HEPATITIS B VIRUS A 3-IN-1 MEDICAL REFERENCE Medical Dictionary Bibliography & Annotated Research Guide TO I NTERNET
R EFERENCES
HEPATITIS B VIRUS 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., 1960Hepatitis B Virus: 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: 0-497-00536-0 1. Hepatitis B Virus-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.
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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 hepatitis B virus. 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 HEPATITIS B VIRUS ................................................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Hepatitis B Virus ........................................................................ 11 E-Journals: PubMed Central ....................................................................................................... 66 The National Library of Medicine: PubMed ................................................................................ 97 CHAPTER 2. NUTRITION AND HEPATITIS B VIRUS ....................................................................... 145 Overview.................................................................................................................................... 145 Finding Nutrition Studies on Hepatitis B Virus....................................................................... 145 Federal Resources on Nutrition ................................................................................................. 149 Additional Web Resources ......................................................................................................... 149 CHAPTER 3. ALTERNATIVE MEDICINE AND HEPATITIS B VIRUS ................................................. 151 Overview.................................................................................................................................... 151 National Center for Complementary and Alternative Medicine................................................ 151 Additional Web Resources ......................................................................................................... 159 General References ..................................................................................................................... 160 CHAPTER 4. DISSERTATIONS ON HEPATITIS B VIRUS ................................................................... 161 Overview.................................................................................................................................... 161 Dissertations on Hepatitis B Virus............................................................................................ 161 Keeping Current ........................................................................................................................ 162 CHAPTER 5. PATENTS ON HEPATITIS B VIRUS ............................................................................. 163 Overview.................................................................................................................................... 163 Patents on Hepatitis B Virus ..................................................................................................... 163 Patent Applications on Hepatitis B Virus ................................................................................. 185 Keeping Current ........................................................................................................................ 209 CHAPTER 6. BOOKS ON HEPATITIS B VIRUS ................................................................................. 211 Overview.................................................................................................................................... 211 Book Summaries: Federal Agencies............................................................................................ 211 Chapters on Hepatitis B Virus................................................................................................... 215 CHAPTER 7. MULTIMEDIA ON HEPATITIS B VIRUS ...................................................................... 217 Overview.................................................................................................................................... 217 Video Recordings ....................................................................................................................... 217 CHAPTER 8. PERIODICALS AND NEWS ON HEPATITIS B VIRUS ................................................... 223 Overview.................................................................................................................................... 223 News Services and Press Releases.............................................................................................. 223 Newsletter Articles .................................................................................................................... 224 Academic Periodicals covering Hepatitis B Virus ..................................................................... 225 CHAPTER 9. RESEARCHING MEDICATIONS .................................................................................. 227 Overview.................................................................................................................................... 227 U.S. Pharmacopeia..................................................................................................................... 227 Commercial Databases ............................................................................................................... 228 Researching Orphan Drugs ....................................................................................................... 229 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 233 Overview.................................................................................................................................... 233 NIH Guidelines.......................................................................................................................... 233 NIH Databases........................................................................................................................... 235 Other Commercial Databases..................................................................................................... 237 APPENDIX B. PATIENT RESOURCES ............................................................................................... 239 Overview.................................................................................................................................... 239 Patient Guideline Sources.......................................................................................................... 239
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Finding Associations.................................................................................................................. 243 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 245 Overview.................................................................................................................................... 245 Preparation................................................................................................................................. 245 Finding a Local Medical Library................................................................................................ 245 Medical Libraries in the U.S. and Canada ................................................................................. 245 ONLINE GLOSSARIES................................................................................................................ 251 Online Dictionary Directories ................................................................................................... 251 HEPATITIS B VIRUS DICTIONARY........................................................................................ 253 INDEX .............................................................................................................................................. 321
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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 hepatitis B virus 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 hepatitis B virus, 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 hepatitis B virus, 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 hepatitis B virus. 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 hepatitis B virus, 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 hepatitis B virus. 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 HEPATITIS B VIRUS Overview In this chapter, we will show you how to locate peer-reviewed references and studies on hepatitis B virus.
The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and hepatitis B virus, 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 “hepatitis B virus” (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: •
Prevention of Hepatitis B Virus in Athletic Training Source: Journal of Athletic Training. 29(2): 107-112. June 1994. Summary: Because of exposure to blood-borne pathogens and potentially infectious materials, athletic training is an allied health care profession with an increased risk of exposure to hepatitis B virus (HBV). This article considers the prevention of HBV in athletic training. Topics include the pathogenesis and epidemiology of HBV; signs and symptoms; transmission; and preventive measures, including immunization, protective equipment, housekeeping, and sharps. The authors stress the importance of information dissemination about prevention of HBV in the athletic training setting to all athletic training staff and students, through in-service training sessions, symposia, and lectures. 1 table. 11 references. (AA-M).
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Adding to the Hepatitis B Virus Treatment Arsenal: Glucosidase Inhibitor Derivatives (editorial) Source: Hepatology. 33(6): 1544-1546. June 2001. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 19106-3399. (800) 654-2452 or (407) 345-4000. Summary: Chronic hepatitis B virus (HBV) infection is a major cause of cirrhosis (scarring) and hepatocellular carcinoma (liver cancer) in the United States and worldwide. Eradication of the infection and prevention of complications of chronic infection are the dual goals of treatment. This editorial comments on an accompanying article which reports on the use of alfa glucosidase inhibitor derivatives in the drug therapy for HBV infections. The agents under consideration (N nonyl DNJ and N nonyl DGJ) appear to have a mechanism of action that is unique and potentially complementary to that of nucleoside analogues. As new agents for treatment of HBV infection become available for clinical use, combination treatment of chronic HBV infection can be anticipated. The editorial stresses that designing the optimal combination therapy for HBV will need to take into account drug potency, mechanism of drug uptake and activation, sites of drug action, effect on cccDNA, and specific viral mutations arising with prolonged therapy. The author concludes that it remains to be seen whether these imino sugars (N nonyl DNJ and N nonyl DGJ) will join the growing list of anti HBV drugs. However, if the present results can be reproduced in animal studies and clinical trials (with humans), this novel class of agents may be a welcome addition to the arsenal of anti HBV drugs. 1 figure. 1 table. 13 references.
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Towards Control of Hepatitis B in the Asia-Pacific Region: Natural History of Hepatitis B Virus Infection in Children Source: Journal of Gastroenterology and Hepatology. 15(Supplement): E16-E19. May 2000. Contact: Available from Blackwell Science. 54 University Street, Carlton South 3053, Victoria, Australia. +61393470300. Fax +61393475001. E-mail:
[email protected]. Website: www.blackwell-science.com. Summary: Hepatitis B virus (HBV) infection during childhood can cause acute, fulminant, or chronic hepatitis, liver cirrhosis (scarring), and liver cancer. This article reviews the natural history of hepatitis B infection in children, with a consideration of strategies towards control of hepatitis B in the Asia Pacific region. Approximately 90 percent of the infants of hepatitis B e antigen (HBeAg) seropositive mothers become hepatitis B surface antigen (HBsAg) carriers. Children chronically infected are mostly asymptomatic. Although liver damage is usually mild during childhood, severe liver disease, including cirrhosis and hepatocellular carcinoma, may develop insidiously for 2 to 7 years. Spontaneous HBeAg seroconversion occurs gradually as the age of the child increases. Viral replication is reduced during this process, which is usually preceded by an elevation of aminotransferases. In a long term followup study, the annual HBeAg seroconversion rate was 4 to 5 percent in children older than 3 years of age and less than 2 percent in children under 3 years. The annual seroconversion rate was very low (0.56 percent). Age at infection, maternal HBeAg and HBeAg status, host immune status, and possibly the HBV strain are the main factors determining the course of HBV infection in children. 22 references.
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Occult Hepatitis B Virus Infection in Patients with Chronic Hepatitis C Liver Disease Source: New England Journal of Medicine. 341(1): 22-26. July 1, 1999. Summary: Hepatitis B virus (HBV) infections in patients who lack detectable hepatitis B surface antigen (HBsAg) are called occult infections. Although such infections have been identified in patients with chronic hepatitis C liver disease, their prevalence and clinical significance are not known. This article reports on a study that searched for HBV DNA in liver and serum samples from 200 HBsAg negative patients with hepatitis C virus (HCV) liver disease (147 with chronic hepatitis, 48 with cirrhosis, and 5 with minimal histologic changes). Of the patients, 100 had detectable antibodies to the HBV core antigen; 100 were negative for all HBV markers. Some patients (n = 83) were treated with interferon alfa. The study also included 50 patients with liver disease who were negative both for HBsAg and for HCV markers. Sixty six of the 200 patients with chronic hepatitis C liver disease (33 percent) had HBV sequences, as did 7 of the 50 patients with liver disease unrelated to hepatitis C. Among the 66 patients, 46 were anti HBc positive and 20 were negative for all HBV markers. Twenty two of these 66 patients (33 percent) had cirrhosis, as compared with 26 of the 134 patients with hepatitis C infection but no HBV sequences (19 percent). HBV sequences were detected in 26 of the 55 patients in whom interferon therapy was ineffective and 7 of the 28 patients in whom interferon therapy was effective. The authors conclude that occult hepatitis B infection occurs frequently in patients with chronic hepatitis C liver disease and may have clinical significance for these patients. 4 tables. 45 references.
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Hepatitis B Virus Mutant Associated with an Epidemic of Fulminant Hepatitis B Source: Liver Update. 5(1): 7-8. Spring 1991. Contact: Available from American Liver Foundation. 1425 Pompton Avenue, Cedar Grove, NJ 07009. (201) 256-2550 or (800) 223-0179. Summary: Infection with hepatitis B virus (HBV) leads to a wide spectrum of liver injury. Fulminant hepatitis B is a rare disease, but carries a high mortality. This brief article reports on a nosocomial outbreak of five cases of fulminant hepatitis B that occurred in Israel. Investigations by the author suggest that the five patients with fulminant hepatitis were infected by the same virus derived from a common source while a subclinical case was infected by another HBV strain at the same time. This study points to a role for naturally occurring viral mutations in the emergence of HBV viral strains capable of producing more severe liver injury.
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Potential for the Use of Modified Hepatitis Delta Virus in the Therapy of Chronic Hepatitis B Virus Infections Source: Viral Hepatitis Reviews. 1(1): 47-52. September 1995. Contact: Available from Journals Subscriptions Department, Harcourt Brace and Company Ltd. High Street, Foots Cray, Sidcup, Kent DA14 5HP UK. Telephone +181 300 3322. Summary: Infections by hepatitis B virus (HBV) continue to be a major source of chronic liver disease, despite the great advancements in our understanding of HBV infections and the widespread availability of an effective vaccine. Once a patient has become chronically infected with HBV, the currently available therapies are not particularly effective, and there is a high risk that infection will proceed to cirrhosis and hepatocellular carcinoma. This article evaluates the potential of a novel therapy: the application of modified forms of hepatitis delta virus (HDV) as part of an antiviral
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strategy for individuals with chronic hepatitis B virus infections. 3 figures. 31 references. (AA-M). •
Efficacy of Granulocyte-Macrophage Colon-Stimulating Factor or Lamivudine Combination with Recombinant Interferon in Non-Responders to Interferon in Hepatitis B Virus-Related Chronic Liver Disease Patients Source: Journal of Gastroenterology and Hepatology. 17(7): 765-771. July 2002. Contact: Available from Blackwell Science. 54 University Street, Carlton South 3053, Victoria, Australia. +61393470300. Fax +61393475001. E-mail:
[email protected]. Website: www.blackwell-science.com. Summary: Non-response to interferon (IFN) monotherapy is a major therapeutic problem in the management of chronic hepatitis B virus (HBV) infection. This article reports on a study in which the effectiveness of combination therapy to enhance the immunomodulatory effect of IFN by combining GMCSF (granulocyte-macrophage colony stimulating factor) or decreasing viral load by adding an antiviral agent such as lamivudine was evaluated prospectively. The study included 24 patients with chronic hepatitis B who were non-responders to previous IFN therapy were randomized to receive an IFN and GMCSF (group A, n = 10) or IFN and lamivudine (group B, n = 14) combination for 6 months. All patients successfully completed both the treatment schedules. At the end of treatment, there was a significant decrease in mean ALT levels. The HBV-DNA and HBeAg loss was seen in six of 10 (60 percent) patients in group ! and seven of 15 (50 percent) patients in group B. During follow up, two of six patients (33 percent) in group A and three of seven (43 percent) patients in group B relapsed with HBV-DNA and HBeAg positivity, which meant an overall sustained response of 40 percent and 28 percent respectively. None of the factors such as HBV viral load, ALT levels or liver histology could predict the non-response to combination therapy or occurrence of relapse. The authors conclude that larger studies using such combination therapies would be helpful in improving treatment strategies for chronic hepatitis B. 4 tables. 34 references.
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Chronic Hepatitis B Virus Infection in Asian Countries Source: Journal of Gastroenterology and Hepatology. 15(12): 1356-1361. December 2000. Contact: Available from Blackwell Science. 54 University Street, Carlton South 3053, Victoria, Australia. +61393470300. Fax +61393475001. E-mail:
[email protected]. Website: www.blackwell-science.com. Summary: Of the estimated 50 million new cases of hepatitis B virus (HBV) infection diagnosed annually, 5 to 10 percent of adults and up to 90 percent of infants will become chronically infected. Of those who become chronically infected, 75 percent are in Asia where hepatitis B is the leading cause of chronic hepatitis (liver infection), cirrhosis (liver scarring), and hepatocellular carcinoma (liver cancer). This article offers detailed statistics on chronic HBV infection in Asian countries, including Indonesia, the Phillipines, Thailand, China, Taiwan, and Malaysia. In the highly endemic countries in Asia (places where HBV is found on a routine basis in the population), the majority of infections are contracted postnatally or perinatally (during birth). Three phases of chronic HBV infection are recognized: phase 1 patients are HBeAg positive with high levels of virus in the serum (blood) and minimal hepatic (liver) inflammation; phase 2 patients have intermittent or continuous hepatitis of varying degrees of severity; phase 3 is the inactive phase during which viral concentrations are low and there is minimal inflammatory activity in the liver. In general, patients who clear HBeAg have a better
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prognosis than patients who remain HBeAg positive for prolonged periods of time. The outcome after anti HBe seroconversion depends on the degree of preexisting liver damage and any subsequent HBV reactivation. Without preexisting cirrhosis, there may be only slight fibrosis or mild chronic hepatitis, but with preexisting cirrhosis, further complications may happen. The annual incidence of hepatic decompensation (reduction in liver function) in HBV related cirrhosis varies from 2 to 10 percent and in these patients, the 5 year survival rate drops dramatically to 14 to 35 percent. The annual risk of developing HCC (liver cancer) in patients with cirrhosis varies between 1 and 6 percent. Chronic hepatitis B is not a static disease and the natural history of the disease is affected by both viral and host factors. The prognosis is poor with decompensated cirrhosis and effective treatment options are limited. The authors conclude that prevention of HBV infection through vaccination is still therefore the best strategy for decreasing the incidence of hepatitis B associated cirrhosis and HCC. 1 table. 32 references. •
Hepatitis B Virus Infection Without Immunological Markers After Open-Heart Surgery Source: Lancet. 345(8946): 355-357. February 11, 1995. Summary: Posttransfusion hepatitis is still an important problem, despite the screening of blood donors for hepatitis B virus (HBV) and hepatitis C virus infections. This article reports on a study in which the researchers assessed whether HBV DNA might be detected by PCR in prospectively collected serum samples of patients with unexplained posttransfusion hepatitis but no immunological HBV markers. They found HBV DNA in 4 (20 percent) of 20 patients with unexplained posttransfusion hepatitis and in 5 patients with mildly increased aminotransferases. The clinical course of these HBV infections was usually mild and self-limiting. The researchers conclude that low-titre, immunologically negative HBV infections do exist and might represent a significant cause of post-transfusion hepatitis.
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Kidney Transplantation in Patients with Chronic Hepatitis B Virus Infection: Is the Prognosis Worse? Source: Digestive Diseases and Sciences. 46(3): 469-475. March 2001. Contact: Available from Kluwer Academic/Plenum Publishers. 233 Spring Street, New York, NY 10013-1578. (212) 620-8000. Fax (212) 807-1047. Summary: The impact of hepatitis B virus (HBV) infection on the long term outcome of kidney transplant patients is controversial. This study included a total of 34 chronic hepatitis B surface antigen (HBsAg) carriers among 143 renal (kidney) allograft recipients (mean follow up period: 5.6 years plus or minus 3.3 years; range 1 to 13 years). During the follow up, one HBsAg positive recipient with preexisting cirrhosis died of liver failure, and seven (21 percent) others developed serious HBV related complications (4 had fulminant hepatitis, 2 hepatocellular carcinoma or liver cancer, and 1 cirrhosis), and four died. Although HBsAg positive recipients had a higher rate of liver related complications and deaths than HBsAg negative recipients did, there were no significant differences in the long term graft and patient survival between the two groups. The survival rates, liver related complications, and deaths in HBsAg positive allograft recipients and 28 HBsAg positive uremic patients under dialysis were similar. The authors conclude that HBV infection is not a contraindication to kidney transplantation. However, pretransplant candidates should be warned of potentially serious liver related complications. 3 figures. 4 tables. 28 references.
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Detection of Hepatitis B Virus (HBV) in HBsAG Negative Individuals with Primary Liver Cancer Source: Digestive Diseases and Sciences. 36(8): 1122-1129. August 1991. Summary: The importance of chronic hepatitis B virus (HBV) infection in the development of primary liver cancer has been established by epidemiological studies. This article discusses the detection of HBV in HBsAG negative individuals with primary liver cancer. The authors report the use of the polymerase chain reaction to detect HBV DNA in the serum and liver of these patients. This technique allows both for the detection and cloning of HBV variants. The authors contend that the laboratory values obtained with this technique reinforce the role of HBV in the pathogenesis of this tumor. 5 figures. 39 references. (AA-M).
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Hepatitis B Virus Source: Scientific American. 264(4): 116-123. April 1991. Summary: This article discusses the hepatitis B virus (HBV) which causes liver diseases and a common form of cancer. During the past decade, evolving understanding of the molecular biology of HBV has found medical applications, particularly for preventing the infection. Mass vaccinations with the recombinant vaccine, the first vaccine for human use ever developed by recombinant DNA technology, will go far in controlling hepatitis B. The authors stress that such a campaign of vaccination would prevent not only the acute liver illness but also the associated cancer. This article emphasizes the epidemiology of hepatitis, the genetic structure and activity of HBV, and genetic engineering techniques used to develop a medical response to HBV. 6 figures. 5 references.
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Towards Control of Hepatitis B in the Asia-Pacific Region: Natural History of Chronic Hepatitis B Virus Infection Source: Journal of Gastroenterology and Hepatology. 15(Supplement): E20-E24. May 2000. Contact: Available from Blackwell Science. 54 University Street, Carlton South 3053, Victoria, Australia. +61393470300. Fax +61393475001. E-mail:
[email protected]. Website: www.blackwell-science.com. Summary: This article highlights four aspects of the natural history of chronic hepatitis B virus (HBV) infection that require clarification: the differences between Caucasians and Asians with chronic HBV infection; the relationship between HBeAg seroconversion and the onset of cirrhosis (liver scarring), the role of precore and core promoter mutations, and when patients develop hepatocellular carcinoma (HCC, or liver cancer) and other complications of cirrhosis. In chronic HBV infection acquired during adulthood, which is the type mostly seen in the Caucasian population, there is biochemical and histologic regression after HBeAg seroconversion, and the risk of death from hepatitis B related causes is low. In chronic HBV infection acquired during birth or early childhood, which is the type most commonly seen in the Asian population, there is a prolonged phases of immunotolerance. The immune clearance phase is characterized by multiple acute exacerbations preceded by elevations in serum HBV DNA levels, HBeAg concentration and HBeAg/anti HBe immune complexes. Of these patients, 2.4 percent may develop hepatic (liver) decompensation during the stage of HBeAg seroconversion. The development of cirrhosis occurs more frequently in patients with episodes of decompensation and with repeated severe acute exacerbations. However,
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progression to cirrhosis can be relatively silent and can occur even in children. After HBeAg seroconversion, precore and core promotor mutations occur frequently in the Asian population. However, there is little correlation between the occurrence of these mutations and alanine aminotransferase elevation in patients who are positive for anti HBe. Although cirrhosis develops during the process of HBeAg seroconversion, 68 percent of the complications of cirrhosis and of hepatocellular carcinoma occur after HBeAg seroconversion. These complications may still occur even after HBsAg seroclearance. 21 references. •
Prevention of Hepatitis B Virus Transmission by Immunization: An Economic Analysis of Current Recommendations Source: JAMA. Journal of the American Medical Association. 274(15): 1201-1208. October 18, 1995. Summary: This article reports on a study to evaluate the outcome of immunization strategies to prevent hepatitis B virus (HBV) transmission. A decision model was used to determine the incremental effects of the following hepatitis B immunization strategies in a birth cohort receiving immunization services in the public sector: prevention of perinatal HBV infection; routine infant vaccination; or routine adolescent vaccination. Over the lifetime of the cohort, the reduction in infections and medical and work-loss costs of HBV-related liver disease were determined for each strategy and compared with the outcome without immunization. Prevention of perinatal infection and routine infant vaccination would lower the 4.8 percent lifetime risk of HBV infection by at least 68 percent, compared with a 45 percent reduction for adolescent vaccination. From a societal perspective, each strategy was found to be cost saving, but was not cost saving with respect to direct medical costs. The authors conclude that routine vaccination of infants in successive birth cohorts to prevent HBV transmission is cost-effective over a wide range of assumptions. While economically less attractive than infant vaccination, adolescent vaccination could serve to protect those children who were not vaccinated as infants. 3 figures. 5 tables. 71 references. (AA-M).
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Prevalence of Syphilis, Hepatitis B Virus (HBV), and Human Immunodeficiency Virus (HIV) Infection in New Arrestees at the Lake County Jail, Crown Point, Indiana Source: Journal of Prison & Jail Health; Vol. 12, no. 2, Winter 1993. Contact: Eli Lilly and Company, Eli Lilly Corporate Center, Indianapolis, IN, 46285, (317) 276-2000, http://www.lilly.com. Summary: This article reviews a study conducted to determine the prevalence in arrestees of syphilis, hepatitis B virus (HBV), and HIV infection by demographic and behavioral characteristics, and to evaluate the costs associated with universal screening for these sexually transmitted diseases compared with a theoretical targeted screening program. Three hundred and nineteen arrestees were screened for syphilis, HBV, and anonymously for HIV infection. The prevalence of syphilis was 2.5 percent; hepatitis B surface antigen prevalence was 1.6 percent; the prevalence of past or present HBV infection was 21.9 percent; and the prevalence of HIV infection was 1.6 percent. Targeted screening for sexually transmitted diseases was found to be more costeffective.
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Variants of Hepatitis B Virus Associated with Fulminant Liver Disease Source: New England Journal of Medicine. 324(24): 1737-1739. June 13, 1991.
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Summary: This editorial, which serves as an introduction for two other articles, considers variants of hepatitis B virus (HBV) that are associated with fulminant liver disease. The author reviews the current literature in this area, with an emphasis on examining the role of host immune responses in the activity and severity of liver disease. The author concludes that the current findings represent a major advance in the understanding of the pathogenesis of fulminant HBV infection and may ultimately lead to new therapeutic strategies to prevent its consequences. 22 references. •
Hepatitis B Virus Infection in Asian Americans Source: Gastroenterology Clinics of North America. 23(3): 523-536. September 1994. Contact: Available from W.B. Saunders Company, Periodicals Fulfillment, 6277 Sea Harbor Drive, Orlando, FL 32887. (800) 654-2452. Summary: This review article summarizes studies on hepatitis B in the Asian American population. The authors include prevalence rates among different Asian subgroups, routes of transmission, and sequelae of both perinatal and childhood-acquired hepatitis B virus infection. The article also covers the rationale for the use of hepatitis B immune globulin and hepatitis B vaccine for Asian infants, and vaccine for children and seronegative adults. The authors review chronic hepatitis B, cirrhosis, and primary hepatocellular carcinoma in adults and screening for early detection of liver cancer. 4 tables. 48 references. (AA-M).
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Treatment of Chronic Hepatitis B Virus Infection in Special Groups of Patients: Decompensated Cirrhosis, Immunosuppressed and Paediatric Patients Source: Journal of Gastroenterology and Hepatology. 15(Supplement): E71-E78. May 2000. Contact: Available from Blackwell Science. 54 University Street, Carlton South 3053, Victoria, Australia. +61393470300. Fax +61393475001. E-mail:
[email protected]. Website: www.blackwell-science.com. Summary: Treatment of special groups of patients (i.e., patients with decompensated cirrhosis, immunocompromised patients, and children) is challenging and requires different treatment strategies. This article explores the management of chronic hepatitis B in these special populations. Patients with decompensated liver disease have a poor prognosis and are difficult to treat. Chances of survival for this group are limited without liver transplantation. Interferon alpha (IFN alpha) is presently the recommended treatment for patients with clinically stable chronic hepatitis B. The aim of treatment is to permanently suppress or eliminate HBV infection and thereby induce remission of liver disease. The author notes that there is increasing interest in the use of nucleoside analogues in the treatment of decompensated liver disease and those going for liver transplantation. The author discusses the use of thymosin alpha 1 and lamivudine as treatment options. Chronic hepatitis B is common in immunosuppressed patients, including antiHIV positive patients, patients with chronic renal failure, and patients undergoing organ transplantation. Unfortunately, their response to IFN therapy is poor, mostly because of high level viraemia (levels of virus in the blood) and depressed cell mediated immunity. The prevalence of hepatitis B in Asian children is probably similar to that in adults. Infection acquired early in life may not progress to liver disease until later in childhood or early adulthood. However, both cirrhosis and liver cancer (hepatocellular carcinoma, or HCC) have been documented in children. It is therefore important to consider effective therapy for children with chronic HBV infection and to monitor these children closely for HCC. 64 references.
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Federally Funded Research on Hepatitis B Virus The U.S. Government supports a variety of research studies relating to hepatitis B virus. 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 hepatitis B virus. 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 hepatitis B virus. The following is typical of the type of information found when searching the CRISP database for hepatitis B virus: •
Project Title: A RANDOMIZED TRIAL OF VACCINE ADHERENCE IN YOUNG IDU Principal Investigator & Institution: Lum, Paula J.; Medicine; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 941222747 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 30-JUN-2007 Summary: (provided by applicant): We propose a study to examine strategies to deliver a promising preventive HIV vaccine candidate-employing a surrogate hepatitis B vaccine-to a cohort of high-risk young injection drug users (IDU) and young male IDU that have sex with men (MSM-IDU). We will screen 750 IDU aged 29 or less in San Francisco and over sample MSM-IDU, who have very high rates of HIV seroconversion. We expect that about 50% of those screened will meet eligibility criteria for prospective study and of those, that 80% will enroll. We will follow this cohort of 300 individuals for one year, administering a combined hepatitis A virus (HAV) inactivated and hepatitis B virus (HBV) recombinant vaccine (Twinrix() to study medical management and implementation issues, including: (1) adherence to multi-dose immunization schedules, (2) novel methods to minimize losses to follow-up, and (3) physiologic and behavioral factors that may alter vaccine effectiveness. The primary purpose of the study is to efficiently compare interventions to improve vaccine series adherence. In particular, we propose a randomized trial using a factorial design to compare the effects of clinical setting (syringe exchange program vs. immunization clinic) and outreach worker support (outreach vs. none) in enhancing adherence to a multiple dose immunization schedule. We have three secondary objectives. The first focuses on transience, one of the major causes of attrition in cohort studies of often-homeless IDU and other disenfranchised populations. For subjects who leave San Francisco during the study period, we will use novel technology to map their travel and achieve immunizations remotely. Secondly, we will compare vaccine effectiveness between HCV-infected and uninfected young IDU. We will measure protective antibody levels after immunizations. Finally, given the potential for reduced vaccine effectiveness in the setting of continued high-risk behavior, we will measure changes in behavior and vaccine attitudes. By
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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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testing strategies for delivering a multi-dose schedule of hepatitis vaccine and developing models for improving future HIV vaccine adherence and effectiveness, we can advance HIV vaccine development for young adult high-risk injection drug users. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ADULT ACTG CENTRAL GROUP Principal Investigator & Institution: Benson, Constance A.; Professor of Medicine; Social and Scientific Systems 7101 Wisconsin Ave, Ste 1300 Bethesda, Md 20814 Timing: Fiscal Year 2002; Project Start 01-JAN-1996; Project End 31-DEC-2004 Summary: (adapted from the application's abstract): The Adult AIDS Clinical Trials Group (AACTG) is a multicenter, multidisciplinary clinical trials group dedicated to the study of HIV pathogenesis and therapy. Since its inception in 1987, the AACTG has evolved into a cooperative group consisting of the Central Group (composed of the Office of the Group Chair, Executive, Scientific and Resource Committee, a state-of-theart laboratory network, a Community Constituency Group, and the Operations Center), 30 AIDS Clinical Trials Units (ACTUs) located at major academic medical centers, and the Statistical and Data Management Center. The AACTG has had an impact on elucidating the current understanding of AIDS pathogenesis and therapy, and has played a role in the development of novel trial designs and analysis strategies. AACTG clinical trials have helped define guidelines for the use of antiretroviral agents and for the prophylaxis and treatment of HIV- associated opportunistic complications. Over 200 manuscripts have been published by the AACTG describing this body of work since submission of the prior competing renewal application in 1995. Group productivity has been aided by collaborations with a wide variety of external investigators and laboratories, U.S. and international clinical trials networks, and members of the pharmaceutical and medical diagnostics industries. The AACTG proposes to build on its accomplishments with the goal of further reducing, and ultimately eliminating, HIVassociated morbidity and mortality. The applicants propose to undertake investigations in a structure that allows for a high degree of efficiency and flexibility in the design and implementation of a broad array of clinical trials with patient management principles, according to the applicant, which are reflective of contemporary clinical practice and designed to ensure the relevance of research findings. Over the next several years the Group proposes to address a number of issues including how best to: provide initial and subsequent treatment to maximally suppress HIV replication; provide optimum treatment strategies following treatment failure; develop approaches to individualization of therapy based on genotypic and phenotypic characteristics of the virus and/or host; eliminate reservoirs of HIV-1 in latently infected cells; ameliorate virologic, immunologic, pharmacologic, and behavioral factors (adherence) that contribute to treatment failure; incorporate new therapies and treatment strategies into future regimens; evaluate new strategies for enhancing immune reconstitution to HIV and OIs; and delay or prevent HIV disease progression, opportunistic complications, complications of therapy, and mortality. To accomplish this agenda, the Group requests funds for 35 ACTUs that are to be evaluated on objective performance criteria. New sites and laboratories have been added to the Group in order to provide additional expertise in virology, immunology, and pharmacology. The Group remains committed to enrolling women and minorities and to continuing support of the Minority AIDS Training Program. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ADULT AIDS CLINICAL TRIALS UNIT Principal Investigator & Institution: Balfour, Henry H.; Professor of Laboratory Medicine, Pathol; Lab Medicine and Pathology; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2002; Project Start 01-MAR-1992; Project End 31-DEC-2004 Summary: (adapted from the application's abstract): The Minnesota AIDS Clinical Trials Unit (ACTU) requests to continue to be a unit of the Adult AIDS Clinical Trials Group (AACTG). The Minnesota ACTU is committed to the Scientific Agenda of the AACTG, in which they have participated continuously since January 1, 1987. In addition to recruiting and retaining a cohort of new HIV-infected patients in clinical trials (estimated to be 85 patients in main studies and 54 patients in substudies annually), the Minnesota ACTU plans to contribute to the Group Scientific agenda with the following specific aims: (1) to correlate the quantity and replication competence of HIV at the cellular level in lymphoid tissue (LT), peripheral blood fractions and other compartments; (2) to develop more sensitive methods to detect HIV and apply these to selection of more effective therapies; (3) to define the natural history of cytomegalovirus (CMV) disease in the era of potent antiretroviral therapy and determine the best assays (virologic and immunologic) to monitor its clinical course (AACTG 360); (4) to identify and properly manage the patients who are at risk for complications of the dyslipidemias associated with potent antiretroviral therapy; (5) to identify resistant CMV strains and assess their pathogenicity; (6) to study relationships between the production of neurotoxins in plasma and cerebrospinal fluid of HIV-infected patients, neuronal loss as measured by proton magnetic resonance spectroscopy and the development or progression of HIV-associated dementia (HAD); and (7) to understand and characterize pharmacokinetic behavior, including drug-drug interactions, of antiretrovirals and other HIV-related drugs in biologic fluids. To help achieve these specific aims, the Minnesota ACTU has both Virology and Pharmacology Advanced Technology Laboratories (ATL). The Virology ATL is focusing on quantitation and characterization of HIV in lymphoid tissue and other body compartments. This laboratory also has expertise in HIV and CMV resistance. The Pharmacology ATL is developing assays for simultaneous determination of levels of protease inhibitors and measurement of intracellular antiretroviral anabolites. The Nebraska subunit has a special interest in neuroAIDS and has identified neurotoxins putatively responsible for pathology in HAD. The Iowa subunit has expertise in the detection of hepatitis C and will be collaborating in studies of the pathogenesis of coinfection with HIV and hepatitis C. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ADULT AIDS CLINICAL TRIALS UNIT Principal Investigator & Institution: Havlir, Diane V.; Professor of Medicine; Medicine; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 941222747 Timing: Fiscal Year 2002; Project Start 01-MAR-1992; Project End 31-DEC-2004 Summary: (adapted from applicant's abstract): As a component of the Adult AIDS Clinical Trials Group, the UCSF AACTG unit's (AACTU) primary aims will be to advance the AACTG's research objectives in the areas of pathogenesis and therapeutics of opportunistic infections and metabolic and neurologic complications of HIV disease and in pharmacologic issues related to the drugs used to treat HIV disease. In the project period, this unit's focus will emphasize scientific leadership and subject accrual in studies designed to investigate the natural history and pathogenesis of HIV-related complications in the HAART era, to improve strategies and therapies for preventing and
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treating these complications, and to use pharmacologic and behavioral science expertise to increase the scientific understanding and clinically relevant knowledge about treatment for HIV disease. The unit plans to enroll 100 new subjects into a variety of trials and substudies each year and to follow these and at least 100 continuing subjects, maintaining compliance with the AACTG's high standards for protocol adherence, data management, and subject retention. Dr. Mark Jacobson, the Principal Investigator of this unit, will continue to be one of the group's key scientific leaders in investigating the treatment, prophylaxis and immunopathogenesis of AIDS-related opportunistic infections. Dr. Kathy Mulligan will continue to be one of the key leaders in the effort to understand, prevent and treat the metabolic complications of HAART. Drs. Francesca Aweeka, Lewis Sheiner, and John Gambertoglio will be leaders of the group's efforts to understand pharmacokinetic (PK) interactions among drugs used to manage HIV infection and its complications; to use statistical simulation for optimizing study designs for explanatory PK/pharmacodynamic and pathophysiologic analyses and adaptive therapy strategies; and to maintain high interlaboratory quality control and assurance for specific drug assays. Dr. Margaret Chesney will lead the group effort to develop standardized measures of adherence that can be easily applied across protocols to evaluate relationships between adherence and clinical, virologic and immunologic outcomes, as well as to test interventions to increase medication adherence. Dr. Paul Volberding will lead the group's first effort to determine how best to utilize intensive combination antiretroviral regimens in acute/early HIV infection in order to maintain long-term suppression of HIV infection. Dr. J. M. McCune will provide expertise and laboratory support for immunologic studies, and Drs. Richard Price and Harry Hollander will provide clinical expertise to support neurologic studies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ADULT AIDS CLINICAL TRIALS UNIT Principal Investigator & Institution: Goldman, Mitchell; Medicine; Indiana Univ-Purdue Univ at Indianapolis 620 Union Drive, Room 618 Indianapolis, in 462025167 Timing: Fiscal Year 2002; Project Start 01-JAN-2000; Project End 31-DEC-2004 Summary: (adapted from application's abstract): The Indiana University proposes to build upon the following in the renewal application: (1) scientific and administrative contributions. The Indiana ACTU ranks among the top 20 percent of ACTUs scientifically; (2) cost efficient accrual into AACTG trials. Indiana ranked third in cost weighed accrual; and (3) recruitment of women and minorities. The ACTU ranked second in recruitment of African- Americans and third in women. The long-term objectives of this site are to: expand scientific and administrative contributions through recruitment of additional investigators; increase accrual potential for women and minorities by expansion of the Wishard Hospital subunit; and increase the patient base by establishing a subunit at Community Hospital of Indianapolis. The first specific aim of the Indiana University ACTU is to contribute scientifically through submission of concept proposals and memberships on AACTG protocol teams and committees. Currently, Indiana investigators hold 32 positions on protocol teams. Concepts are proposed for: (a) salvage therapy for efavirenz failures; (b) evolution of anal dysplasia and the role of HPV in patients on HAART; (c) the role of gp 120 in HIV induced apoptosis of neurological cells in pathogenesis of dementia; (d) the role of GM-CSF and CD4 ligand on immunity to H. Capsulatum and HIV-1; (e) use of in vitro assays for drug interactions with protease inhibitors; and (f) the role of intestinal metabolism and bioavailability of antiretroviral drugs. The second specific aim is to expand the patient base, including women and minorities, though increased support for subunits at
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Wishard Hospital and Community Hospital. The work proposed in this application will be implemented through conduct of clinical trials as a member the AACTG, using an infrastructure that has been refined during 12 years as an ACTU. Specialized immunology, virology, and pharmacology laboratories will support this work. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ADULT THERAPEUTIC CLINICAL TRIALS PROGRAM FOR AIDS Principal Investigator & Institution: Eron, Joseph J.; Associate Professor; Medicine; University of North Carolina Chapel Hill Aob 104 Airport Drive Cb#1350 Chapel Hill, Nc 27599 Timing: Fiscal Year 2002; Project Start 30-SEP-1987; Project End 31-DEC-2004 Summary: (adapted from the application's abstract): The applicants propose to continue their multidisciplinary multi-year research program, that will integrate institutional expertise in infectious diseases, neurology, ophthalmology, gynecology, pharmacology, immunology, retrovirology, herpes viruses, and numerous clinical resources in North Carolina. The main focus is the evaluation of novel therapies for HIV-infected persons. Clinical investigators at the UNC and two satellite units, Greensboro, and Charlotte will study new compounds active against HIV and associated infections, malignancies, and neurologic disorders in new patients and follow previously enrolled patients. This proposes to continue a high rate of accrual among minorities, women, and intravenous (I.V.) drug users. The trials will be of all Phases (I, II, and III) and types. Patients will be followed for in vivo evidence of study drug effects on HIV, Mycobacterium avium intracellular complex (MAC), cytomegalovirus (CMV), herpes simplex virus (HSV), and other opportunistic infections using the ACTG-certified retrovirology and immunology virus laboratory, as well as UNC hospital laboratories. Pharmacokinetics (PK) will be monitored in the General Clinical Research Center (GCRC) and Microbiology and Pharmacology Laboratories. Concepts for new protocols will originate by participation in the Executive, Neurology, and Complications of HIV, HIV Pharmacology and Immunology ACTG committees. The established scientific advisory board (SAB) also will be involved in concept development. The UNC group application has new proposals for many trials including the eradication of HIV, simplification of regimens, novel therapies, improving adherence and immune restoration. Outreach to the community may be accomplished through the community advisory boards (CAB) at each site, the website and through a statewide newsletter. Finally, low protocol costs may be maintained by cost sharing with NIH grants (GCRC, Pediatric ACTU, Center for AIDS Research (CFAR), as well as with UNC Hospitals, and the Departments of Medicine, Neurology, Ophthalmology, Microbiology and School of Pharmacy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: AIDS CLINICAL TRIALS GROUP - ACTU Principal Investigator & Institution: Feinberg, Judith T.; Internal Medicine; University of Cincinnati 2624 Clifton Ave Cincinnati, Oh 45221 Timing: Fiscal Year 2002; Project Start 30-SEP-1987; Project End 31-DEC-2004 Summary: (adapted from the applicantion's abstract): Since its inception in 1987, the University of Cincinnati (UC) ACTU has made contributions to the overall mission of the ACTG in a number of key areas. The UC ACTU has provided both scientific and administrative leadership especially in opportunistic infections, and more recently, in antiretroviral studies, HIV- associated neurologic diseases, research nursing, and study design. In the current cycle, the UC ACTU proposes to continue to perform a broad
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range of clinical trials and substudies to assure maximum UC ACTU contribution to the objectives of the ACTG research agenda. These include to translate the findings of basic research conducted at UC on immunopathogenesis of Pneumocystis carinii and other opportunistic pathogens that may help determine when and if prophylaxis can be discontinued safely in antiretroviral therapy responders. Also, to explore microbial and immunologic measures which define risk for the protection against Pneumocystis as a basis for adjunctive immune- based therapy and prophylaxis. In addition to study the pathogenesis and clinical significance of hepatitis C/HIV co-infection in the HARRT era, and use this knowledge to develop improved treatments. Another Aim is to continue to elucidate the underlying mechanisms in the neuropathogenesis of HIV infection, and exploit these mechanisms in the development of new therapeutic modalities for central nervous system HIV infection, including HIV dementia and multifocal leukoencephalopathy. The UC ACTU will also work to develop treatment strategies for the management of patients with discordant responses to current antiretroviral therapy and to develop simplified, potent treatment strategies, including the use of novel agents, to enhance antiretroviral adherence and therefore improve clinical outcome. The short and longer-term incremental cost of quality-adjusted life expectancy associated with various treatment strategies using utility assessment will also be studied. Finally, the UC ACTU proposes to evaluate whether an intensive educational intervention that is paced by the patient yields improved short and long-term virologic suppression in naive patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: AIDS CLINICAL TRIALS UNIT Principal Investigator & Institution: Hirsch, Martin S.; Professor of Medicine; Medicine; Harvard University (Medical School) Medical School Campus Boston, Ma 02115 Timing: Fiscal Year 2002; Project Start 01-APR-1992; Project End 31-DEC-2004 Summary: (adapted from applicant's abstract): The Harvard Adult ACTU has several clinical centers for trials of promising drugs and drug strategies in the treatment of HIV infection or its complications. Main sites include the Massachusetts General Hospital (MGH), Beth Israel Deaconess Medical Center (BIDMC), and Boston Medical Center (BMC). An ancillary site will be the Brigham and Women's Hospital (BWH). This collaborative group draws from a wide patient catchment area in Massachusetts and throughout New England, including all socio-economic groups. Both sexes are represented and there is a wide diversity of racial and ethnic groups included in studies. All adult risk groups participate, and the number of under-represented and minority population participants has risen steadily in recent years. Studies are conducted on antiretroviral agents, and drugs active against opportunistic pathogens. Studies also are conducted on the pathogenesis of HIV infections, and on the effects of treatment strategies on the natural history of infection. Studies of the metabolic complications of HIV infection and its therapy also are underway. Individuals are studied at all stages of infection, and the current application proposes to extend these studies and to broaden the involvement of under-represented populations in HIV clinical trials. The Harvard Adult ACTU has made contributions to existing knowledge concerning the pathogenesis and therapy of HIV infection, and has contributed to the Scientific Agenda and leadership of the existing ACTG. Harvard has participated in the ACTG Quality Control program since its inception and is conducting critical studies on viral resistance and quantitation, and immunopathogenesis. This Unit plans to expand these research efforts within the framework of the ACTG Advanced Technology Laboratory Program. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: AIDS CLINICAL TRIALS UNIT Principal Investigator & Institution: Friedman, Harvey M.; Professor; Medicine; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 01-APR-1992; Project End 31-DEC-2004 Summary: (adapted from the applicant's abstract): The University of Pennsylvania (Penn) ACTU consists of the main unit located at the Hospital of the University of Pennsylvania (HUP) and a subunit at the Veterans Administration Hospital (VAH) scheduled to open January 1999. This represents a change in the structure of the Penn ACTU since July 1998 when Thomas Jefferson University (TJU) was removed as a subunit. With this reorganization, funding has been redistributed enabling the addition of seven Penn scientists to the core group of investigators consisting of Drs. Friedman (Principal Investigator), MacGregor (Opportunistic Infections), Frank (antiretroviral therapy), Kolson (neuroAIDS/dementia), and Pomerantz (pathogenesis), the last serves as a consultant to our group. The new scientists include Drs. Gross (adherence to therapy), Holmes (quality of life), Rader (metabolic and lipoprotein abnormalities), Kimmel (risk factors for cardiac disease), Weissman (HIV immunology), Grossman (neuroimaging for AIDS dementia) and Jemmott (recruitment and retention of women and minorities). The HIV clinical program at Penn includes 750 patients cared for at HUP, 435 at the VAH, and 250 at Presbyterian Medical Center. Penn ID physicians are primary care providers for the HIV patients, which provides a link between the providers and the clinical research unit housed within the ID division. The demographics of the clinic population match those of the epidemic in Philadelphia; therefore, African Americans, women and IDU subjects (particularly with the addition of the VAH) have ready access to clinical trials. Approximately 60 percent of study patients come from the clinics while 40 percent are referred from physicians practicing throughout the Delaware Valley, enabling many patients to access HIV clinical trials. The investigators have credentials in basic and patient-oriented clinical research. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: AIDS CLINICAL TRIALS UNIT Principal Investigator & Institution: Currier, Judith Silverstein.; Medicine; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2004; Project Start 30-JUN-1986; Project End 31-DEC-2004 Summary: (adapted from the application's abstract): The ACTU has been an active participant in clinical trials for the treatment of human immunodeficiency virus (HIV) and related diseases of the ACTG since 1986. Metropolitan Los Angeles is culturally diverse and its residents are significantly affected by the AIDS epidemic. The UCLA ACTU, located on the west side of Los Angeles, with its subunits in various areas of greater Los Angeles is applying for competitive renewal as part of the ACTG under the group leadership of Robert T. Schooley, M.D. The goal of the UCLA ACTU is to fully participate in the scientific and operational activities of the Group. This would include involvement in the Group scientific and administrative leadership via participation in ACTG research agenda committees, working groups and protocol teams, accruing patients to studies, and providing laboratory expertise in specific areas in which this ACTU has expertise such as immunology. Both the UCLA main site and the HarborUCLA subunit will enroll patients in high priority Phase I, II and III clinical trials of antiretroviral drugs, immune-based therapies and treatments for opportunistic infections, neurologic disorders and complications of HIV treatment. Patients also will be enrolled and maintained in the longitudinal assessment study (ALLRT protocol) to
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help answer important questions about the pathogenesis and clinical management of HIV, as well as in other studies designed to address the specific aims of the ACTG. Administrative oversight, specimen storage and shipping, performance of protocol mandated laboratory assays, data quality assurance, maintenance of a CAB and outreach activities to stimulate greater participation of women and racial/ethnic minorities in ACTG clinical trials will be the responsibility of the UCLA main site. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ANALYZING HEPATITIS B VIRUS PATHOGENESIS Principal Investigator & Institution: Isom, Harriet C.; Distinguished Professor; Microbiology and Immunology; Pennsylvania State Univ Hershey Med Ctr 500 University Drive Hershey, Pa 170332390 Timing: Fiscal Year 2004; Project Start 01-SEP-1978; Project End 31-JAN-2009 Summary: (provided by applicant): The World Health Organization estimates that 350 million people are chronically infected with HBV and approximately twenty-five percent of these individuals will succumb to chronic active hepatitis, cirrhosis, or hepatocellular carcinoma. Although a tremendous amount is known about HBV, our understanding of HBV pathogenesis is by no means complete. Two important areas that require further investigation are the replication intermediate HBV nuclear covalently closed circular (CCC) DNA and drug resistance mutants. CCC DNA is a highly stable molecular that serves as the reservoir for chronicity of infection and rapid rebound of HBV replication and acute hepatitis after release from drug therapy. Use of the nucleoside analogue lamivudine for therapy in patients with chronic HBV has led to the man-made problem of infection with drug resistance mutants. During the last funding period, our laboratory developed a novel transient mechanism for studying HBV gene expression and replication using recombinant wild type and mutant HBV baculoviruses to deliver the HBV genome to human hepatic HepG2 cells. The HBV baculovirus/HepG2 system is the only in vitro system in which CCC DNA is produced at sufficiently high levels that it can be detected by Southern blot analysis. This system recapitulates the replication process in patients in that transcription is driven from CCC DNA, nucleocapsids recycle to the nucleus to deliver CCC DNA to the nucleus and rebound of HBV replication after release from antiviral therapy as a result of stable CCC DNA can be demonstrated. We have also demonstrated that the HBV baculovirus system can be used to study replication of HBV mutants, which has resulted in provocative findings regarding replication of at least one HBV drug resistance mutant. We propose to continue to use the HBV baculovirus to pursue unanswered questions regarding chronic HBV infection that follow directly from ongoing studies in the laboratory or represent extensions of these studies. The Specific Aims are: (1) To investigate whether failure of the HBV drug resistance mutant rtM2041, which contains a mutation in the polymerase, to yield self-perpetuating HBV replication can be corrected by complementation with wild type HBV polymerase; (2) To evaluate transcription from CCC DNA of the 3.5 Kb HBV transcripts; (3) To determine the relationship of phosphorylation status and subcellular localization of core to HBV replication. In addition, to determine the effect of cell cycle on phosphorylation status and subcellular localization of core and recycling of CCC DNA to the nucleus, and (4) To use the HBV recombinant baculovirus/HepG2 system to develop a mouse model for HBV replication in which HBV CCC DNA is expressed. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ANTIVIRAL/ANTITUMOR ROLES OF GANODERMA LUCIDUM SPORES Principal Investigator & Institution: Liu, Rui H.; Associate Professor; Food Science; Cornell University Ithaca Office of Sponsored Programs Ithaca, Ny 14853 Timing: Fiscal Year 2004; Project Start 01-APR-2004; Project End 31-MAR-2006 Summary: (provided by applicant): Over 350 million people worldwide are chronic carriers of hepatitis B virus (HBV) - over one million in the United States alone. Chronic hepatitis B infection is a major risk for the development of primary hepatocellular carcinoma (HCC). More than 500,000 people in the world die each year of HCC and most cases are associated with HBV. Interferon-a and lamivudine are the only FDA approved drugs for treatment of chronic HBV infection. There are frequent side effects and complications associated with the use of interferon-a, which also has limited efficacy with only 30% of patients responding favorably to treatment. Lamivudine is a safe drug but frequent occurrences of drug resistant mutants are observed with extended therapy. In most cases, drug withdrawal is associated with complete recrudescence of viral replication. Therefore, there is an urgent need for novel or alternative treatment methods for HBV therapy. Ganoderma lucidum spores used in Traditional Chinese Medicine (TCM) have been shown to have antiviral and anticancer activity against HBV and HCC in human patients in China. In this proposal we plan to use the woodchuck model of hepatitis B virus infection to investigate experimentally the potential of Ganoderma lucidum for prevention and treatment of HCC. The longterm goal of the project is to determine the antiviral activity Ganoderma lucidum spores against HBV and the anticancer activity of Ganoderma lucidum spores for prevention and treatment of human HCC. The specific aims are to: 1) determine the antiviral activity of Ganoderma lucidum spores against the woodchuck hepatitis virus (WHV) as a preclinical test of their potential for treatment of HBV infection and 2) determine the activity of the Ganoderma lucidum spores in the prevention and treatment of HCC in woodchucks with experimentally induced, chronic WHV infection. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: BEHAVIORAL ASPECTS OF HIV/HBV/HCV RISKS IN NEW INJECTORS Principal Investigator & Institution: Goldsamt, Lloyd A.; National Development & Res Institutes Research Institutes, Inc. New York, Ny 100103509 Timing: Fiscal Year 2003; Project Start 10-JAN-2003; Project End 31-DEC-2006 Summary: (provided by applicant): The proposed study will comprehensively document the injection initiation experiences and early injection careers of young injectors (age 16-25) in New York City, with an emphasis on the impact of pedagogy on the development of injection skills and the acquisition of these skills over time. A large sample (n=600) of cross-sectional interviews, as well as bimonthly interviews with a cohort (n=150) of new injectors will be supplemented with direct ethnographic observations (n=200) of injection events involving young injectors. Data from these interviews and observations will be used to characterize the injection initiation experiences of young injectors, describe the process by which new injectors learn the behavioral practices necessary to prepare and inject drugs, and determine predictors of safer injection behaviors that may prevent the transmission of HIV, HBV, and HCV. A focus on help-seeking skills will inform the development of recommendations for competencies-based interventions aimed at preventing seroconversion among new injectors.
