathogenic H5N1 Avian Influenza A Virus Isolated from Duck Meat. by Tumpey TM, Suarez DL, Perkins LE, Senne DA, Lee JG, Lee YJ, Mo IP, Sung HW, Swayne DE.; 2002 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=136198

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Characterization of a Porcine Lung Epithelial Cell Line Suitable for Influenza Virus Studies. by Seo SH, Goloubeva O, Webby R, Webster RG.; 2001 Oct 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=114519

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Characterization of H5N1 Influenza Viruses That Continue To Circulate in Geese in Southeastern China. by Webster RG, Guan Y, Peiris M, Walker D, Krauss S, Zhou NN, Govorkova EA, Ellis TM, Dyrting KC, Sit T, Perez DR, Shortridge KF.; 2002 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=135698

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Characterization of Human Influenza Virus Variants Selected In Vitro in the Presence of the Neuraminidase Inhibitor GS 4071. by Tai CY, Escarpe PA, Sidwell RW, Williams MA, Lew W, Wu H, Kim CU, Mendel DB.; 1998 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=106027

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Characterization of Influenza Virus NS1 Protein by Using a Novel Helper-Virus-Free Reverse Genetic System. by Enami M, Enami K.; 2000 Jun 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=112042

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Characterization of Influenza Virus PB1 Protein Binding to Viral RNA: Two Separate Regions of the Protein Contribute to the Interaction Domain. by Gonzalez S, Ortin J.; 1999 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=103869

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Characterization of the 1918 "Spanish" Influenza Virus Matrix Gene Segment. by Reid AH, Fanning TG, Janczewski TA, McCall S, Taubenberger JK.; 2002 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=136643

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Characterization of the 1918 "Spanish" influenza virus neuraminidase gene. by Reid AH, Fanning TG, Janczewski TA, Taubenberger JK.; 2000 Jun 6; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=18739

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Characterization of the Influenza A Virus Gene Pool in Avian Species in Southern China: Was H6N1 a Derivative or a Precursor of H5N1? by Hoffmann E, Stech J, Leneva I, Krauss S, Scholtissek C, Chin PS, Peiris M, Shortridge KF, Webster RG.; 2000 Jul 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=112136

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Chemoprophylaxis of Influenza A Virus Infections, with Single Doses of Zanamivir, Demonstrates that Zanamivir Is Cleared Slowly from the Respiratory Tract. by Fenton RJ, Morley PJ, Owens IJ, Gower D, Parry S, Crossman L, Wong T.; 1999 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=89537

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Clearance of an Influenza A Virus by CD4 + T Cells Is Inefficient in the Absence of B Cells. by Topham DJ, Doherty PC.; 1998 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=109454

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Cleavage of Influenza A Virus Hemagglutinin in Human Respiratory Epithelium Is Cell Associated and Sensitive to Exogenous Antiproteases. by Zhirnov OP, Ikizler MR, Wright PF.; 2002 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=136409

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Clinical Evaluation of the ZstatFlu-II Test: a Chemiluminescent Rapid Diagnostic Test for Influenza Virus. by Hamilton MS, Abel DM, Ballam YJ, Otto MK, Nickell AF, Pence LM, Appleman JR, Shimasaki CD, Achyuthan KE.; 2002 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=120541

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Coadministration of DNA Encoding Interleukin-6 and Hemagglutinin Confers Protection from Influenza Virus Challenge in Mice. by Larsen DL, Dybdahl-Sissoko N, McGregor MW, Drape R, Neumann V, Swain WF, Lunn DP, Olsen CW.; 1998 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=124660

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Cocirculation of Avian H9N2 and Contemporary "Human" H3N2 Influenza A Viruses in Pigs in Southeastern China: Potential for Genetic Reassortment? by Peiris JS, Guan Y, Markwell D, Ghose P, Webster RG, Shortridge KF.; 2001 Oct 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=114539

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Cocirculation of Two Distinct Lineages of Equine Influenza Virus Subtype H3N8. by Oxburgh L, Klingeborn B.; 1999 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=85435

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Coinfection with Influenza B Virus Does Not Affect Association of Neisseria meningitidis with Human Nasopharyngeal Mucosa in Organ Culture. by Read RC, Goodwin L, Parsons MA, Silcocks P, Kaczmarski EB, Parker A, Baldwin TJ.; 1999 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=96625

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Collectin-mediated antiviral host defense of the lung: evidence from influenza virus infection of mice. by Reading PC, Morey LS, Crouch EC, Anders EM.; 1997 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=192277

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Combined PCR-Heteroduplex Mobility Assay for Detection and Differentiation of Influenza A Viruses from Different Animal Species. by Ellis JS, Zambon MC.; 2001 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=88493

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Comparative Analysis of Evolutionary Mechanisms of the Hemagglutinin and Three Internal Protein Genes of Influenza B Virus: Multiple Cocirculating Lineages and Frequent Reassortment of the NP, M, and NS Genes. by Lindstrom SE, Hiromoto Y, Nishimura H, Saito T, Nerome R, Nerome K.; 1999 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=104222

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Comparative study of nasopharyngeal aspirate and nasal swab specimens for detection of influenza. by Heikkinen T, Salmi AA, Ruuskanen O.; 2001 Jan 20; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=26590

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Comparison of a New Neuraminidase Detection Assay with an Enzyme Immunoassay, Immunofluorescence, and Culture for Rapid Detection of Influenza A and B Viruses in Nasal Wash Specimens. by Noyola DE, Clark B, O'Donnell FT, Atmar RL, Greer J, Demmler GJ.; 2000 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=86363

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Comparison of Alteration of Cell Surface Carbohydrates of the Chinchilla Tubotympanum and Colonial Opacity Phenotype of Streptococcus pneumoniae during Experimental Pneumococcal Otitis Media with or without an Antecedent Influenza A Virus Infection. by Tong HH, Grants I, Liu X, DeMaria TF.; 2002 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=128169

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Comparison of Complement Fixation and Hemagglutination Inhibition Assays for Detecting Antibody Responses following Influenza Virus Vaccination. by Prince HE, Leber AL.; 2003 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=154979

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Comparison of Efficacies of RWJ-270201, Zanamivir, and Oseltamivir against H5N1, H9N2, and Other Avian Influenza Viruses. by Govorkova EA, Leneva IA, Goloubeva OG, Bush K, Webster RG.; 2001 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=90723

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Comparison of Four Clinical Specimen Types for Detection of Influenza A and B Viruses by Optical Immunoassay (FLU OIA Test) and Cell Culture Methods. by Covalciuc KA, Webb KH, Carlson CA.; 1999 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=85858

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Comparison of Immunogenicity and Safety of a Virosome Influenza Vaccine with Those of a Subunit Influenza Vaccine in Pediatric Patients with Cystic Fibrosis. by Schaad UB, Buhlmann U, Burger R, Ruedeberg A, Wilder-Smith A, Rutishauser M, Sennhauser F, Herzog C, Zellmeyer M, Gluck R.; 2000 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89839

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Comparison of Lateral-Flow Immunoassay and Enzyme Immunoassay with Viral Culture for Rapid Detection of Influenza Virus in Nasal Wash Specimens from Children. by Cazacu AC, Greer J, Taherivand M, Demmler GJ.; 2003 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=154694

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Comparison of Madin-Darby canine kidney cells (MDCK) with a green monkey continuous cell line (Vero) and human lung embryonated cells (MRC-5) in the isolation of influenza A virus from nasopharyngeal aspirates by shell vial culture. by Reina J, Fernandez-Baca V, Blanco I, Munar M.; 1997 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229869

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Comparison of Neutralizing and Hemagglutination-Inhibiting Antibody Responses to Influenza A Virus Vaccination of Human Immunodeficiency Virus-Infected Individuals. by Benne CA, Kroon FP, Harmsen M, Tavares L, Kraaijeveld CA, De Jong JC.; 1998 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=121402

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Comparison of rapid immunofluorescence procedure with TestPack RSV and Directigen FLU-A for diagnosis of respiratory syncytial virus and influenza A virus. by Todd SJ, Minnich L, Waner JL.; 1995 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=228236

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Comparison of the Activities of Zanamivir, Oseltamivir, and RWJ-270201 against Clinical Isolates of Influenza Virus and Neuraminidase Inhibitor-Resistant Variants. by Gubareva LV, Webster RG, Hayden FG.; 2001 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=90844

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Comparison of the Anti-Influenza Virus Activity of RWJ-270201 with Those of Oseltamivir and Zanamivir. by Bantia S, Parker CD, Ananth SL, Horn LL, Andries K, Chand P, Kotian PL, Dehghani A, El-Kattan Y, Lin T, Hutchison TL, Montgomery JA, Kellog DL, Babu YS.; 2001 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=90439

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Comparison of the Denka-Seiken INFLU A[center dot]B-Quick and BD Directigen Flu A +B Kits with Direct Fluorescent-Antibody Staining and Shell Vial Culture Methods for Rapid Detection of Influenza Viruses. by Dunn JJ, Gordon C, Kelley C, Carroll KC.; 2003 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=154708

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Comparison of the Pathogenesis of Two Genetically Different H3N2 Influenza A Viruses in Pigs. by Landolt GA, Karasin AI, Phillips L, Olsen CW.; 2003 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=154671

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Comparisons of Highly Virulent H5N1 Influenza A Viruses Isolated from Humans and Chickens from Hong Kong. by Suarez DL, Perdue ML, Cox N, Rowe T, Bender C, Huang J, Swayne DE.; 1998 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=109865

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Complement Component C1q Enhances the Biological Activity of Influenza Virus Hemagglutinin-Specific Antibodies Depending on Their Fine Antigen Specificity and Heavy-Chain Isotype. by Feng JQ, Mozdzanowska K, Gerhard W.; 2002 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=135831

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Compromised Influenza Virus-Specific CD8 +-T-Cell Memory in CD4 +-T-CellDeficient Mice. by Belz GT, Wodarz D, Diaz G, Nowak MA, Doherty PC.; 2002 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=136883

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Conformational Intermediates and Fusion Activity of Influenza Virus Hemagglutinin. by Korte T, Ludwig K, Booy FP, Blumenthal R, Herrmann A.; 1999 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=112497

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Continued Circulation in China of Highly Pathogenic Avian Influenza Viruses Encoding the Hemagglutinin Gene Associated with the 1997 H5N1 Outbreak in Poultry and Humans. by Cauthen AN, Swayne DE, Schultz-Cherry S, Perdue ML, Suarez DL.; 2000 Jul 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=112169

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Cooperation between the Hemagglutinin of Avian Viruses and the Matrix Protein of Human Influenza A Viruses. by Scholtissek C, Stech J, Krauss S, Webster RG.; 2002 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=135889

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Cross-protection among lethal H5N2 influenza viruses induced by DNA vaccine to the hemagglutinin. by Kodihalli S, Haynes JR, Robinson HL, Webster RG.; 1997 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=191483

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Cross-Reactive, Cell-Mediated Immunity and Protection of Chickens from Lethal H5N1 Influenza Virus Infection in Hong Kong Poultry Markets. by Seo SH, Webster RG.; 2001 Mar 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=115873

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Cross-Reactivity between Hepatitis C Virus and Influenza A Virus DeterminantSpecific Cytotoxic T Cells. by Wedemeyer H, Mizukoshi E, Davis AR, Bennink JR, Rehermann B.; 2001 Dec 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=114725

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Cryopreserved Cell Monolayers for Rapid Detection of Herpes Simplex Virus and Influenza Virus. by Huang YT, Yan H, Sun Y, Jollick, Jr. JA, Baird H.; 2002 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=139648

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Cyclopentane Neuraminidase Inhibitors with Potent In Vitro Anti-Influenza Virus Activities. by Smee DF, Huffman JH, Morrison AC, Barnard DL, Sidwell RW.; 2001 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=90367

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Definition of Amino Acid Residues on the Epitope Responsible for Recognition by Influenza A Virus H1-Specific, H2-Specific, and H1- and H2-Cross-Reactive Murine Cytotoxic T-Lymphocyte Clones. by Tamura M, Kuwano K, Kurane I, Ennis FA.; 1998 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=110370

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Definition of the minimal viral components required for the initiation of unprimed RNA synthesis by influenza virus RNA polymerase. by Lee MT, Bishop K, Medcalf L, Elton D, Digard P, Tiley L.; 2002 Jan 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=99831

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Definitive Assignment of Proton Selectivity and Attoampere Unitary Current to the M2 Ion Channel Protein of Influenza A Virus. by Lin TI, Schroeder C.; 2001 Apr 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=114856

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Depletion of Lymphocytes and Diminished Cytokine Production in Mice Infected with a Highly Virulent Influenza A (H5N1) Virus Isolated from Humans. by Tumpey TM, Lu X, Morken T, Zaki SR, Katz JM.; 2000 Jul 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=112109

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Detection and Quantification of CD4 + T Cells with Specificity for a New Major Histocompatibility Complex Class II-Restricted Influenza A Virus Matrix Protein Epitope in Peripheral Blood of Influenza Patients. by Linnemann T, Jung G, Walden P.; 2000 Sep 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=116386

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Detection of Amantadine-Resistant Influenza A Virus Strains in Nursing Homes by PCR-Restriction Fragment Length Polymorphism Analysis with Nasopharyngeal Swabs. by Saito R, Oshitani H, Masuda H, Suzuki H.; 2002 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=120099

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Detection of Antibody to Avian Influenza A (H5N1) Virus in Human Serum by Using a Combination of Serologic Assays. by Rowe T, Abernathy RA, Hu-Primmer J, Thompson WW, Lu X, Lim W, Fukuda K, Cox NJ, Katz JM.; 1999 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=88628

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Detection of Influenza A Viruses from Different Species by PCR Amplification of Conserved Sequences in the Matrix Gene. by Fouchier RA, Bestebroer TM, Herfst S, Van Der Kemp L, Rimmelzwaan GF, Osterhaus AD.; 2000 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=87547

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Development of a Real-Time Reverse Transcriptase PCR Assay for Type A Influenza Virus and the Avian H5 and H7 Hemagglutinin Subtypes. by Spackman E, Senne DA, Myers TJ, Bulaga LL, Garber LP, Perdue ML, Lohman K, Daum LT, Suarez DL.; 2002 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=130722

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Differences in sialic acid-galactose linkages in the chicken egg amnion and allantois influence human influenza virus receptor specificity and variant selection. by Ito T, Suzuki Y, Takada A, Kawamoto A, Otsuki K, Masuda H, Yamada M, Suzuki T, Kida H, Kawaoka Y.; 1997 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=191479

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Differential Activation of Influenza A Virus Endonuclease Activity Is Dependent on Multiple Sequence Differences between the Virion RNA and cRNA Promoters. by Leahy MB, Zecchin G, Brownlee GG.; 2002 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=135883

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Differential diagnoses of influenza A virus, influenza B virus, and respiratory syncytial virus infections by direct immunofluorescence using mixtures of monoclonal antibodies of different isotypes. by Murphy P, Roberts ZM, Waner JL.; 1996 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229118

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Diminished Primary and Secondary Influenza Virus-Specific CD8 + T-Cell Responses in CD4-Depleted Ig[minus sign]/[minus sign] Mice. by Riberdy JM, Christensen JP, Branum K, Doherty PC.; 2000 Oct 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=112411

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Direct Evidence that the Poly(A) Tail of Influenza A Virus mRNA Is Synthesized by Reiterative Copying of a U Track in the Virion RNA Template. by Poon LL, Pritlove DC, Fodor E, Brownlee GG.; 1999 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=104115

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Direct Measurement of the Anti-Influenza Agent Zanamivir in the Respiratory Tract following Inhalation. by Peng AW, Milleri S, Stein DS.; 2000 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=89995

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Distinct Pathogenesis of Hong Kong-Origin H5N1 Viruses in Mice Compared to That of Other Highly Pathogenic H5 Avian Influenza Viruses. by Dybing JK, SchultzCherry S, Swayne DE, Suarez DL, Perdue ML.; 2000 Feb 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=111479

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DNA Vaccine Encoding Hemagglutinin Provides Protective Immunity against H5N1 Influenza Virus Infection in Mice. by Kodihalli S, Goto H, Kobasa DL, Krauss S, Kawaoka Y, Webster RG.; 1999 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=104453

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DNA Vaccines for Influenza Virus: Differential Effects of Maternal Antibody on Immune Responses to Hemagglutinin and Nucleoprotein. by Pertmer TM, Oran AE, Moser JM, Madorin CA, Robinson HL.; 2000 Sep 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=112308

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Dose-Dependent Changes in Influenza Virus-Infected Dendritic Cells Result in Increased Allogeneic T-Cell Proliferation at Low, but Not High, Doses of Virus. by Oh S, McCaffery JM, Eichelberger MC.; 2000 Jun 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=112030

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Early Alterations of the Receptor-Binding Properties of H1, H2, and H3 Avian Influenza Virus Hemagglutinins after Their Introduction into Mammals. by Matrosovich M, Tuzikov A, Bovin N, Gambaryan A, Klimov A, Castrucci MR, Donatelli I, Kawaoka Y.; 2000 Sep 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=116362

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Effect of Cytoplasmic Tail Truncations on the Activity of the M2 Ion Channel of Influenza A Virus. by Tobler K, Kelly ML, Pinto LH, Lamb RA.; 1999 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=113015

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Effect of experimental influenza A virus infection on isolation of Streptococcus pneumoniae and other aerobic bacteria from the oropharynges of allergic and nonallergic adult subjects. by Wadowsky RM, Mietzner SM, Skoner DP, Doyle WJ, Fireman P.; 1995 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=173127

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Effect of Influenza A Virus Infection on Nasopharyngeal Colonization and Otitis Media Induced by Transparent or Opaque Phenotype Variants of Streptococcus pneumoniae in the Chinchilla Model. by Tong HH, Weiser JN, James MA, DeMaria TF.; 2001 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=97928

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Effect of Intranasal Administration of Lactobacillus casei Shirota on Influenza Virus Infection of Upper Respiratory Tract in Mice. by Hori T, Kiyoshima J, Shida K, Yasui H.; 2001 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=96107

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Effective inhibition of influenza virus production in cultured cells by external guide sequences and ribonuclease P. by Plehn-Dujowich D, Altman S.; 1998 Jun 23; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=22606

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Effectiveness of neuraminidase inhibitors in treatment and prevention of influenza A and B: systematic review and meta-analyses of randomised controlled trials. by Cooper NJ, Sutton AJ, Abrams KR, Wailoo A, Turner D, Nicholson KG.; 2003 Jun 7; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=161558

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Effectiveness of Reverse Transcription-PCR, Virus Isolation, and Enzyme-Linked Immunosorbent Assay for Diagnosis of Influenza A Virus Infection in Different Age Groups. by Steininger C, Kundi M, Aberle SW, Aberle JH, Popow-Kraupp T.; 2002 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=130702

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Effects of Influenza A Virus NS1 Protein on Protein Expression: the NS1 Protein Enhances Translation and Is Not Required for Shutoff of Host Protein Synthesis. by Salvatore M, Basler CF, Parisien JP, Horvath CM, Bourmakina S, Zheng H, Muster T, Palese P, Garcia-Sastre A.; 2002 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=135795

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Efficacy of Zanamivir against Avian Influenza A Viruses That Possess Genes Encoding H5N1 Internal Proteins and Are Pathogenic in Mammals. by Leneva IA, Goloubeva O, Fenton RJ, Tisdale M, Webster RG.; 2001 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=90446

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Elongation of the Cytoplasmic Tail Interferes with the Fusion Activity of Influenza Virus Hemagglutinin. by Ohuchi M, Fischer C, Ohuchi R, Herwig A, Klenk HD.; 1998 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=109575

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Emergence of an Influenza B Virus with Antigenic Change. by Nakagawa N, Nukuzuma S, Haratome S, Go S, Nakagawa T, Hayashi K.; 2002 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=120617

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Emergence of avian H1N1 influenza viruses in pigs in China. by Guan Y, Shortridge KF, Krauss S, Li PH, Kawaoka Y, Webster RG.; 1996 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=190877

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Emergence of multiple genotypes of H5N1 avian influenza viruses in Hong Kong SAR. by Guan Y, Peiris JS, Lipatov AS, Ellis TM, Dyrting KC, Krauss S, Zhang LJ, Webster RG, Shortridge KF.; 2002 Jun 25; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=124404

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Epidermal Powder Immunization Induces both Cytotoxic T-Lymphocyte and Antibody Responses to Protein Antigens of Influenza and Hepatitis B Viruses. by Chen D, Weis KF, Chu Q, Erickson C, Endres R, Lively CR, Osorio J, Payne LG.; 2001 Dec 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=114750

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Eukaryotic Translation Initiation Factor 4GI Is a Cellular Target for NS1 Protein, a Translational Activator of Influenza Virus. by Aragon T, de la Luna S, Novoa I, Carrasco L, Ortin J, Nieto A.; 2000 Sep 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=86100

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Evaluation of a New Dot Blot Enzyme Immunoassay (Directigen Flu A +B) for Simultaneous and Differential Detection of Influenza A and B Virus Antigens from Respiratory Samples. by Reina J, Padilla E, Alonso F, Ruiz de Gopegui E, Munar M, Mari M.; 2002 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=130707

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Evaluation of a Rapid Optical Immunoassay for Influenza Viruses (FLU OIA Test) in Comparison with Cell Culture and Reverse Transcription-PCR. by Boivin G, Hardy I, Kress A.; 2001 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=87806

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Evaluation of monoclonal antibodies for subtyping of currently circulating human type A influenza viruses. by Tkacova M, Vareckova E, Baker IC, Love JM, Ziegler T.; 1997 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=232728

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Evaluation of the Directigen FluA +B Test for Rapid Diagnosis of Influenza Virus Type A and B Infections. by Chan KH, Maldeis N, Pope W, Yup A, Ozinskas A, Gill J, Seto WH, Shortridge KF, Peiris JS.; 2002 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=130655

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Evaluation of the Subtype Specificity of Monoclonal Antibodies Raised against H1 and H3 Subtypes of Human Influenza A Virus Hemagglutinins. by Vareckova E, Cox N, Klimov A.; 2002 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=130739

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Evidence for Segment-Nonspecific Packaging of the Influenza A Virus Genome. by Bancroft CT, Parslow TG.; 2002 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=136309

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Evolution of Swine H3N2 Influenza Viruses in the United States. by Webby RJ, Swenson SL, Krauss SL, Gerrish PJ, Goyal SM, Webster RG.; 2000 Sep 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=116332

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Evolutionary Changes in Influenza B are Not Primarily Governed by Antibody Selection. by Air GM, Gibbs AJ, Laver WG, Webster RG.; 1990 May 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=54008

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Excess winter mortality: influenza or cold stress? Observational study. by Donaldson GC, Keatinge WR.; 2002 Jan 12; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=64505

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Existing antivirals are effective against influenza viruses with genes from the 1918 pandemic virus. by Tumpey TM, Garcia-Sastre A, Mikulasova A, Taubenberger JK, Swayne DE, Palese P, Basler CF.; 2002 Oct 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=129786

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Expression of Functional Influenza Virus RNA Polymerase in the Methylotrophic Yeast Pichia pastoris. by Hwang JS, Yamada K, Honda A, Nakade K, Ishihama A.; 2000 May 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=111921

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Expression of influenza virus hemagglutinin activates transcription factor NF-kappa B. by Pahl HL, Baeuerle PA.; 1995 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=188737

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Factors influencing childhood influenza immunization. by Grant VJ, Le Saux N, Plint AC, Correll R, Gaboury I, Ellis E, Tam TW.; 2003 Jan 7; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=139316

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Fatty Acids on the A/USSR/77 Influenza Virus Hemagglutinin Facilitate the Transition from Hemifusion to Fusion Pore Formation. by Sakai T, Ohuchi R, Ohuchi M.; 2002 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=155084

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Formation of Wild-Type and Chimeric Influenza Virus-Like Particles following Simultaneous Expression of Only Four Structural Proteins. by Latham T, Galarza JM.; 2001 Jul 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=114331

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Frequency of Amantadine-Resistant Influenza A Viruses during Two Seasons Featuring Cocirculation of H1N1 and H3N2. by Saito R, Sakai T, Sato I, Sano Y, Oshitani H, Sato M, Suzuki H.; 2003 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=154689

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Frequent Reassortment among Influenza C Viruses. by Matsuzaki Y, Mizuta K, Sugawara K, Tsuchiya E, Muraki Y, Hongo S, Suzuki H, Nishimura H.; 2003 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=140804

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Functional Analysis of PA Binding by Influenza A Virus PB1: Effects on Polymerase Activity and Viral Infectivity. by Perez DR, Donis RO.; 2001 Sep 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=115057

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Functional Replacement of the Carboxy-Terminal Two-Thirds of the Influenza A Virus NS1 Protein with Short Heterologous Dimerization Domains. by Wang X, Basler CF, Williams BR, Silverman RH, Palese P, Garcia-Sastre A.; 2002 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=136679

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Fusion Activity of Transmembrane and Cytoplasmic Domain Chimeras of the Influenza Virus Glycoprotein Hemagglutinin. by Schroth-Diez B, Ponimaskin E, Reverey H, Schmidt MF, Herrmann A.; 1998 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=109357

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Gamma Interferon Is Not Required for Mucosal Cytotoxic T-Lymphocyte Responses or Heterosubtypic Immunity to Influenza A Virus Infection in Mice. by Nguyen HH, van Ginkel FW, Vu HL, Novak MJ, McGhee JR, Mestecky J.; 2000 Jun 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=112034

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Generation and Characterization of a Mutant of Influenza A Virus Selected with the Neuraminidase Inhibitor BCX-140. by Bantia S, Ghate AA, Ananth SL, Babu YS, Air GM, Walsh GM.; 1998 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105545

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Generation of a Highly Pathogenic Avian Influenza A Virus from an Avirulent Field Isolate by Passaging in Chickens. by Ito T, Goto H, Yamamoto E, Tanaka H, Takeuchi M, Kuwayama M, Kawaoka Y, Otsuki K.; 2001 May 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=114193

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Generation of influenza A viruses entirely from cloned cDNAs. by Neumann G, Watanabe T, Ito H, Watanabe S, Goto H, Gao P, Hughes M, Perez DR, Donis R, Hoffmann E, Hobom G, Kawaoka Y.; 1999 Aug 3; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=17785

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Genetic Characterization of an H1N2 Influenza Virus Isolated from a Pig In Indiana. by Karasin AI, Olsen CW.; 2000 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=86843

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Genetic Characterization of H1N2 Influenza A Viruses Isolated from Pigs throughout the United States. by Karasin AI, Landgraf J, Swenson S, Erickson G, Goyal S, Woodruff M, Scherba G, Anderson G, Olsen CW.; 2002 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=120269

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Genetic Reassortment of Avian, Swine, and Human Influenza A Viruses in American Pigs. by Zhou NN, Senne DA, Landgraf JS, Swenson SL, Erickson G, Rossow K, Liu L, Yoon KJ, Krauss S, Webster RG.; 1999 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=112910

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Genetically engineered live attenuated influenza A virus vaccine candidates. by Parkin NT, Chiu P, Coelingh K.; 1997 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=191400

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Genotypic Stability of Cold-Adapted Influenza Virus Vaccine in an Efficacy Clinical Trial. by Cha TA, Kao K, Zhao J, Fast PE, Mendelman PM, Arvin A.; 2000 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=86217

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GG167 (4-guanidino-2,4-dideoxy-2,3-dehydro-N-acetylneuraminic acid) is a potent inhibitor of influenza virus in ferrets. by Ryan DM, Ticehurst J, Dempsey MH.; 1995 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=162991

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Global Impact of Influenza Virus on Cellular Pathways Is Mediated by both Replication-Dependent and -Independent Events. by Geiss GK, An MC, Bumgarner RE, Hammersmark E, Cunningham D, Katze MG.; 2001 May 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=114177

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H5 avian and H9 swine influenza virus haemagglutinin structures: possible origin of influenza subtypes. by Ha Y, Stevens DJ, Skehel JJ, Wiley DC.; 2002 Mar 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=125880

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H9N2 Influenza Viruses Possessing H5N1-Like Internal Genomes Continue To Circulate in Poultry in Southeastern China. by Guan Y, Shortridge KF, Krauss S, Chin PS, Dyrting KC, Ellis TM, Webster RG, Peiris M.; 2000 Oct 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=112365

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Haemophilus influenzae Pill are Composite Structures Assembled via the HifB Chaperone. by Geme JW, Pinker JS, Krasan GP, Heuser J, Bullitt E, Smith AL, Hultgren SJ.; 1996 Oct 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=38158

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Hairpin Loop Structure in the 3[prime prime or minute] Arm of the Influenza A Virus Virion RNA Promoter Is Required for Endonuclease Activity. by Leahy MB, Dobbyn HC, Brownlee GG.; 2001 Aug 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=114432

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Heat-Aggregated Noninfectious Influenza Virus Induces a More Balanced CD8 +-TLymphocyte Immunodominance Hierarchy Than Infectious Virus. by Cho Y, Basta S, Chen W, Bennink JR, Yewdell JW.; 2003 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=152137

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Hemagglutinin 1-Specific Immunoglobulin G and Fab Molecules Mediate Postattachment Neutralization of Influenza A Virus by Inhibition of an Early Fusion Event. by Edwards MJ, Dimmock NJ.; 2001 Nov 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=114595

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Hemagglutinin sequence clusters and the antigenic evolution of influenza A virus. by Plotkin JB, Dushoff J, Levin SA.; 2002 Apr 30; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=122937

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Heterogeneity of Influenza B Virus Strains in One Epidemic Season Differentiated by Monoclonal Antibodies and Nucleotide Sequences. by Nakagawa N, Kubota R, Maeda A, Nakagawa T, Okuno Y.; 2000 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=87409

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Human CD4+ T-cell repertoire of responses to influenza A virus hemagglutinin after recent natural infection. by Gelder CM, Welsh KI, Faith A, Lamb JR, Askonas BA.; 1995 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=189688

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Human Cytotoxic T-Lymphocyte Repertoire to Influenza A Viruses. by Jameson J, Cruz J, Ennis FA.; 1998 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=110281

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Human influenza viruses activate an interferon-independent transcription of cellular antiviral genes: Outcome with influenza A virus is unique. by Kim MJ, Latham AG, Krug RM.; 2002 Jul 23; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=126630

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Human Lymphocyte Apoptosis after Exposure to Influenza A Virus. by Nichols JE, Niles JA, Roberts NJ Jr.; 2001 Jul 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=114307

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Human Parainfluenza Virus Type 3 HN-Receptor Interaction: Effect of 4-GuanidinoNeu5Ac2en on a Neuraminidase-Deficient Variant. by Porotto M, Greengard O, Poltoratskaia N, Horga MA, Moscona A.; 2001 Aug 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=114983

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Hyperattenuated Recombinant Influenza A Virus Nonstructural-Protein-Encoding Vectors Induce Human Immunodeficiency Virus Type 1 Nef-Specific Systemic and Mucosal Immune Responses in Mice. by Ferko B, Stasakova J, Sereinig S, Romanova J, Katinger D, Niebler B, Katinger H, Egorov A.; 2001 Oct 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=114458

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Identification of a Coronavirus Hemagglutinin-Esterase with a Substrate Specificity Different from Those of Influenza C Virus and Bovine Coronavirus. by Klausegger A, Strobl B, Regl G, Kaser A, Luytjes W, Vlasak R.; 1999 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=104150

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Identification of a Membrane Targeting and Degradation Signal in the p42 Protein of Influenza C Virus. by Pekosz A, Lamb RA.; 2000 Nov 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=110922

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Identification of Amino Acid Residues of Influenza Virus Nucleoprotein Essential for RNA Binding. by Elton D, Medcalf L, Bishop K, Harrison D, Digard P.; 1999 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=104262

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Identification of GS 4104 as an Orally Bioavailable Prodrug of the Influenza Virus Neuraminidase Inhibitor GS 4071. by Li W, Escarpe PA, Eisenberg EJ, Cundy KC, Sweet C, Jakeman KJ, Merson J, Lew W, Williams M, Zhang L, Kim CU, Bischofberger N, Chen MS, Mendel DB.; 1998 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=105512

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Identification of New Influenza B Virus Variants by Multiplex Reverse Transcription-PCR and the Heteroduplex Mobility Assay. by Zou S, Stansfield C, Bridge J.; 1998 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=104874

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Immune Response Induced by Airway Sensitization after Influenza A Virus Infection Depends on Timing of Antigen Exposure in Mice. by Yamamoto N, Suzuki S, Suzuki Y, Shirai A, Nakazawa M, Suzuki M, Takamasu T, Nagashima Y, Minami M, Ishigatsubo Y.; 2001 Jan 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=113942

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Immunity to Influenza A H9N2 Viruses Induced by Infection and Vaccination. by Lu X, Renshaw M, Tumpey TM, Kelly GD, Hu-Primmer J, Katz JM.; 2001 May 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=114244

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Immunization of Pigs with a Particle-Mediated DNA Vaccine to Influenza A Virus Protects against Challenge with Homologous Virus. by Macklin MD, McCabe D, McGregor MW, Neumann V, Meyer T, Callan R, Hinshaw VS, Swain WF.; 1998 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=124630

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Immunization with Purified N1 and N2 Influenza Virus Neuraminidases Demonstrates Cross-Reactivity Without Antigenic Competition. by Johansson BE, Kilbourne ED.; 1994 Mar 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=43370

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Immunodominance of major histocompatibility complex class I-restricted influenza virus epitopes can be influenced by the T-cell receptor repertoire. by Daly K, Nguyen P, Woodland DL, Blackman MA.; 1995 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=189678

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Immunogenicity and Protective Efficacy in Mice of Influenza B Virus Vaccines Grown in Mammalian Cells or Embryonated Chicken Eggs. by Alymova IV, Kodihalli S, Govorkova EA, Fanget B, Gerdil C, Webster RG.; 1998 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=109684

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Immunogenicity and Protective Efficacy of Replication-Incompetent Influenza VirusLike Particles. by Watanabe T, Watanabe S, Neumann G, Kida H, Kawaoka Y.; 2002 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=136812

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Immunostimulant Patch Containing Heat-Labile Enterotoxin from Escherichia coli Enhances Immune Responses to Injected Influenza Virus Vaccine through Activation

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of Skin Dendritic Cells. by Guebre-Xabier M, Hammond SA, Epperson DE, Yu J, Ellingsworth L, Glenn GM.; 2003 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=153977 •

Impact of patient characteristics on the risk of influenza/ILI-related complications. by Irwin DE, Weatherby LB, Huang WY, Rosenberg DM, Cook SF, Walker AM.; 2001; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=57009

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Impact of Sample Type on Rapid Detection of Influenza Virus A by CytospinEnhanced Immunofluorescence and Membrane Enzyme-Linked Immunosorbent Assay. by Landry ML, Cohen S, Ferguson D.; 2000 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=88742

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Imported Parakeets Harbor H9N2 Influenza A Viruses That Are Genetically Closely Related to Those Transmitted to Humans in Hong Kong. by Mase M, Imada T, Sanada Y, Etoh M, Sanada N, Tsukamoto K, Kawaoka Y, Yamaguchi S.; 2001 Apr 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=114145

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In Vitro and In Vivo Activities of Anti-Influenza Virus Compound T-705. by Furuta Y, Takahashi K, Fukuda Y, Kuno M, Kamiyama T, Kozaki K, Nomura N, Egawa H, Minami S, Watanabe Y, Narita H, Shiraki K.; 2002 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=127093

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In Vitro Characterization of A-315675, a Highly Potent Inhibitor of A and B Strain Influenza Virus Neuraminidases and Influenza Virus Replication. by Kati WM, Montgomery D, Carrick R, Gubareva L, Maring C, McDaniel K, Steffy K, Molla A, Hayden F, Kempf D, Kohlbrenner W.; 2002 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=127111

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In Vitro Selection and Characterization of Influenza A (A/N9) Virus Variants Resistant to a Novel Neuraminidase Inhibitor, A-315675. by Molla A, Kati W, Carrick R, Steffy K, Shi Y, Montgomery D, Gusick N, Stoll VS, Stewart KD, Ng TI, Maring C, Kempf DJ, Kohlbrenner W.; 2002 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=137025

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In vivo anti-influenza virus activity of a zinc finger peptide. by Judd AK, Sanchez A, Bucher DJ, Huffman JH, Bailey K, Sidwell RW.; 1997 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=163772

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In vivo blockade of gamma interferon affects the influenza virus-induced humoral and the local cellular immune response in lung tissue. by Baumgarth N, Kelso A.; 1996 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=190374

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In Vivo Influenza Virus-Inhibitory Effects of the Cyclopentane Neuraminidase Inhibitor RWJ-270201. by Sidwell RW, Smee DF, Huffman JH, Barnard DL, Bailey KW, Morrey JD, Babu YS.; 2001 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=90368

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In vivo proliferation of naive and memory influenza-specific CD8 + T cells. by Flynn KJ, Riberdy JM, Christensen JP, Altman JD, Doherty PC.; 1999 Jul 20; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=17562

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Increased Interleukin-6 Levels in Nasal Lavage Samples following Experimental Influenza A Virus Infection. by Gentile D, Doyle W, Whiteside T, Fireman P, Hayden FG, Skoner D.; 1998 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=95627

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Increased Susceptibility of Diabetic Mice to Influenza Virus Infection: Compromise of Collectin-Mediated Host Defense of the Lung by Glucose? by Reading PC, Allison J, Crouch EC, Anders EM.; 1998 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=109899

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Increasing doses of purified influenza virus hemagglutinin and subvirion vaccines enhance antibody responses in the elderly. by Keitel WA, Cate TR, Atmar RL, Turner CS, Nino D, Dukes CM, Six HR, Couch RB.; 1996 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=170397

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Independence of Evolutionary and Mutational Rates after Transmission of Avian Influenza Viruses to Swine. by Stech J, Xiong X, Scholtissek C, Webster RG.; 1999 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=104428

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Induction of CD4 + T-Cell-Independent Immunoglobulin Responses by Inactivated Influenza Virus. by Sha Z, Compans RW.; 2000 Jun 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=110851

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Induction of Long-Term Memory CD8 + T Cells for Recall of Viral Clearing Responses against Influenza Virus. by Deliyannis G, Jackson DC, Ede NJ, Zeng W, Hourdakis I, Sakabetis E, Brown LE.; 2002 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=155065

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Infection-Triggered Regulatory Mechanisms Override the Role of STAT 4 in Control of the Immune Response to Influenza Virus Antigens. by Bot A, Rodrigo E, Wolfe T, Bot S, Von Herrath MG.; 2003 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=154013

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Influenza A and B viruses expressing altered NS1 proteins: A vaccine approach. by Talon J, Salvatore M, O'Neill RE, Nakaya Y, Zheng H, Muster T, Garcia-Sastre A, Palese P.; 2000 Apr 11; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=18238

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Influenza A H9N2: Aspects of Laboratory Diagnosis. by Peiris M, Yam WC, Chan KH, Ghose P, Shortridge KF.; 1999 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=85595

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Influenza A Virus Can Undergo Multiple Cycles of Replication without M2 Ion Channel Activity. by Watanabe T, Watanabe S, Ito H, Kida H, Kawaoka Y.; 2001 Jun 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=114278

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Influenza A Virus M2 Ion Channel Activity Is Essential for Efficient Replication in Tissue Culture. by Takeda M, Pekosz A, Shuck K, Pinto LH, Lamb RA.; 2002 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=135863

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Influenza A Virus NEP (NS2 Protein) Downregulates RNA Synthesis of Model Template RNAs. by Bullido R, Gomez-Puertas P, Saiz MJ, Portela A.; 2001 May 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=114247

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Influenza A Virus NS1 Protein Prevents Activation of NF-[kappa]B and Induction of Alpha/Beta Interferon. by Wang X, Li M, Zheng H, Muster T, Palese P, Beg AA, GarciaSastre A.; 2000 Dec 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=112437

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Influenza A Virus RNA Polymerase Has the Ability To Stutter at the Polyadenylation Site of a Viral RNA Template during RNA Replication. by Zheng H, Lee HA, Palese P, Garcia-Sastre A.; 1999 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=112577

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Influenza A Viruses Lacking Sialidase Activity Can Undergo Multiple Cycles of Replication in Cell Culture, Eggs, or Mice. by Hughes MT, Matrosovich M, Rodgers ME, McGregor M, Kawaoka Y.; 2000 Jun 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=110874

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Influenza A Virus-Infected Hosts Boost an Invasive Type of Streptococcus pyogenes Infection in Mice. by Okamoto S, Kawabata S, Nakagawa I, Okuno Y, Goto T, Sano K, Hamada S.; 2003 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=150641

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Influenza B and C Virus NEP (NS2) Proteins Possess Nuclear Export Activities. by Paragas J, Talon J, O'Neill RE, Anderson DK, Garcia-Sastre A, Palese P.; 2001 Aug 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=114972

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Influenza B virus NS1 protein inhibits conjugation of the interferon (IFN)-induced ubiquitin-like ISG15 protein. by Yuan W, Krug RM.; 2001 Feb 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=133459

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Influenza B viruses with site-specific mutations introduced into the HA gene. by Barclay WS, Palese P.; 1995 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=188703

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Influenza C virus CM2 integral membrane glycoprotein is produced from a polypeptide precursor by cleavage of an internal signal sequence. by Pekosz A, Lamb RA.; 1998 Oct 27; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=23766

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Influenza C Virus CM2 Protein Is Produced from a 374-Amino-Acid Protein (P42) by Signal Peptidase Cleavage. by Hongo S, Sugawara K, Muraki Y, Matsuzaki Y, Takashita E, Kitame F, Nakamura K.; 1999 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=103806

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Influenza vaccination in Alberta long-term care facilities. by Russell ML.; 2001 May 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=81068

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Influenza vaccines: present and future. by Palese P, Garcia-Sastre A.; 2002 Jul 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=151037

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Influenza Virus Assembly and Lipid Raft Microdomains: a Role for the Cytoplasmic Tails of the Spike Glycoproteins. by Zhang J, Pekosz A, Lamb RA.; 2000 May 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=111983

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Influenza Virus Assembly: Effect of Influenza Virus Glycoproteins on the Membrane Association of M1 Protein. by Ali A, Avalos RT, Ponimaskin E, Nayak DP.; 2000 Sep 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=116382

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Influenza Virus Can Enter and Infect Cells in the Absence of Clathrin-Mediated Endocytosis. by Sieczkarski SB, Whittaker GR.; 2002 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=136567

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Influenza virus hemagglutinin cleavage into HA1, HA2: No laughing matter. by Taubenberger JK.; 1998 Aug 18; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=33880

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Influenza Virus Hemagglutinin HA-2 N-Terminal Fusogenic Peptides Augment Gene Transfer by Transferrin-Polylysine-DNA Complexes: Toward a Synthetic Virus-Like Gene-Transfer Vehicle. by Wagner E, Plank C, Zatloukal K, Cotten M, Birnstiel ML.; 1992 Sep 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=49829

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Influenza Virus Infection Induces Metallothionein Gene Expression in the Mouse Liver and Lung by Overlapping but Distinct Molecular Mechanisms. by Ghoshal K, Majumder S, Zhu Q, Hunzeker J, Datta J, Shah M, Sheridan JF, Jacob ST.; 2001 Dec 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=99995

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Influenza virus inhibits amiloride-sensitive Na + channels in respiratory epithelia. by Kunzelmann K, Beesley AH, King NJ, Karupiah G, Young JA, Cook DI.; 2000 Aug 29; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=27875

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Influenza Virus Matrix Protein Is the Major Driving Force in Virus Budding. by Gomez-Puertas P, Albo C, Perez-Pastrana E, Vivo A, Portela A.; 2000 Dec 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=112434

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Influenza virus neuraminidase activates latent transforming growth factor beta. by Schultz-Cherry S, Hinshaw VS.; 1996 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=190955

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Influenza Virus NS1 Protein Counteracts PKR-Mediated Inhibition of Replication. by Bergmann M, Garcia-Sastre A, Carnero E, Pehamberger H, Wolff K, Palese P, Muster T.; 2000 Jul 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=112122

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Influenza Virus NS1 Protein Induces Apoptosis in Cultured Cells. by Schultz-Cherry S, Dybdahl-Sissoko N, Neumann G, Kawaoka Y, Hinshaw VS.; 2001 Sep 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=115031

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Influenza Virus Nucleoprotein Interacts with Influenza Virus Polymerase Proteins. by Biswas SK, Boutz PL, Nayak DP.; 1998 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=110190

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Influenza virus nucleoprotein-specific immunoglobulin G subclass and cytokine responses elicited by DNA vaccination are dependent on the route of vector DNA delivery. by Pertmer TM, Roberts TR, Haynes JR.; 1996 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=190634

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Influenza Virus-Infected Epithelial Cells Present Viral Antigens to Antigen-Specific CD8 + Cytotoxic T Lymphocytes. by Nguyen HH, Boyaka PN, Moldoveanu Z, Novak MJ, Kiyono H, McGhee JR, Mestecky J.; 1998 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=109702

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Inhibition of Human Immunodeficiency Virus Type 1 Replication prior to Reverse Transcription by Influenza Virus Stimulation. by Pinto LA, Blazevic V, Patterson BK, Mac Trubey C, Dolan MJ, Shearer GM.; 2000 May 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=111970

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Inhibition of Influenza A Virus Replication by Compounds Interfering with the Fusogenic Function of the Viral Hemagglutinin. by Plotch SJ, O'Hara B, Morin J, Palant O, LaRocque J, Bloom JD, Lang SA Jr, DiGrandi MJ, Bradley M, Nilakantan R, Gluzman Y.; 1999 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=103817

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Inhibition of Influenza Virus Replication by Nitric Oxide. by Rimmelzwaan GF, Baars MM, de Lijster P, Fouchier RA, Osterhaus AD.; 1999 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=112914

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Inhibition of Influenza Virus Replication by Phosphorothioate Oligodeoxynucleotides. by Leiter JM, Agrawal S, Palese P, Zamecnik PC.; 1990 May 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=53914

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Inhibition of influenza virus transcription by 2'-deoxy-2'-fluoroguanosine. by Tisdale M, Ellis M, Klumpp K, Court S, Ford M.; 1995 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=162964

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Innate and acquired humoral immunities to influenza virus are mediated by distinct arms of the immune system. by Baumgarth N, Herman OC, Jager GC, Brown L, Herzenberg LA, Herzenberg LA.; 1999 Mar 2; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=26769

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Interaction cloning of NS1-I, a human protein that binds to the nonstructural NS1 proteins of influenza A and B viruses. by Wolff T, O'Neill RE, Palese P.; 1996 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=190494

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Interaction of the Influenza Virus Nucleoprotein with the Cellular CRM1-Mediated Nuclear Export Pathway. by Elton D, Simpson-Holley M, Archer K, Medcalf L, Hallam R, McCauley J, Digard P.; 2001 Jan 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=113933

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Interdependence of Hemagglutinin Glycosylation and Neuraminidase as Regulators of Influenza Virus Growth: a Study by Reverse Genetics. by Wagner R, Wolff T, Herwig A, Pleschka S, Klenk HD.; 2000 Jul 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=112137

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Intranasal Immunization of Mice with Influenza Vaccine in Combination with the Adjuvant LT-R72 Induces Potent Mucosal and Serum Immunity Which Is Stronger than That with Traditional Intramuscular Immunization. by Barackman JD, Ott G, O'Hagan DT.; 1999 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=96738

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Invariant Chain Targets HLA Class II Molecules to Acidic Endosomes Containing Internalized Influenza Virus. by Lamb CA, Yewdell JW, Bennink JR, Cresswell P.; 1991 Jul 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=52009

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Involvement of the Mannose Receptor in Infection of Macrophages by Influenza Virus. by Reading PC, Miller JL, Anders EM.; 2000 Jun 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=110872

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Isolation and Characterization of H4N6 Avian Influenza Viruses from Pigs with Pneumonia in Canada. by Karasin AI, Brown IH, Carman S, Olsen CW.; 2000 Oct 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=102133

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Isolation of Amantadine-Resistant Influenza A Viruses (H3N2) from Patients following Administration of Amantadine in Japan. by Iwahashi J, Tsuji K, Ishibashi T, Kajiwara J, Imamura Y, Mori R, Hara K, Kashiwagi T, Ohtsu Y, Hamada N, Maeda H, Toyoda M, Toyoda T.; 2001 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=87992

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Isolation of Influenza C Virus during an Outbreak of Influenza A and B Viruses. by Greenbaum E, Morag A, Zakay-Rones Z.; 1998 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=104849

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Isolation of influenza virus in human lung embryonated fibroblast cells (MRC-5) from clinical samples. by de Ona M, Melon S, de la Iglesia P, Hidalgo F, Verdugo AF.; 1995 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=228309

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Low risk of recurrence of oculorespiratory syndrome following influenza revaccination. by Skowronski DM, Strauss B, Kendall P, Duval B, Serres GD.; 2002 Oct 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=128396

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Mass influenza vaccination in Ontario: a sensible move. by Schabas RE.; 2001 Jan 9; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=80630

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Mass influenza vaccination in Ontario: Is it worthwhile? by Demicheli V.; 2001 Jan 9; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=80631

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Measuring the Effects of Reminders for Outpatient Influenza Immunizations at the Point of Clinical Opportunity. by Tang PC, LaRosa MP, Newcomb C, Gorden SM.; 1999 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=61350

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Mechanism by Which Mutations at His274 Alter Sensitivity of Influenza A Virus N1 Neuraminidase to Oseltamivir Carboxylate and Zanamivir. by Wang MZ, Tai CY, Mendel DB.; 2002 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=132783

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Membrane Fusion Promoted by Increasing Surface Densities of the Paramyxovirus F and HN Proteins: Comparison of Fusion Reactions Mediated by Simian Virus 5 F, Human Parainfluenza Virus Type 3 F, and Influenza Virus HA. by Dutch RE, Joshi SB, Lamb RA.; 1998 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=110082

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Mice Deficient in Perforin, CD4 + T Cells, or CD28-Mediated Signaling Maintain the Typical Immunodominance Hierarchies of CD8 + T-Cell Responses to Influenza Virus. by Chen W, Bennink JR, Morton PA, Yewdell JW.; 2002 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=136568

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Microwave-accelerated direct immunofluorescent staining for respiratory syncytial virus and influenza A virus. by Hite SA, Huang YT.; 1996 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229125

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Mink Lung Cells and Mixed Mink Lung and A549 Cells for Rapid Detection of Influenza Virus and Other Respiratory Viruses. by Huang YT, Turchek BM.; 2000 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=88739

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Mink Lung Epithelial Cells: Unique Cell Line That Supports Influenza A and B Virus Replication. by Schultz-Cherry S, Dybdahl-Sissoko N, McGregor M, Hinshaw VS.; 1998 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=105273

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Modification of the Cytoplasmic Domain of Influenza Virus Hemagglutinin Affects Enlargement of the Fusion Pore. by Kozerski C, Ponimaskin E, Schroth-Diez B, Schmidt MF, Herrmann A.; 2000 Aug 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=112273

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Modulation of Nuclear Localization of the Influenza Virus Nucleoprotein through Interaction with Actin Filaments. by Digard P, Elton D, Bishop K, Medcalf E, Weeds A, Pope B.; 1999 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=104467

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Molecular Basis for the Generation in Pigs of Influenza A Viruses with Pandemic Potential. by Ito T, Couceiro JN, Kelm S, Baum LG, Krauss S, Castrucci MR, Donatelli I, Kida H, Paulson JC, Webster RG, Kawaoka Y.; 1998 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=109961

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Molecular characterization of H9N2 influenza viruses: Were they the donors of the "internal" genes of H5N1 viruses in Hong Kong? by Guan Y, Shortridge KF, Krauss S, Webster RG.; 1999 Aug 3; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=17788

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Molecular Correlates of Influenza A H5N1 Virus Pathogenesis in Mice. by Katz JM, Lu X, Tumpey TM, Smith CB, Shaw MW, Subbarao K.; 2000 Nov 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=110957

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Molecular Evolution of H6 Influenza Viruses from Poultry in Southeastern China: Prevalence of H6N1 Influenza Viruses Possessing Seven A/Hong Kong/156/97 (H5N1)-Like Genes in Poultry. by Chin PS, Hoffmann E, Webby R, Webster RG, Guan Y, Peiris M, Shortridge KF.; 2002 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=136834

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Molecular mechanism underlying the action of a novel fusion inhibitor of influenza A virus. by Luo G, Torri A, Harte WE, Danetz S, Cianci C, Tiley L, Day S, Mullaney D, Yu KL, Ouellet C, Dextraze P, Meanwell N, Colonno R, Krystal M.; 1997 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=191559

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85

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Molecular Mechanisms of Serum Resistance of Human Influenza H3N2 Virus and Their Involvement in Virus Adaptation in a New Host. by Matrosovich M, Gao P, Kawaoka Y.; 1998 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=109785

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Mucosal Delivery of Inactivated Influenza Vaccine Induces B-Cell-Dependent Heterosubtypic Cross-Protection against Lethal Influenza A H5N1 Virus Infection. by Tumpey TM, Renshaw M, Clements JD, Katz JM.; 2001 Jun 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=114919

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Multiplex PCR for Typing and Subtyping Influenza and Respiratory Syncytial Viruses. by Stockton J, Ellis JS, Saville M, Clewley JP, Zambon MC.; 1998 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105099

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Multiplex reverse transcription-PCR for surveillance of influenza A and B viruses in England and Wales in 1995 and 1996. by Ellis JS, Fleming DM, Zambon MC.; 1997 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229906

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Mutagenic Analysis of the 5[prime prime or minute] Arm of the Influenza A Virus Virion RNA Promoter Defines the Sequence Requirements for Endonuclease Activity. by Leahy MB, Pritlove DC, Poon LL, Brownlee GG.; 2001 Jan 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=113906

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Mutant Influenza Viruses with a Defective NS1 Protein Cannot Block the Activation of PKR in Infected Cells. by Hatada E, Saito S, Fukuda R.; 1999 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=104489

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Mutation of Neuraminidase Cysteine Residues Yields Temperature-Sensitive Influenza Viruses. by Basler CF, Garcia-Sastre A, Palese P.; 1999 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=112825

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Mutational Analysis of Influenza A Virus Nucleoprotein: Identification of Mutations That Affect RNA Replication. by Mena I, Jambrina E, Albo C, Perales B, Ortin J, Arrese M, Vallejo D, Portela A.; 1999 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=103939

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Mutational analysis of influenza B virus RNA transcription in vitro. by Lee YS, Seong BL.; 1996 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=189934

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Mutations in a Conserved Residue in the Influenza Virus Neuraminidase Active Site Decreases Sensitivity to Neu5Ac2en-Derived Inhibitors. by McKimm-Breschkin JL, Sahasrabudhe A, Blick TJ, McDonald M, Colman PM, Hart GJ, Bethell RC, Varghese JN.; 1998 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=109546

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N- and C-terminal residues combine in the fusion-pH influenza hemagglutinin HA2 subunit to form an N cap that terminates the triple-stranded coiled coil. by Chen J, Skehel JJ, Wiley DC.; 1999 Aug 3; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=17716

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Near patient testing for influenza in children in primary care: comparison with laboratory test. by Harnden A, Brueggemann A, Shepperd S, White J, Hayward AC, Zambon M, Crook D, Mant D.; 2003 Mar 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=150182

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Neuraminidase-specific antibody responses to inactivated influenza virus vaccine in young and elderly adults. by Powers DC, Kilbourne ED, Johansson BE.; 1996 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=170398

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Neurovirulence in Mice of H5N1 Influenza Virus Genotypes Isolated from Hong Kong Poultry in 2001. by Lipatov AS, Krauss S, Guan Y, Peiris M, Rehg JE, Perez DR, Webster RG.; 2003 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=149508

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Novel [alpha]- and [beta]-Amino Acid Inhibitors of Influenza Virus Neuraminidase. by Kati WM, Montgomery D, Maring C, Stoll VS, Giranda V, Chen X, Laver WG, Kohlbrenner W, Norbeck DW.; 2001 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=90693

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NS1 Protein of Influenza A Virus Down-Regulates Apoptosis. by Zhirnov OP, Konakova TE, Wolff T, Klenk HD.; 2002 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=135891

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NS1-Binding Protein (NS1-BP): a Novel Human Protein That Interacts with the Influenza A Virus Nonstructural NS1 Protein Is Relocalized in the Nuclei of Infected Cells. by Wolff T, O'Neill RE, Palese P.; 1998 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=109939

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Oral Administration of a Prodrug of the Influenza Virus Neuraminidase Inhibitor GS 4071 Protects Mice and Ferrets against Influenza Infection. by Mendel DB, Tai CY, Escarpe PA, Li W, Sidwell RW, Huffman JH, Sweet C, Jakeman KJ, Merson J, Lacy SA, Lew W, Williams MA, Zhang L, Chen MS, Bischofberger N, Kim CU.; 1998 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105511

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Oral Administration of Cyclopentane Neuraminidase Inhibitors Protects Ferrets against Influenza Virus Infection. by Sweet C, Jakeman KJ, Bush K, Wagaman PC, Mckown LA, Streeter AJ, Desai-Krieger D, Chand P, Babu YS.; 2002 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=127099

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Oral Administration of Influenza Vaccine in Combination with the Adjuvants LTK63 and LT-R72 Induces Potent Immune Responses Comparable to or Stronger than Traditional Intramuscular Immunization. by Barackman JD, Ott G, Pine S, O'Hagan DT.; 2001 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=96119

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Oral immunization with a replication-deficient recombinant vaccinia virus protects mice against influenza. by Bender BS, Rowe CA, Taylor SF, Wyatt LS, Moss B, Small PA Jr.; 1996 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=190672

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Origin and evolution of the 1918 "Spanish" influenza virus hemagglutinin gene. by Reid AH, Fanning TG, Hultin JV, Taubenberger JK.; 1999 Feb 16; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=15547

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87

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PA Subunit from Influenza Virus Polymerase Complex Interacts with a Cellular Protein with Homology to a Family of Transcriptional Activators. by Huarte M, SanzEzquerro JJ, Roncal F, Ortin J, Nieto A.; 2001 Sep 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=115105

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Palmitylation of the influenza virus hemagglutinin (H3) is not essential for virus assembly or infectivity. by Jin H, Subbarao K, Bagai S, Leser GP, Murphy BR, Lamb RA.; 1996 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=189960

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Pandemic Threat Posed by Avian Influenza A Viruses. by Horimoto T, Kawaoka Y.; 2001 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=88966

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Pathogenesis of Avian Influenza A (H5N1) Viruses in Ferrets. by Zitzow LA, Rowe T, Morken T, Shieh WJ, Zaki S, Katz JM.; 2002 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=155091

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Pathogenesis of Influenza A (H5N1) Virus Infection in a Primate Model. by Rimmelzwaan GF, Kuiken T, van Amerongen G, Bestebroer TM, Fouchier RA, Osterhaus AD.; 2001 Jul 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=114392

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Pattern of mutation in the genome of influenza A virus on adaptation to increased virulence in the mouse lung: Identification of functional themes. by Brown EG, Liu H, Kit LC, Baird S, Nesrallah M.; 2001 Jun 5; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=34447

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Pharmacodynamic Evaluation of RWJ-270201, a Novel Neuraminidase Inhibitor, in a Lethal Murine Model of Influenza Predicts Efficacy for Once-Daily Dosing. by Drusano GL, Preston SL, Smee D, Bush K, Bailey K, Sidwell RW.; 2001 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=90609

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Phase 1 Evaluation of Intranasal Virosomal Influenza Vaccine with and without Escherichia coli Heat-Labile Toxin in Adult Volunteers. by Gluck U, Gebbers JO, Gluck R.; 1999 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=104305

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pH-Dependent Changes in Photoaffinity Labeling Patterns of the H1 Influenza Virus Hemagglutinin by Using an Inhibitor of Viral Fusion. by Cianci C, Yu KL, Dischino DD, Harte W, Deshpande M, Luo G, Colonno RJ, Meanwell NA, Krystal M.; 1999 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=104417

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Phosphatidylserine-Mediated Phagocytosis of Influenza A Virus-Infected Cells by Mouse Peritoneal Macrophages. by Shiratsuchi A, Kaido M, Takizawa T, Nakanishi Y.; 2000 Oct 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=102123

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Phylogenetic Analysis of H7 Avian Influenza Viruses Isolated from the Live Bird Markets of the Northeast United States. by Suarez DL, Garcia M, Latimer J, Senne D, Perdue M.; 1999 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=104129

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Phylogenetic Analysis of the Entire Genome of Influenza A (H3N2) Viruses from Japan: Evidence for Genetic Reassortment of the Six Internal Genes. by Lindstrom SE, Hiromoto Y, Nerome R, Omoe K, Sugita S, Yamazaki Y, Takahashi T, Nerome K.; 1998 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=110138

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Plasmid-Driven Formation of Influenza Virus-Like Particles. by Neumann G, Watanabe T, Kawaoka Y.; 2000 Jan 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=111569

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Plasminogen-Binding Activity of Neuraminidase Determines the Pathogenicity of Influenza A Virus. by Goto H, Wells K, Takada A, Kawaoka Y.; 2001 Oct 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=114497

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Polarization of Allogeneic T-Cell Responses by Influenza Virus-Infected Dendritic Cells. by Oh S, Eichelberger MC.; 2000 Sep 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=112302

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Polyadenylation of Influenza Virus mRNA Transcribed In Vitro from Model Virion RNA Templates: Requirement for 5[prime prime or minute] Conserved Sequences. by Pritlove DC, Poon LL, Fodor E, Sharps J, Brownlee GG.; 1998 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=124606

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Polyuridylated mRNA Synthesized by a Recombinant Influenza Virus Is Defective in Nuclear Export. by Poon LL, Fodor E, Brownlee GG.; 2000 Jan 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=111553

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Practical and Sensitive Screening Strategy for Detection of Influenza Virus. by Newton DW, Mellen CF, Baxter BD, Atmar RL, Menegus MA.; 2002 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=139677

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Preferential selection of receptor-binding variants of influenza virus hemagglutinin by the neutralizing antibody repertoire of transgenic mice expressing a human immunoglobulin mu minigene. by Laeeq S, Smith CA, Wagner SD, Thomas DB.; 1997 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=191380

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Prevention of influenza and pneumococcal pneumonia in Canadian long-term care facilities: How are we doing? by Stevenson CG, McArthur MA, Naus M, Abraham E, McGeer AJ.; 2001 May 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=81067

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Profound Protection against Respiratory Challenge with a Lethal H7N7 Influenza A Virus by Increasing the Magnitude of CD8 + T-Cell Memory. by Christensen JP, Doherty PC, Branum KC, Riberdy JM.; 2000 Dec 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=112451

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Prophylactic and therapeutic efficacies of poly(IC.LC) against respiratory influenza A virus infection in mice. by Wong JP, Saravolac EG, Sabuda D, Levy HB, Kende M.; 1995 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=162988

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89

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Protection against a Lethal Avian Influenza A Virus in a Mammalian System. by Riberdy JM, Flynn KJ, Stech J, Webster RG, Altman JD, Doherty PC.; 1999 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=103970

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Protection against Influenza Virus Infection of Mice Fed Bifidobacterium breve YIT4064. by Yasui H, Kiyoshima J, Hori T, Shida K.; 1999 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=95685

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Protective CD4 + and CD8 + T Cells against Influenza Virus Induced by Vaccination with Nucleoprotein DNA. by Ulmer JB, Fu TM, Deck RR, Friedman A, Guan L, DeWitt C, Liu X, Wang S, Liu MA, Donnelly JJ, Caulfield MJ.; 1998 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=110229

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Protective cellular immunity: cytotoxic T-lymphocyte responses against dominant and recessive epitopes of influenza virus nucleoprotein induced by DNA immunization. by Fu TM, Friedman A, Ulmer JB, Liu MA, Donnelly JJ.; 1997 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=191393

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Protective Cross-Reactive Cellular Immunity to Lethal A/Goose/Guangdong/1/96-Like H5N1 Influenza Virus Is Correlated with the Proportion of Pulmonary CD8 + T Cells Expressing Gamma Interferon. by Seo SH, Peiris M, Webster RG.; 2002 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=136145

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Protective Role of Gamma Interferon during the Recall Response to Influenza Virus. by Bot A, Bot S, Bona CA.; 1998 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=109853

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Protein Synthesis Shut-Off Induced by Influenza Virus Infection Is Independent of PKR Activity. by Zurcher T, Marion RM, Ortin J.; 2000 Sep 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=116394

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QuickVue Influenza Test for Rapid Detection of Influenza A and B Viruses in a Pediatric Population. by Quach C, Newby D, Daoust G, Rubin E, McDonald J.; 2002 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=120042

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Rapid Evolution of H5N1 Influenza Viruses in Chickens in Hong Kong. by Zhou NN, Shortridge KF, Claas EC, Krauss SL, Webster RG.; 1999 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=104101

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Rapid virological surveillance of community influenza infection in general practice. by Carman WF, Wallace LA, Walker J, McIntyre S, Noone A, Christie P, Millar J, Douglas JD.; 2000 Sep 23; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=27488

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Reassortment and Insertion-Deletion Are Strategies for the Evolution of Influenza B Viruses in Nature. by McCullers JA, Wang GC, He S, Webster RG.; 1999 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=104260

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Recognition of N-Glycolylneuraminic Acid Linked to Galactose by the [alpha]2,3 Linkage Is Associated with Intestinal Replication of Influenza A Virus in Ducks. by

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Ito T, Suzuki Y, Suzuki T, Takada A, Horimoto T, Wells K, Kida H, Otsuki K, Kiso M, Ishida H, Kawaoka Y.; 2000 Oct 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=102129 •

Recombinant Sindbis Viruses Expressing a Cytotoxic T-Lymphocyte Epitope of a Malaria Parasite or of Influenza Virus Elicit Protection against the Corresponding Pathogen in Mice. by Tsuji M, Bergmann CC, Takita-Sonoda Y, Murata KI, Rodrigues EG, Nussenzweig RS, Zavala F.; 1998 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=109904

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Regulation of a nuclear export signal by an adjacent inhibitory sequence: The effector domain of the influenza virus NS1 protein. by Li Y, Yamakita Y, Krug RM.; 1998 Apr 28; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=20179

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Regulation of eukaryotic protein synthesis: Selective influenza viral mRNA translation is mediated by the cellular RNA-binding protein GRSF-1. by Park YW, Wilusz J, Katze MG.; 1999 Jun 8; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=21977

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Rescue of Influenza A Virus from Recombinant DNA. by Fodor E, Devenish L, Engelhardt OG, Palese P, Brownlee GG, Garcia-Sastre A.; 1999 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=113010

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Rescue of influenza B virus from eight plasmids. by Hoffmann E, Mahmood K, Yang CF, Webster RG, Greenberg HB, Kemble G.; 2002 Aug 20; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=123270

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Residue 627 of PB2 Is a Determinant of Cold Sensitivity in RNA Replication of Avian Influenza Viruses. by Massin P, van der Werf S, Naffakh N.; 2001 Jun 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=114948

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Reversible Merger of Membranes at the Early Stage of Influenza Hemagglutininmediated Fusion. by Leikina E, Chernomordik LV.; 2000 Jul 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=14925

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Reversible stages of the low-pH-triggered conformational change in influenza virus hemagglutinin. by Leikina E, Ramos C, Markovic I, Zimmerberg J, Chernomordik LV.; 2002 Nov 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=131056

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Role of a Transbilayer pH Gradient in the Membrane Fusion Activity of the Influenza Virus Hemagglutinin: Use of the R18 Assay to Monitor Membrane Merging. by Ramalho-Santos J, Pedroso de Lima MC.; 1999; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=140115

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Role of different lymphoid tissues in the initiation and maintenance of DNA-raised antibody responses to the influenza virus H1 glycoprotein. by Boyle CM, Morin M, Webster RG, Robinson HL.; 1996 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=191015

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Role of Hemagglutinin Surface Density in the Initial Stages of Influenza Virus Fusion: Lack of Evidence for Cooperativity. by Gunther-Ausborn S, Schoen P, Bartoldus I, Wilschut J, Stegmann T.; 2000 Mar 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=111761

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91

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Role of Interleukin-12 in Primary Influenza Virus Infection. by Monteiro JM, Harvey C, Trinchieri G.; 1998 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=110027

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Role of Picornaviruses in Flu-Like Illnesses of Adults Enrolled in an Oseltamivir Treatment Study Who Had No Evidence of Influenza Virus Infection. by Boivin G, Osterhaus AD, Gaudreau A, Jackson HC, Groen J, Ward P.; 2002 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=153349

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Role of Protein Kinase C [beta]II in Influenza Virus Entry via Late Endosomes. by Sieczkarski SB, Brown HA, Whittaker GR.; 2003 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=140583

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Role of Quail in the Interspecies Transmission of H9 Influenza A Viruses: Molecular Changes on HA That Correspond to Adaptation from Ducks to Chickens. by Perez DR, Lim W, Seiler JP, Yi G, Peiris M, Shortridge KF, Webster RG.; 2003 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=149770

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Role of Ribosome and Translocon Complex during Folding of Influenza Hemagglutinin in the Endoplasmic Reticulum of Living Cells. by Chen W, Helenius A.; 2000 Feb 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=14808

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Role of the Influenza Virus M1 Protein in Nuclear Export of Viral Ribonucleoproteins. by Bui M, Wills EG, Helenius A, Whittaker GR.; 2000 Feb 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=111655

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Safety and Efficacy of Intravenous Zanamivir in Preventing Experimental Human Influenza A Virus Infection. by Calfee DP, Peng AW, Cass LM, Lobo M, Hayden FG.; 1999 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=89333

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Safety and efficacy of long-term use of rimantadine for prophylaxis of type A influenza in nursing homes. by Monto AS, Ohmit SE, Hornbuckle K, Pearce CL.; 1995 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=162919

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Safety and immunoenhancing effect of a Chlorella-derived dietary supplement in healthy adults undergoing influenza vaccination: randomized, double-blind, placebocontrolled trial. by Halperin SA, Smith B, Nolan C, Shay J, Kralovec J.; 2003 Jul 22; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=164975

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Selection of a single amino acid substitution in the hemagglutinin molecule by chicken eggs can render influenza A virus (H3) candidate vaccine ineffective. by Kodihalli S, Justewicz DM, Gubareva LV, Webster RG.; 1995 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=189303

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Selective Perturbation of Apical Membrane Traffic by Expression of Influenza M2, an Acid-activated Ion Channel, in Polarized Madin --Darby Canine Kidney Cells. by Henkel JR, Apodaca G, Altschuler Y, Hardy S, Weisz OA.; 1998 Sep 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=25516

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Selective Translation of Eukaryotic mRNAs: Functional Molecular Analysis of GRSF1, a Positive Regulator of Influenza Virus Protein Synthesis. by Kash JC, Cunningham DM, Smit MW, Park Y, Fritz D, Wilusz J, Katze MG.; 2002 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=136571

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Sequence of an Influenza Virus Hemagglutinin Determined Directly from a Clinical Sample. by Rajakumar A, Swierkosz EM, Schulze IT.; 1990 Jun 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=54066

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Sequence of the 1918 pandemic influenza virus nonstructural gene (NS) segment and characterization of recombinant viruses bearing the 1918 NS genes. by Basler CF, Reid AH, Dybing JK, Janczewski TA, Fanning TG, Zheng H, Salvatore M, Perdue ML, Swayne DE, Garcia-Sastre A, Palese P, Taubenberger JK.; 2001 Feb 27; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=30210

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Sequence Variation in a Newly Identified HLA-B35-Restricted Epitope in the Influenza A Virus Nucleoprotein Associated with Escape from Cytotoxic T Lymphocytes. by Boon AC, de Mutsert G, Graus YM, Fouchier RA, Sintnicolaas K, Osterhaus AD, Rimmelzwaan GF.; 2002 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=153818

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Sequences in Influenza A Virus PB2 Protein That Determine Productive Infection for an Avian Influenza Virus in Mouse and Human Cell Lines. by Yao Y, Mingay LJ, McCauley JW, Barclay WS.; 2001 Jun 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=114950

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Sequential addition of temperature-sensitive missense mutations into the PB2 gene of influenza A transfectant viruses can effect an increase in temperature sensitivity and attenuation and permits the rational design of a genetically engineered live influenza A virus vaccine. by Subbarao EK, Park EJ, Lawson CM, Chen AY, Murphy BR.; 1995 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=189492

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Serum and Mucosal Immune Responses to an Inactivated Influenza Virus Vaccine Induced by Epidermal Powder Immunization. by Chen D, Periwal SB, Larrivee K, Zuleger C, Erickson CA, Endres RL, Payne LG.; 2001 Sep 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=115039

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Sialic Acid Species as a Determinant of the Host Range of Influenza A Viruses. by Suzuki Y, Ito T, Suzuki T, Holland RE Jr, Chambers TM, Kiso M, Ishida H, Kawaoka Y.; 2000 Dec 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=112465

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Simultaneous Detection and Typing of Influenza Viruses A and B by a Nested Reverse Transcription-PCR: Comparison to Virus Isolation and Antigen Detection by Immunofluorescence and Optical Immunoassay (FLU OIA). by Herrmann B, Larsson C, Zweygberg BW.; 2001 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=87692

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Simultaneous Detection of Influenza Viruses A and B Using Real-Time Quantitative PCR. by van Elden LJ, Nijhuis M, Schipper P, Schuurman R, van Loon AM.; 2001 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=87701

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Studies on influenza haemagglutinin fusion peptide mutants generated by reverse genetics. by Cross KJ, Wharton SA, Skehel JJ, Wiley DC, Steinhauer DA.; 2001 Aug 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=125568

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Studies using double mutants of the conformational transitions in influenza hemagglutinin required for its membrane fusion activity. by Steinhauer DA, Martin J, Lin YP, Wharton SA, Oldstone MB, Skehel JJ, Wiley DC.; 1996 Nov 12; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=24013

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Synergistic anti-influenza virus A (H1N1) activities of PM-523 (polyoxometalate) and ribavirin in vitro and in vivo. by Shigeta S, Mori S, Watanabe J, Soeda S, Takahashi K, Yamase T.; 1997 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=163933

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Targeted Infection of Endothelial Cells by Avian Influenza Virus A/FPV/Rostock/34 (H7N1) in Chicken Embryos. by Feldmann A, Schafer MK, Garten W, Klenk HD.; 2000 Sep 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=112334

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Temperature-Sensitive Lesions in Two Influenza A Viruses Defective for Replicative Transcription Disrupt RNA Binding by the Nucleoprotein. by Medcalf L, Poole E, Elton D, Digard P.; 1999 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=104261

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The active sites of the influenza cap-dependent endonuclease are on different polymerase subunits. by Li ML, Rao P, Krug RM.; 2001 Apr 17; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=125234

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The Anti-Influenza Virus Agent 4-GU-DANA (Zanamivir) Inhibits Cell Fusion Mediated by Human Parainfluenza Virus and Influenza Virus HA. by Greengard O, Poltoratskaia N, Leikina E, Zimmerberg J, Moscona A.; 2000 Dec 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=113191

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The Anti-Influenza Virus Drug Rimantadine Has Trypanocidal Activity. by Kelly JM, Miles MA, Skinner AC.; 1999 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89245

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The B-cell response in lymphoid tissue of mice immunized with various antigenic forms of the influenza virus hemagglutinin. by Justewicz DM, Doherty PC, Webster RG.; 1995 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=189386

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The Influenza A Virus NS1 Protein Inhibits Activation of Jun N-Terminal Kinase and AP-1 Transcription Factors. by Ludwig S, Wang X, Ehrhardt C, Zheng H, Donelan N, Planz O, Pleschka S, Garcia-Sastre A, Heins G, Wolff T.; 2002 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=136597

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The Lipid-anchored Ectodomain of Influenza Virus Hemagglutinin (GPI-HA) Is Capable of Inducing Nonenlarging Fusion Pores. by Markosyan RM, Cohen FS, Melikyan GB.; 2000 Apr 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=14837

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The M2 Ectodomain Is Important for Its Incorporation into Influenza A Virions. by Park EK, Castrucci MR, Portner A, Kawaoka Y.; 1998 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=109545

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The Magnitude and Specificity of Influenza A Virus-Specific Cytotoxic TLymphocyte Responses in Humans Is Related to HLA-A and -B Phenotype. by Boon AC, de Mutsert G, Graus YM, Fouchier RA, Sintnicolaas K, Osterhaus AD, Rimmelzwaan GF.; 2002 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=136822

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The NB Protein of Influenza B Virus Is Not Necessary for Virus Replication In Vitro. by Hatta M, Kawaoka Y.; 2003 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=154028

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The N-Terminal Extension of the Influenza B Virus Nucleoprotein Is Not Required for Nuclear Accumulation or the Expression and Replication of a Model RNA. by Stevens MP, Barclay WS.; 1998 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=116436

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The Replication Activity of Influenza Virus Polymerase Is Linked to the Capacity of the PA Subunit To Induce Proteolysis. by Perales B, Sanz-Ezquerro JJ, Gastaminza P, Ortega J, Santaren JF, Ortin J, Nieto A.; 2000 Feb 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=111465

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The RNA Polymerase of Influenza A Virus Is Stabilized by Interaction with Its Viral RNA Promoter. by Brownlee GG, Sharps JL.; 2002 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=136304

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The RNA Polymerase of Influenza Virus, Bound to the 5[prime prime or minute] End of Virion RNA, Acts in cis To Polyadenylate mRNA. by Poon LL, Pritlove DC, Sharps J, Brownlee GG.; 1998 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=110172

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The Role of Alpha/Beta and Gamma Interferons in Development of Immunity to Influenza A Virus in Mice. by Price GE, Gaszewska-Mastarlarz A, Moskophidis D.; 2000 May 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=111913

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The Role of Influenza A Virus Hemagglutinin Residues 226 and 228 in Receptor Specificity and Host Range Restriction. by Vines A, Wells K, Matrosovich M, Castrucci MR, Ito T, Kawaoka Y.; 1998 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=110023

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The Role of Interferon in Influenza Virus Tissue Tropism. by Garcia-Sastre A, Durbin RK, Zheng H, Palese P, Gertner R, Levy DE, Durbin JE.; 1998 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=110265

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The role of neuraminidase inhibitors in the treatment and prevention of influenza. by Naem S.; 2001; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=113777

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The Surface Glycoproteins of H5 Influenza Viruses Isolated from Humans, Chickens, and Wild Aquatic Birds Have Distinguishable Properties. by Matrosovich M, Zhou N, Kawaoka Y, Webster R.; 1999 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=103935

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The total influenza vaccine failure of 1947 revisited: Major intrasubtypic antigenic change can explain failure of vaccine in a post-World War II epidemic. by Kilbourne ED, Smith C, Brett I, Pokorny BA, Johansson B, Cox N.; 2002 Aug 6; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=125033

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The treatment of influenza with antiviral drugs. by Stiver G.; 2003 Jan 7; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=139319

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Therapeutic Effect of Anti-Macrophage Inflammatory Protein 2 Antibody on Influenza Virus-Induced Pneumonia in Mice. by Sakai S, Kawamata H, Mantani N, Kogure T, Shimada Y, Terasawa K, Sakai T, Imanishi N, Ochiai H.; 2000 Mar 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=111734

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Threonine 157 of Influenza Virus PA Polymerase Subunit Modulates RNA Replication in Infectious Viruses. by Huarte M, Falcon A, Nakaya Y, Ortin J, GarciaSastre A, Nieto A.; 2003 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=154019

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Time to peak serum antibody response to influenza vaccine. by Rastogi S, Gross PA, Bonelli J, Dran S, Levandowski RA, Russo C, Weksler ME, Kaye D, Levison M, Abrutyn E.; 1995 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=170112

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Transfectant Influenza A Viruses with Long Deletions in the NS1 Protein Grow Efficiently in Vero Cells. by Egorov A, Brandt S, Sereinig S, Romanova J, Ferko B, Katinger D, Grassauer A, Alexandrova G, Katinger H, Muster T.; 1998 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=109801

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Tumor Necrosis Factor Alpha Exerts Powerful Anti-Influenza Virus Effects in Lung Epithelial Cells. by Seo SH, Webster RG.; 2002 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=135862

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Type- and subtype-specific detection of influenza viruses in clinical specimens by rapid culture assay. by Ziegler T, Hall H, Sanchez-Fauquier A, Gamble WC, Cox NJ.; 1995 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=227940

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Typing and Subtyping Influenza Virus Using DNA Microarrays and Multiplex Reverse Transcriptase PCR. by Li J, Chen S, Evans DH.; 2001 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=87799

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Typing and subtyping of influenza viruses in clinical samples by PCR. by Wright KE, Wilson GA, Novosad D, Dimock C, Tan D, Weber JM.; 1995 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=228127

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Ultrastructural and Functional Analyses of Recombinant Influenza Virus Ribonucleoproteins Suggest Dimerization of Nucleoprotein during Virus Amplification. by Ortega J, Martin-Benito J, Zurcher T, Valpuesta JM, Carrascosa JL, Ortin J.; 2000 Jan 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=111524

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Use of Recombinant Nucleoproteins in Enzyme-Linked Immunosorbent Assays for Detection of Virus-Specific Immunoglobulin A (IgA) and IgG Antibodies in Influenza Virus A- or B-Infected Patients. by Voeten JT, Groen J, van Alphen D, Claas EC, de Groot R, Osterhaus AD, Rimmelzwaan GF.; 1998 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105234

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Vaccination with a Recombinant Vesicular Stomatitis Virus Expressing an Influenza Virus Hemagglutinin Provides Complete Protection from Influenza Virus Challenge. by Roberts A, Kretzschmar E, Perkins AS, Forman J, Price R, Buonocore L, Kawaoka Y, Rose JK.; 1998 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=109996

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Value of Immunological Markers in Predicting Responsiveness to Influenza Vaccination in Elderly Individuals. by Goronzy JJ, Fulbright JW, Crowson CS, Poland GA, O'Fallon WM, Weyand CM.; 2001 Dec 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=116115

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Variable efficacy of repeated annual influenza vaccination. by Smith DJ, Forrest S, Ackley DH, Perelson AS.; 1999 Nov 23; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=24180

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Virus Clearance through Apoptosis-Dependent Phagocytosis of Influenza A VirusInfected Cells by Macrophages. by Fujimoto I, Pan J, Takizawa T, Nakanishi Y.; 2000 Apr 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=111841

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Virus-neutralizing antibodies of immunoglobulin G (IgG) but not of IgM or IgA isotypes can cure influenza virus pneumonia in SCID mice. by Palladino G, Mozdzanowska K, Washko G, Gerhard W.; 1995 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=188873

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Virus-specific antigen presentation by different subsets of cells from lung and mediastinal lymph node tissues of influenza virus-infected mice. by Hamilton-Easton A, Eichelberger M.; 1995 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=189535

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X-ray structures of H5 avian and H9 swine influenza virus hemagglutinins bound to avian and human receptor analogs. by Ha Y, Stevens DJ, Skehel JJ, Wiley DC.; 2001 Sep 25; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=58807

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Zanamivir Susceptibility Monitoring and Characterization of Influenza Virus Clinical Isolates Obtained during Phase II Clinical Efficacy Studies. by Barnett JM, Cadman A, Gor D, Dempsey M, Walters M, Candlin A, Tisdale M, Morley PJ, Owens IJ, Fenton RJ, Lewis AP, Claas EC, Rimmelzwaan GF, De Groot R, Osterhaus AD.; 2000 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89632

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The National Library of Medicine: PubMed One of the quickest and most comprehensive ways to find academic studies in both English and other languages is to use PubMed, maintained by the National Library of Medicine.6 The advantage of PubMed over previously mentioned sources is that it covers a greater number of domestic and foreign references. It is also free to use. If the publisher has a Web site that offers full text of its journals, PubMed will provide links to that site, as well as to sites offering other related data. User registration, a subscription fee, or some other type of fee may be required to access the full text of articles in some journals. To generate your own bibliography of studies dealing with influenza, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “influenza” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for influenza (hyperlinks lead to article summaries): •

A functional link between the actin cytoskeleton and lipid rafts during budding of filamentous influenza virions. Author(s): Simpson-Holley M, Ellis D, Fisher D, Elton D, McCauley J, Digard P. Source: Virology. 2002 September 30; 301(2): 212-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12359424&dopt=Abstract

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A national survey of physician practices regarding influenza vaccine. Author(s): Davis MM, McMahon SR, Santoli JM, Schwartz B, Clark SJ. Source: Journal of General Internal Medicine : Official Journal of the Society for Research and Education in Primary Care Internal Medicine. 2002 September; 17(9): 670-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12220362&dopt=Abstract

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A point mutation in influenza B neuraminidase confers resistance to peramivir and loss of slow binding. Author(s): Baum EZ, Wagaman PC, Ly L, Turchi I, Le J, Bucher D, Bush K. Source: Antiviral Research. 2003 June; 59(1): 13-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12834856&dopt=Abstract

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A randomized controlled trial comparing split and subunit influenza vaccines in adults in Colombia. Author(s): Morales A, Arias Salazar J, Salazar Y, Garcia A, Arnoux S, Arancibia A, Deroche C, Rey E. Source: Medicina (B Aires). 2003; 63(3): 197-204. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12876902&dopt=Abstract

6 PubMed was developed by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM) at the National Institutes of Health (NIH). The PubMed database was developed in conjunction with publishers of biomedical literature as a search tool for accessing literature citations and linking to full-text journal articles at Web sites of participating publishers. Publishers that participate in PubMed supply NLM with their citations electronically prior to or at the time of publication.

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A rare appearance of influenza A(H1N2) as a reassortant in a community such as Yamagata where A(H1N1) and A(H3N2) co-circulate. Author(s): Mizuta K, Katsushima N, Ito S, Sanjoh K, Murata T, Abiko C, Murayama S. Source: Microbiology and Immunology. 2003; 47(5): 359-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12825897&dopt=Abstract

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A seasonal model to simulate influenza oscillation in Tokyo. Author(s): Urashima M, Shindo N, Okabe N. Source: Japanese Journal of Infectious Diseases. 2003 April; 56(2): 43-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12824683&dopt=Abstract

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ACIP releases 2002 guidelines on the prevention and control of influenza. Advisory Committee on Immunization Practices. Author(s): Ressel GW. Source: American Family Physician. 2002 September 1; 66(5): 894, 896, 899-900 Passim. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12322779&dopt=Abstract

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ACIP releases 2003 guidelines on the prevention and control of influenza. Author(s): Ressel GW; Advisory Committee on Immunization Practices. Source: American Family Physician. 2003 October 1; 68(7): 1426, 1429-30, 1433. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14567494&dopt=Abstract

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Activation of tumor antigen-specific cytotoxic T lymphocytes (CTLs) by human dendritic cells infected with an attenuated influenza A virus expressing a CTL epitope derived from the HER-2/neu proto-oncogene. Author(s): Efferson CL, Schickli J, Ko BK, Kawano K, Mouzi S, Palese P, Garcia-Sastre A, Ioannides CG. Source: Journal of Virology. 2003 July; 77(13): 7411-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12805440&dopt=Abstract

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An advisory committee statement (ACS). National Advisory Committee on Immunization (NACI). Statement on influenza vaccination for the 2003-2004 season. Author(s): National Advisory Committee on Immunization. Source: Can Commun Dis Rep. 2003 August 15; 29: 1-20. English, French. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12961958&dopt=Abstract

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An amantadine hydrochloride dosing program adjusted for renal function during an influenza outbreak in elderly institutionalized patients. Author(s): Kolbe F, Sitar DS, Papaioannou A, Campbell G. Source: Can J Clin Pharmacol. 2003 Fall; 10(3): 119-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14506511&dopt=Abstract

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Annual report of the National Influenza Surveillance Scheme, 2001. Author(s): Roche P, Spencer J, Hampson A. Source: Commun Dis Intell. 2002; 26(2): 204-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12206371&dopt=Abstract

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Annual report of the National Influenza Surveillance Scheme, 2002. Author(s): Yohannes K, Roche P, Spencer J, Hampson A. Source: Commun Dis Intell. 2003; 27(2): 162-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12926731&dopt=Abstract

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Antiviral function of pyrrolidine dithiocarbamate against influenza virus: the inhibition of viral gene replication and transcription. Author(s): Uchide N, Ohyama K. Source: The Journal of Antimicrobial Chemotherapy. 2003 July; 52(1): 8-10. Epub 2003 May 29. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12775674&dopt=Abstract

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ASK1 regulates influenza virus infection-induced apoptotic cell death. Author(s): Maruoka S, Hashimoto S, Gon Y, Nishitoh H, Takeshita I, Asai Y, Mizumura K, Shimizu K, Ichijo H, Horie T. Source: Biochemical and Biophysical Research Communications. 2003 August 8; 307(4): 870-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12878192&dopt=Abstract

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Asthma and influenza vaccination. Author(s): Eisner MD. Source: Chest. 2003 September; 124(3): 775-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12969993&dopt=Abstract

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Asthma and influenza vaccination: findings from the 1999-2001 National Health Interview Surveys. Author(s): Ford ES, Mannino DM, Williams SG. Source: Chest. 2003 September; 124(3): 783-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12969998&dopt=Abstract

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Attitudes of pediatricians regarding influenza self-immunization: a survey in a Swiss university children's hospital. Author(s): Heininger U, Bachler M, Schaad UB. Source: The Pediatric Infectious Disease Journal. 2003 May; 22(5): 391-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12792377&dopt=Abstract

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Avian influenza. Author(s): Goldrick BA, Halloran EJ. Source: The American Journal of Nursing. 2003 July; 103(7): 22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12877125&dopt=Abstract

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Avian influenza. Author(s): Johnston M. Source: J R Soc Health. 2003 June; 123(2): 80. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12852190&dopt=Abstract

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Bacterial pneumonia. Managing a deadly complication of influenza in older adults with comorbid disease. Author(s): Sethi S. Source: Geriatrics. 2002 March; 57(3): 56-61. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11899549&dopt=Abstract

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Baculovirus induces an innate immune response and confers protection from lethal influenza virus infection in mice. Author(s): Abe T, Takahashi H, Hamazaki H, Miyano-Kurosaki N, Matsuura Y, Takaku H. Source: Journal of Immunology (Baltimore, Md. : 1950). 2003 August 1; 171(3): 1133-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12874198&dopt=Abstract

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Basic residues of the helix six domain of influenza virus M1 involved in nuclear translocation of M1 can be replaced by PTAP and YPDL late assembly domain motifs. Author(s): Hui EK, Barman S, Yang TY, Nayak DP. Source: Journal of Virology. 2003 June; 77(12): 7078-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12768027&dopt=Abstract

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Bedside diagnosis of influenzavirus infections in hospitalized children. Author(s): Poehling KA, Griffin MR, Dittus RS, Tang YW, Holland K, Li H, Edwards KM. Source: Pediatrics. 2002 July; 110(1 Pt 1): 83-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12093950&dopt=Abstract

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Boosting immunity to influenza H5N1 with MF59-adjuvanted H5N3 A/Duck/Singapore/97 vaccine in a primed human population. Author(s): Stephenson I, Nicholson KG, Colegate A, Podda A, Wood J, Ypma E, Zambon M. Source: Vaccine. 2003 April 2; 21(15): 1687-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12639491&dopt=Abstract

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Boosting influenza immunisation for the over-65s. Author(s): Kassianos G. Source: The British Journal of General Practice : the Journal of the Royal College of General Practitioners. 2002 September; 52(482): 710-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12236272&dopt=Abstract

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Boosting uptake of influenza immunisation: a randomised controlled trial of telephone appointing in general practice. Author(s): Hull S, Hagdrup N, Hart B, Griffiths C, Hennessy E. Source: The British Journal of General Practice : the Journal of the Royal College of General Practitioners. 2002 September; 52(482): 712-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12236273&dopt=Abstract

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Burden of interpandemic influenza in children younger than 5 years: a 25-year prospective study. Author(s): Neuzil KM, Zhu Y, Griffin MR, Edwards KM, Thompson JM, Tollefson SJ, Wright PF. Source: The Journal of Infectious Diseases. 2002 January 15; 185(2): 147-52. Epub 2001 December 17. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11807687&dopt=Abstract

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Case definition for influenza surveillance. Author(s): Hannoun C. Source: European Journal of Epidemiology. 2003; 18(8): 737-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12974545&dopt=Abstract

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Caspase 3 activation is essential for efficient influenza virus propagation. Author(s): Wurzer WJ, Planz O, Ehrhardt C, Giner M, Silberzahn T, Pleschka S, Ludwig S. Source: The Embo Journal. 2003 June 2; 22(11): 2717-28. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12773387&dopt=Abstract

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Characterization of 2 influenza A(H3N2) clinical isolates with reduced susceptibility to neuraminidase inhibitors due to mutations in the hemagglutinin gene. Author(s): Abed Y, Bourgault AM, Fenton RJ, Morley PJ, Gower D, Owens IJ, Tisdale M, Boivin G. Source: The Journal of Infectious Diseases. 2002 October 15; 186(8): 1074-80. Epub 2002 September 30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12355356&dopt=Abstract

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Characterization of H9 subtype influenza viruses from the ducks of southern China: a candidate for the next influenza pandemic in humans? Author(s): Li KS, Xu KM, Peiris JS, Poon LL, Yu KZ, Yuen KY, Shortridge KF, Webster RG, Guan Y. Source: Journal of Virology. 2003 June; 77(12): 6988-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12768017&dopt=Abstract

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Chemokine receptor expression and chemotactic responsiveness of human monocytes after influenza A virus infection. Author(s): Salentin R, Gemsa D, Sprenger H, Kaufmann A. Source: Journal of Leukocyte Biology. 2003 August; 74(2): 252-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12885942&dopt=Abstract

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Chimeric influenza A viruses with a functional influenza B virus neuraminidase or hemagglutinin. Author(s): Flandorfer A, Garcia-Sastre A, Basler CF, Palese P. Source: Journal of Virology. 2003 September; 77(17): 9116-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12915528&dopt=Abstract

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Clinical characteristics of children with influenza A virus infection requiring hospitalization. Author(s): Wang YH, Huang YC, Chang LY, Kao HT, Lin PY, Huang CG, Lin TY. Source: J Microbiol Immunol Infect. 2003 June; 36(2): 111-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12886962&dopt=Abstract

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Clinical features of influenza a virus infection in older hospitalized persons. Author(s): Drinka PJ, Krause P, Nest L. Source: Journal of the American Geriatrics Society. 2003 August; 51(8): 1184. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12890092&dopt=Abstract

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Clinical manifestations and diagnosis of influenza. Author(s): Shorman M, Moorman JP. Source: Southern Medical Journal. 2003 August; 96(8): 737-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14515910&dopt=Abstract

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Cluster randomised controlled trial of an educational outreach visit to improve influenza and pneumococcal immunisation rates in primary care. Author(s): Siriwardena AN, Rashid A, Johnson MR, Dewey ME. Source: The British Journal of General Practice : the Journal of the Royal College of General Practitioners. 2002 September; 52(482): 735-40. Erratum In: Br J Gen Pract 2002 October; 52(483): 855. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12236277&dopt=Abstract

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Codon bias and frequency-dependent selection on the hemagglutinin epitopes of influenza A virus. Author(s): Plotkin JB, Dushoff J. Source: Proceedings of the National Academy of Sciences of the United States of America. 2003 June 10; 100(12): 7152-7. Epub 2003 May 14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12748378&dopt=Abstract

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Comparison of SmartCycler real-time reverse transcription-PCR assay in a public health laboratory with direct immunofluorescence and cell culture assays in a medical center for detection of influenza A virus. Author(s): Habib-Bein NF, Beckwith WH 3rd, Mayo D, Landry ML. Source: Journal of Clinical Microbiology. 2003 August; 41(8): 3597-601. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12904361&dopt=Abstract

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Comparison of symptoms of influenza A with abacavir-associated hypersensitivity reaction. Author(s): Keiser P, Nassar N, Skiest D, Andrews C, Yazdani B, White A, Hetherington S. Source: International Journal of Std & Aids. 2003 July; 14(7): 478-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12869229&dopt=Abstract

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Comparison of the Denka-Seiken INFLU A.B-Quick and BD Directigen Flu A+B kits with direct fluorescent-antibody staining and shell vial culture methods for rapid detection of influenza viruses. Author(s): Dunn JJ, Gordon C, Kelley C, Carroll KC. Source: Journal of Clinical Microbiology. 2003 May; 41(5): 2180-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12734274&dopt=Abstract

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Comparison of the Directigen flu A+B test, the QuickVue influenza test, and clinical case definition to viral culture and reverse transcription-PCR for rapid diagnosis of influenza virus infection. Author(s): Ruest A, Michaud S, Deslandes S, Frost EH. Source: Journal of Clinical Microbiology. 2003 August; 41(8): 3487-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12904343&dopt=Abstract

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Complications of influenza. Author(s): Khater F, Moorman JP. Source: Southern Medical Journal. 2003 August; 96(8): 740-3. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14515911&dopt=Abstract

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Compromised constitutions: the Iranian experience with the 1918 influenza pandemic. Author(s): Afkhami A. Source: Bulletin of the History of Medicine. 2003 Summer; 77(2): 367-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12955964&dopt=Abstract

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Contacts between influenza virus N9 neuraminidase and monoclonal antibody NC10. Author(s): Lee JT, Air GM. Source: Virology. 2002 September 1; 300(2): 255-68. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12350356&dopt=Abstract

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Cost-effectiveness of newer treatment strategies for influenza. Author(s): Smith KJ, Roberts MS. Source: The American Journal of Medicine. 2002 September; 113(4): 300-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12361816&dopt=Abstract

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Current strategies for management of influenza in the elderly population. Author(s): Gravenstein S, Davidson HE. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2002 September 15; 35(6): 729-37. Epub 2002 August 20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12203171&dopt=Abstract

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Delayed onset encephalopathy associated with influenza A virus infection. Author(s): Nikaido K, Agatsuma Y, Inoue M, Ohara T, Nihira H, Wakai S, Tsutsumi H. Source: The Pediatric Infectious Disease Journal. 2003 September; 22(9): 849-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14515845&dopt=Abstract

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Delays in the application of outbreak control prophylaxis for influenza A in a nursing home. Author(s): Drinka PJ, Krause P, Nest L, Gravenstein S, Goodman B, Shult P. Source: Infection Control and Hospital Epidemiology : the Official Journal of the Society of Hospital Epidemiologists of America. 2002 October; 23(10): 600-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12400890&dopt=Abstract

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Design of the Dutch prevention of influenza, surveillance and management (PRISMA) study. Author(s): Hak E, van Loon S, Buskens E, van Essen GA, de Bakker D, Tacken MA, van Hout BA, Grobbee DE, Verheij TJ. Source: Vaccine. 2003 April 2; 21(15): 1719-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12639495&dopt=Abstract

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Detection of human influenza virus in Yucatan, Mexico. Author(s): Ayora-Talavera G, Gongora-Biachi RA, Lopez-Martinez I, Moguel-Rodriguez W, Perez-Carrillo H, Vazquez-Zapata V, Bastarrachea-Vazquez D, Canto-Cab A. Source: Revista De Investigacion Clinica; Organo Del Hospital De Enfermedades De La Nutricion. 2002 September-October; 54(5): 410-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12587415&dopt=Abstract

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Detection of influenza virus from throat and pharyngeal swabs with a nested duplex light cycler RT-PCR. Author(s): Koenig M, Kosha S, Hickman M, Heath D, Riddell S, Aldous W. Source: Diagnostic Microbiology and Infectious Disease. 2003 May; 46(1): 35-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12742317&dopt=Abstract

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Detection of type and subtypes of influenza virus by hybrid formation of FRET probe with amplified target DNA and melting temperature analysis. Author(s): Poddar SK. Source: Journal of Virological Methods. 2003 March; 108(2): 157-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12609682&dopt=Abstract

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Determinants of adult influenza and pneumonia immunization rates. Author(s): Kamal KM, Madhavan SS, Amonkar MM. Source: J Am Pharm Assoc (Wash Dc). 2003 May-June; 43(3): 403-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12836791&dopt=Abstract

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Development of a novel influenza A antiviral assay. Author(s): Wagaman PC, Leong MA, Simmen KA. Source: Journal of Virological Methods. 2002 August; 105(1): 105-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12176147&dopt=Abstract

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Development of a protocol to evaluate the quality of clinical influenza data collected by sentinel practitioners in Europe. Author(s): Aguilera JF, Paget WJ, van der Velden J. Source: Euro Surveillance : Bulletin Europeen Sur Les Maladies Transmissibles = European Communicable Disease Bulletin. 2002 November; 7(11): 158-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12631988&dopt=Abstract

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Differences between influenza virus receptors on target cells of duck and chicken. Author(s): Gambaryan A, Webster R, Matrosovich M. Source: Archives of Virology. 2002 June; 147(6): 1197-208. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12111429&dopt=Abstract

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Differential effect of nucleotide substitutions in the 3' arm of the influenza A virus vRNA promoter on transcription/replication by avian and human polymerase complexes is related to the nature of PB2 amino acid 627. Author(s): Crescenzo-Chaigne B, van der Werf S, Naffakh N. Source: Virology. 2002 November 25; 303(2): 240-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12490387&dopt=Abstract

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Disruption of services in an internal medicine unit due to a nosocomial influenza outbreak. Author(s): Sartor C, Zandotti C, Romain F, Jacomo V, Simon S, Atlan-Gepner C, Sambuc R, Vialettes B, Drancourt M. Source: Infection Control and Hospital Epidemiology : the Official Journal of the Society of Hospital Epidemiologists of America. 2002 October; 23(10): 615-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12400893&dopt=Abstract

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Distinct host range of influenza H3N2 virus isolates in Vero and MDCK cells is determined by cell specific glycosylation pattern. Author(s): Romanova J, Katinger D, Ferko B, Voglauer R, Mochalova L, Bovin N, Lim W, Katinger H, Egorov A. Source: Virology. 2003 March 1; 307(1): 90-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12667817&dopt=Abstract

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Divergent evolution of hemagglutinin and neuraminidase genes in recent influenza A:H3N2 viruses isolated in Canada. Author(s): Abed Y, Hardy I, Li Y, Boivin G. Source: Journal of Medical Virology. 2002 August; 67(4): 589-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12116009&dopt=Abstract

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Does antigen-specific cytokine response correlate with the experience of oculorespiratory syndrome after influenza vaccine? Author(s): Skowronski DM, Lu H, Warrington R, Hegele RG, De Serres G, HayGlass K, Stark D, White R, Macnabb J, Li Y, Manson HE, Brunham RC. Source: The Journal of Infectious Diseases. 2003 February 1; 187(3): 495-9. Epub 2003 January 24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12552434&dopt=Abstract

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Does influenza vaccination increase consultations, corticosteroid prescriptions, or exacerbations in subjects with asthma or chronic obstructive pulmonary disease? Author(s): Tata LJ, West J, Harrison T, Farrington P, Smith C, Hubbard R. Source: Thorax. 2003 October; 58(10): 835-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14514932&dopt=Abstract

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Drug resistance and influenza pandemics. Author(s): Tooley P. Source: Lancet. 2002 November 23; 360(9346): 1703-4; Author Reply 1704. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12457835&dopt=Abstract

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Drug under test: influenza--Relenza in daily practice. Experience during the influenza season 1999/2000. Author(s): Schmidt RE. Source: Medical Microbiology and Immunology. 2002 December; 191(3-4): 175-9. Epub 2002 October 22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12458355&dopt=Abstract

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Dual infection with influenza A and B viruses. Author(s): Fonseca K, Tarrant M, Lam S, Li Y. Source: The Pediatric Infectious Disease Journal. 2002 August; 21(8): 795-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12233716&dopt=Abstract

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Dutch veterinarian becomes first victim of avian influenza. Author(s): van Kolfschooten F. Source: Lancet. 2003 April 26; 361(9367): 1444. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12727409&dopt=Abstract

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Economic evaluation of influenza vaccination in Thai chronic obstructive pulmonary disease patients. Author(s): Wongsurakiat P, Lertakyamanee J, Maranetra KN, Jongriratanakul S, Sangkaew S. Source: J Med Assoc Thai. 2003 June; 86(6): 497-508. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12924797&dopt=Abstract

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Effect of a rapid influenza diagnosis. Author(s): Esposito S, Marchisio P, Morelli P, Crovari P, Principi N. Source: Archives of Disease in Childhood. 2003 June; 88(6): 525-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12765923&dopt=Abstract

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Effectiveness of inactivated influenza vaccine in preventing acute otitis media in young children: a randomized controlled trial. Author(s): Hoberman A, Greenberg DP, Paradise JL, Rockette HE, Lave JR, Kearney DH, Colborn DK, Kurs-Lasky M, Haralam MA, Byers CJ, Zoffel LM, Fabian IA, Bernard BS, Kerr JD. Source: Jama : the Journal of the American Medical Association. 2003 September 24; 290(12): 1608-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14506120&dopt=Abstract

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Effectiveness of neuraminidase inhibitors in treatment and prevention of influenza A and B: systematic review and meta-analyses of randomised controlled trials. Author(s): Cooper NJ, Sutton AJ, Abrams KR, Wailoo A, Turner D, Nicholson KG. Source: Bmj (Clinical Research Ed.). 2003 June 7; 326(7401): 1235. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12791735&dopt=Abstract

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Effects of previous influenza vaccination on subsequent readmission and mortality in elderly patients hospitalized with pneumonia. Author(s): Herzog NS, Bratzler DW, Houck PM, Jiang H, Nsa W, Shook C, Weingarten SR. Source: The American Journal of Medicine. 2003 October 15; 115(6): 454-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14563502&dopt=Abstract

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Emergence of influenza A H1N2 reassortant viruses in the human population during 2001. Author(s): Gregory V, Bennett M, Orkhan MH, Al Hajjar S, Varsano N, Mendelson E, Zambon M, Ellis J, Hay A, Lin YP. Source: Virology. 2002 August 15; 300(1): 1-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12202200&dopt=Abstract

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Encephalitis or encephalopathy during an influenza-A epidemic. Author(s): Soldo I, Duvnjak M, Lisnjic D, Timarac J, Peric L, Palic R, Vranjes Z, SoldoButkovic S. Source: Coll Antropol. 2003; 27 Suppl 1: 19-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12955887&dopt=Abstract

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Enhanced recognition of human NK receptors after influenza virus infection. Author(s): Achdout H, Arnon TI, Markel G, Gonen-Gross T, Katz G, Lieberman N, Gazit R, Joseph A, Kedar E, Mandelboim O. Source: Journal of Immunology (Baltimore, Md. : 1950). 2003 July 15; 171(2): 915-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12847262&dopt=Abstract

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Enhancement of mucosal immune responses by chimeric influenza HA/SHIV viruslike particles. Author(s): Guo L, Lu X, Kang SM, Chen C, Compans RW, Yao Q. Source: Virology. 2003 September 1; 313(2): 502-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12954217&dopt=Abstract

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Epidemiology and control of influenza. Author(s): Rao BL. Source: Natl Med J India. 2003 May-June; 16(3): 143-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12929857&dopt=Abstract

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Epidemiology and molecular characterization of co-circulating influenza A/H3N2 virus variants in children: Houston, Texas, 1997-8. Author(s): O'Donnell FT, Munoz FM, Atmar RL, Hwang LY, Demmler GJ, Glezen WP. Source: Epidemiology and Infection. 2003 June; 130(3): 521-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12825738&dopt=Abstract

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Estimating deaths due to influenza and respiratory syncytial virus. Author(s): Glezen WP, Couch RB. Source: Jama : the Journal of the American Medical Association. 2003 May 21; 289(19): 2500; Author Reply 2500-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12759318&dopt=Abstract

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Estimating deaths due to influenza and respiratory syncytial virus. Author(s): Simonsen L, Blackwelder WC, Reichert TA, Miller MA. Source: Jama : the Journal of the American Medical Association. 2003 May 21; 289(19): 2499-500; Author Reply 2500-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12759317&dopt=Abstract

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Estimating deaths due to influenza and respiratory syncytial virus. Author(s): Gay NJ, Andrews NJ, Trotter CL, Edmunds WJ. Source: Jama : the Journal of the American Medical Association. 2003 May 21; 289(19): 2499; Author Reply 2500-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12759316&dopt=Abstract

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Estimating efficacy of trivalent, cold-adapted, influenza virus vaccine (CAIV-T) against influenza A (H1N1) and B using surveillance cultures. Author(s): Halloran ME, Longini IM Jr, Gaglani MJ, Piedra PA, Chu H, Herschler GB, Glezen WP. Source: American Journal of Epidemiology. 2003 August 15; 158(4): 305-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12915495&dopt=Abstract

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Evaluation of a new dot blot enzyme immunoassay (directigen flu A+B) for simultaneous and differential detection of influenza a and B virus antigens from respiratory samples. Author(s): Reina J, Padilla E, Alonso F, Ruiz De Gopegui E, Munar M, Mari M. Source: Journal of Clinical Microbiology. 2002 September; 40(9): 3515-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12202608&dopt=Abstract

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Evaluation of a rapid test (QuickVue) compared with the shell vial assay for detection of influenza virus clearance after antiviral treatment. Author(s): Bellei N, Benfica D, Perosa AH, Carlucci R, Barros M, Granato C. Source: Journal of Virological Methods. 2003 April; 109(1): 85-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12668272&dopt=Abstract

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Evaluation of influenza virus detection by direct enzyme immunoassay (EIA) and conventional methods in asthmatic patients. Author(s): Khanna M, Kumar P, Chugh L, Prasad AK, Chhabra SK. Source: J Commun Dis. 2001 September; 33(3): 163-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12206034&dopt=Abstract

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Exploitation of nucleic acid packaging signals to generate a novel influenza virusbased vector stably expressing two foreign genes. Author(s): Watanabe T, Watanabe S, Noda T, Fujii Y, Kawaoka Y. Source: Journal of Virology. 2003 October; 77(19): 10575-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12970442&dopt=Abstract

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Expression of cytokine and chemokine genes by human middle ear epithelial cells induced by influenza A virus and Streptococcus pneumoniae opacity variants. Author(s): Tong HH, Long JP, Shannon PA, DeMaria TF. Source: Infection and Immunity. 2003 August; 71(8): 4289-96. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12874304&dopt=Abstract

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Factors influencing childhood influenza immunization. Author(s): Grant VJ, Le Saux N, Plint AC, Correll R, Gaboury I, Ellis E, Tam TW. Source: Cmaj : Canadian Medical Association Journal = Journal De L'association Medicale Canadienne. 2003 January 7; 168(1): 39-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12515783&dopt=Abstract

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Factors influencing decisions regarding influenza vaccination and treatment: a survey of healthcare workers. Author(s): Steiner M, Vermeulen LC, Mullahy J, Hayney MS. Source: Infection Control and Hospital Epidemiology : the Official Journal of the Society of Hospital Epidemiologists of America. 2002 October; 23(10): 625-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12400896&dopt=Abstract

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Factors influencing uptake of influenza vaccination in patients with rheumatoid arthritis. Author(s): Bridges MJ, Coady D, Kelly CA, Hamilton J, Heycock C. Source: Annals of the Rheumatic Diseases. 2003 July; 62(7): 685. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12810440&dopt=Abstract

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Farmers kill 23 million birds to stop influenza virus. Author(s): Crabb C. Source: Bulletin of the World Health Organization. 2003; 81(6): 471. Epub 2003 July 25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12894341&dopt=Abstract

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Fatal influenza A virus infection in a child vaccinated against influenza. Author(s): Thomas P, Riffelmann M, Schweiger B, Dominik S, von Konig CH. Source: The Pediatric Infectious Disease Journal. 2003 February; 22(2): 201-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12613460&dopt=Abstract

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Fatty acids on the A/USSR/77 influenza virus hemagglutinin facilitate the transition from hemifusion to fusion pore formation. Author(s): Sakai T, Ohuchi R, Ohuchi M. Source: Journal of Virology. 2002 May; 76(9): 4603-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11932425&dopt=Abstract

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Fragmentation of influenza surveillance in Australia. Author(s): Watts C, Kelly H. Source: Commun Dis Intell. 2002; 26(1): 8-13. Erratum In: Commun Dis Intell 2002; 26(2): 288. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11950209&dopt=Abstract

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Frequency of amantadine-resistant influenza A viruses during two seasons featuring cocirculation of H1N1 and H3N2. Author(s): Saito R, Sakai T, Sato I, Sano Y, Oshitani H, Sato M, Suzuki H. Source: Journal of Clinical Microbiology. 2003 May; 41(5): 2164-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12734269&dopt=Abstract

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Functional balance between haemagglutinin and neuraminidase in influenza virus infections. Author(s): Wagner R, Matrosovich M, Klenk HD. Source: Reviews in Medical Virology. 2002 May-June; 12(3): 159-66. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11987141&dopt=Abstract

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Fusion and infection of influenza and Sendai viruses as modulated by dextran sulfate: a comparative study. Author(s): Ramalho-Santos J, de Lima MC. Source: Bioscience Reports. 2001 June; 21(3): 293-304. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11892996&dopt=Abstract

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Generalized bullous fixed drug eruption after influenza vaccination, simulating bullous pemphigoid. Author(s): Garcia-Doval I, Roson E, Feal C, De la Torre C, Rodriguez T, Cruces MJ. Source: Acta Dermato-Venereologica. 2001 November-December; 81(6): 450-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11859962&dopt=Abstract

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Generation of Ag-specific cytotoxic T lymphocytes by DC transfected with in vitro transcribed influenza virus matrix protein (M1) mRNA. Author(s): Osman Y, Narita M, Ayres F, Takahashi M, Alldawi L, Tatsuo F, Toba K, Hirohashi T, Aizawa Y. Source: Cytotherapy. 2003; 5(2): 161-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12745578&dopt=Abstract

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Generation of influenza A virus from cloned cDNAs--historical perspective and outlook for the new millenium. Author(s): Neumann G, Kawaoka Y. Source: Reviews in Medical Virology. 2002 January-February; 12(1): 13-30. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11787081&dopt=Abstract

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Generation of influenza A viruses with chimeric (type A/B) hemagglutinins. Author(s): Horimoto T, Takada A, Iwatsuki-Horimoto K, Hatta M, Goto H, Kawaoka Y. Source: Journal of Virology. 2003 July; 77(14): 8031-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12829842&dopt=Abstract

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Genetic and antigenic analysis of the first A/New Caledonia/20/99-like H1N1 influenza isolates reported in the Americas. Author(s): Daum LT, Canas LC, Smith CB, Klimov A, Huff W, Barnes W, Lohman KL. Source: Emerging Infectious Diseases. 2002 April; 8(4): 408-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11971776&dopt=Abstract

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Genetic characterization of a porcine H1N2 influenza virus strain isolated in Germany. Author(s): Schrader C, Suss J. Source: Intervirology. 2003; 46(1): 66-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12566701&dopt=Abstract

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Genotypic analysis of plasma HIV-1 RNA after influenza vaccination of patients with previously undetectable viral loads. Author(s): Kolber MA, Gabr AH, De La Rosa A, Glock JA, Jayaweera D, Miller N, Dickinson GM. Source: Aids (London, England). 2002 March 8; 16(4): 537-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11872996&dopt=Abstract

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Global influenza laboratory on the horizon. Author(s): O'Rourke K. Source: J Am Vet Med Assoc. 2002 April 1; 220(7): 952. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12420765&dopt=Abstract

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H5N1 influenza in Hong Kong: virus characterizations. Author(s): Osterhaus AD, de Jong JC, Rimmelzwaan GF, Claas EC. Source: Vaccine. 2002 May 15; 20 Suppl 2: S82-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12110266&dopt=Abstract

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Haemophilus influenza cellulitis. A review and case report. Author(s): Branca G, Dym H. Source: The New York State Dental Journal. 2003 March; 69(3): 34-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12764985&dopt=Abstract

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Haemophilus influenza infection complicating a total knee arthroplasty. Author(s): Bezwada HP, Nazarian DG, Booth RE Jr. Source: Clinical Orthopaedics and Related Research. 2002 September; (402): 202-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12218485&dopt=Abstract

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Haemophilus influenzae type b vaccine formulation and risk of childhood leukaemia. Author(s): Groves F, Sinha D, Auvinen A. Source: British Journal of Cancer. 2002 August 27; 87(5): 511-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12189546&dopt=Abstract

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Haemophilus influenzae type b vaccine: reconstitution of lyophilised PRP-T vaccine with a pertussis-containing paediatric combination vaccine, or a change in the primary series immunisation schedule, may modify the serum anti-PRP antibody responses. Author(s): Vidor E, Hoffenbach A, Fletcher MA. Source: Current Medical Research and Opinion. 2001; 17(3): 197-209. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11900313&dopt=Abstract

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Harmonisation of national influenza surveillance morbidity data from EISS: a simple index. Author(s): Uphoff H, Cohen JM, Fleming D, Noone A. Source: Euro Surveillance : Bulletin Europeen Sur Les Maladies Transmissibles = European Communicable Disease Bulletin. 2003 July; 8(7): 156-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12941981&dopt=Abstract

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Health behavior associated with influenza vaccination among healthcare workers in long-term-care facilities. Author(s): Manuel DG, Henry B, Hockin J, Naus M. Source: Infection Control and Hospital Epidemiology : the Official Journal of the Society of Hospital Epidemiologists of America. 2002 October; 23(10): 609-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12400892&dopt=Abstract

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Healthcare workers and their attitudes to influenza vaccination. Author(s): Stephenson I, Roper JP, Nicholson KG. Source: Commun Dis Public Health. 2002 September; 5(3): 247-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12434697&dopt=Abstract

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Heat-aggregated noninfectious influenza virus induces a more balanced CD8(+)-Tlymphocyte immunodominance hierarchy than infectious virus. Author(s): Cho Y, Basta S, Chen W, Bennink JR, Yewdell JW. Source: Journal of Virology. 2003 April; 77(8): 4679-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12663774&dopt=Abstract

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Heterogeneous case definitions used for the surveillance of influenza in Europe. Author(s): Aguilera JF, Paget WJ, Mosnier A, Heijnen ML, Uphoff H, van der Velden J, Vega T, Watson JM. Source: European Journal of Epidemiology. 2003; 18(8): 751-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12974549&dopt=Abstract

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Hierarchical statistical modelling of influenza epidemic dynamics in space and time. Author(s): Mugglin AS, Cressie N, Gemmell I. Source: Statistics in Medicine. 2002 September 30; 21(18): 2703-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12228886&dopt=Abstract

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High concentration of serum nitrite/nitrate obtained from patients with influenzaassociated encephalopathy. Author(s): Kawashima H, Watanabe Y, Ichiyama T, Mizuguchi M, Yamada N, Kashiwagi Y, Takekuma K, Hoshika A, Mori T. Source: Pediatrics International : Official Journal of the Japan Pediatric Society. 2002 December; 44(6): 705-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12421278&dopt=Abstract

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High frequency of resistant viruses harboring different mutations in amantadinetreated children with influenza. Author(s): Shiraishi K, Mitamura K, Sakai-Tagawa Y, Goto H, Sugaya N, Kawaoka Y. Source: The Journal of Infectious Diseases. 2003 July 1; 188(1): 57-61. Epub 2003 June 23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12825171&dopt=Abstract

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Hospitalizations and deaths due to respiratory illnesses during influenza seasons: a comparison of community residents, senior housing residents, and nursing home residents. Author(s): Menec VH, MacWilliam L, Aoki FY. Source: The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences. 2002 October; 57(10): M629-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12242314&dopt=Abstract

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Human infection by a swine influenza A (H1N1) virus in Switzerland. Author(s): Gregory V, Bennett M, Thomas Y, Kaiser L, Wunderli W, Matter H, Hay A, Lin YP. Source: Archives of Virology. 2003 April; 148(4): 793-802. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12664301&dopt=Abstract

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Human influenza a viral genes responsible for the restriction of its replication in duck intestine. Author(s): Hatta M, Halfmann P, Wells K, Kawaoka Y. Source: Virology. 2002 April 10; 295(2): 250-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12033783&dopt=Abstract

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Human influenza viral infection in utero alters glial fibrillary acidic protein immunoreactivity in the developing brains of neonatal mice. Author(s): Fatemi SH, Emamian ES, Sidwell RW, Kist DA, Stary JM, Earle JA, Thuras P. Source: Molecular Psychiatry. 2002; 7(6): 633-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12140787&dopt=Abstract

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Human influenza viruses activate an interferon-independent transcription of cellular antiviral genes: outcome with influenza A virus is unique. Author(s): Kim MJ, Latham AG, Krug RM. Source: Proceedings of the National Academy of Sciences of the United States of America. 2002 July 23; 99(15): 10096-101. Epub 2002 Jul 11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12114540&dopt=Abstract

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Hyperbaric oxygen therapy (HBOT) in a child with suspected influenza-associated encephalopathy. Author(s): Dohgomori H, Arikawa K, Kanmura Y. Source: Canadian Journal of Anaesthesia = Journal Canadien D'anesthesie. 2003 February; 50(2): 204. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12560321&dopt=Abstract

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Identification of Hsp90 as a stimulatory host factor involved in influenza virus RNA synthesis. Author(s): Momose F, Naito T, Yano K, Sugimoto S, Morikawa Y, Nagata K. Source: The Journal of Biological Chemistry. 2002 November 22; 277(47): 45306-14. Epub 2002 September 10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12226087&dopt=Abstract

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Illness among schoolchildren during influenza season: effect on school absenteeism, parental absenteeism from work, and secondary illness in families. Author(s): Neuzil KM, Hohlbein C, Zhu Y. Source: Archives of Pediatrics & Adolescent Medicine. 2002 October; 156(10): 986-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12361443&dopt=Abstract

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Impact of influenza vaccination on civilian aircrew illness and absenteeism. Author(s): Mixeu MA, Vespa GN, Forleo-Neto E, Toniolo-Neto J, Alves PM. Source: Aviation, Space, and Environmental Medicine. 2002 September; 73(9): 876-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12234038&dopt=Abstract

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Improving uptake of influenza vaccination among older people: a randomised controlled trial. Author(s): Arthur AJ, Matthews RJ, Jagger C, Clarke M, Hipkin A, Bennison DP. Source: The British Journal of General Practice : the Journal of the Royal College of General Practitioners. 2002 September; 52(482): 717-8, 720-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12236274&dopt=Abstract

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Influenza therapy. Author(s): Myers JW. Source: Southern Medical Journal. 2003 August; 96(8): 744-50. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14515912&dopt=Abstract

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Influenza vaccination and chemotherapy: a shot in the dark? Author(s): Ring A, Marx G, Steer C, Harper P. Source: Supportive Care in Cancer : Official Journal of the Multinational Association of Supportive Care in Cancer. 2002 September; 10(6): 462-5. Epub 2002 January 31. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12353124&dopt=Abstract

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Influenza vaccination induced leukocytoclastic vasculitis and pauci-immune crescentic glomerulonephritis. Author(s): Yanai-Berar N, Ben-Itzhak O, Gree J, Nakhoul F. Source: Clinical Nephrology. 2002 September; 58(3): 220-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12356192&dopt=Abstract

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Influenza vaccination is not associated with a reduction in the risk of recurrent coronary events. Author(s): Jackson LA, Yu O, Heckbert SR, Psaty BM, Malais D, Barlow WE, Thompson WW; Vaccine Safety Datalink Study Group. Source: American Journal of Epidemiology. 2002 October 1; 156(7): 634-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12244032&dopt=Abstract

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Influenza vaccine coverage and reasons for non-vaccination in a sample of people above 65 years of age, in Sweden, 1998-2000. Author(s): Dannetun E, Tegnell A, Normann B, Garpenholt O, Giesecke J. Source: Scandinavian Journal of Infectious Diseases. 2003; 35(6-7): 389-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12953950&dopt=Abstract

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Influenza vaccine enlisted to prevent SARS confusion. Author(s): Schlagenhauf P. Source: Lancet. 2003 September 6; 362(9386): 809. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13678898&dopt=Abstract

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Influenza vaccines in children. Author(s): Neuzil KM, Edwards KM. Source: Seminars in Pediatric Infectious Diseases. 2002 July; 13(3): 174-81. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12199613&dopt=Abstract

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Influenza vaccines: why are we missing high-risk patients? Author(s): Perl TM. Source: Journal of General Internal Medicine : Official Journal of the Society for Research and Education in Primary Care Internal Medicine. 2002 September; 17(9): 736-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12220372&dopt=Abstract

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Influenza virus can enter and infect cells in the absence of clathrin-mediated endocytosis. Author(s): Sieczkarski SB, Whittaker GR. Source: Journal of Virology. 2002 October; 76(20): 10455-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12239322&dopt=Abstract

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Influenza virus vaccination of patients with SLE: effects on generation of autoantibodies. Author(s): Abu-Shakra M, Press J, Sukenik S, Buskila D. Source: Clinical Rheumatology. 2002 September; 21(5): 369-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12223983&dopt=Abstract

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Influenza viruses: structure and interspecies transmission mechanisms. Author(s): Donatelli I, Campitelli L, Puzelli S, Affinito C, De Marco MA, Delogu M, Barigazzi G. Source: Veterinary Research Communications. 2003 September; 27 Suppl 1: 115-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14535378&dopt=Abstract

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Influenza. Author(s): Uyeki T, Winquist A. Source: Clin Evid. 2002 June; (7): 645-51. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12230692&dopt=Abstract

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Influenza. Introduction. Author(s): Sarubbi FA. Source: Southern Medical Journal. 2003 August; 96(8): 734. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14515908&dopt=Abstract

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Influenza: a historical perspective. Author(s): Sarubbi FA. Source: Southern Medical Journal. 2003 August; 96(8): 735-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14515909&dopt=Abstract

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Influenza: a preventable lethal disease. Author(s): McElhaney JE. Source: The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences. 2002 October; 57(10): M627-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12242313&dopt=Abstract

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Influenza--WHO cares. Author(s): Stohr K. Source: The Lancet Infectious Diseases. 2002 September; 2(9): 517. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12206966&dopt=Abstract

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Kinetics of influenza hemagglutinin-mediated membrane fusion as a function of technique. Author(s): Mittal A, Leikina E, Bentz J, Chernomordik LV. Source: Analytical Biochemistry. 2002 April 15; 303(2): 145-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11950214&dopt=Abstract

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Knowledge and beliefs about influenza, pneumococcal disease, and immunizations among older people. Author(s): Santibanez TA, Nowalk MP, Zimmerman RK, Jewell IK, Bardella IJ, Wilson SA, Terry MA. Source: Journal of the American Geriatrics Society. 2002 October; 50(10): 1711-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12366627&dopt=Abstract

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Laboratory diagnosis of influenza virus infection. Author(s): Playford EG, Dwyer DE. Source: Pathology. 2002 April; 34(2): 115-25. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12009091&dopt=Abstract

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Laboratory diagnosis of influenza: recent advances. Author(s): Demmler GJ. Source: Seminars in Pediatric Infectious Diseases. 2002 April; 13(2): 85-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12122957&dopt=Abstract

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Laboratory diagnosis of influenza--virology or serology? Author(s): Allwinn R, Preiser W, Rabenau H, Buxbaum S, Sturmer M, Doerr HW. Source: Medical Microbiology and Immunology. 2002 December; 191(3-4): 157-60. Epub 2002 August 30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12458351&dopt=Abstract

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Lack of detection of influenza genes in archived formalin-fixed, paraffin waxembedded brain samples of encephalitis lethargica patients from 1916 to 1920. Author(s): Lo KC, Geddes JF, Daniels RS, Oxford JS. Source: Virchows Archiv : an International Journal of Pathology. 2003 June; 442(6): 5916. Epub 2003 April 15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12695912&dopt=Abstract

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Lack of evidence for human-to-human transmission of avian influenza A (H9N2) viruses in Hong Kong, China 1999. Author(s): Uyeki TM, Chong YH, Katz JM, Lim W, Ho YY, Wang SS, Tsang TH, Au WW, Chan SC, Rowe T, Hu-Primmer J, Bell JC, Thompson WW, Bridges CB, Cox NJ, Mak KH, Fukuda K. Source: Emerging Infectious Diseases. 2002 February; 8(2): 154-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11897066&dopt=Abstract

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Lack of pharmacokinetic interaction between the oral anti-influenza neuraminidase inhibitor prodrug oseltamivir and antacids. Author(s): Snell P, Oo C, Dorr A, Barrett J. Source: British Journal of Clinical Pharmacology. 2002 October; 54(4): 372-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12392584&dopt=Abstract

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Lack of pharmacokinetic interaction between the oral anti-influenza prodrug oseltamivir and aspirin. Author(s): Oo C, Barrett J, Dorr A, Liu B, Ward P. Source: Antimicrobial Agents and Chemotherapy. 2002 June; 46(6): 1993-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12019123&dopt=Abstract

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Large summertime influenza A outbreak among tourists in Alaska and the Yukon Territory. Author(s): Uyeki TM, Zane SB, Bodnar UR, Fielding KL, Buxton JA, Miller JM, Beller M, Butler JC, Fukuda K, Maloney SA, Cetron MS; Alaska/Yukon Territory Respiratory Outbreak Investigation Team. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2003 May 1; 36(9): 1095-102. Epub 2003 April 22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12715302&dopt=Abstract

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Left ventricular pseudoaneurysm after acute influenza A myocardiopericarditis. Author(s): Agnino A, Schena S, Ferlan G, De Luca Tupputi Schinosa L. Source: The Journal of Cardiovascular Surgery. 2002 April; 43(2): 203-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11887056&dopt=Abstract

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Lethal H5N1 influenza viruses escape host anti-viral cytokine responses. Author(s): Seo SH, Hoffmann E, Webster RG. Source: Nature Medicine. 2002 September; 8(9): 950-4. Epub 2002 August 26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12195436&dopt=Abstract

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Leucocytoclastic vasculitis and influenza vaccination. Author(s): Tavadia S, Drummond A, Evans CD, Wainwright NJ. Source: Clinical and Experimental Dermatology. 2003 March; 28(2): 154-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12653702&dopt=Abstract

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Lifesaving opportunities missed: the challenge of vaccinating older Americans for pneumococcal diseases and influenza. Author(s): Tschantz K, Foley LA. Source: Issue Brief (Public Policy Inst (Am Assoc Retired Pers)). 2000 October; (Ib45): 19. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11885591&dopt=Abstract

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Live attenuated intranasal influenza vaccine. Author(s): Belshe RB, Couch RB, Glezen WP, Treanor JT. Source: Vaccine. 2002 October 4; 20(29-30): 3429-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12297386&dopt=Abstract

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Local and systemic immune response in nursing-home elderly following intranasal or intramuscular immunization with inactivated influenza vaccine. Author(s): Muszkat M, Greenbaum E, Ben-Yehuda A, Oster M, Yeu'l E, Heimann S, Levy R, Friedman G, Zakay-Rones Z. Source: Vaccine. 2003 March 7; 21(11-12): 1180-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12559796&dopt=Abstract

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Local surveillance of influenza in the United Kingdom: from sentinel general practices to sentinel cities? Author(s): Regan CM, Johnstone F, Joseph CA, Urwin M. Source: Commun Dis Public Health. 2002 March; 5(1): 17-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12070970&dopt=Abstract

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Localization of influenza virus proteins to nuclear dot 10 structures in influenza virus-infected cells. Author(s): Sato Y, Yoshioka K, Suzuki C, Awashima S, Hosaka Y, Yewdell J, Kuroda K. Source: Virology. 2003 May 25; 310(1): 29-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12788628&dopt=Abstract

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Logistic issues and potential prescribing costs associated with use of neuraminidase inhibitors for the treatment of influenza in primary care. Author(s): Da Silva PR, Nguyen VT, Hayward AC. Source: Journal of the Royal Society of Medicine. 2003 February; 96(2): 66-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12562975&dopt=Abstract

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Low risk of recurrence of oculorespiratory syndrome following influenza revaccination. Author(s): Skowronski DM, Strauss B, Kendall P, Duval B, De Serres G. Source: Cmaj : Canadian Medical Association Journal = Journal De L'association Medicale Canadienne. 2002 October 15; 167(8): 853-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12406942&dopt=Abstract

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Lower respiratory tract infections associated with influenza A and B viruses in an area with a high prevalence of pediatric human immunodeficiency type 1 infection. Author(s): Madhi SA, Ramasamy N, Bessellar TG, Saloojee H, Klugman KP. Source: The Pediatric Infectious Disease Journal. 2002 April; 21(4): 291-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12075759&dopt=Abstract

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Lyme disease presenting as an influenza-like illness. Author(s): Porwancher R. Source: The American Journal of Medicine. 2003 July; 115(1): 73; Author Reply 73-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12867242&dopt=Abstract

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Management of influenza in adults older than 65 years of age: cost-effectiveness of rapid testing and antiviral therapy. Author(s): Ann Intern Med. 2003 Sep 2;139(5 Pt 1):I49 Source: Annals of Internal Medicine. 2003 September 2; 139(5 Pt 1): 321-9. Summary for Patients In: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12965957

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Maritime health: a case for preventing influenza on the high seas. Author(s): Ruben FL, Ehreth J. Source: Int Marit Health. 2002; 53(1-4): 36-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12608587&dopt=Abstract

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Maternal immunization with inactivated influenza vaccine: rationale and experience. Author(s): Englund JA. Source: Vaccine. 2003 July 28; 21(24): 3460-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12850360&dopt=Abstract

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Measuring pKa of activation and pKi of inactivation for influenza hemagglutinin from kinetics of membrane fusion of virions and of HA expressing cells. Author(s): Mittal A, Shangguan T, Bentz J. Source: Biophysical Journal. 2002 November; 83(5): 2652-66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12414698&dopt=Abstract

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Mechanism of neutralization of influenza virus infectivity by antibodies. Author(s): Knossow M, Gaudier M, Douglas A, Barrere B, Bizebard T, Barbey C, Gigant B, Skehel JJ. Source: Virology. 2002 October 25; 302(2): 294-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12441073&dopt=Abstract

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Medical care capacity for influenza outbreaks, Los Angeles. Author(s): Glaser CA, Gilliam S, Thompson WW, Dassey DE, Waterman SH, Saruwatari M, Shapiro S, Fukuda K. Source: Emerging Infectious Diseases. 2002 June; 8(6): 569-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12023911&dopt=Abstract

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Mice deficient in perforin, CD4+ T cells, or CD28-mediated signaling maintain the typical immunodominance hierarchies of CD8+ T-cell responses to influenza virus. Author(s): Chen W, Bennink JR, Morton PA, Yewdell JW. Source: Journal of Virology. 2002 October; 76(20): 10332-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12239309&dopt=Abstract

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Mild to moderate influenza activity in Europe and the detection of novel A(H1N2) and B viruses during the winter of 2001-02. Author(s): Paget WJ, Meerhoff TJ, Goddard NL; EISS. Source: Euro Surveillance : Bulletin Europeen Sur Les Maladies Transmissibles = European Communicable Disease Bulletin. 2002 November; 7(11): 147-57. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12631987&dopt=Abstract

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Mixed outbreak of parainfluenza type 1 and influenza B associated with tourism and air travel. Author(s): Perz JF, Craig AS, Schaffner W. Source: International Journal of Infectious Diseases : Ijid : Official Publication of the International Society for Infectious Diseases. 2001; 5(4): 189-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11962348&dopt=Abstract

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Moclobemide discontinuation syndrome predominantly presenting with influenzalike symptoms. Author(s): Curtin F, Berney P, Kaufmann C. Source: Journal of Psychopharmacology (Oxford, England). 2002 September; 16(3): 2712. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12236637&dopt=Abstract

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Molecular characterization of influenza B viruses circulating in northern Italy during the 2001-2002 epidemic season. Author(s): Ansaldi F, D'Agaro P, De Florentiis D, Puzelli S, Lin YP, Gregory V, Bennett M, Donatelli I, Gasparini R, Crovari P, Hay A, Campello C. Source: Journal of Medical Virology. 2003 July; 70(3): 463-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12767012&dopt=Abstract

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Molecular diagnosis of influenza. Author(s): Ellis JS, Zambon MC. Source: Reviews in Medical Virology. 2002 November-December; 12(6): 375-89. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12410529&dopt=Abstract

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Molecular epidemiology of influenza A(H3N2) virus reinfections. Author(s): Smith CB, Cox NJ, Subbarao K, Taber LH, Glezen WP. Source: The Journal of Infectious Diseases. 2002 April 1; 185(7): 980-5. Epub 2002 March 13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11920323&dopt=Abstract

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Monitoring of influenza in the EISS European network member countries from October 2000 to April 2001. Author(s): Manuguerra JC, Mosnier A, Paget WJ; EISS (European Influenza Surveillance Scheme). Source: Euro Surveillance : Bulletin Europeen Sur Les Maladies Transmissibles = European Communicable Disease Bulletin. 2001 September; 6(9): 127-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11891380&dopt=Abstract

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Mortality associated with influenza and respiratory syncytial virus in the United States. Author(s): Thompson WW, Shay DK, Weintraub E, Brammer L, Cox N, Anderson LJ, Fukuda K. Source: Jama : the Journal of the American Medical Association. 2003 January 8; 289(2): 179-86. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12517228&dopt=Abstract

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Multiple amino acid residues confer temperature sensitivity to human influenza virus vaccine strains (FluMist) derived from cold-adapted A/Ann Arbor/6/60. Author(s): Jin H, Lu B, Zhou H, Ma C, Zhao J, Yang CF, Kemble G, Greenberg H. Source: Virology. 2003 February 1; 306(1): 18-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12620793&dopt=Abstract

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Mutations in human parainfluenza virus type 3 hemagglutinin-neuraminidase causing increased receptor binding activity and resistance to the transition state sialic acid analog 4-GU-DANA (Zanamivir). Author(s): Murrell M, Porotto M, Weber T, Greengard O, Moscona A. Source: Journal of Virology. 2003 January; 77(1): 309-17. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12477836&dopt=Abstract

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Mutations in the N-terminal region of influenza virus PB2 protein affect virus RNA replication but not transcription. Author(s): Gastaminza P, Perales B, Falcon AM, Ortin J. Source: Journal of Virology. 2003 May; 77(9): 5098-108. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12692212&dopt=Abstract

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Myocardial infarction, stroke, and sudden cardiac death may be prevented by influenza vaccination. Author(s): Meyers DG. Source: Current Atherosclerosis Reports. 2003 March; 5(2): 146-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12573201&dopt=Abstract

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Natural and synthetic sialic acid-containing inhibitors of influenza virus receptor binding. Author(s): Matrosovich M, Klenk HD. Source: Reviews in Medical Virology. 2003 March-April; 13(2): 85-97. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12627392&dopt=Abstract

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Near patient testing for influenza in children in primary care: comparison with laboratory test. Author(s): Harnden A, Brueggemann A, Shepperd S, White J, Hayward AC, Zambon M, Crook D, Mant D. Source: Bmj (Clinical Research Ed.). 2003 March 1; 326(7387): 480. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12609945&dopt=Abstract

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Neuraminidase inhibitors for influenza A and B: antivirals need to be protected from adverse conditions to retain effectiveness. Author(s): Arya SC, Agarwal N. Source: Bmj (Clinical Research Ed.). 2003 July 12; 327(7406): 105-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12855538&dopt=Abstract

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Neuraminidase inhibitors for influenza A and B: PROSE may be as useful as POEMs. Author(s): Bradley NC. Source: Bmj (Clinical Research Ed.). 2003 July 12; 327(7406): 105. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12855540&dopt=Abstract

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Neuraminidase inhibitors for influenza A and B: study showed benefits of treatment are marginal. Author(s): Oliver M. Source: Bmj (Clinical Research Ed.). 2003 July 12; 327(7406): 105. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12855537&dopt=Abstract

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Neuraminidase inhibitors for preventing and treating influenza in children. Author(s): Matheson NJ, Symmonds-Abrahams M, Sheikh A, Shepperd S, Harnden A. Source: Cochrane Database Syst Rev. 2003; (3): Cd002744. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12917931&dopt=Abstract

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Neuraminidase inhibitors in pediatric patients: potential place in influenza therapy. Author(s): Noyola DE. Source: Paediatric Drugs. 2003; 5(2): 125-31. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12529164&dopt=Abstract

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Neuraminidase inhibitors in the management of influenza--experience of an outpatient practice. Author(s): Vogel GE. Source: Medical Microbiology and Immunology. 2002 December; 191(3-4): 161-3. Epub 2002 October 25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12458352&dopt=Abstract

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Neuraminidase sequence analysis and susceptibilities of influenza virus clinical isolates to zanamivir and oseltamivir. Author(s): McKimm-Breschkin J, Trivedi T, Hampson A, Hay A, Klimov A, Tashiro M, Hayden F, Zambon M. Source: Antimicrobial Agents and Chemotherapy. 2003 July; 47(7): 2264-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12821478&dopt=Abstract

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Neuraminidase subtyping of human influenza a viruses by RT-PCR and its application to clinical isolates. Author(s): Takao S, Shimazu Y, Fukuda S, Kuwayama M, Miyazaki K. Source: Japanese Journal of Infectious Diseases. 2002 December; 55(6): 204-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12606830&dopt=Abstract

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Neurologic complications associated with influenza vaccination: two adult cases. Author(s): Nakamura N, Nokura K, Zettsu T, Koga H, Tachi M, Terada M, Katoh H, Itoh Y, Osawa H, Ozeki T, Yamamoto H. Source: Intern Med. 2003 February; 42(2): 191-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12636241&dopt=Abstract

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Neutralizing epitopes specific for influenza B virus Yamagata group strains are in the 'loop'. Author(s): Nakagawa N, Kubota R, Nakagawa T, Okuno Y. Source: The Journal of General Virology. 2003 April; 84(Pt 4): 769-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12655076&dopt=Abstract

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New millennium antivirals against pandemic and epidemic influenza: the neuraminidase inhibitors. Author(s): Oxford JS, Novelli P, Sefton A, Lambkin R. Source: Antivir Chem Chemother. 2002 July; 13(4): 205-17. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12495208&dopt=Abstract

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New recommendations for influenza vaccination for children and pregnant women. Author(s): Baltimore RS, Jenson HB. Source: Current Opinion in Pediatrics. 2003 February; 15(1): 74-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12544275&dopt=Abstract

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Nonclinical safety evaluation of Escherichia coli heat-labile toxin mucosal adjuvant as a component of a nasal influenza vaccine. Author(s): Zurbriggen R, Metcalfe IC, Gluck R, Viret JF, Moser C. Source: Expert Rev Vaccines. 2003 April; 2(2): 295-304. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12899579&dopt=Abstract

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Nosocomial influenza at a Canadian pediatric hospital from 1995 to 1999: opportunities for prevention. Author(s): Slinger R, Dennis P. Source: Infection Control and Hospital Epidemiology : the Official Journal of the Society of Hospital Epidemiologists of America. 2002 October; 23(10): 627-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12400897&dopt=Abstract

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Nosocomial influenza infection among post-influenza-vaccinated patients with severe pulmonary diseases. Author(s): Berg HF, Van Gendt J, Rimmelzwaan GF, Peeters MF, Van Keulen P. Source: The Journal of Infection. 2003 February; 46(2): 129-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12634075&dopt=Abstract

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Nosocomial transmission of influenza. Author(s): Stott DJ, Kerr G, Carman WF. Source: Occupational Medicine (Oxford, England). 2002 August; 52(5): 249-53. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12181372&dopt=Abstract

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NOx (nitrite/nitrate) in cerebral spinal fluids obtained from patients with influenzaassociated encephalopathy. Author(s): Kawashima H, Watanabe Y, Morishima T, Togashi T, Yamada N, Kashiwagi Y, Takekuma K, Hoshika A, Mori T. Source: Neuropediatrics. 2003 June; 34(3): 137-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12910436&dopt=Abstract

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Nutrition, exercise, and influenza vaccination. Author(s): McElhaney JE. Source: The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences. 2002 September; 57(9): M555-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12196489&dopt=Abstract

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Obstacles to influenza immunization in primary care. Author(s): Doran T, McCann R. Source: Journal of Public Health Medicine. 2001 December; 23(4): 329-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11873897&dopt=Abstract

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Occurrence of influenza B/Hong Kong-like strains in Brazil, during 2002. Author(s): de Paiva TM, Ishida MA, Goncalves MG, Benega MA, de Souza MC, Cruz AS. Source: Revista Do Instituto De Medicina Tropical De Sao Paulo. 2003 January-February; 45(1): 51-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12751324&dopt=Abstract

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Ocular and respiratory symptoms attributable to inactivated split influenza vaccine: evidence from a controlled trial involving adults. Author(s): Scheifele DW, Duval B, Russell ML, Warrington R, DeSerres G, Skowronski DM, Dionne M, Kellner J, Davies D, MacDonald J. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2003 April 1; 36(7): 850-7. Epub 2003 March 18. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12652385&dopt=Abstract

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Oculo-respiratory syndrome: a new influenza vaccine-associated adverse event? Author(s): Skowronski DM, Strauss B, De Serres G, MacDonald D, Marion SA, Naus M, Patrick DM, Kendall P. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2003 March 15; 36(6): 705-13. Epub 2003 Mar 05. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12627354&dopt=Abstract

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Old drugs for a new bug: influenza, HIV drugs enlisted to fight SARS. Author(s): Vastag B. Source: Jama : the Journal of the American Medical Association. 2003 October 1; 290(13): 1695-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14519691&dopt=Abstract

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Older people's views on the treatment and prevention of influenza in older people. Author(s): Curnock E, Wynne HA. Source: Age and Ageing. 2002 July; 31(4): 322-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12147575&dopt=Abstract

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Origin and evolution of influenza virus hemagglutinin genes. Author(s): Suzuki Y, Nei M. Source: Molecular Biology and Evolution. 2002 April; 19(4): 501-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11919291&dopt=Abstract

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ORS during the 2000-2001 influenza vaccination season. Author(s): Choudhri Y, Walop W, Squires S, Tam T, King A, Skowronski D, Warrington R, Wood J. Source: Can Commun Dis Rep. 2002 September 1; 28: 2-8. English, French. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12219588&dopt=Abstract

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Oseltamivir for treatment of influenza in healthy adults: pooled trial evidence and cost-effectiveness model for Canada. Author(s): O'Brien BJ, Goeree R, Blackhouse G, Smieja M, Loeb M. Source: Value in Health : the Journal of the International Society for Pharmacoeconomics and Outcomes Research. 2003 March-April; 6(2): 116-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12641862&dopt=Abstract

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Outbreak of avian influenza A(H5N1) virus infection in Hong Kong in 1997. Author(s): Chan PK. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2002 May 1; 34 Suppl 2: S58-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11938498&dopt=Abstract

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Outbreak of influenza type A (H1N1) in Iporanga, Sao Paulo State, Brazil. Author(s): de Paiva TM, Ishida MA, Hanashiro KA, Scolaro RM, Goncalves MG, Benega MA, Oliveira MA, Cruz AS, Takimoto S. Source: Revista Do Instituto De Medicina Tropical De Sao Paulo. 2001 NovemberDecember; 43(6): 311-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11781599&dopt=Abstract

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Outbreak of influenza, Madagascar, July-August 2002. Author(s): WHO-GOARN investigation team. Source: Euro Surveillance : Bulletin Europeen Sur Les Maladies Transmissibles = European Communicable Disease Bulletin. 2002 December; 7(12): 172-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12631982&dopt=Abstract

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Outbreaks of influenza A virus infection in neonatal intensive care units. Author(s): Sagrera X, Ginovart G, Raspall F, Rabella N, Sala P, Sierra M, Demestre X, Vila C. Source: The Pediatric Infectious Disease Journal. 2002 March; 21(3): 196-200. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12005081&dopt=Abstract

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Overexpression of the alpha-2,6-sialyltransferase in MDCK cells increases influenza virus sensitivity to neuraminidase inhibitors. Author(s): Matrosovich M, Matrosovich T, Carr J, Roberts NA, Klenk HD. Source: Journal of Virology. 2003 August; 77(15): 8418-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12857911&dopt=Abstract

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Pandemic influenza and the global vaccine supply. Author(s): Fedson DS. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2003 June 15; 36(12): 1552-61. Epub 2003 Jun 05. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12802755&dopt=Abstract

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Pathogenic and antigenic properties of phylogenetically distinct reassortant H3N2 swine influenza viruses cocirculating in the United States. Author(s): Richt JA, Lager KM, Janke BH, Woods RD, Webster RG, Webby RJ. Source: Journal of Clinical Microbiology. 2003 July; 41(7): 3198-205. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12843064&dopt=Abstract

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Poor uptake of influenza vaccinations in patients receiving cytotoxic chemotherapy. Author(s): Ring A, Marx G, Steer C, Prendiville J, Ellis P. Source: Int J Clin Pract. 2003 July-August; 57(6): 542-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12918895&dopt=Abstract

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Population dynamics of rapid fixation in cytotoxic T lymphocyte escape mutants of influenza A. Author(s): Gog JR, Rimmelzwaan GF, Osterhaus AD, Grenfell BT. Source: Proceedings of the National Academy of Sciences of the United States of America. 2003 September 16; 100(19): 11143-7. Epub 2003 Sep 03. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12954978&dopt=Abstract

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Porcine pulmonary collectins show distinct interactions with influenza A viruses: role of the N-linked oligosaccharides in the carbohydrate recognition domain. Author(s): van Eijk M, White MR, Crouch EC, Batenburg JJ, Vaandrager AB, Van Golde LM, Haagsman HP, Hartshorn KL. Source: Journal of Immunology (Baltimore, Md. : 1950). 2003 August 1; 171(3): 1431-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12874235&dopt=Abstract

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Potent anti-influenza activity of cyanovirin-N and interactions with viral hemagglutinin. Author(s): O'Keefe BR, Smee DF, Turpin JA, Saucedo CJ, Gustafson KR, Mori T, Blakeslee D, Buckheit R, Boyd MR. Source: Antimicrobial Agents and Chemotherapy. 2003 August; 47(8): 2518-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12878514&dopt=Abstract

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Potential burden of universal influenza vaccination of young children on visits to primary care practices. Author(s): Szilagyi PG, Iwane MK, Schaffer S, Humiston SG, Barth R, McInerny T, Shone L, Schwartz B. Source: Pediatrics. 2003 October; 112(4): 821-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14523173&dopt=Abstract

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Prenatal exposure to influenza as a risk factor for adult schizophrenia. Author(s): Limosin F, Rouillon F, Payan C, Cohen JM, Strub N. Source: Acta Psychiatrica Scandinavica. 2003 May; 107(5): 331-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12752028&dopt=Abstract

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Preventing and treating influenza. Author(s): Stohr K. Source: Bmj (Clinical Research Ed.). 2003 June 7; 326(7401): 1223-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12791711&dopt=Abstract

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Prevention and control of influenza. Author(s): Lee PP. Source: Southern Medical Journal. 2003 August; 96(8): 751-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14515913&dopt=Abstract

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Prevention and control of influenza. Recommendations of the Advisory Committee on Immunization Practices (ACIP). Author(s): Bridges CB, Harper SA, Fukuda K, Uyeki TM, Cox NJ, Singleton JA; Advisory Committee on Immunization Practices. Source: Mmwr. Recommendations and Reports : Morbidity and Mortality Weekly Report. Recommendations and Reports / Centers for Disease Control. 2003 April 25; 52(Rr-8): 1-34; Quiz Ce1-4. Erratum In: Mmwr Morb Mortal Wkly Rep. 2003 June 6; 52(22): 526. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12755288&dopt=Abstract

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Prime-boost immunization schedules based on influenza virus and vaccinia virus vectors potentiate cellular immune responses against human immunodeficiency virus Env protein systemically and in the genitorectal draining lymph nodes. Author(s): Gherardi MM, Najera JL, Perez-Jimenez E, Guerra S, Garcia-Sastre A, Esteban M. Source: Journal of Virology. 2003 June; 77(12): 7048-57. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12768024&dopt=Abstract

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Progress towards eliminating Hib in Australia: an evaluation of Haemophilus influenzae type b prevention in Australia, 1 July 1993 to 30 June 2000. Author(s): Horby P, Gilmour R, Wang H, McIntyre P. Source: Commun Dis Intell. 2003; 27(3): 324-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14510058&dopt=Abstract

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Public health and aging: influenza vaccination coverage among adults aged > or =50 years and pneumococcal vaccination coverage among adults aged > or =65 years-United States, 2002. Author(s): Centers for Disease Control and Prevention (CDC). Source: Mmwr. Morbidity and Mortality Weekly Report. 2003 October 17; 52(41): 987-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14561957&dopt=Abstract

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Quality control assessment of influenza and RSV testing in Europe: 2000-01 season. Author(s): Valette M, Aymard M. Source: Euro Surveillance : Bulletin Europeen Sur Les Maladies Transmissibles = European Communicable Disease Bulletin. 2002 November; 7(11): 161-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12631989&dopt=Abstract

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Quantification of the influenza virus load by real-time polymerase chain reaction in nasopharyngeal swabs of patients treated with oseltamivir. Author(s): Boivin G, Coulombe Z, Wat C. Source: The Journal of Infectious Diseases. 2003 August 15; 188(4): 578-80. Epub 2003 Aug 05. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12898446&dopt=Abstract

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Quantitative analysis of influenza virus RNP interaction with RNA cap structures and comparison to human cap binding protein eIF4E. Author(s): Hooker L, Sully R, Handa B, Ono N, Koyano H, Klumpp K. Source: Biochemistry. 2003 May 27; 42(20): 6234-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12755627&dopt=Abstract

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QuickVue influenza test for rapid detection of influenza A and B viruses in a pediatric population. Author(s): Quach C, Newby D, Daoust G, Rubin E, McDonald J. Source: Clinical and Diagnostic Laboratory Immunology. 2002 July; 9(4): 925-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12093698&dopt=Abstract

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Racial/ethnic disparities in influenza and pneumococcal vaccination levels among persons aged > or =65 years--United States, 1989-2001. Author(s): Centers for Disease Control and Prevention (CDC). Source: Mmwr. Morbidity and Mortality Weekly Report. 2003 October 10; 52(40): 958-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14534511&dopt=Abstract

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Radiographic and high-resolution CT findings of influenza virus pneumonia in patients with hematologic malignancies. Author(s): Oikonomou A, Muller NL, Nantel S. Source: Ajr. American Journal of Roentgenology. 2003 August; 181(2): 507-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12876036&dopt=Abstract

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Rapid detection of influenza A and B viruses in clinical specimens by Light Cycler real time RT-PCR. Author(s): Smith AB, Mock V, Melear R, Colarusso P, Willis DE. Source: Journal of Clinical Virology : the Official Publication of the Pan American Society for Clinical Virology. 2003 September; 28(1): 51-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12927751&dopt=Abstract

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Recent strategies in the search for new anti-influenza therapies. Author(s): Wilson JC, von Itzstein M. Source: Current Drug Targets. 2003 July; 4(5): 389-408. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12816348&dopt=Abstract

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Receptor-binding properties of modern human influenza viruses primarily isolated in Vero and MDCK cells and chicken embryonated eggs. Author(s): Mochalova L, Gambaryan A, Romanova J, Tuzikov A, Chinarev A, Katinger D, Katinger H, Egorov A, Bovin N. Source: Virology. 2003 September 1; 313(2): 473-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12954214&dopt=Abstract

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Recommendations pertaining to the use of viral vaccines: influenza. Review of influenza activity--2002. Author(s): National Institute for Communicable Diseases. Source: South African Medical Journal. Suid-Afrikaanse Tydskrif Vir Geneeskunde. 2003 April; 93(4): 271. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12806715&dopt=Abstract

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Relapse of severe aplastic anaemia after influenza immunization. Author(s): Hendry CL, Sivakumaran M, Marsh JC, Gordon-Smith EC. Source: British Journal of Haematology. 2002 October; 119(1): 283-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12358945&dopt=Abstract

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Review of the use of neuraminidase inhibitors for prophylaxis of influenza. Author(s): Kirkbride HA, Watson J. Source: Commun Dis Public Health. 2003 June; 6(2): 123-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12889291&dopt=Abstract

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Rheumatoid vasculitis following influenza vaccination. Author(s): Iyngkaran P, Limaye V, Hill C, Henderson D, Pile KD, Rischmueller M. Source: Rheumatology (Oxford, England). 2003 July; 42(7): 907-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12826713&dopt=Abstract

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Risk factors associated with severe influenza infections in childhood: implication for vaccine strategy. Author(s): Quach C, Piche-Walker L, Platt R, Moore D. Source: Pediatrics. 2003 September; 112(3 Pt 1): E197-201. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12949312&dopt=Abstract

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Safety and immunoenhancing effect of a Chlorella-derived dietary supplement in healthy adults undergoing influenza vaccination: randomized, double-blind, placebocontrolled trial. Author(s): Halperin SA, Smith B, Nolan C, Shay J, Kralovec J. Source: Cmaj : Canadian Medical Association Journal = Journal De L'association Medicale Canadienne. 2003 July 22; 169(2): 111-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12874157&dopt=Abstract

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Safety of the trivalent, cold-adapted influenza vaccine in preschool-aged children. Author(s): Piedra PA, Yan L, Kotloff K, Zangwill K, Bernstein DI, King J, Treanor J, Munoz F, Wolff M, Cho I, Mendelman PM, Cordova J, Belshe RB. Source: Pediatrics. 2002 October; 110(4): 662-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12359778&dopt=Abstract

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Selective translation of eukaryotic mRNAs: functional molecular analysis of GRSF-1, a positive regulator of influenza virus protein synthesis. Author(s): Kash JC, Cunningham DM, Smit MW, Park Y, Fritz D, Wilusz J, Katze MG. Source: Journal of Virology. 2002 October; 76(20): 10417-26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12239318&dopt=Abstract

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Severe morbidity and mortality associated with influenza in children and young adults--Michigan, 2003. Author(s): Centers for Disease Control and Prevention (CDC). Source: Mmwr. Morbidity and Mortality Weekly Report. 2003 September 5; 52(35): 83740. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12966358&dopt=Abstract

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Standard and alternative regimens of Haemophilus influenzae type b conjugate vaccine (polyribosylribitol phosphate-tetanus toxoid conjugate vaccine) elicit comparable antibody avidities in infants. Author(s): Campbell JD, Lagos R, Levine MM, Losonsky GA. Source: The Pediatric Infectious Disease Journal. 2002 September; 21(9): 822-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12352802&dopt=Abstract

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Study confirms multiple benefits of influenza vaccination. Author(s): Rollins G. Source: Rep Med Guidel Outcomes Res. 2003 May 2; 14(9): 7-9. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12866509&dopt=Abstract

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Suboptimal detection of influenza virus in adults by the Directigen Flu A+B enzyme immunoassay and correlation of results with the number of antigen-positive cells detected by cytospin immunofluorescence. Author(s): Landry ML, Ferguson D. Source: Journal of Clinical Microbiology. 2003 July; 41(7): 3407-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12843105&dopt=Abstract

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Supplementary statement for the 2002-2003 influenza season: update on oculorespiratory syndrome in association with influenza vaccination. Author(s): Orr P. Source: Can Commun Dis Rep. 2002 September 1; 28: 1. English, French. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12219587&dopt=Abstract

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Synergistic effect of influenza a virus on endotoxin-induced mortality in rat pups: a potential model for sudden infant death syndrome. Author(s): Blood-Siegfried J, Nyska A, Lieder H, Joe M, Vega L, Patterson R, Germolec D. Source: Pediatric Research. 2002 October; 52(4): 481-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12357040&dopt=Abstract

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Systemic cytokine responses in patients with influenza-associated encephalopathy. Author(s): Kawada J, Kimura H, Ito Y, Hara S, Iriyama M, Yoshikawa T, Morishima T. Source: The Journal of Infectious Diseases. 2003 September 1; 188(5): 690-8. Epub 2003 August 20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12934185&dopt=Abstract

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T-cell responses and hypersensitivity to influenza and egg antigens among adults with asthma immunized with the influenza vaccine. Author(s): Miller RL, Cheng M, DiMango EA, Geromanos K, Rothman PB; American Lung Association Asthma Clinical Research Centers. Source: The Journal of Allergy and Clinical Immunology. 2003 September; 112(3): 606-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13679822&dopt=Abstract

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Temporal surveillance of the humoral immunity against influenza vaccine in the elderly over 9 consecutive years. Author(s): Odelin MF, Momplot C, Bourlet T, Gonthier R, Aymard M, Pozzetto B. Source: Gerontology. 2003 July-August; 49(4): 233-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12792158&dopt=Abstract

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The immunodominant influenza matrix T cell epitope recognized in human induces influenza protection in HLA-A2/K(b) transgenic mice. Author(s): Plotnicky H, Cyblat-Chanal D, Aubry JP, Derouet F, Klinguer-Hamour C, Beck A, Bonnefoy JY, Corvaia N. Source: Virology. 2003 May 10; 309(2): 320-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12758178&dopt=Abstract

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The influenza A virus PB1-F2 protein targets the inner mitochondrial membrane via a predicted basic amphipathic helix that disrupts mitochondrial function. Author(s): Gibbs JS, Malide D, Hornung F, Bennink JR, Yewdell JW. Source: Journal of Virology. 2003 July; 77(13): 7214-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12805420&dopt=Abstract

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The influenza and other epidemics. Med J Aust 1919;1:71-72. Author(s): MacLaurin C. Source: The Medical Journal of Australia. 2003 May 19; 178(10): 511. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12776729&dopt=Abstract

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The origin of the 1918 pandemic influenza virus: a continuing enigma. Author(s): Reid AH, Taubenberger JK. Source: The Journal of General Virology. 2003 September; 84(Pt 9): 2285-92. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12917448&dopt=Abstract

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Three years of low influenza activity--no reason for complacency. Author(s): Goddard NL, Joseph CA, Watson JM, Ellis JS, Zambon MC. Source: Commun Dis Public Health. 2003 June; 6(2): 128-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12889292&dopt=Abstract

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Trafficking of viral genomic RNA into and out of the nucleus: influenza, Thogoto and Borna disease viruses. Author(s): Cros JF, Palese P. Source: Virus Research. 2003 September; 95(1-2): 3-12. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12921991&dopt=Abstract

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Traveling waves in a model of influenza A drift. Author(s): Lin J, Andreasen V, Casagrandi R, Levin SA. Source: Journal of Theoretical Biology. 2003 June 21; 222(4): 437-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12781742&dopt=Abstract

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Two phase I studies of low dose recombinant human IL-12 with Melan-A and influenza peptides in subjects with advanced malignant melanoma. Author(s): Cebon J, Jager E, Shackleton MJ, Gibbs P, Davis ID, Hopkins W, Gibbs S, Chen Q, Karbach J, Jackson H, MacGregor DP, Sturrock S, Vaughan H, Maraskovsky E, Neumann A, Hoffman E, Sherman ML, Knuth A. Source: Cancer Immunity [electronic Resource] : a Journal of the Academy of Cancer Immunology. 2003 July 16; 3: 7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12862418&dopt=Abstract

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Unravelling the mysteries of influenza. Author(s): Zambon M, Barclay W. Source: Lancet. 2002 December 7; 360(9348): 1801-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12480355&dopt=Abstract

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Update: influenza activity--United States and worldwide, May-September 2003. Author(s): Centers for Disease Control and Prevention (CDC). Source: Mmwr. Morbidity and Mortality Weekly Report. 2003 September 26; 52(38): 9113. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14508440&dopt=Abstract

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Uptake of influenza vaccination and the reasons for non-vaccination in the high-risk patients of Angus, Scotland. Author(s): Barlow G, Kirk J, Nathwani D. Source: Health Bull (Edinb). 2000 November; 58(6): 505-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12813783&dopt=Abstract

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Uptake of influenza vaccine among Aboriginal and Torres Strait Island adults in north Queensland, 2002. Author(s): Hanna JN, McCulloch BG. Source: Commun Dis Intell. 2003; 27(1): 102-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12725510&dopt=Abstract

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Use of ambulance dispatch data as an early warning system for communitywide influenzalike illness, New York City. Author(s): Mostashari F, Fine A, Das D, Adams J, Layton M. Source: Journal of Urban Health : Bulletin of the New York Academy of Medicine. 2003 June; 80(2 Suppl 1): I43-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12791778&dopt=Abstract

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Use of induced sputum for the diagnosis of influenza and infections in asthma: a comparison of diagnostic techniques. Author(s): Simpson JL, Moric I, Wark PA, Johnston SL, Gibson PG. Source: Journal of Clinical Virology : the Official Publication of the Pan American Society for Clinical Virology. 2003 April; 26(3): 339-46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12637083&dopt=Abstract

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Use of pseudotyped retroviral vectors to analyze the receptor-binding pocket of hemagglutinin from a pathogenic avian influenza A virus (H7 subtype). Author(s): Lin AH, Cannon PM. Source: Virus Research. 2002 February 26; 83(1-2): 43-56. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11864740&dopt=Abstract

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Using live, attenuated influenza vaccine for prevention and control of influenza: supplemental recommendations of the Advisory Committee on Immunization Practices (ACIP). Author(s): Harper SA, Fukuda K, Cox NJ, Bridges CB; Advisory Committee on Immunization Practices. Source: Mmwr. Recommendations and Reports : Morbidity and Mortality Weekly Report. Recommendations and Reports / Centers for Disease Control. 2003 September 26; 52(Rr-13): 1-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14557799&dopt=Abstract

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Using the National Health Interview Survey: time trends in influenza vaccinations among targeted adults. Author(s): Pleis JR, Gentleman JF. Source: Effective Clinical Practice : Ecp. 2002 May-June; 5(3 Suppl): E3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12166924&dopt=Abstract

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Utility of zanamivir for chemoprophylaxis of concomitant influenza A and B in a complex continuing care population. Author(s): Hirji Z, O'Grady S, Bonham J, Mak M, Takata-Shewchuk J, Hawkins K, Gardam M, Law L, Mazzulli T, Conly J. Source: Infection Control and Hospital Epidemiology : the Official Journal of the Society of Hospital Epidemiologists of America. 2002 October; 23(10): 604-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12400891&dopt=Abstract

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Vaccinating against influenza and pneumococcus. Author(s): Umeed M. Source: Nurs Times. 2001 October 18-24; 97(42): 32-4. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11966119&dopt=Abstract

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Vaccination against influenza: UK health care workers not on-message. Author(s): Harrison J, Abbott P. Source: Occupational Medicine (Oxford, England). 2002 August; 52(5): 277-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12181377&dopt=Abstract

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Vaccination for pandemic influenza and severe acute respiratory syndrome: common issues and concerns. Author(s): Fedson DS. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2003 June 15; 36(12): 1562-3. Epub 2003 Jun 05. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12802756&dopt=Abstract

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Vaccination policies in the military: an insight on influenza. Author(s): D'Amelio R, Biselli R, Cali G, Peragallo MS. Source: Vaccine. 2002 December 20; 20 Suppl 5: B36-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12477417&dopt=Abstract

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Viral characteristics of influenza. Author(s): Moorman JP. Source: Southern Medical Journal. 2003 August; 96(8): 758-61. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14515914&dopt=Abstract

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Virosome influenza vaccine in children. Author(s): Herzog C, Metcalfe IC, Schaad UB. Source: Vaccine. 2002 December 20; 20 Suppl 5: B24-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12477414&dopt=Abstract

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Virus-cell interactions in the induction of type 1 interferon by influenza virus in mouse spleen cells. Author(s): Miller JL, Margot Anders E. Source: The Journal of General Virology. 2003 January; 84(Pt 1): 193-202. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12533716&dopt=Abstract

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Virus-neutralizing activity mediated by the Fab fragment of a hemagglutinin-specific antibody is sufficient for the resolution of influenza virus infection in SCID mice. Author(s): Mozdzanowska K, Feng J, Gerhard W. Source: Journal of Virology. 2003 August; 77(15): 8322-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12857901&dopt=Abstract

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What affects influenza vaccination rates among older patients? An analysis from inner-city, suburban, rural, and Veterans Affairs practices. Author(s): Zimmerman RK, Santibanez TA, Janosky JE, Fine MJ, Raymund M, Wilson SA, Bardella IJ, Medsger AR, Nowalk MP. Source: The American Journal of Medicine. 2003 January; 114(1): 31-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12543287&dopt=Abstract

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Who should receive the influenza vaccine? Author(s): Schofield C. Source: Nursing. 2002 November; 32(11 Pt 1): 24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12518735&dopt=Abstract

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Winter viruses: influenza- and respiratory syncytial virus-related morbidity in chronic lung disease. Author(s): Griffin MR, Coffey CS, Neuzil KM, Mitchel EF Jr, Wright PF, Edwards KM. Source: Archives of Internal Medicine. 2002 June 10; 162(11): 1229-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12038940&dopt=Abstract

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World Health Organization, 50 years of influenza surveillance: a challenge for the 21st century. Meeting 17-19 February 1999, WHO, Geneva. Author(s): Bruntland GH. Source: Vaccine. 2002 May 15; 20 Suppl 2: S1-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12110247&dopt=Abstract

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World War I may have allowed the emergence of “Spanish” influenza. Author(s): Oxford JS, Sefton A, Jackson R, Innes W, Daniels RS, Johnson NP. Source: The Lancet Infectious Diseases. 2002 February; 2(2): 111-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11901642&dopt=Abstract

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X-ray structure of the hemagglutinin of a potential H3 avian progenitor of the 1968 Hong Kong pandemic influenza virus. Author(s): Ha Y, Stevens DJ, Skehel JJ, Wiley DC. Source: Virology. 2003 May 10; 309(2): 209-18. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12758169&dopt=Abstract

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Zanamivir (Relenza )--a new treatment for influenza. Author(s): MacConnachie AM. Source: Intensive & Critical Care Nursing : the Official Journal of the British Association of Critical Care Nurses. 1999 December; 15(6): 369-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11868584&dopt=Abstract

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Zanamivir for the treatment of influenza in adults: a systematic review and economic evaluation. Author(s): Burls A, Clark W, Stewart T, Preston C, Bryan S, Jefferson T, Fry-Smith A. Source: Health Technology Assessment (Winchester, England). 2002; 6(9): 1-87. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12065066&dopt=Abstract

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Zanamivir in the prevention of influenza among healthy adults. Author(s): Bower DJ, Slawson JG. Source: The Journal of Family Practice. 1999 October; 48(10): 748. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12224667&dopt=Abstract

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Zanamivir in the treatment of influenza. Author(s): Fleming DM. Source: Expert Opinion on Pharmacotherapy. 2003 May; 4(5): 799-805. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12740002&dopt=Abstract

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Zanamivir is an effective treatment for influenza in children undergoing therapy for acute lymphoblastic leukemia. Author(s): Maeda M, Fukunaga Y, Asano T, Migita M, Ueda T, Hayakawa J. Source: Scandinavian Journal of Infectious Diseases. 2002; 34(8): 632-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12238587&dopt=Abstract

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Zanamivir prophylaxis: an effective strategy for the prevention of influenza types A and B within households. Author(s): Monto AS, Pichichero ME, Blanckenberg SJ, Ruuskanen O, Cooper C, Fleming DM, Kerr C. Source: The Journal of Infectious Diseases. 2002 December 1; 186(11): 1582-8. Epub 2002 November 06. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12447733&dopt=Abstract

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Zanamivir: a significant reduction in viral load during treatment in military conscripts with influenza. Author(s): Puhakka T, Lehti H, Vainionpaa R, Jormanainen V, Pulkkinen M, Sharp S, Kerr C, Dempsey M, Ring CJ, Ward C, Tisdale M. Source: Scandinavian Journal of Infectious Diseases. 2003; 35(1): 52-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12685885&dopt=Abstract

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Zanamivir: an update of its use in influenza. Author(s): Cheer SM, Wagstaff AJ. Source: Drugs. 2002; 62(1): 71-106. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11790157&dopt=Abstract

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CHAPTER 2. NUTRITION AND INFLUENZA Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and influenza.

Finding Nutrition Studies on Influenza The National Institutes of Health’s Office of Dietary Supplements (ODS) offers a searchable bibliographic database called the IBIDS (International Bibliographic Information on Dietary Supplements; National Institutes of Health, Building 31, Room 1B29, 31 Center Drive, MSC 2086, Bethesda, Maryland 20892-2086, Tel: 301-435-2920, Fax: 301-480-1845, E-mail: [email protected]). The IBIDS contains over 460,000 scientific citations and summaries about dietary supplements and nutrition as well as references to published international, scientific literature on dietary supplements such as vitamins, minerals, and botanicals.7 The IBIDS includes references and citations to both human and animal research studies. As a service of the ODS, access to the IBIDS database is available free of charge at the following Web address: http://ods.od.nih.gov/databases/ibids.html. After entering the search area, you have three choices: (1) IBIDS Consumer Database, (2) Full IBIDS Database, or (3) Peer Reviewed Citations Only. Now that you have selected a database, click on the “Advanced” tab. An advanced search allows you to retrieve up to 100 fully explained references in a comprehensive format. Type “influenza” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.

7 Adapted from http://ods.od.nih.gov. IBIDS is produced by the Office of Dietary Supplements (ODS) at the National Institutes of Health to assist the public, healthcare providers, educators, and researchers in locating credible, scientific information on dietary supplements. IBIDS was developed and will be maintained through an interagency partnership with the Food and Nutrition Information Center of the National Agricultural Library, U.S. Department of Agriculture.

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The following information is typical of that found when using the “Full IBIDS Database” to search for “influenza” (or a synonym): •

A hypothesis concerning deficiency of sunlight, cold temperature, and influenza epidemics associated with the onset of acute lymphoblastic leukemia in northern Finland. Author(s): University of Oulu, Department of Internal Medicine, Kajaanintie 50, FIN90220 Oulu, Finland. Source: Timonen, T T Ann-Hematol. 1999 September; 78(9): 408-14 0939-5555

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A new strategy toward the total synthesis of stachyflin, a potent anti-influenza A virus agent: concise route to the tetracyclic core structure. Author(s): Sagami Chemical Research Center, Hayakawa 2743-1, Ayase, Kanagawa 2521193, Japan. Source: Nakatani, M Nakamura, M Suzuki, A Inoue, M Katoh, T Org-Lett. 2002 December 12; 4(25): 4483-6 1523-7060

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A novel approach to antiviral therapy for influenza. Author(s): Biomolecular Research Institute, Parkville, Victoria, Australia. [email protected] Source: Colman, P M J-Antimicrob-Chemother. 1999 November; 44 Suppl B17-22 03057453

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A release-competent influenza A virus mutant lacking the coding capacity for the neuraminidase active site. Author(s): Department of Internal Medicine, University of Virginia, 1300 Jefferson Park Avenue, Jordan Hall Room 2231, PO Box 800473, Charlottesville 22908, USA. [email protected] Source: Gubareva, L V Nedyalkova, M S Novikov, D V Murti, K G Hoffmann, E Hayden, F G J-Gen-Virol. 2002 Nov; 83(Pt 11): 2683-92 0022-1317

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Activity of anthocyanins from fruit extract of Ribes nigrum L. against influenza A and B viruses. Author(s): Department of Microbiology, Asahikawa Medical College, Japan. [email protected] Source: Knox, Y M Hayashi, K Suzutani, T Ogasawara, M Yoshida, I Shiina, R Tsukui, A Terahara, N Azuma, M Acta-Virol. 2001; 45(4): 209-15 0001-723X

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Amantadine and equine influenza: pharmacology, pharmacokinetics and neurological effects in the horse. Source: Rees, W.A. Harkins, J.D. Woods, W.E. Blouin, R.A. Lu, M. Fenger, C. Holland, R.E. Chambers, T.M. Tobin, T. Equine-vet-j. Newmarket, Suffolk : Equine Veterinary Journal Ltd. Mar 1997. volume 29 (2) page 104-110. 0425-1644

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Antigenic and genetic analyses of H 1 N 1 influenza A viruses from European pigs. Source: Brown, I.H. Ludwig, S. Olsen, C.W. Hannoun, C. Scholtissek, C. Hinshaw, V.S. Harris, P.A. McCauley, J.W. Strong, I. Alexander, D.J. J-gen-virol. Reading : Society for General Microbiology. March 1997. volume 78 (pt.3) page 553-562. 0022-1317

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Antipyretic activity of gingyo-san, a traditional medicine, in influenza virus-infected mice. Author(s): Department of Virology, Toyama Medical and Pharmaceutical University, Japan. Source: Kurokawa, M Yamamura, J Li, Z Sato, H Hitomi, N Tatsumi, Y Shiraki, K ChemPharm-Bull-(Tokyo). 1998 September; 46(9): 1444-7 0009-2363

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Antiviral agents in women's health: pharmacotherapeutics of treating influenza and herpes. Source: Burpo, Rebecca H J-Midwifery-Womens-Health. 2002 May-June; 47(3): 182-9 1526-9523

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Antiviral effect of gingyo-san, a traditional Chinese herbal medicine, on influenza A2 virus infection in mice. Author(s): Department of Internal Medicine, University of Texas Medical Branch, Galveston 77555, USA. Source: Kobayashi, M Davis, S M Utsunomiya, T Pollard, R B Suzuki, F Am-J-Chin-Med. 1999; 27(1): 53-62 0192-415X

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Antiviral therapy of influenza. Author(s): Department of Pediatrics, University of Chicago, Chicago, IL 60637, USA. [email protected] Source: Englund, Janet A Semin-Pediatr-Infect-Dis. 2002 April; 13(2): 120-8 1045-1870

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Avian-to-human transmission of the PB1 gene of influenza A viruses in the 1957 and 1968 pandemics. Source: Kawaoka, Y. Krauss, S. Webster, R.G. J-Virol. Washington, D.C. : American Society for Microbiology. November 1989. volume 63 (11) page 4603-4608. 0022-538X

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Blood glycerol and free fatty acids before and after delivery in obese and normal weighing pregnant women. Influenza del parto sul contenuto sierico di glicerolo e di acidi grassi non esterificati in donne obese e normopeso. Source: Adoncecchi, L. Marrocco, W. Perrone, G. Santoro, A. Suraci, C. Boll-Soc-ItalBiol-Sper. Napoli : La Societa. July 1983. volume 59 (7) page 977-982. 0037-8771

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By the way, doctor. I am 68 years old and healthy. For the past two years, I've gotten a flu shot in October. Nonetheless, both winters I experienced what felt like influenza. I was thrilled to read about a new flu treatment. If I get the flu again this year, should I try the drug? Source: Robb Nicholson, C Harv-Womens-Health-Watch. 2000 February; 7(6): 7 1070910X

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Clinical efficacy and safety of the orally inhaled neuraminidase inhibitor zanamivir in the treatment of influenza: a randomized, double-blind, placebo-controlled European study. Author(s): Department of Pulmonary Diseases, University Hospital, Turku, Finland. Source: Makela, M J Pauksens, K Rostila, T Fleming, D M Man, C Y Keene, O N Webster, A J-Infect. 2000 January; 40(1): 42-8 0163-4453

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Comparisons of highly virulent H5N1 influenza A viruses isolated from humans and chickens from Hong Kong. Source: Suarez, D.L. Perdue, M.L. Cox, N. Rowe, T. Bender, C. Huang, J. Swayne, D.E. Jvirol. Washington, D.C. : American Society for Microbiology. August 1998. volume 72 (8) page 6678-6688. 0022-538X

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Cost effectiveness of zanamivir for the treatment of influenza in a high risk population in Australia. Author(s): Research Triangle Institute, Research Triangle Park, North Carolina, USA. [email protected] Source: Mauskopf, J A Cates, S C Griffin, A D Neighbors, D M Lamb, S C Rutherford, C Pharmacoeconomics. 2000 June; 17(6): 611-20 1170-7690

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Costimulatory activity of inactivated influenza virus in response of human peripheral blood mononuclear cells to phytohemagglutinin A and anti-CD3 antibody. Author(s): Pathology Institute, Sourasky Tel-Aviv Medical Center, Israel. Source: Eisenthal, A Marder, O Gelfend, A Skornick, Y Lifschitz Mercer, B ViralImmunol. 1998; 11(3): 137-45 0882-8245

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Cross-protection among lethal H5N2 influenza viruses induced by DNA vaccine to the hemagglutinin. Source: Kodihalli, S. Haynes, J.R. Robinson, H.L. Webster, R.G. J-virol. Washington, D.C. : American Society for Microbiology. May 1997. volume 71 (5) page 3391-3396. 0022538X

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Current strategies for management of influenza in the elderly population. Author(s): Department of Medicine, Glennan Center for Geriatrics and Gerontology, Eastern Virginia Medical School, Norfolk, VA, 23501, USA. [email protected] Source: Gravenstein, S Davidson, H E Clin-Infect-Dis. 2002 September 15; 35(6): 729-37 1537-6591

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Do neuraminidase inhibitors prevent influenza? Author(s): Canadian Coordinating Office for Health Technology Assessment. Source: Husereau, D R Issues-Emerg-Health-Technol. 2001 November; (27): 1-4 14886324

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Effect of a complete nutritional supplement on antibody response to influenza vaccine in elderly people. Author(s): Department of Clinical Nutrition and Therapeutic Diets, Numico Research B.V., Wageningen, The Netherlands. [email protected] Source: Wouters Wesseling, W Rozendaal, M Snijder, M Graus, Y Rimmelzwaan, G De Groot, L Bindels, J J-Gerontol-A-Biol-Sci-Med-Sci. 2002 September; 57(9): M563-6 10795006

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Effect of immobilization, cold and cold-restraint stress on liver monooxygenase activity and lipid peroxidation of influenza virus-infected mice. Author(s): Department of Medical Physics and Biophysics, Medical University, 2 Zdrave Str., Sofia 1431, Bulgaria. [email protected] Source: Mileva, M Bakalova, R Tancheva, L Galabov, S Arch-Toxicol. 2002 March; 76(2): 96-103 0340-5761

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Effect of oral application of an immunomodulating plant extract on Influenza virus type A infection in mice. Author(s): Schaper & Brummer GmbH & Co. KG, Research and Development Department, Salzgitter, Germany. [email protected] Source: Bodinet, C Mentel, R Wegner, U Lindequist, U Teuscher, E Freudenstein, J Planta-Med. 2002 October; 68(10): 896-900 0032-0943

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Effect of vitamin E supplementation on lipid peroxidation in blood and lung of influenza virus infected mice. Author(s): Department of Medical Physics and Biophysics, Medical University, Sofia, Bulgaria. Source: Mileva, M Bakalova, R Tancheva, L Galabov, A Ribarov, S Comp-ImmunolMicrobiol-Infect-Dis. 2002 January; 25(1): 1-11 0147-9571

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Effects of zinc supplementation on the immune system and on antibody response to multivalent influenza vaccine in hemodialysis patients. Author(s): Department of Internal Medicine, Medical School of Istanbul, Turkey.

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Source: Turk, S Bozfakioglu, S Ecder, S T Kahraman, T Gurel, N Erkoc, R Aysuna, N Turkmen, A Bekiroglu, N Ark, E Int-J-Artif-Organs. 1998 May; 21(5): 274-8 0391-3988 •

Epidemiology and pathogenesis of influenza. Author(s): Enteric and Respiratory Virus Laboratory, London, UK. [email protected] Source: Zambon, M C J-Antimicrob-Chemother. 1999 November; 44 Suppl B3-9 03057453

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Evolution of influenza A virus nucleoprotein genes: implications for the origins of H1N1 human and classical swine viruses. Source: Gorman, O.T. Bean, W.J. Kawaoka, Y. Donatelli, I. Guo, Y. Webster, R.G. J-Virol. Washington, D.C. : American Society for Microbiology. July 1991. volume 65 (7) page 3704-3714. 0022-538X

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Evolutionary pathways of N2 neuraminidases of swine and human influenza A viruses: origin of the neuraminidase genes of two reassortants (H1N2) isolated from pigs. Source: Nerome, K. Kanegae, Y. Yoshioka, Y. Itamura, S. Ishida, M. Gojobori, T. Oya, A. J-Gen-Virol. Reading : Society for General Microbiology. March 1991. volume 72 (pt.3) page 693-698. 0022-1317

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Evolutionary pattern of the H3 haemagglutinin of equine influenza viruses: multiple evolutionary lineages and frozen replication. Source: Endo, A. Pecoraro, R. Sugita, S. Nerome, K. Arch-Virol. Wien : Springer-Verlag. 1992. volume 123 (1/2) page 73-87. 0304-8608

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Exercise and psychosocial factors modulate immunity to influenza vaccine in elderly individuals. Author(s): Department of Health and Human Performance, Iowa State University, Ames 50011, USA. [email protected] Source: Kohut, M L Cooper, M M Nickolaus, M S Russell, D R Cunnick, J E J-GerontolA-Biol-Sci-Med-Sci. 2002 September; 57(9): M557-62 1079-5006

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Fatty acids on the A/USSR/77 influenza virus hemagglutinin facilitate the transition from hemifusion to fusion pore formation. Author(s): Department of Microbiology, Kawasaki Medical School, Kurashiki, Okayama 701-0192, Japan. Source: Sakai, Tatsuya Ohuchi, Reiko Ohuchi, Masanobu J-Virol. 2002 May; 76(9): 460311 0022-538X

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Genetic characterisation of an influenza A virus of unusual subtype (H1N7) isolated from pigs in England. Source: Brown, I.H. Hill, M.L. Harris, P.A. Alexander, D.J. McCauley, J.W. Arch-virol. Wien, Austria : Springer-Verlag. 1997. volume 142 (5) page 1045-1050. 0304-8608

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Health behavior associated with influenza vaccination among healthcare workers in long-term-care facilities. Author(s): Field Epidemiology Training Program, Population and Public Health Branch, Health Canada, Ottawa, Ontario. Source: Manuel, D G Henry, B Hockin, J Naus, M Infect-Control-Hosp-Epidemiol. 2002 October; 23(10): 609-14 0899-823X

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Hemagglutinin mutations related to antigenic variation in H1 swine influenza viruses. Source: Luoh, S.M. McGregor, M.W. Hinshaw, V.S. J-Virol. Washington, D.C. : American Society for Microbiology. February 1992. volume 66 (2) page 1066-1073. 0022538X

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Henoch-Schonlein purpura with antiphospholipid antibodies following an influenza vaccination. Author(s): Department of Pediatrics, Niigata City General Hospital, 2-6-1 Shichikuyama, Niigata 950-8739, Japan. [email protected] Source: Watanabe, T Onda, H Pediatr-Nephrol. 2001 May; 16(5): 458-9; discussion 460-2 0931-041X

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Identification and characterisation of an H7N3 influenza A virus from an outbreak of virulent avian influenza in Victoria. Source: Selleck, P.W. Gleeson, L.J. Hooper, P.T. Westbury, H.A. Hansson, E. Aust-vet-j. Brunswick, Vic. : Australian Veterinary Association, 1927-. April. 1997. volume 75 (4) page 289-292. 0005-0423

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Impact of zanamivir treatment on productivity, health status and healthcare resource use in patients with influenza. Zanamivir Study Group. Author(s): Department of Medical Microbiology, University of Manitoba, Winnipeg, Canada. Source: Aoki, F Y Fleming, D M Griffin, A D Lacey, L A Edmundson, S Pharmacoeconomics. 2000 February; 17(2): 187-95 1170-7690

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In vivo antiinfluenza virus activity of Kampo medicine Sho-seiryu-to through mucosal immune system. Author(s): Oriental Medicine Research Center, Kitasato Institute, Tokyo, Japan. Source: Yamada, H Nagai, T Methods-Find-Exp-Clin-Pharmacol. 1998 April; 20(3): 18592 0379-0355

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Influenza in the acute hospital setting. Author(s): University of Virginia Health System, Charlottesville, VA 22908, USA. Source: Salgado, Cassandra D Farr, Barry M Hall, Keri K Hayden, Frederick G LancetInfect-Dis. 2002 March; 2(3): 145-55 1473-3099

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Influenza vaccine, anti-influenza drugs, and rapid diagnosis in Japan. Author(s): Department of Pediatrics, Nippon Kokan Hospital, 1-2-1 Kokandori, Kawasaki-ku, Kawasaki, Kanagawa 210-0852, Japan. [email protected] Source: Sugaya, N J-Infect-Chemother. 2000 June; 6(2): 77-80 1341-321X

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Influenza virus hemagglutinin stimulates the protein kinase C activity of human polymorphonuclear leucocytes. Author(s): Virology Research Center, Institut Armand-Frappier, Laval, Quebec, Canada. Source: Arora, D J Gasse, N Arch-Virol. 1998; 143(10): 2029-37 0304-8608

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Influenza. Author(s): Centers for Disease Control and Prevention, National Center for Infectious Diseases, Division of Viral and Rickettsial Diseases, Influenza Branch, Atlanta, Georgia, USA. Source: Uyeki, T Winquist, A Clin-Evid. 2002 June; (7): 645-51 1462-3846

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Inhibition of influenza virus infection by tea polyphenols. Source: Shimamura, T. ACS-symp-ser. Washington, D.C. : American Chemical Society, 1974-. 1994. (547) page 101-104. 0097-6156

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Inhibition of nuclear export of ribonucleoprotein complexes of influenza virus by leptomycin B. Author(s): Laboratory of Molecular Medical Engineering, Department of Biological Information, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, 4259 Nagatsuta, Midori-ku, 226-8501, Yokohama, Japan. Source: Watanabe, K Takizawa, N Katoh, M Hoshida, K Kobayashi, N Nagata, K VirusRes. 2001 September; 77(1): 31-42 0168-1702

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Large outbreak of swine influenza in southern Japan caused by reassortant (H1N2) influenza viruses: its epizootic background and characterization of the causative viruses. Source: Ouchi, A. Nerome, K. Kanegae, Y. Ishida, M. Nerome, R. Hayashi, K. Hashimoto, T. Kaji, M. Kaji, Y. Inaba, Y. J-gen-virol. Reading : Society for General Microbiology. August 1996. volume 77 (pt.8) page 1751-1759. 0022-1317

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Measures for control of influenza. Author(s): Department of Microbiology and Immunology, Baylor College of Medicine, Houston, Texas, USA. Source: Couch, R B Pharmacoeconomics. 1999; 16 Suppl 141-5 1170-7690

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Molecular evidence for a role of domestic ducks in the introduction of avian H3 influenza viruses to pigs in southern China, where the A/Hong Kong/68 (H3N2) strain emerged. Source: Yasuda, J. Shortridge, K.F. Shimizu, Y. Kida, H. J-Gen-Virol. Reading : Society for General Microbiology. August 1991. volume 72 (pt.8) page 2007-2010. 0022-1317

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Molecular pathotyping of two avian influenza viruses isolated during the Victoria 1976 outbreak. Source: Bashiruddin, J.B. Gould, A.R. Westbury, H.A. Aust-Vet-J. Brunswick, Victoria : Australian Veterinary Association. June 1992. volume 69 (6) page 140-142. 0005-0423

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Neuraminidase inhibitors and relief of influenza symptoms. Source: Lemon, M Meade, F S-D-J-Med. 2000 March; 53(3): 99-100 0038-3317

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Nucleo-cytoplasmic localization of influenza virus nucleoprotein depends on cell density and phosphorylation. Author(s): Department of Cell Biology, Yale University School of Medicine, New Haven, CT, USA. Source: Bui, Matthew Myers, Julie E Whittaker, Gary R Virus-Res. 2002 March 20; 84(12): 37-44 0168-1702

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Pinellic acid from the tuber of Pinellia ternata Breitenbach as an effective oral adjuvant for nasal influenza vaccine. Author(s): Oriental Medicine Research Center, The Kitasato Institute, Tokyo, Japan. Source: Nagai, T Kiyohara, H Munakata, K Shirahata, T Sunazuka, T Harigaya, Y Yamada, H Int-Immunopharmacol. 2002 July; 2(8): 1183-93 1567-5769

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Prevention and control of influenza. Recommendations of the Advisory Committee on Immunization Practices (ACIP). Author(s): Division of Viral and Rickettsial Diseases, National Center for Infectious Diseases, USA. Source: Bridges, Carolyn B Fukuda, Keiji Uyeki, Timothy M Cox, Nancy J Singleton, James A MMWR-Recomm-Repage 2002 April 12; 51(RR-3): 1-31 1057-5987

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Randomized, placebo-controlled studies of inhaled zanamivir in the treatment of influenza A and B: pooled efficacy analysis. Author(s): Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, USA. [email protected] Source: Monto, A S Webster, A Keene, O J-Antimicrob-Chemother. 1999 November; 44 Suppl B23-9 0305-7453

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Rapid pharmacotherapeutic intervention for an influenza A outbreak in the Canadian Arctic: lessons from the Sanikiluaq experience. Author(s): Department of Medical Microbiology, University of Manitoba, Canada. [email protected] Source: Van Caeseele, P Macaulay, A Orr, P Aoki, F Martin, B Int-J-Circumpolar-Health. 2001 November; 60(4): 640-8 1239-9736

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Recent H3N2 swine influenza virus with haemagglutinin and nucleoprotein genes similar to 1975 human strains. Source: Bikour, M.H. Frost, E.H. Deslandes, S. Talbot, B. Weber, J.M. Elazhary, Y. J-genvirol. Reading : Society for General Microbiology. March 1995. volume 76 (pt.3) page 697-703. 0022-1317

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Relationship between the response to influenza vaccination and the nutritional status in institutionalized elderly subjects. Author(s): Department of Medicine, Faculty of Medicine, University of Sherbrooke, Quebec, Canada. [email protected] Source: Fulop, T Wagner, J R Khalil, A Weber, J Trottier, L Payette, H J-Gerontol-A-BiolSci-Med-Sci. 1999 February; 54(2): M59-64 1079-5006

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Role of G protein and protein kinase signalling in influenza virus budding in MDCK cells. Author(s): Department of Microbiology, Immunology and Molecular Genetics, Jonsson Comprehensive Cancer Center (JCCC), UCLA School of Medicine, Los Angeles, CA 90095-1747, USA. Source: Hui, E K Nayak, D P J-Gen-Virol. 2002 December; 83(Pt 12): 3055-66 0022-1317

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Safety and efficacy of the neuraminidase inhibitor zanamivir in treating influenza virus infection in adults: results from Japan. GG167 Group. Author(s): Nagasaki University, Japan. [email protected] Source: Matsumoto, K Ogawa, N Nerome, K Numazaki, Y Kawakami, Y Shirato, K Arakawa, M Kudoh, S Shimokata, K Nakajima, S Yamakido, M Kashiwagi, S Nagatake, T Antivir-Ther. 1999; 4(2): 61-8 1359-6535

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Stachyflin and acetylstachyflin, novel anti-influenza A virus substances, produced by Stachybotrys sp. RF-7260. I. Isolation, structure elucidation and biological activities. Author(s): Shionogi Research Laboratories, Shionogi & Co, Ltd, Osaka, Japan. [email protected] Source: Minagawa, Kazuyuki Kouzuki, Shuichi Yoshimoto, June Kawamura, Yoshimi Tani, Hiroyoshi Iwata, Tatsuo Terui, Yoshihiro Nakai, Hiroshi Yagi, Shigenori Hattori, Naohiko Fujiwara, Tamio Kamigauchi, Toshiyuki J-Antibiot-(Tokyo). 2002 February; 55(2): 155-64 0021-8820

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Synthesis and membrane binding properties of a lipopeptide fragment from influenza virus a hemagglutinin. Author(s): Universitat Karlsruhe, Institut fur Organische Chemie Richard-WillstatterAllee 2 76128 Karlsruhe, Germany. Source: Eisele, F Kuhlmann, J Waldmann, H Chemistry. 2002 August 2; 8(15): 3362-76 0947-6539

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The hemagglutinins of duck and human H1 influenza viruses differ in sequence conservation and in glycosylation. Source: Inkster, M.D. Hinshaw, V.S. Schulze, I.T. J-Virol. Washington, D.C. : American Society for Microbiology. December 1993. volume 67 (12) page 7436-7443. 0022-538X

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The management of influenza in people of working age. Author(s): Birmingham Research Unit of the Royal College of General Practitioners, 54 Lordswood Road, Birmingham B17 9DB, UK. [email protected] Source: Fleming, D M Occup-Med-(Lond). 2002 August; 52(5): 259-63 0962-7480

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The roles of IL-1, IL-6, and TNFalpha in the feeding responses to endotoxin and influenza virus infection in mice. Author(s): Department of Pharmacology and Therapeutics, Louisiana State University Medical Center, Shreveport, Louisiana 71103, USA. Source: Swiergiel, A H Dunn, A J Brain-Behav-Immun. 1999 September; 13(3): 252-65 0889-1591

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Vaccinia virus expression and sequence of an avian influenza nucleoprotein gene: potential use in diagnosis. Source: Harley, V.R. Hudson, P.J. Coupar, B.E.H. Selleck, P.W. Westbury, H. Boyle, D.B. Arch-Virol. Wien : Springer-Verlag. 1990. volume 113 (1/2) page 133-141. 0304-8608

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Zanamivir (Relenza )--a new treatment for influenza. Source: MacConnachie A, M Intensive-Crit-Care-Nurs. 1999 December; 15(6): 369-70 0964-3397

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Zanamivir for the treatment of influenza in adults: a systematic review and economic evaluation. Author(s): Department of Public Health and Epidemiology, University of Birmingham, UK. Source: Burls, A Clark, W Stewart, T Preston, C Bryan, S Jefferson, T Fry Smith, A Health-Technol-Assess. 2002; 6(9): 1-87 1366-5278

Federal Resources on Nutrition In addition to the IBIDS, the United States Department of Health and Human Services (HHS) and the United States Department of Agriculture (USDA) provide many sources of information on general nutrition and health. Recommended resources include: •

healthfinder®, HHS’s gateway to health information, including diet and nutrition: http://www.healthfinder.gov/scripts/SearchContext.asp?topic=238&page=0

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The United States Department of Agriculture’s Web site dedicated to nutrition information: www.nutrition.gov

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The Food and Drug Administration’s Web site for federal food safety information: www.foodsafety.gov

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The National Action Plan on Overweight and Obesity sponsored by the United States Surgeon General: http://www.surgeongeneral.gov/topics/obesity/

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The Center for Food Safety and Applied Nutrition has an Internet site sponsored by the Food and Drug Administration and the Department of Health and Human Services: http://vm.cfsan.fda.gov/

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Center for Nutrition Policy and Promotion sponsored by the United States Department of Agriculture: http://www.usda.gov/cnpp/

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Food and Nutrition Information Center, National Agricultural Library sponsored by the United States Department of Agriculture: http://www.nal.usda.gov/fnic/

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Food and Nutrition Service sponsored by the United States Department of Agriculture: http://www.fns.usda.gov/fns/

Additional Web Resources A number of additional Web sites offer encyclopedic information covering food and nutrition. The following is a representative sample: •

AOL: http://search.aol.com/cat.adp?id=174&layer=&from=subcats

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Family Village: http://www.familyvillage.wisc.edu/med_nutrition.html

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Google: http://directory.google.com/Top/Health/Nutrition/

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Healthnotes: http://www.healthnotes.com/

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Open Directory Project: http://dmoz.org/Health/Nutrition/

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Yahoo.com: http://dir.yahoo.com/Health/Nutrition/

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WebMD®Health: http://my.webmd.com/nutrition

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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html

The following is a specific Web list relating to influenza; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: •

Vitamins Vitamin C Source: Healthnotes, Inc.; www.healthnotes.com

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Food and Diet Fasting Diet Source: Healthnotes, Inc.; www.healthnotes.com Garlic Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca Refined Sweeteners Source: Healthnotes, Inc.; www.healthnotes.com

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CHAPTER 3. ALTERNATIVE MEDICINE AND INFLUENZA Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to influenza. At the conclusion of this chapter, we will provide additional sources.

National Center for Complementary and Alternative Medicine The National Center for Complementary and Alternative Medicine (NCCAM) of the National Institutes of Health (http://nccam.nih.gov/) has created a link to the National Library of Medicine’s databases to facilitate research for articles that specifically relate to influenza and complementary medicine. To search the database, go to the following Web site: http://www.nlm.nih.gov/nccam/camonpubmed.html. Select “CAM on PubMed.” Enter “influenza” (or synonyms) into the search box. Click “Go.” The following references provide information on particular aspects of complementary and alternative medicine that are related to influenza: •

A controlled evaluation of a homoeopathic preparation in the treatment of influenzalike syndromes. Author(s): Ferley JP, Zmirou D, D'Adhemar D, Balducci F. Source: British Journal of Clinical Pharmacology. 1989 March; 27(3): 329-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2655683&dopt=Abstract

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A homeopathic nosode for influenza-like syndromes. Author(s): de Lange de Klerk E. Source: Forschende Komplementarmedizin. 1999 February; 6(1): 31; Discussion 31-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10336310&dopt=Abstract

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A randomized trial in the prevention of influenza-like syndromes by homeopathic management. Author(s): Attena F, Toscano G, Agozzino E, Del Giudice N.

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Source: Revue D'epidemiologie Et De Sante Publique. 1995; 43(4): 380-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7667544&dopt=Abstract •

Ability to activate the alternative complement pathway acquired by human and guinea-pig erythrocytes after contact with influenza virus. Author(s): Lambre C, Thibon M. Source: Ann Immunol (Paris). 1980 March-April; 131C(2): 213-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7416718&dopt=Abstract

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Additional inhibitory effect of tea extract on the growth of influenza A and B viruses in MDCK cells. Author(s): Imanishi N, Tuji Y, Katada Y, Maruhashi M, Konosu S, Mantani N, Terasawa K, Ochiai H. Source: Microbiology and Immunology. 2002; 46(7): 491-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12222936&dopt=Abstract

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Administration of isoferulic acid improved the survival rate of lethal influenza virus pneumonia in mice. Author(s): Sakai S, Ochiai H, Mantani N, Kogure T, Shibahara N, Terasawa K. Source: Mediators of Inflammation. 2001 April; 10(2): 93-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11405556&dopt=Abstract

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Advances in the Diagnosis and Management of Influenza. Author(s): Jefferson T. Source: Current Infectious Disease Reports. 2002 June; 4(3): 206-210. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12015912&dopt=Abstract

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Alkaline-extracted influenza subunit vaccine. Author(s): Eckert EA. Source: Infection and Immunity. 1976 December; 14(6): 1302-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=826484&dopt=Abstract

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An experimental study of the inhibition effect of pang qi ju on influenza viruses. Author(s): Deng RL, Zhu JY, Xu HT, Chen XZ, Zhang RJ, Liu SJ, Xie JM, Ye SY. Source: Acta Acad Med Wuhan. 1984; 4(4): 245-7. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6098885&dopt=Abstract

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Anti-influenza virus activity of crude extract of Ribes nigrum L. Author(s): Knox YM, Suzutani T, Yosida I, Azuma M. Source: Phytotherapy Research : Ptr. 2003 February; 17(2): 120-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12601672&dopt=Abstract

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Antioxidant properties of rimantadine in influenza virus infected mice and in some model systems. Author(s): Mileva M, Hadjimitova V, Tantcheva L, Traykov T, Galabov AS, Savov V, Ribarov S. Source: Z Naturforsch [c]. 2000 September-October; 55(9-10): 824-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11098838&dopt=Abstract

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Antipyretic activity of cinnamyl derivatives and related compounds in influenza virus-infected mice. Author(s): Kurokawa M, Kumeda CA, Yamamura J, Kamiyama T, Shiraki K. Source: European Journal of Pharmacology. 1998 May 1; 348(1): 45-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9650830&dopt=Abstract

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Antipyretic activity of gingyo-san, a traditional medicine, in influenza virus-infected mice. Author(s): Kurokawa M, Yamamura J, Li Z, Sato H, Hitomi N, Tatsumi Y, Shiraki K. Source: Chemical & Pharmaceutical Bulletin. 1998 September; 46(9): 1444-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9775439&dopt=Abstract

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Antiviral activity of Flos verbasci infusion against influenza and Herpes simplex viruses. Author(s): Zgorniak-Nowosielska I, Grzybek J, Manolova N, Serkedjieva J, Zawilinska B. Source: Arch Immunol Ther Exp (Warsz). 1991; 39(1-2): 103-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1666504&dopt=Abstract

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Antiviral effect of gingyo-san, a traditional Chinese herbal medicine, on influenza A2 virus infection in mice. Author(s): Kobayashi M, Davis SM, Utsunomiya T, Pollard RB, Suzuki F. Source: The American Journal of Chinese Medicine. 1999; 27(1): 53-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10354817&dopt=Abstract

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Antiviral effect of Sanicula europaea L. leaves extract on influenza virus-infected cells. Author(s): Turan K, Nagata K, Kuru A. Source: Biochemical and Biophysical Research Communications. 1996 August 5; 225(1): 22-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8769089&dopt=Abstract

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Antiviral properties of garlic: in vitro effects on influenza B, herpes simplex and coxsackie viruses. Author(s): Tsai Y, Cole LL, Davis LE, Lockwood SJ, Simmons V, Wild GC.