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Hepatitis B Virus
Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: COLUMBIA-ADARC-CORNELL AIDS CLINICAL TRIALS UNIT Principal Investigator & Institution: Hammer, Scott M.; Director; Medicine; Columbia University Health Sciences Po Box 49 New York, Ny 10032 Timing: Fiscal Year 2002; Project Start 01-JAN-2000; Project End 31-DEC-2004 Summary: (adapted from the application's abstract): The overall goal of this application is the formation of a clinical site within the Adult AIDS Clinical Trials Group (AACTG) which will effectively execute studies designed to improve the understanding and treatment of HIV disease. This site, a linkage of the Columbia Presbyterian Medical Center (Columbia) with the Aaron Diamond AIDS Research Center (ADARC) will be designated the Columbia-ADARC AIDS Clinical Trials Unit. Columbia will serve as the main unit and ADARC as the sub-unit in this collaboration of two institutions already scientifically linked by the recently awarded Center for AIDS Research (CFAR) grant. The intent is to bring together extensive and complementary clinical trials and basic investigative expertise to facilitate execution of the Group's scientific agenda. A Columbia-ADARC unit may possess the elements necessary to successfully carry out a diverse array of pathogenetically and strategically based clinical trials in a demographically diverse population. The specific aims of this application are: (1) to establish a clinical trials unit that has the capability to conduct studies which advance the knowledge of HIV pathogenesis and treatment. Specifically, this unit will be dedicated to further the AACTG's research agenda through active accrual to protocols sponsored by the scientific committees of the Group; (2) to recruit and retain a diverse population of HIV infected persons in AACTG trials who reflect the affected population in Manhattan, particularly Northern Manhattan, a region which has been severely affected by the HIV epidemic and one that is representative of the penetrance of the epidemic into the inner cities. This will be achieved through recruitment of patients from a large primary care base and broad regional referral network; and (3) to promote the Group's scientific mission by active participation in AACTG protocols and committees by Columbia-ADARC investigators. This will include sharing of new technologies that enhance the sophistication of patient monitoring and thereby generate new hypotheses to test in the context of AACTG trials. Thus, the Columbia-ADARC ACTU will be an active participant in the Group's mission to improve the health of HIV infected individuals and set standards for treatment of HIV disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: COST-EFFECTIVE SCREENING IN INTERNATIONAL ADOPTEES Principal Investigator & Institution: Mandalakas, Anna M.; Pediatrics; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2002; Project Start 04-SEP-2001; Project End 30-JUN-2006 Summary: (provided by applicant): The candidate is a junior academic clinician, trained in pediatrics and epidemiology, whose long-term career goals are to conduct patient oriented research that will improve health care delivery to vulnerable children in the US and in the developing world. The proposed training program was designed to enable the candidate to transition from novice to independent researcher in epidemiology with expertise in international child heath. The specific objectives are to obtain maundered practical experience in patient oriented research and rigorous methodological training in decision analytic methods with an experienced team of mentors and national experts. The training plan describes activities (advanced degree coursework, independent study
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and patient oriented research) focused on further developing skills in epidemiology with immediate applications to cost- effective screening in internationally adopted (IA) children. Two complementary studies are proposed that address the clinical and costeffectiveness of hepatitis B virus (HBV) and tuberculosis (TB) screening in IA children. These studies are based on the hypothesis that focused, rational screening can provide a cost-effective means for improving the long-term health outcomes of immigrant children and is consonant with public health imperatives. Each study involves primary collection of new data that address important gaps regarding the prevalence and risk factors for infectious diseases in IA children, and the utility of markers (skin tests and immunization history) to predict infection, disease or protective immunity. This will provide new information regarding the infectious disease burden, and its expression, in the growing group of IA children in the US. These new data also will provide estimates necessary for cost-effectiveness analyses that will be developed to assess the utility of alternative approaches for immunization and TB screening. The proposal addresses important knowledge gaps about the health of children immigrating to the US from resource-poor environments and may provide important new data for rational and costeffective screening in IA children. The cohort of children developed in this proposal may be followed in future research designed to answer challenging questions with respect to the long-term impact of early screening and preventive TB therapy. Finally, the proposal will provide a key training opportunity to foster the candidate s career development as an epidemiologist with a commitment to patient oriented research. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DIETARY FACTORS IN THE ETIOLOGY OF CANCER IN SHANGHAI Principal Investigator & Institution: Ross, Ronald K.; Professor; Preventive Medicine; University of Southern California 2250 Alcazar Street, Csc-219 Los Angeles, Ca 90033 Timing: Fiscal Year 2002; Project Start 01-APR-1987; Project End 30-JUN-2002 Summary: (Adapted from the Applicant's Abstract): We are requesting continued support for an ongoing cohort study of 18,244 men, ages 45-64, living in a geographically defined area of metropolitan Shanghai, Peoples Republic of China. All cohort members have completed detailed diet and medical histories and have blood and urine samples. Questionnaires have been edited and computerized and blood and urine samples have been processed, aliquoted, and continuously stored at both -20_C and 70_C. The cohort was fully established in 1989. Follow-up of the cohort is proceeding through cancer registration by the population-based Shanghai Cancer Registry, by routine ascertainment of death certificates, and by annual recontact of all cohort members. As of March 1994, 606 have developed cancer and 989 have died. The leading cancers include lung, stomach, liver, and colorectal cancers, while stroke is the number one cause of death. Major accomplishments achieved through this cohort to date include: (1) the first direct evidence linking aflatoxin ingestion to human hepatocellular carcinoma (HCC); (2) strong evidence of synergy between aflatoxin biomarkers and chronic infection with hepatitis B virus in establishing risk of HCC; (3) failure to find an association between H. pylori serology and stomach cancer risk; (4) the absence of an inverse association between antioxidants and fatal stroke; and (5) the first comprehensive and systematic evaluations of smoking-related cancer incidence and mortality in China. We propose to continue to follow this cohort for an additional five years. We will continue to evaluate risk factors for major health outcomes in the cohort, building on previous observations and continuing to exploit the serum and urine banks available for biomarker studies. Although we did not collect buffy coats for genetic
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Hepatitis B Virus
studies on cohort members, we have demonstrated that the stored serum samples contain sufficient cells for conducting selected PCR-based genetic studies. Among the scientific goals for the next five years are: (1) to continue to evaluate the aflatoxin/HCC association and to assess the impact of sequence variations in genes involved in aflatoxin metabolism (GSTM1 and EPHX) in modifying risk; (2) to continue to assess the role of H. pylori in gastric cancer etiology in Shanghai, and to assess the possible protective effect of tea polyphenols on risk; and (3) to better understand the complex interrelationships among carotenoids, smoking, and lung cancer and to assess the possible risk modifying impact of genes involved in metabolism of smoking-related carcinogens. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ELECTROCHEMICAL ENZYME IMMUNOASSAY TO TEST BLOOD HBV Principal Investigator & Institution: Henkens, Robert W.; Alderon Biosciences, Inc. 2810 Meridian Pky, Ste 152 Durham, Nc 277132334 Timing: Fiscal Year 2002; Project Start 15-APR-2000; Project End 30-JUN-2003 Summary: (provided by applicant):Millions of Americans are infected by the hepatitis B virus (HBV)-many of whom have no reason to believe they are infected. There is a need to track down America's millions of HBV victims-as well as a corresponding need for innovative technology to test blood for HBV. HBV is clearly a national medical priority. The overall goal of this project is to further develop and then integrate core sensor and enzyme immunoassay technologies into a novel technique for the rapid and accurate measurement of HBV levels in blood. We are targeting diagnostic (detection) applications as well as quantitative measurement needs (to monitor viral levels and treatment efficacy). The feasibility of our approach was clearly demonstrated during Phase I. The Phase II goal is to demonstrate/validate/optimize the integration of a unique electrochemical measurement method with proprietary electrochemical enzyme immunoassay architecture to produce a new diagnostic/monitoring capability for "real time," cost-effective HBV assessment in an outpatient setting. The product we envision is a disposable HBV test strip that can be read by an inexpensive, small (hand-held) instrument. It would represent a key development in medical diagnostics that would address major domestic and international market needs for low-cost HBV screening and monitoring. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: EPIDEMIOLOGY OF HEPATOCELLULAR HEPATITIS B VIRUS IN 3 POPULATIONS
CARCINOMA
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Principal Investigator & Institution: London, W. Thomas.; Senior Member; Fox Chase Cancer Center Philadelphia, Pa 191112434 Timing: Fiscal Year 2002; Project Start 01-APR-2001; Project End 31-MAR-2003 Summary: (Applicant's Description) Prospective studies of 60,984 men in Haimen City, China and 19,469 men in Senegal, west Africa revealed a 14-fold greater death rate from hepatocellular carcinoma (HCC) among the Haimen (168 per 100,000) than the Senegalese cohort (12 per 100,000). Even though chronic infection with hepatitis B virus (HBV) is the major risk factor for HCC in both populations, the age-adjusted prevalence of chronic infection is about 20% in both cohorts. Exposure to aflatoxin, a postulated major risk factor for HCC, is also similar or greater in the Senegalese population. The prevalence of viremia (HBV DNA in serum) among HBV carriers throughout adult life,
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however, is much higher among the Chinese than the Senegalese population. Nevertheless, within the Chinese cohort, viremia at study entry is not a risk factor for HCC after four years of follow-up. The aims of this project focus on factors that may account for variation in HCC risk in the Chinese and Senegalese cohorts and a cohort of Asian-American HBV carriers living in the Philadelphia area. Continued tracking of these three cohorts will test the hypothesis that with longer duration of follow-up, H B V v iremia and liver damage at study entry are associated with person-specific risks of HCC and that aflatoxin-B1 (AFB1)-albumin adducts are a s s ociated with development of HCC among viremic individuals and/or genotypically determined poor detoxifiers of AFB1 (in collaboration with Project 2). In close cooperation with the studies of WHV in woodchucks (Project 3), an intensive longitudinal study of 1000 male and female HBV carriers in these three populations will be conducted to: a) examine whether perturbations of the stability of HBV serum markers are associated with acute illnesses, aflatoxin exposure, and/or outgrowth of viral mutants; b) assay hepatocyte turnover and immune responses in liver biopsies; c) correlate these measures with viral load; d) examine the relationship of sex differences in changes in HBV serum markers over time to the lower HCC risk of female HBV carriers. Because present studies show that an episode of acute hepatitis in adulthood approximately doubles HCC risk among both HBV carriers and non-carriers, the causes and outcomes of 200 cases of acute hepatitis in Haimen City will be characterized. This research will lead to a new level of understanding of the factors that lead to HCC and to new strategies for the prevention of this lethal disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ETIOLOGY AND PREVENTION OF BLOOD BORNE VIRUSES IN IDUS Principal Investigator & Institution: Hagan, Holly C.; Deputy Director; National Development & Res Institutes Research Institutes, Inc. New York, Ny 100103509 Timing: Fiscal Year 2002; Project Start 30-SEP-2001; Project End 31-MAR-2007 Summary: (provided by applicant): The etiology and prevention of blood-borne viral infections in injection drug users (IDUs) have not been fully characterized, and many questions remain regarding which injection practices may result in I infection. Viral hepatitis infections in IDUs are among the most frequently occurring 81ood-bornel l infections in humans; in low HIV-prevalence settings, morbidity and mortality in IDUs attributable to l hepatitis virus infections may exceed that for HIV. Hepatitis C virus (HCV) is highly prevalent in IDU- populations, and is more efficiently transmitted l abouty injection than HIV. Because sexual HCV transmission is relatively rare, it may serve as a highly sensitive biologic marker of direct percutaneous exposure to these infections in drug injectors, and may contribute to understanding the mechanism of transmission of other infections via injection practices. The long-term goal of our research is to advance knowledge of the epidemiology, etiology and-prevention of HIV and hepatitis infections in IDUs. We propose studies that will make new contributions toward our long-term goal: Aim 1. Examine the extent to which HCV prevention education at the Seattle needle exchange program has reduced the risk of HCV infection. Aim 2. Measure the risk of HCV seroconversion associated with specific injection risk behaviors, and calculate the risk of HCV attributable to these practices in the IDUpopulation. Aim 3. Compare reporting of socially-undesirable or stigmatized injection and sexual risk behavior collected by A-CASI to interviewer-administered data collection methods. Aim 4. Assess the feasibility and disease control benefits of HBV and HCV partner notification for IDUs. Aim 5. Study whether changes in hepatitis C
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Hepatitis B Virus
reporting laws are associated with increased reporting in IDUs. The significance of this research is its potential contribution to our understanding of the etiology of these l infections, and examines many practical questions related to the effectiveness of public health surveillance and prevention programs. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: EVOLUTION OF IMMUNE RECOGNITION AND EVASION Principal Investigator & Institution: Hughes, Austin L.; Professor; Biological Sciences; University of South Carolina at Columbia Byrnes Bldg., Room 501 Columbia, Sc 29208 Timing: Fiscal Year 2003; Project Start 01-SEP-1990; Project End 31-MAR-2007 Summary: (provided by applicant): The vertebrate immune system includes numerous proteins involved in the recognition and elimination of parasitic organisms. The general goals of this research are to understand the origin and evolution of key molecular components of this system, especially the molecules encoded by the genes of the major histocompatibility complex (MHC), and to understand the evolution of molecular adaptations in parasitic organisms that evade recognition and elimination by the host's immune system. The MHC is a multi-gene family encoding cell-surface glycoproteins, which play an important role in the immune system, binding foreign proteins and presenting them to T cells. Several of the MHC loci are highly polymorphic, and there is evidence that this polymorphism is maintained by balancing selection relating to most host immune surveillance. The methods used in this research involve statistical analysis of published DNA sequence data, of which a large amount is now available both for immune system genes and for genes of major human pathogens (particularly viruses). The purposes of these analyses are as follows: (1) to understand the evolutionary origin of MHC class I peptide-binding specificities; (2) to understand the evolutionary origin of MHC-related molecules that have assumed other functions; (3) to test the hypothesis that selection exerted by the host class I MHC and cytotoxic T cell (CTL) recognition system has played a role in the long-term evolution of viruses infecting vertebrates (including human immunodeficiency virus 1, hepatitis B virus, and papilloma viruses); (4) to understand the evolution of overlapping reading frames in viral genomes, with particular emphasis on the role of natural selection exerted by the host class I MHC/CTL recognition system on genes encoded by overlapping reading frames; (5) to understand the process by which the genomes of large DNA viruses (including adenoviruses, herpes viruses, poxviruses and baculoviruses) have "captured" host genes over the course of their evolution, a process which has enabled these viruses to obtain genes encoding immuno-modulating proteins which can interfere with host immune processes; and (6) to understand the evolution of repeat-containing proteins, which are believed to enable parasites to evade the highly specific recognition mechanisms of the host MHC and T cell system, in the genomes of the malaria parasites and DNA viruses. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GENERATION/EMERGENCE OF VARIANT IN HEPADNAVIRUS INFECTON Principal Investigator & Institution: Summers, Jesse; Professor; Cell Biology and Physiology; University of New Mexico Albuquerque Controller's Office Albuquerque, Nm 87131 Timing: Fiscal Year 2004; Project Start 01-JUL-2000; Project End 30-JUN-2005 Summary: The objectives of the proposed research are to understand the mechanisms for the generation and emergence of variants during chronic infection with
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hepadnaviruses. Variants are thought to be important in the pathogenesis or persistence of HBV infections in humans, and are known to be responsible for the development of drug resistance during antiviral therapy and for infection in vaccinated individuals and liver transplant recipients. However, because chronic infection is due to persistent infection at the cellular level, and the liver is a relatively quiescent tissue, it is not clear how variants that are generated during a chronic infection emerge as the dominant species of virus. The research we propose is designed to clarify the mechanisms for emergence of virus strains. Understanding the processes that result in evolution of the virus population in a chronically infected liver requires gaining new fundamental information about the nature of chronic infections; i.e. about how the progeny of the infecting viruses and variants are distributed in the liver, how much viral and cellular turnover occurs during chronic infection, and how virus lineages are segregated in different populations of hepatocytes where selection of individual variants can occur. Because these questions cannot be addressed experimentally in human HBV infections, we will use the duck hepatitis B virus (DHBV) model. DHBV, a member of the hepadnavirus family, closely resembles HBV in virus structure, genome replication, persistence, and tissue tropism. DHBV is the only member of this family of viruses that can be genetically manipulated in vitro and tested conveniently in animal infections. The five specific aims are (1) to measure the spontaneous mutation frequency in a single round of transcription and reverse transcription of the DHBV genome, (2) to determine the nature of mixed infections of the liver at the cellular level, particularly the frequency of doubly and singly infected hepatocytes, cell-to-cell variation in covalently closed circular DNA (cccDNA) copy number, and the effects of liver growth and regeneration on these properties, (3) to measure the dynamic state of in vivo chronic infections, (4) to describe the process of replacement of a cytopathic strain by a noncytopathic reverant in vivo, and (5) to determine the spatial distribution of virus strains in mixed infections. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GLYPICAN-3: A NOVEL MARKER FOR HEPATOCELLULAR CARCINOMA Principal Investigator & Institution: Filmus, Jorge E.; Sunnybrook & Women's Coll Hlth Scis Ctr S132 Toronto, on M4n 3M5 Timing: Fiscal Year 2003; Project Start 01-JUN-2003; Project End 31-MAY-2005 Summary: (provided by applicant): Human hepatocellular carcinoma (HCC) is usually asymptomatic at early stages. As a result, HCC is generally at an advanced stage when discovered, and the therapeutic options very limited. HCC is associated with chronic liver injury, primarily chronic viral hepatitis and alcoholic liver disease. The risk of developing HCC is 50 - 100 fold greater in individuals with chronic hepatitis B virus infection than in non-infected individuals, and the incidence of HCC in cirrhotic carriers of hepatitis C virus (HCV) may be as high as 5% per year. In principle, therefore, screening protocols are justified for chronic HBV carriers and cirrhotic HCV patients. The only molecular marker that has been widely used for the diagnosis and detection of HCC is alfafetoprotein (AFP). However, AFP expression is significantly increased in a considerable number of patients with non-malignant chronic liver diseases. Thus, more specific markers for HCC are required. Results recently obtained in this laboratory have shown that a protein called glypican-3 (GPC3) can be detected in most HCC tissue sections but it is undetectable in normal liver or benign liver disease. In addition, examination of a limited number of patients has shown that whereas GPC3 is undetectable in the serum of healthy individuals, its levels are significantly elevated in a large proportion of HCC patients. These results suggest, therefore, that GPC3 could be a
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Hepatitis B Virus
better marker than AFP for the diagnosis and detection of HCC. The main goal of this study is to test this hypothesis. To this end, serum GPC3 and AFP will be measured in a cohort of 100 patients with HCC, and in patients with benign liver disease. The specificity and sensitivity of both markers will then be compared. GPC3 levels will also be assessed in 50 additional tissue sections from HCC patients, and a similar number of sections from various benign liver diseases. Another objective of this project is to investigate whether GPC3 could be used as a marker of tumor burden in experimental cancer. If this is the case this study will provide a tool that will simplify the search of novel treatments for HCC, and may open the possibility of using GPC3 measurement for the follow-up of HCC patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HAWAII ACTU - ADULT THERAPEUTIC CLINICAL TRIALS PROGRAM Principal Investigator & Institution: Shikuma, Cecilia M.; Associate Professor of Medicine; To Be Determined; University of Hawaii at Manoa Honolulu, Hi 96822 Timing: Fiscal Year 2002; Project Start 01-JAN-1996; Project End 31-DEC-2004 Summary: (adapted from the application's abstract): The HACTU is part of the HIV clinical research arm of the University of Hawaii's program in Retrovirology. The HACTU has been a formal unit of the AACTG since 1990 with funding received under a minority institution initiative. The site brings to the AACTG: (1) an established clinical trials unit within the AACTG with a record in clinical trial management, currently meeting all ACTG standards for site operations; (2) access to Hawaii's ethnically diverse population, having previously contributed 41 percent of all ACTG's enrollees of Asian/Pacific Islander descent; (3) a unit with wide community, state governmental and university support for its operations as the only HIV/AIDS clinical research program in Hawaii; (4) a continued commitment to participate as broadly as feasible not only in AACTG's main antiretroviral trials but also in specialized areas of HIV immunology and complication research targeted at areas of special importance by the AACTG leadership; and (5) a minority unit with a record of increasing scientific contributions to the ACTG over the past five years and a commitment to contribute to the AACTG's scientific agenda in the next five years. The areas of pathogenesis/treatment of HIV/Hepatitis B and C co-infection; HIV-associated interest include metabolic complications; role of insertional mutagenesis and macrophages in the pathogenesis of HIV- associated malignancies; central nervous system (CNS) disease; and the impact of menopause and female replacement hormonal therapy on HIV-1 activity. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: HBV DIPSTICK FOR RESOURCE-LIMITED BLOOD BANKS Principal Investigator & Institution: Lee, Helen H.; Diagnostics for the Real World, Ltd 863-B Mitten Rd Burlingame, Ca 940101311 Timing: Fiscal Year 2002; Project Start 16-SEP-2002; Project End 31-AUG-2003 Summary: (provided by applicant): According to WHO statistics on blood safety, 80 percent of the world's population has access to 20 percent of the world's safe blood supply. However, more than 20 percent (13,000,000 units) of the world blood supply is not tested for the three major transfusion-transmissible infections: HIV, HBV and HCV. Transfusion of unsafe blood accounts for 8-16 million hepatitis B virus infections. If inexpensive, rapid, improved dipsticks with sensitivity comparable to EIA were developed for blood screening, it would greatly improve the safety of the blood supply
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in developing countries.The overall aim of the project is to develop a HBsAg dipstick assay with high sensitivity, designated as the reflex diagnostic. The test can be used in developed countries under circumstances where an immediate result is required. For the developing countries, we propose that this test be integrated into a triplex test (HBV, HIV & HCV) and used as the initial step of pre-donation screening in high prevalence countries. The associated second step is to use the HBsAg reflex diagnostic test in order to identify the agent responsible for the positive Triplex test result.The specific aims of Phase I are to optimize the reagents in order to produce a prototype with sub-nanogram sensitivity and to evaluate the assay in 50 HBV-positive samples. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HBV INDUCED LIVER PATHOGENESIS Principal Investigator & Institution: Siddiqui, Aleem A.; Professor; Microbiology; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, Co 800450508 Timing: Fiscal Year 2002; Project Start 01-APR-1996; Project End 31-MAR-2006 Summary: (provided by applicant): Hepatitis B virus infections are one of the leading causes of chronic hepatitis. Infection results in a broad range of clinical symptoms from mild, nonapparent disease to fulminant hepatitis to hepatocellular carcinoma. Due to lack of in vitro infection system for HBV, the events of infectious processes are poorly understood. HBV encodes a regulatory protein termed HBx. While many functions have been attributed to HBx, a clear picture of how this protein participates in establishing infectious process has not emerged. In this competing renewal grant application, the focus of our study will be on the detailed characterization of HBx s association with mitochondria and exploring the functional consequences of that association. First, we propose to identify the mitochondrial targeting domain within HBx protein. Using those mutants, which fail to associate with mitochondria, further characterization of various possible functions of HBx within mitochondria will be investigated. These include, the ability of HBx via its interaction with the outer membrane channel VDAC to alter mitochondrial membrane potential (delta-psim), generation of reactive oxygen species (ROS). Ca+2 homeostasis. and permeability transition among others. Alteration of these functions will be correlated with induction of gene expression via NF-kB, AP-1, NF-AT and STAT-3 transcription factors. The results of these studies will delineate the molecular mechanisms in the induction of HBV-induced liver disease pathogenesis including hepatocellular carcinoma. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: HBV PREVENTION FOR HOMELESS AT-RISK FOR HBV/HCV/HIV Principal Investigator & Institution: Nyamathi, Adeline M.; Professor and Associate Dean; None; 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 30-JUN-2008 Summary: (provided by applicant): Nationwide, homeless populations are at risk for HIV infection due to disproportionate use of injection drugs, unprotected sexual activity, prostitution and victimization. Infection with the Hepatitis B Virus (HBV) and the Hepatitis C Virus (HCV) is high among homeless adults as they share risk factors with HIV. Hepatitis A Virus (HAV) is also high among populations vulnerable to HBV, HCV, and HIV as modes of transmission for HAV overlap with those of HBV, HCV, and HIV. Thus, education and screening programs for HAV, HBV, HCV, and HW, combined
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with vaccination programs for HAV and HBV, can significantly decrease Hepatitisrelated morbidity and mortality. However, homeless persons, many of whom may be contending with drug and alcohol abuse and unemployment, and live in a disorganized world with little access to health and social services, are often non-compliant. In this prospective two group quasi-experimental design, we will evaluate with approximately 1000 sheltered men and women in the Skid Row area of Los Angeles, the effectiveness of a theoretically-based HAV/HBV vaccination intervention focused primarily on completion of the combined Twinrix HAV/HBV vaccination series and secondarily on risk reduction of HAV, HBV, HCV, and HIV. We will also collect data on the relative cost of each of these programs in terms of completion of HAV/HBV vaccination, the cost effectiveness of improving vaccination completion, the cost per sero-protected case, and the cost per infection prevented. Once determined eligible, participants will be randomized by shelter into one of two programs: a Nurse Case Managed Plus Incentive and Tracking (NCMIT) program and a Standard Plus Incentive and Tracking (SIT) program. The proposed study is innovative in that the comparison of the SIT and NCMIT programs will allow us to look at the effect of a standard intervention combining brief education, incentives and tracking with that of a similar intervention that also includes nurse case management on completion of the HAV/HBV vaccination. Participants in the two programs will receive the 3-series vaccination by trained research nurses at the study clinic over six months, along with either the NCMIT, or the SIT program. All participants will be assessed at baseline and six- and twelve-month followup using a battery of psychosocial, behavioral, health and physical status, as well as HAV, HBV, HCV, and HIV sero-status measurements. This proposed study supports the National Drug Abuse Research Initiative as it is focused on assessing the effectiveness of intervention programs promoting the prevention of medical consequences of HAB, HBV, HCV, and HIV in homeless and drug abusing populations. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HBV-ETHANOL INTERACTIONS IN LIVER DISEASE Principal Investigator & Institution: Feitelson, Mark A.; Associate Professor; Pathology, Anat/Cell Biology; Thomas Jefferson University Office of Research Administration Philadelphia, Pa 191075587 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2008 Summary: (provided by applicant): Chronic alcoholism and hepatitis B virus (HBV) infection are associated with chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC) in millions of people worldwide. Epidemiologic evidence shows a higher frequency of HBV markers among chronic alcoholics compared to the general population, and more severe liver disease among chronically infected alcoholics compared to patients suffering from chronic alcoholism or HBV infection alone. The applicant laboratory has recently developed an HBV transgenic mouse on a severe combined immunodeficient (SCID) host, which supports consistent levels of virus gene expression and replication. Since the SCID host is not tolerant to the virus, adoptive transfer of unprimed syngeneic splenocytes resulted in the development either acute or chronic hepatitis, with either complete or partial clearance of virus markers from serum and liver, respectively. Interestingly, the introduction of ethanol in a liquid LieberDiCarli diet strongly up-regulated HBV gene expression and replication in these mice, and that when ethanol fed mice were adoptively transferred with 5 x 10[7] splenocytes, which usually results in acute hepatitis, they develop chronic liver disease (CLD) instead. Since the pathogenesis of hepatitis B is immune mediated, and T cells play a central role in the clearance of virus infected hepatocytes, the objective of this work is to
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identify the changes in anti-viral T cell immunity that are responsible for the ethanol mediated changes in pathogenesis. This will be addressed by asking whether the shift from acute to chronic liver disease is associated with changes in the presence, frequency, and distribution of T cell responses to one or more virus antigens (aim 1). Experiments will also be conducted to ask whether chronic hepatitis could be converted back to acute, resolving hepatitis by (1) polarizing the immune response toward Th1, or (2) adoptively transferring primed splenocytes to one or more virus antigens (aim2). Together, these experiments will identify the T cell subsets and specificities associated with the ethanol mediated shift from acute to chronic hepatitis, and then therapeutically manipulate T cell immunity so as to prevent the development of CLD in ethanol fed, adoptively transferred mice. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HCV IN ALCOHOLICS Principal Investigator & Institution: Wands, Jack R.; Professor of Medicine; Rhode Island Hospital (Providence, Ri) Providence, Ri 029034923 Timing: Fiscal Year 2003; Project Start 01-DEC-1993; Project End 30-JUN-2007 Summary: (provided by applicant): Chronic hepatitis C (HCV) infections are common in alcoholics with or without liver disease contributing to significant morbidity and mortality. The reasons for high rates of persistent viral hepatitis infection are unknown but may partially relate to the effects of alcohol on the humoral and cellular immune response to viral structural and nonstructural proteins. We established an animal model system of HCV specific antibody stimulation, CD4+ proliferative response, and CD8+ CTL activity in the context of genetic immunization to test this hypothesis. We plan to do the following: Specific Aim #1 - Further establish the differential effects of ethanol on the immune response(s) to HCV structural and nonstructural proteins in the context of genetic immunization with respect to: a. Assess variations in CD4+ T cell proliferative activity particularly against HCV core, NS3, NS3 helicase, NS4, NS5A and NS5B proteins. b. Evaluate Th1 and Th2 responses to determine if ethanol consumption shifts the immune response from the Th1 to Th2 phenotype. c. Characterize CD8+ CTL precursor frequency and function including possible differential effects of ethanol at the epitope level. d. Examine CTL activity in vivo against HCV derived peptides using an animal model of tumor growth. e. Determine the duration and reversibility of ethanol effects on CD4+ and CD8+ T-cell responses by crossover feeding studies with an isocaloric control diet. Specific Aim #2 - Develop approaches to augment and/or amplify humoral and cellular immune responses generated by DNA immunization in the setting of chronic ethanol administration, a. Explore whether systemic administration (murine and human IFN-a2, or pegylated IFN- a2) is more effective than local administration of cytokine expression construct (IL-2, GM-CSF, IL-12) at the site of gene delivery with respect to augmentation of the humoral and cellular immune response(s) to HCV structural/nonstructural proteins. b. Determine the value of coimmunization with CpG motifs as an enhancer of the host B and T cell immune responses. c. Employ chimeric constructs to assess their possible role as a stimulant of virus specific B and T cell activities. Thus, principle long term goals of this application are to develop: a clinical DNA vaccine approach, effective alone or in combination with other antiviral agents (IFN-2a, etc.), to enhance the host immune response in an attempt to eradicate persistent viral infection from the liver in alcoholics; and obtain a clearer understanding of ethanol's effects on the immune response to HCV structural and nonstructural proteins in an experimental animal model system thereby generating principles applicable to chronic alcoholics
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Hepatitis B Virus
Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HDV RNA FOLDING AND PKR PROTEIN REGULATION Principal Investigator & Institution: Bevilacqua, Philip C.; Assistant Professor; Chemistry; Pennsylvania State University-Univ Park 110 Technology Center University Park, Pa 16802 Timing: Fiscal Year 2004; Project Start 01-JAN-1999; Project End 31-JUL-2008 Summary: (provided by applicant): RNA is central to a variety of biological processes including transcription, splicing, translation, gene expression, development, and cell division. It is therefore of interest to understand how RNA folds into the structures necessary to carry out these functions. It is also important to understand how the structures of native RNA and RNA folding intermediates regulate critical biological processes including activation of the interferon-induced anti-viral agent protein kinase PKR. This proposal involves studying RNA folding events that occur during transcription, and understanding their similarities and differences to refolding events that occur upon addition of divalent ions. The importance of transcriptional pausing with the authentic template and polymerase will be investigated. In addition, the ability of non-native, or alternative pairings, to inhibit and, in selected cases, stimulate the folding of the catalytic RNA from hepatitis delta virus (HDV) will be studied. The influence of external factors, such as increased ionic strength and hepatitis delta antigen protein (HDAg), on resolution of alternative pairings will be systematically investigated. The extent to which these RNA folding states can activate PKR will be investigated as well. A recently discovered novel small RNA motif that activates PKR will be studied mechanistically. These studies will be carried out with biochemical and biophysical techniques, including PKR activation and rapid-quench RNA cleavage kinetics; stopped-flow fluorescence and absorbance kinetics; thermodynamic measurements; and RNA structure mapping. It is anticipated that these results may impact upon several areas relevant to human health including understanding replication of HDV, which increases the virulence of hepatitis B virus (HBV) infections, and regulation of PKR protein, which mediates part of the human viral defense mechanism. In addition, these studies may help uncover new roles for the kinase in vivo. Results are expected to be of fundamental interest to the RNA folding community and may impact the understanding of RNA folding in other biologically relevant RNA and RNA-protein systems including catalytic RNAs and the ribosome. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: HEPADNAVIRUS ASSOCIATED HEPATOCELLULAR CARCINOMA Principal Investigator & Institution: Rogler, Charles E.; Professor; Medicine; Yeshiva University 500 W 185Th St New York, Ny 10033 Timing: Fiscal Year 2004; Project Start 01-APR-1984; Project End 30-APR-2006 Summary: (Adapted from the Investigator's abstract): Infection of humans with hepatitis B viruses cause acute and persistent infections of worldwide significance. Persistent infections, in particular, are associated with a very high risk of hepatocellular carcinoma (HCC). HCCs arise in HBV carriers after long periods of immunologically driven liver disease that is characterized by periods of inflammation, regeneration, cirrhosis and finally HCC. One of the hallmarks of HCCs arising in I-IBV carriers is the presence of clonally amplified viral DNA integrations. Our laboratory has carried out studies to understand the mechanisms by which viral DNA integrations may act as mutagenic agents during hepatocarcinogenesis. Our approach has been to study the natural history
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and frequency of integrations in clonal populations of cells. These studies have implicated a minor form of hepadnavirus DNA, specifically, double strand linear (DSL) viral DNA molecules as the precursors for integration and have also shown that DSL DNAs integrate at a higher frequency than wild type DNAs. Furthermmore, we have shown that integrations can be lost from the cells along with cellular DNA in a "hit and run" mutagenesis mechanism. In the current proposal we will utilize a new assay system that can detect single integrations to study integration frequencies of DSL versus WT viral DNA and follow the dynamic flux of integrations in cell culture. We will pursue integration studies during infection of primary hepatocytes under conditions that cause DNA damage and we will also utilize mutational analysis to test the hypothesis that topoisomerase I (top 1) acts as a regulator of viral replication and integration. These studies will increase our understanding of the genetic and physiologic controls of integration and their mutagenic impact on the host cell. Finally, in a new area of research, we will utilize cDNA microarrays to investigate the effects of the HBV X regualtory protein on the transcriptome of murine liver stem cells in both the liver progenitor and hepatocytic differentiation states. These studies will begin to help us understand the impact ofHBx on transcriptional regulation from a global perspective. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HEPATITIS B AND C AMONG HOMELESS ADULTS Principal Investigator & Institution: Gelberg, Lillian; Family Medicine; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2002; Project Start 01-JUL-2001; Project End 31-MAY-2004 Summary: Applicant's Abstract Persons infected with the hepatitis B virus (HBV) or hepatitis C virus (HCV) are at high risk for serious long-term health problems, and they are potentially infectious to others. Because of the seriousness of these infections, the NIH has developed a national agenda for preventing the spread and consequences of HBV and HCV. This agenda includes early detection, treatment, and prevention efforts for high-risk and infected persons. Homelessness has reached crisis proportions in the US today. Recent research by our team and others suggests that homeless adults in urban areas are a group at particularly high risk for HBV and HCV infections due to high rates of risky drug use and risky sexual behaviors. Despite the apparent high risk, however, there is only limited research on viral hepatitis in this group. We propose to conduct epidemiologic and health services research regarding HBV and HCV in a population-based sample of 500 homeless adults. We will recruit a probability sample of homeless adults with oversampling of injection drug users from 30 shelters and meal programs in the Skid Row area of Los Angeles. Respondents will undergo a two-hour interview (including the Diagnostic Interview Schedule-DIS-IV) and blood draw for hepatitis serology. We will estimate the prevalence of HBV and HCV and identify risk factors for each. We will evaluate whether homeless adults with histories of injection and non-injection drug use, risky sex, serious alcohol or mental disorders, or chronic homelessness have an elevated risk for these infections. We will also conduct health services research in which we will describe the respondents' past history of HBV/HCV testing, awareness of infection status, medical care for HBV and HCV, and willingness to return for HBV/HCV test results. Further, we will identify utilization of medical and non-medical settings to identify sites for future screening, treatment, and prevention efforts. We will provide hepatitis B immunization to those that test negative for hepatitis B. We will bridge the gap between research and prevention by using the Theory of Planned Behavior to understand protective behaviors used by homeless adults to avoid exposure to infectious diseases.
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Hepatitis B Virus
Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HEPATITIS B SUBUNIT ORAL VACCINE IN TRANSGENIC PLANTS Principal Investigator & Institution: Thanavala, Yasmin; Professor; Roswell Park Cancer Institute Corp Buffalo, Ny 14263 Timing: Fiscal Year 2003; Project Start 30-SEP-1998; Project End 30-NOV-2007 Summary: (provided by applicant): The proposal describes a series of experiments designed to target and track antigen following oral delivery via edible transgenic plants. The overall objective is to enhance both systemic and mucosal immune responses to orally delivered antigen. During the previous grant period we have demonstrated that mice fed potatoes expressing HBsAg make both primary and secondary antibodies responses in serum and anti-HBs IgA responses in mucosal secretions. We have provided transmission electron microscopic evidence that the transgenic potato cells harbored unusual membrane-bound bodies that contained circular structures that are approximately 17 nm in diameter. These structures are very similar to the virus-like particles (VLP) found in the serum samples of HBV infected patients and the distended ER vesicles are similar to those produced in yeast expressing HBsAg. These images provide the first ever evidence that in transgenic plants antigen is refined within vesicular structures. We also performed a successful double-blind placebo controlled Phase 1 trial to evaluate the safety and immunogenicity of the edible plant vaccine. None of the volunteers who ate nontransgenic potatoes showed changes in anti-HBs antibody titer. However, after volunteers ate transgenic potatoes, serum antibody titers increased in 62% who ate three doses and 53% who ate two doses of transgenic potatoes. Buffering of the stomach pH was not performed nor was any mucosal adjuvant used. This trial firmly establishes that oral vaccination via edible plant vaccines is possible for a non-enteric antigen such as HBsAg. Taken together, these data form a very solid foundation for the studies proposed in this application. In the current application we propose four specific aims designed (1) to improve the expression of HBsAg in transgenic plants, (2) target antigen to M cells in the gut, (3) to track the immune response elicited and (4) to potentiate the immune response to orally administered antigen by use of nontoxic mucosal adjuvants. We have provided significant new preliminary data and we believe that these provide strong documentation of the likelihood of continued success. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: HEPATITIS B VIRUS E ANTIGEN EXPRESSION Principal Investigator & Institution: Tong, Shuping; Rhode Island Hospital (Providence, Ri) Providence, Ri 029034923 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2005 Summary: (provided by applicant): Hepatitis B virus (HBV) infects nearly 1/10th of the world population and causes severe liver diseases including cancer. The e antigen (HBeAg) is a secreted soluble protein that promotes immune tolerance during perinatal infection and buffers immunity against HBcAg. The corresponding anti-HBe immune response plays a critical role in the clearance of HBV infection. Therefore, following seroconversion from HBeAg antigenemia to anti-HBe, HBV escape mutants with reduced or no HBeAg production often replace wild-type HBV genomes. The core promoter mutants have various nucleotide changes around positions 1750 -1770 of the HBV genome, and the most common mutations at 1762 and 1764 are known to reduce HBeAg expression at the transcriptional level. The precore mutants have nonsense or
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frameshift mutations in the HBeAg coding sequence and terminate HBeAg expression at the translational level. Considering the critical importance of HBeAg and anti-HBe in shaping the outcome of HBV infection, we wish to uncover novel regulatory mechanisms for HBeAg expression. In this regard, perinatally infected South African patients seroconvert from HBeAg to anti-HBe at a much accelerated pace than similarly infected Asian patients. Interestingly, the South African HBV variants often harbor two or three point mutations near the precore initiation codon. We plan to verify whether the mutations cause leaky scanning to reduce HbeAg translation. Second, HBeAg maturation requires double proteolytic cleavage events in the secretory pathway. The first cleavage occurs in endoplasmic reticulum to remove the N-terminal signal peptide of 19 residues. A Val to Phe missense mutation at residue 17 is frequently detected in HBV genomes isolated from seroconverted patients. Since an aromatic residue at the -3 position of cleavage site is forbidden, we will test whether this mutation impairs HBeAg cleavage and secretion. Third, we recently identified several naturally occurring core promoter mutants with wild-type level of HBeAg production. Based on the results of preliminary mapping experiments, we will determine whether the number and position of core promoter mutations influence the level of HBeAg expression, and whether missense mutations in the HBeAg coding sequence also regulate HBeAg level. This study promises to verify and identify novel mechanisms regulating HBeAg expression, which has a major impact on the outcome of HBV infection. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HEPATITIS DELTA VIRUS SELF-CLEAVING RNA Principal Investigator & Institution: Been, Michael D.; Professor; Biochemistry; Duke University Durham, Nc 27710 Timing: Fiscal Year 2002; Project Start 30-SEP-1992; Project End 31-AUG-2006 Summary: (provided by applicant): The broad objectives of the proposed research are to understand the structure and mechanism and biological roles of self-cleaving RNA sequences (ribozymes). The ribozymes being studied are associated with the genomic and antigenomic RNAs of hepatitis delta virus (HDV). HDV is a human pathogen that infects only in association with hepatitis B virus. This combination results in more severe symptoms and higher fatalities than hepatitis B virus alone. Ribozyme activity is essential to replication of the HDV RNA genome. Greater understanding of the ribozyme structure, cleavage mechanism and role in replication could lead to a method for blocking viral replication. Beyond the specific medical aspects of HDV infection, the ribozymes from HDV are the first and, so far only, examples of self-cleaving RNAs that function naturally in human cells. Therefore, understanding features of these RNAs should facilitate the design of ribozymes to be used as therapeutics.The specific aims are to: (1) Understand the potential of nucleobases to act as general acid-base catalysts in the antigenomic HDV ribozyme. The experiments will characterize a reaction in which an essential nucleobase hypothesized to function in proton transfer in the antigenomic HDV ribozyme reaction is replaced by an exogenous base in solution. (2) Definition of the contribution and role of metal ions in HDV ribozyme catalysis. Divalent metal ions are required for full activity but how metal ions contribute to catalysis is not known. Ribozyme variants that cleave with a variety of metal ions (mono-, di-, and trivalent) will be exploited in these studies. (3) Characterize sequences that affect folding into the ground-state structure, and define conformational changes in pre- and post-cleavage forms of the ribozyme. A model for regulating a choice between polyadenylation of an mRNA and replication of the genome by alternative structures will be tested. (4) Identify and characterized additional examples of nucleobases in catalysis. HDV codes
34
Hepatitis B Virus
for two related ribozymes; however, catalytic activity of the two reveals some distinct differences. Common and exclusive features of both ribozymes will be examined to obtain a more accurate and complete picture for nucleobase involvement in catalysis. Several other small ribozymes that could also use nucleobases as acid base catalysts will be studied using technologies developed in specific aim 1. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HEPATITIS HBX-MEDIATED PATHOGENESIS Principal Investigator & Institution: Slagle, Betty L.; Assistant to the Director; Molecular Virology & Microbiol; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2004; Project Start 01-JUL-2003; Project End 30-JUN-2008 Summary: (provided by applicant): Chronic infection with HBV is a major risk factor in the development of hepatocellular carcinoma (HCC), and is responsible for over 1 million deaths each year. We have established an HCC cofactor role in transgenic mice that express the HBV regulatory protein (HBx) driven by the human alpha-l-anti-trypsin regulatory sequences (ATX mice). Our recent studies indicate that the cofactor role involves the ability of HBx to deregulate hepatocyte cell cycle controls. Although HBx is essential for virus replication in vivo, the function that it provides is not known. We hypothesize that the essential role of HBx during viral replication is to prepare hepatocytes to become competent to support all steps in virus replication. In the present application, we will explore the effects of HBx on G0 hepatocytes and their transition through early G1, using markers that distinguish these stages of the cell cycle. We additionally hypothesize that HBx holds nondividing cells at a G1 restriction point, and will use RNA inhibition to examine candidate proteins through which HBx may exert this effect. We will also explore the effect of HBx on hepatocyte G0/G1 transition in vivo, and in the presence of the AFBl-induced hotspot p53 mutation. Finally, the livers of ATX mice contain decreased levels of Caspase-3, and we will test the hypothesis that in response to cytotoxic cytokines, HBx inhibits apoptosis as a means of protecting hepatocytes from immune-mediated cell death. HBx is the sole regulatory protein encoded by HBV, we expect it will provide more than one critical role during the virus life cycle. The proposed program builds on our model of HBx-related HCC that indicates an important contribution of HBx effects on cell cycle control. The planned studies examine HBx function in nondividing liver cells, and the results obtained will provide important insight into the rational development of new therapies to treat chronic HBV infection. Our results will also reveal fundamental virus-host interactions that may extend to other viruses that replicate in the liver. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: HEPATITIS VIRUS, ALCOHOL EXPOSURE AND OXIDATIVE STRESS Principal Investigator & Institution: Hassan, Manal M.; Gastrointestinal Med Oncology; University of Texas Md Anderson Can Ctr Cancer Center Houston, Tx 77030 Timing: Fiscal Year 2002; Project Start 30-SEP-2001; Project End 31-AUG-2004 Summary: (provided by applicant) Hepatitis C virus (HCV) infection and alcohol abuse are the 2 major risk factors for hepatocellular carcinoma (HCC) in this country. The higher prevalence of HCV infection in the general population has resulted in a significant increase of the incidence of HCC in the United States. Although both HCV and alcohol can independently induce liver disease, exposure to both agents may accelerate the course of liver pathology and/or lead to more severe injury. The
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mechanism underlying the synergistic effect of HCV and alcohol intake is not well understood. One hypothesis is that both HCV and alcohol intake may contribute to chronic hepatitis, cirrhosis and subsequent liver cancer through enhanced oxidative stress. It is known that alcohol could induce oxidative stress and lipid peroxidation. Interestingly, a recent study has reported that HCV encodes a selenium (Se)-dependent antioxidant enzyme, glutathione peroxidase, GPx, and GPx may have a regulatory role in HCV replication. The virus-induced overexpression of GPx may lead to a decreased level of Se in the host due to the competition of HCV for Se. In fact, patients with HCV have been shown to have a significant decline in their serum Se. On the other hand, the hepatotoxicity of ethanol and its associated malnutrition will further reduce the cellular Se level. This additive decline in the Se level will make the cell more susceptible to reactive oxygen species (ROS). Previous studies have shown an association between oxidative DNA damage and either alcohol exposure or chronic viral infection. It seems that chronic HCV infection may lead to an increased ROS, overexpression of GPx and reduced serum level of Se. When the Se-GPx level is low, the virus will be more provoked for replication, leading to a higher viral load in the infected cell. Eighty newlydiagnosed HCC patients will be recruited from University of Texas MD Anderson Cancer Center (UTMDACC). The current project will explore the effect of dietary selenium intake and its interaction with HCV and alcohol intake in HCC in a casecontrol study. Eighty healthy individuals (first control group), matched with cases by age, sex and ethnicity, will be recruited from the patients non-blood relatives and friends from UTMDACC. To have a control group with comparable prevalence of HCV infection, 80 patients with liver cirrhosis, who have no evidence of HCC (second control group), will be recruited from Baylor College of Medicine. Information on alcohol intake, dietary Se intake and other risk factors will be collected by a questionnaire. The frequency and profile of hepatitis B virus (HBV) and HCV infection will be determined by measuring serum HBsAg, anti-HBC, anti-HCV, and HCV-RNA. Oxidative stress will be evaluated by measuring the levels of serum Se, GPx activity, lipid peroxides, and 8hydroxy-deoxyguanosine (8-OH-dG), a marker of oxidative DNA damage. The expression of GPx and the level of 8-OH-dG will also be measured in tissue samples from cirrhotic and HCC patients. Serum Se, GPx activity, lipid peroxides and oxidative DNA damage will be measured in relation to HCV and alcohol intake history. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HIV DISEASE OUTCOMES IN DRUG USERS IN CLINICAL PRACTICE Principal Investigator & Institution: Moore, Richard D.; Professor; Medicine; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 30-JUN-2008 Summary: (provided by applicant): In 1998, we were awarded an RO-1 (DA11602) from NIDA to conduct a longitudinal study in HIV-infected persons who have a history of illicit drug use (DU). The major aims of that study were to develop a longitudinal cohort of HIV-infected patients in medical care in order to characterize utilization of the new highly active antiretroviral drug therapies (HAART), and assess the effect of these therapies on HIV disease progression in DUs. We established a comprehensive longitudinal clinic-based cohort of over 4600 HIV infected persons; half of who have a history of DU. Our research suggests that DUs have not received the same level of benefit from HAART as non-DUs. Prior to HAART, there was little difference between DUs and non-DUs in HIV progression. Our research has shown that active DU is a barrier to receiving and adhering to HAART, and achieving effective viral and
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Hepatitis B Virus
immunologic improvement on HAART. We hypothesize that the early differences that have emerged between DUs and non-DUs will substantially widen over the next 5 years as HIV resistance to current drugs increases, toxicity limits the use of therapy, and viral hepatitis along with other medical consequences of DU further increase the burden of morbidity. Because of HAART, HIV is now a chronic illness, and DUs have numerous barriers to stable, chronic disease management. We are optimally situated to assess the core factors that impede successful HIV management as the HAART era matures over the next 5 years, and are submitting a new proposal for a competitive continuing RO-I. We propose the following aims, consistent with our overarching goal of improving the outcomes of HIV infection in DUs: 1) Evaluate virologic, immunologic and clinical HIV disease progression for up to 10 years, 2) Assess the impact of viral hepatitis coinfection, 3) Assess other medical consequences of DU including bacterial infection and STDs, 4) Assess adverse effects of HIV therapy. We offer a productive resource to address our aims that is unique in scope and size, cost-efficient in conducting research, highly relevant to the HIV epidemic as it effects DUs, and fully operational from our prior R01. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HIV RISK AND NEIGHBORHOOD NETWORKS OF NEW IDUS Principal Investigator & Institution: Neaigus, Alan; National Development & Res Institutes Research Institutes, Inc. New York, Ny 100103509 Timing: Fiscal Year 2003; Project Start 01-FEB-2003; Project End 31-JAN-2007 Summary: (provided by applicant): New injecting drug users (IDUs) are at risk of becoming infected with the hepatitis C virus (HCV), the hepatitis B virus (HBV) and HIV within the first few years after they start to inject. However, the risk of infection among new injectors varies by race/ethnicity, with African Americans at greater risk of infection than white new IDUs. Risk behaviors alone do not sufficiently explain why African American IDUs are at greater risk of infection. Racial/ethnic differences in the risk of infection among new injectors may be related to different probabilities in the risk of exposure to infection, which may stem from differences in sociocentric (groups of directly and indirectly connected IDUs) and egocentric (groups of directly connected IDUs) transmission networks. Variation by race/ethnicity in the transmission networks of new IDUs may also be influenced by neighborhood differences in the provision of harm reduction and other health services, as well as other differences in the social and physical environment of neighborhoods, since IDUs are often geographically separated by race/ethnicity into different neighborhoods. In this study, we will investigate the sociocentric and egocentric network risks for infection with HIV, HCV and HBV in two high-risk neighborhoods in New York City, one of which is predominantly AfricanAmerican and the other in which new IDUs are predominantly white. Using a sequential cross-section design with an imbedded prospective cohort, we will compare a predominantly African-American group of new injectors and a predominantly white group of new injectors m geographically separate neighborhoods to determine differences in: (1) The prevalence and incidence of HIV, HCV and HBV; (2) The relationship of sociocentric and egocentric networks to HIV, HCV, and HBV transmission; (3) The relationship of sociocentric and egocentric networks to risk and risk reduction behaviors, knowledge of infection risk and prevention, and access to and utilization of harm reduction and other health services; (4) Factors associated with the maintenance or change in sociocentric and egocentric networks and risk and risk reduction behaviors and practices, and the relationship of these factors to the rate of HIV, HCV, and HBV seroconversions; and (5) using ethnographic methods and Geographic Information Systems, to explore the relationship of neighborhood factors to
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network and behavioral infection risk. Understanding the extent to which the multilevel influences of neighborhood context, network characteristics and behavior shape the risk of acquiring or transmitting HIV, HCV and HBV among new injectors can contribute towards the development of structural interventions targeted at new injectors and their injecting and sex partners in high-risk neighborhoods. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HOST AND VIRAL GENETIC VARIABILITY IN HBV CARRIERS Principal Investigator & Institution: Evans, Alison A.; Associate Member; Fox Chase Cancer Center Philadelphia, Pa 191112434 Timing: Fiscal Year 2002; Project Start 01-JUN-2001; Project End 31-MAY-2006 Summary: Chronic carriers of hepatitis B virus (HBV) are at increased risk for hepatocellular carcinoma (HCC). Worldwide, however, the risk of HCC and other adverse outcomes varies substantially both between and within populations of HBV carriers. The reasons for these differences in the natural history of infection are not known. Our analysis of cohort studies in three endemic populations have suggested that the long term maintenance of high-titer viremia (i.e., equal to or > 1 pg/ml) is an important predictor of HCC. The mechanism behind the maintenance of viremia is, however, not well understood although it is clear that the host immune response plays a key role. In this application, we focus on molecular variants of the virus itself and polymorphisms of human immunoregulatory genes as potential predictive or explanatory factors in maintenance of viremia. We will draw upon established prospective cohorts of chronic HBV carriers in China, West Africa, and AsianAmericans. Our preliminary data support a relationship between deletions in the C ORF of HBV and clearance of active viral replication. In the proposed project we will test this hypothesis and extend our studies of molecular variation of HBV by application of novel statistical methods to sequence data. We will also test the hypothesis that maintenance of HBV viremia is associated with polymorphisms of the vitamin D receptor (VDR) and tumor necrosis factor alpha (TNFalpha) promoter. Allele frequencies for polymorphisms of lesser-studied immunomodulatory genes in our cohorts will be estimated in order to develop hypotheses about their relationship to maintenance of viremia in HBV carriers. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: 'IMMATURE SECRETION' VARIANTS OF HUMAN HEPATITIS B VIRUS Principal Investigator & Institution: Shih, Chiaho; Professor; Pathology; University of Texas Medical Br Galveston 301 University Blvd Galveston, Tx 77555 Timing: Fiscal Year 2002; Project Start 04-FEB-2000; Project End 31-JAN-2005 Summary: Our long-term goal is to understand the pathobiology of viral hepatitis. Hepatitis B virus (HBV) is the 4th most common infectious agent in humans worldwide. Chronic infection with HBV is tightly associated with the development of liver cancer. The mechanism of how HBV chronic infection is established and its pathogenesis remains to be fully explored. Recently, there has been increasing evidence that HBV chronicity may be influenced by the presence of genetic variants that evolve in patients as liver disease progresses. Since the invention of polymerase chain reaction technology, many HBV sequence variants have been reported. However, a common frustration in the research of HBV variants is that the majority of these reported sequence variants has no known functional significance and does not exhibit a strong
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Hepatitis B Virus
phenotype distinctively different from the wild type virus. The most frequent missense mutation found in the HBV core antigen occurs at codon 97 in chronic carriers worldwide (in 83 percent hepatoma patients). Our recent functional characterization of this mutant uncovered a novel and strong phenotype, dubbed an "immature secretion" phenotype. Unlike wild type HBV, the secreted Dane particles of codon 97 mutants contain predominantly the immature form (lower molecular weight) of the HBV DNA genome. In this application, we propose 1) to extend our observation of the "immature secretion" phenomenon from tissue culture to patients and animal models. We also attempt to extend the "immature secretion" phenotype to other viral subtypes prevalent in different geographic locations. 2) to investigate the mechanism of "immature secretion" by both genetic and biochemical approaches. One of the several hypotheses to be tested is that "immature secretion" could be caused by hyper-efficient interactions between wild type envelope and mutant core proteins. 3) Finally, we will compare the infectivity of the highly frequent codon 97 mutants and wild type HBV via in vitro infection assays. Successful completion of this work will help understand the fundamental rules governing HBV morphogenesis and virion secretion, in addition to the important implications for chronic viral hepatitis as well as many other chronic progressive viral diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: IMMUNE REGULATION OF CNS VIRAL RECRUDESCENCE Principal Investigator & Institution: Bergmann, Cornelia C.; Associate Professor; Neurology; University of Southern California 2250 Alcazar Street, Csc-219 Los Angeles, Ca 90033 Timing: Fiscal Year 2002; Project Start 15-MAY-2001; Project End 31-MAR-2006 Summary: (provided by applicant): A variety of human viruses, including herpes viruses, hepatitis B virus and HIV, produce acute infections followed by persistence or recrudescence. However, the mechanism(s) regulating persistence and recrudescence depend on a balance between viral replication and the host immune response. Viral tropism and antigenic load provide additional determinants in this complex scheme. This proposal examines the contribution of cell mediated and humoral immunity in controlling recrudescence of a neurotropic virus following initial clearance. Infection of immunocompetent mice induces an acute encephalomyelitis, followed by persistence without infectious virus. During acute infection cell mediated immunity, predominantly the CD8+ T cells, are crucial in controlling virus replication within the central nervous system (CNS). However, in the absence of B cells, these effector functions do not suffice to suppress virus to undetectable levels, thereby allowing virus reactivation. Importantly, transfer of anti-viral antibody (Ab) prevents virus reactivation, implicating a crucial role for Ab and/or B cells in controlling persistence. However, analysis of virus specific T cells using class I tetramet technology revealed that the percentage of virus specific CD8+ T cells in the CNS is reduced compared to immunocompetent mice. In addition, there is no increase in virus specific T cells during reactivation. These data suggested that CD8+ T cells may be functionally impaired or exhausted due to increased antigen load. This proposal distinguishes between the requirement(s) for potent CD8+ T cell function vs Ab in controlling virus reactivation in a persistently infected host. The contribution of both neutralizing and non neutralizing Ab, Fc receptor (FcR) activity and complement are examined by Ab transfers and using mice deficient in FeR. These experiments will determine the mechanism of Ab mediated prevention of virus reactivation in an Ab deficient milieu. The possibility that the absence of Ab and/or B cells results in defective CD8+ T cell priming, ultimately leading to exhaustion during
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recrudescence is tested by functional and phenotypic analysis of CD8+ T cells during priming and recrudescence. Intervention via transfer of protective Ab or CD8+ T cells activated in vitro will determine if functionally impaired CD8+ T cells can be overcome. These experiments may have direct implications for therapeutic interventions during persistent viral infections. Finally, virus reactivation will be tested in an Ab deficient mouse with a normal B cell compartment. These experiments will distinguish between the possibilities of an Ab independent effect of B cells and a CD8+ T cell defect related to the absence of B cells. This proposal will provide insight into the immunological regulation of both virus recrudescence and the CNS as a target organ. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: INITIATION OF HEPATITIS B VIRUS REPLICATION Principal Investigator & Institution: Mclachlan, Alan; Associate Professor; Scripps Research Institute Tpc7 La Jolla, Ca 92037 Timing: Fiscal Year 2003; Project Start 15-JUL-2003; Project End 30-JUN-2005 Summary: (provided by applicant): Hepatitis B virus (HBV) infection is a worldwide health problem. It is estimated that there are 200 to 500 million HBV chronic carriers in the world for whom, to date, there is no reliable treatment. HBV causes both acute and chronic liver disease and the estimated relative risk of primary hepatocellular carcinoma (PHC) in chronic HBV carriers is approximately 100 times greater than in uninfected individuals. Therefore, effective treatments for chronic HBV infection are required. In these studies, the mechanism(s) regulating the initial steps in the synthesis of hepatitis B virus (HBV) DNA will be investigated. HBV DNA synthesis is initiated by binding of the viral polymerase to a stem-loop structure, epsilon, located at the 5'-end of the HBV pregenomic RNA. Initially, the first three nucleotides of HBV minus-strand DNA are synthesized utilizing the amino-terminal domain of the polymerase as a primer and the bulge region of epsilon as a template. The HBV polymerase with the covalently attached trinucleotide sequence is subsequently translocated to the DR1 sequence at the 3'-end of the pregenomic RNA. HBV minus-strand DNA synthesis then proceeds by the reverse transcription of the pregenomic RNA. The mechanism(s) regulating the translocation step are unknown. Recently, a regulatory sequence element, phi, located immediately upstream of the DR1 sequence at the 3'-end of the pregnomic RNA that is important for efficient viral replication and is complementary to the 5'-half of epsilon was identified. This finding suggests that the translocation of the minus-strand primer from epsilon to DR1 might be mediated by a conformational change in the pregenomic RNA that brings the primer into proximity with the DR1 sequence at the 3'-end of the pregenomic RNA. The conservation of the complementarity between epsilon and phi in the woodchuck hepatitis virus (WHV) and the duck hepatitis B virus (DHBV) genomes also supports this contention. Therefore, the role of the complementarity between epsilon and phi in regulating HBV replication will be examined directly by mutational analysis of these sequence elements. This approach is aimed at identifying possible targets for therapeutic intervention in chronic HBV infection. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: INNOVATIVE FORMULATION
SINGLE-DOSE
HEPATITIS
B
VACCINE
Principal Investigator & Institution: Kitchell, J P.; Director, Biodegradable Implants; Biotek, Inc. Woburn, Ma 01801 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JAN-2004
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Hepatitis B Virus
Summary: (provided by applicant): Hepatitis B (HBV) is a serious viral disease that can result in acute massive hepatic necrosis, chronic active hepatitis, and cirrhosis of the liver. HBV vaccines are commercially available and HBV vaccination is now recommended for all infants, adolescents, health workers and others who may be exposed to the virus through their work. Three HBV vaccine injections are required to generate protective immunity. Compliance depends on completing three visits to the healthcare provider. Incomplete vaccination is common and often attributed to scheduling difficulties. The vaccination success rate could be improved if only one dose were needed for full protection. There have been many attempts to address the need for single dose formulations for vaccines. Kitchell and Crooker (1997) studied the physicochemical properties of alum, the adjuvant used in the approved HBV vaccine, and they made an important observation about the hydration behavior of this material. Their discovery led to a simple and elegant method of formulating alum-adjuvanted hepatitis A vaccine as a single-dose injection giving multiple delayed pulses. This innovative approach to reformulation is also appropriate for the HBV vaccine. BIOTEK believes that it has gained further insight into the techniques needed to prepare a single dose HBV vaccine which provides three discrete pulses of vaccine exposure. The formulation will utilize the established HBV vaccine antigen and adjuvant, and a FDA approved biodegradable polymeric excipient. The specific aims of the Phase I project are to prepare and test in vivo both one month and four month delayed pulse formulations. PROPOSED COMMERCIAL APPLICATIONS: The technology, first directed at an improved hepatitis B vaccine formulation, could be transferred to hepatitis A vaccine and to the childhood DPT vaccination series. One important application in the future may be with an AIDS vaccine, where relaible single-dose protection for high risk populations may be especially important. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: INTERNATIONAL CONFERENCE ON THE HEPATITIS B VIRUSES Principal Investigator & Institution: Tavis, John E.; Molecular Microbiol and Immun; St. Louis University St. Louis, Mo 63103 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2004 Summary: (provided by applicant): The 350 million chronic carriers of Hepati tis B Virus (HBV) worldwide are at risk of hepatitis, cirrhosis, and hepatocellular carcinoma. A recombinant subunit vaccine is available, but it has a 5-10% failure rate, and there is no widely effective therapy for HBV infection. The development of effective therapies could be advanced more rapidly by a better understanding of the mechanisms of pathogenesis, the immune response, and function of the proteins involved in HBV replication. This conference will gather about 200 scientists who study different aspects of HBV, animal hepadnaviruses, and Hepatitis Delta Virus for discussions of the latest conceptual and technical advances. This meeting has been held annually since 1985, and is the only basic science HBV and HDV meeting of its kind. The primary goal of this application is to raise funds to support travel grants for junior scientists. The 2003 HBV Meeting will be organized by Drs. Antonio Bertoletti and John Tavis. The meeting will be modeled on the successful traditions of this series: intimate interactions through small size, presentation of work-in-progress, and a focus on training younger scientists. The meeting will have 9 oral sessions, two poster sessions, a keynote speaker, and one workshop. The oral session will be: New Models & Viral Entry, RNA & DNA Synthesis, Assembly, Morphogenesis & Trafficking, Regulatory Proteins and Variants, Immune Responses, Pathogenesis, Hepatitis Delta Virus, Hepatocellular Carcinoma & Oncogenesis, and Antivirals & Immunomodulation. Involvement of women and
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minorities in leadership positions will be emphasized. Each session will have approximately 7 talks selected through peer-review by the organizers of submitted abstracts. Posters for each topic will be presented in the poster sessions. A theme of the meeting will be to compare and contrast HBV with Hepatitis C Virus (HCV), the other most medically important hepatitis virus. The keynote speaker, Dr. Raft Bartenschlager, will contrast the molecular biology of HCB with that of HBV. The workshop will compare HBV and HCV immunology and pathogenesis. This conference will advance HBV research by introducing ideas from the HCV field, promoting constructive interactions between researchers, encouraging exchange of unpublished data and key reagents, and educating graduate students and post-doctoral trainees. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: INTERVENTIONS TO INCREASE HBV VACCINATION IN STD CLINICS Principal Investigator & Institution: Zimet, Gregory D.; Professor; Pediatrics; Indiana Univ-Purdue Univ at Indianapolis 620 Union Drive, Room 618 Indianapolis, in 462025167 Timing: Fiscal Year 2002; Project Start 05-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): The objective of this study is to evaluate interventions to increase acceptance of, and follow through with, hepatitis B virus (HBV) immunization among patients attending sexually transmitted disease (STD) clinics in Chicago, IL and Indianapolis, IN. This research will have implications for the design of interventions that may increase HBV vaccine uptake in at-risk groups. The interventions may also be applicable to other STD vaccines as they become available. The first specific aim is to assess the effect of message framing on vaccine acceptance. Prospect theory will be used to guide the development of the message-framing interventions. This theory suggests that positively framed messages (i.e., benefits of getting vaccine) are more effective than negatively framed messages (i.e., dangers of not getting vaccine) in stimulating preventive health behaviors. Research on Prospect Theory and engagement in health behaviors suggests also that the effects may be moderated by other attitudinal factors, including perceived risk of the behavior and degree of involvement in the message. The second aim is to evaluate the effect of provider-based interventions. Prior research suggests that recommendations by health providers are very important in patients' decisions regarding acceptance of healthcare procedures. The third aim is to examine the effect of the interventions on follow-through with the second and third recommended vaccination. During Year 1 of the proposed plan, the message framing interventions will be developed and pilot tested and healthcare providers in Chicago and Indianapolis will be trained in the provider-based interventions. During Years 1-5, 3,344 patients (18 years and older) will be recruited and followed from Chicago and Indianapolis STD clinics during routine medical visits. An audio computer-assisted self-interview (A-CASI) will cover demographics, risk behaviors, and perceived risk associated with vaccination. Subjects then will be randomized to receive a gain-framed, loss-framed, or information only message regarding HBV immunization (also delivered by A-CASI). Upon completion of the message-framing intervention, subjects will be complete additional attitude questions via A-CASI, then will be randomly assigned to one of two provider intervention conditions: 1. vaccine-offered or 2. vaccine-recommended. For both conditions free HBV immunization will be provided by a nurse practitioner. Debriefing interviews will be carried out. Subsequently, postcard reminders will be sent and phone call reminders made for follow-up appointments for those receiving the first and second doses of
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Hepatitis B Virus