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Anti-virus action of some Bulgarian plants on reproduction of the influenza virus. Author(s): Manolova N, Nikolov P, Bakalova D, Gagov I. Source: Dokl Bulg Acad Nauk. 1969; 22(5): 591-3. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5396355&dopt=Abstract

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Association of a ribonuclease with the purified influenza virus. Author(s): Arora DJ, Pavilanis V, Soula A, Robert P, Croteau G. Source: Canadian Journal of Microbiology. 1976 January; 22(1): 57-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=814984&dopt=Abstract

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Binding of human collectins (SP-A and MBP) to influenza virus. Author(s): Malhotra R, Haurum JS, Thiel S, Sim RB. Source: The Biochemical Journal. 1994 December 1; 304 ( Pt 2): 455-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7998980&dopt=Abstract

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Botanical sources of influenza inhibitors. Author(s): Cochran KW, Nishikawa T, Beneke ES. Source: Antimicrobial Agents Chemother. 1966; 6: 515-20. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5985281&dopt=Abstract

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Camptothecin: an inhibitor of influenza virus replication. Author(s): Kelly DC, Avery RJ, Dimmock NJ. Source: The Journal of General Virology. 1974 December; 25(3): 427-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4475096&dopt=Abstract

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Chemotherapy of influenza. Author(s): Esanu V. Source: Virologie. 1982 October-December; 33(4): 283-302. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6761956&dopt=Abstract

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Combined antiinfluenza virus activity of Flos verbasci infusion and amantadine derivatives. Author(s): Serkedjieva J. Source: Phytotherapy Research : Ptr. 2000 November; 14(7): 571-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11054856&dopt=Abstract

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Combined effect of selected antiviral substances of natural and synthetic origin. II. Anti-influenza activity of a combination of a polyphenolic complex isolated from

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Geranium sanguineum L. and rimantadine in vivo. Author(s): Gegova G, Manolova N, Serkedzhieva Iu, Maksimova V, Uzunov S, Dzeguze D, Indulen M. Source: Acta Microbiol Bulg. 1993; 30: 37-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8285131&dopt=Abstract •

Complete metal ion requirement of influenza virus N1 neuraminidases. Brief report. Author(s): Carroll SM, Paulson JC. Source: Archives of Virology. 1982; 71(3): 273-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6808973&dopt=Abstract

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Current strategies for management of influenza in the elderly population. Author(s): Gravenstein S, Davidson HE. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2002 September 15; 35(6): 729-37. Epub 2002 August 20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12203171&dopt=Abstract

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Detection of influenza virus resistance to neuraminidase inhibitors by an enzyme inhibition assay. Author(s): Gubareva LV, Webster RG, Hayden FG. Source: Antiviral Research. 2002 January; 53(1): 47-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11684315&dopt=Abstract

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Effect of a complete nutritional supplement on antibody response to influenza vaccine in elderly people. Author(s): Wouters-Wesseling W, Rozendaal M, Snijder M, Graus Y, Rimmelzwaan G, De Groot L, Bindels J. Source: The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences. 2002 September; 57(9): M563-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12196491&dopt=Abstract

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Effect of Ca++ on the stability of influenza virus neuraminidase. Author(s): Baker NJ, Gandhi SS. Source: Archives of Virology. 1976; 52(1-2): 7-18. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=63277&dopt=Abstract

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Effect of Hochu-ekki-to (TJ-41), a Japanese herbal medicine, on the survival of mice infected with influenza virus. Author(s): Mori K, Kido T, Daikuhara H, Sakakibara I, Sakata T, Shimizu K, Amagaya S, Sasaki H, Komatsu Y. Source: Antiviral Research. 1999 December 15; 44(2): 103-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10669260&dopt=Abstract

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Effect of interleukin-12 level augmented by Kakkon-to, a herbal medicine, on the early stage of influenza infection in mice. Author(s): Kurokawa M, Tsurita M, Brown J, Fukuda Y, Shiraki K. Source: Antiviral Research. 2002 November; 56(2): 183-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12367723&dopt=Abstract

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Effect of long-term dietary antioxidant supplementation on influenza virus infection. Author(s): Han SN, Meydani M, Wu D, Bender BS, Smith DE, Vina J, Cao G, Prior RL, Meydani SN. Source: The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences. 2000 October; 55(10): B496-503. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11034223&dopt=Abstract

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Effect of oral application of an immunomodulating plant extract on Influenza virus type A infection in mice. Author(s): Bodinet C, Mentel R, Wegner U, Lindequist U, Teuscher E, Freudenstein J. Source: Planta Medica. 2002 October; 68(10): 896-900. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12391552&dopt=Abstract

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Effect of vitamin E supplementation on lipid peroxidation in blood and lung of influenza virus infected mice. Author(s): Mileva M, Bakalova R, Tancheva L, Galabov A, Ribarov S. Source: Comparative Immunology, Microbiology and Infectious Diseases. 2002 January; 25(1): 1-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11831742&dopt=Abstract

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Effect of zinc or zinc plus arginine supplementation on antibody titre and lymphocyte subsets after influenza vaccination in elderly subjects: a randomized controlled trial. Author(s): Provinciali M, Montenovo A, Di Stefano G, Colombo M, Daghetta L, Cairati M, Veroni C, Cassino R, Della Torre F, Fabris N. Source: Age and Ageing. 1998 November; 27(6): 715-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10408666&dopt=Abstract

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Effects of alprazolam on influenza virus infection in stressed mice. Author(s): Freire-Garabal M, Balboa JL, Fernandez-Rial JC, Nunez MJ, Belmonte A. Source: Pharmacology, Biochemistry, and Behavior. 1993 September; 46(1): 167-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8255908&dopt=Abstract

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Effects of zinc supplementation on the immune system and on antibody response to multivalent influenza vaccine in hemodialysis patients. Author(s): Turk S, Bozfakioglu S, Ecder ST, Kahraman T, Gurel N, Erkoc R, Aysuna N, Turkmen A, Bekiroglu N, Ark E.

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Efficacy and safety of the standardised Ginseng extract G115 for potentiating vaccination against the influenza syndrome and protection against the common cold [corrected] Author(s): Scaglione F, Cattaneo G, Alessandria M, Cogo R. Source: Drugs Exp Clin Res. 1996; 22(2): 65-72. Erratum In: Drugs Exp Clin Res 1996; 22(6): 338. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8879982&dopt=Abstract

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Enzymological characteristics of avian influenza A virus neuraminidase. Author(s): Kiyotani K, Takei N, Senoo M, Takao S, Otsuki K, Tsubokura M, Yoshida T. Source: Microbiology and Immunology. 1987; 31(11): 1131-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2451112&dopt=Abstract

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Enzymological heterogeneity of influenza B virus neuraminidase demonstrated by the fluorometric assay method. Author(s): Kiyotani K, Takei N, Matsuo Y. Source: Zentralbl Bakteriol Mikrobiol Hyg [a]. 1985 October; 260(2): 273-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2867656&dopt=Abstract

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Evaluation of the treatment of influenza with bioflavonoids and antibiotics. Author(s): LECCA GG. Source: Antibiot Med Clin Ther. 1958 September; 5(9): 562-6. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13571960&dopt=Abstract

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Factors influencing adherence of Staphylococcus aureus to influenza A virus-infected cell cultures. Author(s): Davison VE, Sanford BA. Source: Infection and Immunity. 1982 September; 37(3): 946-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6813268&dopt=Abstract

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Flavanone glycosides from Citrus junos and their anti-influenza virus activity. Author(s): Kim HK, Jeon WK, Ko BS. Source: Planta Medica. 2001 August; 67(6): 548-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11509977&dopt=Abstract

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Fusion of membrane vesicles bearing only the influenza hemagglutinin with erythrocytes, living cultured cells, and liposomes. Author(s): Lapidot M, Nussbaum O, Loyter A.

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Glycyrrhizin, an active component of licorice roots, reduces morbidity and mortality of mice infected with lethal doses of influenza virus. Author(s): Utsunomiya T, Kobayashi M, Pollard RB, Suzuki F. Source: Antimicrobial Agents and Chemotherapy. 1997 March; 41(3): 551-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9055991&dopt=Abstract

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Health behavior associated with influenza vaccination among healthcare workers in long-term-care facilities. Author(s): Manuel DG, Henry B, Hockin J, Naus M. Source: Infection Control and Hospital Epidemiology : the Official Journal of the Society of Hospital Epidemiologists of America. 2002 October; 23(10): 609-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12400892&dopt=Abstract

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Hemagglutinating and sialidase activities of subpopulations of influenza A viruses. Author(s): Pinto AM, Cabral MC, Couceiro JN. Source: Brazilian Journal of Medical and Biological Research = Revista Brasileira De Pesquisas Medicas E Biologicas / Sociedade Brasileira De Biofisica. [et Al.]. 1994 May; 27(5): 1141-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8000335&dopt=Abstract

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Homeopathic treatment of influenza. Author(s): SAYRES GA. Source: Hahnemannian. 1963 March; 98: 8-10. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13976453&dopt=Abstract

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Homoeopathic Oscillococcinum for preventing and treating influenza and influenzalike syndromes. Author(s): Vickers AJ, Smith C. Source: Cochrane Database Syst Rev. 2000; (2): Cd001957. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10796675&dopt=Abstract

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Human mannan-binding lectin inhibits the infection of influenza A virus without complement. Author(s): Kase T, Suzuki Y, Kawai T, Sakamoto T, Ohtani K, Eda S, Maeda A, Okuno Y, Kurimura T, Wakamiya N. Source: Immunology. 1999 July; 97(3): 385-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10447758&dopt=Abstract

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Hyperbaric oxygen therapy (HBOT) in a child with suspected influenza-associated encephalopathy. Author(s): Dohgomori H, Arikawa K, Kanmura Y. Source: Canadian Journal of Anaesthesia = Journal Canadien D'anesthesie. 2003 February; 50(2): 204. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12560321&dopt=Abstract

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Immunomodulatory action of propolis. II. Effect of water-soluble fraction on influenza infection in mice. Author(s): Neychev H, Dimov V, Vuleva V, Shirova L, Slavcheva E, Gegova G, Manolova N, Bankova V. Source: Acta Microbiol Bulg. 1988; 23: 58-62. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3247873&dopt=Abstract

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In vitro anti-influenza virus activity of a plant preparation from Geranium sanguineum L. Author(s): Serkedjieva J, Hay AJ. Source: Antiviral Research. 1998 February; 37(2): 121-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9588844&dopt=Abstract

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In vitro anti-influenza virus activity of isoquinoline alkaloids from thalictrum species. Author(s): Serkedjieva J, Velcheva M. Source: Planta Medica. 2003 February; 69(2): 153-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12624821&dopt=Abstract

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In vivo anti-influenza virus activity of kampo (Japanese herbal) medicine “shoseiryu-to” and its mode of action. Author(s): Nagai T, Yamada H. Source: International Journal of Immunopharmacology. 1994 August; 16(8): 605-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7527377&dopt=Abstract

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In vivo anti-influenza virus activity of Kampo (Japanese herbal) medicine “Shoseiryu-to”--effects on aged mice, against subtypes of a viruses and B virus, and therapeutic effect. Author(s): Nagai T, Urata M, Yamada H. Source: Immunopharmacology and Immunotoxicology. 1996 May; 18(2): 193-208. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8771367&dopt=Abstract

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In vivo anti-influenza virus activity of Kampo (Japanese herbal) medicine “shoseiryu-to”--stimulation of mucosal immune system and effect on allergic pulmonary inflammation model mice. Author(s): Nagai T, Yamada H.

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In vivo antiinfluenza virus activity of Kampo medicine Sho-seiryu-to through mucosal immune system. Author(s): Yamada H, Nagai T. Source: Methods Find Exp Clin Pharmacol. 1998 April; 20(3): 185-92. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9646280&dopt=Abstract

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In vivo anti-influenza virus activity of plant flavonoids possessing inhibitory activity for influenza virus sialidase. Author(s): Nagai T, Miyaichi Y, Tomimori T, Suzuki Y, Yamada H. Source: Antiviral Research. 1992 September; 19(3): 207-17. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1444327&dopt=Abstract

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Influenza and influenzosis. Author(s): GUTMAN W. Source: J Am Inst Homeopath. 1961 November-December; 54: 164-5. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13903191&dopt=Abstract

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Influenza and its osteopathic management. 1937. Author(s): Ward EA. Source: J Am Osteopath Assoc. 2000 May; 100(5): 325-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10850020&dopt=Abstract

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Influenza vaccination in chronic hemodialysis patients. The effect of zinc supplementation. Author(s): Grekas D, Alivanis P, Kotzadamis N, Kiriazopoulou V, Pyrpasopoulos M, Tourkantonis A. Source: Renal Failure. 1992; 14(4): 575-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1462010&dopt=Abstract

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Influenza virus can enter and infect cells in the absence of clathrin-mediated endocytosis. Author(s): Sieczkarski SB, Whittaker GR. Source: Journal of Virology. 2002 October; 76(20): 10455-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12239322&dopt=Abstract

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Inhibition of glycoprotein oligosaccharide processing in vitro and in influenza-virusinfected cells by alpha-D-mannopyranosylmethyl-p-nitrophenyltriazene. Author(s): McDowell W, Tlusty A, Rott R, BeMiller JN, Bohn JA, Meyers RW, Schwarz RT.

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Inhibition of influenza virus infection by pine cone antitumor substances. Author(s): Nagata K, Sakagami H, Harada H, Nonoyama M, Ishihama A, Konno K. Source: Antiviral Research. 1990 January; 13(1): 11-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2334167&dopt=Abstract

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Inhibition of influenza virus protein synthesis by a plant preparation from Geranium sanguineum L. Author(s): Serkedjieva J. Source: Acta Virol. 1995 February; 39(1): 5-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7572469&dopt=Abstract

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Inhibition of influenza virus sialidase and anti-influenza virus activity by plant flavonoids. Author(s): Nagai T, Miyaichi Y, Tomimori T, Suzuki Y, Yamada H. Source: Chemical & Pharmaceutical Bulletin. 1990 May; 38(5): 1329-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2393958&dopt=Abstract

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Inhibition of several strains of influenza virus in vitro and reduction of symptoms by an elderberry extract (Sambucus nigra L.) during an outbreak of influenza B Panama. Author(s): Zakay-Rones Z, Varsano N, Zlotnik M, Manor O, Regev L, Schlesinger M, Mumcuoglu M. Source: Journal of Alternative and Complementary Medicine (New York, N.Y.). 1995 Winter; 1(4): 361-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9395631&dopt=Abstract

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Inhibition of synthesis of influenza virus proteins: evidence of two host-celldependent events during multiplication. Author(s): Minor PD, Dimmock NJ. Source: Virology. 1975 September; 67(1): 114-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=51536&dopt=Abstract

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Inhibition of the infectivity of influenza virus by tea polyphenols. Author(s): Nakayama M, Suzuki K, Toda M, Okubo S, Hara Y, Shimamura T. Source: Antiviral Research. 1993 August; 21(4): 289-99. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8215301&dopt=Abstract

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Inhibitors of influenza virus replication. Author(s): Schild GC, Oxford JS.

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Inhibitory effect of (+)-catechin on the growth of influenza A/PR/8 virus in MDCK cells. Author(s): Mantani N, Imanishi N, Kawamata H, Terasawa K, Ochiai H. Source: Planta Medica. 2001 April; 67(3): 240-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11345695&dopt=Abstract

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Inhibitory effect of Bergenia ligulata on influenza virus A. Author(s): Rajbhandari M, Wegner U, Schopke T, Lindequist U, Mentel R. Source: Pharmazie. 2003 April; 58(4): 268-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12749411&dopt=Abstract

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Inhibitory effect of Ephedrae herba, an oriental traditional medicine, on the growth of influenza A/PR/8 virus in MDCK cells. Author(s): Mantani N, Andoh T, Kawamata H, Terasawa K, Ochiai H. Source: Antiviral Research. 1999 December 31; 44(3): 193-200. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10651070&dopt=Abstract

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Inhibitory effect of ferulic acid and isoferulic acid on murine interleukin-8 production in response to influenza virus infections in vitro and in vivo. Author(s): Hirabayashi T, Ochiai H, Sakai S, Nakajima K, Terasawa K. Source: Planta Medica. 1995 June; 61(3): 221-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7617763&dopt=Abstract

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Maternal influenza infection causes marked behavioral and pharmacological changes in the offspring. Author(s): Shi L, Fatemi SH, Sidwell RW, Patterson PH. Source: The Journal of Neuroscience : the Official Journal of the Society for Neuroscience. 2003 January 1; 23(1): 297-302. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12514227&dopt=Abstract

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Microtubule-acting drugs lead to the nonpolarized delivery of the influenza hemagglutinin to the cell surface of polarized Madin-Darby canine kidney cells. Author(s): Rindler MJ, Ivanov IE, Sabatini DD. Source: The Journal of Cell Biology. 1987 February; 104(2): 231-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2879845&dopt=Abstract

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Minnesota director clarifies avian influenza inaccuracies. Author(s): Hartmann WL.

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Source: J Am Vet Med Assoc. 2003 January 1; 222(1): 22; Author Reply 22. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12523472&dopt=Abstract •

Mode of action of the anti-influenza virus activity of plant flavonoid, 5,7,4'trihydroxy-8-methoxyflavone, from the roots of Scutellaria baicalensis. Author(s): Nagai T, Moriguchi R, Suzuki Y, Tomimori T, Yamada H. Source: Antiviral Research. 1995 January; 26(1): 11-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7741518&dopt=Abstract

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Modulation by immunosuppressive agents of peripheral blood mononuclear cell responses to influenza A virus. Author(s): Gorse GJ, Kopp WC. Source: The Journal of Laboratory and Clinical Medicine. 1987 November; 110(5): 592601. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2444663&dopt=Abstract

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Neuraminidase activity of influenza virus-infected cells: localization and properties. Author(s): Orlova TG, Orlova NG. Source: Acta Virol. 1975 April; 19(2): 130-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=239558&dopt=Abstract

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One hundred thousand cases of influenza with a death rate of one-fortieth of that officially reported under conventional medical treatment. 1919. Author(s): Smith RK. Source: J Am Osteopath Assoc. 2000 May; 100(5): 320-3. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10850019&dopt=Abstract

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Osteopathic success in the treatment of influenza and pneumonia. 1919. Author(s): Riley GW. Source: J Am Osteopath Assoc. 2000 May; 100(5): 315-9. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10850018&dopt=Abstract

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Pinellic acid from the tuber of Pinellia ternata Breitenbach as an effective oral adjuvant for nasal influenza vaccine. Author(s): Nagai T, Kiyohara H, Munakata K, Shirahata T, Sunazuka T, Harigaya Y, Yamada H. Source: International Immunopharmacology. 2002 July; 2(8): 1183-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12349955&dopt=Abstract

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Plant polyphenolic complex inhibits the reproduction of influenza and herpes simplex viruses. Author(s): Serkedjieva J, Manolova N.

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Source: Basic Life Sci. 1992; 59: 705-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1329716&dopt=Abstract •

Preparation-conditioned changes of the antigenicity of influenza virus neuraminidases. Author(s): Desselberger U. Source: Archives of Virology. 1977; 53(4): 335-49. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=68766&dopt=Abstract

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Prevention of murine influenza A virus pneumonitis by surfactant nano-emulsions. Author(s): Donovan BW, Reuter JD, Cao Z, Myc A, Johnson KJ, Baker JR Jr. Source: Antivir Chem Chemother. 2000 January; 11(1): 41-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10693653&dopt=Abstract

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Prophylactic effect of a Beta vulgaris extract on experimental influenza infection in mice. Author(s): Prahoveanu E, Esanu V, Anton G, Frunzulica S. Source: Virologie. 1986 April-June; 37(2): 121-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3727395&dopt=Abstract

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Protection of epithelial cells against influenza A virus by a plant derived biological response modifier Ledretan-96. Author(s): Badmaev V, Nowakowski M. Source: Phytotherapy Research : Ptr. 2000 June; 14(4): 245-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10861966&dopt=Abstract

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Purification of bovine serum beta-inhibitor by chromatographic methods and its reaction with A1 influenza virus. Author(s): Krizanova O, Sokol F. Source: Acta Virol. 1966 January; 10(1): 35-42. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4380769&dopt=Abstract

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Quantitative determination of virus-membrane fusion events. Fusion of influenza virions with plasma membranes and membranes of endocytic vesicles in living cultured cells. Author(s): Nussbaum O, Loyter A. Source: Febs Letters. 1987 August 31; 221(1): 61-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3622762&dopt=Abstract

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Rational design of potent sialidase-based inhibitors of influenza virus replication. Author(s): von Itzstein M, Wu WY, Kok GB, Pegg MS, Dyason JC, Jin B, Van Phan T, Smythe ML, White HF, Oliver SW, et al.

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Source: Nature. 1993 June 3; 363(6428): 418-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8502295&dopt=Abstract •

Response to influenza vaccine in adjuvant 65-4. Author(s): Smith JW, Fletcher WB, Peters M, Westwood M, Perkins FJ. Source: J Hyg (Lond). 1975 April; 74(2): 251-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1054729&dopt=Abstract

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Safety and immunoenhancing effect of a Chlorella-derived dietary supplement in healthy adults undergoing influenza vaccination: randomized, double-blind, placebocontrolled trial. Author(s): Halperin SA, Smith B, Nolan C, Shay J, Kralovec J. Source: Cmaj : Canadian Medical Association Journal = Journal De L'association Medicale Canadienne. 2003 July 22; 169(2): 111-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12874157&dopt=Abstract

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Selective inhibition of influenza virus protein synthesis by inhibitors of DNA function. Author(s): Minor PD, Dimmock NJ. Source: Virology. 1977 May 15; 78(2): 393-406. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=141164&dopt=Abstract

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Studies on the neuraminidase of influenza virus. ii. additional properties of the enzymes from the asian and pr 8 strains. Author(s): RAFELSON ME Jr, SCHNEIR M, WILSON VW Jr. Source: Archives of Biochemistry and Biophysics. 1963 December; 103: 424-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14099553&dopt=Abstract

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Studies on the replication of influenza virus RNA. Author(s): Pons MW. Source: Virology. 1972 March; 47(3): 823-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4622296&dopt=Abstract

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Studies on the role of myxovirus neuraminidase in virus-cell receptors interaction by means of direct determination of sialic acid split from cells. I. Experiments on influenza virus-RBC cell system. Author(s): Tsvetkova IV, Lipkind MA. Source: Arch Gesamte Virusforsch. 1968; 23(4): 299-312. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4971430&dopt=Abstract

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Swainsonine prevents the processing of the oligosaccharide chains of influenza virus hemagglutinin. Author(s): Elbein AD, Dorling PR, Vosbeck K, Horisberger M.

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Source: The Journal of Biological Chemistry. 1982 February 25; 257(4): 1573-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6799507&dopt=Abstract •

The antiviral effect of keishi-ni-eppi-ichi-to, a traditional Chinese herbal medicine, on influenza A2(H2N2) virus infection in mice. Author(s): Ball MA, Utsunomiya T, Ikemoto K, Kobayashi M, Pollard RB, Suzuki F. Source: Experientia. 1994 August 15; 50(8): 774-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7520870&dopt=Abstract

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The characterization of subviral particles derived from influenza virus. Author(s): Skehel JJ. Source: Virology. 1971 May; 44(2): 409-17. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4105259&dopt=Abstract

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The effect of an aqueous horse-radish extract, applied as such or in association with caffeine, on experimental influenza in mice. Author(s): Esanu V, Prahoveanu E. Source: Virologie. 1985 April-June; 36(2): 95-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4036004&dopt=Abstract

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The effect of an aqueous propolis extract, of rutin and of a rutin-quercetin mixture on experimental influenza virus infection in mice. Author(s): Esanu V, Prahoveanu E, Crisan I, Cioca A. Source: Virologie. 1981 July-September; 32(3): 213-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7303493&dopt=Abstract

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The effect of garlic extract, applied as such or in association with NaF, on experimental influenza in mice. Author(s): Esanu V, Prahoveanu E. Source: Virologie. 1983 January-March; 34(1): 11-7. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6304996&dopt=Abstract

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The epidemiology and control of avian influenza and Newcastle disease. Author(s): Alexander DJ. Source: Journal of Comparative Pathology. 1995 February; 112(2): 105-26. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7769142&dopt=Abstract

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The human cell line PER.C6 provides a new manufacturing system for the production of influenza vaccines. Author(s): Pau MG, Ophorst C, Koldijk MH, Schouten G, Mehtali M, Uytdehaag F.

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Source: Vaccine. 2001 March 21; 19(17-19): 2716-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11257414&dopt=Abstract •

The use of oral dehydroepiandrosterone sulfate as an adjuvant in tetanus and influenza vaccination of the elderly. Author(s): Evans TG, Judd ME, Dowell T, Poe S, Daynes RA, Araneo BA. Source: Vaccine. 1996 November; 14(16): 1531-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9014295&dopt=Abstract

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Thoracic lymphatic pumping and the efficacy of influenza vaccination in healthy young and elderly populations. Author(s): Breithaupt T, Harris K, Ellis J, Purcell E, Weir J, Clothier M, Boesler D. Source: J Am Osteopath Assoc. 2001 January; 101(1): 21-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11234217&dopt=Abstract

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Thujaplicin-copper chelates inhibit replication of human influenza viruses. Author(s): Miyamoto D, Kusagaya Y, Endo N, Sometani A, Takeo S, Suzuki T, Arima Y, Nakajima K, Suzuki Y. Source: Antiviral Research. 1998 August; 39(2): 89-100. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9806486&dopt=Abstract

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Two new lignans with activity against influenza virus from the medicinal plant Rhinacanthus nasutus. Author(s): Kernan MR, Sendl A, Chen JL, Jolad SD, Blanc P, Murphy JT, Stoddart CA, Nanakorn W, Balick MJ, Rozhon EJ. Source: Journal of Natural Products. 1997 June; 60(6): 635-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9214738&dopt=Abstract

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Variation in the divalent cation requirements of influenza a virus n2 neuraminidases. Author(s): Johansson BE, Brett IC. Source: Journal of Biochemistry. 2003 September; 134(3): 345-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14561719&dopt=Abstract

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Virucidal effects of the steam distillate from Houttuynia cordata and its components on HSV-1, influenza virus, and HIV. Author(s): Hayashi K, Kamiya M, Hayashi T. Source: Planta Medica. 1995 June; 61(3): 237-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7617766&dopt=Abstract

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Vitamin E supplementation decreases lung virus titers in mice infected with influenza. Author(s): Hayek MG, Taylor SF, Bender BS, Han SN, Meydani M, Smith DE, Eghtesada S, Meydani SN.

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Source: The Journal of Infectious Diseases. 1997 July; 176(1): 273-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9207381&dopt=Abstract •

Vitamin E supplementation increases T helper 1 cytokine production in old mice infected with influenza virus. Author(s): Han SN, Wu D, Ha WK, Beharka A, Smith DE, Bender BS, Meydani SN. Source: Immunology. 2000 August; 100(4): 487-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10929076&dopt=Abstract

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World War I may have allowed the emergence of “Spanish” influenza. Author(s): Oxford JS, Sefton A, Jackson R, Innes W, Daniels RS, Johnson NP. Source: The Lancet Infectious Diseases. 2002 February; 2(2): 111-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11901642&dopt=Abstract

Additional Web Resources A number of additional Web sites offer encyclopedic information covering CAM and related topics. The following is a representative sample: •

Alternative Medicine Foundation, Inc.: http://www.herbmed.org/

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AOL: http://search.aol.com/cat.adp?id=169&layer=&from=subcats

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Chinese Medicine: http://www.newcenturynutrition.com/

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drkoop.com®: http://www.drkoop.com/InteractiveMedicine/IndexC.html

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Family Village: http://www.familyvillage.wisc.edu/med_altn.htm

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Google: http://directory.google.com/Top/Health/Alternative/

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Healthnotes: http://www.healthnotes.com/

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MedWebPlus: http://medwebplus.com/subject/Alternative_and_Complementary_Medicine

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Open Directory Project: http://dmoz.org/Health/Alternative/

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HealthGate: http://www.tnp.com/

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WebMD®Health: http://my.webmd.com/drugs_and_herbs

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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html

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Yahoo.com: http://dir.yahoo.com/Health/Alternative_Medicine/

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The following is a specific Web list relating to influenza; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: •

General Overview Bronchitis Source: Healthnotes, Inc.; www.healthnotes.com Chronic Obstructive Pulmonary Disease Source: Healthnotes, Inc.; www.healthnotes.com Cold Sores Source: Healthnotes, Inc.; www.healthnotes.com Colds and Flus Source: Prima Communications, Inc.www.personalhealthzone.com Common Cold Source: Integrative Medicine Communications; www.drkoop.com Common Cold/sore Throat Source: Healthnotes, Inc.; www.healthnotes.com Congestive Heart Failure Source: Integrative Medicine Communications; www.drkoop.com Erythema Source: Integrative Medicine Communications; www.drkoop.com Flu Source: Integrative Medicine Communications; www.drkoop.com Gastritis Source: Healthnotes, Inc.; www.healthnotes.com HIV and AIDS Support Source: Healthnotes, Inc.; www.healthnotes.com Immune Function Source: Healthnotes, Inc.; www.healthnotes.com Infection Source: Healthnotes, Inc.; www.healthnotes.com Influenza Source: Healthnotes, Inc.; www.healthnotes.com Meningitis Source: Integrative Medicine Communications; www.drkoop.com

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Serum Sickness Source: Integrative Medicine Communications; www.drkoop.com •

Alternative Therapy Homeopathy Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,703,00.html

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Chinese Medicine Bohe Alternative names: Peppermint; Herba Menthae Source: Chinese Materia Medica Chaihu Alternative names: Chinese Thorowax Root; Radix Bupleuri Source: Chinese Materia Medica Cuitang Wan Alternative names: Cuitang Pills Source: Pharmacopoeia Commission of the Ministry of Health, People's Republic of China Dandouchi Alternative names: Fermented Soybean; Semen Sojae Preparatum Source: Chinese Materia Medica Nambaniangan Alternative names: Baphicacanthus Root; Rhizoma et Radix Baphicacanthis Cusae Source: Chinese Materia Medica Niubangzi Alternative names: Great Burdock Achene; Fructus Arctii Source: Chinese Materia Medica Qingre Jiedu Koufuye Alternative names: Qingre Jiedu Oral Liquid Source: Pharmacopoeia Commission of the Ministry of Health, People's Republic of China Reyanning Keli Alternative names: Reyanning Granules; Reyanning Keli
(Rey Yan Ning Ke Li) Source: Pharmacopoeia Commission of the Ministry of Health, People's Republic of China

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Shi'erwei Yishou San Alternative names: Shi'erwei Yishou Powder; Shi'erwei Yishou San
(Shi’ Erwei Yi Shou San) Source: Pharmacopoeia Commission of the Ministry of Health, People's Republic of China •

Homeopathy Aconitum Napellus Source: Healthnotes, Inc.; www.healthnotes.com Apis Mellifica Source: Healthnotes, Inc.; www.healthnotes.com Arsenicum Album Source: Healthnotes, Inc.; www.healthnotes.com Belladonna Source: Healthnotes, Inc.; www.healthnotes.com Bryonia Source: Healthnotes, Inc.; www.healthnotes.com Eupatorium Perfoliatum Source: Healthnotes, Inc.; www.healthnotes.com Ferrum Phosphoricum Source: Healthnotes, Inc.; www.healthnotes.com Gelsemium Source: Healthnotes, Inc.; www.healthnotes.com Nux Vomica Source: Healthnotes, Inc.; www.healthnotes.com Oscillococcinum Source: Healthnotes, Inc.; www.healthnotes.com Phosphorus Source: Healthnotes, Inc.; www.healthnotes.com Rhus Toxicodendron Source: Healthnotes, Inc.; www.healthnotes.com Sulphur Source: Healthnotes, Inc.; www.healthnotes.com

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Herbs and Supplements Acetaminophen Source: Healthnotes, Inc.; www.healthnotes.com

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Aloe Alternative names: Aloe vera L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Amantadine Source: Healthnotes, Inc.; www.healthnotes.com Androstenedione Source: Healthnotes, Inc.; www.healthnotes.com Angelica Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca Antiviral Drugs Source: Healthnotes, Inc.; www.healthnotes.com Asian Ginseng Alternative names: Panax ginseng Source: Healthnotes, Inc.; www.healthnotes.com Astragalus Alternative names: Astragalus membranaceus, Astragalus membranaceus var. mongholicus, Huang-qi, Milk-Vetch Root Source: Integrative Medicine Communications; www.drkoop.com Astragalus Membranaceus Source: Integrative Medicine Communications; www.drkoop.com Astragalus Mongholicus Alternative names: Astragalus membranaceus, Astragalus membranaceus var. mongholicus, Huang-qi, Milk-Vetch Root Source: Integrative Medicine Communications; www.drkoop.com Boneset Alternative names: Eupatorium perfoliatum Source: Healthnotes, Inc.; www.healthnotes.com Boneset Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca Cimicifuga Alternative names: Black Cohosh; Cimicifuga racemosa (NUTT.) Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Echinacea Alternative names: Echinacea purpurea, Echinacea angustifolia, Echinacea pallida Source: Healthnotes, Inc.; www.healthnotes.com

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Elder Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca Elderberry Alternative names: Sambucus nigra Source: Healthnotes, Inc.; www.healthnotes.com Elderberry Source: Prima Communications, Inc.www.personalhealthzone.com Eleuthero Alternative names: Eleutherococcus senticosus, Acanthopanax senticosus Source: Healthnotes, Inc.; www.healthnotes.com Ephedrine and Pseudoephedrine Source: Healthnotes, Inc.; www.healthnotes.com Ginseng Source: Prima Communications, Inc.www.personalhealthzone.com Glycyrrhiza Glabra Source: Integrative Medicine Communications; www.drkoop.com Glycyrrhiza1 Alternative names: Licorice; Glycyrrhiza glabra L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Golden Rod Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca Goldenrod Alternative names: Solidago virgaurea Source: Integrative Medicine Communications; www.drkoop.com Goldenseal Alternative names: Hydrastis canadensis Source: Healthnotes, Inc.; www.healthnotes.com Huang-qi Source: Integrative Medicine Communications; www.drkoop.com Influenza Vaccine Alternative names: FluShield, Fluvirin, Fluzone Source: Prima Communications, Inc.www.personalhealthzone.com Influenza Virus Vaccine Source: Healthnotes, Inc.; www.healthnotes.com

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Licorice Alternative names: Glycyrrhiza glabra, Spanish Licorice Source: Integrative Medicine Communications; www.drkoop.com Lomatium Alternative names: Lomatium dissectum Source: Healthnotes, Inc.; www.healthnotes.com Meadowsweet Alternative names: Filipendula ulmaria Source: Healthnotes, Inc.; www.healthnotes.com Melissa Source: Prima Communications, Inc.www.personalhealthzone.com Milk-vetch Root Source: Integrative Medicine Communications; www.drkoop.com Phytolacca Alternative names: Poke root, Endod; Phytolacca dodecandra L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Sambucus Alternative names: Black Elderberry; Sambucus nigra L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Solidago Virgaurea Source: Integrative Medicine Communications; www.drkoop.com Spanish Licorice Source: Integrative Medicine Communications; www.drkoop.com St. John's Wort Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,824,00.html Thuja Plicata Alternative names: Western Red Cedar Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Verbascum Alternative names: Mullein; Verbascum thapsus L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Viburnum Alternative names: Cramp Bark, Highbush Cranberry; Viburnum sp. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Wild Indigo Alternative names: Baptisia tinctoria Source: Healthnotes, Inc.; www.healthnotes.com

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General References A good place to find general background information on CAM is the National Library of Medicine. It has prepared within the MEDLINEplus system an information topic page dedicated to complementary and alternative medicine. To access this page, go to the MEDLINEplus site at http://www.nlm.nih.gov/medlineplus/alternativemedicine.html. This Web site provides a general overview of various topics and can lead to a number of general sources.

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CHAPTER 4. DISSERTATIONS ON INFLUENZA Overview In this chapter, we will give you a bibliography on recent dissertations relating to influenza. We will also provide you with information on how to use the Internet to stay current on dissertations. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical dissertations that use the generic term “influenza” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on influenza, we have not necessarily excluded non-medical dissertations in this bibliography.

Dissertations on Influenza ProQuest Digital Dissertations, the largest archive of academic dissertations available, is located at the following Web address: http://wwwlib.umi.com/dissertations. From this archive, we have compiled the following list covering dissertations devoted to influenza. You will see that the information provided includes the dissertation’s title, its author, and the institution with which the author is associated. The following covers recent dissertations found when using this search procedure: •

A Cruel Wind: America Experiences Pandemic Influenza, 1918-1920. a Social History. by Pettit, Dorothy Ann, PhD from University of New Hampshire, 1976, 340 pages http://wwwlib.umi.com/dissertations/fullcit/7710263

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Age-associated Changes in Influenza A-specific Cd8-positive Lymphocyte Responses in C57bl/6 Mice by Po, John Leander Zapanta; PhD from MCP Hahnemann University, 2002, 175 pages http://wwwlib.umi.com/dissertations/fullcit/3043451

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'black October': the Impact of the Spanish Influenza Epidemic of 1918 on South Africa by Phillips, Howard, PhD from University of Cape Town (South Africa), 1984 http://wwwlib.umi.com/dissertations/fullcit/f2278981

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Cost-effectiveness of Influenza Vaccination by Najib, Mohammad Mahmoud; PhD from University of Illinois at Chicago, Health Sciences Center, 2003, 200 pages http://wwwlib.umi.com/dissertations/fullcit/3083951

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Determinants of Influenza Vaccination Timing by Yoo, Byung Kwang; PhD from The Johns Hopkins University, 2002, 277 pages http://wwwlib.umi.com/dissertations/fullcit/3046584

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Host Cell and Viral Determinants Involved in the Formation of Filamentous Influenza a Virus Particles by Munguia, Audelia; PhD from Wayne State University, 2003, 146 pages http://wwwlib.umi.com/dissertations/fullcit/3089207

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Host Nutritional Status Is a Driving Force in Influenza a Pathogenesis by Nelson, Heather Katherine; PhD from The University of North Carolina at Chapel Hill, 2003, 165 pages http://wwwlib.umi.com/dissertations/fullcit/3086589

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Immunodiffusion Studies on the Antigens of Myxovirus Influenza A/pr8 by Johnson, Christine Margaret; Advdeg from University of Ottawa (Canada), 1967 http://wwwlib.umi.com/dissertations/fullcit/NK04336

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Impact of Influenza Circulation in the Community on the Risk of Maternal Morbidity and Preterm Birth by Lindsay, Lisa; PhD from The University of North Carolina at Chapel Hill, 2003, 143 pages http://wwwlib.umi.com/dissertations/fullcit/3086562

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Influenza Epidemic 1918-1919: a Misplaced Chapter in United States Social and Institutional History by Noyes, William Raymond, PhD from University of California, Los Angeles, 1968, 294 pages http://wwwlib.umi.com/dissertations/fullcit/6911929

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Influenza Hemagglutinin-mediated Membrane Fusion: from Kinetics to Architecture of the Fusion Site by Mittal, Aditya; PhD from Drexel University, 2002, 183 pages http://wwwlib.umi.com/dissertations/fullcit/3035740

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Influenza Immunization and Immunoglobulins in the Equine Species by Rouse, Barry T; AdvDeg from University of Guelph (Canada), 1970 http://wwwlib.umi.com/dissertations/fullcit/NK06565

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Influenza Vaccination in the Elderly: Identifying Disparities, Predictors of Countylevel Dissemination, and Methodologic Examination of Classification and Regression Tree Analysis by Lemon, Stephenie Christine; PhD from Brown University, 2002, 90 pages http://wwwlib.umi.com/dissertations/fullcit/3050924

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Influenza Vaccination: Impact on Certificated School Staff Absenteeism by Spurzem, Candace Wang, EDD from The University of Nebraska - Lincoln, 1996, 75 pages http://wwwlib.umi.com/dissertations/fullcit/9712529

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Influenza Virus Entry into Host Cells: Internalization Pathways, Endocytic Trafficking, and the Role of Protein Kinase C by Sieczkarski, Sara Beth; PhD from Cornell University, 2003, 238 pages http://wwwlib.umi.com/dissertations/fullcit/3081359

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Influenza Virus Hemagglutinin-mediated Membrane Fusion: Mechanistic Studies and Potential Applications by Vadrucci, Sonia; Drscnat from Eidgenoessische Technische Hochschule Zuerich (Switzerland), 2002, 135 pages http://wwwlib.umi.com/dissertations/fullcit/f409713

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Influenza Virus Receptors and Genomic Packaging by Bancroft, Christa Tobey; PhD from University of California, San Francisco, 2002, 119 pages http://wwwlib.umi.com/dissertations/fullcit/3051034

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Initial Structural Characterization of the Integrated Membrane M2 Proton Channel from Influenza a Virus Using Solid State and Solution State Nmr by Tian, Changlin; PhD from The Florida State University, 2003, 251 pages http://wwwlib.umi.com/dissertations/fullcit/3093112

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Mass Mediated Disease: a Case Study Analysis of News Reporting and Three Influenza Pandemics and Public Health Policy by Blakely, Debra Ellen Menconi; PhD from The University of Southern Mississippi, 2001, 234 pages http://wwwlib.umi.com/dissertations/fullcit/3038672

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Mathematical Model of Influenza for Interspecies Transmission between Humans and Pigs, and Its Role in Human Influenza Infection by Lee, Jungmin; Msc from University of Alberta (canada), 2002, 93 pages http://wwwlib.umi.com/dissertations/fullcit/MQ69725

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Molecular Diagnosis, Epidemiology and Pathogenesis of Swine Influenza Virus Infection in Pigs by Choi, Young-ki; PhD from University of Minnesota, 2002, 182 pages http://wwwlib.umi.com/dissertations/fullcit/3072655

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Neutral Protease Activity during the Course of Influenza Virus Infection by Ewasyshyn, Mary Elizabeth; PhD from University of Windsor (Canada), 1983 http://wwwlib.umi.com/dissertations/fullcit/NK61975

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Optimization of Influenza Vaccine Strain Selection by Wu, Joseph Tszkei; PhD from Massachusetts Institute of Technology, 2003 http://wwwlib.umi.com/dissertations/fullcit/f196001

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Racial and Ethnic Disparities in Influenza Vaccination by Rangel, Maria Cristina; PhD from The University of North Carolina at Chapel Hill, 2002, 133 pages http://wwwlib.umi.com/dissertations/fullcit/3061715

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Structural Studies of the Influenza Virus Matrix Protein M1 by Harris, Audray Kenkay; PhD from The University of Alabama at Birmingham, 2002, 155 pages http://wwwlib.umi.com/dissertations/fullcit/3078530

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Structural Studies of Two Influenza Virus Proteins Involved in Virus Assembly and Release by Lommer, Barbara S.; PhD from The University of Alabama at Birmingham, 2002, 163 pages http://wwwlib.umi.com/dissertations/fullcit/3066322

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Studies on Pathogenicity and Control of H5n1 Influenza a Viruses in Mice by Bright, Rick Arthur; PhD from Emory University, 2002, 164 pages http://wwwlib.umi.com/dissertations/fullcit/3071411

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Studies on the Pathogenesis of Virulent and Avirulent Influenza a Virus Infections in Turkeys by Narayan, Opendra; Advdeg from University of Guelph (Canada), 1970 http://wwwlib.umi.com/dissertations/fullcit/NK07176

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The Antigenic Relationships of Influenza a Viruses and the Incidence in Animals of Anti Influenza a Antibodies: a Study by Immunodiffusion in Cellulose Acetate by Fyson, Raina E; PhD from University of Ottawa (Canada), 1972 http://wwwlib.umi.com/dissertations/fullcit/NK16805

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The French Experience of Pandemic Influenza during the Great War by Talbert, Joseph Allen; PhD from The Ohio State University, 2000, 163 pages http://wwwlib.umi.com/dissertations/fullcit/9982989

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The Relationship between Utilization of Complementary Care Providers and Influenza Immunization Status among Adult Canadians by Stoian, Cristina Ana; MSC from University of Calgary (Canada), 2002, 147 pages http://wwwlib.umi.com/dissertations/fullcit/MQ72191

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The Role of Structural Changes in Influenza Hemagglutinin Mediated Fusion by Gruenke, Jennifer Ann; PhD from University of Virginia, 2002, 135 pages http://wwwlib.umi.com/dissertations/fullcit/3030677

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The Spread of Influenza Epidemics in a Small Community (michigan) by Santiago, Victor Antonio, PhD from The University of Michigan, 1984, 148 pages http://wwwlib.umi.com/dissertations/fullcit/8422326

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Type I Ifn Antagonist Function of the Influenza Virus Ns1 Protein by Wang, Xiuyan; PhD from Mount Sinai School of Medicine of New York University, 2002, 171 pages http://wwwlib.umi.com/dissertations/fullcit/3043112

Keeping Current Ask the medical librarian at your library if it has full and unlimited access to the ProQuest Digital Dissertations database. From the library, you should be able to do more complete searches via http://wwwlib.umi.com/dissertations.

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CHAPTER 5. CLINICAL TRIALS AND INFLUENZA Overview In this chapter, we will show you how to keep informed of the latest clinical trials concerning influenza.

Recent Trials on Influenza The following is a list of recent trials dedicated to influenza.8 Further information on a trial is available at the Web site indicated. •

Immune Response to Influenza Vaccination in HIV-Infected Condition(s): HIV Infections Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID) Purpose - Excerpt: The purpose of this protocol is to evaluate the effect of HIV viral load and CD4 counts on the generation of influenza-specific antibodies and influenza-specific B cell responses in HIV-infected adults. HIV-infected subjects will be enrolled to receive the influenza vaccine appropriate to the on-going USA influenza season (Oct-March). Laboratory studies (including influenza titers, influenza-specific B cell frequencies, CD4 counts, and HIV viral loads) will be obtained at baseline (day of vaccination), day 7, 28, and 54 post-vaccination. HIV-negative healthy volunteers will serve as controls. Although there are some risks to influenza vaccine, the CDC Advisory Committee on Immunizations recommends influenza vaccination for HIV-infected patients. The primary study risks are those of phlebotomy and the inconvenience of multiple visits. Subjects will be compensated for participation in the study. Total enrollment of the study is a maximum of 165 subjects (132 HIV-infected individuals and 33 HIV-negative controls). Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00069914

8

These are listed at www.ClinicalTrials.gov.

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Studies of Influenza Vaccine and Tetanus-Pneumococcal Vaccine in HIV-infected Patients Receiving Interleukin-2 Condition(s): HIV Infections Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID) Purpose - Excerpt: This investigation is a sub-study of the 6-year multinational ESPRIT (Evaluation of Subcutaneous Proleukin in a Randomized International Trial) protocol. It will compare the effectiveness of the influenza (FLUVAC) and tetanus-pneumococcal (TEPVAC) vaccines in HIV-infected patients receiving interleukin-2 (IL-2) plus anti-HIV drugs with those receiving only anti-HIV drugs. IL-2 is a protein naturally produced by immune cells called lymphocytes. Lymphocytes from patients with HIV do not produce IL-2 normally. The ESPRIT trial is evaluating whether HIV-infected patients treated with antiretroviral drugs plus IL-2 have fewer serious infections and improved survival than those receiving only anti-HIV drugs. Participants in this sub-study will be drawn from patients enrolled in ESPRIT. They must be 18 years of age or older, have HIV infection with no symptoms of significant HIV illness. They will be vaccinated against either influenza or tetanus and pneumococcus, as follows: FLUVAC Potentially eligible patients will be screened for the FLUVAC study during an ESPRIT follow-up visit. Those who are eligible and agree to participate will have 10 ml (1 tablespoon) of blood drawn to assess baseline antibody levels and then receive the vaccination. They will be vaccinated annually for 3 years. A blood sample (10 ml) will be drawn 1 month after each vaccination to measure the immune response. Some of the blood drawn for this study will be stored and used for research purposes. TEPVAC Participants will have 10 ml of blood drawn to assess their baseline antibody levels. They will receive two vaccinations (tetanus and pneumococcus) 12 months after enrolling in ESPRIT and another two vaccinations 24 months after enrollment. A blood sample (10 ml) will be drawn 1 month after each vaccination to measure the immune response. Some of the blood drawn for this study will be stored and used for research purposes. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00050726

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Half-Dose Flu Vaccine Study in Healthy Adults Condition(s): Influenza Study Status: This study is no longer recruiting patients. Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID) Purpose - Excerpt: It appears likely that there will be a delay and possibly a reduction in the amount of influenza vaccine available for the 2000-2001 influenza season. One possible way of increasing the availability of influenza vaccine for this year is to use a half-dose in healthy adults. The objective of this study is to determine if the immune system responds to a half-dose the same way it responds to a whole dose. This study will use the currently approved inactivated influenza vaccine in healthy adults ages 18 to 49 years old. If the immune response to the half-dose is not significantly different than the immune response generated to the whole dose, this could be a strategy to extend the amount of vaccine that could be available in this age group. Phase(s): Phase II

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Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00006146 •

Study of a Flu Vaccine in Children. Condition(s): Influenza Study Status: This study is no longer recruiting patients. Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID); Aviron Purpose - Excerpt: This study tests the safety and effectiveness of a flu vaccine in school children. School children are usually the first members of a community to come down with the flu, and they often give the flu to their younger siblings, parents, and grandparents. It is hoped that giving school children a flu vaccine can help prevent the spread of the flu to other members of the community. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001127

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Influenza Vaccine in HIV Infection: Immune Response and Effect on Viral Load Condition(s): HIV Infection Study Status: This study is completed. Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID) Purpose - Excerpt: This 2-part study will examine 1) the immune response to influenza (flu) vaccine in HIV-infected patients, and 2) the effect of flu vaccine on HIV viral loads. Earlier studies have shown that people with HIV infection do not respond as well to flu vaccine as healthy subjects; that is, they don't make as many antibodies in response to the vaccine. Also, studies done before the use of HAART (highly active antiretroviral treatment) have shown that HIV levels increase for a period of time after flu vaccination. One small study showed a small brief increase in HIV even in patients taking HAART. The current trial will examine whether the flu vaccine does, in fact, cause an elevation in viral load and whether this increase is harmful or indicates a better response to the vaccine. HIV-infected patients and healthy normal volunteers between 18 and 60 years of age may be eligible for part1of this study. (Healthy volunteers will serve as control subjects to make sure the flu vaccine stimulates production of enough antibody to protect against the flu). Part 2 will include only HIV-infected patients with fewer than 50 copies per milliliter of HIV. Patients in both parts of the study must have been receiving HAART (consisting of at least two nucleoside reverse transcriptase inhibitors plus a non-nucleoside reverse transcriptase inhibitor or a protease inhibitor) for at least 3 months before enrollment in the study. Candidates will be screened with a medical history and blood tests, including HLA testing (a genetic test of immune system markers). Women who are able to have children will have a pregnancy test. Pregnant women are excluded from the study. Participants will undergo the following procedures: - Part 1 - Immune Response to Flu Vaccine In the first of two visits, participants will have blood drawn for flu antibody levels before vaccination and, in HIV-infected patients, measures of T cell count and viral load. They will then receive the flu vaccine. Blood will be drawn at a second visit 28 days later for the same tests. - Part 2

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- Effect of Flu Vaccine on Viral Levels Participants will be randomly assigned to receive the flu vaccine either at the beginning of their enrollment in the study (immediate) or 3 weeks after enrollment (deferred). Those in the immediate group receive the flu vaccine on the first day (day 0) and have blood drawn on days 0, 3, 7, 10, 14, 17, 21, 24, 28, 31, 35, 38 and 42. Those in the deferred group are vaccinated on day 21 and have blood drawn on days 0, 3, 7, 10, 14, 17, 21, 24, 28, 31, 35, 38, 42 and 49. The blood is tested for viral load, CD4 cell counts and antibody levels. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00025922

Keeping Current on Clinical Trials The U.S. National Institutes of Health, through the National Library of Medicine, has developed ClinicalTrials.gov to provide current information about clinical research across the broadest number of diseases and conditions. The site was launched in February 2000 and currently contains approximately 5,700 clinical studies in over 59,000 locations worldwide, with most studies being conducted in the United States. ClinicalTrials.gov receives about 2 million hits per month and hosts approximately 5,400 visitors daily. To access this database, simply go to the Web site at http://www.clinicaltrials.gov/ and search by “influenza” (or synonyms). While ClinicalTrials.gov is the most comprehensive listing of NIH-supported clinical trials available, not all trials are in the database. The database is updated regularly, so clinical trials are continually being added. The following is a list of specialty databases affiliated with the National Institutes of Health that offer additional information on trials: •

For clinical studies at the Warren Grant Magnuson Clinical Center located in Bethesda, Maryland, visit their Web site: http://clinicalstudies.info.nih.gov/

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For clinical studies conducted at the Bayview Campus in Baltimore, Maryland, visit their Web site: http://www.jhbmc.jhu.edu/studies/index.html

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For cancer trials, visit the National Cancer Institute: http://cancertrials.nci.nih.gov/

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For eye-related trials, visit and search the Web page of the National Eye Institute: http://www.nei.nih.gov/neitrials/index.htm

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For heart, lung and blood trials, visit the Web page of the National Heart, Lung and Blood Institute: http://www.nhlbi.nih.gov/studies/index.htm

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For trials on aging, visit and search the Web site of the National Institute on Aging: http://www.grc.nia.nih.gov/studies/index.htm

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For rare diseases, visit and search the Web site sponsored by the Office of Rare Diseases: http://ord.aspensys.com/asp/resources/rsch_trials.asp

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For alcoholism, visit the National Institute on Alcohol Abuse and Alcoholism: http://www.niaaa.nih.gov/intramural/Web_dicbr_hp/particip.htm

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For trials on infectious, immune, and allergic diseases, visit the site of the National Institute of Allergy and Infectious Diseases: http://www.niaid.nih.gov/clintrials/

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For trials on arthritis, musculoskeletal and skin diseases, visit newly revised site of the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health: http://www.niams.nih.gov/hi/studies/index.htm

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For hearing-related trials, visit the National Institute on Deafness and Other Communication Disorders: http://www.nidcd.nih.gov/health/clinical/index.htm

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For trials on diseases of the digestive system and kidneys, and diabetes, visit the National Institute of Diabetes and Digestive and Kidney Diseases: http://www.niddk.nih.gov/patient/patient.htm

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For drug abuse trials, visit and search the Web site sponsored by the National Institute on Drug Abuse: http://www.nida.nih.gov/CTN/Index.htm

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For trials on mental disorders, visit and search the Web site of the National Institute of Mental Health: http://www.nimh.nih.gov/studies/index.cfm

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For trials on neurological disorders and stroke, visit and search the Web site sponsored by the National Institute of Neurological Disorders and Stroke of the NIH: http://www.ninds.nih.gov/funding/funding_opportunities.htm#Clinical_Trials

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CHAPTER 6. PATENTS ON INFLUENZA Overview Patents can be physical innovations (e.g. chemicals, pharmaceuticals, medical equipment) or processes (e.g. treatments or diagnostic procedures). The United States Patent and Trademark Office defines a patent as a grant of a property right to the inventor, issued by the Patent and Trademark Office.9 Patents, therefore, are intellectual property. For the United States, the term of a new patent is 20 years from the date when the patent application was filed. If the inventor wishes to receive economic benefits, it is likely that the invention will become commercially available within 20 years of the initial filing. It is important to understand, therefore, that an inventor’s patent does not indicate that a product or service is or will be commercially available. The patent implies only that the inventor has “the right to exclude others from making, using, offering for sale, or selling” the invention in the United States. While this relates to U.S. patents, similar rules govern foreign patents. In this chapter, we show you how to locate information on patents and their inventors. If you find a patent that is particularly interesting to you, contact the inventor or the assignee for further information. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical patents that use the generic term “influenza” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on influenza, we have not necessarily excluded non-medical patents in this bibliography.

Patents on Influenza By performing a patent search focusing on influenza, you can obtain information such as the title of the invention, the names of the inventor(s), the assignee(s) or the company that owns or controls the patent, a short abstract that summarizes the patent, and a few excerpts from the description of the patent. The abstract of a patent tends to be more technical in nature, while the description is often written for the public. Full patent descriptions contain much more information than is presented here (e.g. claims, references, figures, diagrams, etc.). We

9Adapted

from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.

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will tell you how to obtain this information later in the chapter. The following is an example of the type of information that you can expect to obtain from a patent search on influenza: •

Adenovirus vector with multiple expression cassettes Inventor(s): Wang; Danher (Mt. Pleasant, SC) Assignee(s): GenPhar, Inc. (Mt. Pleasant, SC) Patent Number: 6,544,780 Date filed: June 2, 2000 Abstract: Genetic vaccines and methods are provided for enhancing the immunity of a host such as a human to one or more pathogens. In one embodiment, a recombinant benign virus is provided as the genetic vaccine. The recombinant virus comprises: an antigen sequence heterologous to the recombinant virus that encodes a viral antigen from a pathogenic virus, expression of the viral antigen eliciting an immune response directed against the viral antigen and cells expressing the viral antigen in a host upon infection of the host by the recombinant virus; and an immuno-stimulator sequence heterologous to the recombinant virus that encodes an immuno-stimulator whose expression in the host enhances the immunogenicity of the viral antigen. The recombinant virus is replication-incompetent and does not causes a malignancy naturally associated with the pathogenic virus in the host. The genetic vaccines can be used for immunizing a host against a wide variety of pathogens, such as HIV, Ebola virus, hepatitis B virus, hepatitis C virus, influenza virus, pathogenic bacteria and parasites. Excerpt(s): This invention relates to vaccines for stimulating immune responses in human and other hosts, and, in particular, relates to recombinant viruses that express heterologous antigens of pathogenic viruses, such as Ebola, HIV, hepatitis, and influenza viruses. Current techniques for developing vaccines are largely based on the concept of using denatured virus or purified viral proteins made from bacteria. These types of vaccines may be effective for only a limited number of infectious agents, and the protection rates are limited. For viruses that contain membrane (envelope) glycoproteins (GPs), including the Ebola virus and the HIV virus, use of denatured virus or purified viral proteins often does not work satisfactorily. There may be several reasons for this. First, the GPs of these viruses are sensitive to the denaturing procedures so that the epitopes of the proteins are altered by the denaturing process. Second, the sugar moieties of the GPs are important antigenic determinants for neutralizing antibodies. In comparison, proteins made in bacteria are not properly glycosylated and can fold into somewhat different structures that can have antigenecities different from those of the natural viral proteins. Further, many vaccines that are based on attenuated or denatured virus provide a weak immune response to poorly immunogenic antigens. In addition, the vaccine preparations frequently offer only limited protection, not lifelong immunity as desired. Web site: http://www.delphion.com/details?pn=US06544780__

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•

Animal cells and processes for the replication of influenza viruses Inventor(s): Groner; Albrecht (Fasanenweg, DE), Vorlop; Jurgen (Marburg, DE) Assignee(s): Chiron Behring GmbH & Co. (Marburg, DE) Patent Number: 6,455,298 Date filed: September 29, 1998 Abstract: Animal cells are described which can be infected by influenza viruses and which are adapted to growth in suspension in serum-free medium. Processes for the replication of influenza viruses in cell culture using these cells are furthermore described, as well as vaccines which contain the influenza viruses obtainable by the process or constituents thereof. Excerpt(s): The present invention relates to animal cells which can be infected by influenza viruses and are adapted to growth in suspension in serum-free medium, and to processes for the replication of influenza viruses in cell culture using these cells. The present invention further relates to the influenza viruses obtainable by the process described and to vaccines which contain viruses of this type or constituents thereof. All influenza vaccines which have been used since the 40s until today as permitted vaccines for the treatment of humans and animals consist of one or more virus strains which have been replicated in embryonate hens' eggs. These viruses are isolated from the allantoic fluid of infected hen' eggs and their antigens are used as vaccine either as intact virus particles or as virus particles disintegrated by detergents and/or solvents--so-called cleaved vaccine--or as isolated, defined virus proteins--so-called subunit vaccine. In all permitted vaccines, the viruses are inactivated by processes known to the person skilled in the art. The replication of live attenuated viruses, which are tested in experimental vaccines, is also carried out in embryonate hen' eggs. The use of embryonate hen' eggs for vaccine production is time-, labor- and cost-intensive. The eggs-- from healthy flocks of hens monitored by veterinarians--have to be incubated before infection, customarily for 12 days. Before infection, the eggs have to be selected with respect to living embryos, as only these eggs are suitable for virus replication. After infection the eggs are again incubated, customarily for 2 to 3 days. The embryos still alive at this time are killed by cold and the allantoic fluid is then obtained from the individual eggs by aspiration. By means of laborious purification processes, substances from the hen's egg which lead to undesired side effects of the vaccine are separated from the viruses, and the viruses are concentrated. As eggs are not sterile (pathogen-free), it is additionally necessary to remove and/or to inactivate pyrogens and all pathogens which are possibly present. Web site: http://www.delphion.com/details?pn=US06455298__

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Antibodies to aglyco products and methods of use Inventor(s): Bogoch; Elenore S. (46 E. 91st St., New York, NY 10028), Bogoch; Samuel (46 E. 91st St., New York, NY 10028) Assignee(s): none reported Patent Number: 6,638,505 Date filed: March 27, 2001 Abstract: Glycoconjugates, therapeutic compositions containing the glycoconjugates and therapeutic methods of using the glycoconjugates are disclosed. In particular, peptide constituents of aglyco 10B, which are immunogenic epitopes responsible for recognition

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of antigens by the immune system are provided. These glycoconjugates are useful in prevention of influenza virus binding to cells, treatment of schizophrenia and diagnosing chronic viral disease associated with development of cancer. Excerpt(s): This invention concerns the discovery of products and methods to aid in the diagnosis and treatment of disorders of conjugated carbohydrate constituents of living organisms which contribute to cell dysfunction and cell death. Many seemingly unrelated observations made in the past, which were not understood and could not be understood, in terms of cell dysfunction, cell death and specific disease states can now be understood in the light of the methods and compositions of the present invention which defines for the first time the state of, and the consequences of, aglyco pathology, its products, as well as products and processes for its detection and treatment. In another aspect of the invention there is provided, a method of preventing or inhibiting the attachment of influenza virus particles to a human patient's cells, comprising administering to the patient a therapeutically effective amount of a glycoconjugate to thereby bind to said influenza virus particles and prevent or inhibit attachment of the particles to cell receptors. Web site: http://www.delphion.com/details?pn=US06638505__ •

Anti-inflammatory composition comprising tetracycline Inventor(s): Gardner; Wallace J. (1791 Mass Ave., Cambridge, MA 02140) Assignee(s): none reported Patent Number: 6,610,274 Date filed: December 18, 2001 Abstract: Therapeutic composition having anti-infective activity. The therapeutic composition is a formulation comprising an antibiotic, preferably a tetracycline, most preferably doxycycline, which has not been chemically modified to eliminate antimicrobial efficacy. The antibiotic is preferably in a liquid vehicle, most preferably one that contains at least 20% alcohol by volume. The therapeutic composition is preferably in local delivery form and is self-administered orally or via the nasal cavity. Administration of the therapeutic composition of the present invention treats diseases that originate from the oral cavity or that do not originate in the oral cavity, but are affected by contaminants, such as viruses or bacteria, in the oral cavity entering the bloodstream including but not limited to periodontal disease, sinusitis, gingivitis, the common cold, sore throat, influenza, allergies (particularly to tree pollen), resistant pneumonia, diseases of the gastrointestinal tract, inflammatory diseases such as rheumatoid arthritis, cancer, ulcers, heart disease, etc. Excerpt(s): The accumulation bacteria in the oral cavity, such as on the teeth or tongue has been identified as a contributor or cause of various inflammatory conditions, including gingivitis, periodontitis and other gum diseases. Treatment of the oral cavity with antibiotics to reduce or eliminate the effects of bacteria is known. For example, broad spectrum antibiotics such as tetracyclines and metronidazole have been used in the treatment of periodontal disease to reduce oral cavity microflora. Typically such use has been systemic, which can result in various undesirable side effects, including the threat or danger or building allergies or immunity to the antibiotic, overgrowth of opportunistic yeast and fungi and intestinal disturbances. Many other common inflammatory diseases, such as sinusitis, diseases of the gastrointestinal tract (including those that manifest themselves in stomach and bowel problems), the common cold,

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influenza, allergies, halitosis, pneumonia, etc., also may be caused by viruses and/or bacteria. Often the source of the bacteria and viruses is the oral cavity, especially the ear, nose and throat passages, and the sinuses. Once the bacteria and/or viruses are resident in the oral cavities or sinuses (e.g., the maxillary, frontal and ethmoid), they can continually cause infection through circulation in the blood stream. Continual reduction or elimination of these bacteria and viruses would reduce chronic infection in the body. The problems of the prior art have been overcome by the present invention, which provides a therapeutic composition having anti-infective activity. In a preferred embodiment, the therapeutic composition is a formulation comprising an antibiotic, preferably a tetracycline, most preferably doxycycline, which has not been chemically modified to eliminate antimicrobial efficacy. The antibiotic is preferably in a liquid vehicle, most preferably one that contains at least 20% alcohol by volume. The therapeutic composition is preferably in local delivery form and is preferably selfadministered orally or via-the nasal cavity. The therapeutic composition most preferably is a self-delivered formulation in local delivery form that consists essentially of a tetracycline, most preferably doxycline, which has not been chemically modified to eliminate antimicrobial efficacy, and a liquid vehicle, more preferably one which contains at least 20% alcohol by volume, and most preferably one which consists essentially of sterile water or Listerine or the like, which tetracyline is preferably present in the formulation in the amount of between 50 to 100 mgs per ounce of liquid vehicle. Web site: http://www.delphion.com/details?pn=US06610274__ •

Attenuated vaccination and gene-transfer virus, a method to make the virus and a pharmaceutical composition comprising the virus Inventor(s): Hobom; Gerd (Arndtstrasse 14, D 35392 Giessen, DE), Menke; Annette (Marburg, DE), Neumann; Gabriele (Maintal, DE) Assignee(s): Hobom; Gerd (Giessen, DE) Patent Number: 6,524,588 Date filed: March 24, 1997 Abstract: RNA polymerase I transcription in vivo in transiently DNA-transfected cells has been used for expression of influenza vRNA molecules coding for chloramphenicol acetyltransferase (CAT) in anti-sense orientation. Influenza virus superinfection served to provide viral RNA polymerase and other proteins for transcriptional conversion of minus-strand vRNA into plus-strand viral mRNA molecules expressing CAT activity. This system has been used for an analysis via nucleotide exchanges as well as deletions and insertions of both terminal segments of the vRNA sequence which cooperatively constitute the vRNA promoter structure. Several mutants with greatly enhanced expression rates over wild-type levels have been constructed, which also can be packaged and serially passaged into progeny virus. The data obtained for the mutations in various promoter elements support a model of consecutive, double strand vRNA promoter structures in binding of viral polymerase and initiation of RNA synthesis. Preparations of attenuated influenza virus for vaccination purposes include a single recombinant segment with promoter up mutation(s) for over-expression of an own or foreign gene product, which at the same time because of its over-replication serves to decrease the number of helper virus RNP segments. The same viruses further have been passaged through a step of ribozyme cleavage acting at one of the helper viral segments, which will delete this vital function and structure with high rates from the virus

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progeny. The resulting attenuated viruses will interact with their target cells in only one round of abortive infection, and are unable to produce viral progeny. Excerpt(s): The object of the present invention was to make a vaccination virus. This objective has been fulfilled with the segmented virus constructed as described herein. The genome of influenza A viruses consists of 8 different single-stranded viral RNA (vRNA) molecules of negative polarity, which have in common 5' and 3' terminal sequences largely complementary to each other. These conserved segments 13 and 12 nucleotides in length are known to form double-stranded RNA panhandle structures (Hsu et al., 1987; Fodor et al., 1993) which have been analysed in more detail recently in vitro using internally deleted model RNAs (Baudin et al., 1994; Tiley et al., 1994). In the virion the panhandle ends of all RNA segments are found in specific binding to viral RNA polymerase complexes, while the remaining internal segments stay singlestranded with viral nucleoprotein (NP) in cooperative binding (Compans et al., 1972; Honda et al., 1988; Martin et al., 1992). Upon infection these viral RNPs initially serve as templates for the synthesis of viral mRNAs by a specific cap-snatching mechanism (Plotch et al., 1979; Braam et al., 1983), and later on will direct synthesis of full-length complementary RNAs (cRNAs), probably dependent on the absence or presence of newly synthesized NP protein (Shapiro and Krug, 1988). The plus-strand cRNAs are then used as templates for progeny vRNA synthesis. The viral RNA polymerase complex consisting of proteins PB1, PB2, and PA is involved in all three different modes of RNA synthesis during the viral replication cycle, following its specific binding to the terminal panhandle segments of both vRNAs and cRNAs. Sequence comparison reveals that the vRNA and cRNA termini have similar, but not identical sequences. For that reason vRNA and cRNA recognition may be distinguished because of these structural alterations allowing for asymmetries in initiation of plus and minus strand RNA synthesis, and possibly in viral RNP packaging, which has also been suggested to be controlled by the panhandle RNA sequence (Hsu et al., 1987). Web site: http://www.delphion.com/details?pn=US06524588__ •

Biflavanoids and derivatives thereof as antiviral agents Inventor(s): Flavin; Michael T. (Darien, IL), Lin; Yuh-Meei (Naperville, IL), Schure; Ralph (Darien, IL), Zembower; David E. (La Grange Park, IL), Zhao; Geng-Xian (Woodridge, IL) Assignee(s): Advanced Life Sciences, Inc. (Lemont, IL) Patent Number: 6,399,654 Date filed: April 15, 1998 Abstract: Substantially purified antiviral biflavanoids robustaflavone, hinokiflavone, amentoflavone, agathisflavone, volkensiflavone, morelloflavone, rhusflavanone, succedaneaflavanone, GB-1a, and GB-2a are provided. Antiviral biflavanoid derivatives and salt forms thereof, e.g., robustaflavone tetrasulfate potassium salt, and methods for preparing the same are also disclosed. Pharmaceutical compositions which include the antiviral biflavanoids, derivatives or salts thereof are also provided alone or in combination with at least one antiviral agent such as 3TC. Also disclosed is an improved method for obtaining substantially pure robustaflavone from plant material. The biflavanoid compounds, derivatives or salts thereof of the invention may be used in a method for treating and/or preventing viral infections caused by viral agents such as influenza, e.g., influenza A and B; hepatitis, e.g., hepatitis B; human immunodeficiency virus, e.g., HIV-1; Herpes viruses (HSV-1 and HSV-2); Varicella Zoster virus (VZV); and

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measles. For instance, semi-synthetic hexa-O-acetate and hexa-O-methyl ether derivatives of robustaflavone have been found to be effective in a method for treating or preventing hepatitis B viral infections. Compositions which include these robustaflavone derivatives along with methods for preparing and using the same are also provided. These compositions may be used alone or in combination with at least one antiviral agent such as 3TC. Excerpt(s): The present invention relates to substantially pure antiviral biflavanoids, e.g., robustaflavone, biflavanoid derivatives and salts thereof such as esters, ethers, amines, sulfates, ethylene oxide adducts, and acid salts, and pharmaceutical compositions containing the same. Representative examples include hexa-O-acetate and hexa-Omethyl ether derivatives of robustaflavone and robustaflavone tetrasodium salt. The present invention also relates to methods for extracting substantially pure robustaflavone from plant material. The present invention also relates to a method for preventing and/or treating viral infections such as hepatitis B, influenza A and B, and HIV which employ robustaflavone or derivatives thereof alone or in combination with at least one antiviral agent such as 3TC. Viruses, an important etiologic agent in infectious disease in humans and other mammals, are a diverse group of infectious agents that differ greatly in size, shape, chemical composition, host range, and effects on hosts. After several decades of study, only a limited number of antiviral agents are available for the treatment and/or prevention of diseases caused by viruses such as hepatitis B, influenza A and B and HIV. Because of their toxic effects on a host, many antiviral agents are limited to topical applications. Accordingly, there is a need for safe and effective antiviral agents with a wide-spectrum of anti-viral activity with reduced toxicity to the host. Since the identification of the human immunodeficiency virus (HIV) as the causative agent of AIDS,.sup.36,46 the search for safe and effective treatments for HIV infection has become a major focus for drug discovery groups around the world. Investigations into the molecular processes of HIV have identified a number of macromolecular targets for drug design, such as HIV-1 reverse transcriptase (HIV-RT), protease and integrase enzymes, and regulatory proteins (e.g., TAT and REV). Other targets are enzymes which aid in virus attachment and fusion. HIV-RT is an essential enzyme in the life cycle of HIV, which catalyzes the transcription of HIV-encoded single-stranded RNA into double-stranded DNA. Furthermore, the RNA-dependent DNA polymerase function of HIV-RT does not have an analogous process in mammalian metabolism, and thus is a suitable target for a chemotherapeutic agent. Web site: http://www.delphion.com/details?pn=US06399654__ •

Boraadamantane compounds for the treatment of pathogenic viruses and other medical applications Inventor(s): Chang; Yu-An (3631 Hamilton St., Irvine, CA 92614) Assignee(s): Chang; Yu-An (Irvine, CA) Patent Number: 6,613,507 Date filed: March 21, 2001 Abstract: Methods for treating patients with viral infections and Parkinson's disease with pharmaceutical agents are disclosed. In one embodiment, the viruses are Hepatitis C, Influenza A and B. The Pharmaceutical agents are 1-boraadamantane and the conjugate amines described in this patent application.

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Excerpt(s): Hepatitis C infection is associated with advanced liver disease (Liang, et al. Hepatology 18:1326-1333, (1993) and Tsukuma, et. al. The New England Journal of Medicine 328:1797-1801 (1993)), and liver failure due to hepatitis C infection is the most common indication for liver transplantation. Currently, the approved treatment for hepatitis C infection is.alpha.-interferon with or without combination of another pharmaceutical agents, e.g. ribavirin. However, many of those responding to these treatments will relapse upon discontinuation of the therapies (Davis, et al. The New England Journal of Medicine 321:1501-1506 (1989) and Di Bisceglie, et al. The New England Journal of Medicine 321:1506-1510 (1989)). Most of the patients who are retreated will again relapse if these drugs were withdrawed (Tine et al. Journal of Hepatology 13:192-199 (1991)). For those patients who do not respond to the initial interferon therapies, heavier dose treatments only produced little positive results. Significant increase of side effects has been observed on those patients treated with high dose regiments (Poynard et al. New England Journal of Medicine 332:1457-1462 (1995)). The low response rate and significant positive synergistic effect of combination of.alpha.-interferon with other pharmaceutical agent such as ribavirin have prompt investigators to search for other drugs which may be active against hepatitis C virus. Smith J P (Digestive Diseases Sciences 1997 August; 42(8):1681-7) of Pennsylvania State University performed an open-labeled prospective pilot study to test the safety and efficacy of the antiviral drug, amantadine, in patients with chronic hepatitis C infection who had previously failed therapy with interferon-alpha 2b. Their clinical results indicated that amantadine improved both biochemical and virological markers in patients with hepatitis C who had previously not responded to treatment with interferon. Amantadine Hydrochloride, N. F. (Orth R. E. in "Principels of Medicinal Chemistry, 2.sup.nd edition, page 866-867. Ed. Foye, W. O. (1981)) has been approved by the FDA for the treatment of influenza A2 infection. It is active against influenza A, A1 and A2, Sendai and rubella viruses. Amantadine (Neumeyer J. L. in Principles of Medicinal Chemistry, 2.sup.nd edition, page 248-249. Ed. Foye W. O. (1981)) also has clinically significant anti-parkinsonian effects. It appears to increase the release of dopamine and enhance accumulation of brain dopamine with fewer side effects than levodopa or the anticholinergic drugs. Web site: http://www.delphion.com/details?pn=US06613507__ •

Capped synthetic RNA, analogs, and aptamers Inventor(s): Benseler; Fritz (Rahway, NJ), Cole; James L. (Rahway, NJ), Kuo; Lawrence C. (Rahway, NJ), Olsen; David B. (Rahway, NJ) Assignee(s): Merck & Co., Inc. (Rahway, NJ) Patent Number: 6,369,208 Date filed: March 30, 1998 Abstract: A method is provided for making synthetic capped RNAs. These compounds serve as substrates for the virally encoded endonuclease associated with influenza virus. We are able to assay for this unique and specific viral activity of cleavage of a capped RNA in vitro. Therefore, screening of inhibitors of this activity is possible. In addition, short non-extendible (due to their length or because of the modification of the 3'-end of the oligo, i.e. 3'-dA) RNAs are potent inhibitors of the cleavage of capped RNAs by influenza endonuclease. Finally, these compounds may be used to investigate viral and cellular mechanisms of transcription/translation or mRNA maturation.

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Excerpt(s): This invention is directed towards synthetic ribonucleic acid (RNA), analogs, and aptamers which have been capped in vitro and to methods of making them. Most viral and cellular mRNA molecules contain a 5'-methylated cap structure. The presence of such a structure is important for mRNA maturation, initiation of translation and protects the mRNA against degradation by various RNases present in the cell. There are various types of RNA caps known. The general structure of a capped RNA can be designated as m.sup.7 G(5')ppp(5')Pu, (where Pu, the penultimate base, is typically a purine nucleoside). In the so-called "Cap 0", the penultimate base is unmodified. "Cap 0" is found commonly in yeast, the majority of slime molds, and in plant viruses. Web site: http://www.delphion.com/details?pn=US06369208__ •

Cells for detection of influenza and parainfluenza viruses Inventor(s): Huang; Yung T. (Richmond Heights, OH) Assignee(s): University Hospitals of Cleveland (Cleveland, OH) Patent Number: 6,610,474 Date filed: April 25, 2002 Excerpt(s): The invention provides cell lines which are useful for the rapid detection and production of influenza and parainfluenza viruses. In particular, the invention relates to transgenic mink lung cells which show increased sensitivity to infection by influenza A, influenza B, or parainfluenza 3 viruses, or which are capable of enhanced productivity of infectious virions. The invention is suitable for use in culturing clinical influenza and parainfluenza virus isolates and for the production of influenza and parainfluenza virus for vaccine formulations, as antigen preparations for diagnostic applications, and for screening antiviral drugs. Mink lung cells and mixed mink lung cell cultures are extremely sensitive for the rapid detection of various influenza and parainfluenza viruses (See, U.S. Pat. No. 6,168,915 herein incorporated by reference in its entirety; and Huang and Turchek, J. Clin. Microbiol. 38:422-423 [2000]). Additionally, mink lung cells have also been proposed as a potential replacement for chicken embryonated eggs and/or Madin-Darby canine kidney (MDCK) cells for the production of flu vaccines (Schultz-Cherry et al., J. Clin. Microbiol. 36:3718-3720 [1998]). However, one major drawback to the use of mink lung cells for the detection and production of influenza and parainfluenza viruses is that the virions produced from mink lung cells are not very infectious. Thus, mink lung cells are expected to be less sensitive than desirable for the late detection of cultured clinical specimens, and are not expected to be capable of producing high titer virus stocks for influenza and parainfluenza vaccine formulations. Thus, what is needed are cells with enhanced sensitivity to influenza and parainfluenza virus infection to permit rapid detection of these respiratory viruses. Additionally, there is need in the art for cultured cells capable of producing high titers of infectious influenza and parainfluenza for use in influenza and parainfluenza vaccines. Web site: http://www.delphion.com/details?pn=US06610474__

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Cold -adapted equine influenza viruses Inventor(s): Dowling; Patricia W. (Pittsburgh, PA), Youngner; Julius S. (Pittsburgh, PA) Assignee(s): The University of Pittsburgh of The Commonwealth System of Higher Education (Pittsburgh, PA) Patent Number: 6,436,408 Date filed: August 9, 2000 Abstract: The present invention provides experimentally-generated cold-adapted equine influenza viruses, and reassortant influenza A viruses comprising at least one genome segment of such an equine influenza virus, wherein the equine influenza virus genome segment confers at least one identifying phenotype of the cold-adapted equine influenza virus, such as cold-adaptation, temperature sensitivity, dominant interference, or attenuation. Such viruses are formulated into therapeutic compositions to protect animals from diseases caused by influenza A viruses, and in particular, to protect horses from disease caused by equine influenza virus. The present invention also includes methods to protect animals from diseases caused by influenza A virus utilizing the claimed therapeutic compositions. Such methods include using a therapeutic composition as a vaccine to generate a protective immune response in an animal prior to exposure to a virulent virus, and using a therapeutic composition as a treatment for an animal that has been recently infected with a virulent virus, or is likely to be subsequently exposed to virulent virus in a few days whereby the therapeutic composition interferes with the growth of the virulent virus, even in the absence of immunity. The present invention also provides methods to produce cold-adapted equine influenza viruses, and reassortant influenza A viruses having at least one genome segment of an equine influenza virus generated by cold-adaptation. Excerpt(s): The present invention relates to experimentally-generated cold-adapted equine influenza viruses, and particularly to cold-adapted equine influenza viruses having additional phenotypes, such as attenuation, dominant interference, or temperature sensitivity. The invention also includes reassortant influenza A viruses which contain at least one genome segment from such an equine influenza virus, such that the reassortant virus includes certain phenotypes of the donor equine influenza virus. The invention further includes genetically-engineered equine influenza viruses, produced through reverse genetics, which comprise certain identifying phenotypes of a cold-adapted equine influenza virus of the present invention. The present invention also relates to the use of these viruses in therapeutic compositions to protect animals from diseases caused by influenza viruses. Equine influenza virus has been recognized as a major respiratory pathogen in horses since about 1956. Disease symptoms caused by equine influenza virus can be severe, and are often followed by secondary bacterial infections. Two subtypes of equine influenza virus are recognized, namely subtype-1, the prototype being A/Equine/Prague/1/56 (H7N7), and subtype-2, the prototype being A/Equine/Miami/1/63 (H3N8). Presently, the predominant virus subtype is subtype-2, which has further diverged among Eurasian and North American isolates in recent years. The currently licensed vaccine for equine influenza is an inactivated (killed) virus vaccine. This vaccine provides minimal, if any, protection for horses, and can produce undesirable side effects, for example, inflammatory reactions at the site of injection. See, e.g., Mumford, 1987, Equine Infectious Disease IV, 207-217, and Mumford, et al., 1993, Vaccine II, 1172-1174. Furthermore, current modalities cannot be used in young foals, because they cannot overcome maternal immunity, and can induce tolerance in a younger animal. Based on the severity of disease, there remains a need for

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safe, effective therapeutic compositions to protect horses against equine influenza disease. Web site: http://www.delphion.com/details?pn=US06436408__ •

Composition for treating symptoms of influenza Inventor(s): Nachman; Leslie (Henderson, NV), Voorhees; John (Henderson, NV) Assignee(s): East Park Research, Inc. (Las Vegas, NV) Patent Number: 6,455,070 Date filed: February 15, 2001 Abstract: A composition for relief of symptoms of colds and influenza, containing, by weight, about 80-88% olive leaf extract powder containing oleuropein, about 5-10% neem leaf powder and up to about 8% of a homeopathic blend for symptom relief which preferably comprises aconitum napelius, belladonna, eupatorium perfoliatum, gelsemium sempervirens, Echinacea angustifolia and ferrum phosphoricum. Excerpt(s): The invention relates to the field of natural compositions, particularly herbal compositions, for treating symptoms of influenza. Colds and influenza are major causes of illness and loss of productivity both within the United States, and throughout the world at large. Approximately 10-15% of adult colds are thought to be caused by viruses which are also responsible for other serious illnesses, including influenza. An effective treatment for a wide variety of illnesses caused by viruses and bacteria has long been sought, both in terms of antiviral and antimicrobial action, and in terms of symptom relief. Some traditional Chinese medicine herbal formulas have been found somewhat effective in this regard, as is disclosed, for example, in U.S. Pat. Nos. 5,834,000, 5,989,556 and 6,083,291. Some of the traditional compositions have contained stimulants such as caffeine and ephedrine, which have proved to be undesirable. Web site: http://www.delphion.com/details?pn=US06455070__

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Cyclopentane and cyclopentene compounds and use for detecting influenza virus Inventor(s): Babu; Yarlagadda S. (Birmingham, AL), Bantia; Shanta (Birmingham, AL), Chand; Pooran (Birmingham, AL) Assignee(s): Biocryst Pharmaceuticals, Inc. (Birmingham, AL) Patent Number: 6,503,745 Date filed: May 7, 2001 Abstract: New cyclopentane and cyclopentene compounds are provided along with their use in method for detecting influenza virus. Excerpt(s): The present invention is concerned with a new group of cyclopentane and cyclopentene compounds and their use as diagnostic agents for detecting influenza A and B. The compounds of the present invention bind to influenza A and B neuraminidase. Moreover, these compounds possess functionality which allows them to be bound to a surface or to a detectable label. The diagnostic method of the present invention depends upon the ability of the disclosed compounds to bind specifically to the active site of influenza virus neuraminidase, or functionalized derivatives of such compounds, as binding and/or detecting agents to identify influenza virus in clinical

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specimens. The term "neuraminidase binders" is used hereinafter to refer to these compounds and their functionalized derivatives. The method and compounds of the present invention can function either in the presence or the absence of compounds binding non-specifically to influenza virus neuraminidase. Influenza A and B viruses are major causes of acute respiratory disease, with an estimated 30-50 million infections annually in the United States alone. Influenza A has been responsible for major epidemics, such as the "Spanish flu" of 1919 which killed millions of people. Many viral and bacterial infections may exhibit symptoms similar to those of influenza. The rapid identification of respiratory viruses would enable physicians to use the most appropriate therapy early in the illness. For example, an early and accurate diagnosis would allow decisions regarding the use of antibacterial therapy and hospitalization of children and the elderly. Web site: http://www.delphion.com/details?pn=US06503745__ •

Dimeric inhibitors of influenza neuraminidase Inventor(s): Jin; Betty (Victoria, AU), Wu; Wen-Yang (Victoria, AU) Assignee(s): Biota Scientific Management Pty. Ltd. (Victoria, AT) Patent Number: 6,548,476 Date filed: September 8, 2000 Abstract: This invention relates to novel dimeric compounds, methods for their preparation, pharmaceutical formulations thereof, and their use as antiviral agents. The compounds are particularly useful against influenza virus. In particular the invention provides a dimeric compound which comprises two neuraminidase binding groups attached to a spacer or linking group. Preferably the dimeric molecule comprises two neuraminidase-binding neuraminic acid (sialic acid) or cyclopentyl or cyclohexenyl carboxylic acid derivatives covalently attached to a common spacer group. Pharmaceutical compositions and methods of treatment, prophylaxis and diagnosis are disclosed and claimed. Excerpt(s): This invention relates to a new class of chemical compounds and their use in medicine. In particular the invention concerns novel dimeric compounds, methods for their preparation, pharmaceutical formulations thereof and their use as antiviral agents. Enzymes with the ability to cleave N-acetyl neuraminic acid (NANA), also known as sialic acid, from other carbohydrates are present in many microorganisms. These include bacteria such as Vibrio cholerae, Clostridium perfringens, Streptococcus pneumoniae and Arthrobacter sialophilus, and viruses such as influenza virus, parainfluenza virus, mumps virus, Newcastle disease virus and Sendai virus. Most of these viruses are of the orthomyxovirus or paramyxovirus groups, and carry a neuraminidase activity on the surface of the virus particles. Many of these neuraminidase-possessing organisms are major pathogens of man and/or animals, and some, such as influenza virus and Newcastle disease virus, cause diseases of enormous importance. In addition to the sialic acid based inhibitors mentioned above, other types of highly active inhibitors of influenza virus neuraminidase have also been described, particularly those based on 5- and 6-membered carbocyclic ring systems (eg. International Patent Publications No. WO 96/26933 and No. 97/47194). Web site: http://www.delphion.com/details?pn=US06548476__

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Identification and use of antiviral compounds that inhibit interaction of host cell proteins and viral proteins required for viral replication Inventor(s): Harty; Ronald (Bensalem, PA), O'Neill; Robert (New York, NY), Palese; Peter M (Leonia, NJ) Assignee(s): Mount Sinai School of Medicine of New York University (New York, NY) Patent Number: 6,503,703 Date filed: August 11, 2000 Abstract: The present invention relates to the identification of host cell proteins that interact with viral proteins required for virus replication, and high throughput assays to identify compounds that interfere with the specific interaction between the viral and host cell protein. Interfering compounds that inhibit viral replication can be used therapeutically to treat viral infection. The invention is based, in part, on the Applicants' discovery of novel interactions between viral proteins and a human host cell proteins. One of these host cell proteins, referred to herein as NPI-1, interacts with influenza virus protein NP. Also, host cell proteins, referred to herein as NS1I-1 and NS1-BP interact with influenza virus protein NS.sub.1. In addition, host cell proteins containing WW domains that interact with viral proteins such as Rhabdoviral M protein are described. Compounds that interfere with the binding of the host cell and viral proteins, and inhibit viral replication can be useful for treating viral infection in vivo. Excerpt(s): The present invention relates to the identification of new cellular targets for viral intervention, the identification of antiviral compounds that act on the new targets, and the therapeutic use of such antiviral compounds. Replication of viruses can induce drastic changes in the infected host cell metabolism. The analysis of the replication cycle of viruses by molecular biological techniques has facilitated the identification and study of viral gene products that modulate and affect cellular functions (Knipe, 1996, in Fields Virology-1996, Fields, et al., eds., Raven Publishers, Philadelphia, Pa., p. 273-299). Influenza A virus is a negative strand RNA virus belonging to the orthomyxovinis family. The genome of the virus consists of 8 segments and encodes 10 polypeptides. Experimental evidence generated in the laboratory of Scholtissek indicates that the nucleoprotein (NP) is a major determinant of species specificity of influenza viruses (Scholtissek, et al., 1985, Virology 147: 287-294). Web site: http://www.delphion.com/details?pn=US06503703__

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Immunological combination compositions and methods Inventor(s): Becker; Robert S. (Henryville, PA), Biscardi; Karen S. (South Sterling, PA), Erdile; Lorne F. (Tassin la Demi Lune, FR), Gray; Maryann (Bartonsville, PA), Guy; Bruno (Lyons, FR), Huebner; Robert C. (Stroudsburg, PA) Assignee(s): Connaught Laboratories, Inc. (Swiftwater, PA) Patent Number: 6,379,675 Date filed: January 19, 1996 Abstract: Immunological compositions and methods for making and using them. The compositions contain at least one antigen and at least one lipoprotein and optionally an adjuvant. The lipoprotein can itself be antigenic or immunogenic. The antigen can be influenza HA and the lipoprotein a recombinantly expressed product having an OspA leader for lipidation and PspA for the protein portion. The antigen can be OspC and the

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lipoprotein OspA. The components of the composition are co-administered. A potentiated immunological response is obtained by the compositions and methods. Excerpt(s): The present invention relates to compositions for eliciting an immunological response in a host, animal or human, and methods for making and using the same. The invention further relates to such compositions and methods wherein the composition comprises an antigen and a lipoprotein adsorbed to an adjuvant. More preferably, the lipoprotein is also antigenic or immunogenic, and thus the composition can be a combination, multivalent or "cocktail" composition. Accordingly, the invention also relates to co-administration of at least one antigen and at least one lipoprotein in a composition which can include additional ingredients, such as an adjuvant. The lipoprotein can be a naturally occurring lipoprotein or a recombinant lipoprotein. The recombinant lipoprotein can be from expression by a vector of homologous sequences for the lipidated and protein portions of the lipoprotein, i.e., the sequences for the lipidation and protein can naturally occur together. In such a recombinant lipoprotein, the lipidation thereof can be from expression of a first nucleic acid sequence and the protein thereof can be from expression of a second nucleic acid sequence, wherein the first and second nucleic acid sequences, which do not naturally occur together, and such sequences can be expressed as a contiguous lipoprotein. Thus, the invention relates to compositions and methods involving administration of lipoproteins, including recombinant lipoproteins; and the recombinant lipoproteins can be similar to native proteins, or novel hybrid proteins. The invention further relates to the aforementioned compositions for eliciting an immunological response and methods for making and using the same wherein the lipoprotein is recombinantly expressed lipoprotein from expression of such aforementioned first and second nucleic acid sequences wherein the first nucleic acid sequence encodes a Borrelia lipoprotein leader sequence; preferably such a recombinant lipidated protein expressed using the nucleic acid sequence encoding the OspA leader sequence. In a preferred embodiment the lipoprotein can be OspA; and thus, the invention also relates to recombinant OspA and uses thereof the compositions and methods. Web site: http://www.delphion.com/details?pn=US06379675__ •

Inactivated influenza virus vaccine for nasal or oral application Inventor(s): Barrett; Noel (Klosterneuburg/Weidling, AT), Dorner; Friedrich (Vienna, AT), Gerencer; Marijan (Vienna, AT), Kistner; Otfried (Vienna, AT) Assignee(s): Baxter Healthcare S.A. (Zurich, CH) Patent Number: 6,635,246 Date filed: December 5, 2001 Abstract: The invention relates to nasal or oral administration of a compound containing inactivated influenza virus antigen and aluminum as adjuvant for the prophylaxis of influenza virus infections. Said vaccine is especially suitable for inducing a mucosal IgA immune response and systemic IgG immune response. Excerpt(s): The invention relates to a vaccine composition containing at least one inactivated influenza virus antigen and aluminum as an adjuvant for nasal or oral application for the prophylaxis of influenza virus infections. Influenza virus infections represent an ever greater health risk, especially in the elderly and in persons with chronic diseases, because the infection in these groups often leads to higher mortality rates. Since the introduction in the 1940s of an inactivated influenza vaccine containing

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inactivated virus material from infected incubated eggs, the risk and course of the infection as well as the mortality rates in elderly persons have dropped. To date, inactivated influenza virus vaccines from eggs are licensed for parenteral administration to people, and induce anti-HA-IgG antibodies in the serum. The crossprotection against heterologous influenza viruses, however, can be traced primarily to the cross-reactivity of IgA antibodies in a natural infection. (Liew et al., 1984, Eur. J. Immunol. 14:350-356). Therefore, with the development of new immunization methods against influenza virus infections, an attempt is being made to stimulate the production of the mucosal IgA immune response. Web site: http://www.delphion.com/details?pn=US06635246__ •

Influenza sensor Inventor(s): Schmidt; Jurgen G. (Los Alamos, NM), Silks, III; Louis A. (Los Alamos, NM), Song; Xuedong (Los Alamos, NM), Swanson; Basil I. (Los Alamos, NM), Unkefer; Clifford (Los Alamos, NM) Assignee(s): The Regents of the University of California (Los Alamos, NM) Patent Number: 6,627,396 Date filed: October 27, 2000 Abstract: A sensor for the detection of tetrameric multivalent neuraminidase within a sample is disclosed, where a positive detection indicates the presence of a target virus within the sample. Also disclosed is a trifunctional composition of matter including a trifunctional linker moiety with groups bonded thereto including (a) an alkyl chain adapted for attachment to a substrate, (b) a fluorescent moiety capable of generating a fluorescent signal, and (c) a recognition moiety having a spacer group of a defined length thereon, the recognition moiety capable of binding with tetrameric multivalent neuraminidase. Excerpt(s): The present invention relates to a diagnostic sensor for the detection of influenza virus and to a method of detecting influenza virus with such a diagnostic sensor. This invention was made with government support under Contract No. W-7405ENG-36 awarded by the U.S. Department of Energy. The government has certain rights in the invention. The early diagnosis of influenza infection is important for several reasons. One reason is that it is critical to be able to rapidly screen influenza from other infectious diseases in the event of a bio-agent attack. Most scenarios for bio-agent attacks show a slowed response to the recognition that an attack has taken place primarily because diseases such as anthrax and smallpox present flu-like symptoms. Medical personnel do not have a rapid and simple screen for influenza infection and, consequently, victims can be miss-diagnosed as having the flu and sent home. A delay of even a few days in the recognition of a bio-agent attack can have adverse affect on the minimization of the impact of an attack. Another reason for a rapid diagnostic for influenza is important is in helping to avert a worldwide pandemic in the event that a new strain like the 1918 swine flu appears. Rapid screening with inexpensive fieldable sensors is essential to rapidly pinpoint a new potential outbreak. Although it is also important to specify the strain of the influenza infection, it is first critical to rapidly identify an outbreak and this can only be done using a flexible, inexpensive, fieldable sensor. Web site: http://www.delphion.com/details?pn=US06627396__

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Influenza vaccine composition with chitosan adjuvant Inventor(s): Bacon; Andrew David (London, GB), Makin; Jill Catherine (Liverpool, GB) Assignee(s): West Pharmaceutical Services Drug Delivery & Clinical Research Centre (Nottingham, GB) Patent Number: 6,534,065 Date filed: May 30, 2000 Abstract: A vaccine composition adapted for mucosal administration is provided. The composition includes one or more influenza vaccine antigens and an effective adjuvant amount of an acid addition salt of a chitosan wherein the chitosan is a deacetylated chitin which is at least 80% deacetylated and has a weight average molecular weight of between 10,000 and 100,000. Excerpt(s): This invention relates to a vaccine composition for intranasal administration comprising one or more influenza antigens, and a chitosan as a mucosal adjuvant. The invention also relates to methods of immunization using the vaccine compositions, and to the use of certain chitosans for enhancing the immunogenicity of influenza viral antigens, when administered intranasally. Current influenza vaccines consist of either inactivated whole virus, disrupted virus (split vaccines) or purified preparations of the membrane glycoproteins haemagglutinin (HA) and neuraminidase (NA) sub-unit vaccines. Haemagglutinin and neuraminidase are the antigens to which protective antibody responses are directed, haemagglutinin being the major protective antigen. Estimates of the efficacy of these parenterally administered vaccines vary greatly. Such vaccines are believed to act primarily by eliciting circulating anti-haemagglutinin IgG antibodies that transudate into the lower respiratory tract. M. L. Clements et al, J. Clinical Microbiology 24, 157-160, 1986, have previously reported that both secretory IgA and serum IgG participate in immunity to influenza virus. Moreover, in mice, a number of published studies have demonstrated the importance of respiratory IgA to protection against influenza infection. It has also been found that an advantage of stimulating a local IgA response to influenza is that it is often of a broader specificity than the serum response and thus can provide cross-protection against viruses possessing haemagglutinin molecules different from those present in the vaccine. Accordingly, influenza vaccines that elicit both local secretory and serum antihaemagglutinin responses should provide superior immunity to current vaccines. However, parenteral vaccination (intramuscular, sub-cutaneous etc.) is not effective at eliciting local antibody production, if there has been no previous mucosal exposure (e.g. infection). In order to stimulate the mucosal immune system, the vaccine must be applied topically to a mucosal surface. Web site: http://www.delphion.com/details?pn=US06534065__

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Influenza virus vaccine composition Inventor(s): Barrett; Noel (Klosterneuburg/Weidling, AT), Dorner; Friedrich (Vienna, AT), Kistner; Otfried (Vienna, AT), Mundt; Wolfgang (Vienna, AT) Assignee(s): Baxter Aktiengesellschaft (Vienna, AT) Patent Number: 6,372,223 Date filed: June 12, 2001

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Abstract: This invention describes an influenza virus vaccine containing an influenza virus antigen obtained from a cell culture, with an influenza virus antigen content between 1.mu.g and 5.mu.g per dose and aluminum as an adjuvant as well as a method for its preparation. Excerpt(s): The present invention concerns an influenza virus vaccine composition with a reduced influenza virus antigen content and with aluminum as an adjuvant. In addition, the present invention concerns the use of the vaccine composition in the production of a drug and for the induction of an effective immune response in higher vertebrates, in particular in humans. Influenza virus infections pose an increasing risk to the health, particularly to the health of the elderly and of persons suffering from chronic diseases, since the infection in these groups of persons frequently leads to an increase in the mortality rate. Since the introduction of an inactive influenza vaccine containing inactive virus material from infected embryonated chicken eggs in the 1940s, the risk and the course of the infection have improved and the mortality rate in the elderly has decreased. For a vaccine which leads to a positive ratio between the vaccine dose and the IgG antibody response to be effective, health authorities recommend a vaccine dose between 10.mu.g and 15.mu.g of HA (hemagglutination) antigen per dose. Web site: http://www.delphion.com/details?pn=US06372223__ •

Intranasal delivery system Inventor(s): Penner; Steven J. (Broomfield, CO), Sebring; Randal W. (Fort Collins, CO) Assignee(s): Heska Corporation (Fort Collins, CO) Patent Number: 6,398,774 Date filed: September 29, 1999 Abstract: This invention relates to apparatus and methods of delivering various compositions including medicaments to a variety of targets. The invention also includes an intranasal delivery device for the delivery of such compositions or medicaments including live virus vaccines to both humans and animals. Specifically, the invention addresses the difficulties of delivering cold-adapted live equine influenza viruses intranasally to equids. Excerpt(s): This invention relates to an equine intranasal delivery system for the delivery of cold-adapted equine viruses. The invention also includes both apparatus and methods for the intranasal delivery of various materials, compositions or medicaments to both humans and animals. Generally, the invention provides basic technology for the delivery of various compositions to target locations. There are many advantages to intranasal administration of medications and other compositions which include, among others, a direct route to the blood stream, avoidance of hepatic first pass metabolism, bioavailability, ease and convenience, and proximity to the central nervous system. See Y. W. Chien et al., Anatomy and Physiology of the Nose, Nasal Systemic Drug Delivery, Chapter 1, 1-26, 1989. Various types of compositions, therapeutics, prophylactics or otherwise, may be delivered intranasally including, but not limited to, topical anesthetics, sedatives, hypnotics, analgesics, ketamines, opiates, glucagons, vaccines, anti-nausea and motion sickness medications, antihistamines, antihypertensive drugs, psychoactive medications, antibiotics, and hormones. See, as examples, M. R. Nott et al., Topical Anaesthesia for the Insertion of Nasogastric Tubes, European Journal of Anaesthesiology, 12(3), May 1995; R. J. Henry et al, A pharmacokinetic Study of Midazolam in Dogs: Nasal Drop Versus Atomizer Administration, Journal of the

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American Academy of Pediatric Dentistry, 20(5), 321-326, 1998; J. Lithander et al., Sedation with nasal Ketamine and Midazolam for Cryotherapy in Retinopathy of Prematurity, British Journal of Ophthalmology, 77(8), 529-530, 1993; F. E. Ralley, Intranasal Opiates: Old Route For New Drugs, Canadian Journal of Anesthesiology, 36(5) 491-493, 1989; B. Haneberg et al, Intranasal Administration of Mengiococcal outer membrane vesicle vaccine induces persistent local Mucosal Antibodies and Serum Antibodies with Strong Bactericidal Activity in Humans, Infection and Immunity, 66(4), 1334-1341, 1998; B. K. Wager et al, A Double Blind Placebo-Controlled Evaluation of Intranasal Metoclopramide in the Prevention of Postoperative nausea and Vomiting, Pharmacotherapy, 16(6), 1063-1069 1996; and J. Q. Wang, et al., An Experimental Study on Nasal Absorption of Gentamycin in Dogs, Chinese Medical Journal, 107(3), 219-221, 1994. Specifically with respect to live virus vaccines, it has been shown that they are often too pathogenic for use as immunogens for either humans or animals as described in U.S. Pat. No. 3,953,592. Attempts to vaccinate against viral infection With inactivated virus, however, may not offer effective protection and can produce undesirable side effects as indicated in U.S. Pat. No. 3,953,592; R. Belshe et al, Immunization of Infants and Young Children with Live Attenuated Trivalent Cold-Recombinant Influenza A H1N1, H3N2, and B Vaccine, The Journal of Infectious Disease, Volume 165, 727-732, 1992; K. M. Nelson et al., Local and Systemic Isotype-specific Antibody Responses to Equine Influenza Virus Infection Versus Conventional Vaccination, Vaccine, Volume 16, Number 13, 1998. Injection of equids with inactivated viruses may cause, for example, inflammatory reactions at the site of injection. See Mumford et al., Serological Methods for Identification of Slowly-Groweing Herpesviruses Isolated from the Respiratory Tract of Horses, Equine Infectious Disease IV, 49-52, 1978; Mumford et al., Consultation on Newly Emerging Strains of equine Influenza,Vaccine 11, 1172-1174, 1993. It has also been shown that protective responses to viral infection are not limited to the production of antibodies but that a local antibody system and an interferon production mechanism operate at the primary site of infection in the nasal passage membranes as disclosed by U.S. Pat. No. 4,132,775; T. Tomoda et al., Prevention of influenza by the Intranasal Administration of Cold-Recombinant, Live-attenuated Influenza Virus Vaccine: Importance of Interferon-.gamma. Production and Local IgA Response, Vaccine, Volume 13, Number 2, 185-190, 1995; and Holmes, Lamb, Coggins, et al, Live Temperature Sensitive Equine-2 Influenza A Virus Vaccine: Production and Eficacy in Experimental Ponies, Equine infectious disease VI, 253-258, 1992. Web site: http://www.delphion.com/details?pn=US06398774__ •

Method of preservation of vaccines with polybiguanide Inventor(s): Greally; Declan (Liverpool, GB), Lawrence; Michelle Irene Gregarach (Liverpool, GB) Assignee(s): Medeva Europe Limited (London, GB) Patent Number: 6,403,363 Date filed: July 12, 2001 Abstract: A method for preventing or reducing bacterial contamination of a viral vaccine is disclosed. The method comprises adding an effective preserving amount of a polybiguanide-containing preservative composition to a solution containing vaccine virus or virus antigen. The method is particularly useful in preventing or reducing bacterial contamination of process solutions involved in the manufacture of influenza vaccines.

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Excerpt(s): This invention relates to methods of preventing or reducing microbial, and in particular, bacterial, contamination of viral vaccines such as influenza vaccines, during manufacture. Current influenza vaccines consist of either inactivated whole virus, disrupted virus (split vaccines) or purified preparations of the membrane glycoproteins haemagglutinin (HA) and neuraminidase (NA) sub-unit vaccines. Haemagglutinin and neuraminidase are the antigens to which protective antibody responses are directed, haemagglutinin being the major protective antigen. The haemagglutinin and neuraminidase antigens may be present in the vaccine in the form of rosettes, e.g. particles with a radius in the range 10 to 25 nanometer. One example of a commercially available haemagglutinin/neuraminidase preparation is the "Fluvirin" product manufactured and sold by Evans Medical Limited of Speke, Merseyside, United Kingdom; see also S. Renfrey and A. Watts, Vaccine, 1994, Volume 12, Number 8, pp 747-752. During the manufacture of viral vaccines such as the aforementioned influenza vaccines, preservatives can be used to reduce or prevent microbial contamination of the solutions isolated from the viral growth medium, and subsequent solutions containing partially purified or purified viral antigens. For example, with viral vaccines such as influenza vaccines in which eggs are used as the viral growth medium, a preservative can be added to the allantoic fluid harvested from the eggs after incubation with the virus. The purpose of the preservative is to reduce levels of contamination due to the inherent non-sterility of the egg, and also to reduce or prevent bacterial contamination during subsequent processing of the harvested allantoic fluid. Web site: http://www.delphion.com/details?pn=US06403363__ •

Methods and apparatus to prevent colds, flus, and infections of the human respiratory system Inventor(s): Vail, III; William Banning (Bothell, WA), Vail; Marilyn L. (Bothell, WA) Assignee(s): Inhalation, Inc. (Woodinville, WA) Patent Number: 6,447,816 Date filed: April 3, 2000 Abstract: Strong vapors from eucalyptus oil and tea tree oil are inhaled periodically to prevent the infection of the human respiratory system by pathogens that cause colds, influenza, pneumonia, and tuberculosis. Apparatus suitable for the periodic inhalation of strong vapors from eucalyptus oil and tea tree oil are provided. Excerpt(s): One of the inventors has poor respiratory health, has had repeated bouts with pneumonia, colds, flu, asthma, and has been recently diagnosed with the initial stages of emphysema--despite all that modern medicine has had to offer. This first inventor also comes from a family known for a long history of respiratory problems. Therefore, the inventors decided to look beyond conventional "modern medicine" to help the first inventor, and as a result, have conceived methods to substantially prevent colds, flus, and infections of the human respiratory system. These methods include the inhalation of the vapors from eucalyptus oil and/or tea tree oil that are theorized to form a protective, and infection-preventing, thin layer within the entire respiratory system, including the lungs, bronchial tubes, and the nasal cavities. This thin layer maintains its anti-pathogenic properties for a period of time following the inhalation of the vapors for at least one-half hour, and perhaps longer. This thin anti-pathogenic layer substantially prevents the initial infection of colds, flus, and other pathogens for a period of time following inhalation. The inventors also propose the prophylactic use of inhaled eucalyptus oil and/or tea tree to prevent additional pathogenic infections such

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as tuberculosis, which is becoming a major health problem in the United States. The field of invention relates to the prevention of colds, flus, and other pathogens within the respiratory system of human beings by the inhalation of vapors from highly volatile essential oils such as eucalyptus oil and/or tea tree oil. Following the inhalation of the vapors, a thin anti-pathogenic layer is formed in the respiratory system that protects against infection for a certain duration of time following inhalation. While certain medical uses for eucalyptus oil and tea tree oil have been previously disclosed, to the inventor's best knowledge, none of those previously disclosed methods have suggested, or proposed, that the periodic inhalation of eucalyptus oil and/or tea tree oil may be used as prophylactic agents to substantially prevent infection of colds, flus, and other pathogens within the respiratory system of human beings for a duration of time following that inhalation. AFTER the infection of human beings with certain pathogens, previous inhalation therapies have suggested using eucalyptus oil and or tea tree oil to aid in the recovery from certain respiratory diseases. However, none of these previous methods have suggested using eucalyptus oil and/or tea tree oil as prophylactic agents to routinely and substantially PREVENT the initial infection of pathogens for a duration of time following their inhalation as a primary method of preventing disease. Web site: http://www.delphion.com/details?pn=US06447816__ •

Methods for detecting anti-viral activity of calcium-dependent lectins Inventor(s): Wakamiya; Nobutaka (Ibaraki, JP) Assignee(s): Fuso Pharmaceutical Industries, Ltd. (Osaka, JP) Patent Number: 6,365,342 Date filed: August 3, 1998 Abstract: A recombinant conglutinin which contains a collagen region consisting of six amino acids containing two amino acid sequences Gly-Xaa-Xaa (SEQ ID NO:3, wherein Xaa stands for a protein-constituting amino acid), the neck region of natural conglutinin and the sugar chain recognition region of natural conglutinin, has an antiviral activity (virus neutralizing activity), and is expected to be applicable to drugs; and a process for detecting anti-influenza A virus activity of a mannose-binding protein (MBP) or a human mannose-binding protein (hMBP) involving the step of treating influenza A virus-infected cells with the MBP or hMBP and measuring the level of the suppression of the budding of the virus in the virus-infected cells. An MBP and an hMBP having an anti-influenza A virus activity are disclosed. Excerpt(s): The present invention relates to recombinant conglutinin having anti-virus activities (neutralization activities) which are expected to be applied to medicines and producing method thereof, and a method for detecting physiological activities of collecting. Conglutinin is an animal lectin belonged to calcium-dependent mammalian C-type lectin family and existed in the bovine serum. Whole amino acids sequence (SEQ ID No.: 1) had been analyzed by Lee et al., [Lee et al., J Biol. Chem., Vol. 266, pp. 27152723, 1991]. C-type lectin comprises basic unit having the four unique regions of (1) Nterminal region contained much cysteine, (2) collagen-like region, (3) neck region and (4) carbohydrate recognition domain (CRD) [Malhortra et al., European Journal Immunology, Vol. 22, pp. 1437-1445, 1992]. Web site: http://www.delphion.com/details?pn=US06365342__

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Methods for the detection of antibodies associated with autoimmune disorders and infectious agents employing immunoretroid peptides derived from antigens associated with said disorders and agents Inventor(s): Briand; Jean-Paul (Strasbourg, FR), Guichard; Gilles (Strasbourg, FR), Muller; Sylviane (Strasbourg, FR), Van Regenmortel; Marc (Strasbourg, FR) Assignee(s): Biomerieux S.A. (Marcy-L'Etoile, FR) Patent Number: 6,455,244 Date filed: September 13, 1996 Abstract: This invention is directed toward methods and kits for the detection of antibodies associated with autoimmune disorders or infectious agents in an individual employing immunoretroid peptides derived from antigens associated with said disorders and agents. These immunoretroid compounds are derived from the following group of peptides: the foot-and-mouth disease virus major antigenic determinant VP1 peptide [A], the foot-and-mouth disease virus major antigenic determinant VP1 peptide [USA], the influenza virus strain X31 site A peptide, the C-terminal epitope of the histone protein H3 consisting of amino acids 130-135, an internal epitope of the histone protein H3 consisting of amino acids 28-45, an internal epitope of the recombinant 52 kDa autoimmune protein SSA/Ro (Ro52) consisting of amino acids 277-291, an internal epitope of the recombinant 60 kDa autoimmune protein SSA/Ro (Ro60) consisting of amino acids 304-324, the foot-and-mouth disease virus immunodominant loop peptide FP, the foot-and-mouth disease virus immunodominant loop peptide FL, and the footand-mouth disease virus immunodominant loop peptide SL. The immunoretroids derived from these peptides are capable of binding to the aforementioned antibodies with equal affinity as compared to the native antigen. Excerpt(s): The present invention relates to retro peptides, as well as antibodies thereto, and to their uses, chiefly in the field of preparation of pharmaceutical compositions, in particular vaccines, and for in vitro diagnosis of various pathologies. The development of neuropeptides, peptide hormones and antibiotics based on peptides or of synthetic vaccines based on peptides faces great problems due to the high sensitivity of peptides to proteolysis, which limits, inter alia, oral and parenteral administration. For several years, attention has been paid to the synthesis of peptide analogues in order to investigate peptides which mimic natural peptides or proteins and have an increased activity and longer biological half-life compared to the latter. For example, peptide analogues have been obtained by replacing the L amino acids of the natural peptide by the corresponding D amino acids, or by non-natural residues (for example sarcosine and.beta.-alanine), or also by modification of peptide bonds of the natural peptide (Chorev, M. & Goodman, M. (1993), Acc. Chem. Res. 26, 266-273; Marraud et al., (1993), Biopolymers, 33, 1135-1148). Web site: http://www.delphion.com/details?pn=US06455244__

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Noninvasive genetic immunization, expression products therefrom and uses thereof Inventor(s): Curiel; David T. (Birmingham, AL), Marks; Donald H. (Rockaway, NJ), Shi; Zhongkai (Birmingham, AL), Tang; De-chu C. (Birmingham, AL), van Kampen; Kent Rigby (Hoover, AL) Assignee(s): The UAB Research Foundation (Birmingham, AL) Patent Number: 6,348,450 Date filed: May 3, 2000 Abstract: Disclosed and claimed are methods of non-invasive genetic immunization in an animal and/or methods of inducing a systemic immune or therapeutic response in an animal, products therefrom and uses for the methods and products therefrom. The methods can include contacting skin of the animal with a vector in an amount effective to induce the systemic immune or therapeutic response in the animal. The vector can include and express an exogenous nucleic acid molecule encoding an epitope or gene product of interest. The systemic immune response can be to or from the epitope or gene product. The nucleic acid molecule can encode an epitope of interest and/or an antigen of interest and/or a nucleic acid molecule that stimulates and/or modulates an immunological response and/or stimulates and/or modulates expression, e.g., transcription and/or translation, such as transcription and/or translation of an endogenous and/or exogenous nucleic acid molecule; e.g., one or more of influenza hemagglutinin, influenza nuclear protein, tetanus toxin C-fragment, anthrax protective antigen, HIV gp 120, human carcinoembryonic antigen, and/or a therapeutic, an immunomodulatory gene, such as co-stimulatory gene and/or a cytokine gene. The immune response can be induced by the vector expressing the nucleic acid molecule in the animal's cells. The immune response can be against a pathogen or a neoplasm. A prophylactic vaccine or a therapeutic vaccine or an immunological composition can include the vector. Excerpt(s): The present invention relates generally to the fields of immunology and vaccine technology. The present invention also relates to techniques of skin-targeted non-invasive gene delivery to elicit immune responses and uses thereof. The invention further relates to methods of non-invasive genetic immunization in an animal and/or methods of inducing an immunulogical, e.g., systemic immune response or a therapeutic, e.g., a systemic therapeutic response, in an animal, products therefrom and uses for the methods and products therefrom. The invention yet further relates to such methods comprising contacting skin of the animal with a vector in an amount effective to induce the response, e.g., systemic immune response, in the animal. Even further, the invention relates to such methods wherein the vector comprises and express an exogenous nucleic acid molecule encoding an epitope or gene product of interest, e.g., an antigen or therapeutic. Still further, the invention relates to such methods wherein the response, e.g., systemic immune or therapeutic response, can be to or from the epitope or gene product. The invention yet further still relates to such methods wherein the nucleic acid molecule can encode an epitope of interest and/or an antigen of interest and/or a nucleic acid molecule that stimulates and/or modulates an immunological response and/or stimulates and/or modulates expression, e.g., transcription and/or translation, such as transcription and/or translation of an endogenous and/or exogenous nucleic acid molecule. The invention additionally relates to such methods wherein the nucleic acid molecule can be exogenous to the vector. The invention also relates to such methods wherein the exogenous nucleic acid molecule encodes one or more of an antigen or portion thereof, e.g., one or more of an epitope of interest from a pathogen, e.g., an epitope, antigen or gene product which modifies allergic response, an

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epitope antigen or gene product which modifies physiological function, influenza hemagglutinin, influenza nuclear protein, influenza M2, tetanus toxin C-fragment, anthrax protective antigen, anthrax lethal factor, rabies glycoprotein, HBV surface antigen, HIV gp 120, HIV gp 160, human carcinoembryonic antigen, malaria CSP, malaria SSP, malaria MSP, malaria pfg, and mycobacterium tuberculosis HSP; and/or a therapeutic or an immunomodulatory gene, a co-stimulatory gene and/or a cytokine gene. Even further, the invention relates to such methods wherein the immune response can be induced by the vector expressing the nucleic acid molecule in the animal's cells, e.g., epidermal cells. The invention still further relates to such methods wherein the immune response can be against a pathogen or a neoplasm. Web site: http://www.delphion.com/details?pn=US06348450__ •

Pharmaceutical composition comprising serum amyloid P component for prophylactic or therapeutic treatment of virus infections and a kit for detecting binding of compositions to virus components Inventor(s): Andersen; Ove (Odense M, DK), Nielsen; Ellen Holm (Kerteminde, DK), Svehang; Sven-Erik (Odense, DK) Assignee(s): Profylakse Aps (Odense NV, DK) Patent Number: 6,406,698 Date filed: July 24, 1998 Abstract: Pharmaceutical compositions comprising a protein serum amyloid P component (SAP) capable of binding viruses, especially myxovirus, e.g. influenza viruses and thereby preventing the transmission and infection with such viruses. Preferred is mucosal administration, e.g. SAP incorporated in a nose spray or nose drops. Also provided is a method for measuring the binding of SAP to the hemagglutinin of the prevailing influenza virus subtype and strain. Excerpt(s): b) a physiologically acceptable carrier. The pharmaceutical composition comprises serum amyloid P component (SAP) (a naturally occurring protein) or a binder-functional subunit thereof. The reduction of pathogenic properties results in prophylaxis, alleviation or cure of infectious diseases caused by said virus component. Web site: http://www.delphion.com/details?pn=US06406698__

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Pharmaceutical composition for treating or preventing influenza, and novel capped oligonucleotide Inventor(s): Hatta; Toshifumi (Ibaraki, JP), Ishikawa; Masahide (Saitama, JP), Miura; Kin-ichiro (Tokyo, JP), Takai; Kazuyuki (Chiba, JP), Takaku; Hiroshi (Chiba, JP) Assignee(s): Chiba Institute of Technology (Chiba, JP) Patent Number: 6,495,675 Date filed: June 26, 2000 Abstract: A pharmaceutical composition comprising a capped oligonucleotide capable of binding to a PB2 protein of an influenza virus RNA polymerase, and a pharmaceutically acceptable carrier or dilute, said capped oligonucleotide having a structure of the formula (I):m.sup.7 GpppXpY (I)wherein ppp is a triphosphate bridge, p is a monophosphate bridge, m.sup.7 G is 7-methylguanosine group binding at 5' end

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thereof to said ppp, X is a 2'-O-methyl guanosine group or guanosine group, said 2'-Omethyl guanosine group or guanosine group binds at a 5' end thereof to said ppp, and at a 3' end thereof to said p, and Y is an oligoribonucleotide moiety binding at 5' end thereof to said p, and having 5 to 11 bases is disclosed. The pharmaceutical composition can inhibit a protein expression of an influenza virus. Excerpt(s): The present invention relates to a pharmaceutical composition for treating or preventing influenza, and a novel capped oligonucleotide. Influenza is extremely prevalent, repeatedly on a worldwide scale. Most people are infected by airborne germs. The influenza virus is highly infectious, and therefore, when a new subtype of the virus is generated, the prevailing scale thereof is enlarged beyond comparison with the infection of those suffering from the acquired immunodeficiency syndrome (AIDS). The influenza virus belongs to orthomyxoviridae, and has a minus strand, i.e. a single strand RNA virus. The gene of the influenza virus is composed of eight segments. Among proteins encoded by the eight segmentation genes are hemagglutinin (HA) and neuraminidase (NA), which are two spikes on a surface of a virus particle and project from an envelope. There is also a segmentation gene encoding M2, one of the membrane proteins. On the surface of the virus particle exist two glycoproteins in the form of spikes embedded in a lipid bilayer (envelope) stemming from a host. Furthermore, there is another membrane protein, M1. The segmentation gene encoding M2 is also contained in the virus gene, A ribonucleoprotein (RNP) complex is located at the center of the virus, and composed of the gene RNA, three RNA polymerase subunits (PB1, PB2, and PA), and a nucleoprotein (NP). The segments encoding the proteins, PB1, PB2, PA, and NP, are also contained in the virus gene. A non-structural protein is synthesized from the 8th segmentation gene. Web site: http://www.delphion.com/details?pn=US06495675__ •

Receptor-binding pocket mutants of influenza a virus hemagglutinin for use in targeted gene delivery Inventor(s): Bates; Paul (Swarthmore, PA), Mir-Shekari; Yasamin (London, GB) Assignee(s): The Trustees of the University of Pennsylvania (Philadelphia, PA) Patent Number: 6,416,997 Date filed: March 15, 2000 Abstract: The invention relates to a lipid containing vector capable of fusing to a cell membrane and delivering a compounds contained therein to a cell, and methods of use thereof. Excerpt(s): The field of the invention is gene therapy, particularly the use of enveloped vectors for gene delivery. Infection of a host cell by an enveloped virus is initiated by binding of at least one viral envelope protein to a cognate virus receptor molecule on the cell surface. The viral envelope protein not only binds to the receptor but also catalyzes fusion of the viral envelope and the host cell membrane. The presence or absence on a cell of a cognate virus receptor molecule is a primary determinant of the host range and the tissue tropism of any given virus. Hemagglutinin (HA) is the major surface protein of influenza A virus, and it is perhaps the best-characterized membrane protein. HA is synthesized as a single polypeptide precursor, HO, which is proteolytically cleaved into two subunits HA1 and HA2, either in the late Golgi or extracellularly, depending on the nature of the cleavage site as reviewed in Klenk and Garten (Trends Microbiol. 2:39-43). HA initiates infection by binding a sialic acid-containing virus receptor molecule on the

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surface of a target cell (Paulson, 1985, In: The Receptors, Vol. 2, pp.131-219, Conn, ed., Academic Press, Orlando, Fla.). Detailed structural studies further revealed that there is a region in the HA1 subunit that binds sialic acid which region has been named the receptor binding pocket (RBP) (Weis et al., 1988, 333:426-431). The RBP comprises several highly conserved amino acid residues, all of which are involved in the hydrogen-bond network which defines the RBP topography, and some of which are directly involved in sialic acid binding (Weis et al., supra). Web site: http://www.delphion.com/details?pn=US06416997__ •

Recombinant trytophan mutants of influenza Inventor(s): Parkin; Neil T. (Belmont, CA) Assignee(s): Med Immune Vaccines, Inc. (Gaithersburg, MD) Patent Number: 6,528,064 Date filed: November 26, 2001 Abstract: Recombinant PB2 tryptophan variant influenza viruses, RNA, cDNA and vectors are provided. Also provided are immunogenic compositions containing the variant viruses, methods of producing such viruses and methods for the prophylactic treatment of influenza in humans. Excerpt(s): This invention relates to influenza virus immunogenic compositions and methods of producing such compositions. More specifically, this invention relates to influenza virus immunogenic compositions having discreet, specifically engineered mutations in the native PB2 polymerase RNA sequence of influenza resulting in the deletion of, and/or substitution of, at least one of the native tryptophan amino acid residues in the PB2 protein. Influenza is an enveloped, single-stranded, negative-sense RNA virus that causes serious respiratory ailments throughout the world. It is the only member of the Orthomyxoviridae family and has been subgrouped into three types, A, B and C. Influenza virions consist of an internal ribonucleoprotein core containing the single-stranded RNA genome and an outer lipoprotein envelope lined inside by a matrix (hereinafter "M1") protein. The segmented genome of influenza A consists of eight molecules of linear, negative polarity, single-stranded RNA sequences that encode ten polypeptides. Segment 1 is 2341 nucleotides in length and encodes PB2, a 759 amino acid polypeptide which is one of the three proteins which comprise the RNA-dependent RNA polymerase complex. The remaining two polymerase proteins, PB1, a 757 amino acid polypeptide, and PA, a 716 amino acid polypeptide, are encoded by a 2341 nucleotide sequence and a 2233 nucleotide sequence (segments 2 and 3), respectively. Segment 4 of the genome consists of a 1778 nucleotide sequence encoding a 566 amino acid hemagglutin (HA) surface glycoprotein which projects from the lipoprotein envelope and mediates attachment to and entry into cells. Segment 5 consists of 1565 nucleotides encoding a 498 amino acid nucleoprotein (NP) protein that forms the nucleocapsid. Segment 6 consists of a 1413 nucleotide sequence encoding a 454 amino acid neuraminidase (NA) envelope glycoprotein. Segment 7 consists of a 1027 nucleotide sequence encoding a 252 amino acid M1 protein, and a 96 amino acid M2 protein, which is translated from a spliced variant of the M RNA. Segment 8 consists of a 890 nucleotide sequence encoding two nonstructural proteins, NS 1 and NS2, composed of 230 and 121 amino acids respectively, whose function is not well defined. NS2 is translated from a spliced variant of the NS RNA. Web site: http://www.delphion.com/details?pn=US06528064__

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Safe botanical drug for treatment and prevention of influenza and increasing immune function Inventor(s): Liu; Yaguang (67-08 168th St., Flushing, NY 11365) Assignee(s): none reported Patent Number: 6,475,531 Date filed: February 28, 2001 Abstract: This invention relates to new safe botanical drug, which is used for treatment and prevention of influenza and increasing immune function. Specifically, this invention provides a method for producing pure Banlangensu (PBLG), BLG's Polysaccharide and Isatin B. Excerpt(s): The present invention related to novel pharmaceutical composition for treatment and prevention of influenza caused by viruses and increase immune function, processed for the production of these pharmaceutical compositions and the use thereof The bifunctional pharmaceutical composition is nontoxic. Specifically, this invention provides a new safe pharmaceutical composition of pure Banlangensu, which is extracted from among Isatis tinctoria L, I. Indigotica Fort or Baphicacanthus cusia Bremek. The major antiviral drugs can inhibit viral replication but also inhibit some host cell function and possess serious toxicity. For example, amantadine, idoxuridine, cytarabine, vidarabine are major antiviral drugs using in clinic now. Amantadine can inhibit myxoviruses, e.g., influenza A, rubella. The most marked toxic effects of amantadine are central nervous system sign, insomnia, slurred speech, dizziness and ataxia. Idoxuridine can inhibit the replication of herpes simplex virus n the cornea, however DNA synthesis of host cells is also inhibited. Cytarabine can inhibit DNA synthesis and interferes with replication of DNA viruses. But cytarabine also inhibits immune function in human. By weight it is about 10 times more effective than idoxuridine, and it is also 10 times more toxic for host cell. Vidarabine can inhibit herpesvirus, but it is also produce more marked adverse gastrointestinal or neurological side effects. Web site: http://www.delphion.com/details?pn=US06475531__

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Substituted pyrrolidine compounds useful as neuraminidase inhibitors Inventor(s): Babu; Yarlagadda S. (Birmingham, AL), Chand; Pooran (Birmingham, AL), Kotian; Pravin L. (Birmingham, AL), Montgomery; John A. (Birmingham, AL) Assignee(s): BioCryst Pharmaceuticals, Inc. (Birmingham, AL) Patent Number: 6,518,299 Date filed: October 20, 2000 Abstract: Certain substituted pyrrolidine compounds, pharmaceutically acceptable salts thereof, and their method of preparation are disclosed as well as use as influenza virus neuraminidase inhibitors. Excerpt(s): This invention relates to novel substituted pyrrolidine compounds and derivatives thereof useful as neuraminidase inhibitors, to pharmaceutical compositions containing said compounds useful for the prevention, treatment or amelioration of viral, bacterial and other infections, and to methods of using said compounds. The present invention is also concerned with novel intermediates or precursors for producing the novel substituted pyrrolidine compounds of the present invention. Despite the wealth of

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information available, influenza go remains a potentially devastating disease of man, lower mammals, and birds. No effective vaccine exists and no cure is available once the infection has been initiated. Influenza viruses consist of eight pieces of single stranded is RNA, packaged in orderly fashion within the virion. Each piece codes for one of the major viral proteins. The replication complex is enclosed with a membrane composed of matrix protein associated with a lipid bilayer. Embedded in the lipid bilayer are two surface glycoprotein spikes, hemagglutinin (HA) and the enzyme neuraminidase (NA). All of the viral genes have been cloned and the three-dimensional structures of the surface glycoproteins have been determined. Web site: http://www.delphion.com/details?pn=US06518299__ •

Syntheses of 4-alkyl chromogenic glycosides and 7-alkyl chromogenic glycosides of N-acetylneuraminic acids Inventor(s): Bundle; David R. (Edmonton, CA), Du; Minghui (Edmonton, CA), Hingsgaul; Ole (Edmonton, CA), Srivastava; Geeta (Edmonton, CA), Srivastava; Om (Edmonton, CA) Assignee(s): Zymetx, Inc. (Oklahoma City, OK) Patent Number: 6,420,552 Date filed: August 29, 2000 Abstract: The present invention provides improved method of preparing a 4-O-alkyl chromogenic ketoside of N-acetylneuraminic acid (Neu5Ac) and a 7-O-alkyl chromogenic ketoside of N-acetylneuraminic acid (Neu5Ac) for use in the selective detection of various influenza viruses and parainfluenza viruses. The ketosides are substrates that are selectively cleaved by a neuraminidase on the virus to be detected, but not by neuraminidases found on other viruses or on bacteria, or on the cells of the host. The syntheses are efficient and provide large quantities of the ketosides for commercial development. The synthesis includes a step of alkylating the 4- or 7hydroxyl groups of a protected alkyl ester alkyl ketoside derivative of Neu5Ac by processes that include contacting the derivative with a composition comprising an alkyl halide to form a 4- or a 7-O-alkyl protected alkyl ester alkyl ketoside derivative of Neu5Ac. The syntheses alternatively include protecting the 8- and 9-hydroxyl groups of an alkyl ester alkyl ketoside derivative of Neu5Ac by forming an 8,9-ketal or an 8,9epoxide protected alkyl ester alkyl ketoside derivative of Neu5Ac. Excerpt(s): This invention relates to an improved synthesis of derivatives of Nacetylneuraminic acid monoalkylated at either the 4- or the 7-position. The synthetic procedures represent improvements and enhancements that permit obtaining large quantities of the products suitable for commercial production. These derivatives of Nacetylneuraminic acid can be used as chromogenic substrates for the detection of viral neuraminidases. Viral infections are a principal cause of illness due to communicable diseases that affect the public at large. Of these, influenza viruses, including types A and B, are a significant factor responsible for causing respiratory symptoms as well as systemic malaise; other respiratory viruses include parainfluenza 1, 2, 3, and 4, respiratory syncytial virus, and adenovirus. The influenza viruses undergo rapid mutation of strains, producing pathogens with varying degrees of virulence and severity of symptoms. Recently, influenza infection has been as high as the fifth leading cause of death from acute respiratory disease in the United States (Morbidity and Mortality Weekly Report, 36 (1987) 2). Influenza virus types A, B, and C belong to the family of Orthomyxoviridae. Influenza A and B are significant pathogens in children

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and adults causing sever lower respiratory tract disease, whereas influenza C can cause sporadic upper respiratory tract. illness. Influenza virus is highly contagious and can affect large proportions of the population each winter. Influenza A epidemics occur every 2-3 years, whereas influenza B epidemics appear every 4-6 years. Symptoms include moderate to high fever together with chills, headache, myalgia, rhinorrhea, among others. Importantly, virus progeny are detectable 24 hours prior to the appearance of symptoms, and virus titers peak 24-48 hours after symptoms arise. Web site: http://www.delphion.com/details?pn=US06420552__ •

Therapy of respiratory influenza virus infection using free and liposomeencapsulated ribonucleotides Inventor(s): Nagata; Leslie P. (Medicine Hat, CA), Wong; Jonathan P. H. (Medicine Hat, CA) Assignee(s): Her Majesty the Queen in right of Canada, as represented by the Minister of (Ottawa, CA) Patent Number: 6,544,958 Date filed: March 26, 2001 Abstract: The present invention relates to novel ribonucleotide oligonucleotides (RNOs) that are specifically designed to inhibit viral replication. The RNOs are capable of binding to both the negative and positive strands of influenza RNA segments, thereby inhibiting the virus' ability to produce various viral components, thus inhibiting viral propagation, and effectively killing the virus at the intracellular sites of infection in the respiratory tract. The RNOs provided may act independently, or in combination to optimize their antiviral activity. In addition, the RNOs provided may be formulated in liposomes, which facilitate their therapeutic delivery to intracellular sites of infection, and additionally increase antiviral efficacies. Excerpt(s): The present invention relates to novel nucleotides, and more specifically, ribonucleotide oligonucleotides (RNOs) that are specifically designed to inhibit viral replication at the intracellular sites of infection in the respiratory tract. The RNOs are capable of binding to both the negative and positive strands of influenza RNA segments, thereby inhibiting the virus' ability to produce various viral components, and therefore inhibit viral propagation. The RNOs provided may be formulated in liposomes, which facilitate their therapeutic delivery to intracellular sites of infection, and additionally increase antiviral efficacies. Despite recent advances in antiviral therapy and vaccination; acute respiratory infections caused by influenza viruses are important causes of human mortality and morbidity worldwide. Although influenza viruses generally cause a mild malaise in healthy individuals, for the high-risk segments of the population, such as the elderly, the young, and individuals with underlying chronic illness, influenza and the complications resulting from secondary infections, can be life threatening. It is estimated that in the United States alone, more than 10,000 people die each year from influenza and complications from influenza. Vaccination, or immunoprophylaxis, using inactivated or killed whole virus is a widely used conventional preventative measure used to reduce the impact of influenza [Centers for Disease Control, Prevention and control of influenza: recommendations of the Immunization Practices Advisory Committee Weekly Report, 1991; 41 (RR-9) 1-5]. However, there are significant limitations and drawbacks in such an antiviral vaccination.

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Web site: http://www.delphion.com/details?pn=US06544958__ •

Vaccine compositions including chitosan for intranasal administration and use thereof Inventor(s): Chatfield; Steven Neville (Berkshire, GB), Illum; Lisbeth (Nottingham, GB) Assignee(s): West Pharmaceutical Services Drug Delivery & Clinical Research Centre (Nottingham, GB) Patent Number: 6,391,318 Date filed: June 1, 1998 Abstract: A variety of different types of nasal vaccine systems have been described including cholera toxin, microspheres, nanoparticles, liposomes, attenuated virus, and outer membrane proteins (proteosomes). The present invention is directed toward a novel nasal vaccine composition that utilizes the cationic polysaccharide, chitosan, as a delivery system. Chitosan is a polysaccharide comprising copolymers of glucosamine and N-acetylglucosamine. The term chitosan encompasses a series of chitosan polymers with different molecular weights (50 kDa-2,000 kDa) and degree of acetylation (40%98%). Several vaccine animal studies were carried out employing influenza or pertussis antigens in combination with chitosan. Nasal administration of chitosan-antigen nasal vaccines induced significant serum IgG responses and secretory IgA levels. Animals vaccinated via the nasal route with various chitosan-antigen vaccines were also found to be protected against the appropriate challenge. Excerpt(s): The invention is generally in the field of vaccine compositions, and specifically those for intranasal administration. Vaccines are preparations of antigenic materials, administered to recipients with a view to enhancing resistance to infection by inducing active immunity to specific microorganisms, for example bacteria or viruses. Vaccines, which may be as single or mixed component vaccines, are presented in a variety of forms. For example, current influenza vaccines consist of either inactivated whole virus, disrupted virus (split vaccines) or purified preparations of antigenic proteins. Web site: http://www.delphion.com/details?pn=US06391318__

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Vaccines containing paucilsmellar lipid vesicles as immunological adjuvants Inventor(s): Wallach; Donald F. H. (Geneva, CH), Wright; D. Craig (Gaithersburg, MD) Assignee(s): Novavax, Inc. (Rockville, MD) Patent Number: 6,387,373 Date filed: April 24, 1997 Abstract: The present invention features an adjuvanted vaccine, and methods for preparing an adjuvanted vaccine, preferably for immunizing against influenza, where the adjuvant is a lipid vesicle, and preferably is a nonphospholipid, paucilamellar lipid vesicle. The antigen may be encapsulated in the central cavity of the adjuvant, or mixed in solution with the adjuvant. Moreover, the adjuvant may carry a secondary adjuvant to further improve the immune response. Excerpt(s): The present invention relates to an adjuvanted vaccine, where lipid vesicles, particularly nonphospholipid lipid vesicles, serve as the adjuvant, together with

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methods of preparing the vaccine. Immunological adjuvants are the component of the vaccine which augment the immune response to the antigen. Immunological adjuvants function by, inter alia, attracting macrophages to the antigen and then to present that antigen to the regional lymph nodes and initiate an effective antigenic response. Adjuvants may also act as carriers themselves for the antigen. Many of the known immunological adjuvants, such as Freund's complete adjuvant, alum, aluminum hydroxides, and Freund's incomplete adjuvant, while effective at initiating the antigenic response, produce undesirable reactions in humans, such as inflammation at the point of injection. These side effects prevent use of such adjuvants in humans, and have led to the search for alternative immunological adjuvants. Lipid vesicles are substantially spherical structures made of amphiphiles, e.g., surfactants or phospholipids. The lipids of these spherical vesicles are generally organized in the form of lipid bilayers, e.g., multiple onion-like shells of lipid bilayers which encompass an aqueous volume between the bilayers. Certain types of lipid vesicles have an unstructured central cavity which can be used to encapsulate and transport a variety of materials. Paucilamellar lipid vesicles, for example, have 2-10 peripheral bilayers surrounding a large, unstructured central cavity. Until recently, liposome technology has been concerned mostly with vesicles composed of phospholipids. This is primarily because phospholipids are the principal structural components of natural membranes and, accordingly, lipid vesicles have been used as a model system for studying natural membranes. However, there are a number of problems associated with using phospholipids as synthetic membranes. Phospholipid liposomes placed in an in vivo environment are rapidly degraded. Moreover, phospholipids are labile and expensive to purify or synthesize. In addition, classic phospholipid liposomes are in the form of multilamellar as opposed to paucilamellar vesicles and have poor carrying capacities, especially for lipophilic materials, and have poor shelf lives unless lyophilized in the dark with antioxidants. Finally, phospholipids degrade too rapidly in vivo for most pharmaceutical or vaccine applications. Web site: http://www.delphion.com/details?pn=US06387373__

Patent Applications on Influenza As of December 2000, U.S. patent applications are open to public viewing.10 Applications are patent requests which have yet to be granted. (The process to achieve a patent can take several years.) The following patent applications have been filed since December 2000 relating to influenza: •

Aglyco products and methods of use Inventor(s): Bogoch, Elenore S.; (New York, NY), Bogoch, Samuel; (New York, NY) Correspondence: Kenyon & Kenyon; 1500 K Street, N.W., Suite 700; Washington; DC; 20005; US Patent Application Number: 20030023047 Date filed: March 27, 2001 Abstract: Glycoconjugates, therapeutic compositions containing the glycoconjugates and therapeutic methods of using the glycoconjugates are disclosed. In particular, peptide constituents of aglyco 10B which are immunogenic epitopes responsible for recognition

10

This has been a common practice outside the United States prior to December 2000.

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of antigens by the immune system are provided. These glycoconjugates are useful in prevention of influenza virus binding to cells, treatment of schizophrenia and diagnosing chronic viral disease associated with development of cancer. Excerpt(s): This application is a continuation-in-part of co-pending application Ser. No. 08/198,139 filed Feb. 17, 1994 which is incorporated herein in its entirety by reference thereto. This invention concerns the discovery of products and methods to aid in the diagnosis and treatment of disorders of conjugated carbohydrate constituents of living organisms which contribute to cell dysfunction and cell death. Many seemingly unrelated observations made in the past, which were not understood and could not be understood, in terms of cell dysfunction, cell death and specific disease states can now be understood in the light of the methods and compositions of the present invention which defines for the first time the state of, and the consequences of, aglyco pathology, its products, as well as products and processes for its detection and treatment. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Cold-adapted equine influenza viruses Inventor(s): Dowling, Paticia W.; (Pittsburgh, PA), Youngner, Julius S.; (Pittsburgh, PA) Correspondence: Heska Corporation; Intellectual Property DEPT.; 1613 Prospect Parkway; Fort Collins; CO; 80525; US Patent Application Number: 20030180322 Date filed: June 26, 2002 Abstract: The present invention provides experimentally-generated cold-adapted equine influenza viruses, and reassortant influenza A viruses comprising at least one genome segment of such an equine influenza virus, wherein the equine influenza virus genome segment confers at least one identifying phenotype of the cold-adapted equine influenza virus, such as cold-adaptation, temperature sensitivity, dominant interference, or attenuation. Such viruses are formulated into therapeutic compositions to protect animals from diseases caused by influenza A viruses, and in particular, to protect horses from disease caused by equine influenza virus. The present invention also includes methods to protect animals from diseases caused by influenza A virus utilizing the claimed therapeutic compositions. Such methods include using a therapeutic composition as a vaccine to generate a protective immune response in an animal prior to exposure to a virulent virus, and using a therapeutic composition as a treatment for an animal that has been recently infected with a virulent virus, or is likely to be subsequently exposed to virulent virus in a few days whereby the therapeutic composition interferes with the growth of the virulent virus, even in the absence of immunity. The present invention also provides methods to produce cold-adapted equine influenza viruses, and reassortant influenza A viruses having at least one genome segment of an equine influenza virus generated by cold-adaptation. Excerpt(s): The present invention relates to experimentally-generated cold-adapted equine influenza viruses, and particularly to cold-adapted equine influenza viruses having additional phenotypes, such as attenuation, dominant interference, or temperature sensitivity. The invention also includes reassortant influenza A viruses which contain at least one genome segment from such an equine influenza virus, such that the reassortant virus includes certain phenotypes of the donor equine influenza virus. The invention further includes genetically-engineered equine influenza viruses, produced through reverse genetics, which comprise certain identifying phenotypes of a

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cold-adapted equine influenza virus of the present invention. The present invention also relates to the use of these viruses in therapeutic compositions to protect animals from diseases caused by influenza viruses. Equine influenza virus has been recognized as a major respiratory pathogen in horses since about 1956. Disease symptoms caused by equine influenza virus can be severe, and are often followed by secondary bacterial infections. Two subtypes of equine influenza virus are recognized, namely subtype-1, the prototype being A/Equine/Prague/1/56 (H7N7), and subtype-2, the prototype being A/Equine/Miami/1/63 (H3N8). Presently, the predominant virus subtype is subtype-2, which has further diverged among Eurasian and North American isolates in recent years. The currently licensed vaccine for equine influenza is an inactivated (killed) virus vaccine. This vaccine provides minimal, if any, protection for horses, and can produce undesirable side effects, for example, inflammatory reactions at the site of injection. See, e.g., Mumford, 1987, Equine Infectious Disease IV, 207-217, and Mumford, et al., 1993, Vaccine 11, 1172-1174. Furthermore, current modalities cannot be used in young foals, because they cannot overcome maternal immunity, and can induce tolerance in a younger animal. Based on the severity of disease, there remains a need for safe, effective therapeutic compositions to protect horses against equine influenza disease. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Complementing cell lines Inventor(s): Havenga, Menzo; (Alphen San Den Rijn, NL), Mehtali, Majid; (Plobsheim, FR), Vogels, Ronald; (Linschoten, NL) Correspondence: Trask Britt; P.O. Box 2550; Salt Lake City; UT; 84110; US Patent Application Number: 20030119192 Date filed: October 15, 2002 Abstract: A packaging cell line capable of complementing recombinant adenoviruses based on serotypes from subgroup B, preferably adenovirus type 35. The cell line is preferably derived from primary diploid human cells transformed by adenovirus E1 sequences either operatively linked on one or two DNA molecules, the sequences operatively linked to regulatory sequences enabling transcription and translation of encoded proteins. Also, a cell line derived from PER.C6 that expresses functional Ad35E1B sequences. The Ad35-E1B sequences are driven by the E1B promoter and terminated by a heterologous poly-adenylation signal. The new cell lines are useful for producing recombinant adenoviruses. The cell lines can be used to produce human recombinant therapeutic proteins such as human antibodies. In addition, the cell lines are useful for producing human viruses other than adenovirus such as influenza, herpes simplex, rotavirus, and measles. Excerpt(s): This application is a continuation of application Ser. No. 09/713,678, filed Nov. 15, 2000, pending (the contents of the entirety of which are incorporated by this reference), now U.S. Pat. No. ______, which is a continuation-in-part of application Ser. No. 09/573,740, filed May 18, 2000, pending, which claims benefit, under 35 U.S.C.sctn. 119(e), of the filing date of U.S. Provisional Application Serial No. 60/134,764, filed May 18, 1999. The invention relates to the field of biotechnology generally and, more specifically, to adenoviral-based complementing cell lines. Typically, vector and packaging cells are adapted to one another so that they have all the necessary elements, but they do not have overlapping elements which lead to replication-competent virus by recombination. Therefore, the sequences necessary for proper transcription of the

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packaging construct may be heterologous regulatory sequences derived from, for example, other human adenovirus ("Ad") serotypes, nonhuman adenoviruses, other viruses including, but not limited to, SV40, hepatitis B virus ("HBV"), Rous Sarcoma Virus ("RSV"), cytomegalovirus ("CMV"), etc. or from higher eukaryotes such as mammals. In general, these sequences include a promoter, enhancer and polyadenylation sequences. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Composition comprising extracts of flos lonicerae, fructus forsythiae and radix scutellariae, uses and preparation thereof Inventor(s): Hong, Xiao Kun; (Shanghai, CN), Ruan, Ke Feng; (Shanghai, CN), Shen, Ping Niang; (Shanghai, CN), Wang, Xin Hong; (Shanghai, CN), Wang, Yu Lan; (Shanghai, CN), Yu, Wei; (Shanghai, CN), Zhang, Wen Oing; (Shanghai, CN) Correspondence: Albert Wai-kit Chan; Law Offices OF Albert Wai-kit Chan, Llc; World Plaza, Suite 604; 141 - 07 20th Avenue; Whitestone; NY; 11357; US Patent Application Number: 20020168426 Date filed: October 24, 2001 Abstract: The invention provides a new formulation of the composition comprising Flos Lonicerae Fructus Forsythiae and Radix Scutellariae. This invention also provides a method for identification with HPLC and the characteristic peaks of the compositions of said composition. The composition possesses antiviral effective, namely, inhibition of influenza virus, parainfluenza virus, herpes I virus and herpes II virus. The invention refers to a method for preparation and control of the active components of Flos Lonicerae Fructus Forsythiae and Radix Scutellariae for its biological activity. The invention also provides a unique raw materials and intermediate formulation. Excerpt(s): Throughout this application, various publications are referenced to and the disclosures of these publications are hereby incorporated by reference into this application in order to more fully describe the state of the art as known to the skilled therein as of this date of the invention described and claimed herein. This invention relates to a composition comprising extracts of flos lonicerae, fructus forsythiae and radix scutellariae, uses and preparation thereof. This composition could be used for the inhibition of influenza virus, parainfluenza virus, herpes I virus and herpes II virus. Influenza is the most frequent cause of acute respiratory illness that could require medical intervention. It affects all age groups and it can recur to any individual. A study involving some residents of a nursing home that suffer from respiratory viral diseases was conducted between 1988 and 1999. The results showed a thirty-day mortality of 4.7% (15/322) for influenza A, 5.4% (7/129) for influenza B, 6.1% (3/49) for parainfluenza type I, 0% (0/26) for parainfluenza type II, type III and type IV, 0% (0/26) for respiratory syncytial virus (RSV), and 1.6% (1/61) for rhinovirus. The herpes simplex virus infection is an important risk factor caused cervical carcinoma, AIDS, Alzheimer's disease. The rates of herpes simplex virus (HSV) infection are rising, the highest prevalence being in the group infected with the Human Immunodeficiency Virus (HIV). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Detection of respiratory viruses Inventor(s): Bai, Yue-Luen; (Hsinchu, TW), Terng, Harn-Jing; (Hsinchu, TW) Correspondence: Fish & Richardson PC; 225 Franklin ST; Boston; MA; 02110; US Patent Application Number: 20030130497 Date filed: January 4, 2002 Abstract: Specific nucleic acid sequences, e.g., SEQ ID NOs:1-57, for simultaneous detection of seven most common viruses that cause respiratory infections in human, i.e., human parainfluenza virus 1, human parainfluenza virus 2, human parainfluenza virus 3, respiratory syncytial virus, influenza virus A, influenza virus B, and adenovirus. Also disclosed is a method of simultaneously detecting these viruses. The method includes providing a nucleic acid prepared from a sample suspected of containing a virus to be detected, amplifying the nucleic acid with a set of primers specific for one or more of the seven viruses, and detecting amplification products. Detection of an amplification product specific for any one of the seven viruses indicates the presence of that particular virus. Excerpt(s): Respiratory tract infections cause nearly half of the deaths due to infectious diseases in the United States (Wei, et al., Obstet Gynecol Clin North Am (2001)28 (2): 283-304). About 75 percent of acute respiratory illnesses are caused by viruses. Human parainfluenza virus 1, human parainfluenza virus 2, human parainfluenza virus 3, respiratory syncytial virus, influenza virus A, influenza virus B, and adenovirus are the most common viruses that cause respiratory infections in both children and adults. Detection of these viruses is essential for diagnosis, prevention and treatment of respiratory diseases. The present invention relates to specific nucleic acid sequences for simultaneously detecting multiple respiratory viruses including human parainfluenza virus 1, human parainfluenza virus 2, human parainfluenza virus 3, respiratory syncytial virus, influenza virus A, influenza virus B, and adenovirus. In one aspect, this invention features a PCR primer set that contains two primer pairs for detecting two respiratory viruses, human parainfluenza virus 2 and adenovirus. One of the human parainfluenza virus 2 primers contains an oligo-nucleotide selected from the hemagglutinin-neuraminidase gene region (e.g., SEQ ID NO:5 or 6), and the other primer contains another oligo-nucleotide also selected from the same region (e.g., SEQ ID NO:7). One of the adenovirus primers contains an oligo-nucleotide selected from the hexon gene region, and the other primer contains another oligo-nucleotide also selected from the same region. For example, the oligo-nucleotides in an adenovirus primer pair can be, SEQ ID NOs:24 and 26, SEQ ID NOs:24 and 27, or SEQ ID NOs:25 and 27. Each oligo-nucleotide has 14-40 (e.g., 14-35, 14-30, 14-25, or 14-20) nucleotides in length. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Diagnostic methods and devices Inventor(s): Chidebelu-Eze, Chibueze O.; (Atlanta, GA), Folkenberg, Laura Michelle; (Alpharetta, GA), Kaylor, Rosann Marie; (Cumming, GA), Williamson, Bruce Scott; (Alpharetta, GA) Correspondence: Kimberly-clark Worldwide, INC.; 401 North Lake Street; Neenah; WI; 54956 Patent Application Number: 20030119209 Date filed: December 21, 2001

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Abstract: Diagnostic methods and devices are provided to aid health-care professionals and non-professionals to determine whether a person's upper respiratory ailments are caused by a viral infection, bacterial infection, fungal infection, and/or allergy. In one embodiment, the method comprises contacting a sample to a surface that is printed with a binder that will bind, react or otherwise associate with a particular biomarker for these causes (e.g., bacterial infection) and diffract light that is reflected off of or that is transmitted through the printed surface. In another embodiment, the method comprises contacting a sample to a surface that is printed with a binder that will bind, react or otherwise associate with IgE antibodies to diffract light that is reflected off of or that is transmitted through the printed surface. In yet another embodiment, the method comprises contacting a sample to a surface that is printed with a binder that will bind, react or otherwise associate with a biomarker indicative of a viral infection (e.g., antiInfluenza A antibodies) and diffract light that is reflected off of or that is transmitted Excerpt(s): This application claims the priority of (1) U.S. patent application entitled "Diagnostic Device, System and Method" and further identified as Express Mail Label no. EL188516562US, filed Dec. 21, 2001, and (2) U.S. patent application entitled "Sensors and Methods of Detection for Proteinase Enzymes" and further identified as Express Mail Label no. EL602999586US, filed Dec. 21, 2001. The complete text, claims and drawings of all of the above applications are incorporated herein by reference in their entirety. The present invention relates to methods and devices that can be used to detect for the presence of a specific analyte or a specific class of analytes in a sample. Particularly, the present invention relates to methods and devices for detecting one or more analytes that will help users of the methods and devices determine whether an ailment is related to an allergy, a bacterial infection, a viral infection or a fungal infection. Persons suffering from upper respiratory symptoms, such as sneezing, coughing, congestion, runny nose, etc. often have difficulty determining the cause or causes of their symptoms. Any and all of the above-mentioned afflictions may be symptoms of one of a variety of illnesses. Any one of the following may cause these upper respiratory symptoms: a viral infection, such as cold or influenza; bacterial infection, such as pneumonia; an allergy; or a fungal infection, such as Aspergillus. Although these illnesses produce similar symptoms, the illnesses are very dissimilar and are treated differently. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

DNA vaccine using liposome-encapsulated hemagglutinin protein of influenza virus

plasmid

DNA

encoding

for

Inventor(s): Nagata, Leslie P.; (Medicine Hat, CA), Wong, Jonathan P.; (Medicine Hat, CA) Correspondence: Rader Fishman & Grauer Pllc; Lion Building; 1233 20th Street N.W., Suite 501; Washington; DC; 20036; US Patent Application Number: 20030008000 Date filed: March 7, 2002 Abstract: DNA vaccination using plasmid encoding the hemagglutinin (HA) gene of influenza virus to induce long-lasting protective immunity against respiratory infection is disclosed. Efficacy of DNA vaccines is shown using a lethal influenza infection model in mice by employing liposomes as carriers. Mice immunized intranasally or intramuscularly with liposome-encapsulated pCI plasmid endcoding HA (pCI-HA10) are completely protected against an intranasal 5 LD.sub.50 influenza virus challenge.

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Mice immunized with liposome-encapsulated pCI-HA10, but not naked pCI-HA10, by intranasal administration are found to produce high titers of serum IgA. The present invention shows that DNA vaccines encapsulated in liposomes are efficacious in inducing complete protective immunity against respiratory influenza virus infection. Excerpt(s): Despite recent advances in antiviral chemotherapy and vaccine development, infection and complications from influenza remain a leading cause of human mortality or morbidity globally. Influenza can be particularly fatal amongst the elderly and individuals with underlying medical problems, including immunocompromised conditions. To date, vaccination using killed whole virus remains the most effective preventive measure against influenza. Genetic vaccination using plasmid DNA represents an alternate and more desirable means of inducing protective immunity against viral infections. This new generation of vaccines provides many advantages over conventional live or killed vaccines. Unlike live or attenuated vaccines, DNA vaccines do not produce infection and therefore do not pose inherent safety concerns associated with live or attenuated vaccines. In addition, most subcellular vaccines only induce either humoral or cell-mediated immunity. DNA vaccines, on the other hand, can stimulate both humoral and cellular immune responses. These attributes make DNA vaccines attractive and promising candidates for treating respiratory viruses, including influenza. Efficient expression of genes in plasmid DNA encoding the protective antigens requires the physical uptake of the plasmid by the target cells. Although there is ample evidences which suggest that naked plasmid DNA injected directly into the muscles can express the gene of interest and induce protective immunity, its ability to be taken up by mucosal-associated lymphoid tissues and to induce mucosal immunity has not been well documented. Furthermore, needle injection of the DNA vaccines in muscles in humans can be painful and may present healthrelated safety concerns. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Efficient method for producing compositions enriched in total phenols Inventor(s): Bailey, David T.; (Boulder, CO), Daugherty, F. Joseph; (Omaha, NE), Freeberg, Delano R.; (Algonquin, IL), Gourdin, Gerald T.; (Boulder, CO), Nichols, Rebecca L.; (Broomfield, CO), Richheimer, Steven L.; (Westminster, CO), Tempesta, Michael S.; (El Granada, CA) Correspondence: Hogan & Hartson Llp; One Tabor Center, Suite 1500; 1200 Seventeenth ST; Denver; CO; 80202; US Patent Application Number: 20030149252 Date filed: November 22, 2002 Abstract: This invention provides a process for the preparation of compositions enriched in total phenols from a crude plant extract. The process includes a novel column purification step using a brominated polystyrene resin. This invention also includes compositions enriched in total phenols. The enriched compositions are characterized as containing monomeric, oligomeric and polymeric phenols and having HPLC chromatograms substantially as set forth in FIGS. 10-13. This invention encompasses methods of using the total phenol-enriched compositions for treating warm-blooded animals, including humans, infected with paramyxovaridae such as respiratory syncytial virus, orthomyoxovaridae such as influenza A, B, and C, parainfluenza, Herpes viruses such as HSV-1 and HSV-2, and Flaviviruses such as West Nile Virus, and for treating inflammation such as caused by arthritis, stress and digestive disease.

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Excerpt(s): The present invention relates to the extraction and purification of flavonoid compounds from plant material, and more specifically to the production of compositions enriched in total phenols. Flavonoid compounds are present in all aerial parts of plants, with high concentrations found in the skin, bark, and seeds. Such compounds are also found in numerous beverages of botanical origin, such as tea, cocoa, and wine. The flavonoids are a member of a larger family of compounds called polyphenols. That is, these compounds contain more than one hydroxyl group (OH) on one or more aromatic rings. The physical and chemical properties, analysis, and biological activities of polyphenols and particularly flavonoids have been studied for many years. Anthocyanins are a particular class of naturally occurring flavonoid compounds that are responsible for the red, purple, and blue colors of many fruits, vegetables, cereal grains, and flowers. For example, the colors of fruits such as blueberries, bilberries, strawberries, raspberries, boysenberries, marionberries, cranberries, elderberries, etc. are due to many different anthocyanins. Over 300 structurally distinct anthocyanins have been identified in nature. Because anthocyanins are naturally occurring, they have attracted much interest for use as colorants for foods and beverages. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Equine herpesvirus vaccine Inventor(s): Mellencamp, Mark W.; (St. Joseph, MO) Correspondence: Foley & Lardner; 777 East Wisconsin Avenue; Suite 3800; Milwaukee; WI; 53202-5308; US Patent Application Number: 20030206924 Date filed: March 20, 2001 Abstract: A vaccine for protecting a horse against diseases associated with EHV-1 and/or EHV-4 is provided. The vaccine commonly includes inactivated EHV-1 (e.g., chemically inactivated EHV-1 KyA virus) and an adjuvant. The adjuvant can include a cross-linked olefinically unsaturated carboxylic acid polymer which may have bioadhesive properties. The vaccine may also include antigens against other equine pathogens such as inactivated EHV-4 and inactivated A1 and/or A2 strains of equine influenza virus. Methods for protecting horses against diseases associated with EHV-1 and/or EHV-4 and methods of producing the equine herpesvirus vaccine are also provided. Excerpt(s): Respiratory diseases are a major cause of economic loss to the equine industry. Equine herpesviruses (EHV), equine influenza viruses (EIV), and the bacterium, Streptococcus equi are pathogens most often associated with infectious respiratory disease in horses. World wide, equine herpesviruses are major pathogens associated with morbidity in horses as a result of respiratory infection. Both equine herpesvirus type 1 (EHV-1) and type 4 (EHV-4) can cause respiratory disease. EHV-1 is also associated with abortions and neurological disease. Because of the high degree of mobility and the international nature of the equine industry, efficacious vaccines are needed to reduce the disease and control the spread of these pathogens. A number of EHV vaccines are available commercially. None, however, generally is capable of conferring long lasting protection and most require frequent booster immunizations to achieve a significant level of protection against EHV infection. The most commonly recommended route of administration is via intramuscular injection, despite the respiratory system being a primary site of the infection in many instances. In addition,

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some of the commercial vaccines have been reported to cause undesirable side effects. A number of attempts at developing a recombinant vaccine for EHV have been reported. This approach, however, has not yet resulted in the introduction of a commercial recombinant vaccine which has achieved widespread acceptance. Literature reports have consistently documented a high degree of variability in the capability of vaccines based on EHV-1 strains to provide cross protection against infection by EHV-4 strains. While vaccines based on EHV-4 strains have shown a greater propensity to provide some protection against both EHV-1 and EHV-4 strains, cross protection based on EHV4 strains has also been reported to show variability. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Haemophilus influenza outer membrane protein and use thereof in vaccination Inventor(s): Berthet, Francois-Xavier Jacques; (Barcelona, ES), Denoel, Philippe; (Rixensart, BE), Poolman, Jan; (Rixensart, BE), Thonnard, Joelle; (Rixensart, BE) Correspondence: Smithkline Beecham Corporation; Corporate Intellectual Property-us, Uw2220; P. O. Box 1539; King OF Prussia; PA; 19406-0939; US Patent Application Number: 20030096370 Date filed: October 21, 2002 Abstract: This invention relates to recombinant bacterial outer membrane proteins comprising one or more LB1(f) peptides from surface-exposed loop 3 of MOMP P5 of non-typeable H. influenzae. Polynucleotides encoding these recombinant proteins are also covered. The invention also relates to a method of isolating the recombinant proteins and a vaccine composition for use in the treatment of Haemophilus influenzae infection. Excerpt(s): This invention relates to newly identified Haemophilus influenzae chimeric proteins and polynucleotides encoding these proteins. The invention also relates to a method of isolating the chimeric proteins and a vaccine composition for use in the treatment of Haemophilus influenzae infection. Haemophilus influenzae (Hi) is a gramnegative coccobacillus and a strict human commensal. Strains of Hi are either encapsulated in a polysaccharide capsule or are non-encapsulated and are accordingly classified into typeable (encapsulated) and non-typeable (non-encapsulated) strains. Encapsulated pathogenic strains of Hi cause mainly, but not exclusively, invasive disease in children under six years of age. Haemophilus influenzae type b (Hib), for example, is a major cause of meningitis and other invasive infections in children. Effective vaccines exist against Hib infections, and are based on producing antibodies to the polysaccharide capsule, and are therefore ineffective against non-typeable Haemophilus influenzae (ntHi). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Human monoclonal antibodies to influenza M2 protein and methods of making and using same Inventor(s): Cheroutre, Hilde; (Del Mar, CA), Kato, Shinichiro; (San Diego, CA), Mikayama, Toshifumi; (Takasaki, JP), Wang, Rongfang; (San Diego, CA) Correspondence: Pillsbury Winthrop Llp; Intellectual Property Group; P.O. Box 10500; Mclean; VA; 22102; US Patent Application Number: 20030219442 Date filed: March 13, 2003 Abstract: Human, humanized and chimeric monoclonal antibodies that bind to influenza M2 protein. The antibodies are useful for, among other things, treatment, diagnostics, purifying and isolating M2 or influenza virus, and identifying the presence of M2 or influenza virus in a sample or a subject. Excerpt(s): This application claims priority to U.S. Provisional Application Serial No. 60/364,997, filed Mar. 13, 2002. The invention relates to antibodies, more particularly to human, humanized and chimeric antibodies that specifically bind to influenza virus M2 protein. Influenza types A or B viruses cause epidemics of disease almost every winter in all countries and are a leading cause of death in the developed world. In the United States, these winter influenza epidemics can cause illness in 10% to 20% of people and are associated with an average of 20,000 deaths and 114,000 hospitalizations per year. The present strategy for control of influenza is yearly vaccination with inactivated whole-virus or sub-unit vaccines. The major neutralizing antigen of the influenza virus is hemagglutinin (HA) (Frace et al., Vaccine 17:2237 (1999)). However, due to frequent and unpredictable antigenic variation of HA, the vaccine frequently fails to provide optimal protective immunity against divergent viral strains. Moreover, for immunocompromised individuals such as elderly patients, cancer patients and other patients who are immuno-incompetent due to ongoing treatment and/or disease, vaccination may not provide effective protection. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Immunostimulating and immunopotentiating reconstituted influenza virosomes and vaccines containing them Inventor(s): Cusi, Maria Grazia; (Siena, IT), Gluck, Reinhard; (Bern-Spiegel, CH), Walti, Ernst; (Munchenbuchsee, CH) Correspondence: Pillsbury Winthrop Llp; Intellectual Property Group; Suite 200; 11682 EI Camino Real; San Diego; CA; 92130; US Patent Application Number: 20030113347 Date filed: October 10, 2002 Abstract: Described are virosomes comprising cationic lipids, biologically active influenza hemagglutinin protein or biologically active derivatives thereof and nucleic acids encoding antigens from pathogenic sources in their insides, preferably antigens from mumps virus wherein said antigens are derived from conserved external and internal proteins of said virus. Provided are virosomes which may advantageously be formulated as vaccines capable of inducing strong neutralizing antibody and cytotoxic T cell responses as well as protection to pathogenic sources such as a mumps virus.

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Furthermore, vaccines comprising recombinant DNA derived from DNA encoding conserved external and internal proteins from mumps virus are described. Excerpt(s): This application claims the benefit of priority under 35 USC.sctn.120 of PCT application serial No. PCT/EP98/03050, filed May 22, 1998, which claims priority from European application serial no. EP97108390.2, filed May 23, 1997, and the present application is a continuation-in-part of U.S. application Ser. No. 08/225,740, filed Apr. 11, 1994 (pending), which is a continuation-in-part application of U.S. application Ser. No. 07/965,246, filed Mar. 3, 1993 (issued), which claims priority from PCT application no. PCT/EP92/01014, filed May 8, 1992, European application No. EP91107527.3 filed May 8, 1991 and European application no. 91107647.9, filed May 10, 1991. The disclosure of the prior applications is considered part of (and is incorporated by reference in) the disclosure of this application. The present invention relates to virosomes comprising cationic lipids, biologically active influenza hemagglutinin protein or biologically active derivatives thereof and nucleic acids encoding antigens from pathogenic sources in their insides. The nucleic acids are most advantageously DNA. It is preferred that the DNA encodes antigens from mumps virus wherein said antigens are derived from conserved external and internal proteins of said virus. The virosome of the invention may advantageously be formulated as vaccines. It could be show-n in accordance with the present invention that such vaccines induce strong neutralizing antibody as well as cytotoxic T cell responses. Most importantly, protection to pathogenic sources such as a mumps virus could be demonstrated. The present invention further relates to vaccines comprising recombinant DNA derived from DNA encoding conserved external and internal proteins from mumps virus. The use of purified preparations of plasmid DNA (deoxyribonucleic acid) constitutes a new approach to vaccine development. Plasmid DNA vaccines may find application as preventive vaccines, immunizing agents for the preparation of hyperimmune globuline products or diagnostics and therapeutic vaccines for infectious diseases or for other indications such as cancer. Plasmid DNA vaccines are defined as purified preparations of plasmid DNA designed to contain a gene or genes for the intended vaccine antigen as well as genes incorporated into the construct to allow for production in a suitable host system. Plasmid DNA vaccines currently under development are constructs derived from bacterial plasmids that contain one or more genes from an infectious agent. These plasmids possess DNA sequences necessary for selection and replication in bacteria, eukaryotic promoters and enhancers and transcription termination/polyadenylation addition sequences for gene expression. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Inactivated vaccines for aids and other infectious diseases Inventor(s): Ilyinskii, Petr O.; (Somerville, MA), Lallos, Lisa; (Chelmsford, MA), Castor, Trevor P.; (Arlington, MA) Correspondence: Law Office OF Stephen J Gaudet, Llc; 68h Stiles Road; Salem; NH; 03079; US Patent Application Number: 20030108918 Date filed: December 31, 2002 Abstract: Presented herein is a description for the manufacturing of inactivated HIV for use in vaccines against AIDS, as well as other inactivated viruses for other infectious diseases. This invention incorporates methods for inactivating infectious virus particles while retaining protein integrity and antigenicity. The methods utilize critical, near-

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critical or supercritical fluids with or without polar cosolvents. This invention would allow for the creation of HIV vaccines from genetically attenuated HIV strains for a greater degree of product safety, and from combinations of different HIV strains for broader protection. This HIV vaccine manufacturing technology is inexpensive, amenable to large-scale processing and portable, i.e. it can be readily implemented in a host country site. This invention can be utilized for other viral and bacterial infectious diseases, such as influenza and hepatitis. Excerpt(s): This application claims the benefit of Provisional Application No. 60/317,359, filed Sep. 5, 2001. This invention relates to inactivated vaccines for AIDS and other infectious diseases. This invention incorporates methods for inactivating infectious virus particles while retaining protein integrity and antigenicity. When introduced into the organism, the inactivated virions will stimulate the human immune response (IR) against the virus, and thus help to establish protective immunity in the vaccinee. The methods also relate to the immunization of animals and livestock. The methods feature critical, near-critical or supercritical fluids with or without polar cosolvents, hereinafter referred to as SuperFluids. Acquired immunodeficiency syndrome (AIDS), identified in 1981, was initially thought to be confined within several risk groups, different from the general population. The isolation of HIV, the infectious agent responsible for AIDS, soon followed and prompted optimistic forecasts regarding the prospects for a future vaccine. These assumptions soon proved unwarranted, since none of the conventional vaccine development strategies was efficient against HIV. At the same time, the disease spread rapidly, affecting millions of people. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Influenza immunogen and vaccine Inventor(s): Birkett, Ashley J.; (Escondido, CA) Correspondence: Welsh & Katz, Ltd; 120 S Riverside Plaza; 22nd Floor; Chicago; IL; 60606; US Patent Application Number: 20030175863 Date filed: February 21, 2002 Abstract: A chimeric, carboxy-terminal truncated hepatitis B virus nucleocapsid protein (HBc) is disclosed that contains an immunogen for inducing the production of antibodies to the influenza M2 protein. An immunogenic influenza epitope is preferably expressed at or near the N-terminus or in the HBc immunogenic loop sequence. The chimer preferably contains an influenza-specific T cell epitope and is preferably engineered for both enhanced stability of self-assembled particles and enhanced yield of those chimeric particles. Methods of making and using the chimers are also disclosed. Excerpt(s): This is a continuation-in-part of application Serial No. 09/930,915, filed Aug. 15, 2001, whose disclosures are incorporated herein by reference. The present invention relates to the intersection of the fields of immunology and protein engineering, and particularly to an immunogen and vaccine useful in prevention of influenza infection by influenza A virus. The family hepadnaviridae are enveloped DNA-containing animal viruses that can cause hepatitis B in humans (HBV). The hepadnavirus family includes hepatitis B viruses of other mammals, e.g., woodchuck (WHV), and ground squirrel (GSHV), and avian viruses found in ducks (DHV) and herons (HeHV). Hepatitis B virus (HBV) used herein refers to a member of the family hepadnaviridae

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that infects mammals, as compared to a virus that infects an avian host, unless the discussion refers to a specific example of a non-mammalian virus. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Influenza vaccine Inventor(s): Deroo, Tom Maria; (Kuurne, BE), Fiers, Walter Charles; (Destelbergen, BE), Min Jou, Willy Alfons; (Destelbergen, BE) Correspondence: Barbara E. Johnson; Webb Ziesenheim Logsdon Orkin & Hanson; 700 Koppers Building; 436 Seventh Avenue; Pittsburgh; PA; 15219; US Patent Application Number: 20030129197 Date filed: February 20, 2002 Abstract: A method for manufacturing recombinant neuraminidase by culturing in a suitable culture medium host cells which are transformed with a neuraminidase expression vector or infected with a virus which is transformed with a neuraminidase expression vector, wherein the expression vector comprises at least a part of the coding region of a neuraminidase gene of an influenza virus minus the region which codes for the membrane anchor, or a modified version thereof, preceded in phase by a signal sequence; and isolating the expression product neuraminidase from the culture medium. The invention further relates to vectors expressing the neuraminidase. Excerpt(s): The present invention relates to a recombinant influenza neuraminidase, an expression vector with which the recombinant neuraminidase can be expressed in host cells, methods for producing and purifying recombinant neuraminidase, vaccines against influenza and the use of recombinant neuraminidase according to the invention. Influenza A and B virus epidemics cause considerable discomfort to those affected and have a great influence a on social and economic life. They cause a significant mortality rate in older people and in patients with chronic illnesses. Since their introduction during the 1940s, inactivated vaccines based on virus material cultured in chicken eggs have been found to be clearly effective against influenza infection and have resulted in a significant fall in the mortality rate of high-risk populations. The influenza viruses are unique among the viruses of the bronchial tubes because they undergo a significant antigenic variation (so-called "drift") in their two surface antigens, that is, the hemagglutinin (HA) and the neuraminidase (NA). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Influenza viruses with enhanced transcriptional and replicational capacities Inventor(s): Hobom, Gert; (Freiburg, DE), Menke, Annette; (Koln, DE) Correspondence: Kurt Briscoe; Norris, Mclaughlin & Marcus, P.A.; 220 East 42nd Street, 30th Floor; New York; NY; 10017; US Patent Application Number: 20030099670 Date filed: February 8, 2002 Excerpt(s): The present invention provides human influenza viruses comprising an RNA-sequence encoding a modified RNA-polymerase, a process for the preparation thereof, pharmaceutical compositions comprising said human influenza viruses and their use for gene transfer into mammalian cells, for ex vivo gene transfer into antigen-

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presenting cells, such as dendritic cells, for in vivo somatic gene therapy, or in vivo vaccination purposes. The invention also relates to other non-avian influenza viruses, including equine, porcine (swine) influenza viruses. The RNA-dependent RNApolymerase of the influenza virus, which is comprised of three viral polymerase (P) subunits, PB1, PB2 and PA, catalyses the synthesis of both viral mRNA (transcription) as well as complementary RNA and progeny viral RNA (replication) in infected cells (Lamb R. A., Krug R. M. Fields Virology 3: pp 1353-1445 (1996)). In the virion the enzyme is found tightly associated at each of the eight different species of viral RNAs (vRNAs) with their 5' and 3' ends, which in combination constitute the promoter structure, while all other parts of the vRNA molecules are covered by a large number of influenza nuclear protein (NP) molecules, one per 24 nucleotides in average (Ortega, J. et al., J. Virol. 74, 156-163 (2000)), altogether described as the viral RNP complexes. Upon infection the vRNPs are released from the virion and transferred into the nucleus of the infected cell, where viral mRNA synthesis is initiated by the promoter-associated enzyme according to the cap-snatching scheme, i.e. employing primer oligonucleotides that are derived from cellular mRNAs or hnRNAs by endonucleolytic cleavage (Krug R. M. et al., The Influenza Viruses, Plenum Press, New York, N.Y., pp. 1-87 (1989)). While during progression of mRNA synthesis along the vRNA template molecule its 3' end looses contact to viral polymerase, the enzyme maintains its tight association with the 5' vRNA end throughout the entire first and all consecutive rounds of transcription. Synthesis of mRNA molecules is terminated via poly-adenylation at a 5' promoter sequence-adjacent series of 5 or 6 uridine template residues, i.e. the very 5'-terminal sequence covered by the enzyme is not transcribed into viral mRNA. The conformation of the vRNA promoter sequence in its association with viral polymerase has been demonstrated by reverse genetic analysis to constitute a "corkscrew" structure, with exposed single-stranded tetranucleotide sequences supported by two intra-strand basepairs in both the 5' and 3' branches of the promoter sequence. In the course of that analysis also several promoter-up variants of the terminal vRNA sequence have been described, mainly through base-pair exchanges involving positions 3 and 8 from the 3' end, and positions 3 and 8 from the 5' end (Neumann G., Hobom G., J. Gen Virol. 76 (
Method for preventing infectious respiratory diseases Inventor(s): Madhat, Maher N.; (Lexington, KY) Correspondence: Maher Madhat; 3305 Grasmere Drive; Lexington; KY; 40503; US Patent Application Number: 20030045577 Date filed: August 15, 2001 Abstract: A method and composition for treating patients with viral infection with pharmaceutical agents is disclosed. In one embodiment, the virus is influenza A and the pharmaceutical agent is rimantadine or amantadine. The methods of the present invention can be used as a way of eradicating influenza virus topically by direct administration of a dose--nasally--that is much lower than an oral therapeutic dose.

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Thereby avoiding the side effects associated with oral administration. Consequently, the low dose of the drug administered by this method will be well tolerated among age groups Excerpt(s): The present invention pertains to the prevention of viral disease in humans utilizing nasal pharmaceutical compositions. In particular, the present invention pertains to the method of the prevention of influenza A viral infection in humans with rimantadine or amantadine or their water soluble or insoluble salts thereof administered nasally. Epidemic influenza continues to be associated with significant morbidity in general population and mortality in the elderly and other risk patients. Although the case fatality rate averages less than 0.01%, tens of thousands of deaths occur each year. Amantadine is a drug developed in 1960s with diverse uses ranging from prevention of influenza A to the treatment of patients with Parkinson's disease [Aoki and Sitar, Clin Pharm 14:35-51, 1988]. Amantadine hydrochloride is a well known compound commercially available as Symmetral. Available dosage forms of Symmetrel.RTM. are soft gelatin capsules and oral syrup [U.S. Pat. No. 3,310,469 assigned to Du Pont describes composition-containing amantadine]. Elimination of amantadine is primarily through renal clearance by both glomerular filtration and tubular secretion. Amantadine accumulates in patients with renal dysfunction. Therefore, doses must be reduced in such patients to avoid toxicity [Aoki and Sitar, 1988]. Further, amantadine as an antiviral agent-of nucleic acid derivative type-is likely to bring about side effects such as deterioration of liver function, mutagenicity, sub-acute toxicity, teratogenicity and a decrease in reproductive efficiency [Virology--published by Raven press, pp 323-348, 1985]. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Method for the detection of influenza a/b viruses Inventor(s): Klepp, Juergen; (Graben-Neudorf, DE), Schlipfenbacher, Reiner; (Bad Duerkheim, DE) Correspondence: Roche Diagnostics Corporation; 9115 Hague Road Bldg D; PO Box 50457; Indianapolis; IN; 46250-0457; US Patent Application Number: 20030143530 Date filed: December 13, 2002 Abstract: The invention concerns a method for the detection of an infection with influenza A and/or influenza B virus comprising the steps: i) obtaining a saliva sample, ii) preparing the saliva sample for a detection reaction and iii) detecting the influenza A and/or influenza B virus in the saliva sample. The invention in addition concerns a test kit for the detection of an infection by the influenza A and/or influenza B virus containing: i) a device for the collection of a saliva sample and ii) reagents and auxiliary agents for the detection of influenza A and/or influenza B viruses. Furthermore the invention concerns the use of saliva as a sample material for the detection of an infection with the influenza A and/or influenza B virus. Excerpt(s): The invention concerns a method for the detection of influenza A/B viruses, a corresponding test kit and the use of saliva as a sample material for the detection of influenza A/B viruses. Influenza is a frequently underestimated infectious disease which can result in high morbidity and mortality rates especially in elderly persons and in high-risk patients. Influenza A and/or influenza B viruses (also abbreviated influenza A/B viruses in the following) are responsible for genuine virus influenza which is contracted by several 100 million persons worldwide each year. The influenza A and B viruses primarily infect the nasopharyngeal and oropharyngeal cavities and

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initially cause general respiratory symptoms in the affected persons. It is not possible even for experienced medical professionals to very reliably diagnose influenza solely on the basis of the patient's clinical symptoms since other viruses which infect the nasal or pharyngeal cavity such as adenoviruses, parainfluenza viruses or respiratory syncitial viruses (RS viruses) cause similar symptoms. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Method of preventing respiratory infections Inventor(s): Rezakhany, Saeed; (San Jose, CA) Correspondence: Saeed Rezakhany; 6933 Melvin DR; San Jose; CA; 95129; US Patent Application Number: 20030215533 Date filed: April 10, 2003 Abstract: A method is presented for prevention of various respiratory infections which can be caused by one or more pathogens (bacteria, viruses, and fungi) including, but not limited to, those causing the various forms of upper respiratory tract infection (common cold), influenza, bronchitis, laryngitis, etc. in human being, by using a non-toxic, easily accessible to public "effective formula" to attack the newly activated or the newly invading pathogen and rendering it ineffective. If the infection has already fully taken effect, the present method helps reduce the symptoms of the infection (illness) and its duration by preventing occurrence of secondary infections. This method may also be applied to other mammals. Excerpt(s): This application claims benefit of provisional application No. 60/371,882, filed Apr. 11, 2002, the entire disclosure of which is considered to be part of the disclosure of this application and is hereby incorporated by reference. Respiratory infections, particularly upper respiratory tract infections are very common and cause substantial suffering and hundreds of millions of dollars of economic loss every year. The majority of the pathogens contributing to upper respiratory tract infections are spread through air and through touching of the infected surfaces and then touching one's eyes or nose. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Methods of use of viral vectors to deliver antigen to dendritic cells Inventor(s): Bhardwaj, Nina; (West Orange, NJ), Steinman, Ralph M.; (Westport, CT) Correspondence: Morgan & Finnegan, L.L.P.; 345 Park Avenue; New York; NY; 101540053; US Patent Application Number: 20020192825 Date filed: July 11, 2002 Abstract: This invention relates to methods and compositions useful for delivering antigens to dendritic cells which are then useful for inducing T antigen specific cytotoxic T lymphocytes. This invention also provides assays for evaluating the activity of cytotoxic T lymphocytes. According to the invention, antigens are provided to dendritic cells using a viral vector such as influenza virus which may be modified to express nonnative antigens for presentation to the dendritic cells. The dendritic cells which are

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infected with the vector are then capable of presenting the antigen and inducing cytotoxic T lymphocyte activity or may also be used as vaccines. Excerpt(s): This invention relates to targeted antigen presentation in the immune system. More specifically, this invention relates to the use of viral vectors to deliver antigens to dendritic cells for processing and presentation to the immune system. This invention also relates to methods and compositions having preventive, diagnostic and therapeutic applications. The potential role of CD8+, cytolytic T lymphocytes [CTLs] in resistance to infectious and malignant diseases has been emphasized by recent developments in immunology. Antigen-specific CTLs are recognized as a possible defense mechanism in infection with HIV-1 (1-3), cytomegalovirus (4), and in malaria (5). Antigens that are recognized by melanoma-specific CTLs also have been identified by Boone and colleagues (6,7). These studies document the specificity of CTLs that recognize clinically important targets. Less is understood about the initial generation of these CTLs, however. As in most T cell responses, the precursors for active CTLs are quiescent lymphocytes that must be induced to expand clonally and develop effector functions. For CTL activation to occur, not only must antigens be presented as peptide fragments on MHC products, but the antigen-MHC complexes must also be introduced on cells with the requisite accessory functions that lead to T cell growth and cytolytic activity. Studies of killer cells response to transplantation antigens, provide evidence that an effective way to induce human CTLs is to present antigens on dendritic cells (8). Dendritic cells are specialized accessory cells for the initiation of many T cell dependent immune responses [reviewed in (9)]. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Methods to identify mutant cells with altered sialic acid Inventor(s): Kawaoka, Yoshihiro; (Madison, WI) Correspondence: Schwegman, Lundberg, Woessner & Kluth, P.A.; P.O. Box 2938; Minneapolis; MN; 55402; US Patent Application Number: 20020197705 Date filed: February 22, 2002 Abstract: The invention provides cells useful to propagate influenza virus mutants having reduced sialidase activity. Excerpt(s): This application claims the benefit of the filing date of U.S. application Serial No. 60/271,044, filed on Feb. 23, 2001, under 35 U.S.C.sctn.119(e), the disclosure of which is incorporated by reference herein. Influenza A viruses possess two surface spike proteins, hemagglutinin (HA) and neuraminidase (NA) (Lamb et al., 1996). The HA protein, a trimeric type I membrane protein, is responsible for binding to sialyloligosaccharides (oligosaccharides containing terminal sialic acid linked to galactose) on host cell surface glycoproteins or glycolipids (reviewed Wiley et al., 1987). This protein is also responsible for fusion between viral and host cell membranes, following virion internalization by endocytosis. Neuraminidase (NA), a tetrameric type II membrane protein, is a sialidase that cleaves terminal sialic acid residues from the glycoconjugates of host cells and the HA and NA, and thus is recognized as receptordestroying enzyme (Air et al., 1989). This sialidase activity is necessary for efficient release of progeny virions from the host cell surface, as well as prevention of progeny aggregation due to the binding activity of viral HAs with other glycoproteins (Pause et al., 1974; Shibata et al., 1993). Thus, the receptor-binding activity of the HA and the

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receptor-destroying activity of the NA likely act as counterbalances, allowing efficient replication of influenza virus, e.g., influenza A virus. Influenza A viruses of all known subtypes have been isolated from a variety of animals, including humans, wild and domestic birds, pigs, horses, and sea mammals (Webster et al., 1992). Viruses responsible for the 1957 and 1968 influenza pandemics were reassortants between human and avian viruses, with the PB1, HA and/or NA genes derived from the latter (Kawaoka et al., 1989; Laver et al., 1973; Scholtissek et al., 1978). Such interspecies transmission of avian virus genes forces adaptation of the gene products to the new environment (i.e., human respiratory organs). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Microparticle compositions and methods for the manufacture thereof Inventor(s): Fang, Jia-Hwa; (Oakland, CA), Hora, Maninder; (Danville, CA), O'Hagan, Derek; (Berkeley, CA), Singh, Manmohan; (Hercules, CA) Correspondence: Mayer, Fortkort & Williams, PC; 251 North Avenue West; 2nd Floor; Westfield; NJ; 07090; US Patent Application Number: 20020136776 Date filed: September 28, 2001 Abstract: Microparticles with adsorbed complexes of macromolecule and detergent, methods of making such microparticles, and uses thereof, are disclosed. The microparticles comprise a polymer, such as a poly(.alpha.-hydroxy acid), a polyhydroxy butyric acid, a polycaprolactone, a polyorthoester, a polyanhydride, and the like, and are formed using cationic, anionic, or nonionic detergents. The surfaces of the microparticles have adsorbed thereon a complex of biologically active macromolecules, such as nucleic acids, polypeptides, antigens, and adjuvants, and a detergent. Preferred polymers are poly(D,L-lactide-co-glycolides), more preferably those having a lactide/glycolide molar ratio ranging from 40:60 to 60:40 and having a molecular weight ranging from 30,000 Daltons to 70,000 Daltons. Preferred macromolecules are bacterial and viral antigens (such as HIV antigens, meningitis B antigens, streptococcus B antigens, and Influenza A hemagglutinin antigens) as well as polynucleotides that encode for such antigens. Excerpt(s): This application is related to patent application Ser. No. 60/236,077, filed Sep. 28, 2000. This application is incorporated herein by reference in its entirety. The present invention relates generally to pharmaceutical compositions. In particular, the invention relates to microparticles with adsorbent surfaces, methods for preparing such microparticles, and uses thereof Additionally, the invention relates to compositions comprising biodegradable microparticles wherein biologically active agents, such as therapeutic polynucleotides, polypeptides, antigens, and adjuvants, are adsorbed on the surface of the microparticles. Particulate carriers have been used in order to achieve controlled, parenteral delivery of therapeutic compounds. Such carriers are designed to maintain the active agent in the delivery system for an extended period of time. Examples of particulate carriers include those derived from polymethyl methacrylate polymers, as well as microparticles derived from poly(lactides) (see, e.g., U.S. Pat. No. 3,773,919), poly(lactide-co-glycolides), known as PLG (see, e.g., U.S. Pat. No. 4,767,628) and polyethylene glycol, known as PEG (see, e.g., U.S. Pat. No. 5,648,095). Polymethyl methacrylate polymers are nondegradable while PLG particles biodegrade by random nonenzymatic hydrolysis of ester bonds to lactic and glycolic acids, which are excreted along normal metabolic pathways.

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Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Modified nucleosides for the treatment of viral infections and abnormal cellular proliferation Inventor(s): Stuyver, Lieven; (Snellville, GA), Watanabe, Kyoichi; (Stone Mountain, GA) Correspondence: King & Spalding; 191 Peachtree Street, N.E.; Atlanta; GA; 30303-1763; US Patent Application Number: 20030087873 Date filed: October 18, 2001 Abstract: The disclosed invention is a composition for and a method of treating a Flaviviridae (including BVDV and HCV), Orthomyxoviridae (including Influenza A and B) or Paramyxoviridae (including RSV) infection, or conditions related to abnormal cellular proliferation, in a host, including animals, and especially humans, using a nucleoside of general formula (I)-(XXIII) or its pharmaceutically acceptable salt or prodrug.This invention also provides an effective process to quantify the viral load, and in particular BVDV, HCV or West Nile Virus load, in a host, using real-time polymerase chain reaction ("RT-PCR"). Additionally, the invention discloses probe molecules that can fluoresce proportionally to the amount of virus present in a sample. Excerpt(s): This application claims priority to U.S. provisional application No. 60/241,488, filed Oct. 18, 2000 and U.S. provisional application No. 60/282,156, filed on Apr. 6, 2001. The present invention includes compounds and methods for the treatment of Flaviviridae, Orthomyxoviridae, Paramyxoviridae infections and abnormal cellular proliferation. The Flaviviridae is a group of positive single-stranded RNA viruses with a genome size from 9-15 kb. They are enveloped viruses of approximately 40-50 nm. An overview of the Flaviviridae taxonomy is available from the International Committee for Taxonomy of Viruses. The Flaviviridae consists of three genera. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Multivalent vaccination using recombinant adenovirus Inventor(s): Wang, Danher; (Mt. Pleasant, SC) Correspondence: Wilson Sonsini Goodrich & Rosati; 650 Page Mill Road; Palo Alto; CA; 943041050 Patent Application Number: 20030219458 Date filed: February 5, 2003 Abstract: Genetic vaccines and multivalent vaccination methods are provided for enhancing the immunity of a host such as a human to one or more pathogens. In one embodiment, a recombinant adenovirus is provided for eliciting immune response of a host to viral pathogens. The recombinant adenovirus comprises: a first antigen sequence that is heterologous to a native progenitor of the recombinant adenovirus and encodes a first viral antigen from a first pathogenic virus, expression of which is under the transcriptional control of a first promoter; and a second antigen sequence that is heterologous to a native progenitor of the recombinant adenovirus and encodes a second viral antigen from a second pathogenic virus, expression of which is under the transcriptional control of a second promoter. Expression of the first and second antigen

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sequences elicit an immune response directed against the first and second viral antigens upon infection of the host by the recombinant virus. The genetic vaccines can be used for immunizing a host against a wide variety of pathogens, such as HIV, Ebola virus, Marburg virus, hepatitis virus, influenza virus, respiratory syncytial virus, and human papilloma virus. Excerpt(s): This application is a continuation of U.S. patent application entitled "GENETIC VACCINE AGAINST HUMAN IMMUNODEFICIENCY VIRUS", application Ser. No. 10/003,035, Filed: Nov. 1, 2001, which is a continuation-in-part of PCT application entitled "GENETIC VACCINE THAT MIMICS NATURAL VIRAL INFECTION AND INDUCES LONG-LASTING IMMUNITY TO PATHOGEN", application Ser. No.: PCT US01/18238, Filed: Jun. 4, 2001, which is a continuation-inpart of U.S. patent application entitled "GENETIC VACCINE THAT MIMICS NATURAL VIRAL INFECTION AND INDUCES LONG-LASTING IMMUNITY TO PATHOGEN", application Ser. No.: 09/585,599, Filed: Jun. 2, 2000. The above applications are incorporated herein by reference. This invention relates to vaccines for stimulating immune responses in human and other hosts, and, in particular, relates to recombinant viruses that express heterologous antigens of human immunodeficiency virus (HIV) in a host and elicit immune response to HIV infection. Current techniques for developing vaccines are largely based on the concept of using denatured virus or purified viral proteins made from bacteria. These types of vaccines may be effective for only a limited number of infectious agents, and the protection rates are limited. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

NEURAMINIC ACID DERIVATIVES, THEIR PREPARATION AND THEIR MEDICAL USE Inventor(s): Honda, Takeshi; (Tokyo, JP), Kobayashi, Yoshiyuki; (Sagamihara-shi, JP), Yamashita, Makoto; (Urawa-shi, JP) Correspondence: Frishauf, Holtz, Goodman &; Langer & Chick, PC; 767 Third Avenue; 25th Floor; New York; NY; 10017-2023; US Patent Application Number: 20020137791 Date filed: October 3, 2001 Abstract: Compounds of formula (I) or their salts or esters: 1[wherein R.sup.1 is alkyl or haloalkyl; R.sup.2 and R.sup.3 each represents hydrogen or aliphatic acyl; X is hydroxy, halogen, alkoxy, or a group of formula R.sup.aO--, where R.sup.a is aliphatic acyl; Y is a group of formula R.sup.bR.sup.cN-- or R.sup.bR.sup.cN--O--, where R.sup.b and R.sup.c each is hydrogen or alkyl; and Z is oxygen or sulfur] have excellent sialidase inhibitory activity and are therefore useful for the treatment and prevention of influenza and other viral diseases where the replication of the virus is susceptible to sialidase inhibitors. Excerpt(s): (2) a C-I-P of Ser. No. 09/249,420 filed Feb. 12, 1999, which is a continuation of International Application No. PCT/JP97/02810 filed Aug. 12, 1997. The present invention relates to a series of new neuraminic acid derivatives which have excellent sialidase inhibitory activity and which are therefore useful for the treatment and prevention of influenza and other viral diseases where the replication of the virus is susceptible to sialidase inhibitors. The invention also provides methods and compositions using these compounds for the treatment or prevention of influenza and similar viral infections, as well as processes for the preparation of these compounds. The

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compounds of the present invention have a 2-deoxy-2,3-didehydro-N-acylneuraminic acid structure. Sialic acid is N-acetylneuraminic acid. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Neuraminidase-supplemented compositions Inventor(s): Hackett, Craig S.; (Wallingford, CT), Johansson, Bert E.; (Armonk, NY), Kilbourne, Edwin D.; (Madison, CT), Matthews, James T.; (Allamuchy, NJ), Smith, Gale Eugene; (Wallingford, CT), Volvovitz, Franklin; (Woodbridge, CT), Voznesensky, Andrei I.; (West Hartford, CT), Wilkinson, Bethanie E.; (Higganum, CT) Correspondence: Frommer Lawrence & Haug; 745 Fifth Avenue- 10th FL.; New York; NY; 10151; US Patent Application Number: 20030165521 Date filed: October 4, 2002 Abstract: An anti-influenza vaccine composition wherein the improvement is that the vaccine includes, as an additive, neuraminidase (NA). The base anti-influenza vaccine can be any commercially available anti-influenza vaccine. The composition can include and be administered with an adjuvant. The vaccine composition provides protection in a host, animal or human, against influenza infection, including viral replication and systemic infection. Oral, nasal or other mucosal or per needle administration, including intracutaneous, intradermal, intermuscular, intravascular, and intravenous injections, are included. Excerpt(s): This application is a continuation-in-part of: U.S. application Ser. No. 08/430,971, filed Apr. 28, 1995 (allowed); U.S. application Ser. No. 09/235,901, filed Jan. 22, 1999; U.S. application Ser. No. 09/169,027, filed Oct. 9, 1998, which is a divisional of U.S. application Ser. No. 08/453,848, filed May 30, 1995 (now U.S. Pat. No. 5,858,368), as a continuation-in-part of U.S. application Ser. No. 08/120,607, filed Sep. 13, 1993 (now U.S. Pat. No. 5,762,939); and, U.S. application Ser. No. 08/843,519, filed Apr. 16, 1997. The disclosures of all these applications and Patents, the references cited therein and the references cited during the prosecution of those applications and Patents, as well as the references cited herein, are all expressly incorporated herein by reference. The present invention relates to a Neuraminidase (NA) supplemented compositions, and methods employing the same, including routes of administration. More specifically, the present invention relates to an immunological, antigenic, immunogenic, or vaccine composition comprising an anti-influenza vaccine wherein the improvement comprises having as an additive neuraminidase (NA) from at least one influenza virus strain; and, to methods for making and using the same. Such compositions and methods have advantages such as improved efficacy. Several documents are cited in the text, with full citation thereat, or in the portion headed "References", and each document cited herein ("herein cited documents") and each document referenced or cited in herein cited documents are hereby incorporated herein by reference. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Novel assay for detecting immune responses involving antigen specific cytokine and/or antigen specific cytokine secreting T-cells Inventor(s): Brice, Gary Todd; (Alexandria, VA), Doolan, Denise L.; (Rockville, MD), Hoffman, Stephen L.; (Gaithersburg, MD) Correspondence: Naval Medical Research Center; Attn: (code 00l); 503 Robert Grant Avenue; Silver Spring; MD; 20910-7500; US Patent Application Number: 20030143641 Date filed: October 18, 2001 Abstract: Here, we describe a sensitive and specific assay and kit for the detection of chemokines having activity that is upregulated by Th-1 cytokines (such IFN-.gamma.) and chemokines that upregulate the activity of Th-1 cytokines (such as IFN-.gamma.). In a typical embodiment, detection of the chemokine monokine induced by gamma interferon (MIG) provides a measure of the biological effect of IFN-.gamma. rather than direct quantitation of IFN-.gamma. or IFN-.gamma. secreting cells per se. Upregulation of MIG expression was observed following in vitro activation of PBMC with defined CD8.sup.+ T cell epitopes derived from influenza virus, CMV, or EBV, and in all cases this was antigen-specific, genetically restricted and dependent on both CD8.sup.+ T cells and IFN-.gamma. Responses as assessed by the MIG assay paralleled those detected by conventional IFN-.gamma. ELISPOT, but the magnitude of response and sensitivity of the MIG assay were superior. Our data validate this novel method for the detection of high as well as low levels of antigen-specific and genetically restricted IFN-.gamma. activity or MIG. Excerpt(s): Here, we describe a sensitive and specific assay and kit for the detection of chemokines having activity that is upregulated by Th-1 cytokines such as IFN-.gamma. (interferon-.gamma.) and chemokines that upregulate the activity of Th-1 cytokines (such as IFN-.gamma.). The invention also relates to a sensitive and novel immunoassay method and kit for detecting MIG (Monokine Induced by interferon-.gamma.) or other chemokines whose production is upregulated by IFN-.gamma. Also, the invention relates to a method of assessing the effectiveness of a compound or system in inducing an immune response by detecting the induction of the expression of such a chemokine. All references mentioned in this application are incorporated herein by reference, in their entirety. The ability to assess specific immune responses is critical for understanding the immune mechanisms underlying disease, defining the types of responses to be induced by vaccination, and evaluating vaccine efficacy. Particular emphasis has been placed on the measurement of T cell mediated responses and the identification of immune markers thought to correlate with protection. In this specification and the claims that follow, the term "immune response" includes responses that modify a pre-existing immune response. Cytokines are immune system proteins that are biological response modifiers. Monokines are chemokines secreted from monocytes. Chemokines are cytokines that have chemoattractant properties. These biological proteins are discussed, for example, in the Illustrated Dictionary of Immunology, ed. Cruse, J. M. and Lewis, R. E., CRC Press, N.Y., (1995). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Novel carbapenem derivatives Inventor(s): Aihara, Kazuhiro; (Yokohama-Shi, JP), Akiyama, Yoshihisa; (Yokohama-Shi, JP), Ando, Takashi; (Yokohama-Shi, JP), Atsumi, Kunio; (Yokohama-Shi, JP), Ida, Takashi; (Yokohama-Shi, JP), Iwamatsu, Katsuyoshi; (Yokohama-Shi, JP), Kano, Yuko; (Yokohama-Shi, JP), Kitagawa, Hideo; (Yokohama-Shi, JP), Maruyama, Takahisa; (Yokohama-Shi, JP), Sambongi, Yumiko; (Yokohama-Shi, JP), Sasaki, Toshiro; (Yokohama-Shi, JP), Takizawa, Hiromasa; (Yokohama-Shi, JP), Tanabe, Kiyoshi; (Yokohama-Shi, JP) Correspondence: Wenderoth, Lind & Ponack, L.L.P.; 2033 K Street N. W.; Suite 800; Washington; DC; 20006-1021; US Patent Application Number: 20030149016 Date filed: August 14, 2002 Abstract: Disclosed is a novel carbapenem derivative having a substituted imidazo[5,1b]thiazole group at the 2-position on the, carbapenem ring have high anti-microbial activities against.beta.-lactamase producing bacteria, MRSA, resistant-Pseudomonas aeruginosa, PRSP, enterococci, and influenza, and high stabilities to DHP-1. According to the present invention, there is provided a compound represented by the formula (I), or a pharmacologically acceptable salt thereof or an ester at the 3-position on the carbapenem ring thereof: 1 Excerpt(s): The present invention relates to a carbapenem compound which has excellent antimicrobial activity and wide range of anti-microbial spectrum, and can be administered not only as an injection but also orally. More particularly, the present invention relates to a novel carbapenem derivative which has a substituted imidazo[5,1b]thiazole group or a salt thereof. Carbapenem derivatives, by virtue of potent antibacterial activity against a wide spectrum of bacteria, have been energetically studied as a highly useful.beta.-lactam agent, and Imipenem, Panipenem, and Meropenem have been clinically used. Both Imipenem and Panipenem, however, are used as a mixture due to instability against renal dehydropeptidase-1 ("DHP-1") in the case of Imipenem and in order to reduce nephrotoxicity in the case of Panipenem. Meropenem which has recently been marketed has a methyl group at the 1.beta.position, so that it has increased stability to DHP-1 and thus can be used alone. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Nucleic acid immunization Inventor(s): Haynes, Joel R.; (Madison, WI), Macklin, Michael D.; (Madison, WI), Payne, Lendon G.; (Madison, WI) Correspondence: Thomas P. Mccracken; Powderject Technologies INC.; 6511 Dumbarton Circle; Fremont; CA; 94555; US Patent Application Number: 20020165176 Date filed: April 30, 2001 Abstract: Recombinant nucleic acid molecules are described. The molecules have a sequence or sequences encoding an influenza virus M2 antigen. Vectors and compositions containing these molecules are also described. Methods for eliciting an immune response using these molecules and compositions are also described.