vaccine. Outcome measures of interest include: (1) acceptance vs. rejection; (2) compliance with two doses vs. one dose only; and (3) completion of immunization vs. two doses only. The relationships of the interventions, socio-demographics, attitudes and behaviors to the outcome measures will be assessed with multiple logistic regression (MLR) and path analysis via structural equation modeling. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: JOHNS HOPKINS ADULT AIDS CLINICAL TRIALS UNIT Principal Investigator & Institution: Flexner, Charles W.; Associate Professor; Medicine; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002; Project Start 01-JAN-2000; Project End 31-DEC-2004 Summary: (adapted from applicant's abstract): Johns Hopkins University has had an ACTU since its inception in 1986. The Unit is administratively within the Division of Infectious Diseases as a component of the Johns Hopkins HIV Care Program, but it is configured to make maximum use of relevant institutional resources with investigators from multiple departments and divisions including Pharmacology, Neurology, Ophthalmology, Gynecology, Pathology and Internal Medicine. The Hopkins ACTU has provided leadership to the ACTG scientific agenda and has provided HIV clinical trials to Baltimore, a city that ranks ninth among metropolitan areas in AIDS rates. The performance record for the last grant cycle shows average enrollment, data performance and a rank of No. 3 in scientific contributions. Assets of this ACTU include leadership and scientific expertise in virology (B. Jackson), immunology (H. Lederman, T. Quinn, R. Bollinger), quality of life assessment (A. Wu), neurology (J. McArthur), pharmacology (C. Flexner), CMV retinitis (D. Jabs), and mycobacteriology (R. Chaisson). This unit has a subunit in the prison system, has developed an ACTG study of tuberculosis in Haiti and has high enrollment of injection drug users and African-Americans. This application proposes to continue a scientific portfolio that has depth and diversity to support the ACTG scientific agenda and a clinical trials program that includes good data performance and the enrollment of high priority participants. All current investigators will continue in their present roles as will the three advanced technology laboratories. Three new investigators, Dr. R. Siliciano (latent reservoirs of HIV), Dr. Richard Moore (HIV outcomes, cost and cost effectiveness), and Dr. David Thomas (hepatitis C coinfection) will be added. Preference will be given to protocols that reflect emphasis areas of the Hopkins ACTU, especially pharmacology, neurology, immunology, mycobacteriology, hepatitis C, long-term outcomes (quality of life and cost analyses) and simplified ART regimens (to better serve the patients). There will be emphasis on enhanced enrollment with a new peer recruiter and a new subunit to increase the catchment area. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: LEICA TCS SP2 ADBS CONFOCAL MICROSCOPE Principal Investigator & Institution: Borowiec, James A.; Associate Professor; Biochemistry; New York University School of Medicine 550 1St Ave New York, Ny 10016 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2004 Summary: (provided by applicant): The application requests support for a Leica TCS SP2 AOBS Spectral Confocal Microscope. The recently introduced spectrally programmable Leica AOBS technology allows a filter-free operation, which increases the signal strength allowing reduced photobleaching and longer cell lifetimes. The
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microscope will be a shared facility used by members of the Departments of Microbiology (4 major and 1 minor users) and Biochemistry (3 major and 2 minor users) at New York University School of Medicine (NYU SOM). Between them, the users have 18 NIH grants. The proposed studies of these investigators primarily characterize the components of signaling pathways that regulate cell growth in normal and virallyinfected or stressed cells. These projects involve the determination of sub-cellular localization of proteins in living and fixed cells, and analysis in living cells of nucleocytoplasmic shuttling using FRAP and interactions of multiple protein factors using FRET. The projects of the major users include studies of: i) transcriptional control of lytic and latent gene expression in herpesviruses (Wilson), ii) modulation of mRNA translation by Us11 in herpesvirus-infected cells (Mohr), iii) maintenance of a nonreplicating Hepatitis B virus DNA episome in the infected cell nucleus (Schneider), iv) characterization of a novel mechanism for regulating p53 stability through a nucleolinp53 interaction (Borowiec), v) the mechanism of retinal degeneration caused by defects in RP2, a causative factor in retinitis pigmentosa (Cowan), vi) localization of glucocorticoid receptor phosphorylation isoforms (Garabedian), and vii) trafficking of K+ channel proteins of the Kv4 subfamily and the dynamics of their interactions with associated proteins (Rudy). Significant progress towards these studies is currently prevented because confocal facilities at NYU SOM are heavily over-subscribed and access is severely limited. The success of these NIH-supported projects therefore requires full-time access to a high-resolution confocal microscope. As additional benefits, the instrument will enhance the training of students and postdoctoral fellows in the two departments, and provide increased synergy between user groups that will generate new research directions. The Department chairs and user groups have committed sufficient funds for instrument maintenance and training. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: LIVER CANCER CONTROL AMONG NORTH AMERICAN CHINESE Principal Investigator & Institution: Taylor, Victoria M.; Fred Hutchinson Cancer Research Center Box 19024, 1100 Fairview Ave N Seattle, Wa 98109 Timing: Fiscal Year 2003; Project Start 25-JUL-2003; Project End 30-JUN-2007 Summary: (provided by applicant): Little is known about the disease prevention behavior of Chinese in North America, and few studies have addressed cancer control in this group. However, Chinese American men and women are four times more likely to be diagnosed with liver cancer than their non-Latino White counterparts. This excess risk is attributable to high rates of hepatitis B virus (HBV) infection combined with low levels of hepatitis B vaccination coverage. The goal of this research is to increase the proportion of less acculturated Chinese adults who have been tested for HBV (and, therefore, either have been vaccinated, are screened for liver cancer, or know they are immune to the disease). Objectives are to: obtain qualitative and quantitative information about the liver cancer prevention behavior of Chinese Americans and Canadians; develop a culturally and linguistically appropriate outreach intervention targeting hepatitis B and liver cancer among Chinese; and conduct a randomized controlled trial to evaluate the effectiveness, feasibility, and acceptability of the intervention program. To increase the generalizability of our findings, the research will be conducted in two cities: Seattle, Washington and Vancouver, British Columbia. The project will emphasize community involvement. PRECEDE and qualitative methods (i.e., forty in-depth interviews and eight focus groups) will be used to develop a quantitative survey instrument as well as intervention components. Six hundred Chinese men and women aged 18-64 who have not been serologically tested for HBV
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Hepatitis B Virus
will be identified from a community-based survey of 1,200 individuals, and randomized to intervention or control status. Individuals in the experimental group will receive an outreach worker intervention (which will include a home visit and follow-up telephone call, tailored counseling and logistic assistance, and the use of audiovisual and print materials). Outcome evaluation will be based on data from a follow-up survey as well as medical record verification. If effective, our outreach intervention could be used by health care facilities and community organizations serving less acculturated Chinese in North America. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: LIVER DISEASE AND HIV-HBV COINFECTION IN THE HAART ERA Principal Investigator & Institution: Thio, Chloe L.; Assistant Professor; Medicine; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2004; Project Start 01-MAY-2004; Project End 30-APR-2009 Summary: (provided by applicant): Chronic hepatitis B (CH-B) is common in HIVinfected persons, and HIV accelerates the rate of hepatitis B-related liver disease progression. In the Multicenter AIDS Cohort Study (MACS), the risk of liver-related death was nearly 18 times higher in those coinfected with HIV-HBV compared to those with CH-B alone. Furthermore, the rate was two times higher after compared to before 1996, the time of the introduction of highly active antiretroviral therapy (HAART). These data support the need to study the effects of HAART on liver disease progression in HIV-HBV coinfected persons. This proposal investigates CH-B in HIV-infected persons receiving HAART in a cohort of HIV-HBV coinfected patients from the MACS and two well-characterized Australian cohorts, one in Melbourne and one in Sydney. The first aim will test the hypothesis that long-term HAART active against HBV will alter the rate of HAART-related hepatotoxicity in HIV-HBV coinfected persons. We will determine the rates of hepatotoxicity over a five-year period following HAART initiation. In the second aim the magnitude and durability of HBV DNA suppression with a HBV active HAART regimen will be determined by prospectively following HBV DNA levels. The third aim is designed to study the evolution of resistance mutations that occur in persons who do not have a durable suppression of their HBV DNA with HBV-active HAART. The entire HBV genome will be sequenced at the time of relapse and then followed subsequently for the development of compensatory mutations. These mutant viruses will be tested for anti-viral drug sensitivity and replication competence. These aims are integrated in the fourth aim, which tests the hypothesis that an effective HBV active HAART regimen will slow the rate of liver disease progression. In this aim, paired liver biopsies will be examined to determine the rates of liver disease progression and analyzed with respect to the ability to maintain a durable HBV DNA response, to the development of drug-resistant mutants, and to intrahepatic levels of HBV DNA and ccc DNA. Given the experience of the investigative team and the well-characterized cohorts involved, the results from this proposal will yield insights into the management of HIV-HBV co-infected patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MEASLES VIRUSES WITH ADDED VACCINE SPECIFICITIES Principal Investigator & Institution: Cattaneo, Roberto B.; Professor; Mayo Clinic Coll of Medicine, Rochester 200 1St St Sw Rochester, Mn 55905 Timing: Fiscal Year 2004; Project Start 01-DEC-2003; Project End 30-NOV-2007
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Summary: (provided by applicant): The live attenuated measles vaccine has an outstanding efficiency and safety record and induces enduring immunity. We hypothesize that a currently used measles virus (MV) vaccine strain is an ideal platform for the development of pediatric vaccines eliciting immunity against other pathogens. We will test two propositions of this hypothesis: first that vectored MVs can protect against infection with another pathogen. Second, that they can elicit a strong immune response against other human pathogens whilst maintaining vaccine function against measles. To test the first proposition we will complete the production of a panel of vectored MV with the potential of inducing strong humoral and/or cellular immune responses to a mouse pathogen. We will take advantage of the detailed knowledge of the determinants of the immune response against the Daniels strain of the picornavirus Theiler. Proteins or peptides of this virus will be expressed in MV vectors with different scopes: induction of high neutralizing antibody titers, of specific cytotoxic T lymphocytes, or of both. The quality and strength of the immune response and the efficiency of protection against challenge with Theiler virus will then be measured in genetically modified mice permissive for MV infection. The correlates of vaccine efficiency will be established. To test the second proposition we will produce recombinant MVs with the potential of eliciting strong and sustained immune responses against two human pathogens for which an inexpensive vaccine requiring a single immunization is highly desirable. Recombinant MV expressing the surface antigen of the hepatitis B virus at different levels will be used to define the expression strategy most effective in inducing a strong humoral immune response. Recombinant MV expressing different proteins and CTL-inducing peptides of the hepatitis C virus will also be produced, and the strength of the induced humoral and cellular immune responses measured. Those viruses inducing the strongest immune response against hepatitis B and hepatitis C virus components in genetically modified mice will be inoculated into juvenile macaques. Their efficacy in protecting these primates against wild type measles infection and in inducing an immune response against the additional pathogen will be measured. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: REPLICATION
MECHANISMS
OF
HEPADNAVIRUS
ASSEMBLY
AND
Principal Investigator & Institution: Hu, Jianming; Assistant Professor; Microbiology; Boston University Medical Campus 715 Albany St, 560 Boston, Ma 02118 Timing: Fiscal Year 2002; Project Start 15-FEB-1999; Project End 31-JAN-2004 Summary: Hepadnaviruses, or hepatitis B viruses, are small, hepatotropic DNA viruses that replicate through an RNA intermediate (the pregenomic RNA or pgRNA) by reverse transcription. A critical early step in viral replication is the assembly of a ribonucleoprotein (RNP) complex comprised of the viral reverse transcriptase (RT) and pgRNA, which triggers both the assembly of nucleocapsids, the site of viral DNA synthesis, and the initiation of reverse transcription, which is primed by RT itself (the protein priming reaction). Through a complex multi- step reverse transcription pathway, the pgRNA is subsequently converted, within the context of the nucleocapsids, into the characteristic, relaxed circular DNA genome which can then exit the cell. The broad, long term objective of this proposal is to elucidate the molecular mechanisms of hepadnavirus replication, focusing on the virus-cell interactions critical for viral assembly and replication. The first specific aim is to identify host factors required for the interaction between RT and pgRNA and for protein priming. A combined approach based on physical association with RT, pgRNA and viral particles
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Hepatitis B Virus
and biochemical fractionation and reconstitution will be used for this purpose, taking advantage of an established cell-free system that can recapitulate these early events in viral replication. The second aim is to elucidate the determinants on both RT and pgRNA responsible for specific RNA-protein interaction. Optimal conditions for RTbinding and crosslinking will be sought. The RT and contact sites in the RNP complex will then be identified through protein and RNA sequence analyses. This will, in turn, guide further mutagenesis studies to elucidate the specific requirements of RT and pgRNA for RNP formation. The third aim is to determine the requirements for individual steps of the viral reverse transcription pathway, using a recently developed synchronized viral replication system. Nucleocapsids from every stage of reverse transcription will be isolated to determine their structural changes, which accompany, and may be required for, the progression of viral DNA synthesis. Furthermore, specific host factors required for the different steps of reverse transcription will be identified by (1) carrying out viral DNA synthesis with the isolated nucleocapsids under cell-free reconstitution conditions and (2) treating virus-producing cells, at different stages of reverse transcription, with agents that target candidate host factors. The accomplishment of these goals should reveal novel cellular, as well as viral, targets for developing effective antivirals which is urgently needed for the treatment of over 300 million patients worldwide infected with the hepatitis B virus, who are at great risk of developing hepatic failure and hepatocellular carcinoma. In addition, studies on how host factors facilitate viral replication will also provide important insights into the normal cellular functions of these factors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MIAMI ADULT AIDS CLINICAL TRIALS GROUP, AACTG Principal Investigator & Institution: Fischl, Margaret A.; Associate Professor; Medicine; University of Miami-Medical Box 248293 Coral Gables, Fl 33124 Timing: Fiscal Year 2002; Project Start 01-APR-1992; Project End 31-DEC-2004 Summary: (adapted from application's abstract): The Miami ACTU has been a member of the AACTG since its inception and has contributed to a number of AACTG studies that led to the approval of seven antiretroviral drugs and numerous HIV treatment strategies including lower and alternative dosing schedules for all three classes of antiretroviral agents, early treatment intervention, combination therapies with dual NRTIs and triple-drug therapy. The Miami ACTU has also actively participated in the Virology Laboratory Subcommittee working groups with an active role in the standardization of a PBMC culture assay for determining drug susceptibility, the assessment of interlaboratory concordance of DNA sequencing analysis of HIV RT, and the development of a consensus sequencing protocol to detect drug resistant mutations. This unit has also been involved with the Surrogate Markers Subcommittee with an active role in the assessment of plasma cytokines and soluble markers, cytotoxic Tlymphocyte activity, lymphocyte proliferation and advanced flow cytometry, and defining and validating immunologic markers as surrogate markers independent of CD4 and HIV RNA. Finally, this unit has contributed to the Pharmacology Committee with the evaluation of targeted- concentration control studies and the correlation of drug exposure with treatment response and failure parameters. The Miami ACTU will actively participate in HIV Disease RAC efforts and provide expertise to address study treatment strategies for initial therapy, treatment options for virologic failure and utilization of phenotypic and genotypic assessments to direct subsequent therapy and treatment intensification. The Miami ACTU will also bring expertise in the areas of hepatitis B and C pathogenesis and treatment, metabolic complications of HIV-1
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protease inhibitor pathogenesis and treatment, HIV dementia pathogenesis and treatment and peripheral neuropathy pain assessment, Kaposi sarcoma (KS) pathogenesis, intensive immunologic monitoring and definition, and validation of immunologic determinants of treatment response. The Miami ACTU plans to enroll 100 subjects per year across AACTG studies and 70 patients into AACTG substudies, including but limited to Compartmental, Virology, Viral Dynamics, Pharmaceuticals, Metabolic, Neurologic, Women's Health and Adherence and Outcomes substudies. With a support system in place for the long-term follow-up of patients, the Miami ACTU anticipates to enroll approximately 80 patients into the ALLRT study (ACTG 5001) over a 2-year period. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MODELING VIRAL AND T LYMPHOCYTE DYNAMICS Principal Investigator & Institution: Perelson, Alan S.; Staff Member; None; University of Calif-Los Alamos Nat Lab Ms G758 Los Alamos, Nm 87545 Timing: Fiscal Year 2002; Project Start 19-APR-1991; Project End 31-MAR-2005 Summary: Mathematical modeling combined with experiment has led to increased understanding of the processes that underlie HIV-1 infection in humans and the development of improved therapies. Nevertheless HIV has not been eradicated from infected individuals and various reservoirs including latently-infected cells, virus trapped on folliculary dendritic cells (FDC), and virus in semen have been identified. This application proposes to continue the development of more realistic models of HIV infection with particular emphasis on events that occur in lymphoid tissue. The applicants propose to develop models that explicitly take into consideration infection in blood and tissue, the role of FDC, and possible incomplete penetrance of drugs into various cell populations and tissues. The primary health-related effects of HIV infection are consequences of CD4+ T cell depletion. Nevertheless, the population dynamics of T cells in vivo are poorly characterized. It is proposed to develop theory and analyze data from in vivo labeling studies that will help characterize the rates of proliferation and death of T cells in uninfected, HIV-infected, and HIV-infected individuals under potent antiretroviral treatment. Infection by hepatitis C virus (HCV) and hepatitis B virus (HBV) continue to cause liver failure and hepatocellular carcinoma in many infected individuals. Antiviral therapy for these agents lags behind developments in HIV. The applicants propose to use the modeling and analysis tools that they have developed for HIV to increase understanding of the in vivo kinetics of HCV and HBV infection and the effects of antiviral therapy. In addition to gaining basic understanding, this approach aims to put information into a practical setting, and the applicants hope to interact with clinical groups in the design and evaluation of new treatment protocols. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MODULATION OF OXIDATIVE DAMAGE BY TEA POLYPHENOLS Principal Investigator & Institution: Wang, Jia-Sheng; None; Texas Tech University Health Scis Center Health Sciences Center Lubbock, Tx 79430 Timing: Fiscal Year 2002; Project Start 30-SEP-2001; Project End 31-AUG-2003 Summary: (provided by applicant) The primary objective of this research project is to study the modulating effects of green tea polyphenols on reducing hepatocarcinogeninduced oxidative damages in high-risk human populations. Oxidative damage induced by reactive oxygen species in vivo plays important roles in human hepatocarcinogenesis primarily caused by chronic infection of hepatitis B/C viruses and exposure to dietary
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Hepatitis B Virus
aflatoxins. The level of 8-hydroxy-2'- deoxyguanosine, a biomarker for oxidative DNA damage, increases in hepatitis B virus surface antigen positive and aflatoxin-exposed humans and in aflatoxin- treated animals. Dietary antioxidants are important components of cancer modulating agents, which have been proven to effectively target carcinogen biomarkers, including oxidative damages, in high-risk human populations. Among various identified dietary associated antioxidants, green tea and its polyphenols have been shown to be safe and highly effective in inhibition of a variety of carcinogeninduced oxidative damages, mutagenesis, and tumorigenesis in in vitro bioassays and in vivo animal models. The general hypothesis underlying this proposal is that green tea polyphenols have a protective effect against oxidative stress or damage induced by aflatoxin and hepatitis B/C viruses through the mechanisms of modulating aflatoxin metabolism and oxidated DNA damage. The specific aims include: (1) to determine antioxidative role of green tea polyphenols in inhibition of the level of 8-hydroxy-2'deoxyguanosine in urine samples collected from an intervention study of 120 participants who are double positive for hepatitis B virus surface antigen and aflatoxinalbumin adducts, and (2) to determine the modulating effect of green tea polyphenols on excretion of carcinogen detoxifying product, aflatoxin Bl-mercapturic acid in urine samples collected from the study participants. The results of this proposed study will help to understand the mechanisms of antioxidative role of tea polyphenols in modulating human hepatocarcinogenesis caused by hepatitis B/C viruses and aflatoxins. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MOLECULAR BIOLOGY OF THE HEPATITIS B TYPE VIRUSES Principal Investigator & Institution: Ganem, Don E.; Professor & Howard Hughes Investigator; Microbiology and Immunology; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 941222747 Timing: Fiscal Year 2002; Project Start 01-SEP-1982; Project End 31-MAR-2003 Summary: Hepatitis B virus (HBV) and hepatitis D virus (HDV) are important causes of acute and chronic hepatitis in humans. Although much is known about the replication of these viruses, less is known about how replication causes disease. Evidence suggests that, in HBV infection, host immune responses trigger liver injury and affect viral replication. This application proposes studies to further examine the nature of these immune responses and to determine if similar responses can occur in HDV infection; the ability of such responses to affect HDV RNA replication will also be examined. In addition, detailed studies of the mechanisms of HDV RNA replication will be conducted, with emphasis on the involvement of host factors in this important reaction. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MOLECULAR DITHIOLETHIONES
MECHANISMS
OF
CHEMOPREVENTION--
Principal Investigator & Institution: Kensler, Thomas W.; Professor; Environmental Health Sciences; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002; Project Start 01-SEP-1985; Project End 31-JAN-2004 Summary: Cancer prevention involving reduction or elimination of human exposure to environmental carcinogens may not always be possible. Inhibition of the development of cancer by the administration of anticarcinogenic age may offer a practical alternative for reducing human cancer burden. However, the successful utilization of chemopreventive interventions will require solid mechanistic understanding of the
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action(s) of these agents. The proposed studies will continue to investigate the modes of protection afforded by oltipraz and other 1,2-dithiole-3-thiones on aflatoxin (AFB1) hepatocarcinogenesis in the rat. Oltipraz is an effective and potent inhibitor of experimental carcinogenesis induced by many agents in many tissues. Oltipraz is currently being evaluated in Phase I and II clinical chemoprevention trials. This project will continue the development and evaluation of dithiolethiones more active than oltipraz on a) inhibition of AFB1-induced tumorigenesis in rats; b) altered AFB- DNA adduct formation; and c) induction of carcinogen detoxication ("phase 2") enzymes. Using a large series of analogs synthesized previously, the structure-activity relationships for inhibition of cytochrome P450 activation of AFB1 metabolism will also be determined. Using molecular genetic approaches, the identification and characterization of genes induced by dithiolethiones in rat liver will be continued together with elucidation of the role(s) of these gene products in protection against aflatoxin toxicity and carcinogenicity. Several novel inducible genes recently identified may protect against inflammation and oxidative stress. Finally, the chemopreventive actions and efficacy of oltipraz will be evaluated in a unique experimental model, the tree shrew, in which infection with human hepatitis B virus and exposure to AFB1 synergistically enhance the incidence of liver cancer, as occurs in humans. Collectively, these multifaceted, integrated studies will more fully define the chemical, molecular, biochemical and biological mechanisms of action of this versatile class of chemoprotective agents. The long-term goal of this project is to facilitate the most efficient and effective use dithiolethiones as protective agents in human populations exposed to environmental toxicants. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MURINE MODEL FOR HEPATITIS ANTIVIRAL/ANTICANCER TESTING Principal Investigator & Institution: Melegari, Margherita; Marmotech, Inc. 4 Sunny Knoll Ithaca, Ny 14850 Timing: Fiscal Year 2004; Project Start 01-APR-2004; Project End 31-MAR-2005 Summary: (provided by applicant): Persistent infection with hepatitis viruses, hepatitis B virus (HBV) and hepatitis C virus, (HCV) constitute a worldwide health problem that is growing in prevalence in the United States. Persistent infections are increasing the occurrence of primary hepatocellular carcinoma, (HCC), a cancer for which there is no effective therapy. Therefore, there is an urgent need for experimental systems that can model the process of persistent hepatitis infection and hepatocarcinogenesis. The woodchuck hepatitis virus (WHV) animal model has been integral in the testing and licensing of antiviral drugs for HBV. The aim of this application is to validate a novel murine-based model for large scale antiviral and anticancer testing. The model extends the usefulness of the WHV model by duplicating the persistent infection phase and modeling the hepatocarcinogenesis phase in mice in a much shorter time frame and potentially at a lower cost. The new model involves the transplantation of woodchuck or tupaia hepatocytes into immunocompromised "universal recipient" transgenic mice that contain a urokinase plasminogen activator, uPA transgene. This gene creates a mouse liver that readily accepts and allows growth of transplanted xenogenic hepatocytes. Recently, a dipeptidyl peptidase IV knockout allele (DPPIV-/-) has been added to the genotype of the recipient mice and this allows direct detection and quantitation of transplanted hepatocytes in a rapid and simple manner. This advance will simplify quantitative hepatocarcinogenesis assays and expand the use of the model into anticancer applications. Recent demonstration of transplantation of tupaia hepatocytes
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Hepatitis B Virus
and their HBV infection in the model will be exploited to directly study antiviral and anticancer treatments for HBV. The experiments outlined are those needed to validate the woodchuck, and tupaia transplantation systems ("woodmice and tupaiamice" respectively) for large scale antiviral and anticancer testing. These studies also will position the tupaiamouse system for HCV research if the model is shown to be suitable for HCV infection in future studies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NEW HEPATITIS B SMALL MOLECULE INHIBITORS Principal Investigator & Institution: Mehta, Anand S.; Associate Professor; Synergy Pharmaceuticals, Inc. 2 Executive Dr, Ste 450 Somerset, Nj 08873 Timing: Fiscal Year 2002; Project Start 01-SEP-2001; Project End 31-AUG-2003 Summary: (provided by applicant): The over-all goal of this "fast track" proposal is to develop a new class of orally available compounds for the treatment of chronic human hepatitis B virus (HBV) infection through a "proof of principle" Phase I/IIa Human clinical trial. With our colleagues, we have shown that alkylated imino sugars, called "alkovirs," are novel and effective in preventing HBV replication in tissue culture systems under conditions where there is no detectable cyto-toxicity. The alkovirs are previously undescribed synthetic (hence completely characterized) small molecules. Unlike the glucosidase inhibitors, (another class of imino sugars that we have been studying) alkovirs do not inhibit glucosidases, making them distinct and conferring certain advantages. Moreover, although alkovirs inhibit HBV replication, they do not target the viral polymerase, as do most nucleoside analogues. Thus, alkovirs should be effective against lamivudine "resistant" HBV mutants. The objectives of this "fast track" proposal are intended to be straightforward and defined by clear milestones: In phase I, the Alkovir(s) with the most potent anti-HBV activity against wild type virus and lamivudine resistant virus will be selected and tested for in vivo toxicity and pharmacokinetics in a rat model. In Phase II, the efficacy and toxicity of the candidate Alkovir(s) selected in Phase I will be evaluated in the woodchuck model of chronic hepatitis virus infection both as monotherapy and in combination with 3TC-lamivudine. Other work, to be performed in parallel with this study, will explore the precise mechanism of action of alkovirs and possibility that (a) they are effective against other viruses and (b) are a class of compounds to which mutant viruses do not frequently emerge. Accomplishment of these Aims will permit the introduction of alkovirs for human clinical trials. Given the need to find complements to nucleoside analogues, the introduction of new anti-hepatitis B virus agents as described here is extremely important. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: NUCLEOSIDES WITH DUAL ANTI-HIV AND HBV ACTIVITY Principal Investigator & Institution: Schinazi, Raymond F.; Professor; Pediatrics; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2002; Project Start 01-AUG-1997; Project End 31-JUL-2005 Summary: (Adapted from the Investigator's Abstract): The long-term goal of this application is to study the antiviral, biochemical, and pharmacological profiles of new bD- and b-L chiral nucleosides. The specific aims of the current application are concerned with these studies on b-D-2',3'-didehydro-2',3'-dideoxy-5-fluorocytidine (D-D4FC) and the related class of D-2',3'-didehydro-2',3'-dideoxy-2'-fluoronucleosides (D-2'-F-d4Ns). Both in vitro and in vivo investigations are proposed. The rationale for the choice of
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these compounds for the studies proposed is based on the observation of the discovery that certain 2',3'-didehydro-2',3'-dideoxynucleosides (d4N) and their 2'-fluoro analogs are antiviral agents that possess selective activity against the M184V HIV-1 variants, that lack cross-resistance with some known antiviral agents, and that have dual antiviral activity against HIV-1 and HBV. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PATHOGENESIS OF GROUND GLASS CELLS IN HEPATITIS B Principal Investigator & Institution: Yen, Tien-Sze Benedict.; Professor; Northern California Institute Res & Educ 4150 Clement Street (151-Nc) San Francisco, Ca 941211545 Timing: Fiscal Year 2002; Project Start 05-MAR-1992; Project End 31-MAR-2006 Summary: (Adapted from the Investigator's abstract): Hepatitis B virus (HBV) causes chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC), and is especially common among minorities such as African Americans and Asian Americans. The mechanism by which HBV causes HCC is unclear, but it is likely that HCC results from both specific viral factors and non-specific mutagenesis due to constant cell turnover. One candidate viral factor is the large surface protein, since expression of this protein in transgenic mice results in HCC. We have recently shown that large surface protein can activate cellular genes at the transcriptional level, apparently by forming non-secretable particles in the endoplasmic reticulum (ER) and activating ER stress. Further preliminary data indicate that large surface protein causes cell death, probably by apoptosis. Since hepatocytes containing large surface protein particles within the ER ("ground glass cells") are seen in the livers of people with chronic hepatitis B, our results point to a specific mechanism whereby HBV may cause HCC. However, the reason for ground glass cell formation in infected livers is still unclear. For the next cycle of this project, we propose to study events both up-stream and down-stream of the formation of ground glass cells. First, we wish to validate our hypothesis that mutations in the viral genome can lead to ground glass cells, and determine if two common naturally occurring viral mutants can cause ground glass cells and HCC in transgenic mice. Second, we will clone out HBV genomes from human ground glass cells, and look for additional mutations that may be responsible for ground glass cell formation. Third, we will determine how large surface protein causes cell death, and whether it is by apoptosis. We will also determine if there is increased apoptosis of ground glass cells in transgenic mice, and look for activation of apoptotic pathways in human livers with ground glass cells. These experiments should give novel insights into the mechanism by which HBV causes liver disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PATHOGENESIS OF LIVER DISEASE IN HEPATITIS Principal Investigator & Institution: Chisari, Francis V.; Professor & Head; Scripps Research Institute Tpc7 La Jolla, Ca 92037 Timing: Fiscal Year 2002; Project Start 01-JUL-1983; Project End 30-JUN-2003 Summary: (adapted from the investigator's abstract) During the current funding interval Dr. Chisari established the technology required to detect, quantitative and characterize the cytotoxic T lymphocyte (CTL) response to the hepatitis B and C viruses. Using this technology he defined the salient features of the host-virus relationship during the acute and chronic phases of these infections and, in the process, established the rationale and identified the immunological targets for antigen-specific immunotherapy of chronic
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hepatitis. Despite these advances, the very early aspects of the host-virus relationship during HBV and HCV infection are completely unexplored because, for practical and ethical reasons, it is extremely difficult to access the incubation period in infected patients. Nonetheless, these early host-virus interactions are likely to be key determinants of the outcome of these infections. In the next funding interval, he will examine the virological, immunological and pathological features of the host-virus relationship from the moment of HBV and HCV infection until their final outcome in experimentally infected chimpanzees. As in humans, almost all adult onset HBV infections in chimps are self limited, while only half of chimp HCV infections are self limited and the rest become persistent. Thus, he will compare and contrast the early intrahepatic T cell responses to HBV and HCV to test the hypothesis that the outcome of these infections is determined by the kinetics, vigor, diversity and cytokine profiles of the intrahepatic T cell response and the ability of the virus to spread and to evade immune recognition during the early incubation period of each infection. Thanks to the close relatedness of chimps and humans, most of the reagents and techniques required to define the intrahepatic antigen specific T cell response to these viruses are already available. The information forthcoming from these studies will, for the first time, define the virological and immunological features of early HBV and HCV infection and determine the extent to which they influence viral clearance and disease pathogenesis in these diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: RECOMBINANT ATTENUATED SALMONELLA VACCINES FOR HUMANS Principal Investigator & Institution: Curtiss, Roy Iii.; Professor; Biology; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 31-DEC-2007 Summary: (provided by applicant): Of the 18.9 million annual deaths (1997) due to infectious diseases, about 7.5 million, in addition to significant morbidity, are the result of infections by Salmonella typhi, S. paratyphi A, hepatitis B virus (HBV), Plasmodium falciparum, Streptococcus pneumoniae and Mycobacterium tuberculosis. In the belief that improving health, nutrition and economic well-being (the later dependant on the first two) provides the best means to enhance the quality of life globally and thus reduces conditions that result in warlike and terrorist behavior, we propose a vaccine development program based on our recent technical developments in using recombinant attenuated Salmonella vaccines. Our objectives include: (a) to design, construct and evaluate an attenuated derivative of S. paratyphi A that will serve as an antigen delivery vector by exhibiting regulated delayed lysis within effector lymphoid tissues in the immunized individual to release hepatitis B virus (HBV) core particles encoding (i) HBV pre $1, pre $2 and T-cell epitopes as a preventative/therapeutic vaccine against HBV and (ii) P. falciparum circumsporozoite epitopes as a vaccine against malaria; (b) to construct and evaluate the contribution of strain background and the RpoS* phenotype on immunogenicity of a recombinant antigen expressed by attenuated S. typhi vaccine strains; and (c) to design, construct and evaluate recombinant attenuated S. typhi vaccines to express and deliver protective antigens specified by genetic information from (i) S. pneumoniae to prevent pneumococcal disease caused by strains with diverse capsular serotypes and (ii) M. tuberculosis as a preventative/therapeutic vaccine. The S. paratyphi A and S. typhi recombinant vaccines should also provide immunity to infection by S. paratyphi A and S. typhL We will also develop our Master File, prepare and fully characterize candidate vaccine Master Seeds
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for stability and safety, prepare and submit protocols for IRB approvals, submit information necessary to obtain INDs, and perform any other work needed to arrange that the best candidate vaccines be clinically evaluated in human volunteers. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: RECURRENT HEPATITIS B AFTER LIVER TRANSPLANTATION Principal Investigator & Institution: Lok, Anna S.; Professor; Internal Medicine; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2002; Project Start 01-JUN-2001; Project End 31-MAY-2008 Summary: Hepatitis B accounts for approximately 5000 deaths/yr in the United States. Early results with orthotopic liver transplantation (OLT) for hepatitis B were poor with recurrence rates of >80% and 2-year mortality rates of 50%. Recent studies found that continuous high dose IV hepatitis B immune globulin (HBIG) can decrease the rate of reinfection to <20%. However, high dose HBIG is very expensive ($30,000-$50,000/yr) and the efficacy is low in patients with replicative infection pre-OLT. Pilot studies showed that lamivudine (LAM, an oral nucleoside analog which costs $1,200-$1,500 per yr) can decrease the rate of recurrent hepatitis B to <30% during the first post-OLT year but the long-term efficacy is limited by drug resistant mutants. Three pilot studies reported that combination therapy of HBIG and LAM is more effective than either agent alone with recurrence rates <5%, but it is not clear how long HBIG needs to be administered. Given the high costs and the inconvenience of life-long HBIG therapy, there is a need for a prospective, randomized controlled trial to determine if prophylaxis with LAM and short-term HBIG is as effective as LAM and long-term HBIG in the prevention of recurrent hepatitis B post-OLT. The use of antiviral agents with potential activity against LAM resistant HBV mutants, such as adefovir dipivoxil, also needs to be evaluated. The specific aims of our study are: (1) To compare the safety, efficacy and cost-effectiveness of combination therapy with LAM and a 6-month course of HBIG with LAM and a 3-yr course of HBIG in the prevention of recurrent hepatitis B postOLT. (2) To identify the epidemiological, clinical and virological factors that are associated with recurrent hepatitis B post-OLT. (3) To determine the safety and efficacy of adefovir dipivoxil in the suppression of HBV replication in patients who have developed LAM resistant HBV mutants and to compare the rate of recurrent hepatitis B post-OLT in patients with and without LAM resistant mutants prior to transplant. This is a prospective, randomized, multi-center clinical trial involving 20 liver transplant centers in N. America, to be conducted under an investigator IND 59,167. 290 patients with hepatitis B who are listed for OLT as UNOS status 1 or 2 will be enrolled. Open label LAM will be administered to decrease virus load pre-OLT. Patients will be randomized after OLT to Group I: LAM and 3 yr-course of HBIG or Group II: LAM and 6-month course of HBIG. Patients who develop LAM resistant mutants pre- or postOLT will additionally receive adefovir dipivoxil. The primary end-point of this trial is the rate of recurrent hepatitis B during the first 3 yr post-OLT. This trial will provide definitive answers whether combination therapy with LAM and a 6-mon course of HBIG is as efficacious and more cost-effective than LAM and a 3-yr course of HBIG in the prevention of recurrent hepatitis B post-OLT. In addition, crucial data will be generated on the efficacy of pre-OLT LAM in virus clearance, incidence and outcome of silent allograft infection, clinical outcome of patients with LAM resistant HBV mutants, and management of patients with LAM resistant mutants. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: REGULATION OF HBV REPLICATION BY THE IMMUNE SYSTEM Principal Investigator & Institution: Guidotti, Luca G.; Associate Professor; Scripps Research Institute Tpc7 La Jolla, Ca 92037 Timing: Fiscal Year 2002; Project Start 01-JAN-1997; Project End 31-DEC-2006 Summary: (provided by applicant): The hepatitis B virus (HBV) causes acute and chronic necroinflammatory liver disease and hepatocellular carcinoma. Over 350 million people worldwide are persistently infected by HBV, representing an enormous reservoir for horizontal and vertical spread of this virus to others. The long term objective of this application is to elucidate the molecular basis for liver disease, viral clearance and viral persistence in the pathogenesis of HBV infection with the ultimate hope that this knowledge will lead to the development of new therapeutic strategies to terminate persistent infection and its attendant costs and complications. Using transgenic mice that replicate HBV at high levels in the liver as recipients of HBV-specific CTLs, we have shown that the antiviral potential of the CTLs is primarily mediated by noricytolytic mechanisms that involve the intrahepatic production of type I inflammatory cytokines by these cells. This occurs after the CTLs specifically recognize viral antigens on the surface of the hepatocyte. Following antigen recognition, the CTLs also trigger the death of a small number of hepatocytes and this process leads to the recruitment of many hostderived lymphomononuclear and polymorphonuclear cells into the liver that contribute to the formation of necroinflaminatory foci histologically identical to classical viral hepatitis in man. The recruited inflammatory cells are likely to be responsible for antigen-nonspecific amplification mechanisms that greatly enhance the liver damage initiated by the CTLs. The recruitment of these cells is probably mediated by secretion of chemokines by either the antigen-activated CTLs or other cellular components of the liver. In support of this, we have performed preliminary experiments showing that a large variety of chemokines are rapidly and strongly induced in the liver of HBV transgenic mice after CTL transfer and their expression is regulated by type 1 inflammatory cytokines. Chemokines are likely to play a role in viral pathogenesis by regulating the trafficking of inflammatory cells to tissue sites of infection and, perhaps, by directly inhibiting viral replication. Whether this is the case during HBV infection is not known. To explore these hypotheses, we will use in vivo (HBV-replicating transgenic mice) and in vitro (HBV-replicating hepatocytes) systems to determine the function of chemokines and chemokine receptors on the recruitment, antiviral and pathogenic effector functions of CTLs and other inflammatory cells. We will also define the role that type 1 inflammatory cytokines may play in these processes. The results of these experiments will provide insight into the basic immunological processes that may determine liver disease, viral clearance and viral persistence in the pathogenesis of HBV infection. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: REGULATION OF TBP BY HBV X ON TRANSFORMATION Principal Investigator & Institution: Johnson, Deborah L.; Associate Professor; Molecular Pharm & Toxicology; University of Southern California 2250 Alcazar Street, Csc-219 Los Angeles, Ca 90033 Timing: Fiscal Year 2002; Project Start 10-MAY-1997; Project End 31-JAN-2005 Summary: (Adapted from the investigator's abstract) The Hepatitis B virus (HBV) is a common infectious agent. The HBV protein product, X, has shown to be essential for viral replication, and it is strongly implicated in the development of hepatocellular carcinoma in chronically infected HBV patients, yet its role in these events is not well-
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understood. Our previous work has comprehensively defined the mechanism for how X transactivated RNA polymerase I and III promoters. We made the interesting discovery that X induces the promoters by activating the Ras signal transduction pathway which then increases the cellular levels of the central transcription factor, TATA-binding protein (TBP). Increases in cellular TBP augment RNA pol I and III transcription and differentially regulate RNA pol II promoters. Our research plan will clearly delineate how X, an oncogenic Ras, increase cellular TBP levels. The proposed aims will rigorously investigate each event in the TBP gene expression process that gives rise to the final TBP product. By examining the individual contribution of each process, and how it differs when either X or oncegenic Ras is expressed in cells, we will obtain a good quantitative picture of how this X- and oncogenic Ras-mediated increase in TBP occurs. We have promising new data indicating that a key step leading to the increase in TBP is due to an increase in TBP promoter activity. Therefore, a major focus of the proposed studies will be to examine how the TBP promoter is regulated by X and by oncogenic Ras. We will comprehensively define the X-mediated signaling events downstream of Ras to the promoter that modulate TBP promoter activity. Since X has been shown to transform cells, and Ras is strongly oncegenic, we will also determine how alterations in the cellular levels of TBP can affect the transformation potential of cells. Focus formation, growth in soft agar, and mouse tumorigenesis assays will be used to assess whether directly overexpressing TBP can enhance transforming activity or whether down-regulating its production in cells can prevent Ras-induced transformation. Using mutant TBP proteins that are specifically defective in RNA pol II or pol III transcription, we will define specific changes in cellular gene expression occurring in TBPoverexpressing cells that contribute to transformation. These studies promise to make unique and important new contributions to our understanding of the function of the HBV X protein and oncegenic Ras, the regulation of TBP, and their consequences on cellular gene activity that leads to cellular transformation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: RIBOZYMES-- CATALYSIS AND ANTIVIRAL ACTIVITY Principal Investigator & Institution: Burke, John M.; Professor; Microbiol & Molecular Genetics; University of Vermont & St Agric College 340 Waterman Building Burlington, Vt 05405 Timing: Fiscal Year 2002; Project Start 01-DEC-1990; Project End 31-JAN-2005 Summary: The goal of this project is to move quantitative, carefully controlled analysis of RNA enzymes from the test tube into the cell, through a systematic series of experiments designed to address both fundamental issues regarding biological catalysis by RNA, and the development of ribozymes as selective tools for targeted cleavage of cellular and viral RNAs. Following on collaborations in which we demonstrated that engineered hairpin ribozymes can selectively inhibit replication of HIV-1 and hepatitis B virus, we have focused on studies conducted entirely within the PI's lab in which we have demonstrated inhibition of Sindbis virus in BHK-21 cells stably expressing hairpin ribozymes. Specific Aims of this proposal are-(1) Explore the activity of a new class of hairpin ribozymes that do not require G at the cleavage site; (2) Determine the inhibitory mechanism, site of action, and sequence selectivity of hairpin ribozyme-mediated inhibition of Sindbis virus replication; (3) Evaluate and optimize the enzymatic activity and sequence selectivity of engineered hairpin ribozymes in trans-cleavage reactions within mammalian cells; (4) Evaluate and optimize ribozyme inhibition of gene expression using Sindbis virus as a model system. By combining strength and experience in in vitro biochemistry with skills in virology and cell biology, we believe
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that we are poised to make strong and unique contributions to the fields of biological by RNA and to targeted RNA inactivation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: RISK FACTORS FOR AIDS AMONG IV DRUG USERS Principal Investigator & Institution: Des Jarlais, Don C.; Director of Research; Beth Israel Medical Ctr (New York) 1St Ave at 16Th St New York, Ny 10003 Timing: Fiscal Year 2002; Project Start 10-SEP-1994; Project End 30-JUN-2004 Summary: With over 50,000 cases of AIDS and 100,000 cases of HIV infection, the HIV epidemic among injecting drug users (IDUs) in New York City is by far the largest local HIV epidemic among IDUs in the world. Recently, we have observed important positive developments in this epidemic, including: continuing reductions in risk behavior, declining HIV seroprevalence, and low HIV incidence. Whether these positive trends continue will have very important implications for the study of large, high seroprevalence HIV epidemics, which account for the majority of new HIV infections in the U.S. and in industrialized countries. The specific aims for this competing, continuation proposal are to study: 1. Long-term trends in HIV seroprevalence among IDUs in New York City, possible differences in seroprevalence trends in different demographic subgroups, and to monitor estimated HIV incidence. 2. Long-term trends in HIV risk behavior among IDUs in New York City, and characteristics of persons who continue or relapse to high risk behavior. 3. Social network and "mixing" patterns among IDUs, and how these relate to HIV infection and risk reduction. 4. Transitions between non-injecting and injecting drug use, and characteristics of new injectors, including risk behavior, social networks, and HIV, hepatitis B virus (HBV), and hepatitis C virus (HCV) infection. 5. Audio- computer assisted self interviewing as a method for obtaining more complete reporting of HIV risk behaviors. These aims will be accomplished through continuation of cross- sectional surveys of 1000 persons per year entering Beth Israel Medical Center drug treatment programs in New York City. These surveys will include an extensive questionnaire and HIV, HBV, and HCV testing. A random assignment comparison of audio-computer interviewing versus face-to-face interviewing will be embedded in the first 15 months of data collection. The proposed research will provide information of great scientific interest and public health importance regarding the dynamics of high seroprevalence HIV epidemics, the ability of IDUs to sustain risk reduction over long time periods, transitions between non-injecting and injecting drug use, and methods for improving collection of HIV risk behavior data. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ROLE OF GLYCINE DECARBOXYLASE IN HEPADNAVIRAL INFECTION Principal Investigator & Institution: Li, Jisu; Assistant Professor; Rhode Island Hospital (Providence, Ri) Providence, Ri 029034923 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2004 Summary: Hepatitis B virus is a major cause of liver cirrhosis and hepatocellular carcinoma (HCC). A better understanding of the viral life cycle may provide targets for the intervention of HBV infection, thus reducing the risk of HBV-related HCC. However, the early stages of the viral life cycle and viral-host interactions that contribute to viral infection and pathogenicity are poorly understood. This 421 exploratory proposal focuses on studies on a hepadna virus interacting protein, p120/glycine decarboxylase. We have previous found that p120 is a binding partner of
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an avian hepatitis B virus envelope protein. It is expressed only in the virus infectable tissues and its expression level is directly correlated with the cellular susceptibility to virus infection. It is expressed only in the virus infectable tissues and its expression level is directly correlated with the cellular susceptibility to virus infection. Moreover, viral mutants with an ablated p120-binding site showed reduced infectivity despite wild-type replication capacity. These findings suggest that p120 is associated with the early stage of the viral life cycle. Therefore, we plan to further establish its role in the viral life cycle by genetic approaches. Specific Aim #1 will determine if inhibition of p120 expression or function in well-differentiated duck hepatocytes will reduce susceptibility to viral infection. Specific Aim #2 will examine whether reconstitution of p120 in dedifferentiated duck hepatocytes will restore productive viral infection. In addition, we will determine if p120 is defective in Muscovy ducks, a duck species resistant to hepadnavirus. We will also explore the possibility to restore viral infection by p120 derived from a susceptible Pekin ducks. These studies will provide further information on virus-cell interactions and may lead to development of novel anti-viral strategies for prevention of HBV induced liver cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ROLE OF HBX PROTEIN IN HBV REPLICATION Principal Investigator & Institution: Schneider, Robert J.; Professor; Biochemistry; New York University School of Medicine 550 1St Ave New York, Ny 10016 Timing: Fiscal Year 2002; Project Start 01-APR-1992; Project End 31-MAR-2006 Summary: (provided by applicant): The long term objectives of this proposal are to understand the roles of the hepatitis B virus (HBV) HBx gene in viral infection. Please note that the title of this grant has been changed from "Transcription and Transformation by Hepatitis B Virus HBx Protein," to" Role of HBx protein in HBV replication" to reflect the progression of our studies on HBx. AIM 1: Molecular mechanism for human hepatitis B virus (HBV) HBx protein action. HBx activates cytoplasmic signal transduction pathways. HBx activation of the Pyk2-Src tyrosine kinase signalling pathway represents an important activity for viral replication in hepatocytic cell lines. Studies are outlined to understand the molecular mechanism for HBx activation of Pyk2-Src signal transduction, since it is tightly linked to HBx stimulation of viral replication. In addition, HBx appears to possess nuclear functions that may stimulate viral transcription. Studies will also investigate the mechanism by which HBx functions in viral transcription, including a possible role in the nucleus, and its impact on viral replication. AIM 2: Role of HBx protein in HBVreplication. Studies are proposed to determine the molecular basis for HBx activation of HBV reverse transcription and DNA replication. Model systems have been developed for delivery of hepadnavirus genomes to differentiated hepatocytic cell lines and rodent primary hepatocytes in culture, that permit viral replication in an HBx-dependent manner. Studies will investigate the role of HBx in viral replication in a biologically relevant system, focusing on HBx induction of HBV core protein phosphorylation, control of the cell cycle, and induction of nucleotide metabolism. HBx-dependent HBV replication will also be studied in primary hepatocytes prepared from mice that are deficient in genes that impact on HBV replication, including knockouts of Src and Pyk2 kinases, to better understand their importance for viral replication. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: SPECIES DIFFERENCE IN THE BIOTRANSFORMATION OF AFLATOXIN Principal Investigator & Institution: Eaton, David L.; Associate Dean for Research; Environmental and Occupational Health Studies; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2002; Project Start 01-MAY-1991; Project End 31-JUL-2004 Summary: Numerous studies have demonstrated that biologically active, natural components of the diet may confer resistance to chemical carcinogens via induction and/or inhibition of biotransformation enzymes. In particular, specific chemical components of the diet, such as flavonoids, isocyanates, glucosinolates, indoles, dithiolthiones, and polyphenols have been identified as effective inducers and/or inhibitors of carcinogen activation/detoxification pathways in animal models. There is much supporting data from human epidemiological studies on the important relationship between diet and cancer in humans, although the diversity and complexity of the diet, and uncertainty of specific exposures, in such studies makes identification of specific active components nearly impossible. Although animal models are useful for "hypothesis testing", species differences in carcinogen activation and detoxification pathways, as well as differences in gene regulation and expression in response to inducers, make extrapolation of animal data to the human situation tentative, at best. Thus, there is a need to develop model systems that utilize human cells/tissues to determine the efficacy of specific dietary components and/or putative chemoprotectant drugs to favorably modify the biotransformation of human carcinogens. One such model human carcinogen is aflatoxin B1. Aflatoxins are mycotoxins produced by the common fungal molds, Aspergillus flavus and Aspergillus parasiticus. Worldwide, aflatoxins are considered a major public health problem because of their potent carcinogenic effects. Human epidemiological data has documented that humans are susceptible to AFB-induced hepatocarcinogenesis, especially in combination with hepatitis B virus infection. However, there are large species differences in the susceptibility to aflatoxin carcinogenesis. Rats are highly sensitive, whereas mice are very resistant. The mechanism for this difference is associated with the expression of a specific enzyme, glutathione S-transferase A3-3 (mGSTA3-3), which is present in the livers of mice, but not rats. Treatment of rats with the drug, oltipraz, or the food additive, ethoxyquin, protects rats from aflatoxin-induced liver cancer. The mechanism for this protection is due to the ability of these chemicals to "turn on" a gene for a glutathione S-transferase, rGSTA5-5, that is normally not expressed in rat liver, but which efficiently detoxifies aflatoxin. Human liver tissue has very low ability to detoxify aflatoxin -- in fact, worse than the poor ability of rats. There has been considerable interest in devising a dietary or chemointervention strategy for humans that increases resistance to AFB by induction of GSTs. The long range goals of this proposal are to: 1) establish in vitro models that utilize isolated human hepatocytes in culture and human cDNA expressing yeast, to assess the efficacy of specific dietary components as putative chemoprotectors against AFB and other chemical carcinogens, and 2) complete the characterization of species differences in glutathione S-transferases with activity toward AFB-epoxide. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: STRUCTURE/FUNCTION STUDIES OF S100 PROTEINS AND P53 Principal Investigator & Institution: Weber, David J.; Associate Professor; Biochem and Molecular Biology; University of Maryland Balt Prof School Baltimore, Md 21201 Timing: Fiscal Year 2003; Project Start 01-FEB-1999; Project End 31-JAN-2007
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Summary: (provided by applicant): During the last 3 years, (i) high yields (>30 mg purified protein/liter media) of S 100B, S 100A 1, S 100A3, CAN19, mtsl, p53, p53(324393), p53(303-393), p53(303-367), hepatitis B viral protein X (HBVX), SUMO-1, Cterminal fragment of myosin IIA(1900-1961), and the HMG A box of the high mobility group protein- 1 (HMG-1) were prepared in minimal media as necessary for isotopic labeling (2H, 13C, 15N, etc). (ii) We determined the solution structures of apo-S 100B, apo-S 100A 1, calcium-bound S 100B, and calcium-bound S 100B in a complex with the negative regulatory domain of p53 (residues 367-388). (iii) We showed that dimeric S 100B is the physiologically relevant oligomerization state of S 100B, and that S 100B inhibits protein kinase C (PKC) phosphorylation of p53. (iv) We developed cellularbased assays for p53 and showed that p53 function is inhibited in tumor cell lines as a result of the calcium-dependent p53-S 100B interaction. This interaction includes both the oligomerization and negative regulatory domains at the C-terminus of p53. We plan to continue characterizing the calcium-dependent interaction of S 100B with the tumor suppressor protein p53. The effects that p53 phosphorylation, acetylation, and sumoylation have on S 100B binding will be examined. The binding of zinc to S 100B and heterodimer formation (i.e. S 100A 1/S 100B, CaN 19/S 100B and mts 1/S 100B etc.) will also be characterized. These data are necessary to determine whether covalent modifications of p53 and/or other S100B binding events affect S100B-p53 complex formation and function We will also determine the 3D structure of calcium-bound S100B complexed with a larger construct of p53 that includes both the oligomerization and the C-terminal regulatory domains of p53 (residues 324-393; Kd=24nM). Heteronuclear relaxation measurements for backbone and sidechain resonances are planned for all of the structures that we solve (or have solved) in order to clarify how calcium and p53 binding affects the dynamics of S100B (and p53). These dynamic data will be used in a search for small molecule inhibitors of the S 100B-p53 interaction. Lastly, the 3D solution structures of other proteins that bind the C-terminus of p53 will be examined including the metastasis protein 1 (mts 1), S100A3, the CaN 19 tumor suppressor, the hepatitis B viral protein (HBVX), the p53 binding domain of BLM, and the A box ofHMG-1. It will be interesting to determine whether these or other p53-binding proteins enhance and/or compete with the S 100B-p53 interaction. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: STUDIES OF THE PATHOGENIC MECHANISM OF HIV Principal Investigator & Institution: Cloyd, Miles W.; Professor; Microbiology and Immunology; University of Texas Medical Br Galveston 301 University Blvd Galveston, Tx 77555 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2004 Summary: (provided by applicant): Although there are numerous theories concerning how HIV causes depletion of CD4 lymphocytes, three appear to be the most viable. The first states that HIV causes "global immune inactivation" with the concomitant increase in activation-induced cell death of CD4 lymphocytes, leading to their eventual exhaustion. The second states that HIV retards production of new CD4 lymphocytes, leading to their eventual disappearance. The third states that HIV's pathogenic mechanism is on resting CD4 lymphocytes (non-permissive for virus replication), which come into contact with HIV-coated follicular dendritic cells or productively infected cells in lymphoid tissues and are thereby signaled, resulting in enhanced homing back to lymph nodes (LNs), after entering the blood stream, and upregulation of Fas. These cells are secondarily signaled during the homing process, which leads to induction of apoptosis in many of them. Each of these theories has unique features which allow
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certain predictions, and these will be explored in HIV+ subjects. Our overall hypothesis is that one of these theories will be the predominant mechanism of HIV depletion of CD4 lymphocytes, and three specific aims will address this hypothesis: (1) to quantitate the frequencies of dying CD4 lymphocytes in LN biopsies of HIV patients that are Ki67+ (i.e., are activated and are undergoing "activation-induced cell death") or are thymidine phosphorylase+ (i.e., are resting cells signaled by virus contact); (2) to quantitate the frequencies of new CD4 lymphocytes in the blood of HIV patients in comparison to patients infected with viruses (HBV, HCV) which do not lead to depletion of CD4 lymphocytes; and (3) to quantitate the frequencies of dying CD4 lymphocytes in LN biopsies of HIV patients which express markers of homing receptor signaling. These in vivo studies should clarify the relative importance of each of these mechanisms in HIV patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TARGETED GENE DELIVERY AND EXPRESSION IN HEPATOCYTES Principal Investigator & Institution: Wu, George Y.; Chief, Div of Gastroenterology; Medicine; University of Connecticut Sch of Med/Dnt Bb20, Mc 2806 Farmington, Ct 060302806 Timing: Fiscal Year 2002; Project Start 01-JAN-1990; Project End 31-JAN-2006 Summary: (Adapted from the Applicant's Abstract): In the previous grant period, we developed a multicomponent DNA carrier that, through the incorporation of endosomolytic peptides, is capable of releasing targeted nucleic acids directly to the cytoplasm of hepatocytes. Using multicomponent carriers, the efficiency of delivery of nucleic acids into cells was increased by 3 orders of magnitude, and the amount of DNA introduced into the nuclei in animals was increased 1 to 2 orders of magnitude compared to the originally described system. Recently, we have developed new approaches to enhance integration of targeted genes in cell culture resulting in persistent transgene expression. The objective of the current project is to take advantage of these advances to evaluate a novel therapeutic strategy against hepatitis B viral infection: transfection-mediated therapeutic selection. The hypothesis is: integrative transfection of antiviral genes will result in continuous inhibition of HBV gene expression, and block production of viral antigens. Under the pressure of host cellmediated immune response against cells bearing HBV antigens, there will be a selective survival advantage to transfected cells and their progeny. The antiviral agents are proposed to be generated from genes whose products are directed against unique features of the HBV life cycle, blocking translation, and replication. These areas distinguish viral processes from those of the mammalian host in order to achieve efficacy without toxicity. Candidates will be screened using stable HBV expression models in cell culture first to identify optimal constructs. Agents will be targeted to liver by complexation with multicomponent carriers, and also by genetic engineering into chimeric adeno-associated viral vectors all with integration enhancement capability. After optimization and comparison in an HBV cell culture model system, antiviral agents will be used to test the therapeutic approach in an animal model of HBV infection. Agents will be prepared against analogous sequences in the Woodchuck Hepatitis Virus (WHV), a homologous hepadna virus. Efficacy of long-term inhibition of HBV gene expression and replication, and evidence of selective survival advantage of cells bearing integrated antiviral genes will be determined over the time course, and optimal agents compared. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: TRANSCRIPTION ACTIVATION BY HIV, TAT, HTLV TAX & HBV PX Principal Investigator & Institution: Green, Michael R.; Professor; Molecular Medicine; Univ of Massachusetts Med Sch Worcester Office of Research Funding Worcester, Ma 01655 Timing: Fiscal Year 2002; Project Start 01-SEP-1990; Project End 30-JUN-2005 Summary: (from investigator's abstract): This is a competitive renewal application. The previous grant was for studying how the trancriptional regulatory proteins of three pathogenic viruses activate transcription, specifically, the Tat protein of human immunodeficiency virus type 1 (HIV-1), the Tax protein of human T-cell leukemia virus type 1 (HTLV-1), and the pX protein of hepatitis B virus (HBV). In this application, the applicant seeks to understand in greater detail the mechanism of action of these viral regulatory proteins and their role in viral replication and human disease. The rationale for the proposal relies heavily on two relatively new technologies. First, the chromatin immunoprecipitation (ChIP) assay, which allows for the detection of specific proteins that are physically associated with DNA in living cells. Second, the genome-wide expression analysis using high density DNA microarrays, which enables the analysis of transcription profiles of a large array of human genes. The specific aims are: (1) To understand in greater detail how HIV-1 Tat stimulates transcription in vitro and in vivo. The investigator has identified a Tat cofactor, Tat-SF1, and has shown that it is a general transcription elongation factor. A second elongation factor has been implicated, AIEF, and remains to be identified. Tat-SF1 and AIEF and the mechanisms of Tat activation in vivo will be investigated further. (2) To study how HTLV-1 Tax and HBV pX regulates DNA binding of cellular bZIP proteins. The investigator has shown that Tax and pX dramatically increase the DNA binding activity and alter the target selectivity of a wide variety of cellular proteins that possess a basic region-leucine zipper (bZIP) DNA binding domain, through promotion of dimerization. Experiments are proposed to undersstand the basis of altered DNA binding specificity, the cellular proteins involved, and details of the DNA-protein interactions. (3) To analyze how HTLV-1 Tax and HBV pX activate transcription in vivo and transform cells. To test the prediction of different models of how these proteins activate transcription, to identify cellular proteins involved in the activation, and to identify cellular genes activated that may contribute to disease. (4) To understand the mechanism of BEF action. The investigator has identified a nuclear protein BEF (for bZIP-enhancing factor) which is required for bZIP prtoein functions, work synergistically with Tax and pX. However, BEF works by a different mechanism, as a molecular chaperone. Experiments are proposed to further study the mechanism of BEF action. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: TRANSIENT GLUCOSYLATION OF GLYCOPROTEINS Principal Investigator & Institution: Parodi, Armando J.; Leloir Institute Oblgado 2490 Buenos Aires 28, Timing: Fiscal Year 2002; Project Start 15-AUG-1990; Project End 31-MAY-2004 Summary: Protein glycosylation is initiated in the endoplasmic reticulum (ER) by transfer of an oligosaccharide (Glc3Man9GlcNAc2) to nascent polypeptide chains. Processing of the oligosaccharide by glucosidases I and II yields unglucosylated oligosaccharides that are reglucosylated by the UDP-Glc:glycoprotein glucosyltransferase (GT) only if the protein moieties of glycoproteins are not properly folded, as GT behaves as a sensor of glycoprotein conformations. Interaction of
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monoglucosylated glycoproteins (created by partialdeglucosylation of the transferred compound or by GT-mediated reglucosylation) with ER lectins (calnexin and calreticulin) facilitates acquisition of the proper tertiary structures and prevents secretion of not yet properly folded species. Folding facilitation mediated by the interaction of monoglucosylated glycoproteins and ER lectins is necessary for production of infective viral particles (vesicular stomatitis virus, HIV, hepatitis B virus) and also for the viability of yeasts when under severe ER stress conditions. The long term objective of the proposal is to gain thorough information of the structural features leading to the monoglucosylated glycoprotein-lectin interaction as this knowledge will undoubtedly provide useful information for understanding and/or preventing production of the etiological agents of several diseases. Within this long term objective, the Specific Aims of the proposed research are: a) to define the structural elements exclusively exposed in misfolded glycoproteins whose recognition is required for GTmediated glucosylation; b) to define GT domains responsible for substrate donor (UDPGlc), and substrate acceptor (N-oligosaccharide) recognition and for the exclusive glucosylation of misfolded species and c) to study the possibility that folding facilitation mediated by the interaction of cruzipain, a cysteine proteinase from the protozoan parasite Trypanosoma cruzi and ER lectins could be absolutely necessary for parasite infectivity. T. cruzi is the causative agent of a disease endemic in Latin America (Chagas's disease) that affects about 16 million people. Cruzipain has been identified as one of the T. cruzi virulence factors and has been found to be the only glycoprotein interacting with ER lectins in the protozoon. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: VALIDATION AND APPLICATION OF RISK, BIOMARKERS IN HUMAN STUDIES Principal Investigator & Institution: Groopman, John D.; Associate Director of Cancer Prevention; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002; Project Start 07-APR-1993; Project End 31-MAY-2007 Summary: (provided by applicant): The goals of this Project are to develop and validate biomarkers of biologically effective dose and risk induced by environmental carcinogens. It is now axiomatic in human cancer that ambient exposures to multiple environmental carcinogens are significant factors in the development and progression of many cancer types. Thus, an understanding of the dose-response relationships between exposure and outcomes in critical targets such as DNA may characterize disease potential. While Dr. Tannenbaum's Project has a major focus on the development of novel, sensitive methods for the detection of DNA and protein adducts, this Project extends these strategies into risk-biomarker analysis. Since there are critical genetic targets in cells, such as tumor suppressor genes, for environmental carcinogens, then it is possible that these targets might prove to be useful biomarkers for risk analysis. Cooccurring environmental exposures and genetic susceptibility may modify the above dose-response effects and consequently these parameters will also be considered. The linkage between carcinogen-induced DNA damage and heritable change in genetic targets is a cornerstone of this Program Project's paradigm. Recently, the discovery that DNA from cells undergoing apoptosis and other turnover processes is found in the blood has resulted in the ability to noninvasively measure mutations in targets such as p53 offering the potential to quantify early biological effects in risk individuals. Therefore, a combined use of biologically effective dose biomarkers, susceptibility biomarkers and genetic biomarkers might reveal the subset of high risk people within a population who will benefit from targeted interventions, which is the outcome of
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studies proposed in Project 3. It is the hypothesis that levels of biomarkers of biologically effective dose in combination with gene mutations are predictive of disease outcome characterizing risk in individuals. Thus, specific aim 1 is to determine the power of p53 mutations and other genetic alterations in sera using the Short Oligonucleotide Mass Analysis (SOMA) methodology combined with aflatoxin-DNA adducts in urine to predict cancer outcome and disease risk in cohorts in rural China and West Africa. Specific aim 2 is designed to extend the investigators' observations on the high level of aflatoxin biomarkers in West African children in order to assess the impact on growth and immune status, including susceptibility to hepatitis B virus (HBV) infection. West African children, unlike adults, have elevated aflatoxin biomarker levels when infected with HBV. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: VANDERBILT ADULT AIDS CLINICAL TRIALS UNIT Principal Investigator & Institution: Haas, David W.; Associate Professor of Medicine; Medicine; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2002; Project Start 01-JAN-2000; Project End 31-DEC-2004 Summary: (adapted from applicant's abstract): An estimated 700,000 people in the United States are infected with HIV. Effective treatment of HIV infection requires prolonged administration of multiple antiretroviral agents. Incorporating clinical pharmacology expertise into the design, performance, and analysis of HIV clinical trials is therefore essential. Establishment of a main AIDS Clinic Trial Unit (ACTU) at Vanderbilt University would bring extensive expertise in clinical pharmacology to the AIDS Clinic Trials Group (ACTG). Vanderbilt ACTU investigators will participate in several studies including: inter-individual variability in response to antiretroviral therapy; drug disposition and metabolism; drug-drug interactions; tissue delivery of protease inhibitors and other drugs by membrane transporters (including Pglycoprotein); and the application of ultra-intensive CSF sampling approaches to study HIV treatment and pathogenesis in the CNS. The investigators also may apply advanced mass spectroscopy techniques to HIV clinical trials. The use of state-of-the-art clinical pharmacology strategies to HIV clinical trials may ultimately improve treatment of HIV infection and its complications, and allow therapy to be appropriately individualized. Vanderbilt University investigators also will contribute expertise to other innovative HIV-related laboratory efforts. These include: developing novel antiretroviral therapeutics; studying HIV-1 virion assembly and HIV-1 accessory proteins; developing novel HIV-related assays; understanding viral pathogenesis of AIDS-related malignancies; characterizing host-pathogen interactions in the gastrointestinal tract during AIDS; and developing strategies to optimize the design of antiretroviral agents and AIDS vaccines. The Principal Investigator leads an established HIV clinical trials program at Vanderbilt University, and the proposed ACTU incorporates a large Vanderbilt- affiliated HIV primary care clinic. Technically demanding studies will be facilitated by the Vanderbilt University General Clinical Research Center (GCRC). The proposed ACTU will not only enroll patients into ACTG clinical trials, but will provide the ACTG the ability to address important questions concerning AIDS treatment and pathogenesis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: VIRAL REPLICATION/ASSEMBL
&
HOST
FUNCTION
IN
TUMOR
VIRUS
Principal Investigator & Institution: Ahlquist, Paul G.; Professor; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2003; Project Start 29-MAY-2003; Project End 30-APR-2008 Summary: This project will extend active collaborations of the Ahlquist group with the Loeb and Lambert groups to define key aspects of virion assembly, genome replication, and virus-host interactions for two of the most important human tumor viruses, hepatitis B virus (HBV) and human papillomavirus (HPV). These experiments use integrated studies in human cells and the genetically tractable yeast Saccharomyces cerevisiae, which the Ahlquist group has pioneered as a model host to study virus replication and virus-host interactions. The project has four aims: For HBV, we will (I) Use confocal microscopy, electron microscopy and cell fractionation to define the intracellular localization, localization determinants, and interaction of the HBV structural proteins [core, reverse transcriptase, and envelope proteins (surface antigens)] when expressed singly and in selected combinations in human hepatoma cells and in yeast; (II)Use targeted and global yeast genetic screens to determine if HBV envelope protein-driven budding into endoplasmic reticulum-associated compartments in yeast depends on host cell functions, including vacuolar protein sorting and ubiquitination functions involved in crucial late steps of plasma membrane budding by retroviruses and other viruses; (III) Extend ongoing experiments to duplicate pregenomic RNA encapsidation and subsequent genome replication steps in yeast for HBV and its major laboratory model, DHBV (duck HBV), to allow study of host contributions to these replication steps in cells whose genome can be freely and systematically manipulated. For HPV, we will (IV) combine the Ahlquist lab's optimization in yeast of HPV protein expression and capsid assembly with the Lambert lab's finding that yeast replicate and stably maintain HPV genomic DNA, to determine the protein and DNA requirements for HPV genome encapsidation and infectious virion assembly in yeast. In addition to defining the assembly determinants, these studies will overcome present limitations of organotypic raft cultures to provide a more facile source of genetically manipulatable, infectious HPV virions with which to study virus entry and early infection steps in mammalian cells. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: VIRAL INDUCED HCC?
ANTIGEN
GLYCOSYLATION--MARKER
FOR
HBV
Principal Investigator & Institution: Block, Timothy M.; Professor and Director; Biochem & Molecular Pharmacol; Thomas Jefferson University Office of Research Administration Philadelphia, Pa 191075587 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2004 Summary: (provided by applicant): In this exploratory program we propose to test the hypothesis that oligosaccharides associated with serum proteins can accurately serve as biomarkers. Oligosaccharide profiles of hepatitis B surface antigens (HBsAg), purified from patient sera of different clinical populations, will be generated using novel HPLC sequencing technology that can reproducibly quantitate greater than 0.1 percent of an individual oligosaccharide in a glycan pool. Our sample population will consist of patients at risk for, or diagnosed with, hepatocellular carcinoma (HCC). The data generated will allow HBsAg oligosaccharides to be compared between different patient populations and the potential diagnostic value to be assessed. Alteration in the
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oligosaccharides associated with glycoproteins is one of the many molecular changes that accompany malignant transformations. In the case of HCC, an increase in fucosylation of secreted liver proteins is a common alteration. This increase in fucosylation has been postulated as a marker for HCC, however, the proteins of interest that show this alteration are typically found in low abundance (e.g. alpha fetoprotein). Our hypothesis is that, in cases where infection with hepatitis B virus (HBV) leads to the development of HCC, the viral glycoproteins (present up to mg/ml concentration) themselves may display aberrant oligosaccharides that could serve as early detection markers for HCC. Infection with HBV is the major etiology of HCC and, although HCC is a less common cancer in the USA, recent studies have shown that the incidence of HCC is rising both in the USA and worldwide. In addition, HCC is one of the most aggressive malignancies with prognosis being poor due to the late diagnosis. With the paucity of organ donors for liver transplantation and the small number of treatable patients (due to, in part, late diagnosis), early diagnosis will allow intervention at an earlier stage. We expect that this pilot study will firstly generate preliminary data to support the stated hypothesis; secondly, the study will allow the feasibility of a larger study to be determined, and thirdly, the parameters required to design a larger study to determine the value of oligosaccharide structures as potential markers of disease status will be obtained. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: VIRAL HEPATITIS IN CHILDREN OF INJECTION DRUG USERS Principal Investigator & Institution: Schwarz, Kathleen B.; Associate Professor; Pediatrics; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002; Project Start 30-SEP-2000; Project End 31-AUG-2004 Summary: (Applicant's Abstract) Hepatitis B virus (HBV) and hepatitis C virus (HCV) are endemic among adult injection drug users (IDUs). Children of IDUs (CIDU) are known to be at risk for HBV and HCV because of maternal-fetal transmission, and possibly, other factors as well. CIDU often live below the poverty level and - 1/3 of homeless children are CIDU. Although both poverty and the condition of being homeless are associated with low immunization rates, strategies to improve immunization for HBV in CIDU have not been systematically studied, and the epidemiology of HCV in this high-risk population has not been characterized. Therefore, the specific aims of this project are: 1) To develop a new multi-component intervention strategy (culturally adapted CD ROM-based educational materials, reminder systems, and clinic/shelter-based vaccines) to improve HBV immunization rates in CIDU and compare this strategy to conventional strategies 2) To characterize the epidemiology of HCV in CIDU. In Baltimore, we have identified three large cohorts of CIDU which are well-suited to accomplish the aims of this proposal: 1) 900 homeless children 2) 100 CIDU in the AIDS Linked to Intravenous Experience (ALIVE) study of adult IDUs and 3) 200 CIDU in the ongoing Risk, Evaluation and Assessment of Community Health (REACH) study of young IDUs. 1. In the immunization studies, we will partner with Hepatitis Foundation International (HFI) and Johns Hopkins Medical Video to adapt HFI educational materials about viral hepatitis to age- and culturally appropriate CDROM based presentations. Subjects will be randomized as to a "standard" or "special" prevention approach and ongoing critique and validation of the materials will be performed. 2. The epidemiologic studies in CIDU will include determination of HCV prevalence and will utilize an Automated Computer Assisted Self Interview to investigate injection drug use by parents and children, and other potential correlates of HCV infection among CIDU (e.g., tattooing, piercing). The novel
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approach of using a salivary anti-HCV (S-anti-HCV) assay for non-invasive screening in CIDU will be studied, after first validating the test in 60 children with chronic HCV infection. CIDU who test S-anti-HCV+ will have blood assayed for serologic markers for HCV, HBV, and human immunodeficiency virus. It has been estimated that complete eradication of hepatitis B and C infection from all children in the U.S. could save at least $200 million over the next 10 years, Preventative strategies emanating from this proposal could contribute significantly to reduction of both the high medical costs and human suffering secondary to these infections in children. 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 “hepatitis B virus” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for hepatitis B virus in the PubMed Central database: •
(-)-cis-5-fluoro-1-[2-(hydroxymethyl)-1,3-oxathiolan-5-yl]cytosine (524W91) inhibits hepatitis B virus replication in primary human hepatocytes. by Condreay LD, Condreay JP, Jansen RW, Paff MT, Averett DR.; 1996 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=163151
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A bulged region of the hepatitis B virus RNA encapsidation signal contains the replication origin for discontinuous first-strand DNA synthesis. by Nassal M, Rieger A.; 1996 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=190133
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A Defective Interference-Like Phenomenon of Human Hepatitis B Virus in Chronic Carriers. by Yuan TT, Lin MH, Chen DS, Shih C.; 1998 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=109410
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A family cluster of an immune escape variant of hepatitis B virus infecting a mother and her two fully immunized children. by Ho MS, Lu CF, Kuo J, Mau YC, Chao WH.; 1995 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=170234
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A Frequent, Naturally Occurring Mutation (P130T) of Human Hepatitis B Virus Core Antigen Is Compensatory for Immature Secretion Phenotype of Another Frequent Variant (I97L). by Yuan TT, Shih C.; 2000 May 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=112021
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 molecularly cloned hepatitis B virus produced in vitro is infectious in a chimpanzee. by Sureau C, Eichberg JW, Hubbard GB, Romet-Lemonne JL, Essex M.; 1988 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=253751
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A novel hepatitis B virus (HBV) genetic element with Rev response element-like properties that is essential for expression of HBV gene products. by Huang J, Liang TJ.; 1993 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=364819
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A novel method for efficient amplification of whole hepatitis B virus genomes permits rapid functional analysis and reveals deletion mutants in immunosuppressed patients. by Gunther S, Li BC, Miska S, Kruger DH, Meisel H, Will H.; 1995 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=189390
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A revised secondary structure model for the 3'-end of hepatitis B virus pregenomic RNA. by Kidd AH, Kidd-Ljunggren K.; 1996 Sep 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=146111
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A short linear sequence in the pre-S domain of the large hepatitis B virus envelope protein required for virion formation. by Bruss V.; 1997 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=230238
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A Single Amino Acid in the Reverse Transcriptase Domain of Hepatitis B Virus Affects Virus Replication Efficiency. by Lin X, Yuan ZH, Wu L, Ding JP, Wen YM.; 2001 Dec 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=114769
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A Small Molecule Inhibits and Misdirects Assembly of Hepatitis B Virus Capsids. by Zlotnick A, Ceres P, Singh S, Johnson JM.; 2002 May 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=136179
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A synthetic peptide vaccine involving the product of the pre-S(2) region of hepatitis B virus DNA: protective efficacy in chimpanzees. by Itoh Y, Takai E, Ohnuma H, Kitajima K, Tsuda F, Machida A, Mishiro S, Nakamura T, Miyakawa Y, Mayumi M.; 1986 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=387097
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A trans-activator function is generated by integration of hepatitis B virus preS/S sequences in human hepatocellular carcinoma DNA. by Caselmann WH, Meyer M, Kekule AS, Lauer U, Hofschneider PH, Koshy R.; 1990 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=53815
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A transcription initiation site for the hepatitis B virus X gene is directed by the promoter-binding protein. by Yaginuma K, Nakamura I, Takada S, Koike K.; 1993 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=237576
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A Truncated Mutant (Residues 58-140) of the Hepatitis B Virus X Protein Retains Transactivation Function. by Kumar V, Jayasuryan N, Kumar R.; 1996 May 28; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=39302
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Absence of hepatitis B virus (HBV) DNA in children born after exposure of their mothers to HBV during in vitro fertilization. by Quint WG, Fetter WP, van Os HC, Heijtink RA.; 1994 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=267195
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Activation and Inhibition of Cellular Calcium and Tyrosine Kinase Signaling Pathways Identify Targets of the HBx Protein Involved in Hepatitis B Virus Replication. by Bouchard MJ, Puro RJ, Wang L, Schneider RJ.; 2003 Jul 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=161925
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Activation of hepatitis B virus S promoter by the viral large surface protein via induction of stress in the endoplasmic reticulum. by Xu Z, Jensen G, Yen TS.; 1997 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=192084
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Affinity capture-polymerase chain reaction for quantitation of hepatitis B virus DNA. by Wang CH, Tschen SY.; 1994 Nov 11; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=308538
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Alpha interferon suppresses hepatitis B virus enhancer activity and reduces viral gene transcription. by Tur-Kaspa R, Teicher L, Laub O, Itin A, Dagan D, Bloom BR, Shafritz DA.; 1990 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=249322
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Amplification of Full-Length Hepatitis B Virus Genomes from Samples from Patients with Low Levels of Viremia: Frequency and Functional Consequences of PCRIntroduced Mutations. by Gunther S, Sommer G, Von Breunig F, Iwanska A, Kalinina T, Sterneck M, Will H.; 1998 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=104572
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An in vitro system for infection with hepatitis B virus that uses primary human fetal hepatocytes. by Ochiya T, Tsurimoto T, Ueda K, Okubo K, Shiozawa M, Matsubara K.; 1989 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=286807
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An RNA stem-loop structure directs hepatitis B virus genomic RNA encapsidation. by Pollack JR, Ganem D.; 1993 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=237666
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Antibodies to the RNase H domain of hepatitis B virus P protein are associated with ongoing viral replication. by Weimer T, Schodel F, Jung MC, Pape GR, Alberti A, Fattovich G, Beljaars H, van Eerd PM, Will H.; 1990 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=248626
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Antigenic Diversity of Hepatitis B Virus Strains of Genotype F in Amerindians and Other Population Groups from Venezuela. by Blitz L, Pujol FH, Swenson PD, Porto L,
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Atencio R, Araujo M, Costa L, Monsalve DC, Torres JR, Fields HA, Lambert S, Van Geyt C, Norder H, Magnius LO, Echevarria JM, Stuyver L.; 1998 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=104602 •
Antiviral l-Nucleosides Specific for Hepatitis B Virus Infection. by Bryant ML, Bridges EG, Placidi L, Faraj A, Loi AG, Pierra C, Dukhan D, Gosselin G, Imbach JL, Hernandez B, Juodawlkis A, Tennant B, Korba B, Cote P, Marion P, Cretton-Scott E, Schinazi RF, Sommadossi JP.; 2001 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=90266
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Assessment of Hepatitis B Virus DNA Stability in Serum by the Chiron Quantiplex Branched-DNA Assay. by Krajden M, Comanor L, Rifkin O, Grigoriew A, Minor JM, Kapke GF.; 1998 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=104546
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Assessment of the COBAS Amplicor HBV Monitor Test for Quantitation of Serum Hepatitis B Virus DNA Levels. by Lopez VA, Bourne EJ, Lutz MW, Condreay LD.; 2002 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=130700
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Automated Multiplex Assay System for Simultaneous Detection of Hepatitis B Virus DNA, Hepatitis C Virus RNA, and Human Immunodeficiency Virus Type 1 RNA. by Meng Q, Wong C, Rangachari A, Tamatsukuri S, Sasaki M, Fiss E, Cheng L, Ramankutty T, Clarke D, Yawata H, Sakakura Y, Hirose T, Impraim C.; 2001 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=88264
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Automated Quantitative Analysis of Hepatitis B Virus DNA by Using the Cobas Amplicor HBV Monitor Test. by Noborg U, Gusdal A, Pisa EK, Hedrum A, Lindh M.; 1999 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=85382
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Baculovirus Expression of Chimeric Hepatitis B Virus Core Particles with Hepatitis E Virus Epitopes and Their Use in a Hepatitis E Immunoassay. by Touze A, Enogat N, Buisson Y, Coursaget P.; 1999 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=84333
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Biochemical and immunological characterization of the duck hepatitis B virus envelope proteins. by Schlicht HJ, Kuhn C, Guhr B, Mattaliano RJ, Schaller H.; 1987 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=283693
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Biosynthesis of hepatitis B virus e antigen: directed mutagenesis of the putative aspartyl protease site. by Jean-Jean O, Salhi S, Carlier D, Elie C, De Recondo AM, Rossignol JM.; 1989 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=251224
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Carboxypeptidase D Is an Avian Hepatitis B Virus Receptor. by Tong S, Li J, Wands JR.; 1999 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=112890
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Changes in the Antigenicity of a Hepatitis B Virus Mutant Stemming from Lamivudine Therapy. by Chen WN, Oon CJ.; 2000 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89956
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Characteristics of Hepatitis B Virus Isolates of Genotype G and Their Phylogenetic Differences from the Other Six Genotypes (A through F). by Kato H, Orito E, Gish RG, Sugauchi F, Suzuki S, Ueda R, Miyakawa Y, Mizokami M.; 2002 Jun 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=136184
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Characterization and genetic analysis of alternatively spliced transcripts of hepatitis B virus in infected human liver tissues and transfected HepG2 cells. by Wu HL, Chen PJ, Tu SJ, Lin MH, Lai MY, Chen DS.; 1991 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=239971
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Characterization of a Conformational Epitope on Hepatitis B Virus Core Antigen and Quasiequivalent Variations in Antibody Binding. by Conway JF, Watts NR, Belnap DM, Cheng N, Stahl SJ, Wingfield PT, Steven AC.; 2003 Jun 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=155010
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Characterization of hepatitis B virus capsid particle assembly in Xenopus oocytes. by Zhou S, Yang SQ, Standring DN.; 1992 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=241070
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Characterization of humoral and CD4+ cellular responses after genetic immunization with retroviral vectors expressing different forms of the hepatitis B virus core and e antigens. by Sallberg M, Townsend K, Chen M, O'Dea J, Banks T, Jolly DJ, Chang SM, Lee WT, Milich DR.; 1997 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=191766
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Characterization of Novel Human Hepatoma Cell Lines with Stable Hepatitis B Virus Secretion for Evaluating New Compounds against Lamivudine- and PenciclovirResistant Virus. by Fu L, Cheng YC.; 2000 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=90212
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Characterization of Nuclear RNases That Cleave Hepatitis B Virus RNA near the La Protein Binding Site. by Heise T, Guidotti LG, Chisari FV.; 2001 Aug 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=114415
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Characterization of the Antiviral Effect of 2[prime prime or minute],3[prime prime or minute]-Dideoxy-2[prime prime or minute], 3[prime prime or minute]-Didehydro[beta]-l-5-Fluorocytidine in the Duck Hepatitis B Virus Infection Model. by Le Guerhier F, Pichoud C, Guerret S, Chevallier M, Jamard C, Hantz O, Li XY, Chen SH, King I, Trepo C, Cheng YC, Zoulim F.; 2000 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89636
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Characterization of Unusual Escape Variants of Hepatitis B Virus Isolated from a Hepatitis B Surface Antigen-Negative Subject. by Grethe S, Monazahian M, Bohme I, Thomssen R.; 1998 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=110046
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cis rescue of a mutated reverse transcriptase gene of human hepatitis B virus by creation of an internal ATG. by Roychoudhury S, Shih C.; 1990 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=249218
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Clinical and Virological Aspects of Blood Donors Infected with Hepatitis B Virus Genotypes B and C. by Kao JH, Chen PJ, Lai MY, Chen DS.; 2002 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=120125
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Cloning and Characterization of a Novel Hepatitis B Virus x Binding Protein That Inhibits Viral Replication. by Melegari M, Scaglioni PP, Wands JR.; 1998 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=109461
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Coexistence of Two Distinct Secretion Mutations (P5T and I97L) in Hepatitis B Virus Core Produces a Wild-Type Pattern of Secretion. by Chua PK, Wen YM, Shih C.; 2003 Jul 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=164791
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Comparative Evaluation of Semiautomated COBAS AMPLICOR Hepatitis B Virus (HBV) MONITOR Test and Manual Microwell Plate-Based AMPLICOR HBV MONITOR Test. by Marin IJ, Poljak M, Seme K, Meglic-Volkar J, Maticic M, Lesnicar G, Brinovec V.; 2001 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=87814
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Comparison of hepatitis B virus DNA extractions from serum by the QIAamp blood kit, GeneReleaser, and the phenol-chloroform method. by Kramvis A, Bukofzer S, Kew MC.; 1996 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229395
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Comparison of methods for detection of hepatitis B virus DNA. by Zaaijer HL, ter Borg F, Cuypers HT, Hermus MC, Lelie PN.; 1994 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=263947
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Comparison of methods for extraction of nucleic acid from hemolytic serum for PCR amplification of hepatitis B virus DNA sequences. by Klein A, Barsuk R, Dagan S, Nusbaum O, Shouval D, Galun E.; 1997 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229868
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Comparison of Sequence Analysis and the INNO-LiPA HBV DR Line Probe Assay for Detection of Lamivudine-Resistant Hepatitis B Virus Strains in Patients under Various Clinical Conditions. by Aberle SW, Kletzmayr J, Watschinger B, Schmied B, Vetter N, Puchhammer-Stockl E.; 2001 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=88061
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Comparison of the Second-Generation Digene Hybrid Capture Assay with the Branched-DNA Assay for Measurement of Hepatitis B Virus DNA in Serum. by Ho SK, Chan TM, Cheng IK, Lai KN.; 1999 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=85256
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Comparison of Three Different Sensitive Assays for Hepatitis B Virus DNA in Monitoring of Responses to Antiviral Therapy. by Chan HL, Leung NW, Lau TC, Wong ML, Sung JJ.; 2000 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=87356
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Complete hepatitis B virus genome analysis in HBsAg positive mothers and their infants with fulminant hepatitis B. by Friedt M, Gerner P, Wintermeyer P, Wirth S.; 2004; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=425580
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Cys residues of the hepatitis B virus capsid protein are not essential for the assembly of viral core particles but can influence their stability. by Zhou S, Standring DN.; 1992 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=289095
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Cytokine-Sensitive Replication of Hepatitis B Virus in Immortalized Mouse Hepatocyte Cultures. by Pasquetto V, Wieland SF, Uprichard SL, Tripodi M, Chisari FV.; 2002 Jun 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=137053
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Cytotoxic T lymphocytes inhibit hepatitis B virus gene expression by a noncytolytic mechanism in transgenic mice. by Guidotti LG, Ando K, Hobbs MV, Ishikawa T, Runkel L, Schreiber RD, Chisari FV.; 1994 Apr 26; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=43662
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DDB2 Induces Nuclear Accumulation of the Hepatitis B Virus X Protein Independently of Binding to DDB1. by Nag A, Datta A, Yoo K, Bhattacharyya D, Chakrabortty A, Wang X, Slagle BL, Costa RH, Raychaudhuri P.; 2001 Nov 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=114612
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Defective hepatitis B virus particles are generated by packaging and reverse transcription of spliced viral RNAs in vivo. by Terre S, Petit MA, Brechot C.; 1991 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=249055
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Degenerate Immunogenicity of an HLA-A2-Restricted Hepatitis B Virus Nucleocapsid Cytotoxic T-Lymphocyte Epitope That Is Also Presented by HLA-B51. by Thimme R, Chang KM, Pemberton J, Sette A, Chisari FV.; 2001 Apr 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=114890
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Deletions in the hepatitis B virus small envelope protein: effect on assembly and secretion of surface antigen particles. by Prange R, Nagel R, Streeck RE.; 1992 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=241459
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Detection and Sequence Analysis of Hepatitis B Virus Integration in Peripheral Blood Mononuclear Cells. by Laskus T, Radkowski M, Wang LF, Nowicki M, Rakela J.; 1999 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=103945
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Detection of Duck Hepatitis B Virus DNA on Filter Paper by PCR and SYBR Green Dye-Based Quantitative PCR. by Wang CY, Giambrone JJ, Smith BF.; 2002 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=120600
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Detection of Hepatitis B Virus DNA in Sera from Patients with Chronic Hepatitis B Virus Infection by DNA Microarray Method. by Kawaguchi K, Kaneko S, Honda M, Kawai HF, Shirota Y, Kobayashi K.; 2003 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=153866
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Detection of Hepatitis B Virus Infection in Wild-Born Chimpanzees (Pan troglodytes verus): Phylogenetic Relationships with Human and Other Primate Genotypes. by MacDonald DM, Holmes EC, Lewis JC, Simmonds P.; 2000 May 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=111941
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Detection of serum hepatitis B virus DNA in patients with chronic hepatitis using the polymerase chain reaction assay. by Kaneko S, Miller RH, Feinstone SM, Unoura M, Kobayashi K, Hattori N, Purcell RH.; 1989 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=286454
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Detection of the Hepatitis B Virus X Protein (HBx) Antigen and Anti-HBx Antibodies in Cases of Human Hepatocellular Carcinoma. by Hwang GY, Lin CY, Huang LM, Wang YH, Wang JC, Hsu CT, Yang SS, Wu CC.; 2003 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=309044
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Development of a Quantitative Real-Time Detection Assay for Hepatitis B Virus DNA and Comparison with Two Commercial Assays. by Pas SD, Fries E, De Man RA, Osterhaus AD, Niesters HG.; 2000 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=87141
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Differential Regulation of Hepatitis B Virus Gene Expression by the Sp1 Transcription Factor. by Li J, Ou JH.; 2001 Sep 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=115085
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Differential regulation of the pre-C and pregenomic promoters of human hepatitis B virus by members of the nuclear receptor superfamily. by Yu X, Mertz JE.; 1997 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=230240
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Differentiation-specific transcriptional regulation of the hepatitis B virus large surface antigen gene in human hepatoma cell lines. by Raney AK, Milich DR, Easton AJ, McLachlan A.; 1990 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=249397
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Digoxigenin-labeled probes for the detection of hepatitis B virus DNA in serum. by Guo KJ, Bowden DS.; 1991 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=269809
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Direct Association and Nuclear Import of the Hepatitis B Virus X Protein with the NF-[kappa]B Inhibitor I[kappa]B[alpha]. by Weil R, Sirma H, Giannini C, Kremsdorf D, Bessia C, Dargemont C, Brechot C, Israel A.; 1999 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=84605
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Direct detection of hepatitis B virus from dried blood spots by polymerase chain reaction amplification. by Gupta BP, Jayasuryan N, Jameel S.; 1992 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=265415
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Direct method for detecting small quantities of hepatitis B virus DNA in serum and plasma using the polymerase chain reaction. by Zeldis JB, Lee JH, Mamish D, Finegold DJ, Sircar R, Ling Q, Knudsen PJ, Kuramoto IK, Mimms LT.; 1989 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=304015
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Distinct Modes of Regulation of Transcription of Hepatitis B Virus by the Nuclear Receptors HNF4[alpha] and COUP-TF1. by Yu X, Mertz JE.; 2003 Feb 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=141100
74
Hepatitis B Virus
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Distribution of Hepatitis B Virus Genotypes among American Blood Donors Determined with a PreS2 Epitope Enzyme-Linked Immunosorbent Assay Kit. by Moriya T, Kuramoto IK, Yoshizawa H, Holland PV.; 2002 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=120221
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Distribution of Hepatitis B Virus Genotypes in Two Different Pediatric Populations from Argentina. by Mbayed VA, Lopez JL, Telenta PF, Palacios G, Badia I, Ferro A, Galoppo C, Campos R.; 1998 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105331
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Duck hepatitis B virus (DHBV) particles produced by transient expression of DHBV DNA in a human hepatoma cell line are infectious in vitro. by Pugh JC, Yaginuma K, Koike K, Summers J.; 1988 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=253480
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Duck Hepatitis B Virus Expresses a Regulatory HBx-Like Protein from a Hidden Open Reading Frame. by Chang SF, Netter HJ, Hildt E, Schuster R, Schaefer S, Hsu YC, Rang A, Will H.; 2001 Jan 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=113909
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Duck hepatitis B virus replicates in the yolk sac of developing embryos. by Tagawa M, Robinson WS, Marion PL.; 1987 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=283692
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Effect of Multiple Freeze-Thaw Cycles on Hepatitis B Virus DNA and Hepatitis C Virus RNA Quantification as Measured with Branched-DNA Technology. by Krajden M, Minor JM, Rifkin O, Comanor L.; 1999 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=84922
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Effect of oxetanocin G, a novel nucleoside analog, on DNA synthesis by hepatitis B virus virions. by Nagahata T, Kitagawa M, Matsubara K.; 1994 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=284529
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Effects of a naturally occurring mutation in the hepatitis B virus basal core promoter on precore gene expression and viral replication. by Buckwold VE, Xu Z, Chen M, Yen TS, Ou JH.; 1996 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=190601
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Effects of mutations within and adjacent to the terminal repeats of hepatitis B virus pregenomic RNA on viral DNA synthesis. by Perri S, Ganem D.; 1997 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=192307
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Efficacies of Entecavir against Lamivudine-Resistant Hepatitis B Virus Replication and Recombinant Polymerases In Vitro. by Levine S, Hernandez D, Yamanaka G, Zhang S, Rose R, Weinheimer S, Colonno RJ.; 2002 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=127388
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Efficacy of the Carbocyclic 2[prime prime or minute]-Deoxyguanosine Nucleoside BMS-200475 in the Woodchuck Model of Hepatitis B Virus Infection. by Genovesi EV, Lamb L, Medina I, Taylor D, Seifer M, Innaimo S, Colonno RJ, Standring DN, Clark JM.; 1998 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=106024
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Efficient Extraction of Virus DNA by NucliSens Extractor Allows Sensitive Detection of Hepatitis B Virus by PCR. by Gobbers E, Oosterlaken TA, van Bussel MJ, Melsert R, Kroes AC, Claas EC.; 2001 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=88546
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Endocytosis of Hepatitis B Immune Globulin into Hepatocytes Inhibits the Secretion of Hepatitis B Virus Surface Antigen and Virions. by Schilling R, Ijaz S, Davidoff M, Lee JY, Locarnini S, Williams R, Naoumov NV.; 2003 Aug 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=167249
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Enhanced replication of a hepatitis B virus mutant associated with an epidemic of fulminant hepatitis. by Hasegawa K, Huang J, Rogers SA, Blum HE, Liang TJ.; 1994 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=236623
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Enhancement of Hepatitis B Virus Infection by Noninfectious Subviral Particles. by Bruns M, Miska S, Chassot S, Will H.; 1998 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=124627
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Enhancement of Hepatitis B Virus Replication by Its X Protein in Transgenic Mice. by Xu Z, Yen TS, Wu L, Madden CR, Tan W, Slagle BL, Ou JH.; 2002 Mar 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=153824
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Enhancer I Predominance in Hepatitis B Virus Gene Expression. by Doitsh G, Shaul Y.; 2004 Feb 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=344184
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European Proficiency Testing Program for Molecular Detection and Quantitation of Hepatitis B Virus DNA. by Valentine-Thon E, van Loon AM, Schirm J, Reid J, Klapper PE, Cleator GM.; 2001 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=88557
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Evaluation of a New Rapid Test for the Combined Detection of Hepatitis B Virus Surface Antigen and Hepatitis B Virus e Antigen. by Clement F, Dewint P, LerouxRoels G.; 2002 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=154615
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Evaluation of enzyme immunoassay for hepatitis B virus DNA based on anti-doublestranded DNA. by Garcia F Jr, Garcia F, Bernal MC, Leyva A, Piedrola G, Maroto MC.; 1995 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=227958
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Evaluation of Quantitative PCR and Branched-Chain DNA Assay for Detection of Hepatitis B Virus DNA in Sera from Hepatocellular Carcinoma and Liver Transplant Patients. by Chen T, Luk JM, Cheung ST, Yu WC, Fan ST.; 2000 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=86641
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Evaluation of SHARP signal system for enzymatic detection of amplified hepatitis B virus DNA. by Valentine-Thon E.; 1995 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=227970
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Evaluation of the INNO-LiPA HBV Genotyping Assay for Determination of Hepatitis B Virus Genotype. by Osiowy C, Giles E.; 2003 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=308976
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Evaluation of Two New Automated Assays for Hepatitis B Virus Surface Antigen (HBsAg) Detection: IMMULITE HBsAg and IMMULITE 2000 HBsAg. by Weber B, Dengler T, Berger A, Doerr HW, Rabenau H.; 2003 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=149549
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Evidence for a base-paired region of hepatitis B virus pregenome encapsidation signal which influences the patterns of precore mutations abolishing HBe protein expression. by Tong SP, Li JS, Vitvitski L, Kay A, Treepo C.; 1993 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=237970
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Evidence for increased in vitro recombination with insertion of human hepatitis B virus DNA. by Hino O, Tabata S, Hotta Y.; 1991 Oct 15; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=52691
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Evidence that a capped oligoribonucleotide is the primer for duck hepatitis B virus plus-strand DNA synthesis. by Lien JM, Aldrich CE, Mason WS.; 1986 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=252719
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Evidence that the 5[prime prime or minute]-End Cap Structure Is Essential for Encapsidation of Hepatitis B Virus Pregenomic RNA. by Jeong JK, Yoon GS, Ryu WS.; 2000 Jun 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=112035
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Export of hepatitis B virus RNA on a Rev-like pathway: inhibition by the regenerating liver inhibitory factor IkappaB alpha. by Roth J, Dobbelstein M.; 1997 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=192368
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Expression and replication of the hepatitis B virus genome under foreign promoter control. by Junker M, Galle P, Schaller H.; 1987 Dec 23; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=339934
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Expression of cloned hepatitis B virus DNA in human cell cultures. by Hirschman SZ, Price P, Garfinkel E, Christman J, Acs G.; 1980 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=350090
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Expression of Functional Hepatitis B Virus Polymerase in Yeast Reveals it to be the Sole Viral Protein Required for Correct Initiation of Reverse Transcription. by Tavis JE, Ganem D.; 1993 May 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=46455
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Expression of hepatitis B virus core antigen gene in Saccharomyces cerevisiae: synthesis of two polypeptides translated from different initiation codons. by Miyanohara A, Imamura T, Araki M, Sugawara K, Ohtomo N, Matsubara K.; 1986 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=253055
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Expression of hepatitis B virus S gene by herpes simplex virus type 1 vectors carrying alpha- and beta-regulated gene chimeras. by Shih MF, Arsenakis M, Tiollais P, Roizman B.; 1984 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=391813
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Expression of Hepatitis B Virus X Protein Does Not Alter the Accumulation of Spontaneous Mutations in Transgenic Mice. by Madden CR, Finegold MJ, Slagle BL.; 2000 Jun 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=110881
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Expression of the hepatitis B virus core gene in vitro and in vivo. by Weimer T, Salfeld J, Will H.; 1987 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=255887
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Expression of the P-protein of the human hepatitis B virus in a vaccinia virus system and detection of the nucleocapsid-associated P-gene product by radiolabelling at newly introduced phosphorylation sites. by Bartenschlager R, Kuhn C, Schaller H.; 1992 Jan 25; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=310354
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Expression of the precore region of an avian hepatitis B virus is not required for viral replication. by Chang C, Enders G, Sprengel R, Peters N, Varmus HE, Ganem D.; 1987 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=255918
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False-positive results with hepatitis B virus DNA dot-hybridization in hepatitis B surface antigen-negative specimens. by Diegutis PS, Keirnan E, Burnett L, Nightingale BN, Cossart YE.; 1986 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=362842
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Formation of a Functional Hepatitis B Virus Replication Initiation Complex Involves a Major Structural Alteration in the RNA Template. by Beck J, Nassal M.; 1998 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=109213
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Free and integrated forms of hepatitis B virus DNA in human hepatocellular carcinoma cells (PLC/342) propagated in nude mice. by Imai M, Hoshi Y, Okamoto H, Matsui T, Tsurimoto T, Matsubara K, Miyakawa Y, Mayumi M.; 1987 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=255955
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Functional Characterization of Naturally Occurring Variants of Human Hepatitis B Virus Containing the Core Internal Deletion Mutation. by Yuan TT, Lin MH, Qiu SM, Shih C.; 1998 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=109512
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Functional characterization of the interferon regulatory element in the enhancer 1 region of the hepatitis B virus genome. by Alcantara FF, Tang H, McLachlan A.; 2002 May 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=113846
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Functions of the internal pre-S domain of the large surface protein in hepatitis B virus particle morphogenesis. by Bruss V, Vieluf K.; 1995 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=189574
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Generation of Replication-Competent Hepatitis B Virus Nucleocapsids in Insect Cells. by Seifer M, Hamatake R, Bifano M, Standring DN.; 1998 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=109721
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Generation of Stable Cell Lines Expressing Lamivudine-Resistant Hepatitis B Virus for Antiviral-Compound Screening. by Walters KA, Tipples GA, Allen MI, Condreay LD, Addison WR, Tyrrell L.; 2003 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=155849
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Genome Replication, Virion Secretion, and e Antigen Expression of Naturally Occurring Hepatitis B Virus Core Promoter Mutants. by Parekh S, Zoulim F, Ahn SH, Tsai A, Li J, Kawai S, Khan N, Trepo C, Wands J, Tong S.; 2003 Jun 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=156182
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Genotypes and Clinical Phenotypes of Hepatitis B Virus in Patients with Chronic Hepatitis B Virus Infection. by Kao JH, Chen PJ, Lai MY, Chen DS.; 2002 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=140384
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Genotyping by multiplex polymerase chain reaction for detection of endemic hepatitis B virus transmission. by Repp R, Rhiel S, Heermann KH, Schaefer S, Keller C, Ndumbe P, Lampert F, Gerlich WH.; 1993 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=262885
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Glucagon Treatment Interferes with an Early Step of Duck Hepatitis B Virus Infection. by Hild M, Weber O, Schaller H.; 1998 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=109694
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Hepatitis B Virus Genotype C Takes a More Aggressive Disease Course Than Hepatitis B Virus Genotype B in Hepatitis B e Antigen-Positive Patients. by Chan HL, Wong ML, Hui AY, Hung LC, Chan FK, Sung JJ.; 2003 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=150268
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Hepatitis D Virus Genotypes in Intravenous Drug Users in Taiwan: Decreasing Prevalence and Lack of Correlation with Hepatitis B Virus Genotypes. by Kao JH, Chen PJ, Lai MY, Chen DS.; 2002 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=120675
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Hepatocyte Nuclear Factor 3[beta] Inhibits Hepatitis B Virus Replication In Vivo. by Banks KE, Anderson AL, Tang H, Hughes DE, Costa RH, McLachlan A.; 2002 Dec 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=136732
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High Prevalence of Hepatitis B Virus Pre-S Mutant in Countries Where It Is Endemic and Its Relationship with Genotype and Chronicity. by Huy TT, Ushijima H, Maung Win K, Luengrojanakul P, Krishna Shrestha P, Zhong ZH, Smirnov AV, Casanovas Taltavull T, Sata T, Abe K.; 2003 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=308995
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High-level hepatitis B virus replication in transgenic mice. by Guidotti LG, Matzke B, Schaller H, Chisari FV.; 1995 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=189513
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HLA class I-restricted human cytotoxic T cells recognize endogenously synthesized hepatitis B virus nucleocapsid antigen. by Bertoletti A, Ferrari C, Fiaccadori F, Penna A, Margolskee R, Schlicht HJ, Fowler P, Guilhot S, Chisari FV.; 1991 Dec 1; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=52945
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Horizontal Transmission of a Hepatitis B Virus Surface Antigen Mutant. by Chen WN, Oon CJ, Koh S.; 2000 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=86257
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Hsp90 is Required for the Activity of a Hepatitis B Virus Reverse Transcriptase. by Hu J, Seeger C.; 1996 Feb 6; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=40030
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Human Hepatitis B Virus Polymerase Interacts with the Molecular Chaperonin Hsp60. by Park SG, Jung G.; 2001 Aug 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=114424
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Human Immunodeficiency Virus (HIV) Type 1 Reverse Transcriptase Resistance Mutations in Hepatitis B Virus (HBV)-HIV-Coinfected Patients Treated for HBV Chronic Infection Once Daily with 10 Milligrams of Adefovir Dipivoxil Combined with Lamivudine. by Delaugerre C, Marcelin AG, Thibault V, Peytavin G, Bombled T, Bochet MV, Katlama C, Benhamou Y, Calvez V.; 2002 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=127167
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Hybrid hepatitis B virus nucleocapsid bearing an immunodominant region from hepatitis B virus surface antigen. by Borisova G, Arya B, Dislers A, Borschukova O, Tsibinogin V, Skrastina D, Eldarov MA, Pumpens P, Skryabin KG, Grens E.; 1993 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=237728
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Hydrodynamic injection of viral DNA: A mouse model of acute hepatitis B virus infection. by Yang PL, Althage A, Chung J, Chisari FV.; 2002 Oct 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=129782
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Identification of a Hepatitis B Virus Genome in Wild Chimpanzees (Pan troglodytes schweinfurthi) from East Africa Indicates a Wide Geographical Dispersion among Equatorial African Primates. by Vartanian JP, Pineau P, Henry M, Hamilton WD, Muller MN, Wrangham RW, Wain-Hobson S.; 2002 Nov 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=136620
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Identification of Different States of Hepatitis B Virus Infection with a Quantitative PCR Assay. by Kessler HH, Preininger S, Stelzl E, Daghofer E, Santner BI, Marth E, Lackner H, Stauber RE.; 2000 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=95865
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Identification of hepatitis B virus indigenous to chimpanzees. by Hu X, Margolis HS, Purcell RH, Ebert J, Robertson BH.; 2000 Feb 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=26492
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Identification of Multiple Transcription Factors, HLF, FTF, and E4BP4, Controlling Hepatitis B Virus Enhancer II. by Ishida H, Ueda K, Ohkawa K, Kanazawa Y, Hosui A, Nakanishi F, Mita E, Kasahara A, Sasaki Y, Hori M, Hayashi N.; 2000 Feb 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=111458
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Identification of SRPK1 and SRPK2 as the Major Cellular Protein Kinases Phosphorylating Hepatitis B Virus Core Protein. by Daub H, Blencke S, Habenberger P, Kurtenbach A, Dennenmoser J, Wissing J, Ullrich A, Cotten M.; 2002 Aug 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=155132
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Immunogenicity and Tolerogenicity of Hepatitis B Virus Structural and Nonstructural Proteins: Implications for Immunotherapy of Persistent Viral Infections. by Kakimi K, Isogawa M, Chung J, Sette A, Chisari FV.; 2002 Sep 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=136410
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Improved Detection of Hepatitis B Virus Surface Antigen by a New Rapid Automated Assay. by Weber B, Bayer A, Kirch P, Schluter V, Schlieper D, Melchior W.; 1999 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=85302
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Improvement of hepatitis B virus DNA vaccines by plasmids coexpressing hepatitis B surface antigen and interleukin-2. by Chow YH, Huang WL, Chi WK, Chu YD, Tao MH.; 1997 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=191037
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In vitro hepatitis B virus infection of human bone marrow cells. by Zeldis JB, Mugishima H, Steinberg HN, Nir E, Gale RP.; 1986 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=423568
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In vitro propagation of human hepatitis B virus in a rat hepatoma cell line. by Shih CH, Li LS, Roychoudhury S, Ho MH.; 1989 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=297831
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In Vitro Susceptibilities of Wild-Type or Drug-Resistant Hepatitis B Virus to ([minus sign])-[beta]-d-2,6-Diaminopurine Dioxolane and 2[prime prime or minute]-Fluoro-5Methyl-[beta]-l-Arabinofuranosyluracil. by Chin R, Shaw T, Torresi J, Sozzi V, Trautwein C, Bock T, Manns M, Isom H, Furman P, Locarnini S.; 2001 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=90683
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In vivo activity of the hepatitis B virus core promoter: tissue specificity and temporal regulation. by Billet O, Grimber G, Levrero M, Seye KA, Briand P, Joulin V.; 1995 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=189474
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In Vivo Regulation of Hepatitis B Virus Replication by Peroxisome Proliferators. by Guidotti LG, Eggers CM, Raney AK, Chi SY, Peters JM, Gonzalez FJ, McLachlan A.; 1999 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=113093
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Inducible expression of human hepatitis B virus (HBV) in stably transfected hepatoblastoma cells: a novel system for screening potential inhibitors of HBV replication. by Ladner SK, Otto MJ, Barker CS, Zaifert K, Wang GH, Guo JT, Seeger C, King RW.; 1997 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=163991
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Infection Process of the Hepatitis B Virus Depends on the Presence of a Defined Sequence in the Pre-S1 Domain. by Le Seyec J, Chouteau P, Cannie I, GuguenGuillouzo C, Gripon P.; 1999 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=104448
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Influence of a Putative Intermolecular Interaction between Core and the Pre-S1 Domain of the Large Envelope Protein on Hepatitis B Virus Secretion. by Le Pogam S, Shih C.; 2002 Jul 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=136289
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Inhibition of Duck Hepatitis B Virus Replication by 9-(2Phosphonylmethoxyethyl)adenine, an Acyclic Phosphonate Nucleoside Analogue. by Nicoll AJ, Colledge DL, Toole JJ, Angus PW, Smallwood RA, Locarnini SA.; 1998 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=106011
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Inhibition of episomal hepatitis B virus DNA in vitro by 2,4-diamino-7- (2-deoxy-2by Ojwang JO, fluoro-beta-D-arabinofuranosyl)-pyrrolo[2,3-d]pyrimidine. Bhattacharya BK, Marshall HB, Korba BE, Revankar GR, Rando RF.; 1995 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=162987
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Inhibition of hepatitis B virus in tissue culture by alpha interferon. by Davis MG, Jansen RW.; 1994 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=188309
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Inhibition of Hepatitis B Virus Replication by Interferon Requires Proteasome Activity[dagger]. by Robek MD, Wieland SF, Chisari FV.; 2002 Apr 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=136040
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Inhibition of Hepatitis B Virus Replication by the Interferon-Inducible MxA Protein. by Gordien E, Rosmorduc O, Peltekian C, Garreau F, Brechot C, Kremsdorf D.; 2001 Mar 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=115893
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Inhibition of Hepatitis B Virus Replication during Adenovirus and Cytomegalovirus Infections in Transgenic Mice. by Cavanaugh VJ, Guidotti LG, Chisari FV.; 1998 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=109701
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Inhibition of Human Hepatitis B Virus Replication by AT-61, a Phenylpropenamide Derivative, Alone and in Combination with ([minus sign])[beta]-l-2[prime prime or minute],3[prime prime or minute]-Dideoxy-3[prime prime or minute]-Thiacytidine. by King RW, Ladner SK, Miller TJ, Zaifert K, Perni RB, Conway SC, Otto MJ.; 1998 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=106020
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Inhibition of intrahepatic hepatitis B virus replication by antiviral drugs in a novel transgenic mouse model. by Nagahata T, Araki K, Yamamura K, Matsubara K.; 1992 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=192434
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Inhibition of replication of hepatitis B virus by cytallene in vitro. by Zhu YL, Pai SB, Liu SH, Grove KL, Jones BC, Simons C, Zemlicka J, Cheng YC.; 1997 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=163999
82
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Inhibition of the replication of hepatitis B virus by the carbocyclic analogue of 2'deoxyguanosine. by Price PM, Banerjee R, Acs G.; 1989 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=298318
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Initiation and termination of duck hepatitis B virus DNA synthesis during virus maturation. by Lien JM, Petcu DJ, Aldrich CE, Mason WS.; 1987 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=256000
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Insertions within the hepatitis B virus capsid protein influence capsid formation and RNA encapsidation. by Beames B, Lanford RE.; 1995 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=189596
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Integrated Hepatitis B Virus DNA Preserves the Binding Sequence of Transcription Factor Yin and Yang 1 at the Virus-Cell Junction. by Nakanishi-Matsui M, Hayashi Y, Kitamura Y, Koike K.; 2000 Jun 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=112043
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Interaction between Hepatitis B Virus Core Protein and Reverse Transcriptase. by Lott L, Beames B, Notvall L, Lanford RE.; 2000 Dec 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=112427
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Interaction between STAT-3 and HNF-3 Leads to the Activation of Liver-Specific Hepatitis B Virus Enhancer 1 Function. by Waris G, Siddiqui A.; 2002 Mar 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=135980
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Interactions of the transcription factors MIBP1 and RFX1 with the EP element of the hepatitis B virus enhancer. by Blake M, Niklinski J, Zajac-Kaye M.; 1996 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=190627
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Interferon gene transfer by a hepatitis B virus vector efficiently suppresses wild-type virus infection. by Protzer U, Nassal M, Chiang PW, Kirschfink M, Schaller H.; 1999 Sep 14; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=17966
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Interferon inhibits hepatitis B virus replication in a stable expression system of transfected viral DNA. by Hayashi Y, Koike K.; 1989 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=250847
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Interferon-Regulated Pathways That Control Hepatitis B Virus Replication in Transgenic Mice. by Guidotti LG, Morris A, Mendez H, Koch R, Silverman RH, Williams BR, Chisari FV.; 2002 Mar 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=135990
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Interleukin-12 inhibits hepatitis B virus replication in transgenic mice. by Cavanaugh VJ, Guidotti LG, Chisari FV.; 1997 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=191456
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Interleukin-18 Inhibits Hepatitis B Virus Replication in the Livers of Transgenic Mice. by Kimura K, Kakimi K, Wieland S, Guidotti LG, Chisari FV.; 2002 Nov 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=136645
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Interleukin-2 and alpha/beta interferon down-regulate hepatitis B virus gene expression in vivo by tumor necrosis factor-dependent and -independent pathways. by Guidotti LG, Guilhot S, Chisari FV.; 1994 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=236579
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Intracellular Hepatitis B Virus Nucleocapsids Survive Cytotoxic T-LymphocyteInduced Apoptosis. by Pasquetto V, Wieland S, Chisari FV.; 2000 Oct 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=112416
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Intracellular Retention of Hepatitis B Virus Surface Proteins Reduces Interleukin-2 Augmentation after Genetic Immunizations. by Geissler M, Bruss V, Michalak S, Hockenjos B, Ortmann D, Offensperger WB, Wands JR, Blum HE.; 1999 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=104209
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Intracellular retention of surface protein by a hepatitis B virus mutant that releases virion particles. by Xu Z, Yen TS.; 1996 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=189797
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Intrahepatic Induction of Alpha/Beta Interferon Eliminates Viral RNA-Containing Capsids in Hepatitis B Virus Transgenic Mice. by Wieland SF, Guidotti LG, Chisari FV.; 2000 May 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=111931
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Involvement of Crm1 in Hepatitis B Virus X Protein-Induced Aberrant Centriole Replication and Abnormal Mitotic Spindles. by Forgues M, Difilippantonio MJ, Linke SP, Ried T, Nagashima K, Feden J, Valerie K, Fukasawa K, Wang XW.; 2003 Aug 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=165739
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Isolation and characterization of a hepatitis B virus endemic in herons. by Sprengel R, Kaleta EF, Will H.; 1988 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=253529
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Kinetic Analysis of Wild-Type and YMDD Mutant Hepatitis B Virus Polymerases and Effects of Deoxyribonucleotide Concentrations on Polymerase Activity. by Gaillard RK, Barnard J, Lopez V, Hodges P, Bourne E, Johnson L, Allen MI, Condreay P, Miller WH, Condreay LD.; 2002 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=127103
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La Autoantigen Specifically Recognizes a Predicted Stem-Loop in Hepatitis B Virus RNA. by Heise T, Guidotti LG, Chisari FV.; 1999 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=112637
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Leptomycin B Inhibits Equine Infectious Anemia Virus Rev and Feline Immunodeficiency Virus Rev Function but Not the Function of the Hepatitis B Virus Posttranscriptional Regulatory Element. by Otero GC, Harris ME, Donello JE, Hope TJ.; 1998 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=110012
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Liver-specific expression of hepatitis B virus is determined by the combined action of the core gene promoter and the enhancer. by Honigwachs J, Faktor O, Dikstein R, Shaul Y, Laub O.; 1989 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=247766
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Localization of the N terminus of hepatitis B virus capsid protein by peptide-based difference mapping from cryoelectron microscopy. by Conway JF, Cheng N, Zlotnick A, Stahl SJ, Wingfield PT, Steven AC.; 1998 Dec 8; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=24499
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Low frequency of mutations in the core promoter and precore regions of hepatitis B virus in anti-HBe positive Brazilian carriers. by Castro LD, Niel C, Gomes SA.; 2001; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=35280
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Low-Level Secretion of Human Hepatitis B Virus Virions Caused by Two Independent, Naturally Occurring Mutations (P5T and L60V) in the Capsid Protein. by Le Pogam S, Yuan TT, Sahu GK, Chatterjee S, Shih C.; 2000 Oct 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=102108
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Mapping of Amino Acid Side Chains on the Surface of Hepatitis B Virus Capsids Required for Envelopment and Virion Formation. by Ponsel D, Bruss V.; 2003 Jan 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=140605
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Mapping of B-cell epitopes of the human hepatitis B virus X protein. by Stemler M, Weimer T, Tu ZX, Wan DF, Levrero M, Jung C, Pape GR, Will H.; 1990 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=249461
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Mapping of Homologous Interaction Sites in the Hepatitis B Virus Core Protein. by Konig S, Beterams G, Nassal M.; 1998 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=110062
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Mapping of the Hepatitis B Virus Reverse Transcriptase TP and RT Domains by Transcomplementation for Nucleotide Priming and by Protein-Protein Interaction. by Lanford RE, Kim YH, Lee H, Notvall L, Beames B.; 1999 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=104429
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Mechanism of Suppression of Hepatitis B Virus Precore RNA Transcription by a Frequent Double Mutation. by Li J, Buckwold VE, Hon MW, Ou JH.; 1999 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=103946
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Mechanisms of Inhibition of Nuclear Hormone Receptor-Dependent Hepatitis B Virus Replication by Hepatocyte Nuclear Factor 3[beta]. by Tang H, McLachlan A.; 2002 Sep 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=136416
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Microdeletion associated with the integration process of hepatitis B virus DNA. by Nakamura T, Tokino T, Nagaya T, Matsubara K.; 1988 Jun 10; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=336702
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Mitochondrially Associated Hepatitis B Virus X Protein Constitutively Activates Transcription Factors STAT-3 and NF-[kappa]B via Oxidative Stress. by Waris G, Huh KW, Siddiqui A.; 2001 Nov 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=99943
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Molecular Chaperone GRP78/BiP Interacts with the Large Surface Protein of Hepatitis B Virus In Vitro and In Vivo. by Cho DY, Yang GH, Ryu CJ, Hong HJ.; 2003 Feb 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=141094
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Molecular Epidemiology of Hepatitis B Virus Variants in Nonhuman Primates. by Grethe S, Heckel JO, Rietschel W, Hufert FT.; 2000 Jun 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=110896
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Molecular Modeling and Biochemical Characterization Reveal the Mechanism of Hepatitis B Virus Polymerase Resistance to Lamivudine (3TC) and Emtricitabine (FTC). by Das K, Xiong X, Yang H, Westland CE, Gibbs CS, Sarafianos SG, Arnold E.; 2001 May 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=114232
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Monitoring Drug Resistance in Chronic Hepatitis B Virus (HBV)-Infected Patients during Lamivudine Therapy: Evaluation of Performance of INNO-LiPA HBV DR Assay. by Lok AS, Zoulim F, Locarnini S, Mangia A, Niro G, Decraemer H, Maertens G, Hulstaert F, De Vreese K, Sablon E.; 2002 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=130856
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Monitoring the Emergence of Hepatitis B Virus Polymerase Gene Variants during Lamivudine Therapy Using the LightCycler. by Whalley SA, Brown D, Teo CG, Dusheiko GM, Saunders NA.; 2001 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=87954
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Multiple integration site of hepatitis B virus DNA in hepatocellular carcinoma and chronic active hepatitis tissues from children. by Yaginuma K, Kobayashi H, Kobayashi M, Morishima T, Matsuyama K, Koike K.; 1987 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=254183
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Multiple liver-specific factors bind to the hepatitis B virus core/pregenomic promoter: trans-activation and repression by CCAAT/enhancer binding protein. by LopezCabrera M, Letovsky J, Hu KQ, Siddiqui A.; 1990 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=54263
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Murine Retroviral Pseudotype Virus Containing Hepatitis B Virus Large and Small Surface Antigens Confers Specific Tropism for Primary Human Hepatocytes: a Potential Liver-Specific Targeting System. by Sung VM, Lai MM.; 2002 Jan 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=136820
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Mutational analysis of the cysteine residues in the hepatitis B virus small envelope protein. by Mangold CM, Streeck RE.; 1993 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=237843
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Mutations in the Carboxyl-Terminal Domain of the Small Hepatitis B Virus Envelope Protein Impair the Assembly of Hepatitis Delta Virus Particles. by Jenna S, Sureau C.; 1999 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=104099
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Mutations in the epsilon sequences of human hepatitis B virus affect both RNA encapsidation and reverse transcription. by Fallows DA, Goff SP.; 1995 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=189007
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Myristylation is involved in intracellular retention of hepatitis B virus envelope proteins. by Prange R, Clemen A, Streeck RE.; 1991 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=241429
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Naturally occurring escape mutants of hepatitis B virus with various mutations in the S gene in carriers seropositive for antibody to hepatitis B surface antigen. by
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Naturally Occurring Mutations Define a Novel Function of the Hepatitis B Virus Core Promoter in Core Protein Expression. by Baumert TF, Marrone A, Vergalla J, Liang TJ.; 1998 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=109887
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New Enzyme Immunoassay for Detection of Hepatitis B Virus Core Antigen (HBcAg) and Relation between Levels of HBcAg and HBV DNA. by Kimura T, Rokuhara A, Matsumoto A, Yagi S, Tanaka E, Kiyosawa K, Maki N.; 2003 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=154683
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Novel and frequent mutations of hepatitis B virus coincide with a major histocompatibility complex class I-restricted T-cell epitope of the surface antigen. by Tai PC, Banik D, Lin GI, Pai S, Pai K, Lin MH, Yuoh G, Che S, Hsu SH, Chen TC, Kuo TT, Lee CS, Yang CS, Shih C.; 1997 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=191713
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Nuclear Covalently Closed Circular Viral Genomic DNA in the Liver of Hepatocyte Nuclear Factor 1[alpha]-Null Hepatitis B Virus Transgenic Mice. by Raney AK, Eggers CM, Kline EF, Guidotti LG, Pontoglio M, Yaniv M, McLachlan A.; 2001 Mar 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=115916
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Nuclear import of hepatitis B virus capsids and release of the viral genome. by Rabe B, Vlachou A, Pante N, Helenius A, Kann M.; 2003 Aug 19; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=187862
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Nucleic Acid-Based Cross-Linking Assay for Detection and Quantification of Hepatitis B Virus DNA. by Lai VC, Guan R, Wood ML, Lo SK, Yuen MF, Lai CL.; 1999 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=84196
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Nucleotide priming and reverse transcriptase activity of hepatitis B virus polymerase expressed in insect cells. by Lanford RE, Notvall L, Beames B.; 1995 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=189185
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Occult Hepatitis B Virus Infection and Clinical Outcomes of Patients with Chronic Hepatitis C. by Kao JH, Chen PJ, Lai MY, Chen DS.; 2002 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=139665
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Paracrine in vivo inhibitory effects of hepatitis B virus X protein (HBx) on liver cell proliferation: An alternative mechanism of HBx-related pathogenesis. by Tralhao JG, Roudier J, Morosan S, Giannini C, Tu H, Goulenok C, Carnot F, Zavala F, Joulin V, Kremsdorf D, Brechot C.; 2002 May 14; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=124516
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Penciclovir is a selective inhibitor of hepatitis B virus replication in cultured human hepatoblastoma cells. by Korba BE, Boyd MR.; 1996 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=163310
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Phenylpropenamide Derivatives AT-61 and AT-130 Inhibit Replication of Wild-Type and Lamivudine-Resistant Strains of Hepatitis B Virus In Vitro. by Delaney IV WE, Edwards R, Colledge D, Shaw T, Furman P, Painter G, Locarnini S.; 2002 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=127422