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Excerpt(s): This application is related to U.S. provisional application serial No. 60/200,968, filed May 1, 2000, and U.S. provisional application serial No. 60/210,580, filed Jun. 8, 2000, from which applications priority is claimed pursuant to 35 U.S.C.sctn.119(e)(1) and which applications are incorporated herein by reference in their entirety. The invention relates to the fields of molecular biology and immunology, and generally relates to nucleic acid immunization techniques. More specifically, the invention relates to polynucleotides encoding an influenza antigen, and to nucleic acid immunization strategies employing such polynucleotides. Techniques for the injection of DNA and mRNA into mammalian tissue for the purposes of immunization against an expression product have been described in the art. The techniques, termed "nucleic acid immunization" herein, have been shown to elicit both humoral and cell-mediated immune responses. For example, sera from mice immunized with a DNA construct encoding the envelope glycoprotein, gp160, were shown to react with recombinant gp160 in immunoassays, and lymphocytes from the injected mice were shown to proliferate in response to recombinant gp120. Wang et al. (1993) Proc. Natl. Acad. Sci. USA 90:4156-4160. Similarly, mice immunized with a human growth hormone (hGH) gene demonstrated an antibody-based immune response. Tang et al. (1992) Nature 356:152-154. Intramuscular injection of DNA encoding influenza nucleoprotein driven by a mammalian promoter has been shown to elicit a CD8+ CTL response that can protect mice against subsequent lethal challenge with virus. Ulmer et al. (1993) Science 259:1745-1749. Immunohistochemical studies of the injection site revealed that the DNA was taken up by myeloblasts, and cytoplasmic production of viral protein could be demonstrated for at least 6 months. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Pharmaceutical composition for treating or preventing influenza, and novel oligonucleotide Inventor(s): Hatta, Toshifumi; (Ibaraki, JP), Mizuta, Tadashi; (Kanagawa, JP), Shigeta, Shiro; (Fukushima, JP), Takai, Kazuyuki; (Chiba, JP), Takaku, Hiroshi; (Chiba, JP), Yokota, Tomoyuki; (Fukushima, JP) Correspondence: Sughrue Mion Zinn,; Macpeak & Seas, Pllc; 2100 Pennsylvania Avenue, NW; Washington; DC; 20037-3213; US Patent Application Number: 20030087851 Date filed: July 19, 2001 Abstract: A pharmaceutical composition for treating or preventing influenza comprising an oligonucleotide containing a base sequence complementary to a base sequence of a target region containing a translational initiation codon AUG of a PB2 gene or a PA gene, a liposome stable in blood, and a pharmaceutically acceptable carrier or dilute is disclosed. The pharmaceutical composition for treating or preventing influenza can be used in an effective treatment of or prevention of an infection by influenza viruses. Excerpt(s): The present invention relates to a pharmaceutical composition for treating or preventing influenza, comprising an anti-influenza-viral antisense oligonucleotide and a liposome. An influenza virus causes a severe cold with strong generalized symptoms. Particularly, in an aged patient or a high-risk patient suffering from a chronic respiratory disorder or a heart disease, influenza is a very infectious disease that often leads to a lethal pneumonia. The influenza viruses are classified into three types, A, B, and C, on the basis of the differences in serotypes of nucleoproteins (NP) and membrane

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proteins (M). Of these types, the influenza A virus and influenza B virus are prevalent every year. The influenza A virus has two glycoproteins, i.e., a hemaglutinin (HA) and a neuraminidase (NA), on the surface of an envelope thereof, and thus is classified into subtypes such as H1N1 (Soviet Union subtype), H2N2 (Asian subtype), and H3N2 (Hong Kong subtype), on the basis of the antigenecities thereof. The influenza B virus has both HA and NA, but there is only one subtype. Unlike the influenza A virus and the influenza B virus, the influenza C virus has only a hemaglutinin-esterase (HE) as a glycoprotein on the surface of the envelope, and thus, there is only one subtype. The influenza virus belongs to the orthomyxoviridae family, and has a minus strand, i.e., a single-stranded RNA virus. The gene of the influenza virus is composed of eight segments. Proteins encoded by the eight segmentation genes include HA and NA, as well as M1 and M2, which are the membrane protein, on the surface of the envelope. Furthermore, a nucleoprotein complex (RNP) is located at the center of the virus and is composed of the RNA gene, three RNA polymerase subunits (PB1, PB2, and PA), and a nucleoprotein (NP). A non-structural protein (NS) is synthesized from the eighth segmentation gene. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Processes for the replication of influenza viruses in cell culture, and the influenza viruses obtainable by the process Inventor(s): Groner, Albrecht; (Seeheim, DE) Correspondence: Chiron Corporation; Intellectual Property; PO Box 8097; Emeryville; CA; 94662-8097; US Patent Application Number: 20030119183 Date filed: September 16, 2002 Abstract: Novel processes for the replication of influenza viruses in cell culture, and vaccines and diagnostic compositions which contain the influenza viruses obtainable by the process or constituents thereof, are described. Excerpt(s): The present invention relates to processes for the replication of influenza viruses in cell culture at reduced temperatures, and to the influenza viruses obtainable by the process described and to vaccines which contain viruses of this type or constituents thereof. All influenza vaccines which have been used since the 40s until today as permitted vaccines for the treatment of humans and animals consist of one or more virus strains which have been replicated in embryonate hens' eggs. These viruses are isolated from the allantoic fluid of infected hens' eggs and their antigens are used as vaccine either as intact virus particles or as virus particles disintegrated by detergents and/or solvents--so-called cleaved vaccine--or as isolated, defined virus proteins--socalled subunit vaccine. In all permitted vaccines, the viruses are inactivated by processes known to the person skilled in the art. Even the replication of live attenuated viruses, which are tested in experimental vaccines, is carried out in embryonate hens' eggs. The use of embryonate hens' eggs for vaccine production is time-, labor- and cost-intensive. The eggs--from healthy flocks of hens monitored by veterinarians--have to be incubated before infection, customarily for 12 days. Before infection, the eggs have to be selected with respect to living embryos, as only these eggs are suitable for virus replication. After infection the eggs are again incubated, customarily for 2 to 3 days. The embryos still alive at this time are killed by cold and the allantoic fluid is then obtained from the individual eggs by aspiration. By means of laborious purification processes, substances from the hen's egg which lead to undesired side effects of the vaccine are separated from

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the viruses, and the viruses are concentrated. As eggs are not sterile (pathogen-free), it is additionally necessary to remove and/or to inactivate pyrogens and all pathogens which are possibly present. To increase the virus yield, the replication of the influenza viruses in hens' eggs as a rule is carried out at reduced temperatures (about 34.degree. C.). Even viruses which cause respiratory diseases can be replicated in cell culture. Here too, in some cases reduced temperatures are used (about 33.degree. C.) which, however, have no effect on the quality of a vaccine which may be obtained, but only favor replication. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Processes of making North American ginseng fractions, products containing them, and use as immunomodulators Inventor(s): Huang, Buhan; (Edmonton, CA), Ling, Lei; (Edmonton, CA), Pang, Peter K. T.; (Edmonton, CA), Shan, Jacqueline J.; (Edmonton, CA) Correspondence: Arent Fox Kintner Plotkin & Kahn; 1050 Connecticut Avenue, N.W.; Suite 400; Washington; DC; 20036; US Patent Application Number: 20030077341 Date filed: July 2, 2002 Abstract: The invention is directed to chemical processes of preparing fractions from North American ginseng (Panax quinquefolium) and pharmaceutical compositions containing these fractions. The products of the present invention may be used to stimulate the production of cytokines and/or antibodies, or as therapeutics targeted at conditions characterized by low immunity, such as the common cold, influenza, chronic fatigue syndrome, AIDS and cancer. Excerpt(s): This invention relates to chemical processes of making fractions from North American ginseng (Panax quinquefolium) and compositions containing these fractions. The products of the present invention may be used to stimulate the production of antibodies, or as therapeutics targeted at conditions characterized by low immunity, such as the common cold, influenza, chronic fatigue syndrome, AIDS, cancer, etc. The products of the present invention may also be used as a supplement for cancer patients undergoing chemotherapy or radiation therapy, which is known to cause serious suppression of the immune system. For hundreds of years, the use of certain non-toxic agents such as herbal compounds has been widely accepted for a variety of physiological conditions, especially in the Orient. Panax ginseng C. A. Meyer is the best known traditional Chinese medicine. The important pharmacological activities of ginseng extracts, alone or in combination with other drugs, include alleviation of renal impairment, inhibition of carcinogenesis and prevention of stress. There are also a number of reports on the influence of ginseng on the immunological responsiveness of the individual. Some immunomodulatory properties that have been reported include enhancement of host resistance against infection, anti-inflammatory effect, inhibition of tumor growth, as well as modulation of some basic immune function at the cellular level. American ginseng, Panax quinquefolium, is another specie of ginseng which has gained popularity as a health supplement having many beneficial health effects. Several groups of scientists have attempted to isolate and elucidate the structure of the polysaccharides present in ginseng. Some of the polysaccharides have been demonstrated to be active in modulating the immune system. A series of studies on the isolation, characterization, and biological evaluation of ginseng polysaccharides was carried out by Tomoda's group in Kyoritsu College of Pharmacy, Japan. In one set of

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studies, ginseng polysaccharides were fractionated based on their acidity. Two acidic polysaccharides having immunological activities have been isolated from root of Korean ginseng (Panax ginseng).sup.[1,2]. The sliced roots were extracted with hot water. The extract was treated with cetyltrimethylammonium bromide (CTAB) in the presence of sodium sulfate. The precipitate was separated, dialyzed, and applied to a Sephadex G25 column, DEAE-Sephacel (Pharmacia) column to give two pure polysaccharides, which were designated as ginsenan PA and ginsenan PB. Gel chromatography on Toyopearl HW-55F gave the values of 1.6.times.10.sup.5and 5.5.times.10.sup.4 for the molecular weight of ginsenan PA and ginsenan PB, respectively. Quantitative analyses showed that ginsenan PA contained 21.3% arabinose, 53.4% galactose, 2.0% rhamnose, 16.0% galacturonic acid and 2.7% glucuronic acid. The molar ratio of these component sugars was 11:22:1:6:1. Ginsenan PB contained 11.0% arabinose, 32.2% galactose, 8.1% rhamnose, 39.9% galacturonic acid, and 5.0% glucuronic acid. The molar ratio was 3:7:2:8:1. Both polysaccharides showed marked reticuloendothelial system-potentiating activity in a carbon clearance test, and pronounced anti-complementary activity and alkaline phosphatase-inducing activity in a dose dependent manner. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Recombinant conglutinin and producing method thereof Inventor(s): Wakamiya, Nobutaka; (Osaka, JP) Correspondence: Marshall, Gerstein & Borun; 6300 Sears Tower; 233 South Wacker; Chicago; IL; 60606-6357; US Patent Application Number: 20020168627 Date filed: November 8, 2001 Abstract: A recombinant conglutinin which contains a collagen region consisting of six amino acids containing two amino acid sequences Gly-Xaa-Xaa (SEQ ID NO:3, wherein Xaa stands for a protein-constituting amino acid), the neck region of natural conglutinin and the sugar chain recognition region of natural conglutinin, has an antiviral activity (virus neutralizing activity), and is expected to be applicable to drugs; and a process for detecting anti-influenza A virus activity of a mannose-binding protein (MBP) or a human mannose-binding protein (hMBP) involving the step of treating influenza A virus-infected cells with the MBP or hMBP and measuring the level of the suppression of the budding of the virus in the virus-infected cells. An MBP and an hMBP having an anti-influenza A virus activity are disclosed. Excerpt(s): The present invention relates to recombinant conglutinin having anti-virus activities (neutralization activities) which are expected to be applied to medicines and producing method thereof, and a method for detecting physiological activities of collecting. Conglutinin is an animal lectin belonged to calcium-dependent mammalian C-type lectin family and existed in the bovine serum. Whole amino acids sequence (SEQ ID No.: 1) had been analyzed by Lee et al., [Lee et al., J. Biol. Chem., Vol. 266, pp. 27152723, 1991]. C-type lectin comprises basic unit having the four unique regions of (1) Nterminal region contained much cysteine, (2) collagen-like region, (3) neck region and (4) carbohydrate recognition domain (CRD) [Malhortra et al., European Journal Immunology, Vol. 22, pp. 1437-1445, 1992]. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Recombinant influenza a viruses Inventor(s): Egorov, Andre; (Vienna, AT), Ferko, Boris; (Wiener Neudorf, AT), Voglauer, Regina; (Vienna, AT) Correspondence: Oliff & Berridge; PO Box 19928; Alexandria; VA; 22320; US Patent Application Number: 20030147916 Date filed: October 30, 2002 Abstract: The invention relates to a recombinant NS gene of an influenza A virus comprising a functional RNA binding domain and a gene sequence modification after nucleotide position 400 of the NS1 gene segment, counted on the basis of influenza A/PR/8/34 Virus, wherein the modification bars transcription of the remaining portion of the NS1 gene segment. It further relates to embodiments, wherein the modification comprises deletions, insertions, or a shift of the open reading frame, and particularly to constructs comprising an insertion of an autocleavage site 2A, the nef gene from HIV-1 or the sequence encoding the ELDKWA-epitope of gp4l of HIV-1. The invention also relates to influenza virus transfectants that contain the modified NS gene and have an IFN inducing phenotype but which may or may not be sensitive towards IFN. The invention also relates to vaccines comprising such a chimeric virus. Excerpt(s): The invention is in the fields of vaccine development and application and relates to attenuated live vaccine vectors, more specifically to such vectors based on or derived from genetically modified influenza A virus strains, and to the manufacture of recominant influenza viruses and vaccines. (iv) attenuated influenza viruses as live influenza vaccines, which were shown to be safe and immunogenic in humans, are available. Preceding investigations in connection with the present invention have indicated that the NS gene of influenza A virus may be a promising alternative to HA as a viral carrier for presenting a desired foreign antigen to the animal or human immune system. The recently established method of reverse genetics (Egorov et al., 1998, J Virol 72(8), 6437-41) allows to rescue influenza viruses containing long deletions or insertions of foreign sequences at the carboxyl side of the non-structural Protein 1 (NS1 protein). NS1 protein is abundant in influenza virus-infected cells and stimulates cytotoxic T-lymphocyte (CTL) responses as well as antibody responses during the natural course of influenza virus infection. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Recombinant influenza viruses for vaccines and gene therapy Inventor(s): Kawaoka, Yoshihiro; (Middleton, WI), Neumann, Gabriele; (Nanuet, NY) Correspondence: Nicholas J. Seay; Quarles & Brady Llp; P O Box 2113; Madison; WI; 53701-2113; US Patent Application Number: 20030035814 Date filed: October 4, 2001 Abstract: The invention provides a composition useful to prepare influenza A viruses, e.g., in the absence of helper virus. Excerpt(s): The ability to generate infectious RNA viruses from cloned cDNAs has contributed greatly to the biological understanding of these pathogens and hence to improved methods of disease control (Palese et al., 1996). However, this progress had been relatively limited for negative-sense as compared with positive-sense RNA viruses,

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because neither the genomic viral RNA (vRNA) nor the antigenomic complementary RNA (cRNA) of negative-sense RNA viruses can serve as a direct template for protein synthesis. Rather, the vRNA, after its encapsidation by viral nucleoprotein (NP), must be transcribed into positive-sense mRNA by the viral RNA polymerase complex. Thus, the minimal replication unit is formed by the genomic vRNA complexed with NP and the polymerase proteins. Despite these obstacles, reverse genetics methods have been established to produce nonsegmented negative-sense RNA viruses, including rabies virus (Snell et al., 1994), vesicular stomatitis virus (Lawson et al., 1995); Whelan et al., 1995), measles virus (Radecke et al., 1995), respiratory syncytial virus (Collins et al., 1995), Sendai virus (Garcin et al., 1995; Kato et al., 1996), rinderpest virus (Baron et al., 1997), human parainfluenza virus type 3 (Hoffman et al., 1997) and SV5 (He et al., 1997). The Orthomyxoviridae, Arenaviridae, and Bunyaviridae families contain segmented, negative strand RNA genomes and include several human and animal pathogens, for example, influenza virus types A, B, and C (Orthomyxoviridae), lymphocytic choriomeningitis virus (LCMV) (Arenaviridae), and encephalitic and hemorrhagic fever viruses (Bunyaviridae, Arenaviridae). Their genomes consist of two (Arenaviridae), three (Bunyaviridae), or six to eight (Orthomyxoviridae) single-stranded RNA molecules of negative polarity (complementary to mRNA). The vRNAs interact with NP and viral RNA-dependent RNA-polymerase to form ribonucleoprotein complexes (RNPs). The RNPs are surrounded by a lipid bilayer derived from the host cell. Inserted in this envelope are viral glycoproteins, which are essential for receptor binding and entry into the host cell. Thus, generating segmented negative-sense RNA viruses from cloned cDNAs poses a formidable challenge, as one must produce a separate vRNA for each gene segment. Bridgen and Elliott (1996) produced a Bunyamwera virus (family Bunyaviridae) from cloned cDNAs encoding three segments of antigenomic, positivesense vRNA. However, the efficiency of virus recovery was low. None of the orthomyxoviruses, which contain six (thogotovirus), seven (influenza C virus) or eight (influenza A and B viruses) segments of negative-sense RNA have been produced entirely from cloned cDNAs. This lag in progress has been felt most acutely in efforts to control influenza virus infections. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Recombinant papillomavirus vaccine and method for production and treatment Inventor(s): Bruck, Claudine; (Rixensart, BE), Delisse, Anne-Marie Eva Fernande; (Gosselies, BE), Gerard, Catherine Marie Ghislaine; (Rhode Saint Genese, BE), Lombardo-Bencheikh, Angela; (Wavre, BE), Silva, Teresa Cabezon; (Lenkebeek, BE) Correspondence: Glaxosmithkline; Corporate Intellectual Property - Uw2220; P.O. Box 1539; King OF Prussia; PA; 19406-0939; US Patent Application Number: 20020182221 Date filed: November 1, 2001 Abstract: The present invention relates to fusions proteins, comprising a protein or part of a protein that provides T helper epitopes and an antigen from a human-papilloma virus. In particular the invention relates to fusion proteins comprising an E6 or E7 protein from HPV strain 16 or 18 linked to protein D from Haemophilus influenza B. The invention also provides vaccine compositions that are useful in the treatment or prophylaxis of human papilloma induced tumors. Excerpt(s): The present invention relates to fusions proteins, comprising a protein or part of a protein that provides T helper epitopes and an antigen from a human-

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papilloma virus that find utility in the treatment or prophylaxis of human papilloma induced tumours. In particular the invention relates to fusion proteins comprising an E6 or E7 protein from HPV strain 16 or 18 linked to protein D from Heamophilius influenza B. Papillomaviruses are small naked DNA tumour viruses (7.9 kilobases, double strand), which are highly species-specific. Over 70 individual human papillomavirus (HPV) genotypes have been described. Papillomaviruses are classified on the basis of species of origin (human, bovine etc.) and of the degree of genetic relatedness with other papillomaviruses from the same species. HPVs are generally specific for the skin or mucosal surfaces and have been broadly classified into "low" and "high" risk on the basis of rare and common, respectively, detection in abnormal or tumour tissue. Low risk HPVs usually cause benign lesions (warts or papillomas) that persist for several months or years. High risk HPVs are associated with cancer. The strongest positive association between an HPV virus and human cancer is that which exist between HPV 16 and 18 and cervical carcinoma. More than ten other HPV types have also been found in cervical carcinomas including HPV 31 and HPV 33 although at less frequency. Genital HPV infection in young sexually active women is common and most individuals either clear the infection, or if lesions develop, these regress. Only a subset of infected individuals has lesions which progress to high grade intraephithelial neoplasia and only a fraction of these progress further to invasive carcinoma. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Replikin peptides in rapid replication of glioma cells and in influenza epidemics Inventor(s): Bogoch, Elenore S.; (New York, NY), Bogoch, Samuel; (New York, NY) Correspondence: Kenyon & Kenyon; 1500 K Street, N.W., Suite 700; Washington; DC; 20005; US Patent Application Number: 20030180328 Date filed: March 26, 2002 Abstract: Peptides of influenza virus hemagglutinin protein and Plasmodium falciparum malaria antigen, antibodies specific for the peptides, influenza vaccines, malaria vaccines and methods of stimulating the immune response of a subject to produce antibodies to influenza virus or malaria are disclosed. Also disclosed are methods for formulating vaccines for influenza virus. Excerpt(s): This application is a Continuation-In-Part Application of U.S. Ser. No. 09/984,057, filed Nov. 26, 2001, which claims priority from Provisional Application No. 60/303,396, filed Jul. 9, 2001 and Provisional Application U.S. 60/278,761 filed Mar. 27, 2001, the subject matter of which is incorporated by reference hereto. This invention relates to the identification and use of Replikins, a class of peptides that share structural characteristics. In particular, this invention relates to Replikins which have been identified in influenza viruses and their use in designing influenza virus vaccines. Influenza is an acute respiratory illness of global importance. Despite international attempts to control influenza virus outbreaks through vaccination influenza infections remain an important cause of morbidity and mortality. Worldwide influenza pandemics have occurred at irregular and previously unpredictable intervals throughout history and it is expected that they will continue to occur in the future. The impact of pandemic influenza is substantial in terms of morbidity, mortality and economic cost. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Synthetic soil-extract materials and medicaments for influenza viruses based thereon Inventor(s): Laub, Richard J.; (Newport Beach, CA) Correspondence: Knobbe Martens Olson & Bear Llp; 620 Newport Center Drive; Sixteenth Floor; Newport Beach; CA; 92660; US Patent Application Number: 20030044381 Date filed: May 8, 2002 Abstract: Phenolic polymers are prepared by oxidizing and polymerizing starting organic compounds comprising at least one hydroxyl group and at least one carbonyl group or at least two hydroxyl groups on an aromatic structure. One or more inorganic compounds or salts is added and the solution is allowed to stand at about 20.degree. C. to 80.degree. C. for a period of about at least 2 hours. Salt molecules as well as starting compounds and other low molecular-weight materials below about 500 to about 10,000 daltons are removed from the product solution. Purified phenolic polymers are prepared in concentrated aqueous solution or in dried powder form in a final step, if necessary. The resultant phenolic polymers exhibit physicochemical properties strongly resembling those of typical commercially-available natural-product soil extracts. The materials are active influenza anti-viral agents, and are effective in anti-viral compositions for treating or preventing influenza viral diseases. Excerpt(s): This application claims the benefit under 35 U.S.C.sctn.119(e) of U.S. Provisional Application Serial No. 60/297,669, filed Jun. 12, 2001 and is a continuationin-part of application Ser. No. 09/345,865, filed Jul. 1, 1999, which is a divisional of application Ser. No. 08/798,329, filed Feb. 10, 1997, now U.S. Pat. No. 5,945,446, issued Aug. 31, 1999. This invention relates to synthetic soil extract substances comprised of phenolic polymers, and to compositions and methods for employing these synthetic phenolic polymers for preventing, reducing, treating, or eliminating influenza viral diseases. Soil extract materials, particularly the classes of substances known collectively as "humus," "humics," "humic acid(s)," or "humates," have been widely used in a number of applications for many years, as reviewed by F. J. Stevenson, Humus Chemistry. Genesis Composition Reactions; New York: Wiley, 1964; and, more recently, by A. Piccolo, Humic Substances in Terrestrial Ecosystems; New York: Elsevier, 1996. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Tannate compositions and methods of treatment Inventor(s): Venkataraman, Balaji; (Roswell, GA) Correspondence: Leydig Voit & Mayer, Ltd; Two Prudential Plaza, Suite 4900; 180 North Stetson Avenue; Chicago; IL; 60601-6780; US Patent Application Number: 20030060422 Date filed: January 25, 2002 Abstract: The present invention is directed to methods and compositions for treating upper respiratory indications, such as the treatment, management or mitigation of cough, cold, cold-like symptoms, symptoms related to upper respiratory infections, influenza symptoms and allergic rhinitis, perennial rhinnitis, nasal and Eustachian tube congestion in an animal by administration of tannate compositions comprising single

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agent formulations or combinations of at least one or more agents into a single administrative dose. Excerpt(s): The present invention is directed to methods and compositions for the treatment of symptoms of upper respiratory conditions, including allergic rhinitis, coryza, influenza, rhinovirus and other viral infections. More particularly the invention relates to tannate compositions for the treatment of upper respiratory indications, wherein the agent or agents are provided in a single administrative dose. Upper respiratory symptoms, resulting from a cold or influenza infection or allergic reactions, though not generally life threatening are some of the most annoying symptoms to have. Work days and hours are lost when employees are debilitated by these symptoms. The symptoms include nasal congestion, cough, sinusitis, cold, cold-like symptoms, influenza symptoms and allergic rhinitis. Additionally other symptoms of upper respiratory mucosal congestions such as those seen in perennial and allergic rhinnitis and Eustachian tube congestion. These symptoms are treated with a variety of therapeutic agents. For example, antihistamines interact with histamine released in the body in an allergic reaction by competing for the histamine H.sub.1-receptor. Antihistamines reduce the effects of histamine in allergic reactions and tissue injury response. Antihistamines offset the histamine effects of increased capillary permeability and edema formation, particularly in the nasal mucosa where vascular engorgement, mucosa edema, irritation, sneezing and watery secretions result from histamine release. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Use of a live attenuated Mycoplasma gallisepticum strain as a vaccine and vector for the protection of chickens and turkeys from respiratory disease Inventor(s): Geary, Steven J.; (Storrs, CT), Marcus, Philip; (Storrs, CT), Sekellick, Margaret; (Storrs, CT), Silbart, Lawrence; (Willington, CT) Correspondence: Cummings & Lockwood; P.O. Box 1960; New Haven; CT; 06506-1960; US Patent Application Number: 20020187162 Date filed: April 19, 2002 Abstract: The present invention relates to a live cytadherence-deficient M. gallisepticum strain that does not express at least two of three proteins, the Gap-A molecule, crnA protein, and the 45 kDa protein, expressed by wildtype M. gallisepticum Strain R and its use as a vaccine for preventing and protecting birds, especially chickens and turkeys against the respiratory diseases attendant with wildtype Mycoplasma gallispeticum infection. The invention also relates to the use of the vaccine as a vector for the delivery of genes encoding protective antigens from other bacterial and viral avian pathogens, such as avian influenza virus. There is also disclosed a method for identifying the attenuated cytadherence-deficient M. gallisepticum R.sub.high or a strain thereof. Excerpt(s): This application claims benefit under Title 35 U.S.C.sctn. 119(e) of United States Provisional Serial No. 60/285,569 filed Apr. 21, 2001. 2. Background of the Invention Viral diseases represent a continuous threat to the poultry industry. Poultry flocks are susceptible to a number of respiratory infections. Some of these infections result in mild illnesses, while outbreaks of others may result in a high number of deaths. Regardless of whether the birds are raised for meat, breeding, or eggs, respiratory infections result in decreased performance and pose disease hazards for other poultry on the premises. There are numerous causative agents of respiratory infections in birds.

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Of those causative agents that have been identified over the years, each can be classified as either a virus (e.g., Newcastle disease, infectious bronchitis, laryngotracheitis, quail bronchitis, influenza/parainfluenza), a bacteria (e.g., mycoplasmosis, infectious coryza, endemic fowl cholera, psitticosis/omithosis) or a mold (e.g., aspergillus (brooder pneumonia)). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Use of conjugated acid derivatives Inventor(s): Cain, Frederick William; (Wormerveer, NL), Mohede, Ingrid Celestina Maria; (Wormerveer, NL), O'Shea, Marianne; (Channahon, IL), Schmid, Ulrike; (Wormerveer, NL) Correspondence: Morgan Lewis & Bockius Llp; 1111 Pennsylvania Avenue NW; Washington; DC; 20004; US Patent Application Number: 20030215465 Date filed: April 17, 2003 Abstract: The invention concerns the use of conjugated linoleic acid (=CLA) or derivatives thereof, such as partial glycerides or triglycerides, alkyl esters or salts for the production of a food, a food supplement or a pharmaceutical preparation with the property to prevent or to cure influenza, to boost the effects of an influenza vaccination and/or to alleviate the effects of an influenza vaccination in humans and/or animals. Excerpt(s): the nature of the illness caused by the different viruses is different. Thogoto viruses leading to a more severe illness than influenza viruses such as optic neuritis and fatal meningitis. Because of these basic differences in mechanism a man skilled in the art never would have expected that CLA could have a positive effect on all the family members of the whole Orthomyxovirus family. U.S. Pat. No. 5,827,885 being the mother patent of above U.S. Pat. No. 376 has a similar teaching although the claims now are limited to the anti viral effects of CLA. Again influenza is not disclosed in this document. Here the same argument as above will account. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Use of substances that act as cascade inhibitors of the raf/mek/erk signal cascade, for producing a medicament to treat dna and rna viruses Inventor(s): Ludwig, Stephan; (Wurzburg, DE), Pleschka, Stephan; (Giessen, DE) Correspondence: Mark D Wieczorek; PO Box 70072; San Diego; CA; 91267; US Patent Application Number: 20030060469 Date filed: October 4, 2002 Abstract: The invention consists in that substances acting as cascade inhibitors of the Raf/MEK/ERK signaling path-way, in particular MEK inhibitors, are used for the production of a drug for the preventive and antiviral therapy against DNA and RNA viruses, in particular against intranuclear-replicating negative strand RNA viruses, for instance influenza or Borna disease viruses. Excerpt(s): The present invention is based on the first observation that an infection with the intranuclear-replicating negative strand viruses, in particular influenza A virus and

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Borna disease virus (BDV), will lead to an activation of the Raf/MEK/ERK cascade, and that surprisingly the inhibition of this cascade in particular by a MEK inhibitor considerably inhibits the replication of this virus group, without having a toxic effect on the cells. An improved therapy against DNA and RNA viruses the multiplication of which is dependent on the activity of the Raf/MEK/ERK cascade, is preferably directed therefore to this signaling pathway. It has been found that this signaling pathway is blocked by the application of a non-toxic pharmacological inhibitor, This non-toxic pharmacological inhibitor of the Raf/MEK/ERK signaling pathway is according to the invention a cascade inhibitor, in particular a MEK inhibitor. Virus infections are a considerable risk for the health of man and animal. In particular infections with the influenza A virus still belong to the big epidemics of mankind and are responsible year for year not only for a multitude of fatalities, but are also an immense cost factor for the whole economy, for instance by absence from work due to diseases [12]. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Viruses for the treatment of cellular proliferative disorders Inventor(s): Coffey, Matthew C.; (Calgary, CA), Thompson, Bradley G.; (Calgary, CA) Correspondence: Burns Doane Swecker & Mathis L L P; Post Office Box 1404; Alexandria; VA; 22313-1404; US Patent Application Number: 20020187465 Date filed: May 1, 2002 Abstract: Methods for treating cell proliferative disorders by administering virus to proliferating cells having an activated Ras-pathway are disclosed. The virus is administered so that it ultimately directly contacts proliferating cells having an activated Ras-pathway. Proliferative disorders include but are not limited to neoplasms. Representative viruses include modified adenovirus, modified HSV, modified vaccinia virus, modified parapoxvirus orf virus, and modified influenza virus. Also disclosed are methods for treating cell proliferative disorders by further administering a immunosuppressive agent. Excerpt(s): This application is a continuation-in-part of U.S. application Ser. No. 09/708,663, filed Nov. 9, 2000, which claims the benefit of U.S. Provisional Application Serial No. 60/164,878, filed Nov. 12, 1999, which are both incorporated herein by reference in their entirety. The present invention pertains to methods for treating cellular proliferative disorders in a mammal that are mediated by Ras-activation using modified viruses. 33. Bergmann, M. et al., Can. Res. (2001) 61(22): 8188-8193. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

Keeping Current In order to stay informed about patents and patent applications dealing with influenza, you can access the U.S. Patent Office archive via the Internet at the following Web address: http://www.uspto.gov/patft/index.html. You will see two broad options: (1) Issued Patent, and (2) Published Applications. To see a list of issued patents, perform the following steps: Under “Issued Patents,” click “Quick Search.” Then, type “influenza” (or synonyms) into

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the “Term 1” box. After clicking on the search button, scroll down to see the various patents which have been granted to date on influenza. You can also use this procedure to view pending patent applications concerning influenza. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.

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CHAPTER 7. BOOKS ON INFLUENZA Overview This chapter provides bibliographic book references relating to influenza. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on influenza include the Combined Health Information Database and the National Library of Medicine. Your local medical library also may have these titles available for loan.

Book Summaries: Federal Agencies The Combined Health Information Database collects various book abstracts from a variety of healthcare institutions and federal agencies. To access these summaries, go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. You will need to use the “Detailed Search” option. To find book summaries, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer. For the format option, select “Monograph/Book.” Now type “influenza” (or synonyms) into the “For these words:” box. You should check back periodically with this database which is updated every three months. The following is a typical result when searching for books on influenza: •

Annual Review of Diabetes 2000 Source: Alexandria, VA: American Diabetes Association. 2000. 384 p. Contact: Available from American Diabetes Association (ADA). Order Fulfillment Department, P.O. Box 930850, Atlanta, GA 31193-0850. (800) 232-6733. Fax (770) 4429742. Website: www.diabetes.org. PRICE: $49.95 plus shipping and handling. Summary: This book serves as a compendium of diabetes research articles that appeared in American Diabetes Association journals. Articles in section one focus on the pathogenesis of diabetes. Topics include the applicability of the thrifty genotype to obesity and type 2 diabetes, the role of cow's milk in the etiology of type 1 diabetes, the preservation of beta cell function in type 1 diabetes, the regulation and possible significance of leptin in humans, the genetic aspects of type 1 diabetes, the pathology and pathogenesis of diabetic neuropathy, and the aldose reductase pathway and nonenzymatic glycation in the pathogenesis of diabetic neuropathy. Articles in section

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two explore options for treating diabetes in children, adolescents, the elderly, and the obese. Other articles in this section focus on insulin secretagogues, intensive insulin therapy, pancreas and islet transplantation, and gene therapy. In addition, articles examine the impact of smoking on diabetes, the use of influenza and pneumococcal vaccines in people who have diabetes, the measurement of patient well being, the assessment of diabetes specific quality of life, and the economic aspects of diabetes interventions. Articles in the final section deal with diabetic complications, including diabetic nephropathy; cardiovascular diseases; foot wounds; somatic neuropathy; gastrointestinal, genitourinary, and neurovascular disturbances; and macrosomia. Another article in this section reviews current and emerging treatments for diabetic neuropathies. Numerous figures. Numerous tables. Numerous references. •

Predicting AIDS and Other Epidemics Contact: Franklin Watts, Incorporated, 387 Park Ave S, New York, NY, 10016, (212) 6867070. Summary: This monograph studies the history of epidemiology through the centuries, and concludes by relating it to Acquired immunodeficiency syndrome (AIDS). It opens with a history of the worst epidemics, including the 14th-century plague and the influenza epidemic of 1918-19. The monograph explains little was known about the mechanisms of disease until the 19th century. Next, it analyzes the body's defenses, including the immune system, and discusses the development of vaccines and other methods of treatment. It shows how epidemiologists act as detectives, tracking the origins of epidemics, and says that they also attempt to predict the future course of disease. In the final chapter, the monograph says that AIDS may yet rival the great plagues of history, and that many are worried that it may someday swamp the entire health-care system. It gives a history of the epidemic and the opportunistic infections associated with it, and explains its transmission through infected blood.

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Herd Immunity and the HIV Epidemic Contact: HIVE Foundation, PO Box 808, Vacaville, CA, 95696. Summary: This monograph suggests that persons with HIV infection are more susceptible to infection by a number of other viruses, and because they carry these viruses in their bodies for longer periods of time than normal, they are a potential source of epidemics among the general population. It looks at the rising incidence of a number of illnesses, including syphilis, salmonella, tuberculosis, hepatitis, cytomegalovirus, and influenza. The monograph advocates increased reporting, tracking, and screening of HIV-infected persons in order to prevent epidemics.

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Foods That Harm, Foods That Heal: An A-Z Guide to Safe and Healthy Eating Source: Pleasantville, NY: Reader's Digest. 1997. 400 p. Contact: Available from Customer Service, Reader's Digest. Pleasantville, NY 10570. (800) 846-2100. PRICE: $30.00. ISBN: 0895779129. Summary: This nutrition reference book features more than 400 photographs and illustrations with more than 400 A to Z entries on a vast range of foods and health concerns, include caffeine, cancer, diabetes, fast food, garlic, heart disease, influenza, osteoporosis, pregnancy, sexually transmitted diseases, and vegetarianism. The book is designed to provide families with information to help understand the close links between foods and wellness. Each food entry provides at-a-glance information on its

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nutrients (or lack of) and its benefits and drawbacks. Each ailment is accompanied by a list of foods and beverages that are considered safe, and what foods or beverages should be cut down or avoided altogether. Personalized case studies help to illustrate various topics. There are special features on eating during different life stages, from infancy to old age, as well as such issues as genetically altered foods, irradiation, pesticides, and pollution. Other topics include how to cook foods to achieve maximum nutritional benefits; which dietary supplements really work; tips on exercising, storing food, and reading food labels; an instructive analysis of the most popular diet regimens; and controversial foods and additives such as eggs, nitrites, bran, cheese, milk, fat, wine, and alcohol. A glossary defines unfamiliar or technical terms; there is also a listing of organizations that can provide further information and resources. Topics specifically related to digestive diseases include allergic reactions to food, anorexia nervosa, antioxidants, appetite loss, basic food groups, carbohydrates, celiac disease, childhood and adolescent nutrition, cholesterol, constipation, convenience foods, Crohn's disease, diarrhea, dieting and weight control, digestive and malabsorption disorders, diverticulitis, fats, fiber, food poisoning, gastritis, gastroenteritis, gout, hiatal hernia, indigestion and heartburn, intolerance to milk and other foods, irritable bowel syndrome, malnutrition, medicine-food interactions, minerals, obesity, organic and health foods, preparation and storage of food, restaurants and eating out, smoking and diet, sports nutrition, supplements, traveler's health, ulcers, vitamins, and worms and other parasites.

Book Summaries: Online Booksellers Commercial Internet-based booksellers, such as Amazon.com and Barnes&Noble.com, offer summaries which have been supplied by each title’s publisher. Some summaries also include customer reviews. Your local bookseller may have access to in-house and commercial databases that index all published books (e.g. Books in Print®). IMPORTANT NOTE: Online booksellers typically produce search results for medical and non-medical books. When searching for “influenza” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “influenza” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “influenza” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •

2003 Essential Medical Guide to SARS (Severe Acute Respiratory Syndrome) and Atypical Pneumonia, Influenza (Flu), Antiviral Drugs, Respiratory and Lung Diseases, Infection Control, Coronavirus - Authoritative Federal Information from the CDC, FDA, and NIH for Health Care Providers, Physicians, and Patients (Two CDROM Set) by PM Medical Health News (2003); ISBN: 1592482163; http://www.amazon.com/exec/obidos/ASIN/1592482163/icongroupinterna

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21st Century Collection Centers for Disease Control (CDC) Emerging Infectious Diseases (EID) - Comprehensive Collection from 1995 to 2002 with Accurate and Detailed Information on Dozens of Serious Virus and Bacteria Illnesses - Hantavirus, Influenza, AIDS, Malaria, TB, Pox, Bioterrorism, Smallpox, Anthrax, Vaccines, Lyme Disease, Rabies, West Nile Virus, Hemorrhagic Fevers, Ebola, Encephalitis (Core Federal Information Series) by U.S. Government; ISBN: 1592480675; http://www.amazon.com/exec/obidos/ASIN/1592480675/icongroupinterna

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21st Century Collection Centers for Disease Control (CDC) Emerging Infectious Diseases (EID) ¿ Guide to SARS (Severe Acute Respiratory Syndrome) and Atypical Pneumonia, Influenza (Flu), Antiviral Drugs, Respiratory and Lung Diseases,

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Infection Control, Coronavirus ¿ Authoritative Information from the CDC, FDA, WHO, and NIH for Health Care Providers, Physicians, and Patients (Two CD-ROM Set) by PM Medical Health News; ISBN: 1592482317; http://www.amazon.com/exec/obidos/ASIN/1592482317/icongroupinterna •

America's Forgotten Pandemic : The Influenza of 1918 by Alfred W. Crosby (Author) (2003); ISBN: 0521541751; http://www.amazon.com/exec/obidos/ASIN/0521541751/icongroupinterna

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Basic and Applied Influenza Research by Beare; ISBN: 0849362504; http://www.amazon.com/exec/obidos/ASIN/0849362504/icongroupinterna

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Black October : the impact of the Spanish Influenza Epidemic of 1918 on South Africa by H. Phillips; ISBN: 0797015809; http://www.amazon.com/exec/obidos/ASIN/0797015809/icongroupinterna

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Chemotherapy and control of influenza; ISBN: 0125317506; http://www.amazon.com/exec/obidos/ASIN/0125317506/icongroupinterna

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Contemporary Diagnosis, Prevention, and Management of Influenza by Arnold S. Monto; ISBN: 1931981086; http://www.amazon.com/exec/obidos/ASIN/1931981086/icongroupinterna

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Devil's Flu: The World's Deadliest Influenza Epidemic and the Scientific Hunt for the Virus That Caused It by Pete Davies (2000); ISBN: 0805066225; http://www.amazon.com/exec/obidos/ASIN/0805066225/icongroupinterna

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Epidemics: Deadly Diseases Throughout History: The Plague, AIDS, Tuberculosis, Cholera, Small Pox, Polio, Influenza, Malaria (Epidemics: Deadly Diseases Throughout History Series) by Holly Cefrey, et al; ISBN: 0823992020; http://www.amazon.com/exec/obidos/ASIN/0823992020/icongroupinterna

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Flu : The Story Of The Great Influenza Pandemic by Gina Kolata (Author); ISBN: 0743203984; http://www.amazon.com/exec/obidos/ASIN/0743203984/icongroupinterna

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Genetic Variation Among Influenza Viruses by Debi Nayak; ISBN: 0125150806; http://www.amazon.com/exec/obidos/ASIN/0125150806/icongroupinterna

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Genetics of Influenza Viruses by P. Palese (Editor), David W. Kingsbury; ISBN: 0387817433; http://www.amazon.com/exec/obidos/ASIN/0387817433/icongroupinterna

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Highly pathogenic avian influenza : a threat to U.S. poultry (SuDoc A 1.68:1704) by U.S. Dept of Agriculture; ISBN: B000115DGY; http://www.amazon.com/exec/obidos/ASIN/B000115DGY/icongroupinterna

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History, Science and Politics: Influenza in America, 1918-1976 by June E. Osborn; ISBN: 0882021761; http://www.amazon.com/exec/obidos/ASIN/0882021761/icongroupinterna

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How to Win Friends & Influenza by Edward Kurtz (2002); ISBN: 1553698363; http://www.amazon.com/exec/obidos/ASIN/1553698363/icongroupinterna

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Inactivated Influenza Vaccines Prepared in Cell Culture (Developments in Biological Standardization, Vol 98) by F. Brown (Editor), et al (1999); ISBN: 3805568967; http://www.amazon.com/exec/obidos/ASIN/3805568967/icongroupinterna

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Influenza by J. Mulder (1973); ISBN: 9001603157; http://www.amazon.com/exec/obidos/ASIN/9001603157/icongroupinterna

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Influenza by C. W. Potter (Editor); ISBN: 0444506276; http://www.amazon.com/exec/obidos/ASIN/0444506276/icongroupinterna

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Influenza; ISBN: 0521260558; http://www.amazon.com/exec/obidos/ASIN/0521260558/icongroupinterna

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Influenza by Edwin D. Kilbourne; ISBN: 0306424568; http://www.amazon.com/exec/obidos/ASIN/0306424568/icongroupinterna

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Influenza by Donald Emmeluth, et al; ISBN: 079107305X; http://www.amazon.com/exec/obidos/ASIN/079107305X/icongroupinterna

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Influenza by Douglas Borland; ISBN: 0946717303; http://www.amazon.com/exec/obidos/ASIN/0946717303/icongroupinterna

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Influenza (Epidemics) by Fred Ramen (2001); ISBN: 0823933474; http://www.amazon.com/exec/obidos/ASIN/0823933474/icongroupinterna

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Influenza (Soviet Medical Reviews Series, Section E) by A.F. Frolov (Editor), et al; ISBN: 371864942X; http://www.amazon.com/exec/obidos/ASIN/371864942X/icongroupinterna

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Influenza : a Royal Society discussion, held on 21 and 22 February 1979; ISBN: 0854031383; http://www.amazon.com/exec/obidos/ASIN/0854031383/icongroupinterna

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Influenza : the viruses and the disease by Charles H. Stuart-Harris; ISBN: 071314274X; http://www.amazon.com/exec/obidos/ASIN/071314274X/icongroupinterna

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Influenza : virus, vaccines, and strategy : proceedings of a Working Group on Pandemic Influenza, Rougemont, 26-28 January 1976; ISBN: 0126359504; http://www.amazon.com/exec/obidos/ASIN/0126359504/icongroupinterna

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Influenza 1918: The Worst Epidemic in American History (The American Experience) by Lynette Iezzoni, David McCullough; ISBN: 1575001837; http://www.amazon.com/exec/obidos/ASIN/1575001837/icongroupinterna

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Influenza and Other Viruses by Judy Monroe (2001); ISBN: 0736810250; http://www.amazon.com/exec/obidos/ASIN/0736810250/icongroupinterna

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Influenza immunizations paid for by Medicare (SuDoc HE 22.21/4:) by U.S. Dept of Health and Human Services; ISBN: B00010TH08; http://www.amazon.com/exec/obidos/ASIN/B00010TH08/icongroupinterna

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Influenza in Practice (In Practice) by R. Jennings, R.C. Read; ISBN: 1853155144; http://www.amazon.com/exec/obidos/ASIN/1853155144/icongroupinterna

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Influenza Models by Philip Selby; ISBN: 0852004591; http://www.amazon.com/exec/obidos/ASIN/0852004591/icongroupinterna

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Influenza pandemic plan needed for federal and state response : report to congressional requesters (SuDoc GA 1.13:GAO-0104) by U.S. General Accounting Office; ISBN: B00011452C; http://www.amazon.com/exec/obidos/ASIN/B00011452C/icongroupinterna

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Influenza: The Last Great Plague: An Unfinished Story of Discovery by William Ian Beardmore Beveridge; ISBN: 0882021184; http://www.amazon.com/exec/obidos/ASIN/0882021184/icongroupinterna

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Influenza: The Last Great Plague; An Unfinished Story by W. I. B. Beveridge; ISBN: 0882021257; http://www.amazon.com/exec/obidos/ASIN/0882021257/icongroupinterna

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Informed Consent: Influenza Facts and Myths by Walter Dowdle, Jack LA Patra; ISBN: 0882297414; http://www.amazon.com/exec/obidos/ASIN/0882297414/icongroupinterna

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International Symposium on Influenza Immunization : proceedings of the 53rd symposium organized by the International Association of Biological Standardization and held at the WHO Auditorium, Geneva, Switzerland, 1-3 June 1977; ISBN: 3805527861; http://www.amazon.com/exec/obidos/ASIN/3805527861/icongroupinterna

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Managing Influenza in Primary Care by Nicholson; ISBN: 0632054948; http://www.amazon.com/exec/obidos/ASIN/0632054948/icongroupinterna

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Molecular Virology and Epidemiology of Influenza by Charles H. Stuart-Harris (Editor), C. W. Potter (Editor); ISBN: 0126747407; http://www.amazon.com/exec/obidos/ASIN/0126747407/icongroupinterna

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Options for the Control of Influenza (UCLA Symposia on Molecular and Cellular Biology New Series, Vol 36) by Alan P. Kendal, Peter A. Patriarca (Editor); ISBN: 0471851647; http://www.amazon.com/exec/obidos/ASIN/0471851647/icongroupinterna

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Options for the control of influenza : proceedings of a Viratek-UCLA Symposium, held in Keystone, Colorado, April 20-25, 1985; ISBN: 0845126350; http://www.amazon.com/exec/obidos/ASIN/0845126350/icongroupinterna

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Options for the Control of Influenza II: Proceedings of the International Conference on Options for the Control of Influenza, Courchevel, 27 Septemb by C. Hannoun, A.P. Kendal; ISBN: 0444815368; http://www.amazon.com/exec/obidos/ASIN/0444815368/icongroupinterna

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Options for the Control of Influenza III by International Conference on Options for the Control of Influenza 1996, et al; ISBN: 0444824618; http://www.amazon.com/exec/obidos/ASIN/0444824618/icongroupinterna

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Options for the Control of Influenza IV by Albert D. M. E. Osterhaus (Editor), et al; ISBN: 044450575X; http://www.amazon.com/exec/obidos/ASIN/044450575X/icongroupinterna

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Pandemic Influenza 1700-1900 by K. David Patterson; ISBN: 0847675122; http://www.amazon.com/exec/obidos/ASIN/0847675122/icongroupinterna

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Pointers to the Common Remedies: Colds, Influenza, Sore Throats, Coughs, Croup, Acute Chests, Asthma by M.L. Tyler (1981); ISBN: 0946717265; http://www.amazon.com/exec/obidos/ASIN/0946717265/icongroupinterna

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Queensland Aborigines and the Spanish influenza pandemic of 1918-1919 by Gordon Briscoe; ISBN: 0855752882; http://www.amazon.com/exec/obidos/ASIN/0855752882/icongroupinterna

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Recent Developments in Influenza Virus Research by Asst. Prof. Yukiharu Hayase; ISBN: 8177360728; http://www.amazon.com/exec/obidos/ASIN/8177360728/icongroupinterna

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SELF-HELP/COLDS AND INFLUENZA by George J Hall; ISBN: 0722502184; http://www.amazon.com/exec/obidos/ASIN/0722502184/icongroupinterna

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Spatial Aspects of Influenza Epidemics by A.D. Cliff, et al; ISBN: 0850861039; http://www.amazon.com/exec/obidos/ASIN/0850861039/icongroupinterna

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Structure and variation in influenza virus : proceedings of the International Workshop on Structure and Variation in Influenza Virus, Thredbo, Australia, December 10-12, 1979; ISBN: 0444004009; http://www.amazon.com/exec/obidos/ASIN/0444004009/icongroupinterna

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Textbook of Influenza by Karl G. Nicholson (Editor), et al; ISBN: 0632048034; http://www.amazon.com/exec/obidos/ASIN/0632048034/icongroupinterna

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The 1918-1919 Pandemic of Influenza: The Urban Experience in the Western World by Fred R. Van Hartesveldt (Editor) (1993); ISBN: 0773491953; http://www.amazon.com/exec/obidos/ASIN/0773491953/icongroupinterna

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The Common Cold and Influenza (Understanding Disease) by Nancy Stedman, Michael Reingold (Illustrator); ISBN: 0671600222; http://www.amazon.com/exec/obidos/ASIN/0671600222/icongroupinterna

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The Diffusion of Influenza by Gerald F. Pyle; ISBN: 0847674290; http://www.amazon.com/exec/obidos/ASIN/0847674290/icongroupinterna

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The Great Influenza: The Epic Story of the Deadliest Plague In History by John M. Barry (2004); ISBN: 0670894737; http://www.amazon.com/exec/obidos/ASIN/0670894737/icongroupinterna

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The Homeopathic Treatment of Influenza: Surviving Influenza Epidemics and Pandemics Past, Present and Future With Homeopathy by Sandra J., Ph.D. Perko (1999); ISBN: 0965318710; http://www.amazon.com/exec/obidos/ASIN/0965318710/icongroupinterna

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The Influenza Pandemic of 1918 by Virginia Aronson; ISBN: 079105263X; http://www.amazon.com/exec/obidos/ASIN/079105263X/icongroupinterna

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The Influenza Virus Hemagglutinin Symposium, Baden Near Vienna, March 21-23, 1977 by William Graeme Laver, et al; ISBN: 0387814590; http://www.amazon.com/exec/obidos/ASIN/0387814590/icongroupinterna

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The Influenza Viruses (The Viruses) by Robert M. Krug (Editor) (1989); ISBN: 0306431912; http://www.amazon.com/exec/obidos/ASIN/0306431912/icongroupinterna

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The Influenza viruses and influenza; ISBN: 0124070507; http://www.amazon.com/exec/obidos/ASIN/0124070507/icongroupinterna

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The Official Patient's Sourcebook on Influenza: A Revised and Updated Directory for the Internet Age by Icon Health Publications (2002); ISBN: 0597830568; http://www.amazon.com/exec/obidos/ASIN/0597830568/icongroupinterna

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The Origin of Pandemic Influenza Viruses by W. G. Laver (Editor); ISBN: 044400811X; http://www.amazon.com/exec/obidos/ASIN/044400811X/icongroupinterna

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The Plague of the Spanish Lady: The Influenza Panademic of 1918-1919 by Richard Collier; ISBN: 0749002468; http://www.amazon.com/exec/obidos/ASIN/0749002468/icongroupinterna

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The Plague of the Spanish Lady: The Influenza Pandemic of 1918-1919 by Richard, Collier; ISBN: 0689105924; http://www.amazon.com/exec/obidos/ASIN/0689105924/icongroupinterna

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The Transmission of Epidemic Influenza (The Language of Science) by R. Edgar Hope-Simpson (1992); ISBN: 0306440733; http://www.amazon.com/exec/obidos/ASIN/0306440733/icongroupinterna

The National Library of Medicine Book Index The National Library of Medicine at the National Institutes of Health has a massive database of books published on healthcare and biomedicine. Go to the following Internet site, http://locatorplus.gov/, and then select “Search LOCATORplus.” Once you are in the search area, simply type “influenza” (or synonyms) into the search box, and select “books only.” From there, results can be sorted by publication date, author, or relevance. The following was recently catalogued by the National Library of Medicine:11 •

"Spanish influenza," "three-day fever," "the flu". Author: United States. Public Health Service.; Year: 1964; Washington, Govt. print. off., 1918

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A review of the literature on influenza and the common cold, by J. G. Townsend. Author: Townsend, James G. (James Gayley),; Year: 1966; Washington, Govt. print. off., 1924

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A study of epidemic influenza: with special reference to the 1936-7 epidemic, by C. H. Stuart-Harris, C. H. Andrewes and Wilson Smith, with D. K. M. Chalmers, E. G. H. Cowen, and D. L. Hughes. Author: Stuart-Harris, Charles H. (Charles Herbert),; Year: 1968; London, H. M. Stationery off., 1938

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Experiments on the etiology of the influenza epidemic of 1928-1929, by I. S. Falk, R. W. Harrison, R. A. McKinney and G. W. Stuppy. Author: Falk, I. S. (Isidore Sydney),; Year: 1959; Baltimore, Md., 1931

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Influenza and other virus infections of the respiratory tract. Author: Stuart-Harris, Charles H. (Charles Herbert),; Year: 1965; London, Arnold [1965]

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Influenza, 1957. Author: Wyeth, Inc.; Year: 1950; [Philadelphia, 1957]

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Influenza; a review of current research. Contributors: C. H. Andrewes [and others]. Author: Andrewes, C. H. (Christopher Howard),; Year: 1966; Geneva, World Health Organization, 1954

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Influenza; a survey of the last 50 years in the light of modern work on the virus of epidemic influenza, by F. M. Burnet and Ellen Clark. Author: Burnet, F. M. (Frank Macfarlane),; Year: 1965; Melbourne, Macmillan [1942]

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Investigation and control of pneumonia, influenza, and the common cold. Hearings before a subcommittee of the Committee on Education and Labor, United States Senate, Seventy-sixth congress, third session, on S. 3914. A bill to impose additional duties upon the United States Public Health Service in connection with investigation and control of pneumonia, influenza, and the common cold. May 6 and 10, 1940. Author: United States. Congress. Senate. Committee on Education and Labor.; Year: 1942; Washington, U. S. Govt. Print. Off., 1940

11

In addition to LOCATORPlus, in collaboration with authors and publishers, the National Center for Biotechnology Information (NCBI) is currently adapting biomedical books for the Web. The books may be accessed in two ways: (1) by searching directly using any search term or phrase (in the same way as the bibliographic database PubMed), or (2) by following the links to PubMed abstracts. Each PubMed abstract has a "Books" button that displays a facsimile of the abstract in which some phrases are hypertext links. These phrases are also found in the books available at NCBI. Click on hyperlinked results in the list of books in which the phrase is found. Currently, the majority of the links are between the books and PubMed. In the future, more links will be created between the books and other types of information, such as gene and protein sequences and macromolecular structures. See http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Books.

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Live virus influenza vaccine discoveries. Hearing. Ninety-second Congress, second session, on discussions on any discoveries with respect to live virus influenza vaccine, August 17, 1972. Author: United States. Congress. House. Committee on Interstate and Foreign Commerce. Subcommittee on Public Health and Environment.; Year: 2003; Washington, U. S. Govt. Print. Off., 1972

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Observations on the late influenza: the febris catarrhalis epidemica of Hippocrates, as it appeared at London in 1775 & 1782 Author: Grant, William,; Year: 1970; London: Printed for the author, and sold by T. Cadell. Richardson and Urquhart. Sewel. and J. Johnson., [1782]

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Prevention of the neurotropic complications of polio, influenza and common cold. Author: Coole, Walter Alton,; Year: 1953; Houston? Texas [1945?]

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Proceedings. Symposium on Live Influenza Vaccine, 6 & 7 October 1971. Symposium on Bacterial Vaccines, 27 & 28 October 1971. Editor: Branimir Gusi´c. Author: Gusi´c, Branimir.; Year: 1958; Zagreb, Yugoslav Academy of Sciences and Arts, 1971

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Scenario analysis of the expected number of hospitalisations and deaths due to pandemic influenza in the Netherlands Author: Genugten, M. L. L. van.; Year: 1931; Bilthoven: RIVM, 2001

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Studies in the aetiology of epidemic influenza, by James McIntosh, M. D. Author: McIntosh, James,; Year: 1967; London, H. M. Stationery off. [printed by F. Hall, at the University press, Oxford] 1922

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Studies of influenza in hospitals of the British armies in France, 1918. Author: Great Britain. National Health Insurance Joint Committee. Medical Research Committee.; Year: 1966; [Oxford, Printed under the authority of H. M. Stationery off. at the University press, 1919]

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Studies on the antigenic composition of human influenza virus A strains, with the aid of the haemagglutination inhibition technique, by J. van der Veen and J. Mulder. Author: Veen, J. van der.; Year: 1966; Leiden, Kroese, 1950

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Studies on the influenza A-epidemic of January-March 1941 at Groningen, Holland, by J. A. R. van Bruggen [et al.]. Author: Bruggen, Jacobus Adriaan Rijkel van.; Year: 1967; Leiden, Stenfert Kroese, 1947

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The common cold and influenza and their relationship to other infections in man and animals. Author: McDonagh, J. E. R. (James Eustace Radclyffe),; Year: 1967; London, Heinemann, 1936

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The histopathology of the respiratory tract in human influenza. Author: Hers, J. F. Ph.; Year: 1940; Leiden, Stenfert Kroese, 1955

Chapters on Influenza In order to find chapters that specifically relate to influenza, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and influenza using the “Detailed Search” option. Go to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find book chapters, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Book Chapter.” Type “influenza” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on influenza:

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Infection and Diabetes Source: in Harris, M.I., et al., eds., for the National Diabetes Data Group (NDDG). Diabetes in America. 2nd ed. Bethesda, MD: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health. 1995. p. 485-499. Contact: Available from National Diabetes Information Clearinghouse (NDIC). 1 Information Way, Bethesda, MD 20892-3560. (800) 860-8747 or (301) 654-3327. Fax (301) 634-0716. E-mail: [email protected]. Also available at http://www.niddk.nih.gov/. PRICE: Full-text book and chapter available online at no charge; book may be purchased for $20.00. Order number: DM-96 (book). Summary: This chapter on infection and diabetes is from a compilation and assessment of data on diabetes and its complications in the United States. The authors characterize infections related to diabetes as 'probable' (the data support the presence of the association), 'possible' (presence or absence of an association cannot be established from current data) and 'doubtful' (data argue for no association). People with diabetes probably have a higher risk of the following infections: asymptomatic bacteriuria, lower extremity infections, reactivation tuberculosis in American Indians, infections in surgical wounds after sternotomy and total hip replacement, and group B streptococcal. Support for these associations comes from controlled observational studies in all cases, except for lower extremity infections, where the magnitude of the association between foot and ankle infection and diabetes from hospital-based data appears too great to be explained by detection, selection, or other potential biases. Local and systemic immunologic defects probably account for higher infection rates in patients with diabetes. Autonomic and sensory neuropathy probably account for higher bacteriuria and lower extremity infection rates, while systemic immunologic effects of diabetes may be responsible for the increased risk of surgical wound infection and tuberculosis reinfection. Populationbased data also support a probable higher influenza and pneumonia mortality rate in patients with diabetes. There is a possible association between diabetes and prevalence of the following infections: cystitis, pyelonephritis, candida vulvovaginitis and cystitis, pneumonia, influenza, chronic bronchitis, bacteremia, primary tuberculosis, reactivation tuberculosis in non-American Indians, mucormycosis, malignant otitis externa, and Fournier's gangrene. Doubtful associations exist between diabetes and prevalence of chronic sinusitis or S. aureus colonization (staph infection). 6 tables. 103 references. (AA-M).

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Infections Source: in Daugirdas, J.T. and Ing, T.S., eds. Handbook of Dialysis. 2nd ed. Boston, MA: Little, Brown and Company. 1994. p. 469-490. Contact: Available from Lippincott-Raven Publishers. 12107 Insurance Way, Hagerstown, MD 21740. (800) 777-2295. Fax (301) 824-7390. E-mail: [email protected]. Website: http://www.lrpub.com. PRICE: $37.95. ISBN: 0316173835. Summary: This chapter on infections is from a handbook that outlines all aspects of dialysis therapy, emphasizing the management of dialysis patients. Topics include the derangement of immune function in uremia, including etiology and the increased susceptibility to infection; the derangement of temperature control in uremia; the incidence and management of bacterial infections in hemodialysis and peritoneal dialysis patients; infections unrelated to the access site, including urinary tract infection, pneumonia, intraabdominal infections, tuberculosis, listeriosis, Salmonella septicemia, Yersinia septicemia, and mucormycosis; viral infections, including hepatitis A, hepatitis

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B, hepatitis C, cytomegalovirus and mononucleosis, influenza, AIDS, routine screening, and dialysis in patients who are HIV positive; vaccination in dialysis patients; and antimicrobial usage in dialysis patients. The authors present information in outline form, for easy reference. The chapter features a lengthy chart outlining the usual nonuremic dosage, dialysis patient dosage, post-hemodialysis supplements, and dosage for CAPD for each antimicrobial agent in common use. 3 tables. 21 references. •

Treatment of Chronic Hepatitis C: Transplant Recipients Source: in Gordon, S.C. Management of Chronic Viral Hepatitis. New York, NY: Marcel Dekker Inc. 2002. p. 263-293. Contact: Available from Marcel Dekker, Inc. 270 Madison Avenue, New York, NY 10016. (212) 696-9000. Fax (212) 685-4540. Website: www.dekker.com. PRICE: $150.00 plus shipping and handling. ISBN: 0824705823. Summary: This chapter on the treatment of chronic hepatitis C in transplant recipients is from a monograph on the management of chronic viral hepatitis (liver inflammation), bringing the advances of clinical and basic research into the doctor's office. This chapter uses a clinical case presentation in order to address the real life intricacies of managing patients who present with viral hepatitis. The case patient was a 45 year old female who presented with chronic hepatitis C with cirrhosis (liver scarring). She was referred for liver transplantation 1 year after diagnosis, due to deterioration of her condition. Although her hepatitis recurred after transplant and contributed to three serious episodes of rejection, the patient is now clinically stable. Recurrent hepatitis occurs in 40 to 80 percent of patients; it is usually found during the first year posttransplant. Recurrence of HCV infection leads to cirrhosis in 10 percent of patients 5 years after transplant. The clinical presentation of HCV recurrence and acute graft infection after transplantation varies from asymptomatic or minimal liver damage to an influenza like syndrome with or without jaundice. Risk factors involved in a more severe recurrence are still being studied. Immunosuppressive medications result in increased viral proliferation and a worse outcome of hepatitis C recurrence. Histological features are important, but can be confusing in differentiating HCV recurrence from other post transplantation complications such as acute rejection. Combination therapy with inferon and ribavirin may lead to an improved liver histology in patients with severe recurrence, but few patients have a sustained viral response and further advances in the management of this group of patients are required. 1 figure. 4 tables. 107 references.

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Streptococcal Toxic Shock Syndrome Associated With Necrotizing Fasciitis Source: in Coggins, C.H.; Hancock, E.W.; Levitt, L.J., eds. Annual Review of Medicine, Volume 51, 2000. Palo Alto, CA: Annual Reviews, Inc. 2000. p. 271-288. Contact: Available from Annual Reviews. 4139 El Camino Way, P.O. Box 10139, Palo Alto, CA 94303-0139. (650) 493-4400. E-mail: [email protected]. Website: www.AnnualReviews.org. Summary: This chapter provides health professionals with information on the demographics, symptoms, signs, diagnosis, clinical course, and treatment of streptococcal toxic shock syndrome (strep TSS) with associated necrotizing fasciitis. Strep TSS is the early onset of shock and organ failure associated with any infection caused by Streptococcus pyogenes. It is a rapidly progressive process that kills 30 to 60 percent of patients in 72 to 96 hours. The initial symptoms of strep TSS depend largely on the site of primary infection. Of all patients with strep TSS, 20 percent experience an influenza like syndrome characterized by fever, chills, myalgia, and diarrhea. In

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patients who develop deep soft tissue infections, such as necrotizing fasciitis or intrauterine infection, severe pain is the most common initial symptom of strep TSS. Violaceous bullae, hypotension, fever, and evidence of organ failure are late clinical manifestations. Diagnosis is not difficult when all the clinical features of strep TSS are manifest; however, the signs and symptoms may be quite subtle early in the course of illness, and laboratory tests may provide valuable clues to the diagnosis. The challenge to clinicians is to make an early diagnosis and to intervene with aggressive fluid replacement, emergent surgical debridement, and general supportive measures. Superantigens such as pyrogenic exotoxin A interact with monocytes and T lymphocytes in unique ways, resulting in T cell proliferation and watershed production of monokines and lymphokines. Penicillin, though efficacious in mild S. pyogenes infection, is less effective in severe infections because of its short postantibiotic effect, inoculum effect, and reduced activity against stationary phase organisms. Emerging treatments for strep TSS include clindamycin and intravenous gamma globulin. 2 tables and 81 references. (AA-M). •

Infection Source: Cambridge, MA: Harvard University Press. 1991. 13 p. Contact: Available from Harvard University Press. 79 Garden Street, Cambridge, MA 02138-9983. (617) 495-2577 or (617) 495-2480. PRICE: $24.95 plus shipping and handling. ISBN: 067464235X. Summary: This chapter, from a patient education book about organ transplantation, discusses the task of preventing infection in patients who have received donor organs. Topics include the role of good tissue typing and matching in prevention of infection; reducing the risks of infection; preoperative, perioperative and postoperative measures taken to reduce the risk of infection; a timetable used to divide the times when the recipient is susceptible; urinary tract infection; pneumonia; special viral infections including general infections like influenza and those infections for which the transplant recipient faces a higher-than-average risk; the herpes group of viruses, including cytomegalovirus, Epstein-Barr virus, herpes simplex virus, and varicella-zoster virus; hepatitis; and suggestions for reducing the risks of acquiring a contagious disease. The chapter presents detailed medical information about these topics in clear, easy-tounderstand language designed for the layperson.

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CHAPTER 8. MULTIMEDIA ON INFLUENZA Overview In this chapter, we show you how to keep current on multimedia sources of information on influenza. We start with sources that have been summarized by federal agencies, and then show you how to find bibliographic information catalogued by the National Library of Medicine.

Video Recordings An excellent source of multimedia information on influenza is the Combined Health Information Database. You will need to limit your search to “Videorecording” and “influenza” using the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find video productions, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Videorecording (videotape, videocassette, etc.).” Type “influenza” (or synonyms) into the “For these words:” box. The following is a typical result when searching for video recordings on influenza: •

AIDS and Other Epidemics Contact: Films for the Humanities and Sciences, PO Box 2053, Princeton, NJ, 08543, (800) 257-5126. Summary: This videorecording discusses AIDS and other epidemics including bubonic plague, black death, influenza, polio, small pox, malaria, and yellow fever. Recent epidemics include AIDS, lyme disease and the rising spread of tuberculosis (TB). The videorecording states that prevention needs to be emphasized and implemented when addressing these diseases.

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The Health Century, Episode One: The Fight Against Infectious Disease; From Yellow Fever to AIDS Contact: Maryland Public Television, Public Broadcasting System Video, 11767 Owings Mills Blvd, Owings Mills, MD, 21117, (301) 356-5600.

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Summary: This videorecording, part of a series broadcast on Maryland Public Television, examines the history of infectious diseases up through the current epidemic of Acquired immunodeficiency syndrome (AIDS). Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases (NIAID), and Cecil Fox, a senior scientist at the National Institutes of Health (NIH), appear in an opening segment that discusses AIDS and the work being done on developing a vaccine. NIH's work in funding research programs is discussed. After pointing out that AIDS research is also feeding results back into other fields, the videorecording turns to the history of NIH, which goes back to the cholera epidemic of 1878, when a one-man staff began work in a New York City laboratory. Moving on through history, the videorecording looks at epidemics of pellagra, influenza, and polio, examining the research that went into developing penicillin and the massive efforts that went into producing the polio vaccine. During the last 15 minutes of the program, Dr. Michael Clement of San Francisco General Hospital talks about azidothymidine (AZT) and treating persons with Human immunodeficiency virus (HIV) infection, and Dr. Robert Gallo, co-discoverer of HIV, talks about research methods.

Audio Recordings The Combined Health Information Database contains abstracts on audio productions. To search CHID, go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find audio productions, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Sound Recordings.” Type “influenza” (or synonyms) into the “For these words:” box. The following is a typical result when searching for sound recordings on influenza: •

Infectious Diseases and HIV Drug Abusers Contact: Audio Visual, Incorporated, 5542 Tuxedo Rd, Cheverly, MD, 20781, (301) 3225600. Summary: This sound recording of a National Institute on Drug Abuse Conference presents a panel discussion held January 15, 1991 of a variety of infectious diseases which affect people with Human immunodeficiency virus (HIV) infection or Acquired immunodeficiency syndrome (AIDS). The first speaker describes the diseases, besides HIV, which he found in a cohort of 800 Intravenous drug users (IVDU's) in the Bronx. Tuberculosis (TB), bacterial pneumonia, and pneumocystis carinii pneumonia (PCP) were among the most common ones found. The second speaker examines vaccines which HIV-positive people may take without ill effects. These include hepatitis, pneumococcal, and various influenza vaccines. Oral polio vaccine should never be given. The third speaker discusses results of examining the death certificates of drug addicts.

Bibliography: Multimedia on Influenza The National Library of Medicine is a rich source of information on healthcare-related multimedia productions including slides, computer software, and databases. To access the multimedia database, go to the following Web site: http://locatorplus.gov/. Select “Search LOCATORplus.” Once in the search area, simply type in influenza (or synonyms). Then, in the option box provided below the search box, select “Audiovisuals and Computer Files.”

Multimedia 267

From there, you can choose to sort results by publication date, author, or relevance. The following multimedia has been indexed on influenza: •

[Asian influenza vaccination] [motion picture] Source: [produced by Communicable Disease Center, United States Public Health Service]; Year: 1957; Format: Asian influenza vaccination; [United States: The Center, 1957]

•

A colour atlas and text on avian influenza = Influenza aviaria: testo e atlante = Atlas sobre la influenza aviar Source: Ilaria Capua, Franco Mutinelli; Year: 2001; Bologna: Papi editore, 2001

•

A framework for an Australian influenza pandemic plan [electronic resource]: Source: from the Influenza Pandemic Planning Committee of the Communicable Diseases Network Australia and New Zealand; Year: 1999; Format: Electronic resource; Canberra: Commonwealth Dept. of Health and Aged Care, 1999

•

An evaluation of the free influenza vaccination programme [electronic resource] Source: Simon Baker; Year: 2001; Format: Electronic resource; Auckland: Ministry of Health, 2001

•

Body story. Infiltration by influenza B [videorecording] Source: a presentation of Films for the Humanities & Sciences; a Wall to Wall Television Ltd production for Discovery Channel, Channel Four, and ITEL; Year: 1999; Format: Videorecording; Princeton, N.J.: Films for the Humanities & Sciences, c1999

•

FluNet [electronic resource]: global influenza surveillance network. Year: 9999; Format: Electronic resource; Geneva: World Health Organization, Communicable Disease Surveillance and Response

•

Infections and influenza vaccine in the elderly [videorecording] Source: presented by Center for the Study of Aging in cooperation with the Health Communications Network and the Geriatric Education Center, University of Alabama at Birmingham; produced by the H; Year: 1992; Format: Videorecording; Charleston, S.C.: Medical University of South Carolina, c1992

•

Influenza: this year and next [videorecording] Source: University of Texas System Cancer Center M. D. Anderson Hospital and Tumor Institute; Year: 1976; Format: Videorecording; Houston: The Institute, 1976

•

Influenza [videorecording]: prevention, detection, and control Source: Centers for Disease Control and Prevention, Public Health Training Network; Year: 2001; Format: Videorecording; [Atlanta, Ga.]: Public Health Training Network, [2001]

•

Influenza [videorecording]. Year: 2002; Format: Videorecording; Princeton, NJ: Films for the Humanities & Sciences, 2002

•

Influenza 1918 [videorecording] Source: a Robert Kenner Films production for the American Experience; WGBH; Year: 1998; Format: Videorecording; [Boston, Mass.]: WGBH Educational Foundation, c1998

•

Influenza virus isolation [motion picture] Source: Communicable Disease Center, Laboratory Branch; produced by Public Health Service Audiovisual Facility; Year: 1965; Format: Motion picture; [Atlanta: The Center: for loan by National Medical Audiovisual Center; Washington: for sale by National Audiovisual Center, 1965]

•

Laboratory diagnosis of influenza [motion picture] Source: a Communicable Disease Center production; Year: 1951; Format: Motion picture; United States: U.S. Dept. of Health, Education, and Welfare, Public Health Service, [1951]

•

Pandemic influenza [electronic resource]: a planning guide for state and local officials Source: CDC, National Vaccine Program Office; principal authors of this guide include

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Peter A. Patriarca. [et al.]; Year: 2000; Format: Electronic resource; Atlanta, GA: National Vaccine Program Office, Centers for Disease Control, [2000] •

Polyvalency [videorecording]: from influenza to anthrax Source: Office of Research Services, Medical Arts and Photography Branch; Year: 2003; Format: Videorecording; [Bethesda, Md.: National Institutes of Health, 2003]

•

Prospects for control of influenza [videorecording] Source: William C. Marine; Year: 1971; Format: Videorecording; [Atlanta: Emory Univ., 1971?]

•

Treating influenza [videorecording]: an update on antiviral chemotherapy Source: with W. Lee Fanning; Year: 1985; Format: Videorecording; Secaucus, N.J.: Network for Continuing Medical Education, 1985

•

WHO manual on animal influenza diagnosis and surveillance [electronic resource] Source: WHO Global Influenza Programme; Year: 2002; Format: Electronic resource; Geneva: World Health Organization, Dept. of Communicable Disease Surveillance and Response, [2002]

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CHAPTER 9. PERIODICALS AND NEWS ON INFLUENZA Overview In this chapter, we suggest a number of news sources and present various periodicals that cover influenza.

News Services and Press Releases One of the simplest ways of tracking press releases on influenza is to search the news wires. In the following sample of sources, we will briefly describe how to access each service. These services only post recent news intended for public viewing. PR Newswire To access the PR Newswire archive, simply go to http://www.prnewswire.com/. Select your country. Type “influenza” (or synonyms) into the search box. You will automatically receive information on relevant news releases posted within the last 30 days. The search results are shown by order of relevance. Reuters Health The Reuters’ Medical News and Health eLine databases can be very useful in exploring news archives relating to influenza. While some of the listed articles are free to view, others are available for purchase for a nominal fee. To access this archive, go to http://www.reutershealth.com/en/index.html and search by “influenza” (or synonyms). The following was recently listed in this archive for influenza: •

Influenza resistance mutations to zanamivir rare, in animal study Source: Reuters Industry Breifing Date: November 14, 2003

•

Scientists develop novel influenza strategy Source: Reuters Industry Breifing Date: October 20, 2003

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•

Influenza, pneumococcal vaccination rates far from optimal Source: Reuters Medical News Date: October 16, 2003

•

Influenza, pneumococcal vaccination rates still influenced by race/ethnicity Source: Reuters Medical News Date: October 09, 2003

•

Influenza vaccine seems safe in patients with asthma or COPD Source: Reuters Industry Breifing Date: October 03, 2003

•

Anti-influenza therapy cost effective for older adults Source: Reuters Medical News Date: September 01, 2003

•

US health officials suspend tiered influenza vaccination schedule Source: Reuters Medical News Date: August 21, 2003

•

Oseltamivir use reduces influenza complications Source: Reuters Health eLine Date: July 29, 2003

•

Rapid influenza tests cost-effective in children with influenza-like illness Source: Reuters Industry Breifing Date: July 07, 2003

•

Study: Influenza may be next bioterror weapon Source: Reuters Health eLine Date: July 01, 2003

•

Immunostimulating patch may boost immune response to influenza vaccine Source: Reuters Medical News Date: May 21, 2003

•

Oculorespiratory symptoms infrequent with newest influenza vaccine Source: Reuters Medical News Date: April 25, 2003

•

Federal advisory committee updates influenza vaccination guidelines Source: Reuters Industry Breifing Date: April 24, 2003

•

Oculorespiratory syndrome associated with influenza vaccine Source: Reuters Medical News Date: April 14, 2003

•

Liposomal influenza vaccine safe and immunogenic in young adults Source: Reuters Industry Breifing Date: April 07, 2003

•

Cold-adapted influenza virus could make vaccine production safer, faster Source: Reuters Industry Breifing Date: April 07, 2003

•

Influenza vaccination reduces cardiac events and stroke in elderly Source: Reuters Industry Breifing Date: April 02, 2003

Periodicals and News

•

271

Short-lived, generalized immunity needed to restrict influenza diversity Source: Reuters Medical News Date: March 26, 2003 The NIH

Within MEDLINEplus, the NIH has made an agreement with the New York Times Syndicate, the AP News Service, and Reuters to deliver news that can be browsed by the public. Search news releases at http://www.nlm.nih.gov/medlineplus/alphanews_a.html. MEDLINEplus allows you to browse across an alphabetical index. Or you can search by date at the following Web page: http://www.nlm.nih.gov/medlineplus/newsbydate.html. Often, news items are indexed by MEDLINEplus within its search engine. Business Wire Business Wire is similar to PR Newswire. To access this archive, simply go to http://www.businesswire.com/. You can scan the news by industry category or company name. Market Wire Market Wire is more focused on technology than the other wires. To browse the latest press releases by topic, such as alternative medicine, biotechnology, fitness, healthcare, legal, nutrition, and pharmaceuticals, access Market Wire’s Medical/Health channel at http://www.marketwire.com/mw/release_index?channel=MedicalHealth. Or simply go to Market Wire’s home page at http://www.marketwire.com/mw/home, type “influenza” (or synonyms) into the search box, and click on “Search News.” As this service is technology oriented, you may wish to use it when searching for press releases covering diagnostic procedures or tests. Search Engines Medical news is also available in the news sections of commercial Internet search engines. See the health news page at Yahoo (http://dir.yahoo.com/Health/News_and_Media/), or you can use this Web site’s general news search page at http://news.yahoo.com/. Type in “influenza” (or synonyms). If you know the name of a company that is relevant to influenza, you can go to any stock trading Web site (such as http://www.etrade.com/) and search for the company name there. News items across various news sources are reported on indicated hyperlinks. Google offers a similar service at http://news.google.com/. BBC Covering news from a more European perspective, the British Broadcasting Corporation (BBC) allows the public free access to their news archive located at http://www.bbc.co.uk/. Search by “influenza” (or synonyms).

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Newsletters on Influenza Find newsletters on influenza using the Combined Health Information Database (CHID). You will need to use the “Detailed Search” option. To access CHID, go to the following hyperlink: http://chid.nih.gov/detail/detail.html. Limit your search to “Newsletter” and “influenza.” Go to the bottom of the search page where “You may refine your search by.” Select the dates and language that you prefer. For the format option, select “Newsletter.” Type “influenza” (or synonyms) into the “For these words:” box. The following list was generated using the options described above: •

Drug-Induced Rheumatic Syndromes Source: Bulletin on the Rheumatic Diseases. 51(4): 1-4. 2002. Contact: Available from Arthritis Foundation. 1330 West Peachtree Street, Atlanta, GA 30309. (800) 268-6942 or (404) 872-7100. Fax (404) 872-9559. Website: www.arthritis.org. Summary: This newsletter provides health professionals with information on drug induced rheumatic syndromes. Categories of drug induced rheumatic diseases are drug induced lupus (DIL), drug induced myopathy/myositis (DIM), and drug induced vasculitis (DIV). Although more than 100 drugs have been implicated in DIL, the drugs most studied have been procainamide and hydralazine. However, these drugs are not commonly prescribed today, and the illness they produce is often different from those recently implicated in DIL. Minocycline is a treatment used for acne and rheumatoid arthritis that has caused immune and autoimmune phenomena. Several of the new recombinant biologics have been implicated in DIL, including interferon alpha, interferon gamma, and antitumor necrosis factor therapies. It is not possible to predict who will develop DIL, so patients with idiopathic lupus should be allowed to take potentially lupus inducing drugs but with careful monitoring. Drugs associated with the development of DIV include hematopoietic growth factors such as G-CSF and GM-CSF; vaccines for hepatitis B, influenza, and others; and leukotriene inhibitors. The article concludes that the number of drugs that are capable of inducing rheumatic syndromes is growing. Elements in the assessment of a possible association between exposure and the development of a rheumatic disorder include temporal association, lack of likely alternative explanations, rechallenge, and biological plausibility. 1 table and 23 references.

Newsletter Articles Use the Combined Health Information Database, and limit your search criteria to “newsletter articles.” Again, you will need to use the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. Go to the bottom of the search page where “You may refine your search by.” Select the dates and language that you prefer. For the format option, select “Newsletter Article.” Type “influenza” (or synonyms) into the “For these words:” box. You should check back periodically with this database as it is updated every three months. The following is a typical result when searching for newsletter articles on influenza: •

Growing Older: Health Issues for Minorities Source: Closing the Gap. p.1-2. May 2000.

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Contact: Department of Health and Human Services. Office of Public Health and Science. Office of Minority Health Resource Center, P.O. Box 37337, Washington, DC 20013-7337. Summary: This article reviews the health issues facing minorities who are age 65 and older. Cardiovascular disease, diabetes, and immunizations are of special concern to this population. Cardiovascular disease is the leading killer among men and women, across all racial and ethnic groups. Diabetes affects 6.3 million people age 65 and over, and occurs most often among older African Americans, Hispanic Americans, and American Indians. Influenza and pneumonia were the fifth leading cause of death for African Americans and Hispanics age 65 and older. The article discusses the health issues for older Asian Americans and Pacific Islanders, Native Americans and Alaska Natives, African Americans, and Hispanics and Latinos.

Academic Periodicals covering Influenza Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to influenza. In addition to these sources, you can search for articles covering influenza that have been published by any of the periodicals listed in previous chapters. To find the latest studies published, go to http://www.ncbi.nlm.nih.gov/pubmed, type the name of the periodical into the search box, and click “Go.” If you want complete details about the historical contents of a journal, you can also visit the following Web site: http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi. Here, type in the name of the journal or its abbreviation, and you will receive an index of published articles. At http://locatorplus.gov/, you can retrieve more indexing information on medical periodicals (e.g. the name of the publisher). Select the button “Search LOCATORplus.” Then type in the name of the journal and select the advanced search option “Journal Title Search.”

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CHAPTER 10. RESEARCHING MEDICATIONS Overview While a number of hard copy or CD-ROM resources are available for researching medications, a more flexible method is to use Internet-based databases. Broadly speaking, there are two sources of information on approved medications: public sources and private sources. We will emphasize free-to-use public sources.

U.S. Pharmacopeia Because of historical investments by various organizations and the emergence of the Internet, it has become rather simple to learn about the medications recommended for influenza. One such source is the United States Pharmacopeia. In 1820, eleven physicians met in Washington, D.C. to establish the first compendium of standard drugs for the United States. They called this compendium the U.S. Pharmacopeia (USP). Today, the USP is a nonprofit organization consisting of 800 volunteer scientists, eleven elected officials, and 400 representatives of state associations and colleges of medicine and pharmacy. The USP is located in Rockville, Maryland, and its home page is located at http://www.usp.org/. The USP currently provides standards for over 3,700 medications. The resulting USP DI® Advice for the Patient® can be accessed through the National Library of Medicine of the National Institutes of Health. The database is partially derived from lists of federally approved medications in the Food and Drug Administration’s (FDA) Drug Approvals database, located at http://www.fda.gov/cder/da/da.htm. While the FDA database is rather large and difficult to navigate, the Phamacopeia is both user-friendly and free to use. It covers more than 9,000 prescription and over-the-counter medications. To access this database, simply type the following hyperlink into your Web browser: http://www.nlm.nih.gov/medlineplus/druginformation.html. To view examples of a given medication (brand names, category, description, preparation, proper use, precautions, side effects, etc.), simply follow the hyperlinks indicated within the United States Pharmacopeia (USP). Below, we have compiled a list of medications associated with influenza. If you would like more information on a particular medication, the provided hyperlinks will direct you to ample documentation (e.g. typical dosage, side effects, drug-interaction risks, etc.). The

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following drugs have been mentioned in the Pharmacopeia and other sources as being potentially applicable to influenza: Amantadine •

Systemic - U.S. Brands: Symmetrel http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202024.html

Antihistamines, Decongestants, and Analgesics •

Systemic - U.S. Brands: Aclophen; Actifed Cold & Sinus; Actifed Cold & Sinus Caplets; Actifed Sinus Nighttime; Actifed Sinus Nighttime Caplets; Alka-Seltzer Plus Allergy Medicine Liqui-Gels; Alka-Seltzer Plus Cold Medicine; Alka-Seltzer Plus Cold Medicine Liqui-Gels; Allerest http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202062.html

Benzonatate •

Systemic - U.S. Brands: Tessalon http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202085.html

Dextromethorphan •

Systemic - U.S. Brands: Cough-X; Creo-Terpin; Trocal http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202187.html

Flucytosine •

Systemic - U.S. Brands: Ancobon http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202243.html

Fludarabine •

Systemic - U.S. Brands: Fludara http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202630.html

Fludrocortisone •

Systemic - U.S. Brands: Florinef http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202244.html

Fluoroquinolones •

Systemic - U.S. Brands: Avelox; Cipro; Cipro I.V.; Floxin; Floxin I.V.; Levaquin; Maxaquin; Noroxin; Penetrex; Tequin; Zagam http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202656.html

Fluorouracil •

Systemic - U.S. Brands: Adrucil http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202245.html

•

Topical - U.S. Brands: Efudex; Fluoroplex http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202246.html

Fluoxetine •

Systemic - U.S. Brands: Prozac; Sarafem http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202247.html

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Fluticasone •

Inhalation-Local - U.S. Brands: Flovent http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203649.html

•

Nasal - U.S. Brands: Flonase http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203588.html

Fluticasone and Salmeterol •

Nasal - U.S. Brands: http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203588.html

Fluvoxamine •

Systemic - U.S. Brands: Luvox http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202919.html

Headache Medicines, Ergot Derivative-Containing •

Systemic - U.S. Brands: Cafergot; Cafertine; Cafetrate; D.H.E. 45; Ercaf; ErgoCaff; Ergomar; Ergostat; Gotamine; Migergot; Wigraine http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202216.html

Influenza Virus Vaccine •

Systemic - U.S. Brands: FluShield; Fluvirin; Fluzone http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202297.html

Oseltamivir •

Systemic - U.S. Brands: Tamiflu http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/500062.html

Ribavirin •

Systemic - U.S. Brands: Virazole http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202509.html

Rifampin •

Systemic - U.S. Brands: Rifadin; Rimactane http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202511.html

Rimantadine •

Systemic - U.S. Brands: Flumadine http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202771.html

Zanamivir •

Inhalation--Systemic - U.S. Brands: Relenza http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/500004.html

Commercial Databases In addition to the medications listed in the USP above, a number of commercial sites are available by subscription to physicians and their institutions. Or, you may be able to access these sources from your local medical library.

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Mosby’s Drug Consult™ Mosby’s Drug Consult™ database (also available on CD-ROM and book format) covers 45,000 drug products including generics and international brands. It provides prescribing information, drug interactions, and patient information. Subscription information is available at the following hyperlink: http://www.mosbysdrugconsult.com/. PDRhealth The PDRhealth database is a free-to-use, drug information search engine that has been written for the public in layman’s terms. It contains FDA-approved drug information adapted from the Physicians’ Desk Reference (PDR) database. PDRhealth can be searched by brand name, generic name, or indication. It features multiple drug interactions reports. Search PDRhealth at http://www.pdrhealth.com/drug_info/index.html. Other Web Sites Drugs.com (www.drugs.com) reproduces the information in the Pharmacopeia as well as commercial information. You may also want to consider the Web site of the Medical Letter, Inc. (http://www.medletter.com/) which allows users to download articles on various drugs and therapeutics for a nominal fee. If you have any questions about a medical treatment, the FDA may have an office near you. Look for their number in the blue pages of the phone book. You can also contact the FDA through its toll-free number, 1-888-INFO-FDA (1-888-463-6332), or on the World Wide Web at www.fda.gov.

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APPENDICES

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APPENDIX A. PHYSICIAN RESOURCES Overview In this chapter, we focus on databases and Internet-based guidelines and information resources created or written for a professional audience.

NIH Guidelines Commonly referred to as “clinical” or “professional” guidelines, the National Institutes of Health publish physician guidelines for the most common diseases. Publications are available at the following by relevant Institute12: •

Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm

•

National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/news/facts/

•

National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html

•

National Cancer Institute (NCI); guidelines available at http://www.cancer.gov/cancerinfo/list.aspx?viewid=5f35036e-5497-4d86-8c2c714a9f7c8d25

•

National Eye Institute (NEI); guidelines available at http://www.nei.nih.gov/order/index.htm

•

National Heart, Lung, and Blood Institute (NHLBI); guidelines available at http://www.nhlbi.nih.gov/guidelines/index.htm

•

National Human Genome Research Institute (NHGRI); research available at http://www.genome.gov/page.cfm?pageID=10000375

•

National Institute on Aging (NIA); guidelines available at http://www.nia.nih.gov/health/

12

These publications are typically written by one or more of the various NIH Institutes.

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•

National Institute on Alcohol Abuse and Alcoholism (NIAAA); guidelines available at http://www.niaaa.nih.gov/publications/publications.htm

•

National Institute of Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/

•

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm

•

National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm

•

National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/

•

National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/

•

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm

•

National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html

•

National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm

•

National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/practitioners/index.cfm

•

National Institute of Neurological Disorders and Stroke (NINDS); neurological disorder information pages available at http://www.ninds.nih.gov/health_and_medical/disorder_index.htm

•

National Institute of Nursing Research (NINR); publications on selected illnesses at http://www.nih.gov/ninr/news-info/publications.html

•

National Institute of Biomedical Imaging and Bioengineering; general information at http://grants.nih.gov/grants/becon/becon_info.htm

•

Center for Information Technology (CIT); referrals to other agencies based on keyword searches available at http://kb.nih.gov/www_query_main.asp

•

National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/

•

National Center for Research Resources (NCRR); various information directories available at http://www.ncrr.nih.gov/publications.asp

•

Office of Rare Diseases; various fact sheets available at http://rarediseases.info.nih.gov/html/resources/rep_pubs.html

•

Centers for Disease Control and Prevention; various fact sheets on infectious diseases available at http://www.cdc.gov/publications.htm

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NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.13 Physician-oriented resources provide a wide variety of information related to the biomedical and health sciences, both past and present. The format of these resources varies. Searchable databases, bibliographic citations, full-text articles (when available), archival collections, and images are all available. The following are referenced by the National Library of Medicine:14 •

Bioethics: Access to published literature on the ethical, legal, and public policy issues surrounding healthcare and biomedical research. This information is provided in conjunction with the Kennedy Institute of Ethics located at Georgetown University, Washington, D.C.: http://www.nlm.nih.gov/databases/databases_bioethics.html

•

HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html

•

NLM Online Exhibitions: Describes “Exhibitions in the History of Medicine”: http://www.nlm.nih.gov/exhibition/exhibition.html. Additional resources for historical scholarship in medicine: http://www.nlm.nih.gov/hmd/hmd.html

•

Biotechnology Information: Access to public databases. The National Center for Biotechnology Information conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information for the better understanding of molecular processes affecting human health and disease: http://www.ncbi.nlm.nih.gov/

•

Population Information: The National Library of Medicine provides access to worldwide coverage of population, family planning, and related health issues, including family planning technology and programs, fertility, and population law and policy: http://www.nlm.nih.gov/databases/databases_population.html

•

Cancer Information: Access to cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html

•

Profiles in Science: Offering the archival collections of prominent twentieth-century biomedical scientists to the public through modern digital technology: http://www.profiles.nlm.nih.gov/

•

Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html

•

Clinical Alerts: Reports the release of findings from the NIH-funded clinical trials where such release could significantly affect morbidity and mortality: http://www.nlm.nih.gov/databases/alerts/clinical_alerts.html

•

Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html

•

MEDLINE: Bibliographic database covering the fields of medicine, nursing, dentistry, veterinary medicine, the healthcare system, and the pre-clinical sciences: http://www.nlm.nih.gov/databases/databases_medline.html

13

Remember, for the general public, the National Library of Medicine recommends the databases referenced in MEDLINEplus (http://medlineplus.gov/ or http://www.nlm.nih.gov/medlineplus/databases.html). 14 See http://www.nlm.nih.gov/databases/databases.html.

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•

Toxicology and Environmental Health Information (TOXNET): Databases covering toxicology and environmental health: http://sis.nlm.nih.gov/Tox/ToxMain.html

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Visible Human Interface: Anatomically detailed, three-dimensional representations of normal male and female human bodies: http://www.nlm.nih.gov/research/visible/visible_human.html The Combined Health Information Database

A comprehensive source of information on clinical guidelines written for professionals is the Combined Health Information Database. You will need to limit your search to one of the following: Brochure/Pamphlet, Fact Sheet, or Information Package, and “influenza” using the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find associations, use the drop boxes at the bottom of the search page where “You may refine your search by.” For the publication date, select “All Years.” Select your preferred language and the format option “Fact Sheet.” Type “influenza” (or synonyms) into the “For these words:” box. The following is a sample result: •

Prevention and Control of Influenza: Part I, Vaccines; Recommendations of the Advisory Committee on Immunization Practices (ACIP) Contact: US Government Printing Office, PO Box 371954, Pittsburgh, PA, 15250-7954, (202) 512-1800, http://www.access.gpo.gov. Massachusetts Medical Society, Medical Publishing Group, CSPO Box 9121, Waltham, MA, 02254, (800) 843-6356. Summary: This report looks at recommendations of the Immunization Practices Advisory Committee (ACIP) on preventing and controlling the spread of influenza. After providing background information on the illness, it looks at options for controlling its spread, including vaccination. The section on persons with Human immunodeficiency virus (HIV) infection says that symptoms may be prolonged and complications may increase. Therefore, vaccination is a prudent precaution. However, it does point out that antibody response to the vaccine may be low in persons with advanced HIV illness.

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Update: Influenza Activity - United States, 1995-96 Season Source: Morbidity and Mortality Weekly Report, Vol. 45, No. 6, February 16, 1996. Contact: US Government Printing Office, PO Box 371954, Pittsburgh, PA, 15250-7954, (202) 512-1800, http://www.access.gpo.gov. Summary: This report provides details on an increase in influenza activity in the United States from late October through mid- to late December 1995. Although activity began to decline during January 1996, for the week ending February 3, a total of 19 states reported continuing regional or widespread activity. Influenza type A(H1N1) predominated in all regions except the Mountain, Pacific, and New England regions, where type A(H3N2) predominated. Influenza type B accounted for only 1 percent of all isolates nationwide.

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The NLM Gateway15 The NLM (National Library of Medicine) Gateway is a Web-based system that lets users search simultaneously in multiple retrieval systems at the U.S. National Library of Medicine (NLM). It allows users of NLM services to initiate searches from one Web interface, providing one-stop searching for many of NLM’s information resources or databases.16 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “influenza” (or synonyms) into the search box and click “Search.” The results will be presented in a tabular form, indicating the number of references in each database category. Results Summary Category Journal Articles Books / Periodicals / Audio Visual Consumer Health Meeting Abstracts Other Collections Total

Items Found 34529 810 344 350 16 36049

HSTAT17 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.18 These documents include clinical practice guidelines, quickreference guides for clinicians, consumer health brochures, evidence reports and technology assessments from the Agency for Healthcare Research and Quality (AHRQ), as well as AHRQ’s Put Prevention Into Practice.19 Simply search by “influenza” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

Coffee Break: Tutorials for Biologists20 Coffee Break is a general healthcare site that takes a scientific view of the news and covers recent breakthroughs in biology that may one day assist physicians in developing treatments. Here you will find a collection of short reports on recent biological discoveries. Each report incorporates interactive tutorials that demonstrate how bioinformatics tools are used as a part of the research process. Currently, all Coffee Breaks are written by NCBI 15

Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.

16

The NLM Gateway is currently being developed by the Lister Hill National Center for Biomedical Communications (LHNCBC) at the National Library of Medicine (NLM) of the National Institutes of Health (NIH). 17 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 18 19

The HSTAT URL is http://hstat.nlm.nih.gov/.

Other important documents in HSTAT include: the National Institutes of Health (NIH) Consensus Conference Reports and Technology Assessment Reports; the HIV/AIDS Treatment Information Service (ATIS) resource documents; the Substance Abuse and Mental Health Services Administration's Center for Substance Abuse Treatment (SAMHSA/CSAT) Treatment Improvement Protocols (TIP) and Center for Substance Abuse Prevention (SAMHSA/CSAP) Prevention Enhancement Protocols System (PEPS); the Public Health Service (PHS) Preventive Services Task Force's Guide to Clinical Preventive Services; the independent, nonfederal Task Force on Community Services’ Guide to Community Preventive Services; and the Health Technology Advisory Committee (HTAC) of the Minnesota Health Care Commission (MHCC) health technology evaluations. 20 Adapted from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html.

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staff.21 Each report is about 400 words and is usually based on a discovery reported in one or more articles from recently published, peer-reviewed literature.22 This site has new articles every few weeks, so it can be considered an online magazine of sorts. It is intended for general background information. You can access the Coffee Break Web site at the following hyperlink: http://www.ncbi.nlm.nih.gov/Coffeebreak/.

Other Commercial Databases In addition to resources maintained by official agencies, other databases exist that are commercial ventures addressing medical professionals. Here are some examples that may interest you: •

CliniWeb International: Index and table of contents to selected clinical information on the Internet; see http://www.ohsu.edu/cliniweb/.

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Medical World Search: Searches full text from thousands of selected medical sites on the Internet; see http://www.mwsearch.com/.

21 The figure that accompanies each article is frequently supplied by an expert external to NCBI, in which case the source of the figure is cited. The result is an interactive tutorial that tells a biological story. 22 After a brief introduction that sets the work described into a broader context, the report focuses on how a molecular understanding can provide explanations of observed biology and lead to therapies for diseases. Each vignette is accompanied by a figure and hypertext links that lead to a series of pages that interactively show how NCBI tools and resources are used in the research process.

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APPENDIX B. PATIENT RESOURCES Overview Official agencies, as well as federally funded institutions supported by national grants, frequently publish a variety of guidelines written with the patient in mind. These are typically called “Fact Sheets” or “Guidelines.” They can take the form of a brochure, information kit, pamphlet, or flyer. Often they are only a few pages in length. Since new guidelines on influenza can appear at any moment and be published by a number of sources, the best approach to finding guidelines is to systematically scan the Internet-based services that post them.

Patient Guideline Sources The remainder of this chapter directs you to sources which either publish or can help you find additional guidelines on topics related to influenza. Due to space limitations, these sources are listed in a concise manner. Do not hesitate to consult the following sources by either using the Internet hyperlink provided, or, in cases where the contact information is provided, contacting the publisher or author directly. The National Institutes of Health The NIH gateway to patients is located at http://health.nih.gov/. From this site, you can search across various sources and institutes, a number of which are summarized below. Topic Pages: MEDLINEplus The National Library of Medicine has created a vast and patient-oriented healthcare information portal called MEDLINEplus. Within this Internet-based system are “health topic pages” which list links to available materials relevant to influenza. To access this system, log on to http://www.nlm.nih.gov/medlineplus/healthtopics.html. From there you can either search using the alphabetical index or browse by broad topic areas. Recently, MEDLINEplus listed the following when searched for “influenza”:

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Guides on influenza Influenza http://www.nlm.nih.gov/medlineplus/influenza.html

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Other guides Childhood Immunization http://www.nlm.nih.gov/medlineplus/childhoodimmunization.html Common Cold http://www.nlm.nih.gov/medlineplus/commoncold.html Meningitis http://www.nlm.nih.gov/medlineplus/meningitis.html

Within the health topic page dedicated to influenza, the following was listed: •

General/Overviews Beat the Winter Bugs: How to Hold Your Own Against Colds and Flu Source: Food and Drug Administration http://www.fda.gov/fdac/features/2001/601_flu.html Flu Season 2003-04: Flu Facts for Everyone Source: National Immunization Program http://www.cdc.gov/nip/Flu/Public.htm What is Influenza (Flu)? Source: American Lung Association http://www.lungusa.org/diseases/c&f02/influenza.html

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Diagnosis/Symptoms Is it a Cold or the Flu? http://www.niaid.nih.gov/publications/cold/sick.pdf

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Treatment Antiviral Drug Information Source: National Center for Infectious Diseases http://www.cdc.gov/ncidod/diseases/flu/fluviral.htm Flu Drugs Source: National Institute of Allergy and Infectious Diseases http://www.niaid.nih.gov/factsheets/fludrugs.htm

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Specific Conditions/Aspects Cold and Flu: What to Do If You've Got Asthma Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=AA00011

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Hashimoto's Disease and the Flu Shot Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=AN00676 Influenza (Flu): Health Information for International Travel: 2003 - 2004 Source: Centers for Disease Control and Prevention http://www.cdc.gov/travel/diseases/influenza.htm Influenza (the Flu) Questions & Answers Source: National Center for Infectious Diseases http://www.cdc.gov/ncidod/diseases/flu/facts.htm Mercury in Flu Shots? Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=AN00680 •

Children Influenza (Flu) Source: Nemours Foundation http://kidshealth.org/parent/infections/bacterial_viral/flu.html Tips for Treating the Flu Source: Nemours Foundation http://kidshealth.org/parent/infections/common/tips_take_care.html What the Flu Does to You Source: Nemours Foundation http://kidshealth.org/kid/ill_injure/sick/flu.html

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From the National Institutes of Health Flu Source: National Institute of Allergy and Infectious Diseases http://www.niaid.nih.gov/factsheets/flu.htm

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Latest News Advisory Committee on Immunization Practices Vote to Recommend Influenza Vaccination for Children Aged 6 to 23 Months Source: 10/16/2003, Centers for Disease Control and Prevention http://www.cdc.gov/od/oc/media/pressrel/r031016.htm Cuba Produces Key Synthetic Vaccine for Children Source: 11/24/2003, Reuters Health http://www.nlm.nih.gov//www.nlm.nih.gov/medlineplus/news/fullstory_14818 .html Early Evidence Suggests Current Flu Season Could Be Severe Source: 11/17/2003, Centers for Disease Control and Prevention http://www.cdc.gov/od/oc/media/pressrel/r031117.htm

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FDA and CDC Statement Concerning Rumors about Recalled Lot of Influenza Vaccine Source: 10/17/2003, Centers for Disease Control and Prevention, Food and Drug Administration http://www.cdc.gov/od/oc/media/pressrel/r031017a.htm Flu Season Early, CDC Urges Flu Shot Source: 11/18/2003, United Press International http://www.nlm.nih.gov//www.nlm.nih.gov/medlineplus/news/fullstory_14718 .html Putting a Chill on Important Pills: Antibiotics Can't Cure Colds And Flus - And Overuse Puts All of US at Risk Source: 11/10/2003, New York Times Syndicate http://www.nlm.nih.gov//www.nlm.nih.gov/medlineplus/news/fullstory_14587 .html •

Organizations American Lung Association http://www.lungusa.org/ National Center for Infectious Diseases http://www.cdc.gov/ncidod/index.htm National Institute of Allergy and Infectious Diseases http://www.niaid.nih.gov/

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Pictures/Diagrams Influenza Source: Immunization Action Coalition http://www.immunize.org/images/ca.d/ipcd1861/img0024.htm

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Prevention/Screening First Nasal Mist Flu Vaccine Approved Source: Food and Drug Administration http://www.fda.gov/bbs/topics/NEWS/2003/NEW00913.html Flu Shot Locator Source: American Lung Association http://www.findaflushot.com/lungusa/ Influenza Vaccine (Flu Shot): Questions & Answers 2003-2004 Source: National Center for Infectious Diseases http://www.cdc.gov/ncidod/diseases/flu/vacfacts.htm Influenza Virus Vaccine Source: Food and Drug Administration http://www.fda.gov/cber/flu/flu.htm Nasal Flu Vaccine Approved Source: Food and Drug Administration http://www.fda.gov/fdac/features/2003/503_flu.html

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Questions and Answers on FluMist (Influenza Virus Vaccine Live, Intranasal) Source: Food and Drug Administration http://www.fda.gov/cber/flu/flumistqa.htm What to Do for Colds and Flu http://www.fda.gov/opacom/lowlit/clds&flu.html Who Should Get a Flu Shot (Influenza Vaccine) Source: National Center for Infectious Diseases http://www.cdc.gov/ncidod/diseases/flu/who.htm •

Research Focus on the Flu: Working Toward a Nasal Spray Flu Vaccine Source: National Institute of Allergy and Infectious Diseases http://www.niaid.nih.gov/newsroom/focuson/flu00/flumist.htm Influenza Vaccination or Antiviral Treatment for Healthy Working Adults: An Economic Analysis Source: American College of Physicians http://www.annals.org/cgi/content/full/137/4/I-22

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Statistics CDC Finds Annual Flu Deaths Higher Than Previously Estimated Source: Centers for Disease Control and Prevention http://www.cdc.gov/od/oc/media/pressrel/r030107.htm Flu and Cold: Statistics [January 2002] Source: American Lung Association http://lungusa.org/press/lung_dis/asn_c&f_1802b.html Percent of Adults Aged 18 Years and Over Who Received Influenza Vaccine During the Past 12 Months, by Age Group and Quarter: United States, 1997 - 2002 Source: National Center for Health Statistics http://www.cdc.gov/nchs/about/major/nhis/released200212/figures04_14_3.htm

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Teenagers Flu Facts Source: Nemours Foundation http://kidshealth.org/teen/infections/bacterial_viral/flu.html

You may also choose to use the search utility provided by MEDLINEplus at the following Web address: http://www.nlm.nih.gov/medlineplus/. Simply type a keyword into the search box and click “Search.” This utility is similar to the NIH search utility, with the exception that it only includes materials that are linked within the MEDLINEplus system (mostly patient-oriented information). It also has the disadvantage of generating unstructured results. We recommend, therefore, that you use this method only if you have a very targeted search.

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The Combined Health Information Database (CHID) CHID Online is a reference tool that maintains a database directory of thousands of journal articles and patient education guidelines on influenza. CHID offers summaries that describe the guidelines available, including contact information and pricing. CHID’s general Web site is http://chid.nih.gov/. To search this database, go to http://chid.nih.gov/detail/detail.html. In particular, you can use the advanced search options to look up pamphlets, reports, brochures, and information kits. The following was recently posted in this archive: •

Reye's Syndrome Source: Cedar Grove, NJ: American Liver Foundation. 1997. 2 p. Contact: Available from American Liver Foundation. Information and Distribution Center, 1425 Pompton Avenue, Suite 3, Cedar Grove, NJ 07009-1000. (800) GO-LIVER, ext. 234 or (888) HEP-ABC. Fax (973) 256-3214. E-mail: [email protected]. Website: www.liverfoundation.org. PRICE: $0.50 for single copy; bulk orders available; plus shipping and handling. Summary: A recently recognized childhood disease, Reye's syndrome is a rare complication of common respiratory infections, including chickenpox. This fact sheet from the American Liver Foundation (ALF) offers a brief overview of Reye's syndrome. Reye's syndrome should be suspected when vomiting begins 3 to 7 days after the onset of flu or chickenpox. Usually the vomiting becomes increasingly severe over a period of 8 to 12 hours. If the vomiting is associated with signs of disordered brain function, such as staring spells, stupor, delirium, or strange behavior, a medical examination. The fact sheet notes that Reye's syndrome can occur at any time, but it is most frequent during winter months, in association with influenza and similar respiratory infections. Diagnosis of Reye's syndrome is accomplished through the patient's recent history of flu like illness, persistent vomiting, elevation of certain liver enzymes (serum SGPT) with a normal bilirubin, and exclusion of meningitis and encephalitis. Almost all cases of Reye's syndrome have increased serum concentrations of certain liver enzymes, notably serum glutamic pyruvic transaminase (SGPT). The fact sheet notes that aspirin may contribute to the problem of Reye's syndrome; until conclusive evidence is obtained, doctors advise against the use of aspirin in chickenpox and during outbreaks of flu like illness. The fact sheet concludes with a list of medications that contain salicylates, including cold medications. Acetaminophen is the preferred antifever medicine during chickenpox and flu illnesses in children. The fact sheet offers the contact information for ALF (800-GO-LIVER, www.liverfoundation.org ).

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Gilbert's Syndrome Source: Toronto, Ontario: Canadian Liver Foundation. 200x. 2 p. Contact: Available from Canadian Liver Foundation. Suite 1500, 2235 Sheppard Avenue East, Toronto Ontario, M2J 5B5. (416) 491-3353 or (800) 563-5483. Fax (416) 491-4952. Email: [email protected]. Website: [email protected]. PRICE: Full-text available online at no charge; Contact organization for print copies. Summary: Gilbert's syndrome is a fairly common, mild liver disorder. People with this disorder have a moderate, fluctuating increase in serum bilirubin, a yellow pigment excreted by the liver into bile. This fact sheet, from the Canadian Liver Foundation, reviews Gilbert's syndrome. Written in question-and-answer format, the fact sheet covers the symptoms and pathology of Gilbert's syndrome, diagnosis, and treatment. The author notes that often Gilbert's syndrome is diagnosed by chance when blood is

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examined for another reason. Serum bilirubin increases with fasting or an intercurrent illness such as influenza. Gilbert's syndrome rarely requires any treatment. People with the disorder lead normal, healthy lives. The fact sheet concludes with the contact information for the Canadian Liver Foundation (www.liver.ca or 800-563-5483). •

Summary of Recommendations for Adult Immunization Source: St. Paul, MN: Immunization Action Coalition. 1998. 2 p. Contact: Available from Hepatitis B Coalition. 1573 Selby Avenue, Suite 229, St. Paul, MN 55104-6328. (612) 647-9009. Fax (651) 647-9131. E-mail: [email protected]. Website: www.immunize.org. PRICE: Full-text available online at no charge; $1.00 for single copy. Item number: P2011. Summary: This chart summarizes recommendations for adult immunization. The chart notes the vaccine name and storage temperature, for whom it is recommended, the usual schedule, the schedule for those who have fallen behind, contraindications and precautions, rules of simultaneous administration, and route (intramuscular, subcutaneous). Recommendations are provided for influenza, pneumococcal, hepatitis B, hepatitis A, TD (tetanus, diphtheria), MMR (measles, mumps, rubella), varicella (chicken pox), and polio vaccines. The chart lists information adapted from the Advisory Committee on Immunization Practices (ACIP). The chart was developed to combine the recommendations of adult immunization onto one page. It was devised especially to assist health care workers in determining appropriate use and scheduling of vaccines. The chart can be posted in immunization clinics or clinicians' offices. (AA-M).

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Are You 11-19 Years Old? Then You Need to Be Vaccinated Against These Serious Diseases! Source: St. Paul, MN: Immunization Action Coalition. 1996. 1 p. Contact: Available from Hepatitis B Coalition. 1573 Selby Avenue, Suite 229, St. Paul, MN 55104. (612) 647-9009. Fax (612) 647-9131. PRICE: $1.00. Summary: This fact sheet reviews the immunizations needed for adolescents (ages 11 to 19 years). The fact sheet reminds readers that getting immunized is a lifelong, lifeprotecting job. The fact sheet lists the vaccines and the recommendations for each. Included are: hepatitis B, MMR (measles, mumps, rubella), Td (tetanus, diphtheria), varicella (chicken pox), hepatitis A, influenza vaccine (flu shot), and pneumococcal vaccine. The fact sheet also notes recommendations for people who travel outside the U.S. The fact sheet is illustrated with line drawings of young adults.

•

Vaccinations for Adults With Hepatitis C Virus Infection Contact: Immunization Action Coalition, 1573 Selby Ave Ste 234, St Paul, MN, 55104, (651) 647-9009, http://www.immunize.org. Summary: This fact sheet, written for individuals the hepatitis C virus (HCV), makes recommendations regarding vaccinations for persons with compromised immune systems. The fact sheet lists several diseases that can be prevented with periodic vaccinations. It provides a recommended schedule of shots for HCV-positive individuals, their caregivers, and roommates regarding the following diseases: pneumococcal, influenza, hepatitis A and B, tetanus/diptheria, measles, mumps, rubella, and varicella.

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Put prevention into practice: Education and action kit Source: Washington, DC: Public Health Service, U.S. Department of Health and Human Services. 1994. 2 health guides; 1 clinician's handbook, 3 flow charts, 16 chart stickers, 2 posters. Contact: Available from Superintendent of Documents, U.S. Government Printing Office, P.O. Box 371954, Pittsburgh, PA 15250-7954. Telephone: (202) 512-1991 for public information (D.C. office) or (202) 512-1800 for ordering and publication information (D.C. office) / fax: (202) 512-1293 (public information); (202) 512-2250 (ordering) / Web site: http://www.access.gpo.gov. $57.00. Summary: This kit, produced through the 'Put Prevention into Practice' initiative of the Public Health Service, contains materials to facilitate and enhance the practice of preventive medicine for both clinicians and the public. The 'Clinician's Handbook of Preventive Services' is the core element of the kit. After an overview of preventive care implementation, this manual provides guidelines for screening, immunization/prophylaxis, and counseling divided into two major sections, one for children and adolescents and one for adults and older adults. The screening section for children and adolescents focuses on anemia, blood pressure, body measurement, cholesterol, depression and suicide, hearing, lead, newborn screening, tuberculosis, urinalysis, and vision. The immunization/prophylaxis section covers DPT, Hepatitis B, MMR, Polio myelitis, and Haemophilus influenzae Type b inoculations. The counseling section focuses on alcohol and drug use, dental and oral health, nutrition, physical activity, safety, STDs and HIV infection, tobacco use, unintended pregnancy, and firearms and violent behavior. Screening guidelines for adults cover the same areas as previously mentioned along with cancer detection, cognitive and functional impairment, fecal occult blood, sigmoidoscopy, and thyroid function. The adult immunization/prophylaxis section contains guidelines on aspirin, hormone replacement therapy, hepatitis B, influenza, pneumococcus, rubella, and tetanus and diphtheria. Counseling guidelines for adults cover the same areas as mentioned above with the addition of polypharmacy. Appendices include risk factor summary tables, a bibliography of references, a varicella (chicken pox) vaccination statement, and a copyright disclaimer. Each section contains implementation tools such as questionnaires, charts, and protocols. The pocket-sized guides for children and adults measure 6 inches high and are designed for patients to take with them on visits to their physician. Each provides space for patients and physicians to enter health information such as blood pressure, weight, cholesterol levels, and immunizations. The guides also provide basic information on how often to monitor certain aspects of health such as breast exams, pap smears, and how often and what types of vaccines children should receive.

•

HIV - 1 - Infected People Benefit From Flu Vaccine Contact: Johns Hopkins Medical Institutions, Johns Hopkins Health System, Office of Public Affairs, 550 N Broadway, Baltimore, MD, 21205, (410) 955-6680. Summary: This news release, from the Johns Hopkins Medical Institutions, announces the efficacy of a single dose of influenza vaccine for asymptomatic persons with Human immunodeficiency virus (HIV) infection. It describes the studies determining antibody production in HIV-infected persons and control persons immunized with influenza vaccine performed by Dr. Kenrod Nelson and co-investigators at Johns Hopkins School of Public Health. Also, it discusses the mortality rate from pneumonia and influenza in

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young persons in cities with a high incidence of Acquired immunodeficiency syndrome (AIDS). •

Immunizations: Not Just Kids' Stuff Source: St. Paul, MN: Immunization Action Coalition. 1997. 1 p. Contact: Available from Hepatitis B Coalition. 1573 Selby Avenue, Suite 229, St. Paul, MN 55104. (612) 647-9009. Fax (612) 647-9131. PRICE: $1.00. Summary: This reproducible brochure reviews some communicable diseases and the immunizations available to prevent them. The brochure reminds adult readers that getting immunized is a lifelong, life-protecting job. The brochure briefly describes each disease and then notes the vaccines and the recommendations for each. Included are: hepatitis B, MMR (measles, mumps, rubella), polio, Td (tetanus, diphtheria), varicella (chicken pox), hepatitis A, influenza vaccine (flu shot), and pneumococcal vaccine. The last page of the brochure features a blank immunization record and encourages readers to keep tract of their own immunization history. The brochure is illustrated with humorous line drawings.

•

Infection Control for the Dental Health Team Contact: Medcom Incorporated, PO Box 6003, Cypress, CA, (800) 541-0253. Summary: This teaching aid, consisting of a videorecording and an accompanying study guide, teaches users about infection-control in the dental practice. It consists of a course introduction, five lessons which include material from the study guide and an accompanying video segment, and a post-test. The lessons address the prevention of various diseases -- including the common cold, influenza, hepatitis B, syphilis, gonorrhea, rubella, mononucleosis, mumps, Acquired immunodeficiency syndrome (AIDS), herpes simplex, tuberculosis, and tetanus -- during dental procedures. The lessons look at handwashing, personal hygiene, the use of personal protective barriers, preventing cross-contamination, and disinfection and sterilization. The National Guideline Clearinghouse™

The National Guideline Clearinghouse™ offers hundreds of evidence-based clinical practice guidelines published in the United States and other countries. You can search this site located at http://www.guideline.gov/ by using the keyword “influenza” (or synonyms). The following was recently posted: •

Immunization and the prevention of influenza and pneumococcal disease in people with diabetes Source: American Diabetes Association - Professional Association; 1999 October (republished 2003 Jan); 3 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3584&nbr=2810&a mp;string=influenza

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Prevention and control of influenza Source: Centers for Disease Control and Prevention - Federal Government Agency [U.S.]; 1984 April (revised 2003 Apr); 36 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3738&nbr=2964&a mp;string=influenza

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Reduction of the influenza burden in children Source: American Academy of Pediatrics - Medical Specialty Society; 2002 December; 7 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3527&nbr=2753&a mp;string=influenza

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Using live, attenuated influenza vaccine for prevention and control of influenza: supplemental recommendations of the Advisory Committee on Immunization Practices (ACIP) Source: Centers for Disease Control and Prevention - Federal Government Agency [U.S.]; 2003 September 26; 8 pages http://www.guideline.gov/summary/summary.aspx?doc_id=4154&nbr=3182&a mp;string=influenza Healthfinder™

Healthfinder™ is sponsored by the U.S. Department of Health and Human Services and offers links to hundreds of other sites that contain healthcare information. This Web site is located at http://www.healthfinder.gov. Again, keyword searches can be used to find guidelines. The following was recently found in this database: •

Age Page - Shots for Safety Summary: This fact sheet recommends immunization against influenza, pneumococcal diseases, tetanus, and diphtheria. A vaccine schedule and additional resources are included. Source: National Institute on Aging, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=451

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Guidelines for the Prevention and Treatment of Influenza and the Common Cold Summary: This online booklet describes the causes and symptoms of cold and flu infections, and offers specific recommendations regarding prevention, complications, and treatment. Source: American Lung Association http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=5034

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Influenza and Colds Fact Sheets and Brochures Summary: This web site presents fact sheets and brochures about influenza (flu) and the common cold as well as related news reports, alerts and advisories. Source: National Institute of Allergy and Infectious Diseases, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=235

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Influenza Antiviral Drugs and Related Information Summary: This web site offers links to several sources of general information about influenza including the influenza vaccine, antiviral drugs that have been approved in the United States for influenza, a list Source: Center for Drug Evaluation and Research, U.S. Food and Drug Administration http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=5621

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Influenza Vaccine Source: Immunization Action Coalition http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=7362

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Medicare Preventive Services: Influenza/Pneumococcal Campaign Summary: Medicare beneficiaries and health care professionals will find answers to questions about Medicare Influenza/Pneumococcal vaccination benefits, including recent policy changes, on this web site. Source: Centers for Medicare and Medicaid Services (CMS), formerly the Health Care Financing Administration http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=5606

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National Vaccine Program Office: Pandemic Influenza Summary: Describes the origin, spread, and impact of influenza pandemics. Chronicles the history of pandemics and the preparations for future ones. Source: National Vaccine Program Office, U.S Department of Health and Human Services http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6455

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What To Do About the Flu Summary: Flu - short for influenza - is usually a mild disease in healthy children, young adults, and middle-age people. However, flu can be life threatening in older people. Source: National Institute on Aging, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=42

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The NIH Search Utility The NIH search utility allows you to search for documents on over 100 selected Web sites that comprise the NIH-WEB-SPACE. Each of these servers is “crawled” and indexed on an ongoing basis. Your search will produce a list of various documents, all of which will relate in some way to influenza. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html. Additional Web Sources A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •

AOL: http://search.aol.com/cat.adp?id=168&layer=&from=subcats

•

Family Village: http://www.familyvillage.wisc.edu/specific.htm

•

Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/

•

Med Help International: http://www.medhelp.org/HealthTopics/A.html

•

Open Directory Project: http://dmoz.org/Health/Conditions_and_Diseases/

•

Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/

•

WebMD®Health: http://my.webmd.com/health_topics

Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to influenza. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with influenza. The National Health Information Center (NHIC) The National Health Information Center (NHIC) offers a free referral service to help people find organizations that provide information about influenza. For more information, see the NHIC’s Web site at http://www.health.gov/NHIC/ or contact an information specialist by calling 1-800-336-4797. Directory of Health Organizations The Directory of Health Organizations, provided by the National Library of Medicine Specialized Information Services, is a comprehensive source of information on associations. The Directory of Health Organizations database can be accessed via the Internet at

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http://www.sis.nlm.nih.gov/Dir/DirMain.html. It is composed of two parts: DIRLINE and Health Hotlines. The DIRLINE database comprises some 10,000 records of organizations, research centers, and government institutes and associations that primarily focus on health and biomedicine. To access DIRLINE directly, go to the following Web site: http://dirline.nlm.nih.gov/. Simply type in “influenza” (or a synonym), and you will receive information on all relevant organizations listed in the database. Health Hotlines directs you to toll-free numbers to over 300 organizations. You can access this database directly at http://www.sis.nlm.nih.gov/hotlines/. On this page, you are given the option to search by keyword or by browsing the subject list. When you have received your search results, click on the name of the organization for its description and contact information. The Combined Health Information Database Another comprehensive source of information on healthcare associations is the Combined Health Information Database. Using the “Detailed Search” option, you will need to limit your search to “Organizations” and “influenza”. Type the following hyperlink into your Web browser: http://chid.nih.gov/detail/detail.html. To find associations, use the drop boxes at the bottom of the search page where “You may refine your search by.” For publication date, select “All Years.” Then, select your preferred language and the format option “Organization Resource Sheet.” Type “influenza” (or synonyms) into the “For these words:” box. You should check back periodically with this database since it is updated every three months. The National Organization for Rare Disorders, Inc. The National Organization for Rare Disorders, Inc. has prepared a Web site that provides, at no charge, lists of associations organized by health topic. You can access this database at the following Web site: http://www.rarediseases.org/search/orgsearch.html. Type “influenza” (or a synonym) into the search box, and click “Submit Query.”

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APPENDIX C. FINDING MEDICAL LIBRARIES Overview In this Appendix, we show you how to quickly find a medical library in your area.

Preparation Your local public library and medical libraries have interlibrary loan programs with the National Library of Medicine (NLM), one of the largest medical collections in the world. According to the NLM, most of the literature in the general and historical collections of the National Library of Medicine is available on interlibrary loan to any library. If you would like to access NLM medical literature, then visit a library in your area that can request the publications for you.23

Finding a Local Medical Library The quickest method to locate medical libraries is to use the Internet-based directory published by the National Network of Libraries of Medicine (NN/LM). This network includes 4626 members and affiliates that provide many services to librarians, health professionals, and the public. To find a library in your area, simply visit http://nnlm.gov/members/adv.html or call 1-800-338-7657.

Medical Libraries in the U.S. and Canada In addition to the NN/LM, the National Library of Medicine (NLM) lists a number of libraries with reference facilities that are open to the public. The following is the NLM’s list and includes hyperlinks to each library’s Web site. These Web pages can provide information on hours of operation and other restrictions. The list below is a small sample of

23

Adapted from the NLM: http://www.nlm.nih.gov/psd/cas/interlibrary.html.

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libraries recommended by the National Library of Medicine (sorted alphabetically by name of the U.S. state or Canadian province where the library is located)24: •

Alabama: Health InfoNet of Jefferson County (Jefferson County Library Cooperative, Lister Hill Library of the Health Sciences), http://www.uab.edu/infonet/

•

Alabama: Richard M. Scrushy Library (American Sports Medicine Institute)

•

Arizona: Samaritan Regional Medical Center: The Learning Center (Samaritan Health System, Phoenix, Arizona), http://www.samaritan.edu/library/bannerlibs.htm

•

California: Kris Kelly Health Information Center (St. Joseph Health System, Humboldt), http://www.humboldt1.com/~kkhic/index.html

•

California: Community Health Library of Los Gatos, http://www.healthlib.org/orgresources.html

•

California: Consumer Health Program and Services (CHIPS) (County of Los Angeles Public Library, Los Angeles County Harbor-UCLA Medical Center Library) - Carson, CA, http://www.colapublib.org/services/chips.html

•

California: Gateway Health Library (Sutter Gould Medical Foundation)

•

California: Health Library (Stanford University Medical Center), http://wwwmed.stanford.edu/healthlibrary/

•

California: Patient Education Resource Center - Health Information and Resources (University of California, San Francisco), http://sfghdean.ucsf.edu/barnett/PERC/default.asp

•

California: Redwood Health Library (Petaluma Health Care District), http://www.phcd.org/rdwdlib.html

•

California: Los Gatos PlaneTree Health Library, http://planetreesanjose.org/

•

California: Sutter Resource Library (Sutter Hospitals Foundation, Sacramento), http://suttermedicalcenter.org/library/

•

California: Health Sciences Libraries (University of California, Davis), http://www.lib.ucdavis.edu/healthsci/

•

California: ValleyCare Health Library & Ryan Comer Cancer Resource Center (ValleyCare Health System, Pleasanton), http://gaelnet.stmarysca.edu/other.libs/gbal/east/vchl.html

•

California: Washington Community Health Resource Library (Fremont), http://www.healthlibrary.org/

•

Colorado: William V. Gervasini Memorial Library (Exempla Healthcare), http://www.saintjosephdenver.org/yourhealth/libraries/

•

Connecticut: Hartford Hospital Health Science Libraries (Hartford Hospital), http://www.harthosp.org/library/

•

Connecticut: Healthnet: Connecticut Consumer Health Information Center (University of Connecticut Health Center, Lyman Maynard Stowe Library), http://library.uchc.edu/departm/hnet/

24

Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.

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•

Connecticut: Waterbury Hospital Health Center Library (Waterbury Hospital, Waterbury), http://www.waterburyhospital.com/library/consumer.shtml

•

Delaware: Consumer Health Library (Christiana Care Health System, Eugene du Pont Preventive Medicine & Rehabilitation Institute, Wilmington), http://www.christianacare.org/health_guide/health_guide_pmri_health_info.cfm

•

Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine, Wilmington), http://www.delamed.org/chls.html

•

Georgia: Family Resource Library (Medical College of Georgia, Augusta), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm

•

Georgia: Health Resource Center (Medical Center of Central Georgia, Macon), http://www.mccg.org/hrc/hrchome.asp

•

Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library, Honolulu), http://hml.org/CHIS/

•

Idaho: DeArmond Consumer Health Library (Kootenai Medical Center, Coeur d’Alene), http://www.nicon.org/DeArmond/index.htm

•

Illinois: Health Learning Center of Northwestern Memorial Hospital (Chicago), http://www.nmh.org/health_info/hlc.html

•

Illinois: Medical Library (OSF Saint Francis Medical Center, Peoria), http://www.osfsaintfrancis.org/general/library/

•

Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital, Lexington), http://www.centralbap.com/education/community/library.cfm

•

Kentucky: University of Kentucky - Health Information Library (Chandler Medical Center, Lexington), http://www.mc.uky.edu/PatientEd/

•

Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation, New Orleans), http://www.ochsner.org/library/

•

Louisiana: Louisiana State University Health Sciences Center Medical LibraryShreveport, http://lib-sh.lsuhsc.edu/

•

Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital, Farmington), http://www.fchn.org/fmh/lib.htm

•

Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center, Lewiston), http://www.cmmc.org/library/library.html

•

Maine: Hadley Parrot Health Science Library (Eastern Maine Healthcare, Bangor), http://www.emh.org/hll/hpl/guide.htm

•

Maine: Maine Medical Center Library (Maine Medical Center, Portland), http://www.mmc.org/library/

•

Maine: Parkview Hospital (Brunswick), http://www.parkviewhospital.org/

•

Maine: Southern Maine Medical Center Health Sciences Library (Southern Maine Medical Center, Biddeford), http://www.smmc.org/services/service.php3?choice=10

•

Maine: Stephens Memorial Hospital’s Health Information Library (Western Maine Health, Norway), http://www.wmhcc.org/Library/

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•

Manitoba, Canada: Consumer & Patient Health Information Service (University of Manitoba Libraries), http://www.umanitoba.ca/libraries/units/health/reference/chis.html

•

Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre, Winnipeg), http://www.deerlodge.mb.ca/crane_library/about.asp

•

Maryland: Health Information Center at the Wheaton Regional Library (Montgomery County, Dept. of Public Libraries, Wheaton Regional Library), http://www.mont.lib.md.us/healthinfo/hic.asp

•

Massachusetts: Baystate Medical Center Library (Baystate Health System), http://www.baystatehealth.com/1024/

•

Massachusetts: Boston University Medical Center Alumni Medical Library (Boston University Medical Center), http://med-libwww.bu.edu/library/lib.html

•

Massachusetts: Lowell General Hospital Health Sciences Library (Lowell General Hospital, Lowell), http://www.lowellgeneral.org/library/HomePageLinks/WWW.htm

•

Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital, Boston), http://www.nebh.org/health_lib.asp

•

Massachusetts: St. Luke’s Hospital Health Sciences Library (St. Luke’s Hospital, Southcoast Health System, New Bedford), http://www.southcoast.org/library/

•

Massachusetts: Treadwell Library Consumer Health Reference Center (Massachusetts General Hospital), http://www.mgh.harvard.edu/library/chrcindex.html

•

Massachusetts: UMass HealthNet (University of Massachusetts Medical School, Worchester), http://healthnet.umassmed.edu/

•

Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm

•

Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/

•

Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html

•

Michigan: Patient Education Resouce Center - University of Michigan Cancer Center (University of Michigan Comprehensive Cancer Center, Ann Arbor), http://www.cancer.med.umich.edu/learn/leares.htm

•

Michigan: Sladen Library & Center for Health Information Resources - Consumer Health Information (Detroit), http://www.henryford.com/body.cfm?id=39330

•

Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center, Missoula)

•

National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html

•

National: National Network of Libraries of Medicine (National Library of Medicine) provides library services for health professionals in the United States who do not have access to a medical library, http://nnlm.gov/

•

National: NN/LM List of Libraries Serving the Public (National Network of Libraries of Medicine), http://nnlm.gov/members/

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•

Nevada: Health Science Library, West Charleston Library (Las Vegas-Clark County Library District, Las Vegas), http://www.lvccld.org/special_collections/medical/index.htm

•

New Hampshire: Dartmouth Biomedical Libraries (Dartmouth College Library, Hanover), http://www.dartmouth.edu/~biomed/resources.htmld/conshealth.htmld/

•

New Jersey: Consumer Health Library (Rahway Hospital, Rahway), http://www.rahwayhospital.com/library.htm

•

New Jersey: Dr. Walter Phillips Health Sciences Library (Englewood Hospital and Medical Center, Englewood), http://www.englewoodhospital.com/links/index.htm

•

New Jersey: Meland Foundation (Englewood Hospital and Medical Center, Englewood), http://www.geocities.com/ResearchTriangle/9360/

•

New York: Choices in Health Information (New York Public Library) - NLM Consumer Pilot Project participant, http://www.nypl.org/branch/health/links.html

•

New York: Health Information Center (Upstate Medical University, State University of New York, Syracuse), http://www.upstate.edu/library/hic/

•

New York: Health Sciences Library (Long Island Jewish Medical Center, New Hyde Park), http://www.lij.edu/library/library.html

•

New York: ViaHealth Medical Library (Rochester General Hospital), http://www.nyam.org/library/

•

Ohio: Consumer Health Library (Akron General Medical Center, Medical & Consumer Health Library), http://www.akrongeneral.org/hwlibrary.htm

•

Oklahoma: The Health Information Center at Saint Francis Hospital (Saint Francis Health System, Tulsa), http://www.sfh-tulsa.com/services/healthinfo.asp

•

Oregon: Planetree Health Resource Center (Mid-Columbia Medical Center, The Dalles), http://www.mcmc.net/phrc/

•

Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center, Hershey), http://www.hmc.psu.edu/commhealth/

•

Pennsylvania: Community Health Resource Library (Geisinger Medical Center, Danville), http://www.geisinger.edu/education/commlib.shtml

•

Pennsylvania: HealthInfo Library (Moses Taylor Hospital, Scranton), http://www.mth.org/healthwellness.html

•

Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System, Pittsburgh), http://www.hsls.pitt.edu/guides/chi/hopwood/index_html

•

Pennsylvania: Koop Community Health Information Center (College of Physicians of Philadelphia), http://www.collphyphil.org/kooppg1.shtml

•

Pennsylvania: Learning Resources Center - Medical Library (Susquehanna Health System, Williamsport), http://www.shscares.org/services/lrc/index.asp

•

Pennsylvania: Medical Library (UPMC Health System, Pittsburgh), http://www.upmc.edu/passavant/library.htm

•

Quebec, Canada: Medical Library (Montreal General Hospital), http://www.mghlib.mcgill.ca/

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•

South Dakota: Rapid City Regional Hospital Medical Library (Rapid City Regional Hospital), http://www.rcrh.org/Services/Library/Default.asp

•

Texas: Houston HealthWays (Houston Academy of Medicine-Texas Medical Center Library), http://hhw.library.tmc.edu/

•

Washington: Community Health Library (Kittitas Valley Community Hospital), http://www.kvch.com/

•

Washington: Southwest Washington Medical Center Library (Southwest Washington Medical Center, Vancouver), http://www.swmedicalcenter.com/body.cfm?id=72

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ONLINE GLOSSARIES The Internet provides access to a number of free-to-use medical dictionaries. The National Library of Medicine has compiled the following list of online dictionaries: •

ADAM Medical Encyclopedia (A.D.A.M., Inc.), comprehensive medical reference: http://www.nlm.nih.gov/medlineplus/encyclopedia.html

•

MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp

•

Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/

•

Multilingual Glossary of Technical and Popular Medical Terms in Eight European Languages (European Commission) - Danish, Dutch, English, French, German, Italian, Portuguese, and Spanish: http://allserv.rug.ac.be/~rvdstich/eugloss/welcome.html

•

On-line Medical Dictionary (CancerWEB): http://cancerweb.ncl.ac.uk/omd/

•

Rare Diseases Terms (Office of Rare Diseases): http://ord.aspensys.com/asp/diseases/diseases.asp

•

Technology Glossary (National Library of Medicine) - Health Care Technology: http://www.nlm.nih.gov/nichsr/ta101/ta10108.htm

Beyond these, MEDLINEplus contains a very patient-friendly encyclopedia covering every aspect of medicine (licensed from A.D.A.M., Inc.). The ADAM Medical Encyclopedia can be accessed at http://www.nlm.nih.gov/medlineplus/encyclopedia.html. ADAM is also available on commercial Web sites such as drkoop.com (http://www.drkoop.com/) and Web MD (http://my.webmd.com/adam/asset/adam_disease_articles/a_to_z/a). The NIH suggests the following Web sites in the ADAM Medical Encyclopedia when searching for information on influenza: •

Basic Guidelines for Influenza Influenza Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000080.htm Influenza immunization (vaccine) Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002025.htm RSV Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001564.htm

•

Signs & Symptoms for Influenza Anemia Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000560.htm Chills Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003091.htm

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Clammy skin Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003216.htm Confusion Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003205.htm Congested nose Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003049.htm Cough Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003072.htm Cyanosis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003215.htm Diarrhea Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003126.htm Dyspnea Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003075.htm Elbow pain Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003172.htm Fatigue Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003088.htm Fever Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003090.htm Headache Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003024.htm Loss of appetite Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003121.htm Malaise Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003089.htm Muscle aches Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003178.htm Myalgia Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003178.htm Nasal congestion Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003049.htm Nasal discharge Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003051.htm

Online Glossaries 309

Nausea and vomiting Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003117.htm Rhinorrhea Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003051.htm Shortness of breath Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003075.htm Sneezing Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003060.htm Sore throat Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003053.htm Vomiting Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003117.htm Weakness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003174.htm •

Diagnostics and Tests for Influenza ANA Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003535.htm Blood culture Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003744.htm Blood differential Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003657.htm CBC Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003642.htm Chest X-ray Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003804.htm Complement Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003456.htm Differential Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003657.htm ELISA Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003332.htm Febrile/cold agglutinins Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003549.htm Nasopharyngeal culture Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003747.htm

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X-ray Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003337.htm •

Background Topics for Influenza Acute Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002215.htm Chemotherapy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002324.htm Chronic Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002312.htm Contraindications Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002314.htm Immunity Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000821.htm Kidney disease Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000457.htm Respiratory Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002290.htm

Online Dictionary Directories The following are additional online directories compiled by the National Library of Medicine, including a number of specialized medical dictionaries: •

Medical Dictionaries: Medical & Biological (World Health Organization): http://www.who.int/hlt/virtuallibrary/English/diction.htm#Medical

•

MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html

•

Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/

•

Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine

311

INFLUENZA DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. Abacavir: A nucleoside analog reverse transcriptase inhibitor (NARTIs) developed by Glaxo Wellcome. [NIH] Abdomen: That portion of the body that lies between the thorax and the pelvis. [NIH] Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Abdominal Pain: Sensation of discomfort, distress, or agony in the abdominal region. [NIH] Absenteeism: Chronic absence from work or other duty. [NIH] Acceptor: A substance which, while normally not oxidized by oxygen or reduced by hydrogen, can be oxidized or reduced in presence of a substance which is itself undergoing oxidation or reduction. [NIH] Acetylcholine: A neurotransmitter. Acetylcholine in vertebrates is the major transmitter at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. It is generally not used as an administered drug because it is broken down very rapidly by cholinesterases, but it is useful in some ophthalmological applications. [NIH] Acetylglucosamine: The N-acetyl derivative of glucosamine. [NIH] Acidosis: A pathologic condition resulting from accumulation of acid or depletion of the alkaline reserve (bicarbonate content) in the blood and body tissues, and characterized by an increase in hydrogen ion concentration. [EU] Acne: A disorder of the skin marked by inflammation of oil glands and hair glands. [NIH] Acquired Immunodeficiency Syndrome: An acquired defect of cellular immunity associated with infection by the human immunodeficiency virus (HIV), a CD4-positive Tlymphocyte count under 200 cells/microliter or less than 14% of total lymphocytes, and increased susceptibility to opportunistic infections and malignant neoplasms. Clinical manifestations also include emaciation (wasting) and dementia. These elements reflect criteria for AIDS as defined by the CDC in 1993. [NIH] Actin: Essential component of the cell skeleton. [NIH] Acute lymphoblastic leukemia: ALL. A quickly progressing disease in which too many immature white blood cells called lymphoblasts are found in the blood and bone marrow. Also called acute lymphocytic leukemia. [NIH] Acute lymphocytic leukemia: ALL. A quickly progressing disease in which too many immature white blood cells called lymphoblasts are found in the blood and bone marrow. Also called acute lymphoblastic leukemia. [NIH] Acyl: Chemical signal used by bacteria to communicate. [NIH] Adaptability: Ability to develop some form of tolerance to conditions extremely different from those under which a living organism evolved. [NIH] Adaptation: 1. The adjustment of an organism to its environment, or the process by which it enhances such fitness. 2. The normal ability of the eye to adjust itself to variations in the

312 Influenza

intensity of light; the adjustment to such variations. 3. The decline in the frequency of firing of a neuron, particularly of a receptor, under conditions of constant stimulation. 4. In dentistry, (a) the proper fitting of a denture, (b) the degree of proximity and interlocking of restorative material to a tooth preparation, (c) the exact adjustment of bands to teeth. 5. In microbiology, the adjustment of bacterial physiology to a new environment. [EU] Adenosine: A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. [NIH] Adenovirus: A group of viruses that cause respiratory tract and eye infections. Adenoviruses used in gene therapy are altered to carry a specific tumor-fighting gene. [NIH] Adenylate Cyclase: An enzyme of the lyase class that catalyzes the formation of cyclic AMP and pyrophosphate from ATP. EC 4.6.1.1. [NIH] Adipocytes: Fat-storing cells found mostly in the abdominal cavity and subcutaneous tissue. Fat is usually stored in the form of tryglycerides. [NIH] Adjustment: The dynamic process wherein the thoughts, feelings, behavior, and biophysiological mechanisms of the individual continually change to adjust to the environment. [NIH] Adjuvant: A substance which aids another, such as an auxiliary remedy; in immunology, nonspecific stimulator (e.g., BCG vaccine) of the immune response. [EU] Adolescence: The period of life beginning with the appearance of secondary sex characteristics and terminating with the cessation of somatic growth. The years usually referred to as adolescence lie between 13 and 18 years of age. [NIH] Adolescent Nutrition: Nutrition of children aged 13-18 years. [NIH] Adoptive Transfer: Form of passive immunization where previously sensitized immunologic agents (cells or serum) are transferred to non-immune recipients. When transfer of cells is used as a therapy for the treatment of neoplasms, it is called adoptive immunotherapy (immunotherapy, adoptive). [NIH] Adrenal Cortex: The outer layer of the adrenal gland. It secretes mineralocorticoids, androgens, and glucocorticoids. [NIH] Adrenal Medulla: The inner part of the adrenal gland; it synthesizes, stores and releases catecholamines. [NIH] Adrenergic: Activated by, characteristic of, or secreting epinephrine or substances with similar activity; the term is applied to those nerve fibres that liberate norepinephrine at a synapse when a nerve impulse passes, i.e., the sympathetic fibres. [EU] Adsorption: The condensation of gases, liquids, or dissolved substances on the surfaces of solids. It includes adsorptive phenomena of bacteria and viruses as well as of tissues treated with exogenous drugs and chemicals. [NIH] Adsorptive: It captures volatile compounds by binding them to agents such as activated carbon or adsorptive resins. [NIH] Adverse Effect: An unwanted side effect of treatment. [NIH] Aerobic: In biochemistry, reactions that need oxygen to happen or happen when oxygen is present. [NIH] Aerobic Exercise: A type of physical activity that includes walking, jogging, running, and dancing. Aerobic training improves the efficiency of the aerobic energy-producing systems that can improve cardiorespiratory endurance. [NIH] Aerosol: A solution of a drug which can be atomized into a fine mist for inhalation therapy.

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[EU]

Aetiology: Study of the causes of disease. [EU] Afferent: Concerned with the transmission of neural impulse toward the central part of the nervous system. [NIH] Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among simple, uniform antigenic determinants such as haptens. Expressed as the association constant (K litres mole -1), which, owing to the heterogeneity of affinities in a population of antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU] Age Groups: Persons classified by age from birth (infant, newborn) to octogenarians and older (aged, 80 and over). [NIH] Age of Onset: The age or period of life at which a disease or the initial symptoms or manifestations of a disease appear in an individual. [NIH] Aged, 80 and Over: A person 80 years of age and older. [NIH] Agglutinins: Substances, usually of biological origin, that cause cells or other organic particles to aggregate and stick to each other. They also include those antibodies which cause aggregation or agglutination of a particulate or insoluble antigen. [NIH] Agonist: In anatomy, a prime mover. In pharmacology, a drug that has affinity for and stimulates physiologic activity at cell receptors normally stimulated by naturally occurring substances. [EU] Airway: A device for securing unobstructed passage of air into and out of the lungs during general anesthesia. [NIH] Alanine: A non-essential amino acid that occurs in high levels in its free state in plasma. It is produced from pyruvate by transamination. It is involved in sugar and acid metabolism, increases immunity, and provides energy for muscle tissue, brain, and the central nervous system. [NIH] Albumin: 1. Any protein that is soluble in water and moderately concentrated salt solutions and is coagulable by heat. 2. Serum albumin; the major plasma protein (approximately 60 per cent of the total), which is responsible for much of the plasma colloidal osmotic pressure and serves as a transport protein carrying large organic anions, such as fatty acids, bilirubin, and many drugs, and also carrying certain hormones, such as cortisol and thyroxine, when their specific binding globulins are saturated. Albumin is synthesized in the liver. Low serum levels occur in protein malnutrition, active inflammation and serious hepatic and renal disease. [EU] Alertness: A state of readiness to detect and respond to certain specified small changes occurring at random intervals in the environment. [NIH] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alimentary: Pertaining to food or nutritive material, or to the organs of digestion. [EU] Alkaline: Having the reactions of an alkali. [EU] Alkaline Phosphatase: An enzyme that catalyzes the conversion of an orthophosphoric

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monoester and water to an alcohol and orthophosphate. EC 3.1.3.1. [NIH] Alkaloid: A member of a large group of chemicals that are made by plants and have nitrogen in them. Some alkaloids have been shown to work against cancer. [NIH] Allantois: An embryonic diverticulum of the hindgut of reptiles, birds, and mammals; in man its blood vessels give rise to those of the umbilical cord. [NIH] Allergen: An antigenic substance capable of producing immediate-type hypersensitivity (allergy). [EU] Allergic Rhinitis: Inflammation of the nasal mucous membrane associated with hay fever; fits may be provoked by substances in the working environment. [NIH] Allograft: An organ or tissue transplant between two humans. [NIH] Alpha Particles: Positively charged particles composed of two protons and two neutrons, i.e., helium nuclei, emitted during disintegration of very heavy isotopes; a beam of alpha particles or an alpha ray has very strong ionizing power, but weak penetrability. [NIH] Alternative medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used instead of standard treatments. Alternative medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Alum: A type of immune adjuvant (a substance used to help boost the immune response to a vaccine). Also called aluminum sulfate. [NIH] Aluminum: A metallic element that has the atomic number 13, atomic symbol Al, and atomic weight 26.98. [NIH] Aluminum Hydroxide: Hydrated aluminum. A compound with many biomedical applications: as a gastric antacid, an antiperspirant, in dentifrices, as an emulsifier, as an adjuvant in bacterins and vaccines, in water purification, etc. [NIH] Amantadine: An antiviral that is used in the prophylactic or symptomatic treatment of Influenza A. It is also used as an antiparkinsonian agent, to treat extrapyramidal reactions, and for postherpetic neuralgia. The mechanisms of its effects in movement disorders are not well understood but probably reflect an increase in synthesis and release of dopamine, with perhaps some inhibition of dopamine uptake. [NIH] Amebiasis: Infection with any of various amebae. It is an asymptomatic carrier state in most individuals, but diseases ranging from chronic, mild diarrhea to fulminant dysentery may occur. [NIH] Amenorrhea: Absence of menstruation. [NIH] Amine: An organic compound containing nitrogen; any member of a group of chemical compounds formed from ammonia by replacement of one or more of the hydrogen atoms by organic (hydrocarbon) radicals. The amines are distinguished as primary, secondary, and tertiary, according to whether one, two, or three hydrogen atoms are replaced. The amines include allylamine, amylamine, ethylamine, methylamine, phenylamine, propylamine, and many other compounds. [EU] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Amino Acid Substitution: The naturally occurring or experimentally induced replacement of one or more amino acids in a protein with another. If a functionally equivalent amino acid is substituted, the protein may retain wild-type activity. Substitution may also diminish or

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eliminate protein function. Experimentally induced substitution is often used to study enzyme activities and binding site properties. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amnion: The extraembryonic membrane which contains the embryo and amniotic fluid. [NIH]

Amniotic Fluid: Amniotic cavity fluid which is produced by the amnion and fetal lungs and kidneys. [NIH] Amplification: The production of additional copies of a chromosomal DNA sequence, found as either intrachromosomal or extrachromosomal DNA. [NIH] Ampoule: A small glass or plastic container capable of being sealed so as to preserve its contents in a sterile condition; used principally for containing sterile parenteral solutions (American English: ampule). [EU] Amyloid: A general term for a variety of different proteins that accumulate as extracellular fibrils of 7-10 nm and have common structural features, including a beta-pleated sheet conformation and the ability to bind such dyes as Congo red and thioflavine (Kandel, Schwartz, and Jessel, Principles of Neural Science, 3rd ed). [NIH] Anaemia: A reduction below normal in the number of erythrocytes per cu. mm., in the quantity of haemoglobin, or in the volume of packed red cells per 100 ml. of blood which occurs when the equilibrium between blood loss (through bleeding or destruction) and blood production is disturbed. [EU] Anaerobic: 1. Lacking molecular oxygen. 2. Growing, living, or occurring in the absence of molecular oxygen; pertaining to an anaerobe. [EU] Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Anal: Having to do with the anus, which is the posterior opening of the large bowel. [NIH] Analgesic: An agent that alleviates pain without causing loss of consciousness. [EU] Analog: In chemistry, a substance that is similar, but not identical, to another. [NIH] Analogous: Resembling or similar in some respects, as in function or appearance, but not in origin or development;. [EU] Analytes: A component of a test sample the presence of which has to be demonstrated. The term "analyte" includes where appropriate formed from the analyte during the analyses. [NIH]

Anaphylatoxins: The family of peptides C3a, C4a, C5a, and C5a des-arginine produced in the serum during complement activation. They produce smooth muscle contraction, mast cell histamine release, affect platelet aggregation, and act as mediators of the local inflammatory process. The order of anaphylatoxin activity from strongest to weakest is C5a, C3a, C4a, and C5a des-arginine. The latter is the so-called "classical" anaphylatoxin but shows no spasmogenic activity though it contains some chemotactic ability. [NIH] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Androgens: A class of sex hormones associated with the development and maintenance of

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the secondary male sex characteristics, sperm induction, and sexual differentiation. In addition to increasing virility and libido, they also increase nitrogen and water retention and stimulate skeletal growth. [NIH] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Anergic: 1. Characterized by abnormal inactivity; inactive. 2. Marked by asthenia or lack of energy. 3. Pertaining to anergy. [EU] Anergy: Absence of immune response to particular substances. [NIH] Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH] Anesthetics: Agents that are capable of inducing a total or partial loss of sensation, especially tactile sensation and pain. They may act to induce general anesthesia, in which an unconscious state is achieved, or may act locally to induce numbness or lack of sensation at a targeted site. [NIH] Animal model: An animal with a disease either the same as or like a disease in humans. Animal models are used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Anionic: Pertaining to or containing an anion. [EU] Ankle: That part of the lower limb directly above the foot. [NIH] Annealing: The spontaneous alignment of two single DNA strands to form a double helix. [NIH]

Anorexia: Lack or loss of appetite for food. Appetite is psychologic, dependent on memory and associations. Anorexia can be brought about by unattractive food, surroundings, or company. [NIH] Anorexia Nervosa: The chief symptoms are inability to eat, weight loss, and amenorrhea. [NIH]

Antagonism: Interference with, or inhibition of, the growth of a living organism by another living organism, due either to creation of unfavorable conditions (e. g. exhaustion of food supplies) or to production of a specific antibiotic substance (e. g. penicillin). [NIH] Anthocyanins: Glycosidic pigments in blue, red, and purple flowers and also found as metabolic byproducts in blood and urine. [NIH] Anthrax: An acute bacterial infection caused by ingestion of bacillus organisms. Carnivores may become infected from ingestion of infected carcasses. It is transmitted to humans by contact with infected animals or contaminated animal products. The most common form in humans is cutaneous anthrax. [NIH] Antiallergic: Counteracting allergy or allergic conditions. [EU] Antibacterial: A substance that destroys bacteria or suppresses their growth or reproduction. [EU] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]

Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] Antibody: A type of protein made by certain white blood cells in response to a foreign

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substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] Antibody-Dependent Cell Cytotoxicity: The phenomenon of antibody-mediated target cell destruction by non-sensitized effector cells. The identity of the target cell varies, but it must possess surface IgG whose Fc portion is intact. The effector cell is a "killer" cell possessing Fc receptors. It may be a lymphocyte lacking conventional B- or T-cell markers, or a monocyte, macrophage, or polynuclear leukocyte, depending on the identity of the target cell. The reaction is complement-independent. [NIH] Anticholinergic: An agent that blocks the parasympathetic nerves. Called also parasympatholytic. [EU] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Antigen-Antibody Complex: The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes immune complex diseases. [NIH] Antigen-presenting cell: APC. A cell that shows antigen on its surface to other cells of the immune system. This is an important part of an immune response. [NIH] Antihypertensive: An agent that reduces high blood pressure. [EU] Anti-infective: An agent that so acts. [EU] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Anti-Inflammatory Agents: Substances that reduce or suppress inflammation. [NIH] Antimetabolite: A chemical that is very similar to one required in a normal biochemical reaction in cells. Antimetabolites can stop or slow down the reaction. [NIH] Antimicrobial: Killing microorganisms, or suppressing their multiplication or growth. [EU] Antimycotic: Suppressing the growth of fungi. [EU] Antineoplastic: Inhibiting or preventing the development of neoplasms, checking the maturation and proliferation of malignant cells. [EU] Antioxidant: A substance that prevents damage caused by free radicals. Free radicals are highly reactive chemicals that often contain oxygen. They are produced when molecules are split to give products that have unpaired electrons. This process is called oxidation. [NIH] Antipyretic: An agent that relieves or reduces fever. Called also antifebrile, antithermic and febrifuge. [EU] Antiserum: The blood serum obtained from an animal after it has been immunized with a particular antigen. It will contain antibodies which are specific for that antigen as well as antibodies specific for any other antigen with which the animal has previously been immunized. [NIH] Antiviral: Destroying viruses or suppressing their replication. [EU]

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Antiviral Agents: Agents used in the prophylaxis or therapy of virus diseases. Some of the ways they may act include preventing viral replication by inhibiting viral DNA polymerase; binding to specific cell-surface receptors and inhibiting viral penetration or uncoating; inhibiting viral protein synthesis; or blocking late stages of virus assembly. [NIH] Anxiety: Persistent feeling of dread, apprehension, and impending disaster. [NIH] Aplastic anaemia: A form of anaemia generally unresponsive to specific antianaemia therapy, often accompanied by granulocytopenia and thrombocytopenia, in which the bone marrow may not necessarily be acellular or hypoplastic but fails to produce adequate numbers of peripheral blood elements. The term actually is all-inclusive and most probably encompasses several clinical syndromes. [EU] Apolipoproteins: The protein components of lipoproteins which remain after the lipids to which the proteins are bound have been removed. They play an important role in lipid transport and metabolism. [NIH] Applicability: A list of the commodities to which the candidate method can be applied as presented or with minor modifications. [NIH] Aqueous: Having to do with water. [NIH] Arenavirus: The only genus in the family Arenaviridae. It contains two groups LCM-Lassa complex viruses and Tacaribe complex viruses, which are distinguished by antigenic relationships and geographic distribution. [NIH] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Aromatic: Having a spicy odour. [EU] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Arthroplasty: Surgical reconstruction of a joint to relieve pain or restore motion. [NIH] Artifacts: Any visible result of a procedure which is caused by the procedure itself and not by the entity being analyzed. Common examples include histological structures introduced by tissue processing, radiographic images of structures that are not naturally present in living tissue, and products of chemical reactions that occur during analysis. [NIH] Aseptic: Free from infection or septic material; sterile. [EU] Aspergillus: A genus of mitosporic fungi containing about 100 species and eleven different teleomorphs in the family Trichocomaceae. [NIH] Aspirate: Fluid withdrawn from a lump, often a cyst, or a nipple. [NIH] Aspiration: The act of inhaling. [NIH] Aspirin: A drug that reduces pain, fever, inflammation, and blood clotting. Aspirin belongs to the family of drugs called nonsteroidal anti-inflammatory agents. It is also being studied in cancer prevention. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Asthenia: Clinical sign or symptom manifested as debility, or lack or loss of strength and energy. [NIH] Astringents: Agents, usually topical, that cause the contraction of tissues for the control of bleeding or secretions. [NIH] Asymptomatic: Having no signs or symptoms of disease. [NIH]

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Ataxia: Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharnyx, larnyx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or peripheral nerve diseases. Motor ataxia may be associated with cerebellar diseases; cerebral cortex diseases; thalamic diseases; basal ganglia diseases; injury to the red nucleus; and other conditions. [NIH] Atopic: Pertaining to an atopen or to atopy; allergic. [EU] Atropine: A toxic alkaloid, originally from Atropa belladonna, but found in other plants, mainly Solanaceae. [NIH] Attenuated: Strain with weakened or reduced virulence. [NIH] Attenuation: Reduction of transmitted sound energy or its electrical equivalent. [NIH] Autoantibodies: Antibodies that react with self-antigens (autoantigens) of the organism that produced them. [NIH] Autoantigens: Endogenous tissue constituents that have the ability to interact with autoantibodies and cause an immune response. [NIH] Autoimmune disease: A condition in which the body recognizes its own tissues as foreign and directs an immune response against them. [NIH] Autoimmunity: Process whereby the immune system reacts against the body's own tissues. Autoimmunity may produce or be caused by autoimmune diseases. [NIH] Autologous: Taken from an individual's own tissues, cells, or DNA. [NIH] Autonomic: Self-controlling; functionally independent. [EU] Autonomic Nervous System: The enteric, parasympathetic, and sympathetic nervous systems taken together. Generally speaking, the autonomic nervous system regulates the internal environment during both peaceful activity and physical or emotional stress. Autonomic activity is controlled and integrated by the central nervous system, especially the hypothalamus and the solitary nucleus, which receive information relayed from visceral afferents; these and related central and sensory structures are sometimes (but not here) considered to be part of the autonomic nervous system itself. [NIH] Autopsy: Postmortem examination of the body. [NIH] Avian: A plasmodial infection in birds. [NIH] Avidity: The strength of the interaction of an antiserum with a multivalent antigen. [NIH] Bacillus: A genus of Bacillaceae that are spore-forming, rod-shaped cells. Most species are saprophytic soil forms with only a few species being pathogenic. [NIH] Bacteremia: The presence of viable bacteria circulating in the blood. Fever, chills, tachycardia, and tachypnea are common acute manifestations of bacteremia. The majority of cases are seen in already hospitalized patients, most of whom have underlying diseases or procedures which render their bloodstreams susceptible to invasion. [NIH] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Bacterial Infections: Infections by bacteria, general or unspecified. [NIH] Bacterial Outer Membrane Proteins: Proteins isolated from the outer membrane of bacteria. [NIH]

Bacterial Physiology: Physiological processes and activities of bacteria. [NIH] Bacteriophage: A virus whose host is a bacterial cell; A virus that exclusively infects

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bacteria. It generally has a protein coat surrounding the genome (DNA or RNA). One of the coliphages most extensively studied is the lambda phage, which is also one of the most important. [NIH] Bacteriophage lambda: A temperate inducible phage and type species of the genus lambdalike Phages, in the family Siphoviridae. Its natural host is E. coli K12. Its virion contains linear double-stranded DNA, except for 12 complementary bases at the 5'-termini of the polynucleotide chains. The DNA circularizes on infection. [NIH] Bacterium: Microscopic organism which may have a spherical, rod-like, or spiral unicellular or non-cellular body. Bacteria usually reproduce through asexual processes. [NIH] Bacteriuria: The presence of bacteria in the urine with or without consequent urinary tract infection. Since bacteriuria is a clinical entity, the term does not preclude the use of urine/microbiology for technical discussions on the isolation and segregation of bacteria in the urine. [NIH] Basal Ganglia: Large subcortical nuclear masses derived from the telencephalon and located in the basal regions of the cerebral hemispheres. [NIH] Basal Ganglia Diseases: Diseases of the basal ganglia including the putamen; globus pallidus; claustrum; amygdala; and caudate nucleus. Dyskinesias (most notably involuntary movements and alterations of the rate of movement) represent the primary clinical manifestations of these disorders. Common etiologies include cerebrovascular disease; neurodegenerative diseases; and craniocerebral trauma. [NIH] Base: In chemistry, the nonacid part of a salt; a substance that combines with acids to form salts; a substance that dissociates to give hydroxide ions in aqueous solutions; a substance whose molecule or ion can combine with a proton (hydrogen ion); a substance capable of donating a pair of electrons (to an acid) for the formation of a coordinate covalent bond. [EU] Base Sequence: The sequence of purines and pyrimidines in nucleic acids and polynucleotides. It is also called nucleotide or nucleoside sequence. [NIH] Basophil: A type of white blood cell. Basophils are granulocytes. [NIH] Belladonna: A species of very poisonous Solanaceous plants yielding atropine (hyoscyamine), scopolamine, and other belladonna alkaloids, used to block the muscarinic autonomic nervous system. [NIH] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]

Beta-pleated: Particular three-dimensional pattern of amyloidoses. [NIH] Beta-Thromboglobulin: A platelet-specific protein which is released when platelets aggregate. Elevated plasma levels have been reported after deep venous thrombosis, preeclampsia, myocardial infarction with mural thrombosis, and myeloproliferative disorders. Measurement of beta-thromboglobulin in biological fluids by radioimmunoassay is used for the diagnosis and assessment of progress of thromboembolic disorders. [NIH] Bewilderment: Impairment or loss of will power. [NIH] Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Bile Acids: Acids made by the liver that work with bile to break down fats. [NIH] Bile Acids and Salts: Steroid acids and salts. The primary bile acids are derived from cholesterol in the liver and usually conjugated with glycine or taurine. The secondary bile acids are further modified by bacteria in the intestine. They play an important role in the digestion and absorption of fat. They have also been used pharmacologically, especially in

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the treatment of gallstones. [NIH] Bile Pigments: Pigments that give a characteristic color to bile including: bilirubin, biliverdine, and bilicyanin. [NIH] Bilirubin: A bile pigment that is a degradation product of heme. [NIH] Bioavailability: The degree to which a drug or other substance becomes available to the target tissue after administration. [EU] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biological response modifier: BRM. A substance that stimulates the body's response to infection and disease. [NIH] Biomarkers: Substances sometimes found in an increased amount in the blood, other body fluids, or tissues and that may suggest the presence of some types of cancer. Biomarkers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and GI tract cancers), and PSA (prostate cancer). Also called tumor markers. [NIH] Biomolecular: A scientific field at the interface between advanced computing and biotechnology. [NIH] Biosynthesis: The building up of a chemical compound in the physiologic processes of a living organism. [EU] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Bioterrorism: The use of biological agents in terrorism. This includes the malevolent use of bacteria, viruses, or toxins against people, animals, or plants. [NIH] Bladder: The organ that stores urine. [NIH] Bloating: Fullness or swelling in the abdomen that often occurs after meals. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Blood-Brain Barrier: Specialized non-fenestrated tightly-joined endothelial cells (tight junctions) that form a transport barrier for certain substances between the cerebral capillaries and the brain tissue. [NIH] Blot: To transfer DNA, RNA, or proteins to an immobilizing matrix such as nitrocellulose. [NIH]

Body Fluids: Liquid components of living organisms. [NIH] Bone Cements: Adhesives used to fix prosthetic devices to bones and to cement bone to bone in difficult fractures. Synthetic resins are commonly used as cements. A mixture of monocalcium phosphate, monohydrate, alpha-tricalcium phosphate, and calcium carbonate with a sodium phosphate solution is also a useful bone paste. [NIH]

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Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bone Marrow Cells: Cells contained in the bone marrow including fat cells, stromal cells, megakaryocytes, and the immediate precursors of most blood cells. [NIH] Bowel: The long tube-shaped organ in the abdomen that completes the process of digestion. There is both a small and a large bowel. Also called the intestine. [NIH] Bowel Movement: Body wastes passed through the rectum and anus. [NIH] Brachytherapy: A collective term for interstitial, intracavity, and surface radiotherapy. It uses small sealed or partly-sealed sources that may be placed on or near the body surface or within a natural body cavity or implanted directly into the tissues. [NIH] Bradykinin: A nonapeptide messenger that is enzymatically produced from kallidin in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from mast cells during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter. [NIH] Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]

Breeding: The science or art of changing the constitution of a population of plants or animals through sexual reproduction. [NIH] Bronchi: The larger air passages of the lungs arising from the terminal bifurcation of the trachea. [NIH] Bronchial: Pertaining to one or more bronchi. [EU] Bronchioles: The tiny branches of air tubes in the lungs. [NIH] Bronchiolitis: Inflammation of the bronchioles. [NIH] Bronchiseptica: A small, gram-negative, motile bacillus. A normal inhabitant of the respiratory tract in man, dogs, and pigs, but is also associated with canine infectious tracheobronchitis and atrophic rhinitis in pigs. [NIH] Bronchitis: Inflammation (swelling and reddening) of the bronchi. [NIH] Buccal: Pertaining to or directed toward the cheek. In dental anatomy, used to refer to the buccal surface of a tooth. [EU] Bullous: Pertaining to or characterized by bullae. [EU] Butyric Acid: A four carbon acid, CH3CH2CH2COOH, with an unpleasant odor that occurs in butter and animal fat as the glycerol ester. [NIH] Caffeine: A methylxanthine naturally occurring in some beverages and also used as a pharmacological agent. Caffeine's most notable pharmacological effect is as a central nervous system stimulant, increasing alertness and producing agitation. It also relaxes smooth muscle, stimulates cardiac muscle, stimulates diuresis, and appears to be useful in the treatment of some types of headache. Several cellular actions of caffeine have been observed, but it is not entirely clear how each contributes to its pharmacological profile. Among the most important are inhibition of cyclic nucleotide phosphodiesterases, antagonism of adenosine receptors, and modulation of intracellular calcium handling. [NIH] Calcium: A basic element found in nearly all organized tissues. It is a member of the

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alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. [NIH] Calculi: An abnormal concretion occurring mostly in the urinary and biliary tracts, usually composed of mineral salts. Also called stones. [NIH] Capillary: Any one of the minute vessels that connect the arterioles and venules, forming a network in nearly all parts of the body. Their walls act as semipermeable membranes for the interchange of various substances, including fluids, between the blood and tissue fluid; called also vas capillare. [EU] Capillary Fragility: The lack of resistance, or susceptibility, of capillaries to damage or disruption under conditions of increased stress. [NIH] Capillary Permeability: Property of blood capillary walls that allows for the selective exchange of substances. Small lipid-soluble molecules such as carbon dioxide and oxygen move freely by diffusion. Water and water-soluble molecules cannot pass through the endothelial walls and are dependent on microscopic pores. These pores show narrow areas (tight junctions) which may limit large molecule movement. [NIH] Capital Financing: Institutional funding for facilities and for equipment which becomes a part of the assets of the institution. [NIH] Capsid: The outer protein protective shell of a virus, which protects the viral nucleic acid. [NIH]

Capsules: Hard or soft soluble containers used for the oral administration of medicine. [NIH] Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen are usually in the proportion to form water, (CH2O)n. The most important carbohydrates are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, polyand heterosaccharides. [EU] Carbon Dioxide: A colorless, odorless gas that can be formed by the body and is necessary for the respiration cycle of plants and animals. [NIH] Carboxy: Cannabinoid. [NIH] Carboxy-terminal: The end of any polypeptide or protein that bears a free carboxyl group. [NIH]

Carcinoembryonic Antigen: A glycoprotein that is secreted into the luminal surface of the epithelia in the gastrointestinal tract. It is found in the feces and pancreaticobiliary secretions and is used to monitor the respone to colon cancer treatment. [NIH] Carcinogen: Any substance that causes cancer. [NIH] Carcinogenesis: The process by which normal cells are transformed into cancer cells. [NIH] Carcinogenic: Producing carcinoma. [EU] Carcinoma: Cancer that begins in the skin or in tissues that line or cover internal organs. [NIH]

Cardiac: Having to do with the heart. [NIH] Cardiorespiratory: Relating to the heart and lungs and their function. [EU] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Cardiovascular disease: Any abnormal condition characterized by dysfunction of the heart and blood vessels. CVD includes atherosclerosis (especially coronary heart disease, which

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can lead to heart attacks), cerebrovascular disease (e.g., stroke), and hypertension (high blood pressure). [NIH] Case report: A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin). [NIH] Catalyse: To speed up a chemical reaction. [EU] Catechin: Extracted from Uncaria gambier, Acacia catechu and other plants; it stabilizes collagen and is therefore used in tanning and dyeing; it prevents capillary fragility and abnormal permeability, but was formerly used as an antidiarrheal. [NIH] Catecholamine: A group of chemical substances manufactured by the adrenal medulla and secreted during physiological stress. [NIH] Causal: Pertaining to a cause; directed against a cause. [EU] Cause of Death: Factors which produce cessation of all vital bodily functions. They can be analyzed from an epidemiologic viewpoint. [NIH] Celiac Disease: A disease characterized by intestinal malabsorption and precipitated by gluten-containing foods. The intestinal mucosa shows loss of villous structure. [NIH] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Cell Count: A count of the number of cells of a specific kind, usually measured per unit volume of sample. [NIH] Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function which takes place during the development of the embryo and leads to the formation of specialized cells, tissues, and organs. [NIH] Cell Division: The fission of a cell. [NIH] Cell Fusion: Fusion of somatic cells in vitro or in vivo, which results in somatic cell hybridization. [NIH] Cell membrane: Cell membrane = plasma membrane. The structure enveloping a cell, enclosing the cytoplasm, and forming a selective permeability barrier; it consists of lipids, proteins, and some carbohydrates, the lipids thought to form a bilayer in which integral proteins are embedded to varying degrees. [EU] Cell Physiology: Characteristics and physiological processes of cells from cell division to cell death. [NIH] Cell proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH] Cell Size: The physical dimensions of a cell. It refers mainly to changes in dimensions correlated with physiological or pathological changes in cells. [NIH] Cellulitis: An acute, diffuse, and suppurative inflammation of loose connective tissue, particularly the deep subcutaneous tissues, and sometimes muscle, which is most commonly seen as a result of infection of a wound, ulcer, or other skin lesions. [NIH] Cellulose: A polysaccharide with glucose units linked as in cellobiose. It is the chief constituent of plant fibers, cotton being the purest natural form of the substance. As a raw material, it forms the basis for many derivatives used in chromatography, ion exchange materials, explosives manufacturing, and pharmaceutical preparations. [NIH]

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Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Central Nervous System Infections: Pathogenic infections of the brain, spinal cord, and meninges. DNA virus infections; RNA virus infections; bacterial infections; mycoplasma infections; Spirochaetales infections; fungal infections; protozoan infections; helminthiasis; and prion diseases may involve the central nervous system as a primary or secondary process. [NIH] Cerebellar: Pertaining to the cerebellum. [EU] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU] Cerebrum: The largest part of the brain. It is divided into two hemispheres, or halves, called the cerebral hemispheres. The cerebrum controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. [NIH] Cervical: Relating to the neck, or to the neck of any organ or structure. Cervical lymph nodes are located in the neck; cervical cancer refers to cancer of the uterine cervix, which is the lower, narrow end (the "neck") of the uterus. [NIH] Cervix: The lower, narrow end of the uterus that forms a canal between the uterus and vagina. [NIH] Character: In current usage, approximately equivalent to personality. The sum of the relatively fixed personality traits and habitual modes of response of an individual. [NIH] Chemokines: Class of pro-inflammatory cytokines that have the ability to attract and activate leukocytes. They can be divided into at least three structural branches: C (chemokines, C), CC (chemokines, CC), and CXC (chemokines, CXC), according to variations in a shared cysteine motif. [NIH] Chemotactic Factors: Chemical substances that attract or repel cells or organisms. The concept denotes especially those factors released as a result of tissue injury, invasion, or immunologic activity, that attract leukocytes, macrophages, or other cells to the site of infection or insult. [NIH] Chemotherapy: Treatment with anticancer drugs. [NIH] Chickenpox: A mild, highly contagious virus characterized by itchy blisters all over the body. [NIH] Child Development: The continuous sequential physiological and psychological maturing of the child from birth up to but not including adolescence. It includes healthy responses to situations, but does not include growth in stature or size (= growth). [NIH] Chimeric Proteins: Proteins in individuals that are derived from genetically different zygotes. [NIH] Chlorophyll: Porphyrin derivatives containing magnesium that act to convert light energy in photosynthetic organisms. [NIH] Cholera: An acute diarrheal disease endemic in India and Southeast Asia whose causative agent is vibrio cholerae. This condition can lead to severe dehydration in a matter of hours unless quickly treated. [NIH] Cholera Toxin: The enterotoxin from Vibrio cholerae. It is a protein that consists of two major components, the heavy (H) or A peptide and the light (L) or B peptide or choleragenoid. The B peptide anchors the protein to intestinal epithelial cells, while the A peptide, enters the cytoplasm, and activates adenylate cyclase, and production of cAMP. Increased levels of cAMP are thought to modulate release of fluid and electrolytes from

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intestinal crypt cells. [NIH] Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. [NIH] Cholesterol Esters: Fatty acid esters of cholesterol which constitute about two-thirds of the cholesterol in the plasma. The accumulation of cholesterol esters in the arterial intima is a characteristic feature of atherosclerosis. [NIH] Chromosomal: Pertaining to chromosomes. [EU] Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chronic Disease: Disease or ailment of long duration. [NIH] Chronic Fatigue Syndrome: Fatigue caused by the combined effects of different types of prolonged fatigue. [NIH] Chronic Obstructive Pulmonary Disease: Collective term for chronic bronchitis and emphysema. [NIH] Chylomicrons: A class of lipoproteins that carry dietary cholesterol and triglycerides from the small intestines to the tissues. [NIH] CIS: Cancer Information Service. The CIS is the National Cancer Institute's link to the public, interpreting and explaining research findings in a clear and understandable manner, and providing personalized responses to specific questions about cancer. Access the CIS by calling 1-800-4-CANCER, or by using the Web site at http://cis.nci.nih.gov. [NIH] Clathrin: The main structural coat protein of coated vesicles which play a key role in the intracellular transport between membranous organelles. Clathrin also interacts with cytoskeletal proteins. [NIH] Cleave: A double-stranded cut in DNA with a restriction endonuclease. [NIH] Clindamycin: An antibacterial agent that is a semisynthetic analog of lincomycin. [NIH] Clinical Medicine: The study and practice of medicine by direct examination of the patient. [NIH]

Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH] Coated Vesicles: Vesicles formed when cell-membrane coated pits invaginate and pinch off. The outer surface of these vesicles are covered with a lattice-like network of coat proteins, such as clathrin, coat protein complex proteins, or caveolins. [NIH] Codon: A set of three nucleotides in a protein coding sequence that specifies individual amino acids or a termination signal (codon, terminator). Most codons are universal, but some organisms do not produce the transfer RNAs (RNA, transfer) complementary to all codons. These codons are referred to as unassigned codons (codons, nonsense). [NIH] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] Cognition: Intellectual or mental process whereby an organism becomes aware of or obtains knowledge. [NIH]

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Cohort Studies: Studies in which subsets of a defined population are identified. These groups may or may not be exposed to factors hypothesized to influence the probability of the occurrence of a particular disease or other outcome. Cohorts are defined populations which, as a whole, are followed in an attempt to determine distinguishing subgroup characteristics. [NIH] Colitis: Inflammation of the colon. [NIH] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline, hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [NIH] Colloidal: Of the nature of a colloid. [EU] Combinatorial: A cut-and-paste process that churns out thousands of potentially valuable compounds at once. [NIH] Commensal: 1. Living on or within another organism, and deriving benefit without injuring or benefiting the other individual. 2. An organism living on or within another, but not causing injury to the host. [EU] Communicable disease: A disease that can be transmitted by contact between persons. [NIH] Communication Disorders: Disorders of verbal and nonverbal communication caused by receptive or expressive language disorders, cognitive dysfunction (e.g., mental retardation), psychiatric conditions, and hearing disorders. [NIH] Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy,

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spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Conception: The onset of pregnancy, marked by implantation of the blastocyst; the formation of a viable zygote. [EU] Concomitant: Accompanying; accessory; joined with another. [EU] Cone: One of the special retinal receptor elements which are presumed to be primarily concerned with perception of light and color stimuli when the eye is adapted to light. [NIH] Confusion: A mental state characterized by bewilderment, emotional disturbance, lack of clear thinking, and perceptual disorientation. [NIH] Congestion: Excessive or abnormal accumulation of blood in a part. [EU] Congestive heart failure: Weakness of the heart muscle that leads to a buildup of fluid in body tissues. [NIH] Conjugated: Acting or operating as if joined; simultaneous. [EU] Conjugation: 1. The act of joining together or the state of being conjugated. 2. A sexual process seen in bacteria, ciliate protozoa, and certain fungi in which nuclear material is exchanged during the temporary fusion of two cells (conjugants). In bacterial genetics a form of sexual reproduction in which a donor bacterium (male) contributes some, or all, of its DNA (in the form of a replicated set) to a recipient (female) which then incorporates differing genetic information into its own chromosome by recombination and passes the recombined set on to its progeny by replication. In ciliate protozoa, two conjugants of separate mating types exchange micronuclear material and then separate, each now being a fertilized cell. In certain fungi, the process involves fusion of two gametes, resulting in union of their nuclei and formation of a zygote. 3. In chemistry, the joining together of two compounds to produce another compound, such as the combination of a toxic product with some substance in the body to form a detoxified product, which is then eliminated. [EU] Conjunctiva: The mucous membrane that lines the inner surface of the eyelids and the anterior part of the sclera. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Consciousness: Sense of awareness of self and of the environment. [NIH] Constipation: Infrequent or difficult evacuation of feces. [NIH] Constriction: The act of constricting. [NIH] Consumption: Pulmonary tuberculosis. [NIH] Contamination: The soiling or pollution by inferior material, as by the introduction of organisms into a wound, or sewage into a stream. [EU]

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Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] Contrast Sensitivity: The ability to detect sharp boundaries (stimuli) and to detect slight changes in luminance at regions without distinct contours. Psychophysical measurements of this visual function are used to evaluate visual acuity and to detect eye disease. [NIH] Control group: In a clinical trial, the group that does not receive the new treatment being studied. This group is compared to the group that receives the new treatment, to see if the new treatment works. [NIH] Convulsions: A general term referring to sudden and often violent motor activity of cerebral or brainstem origin. Convulsions may also occur in the absence of an electrical cerebral discharge (e.g., in response to hypotension). [NIH] Cornea: The transparent part of the eye that covers the iris and the pupil and allows light to enter the inside. [NIH] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary heart disease: A type of heart disease caused by narrowing of the coronary arteries that feed the heart, which needs a constant supply of oxygen and nutrients carried by the blood in the coronary arteries. When the coronary arteries become narrowed or clogged by fat and cholesterol deposits and cannot supply enough blood to the heart, CHD results. [NIH] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [EU] Corticosteroid: Any of the steroids elaborated by the adrenal cortex (excluding the sex hormones of adrenal origin) in response to the release of corticotrophin (adrenocorticotropic hormone) by the pituitary gland, to any of the synthetic equivalents of these steroids, or to angiotensin II. They are divided, according to their predominant biological activity, into three major groups: glucocorticoids, chiefly influencing carbohydrate, fat, and protein metabolism; mineralocorticoids, affecting the regulation of electrolyte and water balance; and C19 androgens. Some corticosteroids exhibit both types of activity in varying degrees, and others exert only one type of effect. The corticosteroids are used clinically for hormonal replacement therapy, for suppression of ACTH secretion by the anterior pituitary, as antineoplastic, antiallergic, and anti-inflammatory agents, and to suppress the immune response. Called also adrenocortical hormone and corticoid. [EU] Cortisol: A steroid hormone secreted by the adrenal cortex as part of the body's response to stress. [NIH] Coryza: Profuse discharge from the mucous membrane of the nose. [NIH] Cowpox: A mild, eruptive skin disease of milk cows caused by cowpox virus, with lesions occurring principally on the udder and teats. Human infection may occur while milking an infected animal. [NIH] Cowpox Virus: A species of orthopoxvirus that is the etiologic agent of cowpox. It is closely related to but antigenically different from vaccina virus. [NIH] Coxsackie virus: Group of viruses that is a common source of infection in kids. It is transmitted primarily by touch. The most common symptoms children experience are simply fever, feeling rundown, and a rash. [NIH]

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Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU] Craniocerebral Trauma: Traumatic injuries involving the cranium and intracranial structures (i.e., brain; cranial nerves; meninges; and other structures). Injuries may be classified by whether or not the skull is penetrated (i.e., penetrating vs. nonpenetrating) or whether there is an associated hemorrhage. [NIH] Crossing-over: The exchange of corresponding segments between chromatids of homologous chromosomes during meiosia, forming a chiasma. [NIH] Cross-Sectional Studies: Studies in which the presence or absence of disease or other health-related variables are determined in each member of the study population or in a representative sample at one particular time. This contrasts with longitudinal studies which are followed over a period of time. [NIH] Croup: A condition characterized by resonant barking cough, hoarseness and persistant stridor and caused by allergy, foreign body, infection, or neoplasm. It occurs chiefly in infants and children. [NIH] Cryoelectron Microscopy: Electron microscopy involving rapid freezing of the samples. The imaging of frozen-hydrated molecules and organelles permits the best possible resolution closest to the living state, free of chemical fixatives or stains. [NIH] Crystallization: The formation of crystals; conversion to a crystalline form. [EU] Cultured cells: Animal or human cells that are grown in the laboratory. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Cutaneous: Having to do with the skin. [NIH] Cyclic: Pertaining to or occurring in a cycle or cycles; the term is applied to chemical compounds that contain a ring of atoms in the nucleus. [EU] Cyst: A sac or capsule filled with fluid. [NIH] Cysteine: A thiol-containing non-essential amino acid that is oxidized to form cystine. [NIH] Cystine: A covalently linked dimeric nonessential amino acid formed by the oxidation of cysteine. Two molecules of cysteine are joined together by a disulfide bridge to form cystine. [NIH]

Cystitis: Inflammation of the urinary bladder. [EU] Cytarabine: An anticancer drug that belongs to the family of drugs called antimetabolites. [NIH]

Cytokine: Small but highly potent protein that modulates the activity of many cell types, including T and B cells. [NIH] Cytomegalovirus: A genus of the family Herpesviridae, subfamily Betaherpesvirinae, infecting the salivary glands, liver, spleen, lungs, eyes, and other organs, in which they produce characteristically enlarged cells with intranuclear inclusions. Infection with Cytomegalovirus is also seen as an opportunistic infection in AIDS. [NIH] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a continuous aqueous solution (cytosol) and the organelles and inclusions suspended in it (phaneroplasm), and is the site of most of the chemical activities of the cell. [EU] Cytoskeletal Proteins: Major constituent of the cytoskeleton found in the cytoplasm of eukaryotic cells. They form a flexible framework for the cell, provide attachment points for organelles and formed bodies, and make communication between parts of the cell possible. [NIH]

Cytoskeleton: The network of filaments, tubules, and interconnecting filamentous bridges

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which give shape, structure, and organization to the cytoplasm. [NIH] Cytotoxic: Cell-killing. [NIH] Cytotoxic chemotherapy: Anticancer drugs that kill cells, especially cancer cells. [NIH] Cytotoxicity: Quality of being capable of producing a specific toxic action upon cells of special organs. [NIH] Data Collection: Systematic gathering of data for a particular purpose from various sources, including questionnaires, interviews, observation, existing records, and electronic devices. The process is usually preliminary to statistical analysis of the data. [NIH] Databases, Bibliographic: Extensive collections, reputedly complete, of references and citations to books, articles, publications, etc., generally on a single subject or specialized subject area. Databases can operate through automated files, libraries, or computer disks. The concept should be differentiated from factual databases which is used for collections of data and facts apart from bibliographic references to them. [NIH] Death Certificates: Official records of individual deaths including the cause of death certified by a physician, and any other required identifying information. [NIH] Decarboxylation: The removal of a carboxyl group, usually in the form of carbon dioxide, from a chemical compound. [NIH] Defense Mechanisms: Unconscious process used by an individual or a group of individuals in order to cope with impulses, feelings or ideas which are not acceptable at their conscious level; various types include reaction formation, projection and self reversal. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Dehydration: The condition that results from excessive loss of body water. [NIH] Dehydroepiandrosterone: DHEA. A substance that is being studied as a cancer prevention drug. It belongs to the family of drugs called steroids. [NIH] Delavirdine: A potent, non-nucleoside reverse transcriptase inhibitor with activity specific for HIV-1. [NIH] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Delirium: (DSM III-R) an acute, reversible organic mental disorder characterized by reduced ability to maintain attention to external stimuli and disorganized thinking as manifested by rambling, irrelevant, or incoherent speech; there are also a reduced level of consciousness, sensory misperceptions, disturbance of the sleep-wakefulness cycle and level of psychomotor activity, disorientation to time, place, or person, and memory impairment. Delirium may be caused by a large number of conditions resulting in derangement of cerebral metabolism, including systemic infection, poisoning, drug intoxication or withdrawal, seizures or head trauma, and metabolic disturbances such as hypoxia, hypoglycaemia, fluid, electrolyte, or acid-base imbalances, or hepatic or renal failure. Called also acute confusional state and acute brain syndrome. [EU] Delivery of Health Care: The concept concerned with all aspects of providing and distributing health services to a patient population. [NIH] Dementia: An acquired organic mental disorder with loss of intellectual abilities of sufficient severity to interfere with social or occupational functioning. The dysfunction is multifaceted and involves memory, behavior, personality, judgment, attention, spatial relations, language, abstract thought, and other executive functions. The intellectual decline is usually progressive, and initially spares the level of consciousness. [NIH]

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Denaturation: Rupture of the hydrogen bonds by heating a DNA solution and then cooling it rapidly causes the two complementary strands to separate. [NIH] Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other neurons. [NIH] Dendritic: 1. Branched like a tree. 2. Pertaining to or possessing dendrites. [EU] Dendritic cell: A special type of antigen-presenting cell (APC) that activates T lymphocytes. [NIH]

Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] Dentifrices: Any preparations used for cleansing teeth; they usually contain an abrasive, detergent, binder and flavoring agent and may exist in the form of liquid, paste or powder; may also contain medicaments and caries preventives. [NIH] Deoxyribonucleic: A polymer of subunits called deoxyribonucleotides which is the primary genetic material of a cell, the material equivalent to genetic information. [NIH] Deoxyribonucleic acid: A polymer of subunits called deoxyribonucleotides which is the primary genetic material of a cell, the material equivalent to genetic information. [NIH] Deoxyribonucleotides: A purine or pyrimidine base bonded to a deoxyribose containing a bond to a phosphate group. [NIH] Depolarization: The process or act of neutralizing polarity. In neurophysiology, the reversal of the resting potential in excitable cell membranes when stimulated, i.e., the tendency of the cell membrane potential to become positive with respect to the potential outside the cell. [EU] Detergents: Purifying or cleansing agents, usually salts of long-chain aliphatic bases or acids, that exert cleansing (oil-dissolving) and antimicrobial effects through a surface action that depends on possessing both hydrophilic and hydrophobic properties. [NIH] Deuterium: Deuterium. The stable isotope of hydrogen. It has one neutron and one proton in the nucleus. [NIH] Dextran Sulfate: Long-chain polymer of glucose containing 17-20% sulfur. It has been used as an anticoagulant and also has been shown to inhibit the binding of HIV-1 to CD4+ Tlymphocytes. It is commonly used as both an experimental and clinical laboratory reagent and has been investigated for use as an antiviral agent, in the treatment of hypolipidemia, and for the prevention of free radical damage, among other applications. [NIH] Diabetes Mellitus: A heterogeneous group of disorders that share glucose intolerance in common. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Dialyzer: A part of the hemodialysis machine. (See hemodialysis under dialysis.) The dialyzer has two sections separated by a membrane. One section holds dialysate. The other holds the patient's blood. [NIH] Diaphragm: The musculofibrous partition that separates the thoracic cavity from the abdominal cavity. Contraction of the diaphragm increases the volume of the thoracic cavity aiding inspiration. [NIH] Diarrhea: Passage of excessively liquid or excessively frequent stools. [NIH] Diarrhoea: Abnormal frequency and liquidity of faecal discharges. [EU] Diffusion: The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself throughout the available space; a major mechanism of biological transport. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH]

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Digestive system: The organs that take in food and turn it into products that the body can use to stay healthy. Waste products the body cannot use leave the body through bowel movements. The digestive system includes the salivary glands, mouth, esophagus, stomach, liver, pancreas, gallbladder, small and large intestines, and rectum. [NIH] Digestive tract: The organs through which food passes when food is eaten. These organs are the mouth, esophagus, stomach, small and large intestines, and rectum. [NIH] Dihydrotestosterone: Anabolic agent. [NIH] Dihydroxy: AMPA/Kainate antagonist. [NIH] Dilatation: The act of dilating. [NIH] Diphtheria: A localized infection of mucous membranes or skin caused by toxigenic strains of Corynebacterium diphtheriae. It is characterized by the presence of a pseudomembrane at the site of infection. Diphtheria toxin, produced by C. diphtheriae, can cause myocarditis, polyneuritis, and other systemic toxic effects. [NIH] Diploid: Having two sets of chromosomes. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Discrimination: The act of qualitative and/or quantitative differentiation between two or more stimuli. [NIH] Disease Progression: The worsening of a disease over time. This concept is most often used for chronic and incurable diseases where the stage of the disease is an important determinant of therapy and prognosis. [NIH] Disease Susceptibility: A constitution or condition of the body which makes the tissues react in special ways to certain extrinsic stimuli and thus tends to make the individual more than usually susceptible to certain diseases. [NIH] Disinfection: Rendering pathogens harmless through the use of heat, antiseptics, antibacterial agents, etc. [NIH] Disorientation: The loss of proper bearings, or a state of mental confusion as to time, place, or identity. [EU] Dissociation: 1. The act of separating or state of being separated. 2. The separation of a molecule into two or more fragments (atoms, molecules, ions, or free radicals) produced by the absorption of light or thermal energy or by solvation. 3. In psychology, a defense mechanism in which a group of mental processes are segregated from the rest of a person's mental activity in order to avoid emotional distress, as in the dissociative disorders (q.v.), or in which an idea or object is segregated from its emotional significance; in the first sense it is roughly equivalent to splitting, in the second, to isolation. 4. A defect of mental integration in which one or more groups of mental processes become separated off from normal consciousness and, thus separated, function as a unitary whole. [EU] Diuresis: Increased excretion of urine. [EU] Diverticula: Plural form of diverticulum. [NIH] Diverticulitis: Inflammation of a diverticulum or diverticula. [NIH] Diverticulum: A pathological condition manifested as a pouch or sac opening from a tubular or sacular organ. [NIH] Dizziness: An imprecise term which may refer to a sense of spatial disorientation, motion of the environment, or lightheadedness. [NIH] Dominance: In genetics, the full phenotypic expression of a gene in both heterozygotes and homozygotes. [EU]

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Dopa: The racemic or DL form of DOPA, an amino acid found in various legumes. The dextro form has little physiologic activity but the levo form (levodopa) is a very important physiologic mediator and precursor and pharmacological agent. [NIH] Dopamine: An endogenous catecholamine and prominent neurotransmitter in several systems of the brain. In the synthesis of catecholamines from tyrosine, it is the immediate precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of dopaminergic receptor subtypes mediate its action. Dopamine is used pharmacologically for its direct (beta adrenergic agonist) and indirect (adrenergic releasing) sympathomimetic effects including its actions as an inotropic agent and as a renal vasodilator. [NIH] Dosage Forms: Completed forms of the pharmaceutical preparation in which prescribed doses of medication are included. They are designed to resist action by gastric fluids, prevent vomiting and nausea, reduce or alleviate the undesirable taste and smells associated with oral administration, achieve a high concentration of drug at target site, or produce a delayed or long-acting drug effect. They include capsules, liniments, ointments, pharmaceutical solutions, powders, tablets, etc. [NIH] Dose-dependent: Refers to the effects of treatment with a drug. If the effects change when the dose of the drug is changed, the effects are said to be dose dependent. [NIH] Doxycycline: A synthetic tetracycline derivative with a range of antimicrobial activity and mode of action similar to that of tetracycline, but more effective against many species. Animal studies suggest that it may cause less tooth staining than other tetracyclines. [NIH] Drive: A state of internal activity of an organism that is a necessary condition before a given stimulus will elicit a class of responses; e.g., a certain level of hunger (drive) must be present before food will elicit an eating response. [NIH] Dross: Residue remaining in an opium pipe which has been smoked; contains 50 % of the morphine present in the original drug. [NIH] Drug Design: The molecular designing of drugs for specific purposes (such as DNAbinding, enzyme inhibition, anti-cancer efficacy, etc.) based on knowledge of molecular properties such as activity of functional groups, molecular geometry, and electronic structure, and also on information cataloged on analogous molecules. Drug design is generally computer-assisted molecular modeling and does not include pharmacokinetics, dosage analysis, or drug administration analysis. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Drug Tolerance: Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from drug resistance wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from maximum tolerated dose and no-observed-adverse-effect level. [NIH] Duodenum: The first part of the small intestine. [NIH] Dura mater: The outermost, toughest, and most fibrous of the three membranes (meninges) covering the brain and spinal cord; called also pachymeninx. [EU] Dyes: Chemical substances that are used to stain and color other materials. The coloring may or may not be permanent. Dyes can also be used as therapeutic agents and test reagents in medicine and scientific research. [NIH] Dyspepsia: Impaired digestion, especially after eating. [NIH] Edema: Excessive amount of watery fluid accumulated in the intercellular spaces, most

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commonly present in subcutaneous tissue. [NIH] Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [NIH] Effector cell: A cell that performs a specific function in response to a stimulus; usually used to describe cells in the immune system. [NIH] Efficacy: The extent to which a specific intervention, procedure, regimen, or service produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is based on the results of a randomized control trial. [NIH] Elastin: The protein that gives flexibility to tissues. [NIH] Elective: Subject to the choice or decision of the patient or physician; applied to procedures that are advantageous to the patient but not urgent. [EU] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electrons: Stable elementary particles having the smallest known negative charge, present in all elements; also called negatrons. Positively charged electrons are called positrons. The numbers, energies and arrangement of electrons around atomic nuclei determine the chemical identities of elements. Beams of electrons are called cathode rays or beta rays, the latter being a high-energy biproduct of nuclear decay. [NIH] Electrophoresis: An electrochemical process in which macromolecules or colloidal particles with a net electric charge migrate in a solution under the influence of an electric current. [NIH]

Emaciation: Clinical manifestation of excessive leanness usually caused by disease or a lack of nutrition. [NIH] Embolus: Bit of foreign matter which enters the blood stream at one point and is carried until it is lodged or impacted in an artery and obstructs it. It may be a blood clot, an air bubble, fat or other tissue, or clumps of bacteria. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Emollient: Softening or soothing; called also malactic. [EU] Emphysema: A pathological accumulation of air in tissues or organs. [NIH] Emulsion: A preparation of one liquid distributed in small globules throughout the body of a second liquid. The dispersed liquid is the discontinuous phase, and the dispersion medium is the continuous phase. When oil is the dispersed liquid and an aqueous solution is the continuous phase, it is known as an oil-in-water emulsion, whereas when water or aqueous solution is the dispersed phase and oil or oleaginous substance is the continuous phase, it is known as a water-in-oil emulsion. Pharmaceutical emulsions for which official standards have been promulgated include cod liver oil emulsion, cod liver oil emulsion with malt, liquid petrolatum emulsion, and phenolphthalein in liquid petrolatum emulsion. [EU] Encapsulated: Confined to a specific, localized area and surrounded by a thin layer of tissue. [NIH]

Encephalitis: Inflammation of the brain due to infection, autoimmune processes, toxins, and other conditions. Viral infections (see encephalitis, viral) are a relatively frequent cause of this condition. [NIH] Encephalitis, Viral: Inflammation of brain parenchymal tissue as a result of viral infection. Encephalitis may occur as primary or secondary manifestation of Togaviridae infections; Herpesviridae infections; Adenoviridae infections; Flaviviridae infections; Bunyaviridae infections; Picornaviridae infections; Paramyxoviridae infections; Orthomyxoviridae

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infections; Retroviridae infections; and Arenaviridae infections. [NIH] Encephalopathy: A disorder of the brain that can be caused by disease, injury, drugs, or chemicals. [NIH] Endemic: Present or usually prevalent in a population or geographical area at all times; said of a disease or agent. Called also endemial. [EU] Endocrine System: The system of glands that release their secretions (hormones) directly into the circulatory system. In addition to the endocrine glands, included are the chromaffin system and the neurosecretory systems. [NIH] Endocytosis: Cellular uptake of extracellular materials within membrane-limited vacuoles or microvesicles. Endosomes play a central role in endocytosis. [NIH] Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart. [NIH] Endothelium: A layer of epithelium that lines the heart, blood vessels (endothelium, vascular), lymph vessels (endothelium, lymphatic), and the serous cavities of the body. [NIH] Endothelium-derived: Small molecule that diffuses to the adjacent muscle layer and relaxes it. [NIH] Endotoxic: Of, relating to, or acting as an endotoxin (= a heat-stable toxin, associated with the outer membranes of certain gram-negative bacteria. Endotoxins are not secreted and are released only when the cells are disrupted). [EU] Endotoxin: Toxin from cell walls of bacteria. [NIH] Energy balance: Energy is the capacity of a body or a physical system for doing work. Energy balance is the state in which the total energy intake equals total energy needs. [NIH] Enhancer: Transcriptional element in the virus genome. [NIH] Environmental Exposure: The exposure to potentially harmful chemical, physical, or biological agents in the environment or to environmental factors that may include ionizing radiation, pathogenic organisms, or toxic chemicals. [NIH] Environmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health. [NIH]

Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Eosinophilia: Abnormal increase in eosinophils in the blood, tissues or organs. [NIH] Ephedrine: An alpha- and beta-adrenergic agonist that may also enhance release of norepinephrine. It has been used in the treatment of several disorders including asthma, heart failure, rhinitis, and urinary incontinence, and for its central nervous system stimulatory effects in the treatment of narcolepsy and depression. It has become less extensively used with the advent of more selective agonists. [NIH] Epidemic: Occurring suddenly in numbers clearly in excess of normal expectancy; said especially of infectious diseases but applied also to any disease, injury, or other healthrelated event occurring in such outbreaks. [EU] Epidemiologic Studies: Studies designed to examine associations, commonly, hypothesized causal relations. They are usually concerned with identifying or measuring the effects of risk factors or exposures. The common types of analytic study are case-control studies, cohort studies, and cross-sectional studies. [NIH] Epidemiological: Relating to, or involving epidemiology. [EU]

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Epidermal: Pertaining to or resembling epidermis. Called also epidermic or epidermoid. [EU] Epidermis: Nonvascular layer of the skin. It is made up, from within outward, of five layers: 1) basal layer (stratum basale epidermidis); 2) spinous layer (stratum spinosum epidermidis); 3) granular layer (stratum granulosum epidermidis); 4) clear layer (stratum lucidum epidermidis); and 5) horny layer (stratum corneum epidermidis). [NIH] Epigastric: Having to do with the upper middle area of the abdomen. [NIH] Epinephrine: The active sympathomimetic hormone from the adrenal medulla in most species. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. It is used in asthma and cardiac failure and to delay absorption of local anesthetics. [NIH] Epithelial: Refers to the cells that line the internal and external surfaces of the body. [NIH] Epithelial Cells: Cells that line the inner and outer surfaces of the body. [NIH] Epithelium: One or more layers of epithelial cells, supported by the basal lamina, which covers the inner or outer surfaces of the body. [NIH] Epitope: A molecule or portion of a molecule capable of binding to the combining site of an antibody. For every given antigenic determinant, the body can construct a variety of antibody-combining sites, some of which fit almost perfectly, and others which barely fit. [NIH]

Epizootic: A disease of high morbidity which is only occasionally present in an animal community: it affects a great number of animals in a large area of land at the same time and spreads with great rapidity over a wide territory. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]

Ethanol: A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in alcoholic beverages. [NIH] Ether: One of a class of organic compounds in which any two organic radicals are attached directly to a single oxygen atom. [NIH] Ethmoid: An unpaired cranial bone which helps form the medial walls of the orbits and contains the themoidal air cells which drain into the nose. [NIH] Ethnic Groups: A group of people with a common cultural heritage that sets them apart from others in a variety of social relationships. [NIH] Ethylene Glycol: A colorless, odorless, viscous dihydroxy alcohol. It has a sweet taste, but is poisonous if ingested. Ethylene glycol is the most important glycol commercially available and is manufactured on a large scale in the United States. It is used as an antifreeze and coolant, in hydraulic fluids, and in the manufacture of low-freezing dynamites and resins. [NIH]

Eucalyptus: A genus of Australian trees of the Myrtaceae family that yields gums, oils, and resins which are used as flavoring agents, astringents, and aromatics, and formerly to treat diarrhea, asthma, bronchitis, and respiratory tract infections. [NIH] Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH]

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Evacuation: An emptying, as of the bowels. [EU] Evoke: The electric response recorded from the cerebral cortex after stimulation of a peripheral sense organ. [NIH] Excitation: An act of irritation or stimulation or of responding to a stimulus; the addition of energy, as the excitation of a molecule by absorption of photons. [EU] Exhaustion: The feeling of weariness of mind and body. [NIH] Exocrine: Secreting outwardly, via a duct. [EU] Exocytosis: Cellular release of material within membrane-limited vesicles by fusion of the vesicles with the cell membrane. [NIH] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Exotoxin: Toxic substance excreted by living bacterial cells. [NIH] Expeditions: Usually refers to planned scientific data-gathering excursions. [NIH] External-beam radiation: Radiation therapy that uses a machine to aim high-energy rays at the cancer. Also called external radiation. [NIH] Extracellular: Outside a cell or cells. [EU] Extracellular Matrix: A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. [NIH] Extraction: The process or act of pulling or drawing out. [EU] Extrapyramidal: Outside of the pyramidal tracts. [EU] Extremity: A limb; an arm or leg (membrum); sometimes applied specifically to a hand or foot. [EU] Eye Infections: Infection, moderate to severe, caused by bacteria, fungi, or viruses, which occurs either on the external surface of the eye or intraocularly with probable inflammation, visual impairment, or blindness. [NIH] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Fasciitis: Inflammation of the fascia. There are three major types: 1) Eosinophilic fasciitis, an inflammatory reaction with eosinophilia, producing hard thickened skin with an orangepeel configuration suggestive of scleroderma and considered by some a variant of scleroderma; 2) Necrotizing fasciitis, a serious fulminating infection (usually by a beta hemolytic Streptococcus) causing extensive necrosis of superficial fascia; 3) Nodular/Pseudosarcomatous/Proliferative fasciitis, characterized by a rapid growth of fibroblasts with mononuclear inflammatory cells and proliferating capillaries in soft tissue, often the forearm; it is not malignant but is sometimes mistaken for fibrosarcoma. [NIH] Fat: Total lipids including phospholipids. [NIH] Fatal Outcome: Death resulting from the presence of a disease in an individual, as shown by a single case report or a limited number of patients. This should be differentiated from death, the physiological cessation of life and from mortality, an epidemiological or statistical concept. [NIH] Fatigue: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. [NIH]