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Phosphorylation of the Core Protein of Hepatitis B Virus by a 46-Kilodalton Serine Kinase. by Kau JH, Ting LP.; 1998 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=109602
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Phylogenetic Origin of Hepatitis B Virus Strains with Precore C-1858 Variant. by Alestig E, Hannoun C, Horal P, Lindh M.; 2001 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=88319
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Point mutation in the S gene of hepatitis B virus for a d/y or w/r subtypic change in two blood donors carrying a surface antigen of compound subtype adyr or adwr. by Okamoto H, Imai M, Tsuda F, Tanaka T, Miyakawa Y, Mayumi M.; 1987 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=255876
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Posttranscriptional Clearance of Hepatitis B Virus RNA by Cytotoxic T LymphocyteActivated Hepatocytes. by Tsui LV, Guidotti LG, Ishikawa T, Chisari FV.; 1995 Dec 19; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=40365
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Posttranscriptional regulation of hepatitis B virus replication by the precore protein. by Scaglioni PP, Melegari M, Wands JR.; 1997 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=191057
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Potent Efficacy of Entecavir (BMS-200475) in a Duck Model of Hepatitis B Virus Replication. by Marion PL, Salazar FH, Winters MA, Colonno RJ.; 2002 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=126982
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Potent inhibition of hepatitis B virus production in vitro by modified pyrimidine nucleosides. by Matthes E, Langen P, von Janta-Lipinski M, Will H, Schroder HC, Merz H, Weiler BE, Muller WE.; 1990 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=171976
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Precore-mediated inhibition of hepatitis B virus progeny DNA synthesis. by Lamberts C, Nassal M, Velhagen I, Zentgraf H, Schroder CH.; 1993 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=237739
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Preferred translation of human hepatitis B virus polymerase from core protein- but not from precore protein-specific transcript. by Ou JH, Bao H, Shih C, Tahara SM.; 1990 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=247932
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Presence of hepatitis B virus DNA in serum of surface-antigen-seronegative immunocompromised patients. by Pao CC, Yang WL, Wu SY, Lai GM, Shih LY, Sun CF, Liaw YF.; 1987 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=265923
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Production and secretion in Escherichia coli of hepatitis B virus pre-S2 antigen as fusion proteins with beta-lactamase. by Kadokura H, Yoda K, Imai M, Yamasaki M.; 1990 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=184836
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Production of hepatitis B virus particles in Hep G2 cells transfected with cloned hepatitis B virus DNA. by Sells MA, Chen ML, Acs G.; 1987 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=304350
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Production of hepatitis delta virus and suppression of helper hepatitis B virus in a human hepatoma cell line. by Wu JC, Chen PJ, Kuo MY, Lee SD, Chen DS, Ting LP.; 1991 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=239875
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Production of infectious hepatitis delta virus in vitro and neutralization with antibodies directed against hepatitis B virus pre-S antigens. by Sureau C, Moriarty AM, Thornton GB, Lanford RE.; 1992 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=240836
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Promoters for synthesis of the pre-C and pregenomic mRNAs of human hepatitis B virus are genetically distinct and differentially regulated. by Yu X, Mertz JE.; 1996 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=190967
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Properties of Monoclonal Antibodies Directed against Hepatitis B Virus Polymerase Protein. by zu Putlitz J, Lanford RE, Carlson RI, Notvall L, de la Monte SM, Wands JR.; 1999 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=104198
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Properties of the human hepatitis B virus enhancer: position effects and cell-type nonspecificity. by Vannice JL, Levinson AD.; 1988 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=253142
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Protease-induced infectivity of hepatitis B virus for a human hepatoblastoma cell line. by Lu X, Block TM, Gerlich WH.; 1996 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=190069
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Proteaselike sequence in hepatitis B virus core antigen is not required for e antigen generation and may not be part of an aspartic acid-type protease. by Nassal M, Galle PR, Schaller H.; 1989 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=250736
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Quantitation of Hepatitis B Virus Genomic DNA by Real-Time Detection PCR. by Abe A, Inoue K, Tanaka T, Kato J, Kajiyama N, Kawaguchi R, Tanaka S, Yoshiba M, Kohara M.; 1999 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=85408
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Quantitative Detection of Hepatitis B Virus by Transcription-Mediated Amplification and Hybridization Protection Assay. by Kamisango K, Kamogawa C, Sumi M, Goto S, Hirao A, Gonzales F, Yasuda K, Iino S.; 1999 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=84293
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Quantitative Detection of Hepatitis B Virus DNA by Real-Time Nucleic Acid Sequence-Based Amplification with Molecular Beacon Detection. by Yates S, Penning M, Goudsmit J, Frantzen I, van de Weijer B, van Strijp D, van Gemen B.; 2001 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=88403
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Quantitative Detection of Hepatitis B Virus DNA in Two International Reference Plasma Preparations. by Heermann KH, Gerlich WH, Chudy M, Schaefer S, Thomssen R.; 1999 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=84170
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Rapid and Sensitive Assays for Determination of Hepatitis B Virus (HBV) Genotypes and Detection of HBV Precore and Core Promoter Variants. by Hussain M, Chu CJ, Sablon E, Lok AS.; 2003 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=179815
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Rapid and Specific Genotyping System for Hepatitis B Virus Corresponding to Six Major Genotypes by PCR Using Type-Specific Primers. by Naito H, Hayashi S, Abe K.; 2001 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=87732
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Rapid purification of hepatitis B virus DNA from serum. by Boom R, Sol CJ, Heijtink R, Wertheim-van Dillen PM, van der Noordaa J.; 1991 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=270215
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Rate of Hepatitis B Virus Infection in Pregnant Women Determined by a Monoclonal Hepatitis B Surface Antigen Immunoassay. by Gotstein MG, Aide PM, Coleman PF, Sanborn MR.; 2002 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=130673
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Rebound of Hepatitis B Virus Replication in HepG2 Cells after Cessation of Antiviral Treatment. by Abdelhamed AM, Kelley CM, Miller TG, Furman PA, Isom HC.; 2002 Aug 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=155168
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Receptor recognition by a hepatitis B virus reveals a novel mode of high affinity virus --receptor interaction. by Urban S, Schwarz C, Marx UC, Zentgraf H, Schaller H, Multhaup G.; 2000 Mar 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=305663
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Recombinant human hepatitis B virus reverse transcriptase is active in the absence of the nucleocapsid or the viral replication origin, DR1. by Seifer M, Standring DN.; 1993 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=237835
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Regulation of Hepatitis B Virus Replication by the Ras-Mitogen-Activated Protein Kinase Signaling Pathway. by Zheng Y, Li J, Johnson DL, Ou JH.; 2003 Jul 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=161924
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Regulation of Hepatocyte Nuclear Factor 1 Activity by Wild-Type and Mutant Hepatitis B Virus X Proteins. by Li J, Xu Z, Zheng Y, Johnson DL, Ou JH.; 2002 Jun 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=136206
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Relative Sensitivity of Hepatitis B Virus and Other Hepatotropic Viruses to the Antiviral Effects of Cytokines. by McClary H, Koch R, Chisari FV, Guidotti LG.; 2000 Mar 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=111707
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Relevance of cysteine residues for biosynthesis and antigenicity of human hepatitis B virus e protein. by Wasenauer G, Kock J, Schlicht HJ.; 1993 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=237499
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Replication and gene expression of hepatitis B virus in a transgenic mouse that contains the complete viral genome. by Farza H, Hadchouel M, Scotto J, Tiollais P, Babinet C, Pourcel C.; 1988 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=253846
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Replication of the Wild Type and a Natural Hepatitis B Virus Nucleocapsid Promoter Variant Is Differentially Regulated by Nuclear Hormone Receptors in Cell Culture. by Tang H, Raney AK, McLachlan A.; 2001 Oct 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=114462
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Replicative intermediates of hepatitis B virus in HepG2 cells that produce infectious virions. by Sells MA, Zelent AZ, Shvartsman M, Acs G.; 1988 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=253719
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Retinoid X receptor RXR alpha binds to and trans-activates the hepatitis B virus enhancer. by Huan B, Siddiqui A.; 1992 Oct 1; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=50064
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RFX1, a transactivator of hepatitis B virus enhancer I, belongs to a novel family of homodimeric and heterodimeric DNA-binding proteins. by Reith W, Ucla C, Barras E, Gaud A, Durand B, Herrero-Sanchez C, Kobr M, Mach B.; 1994 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=358479
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Risk factors for hepatitis B virus infection in Rio de Janeiro, Brazil. by Lewis-Ximenez LL, do O KM, Ginuino CF, Silva JC, Schatzmayr HG, Stuver S, Yoshida CF.; 2002; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=140010
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Role for Calnexin and N-Linked Glycosylation in the Assembly and Secretion of Hepatitis B Virus Middle Envelope Protein Particles. by Werr M, Prange R.; 1998 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=109435
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Role of N Glycosylation of Hepatitis B Virus Envelope Proteins in Morphogenesis and Infectivity of Hepatitis Delta Virus. by Sureau C, Fournier-Wirth C, Maurel P.; 2003 May 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=153980
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Role of NF-[kappa]B and Myc Proteins in Apoptosis Induced by Hepatitis B Virus HBx Protein. by Su F, Theodosis CN, Schneider RJ.; 2001 Jan 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=113915
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Role of Polypyrimidine Tract Binding Protein in the Function of the Hepatitis B Virus Posttranscriptional Regulatory Element. by Zang WQ, Li B, Huang PY, Lai MM, Yen TS.; 2001 Nov 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=114659
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Role of the large hepatitis B virus envelope protein in infectivity of the hepatitis delta virion. by Sureau C, Guerra B, Lanford RE.; 1993 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=237372
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Role of the Pre-S2 Domain of the Large Envelope Protein in Hepatitis B Virus Assembly and Infectivity. by Le Seyec J, Chouteau P, Cannie I, Guguen-Guillouzo C, Gripon P.; 1998 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=110210
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Screening for hepatitis B virus in healthy blood donors by molecular DNA hybridization analysis. by Sun CF, Pao CC, Wu SY, Liaw YF.; 1988 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=266728
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Searching for Interferon-Induced Genes That Inhibit Hepatitis B Virus Replication in Transgenic Mouse Hepatocytes. by Wieland SF, Vega RG, Muller R, Evans CF, Hilbush B, Guidotti LG, Sutcliffe JG, Schultz PG, Chisari FV.; 2003 Jan 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=140855
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Secretion of human hepatitis B virus is inhibited by the imino sugar Nbutyldeoxynojirimycin. by Block TM, Lu X, Platt FM, Foster GR, Gerlich WH, Blumberg BS, Dwek RA.; 1994 Mar 15; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=43345
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Selective synthesis and secretion of particles composed of the hepatitis B virus middle surface protein directed by a recombinant vaccinia virus: induction of antibodies to pre-S and S epitopes. by Cheng KC, Moss B.; 1987 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=254096
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Semiautomated Quantification of Hepatitis B Virus DNA in a Routine Diagnostic Laboratory. by Kessler HH, Stelzl E, Daghofer E, Santner BI, Marth E, Lackner H, Stauber RE.; 2000 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=95971
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Sensitive Enzyme Immunoassay for Hepatitis B Virus Core-Related Antigens and Their Correlation to Virus Load. by Kimura T, Rokuhara A, Sakamoto Y, Yagi S, Tanaka E, Kiyosawa K, Maki N.; 2002 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=153363
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Sequence of a replication competent hepatitis B virus genome with a preX open reading frame. by Loncarevic IF, Zentgraf H, Schroder CH.; 1990 Aug 25; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=332005
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Simultaneous Detection of Multiplex-Amplified Human Immunodeficiency Virus Type 1 RNA, Hepatitis C Virus RNA, and Hepatitis B Virus DNA Using a Flow Cytometer Microsphere-Based Hybridization Assay. by Defoort JP, Martin M, Casano B, Prato S, Camilla C, Fert V.; 2000 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=86341
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Specific hepatitis B virus minus-strand DNA synthesis requires only the 5' encapsidation signal and the 3'-proximal direct repeat DR1. by Rieger A, Nassal M.; 1996 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=189849
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Stability and Morphology Comparisons of Self-Assembled Virus-Like Particles from Wild-Type and Mutant Human Hepatitis B Virus Capsid Proteins. by Newman M, Suk FM, Cajimat M, Chua PK, Shih C.; 2003 Dec 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=296082
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Stable expression and replication of hepatitis B virus genome in an integrated state in a human hepatoma cell line transfected with the cloned viral DNA. by Tsurimoto T, Fujiyama A, Matsubara K.; 1987 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=304224
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Structural and pathological effects of synthesis of hepatitis B virus large envelope polypeptide in transgenic mice. by Chisari FV, Filippi P, Buras J, McLachlan A, Popper H, Pinkert CA, Palmiter RD, Brinster RL.; 1987 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=299194
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Structural rearrangement of integrated hepatitis B virus DNA as well as cellular flanking DNA is present in chronically infected hepatic tissues. by Takada S, Gotoh Y, Hayashi S, Yoshida M, Koike K.; 1990 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=249177
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Subtype-Independent Immature Secretion and Subtype-Dependent Replication Deficiency of a Highly Frequent, Naturally Occurring Mutation of Human Hepatitis B Virus Core Antigen. by Yuan TT, Tai PC, Shih C.; 1999 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=113064
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Suppression of hepatitis B virus expression and replication by hepatitis C virus core protein in HuH-7 cells. by Shih CM, Lo SJ, Miyamura T, Chen SY, Lee YH.; 1993 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=238000
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Synthesis of hepadnavirus particles that contain replication-defective duck hepatitis B virus genomes in cultured HuH7 cells. by Horwich AL, Furtak K, Pugh J, Summers J.; 1990 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=249155
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The Alkylated Imino Sugar, n-(n-Nonyl)-Deoxygalactonojirimycin, Reduces the Amount of Hepatitis B Virus Nucleocapsid in Tissue Culture. by Lu X, Tran T, Simsek E, Block TM.; 2003 Nov 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=254279
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The apical stem --loop of the hepatitis B virus encapsidation signal folds into a stable tri --loop with two underlying pyrimidine bulges. by Flodell S, Schleucher J, Cromsigt J, Ippel H, Kidd-Ljunggren K, Wijmenga S.; 2002 Nov 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=135823
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The Binding Site of Transcription Factor YY1 Is Required for Intramolecular Recombination between Terminally Repeated Sequences of Linear Replicative Hepatitis B Virus DNA. by Hayashi Y, Kitamura Y, Nakanishi M, Koike K.; 2000 Oct 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=112376
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The duck hepatitis B virus core protein contains a highly phosphorylated C terminus that is essential for replication but not for RNA packaging. by Schlicht HJ, Bartenschlager R, Schaller H.; 1989 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=250854
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The duck hepatitis B virus pre-C region encodes a signal sequence which is essential for synthesis and secretion of processed core proteins but not for virus formation. by Schlicht HJ, Salfeld J, Schaller H.; 1987 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=255982
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The encapsidation signal on the hepatitis B virus RNA pregenome forms a stem-loop structure that is critical for its function. by Knaus T, Nassal M.; 1993 Aug 25; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=309979
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The Enhancer I Core Region Contributes to the Replication Level of Hepatitis B Virus In Vivo and In Vitro. by Bock CT, Malek NP, Tillmann HL, Manns MP, Trautwein C.; 2000 Mar 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=111700
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The genome of hepatitis B virus contains a second enhancer: cooperation of two elements within this enhancer is required for its function. by Yuh CH, Ting LP.; 1990 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=247894
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The Hepatitis B Virus Core Promoter Is Strongly Activated by the Liver Nuclear Receptor Fetoprotein Transcription Factor or by Ectopically Expressed Steroidogenic Factor 1. by Gilbert S, Galarneau L, Lamontagne A, Roy S, Belanger L.; 2000 Jun 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=110855
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The hepatitis B virus enhancer modulates transcription of the hepatitis B virus surface antigen gene from an internal location. by Bulla GA, Siddiqui A.; 1988 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=253158
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The Hepatitis B Virus Polymerase Mutation rtV173L Is Selected during Lamivudine Therapy and Enhances Viral Replication In Vitro. by Delaney WE IV, Yang H, Westland CE, Das K, Arnold E, Gibbs CS, Miller MD, Xiong S.; 2003 Nov 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=229343
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The hepatitis B virus post-transcriptional regulatory element contains two conserved RNA stem-loops which are required for function. by Smith GJ 3rd, Donello JE, Luck R, Steger G, Hope TJ.; 1998 Nov 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=147918
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The Hepatitis B Virus X Protein Transactivates Viral Core Gene Expression In Vivo. by Reifenberg K, Wilts H, Lohler J, Nusser P, Hanano R, Guidotti LG, Chisari FV, Schlicht HJ.; 1999 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=113095
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The M539V Polymerase Variant of Human Hepatitis B Virus Demonstrates Resistance to 2[prime prime or minute]-Deoxy-3[prime prime or minute]-Thiacytidine and a Reduced Ability to Synthesize Viral DNA. by Ladner SK, Miller TJ, King RW.; 1998 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105884
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The Mechanism of an Immature Secretion Phenotype of a Highly Frequent Naturally Occurring Missense Mutation at Codon 97 of Human Hepatitis B Virus Core Antigen. by Yuan TT, Sahu GK, Whitehead WE, Greenberg R, Shih C.; 1999 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=112633
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The myc intron-binding polypeptide associates with RFX1 in vivo and binds to the major histocompatibility complex class II promoter region, to the hepatitis B virus enhancer, and to regulatory regions of several distinct viral genes. by Reinhold W, Emens L, Itkes A, Blake M, Ichinose I, Zajac-Kaye M.; 1995 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=230535
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The P gene product of hepatitis B virus is required as a structural component for genomic RNA encapsidation. by Bartenschlager R, Junker-Niepmann M, Schaller H.; 1990 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=248581
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The polymerase L528M mutation cooperates with nucleotide binding-site mutations, increasing hepatitis B virus replication and drug resistance. by Ono SK, Kato N, Shiratori Y, Kato J, Goto T, Schinazi RF, Carrilho FJ, Omata M.; 2001 Feb 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=199250
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The position of heterologous epitopes inserted in hepatitis B virus core particles determines their immunogenicity. by Schodel F, Moriarty AM, Peterson DL, Zheng JA, Hughes JL, Will H, Leturcq DJ, McGee JS, Milich DR.; 1992 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=238265
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The PreS2 activator MHBst of hepatitis B virus activates c-raf-1 /Erk2 signaling in transgenic mice. by Hildt E, Munz B, Saher G, Reifenberg K, Hofschneider PH.; 2002 Feb 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=125852
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The quaternary structure, antigenicity, and aggregational behavior of the secretory core protein of human hepatitis B virus are determined by its signal sequence. by Schlicht HJ, Wasenauer G.; 1991 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=250773
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The role of envelope proteins in hepatitis B virus assembly. by Bruss V, Ganem D.; 1991 Feb 1; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=50954
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The secretory core protein of human hepatitis B virus is expressed on the cell surface. by Schlicht HJ, Schaller H.; 1989 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=251207
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The small envelope protein is required for secretion of a naturally occurring hepatitis B virus mutant with pre-S1 deleted. by Melegari M, Scaglioni PP, Wands JR.; 1997 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=191785
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Tight clustering of human hepatitis B virus integration sites in hepatomas near a triple-stranded region. by Shih C, Burke K, Chou MJ, Zeldis JB, Yang CS, Lee CS, Isselbacher KJ, Wands JR, Goodman HM.; 1987 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=255947
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Tissue preferential expression of the hepatitis B virus (HBV) surface antigen gene in two lines of HBV transgenic mice. by Burk RD, DeLoia JA, elAwady MK, Gearhart JD.; 1988 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=250586
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trans-activation of viral enhancers by the hepatitis B virus X protein. by Spandau DF, Lee CH.; 1988 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=250552
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Transcomplementation of nucleotide priming and reverse transcription between independently expressed TP and RT domains of the hepatitis B virus reverse transcriptase. by Lanford RE, Notvall L, Lee H, Beames B.; 1997 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=191428
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Transcriptional activation of homologous and heterologous genes by the hepatitis B virus X gene product in cells permissive for viral replication. by Colgrove R, Simon G, Ganem D.; 1989 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=250999
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Transcriptional and posttranscriptional control of hepatitis B virus gene expression. by Uprichard SL, Wieland SF, Althage A, Chisari FV.; 2003 Feb 4; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=298769
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Transcriptional regulation of hepatitis B virus by nuclear hormone receptors is a critical determinant of viral tropism. by Tang H, McLachlan A.; 2001 Feb 13; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=29344
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Transcriptional Repression of Human Hepatitis B Virus Genes by a bZIP Family Member, E4BP4. by Lai CK, Ting LP.; 1999 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=104083
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Transfer of Hepatitis B Virus Genome by Adenovirus Vectors into Cultured Cells and Mice: Crossing the Species Barrier. by Sprinzl MF, Oberwinkler H, Schaller H, Protzer U.; 2001 Jun 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=114916
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Translation of the hepatitis B virus P gene by ribosomal scanning as an alternative to internal initiation. by Fouillot N, Tlouzeau S, Rossignol JM, Jean-Jean O.; 1993 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=237876
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Tumor Necrosis Factor Alpha Inhibition of Hepatitis B Virus Replication Involves Disruption of Capsid Integrity through Activation of NF-[kappa]B. by Biermer M, Puro R, Schneider RJ.; 2003 Apr 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=150632
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Tumor necrosis factor alpha negatively regulates hepatitis B virus gene expression in transgenic mice. by Gilles PN, Fey G, Chisari FV.; 1992 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=241189
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Turnover of Hepatitis B Virus X Protein Is Regulated by Damaged DNA-Binding Complex. by Bergametti F, Sitterlin D, Transy C.; 2002 Jul 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=136256
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Two Sensitive PCR-Based Methods for Detection of Hepatitis B Virus Variants Associated with Reduced Susceptibility to Lamivudine. by Allen MI, Gauthier J, DesLauriers M, Bourne EJ, Carrick KM, Baldanti F, Ross LL, Lutz MW, Condreay LD.; 1999 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=85560
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Update on Diagnosis, Management, and Prevention of Hepatitis B Virus Infection. by Mahoney FJ.; 1999 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=88921
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Use of Hepatitis B Virus DNA Quantitation To Predict Hepatitis B e Antigen Reversion in Cases of Chronic Hepatitis B. by Chan HL, Wong ML, Hui AY, Hung LC, Chan FK, Sung JJ.; 2003 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=294957
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Use of the Hepatitis B Virus Recombinant Baculovirus-HepG2 System to Study the Effects of ([minus sign])-[beta]-2[prime prime or minute],3[prime prime or minute]Dideoxy-3[prime prime or minute]-Thiacytidine on Replication of Hepatitis B Virus and Accumulation of Covalently Closed Circular DNA. by Delaney WE IV, Miller TG, Isom HC.; 1999 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89407
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Viral Cross Talk: Intracellular Inactivation of the Hepatitis B Virus during an Unrelated Viral Infection of the Liver. by Guidotti LG, Borrow P, Hobbs MV, Matzke B, Gresser I, Oldstone MB, Chisari FV.; 1996 May 14; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=39321
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Viral Dynamics in Hepatitis B Virus Infection. by Nowak MA, Bonhoeffer S, Hill AM, Boehme R, Thomas HC, McDade H.; 1996 Apr 30; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=39549
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Viral Superinfection in Previously Unrecognized Chronic Carriers of Hepatitis B Virus with Superimposed Acute Fulminant versus Nonfulminant Hepatitis. by Chu CM, Yeh CT, Liaw YF.; 1999 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=84220
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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 hepatitis B virus, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “hepatitis B virus” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for hepatitis B virus (hyperlinks lead to article summaries): •
A combined oligonucleotide and protein microarray for the codetection of nucleic acids and antibodies associated with human immunodeficiency virus, hepatitis B virus, and hepatitis C virus infections. Author(s): Perrin A, Duracher D, Perret M, Cleuziat P, Mandrand B. Source: Analytical Biochemistry. 2003 November 15; 322(2): 148-55. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14596821
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A duck hepatitis B virus strain with a knockout mutation in the putative X ORF shows similar infectivity and in vivo growth characteristics to wild-type virus. Author(s): Meier P, Scougall CA, Will H, Burrell CJ, Jilbert AR. Source: Virology. 2003 December 20; 317(2): 291-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14698667
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A forgotten population with chronic hepatitis C infection: subjects coinfected with hepatitis B virus. Author(s): Liu CJ, Chen PJ, Chen DS. Source: Hepatology (Baltimore, Md.). 2004 July; 40(1): 266; Author Reply 267-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15239113
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A multiplex-PCR to identify hepatitis B virus--enotypes A-F. Author(s): Kirschberg O, Schuttler C, Repp R, Schaefer S. Source: Journal of Clinical Virology : the Official Publication of the Pan American Society for Clinical Virology. 2004 January; 29(1): 39-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14675868
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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 new compound from Micromonospora sp. SA246, 9-hydroxycrisamicin-A, activates hepatitis B virus replication. Author(s): Yoon SW, Park IY, Sohn BH, Lee J, Yeo WH, Lee YI. Source: Biochemical and Biophysical Research Communications. 2004 July 2; 319(3): 85965. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15184062
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A novel cis-acting element facilitates minus-strand DNA synthesis during reverse transcription of the hepatitis B virus genome. Author(s): Shin MK, Lee J, Ryu WS. Source: Journal of Virology. 2004 June; 78(12): 6252-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15163718
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A one-filter-three-probe assay for defective interference (DI) effects of naturally occurring core internal deletion (CID) variants of human hepatitis B virus. Author(s): Shih C, Yuan TT. Source: Methods in Molecular Medicine. 2004; 95: 151-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14762303
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A prospective study on the development of hepatocellular carcinoma from liver cirrhosis with persistent hepatitis B virus infection. Author(s): Obata H, Hayashi N, Motoike Y, Hisamitsu T, Okuda H, Kobayashi S, Nishioka K. Source: International Journal of Cancer. Journal International Du Cancer. 1980 June 15; 25(6): 741-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14768703
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A treatment algorithm for the management of chronic hepatitis B virus infection in the United States. Author(s): Keeffe EB, Dieterich DT, Han SH, Jacobson IM, Martin P, Schiff ER, Tobias H, Wright TL. Source: Clin Gastroenterol Hepatol. 2004 February; 2(2): 87-106. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15017613
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Activating mechanism of transcriptor NF-kappaB regulated by hepatitis B virus X protein in hepatocellular carcinoma. Author(s): Wang T, Wang Y, Wu MC, Guan XY, Yin ZF. Source: World Journal of Gastroenterology : Wjg. 2004 February 1; 10(3): 356-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14760757
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Acute hepatitis B virus superinfection in a Taiwanese patient with chronic hepatitis C. Author(s): Hung CH, Lee CM, Wang JH, Chen CH, Lu SN. Source: J Formos Med Assoc. 2004 April; 103(4): 302-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15175827
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Adefovir dipivoxil added to ongoing lamivudine in chronic hepatitis B with YMDD mutant hepatitis B virus. Author(s): Perrillo R, Hann HW, Mutimer D, Willems B, Leung N, Lee WM, Moorat A, Gardner S, Woessner M, Bourne E, Brosgart CL, Schiff E. Source: Gastroenterology. 2004 January; 126(1): 81-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14699490
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Adefovir dipivoxil: a new antiviral agent for the treatment of hepatitis B virus infection. Author(s): Qaqish RB, Mattes KA, Ritchie DJ. Source: Clinical Therapeutics. 2003 December; 25(12): 3084-99. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14749147
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African links and hepatitis B virus genotypes in the Republic of Yemen. Author(s): Sallam TA, William Tong CY. Source: Journal of Medical Virology. 2004 May; 73(1): 23-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15042643
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Alarming levels of hepatitis B virus detected among rural Tibetans. Author(s): Clift A, Morgan C, Anderson D, Toole M. Source: Trop Doct. 2004 July; 34(3): 156-7. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15267045
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Analysis of gene expression in hepatitis B virus transfected cell line induced by interferon. Author(s): Xiong W, Wang X, Liu XY, Xiang L, Zheng LJ, Liu JX, Yuan ZH. Source: Sheng Wu Hua Xue Yu Sheng Wu Wu Li Xue Bao Acta Biochimica Et Biophysica Sinica. 2003 December; 35(12): 1053-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14673494
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Anti-envelope 1 and 2 immune response in chronic hepatitis C patients: effects of hepatitis B virus co-infection and interferon treatment. Author(s): Zampino R, Marrone A, Mangoni ED, Santarpia L, Sica A, Tripodi MF, Utili R, Ruggiero G, Adinolfi LE. Source: Journal of Medical Virology. 2004 May; 73(1): 33-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15042645
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Antivirals interacting with hepatitis B virus core protein and core mutations may misdirect capsid assembly in a similar fashion. Author(s): Hacker HJ, Deres K, Mildenberger M, Schroder CH. Source: Biochemical Pharmacology. 2003 December 15; 66(12): 2273-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14637185
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Applicability of real-time PCR combined with melting curve analysis for the study of hepatitis B virus genome mutations. Author(s): Rodriguez-Frias F, Jardi R, Buti M, Esteban R. Source: Hepatology (Baltimore, Md.). 2003 February; 37(2): 478-9; Author Reply 479-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12540804
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Association of -238G/A polymorphism of tumor necrosis factor-alpha gene promoter region with outcomes of hepatitis B virus infection in Chinese Han population. Author(s): Lu LP, Li XW, Liu Y, Sun GC, Wang XP, Zhu XL, Hu QY, Li H. Source: World Journal of Gastroenterology : Wjg. 2004 June 15; 10(12): 1810-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15188512
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Bacterial expression, purification, and in vitro N-myristoylation of fusion hepatitis B virus preS1 with the native-type N-terminus. Author(s): Ma HH, Yang L, Yang XY, Xu ZP, Li BL. Source: Protein Expression and Purification. 2003 January; 27(1): 49-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12509984
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Bacterial virus phi29 pRNA as a hammerhead ribozyme escort to destroy hepatitis B virus. Author(s): Hoeprich S, Zhou Q, Guo S, Shu D, Qi G, Wang Y, Guo P. Source: Gene Therapy. 2003 August; 10(15): 1258-67. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12858191
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Baruch Blumberg--work on hepatitis B virus. Author(s): Shampo MA, Kyle RA. Source: Mayo Clinic Proceedings. 2003 September; 78(9): 1186. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12962173
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Basal core promoter mutations of hepatitis B virus increase the risk of hepatocellular carcinoma in hepatitis B carriers. Author(s): Kao JH, Chen PJ, Lai MY, Chen DS. Source: Gastroenterology. 2003 February; 124(2): 327-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12557138
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Beneficial effects of lamivudine in hepatitis B virus-related decompensated cirrhosis. Author(s): Kapoor D, Guptan RC, Wakil SM, Kazim SN, Kaul R, Agarwal SR, Raisuddin S, Hasnain SE, Sarin SK. Source: Journal of Hepatology. 2000 August; 33(2): 308-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10952249
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Beta-catenin mutations are associated with a subset of low-stage hepatocellular carcinoma negative for hepatitis B virus and with favorable prognosis. Author(s): Hsu HC, Jeng YM, Mao TL, Chu JS, Lai PL, Peng SY. Source: American Journal of Pathology. 2000 September; 157(3): 763-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10980116
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BHIVA Guidelines: coinfection with HIV and chronic hepatitis B virus. Author(s): Brook MG, Gilson R, Wilkins EL; British HIV Association. Source: Hiv Medicine. 2003 October; 4 Suppl 1: 42-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14511247
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Biological dynamics of hepatitis B virus load in dialysis population. Author(s): Fabrizi F, Lunghi G, Alongi G, Bisegna S, Campolo G, Mangano S, Limido A, Pagliari B, Tettamanzi F, Ponticelli C. Source: American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation. 2003 June; 41(6): 1278-85. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12776281
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Biological impact of natural COOH-terminal deletions of hepatitis B virus X protein in hepatocellular carcinoma tissues. Author(s): Tu H, Bonura C, Giannini C, Mouly H, Soussan P, Kew M, Paterlini-Brechot P, Brechot C, Kremsdorf D. Source: Cancer Research. 2001 November 1; 61(21): 7803-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11691796
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Blood donors infected with the hepatitis B virus but persistently lacking antibodies to the hepatitis B core antigen. Author(s): Laperche S, Guitton C, Smilovici W, Courouce AM. Source: Vox Sanguinis. 2001 February; 80(2): 90-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11378970
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Brain metastasis from hepatocellular carcinoma associated with hepatitis B virus. Author(s): Frati A, Salvati M, Giarnieri E, Santoro A, Rocchi G, Frati L. Source: J Exp Clin Cancer Res. 2002 September; 21(3): 321-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12385572
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Changes in hepatitis B virus DNA levels with acute HIV infection. Author(s): Thio CL, Netski DM, Myung J, Seaberg EC, Thomas DL. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2004 April 1; 38(7): 1024-9. Epub 2004 March 17. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15034837
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Chronic hepatitis B virus infection and dyslipidemia. Author(s): Su TC, Lee YT, Cheng TJ, Chien HP, Wang JD. Source: J Formos Med Assoc. 2004 April; 103(4): 286-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15175824
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cis-Acting sequences that contribute to the synthesis of relaxed-circular DNA of human hepatitis B virus. Author(s): Liu N, Ji L, Maguire ML, Loeb DD. Source: Journal of Virology. 2004 January; 78(2): 642-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14694095
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Clade analysis and surface antigen polymorphism of hepatitis B virus American genotypes. Author(s): Devesa M, Rodriguez C, Leon G, Liprandi F, Pujol FH. Source: Journal of Medical Virology. 2004 March; 72(3): 377-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14748061
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Classifying hepatitis B virus genotypes. Author(s): Miyakawa Y, Mizokami M. Source: Intervirology. 2003; 46(6): 329-38. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14688448
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Clinical and virological aspects of blood donors infected with hepatitis B virus genotypes B and C. Author(s): Kao JH, Chen PJ, Lai MY, Chen DS. Source: Journal of Clinical Microbiology. 2002 January; 40(1): 22-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11773087
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Clinical characteristics of asymptomatic hepatitis B virus carriers with YMDD mutant not treated with lamivudine. Author(s): Kobayashi S. Source: Kurume Med J. 2003; 50(3-4): 87-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14768470
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Clinical relevance of hepatitis B virus genotypes Ba and Bj in Taiwan. Author(s): Kao JH, Chen DS. Source: Gastroenterology. 2003 December; 125(6): 1916-7; Author Reply 1917-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14727634
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Clinical virology of hepatitis B virus infection. Author(s): Raimondo G, Pollicino T, Squadrito G. Source: Journal of Hepatology. 2003; 39 Suppl 1: S26-30. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14708674
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Cloning and expression of surface antigens from occult chronic hepatitis B virus infections and their recognition by commercial detection assays. Author(s): Jeantet D, Chemin I, Mandrand B, Tran A, Zoulim F, Merle P, Trepo C, Kay A. Source: Journal of Medical Virology. 2004 August; 73(4): 508-15. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15221893
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Comparison of genotypes C and D of the hepatitis B virus in Japan: a clinical and molecular biological study. Author(s): Duong TN, Horiike N, Michitaka K, Yan C, Mizokami M, Tanaka Y, Jyoko K, Yamamoto K, Miyaoka H, Yamashita Y, Ohno N, Onji M. Source: Journal of Medical Virology. 2004 April; 72(4): 551-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14981757
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Complete hepatitis B virus genome analysis in HBsAg positive mothers and their infants with fulminant hepatitis B. Author(s): Friedt M, Gerner P, Wintermeyer P, Wirth S. Source: Bmc Gastroenterology [electronic Resource]. 2004 June 08; 4(1): 11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15186503
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Complete nucleotide sequence and phylogenetic analyses of hepatitis B virus isolated from two pileated gibbons. Author(s): Aiba N, Nishimura H, Arakawa Y, Abe K. Source: Virus Genes. 2003 December; 27(3): 219-26. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14618082
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Compliance with hepatitis B virus vaccination and risk of occupational exposure to blood and other body fluids in intensive care department personnel in Brazil. Author(s): Manso VF, Castro KF, Matos SM, Junqueira AL, Souza SB, Sousa MM, Martins RM, Teles SA. Source: American Journal of Infection Control. 2003 November; 31(7): 431-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14639441
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Hepatitis B Virus
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Comprehensive analysis of class I and class II HLA antigens and chronic hepatitis B virus infection. Author(s): Thio CL, Thomas DL, Karacki P, Gao X, Marti D, Kaslow RA, Goedert JJ, Hilgartner M, Strathdee SA, Duggal P, O'Brien SJ, Astemborski J, Carrington M. Source: Journal of Virology. 2003 November; 77(22): 12083-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14581545
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Comprehensive analysis of risk factors associating with Hepatitis B virus (HBV) reactivation in cancer patients undergoing cytotoxic chemotherapy. Author(s): Yeo W, Zee B, Zhong S, Chan PK, Wong WL, Ho WM, Lam KC, Johnson PJ. Source: British Journal of Cancer. 2004 April 5; 90(7): 1306-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15054446
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Construction of recombinant adenoviruses that produce infectious hepatitis B virus. Author(s): Sprinzl M, Dumortier J, Protzer U. Source: Methods in Molecular Medicine. 2004; 96: 209-18. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14762272
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Correlations between hepatitis B virus genotype and cirrhotic or non-cirrhotic hepatoma. Author(s): Chen CH, Eng HL, Lee CM, Kuo FY, Lu SN, Huang CM, Tung HD, Chen CL, Changchien CS. Source: Hepatogastroenterology. 2004 March-April; 51(56): 552-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15086200
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Critical overview and outlook: pathogenesis, prevention, and treatment of hepatitis and hepatocarcinoma caused by hepatitis B virus. Author(s): Hilleman MR. Source: Vaccine. 2003 December 1; 21(32): 4626-49. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14585670
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Cyclooxygenase-2 pathway correlates with vascular endothelial growth factor expression and tumor angiogenesis in hepatitis B virus-associated hepatocellular carcinoma. Author(s): Cheng AS, Chan HL, To KF, Leung WK, Chan KK, Liew CT, Sung JJ. Source: International Journal of Oncology. 2004 April; 24(4): 853-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15010822
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Deficiency in virion secretion and decreased stability of the hepatitis B virus immune escape mutant G145R. Author(s): Kalinina T, Iwanski A, Will H, Sterneck M. Source: Hepatology (Baltimore, Md.). 2003 November; 38(5): 1274-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14578867
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Delivery of hepatitis B virus therapeutic agents using asialoglycoprotein receptorbased liver-specific targeting. Author(s): Konishi M, Wu CH, Wu GY. Source: Methods in Molecular Medicine. 2004; 96: 163-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14762268
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Detecting the replication of the hepatitis B virus using the ImmunoMax technique following treatment with interferon-alpha in children with chronic hepatitis. Author(s): Kasprzak A, Wysocki J, Zabel M, Surdyk-Zasada J. Source: Medical Science Monitor : International Medical Journal of Experimental and Clinical Research. 2002 January; 8(1): Pr1-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11782686
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Detection of hepatitis B virus polymerase variations resistant to lamivudine therapy. Author(s): Zhang X, Han Y, Lu Z, Zhang D, Cai Y. Source: Chinese Medical Journal. 2000 May; 113(5): 455-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11776105
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Detection of hepatitis B virus variants resistant to lamivudine and famciclovir among randomly selected chronic carriers from Spain. Author(s): Leon P, Pozo F, Echevarria JM. Source: Enfermedades Infecciosas Y Microbiologia Clinica. 2004 March; 22(3): 133-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14987532
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Detection of hepatitis B virus X antigen by immunohistochemistry and Western blotting. Author(s): Liu J, Feitelson MA. Source: Methods in Molecular Medicine. 2004; 95: 71-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14762297
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Detection of the hepatitis B virus X protein (HBx) antigen and anti-HBx antibodies in cases of human hepatocellular carcinoma. Author(s): Hwang GY, Lin CY, Huang LM, Wang YH, Wang JC, Hsu CT, Yang SS, Wu CC. Source: Journal of Clinical Microbiology. 2003 December; 41(12): 5598-603. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14662947
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Determination of hepatitis B virus-specific CD8+ T-cell activity in the liver. Author(s): Nascimbeni M, Rehermann B. Source: Methods in Molecular Medicine. 2004; 96: 65-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14762260
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Hepatitis B Virus
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Determination of serum hepatitis B virus DNA in chronic HBsAg carriers: clinical significance and correlation with serological markers. Author(s): Yalcin K, Degertekin H, Alp MN, Tekes S, Satici O, Budak T. Source: Turk J Gastroenterol. 2003 September; 14(3): 157-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14655057
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Development of real-time detection direct test for hepatitis B virus and comparison with two commercial tests using the WHO international standard. Author(s): Mukaide M, Tanaka Y, Katayose S, Tano H, Murata M, Hikata M, Fujise K, Sakugawa H, Suzuki K, Zaunders J, Nagasawa Y, Toda G, Mizokami M. Source: Journal of Gastroenterology and Hepatology. 2003 November; 18(11): 1264-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14535983
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Different types of ground glass hepatocytes in chronic hepatitis B virus infection contain specific pre-S mutants that may induce endoplasmic reticulum stress. Author(s): Wang HC, Wu HC, Chen CF, Fausto N, Lei HY, Su IJ. Source: American Journal of Pathology. 2003 December; 163(6): 2441-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14633616
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Distinct modes of regulation of transcription of hepatitis B virus by the nuclear receptors HNF4alpha and COUP-TF1. Author(s): Yu X, Mertz JE. Source: Journal of Virology. 2003 February; 77(4): 2489-99. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12551987
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Distinctive sequence characteristics of subgenotype A1 isolates of hepatitis B virus from South Africa. Author(s): Kimbi GC, Kramvis A, Kew MC. Source: The Journal of General Virology. 2004 May; 85(Pt 5): 1211-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15105537
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Distribution of hepatitis B virus genotypes in blood donors and chronically infected patients in a tertiary care hospital in southern India. Author(s): Vivekanandan P, Abraham P, Sridharan G, Chandy G, Daniel D, Raghuraman S, Daniel HD, Subramaniam T. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2004 May 1; 38(9): E81-6. Epub 2004 April 09. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15127358
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Distribution of hepatitis B virus genotypes in HIV-infected patients with chronic hepatitis B: therapeutic implications. Author(s): Perez-Olmeda M, Nunez M, Garcia-Samaniego J, Rios P, Gonzalez-Lahoz J, Soriano V. Source: Aids Research and Human Retroviruses. 2003 August; 19(8): 657-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=13678467
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Divergent roles of hepatitis B virus X-associated protein 2 (XAP2) in human versus mouse Ah receptor complexes. Author(s): Ramadoss P, Petrulis JR, Hollingshead BD, Kusnadi A, Perdew GH. Source: Biochemistry. 2004 January 27; 43(3): 700-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14730974
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Diversity and origin of hepatitis B virus in Dutch blood donors. Author(s): Koppelman MH, Zaaijer HL. Source: Journal of Medical Virology. 2004 May; 73(1): 29-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15042644
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Doctor to patient transmission of hepatitis B virus: implications of HBV DNA levels and potential new solutions. Author(s): Buster EH, van der Eijk AA, Schalm SW. Source: Antiviral Research. 2003 October; 60(2): 79-85. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14638402
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Dynamic analysis of hepatitis B virus DNA and its antigens in 2.2.15 cells. Author(s): Liu MC, Yu M, Zhang NL, Gong WB, Wang Y, Piao WH, Wang QH, Wang GQ. Source: Journal of Viral Hepatitis. 2004 March; 11(2): 124-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14996346
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Dynamics of plasma hepatitis B virus levels after highly active antiretroviral therapy in patients with HIV infection. Author(s): Fang CT, Chen PJ, Chen MY, Hung CC, Chang SC, Chang AL, Chen DS. Source: Journal of Hepatology. 2003 December; 39(6): 1028-35. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14642622
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Effect of acute self-limited hepatitis C virus (HCV) superinfection on hepatitis B virus (HBV)-related cirrhosis. Virological features of HBV-HCV dual infection. Author(s): Akuta N, Suzuki F, Kobayashi M, Tsubota A, Suzuki Y, Hosaka T, Someya T, Kobayashi M, Saitoh S, Arase Y, Ikeda K, Kumada H. Source: Digestive Diseases and Sciences. 2004 February; 49(2): 281-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15104371
108
Hepatitis B Virus
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Effect of IL-18 on peripheral blood mononuclear cells of chronic hepatitis B and hepatitis B virus DNA released by HepG2.2.15 cell lines. Author(s): Sun Y, Chen HY, Xin SJ. Source: Hepatobiliary Pancreat Dis Int. 2004 May; 3(2): 230-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15138116
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Effects of gender, Helicobacter pylori and hepatitis B virus serology status on cardiovascular and renal complications in Chinese type 2 diabetic patients with overt nephropathy. Author(s): Lo MK, Lee KF, Chan NN, Leung WY, Ko GT, Chan WB, So WY, Ng MC, Ho CS, Tam JS, Lam CW, Tong PC, Chan JC. Source: Diabetes, Obesity & Metabolism. 2004 May; 6(3): 223-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15056131
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Efficacy of granulocyte-macrophage colony-stimulating factor (GM-CSF) as a vaccine adjuvant for hepatitis B virus in patients with HIV infection. Author(s): Sasaki MG, Foccacia R, de Messias-Reason IJ. Source: Vaccine. 2003 November 7; 21(31): 4545-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14575766
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Efficacy of tenofovir disoproxil fumarate in antiretroviral therapy-naive and experienced patients coinfected with HIV-1 and hepatitis B virus. Author(s): Dore GJ, Cooper DA, Pozniak AL, DeJesus E, Zhong L, Miller MD, Lu B, Cheng AK; 903 Study Team; 907 Study Team. Source: The Journal of Infectious Diseases. 2004 April 1; 189(7): 1185-92. Epub 2004 March 12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15031786
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Efficient extraction of viral DNA and viral RNA by the Chemagic viral DNA/RNA kit allows sensitive detection of cytomegalovirus, hepatitis B virus, and hepatitis G virus by PCR. Author(s): Kleines M, Schellenberg K, Ritter K. Source: Journal of Clinical Microbiology. 2003 November; 41(11): 5273-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14605182
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Eight genotypes (A-H) of hepatitis B virus infecting patients from San Francisco and their demographic, clinical, and virological characteristics. Author(s): Kato H, Gish RG, Bzowej N, Newsom M, Sugauchi F, Tanaka Y, Kato T, Orito E, Usuda S, Ueda R, Miyakawa Y, Mizokami M. Source: Journal of Medical Virology. 2004 August; 73(4): 516-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15221894
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Enhancement of immune responses to the hepatitis B virus core protein through DNA vaccines with a DNA fragment encoding human IL-1beta 163-171 peptide. Author(s): Shao HJ, Chen L, Shen MS, Yu GF. Source: Acta Virol. 2003; 47(4): 217-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15068376
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Epidemiological and clinical burden of chronic hepatitis B virus/hepatitis C virus infection. A multicenter Italian study. Author(s): Gaeta GB, Stornaiuolo G, Precone DF, Lobello S, Chiaramonte M, Stroffolini T, Colucci G, Rizzetto M. Source: Journal of Hepatology. 2003 December; 39(6): 1036-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14642623
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Epidemiological and sequence differences between two subtypes (Ae and Aa) of hepatitis B virus genotype A. Author(s): Sugauchi F, Kumada H, Acharya SA, Shrestha SM, Gamutan MT, Khan M, Gish RG, Tanaka Y, Kato T, Orito E, Ueda R, Miyakawa Y, Mizokami M. Source: The Journal of General Virology. 2004 April; 85(Pt 4): 811-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15039524
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Epidemiological evidence for vaccinating wastewater treatment plant workers against hepatitis A and hepatitis B virus. Author(s): Arvanitidou M, Mamassi P, Vayona A. Source: European Journal of Epidemiology. 2004; 19(3): 259-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15117120
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Evaluation of a line probe assay for identification of hepatitis B virus precore variants in serum from chronic hepatitis B carriers. Author(s): Cameron-Wilson CL, Muir P, Ballard AL, Corden S, Boxall EH, Sablon E, Stuyver L. Source: Journal of Virological Methods. 2003 December; 114(1): 97-103. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14599684
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Evaluation of the INNO-LiPA HBV genotyping assay for determination of hepatitis B virus genotype. Author(s): Osiowy C, Giles E. Source: Journal of Clinical Microbiology. 2003 December; 41(12): 5473-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14662927
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Hepatitis B Virus
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Evaluation on expression of the recombinant S gene of human hepatitis B virus in vitro and in vivo. Author(s): Yang RY, Zeng QP, Fu LC, Chen ZT. Source: Hepatobiliary Pancreat Dis Int. 2003 May; 2(2): 259-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14599980
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Evolution of hepatitis B virus precore/basal core promoter gene in HBeAg-positive chronic hepatitis B patients receiving lamivudine therapy. Author(s): Lin CL, Liao LY, Wang CS, Chen PJ, Lai MY, Chen DS, Kao JH. Source: Liver International : Official Journal of the International Association for the Study of the Liver. 2004 February; 24(1): 9-15. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15101995
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Evolution of hepatitis B virus sequence from a liver transplant recipient with rapid breakthrough despite hepatitis B immune globulin prophylaxis and lamivudine therapy. Author(s): Kim KH, Lee KH, Chang HY, Ahn SH, Tong S, Yoon YJ, Seong BL, Kim SI, Han KH. Source: Journal of Medical Virology. 2003 November; 71(3): 367-75. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12966541
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Evolution of wild type and mutants of the YMDD motif of hepatitis B virus polymerase during lamivudine therapy. Author(s): Zhang X, Liu C, Gong Q, Zhang S, Zhang D, Lu Z, Wang Y. Source: Journal of Gastroenterology and Hepatology. 2003 December; 18(12): 1353-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14675262
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Exploring the biological basis of hepatitis B e antigen in hepatitis B virus infection. Author(s): Milich D, Liang TJ. Source: Hepatology (Baltimore, Md.). 2003 November; 38(5): 1075-86. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14578844
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Expression of FasL and perforin/granzyme B mRNA in chronic hepatitis B virus infection. Author(s): Lee JY, Chae DW, Kim SM, Nam ES, Jang MK, Lee JH, Kim HY, Yoo JY. Source: Journal of Viral Hepatitis. 2004 March; 11(2): 130-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14996347
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Expression of hepatitis B virus antigen and Helicobacter pylori infection in gastric mucosa of patients with chronic liver disease. Author(s): Chen NL, Bai L, Deng T, Zhang C, Kong QY, Chen H. Source: Hepatobiliary Pancreat Dis Int. 2004 May; 3(2): 223-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15138114
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Factors associated with viral breakthrough in lamivudine monoprophylaxis of hepatitis B virus recurrence after liver transplantation. Author(s): Chan HL, Chui AK, Lau WY, Chan FK, Wong ML, Tse CH, Rao AR, Wong J, Sung JJ. Source: Journal of Medical Virology. 2002 October; 68(2): 182-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12210406
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Failure of combination therapy with lamivudine and famciclovir following lamivudine monotherapy for hepatitis B virus infection in patients coinfected with human immunodeficiency virus-1. Author(s): Matthews GV, Pillay D, Cane P, Ratcliffe D, Gazzard B, Nelson M. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2001 December 15; 33(12): 2049-54. Epub 2001 November 05. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11698987
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Fatal hepatic failure after emergence of the hepatitis B virus mutant during lamivudine therapy in a patient with liver cirrhosis. Author(s): Wang JH, Lu SN, Lee CM, Lee JF, Chou YP. Source: Scandinavian Journal of Gastroenterology. 2002 March; 37(3): 366-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11916202
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Fatal hepatitis B virus reactivation by an escape mutant following rituximab therapy. Author(s): Westhoff TH, Jochimsen F, Schmittel A, Stoffler-Meilicke M, Schafer JH, Zidek W, Gerlich WH, Thiel E. Source: Blood. 2003 September 1; 102(5): 1930. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12930732
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Fatal reactivation of hepatitis B virus following cytotoxic chemotherapy for acute myelogenous leukemia: fibrosing cholestatic hepatitis. Author(s): Kojima H, Abei M, Takei N, Mukai Y, Hasegawa Y, Iijima T, Nagasawa T. Source: European Journal of Haematology. 2002 August; 69(2): 101-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12366713
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Feedback circuits in hepatitis B virus infection. Author(s): Martinet-Edelist C. Source: Acta Biotheoretica. 2003; 51(4): 245-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14669875
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Fibrosing cholestatic hepatitis-like syndrome in a hepatitis B virus and hepatitis C virus-negative renal transplant recipient: a case report with autopsy findings. Author(s): Duseja A, Nada R, Kalra N, Acharya SK, Minz M, Joshi K, Chawla Y. Source: Trop Gastroenterol. 2003 January-March; 24(1): 31-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12974214
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Fidelity of hepatitis B virus polymerase. Author(s): Park SG, Kim Y, Park E, Ryu HM, Jung G. Source: European Journal of Biochemistry / Febs. 2003 July; 270(14): 2929-36. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12846825
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Four cases of hepatitis B virus-related fibrosing cholestatic hepatitis treated with lamivudine. Author(s): Jung S, Lee HC, Han JM, Lee YJ, Chung YH, Lee YS, Kwon Y, Yu E, Suh DJ. Source: Journal of Gastroenterology and Hepatology. 2002 March; 17(3): 345-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11982709
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Frequency and load of hepatitis B virus DNA in first-time blood donors with antibodies to hepatitis B core antigen. Author(s): Hennig H, Puchta I, Luhm J, Schlenke P, Goerg S, Kirchner H. Source: Blood. 2002 October 1; 100(7): 2637-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12239179
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Frequency of infection by hepatitis B virus and its surface mutants in a northern Indian population. Author(s): Singh H, Aggarwal R, Singh RL, Naik SR, Naik S. Source: Indian J Gastroenterol. 2003 July-August; 22(4): 132-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12962435
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Frequent occult hepatitis B virus infection in patients infected with human immunodeficiency virus type 1. Author(s): Santos EA, Yoshida CF, Rolla VC, Mendes JM, Vieira IF, Arabe J, Gomes SA. Source: European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology. 2003 February; 22(2): 92-8. Epub 2003 February 18. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12627282
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Frequent occurrence of hepatitis B virus surface antigen mutants in subtype adw in vaccinated Singapore infants. Author(s): Chen WN, Oon CJ, Lim GK. Source: Vaccine. 2001 December 12; 20(5-6): 639-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11738727
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Full-length sequence and functional analysis of hepatitis B virus genome in a virus carrier: a case report suggesting the impact of pre-S and core promoter mutations on the progression of the disease. Author(s): Kajiya Y, Hamasaki K, Nakata K, Nakagawa Y, Miyazoe S, Takeda Y, Ohkubo K, Ichikawa T, Nakao K, Kato Y, Eguchi K. Source: Journal of Viral Hepatitis. 2002 March; 9(2): 149-56. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11876799
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Fulminant hepatic failure caused by hepatitis B virus activation after chemotherapy for breast cancer treated with liver transplantation: a case report. Author(s): Hung CM, Jeng LB, Lee WC, Yu MC, Kuo LM, Chen MF. Source: Transplantation Proceedings. 2003 February; 35(1): 387-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12591453
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Fulminant hepatitis after infliximab in a patient with hepatitis B virus treated for an adult onset still's disease. Author(s): Michel M, Duvoux C, Hezode C, Cherqui D. Source: The Journal of Rheumatology. 2003 July; 30(7): 1624-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12858469
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Fulminant hepatitis in an asymptomatic chronic carrier of hepatitis B virus mutant after withdrawal of low-dose methotrexate therapy for rheumatoid arthritis. Author(s): Hagiyama H, Kubota T, Komano Y, Kurosaki M, Watanabe M, Miyasaka N. Source: Clin Exp Rheumatol. 2004 May-June; 22(3): 375-6. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15144137
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Fulminant hepatitis subsequent to reactivation of precore mutant hepatitis B virus in a patient with lymphoma treated with chemotherapy and rituximab. Author(s): Hernandez JA, Diloy R, Salat D, del Rio N, Martinez X, Castellvi JM. Source: Haematologica. 2003 June; 88(6): Ecr22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12801855
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Functional characterization of the interferon regulatory element in the enhancer 1 region of the hepatitis B virus genome. Author(s): Alcantara FF, Tang H, McLachlan A. Source: Nucleic Acids Research. 2002 May 1; 30(9): 2068-75. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11972347
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Gene expression profiles in an hepatitis B virus transfected hepatoblastoma cell line and differentially regulated gene expression by interferon-alpha. Author(s): Wang X, Yuan ZH, Zheng LJ, Yu F, Xiong W, Liu JX, Hu GX, Li Y. Source: World Journal of Gastroenterology : Wjg. 2004 June 15; 10(12): 1740-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15188497
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Generation of high affinity human single-chain antibody against PreS1 of hepatitis B virus from immune phage-display antibody library. Author(s): Zhang ZC, Hu XJ, Yang Q. Source: Hepatobiliary Pancreat Dis Int. 2004 February; 3(1): 77-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14969843
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Generation of stable cell lines expressing Lamivudine-resistant hepatitis B virus for antiviral-compound screening. Author(s): Walters KA, Tipples GA, Allen MI, Condreay LD, Addison WR, Tyrrell L. Source: Antimicrobial Agents and Chemotherapy. 2003 June; 47(6): 1936-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12760870
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Genetic changes and expression of the mannose 6-phosphate/insulin-like growth factor II receptor gene in human hepatitis B virus-associated hepatocellular carcinoma. Author(s): Yang EB, Qin LL, Zhao YN, Zhang K, Chow P. Source: International Journal of Molecular Medicine. 2003 June; 11(6): 773-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12736721
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Genetic heterogeneity of the precore and the core promoter region of genotype C hepatitis B virus during lamivudine therapy. Author(s): Kuwahara R, Kumashiro R, Murashima S, Ogata K, Tanaka K, Hisamochi A, Hino T, Ide T, Tanaka E, Koga Y, Sata M. Source: Journal of Medical Virology. 2004 January; 72(1): 26-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14635007
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Genetic variation of hepatitis B surface antigen coding region among infants with chronic hepatitis B virus infection. Author(s): Nainan OV, Khristova ML, Byun K, Xia G, Taylor PE, Stevens CE, Margolis HS. Source: Journal of Medical Virology. 2002 November; 68(3): 319-27. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12226817
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Genome replication, virion secretion, and e antigen expression of naturally occurring hepatitis B virus core promoter mutants. Author(s): Parekh S, Zoulim F, Ahn SH, Tsai A, Li J, Kawai S, Khan N, Trepo C, Wands J, Tong S. Source: Journal of Virology. 2003 June; 77(12): 6601-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12767980
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Genomic analysis of the host response to hepatitis B virus infection. Author(s): Wieland S, Thimme R, Purcell RH, Chisari FV. Source: Proceedings of the National Academy of Sciences of the United States of America. 2004 April 27; 101(17): 6669-74. Epub 2004 Apr 20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15100412
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Genomic mutations with amino acid substitutions of circulating hepatitis B virus found in non-B, non-C patients with hepatocellular carcinoma. Author(s): Nakamoto N, Saito H, Ebinuma H, Tada S, Saito Y, Kurita S, Kitamura K, Ishii H. Source: Intern Med. 2003 April; 42(4): 322-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12729320
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Genotype analysis, using PCR with type-specific primers, of hepatitis B virus isolates from patients coinfected with hepatitis delta virus genotype II from Miyako Island, Japan. Author(s): Moriyama M, Taira M, Matsumura H, Aoki H, Mikuni M, Kaneko M, Shioda A, Iwaguchi K, Arai S, Ichijima S, Iwasaki H, Tanaka N, Abe K, Arakawa Y. Source: Intervirology. 2003; 46(2): 114-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12684550
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Genotype and subtype analyses of hepatitis B virus (HBV) and possible co-infection of HBV and hepatitis C virus (HCV) or hepatitis D virus (HDV) in blood donors, patients with chronic liver disease and patients on hemodialysis in Surabaya, Indonesia. Author(s): Lusida MI, Surayah, Sakugawa H, Nagano-Fujii M, Soetjipto, Mulyanto, Handajani R, Boediwarsono, Setiawan PB, Nidom CA, Ohgimoto S, Hotta H. Source: Microbiology and Immunology. 2003; 47(12): 969-75. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14695447
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Genotype B hepatitis B virus is associated with severe icteric flare-up of chronic hepatitis B virus infection in Hong Kong. Author(s): Chan HL, Tsang SW, Wong ML, Tse CH, Leung NW, Chan FK, Sung JJ. Source: The American Journal of Gastroenterology. 2002 October; 97(10): 2629-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12385451
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Genotype C of hepatitis B virus can be classified into at least two subgroups. Author(s): Huy TT, Ushijima H, Quang VX, Win KM, Luengrojanakul P, Kikuchi K, Sata T, Abe K. Source: The Journal of General Virology. 2004 February; 85(Pt 2): 283-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14769886
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Genotype H: a new Amerindian genotype of hepatitis B virus revealed in Central America. Author(s): Arauz-Ruiz P, Norder H, Robertson BH, Magnius LO. Source: The Journal of General Virology. 2002 August; 83(Pt 8): 2059-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12124470
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Genotype mixtures of hepatitis B virus in patients treated with interferon. Author(s): Hannoun C, Krogsgaard K, Horal P, Lindh M; Interpred trial group. Source: The Journal of Infectious Diseases. 2002 September 15; 186(6): 752-9. Epub 2002 August 28. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12198608
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Genotype, serotype, and phylogenetic characterization of the complete genome sequence of hepatitis B virus isolates from Malawian chronic carriers of the virus. Author(s): Sugauchi F, Orito E, Kato H, Suzuki S, Kawakita S, Sakamoto Y, Fukushima K, Akiba T, Yoshihara N, Ueda R, Mizokami M. Source: Journal of Medical Virology. 2003 January; 69(1): 33-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12436475
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Genotypes and S-gene variability of Mexican hepatitis B virus strains. Author(s): Sanchez LV, Maldonado M, Bastidas-Ramirez BE, Norder H, Panduro A. Source: Journal of Medical Virology. 2002 September; 68(1): 24-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12210427
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Genotypic and phenotypic resistance: longitudinal and sequential analysis of hepatitis B virus polymerase mutations in patients with lamivudine resistance after liver transplantation. Author(s): Ben-Ari Z, Daudi N, Klein A, Sulkes J, Papo O, Mor E, Samra Z, Gadba R, Shouval D, Tur-Kaspa R. Source: The American Journal of Gastroenterology. 2003 January; 98(1): 151-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12526951
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Geographic characterization of hepatitis virus infections, genotyping of hepatitis B virus, and p53 mutation in hepatocellular carcinoma analyzed by in situ detection of viral genomes from carcinoma tissues: comparison among six different countries. Author(s): Ding X, Park YN, Taltavull TC, Thung SN, Jin X, Jin Y, Trung NS, Edamoto Y, Sata T, Abe K. Source: Japanese Journal of Infectious Diseases. 2003 February; 56(1): 12-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12711820
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Global control of hepatitis B virus infection. Author(s): Kao JH, Chen DS. Source: The Lancet Infectious Diseases. 2002 July; 2(7): 395-403. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12127351
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Hepatitis B core antigen stimulates interleukin-10 secretion by both T cells and monocytes from peripheral blood of patients with chronic hepatitis B virus infection. Author(s): Hyodo N, Nakamura I, Imawari M. Source: Clinical and Experimental Immunology. 2004 March; 135(3): 462-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15008979
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Hepatitis B vaccine coverage among infants born to women without prenatal screening for hepatitis B virus infection: effects of the Joint Statement on Thimerosal in Vaccines. Author(s): Thomas AR, Fiore AE, Corwith HL, Cieslak PR, Margolis HS. Source: The Pediatric Infectious Disease Journal. 2004 April; 23(4): 313-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15071284
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Hepatitis B virus epidemiology, disease burden, treatment, and current and emerging prevention and control measures. Author(s): Lavanchy D. Source: Journal of Viral Hepatitis. 2004 March; 11(2): 97-107. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14996343
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Hepatitis B virus gene in liver tissue promotes hepatocellular carcinoma development in chronic hepatitis C patients. Author(s): Fujioka S, Shimomura H, Iwasaki Y, Fujio K, Nakagawa H, Onishi Y, Takagi S, Taniguchi H, Umeoka F, Nakajima H, Moriya A, Nanba K, Piao CY, Shinji T, Koide N, Shiratori Y. Source: Digestive Diseases and Sciences. 2003 October; 48(10): 1920-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14627334
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Hepatitis B virus genotype D prevails in patients with persistently elevated or normal ALT levels in Turkey. Author(s): Yalcin K, Degertekin H, Bahcecioglu IH, Demir A, Aladag M, Yildirim B, Horasanli S, Ciftci S, Badur S. Source: Infection. 2004 February; 32(1): 24-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15007739
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Hepatitis B virus genotype distribution in HIV-1 coinfected patients. Author(s): Zehender C, De Maddalena C, Milazzo L, Piazza M, Galli M, Tanzi E, Bruno R. Source: Gastroenterology. 2003 November; 125(5): 1559-60; Author Reply 1660. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14628817
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Hepatitis B virus genotypes and core promoter variant. Author(s): Kao JH, Chen DS. Source: Gastroenterology. 2004 February; 126(2): 633; Author Reply 633. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14765403
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Hepatitis B virus genotypes and precore and core mutants in Brazilian patients. Author(s): Sitnik R, Pinho JR, Bertolini DA, Bernardini AP, Da Silva LC, Carrilho FJ. Source: Journal of Clinical Microbiology. 2004 June; 42(6): 2455-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15184419
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Hepatitis B virus in a select pediatric population in Delhi, India. Author(s): Kaur R, Berry N, Mittal SK, Mathur MD, Baveja U. Source: J Commun Dis. 2002 June; 34(2): 146-8. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14768833
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Hepatitis B virus infection in Haemodialysis Centres from Santa Catarina State, Southern Brazil. Predictive risk factors for infection and molecular epidemiology. Author(s): Carrilho FJ, Moraes CR, Pinho JR, Mello IM, Bertolini DA, Lemos MF, Moreira RC, Bassit LC, Cardoso RA, Ribeiro-dos-Santos G, Da Silva LC. Source: Bmc Public Health [electronic Resource]. 2004 April 27; 4(1): 13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15113436
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Hepatitis B virus infection--natural history and clinical consequences. Author(s): Ganem D, Prince AM. Source: The New England Journal of Medicine. 2004 March 11; 350(11): 1118-29. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15014185
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Hepatitis B virus reactivation after fludarabine-based regimens for indolent nonHodgkin's lymphomas: high prevalence of acquired viral genomic mutations. Author(s): Picardi M, Pane F, Quintarelli C, De Renzo A, Del Giudice A, De Divitiis B, Persico M, Ciancia R, Salvatore F, Rotoli B. Source: Haematologica. 2003 November; 88(11): 1296-303. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14607759
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Hepatitis B virus reactivation in a case of non-Hodgkin's lymphoma treated with chemotherapy and rituximab: necessity of prophylaxis for hepatitis B virus reactivation in rituximab therapy. Author(s): Tsutsumi Y, Kawamura T, Saitoh S, Yamada M, Obara S, Miura T, Kanamori H, Tanaka J, Asaka M, Imamura M, Masauzi N. Source: Leukemia & Lymphoma. 2004 March; 45(3): 627-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15160930
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Hepatitis B virus X antigen promotes transforming growth factor-beta1 (TGF-beta1) activity by up-regulation of TGF-beta1 and down-regulation of alpha2macroglobulin. Author(s): Pan J, Clayton M, Feitelson MA. Source: The Journal of General Virology. 2004 February; 85(Pt 2): 275-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14769885
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Hepatitis B virus-infected peripheral blood progenitor cell harvests in liquid nitrogen freezer containing non-infectious products. Author(s): Husebekk A, Skaug K, Kolstad A, Dahl IM, Gutteberg T, Skogen B. Source: Transfusion. 2004 June; 44(6): 942-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15157265
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Hepatocellular carcinoma in a patient with human immunodeficiency virus and hepatitis B virus coinfection: an emerging problem? Author(s): Hyun CB, Coyle WJ. Source: Southern Medical Journal. 2004 April; 97(4): 401-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15108838
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Histological spectrum of chronic hepatitis in precore mutants and wild-type hepatitis B virus infection. Author(s): Sakhuja P, Malhotra V, Gondal R, Sarin SK, Guptan R, Thakur V. Source: Trop Doct. 2004 July; 34(3): 147-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15267041
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HIV-1 and hepatitis B virus: time for a re-think? Author(s): Ripamonti D, Maggiolo F, Suter F. Source: Lancet. 2004 April 24; 363(9418): 1400. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15110510
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HLA phenotypes and outcomes of hepatitis B virus infection in Taiwan. Author(s): Wu YF, Wang LY, Lee TD, Lin HH, Hu CT, Cheng ML, Lo SY. Source: Journal of Medical Virology. 2004 January; 72(1): 17-25. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14635006
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Human S15a expression is upregulated by hepatitis B virus X protein. Author(s): Lian Z, Liu J, Li L, Li X, Tufan NL, Wu MC, Wang HY, Arbuthnot P, Kew M, Feitelson MA. Source: Molecular Carcinogenesis. 2004 May; 40(1): 34-46. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15108328
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Identification of antigenic regions of duck hepatitis B virus core protein with antibodies elicited by DNA immunization and chronic infection. Author(s): Thermet A, Robaczewska M, Rollier C, Hantz O, Trepo C, Deleage G, Cova L. Source: Journal of Virology. 2004 February; 78(4): 1945-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14747559
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Identification of rare polymerase variants of hepatitis B virus using a two-stage PCR with peptide nucleic acid clamping. Author(s): Ohishi W, Shirakawa H, Kawakami Y, Kimura S, Kamiyasu M, Tazuma S, Nakanishi T, Chayama K. Source: Journal of Medical Virology. 2004 April; 72(4): 558-65. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14981758
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IL-4 suppresses the expression and the replication of hepatitis B virus in the hepatocellular carcinoma cell line Hep3B. Author(s): Lin SJ, Shu PY, Chang C, Ng AK, Hu CP. Source: Journal of Immunology (Baltimore, Md. : 1950). 2003 November 1; 171(9): 470816. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14568946
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Impact of acute hepatitis C virus superinfection in patients with chronic hepatitis B virus infection. Author(s): Liaw YF, Chen YC, Sheen IS, Chien RN, Yeh CT, Chu CM. Source: Gastroenterology. 2004 April; 126(4): 1024-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15057742
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Impact of chronic hepatitis B virus (HBV) infection on outcomes of patients infected with HIV in an area where HBV infection is hyperendemic. Author(s): Sheng WH, Chen MY, Hsieh SM, Hsiao CF, Wang JT, Hung CC, Chang SC. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2004 May 15; 38(10): 1471-7. Epub 2004 April 28. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15156487
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In vitro analysis of hepatitis B virus specific CD4+ T cells. Author(s): Chokshi S, Naoumov NV. Source: Methods in Molecular Medicine. 2004; 96: 97-109. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14762263
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In vitro and in vivo interactions between the hepatitis B virus protein P22 and the cellular protein gC1qR. Author(s): Laine S, Thouard A, Derancourt J, Kress M, Sitterlin D, Rossignol JM. Source: Journal of Virology. 2003 December; 77(23): 12875-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14610208
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In vitro antiviral susceptibility of full-length clinical hepatitis B virus isolates cloned with a novel expression vector. Author(s): Yang H, Westland C, Xiong S, Delaney WE 4th. Source: Antiviral Research. 2004 January; 61(1): 27-36. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14670591
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In vivo neutralization of hepatitis B virus infection by an anti-preS1 humanized antibody in chimpanzees. Author(s): Hong HJ, Ryu CJ, Hur H, Kim S, Oh HK, Oh MS, Park SY. Source: Virology. 2004 January 5; 318(1): 134-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14972542
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Incidence and routes of transmission of hepatitis B virus in England and Wales, 19952000: implications for immunisation policy. Author(s): Hahne S, Ramsay M, Balogun K, Edmunds WJ, Mortimer P. Source: Journal of Clinical Virology : the Official Publication of the Pan American Society for Clinical Virology. 2004 April; 29(4): 211-20. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15018847
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Influence of hepatitis B virus virema upon serum aminotransferase activity in dialysis population. Author(s): Fabrizi F, Mangano S, Alongi G, Bisegna S, Finazzi S, Lunghi G, Ponticelli C. Source: Int J Artif Organs. 2003 December; 26(12): 1048-55. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14738188
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Influence of HLA class II molecules on the outcome of hepatitis B virus infection in population of Zhejiang Province in China. Author(s): Meng XQ, Chen HG, Ma YL, Liu KZ. Source: Hepatobiliary Pancreat Dis Int. 2003 May; 2(2): 230-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14599975
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Inhibition of hepatitis B virus replication by APOBEC3G. Author(s): Turelli P, Mangeat B, Jost S, Vianin S, Trono D. Source: Science. 2004 March 19; 303(5665): 1829. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15031497
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Inhibition of hepatitis B virus replication by stably expressed shRNA. Author(s): Chen Y, Du D, Wu J, Chan CP, Tan Y, Kung HF, He ML. Source: Biochemical and Biophysical Research Communications. 2003 November 14; 311(2): 398-404. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14592428
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Integration of hepatitis B virus containing mutations in the core promoter/X gene in patients with hepatocellular carcinoma. Author(s): Momosaki S, Hsia CC, Nakashima Y, Kojiro M, Tabor E. Source: Dig Liver Dis. 2003 November; 35(11): 795-800. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14674670
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Interaction of the hepatitis B virus X protein (HBx) with heat shock protein 60 enhances HBx-mediated apoptosis. Author(s): Tanaka Y, Kanai F, Kawakami T, Tateishi K, Ijichi H, Kawabe T, Arakawa Y, Kawakami T, Nishimura T, Shirakata Y, Koike K, Omata M. Source: Biochemical and Biophysical Research Communications. 2004 May 28; 318(2): 461-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15120623
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Interferon alpha inhibits the nuclear factor kappa B activation triggered by X gene product of hepatitis B virus in human hepatoma cells. Author(s): Ohata K, Ichikawa T, Nakao K, Shigeno M, Nishimura D, Ishikawa H, Hamasaki K, Eguchi K. Source: Febs Letters. 2003 October 23; 553(3): 304-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14572641
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Interferon-inducible MyD88 protein inhibits hepatitis B virus replication. Author(s): Xiong W, Wang X, Liu X, Xiang L, Zheng L, Yuan Z. Source: Virology. 2004 February 20; 319(2): 306-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14980490
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Intracellular distribution of hepatitis B virus core protein expressed in vitro depends on the sequence of the isolate and the serologic pattern. Author(s): Jazayeri MS, Dornan ES, Boner W, Fattovich G, Hadziyannis S, Carman WF. Source: The Journal of Infectious Diseases. 2004 May 1; 189(9): 1634-45. Epub 2004 April 19. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15116300
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Involvement of the CXCL12/CXCR4 pathway in the advanced liver disease that is associated with hepatitis C virus or hepatitis B virus. Author(s): Wald O, Pappo O, Safadi R, Dagan-Berger M, Beider K, Wald H, Franitza S, Weiss I, Avniel S, Boaz P, Hanna J, Zamir G, Eid A, Mandelboim O, Spengler U, Galun E, Peled A. Source: European Journal of Immunology. 2004 April; 34(4): 1164-74. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15048728
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Kidney transplantation in patients with chronic hepatitis B virus infection: is the prognosis worse? Author(s): Huo TI, Yang WC, Wu JC, King KL, Loong CC, Lin CY, Chang FY, Lee SD. Source: Digestive Diseases and Sciences. 2001 March; 46(3): 469-75. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11318517
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Kinetic analysis of wild-type and YMDD mutant hepatitis B virus polymerases and effects of deoxyribonucleotide concentrations on polymerase activity. Author(s): Gaillard RK, Barnard J, Lopez V, Hodges P, Bourne E, Johnson L, Allen MI, Condreay P, Miller WH, Condreay LD. Source: Antimicrobial Agents and Chemotherapy. 2002 April; 46(4): 1005-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11897582
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Kinetics of acute hepatitis B virus infection in humans. Author(s): Whalley SA, Murray JM, Brown D, Webster GJ, Emery VC, Dusheiko GM, Perelson AS. Source: The Journal of Experimental Medicine. 2001 April 2; 193(7): 847-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11283157
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Lack of epidemiological evidence for a role of resolved hepatitis B virus infection in hepatocarcinogenesis in patients infected with hepatitis C virus in Japan. Author(s): Hiraoka T, Katayama K, Tanaka J, Ohno N, Joko K, Komiya Y, Kumagai J, Mizui M, Hino K, Miyakawa Y, Yoshizawa H. Source: Intervirology. 2003; 46(3): 171-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12867755
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Lack of 'occult' hepatitis B virus infection in HIV-infected patients. Author(s): Nunez M, Rios P, Perez-Olmeda M, Soriano V. Source: Aids (London, England). 2002 October 18; 16(15): 2099-101. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12370518
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Lack of seroconversion after hepatitis B virus immunization. Author(s): Diamond C. Source: American Journal of Public Health. 2004 March; 94(3): 358; Author Reply 358-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14998792
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Lamivudine and Famciclovir resistant hepatitis B virus associated with fatal hepatic failure. Author(s): Ayres A, Bartholomeusz A, Lau G, Lam KC, Lee JY, Locarnini S. Source: Journal of Clinical Virology : the Official Publication of the Pan American Society for Clinical Virology. 2003 May; 27(1): 111-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12727536
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Lamivudine for the prevention of hepatitis B virus reactivation in hepatitis B santigen seropositive cancer patients undergoing cytotoxic chemotherapy. Author(s): Yeo W, Chan PK, Ho WM, Zee B, Lam KC, Lei KI, Chan AT, Mok TS, Lee JJ, Leung TW, Zhong S, Johnson PJ. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2004 March 1; 22(5): 927-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14990649
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Lamivudine for the treatment of hepatitis B virus-related liver disease after renal transplantation: meta-analysis of clinical trials. Author(s): Fabrizi F, Dulai G, Dixit V, Bunnapradist S, Martin P. Source: Transplantation. 2004 March 27; 77(6): 859-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15077027
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Lamivudine prophylaxis for prevention of chemotherapy-induced hepatitis B virus reactivation in hepatitis B virus carriers with malignancies. Author(s): Idilman R, Arat M, Soydan E, Toruner M, Soykan I, Akbulut H, Arslan O, Ozcan M, Turkyilmaz AR, Bozdayi M, Karayalcin S, Van Thiel DH, Ozden A, Beksac M, Akan H. Source: Journal of Viral Hepatitis. 2004 March; 11(2): 141-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14996349
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125
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Lamivudine therapy for decompensated liver cirrhosis related to hepatitis B virus infection. Author(s): Lee HC, Suh DJ. Source: Intervirology. 2003; 46(6): 388-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14688457
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Lamivudine treatment during pregnancy to prevent perinatal transmission of hepatitis B virus infection. Author(s): van Zonneveld M, van Nunen AB, Niesters HG, de Man RA, Schalm SW, Janssen HL. Source: Journal of Viral Hepatitis. 2003 July; 10(4): 294-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12823596
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Lamivudine treatment for acute hepatitis B virus infection during allogeneic peripheral blood stem cell transplantation. Author(s): Efremov DG, Georgievski B, Cevreska L, Pivkova A, Panovska I. Source: Bone Marrow Transplantation. 2003 March; 31(6): 515-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12665850
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Latent hepatitis B virus (HBV) infection and HBV DNA integration is associated with further transformation of hepatoma cells in vitro. Author(s): Favre D, Petit MA, Trepo C. Source: Altex. 2003; 20(3): 131-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12947486
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Limited value of 18F-2-deoxyglucose positron emission tomography to detect hepatocellular carcinoma in hepatitis B virus carriers. Author(s): Jeng LB, Changlai SP, Shen YY, Lin CC, Tsai CH, Kao CH. Source: Hepatogastroenterology. 2003 November-December; 50(54): 2154-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14696485
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Liver transplantation for hepatitis B virus-related liver disease: indications, prevention of recurrence and results. Author(s): Roche B, Samuel D. Source: Journal of Hepatology. 2003; 39 Suppl 1: S181-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14708701
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Longitudinal analysis of CD8+ T cells specific for structural and nonstructural hepatitis B virus proteins in patients with chronic hepatitis B: implications for immunotherapy. Author(s): Webster GJ, Reignat S, Brown D, Ogg GS, Jones L, Seneviratne SL, Williams R, Dusheiko G, Bertoletti A. Source: Journal of Virology. 2004 June; 78(11): 5707-19. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15140968
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Long-term immunogenicity and efficacy of universal hepatitis B virus vaccination in Taiwan. Author(s): Lin YC, Chang MH, Ni YH, Hsu HY, Chen DS. Source: The Journal of Infectious Diseases. 2003 January 1; 187(1): 134-8. Epub 2002 December 13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12508157
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Low genetic diversity despite hyperendemicity of hepatitis B virus genotype E throughout West Africa. Author(s): Mulders MN, Venard V, Njayou M, Edorh AP, Bola Oyefolu AO, Kehinde MO, Muyembe Tamfum JJ, Nebie YK, Maiga I, Ammerlaan W, Fack F, Omilabu SA, Le Faou A, Muller CP. Source: The Journal of Infectious Diseases. 2004 July 15; 190(2): 400-8. Epub 2004 June 22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15216479
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Low HBeAg serum levels correlate with the presence of the double A1762T/G1764A core promoter mutation and a positive response to interferon in patients with chronic hepatitis B virus infection. Author(s): Marrone A, Zampino R, Luongo G, Utili R, Karayiannis P, Ruggiero G. Source: Intervirology. 2003; 46(4): 222-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12931030
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Low rate of YMDD motif mutations in polymerase gene of hepatitis B virus in chronically infected patients not treated with lamivudine. Author(s): Matsuda M, Suzuki F, Suzuki Y, Tsubota A, Akuta N, Hosaka T, Someya T, Kobayashi M, Saitoh S, Arase Y, Satoh J, Takagi K, Kobayashi M, Ikeda K, Kumada H. Source: Journal of Gastroenterology. 2004 January; 39(1): 34-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14767732
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Low-dose hepatitis B immunoglobulin given "on demand" in combination with lamivudine: a highly cost-effective approach to prevent recurrent hepatitis B virus infection in the long-term follow-up after liver transplantation. Author(s): Di Paolo D, Tisone G, Piccolo P, Lenci I, Zazza S, Angelico M. Source: Transplantation. 2004 April 27; 77(8): 1203-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15114086
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LRH-1/hB1F and HNF1 synergistically up-regulate hepatitis B virus gene transcription and DNA replication. Author(s): Cai YN, Zhou Q, Kong YY, Li M, Viollet B, Xie YH, Wang Y. Source: Cell Research. 2003 December; 13(6): 451-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14728801
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Management of chronic hepatitis B in an HIV-positive patient with 3TC-resistant hepatitis B virus. Author(s): Ristig M, Drechsler H, Crippin J, Lisker-Melman M, Tebas P. Source: Aids Patient Care and Stds. 2003 September; 17(9): 439-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14588080
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Management of the patient with hepatitis B virus-related cirrhosis. Author(s): Perrillo RP. Source: Journal of Hepatology. 2003; 39 Suppl 1: S177-80. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14708700
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Mechanism of intrauterine infection of hepatitis B virus. Author(s): Zhang SL, Yue YF, Bai GQ, Shi L, Jiang H. Source: World Journal of Gastroenterology : Wjg. 2004 February 1; 10(3): 437-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14760774
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Molecular chaperone GRP78/BiP interacts with the large surface protein of hepatitis B virus in vitro and in vivo. Author(s): Cho DY, Yang GH, Ryu CJ, Hong HJ. Source: Journal of Virology. 2003 February; 77(4): 2784-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12552023
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Molecular characterization of hepatitis B virus surface antigen mutants in Singapore patients with hepatocellular carcinoma and hepatitis B virus carriers negative for HBsAg but positive for anti-HBs and anti-HBc. Author(s): Oon CJ, Chen WN, Goh KT, Mesenas S, Ng HS, Chiang G, Tan C, Koh S, Teng SW, Toh I, Moh MC, Goo KS, Tan K, Leong AL, Tan GS. Source: Journal of Gastroenterology and Hepatology. 2002 December; 17 Suppl: S491-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12534784
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Molecular epidemiology of gibbon hepatitis B virus transmission. Author(s): Noppornpanth S, Haagmans BL, Bhattarakosol P, Ratanakorn P, Niesters HG, Osterhaus AD, Poovorawan Y. Source: The Journal of General Virology. 2003 January; 84(Pt 1): 147-55. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12533711
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Molecular epidemiology of hepatitis B virus in Amsterdam 1992-1997. Author(s): van Steenbergen JE, Niesters HG, Op de Coul EL, van Doornum GJ, Osterhaus AD, Leentvaar-Kuijpers A, Coutinho RA, van den Hoek JA. Source: Journal of Medical Virology. 2002 February; 66(2): 159-65. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11782923
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Monitoring the emergence of hepatitis B virus polymerase gene variants during lamivudine therapy in human immunodeficiency virus coinfected patients: performance of CLIP sequencing and line probe assay. Author(s): Roque-Afonso AM, Ferey MP, Mackiewicz V, Fki L, Dussaix E. Source: Antivir Ther. 2003 December; 8(6): 627-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14760897
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Multicenter evaluation of the VERSANT hepatitis B virus DNA 3.0 assay. Author(s): Yao JD, Beld MG, Oon LL, Sherlock CH, Germer J, Menting S, Se Thoe SY, Merrick L, Ziermann R, Surtihadi J, Hnatyszyn HJ. Source: Journal of Clinical Microbiology. 2004 February; 42(2): 800-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14766856
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Multiplex real-time quantitative RT-PCR assay for hepatitis B virus, hepatitis C virus, and human immunodeficiency virus type 1. Author(s): Candotti D, Temple J, Owusu-Ofori S, Allain JP. Source: Journal of Virological Methods. 2004 June 1; 118(1): 39-47. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15158067
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Mutations of the surface protein of hepatitis B virus. Author(s): Zuckerman JN, Zuckerman AJ. Source: Antiviral Research. 2003 October; 60(2): 75-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14638401
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Natural variants of hepatitis B virus X protein have differential effects on the expression of cyclin-dependent kinase inhibitor p21 gene. Author(s): Kwun HJ, Jang KL. Source: Nucleic Acids Research. 2004 April 23; 32(7): 2202-13. Print 2004. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15107488
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New enzyme immunoassay for detection of hepatitis B virus core antigen (HBcAg) and relation between levels of HBcAg and HBV DNA. Author(s): Kimura T, Rokuhara A, Matsumoto A, Yagi S, Tanaka E, Kiyosawa K, Maki N. Source: Journal of Clinical Microbiology. 2003 May; 41(5): 1901-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12734224
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No evidence of hepatitis B virus activity in patients with anti-HBc antibody positivity with or without anti-hepatitis C virus antibody positivity. Author(s): Haushofer AC, Hauer R, Brunner H, Koller U, Trubert-Exinger D, Halbmayer WM, Koidl C, Kessler HH. Source: Journal of Clinical Virology : the Official Publication of the Pan American Society for Clinical Virology. 2004 April; 29(4): 221-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15018848
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Novel assay of competitively differentiated polymerase chain reaction for screening point mutation of hepatitis B virus. Author(s): Peng XM, Chen XJ, Li JG, Gu L, Huang YS, Gao ZL. Source: World Journal of Gastroenterology : Wjg. 2003 August; 9(8): 1743-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12918112
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Novel hepatitis B virus genotype a subtyping assay that distinguishes subtype Aa from Ae and its application in epidemiological studies. Author(s): Hasegawa I, Tanaka Y, Kramvis A, Kato T, Sugauchi F, Acharya SK, Orito E, Ueda R, Kew MC, Mizokami M. Source: Journal of Virology. 2004 July; 78(14): 7575-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15220432
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Novel ring-expanded nucleoside analogs exhibit potent and selective inhibition of hepatitis B virus replication in cultured human hepatoblastoma cells. Author(s): Sood RK, Bhadti VS, Fattom AI, Naso RB, Korba BE, Kern ER, Chen HM, Hosmane RS. Source: Antiviral Research. 2002 February; 53(2): 159-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11750942
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Novel tissue and cell type-specific gene/drug delivery system using surface engineered hepatitis B virus nano-particles. Author(s): Yamada T, Ueda M, Seno M, Kondo A, Tanizawa K, Kuroda S. Source: Current Drug Targets. Infectious Disorders. 2004 June; 4(2): 163-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15180463
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Novel treatment options for hepatitis B virus infection. Author(s): Kumar R, Agrawal B. Source: Curr Opin Investig Drugs. 2004 February; 5(2): 171-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15043391
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Nuclear import of hepatitis B virus capsids and release of the viral genome. Author(s): Rabe B, Vlachou A, Pante N, Helenius A, Kann M. Source: Proceedings of the National Academy of Sciences of the United States of America. 2003 August 19; 100(17): 9849-54. Epub 2003 Aug 08. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12909718
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Nursing staff knowledge of the hepatitis B virus including attitudes and acceptance of hepatitis B vaccination: development of an effective program. Author(s): McGrane J, Staines A. Source: Aaohn Journal : Official Journal of the American Association of Occupational Health Nurses. 2003 August; 51(8): 347-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12934862
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Occult hepatitis B virus (HBV) infection in healthy blood donors. Author(s): Duseja A, Sharma S, Subramanian PG, Agnihotri SK, Chakraborti A, Chawla Y. Source: Indian J Pathol Microbiol. 2003 October; 46(4): 690-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15025384
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Occult hepatitis B virus infection and clinical outcomes of patients with chronic hepatitis C. Author(s): Kao JH, Chen PJ, Lai MY, Chen DS. Source: Journal of Clinical Microbiology. 2002 November; 40(11): 4068-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12409376
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Occult hepatitis B virus infection as a cause of cirrhosis of liver in a region with intermediate endemicity. Author(s): Agarwal N, Naik S, Aggarwal R, Singh H, Somani SK, Kini D, Pandey R, Choudhuri G, Saraswat VA, Naik SR. Source: Indian J Gastroenterol. 2003 July-August; 22(4): 127-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12962434
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Occult hepatitis B virus infection does not affect liver histology or response to therapy with interferon alpha and ribavirin in intravenous drug users with chronic hepatitis C. Author(s): Fabris P, Brown D, Tositti G, Bozzola L, Giordani MT, Bevilacqua P, de Lalla F, Webster GJ, Dusheiko G. Source: Journal of Clinical Virology : the Official Publication of the Pan American Society for Clinical Virology. 2004 March; 29(3): 160-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14962784
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Occult hepatitis B virus infection in HBsAg negative patients undergoing liver transplantation: clinical significance. Author(s): Ghisetti V, Marzano A, Zamboni F, Barbui A, Franchello A, Gaia S, Marchiaro G, Salizzoni M, Rizzetto M. Source: Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. 2004 March; 10(3): 356-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15004761
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Occult hepatitis B virus infection in HIV/hepatitis C virus co-infected patients. Author(s): Fabris P, Giordani MT, Tositti G, Rassu M, De Lalla F. Source: Aids (London, England). 2003 July 4; 17(10): 1581-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12824807
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Occult hepatitis B virus infection in patients with hepatocellular carcinoma: Innocent bystander, cofactor, or culprit? Author(s): Marrero JA, Lok AS. Source: Gastroenterology. 2004 January; 126(1): 347-50. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14699513
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Occult hepatitis B virus infection. Author(s): Allain JP. Source: Transfusion Clinique Et Biologique : Journal De La Societe Francaise De Transfusion Sanguine. 2004 February; 11(1): 18-25. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14980545
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Occupational exposures to human immunodeficiency virus, hepatitis B virus, and hepatitis C virus: risk, prevention, and management. Author(s): Cleveland JL, Cardo DM. Source: Dent Clin North Am. 2003 October; 47(4): 681-96. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14664459
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Oral ganciclovir for treatment of lamivudine-resistant hepatitis B virus infection: a pilot study. Author(s): Bozkaya H, Yurdaydin C, Bozdayi AM, Erkan O, Karayalcin S, Uzunalimoglu O. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2002 October 15; 35(8): 960-5. Epub 2002 September 25. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12355383
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PCR restriction fragment length polymorphism in detection of YMDD variants of viral polymerase in hepatitis B virus patients treated with lamivudine. Author(s): Yang DH, Liang WF, Xie YJ, Zhao NF, Fan J. Source: Hepatobiliary Pancreat Dis Int. 2002 May; 1(2): 232-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14612274
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PGS consensus statement on management of hepatitis B virus infection--2003. Author(s): Abbas Z, Jafri W, Shah SH, Khokhar N, Zuberi SJ; Pakistan Society of Gastroenterology and G.I. Endoscopy. Source: J Pak Med Assoc. 2004 March; 54(3): 150-8. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15129877
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Poor validity of self-reported hepatitis B virus infection and vaccination status among young drug users. Author(s): Kuo I, Mudrick DW, Strathdee SA, Thomas DL, Sherman SG. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2004 February 15; 38(4): 587-90. Epub 2004 January 29. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14765355
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Precision and stability of hepatitis B virus DNA levels in chronic surface antigen carriers. Author(s): Plentz A, Koller G, Weinberger KM, Jilg W. Source: Journal of Medical Virology. 2004 August; 73(4): 522-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15221895
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Precore/core promoter mutations and genotypes of hepatitis B virus in chronic hepatitis B patients with fulminant or subfulminant hepatitis. Author(s): Liu CJ, Kao JH, Lai MY, Chen PJ, Chen DS. Source: Journal of Medical Virology. 2004 April; 72(4): 545-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14981756
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Pre-emptive use of lamivudine in bone marrow transplantation with chronic hepatitis B virus infection. Author(s): Deschenes M, Laneuville P. Source: Hepatology (Baltimore, Md.). 2004 March; 39(3): 867; Author Reply 867-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14999714
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Preemptive use of lamivudine in breast cancer patients carrying hepatitis B virus undergoing cytotoxic chemotherapy: a longitudinal study. Author(s): Dai MS, Wu PF, Lu JJ, Shyu RY, Chao TY. Source: Supportive Care in Cancer : Official Journal of the Multinational Association of Supportive Care in Cancer. 2004 March; 12(3): 191-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15074316
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Prevalence of hepatitis B virus surface antigen (HBsAg) in patients undergoing extraction at the University College Hospital, Ibadan. Author(s): Odaibo GN, Arotiba JT, Fasola AO, Obiechina AE, Olaleye OD, Ajagbe HA. Source: Afr J Med Med Sci. 2003 September; 32(3): 243-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15030081
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Processing of hepatitis B virus surface proteins. Author(s): Bruss V. Source: Methods in Molecular Medicine. 2004; 95: 189-98. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14982058
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Prophylaxis and treatment of hepatitis B virus reinfection following liver transplantation. Author(s): Zheng SS, Wu J, Liang TB, Wang WL, Huang DS, Xu X. Source: Hepatobiliary Pancreat Dis Int. 2002 August; 1(3): 327-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14607701
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Quantification of intrahepatic hepatitis B virus (HBV) DNA in patients with chronic HBV infection. Author(s): Cacciola I, Pollicino T, Squadrito G, Cerenzia G, Villari D, de Franchis R, Santantonio T, Brancatelli S, Colucci G, Raimondo G. Source: Hepatology (Baltimore, Md.). 2000 February; 31(2): 507-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10655278
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Quantitation of hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) in the liver of HBV-infected patients by LightCycler real-time PCR. Author(s): Singh M, Dicaire A, Wakil AE, Luscombe C, Sacks SL. Source: Journal of Virological Methods. 2004 June 15; 118(2): 159-67. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15081611
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Quantitative analysis of hepatitis B virus DNA by real-lime amplification. Author(s): Zanella I, Rossini A, Domenighini D, Albertini A, Cariani E. Source: European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology. 2002 January; 21(1): 22-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11913497
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Quantitative analysis of the interaction between the envelope protein domains and the core protein of human hepatitis B virus. Author(s): Choi KJ, Lim CW, Yoon MY, Ahn BY, Yu YG. Source: Biochemical and Biophysical Research Communications. 2004 July 2; 319(3): 95966. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15184075
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Quantitative detection of hepatitis B virus DNA by real-time nucleic acid sequencebased amplification with molecular beacon detection. Author(s): Yates S, Penning M, Goudsmit J, Frantzen I, van de Weijer B, van Strijp D, van Gemen B. Source: Journal of Clinical Microbiology. 2001 October; 39(10): 3656-65. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11574587
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Quantitative detection of hepatitis B virus DNA in serum by a new rapid real-time fluorescence PCR assay. Author(s): Jardi R, Rodriguez F, Buti M, Costa X, Cotrina M, Valdes A, Galimany R, Esteban R, Guardia J. Source: Journal of Viral Hepatitis. 2001 November; 8(6): 465-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11703579
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Quantitative DNA fragment analysis for detecting low amounts of hepatitis B virus deletion mutants in highly viremic carriers. Author(s): Schlager F, Schaefer S, Metzler M, Gratzki N, Lampert F, Gerlich WH, Repp R. Source: Hepatology (Baltimore, Md.). 2000 November; 32(5): 1096-105. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11050061
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Quantitative hepatitis B virus DNA testing for the early prediction of the maintenance of response during lamivudine therapy in patients with chronic hepatitis B. Author(s): Buti M, Sanchez F, Cotrina M, Jardi R, Rodriguez F, Esteban R, Guardia J. Source: The Journal of Infectious Diseases. 2001 April 15; 183(8): 1277-80. Epub 2001 March 13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11262212
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Quantitative polymerase chain reaction assay for serum hepatitis B virus DNA as a predictive factor for post-treatment relapse after lamivudine induced hepatitis B e antigen loss or seroconversion. Author(s): Lee HC, Suh DJ, Ryu SH, Kim H, Shin JW, Lim YS, Chung YH, Lee YS. Source: Gut. 2003 December; 52(12): 1779-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14633962
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Quasispecies groups in the core promoter region of hepatitis B virus. Author(s): Deng H, Dong J, Cheng J, Huangfu KJ, Shi SS, Hong Y, Ren XM, Li L. Source: Hepatobiliary Pancreat Dis Int. 2002 August; 1(3): 392-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14607713
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Rapid detection and quantitation of hepatitis B virus DNA by real-time PCR using a new fluorescent (FRET) detection system. Author(s): Aliyu SH, Aliyu MH, Salihu HM, Parmar S, Jalal H, Curran MD. Source: Journal of Clinical Virology : the Official Publication of the Pan American Society for Clinical Virology. 2004 June; 30(2): 191-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15125876
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Rapid quantification of hepatitis B virus DNA by automated sample preparation and real-time PCR. Author(s): Stelzl E, Muller Z, Marth E, Kessler HH. Source: Journal of Clinical Microbiology. 2004 June; 42(6): 2445-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15184417
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Reactivation of hepatitis B virus infection with cytotoxic therapy in non-Hodgkin's lymphoma. Author(s): Ozguroglu M, Bilici A, Turna H, Serdengecti S. Source: Medical Oncology (Northwood, London, England). 2004; 21(1): 67-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15034216
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Regulation of hepatitis B virus core promoter by transcription factors HNF1 and HNF4 and the viral X protein. Author(s): Zheng Y, Li J, Ou JH. Source: Journal of Virology. 2004 July; 78(13): 6908-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15194767
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Relationship of genotype rather than race to hepatitis B virus pathogenicity: a study of Japanese and Solomon Islanders. Author(s): Furusyo N, Kubo N, Nakashima H, Kashiwagi K, Hayashi J. Source: The American Journal of Tropical Medicine and Hygiene. 2004 May; 70(5): 571-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15155994
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Remission of hepatitis B virus-related vasculitis with lamivudine. Author(s): Sawabe T, Uenotsuchi T, Imafuku S, Kohno H, Arima J, Horiuchi T. Source: Annals of Internal Medicine. 2004 April 20; 140(8): 672-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15096355
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Response to lamivudine treatment in children with chronic hepatitis B virus infection. Author(s): Hagmann S, Chung M, Rochford G, Jani M, Trinh-Shevrin C, Sitnitskaya Y, Neumann AU, Pollack H. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2003 December 1; 37(11): 1434-40. Epub 2003 November 06. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14614664
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Restoration of immunity and reactivation of hepatitis B virus after immunosuppressive therapy in a patient with severe aplastic anaemia. Author(s): Dai MS, Kao WY, Shyu RY, Chao TY. Source: Journal of Viral Hepatitis. 2004 May; 11(3): 283-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15117333
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Retrospective evaluation of the risk of hepatitis B virus reactivation after transplantation. Author(s): Duhart BT Jr, Honaker MR, Shokouh-Amiri MH, Riely CA, Vera SR, Taylor SL, Al-jedai AH, Gaber AO. Source: Transplant Infectious Disease : an Official Journal of the Transplantation Society. 2003 September; 5(3): 126-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14617300
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Role of hepatitis B virus specific cytotoxic T cells in liver damage and viral control. Author(s): Bertoletti A, Maini M, Williams R. Source: Antiviral Research. 2003 October; 60(2): 61-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14638399
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Selective functional deficit in dendritic cell--T cell interaction is a crucial mechanism in chronic hepatitis B virus infection. Author(s): Zheng BJ, Zhou J, Qu D, Siu KL, Lam TW, Lo HY, Lee SS, Wen YM. Source: Journal of Viral Hepatitis. 2004 May; 11(3): 217-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15117323
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Sequence variation upstream of precore translation initiation codon reduces hepatitis B virus e antigen production. Author(s): Ahn SH, Kramvis A, Kawai S, Spangenberg HC, Li J, Kimbi G, Kew M, Wands J, Tong S. Source: Gastroenterology. 2003 November; 125(5): 1370-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14598253
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Seroprevalence of human immunodeficiency virus, hepatitis B virus and hepatitis C virus among eye donors. Author(s): Mahalakshmi B, Madhavan HN, Pushpalatha R, Margarita S. Source: Indian J Ophthalmol. 2004 March; 52(1): 61-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15132383
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Short-term corticosteroids then lamivudine and plasma exchanges to treat hepatitis B virus-related polyarteritis nodosa. Author(s): Guillevin L, Mahr A, Cohen P, Larroche C, Queyrel V, Loustaud-Ratti V, Imbert B, Hausfater P, Roudier J, Bielefeld P, Petitjean P, Smadja D; French Vasculitis Study Group. Source: Arthritis and Rheumatism. 2004 June 15; 51(3): 482-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15188337
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Significant correlation between expression level of HSP gp96 and progression of hepatitis B virus induced diseases. Author(s): Zhu XD, Li CL, Lang ZW, Gao GF, Tien P. Source: World Journal of Gastroenterology : Wjg. 2004 April 15; 10(8): 1141-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15069714
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Small interfering RNA inhibits hepatitis B virus replication in mice. Author(s): Giladi H, Ketzinel-Gilad M, Rivkin L, Felig Y, Nussbaum O, Galun E. Source: Molecular Therapy : the Journal of the American Society of Gene Therapy. 2003 November; 8(5): 769-76. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14599810
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Specific mutations of hepatitis B virus in plasma predict liver cancer development. Author(s): Kuang SY, Jackson PE, Wang JB, Lu PX, Munoz A, Qian GS, Kensler TW, Groopman JD. Source: Proceedings of the National Academy of Sciences of the United States of America. 2004 March 9; 101(10): 3575-80. Epub 2004 February 27. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14990795
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Specific targeted binding of herpes simplex virus type 1 to hepatocytes via the human hepatitis B virus preS1 peptide. Author(s): Argnani R, Boccafogli L, Marconi PC, Manservigi R. Source: Gene Therapy. 2004 July; 11(13): 1087-98. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15057264
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Subclinical reactivation of hepatitis B virus in liver transplant recipients with past exposure. Author(s): Abdelmalek MF, Pasha TM, Zein NN, Persing DH, Wiesner RH, Douglas DD. Source: Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. 2003 December; 9(12): 1253-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14625824
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Hepatitis B Virus
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Surface expression of squamous cell carcinoma antigen (SCCA) can be increased by the preS1(21-47) sequence of hepatitis B virus. Author(s): Ruvoletto MG, Tono N, Carollo D, Vilei T, Trentin L, Muraca M, Marino M, Gatta A, Fassina G, Pontisso P. Source: The Journal of General Virology. 2004 March; 85(Pt 3): 621-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14993646
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Ten-year persistence of antibody to hepatitis B surface antigen in healthcare workers vaccinated against hepatitis B virus, and response to booster vaccination. Author(s): Durlach R, Laugas S, Freuler CB, Rodriguez VE, Costa M. Source: Infection Control and Hospital Epidemiology : the Official Journal of the Society of Hospital Epidemiologists of America. 2003 October; 24(10): 773-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14587943
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The chimpanzee model: contributions and considerations for studies of hepatitis B virus. Author(s): Gagneux P, Muchmore EA. Source: Methods in Molecular Medicine. 2004; 96: 289-318. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14762278
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The development of hepatocellular carcinoma among prospectively followed children with chronic hepatitis B virus infection. Author(s): Wen WH, Chang MH, Hsu HY, Ni YH, Chen HL. Source: The Journal of Pediatrics. 2004 March; 144(3): 397-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15001956
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The effect of mycophenolate acid on hepatitis B virus replication in vitro. Author(s): Wu J, Xie HY, Jiang GP, Xu X, Zheng SS. Source: Hepatobiliary Pancreat Dis Int. 2003 August; 2(3): 410-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14599949
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The hepatitis B virus X protein inhibits secretion of apolipoprotein B by enhancing the expression of N-acetylglucosaminyltransferase III. Author(s): Kang SK, Chung TW, Lee JY, Lee YC, Morton RE, Kim CH. Source: The Journal of Biological Chemistry. 2004 July 2; 279(27): 28106-12. Epub 2004 April 29. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15123606
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Three novel cis-acting elements required for efficient plus-strand DNA synthesis of the hepatitis B virus genome. Author(s): Lee J, Shin MK, Lee HJ, Yoon G, Ryu WS. Source: Journal of Virology. 2004 July; 78(14): 7455-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15220419
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Transmission of hepatitis B virus in correctional facilities--Georgia, January 1999June 2002. Author(s): Centers for Disease Control and Prevention (CDC). Source: Mmwr. Morbidity and Mortality Weekly Report. 2004 August 6; 53(30): 678-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15295311
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Treatment of chronic hepatitis B virus infection via oral immune regulation toward hepatitis B virus proteins. Author(s): Safadi R, Israeli E, Papo O, Shibolet O, Melhem A, Bloch A, Rowe M, Alper R, Klein A, Hemed N, Segol O, Thalenfeld B, Engelhardt D, Rabbani E, Ilan Y. Source: The American Journal of Gastroenterology. 2003 November; 98(11): 2505-15. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14638356
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Two subtypes of genotype B (Ba and Bj) of hepatitis B virus in Japan. Author(s): Sugauchi F, Kumada H, Sakugawa H, Komatsu M, Niitsuma H, Watanabe H, Akahane Y, Tokita H, Kato T, Tanaka Y, Orito E, Ueda R, Miyakawa Y, Mizokami M. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2004 May 1; 38(9): 1222-8. Epub 2004 April 09. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15127332
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Two subtypes of hepatitis B virus-associated glomerulonephritis are associated with different HLA-DR2 alleles in Koreans. Author(s): Park MH, Song EY, Ahn C, Oh KH, Yang J, Kang SJ, Lee HS. Source: Tissue Antigens. 2003 December; 62(6): 505-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14617034
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Uncommon mutation pattern of a hepatitis B virus isolate from genotype F infecting a patient with AIDS. Author(s): Gomes SA, de Castro L, Niel C, Santos EA. Source: The Journal of Infection. 2004 January; 48(1): 102-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14667799
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Understanding correlates of hepatitis B virus vaccination in men who have sex with men: what have we learned? Author(s): Yee LJ, Rhodes SD. Source: Sexually Transmitted Infections. 2002 October; 78(5): 374-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12407244
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Unraveling hepatitis B virus infection of mice and men (and woodchucks and ducks) Author(s): Menne S, Tennant BC. Source: Nature Medicine. 1999 October; 5(10): 1125-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10502809
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Urine from chronic hepatitis B virus carriers: implications for infectivity. Author(s): Knutsson M, Kidd-Ljunggren K. Source: Journal of Medical Virology. 2000 January; 60(1): 17-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10568757
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Use of adefovir in the treatment of the chronic hepatitis B virus infection with resistance to lamivudine. Author(s): Barcena Marugan R, Cid Gomez L, Lopez Serrano P. Source: Transplantation Proceedings. 2003 August; 35(5): 1841-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12962817
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Use of an HBV-DNA hybridization assay in the evaluation of equivocal hepatitis B virus tests in solid organ donors. Author(s): Domen RE, Yen-Lieberman B, Nelson KA, Chua J, Sholtis W, Tyus H, Isada CM. Source: Progress in Transplantation (Aliso Viejo, Calif.). 2000 March; 10(1): 42-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10941326
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Use of combined treatment of hepatitis B immune globulin and lamivudine as prevention of hepatitis B virus recurrence in liver allograft. Author(s): Albeniz Arbizu E, Barcena Marugan R, Oton Nieto E, Mateo Lindeman M, Garcia Gonzalez M, de Vicente Lopez E, Moraleda Garcia G. Source: Transplantation Proceedings. 2003 August; 35(5): 1844-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12962818
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Use of hepatitis B virus DNA quantitation to predict hepatitis B e antigen reversion in cases of chronic hepatitis B. Author(s): Chan HL, Wong ML, Hui AY, Hung LC, Chan FK, Sung JJ. Source: Journal of Clinical Microbiology. 2003 October; 41(10): 4793-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14532223
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Use of immunomodulatory therapy (other than interferon) for the treatment of chronic hepatitis B virus infection. Author(s): Lau GK. Source: Journal of Gastroenterology and Hepatology. 2000 May; 15 Suppl: E46-52. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10921382
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UVDDB p127-binding modulates activities and intracellular distribution of hepatitis B virus X protein. Author(s): Sitterlin D, Bergametti F, Transy C. Source: Oncogene. 2000 September 7; 19(38): 4417-26. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10980617
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Vaccine therapy for hepatitis B virus carrier. Author(s): Akbar SM, Furukawa S, Horiike N, Onji M. Source: Current Drug Targets. Infectious Disorders. 2004 June; 4(2): 93-101. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15180457
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Vacuolization in hepatitis B virus-infected hepatocytes. Author(s): Roingeard P. Source: Hepatology (Baltimore, Md.). 2003 May; 37(5): 1223-4; Author Reply 1224. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12717405
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Valaciclovir for chronic hepatitis B virus infection after lung transplantation. Author(s): Laube I, Boehler A, Renner EL, Speich R. Source: Infection. 2004 February; 32(1): 51-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15007743
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Variability in the incidence of human immunodeficiency virus, hepatitis B virus, and hepatitis C virus infection among young injecting drug users in New York City. Author(s): Des Jarlais DC, Diaz T, Perlis T, Vlahov D, Maslow C, Latka M, Rockwell R, Edwards V, Friedman SR, Monterroso E, Williams I, Garfein RS. Source: American Journal of Epidemiology. 2003 March 1; 157(5): 467-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12615611
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Variants in TNFRSF5 locus and association analysis with Hepatitis B virus (HBV) infection. Author(s): Zhou G, Zhai Y, Dong X, Li Y, Zhang X, Zhang R, Li S, Li X, He F, Wei H, Chen X, Yao Z, Shen Y, Qiang B, He F. Source: Human Mutation. 2004 January; 23(1): 99-100. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14695541
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Vertical transmission of hepatitis B virus despite maternal lamivudine therapy. Author(s): Kazim SN, Wakil SM, Khan LA, Hasnain SE, Sarin SK. Source: Lancet. 2002 April 27; 359(9316): 1488-9. Erratum In: Lancet 2002 November 9; 360(9344): 1520. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11988251
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Viral genotypes and response to interferon in patients with acute prolonged hepatitis B virus infection of adulthood in Japan. Author(s): Kobayashi M, Arase Y, Ikeda K, Tsubota A, Suzuki Y, Saitoh S, Kobayashi M, Suzuki F, Akuta N, Someya T, Matsuda M, Sato J, Takagi K, Miyakawa Y, Kumada H. Source: Journal of Medical Virology. 2002 December; 68(4): 522-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12376960
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Viral mutants and fulminant hepatitis. A dominant hepatitis B virus population defective in virus secretion because of several S-gene mutations from a patient with fulminant hepatitis. Author(s): Chang MH. Source: Journal of Pediatric Gastroenterology and Nutrition. 2002 April; 34(4): 426. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11981952
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Viral replication modulated by synthetic peptide derived from hepatitis B virus X protein. Author(s): Song CZ, Wang QW, Song CC, Bai ZL. Source: World Journal of Gastroenterology : Wjg. 2004 February 1; 10(3): 389-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14760764
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Virological significance of low-level hepatitis B virus infection in patients with hepatitis C virus associated liver disease. Author(s): Tanaka T, Inoue K, Hayashi Y, Abe A, Tsukiyama-Kohara K, Nuriya H, Aoki Y, Kawaguchi R, Kubota K, Yoshiba M, Koike M, Tanaka S, Kohara M. Source: Journal of Medical Virology. 2004 February; 72(2): 223-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14695663
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Waldenstrom's macroglobulinaemia presenting as reticulate purpura and bullae in a patient with hepatitis B virus infection. Author(s): Cho S, Chang SE, Kim KR, Choi JH, Sung KJ, Moon KC, Koh JK. Source: Clinical and Experimental Dermatology. 2001 September; 26(6): 513-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11678879
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Why can't Chinese Han drink alcohol? Hepatitis B virus infection and the evolution of acetaldehyde dehydrogenase deficiency. Author(s): Lin YP, Cheng TJ. Source: Medical Hypotheses. 2002 August; 59(2): 204-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12208210
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Wide variety of genotypes and geographic origins of hepatitis B virus in Belgian children. Author(s): Liu HF, Sokal E, Goubau P. Source: Journal of Pediatric Gastroenterology and Nutrition. 2001 March; 32(3): 274-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11345175
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Wild-type and 'a' epitope variants in chronic hepatitis B virus carriers positive for hepatitis B surface antigen and antibody. Author(s): Mesenas SJ, Chow WC, Zhao Y, Lim GK, Oon CJ, Ng HS. Source: Journal of Gastroenterology and Hepatology. 2002 February; 17(2): 148-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11966944
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X protein of hepatitis B virus inhibits Fas-mediated apoptosis and is associated with up-regulation of the SAPK/JNK pathway. Author(s): Diao J, Khine AA, Sarangi F, Hsu E, Iorio C, Tibbles LA, Woodgett JR, Penninger J, Richardson CD. Source: The Journal of Biological Chemistry. 2001 March 16; 276(11): 8328-40. Epub 2000 November 30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11099494
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X protein of hepatitis B virus modulates cytokine and growth factor related signal transduction pathways during the course of viral infections and hepatocarcinogenesis. Author(s): Diao J, Garces R, Richardson CD. Source: Cytokine & Growth Factor Reviews. 2001 June-September; 12(2-3): 189-205. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11325602
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CHAPTER 2. NUTRITION AND HEPATITIS B VIRUS Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and hepatitis B virus.