Fatty acids: A major component of fats that are used by the body for energy and tissue

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development. [NIH] Feces: The excrement discharged from the intestines, consisting of bacteria, cells exfoliated from the intestines, secretions, chiefly of the liver, and a small amount of food residue. [EU] Fermentation: An enzyme-induced chemical change in organic compounds that takes place in the absence of oxygen. The change usually results in the production of ethanol or lactic acid, and the production of energy. [NIH] Ferrets: Semidomesticated variety of European polecat much used for hunting rodents and/or rabbits and as a laboratory animal. [NIH] Fetal Development: Morphologic and physiologic growth and development of the mammalian embryo or fetus. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fibrinogen: Plasma glycoprotein clotted by thrombin, composed of a dimer of three nonidentical pairs of polypeptide chains (alpha, beta, gamma) held together by disulfide bonds. Fibrinogen clotting is a sol-gel change involving complex molecular arrangements: whereas fibrinogen is cleaved by thrombin to form polypeptides A and B, the proteolytic action of other enzymes yields different fibrinogen degradation products. [NIH] Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [NIH] Fibrosarcoma: A type of soft tissue sarcoma that begins in fibrous tissue, which holds bones, muscles, and other organs in place. [NIH] Filtration: The passage of a liquid through a filter, accomplished by gravity, pressure, or vacuum (suction). [EU] Firearms: Small-arms weapons, including handguns, pistols, revolvers, rifles, shotguns, etc. [NIH]

Fixation: 1. The act or operation of holding, suturing, or fastening in a fixed position. 2. The condition of being held in a fixed position. 3. In psychiatry, a term with two related but distinct meanings : (1) arrest of development at a particular stage, which like regression (return to an earlier stage), if temporary is a normal reaction to setbacks and difficulties but if protracted or frequent is a cause of developmental failures and emotional problems, and (2) a close and suffocating attachment to another person, especially a childhood figure, such as one's mother or father. Both meanings are derived from psychoanalytic theory and refer to 'fixation' of libidinal energy either in a specific erogenous zone, hence fixation at the oral, anal, or phallic stage, or in a specific object, hence mother or father fixation. 4. The use of a fixative (q.v.) to preserve histological or cytological specimens. 5. In chemistry, the process whereby a substance is removed from the gaseous or solution phase and localized, as in carbon dioxide fixation or nitrogen fixation. 6. In ophthalmology, direction of the gaze so that the visual image of the object falls on the fovea centralis. 7. In film processing, the chemical removal of all undeveloped salts of the film emulsion, leaving only the developed silver to form a permanent image. [EU] Fixatives: Agents employed in the preparation of histologic or pathologic specimens for the purpose of maintaining the existing form and structure of all of the constituent elements. Great numbers of different agents are used; some are also decalcifying and hardening agents. They must quickly kill and coagulate living tissue. [NIH] Flavoring Agents: Substances added to foods and medicine to improve the quality of taste. [NIH]

Flow Cytometry: Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of

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interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake. [NIH] Fluorescence: The property of emitting radiation while being irradiated. The radiation emitted is usually of longer wavelength than that incident or absorbed, e.g., a substance can be irradiated with invisible radiation and emit visible light. X-ray fluorescence is used in diagnosis. [NIH] Fluorescent Dyes: Dyes that emit light when exposed to light. The wave length of the emitted light is usually longer than that of the incident light. Fluorochromes are substances that cause fluorescence in other substances, i.e., dyes used to mark or label other compounds with fluorescent tags. They are used as markers in biochemistry and immunology. [NIH] Focus Groups: A method of data collection and a qualitative research tool in which a small group of individuals are brought together and allowed to interact in a discussion of their opinions about topics, issues, or questions. [NIH] Fold: A plication or doubling of various parts of the body. [NIH] Forearm: The part between the elbow and the wrist. [NIH] Fovea: The central part of the macula that provides the sharpest vision. [NIH] Fractionation: Dividing the total dose of radiation therapy into several smaller, equal doses delivered over a period of several days. [NIH] Fructose: A type of sugar found in many fruits and vegetables and in honey. Fructose is used to sweeten some diet foods. It is considered a nutritive sweetener because it has calories. [NIH] Fungi: A kingdom of eukaryotic, heterotrophic organisms that live as saprobes or parasites, including mushrooms, yeasts, smuts, molds, etc. They reproduce either sexually or asexually, and have life cycles that range from simple to complex. Filamentous fungi refer to those that grow as multicelluar colonies (mushrooms and molds). [NIH] Fungus: A general term used to denote a group of eukaryotic protists, including mushrooms, yeasts, rusts, moulds, smuts, etc., which are characterized by the absence of chlorophyll and by the presence of a rigid cell wall composed of chitin, mannans, and sometimes cellulose. They are usually of simple morphological form or show some reversible cellular specialization, such as the formation of pseudoparenchymatous tissue in the fruiting body of a mushroom. The dimorphic fungi grow, according to environmental conditions, as moulds or yeasts. [EU] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Gamma Rays: Very powerful and penetrating, high-energy electromagnetic radiation of shorter wavelength than that of x-rays. They are emitted by a decaying nucleus, usually between 0.01 and 10 MeV. They are also called nuclear x-rays. [NIH] Ganglion: 1. A knot, or knotlike mass. 2. A general term for a group of nerve cell bodies located outside the central nervous system; occasionally applied to certain nuclear groups within the brain or spinal cord, e.g. basal ganglia. 3. A benign cystic tumour occurring on a aponeurosis or tendon, as in the wrist or dorsum of the foot; it consists of a thin fibrous capsule enclosing a clear mucinous fluid. [EU] Gangrene: Death and putrefaction of tissue usually due to a loss of blood supply. [NIH]

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Gangrenous: A circumscribed, deep-seated, suppurative inflammation of the subcutaneous tissue of the eyelid discharging pus from several points. [NIH] Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] Gas exchange: Primary function of the lungs; transfer of oxygen from inhaled air into the blood and of carbon dioxide from the blood into the lungs. [NIH] Gastric: Having to do with the stomach. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]

Gastritis: Inflammation of the stomach. [EU] Gastroenteritis: An acute inflammation of the lining of the stomach and intestines, characterized by anorexia, nausea, diarrhoea, abdominal pain, and weakness, which has various causes, including food poisoning due to infection with such organisms as Escherichia coli, Staphylococcus aureus, and Salmonella species; consumption of irritating food or drink; or psychological factors such as anger, stress, and fear. Called also enterogastritis. [EU] Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] Gelatin: A product formed from skin, white connective tissue, or bone collagen. It is used as a protein food adjuvant, plasma substitute, hemostatic, suspending agent in pharmaceutical preparations, and in the manufacturing of capsules and suppositories. [NIH] Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]

Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Gene Pool: The total genetic information possessed by the reproductive members of a population of sexually reproducing organisms. [NIH] General practitioner: A medical practitioner who does not specialize in a particular branch of medicine or limit his practice to a specific class of diseases. [NIH] Genetic Code: The specifications for how information, stored in nucleic acid sequence (base sequence), is translated into protein sequence (amino acid sequence). The start, stop, and order of amino acids of a protein is specified by consecutive triplets of nucleotides called codons (codon). [NIH] Genetic Engineering: Directed modification of the gene complement of a living organism by such techniques as altering the DNA, substituting genetic material by means of a virus, transplanting whole nuclei, transplanting cell hybrids, etc. [NIH] Genetic Screening: Searching a population or individuals for persons possessing certain genotypes or karyotypes that: (1) are already associated with disease or predispose to disease; (2) may lead to disease in their descendants; or (3) produce other variations not known to be associated with disease. Genetic screening may be directed toward identifying phenotypic expression of genetic traits. It includes prenatal genetic screening. [NIH] Genetic testing: Analyzing DNA to look for a genetic alteration that may indicate an increased risk for developing a specific disease or disorder. [NIH] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH]

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Genital: Pertaining to the genitalia. [EU] Genitourinary: Pertaining to the genital and urinary organs; urogenital; urinosexual. [EU] Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Giardiasis: An infection of the small intestine caused by the flagellated protozoan Giardia lamblia. It is spread via contaminated food and water and by direct person-to-person contact. [NIH] Ginseng: An araliaceous genus of plants that contains a number of pharmacologically active agents used as stimulants, sedatives, and tonics, especially in traditional medicine. [NIH] Gland: An organ that produces and releases one or more substances for use in the body. Some glands produce fluids that affect tissues or organs. Others produce hormones or participate in blood production. [NIH] Glial Fibrillary Acidic Protein: An intermediate filament protein found only in glial cells or cells of glial origin. MW 51,000. [NIH] Glioma: A cancer of the brain that comes from glial, or supportive, cells. [NIH] Glomerular: Pertaining to or of the nature of a glomerulus, especially a renal glomerulus. [EU]

Glomeruli: Plural of glomerulus. [NIH] Glomerulonephritis: Glomerular disease characterized by an inflammatory reaction, with leukocyte infiltration and cellular proliferation of the glomeruli, or that appears to be the result of immune glomerular injury. [NIH] Glomerulus: A tiny set of looping blood vessels in the nephron where blood is filtered in the kidney. [NIH] Glottis: The vocal apparatus of the larynx, consisting of the true vocal cords (plica vocalis) and the opening between them (rima glottidis). [NIH] Glucocorticoids: A group of corticosteroids that affect carbohydrate metabolism (gluconeogenesis, liver glycogen deposition, elevation of blood sugar), inhibit corticotropin secretion, and possess pronounced anti-inflammatory activity. They also play a role in fat and protein metabolism, maintenance of arterial blood pressure, alteration of the connective tissue response to injury, reduction in the number of circulating lymphocytes, and functioning of the central nervous system. [NIH] Glucose: D-Glucose. A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. [NIH] Glucose Intolerance: A pathological state in which the fasting plasma glucose level is less than 140 mg per deciliter and the 30-, 60-, or 90-minute plasma glucose concentration following a glucose tolerance test exceeds 200 mg per deciliter. This condition is seen frequently in diabetes mellitus but also occurs with other diseases. [NIH] Glucuronic Acid: Derivatives of uronic acid found throughout the plant and animal kingdoms. They detoxify drugs and toxins by conjugating with them to form glucuronides in the liver which are more water-soluble metabolites that can be easily eliminated from the body. [NIH] Glucuronides: Glycosides of glucuronic acid formed by the reaction of uridine diphosphate glucuronic acid with certain endogenous and exogenous substances. Their formation is important for the detoxification of drugs, steroid excretion and bilirubin metabolism to a more water-soluble compound that can be eliminated in the urine and bile. [NIH] Gluten: The protein of wheat and other grains which gives to the dough its tough elastic

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character. [EU] Glycerol: A trihydroxy sugar alcohol that is an intermediate in carbohydrate and lipid metabolism. It is used as a solvent, emollient, pharmaceutical agent, and sweetening agent. [NIH]

Glycerophospholipids: Derivatives of phosphatidic acid in which the hydrophobic regions are composed of two fatty acids and a polar alcohol is joined to the C-3 position of glycerol through a phosphodiester bond. They are named according to their polar head groups, such as phosphatidylcholine and phosphatidylethanolamine. [NIH] Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Glycosidic: Formed by elimination of water between the anomeric hydroxyl of one sugar and a hydroxyl of another sugar molecule. [NIH] Glycosylation: The chemical or biochemical addition of carbohydrate or glycosyl groups to other chemicals, especially peptides or proteins. Glycosyl transferases are used in this biochemical reaction. [NIH] Goats: Any of numerous agile, hollow-horned ruminants of the genus Capra, closely related to the sheep. [NIH] Gonorrhea: Acute infectious disease characterized by primary invasion of the urogenital tract. The etiologic agent, Neisseria gonorrhoeae, was isolated by Neisser in 1879. [NIH] Gout: Hereditary metabolic disorder characterized by recurrent acute arthritis, hyperuricemia and deposition of sodium urate in and around the joints, sometimes with formation of uric acid calculi. [NIH] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Gp120: 120-kD HIV envelope glycoprotein which is involved in the binding of the virus to its membrane receptor, the CD4 molecule, found on the surface of certain cells in the body. [NIH]

Grade: The grade of a tumor depends on how abnormal the cancer cells look under a microscope and how quickly the tumor is likely to grow and spread. Grading systems are different for each type of cancer. [NIH] Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to replace diseased or injured tissue removed from another part of the body. [NIH] Graft Rejection: An immune response with both cellular and humoral components, directed against an allogeneic transplant, whose tissue antigens are not compatible with those of the recipient. [NIH] Graft Survival: The survival of a graft in a host, the factors responsible for the survival and the changes occurring within the graft during growth in the host. [NIH] Gram-negative: Losing the stain or decolorized by alcohol in Gram's method of staining, a primary characteristic of bacteria having a cell wall composed of a thin layer of peptidoglycan covered by an outer membrane of lipoprotein and lipopolysaccharide. [EU] Gram-Negative Bacteria: Bacteria which lose crystal violet stain but are stained pink when treated by Gram's method. [NIH] Gram-positive: Retaining the stain or resisting decolorization by alcohol in Gram's method of staining, a primary characteristic of bacteria whose cell wall is composed of a thick layer of peptidologlycan with attached teichoic acids. [EU] Granule: A small pill made from sucrose. [EU] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into

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three groups: neutrophils, eosinophils, and basophils. [NIH] Granulocytopenia: A deficiency in the number of granulocytes, a type of white blood cell. [NIH]

Granuloma: A relatively small nodular inflammatory lesion containing grouped mononuclear phagocytes, caused by infectious and noninfectious agents. [NIH] Growth: The progressive development of a living being or part of an organism from its earliest stage to maturity. [NIH] Growth factors: Substances made by the body that function to regulate cell division and cell survival. Some growth factors are also produced in the laboratory and used in biological therapy. [NIH] Guanylate Cyclase: An enzyme that catalyzes the conversion of GTP to 3',5'-cyclic GMP and pyrophosphate. It also acts on ITP and dGTP. (From Enzyme Nomenclature, 1992) EC 4.6.1.2. [NIH] Guinea Pigs: A common name used for the family Caviidae. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research. [NIH]

Habitat: An area considered in terms of its environment, particularly as this determines the type and quality of the vegetation the area can carry. [NIH] Habitual: Of the nature of a habit; according to habit; established by or repeated by force of habit, customary. [EU] Hair follicles: Shafts or openings on the surface of the skin through which hair grows. [NIH] Half-Life: The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity. [NIH] Halitosis: An offensive, foul breath odor resulting from a variety of causes such as poor oral hygiene, dental or oral infections, or the ingestion of certain foods. [NIH] Handwashing: The act of cleansing the hands with water or other liquid, with or without the inclusion of soap or other detergent, for the purpose of removing soil or microorganisms. [NIH] Haploid: An organism with one basic chromosome set, symbolized by n; the normal condition of gametes in diploids. [NIH] Haptens: Small antigenic determinants capable of eliciting an immune response only when coupled to a carrier. Haptens bind to antibodies but by themselves cannot elicit an antibody response. [NIH] Headache: Pain in the cranial region that may occur as an isolated and benign symptom or as a manifestation of a wide variety of conditions including subarachnoid hemorrhage; craniocerebral trauma; central nervous system infections; intracranial hypertension; and other disorders. In general, recurrent headaches that are not associated with a primary disease process are referred to as headache disorders (e.g., migraine). [NIH] Headache Disorders: Common conditions characterized by persistent or recurrent headaches. Headache syndrome classification systems may be based on etiology (e.g., vascular headache, post-traumatic headaches, etc.), temporal pattern (e.g., cluster headache, paroxysmal hemicrania, etc.), and precipitating factors (e.g., cough headache). [NIH] Health Care Costs: The actual costs of providing services related to the delivery of health care, including the costs of procedures, therapies, and medications. It is differentiated from health expenditures, which refers to the amount of money paid for the services, and from fees, which refers to the amount charged, regardless of cost. [NIH]

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Health Expenditures: The amounts spent by individuals, groups, nations, or private or public organizations for total health care and/or its various components. These amounts may or may not be equivalent to the actual costs (health care costs) and may or may not be shared among the patient, insurers, and/or employers. [NIH] Health Status: The level of health of the individual, group, or population as subjectively assessed by the individual or by more objective measures. [NIH] Hearing Disorders: Conditions that impair the transmission or perception of auditory impulses and information from the level of the ear to the temporal cortices, including the sensorineural pathways. [NIH] Heart attack: A seizure of weak or abnormal functioning of the heart. [NIH] Heart failure: Loss of pumping ability by the heart, often accompanied by fatigue, breathlessness, and excess fluid accumulation in body tissues. [NIH] Heartbeat: One complete contraction of the heart. [NIH] Heartburn: Substernal pain or burning sensation, usually associated with regurgitation of gastric juice into the esophagus. [NIH] Hemagglutinins: Agents that cause agglutination of red blood cells. They include antibodies, blood group antigens, lectins, autoimmune factors, bacterial, viral, or parasitic blood agglutinins, etc. [NIH] Hematologic malignancies: Cancers of the blood or bone marrow, including leukemia and lymphoma. Also called hematologic cancers. [NIH] Hematopoietic growth factors: A group of proteins that cause blood cells to grow and mature. [NIH] Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. [NIH] Hemodialysis: The use of a machine to clean wastes from the blood after the kidneys have failed. The blood travels through tubes to a dialyzer, which removes wastes and extra fluid. The cleaned blood then flows through another set of tubes back into the body. [NIH] Hemoglobin: One of the fractions of glycosylated hemoglobin A1c. Glycosylated hemoglobin is formed when linkages of glucose and related monosaccharides bind to hemoglobin A and its concentration represents the average blood glucose level over the previous several weeks. HbA1c levels are used as a measure of long-term control of plasma glucose (normal, 4 to 6 percent). In controlled diabetes mellitus, the concentration of glycosylated hemoglobin A is within the normal range, but in uncontrolled cases the level may be 3 to 4 times the normal conentration. Generally, complications are substantially lower among patients with Hb levels of 7 percent or less than in patients with HbA1c levels of 9 percent or more. [NIH] Hemolytic: A disease that affects the blood and blood vessels. It destroys red blood cells, cells that cause the blood to clot, and the lining of blood vessels. HUS is often caused by the Escherichia coli bacterium in contaminated food. People with HUS may develop acute renal failure. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hepadnaviridae: A family of hepatotropic DNA viruses which contains double-stranded DNA genomes and causes hepatitis in humans and animals. There are two genera: Avihepadnavirus and Orthohepadnavirus. Hepadnaviruses include hepatitis B virus, duck hepatitis B virus, heron hepatitis B virus, ground squirrel hepatitis virus, and woodchuck hepatitis B virus. [NIH]

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Hepatic: Refers to the liver. [NIH] Hepatitis: Inflammation of the liver and liver disease involving degenerative or necrotic alterations of hepatocytes. [NIH] Hepatocytes: The main structural component of the liver. They are specialized epithelial cells that are organized into interconnected plates called lobules. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Herpes: Any inflammatory skin disease caused by a herpesvirus and characterized by the formation of clusters of small vesicles. When used alone, the term may refer to herpes simplex or to herpes zoster. [EU] Herpes virus: A member of the herpes family of viruses. [NIH] Herpes Zoster: Acute vesicular inflammation. [NIH] Heterogeneity: The property of one or more samples or populations which implies that they are not identical in respect of some or all of their parameters, e. g. heterogeneity of variance. [NIH]

Heterotrophic: Pertaining to organisms that are consumers and dependent on other organisms for their source of energy (food). [NIH] Heterozygotes: Having unlike alleles at one or more corresponding loci on homologous chromosomes. [NIH] Hiatal Hernia: A small opening in the diaphragm that allows the upper part of the stomach to move up into the chest. Causes heartburn from stomach acid flowing back up through the opening. [NIH] Histamine: 1H-Imidazole-4-ethanamine. A depressor amine derived by enzymatic decarboxylation of histidine. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter. [NIH] Histamine Release: The secretion of histamine from mast cell and basophil granules by exocytosis. This can be initiated by a number of factors, all of which involve binding of IgE, cross-linked by antigen, to the mast cell or basophil's Fc receptors. Once released, histamine binds to a number of different target cell receptors and exerts a wide variety of effects. [NIH] Histidine: An essential amino acid important in a number of metabolic processes. It is required for the production of histamine. [NIH] Histology: The study of tissues and cells under a microscope. [NIH] Hoarseness: An unnaturally deep or rough quality of voice. [NIH] Homodimer: Protein-binding "activation domains" always combine with identical proteins. [NIH]

Homogeneous: Consisting of or composed of similar elements or ingredients; of a uniform quality throughout. [EU] Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] Homozygotes: An individual having a homozygous gene pair. [NIH] Hormonal: Pertaining to or of the nature of a hormone. [EU] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Hormone Replacement Therapy: Therapeutic use of hormones to alleviate the effects of

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hormone deficiency. [NIH] Host: Any animal that receives a transplanted graft. [NIH] Host-cell: A cell whose metabolism is used for the growth and reproduction of a virus. [NIH] Human growth hormone: A protein hormone, secreted by the anterior lobe of the pituitary, which promotes growth of the whole body by stimulating protein synthesis. The human gene has already been cloned and successfully expressed in bacteria. [NIH] Human papillomavirus: HPV. A virus that causes abnormal tissue growth (warts) and is often associated with some types of cancer. [NIH] Humoral: Of, relating to, proceeding from, or involving a bodily humour - now often used of endocrine factors as opposed to neural or somatic. [EU] Humour: 1. A normal functioning fluid or semifluid of the body (as the blood, lymph or bile) especially of vertebrates. 2. A secretion that is itself an excitant of activity (as certain hormones). [EU] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [NIH] Hybridization: The genetic process of crossbreeding to produce a hybrid. Hybrid nucleic acids can be formed by nucleic acid hybridization of DNA and RNA molecules. Protein hybridization allows for hybrid proteins to be formed from polypeptide chains. [NIH] Hydralazine: A direct-acting vasodilator that is used as an antihypertensive agent. [NIH] Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H, atomic number 1, and atomic weight 1. It exists, under normal conditions, as a colorless, odorless, tasteless, diatomic gas. Hydrogen ions are protons. Besides the common H1 isotope, hydrogen exists as the stable isotope deuterium and the unstable, radioactive isotope tritium. [NIH] Hydrogen Peroxide: A strong oxidizing agent used in aqueous solution as a ripening agent, bleach, and topical anti-infective. It is relatively unstable and solutions deteriorate over time unless stabilized by the addition of acetanilide or similar organic materials. [NIH] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hydrophilic: Readily absorbing moisture; hygroscopic; having strongly polar groups that readily interact with water. [EU] Hydrophobic: Not readily absorbing water, or being adversely affected by water, as a hydrophobic colloid. [EU] Hydroxylysine: A hydroxylated derivative of the amino acid lysine that is present in certain collagens. [NIH] Hydroxyproline: A hydroxylated form of the imino acid proline. A deficiency in ascorbic acid can result in impaired hydroxyproline formation. [NIH] Hyperbilirubinemia: Pathologic process consisting of an abnormal increase in the amount of bilirubin in the circulating blood, which may result in jaundice. [NIH] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hyperuricemia: A buildup of uric acid (a byproduct of metabolism) in the blood; a side effect of some anticancer drugs. [NIH]

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Hypoglycaemia: An abnormally diminished concentration of glucose in the blood, which may lead to tremulousness, cold sweat, piloerection, hypothermia, and headache, accompanied by irritability, confusion, hallucinations, bizarre behaviour, and ultimately, convulsions and coma. [EU] Hypotension: Abnormally low blood pressure. [NIH] Hypothalamic: Of or involving the hypothalamus. [EU] Hypothalamus: Ventral part of the diencephalon extending from the region of the optic chiasm to the caudal border of the mammillary bodies and forming the inferior and lateral walls of the third ventricle. [NIH] Hypoxia: Reduction of oxygen supply to tissue below physiological levels despite adequate perfusion of the tissue by blood. [EU] Id: The part of the personality structure which harbors the unconscious instinctive desires and strivings of the individual. [NIH] Idiopathic: Describes a disease of unknown cause. [NIH] Idiotype: The unique antigenic determinant in the variable region. [NIH] Idoxuridine: An analog of DEOXYURIDINE that inhibits viral DNA synthesis. The drug is used as an antiviral agent, particularly in the treatment of herpes simplex keratitis. [NIH] Immune adjuvant: A drug that stimulates the immune system to respond to disease. [NIH] Immune function: Production and action of cells that fight disease or infection. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]

Immune Sera: Serum that contains antibodies. It is obtained from an animal that has been immunized either by antigen injection or infection with microorganisms containing the antigen. [NIH] Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] Immunity: Nonsusceptibility to the invasive or pathogenic microorganisms or to the toxic effect of antigenic substances. [NIH]

effects

of

foreign

Immunization: Deliberate stimulation of the host's immune response. Active immunization involves administration of antigens or immunologic adjuvants. Passive immunization involves administration of immune sera or lymphocytes or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow). [NIH] Immunization Schedule: Schedule giving optimum times usually for primary and/or secondary immunization. [NIH] Immunoassay: Immunochemical assay or detection of a substance by serologic or immunologic methods. Usually the substance being studied serves as antigen both in antibody production and in measurement of antibody by the test substance. [NIH] Immunocompetence: The ability of lymphoid cells to mount a humoral or cellular immune response when challenged by antigen. [NIH] Immunodeficiency: The decreased ability of the body to fight infection and disease. [NIH] Immunodeficiency syndrome: The inability of the body to produce an immune response. [NIH]

Immunofluorescence: A technique for identifying molecules present on the surfaces of cells or in tissues using a highly fluorescent substance coupled to a specific antibody. [NIH]

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Immunogen: A substance that is capable of causing antibody formation. [NIH] Immunogenetics: A branch of genetics which deals with the genetic basis of the immune response. [NIH] Immunogenic: Producing immunity; evoking an immune response. [EU] Immunoglobulin: A protein that acts as an antibody. [NIH] Immunologic: The ability of the antibody-forming system to recall a previous experience with an antigen and to respond to a second exposure with the prompt production of large amounts of antibody. [NIH] Immunological adjuvant: A substance used to help boost the immune response to a vaccine so that less vaccine is needed. [NIH] Immunology: The study of the body's immune system. [NIH] Immunosuppressive: Describes the ability to lower immune system responses. [NIH] Immunosuppressive Agents: Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of suppressor T-cell populations or by inhibiting the activation of helper cells. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of interleukins and other cytokines are emerging. [NIH] Immunosuppressive therapy: Therapy used to decrease the body's immune response, such as drugs given to prevent transplant rejection. [NIH] Immunotherapy: Manipulation of the host's immune system in treatment of disease. It includes both active and passive immunization as well as immunosuppressive therapy to prevent graft rejection. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] Implant radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called [NIH] In situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incision: A cut made in the body during surgery. [NIH] Incontinence: Inability to control the flow of urine from the bladder (urinary incontinence) or the escape of stool from the rectum (fecal incontinence). [NIH] Incubated: Grown in the laboratory under controlled conditions. (For instance, white blood cells can be grown in special conditions so that they attack specific cancer cells when returned to the body.) [NIH] Incubation: The development of an infectious disease from the entrance of the pathogen to the appearance of clinical symptoms. [EU] Incubation period: The period of time likely to elapse between exposure to the agent of the disease and the onset of clinical symptoms. [NIH] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU] Indigestion: Poor digestion. Symptoms include heartburn, nausea, bloating, and gas. Also called dyspepsia. [NIH]

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Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] Infancy: The period of complete dependency prior to the acquisition of competence in walking, talking, and self-feeding. [NIH] Infant, Newborn: An infant during the first month after birth. [NIH] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]

Infectious Mononucleosis: A common, acute infection usually caused by the Epstein-Barr virus (Human herpesvirus 4). There is an increase in mononuclear white blood cells and other atypical lymphocytes, generalized lymphadenopathy, splenomegaly, and occasionally hepatomegaly with hepatitis. [NIH] Infiltration: The diffusion or accumulation in a tissue or cells of substances not normal to it or in amounts of the normal. Also, the material so accumulated. [EU] Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH] Influenza: An acute viral infection involving the respiratory tract. It is marked by inflammation of the nasal mucosa, the pharynx, and conjunctiva, and by headache and severe, often generalized, myalgia. [NIH] Influenza A Virus: The type species of the genus Influenzavirus A, B that causes influenza and other diseases in humans and animals. Antigenic variation occurs frequently between strains, allowing classification into subtypes and variants. Transmission is by aerosol (human and most non-aquatic hosts) or waterborne (ducks). [NIH] Infusion: A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion. [NIH] Ingestion: Taking into the body by mouth [NIH] Inhalation: The drawing of air or other substances into the lungs. [EU] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Initiator: A chemically reactive substance which may cause cell changes if ingested, inhaled or absorbed into the body; the substance may thus initiate a carcinogenic process. [NIH] Inlay: In dentistry, a filling first made to correspond with the form of a dental cavity and then cemented into the cavity. [NIH] Inoculum: The spores or tissues of a pathogen that serve to initiate disease in a plant. [NIH] Inorganic: Pertaining to substances not of organic origin. [EU]

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Inotropic: Affecting the force or energy of muscular contractions. [EU] Insecticides: Pesticides designed to control insects that are harmful to man. The insects may be directly harmful, as those acting as disease vectors, or indirectly harmful, as destroyers of crops, food products, or textile fabrics. [NIH] Insight: The capacity to understand one's own motives, to be aware of one's own psychodynamics, to appreciate the meaning of symbolic behavior. [NIH] Insomnia: Difficulty in going to sleep or getting enough sleep. [NIH] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose. It is also an important regulator of protein and lipid metabolism. Insulin is used as a drug to control insulin-dependent diabetes mellitus. [NIH] Insulin-dependent diabetes mellitus: A disease characterized by high levels of blood glucose resulting from defects in insulin secretion, insulin action, or both. Autoimmune, genetic, and environmental factors are involved in the development of type I diabetes. [NIH] Integrase: An enzyme that inserts DNA into the host genome. It is encoded by the pol gene of retroviruses and also by temperate bacteriophages, the best known being bacteriophage lambda. EC 2.7.7.-. [NIH] Intensive Care: Advanced and highly specialized care provided to medical or surgical patients whose conditions are life-threatening and require comprehensive care and constant monitoring. It is usually administered in specially equipped units of a health care facility. [NIH]

Intensive Care Units: Hospital units providing continuous surveillance and care to acutely ill patients. [NIH] Interferon: A biological response modifier (a substance that can improve the body's natural response to disease). Interferons interfere with the division of cancer cells and can slow tumor growth. There are several types of interferons, including interferon-alpha, -beta, and gamma. These substances are normally produced by the body. They are also made in the laboratory for use in treating cancer and other diseases. [NIH] Interferon-alpha: One of the type I interferons produced by peripheral blood leukocytes or lymphoblastoid cells when exposed to live or inactivated virus, double-stranded RNA, or bacterial products. It is the major interferon produced by virus-induced leukocyte cultures and, in addition to its pronounced antiviral activity, it causes activation of NK cells. [NIH] Interleukin-1: A soluble factor produced by monocytes, macrophages, and other cells which activates T-lymphocytes and potentiates their response to mitogens or antigens. IL-1 consists of two distinct forms, IL-1 alpha and IL-1 beta which perform the same functions but are distinct proteins. The biological effects of IL-1 include the ability to replace macrophage requirements for T-cell activation. The factor is distinct from interleukin-2. [NIH] Interleukin-12: A heterodimeric cytokine that stimulates the production of interferon gamma from T-cells and natural killer cells, and also induces differentiation of Th1 helper cells. It is an initiator of cell-mediated immunity. [NIH] Interleukin-2: Chemical mediator produced by activated T lymphocytes and which regulates the proliferation of T cells, as well as playing a role in the regulation of NK cell activity. [NIH] Interleukin-8: A cytokine that activates neutrophils and attracts neutrophils and Tlymphocytes. It is released by several cell types including monocytes, macrophages, Tlymphocytes, fibroblasts, endothelial cells, and keratinocytes by an inflammatory stimulus. IL-8 is a member of the beta-thromboglobulin superfamily and structurally related to

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platelet factor 4. [NIH] Interleukins: Soluble factors which stimulate growth-related activities of leukocytes as well as other cell types. They enhance cell proliferation and differentiation, DNA synthesis, secretion of other biologically active molecules and responses to immune and inflammatory stimuli. [NIH] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Internal Medicine: A medical specialty concerned with the diagnosis and treatment of diseases of the internal organ systems of adults. [NIH] Internal radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called brachytherapy, implant radiation, or interstitial radiation therapy. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intestinal: Having to do with the intestines. [NIH] Intestine: A long, tube-shaped organ in the abdomen that completes the process of digestion. There is both a large intestine and a small intestine. Also called the bowel. [NIH] Intoxication: Poisoning, the state of being poisoned. [EU] Intracellular: Inside a cell. [NIH] Intracellular Membranes: Membranes of subcellular structures. [NIH] Intramuscular: IM. Within or into muscle. [NIH] Intramuscular injection: IM. Injection into a muscle. [NIH] Intravascular: Within a vessel or vessels. [EU] Intravenous: IV. Into a vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]

Involuntary: Reaction occurring without intention or volition. [NIH] Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as cations; those with a negative charge are anions. [NIH] Iris: The most anterior portion of the uveal layer, separating the anterior chamber from the posterior. It consists of two layers - the stroma and the pigmented epithelium. Color of the iris depends on the amount of melanin in the stroma on reflection from the pigmented epithelium. [NIH] Irradiation: The use of high-energy radiation from x-rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Irradiation is also called radiation therapy, radiotherapy, and x-ray therapy. [NIH] Irritable Bowel Syndrome: A disorder that comes and goes. Nerves that control the muscles in the GI tract are too active. The GI tract becomes sensitive to food, stool, gas, and stress. Causes abdominal pain, bloating, and constipation or diarrhea. Also called spastic colon or

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mucous colitis. [NIH] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Islet: Cell producing insulin in pancreas. [NIH] Isocitrate Lyase: A key enzyme in the glyoxylate cycle. It catalyzes the conversion of isocitrate to succinate and glyoxylate. EC 4.1.3.1. [NIH] Jaundice: A clinical manifestation of hyperbilirubinemia, consisting of deposition of bile pigments in the skin, resulting in a yellowish staining of the skin and mucous membranes. [NIH]

Joint: The point of contact between elements of an animal skeleton with the parts that surround and support it. [NIH] Kb: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [NIH] Keratinocytes: Epidermal cells which synthesize keratin and undergo characteristic changes as they move upward from the basal layers of the epidermis to the cornified (horny) layer of the skin. Successive stages of differentiation of the keratinocytes forming the epidermal layers are basal cell, spinous or prickle cell, and the granular cell. [NIH] Keratitis: Inflammation of the cornea. [NIH] Keto: It consists of 8 carbon atoms and within the endotoxins, it connects poysaccharide and lipid A. [NIH] Killer Cells: Lymphocyte-like effector cells which mediate antibody-dependent cell cytotoxicity. They kill antibody-coated target cells which they bind with their Fc receptors. [NIH]

Kinetic: Pertaining to or producing motion. [EU] Labile: 1. Gliding; moving from point to point over the surface; unstable; fluctuating. 2. Chemically unstable. [EU] Laceration: 1. The act of tearing. 2. A torn, ragged, mangled wound. [EU] Lag: The time elapsing between application of a stimulus and the resulting reaction. [NIH] Language Disorders: Conditions characterized by deficiencies of comprehension or expression of written and spoken forms of language. These include acquired and developmental disorders. [NIH] Laparotomy: A surgical incision made in the wall of the abdomen. [NIH] Large Intestine: The part of the intestine that goes from the cecum to the rectum. The large intestine absorbs water from stool and changes it from a liquid to a solid form. The large intestine is 5 feet long and includes the appendix, cecum, colon, and rectum. Also called colon. [NIH] Laryngitis: Inflammation of the larynx. This condition presents itself with dryness and soreness of the throat, difficulty in swallowing, cough, and hoarseness. [NIH] Larynx: An irregularly shaped, musculocartilaginous tubular structure, lined with mucous membrane, located at the top of the trachea and below the root of the tongue and the hyoid bone. It is the essential sphincter guarding the entrance into the trachea and functioning secondarily as the organ of voice. [NIH] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH] Least-Squares Analysis: A principle of estimation in which the estimates of a set of

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parameters in a statistical model are those quantities minimizing the sum of squared differences between the observed values of a dependent variable and the values predicted by the model. [NIH] Lectin: A complex molecule that has both protein and sugars. Lectins are able to bind to the outside of a cell and cause biochemical changes in it. Lectins are made by both animals and plants. [NIH] Length of Stay: The period of confinement of a patient to a hospital or other health facility. [NIH]

Lenses: Pieces of glass or other transparent materials used for magnification or increased visual acuity. [NIH] Leptin: A 16-kD peptide hormone secreted from white adipocytes and implicated in the regulation of food intake and energy balance. Leptin provides the key afferent signal from fat cells in the feedback system that controls body fat stores. [NIH] Lesion: An area of abnormal tissue change. [NIH] Lethal: Deadly, fatal. [EU] Leucocyte: All the white cells of the blood and their precursors (myeloid cell series, lymphoid cell series) but commonly used to indicate granulocytes exclusive of lymphocytes. [NIH]

Leukaemia: An acute or chronic disease of unknown cause in man and other warm-blooded animals that involves the blood-forming organs, is characterized by an abnormal increase in the number of leucocytes in the tissues of the body with or without a corresponding increase of those in the circulating blood, and is classified according of the type leucocyte most prominently involved. [EU] Leukemia: Cancer of blood-forming tissue. [NIH] Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [NIH] Levodopa: The naturally occurring form of dopa and the immediate precursor of dopamine. Unlike dopamine itself, it can be taken orally and crosses the blood-brain barrier. It is rapidly taken up by dopaminergic neurons and converted to dopamine. It is used for the treatment of parkinsonism and is usually given with agents that inhibit its conversion to dopamine outside of the central nervous system. [NIH] Libido: The psychic drive or energy associated with sexual instinct in the broad sense (pleasure and love-object seeking). It may also connote the psychic energy associated with instincts in general that motivate behavior. [NIH] Library Services: Services offered to the library user. They include reference and circulation. [NIH]

Life cycle: The successive stages through which an organism passes from fertilized ovum or spore to the fertilized ovum or spore of the next generation. [NIH] Ligament: A band of fibrous tissue that connects bones or cartilages, serving to support and strengthen joints. [EU] Ligands: A RNA simulation method developed by the MIT. [NIH] Likelihood Functions: Functions constructed from a statistical model and a set of observed data which give the probability of that data for various values of the unknown model parameters. Those parameter values that maximize the probability are the maximum likelihood estimates of the parameters. [NIH] Lincomycin:

(2S-trans)-Methyl

6,8-dideoxy-6-(((1-methyl-4-propyl-2-

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pyrrolidinyl)carbonyl)amino)-1-thio-D-erythro-alpha-D-galacto-octopyranoside. An antibiotic produced by Streptomyces lincolnensis var. lincolnensis. It has been used in the treatment of staphylococcal, streptococcal, and Bacteroides fragilis infections. [NIH] Linear Models: Statistical models in which the value of a parameter for a given value of a factor is assumed to be equal to a + bx, where a and b are constants. The models predict a linear regression. [NIH] Linkages: The tendency of two or more genes in the same chromosome to remain together from one generation to the next more frequently than expected according to the law of independent assortment. [NIH] Lipid: Fat. [NIH] Lipid A: Lipid A is the biologically active component of lipopolysaccharides. It shows strong endotoxic activity and exhibits immunogenic properties. [NIH] Lipid Bilayers: Layers of lipid molecules which are two molecules thick. Bilayer systems are frequently studied as models of biological membranes. [NIH] Lipid Peroxidation: Peroxidase catalyzed oxidation of lipids using hydrogen peroxide as an electron acceptor. [NIH] Lipophilic: Having an affinity for fat; pertaining to or characterized by lipophilia. [EU] Lipopolysaccharide: Substance consisting of polysaccaride and lipid. [NIH] Lipoprotein: Any of the lipid-protein complexes in which lipids are transported in the blood; lipoprotein particles consist of a spherical hydrophobic core of triglycerides or cholesterol esters surrounded by an amphipathic monolayer of phospholipids, cholesterol, and apolipoproteins; the four principal classes are high-density, low-density, and very-lowdensity lipoproteins and chylomicrons. [EU] Liposome: A spherical particle in an aqueous medium, formed by a lipid bilayer enclosing an aqueous compartment. [EU] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Liver Transplantation: The transference of a part of or an entire liver from one human or animal to another. [NIH] Lobe: A portion of an organ such as the liver, lung, breast, or brain. [NIH] Localization: The process of determining or marking the location or site of a lesion or disease. May also refer to the process of keeping a lesion or disease in a specific location or site. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Locomotion: Movement or the ability to move from one place or another. It can refer to humans, vertebrate or invertebrate animals, and microorganisms. [NIH] Logistic Models: Statistical models which describe the relationship between a qualitative dependent variable (that is, one which can take only certain discrete values, such as the presence or absence of a disease) and an independent variable. A common application is in epidemiology for estimating an individual's risk (probability of a disease) as a function of a given risk factor. [NIH] Long-Term Care: Care over an extended period, usually for a chronic condition or disability, requiring periodic, intermittent, or continuous care. [NIH] Loop: A wire usually of platinum bent at one end into a small loop (usually 4 mm inside diameter) and used in transferring microorganisms. [NIH]

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Low-density lipoprotein: Lipoprotein that contains most of the cholesterol in the blood. LDL carries cholesterol to the tissues of the body, including the arteries. A high level of LDL increases the risk of heart disease. LDL typically contains 60 to 70 percent of the total serum cholesterol and both are directly correlated with CHD risk. [NIH] Lupus: A form of cutaneous tuberculosis. It is seen predominantly in women and typically involves the nasal, buccal, and conjunctival mucosa. [NIH] Lyme Disease: An infectious disease caused by a spirochete, Borrelia burgdorferi, which is transmitted chiefly by Ixodes dammini and pacificus ticks in the United States and Ixodes ricinis in Europe. It is a disease with early and late cutaneous manifestations plus involvement of the nervous system, heart, eye, and joints in variable combinations. The disease was formerly known as Lyme arthritis and first discovered at Old Lyme, Connecticut. [NIH] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Lymph node: A rounded mass of lymphatic tissue that is surrounded by a capsule of connective tissue. Also known as a lymph gland. Lymph nodes are spread out along lymphatic vessels and contain many lymphocytes, which filter the lymphatic fluid (lymph). [NIH]

Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] Lymphatic system: The tissues and organs that produce, store, and carry white blood cells that fight infection and other diseases. This system includes the bone marrow, spleen, thymus, lymph nodes and a network of thin tubes that carry lymph and white blood cells. These tubes branch, like blood vessels, into all the tissues of the body. [NIH] Lymphoblastic: One of the most aggressive types of non-Hodgkin lymphoma. [NIH] Lymphoblasts: Interferon produced predominantly by leucocyte cells. [NIH] Lymphocyte: A white blood cell. Lymphocytes have a number of roles in the immune system, including the production of antibodies and other substances that fight infection and diseases. [NIH] Lymphocyte Count: A count of the number of lymphocytes in the blood. [NIH] Lymphocyte Subsets: A classification of lymphocytes based on structurally or functionally different populations of cells. [NIH] Lymphocytic: Referring to lymphocytes, a type of white blood cell. [NIH] Lymphocytic Choriomeningitis Virus: The type species of arenavirus, part of the LCMLassa complex viruses, producing an inapparent infection in house and laboratory mice. In humans, infection with LCMV can be inapparent, or can present with an influenza-like illness, a benign aseptic meningitis, or a severe meningoencephalomyelitis. The virus can also infect monkeys, dogs, field mice, guinea pigs, and hamsters, the latter an epidemiologically important host. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Lymphokines: Soluble protein factors generated by activated lymphocytes that affect other cells, primarily those involved in cellular immunity. [NIH] Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue. [NIH] Lyssavirus: A genus of the family Rhabdoviridae that includes rabies virus and other rabieslike viruses. [NIH]

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Lytic: 1. Pertaining to lysis or to a lysin. 2. Producing lysis. [EU] Macrophage: A type of white blood cell that surrounds and kills microorganisms, removes dead cells, and stimulates the action of other immune system cells. [NIH] Major Histocompatibility Complex: The genetic region which contains the loci of genes which determine the structure of the serologically defined (SD) and lymphocyte-defined (LD) transplantation antigens, genes which control the structure of the immune responseassociated (Ia) antigens, the immune response (Ir) genes which control the ability of an animal to respond immunologically to antigenic stimuli, and genes which determine the structure and/or level of the first four components of complement. [NIH] Malabsorption: Impaired intestinal absorption of nutrients. [EU] Malaise: A vague feeling of bodily discomfort. [EU] Malaria: A protozoan disease caused in humans by four species of the genus Plasmodium (P. falciparum (malaria, falciparum), P. vivax (malaria, vivax), P. ovale, and P. malariae) and transmitted by the bite of an infected female mosquito of the genus Anopheles. Malaria is endemic in parts of Asia, Africa, Central and South America, Oceania, and certain Caribbean islands. It is characterized by extreme exhaustion associated with paroxysms of high fever, sweating, shaking chills, and anemia. Malaria in animals is caused by other species of plasmodia. [NIH] Malaria Vaccines: Vaccines made from antigens arising from any of the four strains of Plasmodium which cause malaria in humans, or from P. berghei which causes malaria in rodents. [NIH] Malaria, Falciparum: Malaria caused by Plasmodium falciparum. This is the severest form of malaria and is associated with the highest levels of parasites in the blood. This disease is characterized by irregularly recurring febrile paroxysms that in extreme cases occur with acute cerebral, renal, or gastrointestinal manifestations. [NIH] Malaria, Vivax: Malaria caused by Plasmodium vivax. This form of malaria is less severe than malaria, falciparum, but there is a higher probability for relapses to occur. Febrile paroxysms often occur every other day. [NIH] Malignancy: A cancerous tumor that can invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malnutrition: A condition caused by not eating enough food or not eating a balanced diet. [NIH]

Mammography: Radiographic examination of the breast. [NIH] Manifest: Being the part or aspect of a phenomenon that is directly observable : concretely expressed in behaviour. [EU] Mannans: Polysaccharides consisting of mannose units. [NIH] Mastitis: Inflammatory disease of the breast, or mammary gland. [NIH] Maxillary: Pertaining to the maxilla : the irregularly shaped bone that with its fellow forms the upper jaw. [EU] Measles Virus: The type species of morbillivirus and the cause of the highly infectious human disease measles, which affects mostly children. [NIH] Meat: The edible portions of any animal used for food including domestic mammals (the major ones being cattle, swine, and sheep) along with poultry, fish, shellfish, and game. [NIH]

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Medial: Lying near the midsaggital plane of the body; opposed to lateral. [NIH] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] Mediator: An object or substance by which something is mediated, such as (1) a structure of the nervous system that transmits impulses eliciting a specific response; (2) a chemical substance (transmitter substance) that induces activity in an excitable tissue, such as nerve or muscle; or (3) a substance released from cells as the result of the interaction of antigen with antibody or by the action of antigen with a sensitized lymphocyte. [EU] Medicament: A medicinal substance or agent. [EU] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Megakaryocytes: Very large bone marrow cells which release mature blood platelets. [NIH] Meiosis: A special method of cell division, occurring in maturation of the germ cells, by means of which each daughter nucleus receives half the number of chromosomes characteristic of the somatic cells of the species. [NIH] Melanin: The substance that gives the skin its color. [NIH] Melanocytes: Epidermal dendritic pigment cells which control long-term morphological color changes by alteration in their number or in the amount of pigment they produce and store in the pigment containing organelles called melanosomes. Melanophores are larger cells which do not exist in mammals. [NIH] Melanoma: A form of skin cancer that arises in melanocytes, the cells that produce pigment. Melanoma usually begins in a mole. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Membrane Fusion: The adherence of cell membranes, intracellular membranes, or artifical membrane models of either to each other or to viruses, parasites, or interstitial particles through a variety of chemical and physical processes. [NIH] Membrane Glycoproteins: Glycoproteins found on the membrane or surface of cells. [NIH] Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors. [NIH] Memory: Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. [NIH] Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] Meningitis: Inflammation of the meninges. When it affects the dura mater, the disease is termed pachymeningitis; when the arachnoid and pia mater are involved, it is called leptomeningitis, or meningitis proper. [EU] Mental Disorders: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. [NIH] Mental Health: The state wherein the person is well adjusted. [NIH] Mental Retardation: Refers to sub-average general intellectual functioning which originated during the developmental period and is associated with impairment in adaptive behavior. [NIH]

Mercury: A silver metallic element that exists as a liquid at room temperature. It has the

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atomic symbol Hg (from hydrargyrum, liquid silver), atomic number 80, and atomic weight 200.59. Mercury is used in many industrial applications and its salts have been employed therapeutically as purgatives, antisyphilitics, disinfectants, and astringents. It can be absorbed through the skin and mucous membranes which leads to mercury poisoning. Because of its toxicity, the clinical use of mercury and mercurials is diminishing. [NIH] Metabolic disorder: A condition in which normal metabolic processes are disrupted, usually because of a missing enzyme. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] Methacrylate: A vinyl monomer. [NIH] Methionine: A sulfur containing essential amino acid that is important in many body functions. It is a chelating agent for heavy metals. [NIH] Metronidazole: Antiprotozoal used in amebiasis, trichomoniasis, giardiasis, and as treponemacide in livestock. It has also been proposed as a radiation sensitizer for hypoxic cells. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985, p133), this substance may reasonably be anticipated to be a carcinogen (Merck, 11th ed). [NIH] MI: Myocardial infarction. Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [NIH] Microorganism: An organism that can be seen only through a microscope. Microorganisms include bacteria, protozoa, algae, and fungi. Although viruses are not considered living organisms, they are sometimes classified as microorganisms. [NIH] Microscopy: The application of microscope magnification to the study of materials that cannot be properly seen by the unaided eye. [NIH] Microspheres: Small uniformly-sized spherical particles frequently radioisotopes or various reagents acting as tags or markers. [NIH]

labeled

with

Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [NIH] Milliliter: A measure of volume for a liquid. A milliliter is approximately 950-times smaller than a quart and 30-times smaller than a fluid ounce. A milliliter of liquid and a cubic centimeter (cc) of liquid are the same. [NIH] Mineralocorticoids: A group of corticosteroids primarily associated with the regulation of water and electrolyte balance. This is accomplished through the effect on ion transport in renal tubules, resulting in retention of sodium and loss of potassium. Mineralocorticoid secretion is itself regulated by plasma volume, serum potassium, and angiotensin II. [NIH] Mitochondrial Swelling: Increase in volume of mitochondria due to an influx of fluid; it occurs in hypotonic solutions due to osmotic pressure and in isotonic solutions as a result of altered permeability of the membranes of respiring mitochondria. [NIH] Mitosporic Fungi: A large and heterogenous group of fungi whose common characteristic is the absence of a sexual state. Many of the pathogenic fungi in humans belong to this group. [NIH]

Mobility: Capability of movement, of being moved, or of flowing freely. [EU] Mobilization: The process of making a fixed part or stored substance mobile, as by

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separating a part from surrounding structures to make it accessible for an operative procedure or by causing release into the circulation for body use of a substance stored in the body. [EU] Modeling: A treatment procedure whereby the therapist presents the target behavior which the learner is to imitate and make part of his repertoire. [NIH] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] Monitor: An apparatus which automatically records such physiological signs as respiration, pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH] Monkeypox Virus: A species of orthopoxvirus causing an epidemic disease among captive primates. [NIH] Monoclonal: An antibody produced by culturing a single type of cell. It therefore consists of a single species of immunoglobulin molecules. [NIH] Monoclonal antibodies: Laboratory-produced substances that can locate and bind to cancer cells wherever they are in the body. Many monoclonal antibodies are used in cancer detection or therapy; each one recognizes a different protein on certain cancer cells. Monoclonal antibodies can be used alone, or they can be used to deliver drugs, toxins, or radioactive material directly to a tumor. [NIH] Monocytes: Large, phagocytic mononuclear leukocytes produced in the vertebrate bone marrow and released into the blood; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles. [NIH] Monokines: Soluble mediators of the immune response that are neither antibodies nor complement. They are produced largely, but not exclusively, by monocytes and macrophages. [NIH] Mononuclear: A cell with one nucleus. [NIH] Mononucleosis: The presence of an abnormally large number of mononuclear leucocytes (monocytes) in the blood. The term is often used alone to refer to infectious mononucleosis. [EU]

Monophosphate: So called second messenger for neurotransmitters and hormones. [NIH] Morbillivirus: A genus of the family Paramyxoviridae (subfamily Paramyxovirinae) where all the virions have hemagglutinin but not neuraminidase activity. All members produce both cytoplasmic and intranuclear inclusion bodies. MEASLES VIRUS is the type species. [NIH]

Morphine: The principal alkaloid in opium and the prototype opiate analgesic and narcotic. Morphine has widespread effects in the central nervous system and on smooth muscle. [NIH] Morphological: Relating to the configuration or the structure of live organs. [NIH] Motion Sickness: Sickness caused by motion, as sea sickness, train sickness, car sickness, and air sickness. [NIH] Mucins: A secretion containing mucopolysaccharides and protein that is the chief constituent of mucus. [NIH]

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Mucociliary: Pertaining to or affecting the mucus membrane and hairs (including eyelashes, nose hair, .): mucociliary clearing: the clearance of mucus by ciliary movement ( particularly in the respiratory system). [EU] Mucosa: A mucous membrane, or tunica mucosa. [EU] Mucositis: A complication of some cancer therapies in which the lining of the digestive system becomes inflamed. Often seen as sores in the mouth. [NIH] Mucus: The viscous secretion of mucous membranes. It contains mucin, white blood cells, water, inorganic salts, and exfoliated cells. [NIH] Multiple sclerosis: A disorder of the central nervous system marked by weakness, numbness, a loss of muscle coordination, and problems with vision, speech, and bladder control. Multiple sclerosis is thought to be an autoimmune disease in which the body's immune system destroys myelin. Myelin is a substance that contains both protein and fat (lipid) and serves as a nerve insulator and helps in the transmission of nerve signals. [NIH] Multivalent: Pertaining to a group of 5 or more homologous or partly homologous chromosomes during the zygotene stage of prophase to first metaphasis in meiosis. [NIH] Mumps Virus: The type species of rubulavirus that causes an acute infectious disease in humans, affecting mainly children. Transmission occurs by droplet infection. [NIH] Mutagenesis: Process of generating genetic mutations. It may occur spontaneously or be induced by mutagens. [NIH] Mutagenicity: Ability to damage DNA, the genetic material; the power to cause mutations. [NIH]

Mutagens: Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes. [NIH] Myalgia: Pain in a muscle or muscles. [EU] Mycobacterial disease: Any disease caused by Mycobacterium other than M. tuberculosis, M. bovis, and M. avium. [NIH] Mycobacterium: A genus of gram-positive, aerobic bacteria. Most species are free-living in soil and water, but the major habitat for some is the diseased tissue of warm-blooded hosts. [NIH]

Myelitis: Inflammation of the spinal cord. Relatively common etiologies include infections; autoimmune diseases; spinal cord; and ischemia (see also spinal cord vascular diseases). Clinical features generally include weakness, sensory loss, localized pain, incontinence, and other signs of autonomic dysfunction. [NIH] Myocarditis: Inflammation of the myocardium; inflammation of the muscular walls of the heart. [EU] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myopathy: Any disease of a muscle. [EU] Myositis: Inflammation of a voluntary muscle. [EU] Naive: Used to describe an individual who has never taken a certain drug or class of drugs (e. g., AZT-naive, antiretroviral-naive), or to refer to an undifferentiated immune system cell. [NIH] Narcolepsy: A condition of unknown cause characterized by a periodic uncontrollable tendency to fall asleep. [NIH] Narcotic: 1. Pertaining to or producing narcosis. 2. An agent that produces insensibility or

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stupor, applied especially to the opioids, i.e. to any natural or synthetic drug that has morphine-like actions. [EU] Nasal Cavity: The proximal portion of the respiratory passages on either side of the nasal septum, lined with ciliated mucosa, extending from the nares to the pharynx. [NIH] Nasal Mucosa: The mucous membrane lining the nasal cavity. [NIH] Nasal Septum: The partition separating the two nasal cavities in the midplane, composed of cartilaginous, membranous and bony parts. [NIH] Nasopharynx: The nasal part of the pharynx, lying above the level of the soft palate. [NIH] Natural killer cells: NK cells. A type of white blood cell that contains granules with enzymes that can kill tumor cells or microbial cells. Also called large granular lymphocytes (LGL). [NIH] Nausea: An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. [NIH] NCI: National Cancer Institute. NCI, part of the National Institutes of Health of the United States Department of Health and Human Services, is the federal government's principal agency for cancer research. NCI conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the NCI Web site at http://cancer.gov. [NIH] Necrosis: A pathological process caused by the progressive degradative action of enzymes that is generally associated with severe cellular trauma. It is characterized by mitochondrial swelling, nuclear flocculation, uncontrolled cell lysis, and ultimately cell death. [NIH] Need: A state of tension or dissatisfaction felt by an individual that impels him to action toward a goal he believes will satisfy the impulse. [NIH] Neonatal: Pertaining to the first four weeks after birth. [EU] Neoplasia: Abnormal and uncontrolled cell growth. [NIH] Neoplasm: A new growth of benign or malignant tissue. [NIH] Nephropathy: Disease of the kidneys. [EU] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU] Neuraminidase: An enzyme that catalyzes the hydrolysis of alpha-2,3, alpha-2,6-, and alpha-2,8-glycosidic linkages (at a decreasing rate, respectively) of terminal sialic residues in oligosaccharides, glycoproteins, glycolipids, colominic acid, and synthetic substrate. (From Enzyme Nomenclature, 1992) EC 3.2.1.18. [NIH] Neuritis: A general term indicating inflammation of a peripheral or cranial nerve. Clinical manifestation may include pain; paresthesias; paresis; or hypesthesia. [NIH] Neuroendocrine: Having to do with the interactions between the nervous system and the endocrine system. Describes certain cells that release hormones into the blood in response to stimulation of the nervous system. [NIH] Neuronal: Pertaining to a neuron or neurons (= conducting cells of the nervous system). [EU] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon,

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and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] Neuropathy: A problem in any part of the nervous system except the brain and spinal cord. Neuropathies can be caused by infection, toxic substances, or disease. [NIH] Neuropeptides: Peptides released by neurons as intercellular messengers. Many neuropeptides are also hormones released by non-neuronal cells. [NIH] Neurotoxic: Poisonous or destructive to nerve tissue. [EU] Neurotransmitters: Endogenous signaling molecules that alter the behavior of neurons or effector cells. Neurotransmitter is used here in its most general sense, including not only messengers that act directly to regulate ion channels, but also those that act through second messenger systems, and those that act at a distance from their site of release. Included are neuromodulators, neuroregulators, neuromediators, and neurohumors, whether or not acting at synapses. [NIH] Neutralization: An act or process of neutralizing. [EU] Neutrons: Electrically neutral elementary particles found in all atomic nuclei except light hydrogen; the mass is equal to that of the proton and electron combined and they are unstable when isolated from the nucleus, undergoing beta decay. Slow, thermal, epithermal, and fast neutrons refer to the energy levels with which the neutrons are ejected from heavier nuclei during their decay. [NIH] Neutrophils: Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes. [NIH] Nevirapine: A potent, non-nucleoside reverse transcriptase inhibitor used in combination with nucleoside analogues for treatment of HIV infection and AIDS. [NIH] Niacin: Water-soluble vitamin of the B complex occurring in various animal and plant tissues. Required by the body for the formation of coenzymes NAD and NADP. Has pellagra-curative, vasodilating, and antilipemic properties. [NIH] Nitric Oxide: A free radical gas produced endogenously by a variety of mammalian cells. It is synthesized from arginine by a complex reaction, catalyzed by nitric oxide synthase. Nitric oxide is endothelium-derived relaxing factor. It is released by the vascular endothelium and mediates the relaxation induced by some vasodilators such as acetylcholine and bradykinin. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic guanylate cyclase and thus elevates intracellular levels of cyclic GMP. [NIH]

Nitrogen: An element with the atomic symbol N, atomic number 7, and atomic weight 14. Nitrogen exists as a diatomic gas and makes up about 78% of the earth's atmosphere by volume. It is a constituent of proteins and nucleic acids and found in all living cells. [NIH] Non-nucleoside: A member of a class of compounds, including delavirdine, loviride and nevirapine, that acts to directly combine with and block the action of HIV's reverse transcriptase. [NIH] Nonverbal Communication: Transmission of emotions, ideas, and attitudes between individuals in ways other than the spoken language. [NIH] Norepinephrine: Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used

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pharmacologically as a sympathomimetic. [NIH] Nosocomial: Pertaining to or originating in the hospital, said of an infection not present or incubating prior to admittance to the hospital, but generally occurring 72 hours after admittance; the term is usually used to refer to patient disease, but hospital personnel may also acquire nosocomial infection. [EU] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the information (genetic code) for the transfer of genetic information from one generation to the next. [NIH] Nucleocapsid: A protein-nucleic acid complex which forms part or all of a virion. It consists of a capsid plus enclosed nucleic acid. Depending on the virus, the nucleocapsid may correspond to a naked core or be surrounded by a membranous envelope. [NIH] Nucleocapsid Proteins: Viral proteins found in either the nucleocapsid or the viral core (viral core proteins). [NIH] Nucleoprotein: Chromosomes consist largely of nuclei acids and proteins, joined here as complexes called nucleoproteins. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nutritional Status: State of the body in relation to the consumption and utilization of nutrients. [NIH] Occult: Obscure; concealed from observation, difficult to understand. [EU] Occult Blood: Chemical, spectroscopic, or microscopic detection of extremely small amounts of blood. [NIH] Odds Ratio: The ratio of two odds. The exposure-odds ratio for case control data is the ratio of the odds in favor of exposure among cases to the odds in favor of exposure among noncases. The disease-odds ratio for a cohort or cross section is the ratio of the odds in favor of disease among the exposed to the odds in favor of disease among the unexposed. The prevalence-odds ratio refers to an odds ratio derived cross-sectionally from studies of prevalent cases. [NIH] Odour: A volatile emanation that is perceived by the sense of smell. [EU] Ointments: Semisolid preparations used topically for protective emollient effects or as a vehicle for local administration of medications. Ointment bases are various mixtures of fats, waxes, animal and plant oils and solid and liquid hydrocarbons. [NIH] Oligo: Chemical and mineral elements that exist in minimal (oligo) quantities in the body, in foods, in the air, in soil; name applied to any element observed as a microconstituent of plant or animal tissue and of beneficial, harmful, or even doubtful significance. [NIH] Oligosaccharides: Carbohydrates consisting of between two and ten monosaccharides connected by either an alpha- or beta-glycosidic link. They are found throughout nature in both the free and bound form. [NIH] Oncogene: A gene that normally directs cell growth. If altered, an oncogene can promote or allow the uncontrolled growth of cancer. Alterations can be inherited or caused by an

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environmental exposure to carcinogens. [NIH] Oncology: The study of cancer. [NIH] Opacity: Degree of density (area most dense taken for reading). [NIH] Ophthalmology: A surgical specialty concerned with the structure and function of the eye and the medical and surgical treatment of its defects and diseases. [NIH] Opium: The air-dried exudate from the unripe seed capsule of the opium poppy, Papaver somniferum, or its variant, P. album. It contains a number of alkaloids, but only a few morphine, codeine, and papaverine - have clinical significance. Opium has been used as an analgesic, antitussive, antidiarrheal, and antispasmodic. [NIH] Opportunistic Infections: An infection caused by an organism which becomes pathogenic under certain conditions, e.g., during immunosuppression. [NIH] Optic disc: The circular area (disc) where the optic nerve connects to the retina. [NIH] Optic Nerve: The 2nd cranial nerve. The optic nerve conveys visual information from the retina to the brain. The nerve carries the axons of the retinal ganglion cells which sort at the optic chiasm and continue via the optic tracts to the brain. The largest projection is to the lateral geniculate nuclei; other important targets include the superior colliculi and the suprachiasmatic nuclei. Though known as the second cranial nerve, it is considered part of the central nervous system. [NIH] Optic Neuritis: Inflammation of the optic nerve. Commonly associated conditions include autoimmune disorders such as multiple sclerosis, infections, and granulomatous diseases. Clinical features include retro-orbital pain that is aggravated by eye movement, loss of color vision, and contrast sensitivity that may progress to severe visual loss, an afferent pupillary defect (Marcus-Gunn pupil), and in some instances optic disc hyperemia and swelling. Inflammation may occur in the portion of the nerve within the globe (neuropapillitis or anterior optic neuritis) or the portion behind the globe (retrobulbar neuritis or posterior optic neuritis). [NIH] Oral Health: The optimal state of the mouth and normal functioning of the organs of the mouth without evidence of disease. [NIH] Oral Hygiene: The practice of personal hygiene of the mouth. It includes the maintenance of oral cleanliness, tissue tone, and general preservation of oral health. [NIH] Orbital: Pertaining to the orbit (= the bony cavity that contains the eyeball). [EU] Orderly: A male hospital attendant. [NIH] Orf: A specific disease of sheep and goats caused by a pox-virus that is transmissible to man and characterized by vesiculation and ulceration of the lips. [NIH] Orf Virus: The type species of Parapoxvirus which causes a skin infection in natural hosts, usually young sheep. Humans may contract local skin lesions by contact. The virus apparently persists in soil. [NIH] Organ Culture: The growth in aseptic culture of plant organs such as roots or shoots, beginning with organ primordia or segments and maintaining the characteristics of the organ. [NIH] Organ Transplantation: Transference of an organ between individuals of the same species or between individuals of different species. [NIH] Organelles: Specific particles of membrane-bound organized living substances present in eukaryotic cells, such as the mitochondria; the golgi apparatus; endoplasmic reticulum; lysomomes; plastids; and vacuoles. [NIH] Orthomyxoviridae: A family of RNA viruses causing influenza and other diseases. There

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are three recognized genera: Influenzavirus A, B; Influenzavirus C; and thogoto-like viruses. [NIH]

Orthopoxvirus: A genus of the family Poxviridae, subfamily Chordopoxvirninae, comprising many species infecting mammals. Viruses of this genus cause generalized infections and a rash in some hosts. The type species is Vaccinia virus. [NIH] Osteoporosis: Reduction of bone mass without alteration in the composition of bone, leading to fractures. Primary osteoporosis can be of two major types: postmenopausal osteoporosis and age-related (or senile) osteoporosis. [NIH] Otitis: Inflammation of the ear, which may be marked by pain, fever, abnormalities of hearing, hearing loss, tinnitus, and vertigo. [EU] Otitis Media: Inflammation of the middle ear. [NIH] Outpatient: A patient who is not an inmate of a hospital but receives diagnosis or treatment in a clinic or dispensary connected with the hospital. [NIH] Ovalbumin: An albumin obtained from the white of eggs. It is a member of the serpin superfamily. [NIH] Ovary: Either of the paired glands in the female that produce the female germ cells and secrete some of the female sex hormones. [NIH] Ovum: A female germ cell extruded from the ovary at ovulation. [NIH] Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]

Pachymeningitis: Inflammation of the dura mater of the brain, the spinal cord or the optic nerve. [NIH] Paediatric: Of or relating to the care and medical treatment of children; belonging to or concerned with paediatrics. [EU] Palate: The structure that forms the roof of the mouth. It consists of the anterior hard palate and the posterior soft palate. [NIH] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Papilloma: A benign epithelial neoplasm which may arise from the skin, mucous membranes or glandular ducts. [NIH] Papillomavirus: A genus of Papovaviridae causing proliferation of the epithelium, which may lead to malignancy. A wide range of animals are infected including humans, chimpanzees, cattle, rabbits, dogs, and horses. [NIH] Paraffin: A mixture of solid hydrocarbons obtained from petroleum. It has a wide range of uses including as a stiffening agent in ointments, as a lubricant, and as a topical antiinflammatory. It is also commonly used as an embedding material in histology. [NIH] Parainfluenza Vaccines: Vaccines or candidate vaccines used to prevent infection with parainfluenza viruses in humans and animals. [NIH] Parainfluenza Virus 1, Human: The type species of Paramyxovirus also called

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hemadsorption virus 2 (HA2), which causes laryngotracheitis in humans, especially children. [NIH] Parainfluenza Virus 2, Human: A species of Rubulavirus associated particularly with acute laryngotracheitis (croup) in children aged 6 months to 3 years. [NIH] Paramyxovirus: A genus of the family Paramyxoviridae (subfamily Paramyxovirinae) where all the virions have both hemagglutinin and neuraminidase activities and encode a C protein. Human parainfluenza virus 1 is the type species. [NIH] Paranasal Sinuses: Air-filled extensions of the respiratory part of the nasal cavity into the frontal, ethmoid, sphenoid, and maxillary cranial bones. They vary in size and form in different individuals and are lined by the ciliated mucous membranes of the nasal cavity. [NIH]

Parapoxvirus: A genus of the family Poxviridae, subfamily Chordopoxvirinae, which infect ungulates and may infect humans. Orf virus is the type species. [NIH] Parasite: An animal or a plant that lives on or in an organism of another species and gets at least some of its nutrition from that other organism. [NIH] Parasitic: Having to do with or being a parasite. A parasite is an animal or a plant that lives on or in an organism of another species and gets at least some of its nutrients from it. [NIH] Parathyroid: 1. Situated beside the thyroid gland. 2. One of the parathyroid glands. 3. A sterile preparation of the water-soluble principle(s) of the parathyroid glands, ad-ministered parenterally as an antihypocalcaemic, especially in the treatment of acute hypoparathyroidism with tetany. [EU] Parathyroid Glands: Two small paired endocrine glands in the region of the thyroid gland. They secrete parathyroid hormone and are concerned with the metabolism of calcium and phosphorus. [NIH] Parathyroid hormone: A substance made by the parathyroid gland that helps the body store and use calcium. Also called parathormone, parathyrin, or PTH. [NIH] Parenteral: Not through the alimentary canal but rather by injection through some other route, as subcutaneous, intramuscular, intraorbital, intracapsular, intraspinal, intrasternal, intravenous, etc. [EU] Parkinsonism: A group of neurological disorders characterized by hypokinesia, tremor, and muscular rigidity. [EU] Paroxysmal: Recurring in paroxysms (= spasms or seizures). [EU] Particle: A tiny mass of material. [EU] Patch: A piece of material used to cover or protect a wound, an injured part, etc.: a patch over the eye. [NIH] Pathogen: Any disease-producing microorganism. [EU] Pathogenesis: The cellular events and reactions that occur in the development of disease. [NIH]

Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Pathologies: The study of abnormality, especially the study of diseases. [NIH] Patient Education: The teaching or training of patients concerning their own health needs. [NIH]

Patient Selection: Criteria and standards used for the determination of the appropriateness of the inclusion of patients with specific conditions in proposed treatment plans and the

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criteria used for the inclusion of subjects in various clinical trials and other research protocols. [NIH] Pelvic: Pertaining to the pelvis. [EU] Penicillin: An antibiotic drug used to treat infection. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Peptide Fragments: Partial proteins formed by partial hydrolysis of complete proteins. [NIH] Peptide T: N-(N-(N(2)-(N-(N-(N-(N-D-Alanyl L-seryl)-L-threonyl)-L-threonyl) L-threonyl)L-asparaginyl)-L-tyrosyl) L-threonine. Octapeptide sharing sequence homology with HIV envelope protein gp120. It is potentially useful as antiviral agent in AIDS therapy. The core pentapeptide sequence, TTNYT, consisting of amino acids 4-8 in peptide T, is the HIV envelope sequence required for attachment to the CD4 receptor. [NIH] Perception: The ability quickly and accurately to recognize similarities and differences among presented objects, whether these be pairs of words, pairs of number series, or multiple sets of these or other symbols such as geometric figures. [NIH] Perennial: Lasting through the year of for several years. [EU] Periodontal disease: Disease involving the supporting structures of the teeth (as the gums and periodontal membranes). [NIH] Periodontitis: Inflammation of the periodontal membrane; also called periodontitis simplex. [NIH]

Perioperative: Around the time of surgery; usually lasts from the time of going into the hospital or doctor's office for surgery until the time the patient goes home. [NIH] Peripheral blood: Blood circulating throughout the body. [NIH] Peritoneal: Having to do with the peritoneum (the tissue that lines the abdominal wall and covers most of the organs in the abdomen). [NIH] Peritoneal Cavity: The space enclosed by the peritoneum. It is divided into two portions, the greater sac and the lesser sac or omental bursa, which lies behind the stomach. The two sacs are connected by the foramen of Winslow, or epiploic foramen. [NIH] Peritoneal Dialysis: Dialysis fluid being introduced into and removed from the peritoneal cavity as either a continuous or an intermittent procedure. [NIH] Peritoneum: Endothelial lining of the abdominal cavity, the parietal peritoneum covering the inside of the abdominal wall and the visceral peritoneum covering the bowel, the mesentery, and certain of the organs. The portion that covers the bowel becomes the serosal layer of the bowel wall. [NIH] Pertussis: An acute, highly contagious infection of the respiratory tract, most frequently affecting young children, usually caused by Bordetella pertussis; a similar illness has been associated with infection by B. parapertussis and B. bronchiseptica. It is characterized by a catarrhal stage, beginning after an incubation period of about two weeks, with slight fever, sneezing, running at the nose, and a dry cough. In a week or two the paroxysmal stage begins, with the characteristic paroxysmal cough, consisting of a deep inspiration, followed by a series of quick, short coughs, continuing until the air is expelled from the lungs; the close of the paroxysm is marked by a long-drawn, shrill, whooping inspiration, due to spasmodic closure of the glottis. This stage lasts three to four weeks, after which the convalescent stage begins, in which paroxysms grow less frequent and less violent, and finally cease. Called also whooping cough. [EU] Pesticides: Chemicals used to destroy pests of any sort. The concept includes fungicides

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(industrial fungicides), insecticides, rodenticides, etc. [NIH] Petroleum: Naturally occurring complex liquid hydrocarbons which, after distillation, yield combustible fuels, petrochemicals, and lubricants. [NIH] Phallic: Pertaining to the phallus, or penis. [EU] Pharmaceutical Preparations: Drugs intended for human or veterinary use, presented in their finished dosage form. Included here are materials used in the preparation and/or formulation of the finished dosage form. [NIH] Pharmaceutical Solutions: Homogeneous liquid preparations that contain one or more chemical substances dissolved, i.e., molecularly dispersed, in a suitable solvent or mixture of mutually miscible solvents. For reasons of their ingredients, method of preparation, or use, they do not fall into another group of products. [NIH] Pharmacokinetic: The mathematical analysis of the time courses of absorption, distribution, and elimination of drugs. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Pharynx: The hollow tube about 5 inches long that starts behind the nose and ends at the top of the trachea (windpipe) and esophagus (the tube that goes to the stomach). [NIH] Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of yeasts. [NIH] Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor of melanin, dopamine, noradrenalin, and thyroxine. [NIH] Phlebotomy: The letting of blood from a vein. Although it is one of the techniques used in drawing blood to be used in diagnostic procedures, in modern medicine, it is used commonly in the treatment of erythrocytosis, hemochromocytosis, polycythemia vera, and porphyria cutanea tarda. Its historical counterpart is bloodletting. (From Cecil Textbook of Medicine, 19th ed & Wintrobe's Clinical Hematology, 9th ed) Venipuncture is not only for the letting of blood from a vein but also for the injecting of a drug into the vein for diagnostic analysis. [NIH] Phospholipases: A class of enzymes that catalyze the hydrolysis of phosphoglycerides or glycerophosphatidates. EC 3.1.-. [NIH] Phospholipids: Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides; glycerophospholipids) or sphingosine (sphingolipids). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system. [NIH] Phosphorus: A non-metallic element that is found in the blood, muscles, nevers, bones, and teeth, and is a component of adenosine triphosphate (ATP; the primary energy source for the body's cells.) [NIH] Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. [NIH] Physiologic: Having to do with the functions of the body. When used in the phrase "physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH]

Physiology: The science that deals with the life processes and functions of organismus, their cells, tissues, and organs. [NIH] Pigment: A substance that gives color to tissue. Pigments are responsible for the color of

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skin, eyes, and hair. [NIH] Pilot study: The initial study examining a new method or treatment. [NIH] Pituitary Gland: A small, unpaired gland situated in the sella turcica tissue. It is connected to the hypothalamus by a short stalk. [NIH] Plague: An acute infectious disease caused by Yersinia pestis that affects humans, wild rodents, and their ectoparasites. This condition persists due to its firm entrenchment in sylvatic rodent-flea ecosystems throughout the world. Bubonic plague is the most common form. [NIH] Plant Viruses: Viruses parasitic on plants higher than bacteria. [NIH] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] Plasmid: An autonomously replicating, extra-chromosomal DNA molecule found in many bacteria. Plasmids are widely used as carriers of cloned genes. [NIH] Plasmin: A product of the lysis of plasminogen (profibrinolysin) by plasminogen activators. It is composed of two polypeptide chains, light (B) and heavy (A), with a molecular weight of 75,000. It is the major proteolytic enzyme involved in blood clot retraction or the lysis of fibrin and quickly inactivated by antiplasmins. EC 3.4.21.7. [NIH] Plasminogen: Precursor of fibrinolysin (plasmin). It is a single-chain beta-globulin of molecular weight 80-90,000 found mostly in association with fibrinogen in plasma; plasminogen activators change it to fibrinolysin. It is used in wound debriding and has been investigated as a thrombolytic agent. [NIH] Plasminogen Activators: A heterogeneous group of proteolytic enzymes that convert plasminogen to plasmin. They are concentrated in the lysosomes of most cells and in the vascular endothelium, particularly in the vessels of the microcirculation. EC 3.4.21.-. [NIH] Plasticity: In an individual or a population, the capacity for adaptation: a) through gene changes (genetic plasticity) or b) through internal physiological modifications in response to changes of environment (physiological plasticity). [NIH] Platelet Activation: A series of progressive, overlapping events triggered by exposure of the platelets to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug. [NIH] Platelet Aggregation: The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin, collagen) and is part of the mechanism leading to the formation of a thrombus. [NIH] Platelet Factor 4: A high-molecular-weight proteoglycan-platelet factor complex which is released from blood platelets by thrombin. It acts as a mediator in the heparin-neutralizing capacity of the blood and plays a role in platelet aggregation. At high ionic strength (I=0.75), the complex dissociates into the active component (molecular weight 29,000) and the proteoglycan carrier (chondroitin 4-sulfate, molecular weight 350,000). The molecule exists in the form of a dimer consisting of 8 moles of platelet factor 4 and 2 moles of proteoglycan. [NIH]

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Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Platinum: Platinum. A heavy, soft, whitish metal, resembling tin, atomic number 78, atomic weight 195.09, symbol Pt. (From Dorland, 28th ed) It is used in manufacturing equipment for laboratory and industrial use. It occurs as a black powder (platinum black) and as a spongy substance (spongy platinum) and may have been known in Pliny's time as "alutiae". [NIH]

Pneumococcal Vaccines: Vaccines or candidate vaccines used to prevent infections with Streptococcus pneumoniae. [NIH] Pneumonitis: A disease caused by inhaling a wide variety of substances such as dusts and molds. Also called "farmer's disease". [NIH] Point Mutation: A mutation caused by the substitution of one nucleotide for another. This results in the DNA molecule having a change in a single base pair. [NIH] Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [NIH] Pollen: The male fertilizing element of flowering plants analogous to sperm in animals. It is released from the anthers as yellow dust, to be carried by insect or other vectors, including wind, to the ovary (stigma) of other flowers to produce the embryo enclosed by the seed. The pollens of many plants are allergenic. [NIH] Polyethylene: A vinyl polymer made from ethylene. It can be branched or linear. Branched or low-density polyethylene is tough and pliable but not to the same degree as linear polyethylene. Linear or high-density polyethylene has a greater hardness and tensile strength. Polyethylene is used in a variety of products, including implants and prostheses. [NIH]

Polymerase: An enzyme which catalyses the synthesis of DNA using a single DNA strand as a template. The polymerase copies the template in the 5'-3'direction provided that sufficient quantities of free nucleotides, dATP and dTTP are present. [NIH] Polymerase Chain Reaction: In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships. [NIH] Polymers: Compounds formed by the joining of smaller, usually repeating, units linked by covalent bonds. These compounds often form large macromolecules (e.g., polypeptides, proteins, plastics). [NIH] Polymethyl Methacrylate: Polymerized methyl methacrylate monomers which are used as sheets, moulding, extrusion powders, surface coating resins, emulsion polymers, fibers, inks, and films (From International Labor Organization, 1983). This material is also used in tooth implants, bone cements, and hard corneal contact lenses. [NIH] Polypeptide: A peptide which on hydrolysis yields more than two amino acids; called tripeptides, tetrapeptides, etc. according to the number of amino acids contained. [EU] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] Porphyria: A group of disorders characterized by the excessive production of porphyrins or their precursors that arises from abnormalities in the regulation of the porphyrin-heme

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pathway. The porphyrias are usually divided into three broad groups, erythropoietic, hepatic, and erythrohepatic, according to the major sites of abnormal porphyrin synthesis. [NIH]

Porphyria Cutanea Tarda: A form of hepatic porphyria (porphyria, hepatic) characterized by photosensitivity resulting in bullae that rupture easily to form shallow ulcers. This condition occurs in two forms: a sporadic, nonfamilial form that begins in middle age and has normal amounts of uroporphyrinogen decarboxylase with diminished activity in the liver; and a familial form in which there is an autosomal dominant inherited deficiency of uroporphyrinogen decarboxylase in the liver and red blood cells. [NIH] Posterior: Situated in back of, or in the back part of, or affecting the back or dorsal surface of the body. In lower animals, it refers to the caudal end of the body. [EU] Postherpetic Neuralgia: Variety of neuralgia associated with migraine in which pain is felt in or behind the eye. [NIH] Postmenopausal: Refers to the time after menopause. Menopause is the time in a woman's life when menstrual periods stop permanently; also called "change of life." [NIH] Postoperative: After surgery. [NIH] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Potassium: An element that is in the alkali group of metals. It has an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte and it plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. [NIH] Potentiate: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Potentiating: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Potentiation: An overall effect of two drugs taken together which is greater than the sum of the effects of each drug taken alone. [NIH] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH] Practice Management: Business management of medical and dental practices that may include capital financing, utilization management, and arrangement of capitation agreements with other parties. [NIH] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Prenatal: Existing or occurring before birth, with reference to the fetus. [EU] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] Preventive Medicine: A medical specialty primarily concerned with prevention of disease and the promotion and preservation of health in the individual. [NIH] Probe: An instrument used in exploring cavities, or in the detection and dilatation of

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strictures, or in demonstrating the potency of channels; an elongated instrument for exploring or sounding body cavities. [NIH] Procainamide: A derivative of procaine with less CNS action. [NIH] Procaine: A local anesthetic of the ester type that has a slow onset and a short duration of action. It is mainly used for infiltration anesthesia, peripheral nerve block, and spinal block. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1016). [NIH] Prodrug: A substance that gives rise to a pharmacologically active metabolite, although not itself active (i. e. an inactive precursor). [NIH] Progeny: The offspring produced in any generation. [NIH] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Projection: A defense mechanism, operating unconsciously, whereby that which is emotionally unacceptable in the self is rejected and attributed (projected) to others. [NIH] Proline: A non-essential amino acid that is synthesized from glutamic acid. It is an essential component of collagen and is important for proper functioning of joints and tendons. [NIH] Promoter: A chemical substance that increases the activity of a carcinogenic process. [NIH] Promotor: In an operon, a nucleotide sequence located at the operator end which contains all the signals for the correct initiation of genetic transcription by the RNA polymerase holoenzyme and determines the maximal rate of RNA synthesis. [NIH] Prophase: The first phase of cell division, in which the chromosomes become visible, the nucleus starts to lose its identity, the spindle appears, and the centrioles migrate toward opposite poles. [NIH] Prophylaxis: An attempt to prevent disease. [NIH] Propolis: Resinous substance obtained from beehives; contains many different substances which may have antimicrobial or antimycotic activity topically; its extracts are called propolis resin or balsam. Synonyms: bee bread; hive dross; bee glue. [NIH] Proportional: Being in proportion : corresponding in size, degree, or intensity, having the same or a constant ratio; of, relating to, or used in determining proportions. [EU] Prospective study: An epidemiologic study in which a group of individuals (a cohort), all free of a particular disease and varying in their exposure to a possible risk factor, is followed over a specific amount of time to determine the incidence rates of the disease in the exposed and unexposed groups. [NIH] Prostaglandin: Any of a group of components derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway that are extremely potent mediators of a diverse group of physiologic processes. The abbreviation for prostaglandin is PG; specific compounds are designated by adding one of the letters A through I to indicate the type of substituents found on the hydrocarbon skeleton and a subscript (1, 2 or 3) to indicate the number of double bonds in the hydrocarbon skeleton e.g., PGE2. The predominant naturally occurring prostaglandins all have two double bonds and are synthesized from arachidonic acid (5,8,11,14-eicosatetraenoic acid) by the pathway shown in the illustration. The 1 series and 3 series are produced by the same pathway with fatty acids having one fewer double bond (8,11,14-eicosatrienoic acid or one more double bond (5,8,11,14,17-eicosapentaenoic acid) than arachidonic acid. The subscript a or ß indicates the configuration at C-9 (a denotes a substituent below the plane of the ring, ß, above the plane). The naturally occurring PGF's have the a configuration, e.g., PGF2a. All of the

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prostaglandins act by binding to specific cell-surface receptors causing an increase in the level of the intracellular second messenger cyclic AMP (and in some cases cyclic GMP also). The effect produced by the cyclic AMP increase depends on the specific cell type. In some cases there is also a positive feedback effect. Increased cyclic AMP increases prostaglandin synthesis leading to further increases in cyclic AMP. [EU] Prostate: A gland in males that surrounds the neck of the bladder and the urethra. It secretes a substance that liquifies coagulated semen. It is situated in the pelvic cavity behind the lower part of the pubic symphysis, above the deep layer of the triangular ligament, and rests upon the rectum. [NIH] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation. [NIH] Protein Conformation: The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. Quaternary protein structure describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain). [NIH] Protein Engineering: Procedures by which nonrandom single-site changes are introduced into structural genes (site-specific mutagenesis) in order to produce mutant genes which can be coupled to promoters that direct the synthesis of a specifically altered protein, which is then analyzed for structural and functional properties and then compared with the predicted and sought-after properties. The design of the protein may be assisted by computer graphic technology and other advanced molecular modeling techniques. [NIH] Protein S: The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] Proteolytic: 1. Pertaining to, characterized by, or promoting proteolysis. 2. An enzyme that promotes proteolysis (= the splitting of proteins by hydrolysis of the peptide bonds with formation of smaller polypeptides). [EU] Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or vaccine dosages, length of study, routes of administration, who may participate, and other aspects of trial design. [NIH] Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] Protozoa: A subkingdom consisting of unicellular organisms that are the simplest in the animal kingdom. Most are free living. They range in size from submicroscopic to macroscopic. Protozoa are divided into seven phyla: Sarcomastigophora, Labyrinthomorpha, Apicomplexa, Microspora, Ascetospora, Myxozoa, and Ciliophora. [NIH] Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] Psychiatric: Pertaining to or within the purview of psychiatry. [EU] Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders. [NIH] Psychomotor: Pertaining to motor effects of cerebral or psychic activity. [EU]

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Public Health: Branch of medicine concerned with the prevention and control of disease and disability, and the promotion of physical and mental health of the population on the international, national, state, or municipal level. [NIH] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] Publishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing. [NIH]

Pulmonary: Relating to the lungs. [NIH] Pulmonary Artery: The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs. [NIH] Pulmonary Ventilation: The total volume of gas per minute inspired or expired measured in liters per minute. [NIH] Pulse: The rhythmical expansion and contraction of an artery produced by waves of pressure caused by the ejection of blood from the left ventricle of the heart as it contracts. [NIH]

Pupil: The aperture in the iris through which light passes. [NIH] Purifying: Respiratory equipment whose function is to remove contaminants from otherwise wholesome air. [NIH] Purines: A series of heterocyclic compounds that are variously substituted in nature and are known also as purine bases. They include adenine and guanine, constituents of nucleic acids, as well as many alkaloids such as caffeine and theophylline. Uric acid is the metabolic end product of purine metabolism. [NIH] Purpura: Purplish or brownish red discoloration, easily visible through the epidermis, caused by hemorrhage into the tissues. [NIH] Putrefaction: The process of decomposition of animal and vegetable matter by living organisms. [NIH] Pyelonephritis: Inflammation of the kidney and its pelvis, beginning in the interstitium and rapidly extending to involve the tubules, glomeruli, and blood vessels; due to bacterial infection. [EU] Pyridoxal: 3-Hydroxy-5-(hydroxymethyl)-2-methyl-4- pyridinecarboxaldehyde. [NIH] Pyrogenic: Inducing fever. [EU] Pyrogens: Substances capable of increasing body temperature; they may be of microbial origin, often polysaccharides and may contaminate distilled water. [NIH] Quality of Life: A generic concept reflecting concern with the modification and enhancement of life attributes, e.g., physical, political, moral and social environment. [NIH] Quaternary: 1. Fourth in order. 2. Containing four elements or groups. [EU] Quercetin: Aglucon of quercetrin, rutin, and other glycosides. It is widely distributed in the plant kingdom, especially in rinds and barks, clover blossoms, and ragweed pollen. [NIH] Quiescent: Marked by a state of inactivity or repose. [EU] Rabies: A highly fatal viral infection of the nervous system which affects all warm-blooded animal species. It is one of the most important of the zoonoses because of the inevitably fatal outcome for the infected human. [NIH] Rabies Virus: The type species of lyssavirus causing rabies in humans and other animals.