Finding Nutrition Studies on Hepatitis B Virus 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 “hepatitis B virus” (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 “hepatitis B virus” (or a synonym): •
Altered DNA mutation spectrum in aflatoxin b1-treated transgenic mice that express the hepatitis B virus x protein. Author(s): Department of Molecular Virology and Microbiology. Department of Pathology, Baylor College of Medicine, Houston, Texas 77030, USA. Source: Madden, C R Finegold, M J Slagle, B L J-Virol. 2002 November; 76(22): 11770-4 0022-538X
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Characterization of a 120-kilodalton pre-S-binding protein as a candidate duck hepatitis B virus receptor. Source: Li, J.S. Tong, S.P. Wands, J.R. J-virol. Washington, D.C. : American Society for Microbiology. Sept 1996. volume 70 (9) page 6029-6035. 0022-538X
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Chinese medicinal herbs for asymptomatic carriers of hepatitis B virus infection. Author(s): The Cochrane Hepato-Biliary Group, Copenhagen Trial Unit, Centre for Clinical Intervention Research, Copenhagen University Hospital, Dept. 7701, H:S Rigshospitalet, Blegdamsvej 9, Copenhagen, Denmark, DK-2100.
[email protected] Source: Liu, J P McIntosh, H Lin, H Cochrane-Database-Syst-Revolume 2001; (2): CD002231 1469-493X
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Comparison of a non-radioactive hybridization assay for detection of hepatitis B virus DNA with the radioactive method. Author(s): Laboratoire de Virologie, Centre Hospitalier Regional et Universitaire, Caen, France. Source: Quibriac, M Petitjean, J Thiers, V Tiollais, P Brechot, C Freymuth, F Mol-CellProbes. 1989 September; 3(3): 209-12 0890-8508
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Detection of hepatitis B virus DNA in human serum by dot hybridization using a biotin-labelled probe. Source: Roe, I H Roe, J H Lee, D H Korean-J-Intern-Med. 1988 January; 3(1): 9-14 04944712
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Direct binding of hepatitis B virus X protein and retinoid X receptor contributes to phosphoenolpyruvate carboxykinase gene transactivation. Author(s): Center for Ligand and Transcription, Chonnam National University, Kwangju, South Korea. Source: Kong, H J Hong, S H Lee, M Y Kim, H D Lee, J W Cheong, J FEBS-Lett. 2000 October 20; 483(2-3): 114-8 0014-5793
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Effect of interleukin 1 and interleukin 2 on antibody production in asymptomatic hepatitis B virus (HBV) carriers. Author(s): Third Department of Internal Medicine, Osaka City University Medical School, Japan. Source: Takeda, H Mizoguchi, Y Kobayashi, K Yamamoto, S Morisawa, S GastroenterolJpn. 1988 June; 23(3): 287-91 0435-1339
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Effect of Phyllanthus amarus on duck hepatitis B virus replication in vivo. Author(s): Hepatitis Research Unit, Macfarlane Burnet Centre for Medical Research, Fairfield Hospital, Victoria, Australia. Source: Niu, J Z Wang, Y Y Qiao, M Gowans, E Edwards, P ThyagaraJanuary, S P Gust, I Locarnini, S J-Med-Virol. 1990 December; 32(4): 212-8 0146-6615
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Effect of sho-saiko-to(xiao-chai-hu-tang) on HBeAg clearance in children with chronic hepatitis B virus infection and with sustained liver disease. Author(s): Department of Pediatrics, Osaka University Hospital, Japan.
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Source: Tajiri, H Kozaiwa, K Ozaki, Y Miki, K Shimuzu, K Okada, S Am-J-Chin-Med. 1991; 19(2): 121-9 0192-415X •
Effects of acupuncture on the immunological functions in hepatitis B virus carriers. Author(s): First Municipal Hospital, Zhuzhou, Hunan Province. Source: Chen, J Chen, M Zhao, B Wang, Y J-Tradit-Chin-Med. 1999 December; 19(4): 26872 0254-6272
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Efficacy of Phyllanthus amarus for eradication of hepatitis B virus in chronic carriers. Author(s): Department of Medicine, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand. Source: Thamlikitkul, V Wasuwat, S Kanchanapee, P J-Med-Assoc-Thai. 1991 September; 74(9): 381-5 0125-2208
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Expression of hepatitis B virus middle and large surface antigen genes in Saccharomyces cerevisiae. Source: Imamura, T. Araki, M. Miyanohara, A. Nakao, J. Yonemura, H. Ohtomo, N. Matsubara, K. Journal-of-virology (USA). (November 1987). volume 61(11) page 35433549. mankind saccharomyces cerevisiae liver diseases viroses viruses antigens genes genomes 0022-538X
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G1 phase dependent nuclear localization of relaxed-circular hepatitis B virus DNA and aphidicolin-induced accumulation of covalently closed circular DNA. Author(s): Liver Research Unit, Chang Gung Memorial Hospital and Medical College, Taipei, Taiwan. Source: Yeh, C T Chiu, H T Chu, C M Liaw, Y F J-Med-Virol. 1998 May; 55(1): 42-50 0146-6615
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Genus Phyllanthus for chronic hepatitis B virus infection: a systematic review. Author(s): The Cochrane Hepato-Biliary Group, The Copenhagen Trial Unit, Centre for Clinical Intervention Research, Copenhagen University Hospital, Copenhagen, Denmark.
[email protected] Source: Liu, J Lin, H McIntosh, H J-Viral-Hepat. 2001 September; 8(5): 358-66 1352-0504
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Glucagon treatment interferes with an early step of duck hepatitis B virus infection. Author(s): Zentrum fur Molekulare Biologie (ZMBH), Universitat Heidelberg, Germany. Source: Hild, M Weber, O Schaller, H J-Virol. 1998 April; 72(4): 2600-6 0022-538X
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Identification of two separable modules in the duck hepatitis B virus core protein. [Erratum: Apr 1997, v. 71 (4), p. 3363.]. Source: Weizsacker, F. von Wieland, S. Blum, H.E. J-virol. Washington, D.C. : American Society for Microbiology. April 1995. volume 69 (4) page 2704-2707. 0022-538X
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In situ hybridization using a biotinylated DNA probe on formalin-fixed liver biopsies with hepatitis B virus infections: in situ hybridization superior to immunochemistry. Author(s): Department of Pathology, Bronx-Lebanon Hospital Center, New York. Source: Choi, Y J Mod-Pathol. 1990 May; 3(3): 343-7 0893-3952
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Inhibition of hepatitis B virus by oxymatrine in vivo. Author(s): Department of Cell Biology, the Second Military Medical University, Shanghai 200433,China.
[email protected] Source: Chen, X S Wang, G J Cai, X Yu, H Y Hu, Y P World-J-Gastroenterol. 2001 February; 7(1): 49-52 1007-9327
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Lamivudine and glycyrrhizin for treatment of chemotherapy-induced hepatitis B virus (HBV) hepatitis in a chronic HBV carrier with non-Hodgkin lymphoma. Author(s): Second Department of Internal Medicine; Okayama University, Medical School, 2-5-1 Shikata-cho, Okayama, Japan.
[email protected] Source: Matsuo, K Takenaka, K Shimomura, H Fujii, N Shinagawa, K Kiura, K Harada, M Leuk-Lymphoma. 2001 March; 41(1-2): 191-5 1042-8194
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Leptomycin B inhibits equine infectious anemia virus Rev and feline immunodeficiency virus rev function but not the function of the hepatitis B virus posttranscriptional regulatory element. Author(s): Infectious Disease Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, USA. Source: Otero, G C Harris, M E Donello, J E Hope, T J J-Virol. 1998 September; 72(9): 7593-7 0022-538X
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Packaging of up to 240 subunits of a 17 kDa nuclease into the interior of recombinant hepatitis B virus capsids. Author(s): University Hospital Freiburg, Department of Internal Medicine II, Molecular Biology, Hugstetter Str. 55, D-79107 Freiburg, Germany. Source: Beterams, G Bottcher, B Nassal, M FEBS-Lett. 2000 September 15; 481(2): 169-76 0014-5793
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Phenotypic mixing of rodent but not avian hepadnavirus surface proteins into human hepatitis B virus particles. Source: Gerhardt, E. Bruss, V. J-virol. Washington, D.C. : American Society for Microbiology. February 1995. volume 69 (2) page 1201-1208. 0022-538X
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Phytohemagglutinin and concanavalin A activate hepatitis B virus in peripheral blood mononuclear cells of patients with chronic hepatitis B virus infection. Author(s): INSERM U271, Lyon, France. Source: Bouffard, P Lamelin, J P Zoulim, F Lepot, D Trepo, C J-Med-Virol. 1992 August; 37(4): 255-62 0146-6615
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Replication of the wild type and a natural hepatitis B virus nucleocapsid promoter variant is differentially regulated by nuclear hormone receptors in cell culture. Author(s): Department of Cell Biology, The Scripps Research Institute, La Jolla, California 92037, USA. Source: Tang, H Raney, A K McLachlan, A J-Virol. 2001 October; 75(19): 8937-48 0022538X
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Selected mutations of the duck hepatitis B virus P gene RNase H domain affect both RNA packaging and priming of minus-strand DNA synthesis. Source: Chen, Y. Robinson, W.S. Marion, P.L. J-virol. Washington, D.C. : American Society for Microbiology. August 1994. volume 68 (8) page 5232-5238. 0022-538X
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Sustained activation of mitogen-activated protein kinases and activator protein 1 by the hepatitis B virus X protein in mouse hepatocytes in vivo. Author(s): Department of Biochemistry, University of Delhi South Campus, New Delhi110021, India. Source: Nijhara, R Jana, S S Goswami, S K Rana, A Majumdar, S S KuMarch, V Sarkar, D P J-Virol. 2001 November; 75(21): 10348-58 0022-538X
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The proapoptotic effect of hepatitis B virus HBx protein correlates with its transactivation activity in stably transfected cell lines. Author(s): Unite de Recombinaison et Expression Genetique (INSERM U163), Institut Pasteur, Paris, France.
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Source: Bergametti, F Prigent, S Luber, B Benoit, A Tiollais, P Sarasin, A Transy, C Oncogene. 1999 May 6; 18(18): 2860-71 0950-9232 •
The woodchuck model of hepatitis B virus infection. Author(s): Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, USA. Source: Tennant, B C Gerin, J L ILAR-J. 2001; 42(2): 89-102 1084-2020
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Thymosin-alpha1 and famciclovir combination therapy activates T-cell response in patients with chronic hepatitis B virus infection in immune-tolerant phase. Author(s): Departments of Medicine and Pathology, Queen Mary Hospital Clinical Trials Centre, The Institute of Molecular Biology, The University of Hong Kong, Hong Kong SAR, China.
[email protected] Source: Lau, G K Nanji, A Hou, J Fong, D Y Au, W S Yuen, S T Lin, M Kung, H F Lam, S K J-Viral-Hepat. 2002 July; 9(4): 280-7 1352-0504
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 hepatitis B virus; 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: •
Minerals Selenium Source: Prima Communications, Inc.www.personalhealthzone.com
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CHAPTER 3. ALTERNATIVE MEDICINE AND HEPATITIS B VIRUS Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to hepatitis B virus. 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 hepatitis B virus 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 “hepatitis B virus” (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 hepatitis B virus: •
A novel oral adjuvant for hepatitis B virus (HBV) vaccines. Author(s): Ishizaka S, Kuriyama S, Kikuchi E, Nishimura K, Tsujii T. Source: Journal of Hepatology. 1990 November; 11(3): 326-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2290023
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A plant-derived edible vaccine against hepatitis B virus. Author(s): Kapusta J, Modelska A, Figlerowicz M, Pniewski T, Letellier M, Lisowa O, Yusibov V, Koprowski H, Plucienniczak A, Legocki AB. Source: The Faseb Journal : Official Publication of the Federation of American Societies for Experimental Biology. 1999 October; 13(13): 1796-9. Erratum In: Faseb J 1999 December; 13(15): 2339. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10506582
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Active compounds from Saussurea lappa Clarks that suppress hepatitis B virus surface antigen gene expression in human hepatoma cells. Author(s): Chen HC, Chou CK, Lee SD, Wang JC, Yeh SF. Source: Antiviral Research. 1995 May; 27(1-2): 99-109. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7486962
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Acute exacerbation of hepatitis due to reactivation of hepatitis B virus with mutations in the core region after chemotherapy for malignant lymphoma. Author(s): Sato T, Kato J, Kawanishi J, Kogawa K, Ohya M, Sakamaki S, Niitsu Y. Source: Journal of Gastroenterology. 1997 October; 32(5): 668-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9349995
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Acute hepatic injury after discontinuation of chemotherapy in a patient with nonHodgkin's lymphoma and chronic hepatitis B virus infection. Author(s): Haanen JB, Bieger R, van't Wout JW. Source: The Netherlands Journal of Medicine. 1996 December; 49(6): 239-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8990863
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Aflatoxin exposure, hepatitis B virus infection and liver cancer in Swaziland. Author(s): Peers F, Bosch X, Kaldor J, Linsell A, Pluijmen M. Source: International Journal of Cancer. Journal International Du Cancer. 1987 May 15; 39(5): 545-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3570547
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Anti-hepatitis B virus effects of wogonin isolated from Scutellaria baicalensis. Author(s): Huang RL, Chen CC, Huang HL, Chang CG, Chen CF, Chang C, Hsieh MT. Source: Planta Medica. 2000 December; 66(8): 694-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11199123
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Antiviral activities of extracts isolated from Terminalis chebula Retz., Sanguisorba officinalis L., Rubus coreanus Miq. and Rheum palmatum L. against hepatitis B virus. Author(s): Kim TG, Kang SY, Jung KK, Kang JH, Lee E, Han HM, Kim SH. Source: Phytotherapy Research : Ptr. 2001 December; 15(8): 718-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11746867
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Chinese medicinal herbs for asymptomatic carriers of hepatitis B virus infection. Author(s): Liu JP, McIntosh H, Lin H. Source: Cochrane Database Syst Rev. 2001; (2): Cd002231. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11406038
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Combined lamivudine and interferon-alpha therapy for chemotherapy-induced reactivation of hepatitis B virus. Author(s): Ohmoto K, Tsuduki M, Yamamoto S.
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Source: The American Journal of Gastroenterology. 2003 May; 98(5): 1215-6; Author Reply 1217. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12809863 •
Cytotoxicity and anti-hepatitis B virus activities of saikosaponins from Bupleurum species. Author(s): Chiang LC, Ng LT, Liu LT, Shieh DE, Lin CC. Source: Planta Medica. 2003 August; 69(8): 705-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14531019
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Duck hepatitis B virus model for screening of antiviral agents from medicinal herbs. Author(s): Mi Z, Chen H, Zhang X, Shao X, Li Z, Wu X. Source: Chinese Medical Journal. 1995 September; 108(9): 660-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8575230
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Effect of Phyllanthus amarus on chronic carriers of hepatitis B virus. Author(s): Brook MG. Source: Lancet. 1988 October 29; 2(8618): 1017-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2902445
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Effect of Phyllanthus amarus on chronic carriers of hepatitis B virus. Author(s): Thyagarajan SP, Subramanian S, Thirunalasundari T, Venkateswaran PS, Blumberg BS. Source: Lancet. 1988 October 1; 2(8614): 764-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2901611
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Effect of Phyllanthus amarus on duck hepatitis B virus replication in vivo. Author(s): Niu JZ, Wang YY, Qiao M, Gowans E, Edwards P, Thyagarajan SP, Gust I, Locarnini S. Source: Journal of Medical Virology. 1990 December; 32(4): 212-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2081970
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Effect of sho-saiko-to(xiao-chai-hu-tang) on HBeAg clearance in children with chronic hepatitis B virus infection and with sustained liver disease. Author(s): Tajiri H, Kozaiwa K, Ozaki Y, Miki K, Shimuzu K, Okada S. Source: The American Journal of Chinese Medicine. 1991; 19(2): 121-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1816724
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Effect of sizofiran, a polysaccharide, on interferon gamma, antibody production and lymphocyte proliferation specific for hepatitis B virus antigen in patients with chronic hepatitis B. Author(s): Kakumu S, Ishikawa T, Wakita T, Yoshioka K, Ito Y, Shinagawa T.
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Source: International Journal of Immunopharmacology. 1991; 13(7): 969-75. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1761362 •
Effects of acupuncture on the immunological functions in hepatitis B virus carriers. Author(s): Chen J, Chen M, Zhao B, Wang Y. Source: J Tradit Chin Med. 1999 December; 19(4): 268-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10921130
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Effects of Phyllanthus plant extracts on duck hepatitis B virus in vitro and in vivo. Author(s): Shead A, Vickery K, Pajkos A, Medhurst R, Freiman J, Dixon R, Cossart Y. Source: Antiviral Research. 1992 June; 18(2): 127-38. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1416905
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Effects of TJ-9 Sho-saiko-to (kampo medicine) on interferon gamma and antibody production specific for hepatitis B virus antigen in patients with type B chronic hepatitis. Author(s): Kakumu S, Yoshioka K, Wakita T, Ishikawa T. Source: International Journal of Immunopharmacology. 1991; 13(2-3): 141-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1906436
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Efficacy of Phyllanthus amarus for eradication of hepatitis B virus in chronic carriers. Author(s): Thamlikitkul V, Wasuwat S, Kanchanapee P. Source: J Med Assoc Thai. 1991 September; 74(9): 381-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1791391
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Enhancement of interferon-gamma production in glycyrrhizin-treated human peripheral lymphocytes in response to concanavalin A and to surface antigen of hepatitis B virus. Author(s): Shinada M, Azuma M, Kawai H, Sazaki K, Yoshida I, Yoshida T, Suzutani T, Sakuma T. Source: Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N. Y.). 1986 February; 181(2): 205-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3080754
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Epidemiology of hepatitis B virus infection in the Asia-Pacific region. Author(s): Chen CJ, Wang LY, Yu MW. Source: Journal of Gastroenterology and Hepatology. 2000 May; 15 Suppl: E3-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10921373
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Evaluation of anti-hepadnavirus activity of Phyllanthus amarus and Phyllanthus maderaspatensis in duck hepatitis B virus carrier Pekin ducks. Author(s): Munshi A, Mehrotra R, Ramesh R, Panda SK.
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Source: Journal of Medical Virology. 1993 December; 41(4): 275-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8106861 •
Evaluation of Phyllanthus amarus and Phyllanthus maderaspatensis as agents for postexposure prophylaxis in neonatal duck hepatitis B virus infection. Author(s): Munshi A, Mehrotra R, Panda SK. Source: Journal of Medical Virology. 1993 May; 40(1): 53-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8515247
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Experimental studies on the inhibition effects of 1000 Chinese medicinal herbs on the surface antigen of hepatitis B virus. Author(s): Zheng M, Zheng Y. Source: J Tradit Chin Med. 1992 September; 12(3): 193-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1453758
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Fully automated, internally controlled quantification of hepatitis B Virus DNA by real-time PCR by use of the MagNA Pure LC and LightCycler instruments. Author(s): Leb V, Stocher M, Valentine-Thon E, Holzl G, Kessler H, Stekel H, Berg J. Source: Journal of Clinical Microbiology. 2004 February; 42(2): 585-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14766820
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Functional and structural similarity between the X protein of hepatitis B virus and nucleoside diphosphate kinases. Author(s): De-Medina T, Shaul Y. Source: Febs Letters. 1994 September 12; 351(3): 423-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8082807
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Genus Phyllanthus for chronic hepatitis B virus infection: a systematic review. Author(s): Liu J, Lin H, McIntosh H. Source: Journal of Viral Hepatitis. 2001 September; 8(5): 358-66. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11555193
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HBsAg-like structures in immunosuppressed mice inoculated with human hepatitis B virus. Author(s): Schaff Z, Pohl O, Bencsath M, Brojnas J, Lapis K, Kopper L, Hollos I. Source: Virchows Arch B Cell Pathol Incl Mol Pathol. 1982 August; 40(2): 249-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6127839
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Hepatitis B virus and hepatocellular carcinoma--treatment of HBV carriers with Phyllanthus amarus. Author(s): Blumberg BS, Millman I, Venkateswaran PS, Thyagarajan SP.
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Source: Cancer Detection and Prevention. 1989; 14(2): 195-201. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2559794 •
Hepatitis B virus and primary hepatocellular carcinoma: treatment of HBV carriers with Phyllanthus amarus. Author(s): Blumberg BS, Millman I, Venkateswaran PS, Thyagarajan SP. Source: Vaccine. 1990 March; 8 Suppl: S86-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2158192
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Hepatitis B virus X protein enhances transcriptional activity of hypoxia-inducible factor-1alpha through activation of mitogen-activated protein kinase pathway. Author(s): Yoo YG, Oh SH, Park ES, Cho H, Lee N, Park H, Kim DK, Yu DY, Seong JK, Lee MO. Source: The Journal of Biological Chemistry. 2003 October 3; 278(40): 39076-84. Epub 2003 July 10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12855680
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Hepatocellular carcinoma, hepatic cirrhosis, and hepatitis B virus infection in Nigeria. Author(s): Otu AA. Source: Cancer. 1987 November 15; 60(10): 2581-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2822223
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Identification of a protein kinase C (PKC) activator, daphnoretin, that suppresses hepatitis B virus gene expression in human hepatoma cells. Author(s): Chen HC, Chou CK, Kuo YH, Yeh SF. Source: Biochemical Pharmacology. 1996 October 11; 52(7): 1025-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8831721
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In vitro studies on the effect of certain natural products against hepatitis B virus. Author(s): Mehrotra R, Rawat S, Kulshreshtha DK, Patnaik GK, Dhawan BN. Source: The Indian Journal of Medical Research. 1990 April; 92: 133-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2370093
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Osthole increases glycosylation of hepatitis B surface antigen and suppresses the secretion of hepatitis B virus in vitro. Author(s): Huang RL, Chen CC, Huang YL, Hsieh DJ, Hu CP, Chen CF, Chang C. Source: Hepatology (Baltimore, Md.). 1996 September; 24(3): 508-15. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8781315
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Phyllanthus amarus down-regulates hepatitis B virus mRNA transcription and replication. Author(s): Lee CD, Ott M, Thyagarajan SP, Shafritz DA, Burk RD, Gupta S.
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Source: European Journal of Clinical Investigation. 1996 December; 26(12): 1069-76. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9013081 •
Phyllanthus amarus suppresses hepatitis B virus by interrupting interactions between HBV enhancer I and cellular transcription factors. Author(s): Ott M, Thyagarajan SP, Gupta S. Source: European Journal of Clinical Investigation. 1997 November; 27(11): 908-15. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9395786
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Potent synergistic effect of sho-saiko-to, a herbal medicine, during vaccine therapy in a murine model of hepatitis B virus carrier. Author(s): Akbar SM, Yamamoto K, Abe M, Ninomiya T, Tanimoto K, Masumoto T, Michitaka K, Horiike N, Onji M. Source: European Journal of Clinical Investigation. 1999 September; 29(9): 786-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10469167
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Pretreatment of whole blood for use in immunochromatographic assays for hepatitis B virus surface antigen. Author(s): Shin HS, Kim CK, Shin KS, Chung HK, Heo TR. Source: Clinical and Diagnostic Laboratory Immunology. 2001 January; 8(1): 9-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11139189
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Primary prophylaxis with lamivudine of hepatitis B virus reactivation in chronic HbsAg carriers with lymphoid malignancies treated with chemotherapy. Author(s): Rossi G, Pelizzari A, Motta M, Puoti M. Source: British Journal of Haematology. 2001 October; 115(1): 58-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11722410
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Prophylaxis against chemotherapy-induced reactivation of hepatitis B virus infection with Lamivudine. Author(s): Simpson ND, Simpson PW, Ahmed AM, Nguyen MH, Garcia G, Keeffe EB, Ahmed A. Source: Journal of Clinical Gastroenterology. 2003 July; 37(1): 68-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12811213
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Screening of 25 compounds isolated from Phyllanthus species for anti-human hepatitis B virus in vitro. Author(s): Huang RL, Huang YL, Ou JC, Chen CC, Hsu FL, Chang C. Source: Phytotherapy Research : Ptr. 2003 May; 17(5): 449-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12748977
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Simultaneous extraction of hepatitis C virus (HCV), hepatitis B virus, and HIV-1 from plasma and detection of HCV RNA by a reverse transcriptase-polymerase chain
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reaction assay designed for screening pooled units of donated blood. Author(s): Sun R, Schilling W, Jayakar H, Ku J, Wang J, Rosenstraus M, Spadoro J. Source: Transfusion. 1999 October; 39(10): 1111-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10532606 •
Steroid-free chemotherapy decreases risk of hepatitis B virus (HBV) reactivation in HBV-carriers with lymphoma. Author(s): Cheng AL, Hsiung CA, Su IJ, Chen PJ, Chang MC, Tsao CJ, Kao WY, Uen WC, Hsu CH, Tien HF, Chao TY, Chen LT, Whang-Peng J; Lymphoma Committee of Taiwan Cooperative Oncology Group. Source: Hepatology (Baltimore, Md.). 2003 June; 37(6): 1320-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12774010
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Steroid-free chemotherapy decreases the risk of hepatitis flare-up in hepatitis B virus carriers with non-Hodgkin's lymphoma. Author(s): Cheng AL. Source: Blood. 1996 February 1; 87(3): 1202. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8562950
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Subtypes, genotypes and molecular epidemiology of the hepatitis B virus as reflected by sequence variability of the S-gene. Author(s): Magnius LO, Norder H. Source: Intervirology. 1995; 38(1-2): 24-34. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8666521
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The asialoglycoprotein receptor mediates hepatic binding and uptake of natural hepatitis B virus particles derived from viraemic carriers. Author(s): Treichel U, Meyer zum Buschenfelde KH, Stockert RJ, Poralla T, Gerken G. Source: The Journal of General Virology. 1994 November; 75 ( Pt 11): 3021-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7964611
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The hepatitis B virus-associated delta antigen: isolation from liver, development of solid-phase radioimmunoassays for delta antigen and anti-delta and partial characterization of delta antigen. Author(s): Rizzetto M, Shih JW, Gerin JL. Source: Journal of Immunology (Baltimore, Md. : 1950). 1980 July; 125(1): 318-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6769999
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The hepatitis B virus-X protein activates a phosphatidylinositol 3-kinase-dependent survival signaling cascade. Author(s): Lee YI, Kang-Park S, Do SI, Lee YI.
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Source: The Journal of Biological Chemistry. 2001 May 18; 276(20): 16969-77. Epub 2001 March 01. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11278872 •
The proapoptotic effect of hepatitis B virus HBx protein correlates with its transactivation activity in stably transfected cell lines. Author(s): Bergametti F, Prigent S, Luber B, Benoit A, Tiollais P, Sarasin A, Transy C. Source: Oncogene. 1999 May 6; 18(18): 2860-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10362257
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Treatment of hepatitis B virus-associated membranous nephropathy with adenine arabinoside and thymic extract. Author(s): Lin CY, Lo SC. Source: Kidney International. 1991 February; 39(2): 301-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2002643
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 hepatitis B virus; 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 Hepatitis Source: Healthnotes, Inc.; www.healthnotes.com Hives Source: Healthnotes, Inc.; www.healthnotes.com
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Herbs and Supplements Phyllanthus Alternative names: Phyllanthus niruri Source: Healthnotes, Inc.; www.healthnotes.com
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 HEPATITIS B VIRUS Overview In this chapter, we will give you a bibliography on recent dissertations relating to hepatitis B virus. 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 “hepatitis B virus” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on hepatitis B virus, we have not necessarily excluded nonmedical dissertations in this bibliography.
Dissertations on Hepatitis B Virus 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 hepatitis B virus. 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: •
Family behavior and the transmission of hepatitis B virus in Malo, New Hebrides. Ethology, ethnography and epidemiology in the study of the natural history of disease by Dickie, Elizabeth Reed, PhD from UNIVERSITY OF PENNSYLVANIA, 1979, 321 pages http://wwwlib.umi.com/dissertations/fullcit/8009393
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Mucosal DNA vaccines for regionally unique pathogens: Hepatitis B virus and Penicillium marneffei by Wong, Lei Po, PhD from UNIVERSITY OF HONG KONG (PEOPLE'S REPUBLIC OF CHINA), 2003 http://wwwlib.umi.com/dissertations/fullcit/f606881
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Role of the hepatitis B virus X protein in viral replication and transcription by Janvier, Adrien L., PhD from NEW YORK UNIVERSITY, 2004, 185 pages http://wwwlib.umi.com/dissertations/fullcit/3114199
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Superinfection exclusion in duck hepatitis B virus infection by Walters, Kathie-Anne, PhD from UNIVERSITY OF ALBERTA (CANADA), 2003, 191 pages http://wwwlib.umi.com/dissertations/fullcit/NQ88062
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The association of heat shock protein 90 and hepatitis B virus X-associated protein 2 with the peroxisome proliferator activator receptors alpha, beta, and gamma by Sumanasekera, Wasana Kumarihamy, PhD from THE PENNSYLVANIA STATE UNIVERSITY, 2003, 163 pages http://wwwlib.umi.com/dissertations/fullcit/3106331
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The template switches during plus-strand DNA synthesis of the duck hepatitis B virus are mechanistically linked: Sequence and conformational requirements of the 3' end of the minus-strand DNA by Habig, Jeffrey W., PhD from THE UNIVERSITY OF WISCONSIN - MADISON, 2003, 153 pages http://wwwlib.umi.com/dissertations/fullcit/3113698
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. PATENTS ON HEPATITIS B VIRUS 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.8 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 “hepatitis B virus” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on hepatitis B virus, we have not necessarily excluded nonmedical patents in this bibliography.
Patents on Hepatitis B Virus By performing a patent search focusing on hepatitis B virus, 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 will tell you how to obtain this information later in the chapter. 8Adapted
from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.
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The following is an example of the type of information that you can expect to obtain from a patent search on hepatitis B virus: •
6-methylnicotinamide derivatives as antiviral agents Inventor(s): Kim; Jong-Woo (Anyang-si, KR), Kim; Nam-Doo (Inchon-si, KR), Lee; Geun-Hyung (Anyang-si, KR), Lee; Hak-Dong (Anyang-si, KR), Lee; Jin-Soo (Anyang-si, KR), Lee; Sang-Wook (Anyang-si, KR), Park; Hee-Jeong (Anyang-si, KR), Park; Sang-Jin (Seoul, KR), Yoon; Sung-June (Seoul, KR) Assignee(s): Dong Wha Pharm. Ind. Co., Ltd. (Seoul, KR) Patent Number: 6,608,058 Date filed: October 10, 2002 Abstract: The present invention relates to novel 6-methylnicotinamide derivatives and their pharmaceutically acceptable salts, the process for preparing them, and the pharmaceutical compositions containing said compounds as active ingredients. The 6methylnicotinamide derivatives of the present invention exhibit their inhibitory activity against the proliferation of human immunodeficiency virus (HIV) as well as hepatitis B virus (HBV) and hepatitis C virus (HCV), such that they can be used for hepatitis B, hepatitis C and acquired immune deficiency syndrome (AIDS). Excerpt(s): This patent application claims a benefit of priority from Korean Patent Application No. 2000/20137 filed Apr. 17, 2000 and Korean Patent Application No. 2000/31926 filed Jun. 10, 2000 through PCT Application Serial No. PCT/KRO1/00613 filed Apr. 13, 2001, the contents of each of which are incorporated herein by reference. Hepatitis B virus (HBV; referred as "HBV" hereinafter) causes acute or chronic hepatitis, which may progress to liver cirrhosis and liver cancer. It is estimated that three hundred million people are infected with HBV in the world (Tiollais & Buendia, Sci. Am., 264, 48, 1991). There has been much research about the molecular biological characteristics of HBV and their relationship to liver diseases in order to find ways to prevent and treat hepatitis B. Various vaccines and diagnostic drugs have been developed and much effort is being channeled into research to find treatment for hepatitis B. The gene for HBV polymerase comprises 80% of the whole virus genome and produces a protein of 94 kD size with 845 amino acids, which has several functions in the replication of virus genome. This polypeptide includes sequences responsible for activities of protein primer, RNA dependent DNA polymerase, DNA dependent DNA polymerase, and RNase H. Kaplan and his coworkers first discovered reverse transcriptase activities of polymerase, which led to much research in replicating mechanism of HBV. Web site: http://www.delphion.com/details?pn=US06608058__
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Antisense ogligonucleotides against Hepatitis B viral replication Inventor(s): Gerin; John L. (Bethesda, MD), Korba; Brent E. (Laurel, MD) Assignee(s): Georgetown University (Washington, DC) Patent Number: 6,503,533 Date filed: November 25, 1998 Abstract: Antisense oligonucleotides that hybridize to segments of the pres1, S, C, and.epsilon. regions of the hepatitis B virus (HBV) RNA pregenome inhibit replication
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of the virus. Pharmaceutical compositions which contain these oligonucleotides as the active ingredients are effective against HBV infection. Excerpt(s): The present invention was made utilizing funds from contracts NO1-AI72623 and NO1-AI-45179 between the National Institute for Allergy and Infectious Diseases and Georgetown University. The present invention relates to compositions for the treatment of Hepatitis B virus (HBV) infection. In particular, the invention relates to antisense oligonucleotides and their use to inhibit HBV replication. Hepatitis B virus, a member of the Hepadnaviridae family, is a blood-borne, hepatotropic pathogen which infects large numbers of people annually. In 1987 there were approximately 25,000 newly reported cases of disease attributable to HBV infection in the US. It is estimated that 60-70% of HBV infections lead to subclinical (asymptomatic) disease, and it is therefore probable that the actual number of new HBV infections each year is much higher. Of those infected with HBV, 90% make a full recovery, but 2-10% of infected patients develop chronic, persistent HBV infection. It is estimated that 1 million people in the US and 300 million people worldwide are chronically infected with HBV. In parts of Asia and Africa it is thought that between 5 and 20% of the population are chronically infected with HBV. Web site: http://www.delphion.com/details?pn=US06503533__ •
Combination therapy method for treating chronic hepatitis B Inventor(s): Horwitz; David L. (Hillsborough, CA) Assignee(s): SciClone Pharmaceuticals, Inc. (San Mateo, CA) Patent Number: 6,200,952 Date filed: December 22, 1994 Abstract: The present invention is aimed at augmenting the success rate of using thymosin in treatment of chronic hepatitis B, by employing a combination therapy using thymosin with antiviral agents which are effective in inhibiting DNA synthesis or DNA polymerase during replication of the hepatitis B virus. Excerpt(s): The instant invention relates to a method for treating chronic hepatitis B infections. More specifically, the instant invention relates to a method for treating chronic hepatitis B infections using both thymosin and an antiviral drug. Hepatitis B is the most prevalent form of hepatitis and is the second most common infectious disease worldwide. Worldwide estimates of those chronically infected with hepatitis B virus (HBV) are in excess of 300,000,000. The disease is caused by the hepatitis B virus, a DNA virus. The virus is transmitted through blood transfusions, contaminated needles, sexual contact and vertical transmission from mother to child. Moreover, a significant number of people are infected by unknown means. Carriers of the virus can exhibit various forms of disease, one of which is chronic hepatitis B. Approximately 50% of the carriers show chronic inflammatory changes in the liver and, of these, about 50% have histopathologic changes, which are termed "chronic active hepatitis", that may lead to fibrosis and ultimately to cirrhosis and progressive liver failure. Carriers without chronic inflammatory changes may also develop chronic active hepatitis. Liver cancer develops in about 10 to 30% of hepatitis B carriers. It has been estimated that approximately 4 million carriers of hepatitis B virus die each year from liver cancer or cirrhosis. Web site: http://www.delphion.com/details?pn=US06200952__
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Detection of hepatitis B virus Inventor(s): Chan; Ming (Ft. Myers, FL), Garcia; Mariana (Arlington, VA), Lorincz; Attila (North Potomac, MD) Assignee(s): Digene Corporation (Gaithersburg, MD) Patent Number: 6,225,053 Date filed: December 12, 1997 Abstract: An improved assay disclosed for detecting viral nucleic acid sequences. The improvement involves concentration viral particles from a biological sample by centrifugation. Once concentrated, the nucleic acid molecules in the viral particles can be manipulated or detected using any suitable procedure. Many such procedure are know and can be used with the concentrated viral nucleic acid molecules. Preferably, the concentrated viral nucleic acid is detected using a detection assay. Excerpt(s): The present invention relates to the field of detection assays of viruses in general and more particularly relates to improved detection of hepatitis B virus. Hepatitis B virus (HBV), formerly termed serum hepatitis, is a member of a group of small DNA-containing viruses that cause persistent noncytopathic infections of the liver, is an infectious agent of humans that is found worldwide and which is perpetuated among humans in a large reservoir of chronic carriers. It is estimated that about 6 to 7% of the earth's population is infected (300 million carriers). HBV infection in humans can cause severe jaundice, liver degeneration and death. HBV enters predominantly by the parenteral route, has a characteristic incubation period of 60 to 160 days, and may persist in the blood for years in chronic carriers. The prevalence of the infection is not uniform throughout the world. There is a geographic gradient in distribution of HBV. It is lowest in North America and Western Europe, where the virus can be detected in 0.1 to 0.5% of the population, and highest in Southeast Asia and sub-Saharan Africa, where the frequency of infection may vary from 5 to 20% of the population. This skewed distribution parallels that of hepatocellular carcinoma and provides strong epidemiologic evidence for an association between chronic HBV infection and this type of malignancy. Hepatitis B is of great medical importance because it is probably the most common cause of chronic liver disease, including hepatocellular carcinoma in humans. Infected hepatocytes continually secrete viral particles that accumulate to high levels in the blood. These particles are of two types: (i) noninfectious particles consisting of 22 nm spheres and filaments of excess viral coat protein (HBsAg) and containing no nucleic acid (in concentrations of up to 10.sup.13 particles/ml blood) which are referred to as the Australian antigen (AU), and (ii) infectious, DNA-containing particles (Dane particle nucleocapsids) consisting of a 28 nm nucleocapsid core (HBcAg) around which is assembled an envelope containing the major viral coat protein, carbohydrate, and lipid, present in lower concentrations (10.sup.9 particles/ml blood). The human hepatitis B virus is a member of the Hepadna Viridae family, with close relatives including woodchuck hepatitis virus (WHV), duck hepatitis virus (DHV), and ground squirrel hepatitis virus (GHV) (Robinson, 1990). Like retroviruses, the hepadnavirus utilizes reverse transcription of its 3.2 Kb DNA genome (Pugh, 1990). The genome of hepatitis B virus is circular and partially single-stranded, containing an incomplete plus strand. The incomplete plus strand is complexed with a DNA polymerase in the virion which has been shown to elongate the plus strand using the complete minus strand as the template. These morphological and structural features distinguish hepatitis B viruses from all known classes of DNA-containing viruses. Web site: http://www.delphion.com/details?pn=US06225053__
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Hepatitis B virus inhibitors Inventor(s): Dyson; Michael Richard (Edinburgh, GB), Murray; Kenneth (Edinburgh, GB) Assignee(s): Biogen, Inc. (Cambridge, MA) Patent Number: 6,544,520 Date filed: April 29, 1999 Abstract: Peptides and other molecules which inhibit the assembly of the hepatitis B virus, methods of treatment, and pharmaceutical compositions comprising them. Excerpt(s): The present invention relates to peptide compositions specific for the diagnosis, treatment or prevention of hepatitis B virus infection. Hepatitis B virus ("HBV") infects human at a very high rate. It is estimated that at least about 300 million people are chronic carriers of HBV. Despite extensive research, additional safe and effective therapies remain to be identified. Web site: http://www.delphion.com/details?pn=US06544520__
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HLA-restricted hepatitis B virus CTL epitopes Inventor(s): Chesnut; Robert W. (Cardiff by the Sea, CA), Vitiello; Maria A. (La Jolla, CA) Assignee(s): Epimmune, Inc. (San Diego, CA) Patent Number: 6,322,789 Date filed: June 5, 1995 Abstract: Cytotoxic T lymphocyte-stimulating peptides induce HLA-restricted responses to hepatitis B virus antigens. The peptides, derived from CTL epitopic regions of both HBV surface and nucleocapsid antigens, are particularly useful in the treatment and prevention of HBV infection, including the treatment of chronically infected HBV carriers. The peptides can be formulated as HBV vaccines and pharmaceutical compositions, such as lipid-containing compositions for enhancing the HLA-restricted CTL responses. The peptides are also useful in diagnostic methods, such as predicting which HBV-infected individuals are prone to developing chronic infection. Excerpt(s): The hepatitis B virus (HBV) is not believed to be directly responsible for damage to hepatocytes, despite its predilection for infecting such cells. Rather, non-viral host factors are implicated in the pathogenesis of hepatitis. It is suspected that a variation in immune responsiveness to HBV infection may account for the wide diversity of syndromes associated with HBV infection. Following an acute HBV infection, approximately 90% of affected adults recover without sequelae and develop immunity to the virus, although the clinical course of the infection during the acute phase can itself be quite variable. In 5-10% of infected adults, a chronic HBV infection becomes established. Chronic HBV infection can range from asymptomatic carrier state to continuous hepatocellular necrosis and inflammation, and in some instances may lead to hepatocellular carcinoma. Children exposed to HBV infection, particularly those less than one year old, often develop chronic infection and represent the major source of chronic infection. Worldwide, nearly 200 million people are chronically infected with HBV. And finally, in a small percentage of HBV infections (0.1-0.5%) a fulminant hepatitis results in such extreme cell death in the liver that fewer than one-fifth to onethird of these patients survive. The immune response to hepatitis B virus is as complex
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as the disease. A variety of humoral and cellular responses have been identified to different regions of the HBV nucleocapsid core and surface antigens. T cell mediated immunity, particularly involving class I major histocompatibility complex (MHC)restricted cytotoxic T lymphocytes (CTL), is believed to play an important role in resistance to hepatitis as well as several other viral infections. CTL recognize antigen in the form of small peptides in association with the class I histocompatibility molecules. The antigen-specific CTL, when stimulated, can secrete mediators which inhibit viral replication and eliminate infected cells, thereby contributing to an individual's recovery from the infection. Although studies suggest that the T cell repertoire of class I-restricted responses is focused on a limited number of discrete immunodominant epitopes of a viral protein (Braciale et al., Proc. Natl. Acad. Sci. USA 86:277-281 (1989)), for many viruses, including the hepatitis viruses and particularly HBV, few epitopes have been identified. See also Barnaba et al., Nature 345:258 (1990) have identified an All restricted epitope while Jin et al., J. Exp. Med. 168:293 (1988) have identified an A3 restricted epitope. Aichele et al., J. Exp. Med. 171:1815-1820 (1990), have demonstrated induction in vivo of an antiviral CTL response in an MHC class-I dependent fashion with a peptide from the nucleoprotein of lymphocytic choriomeningitis virus. Recently, Kast et al., Proc. Natl. Acad. Sci. USA 88:2283-2287 (1991), described in stimulation of Sendai virus-specific CTL in vivo using free synthetic peptide derived from the nucleoprotein to confer protection against subsequent viral challenge. Web site: http://www.delphion.com/details?pn=US06322789__ •
Human monoclonal antibodies to the hepatitis B surface antigen Inventor(s): Dagan; Shlomo (Rehovot, IL), Reisner; Yair (Old Jaffa, IL) Assignee(s): XTL Biopharmaceuticals Ltd (Rehovot, IL), Yeda Research & Development Co. Ltd (Rehovot, IL) Patent Number: 6,254,867 Date filed: December 10, 1998 Abstract: Disclosed is a process for obtaining hybridoma cell lines which produce human antibodies capable of binding to the hepatitis B virus surface antigen (HBVsAg), as well as the hybridoma cell lines, and antibodies produced by the cell lines. Also disclosed are various uses of said antibodies in the prevention and treatment of HBV infection. Peripheral blood lymphocytes obtained from human donors having a high titer of anti HBVsAg antibodies are engrafted into normal strains of mice which were lethally irradiated and radioprotected with SCID bone marrow. After immunization of such chimeric mice with HBVsAg, human cells are obtained from the mice spleens and fused in vitro with heteromyeloma cells to generate hybridomas secreting human antibodies having a high affinity and specificity to HBVsAg. Excerpt(s): The present invention concerns a process for obtaining hybridoma cell lines which produce human antibodies capable of binding to the hepatitis B virus surface antigen, the hybridoma cell lines, antibodies produced by the cell lines, and various uses thereof. Hepatitis B virus (HBV) infection is a major worldwide health problem. Approximately 5% of the world population is infected by HBV and chronically infected patients carry a high risk of developing cirrhosis and hepatocellular carcinoma. (Progress in Hepatitis Research: Hepatitis B virus (HBV), Hepatitis C virus (HCV) and Hepatitis Delta virus (HDV) Ed. O. Crivelli, Sorin Biomedica, 1991). The immune response to HBV-encoded antigens includes both a cellular immune response which is active in the elimination of HBV infected cells, as well as a humoral antibody response
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to viral envelope antigens which contributes to the clearance of circulating virus particles. The dominant cause of viral persistence during HBV infection is the development of a weak antiviral immune response. Web site: http://www.delphion.com/details?pn=US06254867__ •
Immunopotentiating formulations for vaccinal use Inventor(s): Aguilar Rubido; Julio Cesar (Havana, CU), Carmenate Portilla; Tania (Havana, CU), Cruz Ricondo; Luis Javier (Havana, CU), Diaz Martinez; Maylin (Havana, CU), Guillen Nieto; Gerardo Enrique (Havana, CU), Hechavarria Gay; Maydel (Havana, CU), Herrera Buch; Antonieta (Havana, CU), Iglesias Perez; Enrique (Havana, CU), Leal Angulo; Maria de Jesus (Havana, CU), Madrazo Pinol; Juan Joel (Havana, CU), Mesa Pardillo; Cirse (Havana, CU), Muzio Gonzalez; Verena Lucila (Havana, CU), Penton Arias; Eduardo (Havana, CU), Pichardo Diaz; Dagmara (Havana, CU), Veliz Rios; Gloria (Havana, CU) Assignee(s): Centro de Ingenieria Genetica y Biotechnologia (Havana, CU) Patent Number: 6,355,414 Date filed: January 6, 2000 Abstract: The present invention is related to the field of medicine, particularly to the use of new adjuvant formulations with vaccine antigens. The technical objective pursued with this invention is, precisely, the development of formulations that are able to increase and/or modulate the immune response of the organism to vaccine antigens in the serum and the mucous lining. With this aim, a formulation was developed that contained as the main components the surface antigen of the hepatitis B virus and the acemannan in adequate proportions. As an extension of this result, formulations were developed in which a) HBsAg was used as the homologous or heterologous antigen carrier b) delivery systems of particulated antigens and c) soluble antigens, combined with the acemannan in specific proportions. The formulations of this invention are applicable in the pharmaceutical industry as vaccine formulations for human and veterinary use. Excerpt(s): The present invention is related to the field of medicine, particularly to the development of new formulations for immunological potentiation allowing the increase of the amount and quality of the immune response to vaccine antigens. The technical aim of the invention is the development of formulations that are capable of increasing the levels of the immune response of the body to vaccine antigens. The adjuvants are substances that increase or optimize the immune response to antigens inoculated through the mucosal or systemic routes. The adjuvants or their formulations are combined with the antigen to generate or potentiate the type of response desired, decrease the number of inoculations and reduce the amount of antigen needed to obtain and maintain protection (McElrath, M. C. 1995 Seminars in Cancer Biology 6: 375-385). Web site: http://www.delphion.com/details?pn=US06355414__
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In vitro activity assay for human hepatitis B virus (HBV) DNA polymerase, and its use for screening for inhibitors of HBV DNA polymerase Inventor(s): Chen; Wei Ning (Singapore, SG), Leong; Ai Lin (Singapore, SG), Lim; Gek Keow (Singapore, SG), Oon; Chong Jin (Singapore, SG) Assignee(s): Government of the Republic of Singapore (Singapore, SG) Patent Number: 6,593,082 Date filed: June 18, 2001 Abstract: The present invention provides an in vitro activity assay for human hepatitis B virus (HBV) DNA polymerase, which comprises using, as the 5' oligonucleotide in PCR amplification of HBV DNA polymerase from a sample, an oligonucleotide into which has been incorporated the SP6 viral polymerase promoter, directly transcribing and translating the PCR products in the presence of a radio-labelled agent and measuring the priming of the HBV DNA polymerase. The present invention also provides the use of such an assay to assay activity of various serum samples, to screen for inhibitors of the HBV DNA polymerase and to test and/or screen potential anti-HBV drugs for their ability to inhibit DNA priming activity of human HBV DNA polymerase. Excerpt(s): Polymerases are enzymes of fundamental importance to living organisms. They are responsible for the synthesis of nucleic acids and their transformation into other nucleic acids necessary for the synthesis of proteins. Polymerases are, therefore, found in all types of cells including the causative DNA virus for hepatitis B virus (HBV). Although such active vaccination programme has resulted in a decrease of HBV infection in the population, an increasing number of mutations located within the `a` epitope have been emerging. These vaccine-induced HBV mutants are of concern, as they are capable of escaping the currently available immuno-based diagnostic system and able to replicate independently. The fact that mutations on the `a` epitope of HBsAg give rise to amino acid substitutions in the overlapping HBV DNA polymerase, particularly by their location within the reverse transcriptase domain, may imply that these vaccine-induced mutants have altered reverse transcriptase activity, a key factor for the viral replication. Web site: http://www.delphion.com/details?pn=US06593082__
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Inducing cellular immune responses to hepatitis B virus using peptide and nucleic acid compositions Inventor(s): Celis; Esteban (Rochester, MN), Chesnut; Robert W. (Cardiff-by-the-Sea, CA), Grey; Howard M. (La Jolla, CA), Kubo; Ralph T. (Carlsbad, CA), Livingston; Brian D. (San Diego, CA), Sette; Alessandro (La Jolla, CA), Sidney; John (La Jolla, CA), Southwood; Scott (Santee, CA), Vitiello; Maria A. (La Jolla, CA) Assignee(s): Epimmune Inc. (San Diego, CA) Patent Number: 6,689,363 Date filed: January 27, 1999 Abstract: This invention uses our knowledge of the mechanisms by which antigen is recognized by T cells to develop epitope-based vaccines directed towards HBV. More specifically, this application communicates our discovery of pharmaceutical compositions and methods of use in the prevention and treatment of HBV infection.