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Transmission is mostly by animal bites through saliva. The virus is neurotropic multiplying in neurons and myotubes of vertebrates. [NIH] Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radiation therapy: The use of high-energy radiation from x-rays, gamma rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body in the area near cancer cells (internal radiation therapy, implant radiation, or brachytherapy). Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Also called radiotherapy. [NIH] Radioactive: Giving off radiation. [NIH] Radiolabeled: Any compound that has been joined with a radioactive substance. [NIH] Radiotherapy: The use of ionizing radiation to treat malignant neoplasms and other benign conditions. The most common forms of ionizing radiation used as therapy are x-rays, gamma rays, and electrons. A special form of radiotherapy, targeted radiotherapy, links a cytotoxic radionuclide to a molecule that targets the tumor. When this molecule is an antibody or other immunologic molecule, the technique is called radioimmunotherapy. [NIH] Radius: The lateral bone of the forearm. [NIH] Randomized: Describes an experiment or clinical trial in which animal or human subjects are assigned by chance to separate groups that compare different treatments. [NIH] Reactivation: The restoration of activity to something that has been inactivated. [EU] Reagent: A substance employed to produce a chemical reaction so as to detect, measure, produce, etc., other substances. [EU] Reassortant Viruses: Viruses containing two or more pieces of nucleic acid (segmented genome) from different parents. Such viruses are produced in cells coinfected with different strains of a given virus. [NIH] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Recombinant Proteins: Proteins prepared by recombinant DNA technology. [NIH] Recombination: The formation of new combinations of genes as a result of segregation in crosses between genetically different parents; also the rearrangement of linked genes due to crossing-over. [NIH] Reconstitution: 1. A type of regeneration in which a new organ forms by the rearrangement of tissues rather than from new formation at an injured surface. 2. The restoration to original form of a substance previously altered for preservation and storage, as the restoration to a liquid state of blood serum or plasma that has been dried and stored. [EU] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Recur: To occur again. Recurrence is the return of cancer, at the same site as the original (primary) tumor or in another location, after the tumor had disappeared. [NIH]

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Recurrence: The return of a sign, symptom, or disease after a remission. [NIH] Red blood cells: RBCs. Cells that carry oxygen to all parts of the body. Also called erythrocytes. [NIH] Red Nucleus: A pinkish-yellow portion of the midbrain situated in the rostral mesencephalic tegmentum. It receives a large projection from the contralateral half of the cerebellum via the superior cerebellar peduncle and a projection from the ipsilateral motor cortex. [NIH] Reductase: Enzyme converting testosterone to dihydrotestosterone. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH] Regeneration: The natural renewal of a structure, as of a lost tissue or part. [EU] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Regional lymph node: In oncology, a lymph node that drains lymph from the region around a tumor. [NIH] Regression Analysis: Procedures for finding the mathematical function which best describes the relationship between a dependent variable and one or more independent variables. In linear regression (see linear models) the relationship is constrained to be a straight line and least-squares analysis is used to determine the best fit. In logistic regression (see logistic models) the dependent variable is qualitative rather than continuously variable and likelihood functions are used to find the best relationship. In multiple regression the dependent variable is considered to depend on more than a single independent variable. [NIH]

Regurgitation: A backward flowing, as the casting up of undigested food, or the backward flowing of blood into the heart, or between the chambers of the heart when a valve is incompetent. [EU] Relapse: The return of signs and symptoms of cancer after a period of improvement. [NIH] Relative risk: The ratio of the incidence rate of a disease among individuals exposed to a specific risk factor to the incidence rate among unexposed individuals; synonymous with risk ratio. Alternatively, the ratio of the cumulative incidence rate in the exposed to the cumulative incidence rate in the unexposed (cumulative incidence ratio). The term relative risk has also been used synonymously with odds ratio. This is because the odds ratio and relative risk approach each other if the disease is rare ( 5 percent of population) and the number of subjects is large. [NIH] Remission: A decrease in or disappearance of signs and symptoms of cancer. In partial remission, some, but not all, signs and symptoms of cancer have disappeared. In complete remission, all signs and symptoms of cancer have disappeared, although there still may be cancer in the body. [NIH] Renal failure: Progressive renal insufficiency and uremia, due to irreversible and progressive renal glomerular tubular or interstitial disease. [NIH] Respiration: The act of breathing with the lungs, consisting of inspiration, or the taking into the lungs of the ambient air, and of expiration, or the expelling of the modified air which contains more carbon dioxide than the air taken in (Blakiston's Gould Medical Dictionary, 4th ed.). This does not include tissue respiration (= oxygen consumption) or cell respiration (= cell respiration). [NIH] Respiratory Mucosa: The mucous membrane lining the respiratory tract. [NIH]

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Respiratory syncytial virus: RSV. A virus that causes respiratory infections with cold-like symptoms. [NIH] Respiratory Syncytial Virus Infections: Pneumovirus infections caused by the respiratory syncytial viruses. Humans and cattle are most affected but infections in goats and sheep have been reported. [NIH] Respiratory System: The tubular and cavernous organs and structures, by means of which pulmonary ventilation and gas exchange between ambient air and the blood are brought about. [NIH] Response Elements: Nucleotide sequences, usually upstream, which are recognized by specific regulatory transcription factors, thereby causing gene response to various regulatory agents. These elements may be found in both promotor and enhancer regions. [NIH]

Response rate: The percentage of patients whose cancer shrinks or disappears after treatment. [NIH] Restoration: Broad term applied to any inlay, crown, bridge or complete denture which restores or replaces loss of teeth or oral tissues. [NIH] Retinal: 1. Pertaining to the retina. 2. The aldehyde of retinol, derived by the oxidative enzymatic splitting of absorbed dietary carotene, and having vitamin A activity. In the retina, retinal combines with opsins to form visual pigments. One isomer, 11-cis retinal combines with opsin in the rods (scotopsin) to form rhodopsin, or visual purple. Another, all-trans retinal (trans-r.); visual yellow; xanthopsin) results from the bleaching of rhodopsin by light, in which the 11-cis form is converted to the all-trans form. Retinal also combines with opsins in the cones (photopsins) to form the three pigments responsible for colour vision. Called also retinal, and retinene1. [EU] Retrobulbar: Behind the pons. [EU] Retrospective: Looking back at events that have already taken place. [NIH] Retroviral vector: RNA from a virus that is used to insert genetic material into cells. [NIH] Retrovirus: A member of a group of RNA viruses, the RNA of which is copied during viral replication into DNA by reverse transcriptase. The viral DNA is then able to be integrated into the host chromosomal DNA. [NIH] Reverse Transcriptase Inhibitors: Inhibitors of reverse transcriptase (RNA-directed DNA polymerase), an enzyme that synthesizes DNA on an RNA template. [NIH] Rhamnose: A methylpentose whose L- isomer is found naturally in many plant glycosides and some gram-negative bacterial lipopolysaccharides. [NIH] Rheumatic Diseases: Disorders of connective tissue, especially the joints and related structures, characterized by inflammation, degeneration, or metabolic derangement. [NIH] Rheumatism: A group of disorders marked by inflammation or pain in the connective tissue structures of the body. These structures include bone, cartilage, and fat. [NIH] Rheumatoid: Resembling rheumatism. [EU] Rheumatoid arthritis: A form of arthritis, the cause of which is unknown, although infection, hypersensitivity, hormone imbalance and psychologic stress have been suggested as possible causes. [NIH] Rhinitis: Inflammation of the mucous membrane of the nose. [NIH] Rhinorrhea: The free discharge of a thin nasal mucus. [EU] Rhinovirus: A genus of Picornaviridae inhabiting primarily the respiratory tract of mammalian hosts. It includes the human strains associated with common colds. [NIH]

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Ribavirin: 1-beta-D-Ribofuranosyl-1H-1,2,4-triazole-3-carboxamide. A nucleoside antimetabolite antiviral agent that blocks nucleic acid synthesis and is used against both RNA and DNA viruses. [NIH] Ribonuclease: RNA-digesting enzyme. [NIH] Ribonucleic acid: RNA. One of the two nucleic acids found in all cells. The other is deoxyribonucleic acid (DNA). Ribonucleic acid transfers genetic information from DNA to proteins produced by the cell. [NIH] Ribosome: A granule of protein and RNA, synthesized in the nucleolus and found in the cytoplasm of cells. Ribosomes are the main sites of protein synthesis. Messenger RNA attaches to them and there receives molecules of transfer RNA bearing amino acids. [NIH] Rigidity: Stiffness or inflexibility, chiefly that which is abnormal or morbid; rigor. [EU] Rimantadine: An RNA synthesis inhibitor that is used as an antiviral agent in the prophylaxis and treatment of influenza. [NIH] Rinderpest: A viral disease of cloven-hoofed animals caused by Morbillivirus. It may be acute, subacute, or chronic with the major lesions characterized by inflammation and ulceration of the entire digestive tract. [NIH] Rinderpest Virus: A species of Morbillivirus causing cattle plague, a disease with high mortality. Sheep, goats, pigs, and other animals of the order Artiodactyla can also be infected. [NIH] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Risk patient: Patient who is at risk, because of his/her behaviour or because of the type of person he/she is. [EU] RNA: Ribonucleic acid. One of the two types of nucleic acids found in cells. The other is DNA (deoxyribonucleic acid). RNA plays a role in sending information from DNA to the protein-forming system of the cell. [NIH] RNA Viruses: Viruses whose genetic material is RNA. [NIH] Rod: A reception for vision, located in the retina. [NIH] Rodenticides: Substances used to destroy or inhibit the action of rats, mice, or other rodents. [NIH]

Rotavirus: A genus of Reoviridae, causing acute gastroenteritis in birds and mammals, including humans. Transmission is horizontal and by environmental contamination. [NIH] Rubella Virus: The type (and only) species of Rubivirus causing acute infection in humans, primarily children and young adults. Humans are the only natural host. A live, attenuated vaccine is available for prophylaxis. [NIH] Rubulavirus: A genus of the family Paramyxoviridae (subfamily Paramyxovirinae) where all the species have hemagglutinin and neuraminidase activities but lack a C protein. Mumps virus is the type species. [NIH] Rutin: 3-((6-O-(6-Deoxy-alpha-L-mannopyranosyl)-beta-D-glucopyranosyl)oxy)-2-(3,4dihydroxyphenyl)-5,7-dihydroxy-4H-1-benzopyran-4-one. Found in many plants, including buckwheat, tobacco, forsythia, hydrangea, pansies, etc. It has been used therapeutically to decrease capillary fragility. [NIH] Salicylate: Non-steroidal anti-inflammatory drugs. [NIH] Salicylic: A tuberculosis drug. [NIH] Salicylic Acids: Derivatives and salts of salicylic acid. [NIH]

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Saliva: The clear, viscous fluid secreted by the salivary glands and mucous glands of the mouth. It contains mucins, water, organic salts, and ptylin. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [NIH] Salmonella: A genus of gram-negative, facultatively anaerobic, rod-shaped bacteria that utilizes citrate as a sole carbon source. It is pathogenic for humans, causing enteric fevers, gastroenteritis, and bacteremia. Food poisoning is the most common clinical manifestation. Organisms within this genus are separated on the basis of antigenic characteristics, sugar fermentation patterns, and bacteriophage susceptibility. [NIH] Sarcosine: Methylamino-acetic acid. [NIH] Schizoid: Having qualities resembling those found in greater degree in schizophrenics; a person of schizoid personality. [NIH] Schizophrenia: A mental disorder characterized by a special type of disintegration of the personality. [NIH] Schizotypal Personality Disorder: A personality disorder in which there are oddities of thought (magical thinking, paranoid ideation, suspiciousness), perception (illusions, depersonalization), speech (digressive, vague, overelaborate), and behavior (inappropriate affect in social interactions, frequently social isolation) that are not severe enough to characterize schizophrenia. [NIH] Scleroderma: A chronic disorder marked by hardening and thickening of the skin. Scleroderma can be localized or it can affect the entire body (systemic). [NIH] Scopolamine: An alkaloid from Solanaceae, especially Datura metel L. and Scopola carniolica. Scopolamine and its quaternary derivatives act as antimuscarinics like atropine, but may have more central nervous system effects. Among the many uses are as an anesthetic premedication, in urinary incontinence, in motion sickness, as an antispasmodic, and as a mydriatic and cycloplegic. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Sebaceous: Gland that secretes sebum. [NIH] Secretion: 1. The process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. Any substance produced by secretion. [EU] Secretory: Secreting; relating to or influencing secretion or the secretions. [NIH] Sediment: A precipitate, especially one that is formed spontaneously. [EU] Segmentation: The process by which muscles in the intestines move food and wastes through the body. [NIH] Segregation: The separation in meiotic cell division of homologous chromosome pairs and their contained allelomorphic gene pairs. [NIH] Seizures: Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as epilepsy or "seizure disorder." [NIH] Semen: The thick, yellowish-white, viscid fluid secretion of male reproductive organs discharged upon ejaculation. In addition to reproductive organ secretions, it contains spermatozoa and their nutrient plasma. [NIH] Semisynthetic: Produced by chemical manipulation of naturally occurring substances. [EU]

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Senile: Relating or belonging to old age; characteristic of old age; resulting from infirmity of old age. [NIH] Sensitization: 1. Administration of antigen to induce a primary immune response; priming; immunization. 2. Exposure to allergen that results in the development of hypersensitivity. 3. The coating of erythrocytes with antibody so that they are subject to lysis by complement in the presence of homologous antigen, the first stage of a complement fixation test. [EU] Sensor: A device designed to respond to physical stimuli such as temperature, light, magnetism or movement and transmit resulting impulses for interpretation, recording, movement, or operating control. [NIH] Sensory loss: A disease of the nerves whereby the myelin or insulating sheath of myelin on the nerves does not stay intact and the messages from the brain to the muscles through the nerves are not carried properly. [NIH] Septicaemia: A term originally used to denote a putrefactive process in the body, but now usually referring to infection with pyogenic micro-organisms; a genus of Diptera; the severe type of infection in which the blood stream is invaded by large numbers of the causal. [NIH] Septicemia: Systemic disease associated with the presence and persistence of pathogenic microorganisms or their toxins in the blood. Called also blood poisoning. [EU] Sequence Analysis: A multistage process that includes the determination of a sequence (protein, carbohydrate, etc.), its fragmentation and analysis, and the interpretation of the resulting sequence information. [NIH] Sequence Homology: The degree of similarity between sequences. Studies of amino acid and nucleotide sequences provide useful information about the genetic relatedness of certain species. [NIH] Sequencing: The determination of the order of nucleotides in a DNA or RNA chain. [NIH] Serologic: Analysis of a person's serum, especially specific immune or lytic serums. [NIH] Serology: The study of serum, especially of antigen-antibody reactions in vitro. [NIH] Serotonin: A biochemical messenger and regulator, synthesized from the essential amino acid L-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (receptors, serotonin) explain the broad physiological actions and distribution of this biochemical mediator. [NIH] Serotypes: A cause of haemorrhagic septicaemia (in cattle, sheep and pigs), fowl cholera of birds, pasteurellosis of rabbits, and gangrenous mastitis of ewes. It is also commonly found in atrophic rhinitis of pigs. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Sex Characteristics: Those characteristics that distinguish one sex from the other. The primary sex characteristics are the ovaries and testes and their related hormones. Secondary sex characteristics are those which are masculine or feminine but not directly related to reproduction. [NIH] Sexually Transmitted Diseases: Diseases due to or propagated by sexual contact. [NIH] Shock: The general bodily disturbance following a severe injury; an emotional or moral upset occasioned by some disturbing or unexpected experience; disruption of the circulation, which can upset all body functions: sometimes referred to as circulatory shock. [NIH]

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Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the one sought to be benefited by its administration. [EU] Sigmoid: 1. Shaped like the letter S or the letter C. 2. The sigmoid colon. [EU] Sigmoidoscopy: Endoscopic examination, therapy or surgery of the sigmoid flexure. [NIH] Signal Transduction: The intercellular or intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GABA-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptormediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. [NIH] Signs and Symptoms: Clinical manifestations that can be either objective when observed by a physician, or subjective when perceived by the patient. [NIH] Sinusitis: An inflammatory process of the mucous membranes of the paranasal sinuses that occurs in three stages: acute, subacute, and chronic. Sinusitis results from any condition causing ostial obstruction or from pathophysiologic changes in the mucociliary transport mechanism. [NIH] Skeletal: Having to do with the skeleton (boney part of the body). [NIH] Skeleton: The framework that supports the soft tissues of vertebrate animals and protects many of their internal organs. The skeletons of vertebrates are made of bone and/or cartilage. [NIH] Skin Tests: Epicutaneous or intradermal application of a sensitizer for demonstration of either delayed or immediate hypersensitivity. Used in diagnosis of hypersensitivity or as a test for cellular immunity. [NIH] Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Smallpox: A generalized virus infection with a vesicular rash. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]

Sneezing: Sudden, forceful, involuntary expulsion of air from the nose and mouth caused by irritation to the mucous membranes of the upper respiratory tract. [NIH] Social Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [NIH] Social Support: Support systems that provide assistance and encouragement to individuals with physical or emotional disabilities in order that they may better cope. Informal social support is usually provided by friends, relatives, or peers, while formal assistance is provided by churches, groups, etc. [NIH] Sodium: An element that is a member of the alkali group of metals. It has the atomic symbol

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Na, atomic number 11, and atomic weight 23. With a valence of 1, it has a strong affinity for oxygen and other nonmetallic elements. Sodium provides the chief cation of the extracellular body fluids. Its salts are the most widely used in medicine. (From Dorland, 27th ed) Physiologically the sodium ion plays a major role in blood pressure regulation, maintenance of fluid volume, and electrolyte balance. [NIH] Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] Solvent: 1. Dissolving; effecting a solution. 2. A liquid that dissolves or that is capable of dissolving; the component of a solution that is present in greater amount. [EU] Soma: The body as distinct from the mind; all the body tissue except the germ cells; all the axial body. [NIH] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] Somatic cells: All the body cells except the reproductive (germ) cells. [NIH] Spasmodic: Of the nature of a spasm. [EU] Spastic: 1. Of the nature of or characterized by spasms. 2. Hypertonic, so that the muscles are stiff and the movements awkward. 3. A person exhibiting spasticity, such as occurs in spastic paralysis or in cerebral palsy. [EU] Spatial disorientation: Loss of orientation in space where person does not know which way is up. [NIH] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Species Specificity: Restriction of a characteristic or response to the members of one species; it usually refers to that property of the immune response which differentiates one species from another on the basis of antigen recognition, but the concept is not limited to immunology and is used loosely at levels higher than the species. [NIH] Specificity: Degree of selectivity shown by an antibody with respect to the number and types of antigens with which the antibody combines, as well as with respect to the rates and the extents of these reactions. [NIH] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU] Sperm: The fecundating fluid of the male. [NIH] Spike: The activation of synapses causes changes in the permeability of the dendritic membrane leading to changes in the membrane potential. This difference of the potential travels along the axon of the neuron and is called spike. [NIH] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] Spinal Cord Vascular Diseases: Hypoxic-ischemic and hemorrhagic disorders of the spinal cord. Arteriosclerosis, emboli, and vascular malformations are potential causes of these conditions. [NIH]

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Spirochete: Lyme disease. [NIH] Spleen: An organ that is part of the lymphatic system. The spleen produces lymphocytes, filters the blood, stores blood cells, and destroys old blood cells. It is located on the left side of the abdomen near the stomach. [NIH] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [EU] Spores: The reproductive elements of lower organisms, such as protozoa, fungi, and cryptogamic plants. [NIH] Sputum: The material expelled from the respiratory passages by coughing or clearing the throat. [NIH] Statistically significant: Describes a mathematical measure of difference between groups. The difference is said to be statistically significant if it is greater than what might be expected to happen by chance alone. [NIH] Sterile: Unable to produce children. [NIH] Sterility: 1. The inability to produce offspring, i.e., the inability to conceive (female s.) or to induce conception (male s.). 2. The state of being aseptic, or free from microorganisms. [EU] Sterilization: The destroying of all forms of life, especially microorganisms, by heat, chemical, or other means. [NIH] Steroid: A group name for lipids that contain a hydrogenated cyclopentanoperhydrophenanthrene ring system. Some of the substances included in this group are progesterone, adrenocortical hormones, the gonadal hormones, cardiac aglycones, bile acids, sterols (such as cholesterol), toad poisons, saponins, and some of the carcinogenic hydrocarbons. [EU] Stimulant: 1. Producing stimulation; especially producing stimulation by causing tension on muscle fibre through the nervous tissue. 2. An agent or remedy that produces stimulation. [EU]

Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Stomatitis: Inflammation of the oral mucosa, due to local or systemic factors which may involve the buccal and labial mucosa, palate, tongue, floor of the mouth, and the gingivae. [EU]

Stool: The waste matter discharged in a bowel movement; feces. [NIH] Strand: DNA normally exists in the bacterial nucleus in a helix, in which two strands are coiled together. [NIH] Streptococcal: Caused by infection due to any species of streptococcus. [NIH] Streptococcus: A genus of gram-positive, coccoid bacteria whose organisms occur in pairs or chains. No endospores are produced. Many species exist as commensals or parasites on man or animals with some being highly pathogenic. A few species are saprophytes and occur in the natural environment. [NIH] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] Stroke: Sudden loss of function of part of the brain because of loss of blood flow. Stroke may be caused by a clot (thrombosis) or rupture (hemorrhage) of a blood vessel to the brain. [NIH] Stromal: Large, veil-like cell in the bone marrow. [NIH]

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Stromal Cells: Connective tissue cells of an organ found in the loose connective tissue. These are most often associated with the uterine mucosa and the ovary as well as the hematopoietic system and elsewhere. [NIH] Stupor: Partial or nearly complete unconsciousness, manifested by the subject's responding only to vigorous stimulation. Also, in psychiatry, a disorder marked by reduced responsiveness. [EU] Subacute: Somewhat acute; between acute and chronic. [EU] Subarachnoid: Situated or occurring between the arachnoid and the pia mater. [EU] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] Subcutaneous: Beneath the skin. [NIH] Subspecies: A category intermediate in rank between species and variety, based on a smaller number of correlated characters than are used to differentiate species and generally conditioned by geographical and/or ecological occurrence. [NIH] Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of pain, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses. [NIH]

Substrate: A substance upon which an enzyme acts. [EU] Suction: The removal of secretions, gas or fluid from hollow or tubular organs or cavities by means of a tube and a device that acts on negative pressure. [NIH] Sudden cardiac death: Cardiac arrest caused by an irregular heartbeat. [NIH] Sulfates: Inorganic salts of sulfuric acid. [NIH] Sulfur: An element that is a member of the chalcogen family. It has an atomic symbol S, atomic number 16, and atomic weight 32.066. It is found in the amino acids cysteine and methionine. [NIH] Sulfuric acid: A strong acid that, when concentrated is extemely corrosive to the skin and mucous membranes. It is used in making fertilizers, dyes, electroplating, and industrial explosives. [NIH] Superantigens: Microbial antigens that have in common an extremely potent activating effect on T-cells that bear a specific variable region. Superantigens cross-link the variable region with class II MHC proteins regardless of the peptide binding in the T-cell receptor's pocket. The result is a transient expansion and subsequent death and anergy of the T-cells with the appropriate variable regions. [NIH] Superinfection: A frequent complication of drug therapy for microbial infection. It may result from opportunistic colonization following immunosuppression by the primary pathogen and can be influenced by the time interval between infections, microbial physiology, or host resistance. Experimental challenge and in vitro models are sometimes used in virulence and infectivity studies. [NIH] Supplementation: Adding nutrients to the diet. [NIH] Suppositories: A small cone-shaped medicament having cocoa butter or gelatin at its basis and usually intended for the treatment of local conditions in the rectum. [NIH] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH]

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Suppurative: Consisting of, containing, associated with, or identified by the formation of pus. [NIH] Surface Plasmon Resonance: A biosensing technique in which biomolecules capable of binding to specific analytes or ligands are first immobilized on one side of a metallic film. Light is then focused on the opposite side of the film to excite the surface plasmons, that is, the oscillations of free electrons propagating along the film's surface. The refractive index of light reflecting off this surface is measured. When the immobilized biomolecules are bound by their ligands, an alteration in surface plasmons on the opposite side of the film is created which is directly proportional to the change in bound, or adsorbed, mass. Binding is measured by changes in the refractive index. The technique is used to study biomolecular interactions, such as antigen-antibody binding. [NIH] Surfactant: A fat-containing protein in the respiratory passages which reduces the surface tension of pulmonary fluids and contributes to the elastic properties of pulmonary tissue. [NIH]

Surgical Wound Infection: Infection occurring at the site of a surgical incision. [NIH] Survival Rate: The proportion of survivors in a group, e.g., of patients, studied and followed over a period, or the proportion of persons in a specified group alive at the beginning of a time interval who survive to the end of the interval. It is often studied using life table methods. [NIH] Sympathomimetic: 1. Mimicking the effects of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. 2. An agent that produces effects similar to those of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. Called also adrenergic. [EU] Symphysis: A secondary cartilaginous joint. [NIH] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] Symptomatic treatment: Therapy that eases symptoms without addressing the cause of disease. [NIH] Symptomatology: 1. That branch of medicine with treats of symptoms; the systematic discussion of symptoms. 2. The combined symptoms of a disease. [EU] Synapses: Specialized junctions at which a neuron communicates with a target cell. At classical synapses, a neuron's presynaptic terminal releases a chemical transmitter stored in synaptic vesicles which diffuses across a narrow synaptic cleft and activates receptors on the postsynaptic membrane of the target cell. The target may be a dendrite, cell body, or axon of another neuron, or a specialized region of a muscle or secretory cell. Neurons may also communicate through direct electrical connections which are sometimes called electrical synapses; these are not included here but rather in gap junctions. [NIH] Synaptic: Pertaining to or affecting a synapse (= site of functional apposition between neurons, at which an impulse is transmitted from one neuron to another by electrical or chemical means); pertaining to synapsis (= pairing off in point-for-point association of homologous chromosomes from the male and female pronuclei during the early prophase of meiosis). [EU] Synergistic: Acting together; enhancing the effect of another force or agent. [EU] Syphilis: A contagious venereal disease caused by the spirochete Treponema pallidum. [NIH]

Systemic: Affecting the entire body. [NIH] Tachycardia: Excessive rapidity in the action of the heart, usually with a heart rate above 100 beats per minute. [NIH]

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Tachypnea: Rapid breathing. [NIH] Tea Tree Oil: Essential oil extracted from Melaleuca alternifolia (tea tree). It is used as a topical antimicrobial due to the presence of terpineol. [NIH] Teichoic Acids: Bacterial polysaccharides that are rich in phosphodiester linkages. They are the major components of the cell walls and membranes of many bacteria. [NIH] Temporal: One of the two irregular bones forming part of the lateral surfaces and base of the skull, and containing the organs of hearing. [NIH] Teratogenicity: The power to cause abnormal development. [NIH] Terminator: A DNA sequence sited at the end of a transcriptional unit that signals the end of transcription. [NIH] Testosterone: A hormone that promotes the development and maintenance of male sex characteristics. [NIH] Tetani: Causal agent of tetanus. [NIH] Tetanic: Having the characteristics of, or relating to tetanus. [NIH] Tetanus: A disease caused by tetanospasmin, a powerful protein toxin produced by Clostridium tetani. Tetanus usually occurs after an acute injury, such as a puncture wound or laceration. Generalized tetanus, the most common form, is characterized by tetanic muscular contractions and hyperreflexia. Localized tetanus presents itself as a mild condition with manifestations restricted to muscles near the wound. It may progress to the generalized form. [NIH] Tetanus Toxin: The toxin elaborated by Clostridium tetani. It is a protein with a molecular weight of about 150,000, probably consisting of two fragments, tetanolysin being the hemolytic and tetanospasmin the neurotoxic principle. The toxin causes disruption of the inhibitory mechanisms of the CNS, thus permitting uncontrolled nervous activity, leading to fatal convulsions. [NIH] Tetany: 1. Hyperexcitability of nerves and muscles due to decrease in concentration of extracellular ionized calcium, which may be associated with such conditions as parathyroid hypofunction, vitamin D deficiency, and alkalosis or result from ingestion of alkaline salts; it is characterized by carpopedal spasm, muscular twitching and cramps, laryngospasm with inspiratory stridor, hyperreflexia and choreiform movements. 2. Tetanus. [EU] Tetracycline: An antibiotic originally produced by Streptomyces viridifaciens, but used mostly in synthetic form. It is an inhibitor of aminoacyl-tRNA binding during protein synthesis. [NIH] Thalamic: Cell that reaches the lateral nucleus of amygdala. [NIH] Thalamic Diseases: Disorders of the centrally located thalamus, which integrates a wide range of cortical and subcortical information. Manifestations include sensory loss, movement disorders; ataxia, pain syndromes, visual disorders, a variety of neuropsychological conditions, and coma. Relatively common etiologies include cerebrovascular disorders; craniocerebral trauma; brain neoplasms; brain hypoxia; intracranial hemorrhages; and infectious processes. [NIH] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thermal: Pertaining to or characterized by heat. [EU] Thogoto-Like Viruses: A genus of the family Orthomyxoviridae comprising tick-borne viruses occasionally infecting humans. Dhori and Thogoto viruses were formerly thought to be members of Bunyaviridae. Thogoto virus is the type species. [NIH]

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Threonine: An essential amino acid occurring naturally in the L-form, which is the active form. It is found in eggs, milk, gelatin, and other proteins. [NIH] Threshold: For a specified sensory modality (e. g. light, sound, vibration), the lowest level (absolute threshold) or smallest difference (difference threshold, difference limen) or intensity of the stimulus discernible in prescribed conditions of stimulation. [NIH] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] Thrombocytopenia: A decrease in the number of blood platelets. [NIH] Thrombolytic: 1. Dissolving or splitting up a thrombus. 2. A thrombolytic agent. [EU] Thrombomodulin: A cell surface glycoprotein of endothelial cells that binds thrombin and serves as a cofactor in the activation of protein C and its regulation of blood coagulation. [NIH]

Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thrombus: An aggregation of blood factors, primarily platelets and fibrin with entrapment of cellular elements, frequently causing vascular obstruction at the point of its formation. Some authorities thus differentiate thrombus formation from simple coagulation or clot formation. [EU] Thymidine: A chemical compound found in DNA. Also used as treatment for mucositis. [NIH]

Thymus: An organ that is part of the lymphatic system, in which T lymphocytes grow and multiply. The thymus is in the chest behind the breastbone. [NIH] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH] Thyroid Gland: A highly vascular endocrine gland consisting of two lobes, one on either side of the trachea, joined by a narrow isthmus; it produces the thyroid hormones which are concerned in regulating the metabolic rate of the body. [NIH] Ticks: Blood-sucking arachnids of the order Acarina. [NIH] Tinnitus: Sounds that are perceived in the absence of any external noise source which may take the form of buzzing, ringing, clicking, pulsations, and other noises. Objective tinnitus refers to noises generated from within the ear or adjacent structures that can be heard by other individuals. The term subjective tinnitus is used when the sound is audible only to the affected individual. Tinnitus may occur as a manifestation of cochlear diseases; vestibulocochlear nerve diseases; intracranial hypertension; craniocerebral trauma; and other conditions. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tissue Culture: Maintaining or growing of tissue, organ primordia, or the whole or part of an organ in vitro so as to preserve its architecture and/or function (Dorland, 28th ed). Tissue culture includes both organ culture and cell culture. [NIH] Titre: The quantity of a substance required to produce a reaction with a given volume of another substance, or the amount of one substance required to correspond with a given amount of another substance. [EU] Tolerance: 1. The ability to endure unusually large doses of a drug or toxin. 2. Acquired drug tolerance; a decreasing response to repeated constant doses of a drug or the need for increasing doses to maintain a constant response. [EU] Tooth Preparation: Procedures carried out with regard to the teeth or tooth structures

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preparatory to specified dental therapeutic and surgical measures. [NIH] Topical: On the surface of the body. [NIH] Torsion: A twisting or rotation of a bodily part or member on its axis. [NIH] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxins: Specific, characterizable, poisonous chemicals, often proteins, with specific biological properties, including immunogenicity, produced by microbes, higher plants, or animals. [NIH] Toxoid: The material resulting from the treatment of toxin in such a way that the toxic properties are inactivated whilst the antigenic potency remains intact. [NIH] Trachea: The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi. [NIH] Transaminase: Aminotransferase (= a subclass of enzymes of the transferase class that catalyse the transfer of an amino group from a donor (generally an amino acid) to an acceptor (generally 2-keto acid). Most of these enzymes are pyridoxal-phosphate-proteins. [EU]

Transcriptase: An enzyme which catalyses the synthesis of a complementary mRNA molecule from a DNA template in the presence of a mixture of the four ribonucleotides (ATP, UTP, GTP and CTP). [NIH] Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process. [NIH] Transduction: The transfer of genes from one cell to another by means of a viral (in the case of bacteria, a bacteriophage) vector or a vector which is similar to a virus particle (pseudovirion). [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Transfer Factor: Factor derived from leukocyte lysates of immune donors which can transfer both local and systemic cellular immunity to nonimmune recipients. [NIH] Transferases: Transferases are enzymes transferring a group, for example, the methyl group or a glycosyl group, from one compound (generally regarded as donor) to another compound (generally regarded as acceptor). The classification is based on the scheme "donor:acceptor group transferase". (Enzyme Nomenclature, 1992) EC 2. [NIH] Transforming Growth Factor beta: A factor synthesized in a wide variety of tissues. It acts synergistically with TGF-alpha in inducing phenotypic transformation and can also act as a negative autocrine growth factor. TGF-beta has a potential role in embryonal development, cellular differentiation, hormone secretion, and immune function. TGF-beta is found mostly as homodimer forms of separate gene products TGF-beta1, TGF-beta2 or TGF-beta3. Heterodimers composed of TGF-beta1 and 2 (TGF-beta1.2) or of TGF-beta2 and 3 (TGFbeta2.3) have been isolated. The TGF-beta proteins are synthesized as precursor proteins. [NIH]

Translation: The process whereby the genetic information present in the linear sequence of ribonucleotides in mRNA is converted into a corresponding sequence of amino acids in a

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protein. It occurs on the ribosome and is unidirectional. [NIH] Translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Translocation: The movement of material in solution inside the body of the plant. [NIH] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell to the other at the synapse. [NIH] Transplantation: Transference of a tissue or organ, alive or dead, within an individual, between individuals of the same species, or between individuals of different species. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Trees: Woody, usually tall, perennial higher plants (Angiosperms, Gymnosperms, and some Pterophyta) having usually a main stem and numerous branches. [NIH] Trichomoniasis: An infection with the protozoan parasite Trichomonas vaginalis. [NIH] Trivalent: Having a valence of three. [EU] Tropism: Directed movements and orientations found in plants, such as the turning of the sunflower to face the sun. [NIH] Tryptophan: An essential amino acid that is necessary for normal growth in infants and for nitrogen balance in adults. It is a precursor serotonin and niacin. [NIH] Tuberculosis: Any of the infectious diseases of man and other animals caused by species of Mycobacterium. [NIH] Tumor marker: A substance sometimes found in an increased amount in the blood, other body fluids, or tissues and which may mean that a certain type of cancer is in the body. Examples of tumor markers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and gastrointestinal tract cancers), and PSA (prostate cancer). Also called biomarker. [NIH] Tumour: 1. Swelling, one of the cardinal signs of inflammations; morbid enlargement. 2. A new growth of tissue in which the multiplication of cells is uncontrolled and progressive; called also neoplasm. [EU] Type 2 diabetes: Usually characterized by a gradual onset with minimal or no symptoms of metabolic disturbance and no requirement for exogenous insulin. The peak age of onset is 50 to 60 years. Obesity and possibly a genetic factor are usually present. [NIH] Tyrosine: A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine, thyroid hormones, and melanin. [NIH] Ubiquitin: A highly conserved 76 amino acid-protein found in all eukaryotic cells. [NIH] Ulcer: A localized necrotic lesion of the skin or a mucous surface. [NIH] Ulceration: 1. The formation or development of an ulcer. 2. An ulcer. [EU] Umbilical Cord: The flexible structure, giving passage to the umbilical arteries and vein, which connects the embryo or fetus to the placenta. [NIH] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Urea: A compound (CO(NH2)2), formed in the liver from ammonia produced by the deamination of amino acids. It is the principal end product of protein catabolism and constitutes about one half of the total urinary solids. [NIH] Uremia: The illness associated with the buildup of urea in the blood because the kidneys are not working effectively. Symptoms include nausea, vomiting, loss of appetite, weakness,

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and mental confusion. [NIH] Ureters: Tubes that carry urine from the kidneys to the bladder. [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]

Uric: A kidney stone that may result from a diet high in animal protein. When the body breaks down this protein, uric acid levels rise and can form stones. [NIH] Urinalysis: Examination of urine by chemical, physical, or microscopic means. Routine urinalysis usually includes performing chemical screening tests, determining specific gravity, observing any unusual color or odor, screening for bacteriuria, and examining the sediment microscopically. [NIH] Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] Urinary tract: The organs of the body that produce and discharge urine. These include the kidneys, ureters, bladder, and urethra. [NIH] Urinary tract infection: An illness caused by harmful bacteria growing in the urinary tract. [NIH]

Urine: Fluid containing water and waste products. Urine is made by the kidneys, stored in the bladder, and leaves the body through the urethra. [NIH] Urogenital: Pertaining to the urinary and genital apparatus; genitourinary. [EU] Uterus: The small, hollow, pear-shaped organ in a woman's pelvis. This is the organ in which a fetus develops. Also called the womb. [NIH] Vaccination: Administration of vaccines to stimulate the host's immune response. This includes any preparation intended for active immunological prophylaxis. [NIH] Vaccine: A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. [NIH] Vaccinia: The cutaneous and occasional systemic reactions associated with vaccination using smallpox (variola) vaccine. [NIH] Vaccinia Virus: The type species of Orthopoxvirus, related to cowpox virus, but whose true origin is unknown. It has been used as a live vaccine against smallpox. It is also used as a vector for inserting foreign DNA into animals. Rabbitpox virus is a subspecies of vaccinia virus. [NIH] Vacuoles: Any spaces or cavities within a cell. They may function in digestion, storage, secretion, or excretion. [NIH] Vagina: The muscular canal extending from the uterus to the exterior of the body. Also called the birth canal. [NIH] Valves: Flap-like structures that control the direction of blood flow through the heart. [NIH] Varicella: Chicken pox. [EU] Variola: A generalized virus infection with a vesicular rash. [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vasculitis: Inflammation of a blood vessel. [NIH] Vasodilator: An agent that widens blood vessels. [NIH] VE: The total volume of gas either inspired or expired in one minute. [NIH] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH]

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Vegetarianism: Dietary practice of consuming only vegetables, grains, and nuts. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venereal: Pertaining or related to or transmitted by sexual contact. [EU] Venous: Of or pertaining to the veins. [EU] Ventricle: One of the two pumping chambers of the heart. The right ventricle receives oxygen-poor blood from the right atrium and pumps it to the lungs through the pulmonary artery. The left ventricle receives oxygen-rich blood from the left atrium and pumps it to the body through the aorta. [NIH] Ventricular: Pertaining to a ventricle. [EU] Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Vertigo: An illusion of movement; a sensation as if the external world were revolving around the patient (objective vertigo) or as if he himself were revolving in space (subjective vertigo). The term is sometimes erroneously used to mean any form of dizziness. [EU] Vesicular: 1. Composed of or relating to small, saclike bodies. 2. Pertaining to or made up of vesicles on the skin. [EU] Veterinarians: Individuals with a degree in veterinary medicine that provides them with training and qualifications to treat diseases and injuries of animals. [NIH] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Vial: A small bottle. [EU] Vibrio: A genus of Vibrionaceae, made up of short, slightly curved, motile, gram-negative rods. Various species produce cholera and other gastrointestinal disorders as well as abortion in sheep and cattle. [NIH] Vibrio cholerae: The etiologic agent of cholera. [NIH] Vidarabine: A nucleoside antibiotic isolated from Streptomyces antibioticus. It has some antineoplastic properties and has broad spectrum activity against DNA viruses in cell cultures and significant antiviral activity against infections caused by a variety of viruses such as the herpes viruses, the vaccinia virus and varicella zoster virus. [NIH] Villous: Of a surface, covered with villi. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Viral Core Proteins: Proteins found mainly in icosahedral DNA and RNA viruses. They consist of proteins directly associated with the nucleic acid inside the nucleocapsid. [NIH] Viral Fusion Proteins: Proteins, usually glycoproteins, found in the viral envelopes of a variety of viruses. They promote cell membrane fusion and thereby may function in the uptake of the virus by cells. [NIH] Viral Hepatitis: Hepatitis caused by a virus. Five different viruses (A, B, C, D, and E) most commonly cause this form of hepatitis. Other rare viruses may also cause hepatitis. [NIH] Viral Load: The quantity of measurable virus in the blood. Change in viral load, measured in plasma, is used as a surrogate marker in HIV disease progression. [NIH] Viral Vaccines: Suspensions of attenuated or killed viruses administered for the prevention or treatment of infectious viral disease. [NIH] Viral vector: A type of virus used in cancer therapy. The virus is changed in the laboratory and cannot cause disease. Viral vectors produce tumor antigens (proteins found on a tumor cell) and can stimulate an antitumor immune response in the body. Viral vectors may also

Dictionary 393

be used to carry genes that can change cancer cells back to normal cells. [NIH] Virion: The infective system of a virus, composed of the viral genome, a protein core, and a protein coat called a capsid, which may be naked or enclosed in a lipoprotein envelope called the peplos. [NIH] Virologist: A specialist of the study of viruses and viral disease. [NIH] Virosomes: Semi-synthetic complex derived from nucleic-acid free viral particles. They are essentially reconstituted viral coats, where the infectious nucleocapsid is replaced by a compound of choice. Virosomes retain their fusogenic activity and thus deliver the incorporated compound (antigens, drugs, genes) inside the target cell. They can be used for vaccines (vaccines, virosome), drug delivery, or gene transfer. [NIH] Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [NIH] Virulent: A virus or bacteriophage capable only of lytic growth, as opposed to temperate phages establishing the lysogenic response. [NIH] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH] Virus Diseases: A general term for diseases produced by viruses. [NIH] Virus Replication: The process of intracellular viral multiplication, consisting of the synthesis of proteins, nucleic acids, and sometimes lipids, and their assembly into a new infectious particle. [NIH] Viscera: Any of the large interior organs in any one of the three great cavities of the body, especially in the abdomen. [NIH] Vitro: Descriptive of an event or enzyme reaction under experimental investigation occurring outside a living organism. Parts of an organism or microorganism are used together with artificial substrates and/or conditions. [NIH] Vivo: Outside of or removed from the body of a living organism. [NIH] Vulgaris: An affection of the skin, especially of the face, the back and the chest, due to chronic inflammation of the sebaceous glands and the hair follicles. [NIH] Vulva: The external female genital organs, including the clitoris, vaginal lips, and the opening to the vagina. [NIH] Vulvovaginitis: Inflammation of the vulva and vagina, or of the vulvovaginal glands. [EU] Wakefulness: A state in which there is an enhanced potential for sensitivity and an efficient responsiveness to external stimuli. [NIH] Warts: Benign epidermal proliferations or tumors; some are viral in origin. [NIH] Wheezing: Breathing with a rasp or whistling sound; a sign of airway constriction or obstruction. [NIH] White blood cell: A type of cell in the immune system that helps the body fight infection and disease. White blood cells include lymphocytes, granulocytes, macrophages, and others. [NIH]

Whooping Cough: A respiratory infection caused by Bordetella pertussis and characterized by paroxysmal coughing ending in a prolonged crowing intake of breath. [NIH] Whooping Cough: A respiratory infection caused by Bordetella pertussis and characterized by paroxysmal coughing ending in a prolonged crowing intake of breath. [NIH]

394 Influenza

Windpipe: A rigid tube, 10 cm long, extending from the cricoid cartilage to the upper border of the fifth thoracic vertebra. [NIH] Withdrawal: 1. A pathological retreat from interpersonal contact and social involvement, as may occur in schizophrenia, depression, or schizoid avoidant and schizotypal personality disorders. 2. (DSM III-R) A substance-specific organic brain syndrome that follows the cessation of use or reduction in intake of a psychoactive substance that had been regularly used to induce a state of intoxication. [EU] Womb: A hollow, thick-walled, muscular organ in which the impregnated ovum is developed into a child. [NIH] Xenograft: The cells of one species transplanted to another species. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH] X-ray therapy: The use of high-energy radiation from x-rays to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. X-ray therapy is also called radiation therapy, radiotherapy, and irradiation. [NIH] Yeasts: A general term for single-celled rounded fungi that reproduce by budding. Brewers' and bakers' yeasts are Saccharomyces cerevisiae; therapeutic dried yeast is dried yeast. [NIH] Yellow Fever: An acute infectious disease primarily of the tropics, caused by a virus and transmitted to man by mosquitoes of the genera Aedes and Haemagogus. [NIH] Zoonoses: Diseases of non-human animals that may be transmitted to man or may be transmitted from man to non-human animals. [NIH] Zoster: A virus infection of the Gasserian ganglion and its nerve branches, characterized by discrete areas of vesiculation of the epithelium of the forehead, the nose, the eyelids, and the cornea together with subepithelial infiltration. [NIH] Zygote: The fertilized ovum. [NIH] Zymogen: Inactive form of an enzyme which can then be converted to the active form, usually by excision of a polypeptide, e. g. trypsinogen is the zymogen of trypsin. [NIH]

395

INDEX A Abacavir, 103, 311 Abdomen, 311, 321, 322, 337, 352, 353, 355, 368, 384, 393 Abdominal, 311, 312, 332, 341, 352, 366, 368 Abdominal Pain, 311, 341, 352 Absenteeism, 116, 180, 311 Acceptor, 311, 355, 366, 389 Acetylcholine, 311, 363 Acetylglucosamine, 217, 311 Acidosis, 3, 311 Acne, 272, 311 Acquired Immunodeficiency Syndrome, 212, 311 Actin, 84, 97, 311 Acute lymphoblastic leukemia, 141, 144, 311 Acute lymphocytic leukemia, 311 Acyl, 30, 237, 238, 311 Adaptability, 311, 324 Adaptation, 61, 85, 87, 91, 198, 219, 235, 311, 370 Adenosine, 312, 322, 369 Adenovirus, 190, 215, 220, 221, 222, 236, 251, 312 Adenylate Cyclase, 312, 325 Adipocytes, 312, 354 Adjustment, 311, 312 Adjuvant, 58, 82, 126, 149, 165, 167, 169, 201, 202, 204, 205, 217, 225, 238, 312, 314, 341 Adolescence, 312, 325 Adolescent Nutrition, 255, 312 Adoptive Transfer, 31, 47, 55, 312 Adrenal Cortex, 312, 329 Adrenal Medulla, 312, 324, 337, 363 Adrenergic, 17, 312, 334, 336, 337, 386 Adsorption, 7, 312 Adsorptive, 312 Adverse Effect, 312, 382 Aerobic, 17, 71, 312, 361 Aerobic Exercise, 17, 312 Aerosol, 31, 42, 45, 312, 350 Aetiology, 261, 313 Afferent, 313, 354, 365 Affinity, 8, 25, 43, 209, 313, 355, 383 Age Groups, 42, 72, 221, 232, 313

Age of Onset, 313, 390 Aged, 80 and Over, 313 Agglutinins, 309, 313, 345 Agonist, 313, 334, 336 Airway, 52, 77, 313, 393 Alanine, 209, 313 Albumin, 313, 366 Alertness, 313, 322 Algorithms, 313, 321 Alimentary, 313, 367 Alkaline, 154, 244, 311, 313, 323, 387 Alkaline Phosphatase, 244, 313 Alkaloid, 314, 319, 360, 380 Allantois, 70, 314 Allergen, 9, 314, 381 Allergic Rhinitis, 248, 249, 314 Allograft, 11, 29, 35, 314 Alpha Particles, 314, 376 Alternative medicine, 271, 314 Alum, 218, 314 Aluminum, 202, 205, 218, 314 Aluminum Hydroxide, 218, 314 Amantadine, 45, 51, 52, 59, 62, 70, 74, 83, 98, 111, 114, 144, 156, 174, 196, 214, 231, 232, 276, 314 Amebiasis, 314, 359 Amenorrhea, 314, 316 Amine, 314, 346 Amino Acid Sequence, 62, 208, 244, 314, 316, 341 Amino Acid Substitution, 91, 314 Amnion, 70, 315 Amniotic Fluid, 315 Amplification, 39, 70, 95, 222, 315 Ampoule, 33, 315 Amyloid, 211, 315 Anaemia, 315, 318 Anaerobic, 49, 315, 380 Anaesthesia, 115, 161, 205, 315, 350 Anal, 315, 336, 339 Analgesic, 315, 360, 365 Analog, 17, 50, 124, 311, 315, 326, 348 Analogous, 195, 315, 334, 371, 389 Analytes, 223, 315, 386 Anaphylatoxins, 315, 327 Anatomical, 315, 349 Androgens, 41, 312, 315, 329 Anemia, 294, 307, 316, 357

396 Influenza

Anergic, 56, 316 Anergy, 316, 385 Anesthesia, 19, 313, 316, 373 Anesthetics, 205, 316, 337 Animal model, 15, 26, 316 Anionic, 235, 316 Ankle, 262, 316 Annealing, 316, 371 Anorexia, 255, 316, 341 Anorexia Nervosa, 255, 316 Antagonism, 316, 322 Anthocyanins, 144, 225, 316 Anthrax, 18, 203, 210, 211, 255, 268, 316 Antiallergic, 316, 329 Antibacterial, 19, 200, 240, 316, 326, 333, 383 Antibiotic, 50, 192, 316, 355, 368, 383, 387, 392 Antibody-Dependent Cell Cytotoxicity, 317, 353 Anticholinergic, 196, 317 Anticoagulant, 317, 332, 374 Antigen-Antibody Complex, 317, 327 Antigen-presenting cell, 231, 317, 332 Antihypertensive, 205, 317, 347 Anti-infective, 50, 192, 193, 317, 347 Anti-inflammatory, 192, 243, 317, 318, 329, 342, 366, 379 Anti-Inflammatory Agents, 317, 318, 329 Antimetabolite, 317, 379 Antimicrobial, 42, 99, 119, 126, 130, 156, 160, 192, 193, 199, 240, 263, 317, 332, 334, 373, 387 Antimycotic, 317, 373 Antineoplastic, 317, 329, 392 Antioxidant, 155, 158, 317 Antipyretic, 144, 155, 317 Antiserum, 317, 319 Antiviral Agents, 13, 25, 194, 195, 200, 318 Anxiety, 5, 42, 318 Aplastic anaemia, 133, 318 Apolipoproteins, 318, 355 Applicability, 253, 318 Aqueous, 168, 218, 248, 318, 320, 330, 335, 347, 355 Arenavirus, 318, 356 Arginine, 158, 315, 318, 363 Aromatic, 225, 248, 318, 369 Arterial, 318, 326, 342, 347, 374 Arteries, 22, 318, 321, 329, 356, 359, 390 Arterioles, 318, 321, 323 Arthroplasty, 113, 318

Artifacts, 14, 318 Aseptic, 318, 356, 365, 384 Aspergillus, 223, 250, 318 Aspirate, 66, 318 Aspiration, 191, 242, 318 Aspirin, 119, 292, 294, 318 Assay, 17, 48, 54, 60, 63, 66, 70, 72, 77, 78, 90, 95, 103, 105, 109, 157, 159, 196, 239, 318, 348 Asthenia, 316, 318 Astringents, 318, 337, 359 Asymptomatic, 262, 263, 294, 314, 318 Ataxia, 214, 319, 387 Atopic, 9, 319 Atropine, 319, 320, 380 Attenuation, 63, 92, 198, 219, 319 Autoantibodies, 28, 117, 319 Autoantigens, 319 Autoimmune disease, 34, 46, 319, 361 Autoimmunity, 35, 46, 319 Autologous, 41, 319 Autonomic, 262, 311, 319, 320, 361, 363 Autonomic Nervous System, 319, 320 Autopsy, 13, 319 Avidity, 20, 319 B Bacillus, 30, 51, 316, 319, 322 Bacteremia, 5, 262, 319, 380 Bacteria, 8, 50, 71, 190, 192, 199, 200, 215, 217, 228, 233, 237, 240, 250, 255, 311, 312, 316, 317, 319, 320, 321, 328, 335, 336, 338, 339, 343, 347, 359, 361, 370, 380, 383, 384, 387, 389, 391 Bacterial Infections, 198, 200, 220, 262, 319, 325 Bacterial Outer Membrane Proteins, 226, 319 Bacterial Physiology, 312, 319 Bacteriophage, 319, 320, 351, 380, 389, 393 Bacteriophage lambda, 320, 351 Bacterium, 225, 320, 328, 345 Bacteriuria, 262, 320, 391 Basal Ganglia, 319, 320, 340 Basal Ganglia Diseases, 319, 320 Base, 7, 197, 231, 238, 241, 320, 331, 332, 341, 353, 371, 387 Base Sequence, 241, 320, 341 Basophil, 320, 346 Belladonna, 173, 199, 319, 320 Benign, 190, 247, 320, 340, 344, 356, 362, 366, 376, 393 Beta-pleated, 315, 320

Index 397

Beta-Thromboglobulin, 320, 351 Bewilderment, 320, 328 Bile, 292, 320, 321, 340, 342, 347, 353, 355, 384 Bile Acids, 320, 384 Bile Acids and Salts, 320 Bile Pigments, 321, 353 Bilirubin, 292, 313, 321, 342, 347 Bioavailability, 205, 321 Biochemical, 36, 99, 155, 156, 163, 196, 317, 321, 340, 343, 354, 381 Biological response modifier, 166, 239, 321, 351 Biomarkers, 9, 321 Biomolecular, 34, 144, 321, 386 Biosynthesis, 49, 321 Biotechnology, 59, 97, 149, 220, 260, 271, 283, 321 Bioterrorism, 21, 23, 31, 42, 43, 48, 58, 255, 321 Bladder, 321, 330, 349, 361, 374, 391 Bloating, 321, 349, 352 Blood Coagulation, 321, 323, 388 Blood pressure, 294, 317, 321, 324, 342, 347, 348, 360, 383 Blood vessel, 314, 321, 323, 325, 336, 342, 345, 353, 356, 375, 382, 383, 384, 388, 391 Blood-Brain Barrier, 321, 354 Blot, 43, 72, 109, 321 Body Fluids, 321, 383, 390 Bone Cements, 321, 371 Bone Marrow, 21, 38, 311, 318, 322, 345, 348, 356, 358, 360, 384 Bone Marrow Cells, 38, 322, 358 Bowel, 192, 315, 322, 333, 352, 368, 384 Bowel Movement, 322, 333, 384 Brachytherapy, 322, 352, 376, 394 Bradykinin, 322, 363 Branch, 145, 147, 148, 267, 268, 305, 322, 341, 349, 356, 367, 375, 383, 386, 387 Breeding, 38, 249, 322 Bronchi, 322, 337, 389 Bronchial, 207, 230, 322, 346 Bronchioles, 322 Bronchiolitis, 39, 322 Bronchiseptica, 322, 368 Bronchitis, 171, 233, 250, 262, 322, 326, 337 Buccal, 322, 356, 384 Bullous, 111, 322 Butyric Acid, 235, 322 C Caffeine, 168, 199, 254, 322, 375

Calcium, 208, 244, 321, 322, 327, 367, 382, 387 Calculi, 323, 343 Capillary, 249, 322, 323, 324, 379, 392 Capillary Fragility, 323, 324, 379 Capillary Permeability, 249, 322, 323 Capital Financing, 323, 372 Capsid, 323, 364, 393 Capsules, 232, 323, 334, 341 Carbohydrate, 50, 130, 192, 208, 219, 244, 323, 329, 342, 343, 371, 381 Carbon Dioxide, 323, 331, 339, 341, 377 Carboxy, 74, 229, 323 Carboxy-terminal, 229, 323 Carcinoembryonic Antigen, 210, 211, 323 Carcinogen, 323, 359 Carcinogenesis, 243, 323 Carcinogenic, 323, 350, 373, 384 Carcinoma, 221, 247, 323 Cardiac, 11, 29, 55, 270, 322, 323, 337, 361, 384, 385 Cardiorespiratory, 312, 323 Cardiovascular, 3, 120, 254, 273, 323, 381 Cardiovascular disease, 3, 254, 273, 323 Case report, 113, 324, 338 Catalyse, 324, 389 Catechin, 164, 324 Catecholamine, 17, 324, 334 Causal, 324, 336, 381, 387 Cause of Death, 15, 46, 53, 215, 227, 273, 324, 331 Celiac Disease, 255, 324 Cell Count, 185, 324 Cell Death, 99, 192, 219, 324, 362 Cell Differentiation, 43, 324, 382 Cell Division, 319, 324, 344, 358, 370, 373, 380 Cell Fusion, 33, 93, 324 Cell membrane, 33, 212, 234, 324, 332, 338, 358, 369, 392 Cell Physiology, 51, 324 Cell proliferation, 17, 21, 264, 324, 352, 382 Cell Size, 324, 340 Cellulitis, 113, 324 Cellulose, 181, 324, 340, 370 Central Nervous System Infections, 325, 344 Cerebellar, 319, 325, 377 Cerebral, 127, 319, 320, 321, 325, 329, 331, 337, 338, 357, 374, 383 Cerebrovascular, 320, 324, 325, 387 Cerebrum, 325

398 Influenza

Cervical, 221, 247, 325 Cervix, 325 Character, 50, 325, 331, 343 Chemokines, 239, 325 Chemotactic Factors, 325, 327 Chemotherapy, 41, 99, 116, 119, 126, 130, 156, 160, 224, 243, 256, 268, 310, 325 Chickenpox, 292, 325 Child Development, 35, 325 Chimeric Proteins, 226, 325 Chlorophyll, 325, 340 Cholera, 32, 217, 250, 256, 266, 325, 381, 392 Cholera Toxin, 217, 325 Cholesterol, 22, 255, 294, 320, 326, 329, 355, 356, 384 Cholesterol Esters, 326, 355 Chromosomal, 315, 326, 370, 378 Chromosome, 326, 328, 344, 355, 380 Chronic Disease, 5, 202, 205, 326, 354 Chronic Fatigue Syndrome, 243, 326 Chronic Obstructive Pulmonary Disease, 106, 107, 171, 326 Chylomicrons, 326, 355 CIS, 94, 326, 378 Clathrin, 16, 81, 117, 162, 326 Cleave, 200, 326 Clindamycin, 264, 326 Clinical Medicine, 165, 326, 372 Clinical trial, 6, 25, 183, 186, 283, 326, 329, 368, 374, 376 Cloning, 8, 82, 321, 326 Coated Vesicles, 326 Codon, 103, 241, 326, 341 Cofactor, 326, 374, 388 Cognition, 47, 326 Cohort Studies, 327, 336 Colitis, 327, 353 Collagen, 208, 244, 324, 327, 339, 341, 370, 373 Colloidal, 313, 327, 335 Combinatorial, 8, 327 Commensal, 226, 327 Communicable disease, 215, 295, 327 Communication Disorders, 50, 187, 282, 327 Complement, 19, 50, 67, 68, 154, 160, 309, 315, 317, 327, 328, 341, 357, 360, 381 Complementary and alternative medicine, 153, 177, 327 Complementary medicine, 153, 328 Computational Biology, 283, 328

Conception, 328, 339, 384 Concomitant, 138, 328 Cone, 163, 328, 385 Confusion, 117, 308, 328, 333, 348, 391 Congestion, 223, 248, 249, 308, 328 Congestive heart failure, 54, 328 Conjugated, 192, 219, 250, 320, 328 Conjugation, 44, 80, 328 Conjunctiva, 328, 350 Connective Tissue, 322, 324, 327, 328, 341, 342, 356, 378, 385 Consciousness, 315, 328, 331, 333 Constipation, 255, 328, 352 Constriction, 328, 353, 393 Consumption, 328, 341, 364, 377 Contamination, 206, 207, 295, 328, 379 Contraindications, ii, 293, 329 Contrast Sensitivity, 329, 365 Control group, 5, 329 Convulsions, 329, 348, 387 Cornea, 214, 329, 353, 394 Coronary, 116, 323, 329, 359 Coronary heart disease, 323, 329 Coronary Thrombosis, 329, 359 Cortex, 319, 329, 338, 377 Corticosteroid, 106, 329 Cortisol, 5, 10, 47, 313, 329 Coryza, 249, 250, 329 Cowpox, 329, 391 Cowpox Virus, 329, 391 Coxsackie virus, 155, 329 Cranial, 330, 337, 344, 362, 365, 367 Craniocerebral Trauma, 320, 330, 344, 387, 388 Crossing-over, 330, 376 Cross-Sectional Studies, 330, 336 Croup, 258, 330, 367 Cryoelectron Microscopy, 24, 330 Crystallization, 59, 330 Cultured cells, 45, 71, 159, 166, 197, 330 Curative, 330, 363, 387 Cutaneous, 204, 316, 330, 356, 391 Cyclic, 21, 312, 322, 330, 344, 363, 374 Cyst, 318, 330 Cysteine, 62, 85, 208, 244, 325, 330, 385 Cystine, 330 Cystitis, 262, 330 Cytarabine, 214, 330 Cytomegalovirus, 221, 231, 234, 254, 263, 264, 330 Cytoplasm, 45, 324, 325, 330, 331, 343, 360, 363, 379

Index 399

Cytoskeletal Proteins, 326, 330 Cytoskeleton, 97, 330 Cytotoxic chemotherapy, 130, 331 Cytotoxicity, 47, 331 D Data Collection, 331, 340 Databases, Bibliographic, 283, 331 Death Certificates, 266, 331 Decarboxylation, 331, 346 Defense Mechanisms, 23, 331 Degenerative, 331, 346 Dehydration, 325, 331 Dehydroepiandrosterone, 169, 331 Delavirdine, 331, 363 Deletion, 57, 89, 213, 331 Delirium, 292, 331 Delivery of Health Care, 331, 344 Dementia, 5, 311, 331 Denaturation, 332, 371 Dendrites, 332, 363 Dendritic, 12, 21, 23, 41, 52, 71, 78, 88, 98, 231, 233, 234, 332, 358, 383 Dendritic cell, 12, 21, 23, 41, 52, 98, 231, 233, 234, 332 Density, 10, 90, 149, 332, 340, 355, 365, 371 Dentifrices, 314, 332 Deoxyribonucleic, 228, 332, 379 Deoxyribonucleic acid, 228, 332, 379 Deoxyribonucleotides, 332 Depolarization, 332, 382 Detergents, 191, 235, 242, 332 Deuterium, 332, 347 Dextran Sulfate, 111, 332 Diabetes Mellitus, 3, 332, 342, 345 Diagnostic procedure, 189, 271, 332, 369 Dialyzer, 332, 345 Diaphragm, 332, 346 Diarrhea, 255, 263, 308, 314, 332, 337, 352 Diarrhoea, 332, 341 Diffusion, 259, 323, 332, 350 Digestion, 313, 320, 322, 332, 334, 349, 352, 355, 384, 391 Digestive system, 187, 333, 361 Digestive tract, 333, 379, 382 Dihydrotestosterone, 333, 377 Dihydroxy, 333, 337, 379 Dilatation, 333, 372 Diphtheria, 293, 294, 295, 296, 333 Diploid, 220, 333, 370 Discrimination, 39, 333 Disease Progression, 333, 392 Disease Susceptibility, 37, 333

Disinfection, 295, 333 Disorientation, 328, 331, 333 Dissociation, 313, 333 Diuresis, 322, 333 Diverticula, 333 Diverticulitis, 255, 333 Diverticulum, 314, 333 Dizziness, 214, 333, 392 Dominance, 20, 333 Dopa, 334, 354 Dopamine, 196, 314, 334, 354, 369 Dosage Forms, 232, 334 Dose-dependent, 15, 334 Doxycycline, 192, 193, 334 Drive, ii, vi, 12, 29, 50, 143, 334, 354 Dross, 334, 373 Drug Design, 195, 334 Drug Interactions, 278, 334 Drug Tolerance, 334, 388 Duodenum, 320, 334, 384 Dura mater, 334, 358, 366 Dyes, 315, 334, 340, 363, 385 Dyspepsia, 334, 349 E Edema, 249, 334 Effector, 18, 19, 31, 90, 234, 311, 317, 327, 335, 353, 363 Effector cell, 317, 335, 353, 363 Elastin, 327, 335 Elective, 91, 92, 134, 167, 335 Electrolyte, 329, 331, 335, 359, 372, 383 Electrons, 317, 320, 335, 352, 366, 376, 386 Electrophoresis, 7, 335 Emaciation, 311, 335 Embolus, 335, 350 Embryo, 315, 324, 335, 339, 350, 371, 390 Emollient, 335, 343, 364 Emphysema, 207, 326, 335 Emulsion, 335, 339, 371 Encapsulated, 216, 217, 223, 226, 335 Encephalitis, 108, 119, 255, 292, 335 Encephalitis, Viral, 335 Encephalopathy, 104, 108, 114, 115, 127, 135, 161, 336 Endemic, 46, 250, 325, 336, 357, 384 Endocrine System, 336, 362 Endocytosis, 16, 21, 81, 117, 162, 234, 336 Endothelial cell, 22, 321, 336, 351, 388 Endothelium, 336, 363, 370 Endothelium-derived, 336, 363 Endotoxic, 336, 355 Endotoxin, 135, 151, 336

400 Influenza

Energy balance, 336, 354 Enhancer, 221, 336, 378 Environmental Exposure, 336, 365 Environmental Health, 282, 284, 336 Enzymatic, 60, 323, 327, 336, 346, 371, 378 Eosinophilia, 336, 338 Ephedrine, 175, 199, 336 Epidemic, 3, 27, 40, 51, 55, 76, 95, 108, 114, 123, 126, 179, 180, 232, 254, 256, 257, 260, 261, 266, 336, 360, 384 Epidemiologic Studies, 35, 336 Epidemiological, 3, 57, 336, 338 Epidermal, 24, 72, 92, 211, 337, 353, 358, 393 Epidermis, 337, 353, 375 Epigastric, 337, 366 Epinephrine, 312, 334, 337, 363, 390 Epithelial, 13, 62, 64, 65, 82, 84, 95, 110, 166, 325, 337, 346, 366 Epithelial Cells, 13, 64, 82, 84, 95, 110, 166, 325, 337, 346 Epithelium, 25, 65, 336, 337, 352, 366, 394 Epitope, 12, 28, 47, 58, 59, 69, 90, 92, 98, 136, 209, 210, 229, 245, 337 Epizootic, 149, 337 Erythrocytes, 154, 159, 315, 316, 322, 337, 377, 381 Esophagus, 333, 337, 345, 369, 384 Ethanol, 337, 339 Ether, 195, 337 Ethmoid, 193, 337, 367 Ethnic Groups, 273, 337 Ethylene Glycol, 33, 337 Eucalyptus, 207, 337 Eukaryotic Cells, 330, 337, 365, 390 Evacuation, 328, 338 Evoke, 338, 384 Excitation, 338, 340 Exhaustion, 316, 338, 357 Exocrine, 338, 366 Exocytosis, 338, 346 Exogenous, 8, 65, 210, 312, 338, 342, 390 Exotoxin, 264, 338 Expeditions, 338 External-beam radiation, 338, 352, 376, 394 Extracellular, 58, 315, 328, 336, 338, 339, 383, 387 Extracellular Matrix, 328, 338, 339 Extraction, 7, 15, 39, 225, 338 Extrapyramidal, 314, 334, 338 Extremity, 262, 338

Eye Infections, 312, 338 F Family Planning, 283, 338 Fasciitis, 263, 338 Fat, 255, 312, 320, 322, 329, 335, 338, 342, 354, 355, 361, 378, 383, 386 Fatal Outcome, 338, 375 Fatigue, 30, 37, 308, 326, 338, 345 Fatty acids, 111, 145, 147, 313, 338, 343, 373 Feces, 323, 328, 339, 384 Fermentation, 58, 339, 380 Ferrets, 25, 75, 86, 87, 339 Fetal Development, 35, 339 Fetus, 34, 339, 372, 390, 391 Fibrinogen, 339, 370, 388 Fibroblasts, 57, 338, 339, 351 Fibrosarcoma, 338, 339 Filtration, 232, 339 Firearms, 294, 339 Fixation, 67, 130, 339, 381 Fixatives, 330, 339 Flavoring Agents, 337, 339 Flow Cytometry, 17, 43, 339 Fluorescence, 36, 45, 340 Fluorescent Dyes, 339, 340 Focus Groups, 39, 340 Fold, 5, 190, 340 Forearm, 321, 338, 340, 376 Fovea, 339, 340 Fractionation, 15, 340 Fructose, 49, 340 Fungi, 192, 233, 317, 328, 338, 340, 359, 384, 394 Fungus, 47, 340 G Gallbladder, 311, 333, 340 Gamma Rays, 340, 376 Ganglion, 340, 365, 394 Gangrene, 262, 340 Gangrenous, 341, 381 Gas, 323, 332, 341, 347, 349, 352, 363, 375, 378, 385, 391 Gas exchange, 341, 378 Gastric, 314, 334, 341, 345, 346 Gastrin, 341, 346 Gastritis, 171, 255, 341 Gastroenteritis, 255, 341, 379, 380 Gastrointestinal, 192, 214, 254, 322, 323, 337, 341, 357, 381, 385, 390, 392 Gastrointestinal tract, 192, 323, 337, 341, 381, 390

Index 401

Gelatin, 232, 341, 385, 388 Gene, 8, 13, 18, 21, 28, 29, 30, 35, 37, 38, 47, 50, 52, 55, 57, 62, 65, 68, 70, 80, 81, 86, 92, 99, 101, 145, 151, 193, 201, 210, 212, 222, 223, 224, 228, 230, 235, 241, 242, 245, 246, 254, 260, 312, 321, 333, 341, 346, 347, 351, 364, 370, 378, 380, 389, 393 Gene Expression, 18, 21, 38, 52, 55, 57, 81, 228, 231, 341 Gene Pool, 35, 65, 341 General practitioner, 14, 341 Genetic Code, 341, 364 Genetic Engineering, 53, 321, 326, 341 Genetic Screening, 60, 341 Genetic testing, 341, 371 Genetics, 13, 40, 57, 60, 82, 93, 150, 198, 219, 245, 246, 256, 328, 333, 341, 349 Genital, 247, 342, 391, 393 Genitourinary, 254, 342, 391 Genotype, 253, 342, 369 Giardiasis, 342, 359 Ginseng, 159, 174, 175, 243, 342 Gland, 41, 312, 342, 356, 357, 366, 367, 370, 374, 380, 384, 388 Glial Fibrillary Acidic Protein, 115, 342 Glioma, 247, 342 Glomerular, 232, 342, 377 Glomeruli, 342, 375 Glomerulonephritis, 116, 342 Glomerulus, 342 Glottis, 342, 368 Glucocorticoids, 312, 329, 342 Glucose, 79, 324, 332, 342, 345, 348, 351 Glucose Intolerance, 332, 342 Glucuronic Acid, 244, 342 Glucuronides, 342 Gluten, 324, 342 Glycerol, 145, 322, 343, 369 Glycerophospholipids, 343, 369 Glycoprotein, 25, 36, 52, 61, 62, 64, 74, 80, 90, 162, 211, 213, 215, 241, 242, 323, 339, 343, 388 Glycosidic, 316, 343, 362, 364 Glycosylation, 52, 82, 106, 151, 343 Goats, 343, 365, 378, 379 Gonorrhea, 295, 343 Gout, 255, 343 Governing Board, 343, 372 Gp120, 241, 343, 368 Grade, 247, 343 Graft, 11, 29, 263, 343, 347, 349 Graft Rejection, 343, 349

Graft Survival, 11, 343 Gram-negative, 51, 226, 322, 336, 343, 378, 380, 392 Gram-Negative Bacteria, 336, 343, 378 Gram-positive, 51, 343, 361, 384 Granule, 34, 343, 379 Granulocytes, 320, 343, 344, 354, 382, 393 Granulocytopenia, 318, 344 Granuloma, 47, 344 Growth factors, 344 Guanylate Cyclase, 344, 363 Guinea Pigs, 344, 356 H Habitat, 344, 361 Habitual, 325, 344 Hair follicles, 344, 393 Half-Life, 209, 344 Halitosis, 193, 344 Handwashing, 295, 344 Haploid, 344, 370 Haptens, 313, 344 Headache, 216, 277, 308, 322, 344, 348, 350 Headache Disorders, 344 Health Care Costs, 5, 344, 345 Health Expenditures, 344, 345 Health Status, 49, 148, 345 Hearing Disorders, 327, 345 Heart attack, 324, 345 Heart failure, 336, 345 Heartbeat, 345, 385 Heartburn, 255, 345, 346, 349 Hemagglutinins, 58, 71, 73, 96, 112, 151, 345 Hematologic malignancies, 132, 345 Hematopoietic growth factors, 272, 345 Heme, 321, 345, 371 Hemodialysis, 146, 158, 162, 262, 332, 345 Hemoglobin, 316, 337, 345 Hemolytic, 338, 345, 387 Hemorrhage, 330, 344, 345, 375, 384 Hepadnaviridae, 229, 345 Hepatic, 22, 205, 313, 331, 346, 372 Hepatitis, 4, 6, 69, 72, 190, 194, 195, 196, 221, 229, 237, 254, 262, 263, 264, 266, 272, 293, 294, 295, 345, 346, 350, 392 Hepatocytes, 346 Heredity, 341, 346 Herpes, 69, 145, 155, 165, 194, 214, 220, 221, 224, 264, 295, 346, 348, 392 Herpes virus, 194, 224, 346, 392 Herpes Zoster, 346 Heterogeneity, 18, 64, 76, 159, 313, 346

402 Influenza

Heterotrophic, 340, 346 Heterozygotes, 333, 346 Hiatal Hernia, 255, 346 Histamine, 249, 315, 346 Histamine Release, 249, 315, 346 Histidine, 346 Histology, 263, 346, 366 Hoarseness, 330, 346, 353 Homodimer, 346, 389 Homogeneous, 48, 346, 369 Homologous, 26, 77, 202, 330, 346, 361, 380, 381, 386 Homozygotes, 333, 346 Hormonal, 47, 329, 346 Hormone, 30, 294, 329, 337, 341, 346, 347, 351, 354, 358, 378, 382, 387, 388, 389 Hormone Replacement Therapy, 294, 346 Host-cell, 46, 163, 347 Human growth hormone, 241, 347 Human papillomavirus, 247, 347 Humoral, 21, 22, 23, 24, 27, 28, 42, 78, 82, 135, 224, 241, 343, 347, 348 Humour, 347 Hybrid, 105, 202, 347 Hybridization, 324, 347 Hydralazine, 272, 347 Hydrogen, 213, 237, 311, 314, 320, 323, 332, 347, 355, 360, 363, 366, 374 Hydrogen Peroxide, 347, 355 Hydrolysis, 235, 347, 362, 368, 369, 371, 374 Hydrophilic, 332, 347 Hydrophobic, 332, 343, 347, 355 Hydroxylysine, 327, 347 Hydroxyproline, 327, 347 Hyperbilirubinemia, 347, 353 Hypersensitivity, 103, 135, 314, 347, 378, 381, 382 Hypertension, 324, 344, 347, 388 Hyperuricemia, 343, 347 Hypoglycaemia, 331, 348 Hypotension, 264, 329, 348 Hypothalamic, 5, 348 Hypothalamus, 319, 348, 370 Hypoxia, 331, 348, 387 I Id, 152, 170, 288, 289, 295, 296, 298, 304, 306, 348 Idiopathic, 272, 348 Idiotype, 42, 348 Idoxuridine, 214, 348 Immune adjuvant, 20, 314, 348

Immune function, 34, 43, 47, 55, 214, 243, 262, 348, 349, 389 Immune Sera, 348 Immunization Schedule, 131, 348 Immunoassay, 66, 67, 72, 73, 92, 109, 110, 135, 239, 348 Immunocompetence, 17, 348 Immunodeficiency syndrome, 229, 254, 266, 295, 348 Immunofluorescence, 66, 67, 70, 78, 92, 103, 135, 348 Immunogen, 229, 349 Immunogenetics, 7, 349 Immunogenic, 28, 190, 191, 201, 202, 213, 218, 229, 238, 245, 270, 349, 355 Immunoglobulin, 8, 76, 79, 81, 88, 96, 316, 349, 360 Immunologic, 18, 42, 54, 262, 312, 325, 348, 349, 376 Immunological adjuvant, 217, 218, 349 Immunosuppressive, 11, 55, 165, 251, 263, 349 Immunosuppressive Agents, 165, 349 Immunosuppressive therapy, 349 Immunotherapy, 41, 56, 312, 349 Impairment, 46, 243, 294, 319, 320, 331, 338, 349, 358 Implant radiation, 349, 352, 376, 394 In situ, 36, 349 Incision, 349, 352, 353, 386 Incontinence, 336, 349, 361, 380 Incubated, 191, 203, 242, 349 Incubation, 207, 349, 368 Incubation period, 349, 368 Indicative, 223, 255, 349, 367, 391 Indigestion, 255, 349 Induction, 11, 20, 21, 23, 26, 31, 35, 38, 42, 50, 52, 53, 55, 62, 79, 80, 139, 205, 239, 316, 350 Infancy, 255, 350 Infant, Newborn, 313, 350 Infarction, 124, 320, 329, 350, 359 Infectious Mononucleosis, 350, 360 Infiltration, 267, 342, 350, 373, 394 Infusion, 155, 156, 350 Ingestion, 316, 344, 350, 371, 387 Inhalation, 31, 70, 207, 277, 312, 350, 371 Initiation, 29, 57, 69, 72, 90, 193, 194, 197, 234, 241, 350, 373, 389 Initiator, 350, 351 Inlay, 350, 378 Inoculum, 53, 264, 350

Index 403

Inorganic, 248, 350, 361, 385 Inotropic, 334, 351 Insecticides, 351, 369 Insight, 30, 33, 53, 55, 139, 351 Insomnia, 214, 351 Insulin, 254, 351, 353, 390 Insulin-dependent diabetes mellitus, 351 Integrase, 195, 351 Intensive Care, 129, 351 Intensive Care Units, 129, 351 Interferon, 12, 17, 44, 55, 56, 61, 74, 76, 78, 80, 89, 94, 115, 139, 196, 206, 239, 272, 351, 356 Interferon-alpha, 196, 351 Interleukin-1, 91, 158, 351 Interleukin-12, 91, 158, 351 Interleukin-2, 184, 351 Interleukin-8, 164, 351 Interleukins, 349, 352 Intermittent, 352, 355, 368 Internal Medicine, 25, 97, 106, 117, 121, 140, 144, 145, 146, 352 Internal radiation, 352, 376, 394 Interstitial, 21, 322, 352, 358, 377, 394 Intestinal, 89, 192, 324, 325, 352, 357 Intestine, 62, 115, 320, 322, 352, 353 Intoxication, 331, 352, 394 Intracellular, 16, 17, 22, 216, 322, 326, 350, 352, 358, 363, 372, 374, 382, 393 Intracellular Membranes, 352, 358 Intramuscular, 82, 86, 120, 204, 225, 241, 293, 352, 367 Intramuscular injection, 225, 241, 352 Intravascular, 238, 352 Intravenous, 15, 91, 238, 264, 266, 350, 352, 367 Intrinsic, 42, 313, 352 Invasive, 80, 210, 226, 247, 348, 352 Involuntary, 320, 352, 361, 382 Ions, 320, 333, 335, 347, 352 Iris, 329, 352, 375 Irradiation, 255, 352, 394 Irritable Bowel Syndrome, 255, 352 Ischemia, 353, 361 Islet, 254, 353 Isocitrate Lyase, 30, 353 J Jaundice, 263, 347, 353 Joint, 261, 318, 353, 386 K Kb, 236, 282, 353 Keratinocytes, 351, 353

Keratitis, 348, 353 Keto, 49, 353, 389 Killer Cells, 234, 353 Kinetic, 60, 353 L Labile, 28, 77, 87, 126, 218, 327, 353 Laceration, 353, 387 Lag, 246, 353 Language Disorders, 327, 353 Laparotomy, 19, 353 Large Intestine, 333, 352, 353, 376, 382 Laryngitis, 233, 353 Larynx, 342, 353, 389 Latent, 81, 353 Least-Squares Analysis, 353, 377 Lectin, 160, 208, 244, 354, 358 Length of Stay, 48, 354 Lenses, 354, 371, 377 Leptin, 253, 354 Lesion, 344, 354, 355, 390 Lethal, 26, 52, 53, 69, 85, 87, 88, 89, 100, 118, 120, 146, 154, 160, 211, 223, 241, 354 Leucocyte, 354, 356 Leukaemia, 113, 354 Leukemia, 345, 354 Leukocytes, 322, 325, 343, 351, 352, 354, 360, 363 Levodopa, 196, 334, 354 Libido, 316, 354 Library Services, 304, 354 Life cycle, 45, 195, 340, 354 Ligament, 354, 374 Ligands, 32, 354, 386 Likelihood Functions, 354, 377 Lincomycin, 326, 354 Linear Models, 355, 377 Linkages, 58, 70, 345, 355, 362, 387 Lipid, 10, 24, 33, 36, 80, 93, 97, 146, 158, 212, 215, 217, 246, 318, 323, 343, 351, 353, 355, 361 Lipid A, 25, 355 Lipid Bilayers, 34, 218, 355 Lipid Peroxidation, 146, 158, 355 Lipophilic, 218, 355 Lipopolysaccharide, 343, 355 Lipoprotein, 201, 202, 213, 343, 355, 356, 393 Liposome, 55, 216, 218, 223, 241, 355 Liver Transplantation, 196, 263, 355 Lobe, 347, 355 Localization, 10, 47, 63, 84, 121, 149, 165, 355

404 Influenza

Localized, 38, 333, 335, 339, 350, 355, 361, 370, 380, 387, 390 Locomotion, 355, 370 Logistic Models, 355, 377 Long-Term Care, 80, 88, 355 Loop, 59, 75, 126, 209, 226, 229, 355 Low-density lipoprotein, 355, 356 Lupus, 272, 356 Lyme Disease, 255, 265, 356 Lymph, 34, 52, 96, 131, 325, 336, 347, 350, 356, 377 Lymph node, 34, 52, 96, 131, 325, 356, 377 Lymphatic, 169, 336, 350, 356, 384, 388 Lymphatic system, 356, 384, 388 Lymphoblastic, 356 Lymphoblasts, 311, 356 Lymphocyte Count, 311, 356 Lymphocyte Subsets, 158, 356 Lymphocytic, 46, 246, 356 Lymphocytic Choriomeningitis Virus, 246, 356 Lymphoid, 18, 90, 93, 224, 316, 348, 354, 356 Lymphokines, 264, 356 Lymphoma, 345, 356 Lyssavirus, 356, 375 Lytic, 56, 357, 381, 393 M Macrophage, 22, 95, 317, 351, 357 Major Histocompatibility Complex, 46, 69, 77, 357 Malabsorption, 255, 324, 357 Malaise, 215, 216, 308, 357 Malaria, 27, 90, 211, 234, 247, 255, 256, 265, 357 Malaria Vaccines, 28, 247, 357 Malaria, Falciparum, 357 Malaria, Vivax, 357 Malignancy, 190, 357, 366 Malignant, 137, 234, 262, 311, 317, 338, 357, 362, 376 Malnutrition, 255, 313, 357 Mammography, 48, 357 Manifest, 192, 264, 357 Mannans, 340, 357 Mastitis, 357, 381 Maxillary, 193, 357, 367 Measles Virus, 38, 246, 357 Meat, 64, 249, 357 Medial, 337, 358 Mediate, 32, 33, 36, 37, 44, 76, 334, 353, 358 Mediator, 334, 351, 358, 370, 381

Medicament, 250, 358, 385 MEDLINE, 283, 358 Megakaryocytes, 322, 358 Meiosis, 358, 361, 386 Melanin, 352, 358, 369, 390 Melanocytes, 358 Melanoma, 137, 234, 358 Membrane Fusion, 9, 24, 34, 36, 58, 62, 83, 90, 93, 118, 122, 166, 180, 358 Membrane Glycoproteins, 204, 207, 358 Membrane Proteins, 51, 52, 212, 217, 242, 358 Memory, 17, 18, 21, 22, 27, 28, 29, 31, 53, 55, 56, 64, 68, 78, 79, 88, 316, 331, 358 Meninges, 325, 330, 334, 358 Meningitis, 171, 226, 235, 250, 288, 292, 356, 358 Mental Disorders, 187, 358, 374 Mental Health, iv, 6, 187, 282, 285, 358, 375 Mental Retardation, 327, 358 Mercury, 289, 340, 358 Metabolic disorder, 343, 359 Metabolite, 49, 359, 373 Methacrylate, 235, 359, 371 Methionine, 359, 385 Metronidazole, 192, 359 MI, 310, 359 Microbe, 359, 389 Microorganism, 50, 326, 359, 367, 393 Microscopy, 16, 36, 52, 330, 359 Microspheres, 217, 359 Migration, 31, 359 Milliliter, 185, 359 Mineralocorticoids, 312, 329, 359 Mitochondrial Swelling, 359, 362 Mitosporic Fungi, 318, 359 Mobility, 66, 77, 225, 359 Mobilization, 31, 359 Modeling, 17, 40, 41, 334, 360, 374 Modification, 84, 196, 209, 245, 341, 360, 375 Monitor, 41, 90, 294, 323, 360, 364 Monkeypox Virus, 35, 360 Monoclonal, 8, 20, 32, 63, 70, 73, 76, 104, 227, 352, 360, 376, 394 Monoclonal antibodies, 8, 20, 70, 73, 227, 360 Monocytes, 102, 239, 264, 351, 354, 360 Monokines, 239, 264, 360 Mononuclear, 9, 17, 146, 165, 338, 344, 350, 360

Index 405

Mononucleosis, 263, 295, 360 Monophosphate, 211, 360 Morbillivirus, 357, 360, 379 Morphine, 15, 334, 360, 362, 365 Morphological, 16, 335, 340, 358, 360 Motion Sickness, 205, 360, 362, 380 Mucins, 360, 380 Mucociliary, 361, 382 Mucosa, 66, 249, 324, 356, 361, 362, 384, 385 Mucositis, 361, 388 Mucus, 360, 361, 378 Multiple sclerosis, 361, 365 Multivalent, 146, 158, 202, 203, 236, 319, 361 Mumps Virus, 200, 227, 228, 361 Mutagenesis, 51, 361, 374 Mutagenicity, 232, 361 Mutagens, 361 Myalgia, 216, 263, 308, 350, 361 Mycobacterial disease, 47, 361 Mycobacterium, 30, 46, 211, 361, 390 Myelitis, 294, 361 Myocarditis, 333, 361 Myocardium, 359, 361 Myopathy, 272, 361 Myositis, 272, 361 N Naive, 17, 21, 22, 26, 43, 78, 361 Narcolepsy, 336, 361 Narcotic, 360, 361 Nasal Cavity, 192, 193, 362, 367 Nasal Mucosa, 249, 350, 362 Nasal Septum, 362 Nasopharynx, 50, 362 Natural killer cells, 351, 362 Nausea, 205, 309, 334, 341, 349, 362, 390 NCI, 1, 186, 281, 326, 362 Necrosis, 95, 272, 338, 350, 359, 362 Need, 3, 7, 15, 21, 125, 195, 197, 198, 220, 253, 261, 265, 272, 284, 293, 299, 312, 362, 388 Neonatal, 9, 115, 129, 362 Neoplasia, 247, 362 Neoplasm, 210, 211, 330, 362, 366, 390 Nephropathy, 254, 362 Nerve, 312, 316, 319, 332, 340, 358, 361, 362, 363, 365, 372, 373, 384, 388, 390, 394 Nervous System, 205, 214, 311, 313, 319, 322, 325, 336, 340, 342, 354, 356, 358, 360, 361, 362, 363, 365, 375, 380, 381, 385, 386

Neural, 313, 315, 347, 362 Neuritis, 362, 365 Neuroendocrine, 16, 362 Neuronal, 362, 363 Neurons, 332, 354, 362, 363, 376, 386 Neuropathy, 253, 262, 363 Neuropeptides, 209, 363 Neurotoxic, 363, 387 Neurotransmitters, 360, 363 Neutralization, 19, 76, 122, 208, 244, 363 Neutrons, 314, 352, 363, 376 Neutrophils, 344, 351, 354, 363 Nevirapine, 363 Niacin, 363, 390 Nitric Oxide, 30, 82, 363 Nitrogen, 49, 314, 316, 339, 363, 390 Non-nucleoside, 185, 331, 363 Nonverbal Communication, 327, 363 Norepinephrine, 312, 334, 336, 363 Nosocomial, 19, 106, 127, 364 Nuclei, 86, 314, 328, 335, 341, 363, 364, 365, 374 Nucleocapsid, 38, 64, 213, 229, 364, 392, 393 Nucleocapsid Proteins, 38, 364 Nucleus, 136, 231, 319, 320, 330, 332, 337, 340, 358, 360, 363, 364, 373, 374, 384, 387 Nutritional Status, 150, 180, 364 O Occult, 294, 364 Occult Blood, 294, 364 Odds Ratio, 364, 377 Odour, 318, 364 Ointments, 334, 364, 366 Oligo, 196, 222, 364 Oligosaccharides, 130, 234, 362, 364 Oncogene, 98, 364 Oncology, 365, 377 Opacity, 67, 110, 332, 365 Ophthalmology, 206, 339, 365 Opium, 334, 360, 365 Opportunistic Infections, 254, 311, 365 Optic disc, 365 Optic Nerve, 365, 366 Optic Neuritis, 250, 365 Oral Health, 294, 365 Oral Hygiene, 344, 365 Orbital, 365 Orderly, 215, 365 Orf, 251, 365, 367 Orf Virus, 251, 365 Organ Culture, 46, 66, 365, 388

406 Influenza

Organ Transplantation, 264, 365 Organelles, 326, 330, 358, 360, 365 Orthomyxoviridae, 212, 213, 215, 236, 242, 246, 335, 365, 387 Orthopoxvirus, 329, 360, 366, 391 Osteoporosis, 254, 366 Otitis, 49, 67, 71, 107, 262, 366 Otitis Media, 50, 67, 71, 107, 366 Outpatient, 44, 83, 125, 366 Ovalbumin, 9, 366 Ovary, 366, 371, 385 Ovum, 354, 366, 394 Oxidation, 22, 311, 317, 330, 355, 366 P Pachymeningitis, 358, 366 Paediatric, 113, 125, 366 Palate, 362, 366, 384 Palliative, 366, 387 Pancreas, 254, 311, 321, 333, 351, 353, 366, 390 Papilloma, 237, 246, 247, 366 Papillomavirus, 6, 246, 366 Paraffin, 119, 366 Parainfluenza Vaccines, 197, 366 Parainfluenza Virus 1, Human, 222, 366 Parainfluenza Virus 2, Human, 222, 367 Paramyxovirus, 38, 83, 200, 366, 367 Paranasal Sinuses, 367, 382 Parapoxvirus, 251, 365, 367 Parasite, 28, 90, 367, 390 Parasitic, 345, 367, 370 Parathyroid, 38, 367, 387 Parathyroid Glands, 367 Parathyroid hormone, 38, 367 Parenteral, 203, 204, 209, 235, 315, 367 Parkinsonism, 354, 367 Paroxysmal, 344, 367, 368, 393 Particle, 24, 77, 212, 355, 367, 389, 393 Patch, 77, 270, 367 Pathogen, 7, 18, 21, 22, 23, 35, 40, 46, 58, 90, 191, 198, 210, 220, 233, 243, 349, 350, 367, 385 Pathogenesis, 13, 16, 20, 21, 26, 38, 50, 60, 68, 71, 84, 87, 147, 180, 181, 253, 367 Pathologic, 37, 38, 311, 329, 339, 347, 367 Pathologies, 209, 367 Patient Education, 264, 292, 302, 304, 310, 367 Patient Selection, 4, 367 Pelvic, 368, 374 Penicillin, 264, 266, 316, 368 Peptide Fragments, 34, 46, 234, 368

Peptide T, 34, 368 Perception, 328, 345, 368, 380 Perennial, 248, 249, 368, 390 Periodontal disease, 192, 368 Periodontitis, 192, 368 Perioperative, 11, 264, 368 Peripheral blood, 15, 17, 146, 165, 318, 351, 368 Peritoneal, 87, 262, 368 Peritoneal Cavity, 368 Peritoneal Dialysis, 262, 368 Peritoneum, 368 Pertussis, 113, 217, 368, 393 Pesticides, 255, 351, 368 Petroleum, 366, 369 Phallic, 339, 369 Pharmaceutical Preparations, 324, 337, 341, 369 Pharmaceutical Solutions, 334, 369 Pharmacokinetic, 119, 205, 369 Pharmacologic, 316, 344, 369, 389 Pharynx, 350, 362, 369 Phenotype, 8, 32, 38, 47, 52, 61, 67, 71, 94, 198, 219, 245, 369 Phenylalanine, 369, 390 Phlebotomy, 183, 369 Phospholipases, 369, 382 Phospholipids, 22, 218, 338, 355, 369 Phosphorus, 173, 323, 367, 369 Phosphorylation, 12, 56, 57, 149, 369 Physiologic, 313, 321, 334, 339, 344, 369, 373, 376 Physiology, 44, 205, 369, 385 Pigment, 292, 321, 358, 369 Pilot study, 39, 196, 370 Pituitary Gland, 329, 370 Plague, 254, 256, 257, 258, 259, 265, 370, 379 Plant Viruses, 197, 370 Plants, 156, 225, 314, 319, 320, 321, 322, 323, 324, 342, 354, 363, 370, 371, 379, 384, 389, 390 Plasma, 13, 22, 112, 166, 313, 316, 320, 324, 326, 339, 341, 342, 345, 359, 370, 376, 380, 392 Plasma cells, 316, 370 Plasmid, 88, 223, 224, 228, 231, 370, 391 Plasmin, 370 Plasminogen, 35, 88, 370 Plasminogen Activators, 370 Plasticity, 18, 370 Platelet Activation, 370, 382

Index 407

Platelet Aggregation, 315, 363, 370 Platelet Factor 4, 352, 370 Platelets, 320, 358, 363, 370, 371, 381, 388 Platinum, 355, 371 Pneumococcal Vaccines, 5, 14, 254, 371 Pneumonitis, 30, 166, 371 Point Mutation, 60, 97, 371 Poisoning, 255, 331, 341, 352, 359, 362, 371, 380, 381 Pollen, 192, 371, 375 Polyethylene, 235, 371 Polymerase Chain Reaction, 132, 236, 371 Polymers, 217, 235, 248, 371, 374 Polymethyl Methacrylate, 235, 371 Polypeptide, 80, 212, 213, 314, 323, 327, 339, 347, 370, 371, 374, 394 Polysaccharide, 8, 214, 217, 226, 317, 324, 371 Porphyria, 369, 371, 372 Porphyria Cutanea Tarda, 369, 372 Posterior, 315, 319, 352, 365, 366, 372 Postherpetic Neuralgia, 314, 372 Postmenopausal, 366, 372 Postoperative, 206, 264, 372 Postsynaptic, 372, 382, 386 Potassium, 194, 359, 372 Potentiate, 131, 372 Potentiating, 159, 244, 372 Potentiation, 372, 382 Practice Guidelines, 285, 295, 372 Practice Management, 14, 372 Precursor, 65, 80, 212, 334, 335, 336, 354, 363, 369, 370, 372, 373, 389, 390 Prenatal, 9, 130, 335, 341, 372 Prevalence, 84, 121, 221, 262, 364, 372 Preventive Medicine, 294, 303, 372 Probe, 105, 236, 372 Procainamide, 272, 373 Procaine, 373 Prodrug, 77, 86, 119, 236, 373 Progeny, 193, 194, 216, 231, 234, 328, 373 Progression, 231, 316, 373 Progressive, 263, 324, 331, 334, 344, 362, 370, 373, 377, 390 Projection, 331, 363, 365, 373, 377 Proline, 327, 347, 373 Promoter, 61, 63, 75, 85, 94, 106, 193, 220, 221, 231, 236, 241, 373 Promotor, 373, 378 Prophase, 361, 373, 386 Prophylaxis, 45, 54, 91, 104, 133, 141, 200, 202, 211, 246, 247, 294, 318, 373, 379, 391

Propolis, 161, 168, 373 Proportional, 373, 386 Prospective study, 101, 373 Prostaglandin, 59, 373 Prostate, 41, 321, 374, 390 Protease, 51, 181, 185, 195, 374 Protein C, 10, 44, 65, 81, 85, 202, 241, 313, 314, 318, 320, 326, 355, 374, 390, 393 Protein Conformation, 10, 314, 374 Protein Engineering, 229, 374 Proteolytic, 36, 327, 339, 370, 374 Protocol, 27, 105, 183, 184, 374 Protons, 314, 347, 374, 376 Protozoa, 328, 359, 374, 384 Proximal, 362, 374 Psychiatric, 327, 358, 374 Psychiatry, 115, 339, 374, 385 Psychomotor, 331, 374 Public Policy, 120, 283, 375 Publishing, 59, 284, 375 Pulmonary, 15, 52, 53, 59, 60, 89, 127, 130, 145, 161, 321, 328, 375, 378, 386, 392 Pulmonary Artery, 321, 375, 392 Pulmonary Ventilation, 375, 378 Pulse, 360, 375 Pupil, 329, 365, 375 Purifying, 227, 230, 332, 375 Purines, 320, 375 Purpura, 148, 375 Putrefaction, 340, 375 Pyelonephritis, 262, 375 Pyridoxal, 375, 389 Pyrogenic, 264, 375 Pyrogens, 191, 243, 375 Q Quality of Life, 37, 254, 375 Quaternary, 374, 375, 380 Quercetin, 168, 375 Quiescent, 234, 375 R Rabies, 211, 246, 255, 356, 375 Rabies Virus, 246, 356, 375 Race, 270, 334, 359, 376 Radiation, 243, 336, 338, 340, 352, 359, 376, 394 Radiation therapy, 243, 338, 340, 352, 376, 394 Radioactive, 17, 344, 347, 349, 352, 360, 364, 376, 394 Radiolabeled, 352, 376, 394 Radiotherapy, 322, 352, 376, 394 Radius, 207, 376

408 Influenza

Randomized, 47, 91, 97, 107, 134, 145, 150, 153, 158, 167, 184, 335, 376 Reactivation, 262, 376 Reagent, 32, 39, 332, 376 Reassortant Viruses, 108, 376 Recombinant Proteins, 226, 376 Recombination, 220, 328, 376 Reconstitution, 113, 376 Rectum, 322, 333, 341, 349, 353, 374, 376, 385 Recur, 221, 376 Recurrence, 83, 121, 263, 376, 377 Red blood cells, 337, 345, 372, 377 Red Nucleus, 319, 377 Reductase, 253, 377 Refer, 1, 200, 322, 327, 333, 339, 340, 346, 355, 360, 361, 363, 364, 377 Refraction, 377, 383 Regeneration, 376, 377 Regimen, 11, 335, 377 Regional lymph node, 218, 377 Regression Analysis, 4, 377 Regurgitation, 345, 377 Relapse, 41, 133, 196, 377 Relative risk, 4, 377 Remission, 377 Renal failure, 331, 345, 377 Respiration, 323, 360, 377 Respiratory Mucosa, 249, 377 Respiratory syncytial virus, 6, 39, 67, 70, 84, 109, 124, 140, 215, 221, 222, 224, 237, 246, 378 Respiratory Syncytial Virus Infections, 70, 378 Respiratory System, 42, 207, 225, 361, 378 Response Elements, 44, 378 Response rate, 196, 378 Restoration, 56, 376, 378 Retinal, 328, 365, 378 Retrobulbar, 365, 378 Retrospective, 40, 378 Retroviral vector, 138, 378 Retrovirus, 37, 378 Reverse Transcriptase Inhibitors, 185, 378 Rhamnose, 244, 378 Rheumatic Diseases, 110, 272, 378 Rheumatism, 378 Rheumatoid, 110, 133, 192, 272, 378 Rheumatoid arthritis, 110, 192, 272, 378 Rhinitis, 249, 322, 336, 378, 381 Rhinorrhea, 216, 309, 378 Rhinovirus, 39, 221, 249, 378

Ribavirin, 93, 196, 263, 277, 379 Ribonuclease, 71, 156, 379 Ribonucleic acid, 197, 379 Ribosome, 91, 379, 390 Rigidity, 367, 370, 379 Rimantadine, 44, 51, 91, 93, 155, 157, 231, 232, 277, 379 Rinderpest, 246, 379 Rinderpest Virus, 246, 379 Risk factor, 3, 130, 133, 221, 263, 294, 336, 355, 373, 377, 379 Risk patient, 5, 117, 137, 232, 241, 379 RNA Viruses, 250, 379 Rod, 175, 319, 320, 379, 380 Rodenticides, 369, 379 Rotavirus, 6, 32, 220, 379 Rubella, 196, 214, 293, 294, 295, 379 Rubella Virus, 196, 379 Rubulavirus, 361, 367, 379 Rutin, 168, 375, 379 S Salicylate, 379 Salicylic, 379 Salicylic Acids, 379 Saliva, 232, 376, 380 Salivary, 5, 330, 333, 380 Salivary glands, 330, 333, 380 Salmonella, 254, 262, 341, 380 Sarcosine, 209, 380 Schizoid, 380, 394 Schizophrenia, 130, 192, 219, 380, 394 Schizotypal Personality Disorder, 380, 394 Scleroderma, 338, 380 Scopolamine, 320, 380 Screening, 5, 15, 88, 196, 197, 203, 254, 263, 294, 326, 341, 380, 391 Sebaceous, 380, 393 Secretion, 21, 43, 232, 329, 342, 346, 347, 351, 352, 359, 360, 361, 380, 389, 391 Secretory, 34, 204, 217, 380, 386 Sediment, 380, 391 Segmentation, 212, 242, 380 Segregation, 320, 376, 380 Seizures, 331, 367, 380 Semen, 172, 374, 380 Semisynthetic, 326, 380 Senile, 366, 381 Sensitization, 9, 77, 381 Sensor, 203, 381 Sensory loss, 361, 381, 387 Septicaemia, 381 Septicemia, 262, 381

Index 409

Sequence Analysis, 38, 126, 381 Sequence Homology, 368, 381 Sequencing, 13, 371, 381 Serologic, 70, 348, 381 Serology, 119, 381 Serotonin, 381, 390 Serotypes, 220, 221, 241, 381 Sex Characteristics, 312, 316, 381, 387 Sexually Transmitted Diseases, 254, 381 Shock, 263, 381, 390 Side effect, 28, 191, 192, 196, 198, 206, 214, 218, 220, 226, 232, 242, 275, 312, 347, 382, 389 Sigmoid, 382 Sigmoidoscopy, 294, 382 Signal Transduction, 56, 382 Signs and Symptoms, 264, 377, 382 Sinusitis, 192, 249, 262, 382 Skeletal, 316, 382 Skeleton, 311, 353, 373, 382 Skin Tests, 8, 382 Skull, 330, 382, 387 Small intestine, 326, 334, 342, 346, 352, 382 Smallpox, 203, 255, 382, 391 Smooth muscle, 315, 322, 346, 360, 382, 385 Sneezing, 223, 249, 309, 368, 382 Social Environment, 375, 382 Social Support, 17, 382 Sodium, 244, 321, 343, 359, 382 Soft tissue, 264, 322, 338, 339, 382, 383 Solvent, 337, 343, 369, 383 Soma, 383 Somatic, 8, 231, 254, 312, 324, 347, 358, 383 Somatic cells, 324, 358, 383 Spasmodic, 368, 383 Spastic, 352, 383 Spatial disorientation, 333, 383 Specialist, 298, 383, 393 Species Specificity, 201, 383 Specificity, 9, 12, 25, 32, 35, 40, 46, 47, 62, 68, 69, 70, 73, 76, 94, 204, 234, 313, 383 Spectrum, 39, 47, 192, 195, 240, 383, 392 Sperm, 316, 326, 371, 383 Spike, 36, 80, 234, 383 Spinal cord, 325, 326, 334, 340, 358, 361, 362, 363, 366, 383 Spinal Cord Vascular Diseases, 361, 383 Spirochete, 356, 384, 386 Spleen, 139, 330, 356, 384 Sporadic, 216, 372, 384 Spores, 350, 384

Sputum, 138, 384 Statistically significant, 5, 384 Sterile, 191, 193, 243, 315, 318, 367, 384 Sterility, 207, 384 Sterilization, 295, 384 Steroid, 320, 329, 342, 384 Stimulant, 322, 346, 384 Stimulus, 17, 18, 334, 335, 338, 351, 353, 384, 388 Stomach, 192, 311, 333, 337, 341, 346, 362, 368, 369, 382, 384 Stomatitis, 96, 246, 384 Stool, 349, 352, 353, 384 Strand, 193, 194, 201, 212, 231, 242, 246, 247, 250, 371, 384 Streptococcal, 262, 263, 355, 384 Streptococcus, 8, 26, 50, 51, 67, 71, 80, 110, 200, 225, 235, 263, 338, 371, 384 Stress, 5, 17, 47, 56, 73, 146, 224, 243, 319, 323, 324, 329, 341, 352, 362, 378, 384 Stroke, 124, 187, 270, 282, 324, 384 Stromal, 38, 46, 322, 384, 385 Stromal Cells, 38, 46, 322, 385 Stupor, 292, 362, 385 Subacute, 350, 379, 382, 385 Subarachnoid, 344, 385 Subclinical, 350, 380, 385 Subcutaneous, 184, 293, 312, 324, 335, 341, 367, 385 Subspecies, 383, 385, 391 Substance P, 359, 376, 380, 385 Substrate, 62, 76, 203, 362, 385 Suction, 339, 385 Sudden cardiac death, 124, 385 Sulfates, 195, 385 Sulfur, 237, 332, 359, 385 Sulfuric acid, 385 Superantigens, 18, 264, 385 Superinfection, 27, 193, 385 Supplementation, 146, 158, 162, 169, 170, 385 Suppositories, 341, 385 Suppression, 19, 47, 55, 208, 243, 244, 329, 385 Suppurative, 324, 341, 386 Surface Plasmon Resonance, 51, 386 Surfactant, 166, 386 Surgical Wound Infection, 262, 386 Survival Rate, 154, 386 Sympathomimetic, 334, 337, 364, 386 Symphysis, 374, 386 Symptomatic, 314, 386

410 Influenza

Symptomatic treatment, 314, 386 Symptomatology, 37, 386 Synapses, 363, 383, 386 Synaptic, 382, 386 Synergistic, 27, 93, 135, 196, 386 Syphilis, 254, 295, 386 T Tachycardia, 319, 386 Tachypnea, 319, 387 Tea Tree Oil, 207, 387 Teichoic Acids, 343, 387 Temporal, 135, 272, 344, 345, 387 Teratogenicity, 232, 387 Terminator, 326, 387 Testosterone, 377, 387 Tetani, 387 Tetanic, 387 Tetanus, 134, 169, 184, 210, 211, 293, 294, 295, 296, 387 Tetanus Toxin, 210, 211, 387 Tetany, 367, 387 Tetracycline, 55, 192, 193, 334, 387 Thalamic, 319, 387 Thalamic Diseases, 319, 387 Therapeutics, 26, 39, 57, 151, 205, 243, 278, 387 Thermal, 333, 363, 371, 387 Thogoto-Like Viruses, 366, 387 Threonine, 95, 368, 388 Threshold, 54, 347, 388 Thrombin, 339, 370, 374, 388 Thrombocytopenia, 318, 388 Thrombolytic, 370, 388 Thrombomodulin, 374, 388 Thrombosis, 320, 374, 384, 388 Thrombus, 329, 350, 370, 388 Thymidine, 17, 388 Thymus, 46, 348, 356, 388 Thyroid, 294, 367, 388, 390 Thyroid Gland, 367, 388 Ticks, 356, 388 Tinnitus, 366, 388 Tissue Culture, 16, 25, 79, 388 Titre, 6, 158, 388 Tolerance, 11, 35, 198, 220, 311, 342, 388 Tooth Preparation, 312, 388 Topical, 195, 205, 276, 318, 337, 347, 366, 387, 389 Torsion, 350, 389 Toxic, iv, 195, 214, 233, 243, 251, 263, 319, 328, 331, 333, 336, 338, 348, 363, 389 Toxicity, 41, 195, 214, 232, 334, 359, 389

Toxicology, 26, 58, 284, 389 Toxins, 317, 321, 335, 342, 350, 360, 381, 389 Toxoid, 134, 389 Trachea, 322, 353, 369, 388, 389 Transaminase, 292, 389 Transcriptase, 70, 95, 185, 195, 311, 331, 363, 378, 389 Transcription Factors, 93, 378, 389 Transduction, 382, 389 Transfection, 59, 321, 389 Transfer Factor, 348, 389 Transferases, 343, 389 Transforming Growth Factor beta, 81, 389 Translation, 42, 56, 72, 90, 92, 134, 196, 197, 210, 220, 389 Translational, 41, 54, 72, 241, 390 Translocation, 100, 390 Transmitter, 311, 334, 358, 363, 386, 390 Transplantation, 35, 55, 234, 254, 263, 348, 357, 390 Trauma, 331, 362, 390 Trees, 337, 390 Trichomoniasis, 359, 390 Trivalent, 5, 24, 109, 134, 206, 390 Tropism, 25, 94, 212, 390 Tryptophan, 45, 213, 327, 381, 390 Tumor marker, 321, 390 Tumour, 247, 340, 390 Type 2 diabetes, 253, 390 Tyrosine, 56, 334, 390 U Ubiquitin, 44, 80, 390 Ulcer, 324, 390 Ulceration, 365, 379, 390 Umbilical Cord, 314, 390 Unconscious, 316, 331, 348, 390 Urea, 390 Uremia, 262, 377, 390 Ureters, 391 Urethra, 374, 391 Uric, 343, 347, 375, 391 Urinalysis, 294, 391 Urinary, 262, 264, 320, 323, 330, 336, 342, 349, 380, 390, 391 Urinary tract, 262, 264, 320, 391 Urinary tract infection, 262, 264, 320, 391 Urine, 316, 320, 321, 333, 342, 349, 391 Urogenital, 342, 343, 391 Uterus, 34, 325, 391

Index 411

V Vaccinia, 27, 86, 131, 151, 251, 366, 391, 392 Vaccinia Virus, 27, 86, 131, 251, 391, 392 Vacuoles, 336, 365, 391 Vagina, 325, 391, 393 Valves, 40, 391 Varicella, 4, 194, 264, 293, 294, 295, 391, 392 Variola, 391 Vascular, 249, 336, 344, 350, 363, 370, 383, 388, 391 Vasculitis, 116, 120, 133, 272, 391 Vasodilator, 322, 334, 346, 347, 391 VE, 32, 145, 159, 288, 391 Vector, 81, 110, 190, 202, 210, 212, 220, 230, 234, 249, 389, 391 Vegetarianism, 254, 392 Vein, 352, 364, 369, 390, 392 Venereal, 386, 392 Venous, 320, 374, 392 Ventricle, 348, 375, 392 Ventricular, 120, 392 Venules, 321, 323, 392 Vertigo, 366, 392 Vesicular, 34, 96, 246, 346, 382, 391, 392 Veterinarians, 191, 242, 392 Veterinary Medicine, 283, 392 Vial, 67, 68, 103, 109, 392 Vibrio, 200, 325, 392 Vibrio cholerae, 200, 325, 392 Vidarabine, 214, 392 Villous, 324, 392 Viral Core Proteins, 364, 392 Viral Fusion Proteins, 9, 36, 392 Viral Hepatitis, 263, 392 Viral Load, 112, 141, 183, 185, 236, 392 Viral Vaccines, 133, 207, 392 Viral vector, 55, 233, 234, 392 Virion, 59, 70, 75, 85, 88, 94, 194, 215, 231, 234, 320, 364, 393 Virologist, 48, 393 Virosomes, 227, 228, 393

Virulence, 13, 25, 35, 45, 60, 87, 215, 319, 385, 389, 393 Virulent, 7, 12, 13, 45, 50, 63, 68, 69, 145, 148, 181, 198, 219, 393 Virus Diseases, 318, 393 Virus Replication, 35, 44, 59, 78, 82, 84, 94, 156, 163, 166, 191, 201, 242, 393 Viscera, 383, 393 Vitro, 9, 11, 12, 19, 21, 23, 25, 29, 31, 38, 52, 56, 58, 59, 60, 65, 69, 78, 85, 88, 93, 94, 112, 155, 161, 162, 163, 164, 194, 196, 197, 209, 239, 324, 349, 371, 381, 385, 388, 393 Vivo, 12, 18, 19, 21, 23, 25, 28, 31, 38, 42, 45, 52, 54, 56, 58, 78, 81, 93, 148, 157, 161, 162, 164, 193, 201, 218, 230, 324, 349, 393 Vulgaris, 166, 393 Vulva, 393 Vulvovaginitis, 262, 393 W Wakefulness, 331, 393 Warts, 247, 347, 393 Wheezing, 8, 393 White blood cell, 311, 316, 320, 344, 349, 350, 354, 356, 357, 361, 362, 370, 393 Whooping Cough, 368, 393 Windpipe, 369, 388, 394 Withdrawal, 41, 331, 394 Womb, 391, 394 X Xenograft, 316, 394 X-ray, 24, 44, 51, 58, 96, 140, 309, 310, 340, 352, 364, 376, 394 X-ray therapy, 352, 394 Y Yeasts, 340, 369, 394 Yellow Fever, 265, 394 Z Zoonoses, 375, 394 Zoster, 194, 264, 392, 394 Zygote, 328, 394 Zymogen, 374, 394

412 Influenza

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