Patents 171
Excerpt(s): Chronic infection by hepatitis B virus (HBV) affects at least 5% of the world's population and is a major cause of cirrhosis and hepatocellular carcinoma (Hoofnagle, J., N. Engl. J. Med. 323:337, 1990; Fields, B. and Knipe, D., In: Fields Virology 2:2137, 1990). The World Health Organization lists hepatitis B as a leading cause of death worldwide, close behind chronic pulmonary disease, and more prevalent than AIDS. Chronic HBV infection can range from an asymptomatic carrier state to continuous hepatocellular necrosis and inflammation, and can lead to hepatocellular carcinoma. The immune response to HBV is believed to play an important role in controlling hepatitis B infection. A variety of humoral and cellular responses to different regions of the HBV nucleocapsid core and surface antigens have been identified. T cell mediated immunity, particularly involving class I human leukocyte antigen-restricted cytotoxic T lymphocytes (CTL), is believed to be crucial in combatting established HBV infection. Class I human leukocyte antigen (HLA) molecules are expressed on the surface of almost all nucleated cells. CTL recognize peptide fragments, derived from intracellular processing of various antigens, in the form of a complex with class I HLA molecules. This recognition event then results in the destruction of the cell bearing the HLApeptide complex directly or the activation of non-destructive mechanisms e.g., the production of interferon, that inhibit viral replication. Web site: http://www.delphion.com/details?pn=US06689363__ •
Inhibition and treatment of Hepatitis B virus and Flavivirus by Helioxanthin and its analogs Inventor(s): Cheng; Yung-Chi (Woodbridge, CT), Chou; Chen-Kung (Taipei, TW), Fu; Lei (Hamilton, CA), Kuo; Yueh-Hsiung (Taipei, TW), Yeh; Sheau-Farn (Taipei, TW), Zhu; Juliang (Hamden, CT), Zhu; Yonglian (New Haven, CT) Assignee(s): N. Y. Mu, N.T.U., V.G.H (Taipei, TW), Yale University (New Haven, CT) Patent Number: 6,306,899 Date filed: August 23, 1999 Abstract: This invention relates to anti-viral drugs such as Helioxanthin and its analogs. The present compounds may be used alone or in combination with other drugs for the treatment of Hepatitis B virus (HBV), Hepatitis C virus (HCV), Yellow Fever, Dengue Virus, Japanese Encephalitis, West Nile virus and related flaviviruses. In addition, compounds according to the present invention can be used to prevent hepatoma secondary to virus infection as well as other infections or disease states which are secondary to the virus infection. Excerpt(s): This invention relates to the anti-viral drugs such as Helioxanthin and its analogs compounds. These compounds may be used alone or in combination with other drugs for the treatment of the following: Hepatitis B virus (HBV), Hepatitis C virus (HCV), Yellow Fever, Dengue Virus, Japanese Encephalitis, West Nile virus and related flaviviruses. In addition, compounds according to the present invention can be used to prevent hepatoma secondary to virus infection as well as other infections or disease states which are secondary to the virus infection. Hepatitis B virus infection is a major health problem worldwide. HBV is a causative agent of both an acute and chronic form of hepatitis. More than 300 million people throughout the world are chronic carriers of HBV. Typically, the human host is unaware of infection and HBV infection leads to acute hepatitis and liver damage, abdominal pain, jaundice and elevated blood levels of certain enzymes. Additionally, HBV contributes to the formation of hepatocellular carcinoma and is second only to tobacco as a cause of human cancer. The mechanism by
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which HBV induces cancer is unknown, although it has been postulated that it may directly trigger tumor development or indirectly trigger tumor formation through chronic inflammation, cirrhosis and cell regeneration associated with the infection. The core gene contains the nucleocapsid protein (183-185 aa) and the hepatitis B core antigen. The precore region, upstream of the core region, consists of 87 nucleotides that codes for 29 amino acids and is in phase with the core region. The first 19 amino acids of the precore region act as a signal for membrane translocation and eventual secretion of the precore gene product, the Hbe antigen. Web site: http://www.delphion.com/details?pn=US06306899__ •
Low dose entecavir formulation and use Inventor(s): Colonno; Richard J. (Farmington, CT), Desai; Divyakant (West Windsor, NJ), Fakes; Michael G. (Belle Mead, NJ), Harianawala; Abizer (North Brunswick, NJ), Sprockel; Omar L. (Bridgewater, NJ) Assignee(s): Bristol-Myers Squibb Co. (Princeton, NJ) Patent Number: 6,627,224 Date filed: February 23, 2001 Abstract: Compositions containing a low dose of entecavir are administered on a daily basis to treat hepatitis B virus infection and/or co-infections. Formulations for the oral administration of a low dose of entecavir are provided. Other pharmaceutically active substances can be included in the entecavir composition or can be separately administered for the treatment of hepatitis B virus infection or for the treatment of coinfected patients. Excerpt(s): is an antiviral agent currently undergoing clinical evaluation for the treatment of hepatitis B virus infection. Entecavir and its use in treating hepatitis B are disclosed by Zahler et al. in U.S. Pat. No. 5,206,244. This patent discloses that an effective antiviral dose for oral or parenteral administration will likely be in the range of about 1.0 to 50 mg/kg of body weight and that the desired dose may be administered several times daily at appropriate intervals. Improved methods for the synthesis of entecavir are disclosed by Bisacchi et al. in WO 98/09964. Web site: http://www.delphion.com/details?pn=US06627224__
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Method for immunization against hepatitis B Inventor(s): Mancini; Maryline (Paris, FR), Michel; Marie-Louise (Paris, FR) Assignee(s): Institut de la Sante et de la Recherche Medicale (Paris, FR), Institut Pasteur (Paris, FR) Patent Number: 6,429,201 Date filed: May 12, 2000 Abstract: Nucleotide vector composition containing such vector and vaccine for immunization against hepatitis. Nucleotide vector comprising at least one gene or one complementary DNA coding for at least a portion of a virus, and a promoter providing for the expression of such gene in muscle cells. The gene may be the S gene of the hepatitis B virus. A nucleotide vector composition when administered to even chronic HBV carriers is capable of breaking T cell tolerance to the surface antigens of hepatitis B
Patents 173
virus. A vaccine preparation containing said bare DNA is injected into the host previously treated with a substance capable of inducing a coagulating necrosis of the muscle fibers. Excerpt(s): The present invention relates to compositions for inducing protective antibodies against hepatitis. It also relates to a vector comprising a nucleotide sequence coding for at least a portion of a virus protein, which is capable of being expressed in muscle cells. In addition, the invention relates to compositions capable of inducing a T cell response in chronic HBV carriers. Hepatitis B is a widespread and serious international health problem. In addition to causing acute hepatitis and liver damage, the hepatitis B virus (HBV) can cause cirrhosis and hepatocellular carcinoma (Davis, Hum. Molec. Genet. 2:1847-1851 (1993)). The HBV is a 42-nm particle (Dane particle) consisting of a lipoprotein envelope enclosing a core protein (capsid) and the viral genome, which contains only four genes (S, C, P, X). The major (or small) envelope protein, which includes the surface antigen of HBV (HBsAG) is encoded by the S gene and is organized into dimers of one glycosylated and one unglycosylated polypeptide (Petersen, J. Biol. Chem. 256:6975-6983 (1981)). Present in smaller amounts are the middle and large envelope proteins, which are encoded by the pre-S2 and S or pre-S1, pre-S2 and S genes, respectively. The predominant form of HBsAg secreted by infected cells is not the Dane particle, however, but 22-nm particles or filaments, which are empty viral envelopes composed solely or predominantly of major (small) envelope protein and sometimes small amounts of middle and large proteins (Maupas, Lancet 1:1367-1370 (1976)). The 22-nm particles are seen to persist in the plasma of chronic carriers (Davis, 1993). Web site: http://www.delphion.com/details?pn=US06429201__ •
Method of immunizing against hepatitis B virus Inventor(s): Neurath; Alexander Robert (New York, NY), Pride; Michael W. (Buffalo, NY), Strick; Nathan (New York, NY), Thanavala; Yasmin M. (Buffalo, NY) Assignee(s): Health Research, Inc. (Buffalo, NY) Patent Number: 6,319,501 Date filed: November 12, 1993 Abstract: A method for immunizing a human against hepatitis B virus comprising administering to the human a vaccine comprising a hepatitis B virus surface antigen, wherein included in the vaccine is one or more antigens of non-permitted variant sequences within residues S(139-147) of the hepatitis B virus surface antigen. Excerpt(s): The present invention concerns an improved method for immunizing against hepatitis B virus (HBV) by including in a hepatitis B virus vaccine one or more antigens of non-permitted variant sequences within residues S(139-147) of the hepatitis B virus surface antigen. There are approximately 600,000 persistent carriers of hepatitis B virus (HBV) in the United States; the estimated total number of carriers in the world is 300 million. A considerable portion of HBV carriers have chronic liver disease. The involvement of HBV in liver cancer has been demonstrated (W. Szmuness, Prog. Med. Virol. 24, 40 (1978) and R. P. Beasley, L.-Y. Hwang, C. -C. Ling, C.-S. Chien, Lancet, Nov., 21, 1129 (1981)). The biology, structure and immunochemistry of HBV and the genetic organization of its DNA genome have been reviewed (B. S. Blumberg, Science, 197, 17, (1977)). The cloning and sequencing of the genome of several hepatitis virus
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(HBV) isolates led to the elucidation of the genetic structure of the viral DNA (P. Tiollais, P. Charnay, G. N. Vyas, Science, 213, 406, (1981)). Web site: http://www.delphion.com/details?pn=US06319501__ •
Methods and compositions to investigate infection by hepatitis B virus and agents to prevent and treat the infection Inventor(s): Delaney, IV; William E. (San Bruno, CA), Isom; Harriet C. (Hershey, PA) Assignee(s): The Penn State Research Foundation (University Park, PA) Patent Number: 6,610,471 Date filed: September 5, 2000 Abstract: Methods and compositions that use the hepatitis B virus genome, and fragments or extensions, in a baculovirus vector, to develop anti-HBV agents and to drive high-level expression of a desired gene in a cell of hepatic origin. Excerpt(s): Supported in part by research grants from the National Institutes of Health (CA73045 and CA23931). Methods and compositions are presented that use the hepatitis B virus genome, and fragments or extensions thereof, in a baculovirus vector, to develop anti-HBV agents. Hepatitis B virus (HBV) is a small, double-stranded DNA virus and is the prototype of the hepadnavirus family. HBV is a human pathogen capable of causing both acute and chronic hepatitis. The World Health Organization currently estimates that 350 million people are chronically infected with HBV. Persistent HBV infection is also associated with an increased risk of cirrhosis and hepatocellular carcinoma. Web site: http://www.delphion.com/details?pn=US06610471__
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Mutant human hepatitis B viral strain and uses thereof Inventor(s): Chen; Wei Ning (Singapore, SG), Lim; Gek Keow (Singapore, SG), Oon; Chong Jin (Singapore, SG), Zhao; Yi (Singapore, SG) Assignee(s): Government of Republic of Singapore (Singapore, SG) Patent Number: 6,558,675 Date filed: April 30, 2001 Abstract: An isolated strain of Hepatitis B virus designated Human Hepatitis B Virus Surface Antigen-`S`-133 Oon Strain (Methionine to Threonine) of Cell. Also, an isolated nucleic acid encoding a polypeptide which is a mutant major surface antigen of a strain of hepatitis B virus, such polypeptide having an amino acid sequence which differs from the amino acid sequence of a major surface antigen of a wild type hepatitis B virus in that the amino acid at position number 133 of such polypeptide is a threonine rather than methionine. Excerpt(s): Throughout this application, various references are referred to within parentheses. Disclosures of these publications in their entireties are hereby incorporated by reference into this application to more fully describe the state of the art to which this invention pertains. The present invention concerns the human hepatitis B virus genome, isolated from hepatocellular carcinoma (HCC), and with a mutation at amino acid residue 133 (Methionine to Threonine) within the major surface antigen, its
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nucleotide sequence, the deduced amino acid sequence of the four major proteins, antigen, antibody, detection systems, development of effective vaccines, and antiviral agents. One of the major causes of chronic liver diseases is hepatitis B viral infection. First discovered in 1963 as a human virus that is transmitted parenterally, chronic hepatitis B viral infection has been most commonly implicated in serological undefined pathogenesis of HCC. Despite the fact that hepatitis B virus does not display features of a complete viral oncogene, its involvement in the development of HCC can be attributed to various aspects of its interaction with host hepatocyte cells. These include the promiscuous transcriptional activity of the smallest viral protein, X, which enhances the expression level of many cellular target genes including proto-oncogenes. On the other hand, integrated viral DNA in the host chromosomes is regularly found in HCC patients. There is also evidence for an active role in the development of HCC by the major surface antigen. This protein has served as the main detection marker for carriers of hepatitis B virus. The most antigenic epitope is a highly conserved region spanning 23 amino acid residues and located from amino acid position 124 to 147 of the major surface antigen. This small region designated as the group specific determinant "a" is found in all subtypes and isolates of hepatitis B viral genomes. Its antigenic properties seem due to its proposed double loop structure, to which the vaccine-induced neutralizing antibody binds. Web site: http://www.delphion.com/details?pn=US06558675__ •
Nucleosides with anti-hepatitis B virus activity Inventor(s): Gosselin; Gilles (Montpellier, FR), Imbach; Jean-Louis (Montpellier, FR), Schinazi; Raymond F. (Decatur, GA), Sommadossi; Jean-Pierre (Birmingham, AL) Assignee(s): Emory University (Atlanta, GA) Patent Number: 6,245,749 Date filed: July 9, 1998 Abstract: A method for the treatment of a host, and in particular, a human, infected with hepatitis B virus (HBV) is provided that includes administering an effective amount of a nucleotide prodrug of.beta.- L-2', 3'-dideoxyadenosine, wherein the prodrug component of the nucleotide provides controlled delivery of the active species. Excerpt(s): This invention is in the area of methods for the treatment of hepatitis B virus (also referred to as "HBV") that includes administering an effective amount of one or more of the active compounds disclosed herein, or a pharmaceutically acceptable derivative or prodrug of one of these compounds. Hepatitis B virus has reached epidemic levels worldwide. After a two to six month incubation period in which the host is unaware of the infection, HBV infection can lead to acute hepatitis and liver damage, that causes abdominal pain, jaundice, and elevated blood levels of certain enzymes. HBV can cause fulminant hepatitis, a rapidly progressive, often fatal form of the disease in which massive sections of the liver are destroyed. Patients typically recover from acute viral hepatitis. In some patients, however, high levels of viral antigen persist in the blood for an extended, or indefinite, period, causing a chronic infection. Chronic infections can lead to chronic persistent hepatitis. Patients infected with chronic persistent HBV are most common in developing countries. By mid-1991, there were approximately 225 million chronic carriers of HBV in Asia alone, and worldwide, almost 300 million carriers. Chronic persistent hepatitis can cause fatigue, cirrhosis of the liver, and hepatocellular carcinoma, a primary liver cancer. In western industrialized countries, high risk groups for HBV infection include those in contact with HBV carriers
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or their blood samples. The epidemiology of HBV is in fact very similar to that of acquired immunodeficiency syndrome, which accounts for why HBV infection is common among patients with AIDS or HIV-associated infections. However, HBV is more contagious than HIV. Daily treatments with.alpha.-interferon, a genetically engineered protein, has shown promise. A human serum-derived vaccine has also been developed to immunize patients against HBV. Vaccines have been produced through genetic engineering. While the vaccine has been found effective, production of the vaccine is troublesome because the supply of human serum from chronic carriers is limited, and the purification procedure is long and expensive. Further, each batch of vaccine prepared from different serum must be tested in chimpanzees to ensure safety. In addition, the vaccine does not help the patients already infected with the virus. Web site: http://www.delphion.com/details?pn=US06245749__ •
Nucleosides with anti-hepatitis B virus activity Inventor(s): Gosselin; Gilles (Montpellier, FR), Imbach; Jean-Louis (Montpellier, FR), Schinazi; Raymond F. (Decatur, GA), Sommadossi; Jean-Pierre (Birmingham, AL) Assignee(s): Emory University (Atlanta, GA), University of Alabama Research Foundation, Inc. (Birmingham, AL) Patent Number: 6,525,033 Date filed: November 22, 1999 Abstract: A method for treating HBV infections via administration of 2', 3' dideoxynucleoside compounds. Excerpt(s): This invention is in the area of methods for the treatment of hepatitis B virus (also referred to as "HBV") that includes administering an effective amount of one or more of the active compounds disclosed herein, or a pharmaceutically acceptable derivative or prodrug of one of these compounds. Hepatitis B virus has reached epidemic levels worldwide. After a two to six month incubation period in which the host is unaware of the infection, HBV infection can lead to acute hepatitis and liver damage, that causes abdominal pain, jaundice, and elevated blood levels of certain enzymes. HBV can cause fulminant hepatitis, a rapidly progressive, often fatal form of the disease in which massive sections of the liver are destroyed. Patients typically recover from acute viral hepatitis. In some patients, however, high levels of viral antigen persist in the blood for an extended, or indefinite, period, causing a chronic infection. Chronic infections can lead to chronic persistent hepatitis. Patients infected with chronic persistent HBV are most common in developing countries. By mid-1991, there were approximately 225 million chronic carriers of HBV in Asia alone, and worldwide, almost 300 million carriers. Chronic persistent hepatitis can cause fatigue, cirrhosis of the liver, and hepatocellular carcinoma, a primary liver cancer. In western industrialized countries, high risk groups for HBV infection include those in contact with HBV carriers or their blood samples. The epidemiology of HBV is in fact very similar to that of acquired immunodeficiency syndrome, which accounts for why HBV infection is common among patients with AIDS or HIV-associated infections. However, HBV is more contagious than HIV. Web site: http://www.delphion.com/details?pn=US06525033__
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Nucleotide vector composition containing such vector and vaccine for immunization against hepatitis Inventor(s): Davis; Heather Lynn (Ottawa, CA), Michel; Marie-Louise (Paris, FR), Whalen; Robert Gerald (Paris, FR) Assignee(s): Institut National de la Sant et de la Recherche Medical (Paris, FR), Institut Pasteur (Paris, FR), Universite d'Ottawa (Ottawa, CA) Patent Number: 6,635,624 Date filed: September 2, 1998 Abstract: The invention relates to methods of inducing an immunogenic response in a subject that include administering a nucleotide plasmid vector that includes a gene coding for a surface antigen protein derived from hepatitis B virus and a promoter for the expression of the gene. The invention also relates to vaccine compositions for protecting against hepatitis B virus. Excerpt(s): The present application relates to a vector for immunization against hepatitis. It is also related to a composition containing this vector. Immunization by injection of bare DNA into muscle tissues has been the object of several studies since the beginning of the 1990s. Web site: http://www.delphion.com/details?pn=US06635624__
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Pharmaceutical composition for treating hepatitis B virus (HBV) infection Inventor(s): Blum; Hubert E. (Freiburg, DE), Galun; Eithan (Har Adar, IL), Nahor; Orit (Jerusalem, IL) Assignee(s): Hadasit & Medical Research Services & Development Company, Ltd. (Jerusalem, IL) Patent Number: 6,217,858 Date filed: February 11, 1997 Abstract: The invention provides a pharmaceutical composition for the treatment of hepatitis B virus (HBV) infection, comprising an amount of a soluble active agent which interacts with at least one of the binding sites between hIL6 and pS1 and between hIL6 and hepatocytes and other HBV-permissive cells, the active agent being present in sufficient amount to competitively bind to at least one of the sites and thereby to prevent hIL6-mediated HBV infection of hepatocytes and other HBV-permissive cells. Excerpt(s): The present invention relates to pharmaceutical compositions for the treatment of hepatitis B virus (HBV) infection. In a study reported by Neurath, et al. [A. Neurath, et al., J. Exp. Med., Vol. 175, pp. 461-469 (1992)] hIL-6 was shown to bind the pS1 (aa 21-47) segment of the HBV envelope. Putative candidates for the HBV receptor were recently reported, including Annexin V (endohexin II) [K. Hertogs, et al., Virology, Vol. 197, pp. 549-557 (1993)]; apolipoprotein H [H. Mehdi, et al., Journal of Virology, Vol. 68, pp. 2415-2424 (1994)]; and asialoglycoprotein receptor [U. Treichel, et al., Journal of General Virology, Vol. 75, pp. 3021-3029 (1994)]. Binding experiments have demonstrated that the pre-S1 (pS1) region of the viral envelope protein contains a recognition site for the host cell [A. R. Neurath, et al., Cell, Vol. 46, pp. 429-436 (1986); M. Petit, et al., Virology, Vol. 180, pp. 483-491 (1990); M. Petit, et al., Virology, Vol. 197, pp. 211-222 (1992)]. Although previous studies had suggested that HepG2 cells [R. Bchini, et al., Journal of Virology, Vol. 64, pp. 3025-3032 (1991)] and human hepatocytes [P.
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Gripon, et al., Journal of Virology, Vol. 62, pp. 4136-4143 (1988); T. Ochiya, et al., Proc. Natl. Acad. Sci. U.S.A., Vol. 86, pp. 1875-1879 (1989); P. Gripon, et al., Virology, Vol. 192, pp. 534-540 (1993); P. Galle, et al., Gastroenterology, Vol. 106, pp. 664-673 (1994)] could support HBV infection in vitro, no cellular receptor has as yet been defined in either system, and these models were of low experimental reproducibility. Web site: http://www.delphion.com/details?pn=US06217858__ •
Pharmaceutical compositions and methods for producing antibodies to hepatitis b virus and kits and methods for detecting antibodies to hepatitis b virus Inventor(s): Murray; Kenneth (Heidelberg, DE) Assignee(s): Biogen, Inc. (Cambridge, MA) Patent Number: 6,270,955 Date filed: June 7, 1995 Abstract: Recombinant DNA molecules and hosts transformed with them which produce polypeptides displaying HBV anti-genicity and genes coding therefor and methods of making and using these molecules, hosts, genes and polypeptides. The recombinant DNA molecules of this invention are characterized by structural genes that code for at least one polypeptide displaying HBV antigenicity. In appropriate hosts these recombinant DNA molecules permit the production and identification of genes and polypeptides characteristic of HBV antigenicity and their use in compositions and methods for detecting HBV virus infections in humans and stimulating the production of antibodies against this infection. Excerpt(s): This invention relates to recombinant DNA molecules and their method of production. This invention relates more particularly to recombinant DNA molecules expressed in appropriate host organisms. The recombinant DNA molecules disclosed herein are characterized by the DNA that codes for polypeptides with the specificity of hepatitis B viral antigens. As will be appreciated from the disclosure to follow, the recombinant DNA molecules may be used in the detection of hepatitis B virus in man and the stimulation of antibodies in humans against this virus. The virus that causes hepatitis B or serum hepatitis appears to infect only man. Hepatitis B virus ("HBV") infection in humans is widespread. In the United Kingdom, United States, and Western Europe, approximately 0.1% of all blood donors are chronic carriers of HBV. While the death rate due to viral hepatitis is not high (in 1975 in the United Kingdom it was 3 per million), there are indications that as many as 5% of the population in the United Kingdom and 15% of the population in the United States have been infected. In many African and Asian countries, up to twenty percent of the population are chronic carriers of HBV, and over fifty percent of all adults in those countries have been or are infected with HBV. The hepatitis infection is transmitted by three general mechanisms: (1) by parenteral inoculation of infected blood or body fluids, either in large amounts as in blood transfusions or in minute amounts as through an accidental skinprick; (2) by close family or sexual contact; and (3) by some mothers, who infected during pregnancy, transmit the virus to their new-born children. Under natural conditions, HBV is not highly contagious. Transmission by inhalation occurs rarely, if ever. Web site: http://www.delphion.com/details?pn=US06270955__
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Process for the production of DNA comprising the genome of the hepatitis B virus and vector including it Inventor(s): Charnay; Patrick (Boulogne, FR), Fritsch; Alex (Paris, FR), Pourcel; Christine (Paris, FR), Tiollais; Pierre (Paris, FR) Assignee(s): Institut National de la Santa et de la Recherche Medicale (Paris, FR), Institut Pasteur (Paris, FR) Patent Number: 6,225,458 Date filed: November 23, 1994 Abstract: The invention relates to a process for producing DNA corresponding to that of the DNA of the virus of B hepatitis. It comprises cloning in bacteria the latter DNA, previously repaired by means of the corresponding precursor nucleotides in the presence of a polymerase. The invention also relates to vectors containing said cloned DNA in their genomes. The cloned DNA is useful as a probe for detecting the presence of the virus of B hepatitis in biological samples, particularly blood or plasma. Its expression in bacteria provides a hybrid protein containing a protein fragment having vaccinating properties against hepatitis B. Excerpt(s): The invention relates to a process for the production of a DNA (desoxyribonucleic acid) comprising the genome characteristic of that of the B hepatitis virus. It also relates to DNAs -of which a fragment is constituted by a double strand DNA corresponding to that of viral B hepatitis. Lastly it relates to vectors and compositions including such DNAs, for taking advantages of their biological properties. B hepatitis is a frequent viral disease, more particularly in tropical Africa, in Southeast Asia and in the Far East where about 10% of the people are carriers of the surface viral antigen also designated as HBs antigen. Yet when the genome is repaired in vitro, as disclosed in the articles of SUMMERS, ROBINSON and LANDERS, small strands of DNA are formed in situ along the monocatenary region of the genome. However, these new strands do not connect to form a single strand along the full length of the monocatenary region, SUMMERS also discloses that the DNA polymerase reaction on the Dane particle resulted in a "fully double-stranded product consist(ing of a series of newly synthesized strands 50-500 nucleotides in length duplexed with the unlabeled strand". LANDERS discloses that the "DNA polymerase reaction "closes the single stranded region, resulting in molecules with uniform double-stranded length and a remaining S1-susceptible site (a nick or gap)". ROBINSON noted, regarding the nature of the DNA product of the in vitro endogenous polymerase reaction, that the ends of the repaired portions of the open strand do not appear to be joined to make closed circular DNA, although the single-stranded gaps appear to be closed by the endogenous DNA polymerase reaction. The circular molecules after the DNA polymerase reaction as before have a nuclease S1-sensitive site, and no closed circular DNA is detected by alkaline sucrose gradient sedimentation or equilibrium centrifugation in CsCl density gradient containing ethidium bromide. Web site: http://www.delphion.com/details?pn=US06225458__
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Recombinant proteins with the immunoreactivity of hepatitis B virus e antigen (HBeAg), a process for the preparation thereof and the use thereof in immunoassays and vaccines Inventor(s): Broker; Michael (Marburg, DE), Noah; Michael (Marburg, DE) Assignee(s): Dade Behring Marburg GmbH (Marburg, DE) Patent Number: 6,277,631 Date filed: May 22, 1995 Abstract: Recombinant yeast expression vectors with the features indicated in the patent claims are described. These recombinant yeast expression vectors can be used for the preparation of HBeAg in yeast host organisms. Appropriate expression systems, transformed host organisms, diagnostic aids and medicinal agents are additionally described. Excerpt(s): The invention relates to recombinant proteins with the immunoreactivity of hepatitis B virus e antigen (HBeAg), to a process for the preparation thereof in yeasts and to the use thereof in immunoassays and in vaccines. Immunoassays nowadays play an important part in the diagnosis of hepatitis B virus (HBV) infection. Thus, the acute phase of an infection is characterized by immunological detection of hepatitis B virus surface antigen (HBsAg). Determination of other HBV parameters allows confirmation of the diagnosis or differential diagnosis. Thus, it is assumed that HBsAg- and HBeAgpositive samples are acutely infectious, whereas the appearance of antibodies against HBeAg (anti-HBeAg-antibodies) marks the start of the period of patient convalescence. Radioimmunoassays and enzyme-linked immunoassays have become used world-wide for determining HBeAg and anti-HBeAg-antibodies and have substantially displaced other less sensitive techniques such as agglutination methods. These assays operate on the "sandwich principle". A solid phase, for example the wells of a microtiter plate or beads which are coated with human or mouse anti-HBeAg antibodies, is incubated with the patient's sample. If the sample contains HBeAg, it binds to the solid-phase antibodies. Unbound constituents are removed in a washing step. The HBeAg bound to the solid phase is labeled during a second incubation with an anti-HBeAg antibody which is coupled to an enzyme or radioisotope. After another washing step, detection is carried out by the conversion of a substrate or by measuring the radio-activity of this ternary complex. Web site: http://www.delphion.com/details?pn=US06277631__
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Recombinant VP2 parvoviral pseudo-particles encoding CTL or T-helper cell epitopes Inventor(s): Casal; Ignacio (Madrid, ES), Leclerc; Claude (Paris, FR), Lo-Man; Richard (Paris, FR), Rueda; Paloma (Madrid, ES), Sarraseca; Javier (Madrid, ES), Sedlik; Christine (Argenteuil, FR) Assignee(s): Immunologia Y Genetica Aplicada S.A. (Madrid, ES), Institut Pasteur (Paris, FR) Patent Number: 6,458,362 Date filed: August 30, 1996 Abstract: Attempts to generate modified viral pseudo-particles that are capable of stably incorporating heterologous antigenic determinants has encountered a number of difficulties including inhibition of pseudo-particle formation following epitope insertion
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and failure of the epitope to retain its native configuration. The present invention is directed toward recombinant viral pseudo-particles of the family Parvoviridae that stably encode heterologous epitopes. Hybrid virus-like particles (VLP) were prepared by self-assembly of a modified porcine parvovirus (PPV) VP2 capsid protein carrying a CD8.sup.+ or CD4.sup.+ T cell epitope in the amino terminus. Immunization of mice with hybrid pseudo-particles carrying a lymphocytic choriomeningitis virus (LCMV) nucleoprotein CTL epitope, without adjuvant, induced strong cytotoxic T lymphocyte (CTL) responses against both peptide-coated- or virus-infected-target cells. Immunization of mice with hybrid pseudo-particles carrying a hepatitis B virus (HBV) T helper cell epitope, without adjuvant, induced strong T helper lymphocyte responses against the reporter epitope. These recombinant viral pseudo-particles are easily produced by the baculovirus expression system and, therefore, represent a promising and safe strategy to induce strong CTL and T-helper cell responses for the elimination of virus-infected cells. Excerpt(s): The present invention relates to recombinant viral pseudo-particles of a virus of the Parvoviridae family or of a related virus, useful in particular for inducing cytotoxic CD8.sup.+ T lymphocyte (CTL) and CD4.sup.+ helper T lymphocyte responses in vivo at a high level. Another object is the use of these pseudo-particles for the production of antitumoral vaccines or drugs. It also covers compositions comprising said pseudo-particles in a physiologically acceptable excipient and/or diluent. Web site: http://www.delphion.com/details?pn=US06458362__ •
Regulation of nucleic acid expression by heparan sulfate and biological equivalents thereof Inventor(s): Wagner; William D. (Clemmons, NC) Assignee(s): Wake Forest University (Winston-Salem, NC) Patent Number: 6,221,855 Date filed: March 11, 1999 Abstract: The present invention relates to the use of heparan sulfate, or a biological equivalent thereof, to regulate nucleic acid expression, expression of cell receptors, and infection by hepatitis B virus. Excerpt(s): The present invention relates to regulation of gene expression by heparan sulfate or analogs thereof. Hepadnaviruses, as typified by human hepatitis B virus, the prototype member of this virus family, are small enveloped DNA viruses that produce persistent infections of liver cells and cause acute and chronic hepatitis (Kuroki et al., 1995, J. Biol. Chem. 270:15022-15028). Until recently, the process by which hepatitis B virus particles entered host cells was poorly understood. However, the prior art teaches that human hepatitis B virus binds to cells via a cell receptor protein, i.e., carboxypeptidase D (CPD) which is the human homolog of duck glycoprotein 180 (gp180). Duck gp180, which shares approximately 80% amino acid sequence identity with human carboxypeptidase D, has been demonstrated to serve as the hepatitis B virus receptor which mediates viral entry into cells in a duck hepatocyte infection model (Kuroki et al., 1995, J. Biol. Chem. 270:15022-15028). Carboxypeptidases perform several important functions in a variety of tissues. These proteins may be broadly divided into two groups based on both function and homology (Skidgel, 1988, Trends Pharmacol. Sci. 9:299-304). One group, which consists of proteins typically 30 to 40 kDa in size, includes the digestive enzymes carboxypeptidase A and carboxypeptidase B. The second group,
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which includes carboxypeptidase D, is a family of regulatory mammalian basic metallocarboxypeptidases related to ancestral digestive pancreatic carboxypeptidase B. These enzymes, which are typically 50 to 60 kDa in size, specifically cleave C-terminal arginine or lysine residues from peptides and proteins (McGwire et al., 1997, Life Sciences 60:715-724). Web site: http://www.delphion.com/details?pn=US06221855__ •
Single-stranded antibody against hepatitis B virus core protein, gene thereof, and therapeutic agent for hepatitis B containing these Inventor(s): Hayashi; Norio (Kawanishi, JP), Tohdoh; Naoki (Kobe, JP), Yamamoto; Hiroko (Higashiosaka, JP), Yamamoto; Masato (Hoover, AL) Assignee(s): Sumitomo Pharmaceuticals Company, Limited (Osaka-fu, JP) Patent Number: 6,562,599 Date filed: April 27, 2000 Abstract: A DNA characterized by coding for a single-stranded antibody capable of binding to a hepatitis B virus core protein: a single-stranded antibody coding for the DNA: a therapeutic agent for hepatitis B comprising the single-stranded antibody as the active ingredient; and a gene therapeutic agent containing the DNA as the active ingredient. Excerpt(s): The present invention relates to single-chain antibodies against hepatitis B virus core protein, genes thereof, and therapeutic agents for hepatitis B using the same. In particular, the present invention relates to single-chain antibodies characterized in that they inhibit DNA synthesis of hepatitis B virus by binding to the core protein of said virus, DNAs encoding said single-chain antibodies, vectors comprising said DNAs, transformants transformed with said vectors, a process for producing said single-chain antibodies, and therapeutic agents for hepatitis B using such single-chain antibodies or genes thereof. In Japan, hepatitis B virus (hereinafter sometimes abbreviated as HBV) accounts for a large part of the etiology of chronic hepatitis, as well as hepatitis C virus. Although the proportion of the virus carriers tends to decrease as a result of the recent preventive treatment by vaccination, there still exists a substantial number of patients with chronic hepatitis B, and medical treatments for this disease is quite important in terms of prophylaxis of primary hepatic cancer. As medical treatments for patients with chronic hepatitis B, those treatments that aim to exclude the virus by eliciting the host immunity, such as the interferon therapy, the steroid withdrawal therapy, and the propagermanium therapy, or the antiviral agent therapies (adenine arabinoside monophosphate, hereinafter sometimes abbreviated as ara-AMP), Lamivudine) are now being used. In the interferon therapy, however, a long-term clinical improvement cannot be observed, although a transient decrease in amount of serological markers of viral activities occurs. Likewise, although ara-AMP has been used with some effect, it is hard to say that the results are satisfactory at present. A treatment in which interferon and ara-AMP are combined and alternately administered exhibits neurotoxicity, and therefore has problems in its use. Furthermore, fulminant hepatitis B, which is one of the forms of acute hepatitis B, is a disease causing a high lethality, and there exist no effective therapeutic agents for this disease presently. Thus, although there is a strong need for developing an anti-hepatitis B virus therapy based on a different mechanism from those of conventional methods, no useful therapies have not yet been developed. Web site: http://www.delphion.com/details?pn=US06562599__
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Steroid/thyroid hormone receptor-related gene which is inappropriately expressed in human hepatocellular carcinoma and which is a retinoic acid receptor Inventor(s): de The; Hugues Blaudin (Paris, FR), Dejean; Anne (Paris, FR), Marchio; Agnes (Paris, FR), Tiollais; Pierre (Paris, FR) Assignee(s): Institut Pasteur (Paris, FR) Patent Number: 6,531,585 Date filed: February 1, 1991 Abstract: A previously isolated hepatitis B virus (HBV) integration in a 147 bp cellular DNA fragment linked to hepatocellular carcinoma (HCC) was used as a probe to clone the corresponding complementary DNA from a human liver cDNA library. Nucleotide sequence analysis revealed that the overall structure of the cellular gene, which has been named hap, is similar to that of the DNA-binding hormone receptors. Six out of seven hepatoma and hepatoma-derived cell-lines express a 2.5 kb hap mRNA species which is undetectable in normal adult and fetal livers, but present in all nonhepactic tissues analyzed. Low stringency hybridization experiments revealed the existence of hap related genes in the human genome. The cloned DNA sequence is useful in the preparation of pure hap protein and as a probe in the detection and isolation of complementary DNA and RNA sequences. The hap protein is a retinoic acid (RA) receptor identified as RAR-.beta. Excerpt(s): This invention relates to nucleotide sequences, polypeptides encoded by the nucleotide sequences, and to their use in diagnostic and pharmaceutical applications. Primary hepatocellular carcinoma (HCC) represents the most common cancer, especially in young men, in many parts of the world (as in China and in much of Asia and Africa) (reviewed in Tiollais, et al., 1985). Its etiology was investigated mostly by epidemiological studies, which revealed that, beyond some minor potential agents such as aflatoxin and sex steroids, hormones, Hepatitis B virus (HBV) chronic infection could account for a large fraction of liver cancers (Beasley and Hwang, 1984). Liganddependent transcriptional activators, such as steroid or thyroid hormone receptors, have recently been cloned allowing rapid progress in the understanding of their mechanism of action. Nevertheless, there exists a need in the art for the identification of transcripts that may encode for activational elements, such as nuclear surface receptors, that may play a role in hepatocellular carcinoma. Such findings would aid in identifying corresponding transcripts in susceptible individuals. In addition, identification of transcripts could aid in elucidating the mechanisms by which HCC occurs. Web site: http://www.delphion.com/details?pn=US06531585__
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Synthetic peptides that bind to the hepatitis B virus core and e antigens Inventor(s): Sallberg; Matti (Alvsjo, SE) Assignee(s): Tripep AB (Huddinge, SE) Patent Number: 6,417,324 Date filed: April 21, 2000 Abstract: The present invention relates generally to the field of virology. More particularly, the invention relates to the discovery that peptides, which bind to the Hepatitis B virus (HBV) core and e antigens, can be used to inhibit HBV infection. Embodiments concern "binding partners", which include peptides, peptidomimetics,
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and chemicals that resemble these molecules that interact with HBV core and e antigens, biological complexes having HBV core and e antigens joined to said binding partners, methods of identifying such binding partners, pharmaceuticals having binding partners, and methods of treatments and prevention of HBV infection. Excerpt(s): The present invention relates generally to the field of virology. More particularly, the invention relates to the discovery that peptides that bind to the hepatitis B virus (HBV) core and e antigens can be used to inhibit HBV infection. Of the many viral causes of human hepatitis, few are of greater global importance than hepatitis B virus (HBV). Approximately 300 million people worldwide are chronically infected and some of these chronically infected individuals develop severe pathologic consequences including chronic hepatic insufficiency, cirrhosis, and hepatocellular carcinoma (HCC). (See Fields Virology, third ed., edited by Fields et al., LipponcottRaven Publishers, Philidelphia 1996 pp. 2703 and Lee et al., Cancer, 72:2564-7 (1993)). Primary infection may be asymptomatic (e.g, in chronically infected individuals) or may result in varying degrees of acute liver injury. (Milich et al., Springer Seminars in Immunopathology, 17:149-66 (1995)). The invention described herein concerns the identification and manufacture of molecules that interact with HBcAg and/or HBeAg and thereby inhibit HBV infection or modulate a host immune system response or both. Molecules that interact with HBcAg and/or HBeAg, also referred to as "binding partners", are designed from fragments of antibodies and other proteins that interact with HBcAg and/or HBeAg. Accordingly, an amino acid sequence corresponding to the binding domains of monoclonal or polyclonal antibodies or proteins that bind HBcAg and/or HBeAg is used as a template for the design of synthetic molecules, including but not limited to, peptides, derivative or modified peptides, peptidomimetics, and chemicals. A preferred binding partner, for example, is a molecule called a "specificity exchanger", which comprises a first domain that interacts with HBcAg and/or HBeAg and a second domain that has an epitope for a high titer antibody, preferably an epitope on a pathogen or a toxin. The binding partners described herein can be manufactured by conventional techniques in peptide chemistry and/or organic chemistry. Web site: http://www.delphion.com/details?pn=US06417324__ •
Treatment of hepatitis B infection with thymosin alpha 1 in combination with lamivudine or in combination with lamivudine and famciclovir Inventor(s): Leung; Ying-Kit (Hong Kong, CN) Assignee(s): SciClone Pharmaceuticals, Inc. (San Mateo, CA) Patent Number: 6,288,033 Date filed: October 9, 1998 Abstract: A method of treatment of hepatitis B virus (HBV) infection in a patient by administering to the patient a drug regimen including an antiviral-effective amount of thymosin alpha 1 (T.alpha.1), an antiviral-effective amount of lamivudine, and optionally an antiviral-effective amount of famciclovir is disclosed. Excerpt(s): The present invention relates to the field of hepatitis B treatment. Chronic hepatitis B virus (HBV) infection is a serious global health problem affecting around 300 million individuals. Among them, approximately seventy-five percent are believed to be Asian. It also is estimated that 25-40% of these HBV carriers will die of cirrhosis or hepatocellular carcinoma. In contrast to the course of the disease in Caucasians, the natural history of chronic HBV infection in Asians is characterized by an initial active
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viral replicative state with minimal liver damage (immune tolerance phase), followed by an active immune clearance phase with chronic active hepatitis, and later an inactive HBV non-replicative phase with the development of cirrhosis that may be complicated by hepatocellular carcinoma (HCC). In addition, a fourth phase, characterized by viremia and chronic active hepatitis in the absence of HBE antigenaemia may follow. The main aim of current treatment is to suppress HBV replication before there is any significant irreversible liver disease. As most of the liver damage occurs during the immune clearance phase (when HBV replication is being suppressed spontaneously), it would be ideal to suppress HBV replication in an earlier phase (immune tolerant phase). Web site: http://www.delphion.com/details?pn=US06288033__
Patent Applications on Hepatitis B Virus As of December 2000, U.S. patent applications are open to public viewing.9 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 hepatitis B virus: •
Assay for the detection and quantification of HBV cccDNA by real-time PCR Inventor(s): He, Ming Liang; (Hong Kong, CN), Kung, Hsiang-Fu; (Hong Kong, CN), Lin, Marie Chia Mi; (Hong Kong, CN) Correspondence: William Collard; Collard & Roe, P.C.; 1077 Northern Boulevard; Roslyn; NY; 11576; US Patent Application Number: 20040058314 Date filed: May 29, 2003 Abstract: The persistence of covalently closed circular (ccc) DNA of Hepatitis B Virus (HBV) in liver cells is believed to be the major reason for relapse after completion of HBV antiviral therapy. Up to now, there is no sensitive method to quantify cccDNA in infected liver cells. A set of primers were designed to specifically amplify DNA fragments from HBV cccDNA but not from viral genomic DNA. A good linear range was obtained when 100 to 10.sup.7 copies of HBV cccDNA were used as template in the quantitative real-time PCR. Not only is this method rapid, economical, highly sensitive, it can be used to monitor HBV cccDNA in infected human liver biopsies and to guide patients undergoing long-term anti-HBV therapy. Excerpt(s): This application is based upon provisional application serial No. 60/383,953 filed on May 29, 2002 wherein priority is claimed under 35 U.S.C. 119e. Chronic Hepatitis B virus (HBV) infection is one of the leading causes of death in the world. In Asia, more than 10% of the population is chronic infected by HBV See Seeger C. & Masson, W. S. (2000) Hepatitis B Virus Biology Micro Molec Biol Review 64, 51-58; and Orito E. et al (2001) Geographic Distribution of Hepatitis B Virus (HBV) genotype in patients with chronic HBV infection in Japan Hepatology 34, 590-594. See also He et al (2002) A New and Sensitive Method for the Quantification of HBV cccDNA by real time PCR, Academic Press: Biochemical and Biophysical Research Communications 295, 1102-1107 incorporated herein by reference. It is believed that HBV covalently closed circular DNA (cccDNA) contributes to the relapse after discontinuation of antiviral
9
This has been a common practice outside the United States prior to December 2000.
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therapy See Yokosuka O. et al (1985) Changes of hepatitis B virus DNA in liver and serum caused by recombinant Leukocyte interferon treatment: analysis of intrahepatic replicative hepatitis B virus DNA, Hepatology 5, 728-734. To better treat this disease, it is necessary to monitor individual patients virologic profile in the antiviral therapy, especially the change of cccDNA level in the infected hepatocytes. The replication of HBV undergoes an unusual intermediate form-cccDNA. In the viral particles, viral genome is partially double-stranded open circular DNA. Upon infection, the virus transports its DNA to the hepatocyte nucleus and converts it to a cccDNA using host cell enzymes. See Newbold, J. E. et al. (1995) The covalently closed duplex form of the hepadnavirus genome exists in situ as a heterogenous population of viral minochromosomes, Jornal of Virology 69, 3350-3357; see also Seeger and Masson (2000). Then the HBV cccDNA serves as the template to transcribe viral RNAs, which serve either as viral pregenome RNAs, or as mRNAs coding for the multifunctional polymerase, core, X and envelope (S) proteins. The pregenomic RNA is encapsulated by the virion core particle and reversely transcribed by the viral polymerase, forming a single-strand DNA (negative strand). There is a great probability to generate HBV variants at this step since the reverse transcriptase lacks proofreading activity. Summers J. and Mason W. S. (1982) Replication of the genome of a hepatitis B-like virus by reverse transcription of an RATA intermediate. Cell 29, 403-415; See also Seeger, C. & Masson, W. S. (2000). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Combination therapy to treat hepatitis B virus Inventor(s): Barry, David W.; (Chapel Hill, NC), Furman, Phillip A.; (Durham, NC), Painter, George R. III; (Chapel Hill, NC), Rousseau, Franck; (Durham, NC) Correspondence: Clark G. Sullivan, ESQ.; King & Spalding Llp; 45th Floor; 191 Peachtree Street, N.E.; Atlanta; GA; 30303; US Patent Application Number: 20030158150 Date filed: February 25, 2003 Abstract: The present invention is directed to a method for treating hepatitis B virus infection in humans comprising administering a synergistically effective amount of agents having known anti-hepatitis B virus activity in combination or alternation. Specifically, the invention is directed to a method for treating hepatitis B virus infection comprising administering FTC in combination or alternation with penciclovir, famciclovir or Bis-POM-PMEA. Additionally, the invention is directed to a method for treating hepatitis B virus infection comprising administering L-FMAU in combination or alternation with DAPD, penciclovir or Bis-POM-PMEA. The invention is further directed to a method for treating hepatitis B virus infection comprising administering DAPD in combination or alternation with Bis-POM-PMEA. Excerpt(s): This invention is in the area of methods for the treatment of hepatitis B virus (also referred to as "HBV") that includes administering to a host in need thereof, an effective combination of nucleosides which have known anti-hepatitis B activity. This application claims priority to U.S. provisional patent application No. 60/106,664, filed on Nov. 2, 1998. HBV is second only to tobacco as a cause of human cancer. The mechanism by which HBV induces cancer is unknown, although it is postulated that it may directly trigger tumor development, or indirectly trigger tumor development through chronic inflammation, cirrhosis, and cell regeneration associated with the infection. Hepatitis B virus has reached epidemic levels worldwide. After a two to three
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month incubation period in which the host is unaware of the infection, HBV infection can lead to acute hepatitis and liver damage, that causes abdominal pain, jaundice, and elevated blood levels of certain enzymes. HBV can cause fulminant hepatitis, a rapidly progressive, often fatal form of the disease in which massive sections of the liver are destroyed. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Complex of Hepatitis B virus polymerase with p11 and method for controlling movement of the complex in HepG2 cell Inventor(s): Choi, Juhyun; (Bucheon-si, KR), Han, Ye Sun; (Seoul, KR), Lim, Dae-Sik; (Seoul, KR) Correspondence: Pennie & Edmonds, Llp; 3300 Hillview Avenue; Palo Alto; CA; 94304; US Patent Application Number: 20040043036 Date filed: August 7, 2003 Abstract: Disclosed is a complex of the 11 kDa Ca.sup.2+ binding protein of 11 and Hepatitis B virus polymerase (HBVPol) which moves to Promyelocytic Leukemia Nuclear Body (PMLNB). Furthermore, the present invention discloses a method for controlling movement of the HBVPol/p11 complex into the nucleus of HepG2 cell with adjusting of intracellular Ca.sup.2+ ion concentration by administrating an agent for controlling calcium ion concentration in HepG2 cells. Excerpt(s): The present invention relates to a complex of the 11 kDa Ca.sup.2+ binding protein and Hepatitis B virus polymerase (HBVPol) which is involved in Hepatitis B. A connection with liver cancer with infection by Hepatitis B virus (HBV) and use of interferone or a nucleoside analogue for treating the HBV infection, have been reported. However, such treatment has been applicable only for some of the infected patients and could not remove HBV completely. Therefore, there is a need for substrate materials to enhance the curative efficiency against HBV infection. Studies for finding intracellular factors which bind to HBVPol have been well advanced, and Pol of duck hepatitis B virus, which binds to Hsp90, p23 and Hsp70, shows a possible important role in the virus growth (Hu, J. et al., Hepadnavirus assembly and reverse transcription require a multi-component chaperone complex which is incorporated into nucleocapsids, EMBO J., 16 (1997) 59-68). Although this research was not carried out on HBV capable of infecting humans, HBVPol with multiple enzymatic activities as a single protein, has high possibility of binding intracellular factors and is believed to complete the multiple enzymatic activities through such processing. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Compositions and methods for detecting hepatitis B virus Inventor(s): Dockter, Janel M.; (Oceanside, CA), Getman, Damon K.; (Poway, CA), HoSing-Loy, Martha K.; (San Diego, CA), Kolk, Daniel P.; (Ramona, CA), Linnen, Jeffrey M.; (Poway, CA), Pollner, Reinhold B.; (San Diego, CA), Stringfellow, Leslie A.; (San Diego, CA), Yoshimura, Tadashi; (Chiba, JP) Correspondence: Gen Probe Incorporated; 10210 Genetic Center Drive; San Diego; CA; 92121 Patent Application Number: 20040029111 Date filed: June 13, 2003 Abstract: Compositions, methods and kits for detecting viral nucleic acids. Targets that can be detected in accordance with the invention include HBV and/or HIV-1 and/or HCV nucleic acids. Particularly described are oligonucleotides that are useful as hybridization probes and amplification primers that facilitate detection of very low levels of HBV nucleic acids. Excerpt(s): This application claims the benefit of U.S. Provisional Application No. 60/389,393, filed Jun. 14, 2002. The entire disclosure of this prior application is hereby incorporated by reference. The present invention relates to the field of biotechnology. More specifically, the invention relates to diagnostic assays for detecting the nucleic acids of any or all of hepatitis B virus, human immunodeficiency virus type 1, and hepatitis C virus. Infection by the hepatitis B virus (HBV) occurs worldwide and is an important cause of both acute and chronic viral hepatitis. HBV is a partially doublestranded circular DNA virus having a viral particle size of 42 nm. This particle includes an outer lipoprotein coat and the hepatitis B surface antigen (HBsAg). The HBsAg, circulates in the blood as a viral particle-bound form, or as a free, noninfectious protein aggregated into 22-nm spherical and tubular particles. Transmission of HBV is mediated primarily through blood and/or sexual contact. The incubation period for this virus ranges as high as 180 days (Gitlin, Clin. Chem. 43:1500 (1997)). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Diagnostic assay Inventor(s): Chen, Wei Ning; (Singapore, SG), Oon, Chong Jin; (Singapore, SG) Correspondence: Wilson Sonsini Goodrich & Rosati; 650 Page Mill Road; Palo Alto; CA; 943041050 Patent Application Number: 20030165817 Date filed: May 30, 2001 Abstract: The present invention relates generally to a nucleic acid-based assay to detect the presence of a viral pathogen and, in particular, hepatitis B virus. More particularly, the present invention provides a single-step amplification assay to detect hepatitis B viral nucleic acid sequences. The assay of the present invention is readily adaptable for automation and permits the rapid through-put of samples to be tested. The present invention further provides agents useful for performing a nucleic acid-based detection assay for hepatitis B virus and a kit comprising said agents. Excerpt(s): Bibliographic details of the publications numerically referred to in this specification are collected at the end of the description. Hepatitis B virus (hereinafter referred to as "HBV") can cause debilitating disease conditions and can lead to acute
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liver failure, bleeding from cirrhosis and primary liver cancer. HBV infects millions of individuals annually and contributes to at least a million deaths each year. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Enzyme inhibitors Inventor(s): Neuner, Philippe Jean Sigfried; (Albano Laziale, IT), Summa, Vincenzo; (Velletri, IT) Correspondence: Merck And CO Inc; P O Box 2000; Rahway; NJ; 070650907 Patent Application Number: 20030207922 Date filed: September 10, 2002 Abstract: Diketoacids of Formula A are useful as inhibitors of viral polymerases. In particular hepatitis C virus RNA dependent RNA polymerase (HCV RdRp), hepatitis B virus polymerase (HBV pol) and reverse transcriptase of human immunodeficiency virus (HIV RT): 1The group R may be broadly chosen and is an organic moiety which contains 2 to 24 carbon atoms and includes an optionally cyclic or heterocyclic group in which the atom directly bonded to the adjacent carbonyl in the diketoacid is part of the ring structure. Excerpt(s): The present invention relates to compounds useful as enzyme inhibitors, in particular as inhibitors of enzymes involved in the transfer of phosphoryl groups and, especially as inhibitors of polymerases. The invention further relates to pharmaceutical compositions containing such compounds, and to their use in the treatment of viral infections. Polymerases are the enzymes which catalyse the formation of phosphodiester bonds in RNA and DNA. They play an essential role in viral replication and, therefore, are an important target in the fight against viral diseases such as human immunodeficiency virus (HIV), hepatitis, and poliomyelitis. U.S. Pat. No. 5,475,109 describes dioxobutanoic acids substituted with piperidine or similar N-substituted saturated cycloalkyls as inhibitors of the cap-dependent endonuclease of influenza virus. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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HBV core antigen particles with multiple immunogenic components attached via peptide ligands Inventor(s): Murray, Kenneth; (Edinburgh, GB) Correspondence: Fish & Neave; 1251 Avenue OF The Americas; 50th Floor; New York; NY; 10020-1105; US Patent Application Number: 20030198649 Date filed: May 29, 2003 Abstract: This invention relates to hepatitis B virus ("HBV") core antigen particles that are characterized by multiple immunogen specificities. More particularly, the invention relates to HBV core antigen particles comprising immunogens, epitopes, or other related structures, crosslinked thereto by ligands which are HBV capsid-binding peptides that selectively bind to HBV core protein. Such particles may be used as delivery systems for a diverse range of immunogenic epitopes, including the HBV capsid-binding peptides, which advantageously also inhibit and interfere with HBV viral assembly by blocking
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the interaction between HBV core protein and HBV surface proteins. Mixtures of different immunogens and/or capsid-binding peptide ligands may be crosslinked to the same HBV core particle. Such resulting multicomponent or multivalent HBV core particles may be advantageously used in therapeutic and prophylactic vaccines and compositions, as well as in diagnostic compositions and methods using them. Excerpt(s): The front-line of clinical immunotherapeutic regimens includes patient immunizations against infectious pathogens and other health-threatening agents. Despite the plethora of immunization agents, inoculations may afford, at best, partial immunity, requiring frequent re-immunizations. Such is the case for various conventional monovalent or polyvalent vaccines. And even among such vaccines, the number of single agent inoculants capable of eliciting immunity against a variety of immunogens is limited. Furthermore, antigenic variation among pathogens may limit the efficacy of conventional vaccines. Due to such obstacles, efforts have focused on methodologies for enhancing the immune system response to given immunogens. To that end, immunogenic conjugates have been produced by linking immunogens to hepatitis B virus ("HBV") core particles (also referred to as nucleocapsids or nucleocapsid shells), in efforts to enhance the immunogenicity of the linked immunogen, through the operation of T cell dependent and T cell independent determinants of HBV core antigen. See, for example, U.S. Pat. No. 4,818,527 and R. Ulrich et al., "Core Particles of Hepatitis B Virus as Carrier for Foreign Epitopes", Adv. Virus. Res., 50, pp. 141-82 (1998). Enhanced immunogenicity of epitopes of interest has also been approached via hybrid viral particle-forming proteins, comprising at least a portion of a naturally occurring viral particle forming protein, for example HBV surface antigen, and one or more epitopic sites of interest. See U.S. Pat. No. 5,965,140. As evident from such efforts, proteins of HBV have been used as platforms for presenting immunogens of interest to the immune system. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
HBV/HCV virus-like particle Inventor(s): Glazer, Edward; (Oakland, CA), Houghton, Michael; (Berkeley, CA), Selby, Mark; (San Francisco, CA) Correspondence: Chiron Corporation; Intellectual Property - R440; P.O. Box 8097; Emeryville; CA; 94662-8097; US Patent Application Number: 20040146529 Date filed: November 17, 2003 Abstract: Chimeric antigens derived from hepatitis B virus (HBV) and hepatitis C virus (HCV) are described which form virus-like particles when co-expressed with an excess of hepatitis B virus surface antigen (HBsAg). The chimeric antigens are fusion proteins containing an immunogenic peptide derived from an HCV protein coupled to the amino terminus of HBsAg. Also described are nucleic acid constructs and vectors for transfection of cells and expression of the chimeric antigens. The invention further provides methods for producing HBV/HCV virus-like particles containing the chimeric antigens, cell lines for producing the virus-like particles, combination vaccines containing the virus-like particles, and DNA vaccines that express the virus-like particles. Excerpt(s): This application is related to provisional patent application serial No. 60/167,224, filed Nov. 24, 1999, from which priority is claimed under 35
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USC.sctn.119(e)(1) and which is incorporated herein by reference in its entirety. The invention is related to the area of recombinant vaccines. It is particularly related to the field of chimeric antigens and virus-like particles for use in vaccines, especially combination vaccines for Hepatitis B virus (HBV) and Hepatitis C virus (HCV). Hepatitis C virus (HCV) infects approximately 1% of the world's population and causes serious health problems. Over 75% of acutely infected individuals eventually progress to a chronic carrier state that can result in cirrhosis, liver failure, and hepatocellular carcinoma. A very small fraction of chronically infected patients clear HCV naturally and resolve chronic hepatitis. See Alter et al. (1992) N. Engl. J. Med. 327:1899-1905; Resnick and Koff. (1993) Arch. Intem. Med. 153:1672-1677; Seeff (1995) Gastrointest. Dis. 6:20-27; Tong et al. (1995) N. Engl. J. Med. 332:1463-1466. Immunization against E2 glycoproteins of some flaviviruses (see e.g., Konishi et al., (1992) Virology 188: 714-720), including HCV (Ishii et al., (1998) Hepatology 28: 1117-1120), may protect against infection. However, attempts to express recombinant HCV E1 and E2 glyocoproteins have been frustrated by the fact that these proteins are not secreted from the host cell but are retained within the endoplasmic reticulum (Dubuisson et al. (1994) J. Virology 68: 6147-6160). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Hepatitis B virus binding proteins and uses thereof Inventor(s): Shaul, Yosef; (Mobile Post Sde Gat, IL), Zemel, Romi; (Tel Aviv, IL) Correspondence: G.E. Ehrlich (1995) LTD.; C/o Anthony Castorina; Suite 207; 2001 Jefferson Davis Highway; Arlington; VA; 22202; US Patent Application Number: 20030185857 Date filed: May 23, 2003 Abstract: An isolated nucleic acid, a recombinant protein encoded thereby and uses thereof. The isolated nucleic acid including (a) a polynucleotide at least 60% identical to SEQ ID NOs:1, 3, 5 or portions thereof as determined using the Bestfit procedure of the DNA sequence analysis software package developed by the Genetic Computer Group (GCG) at the university of Wisconsin (gap creation penalty--50, gap extension penalty-3); (b) a polynucleotide encoding a polypeptide being at least 60% homologous with SEQ ID NOs:2, 4, 6 or portions thereof as determined using the Bestfit procedure of the DNA sequence analysis software package developed by the Genetic Computer Group (GCG) at the university of Wisconsin (gap creation penalty--50, gap extension penalty-3); or (c) a polynucleotide hybridizable with SEQ ID NOs:1, 3, 5 or portions thereof at 68.degree. C. in 6.times.SSC, 1% SDS, 5.times. Denharts, 10% dextran sulfate, 100.mu.g/ml salmon sperm DNA, and.sup.32p labeled probe and wash at 68.degree. C. with 3.times.SSC and 0.1% SDS. Excerpt(s): This is a divisional of U.S. patent application Ser. No. 09/409,096, filed Sep. 30, 1999. The present invention relates to a group of genes, and the proteins encoded thereby, which are capable of interfering with Hepatitis B virus (HBV) infection and to methods for identifying, purifying, isolating and characterizing related genes and gene products. The present invention further relates to isolation of soluble forms of the cellular receptor(s) for HBV on hepatocytes from bodily fluids, including, but not limited to, urine, and to purification of these soluble form binding proteins by means including, but not limited to, affinity columns. The present invention further relates to the use of these genes and their translation products to establish experimental models for HBV infection, whether in cell culture or in animals. The present invention further
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relates to the use of these genes and their translation products for therapeutic purposes. The present invention further relates to the use of these genes and their translation products to screen for additional binding protein interactions. The present invention further relates to the use of these genes and their translation products to prepare specific detectors of these proteins, including, but not limited to, antibodies, phage-display libraries, specific PCR primers, lectins, DNA probes, RNA probes, and non-antibody proteins for diagnostic and therapeutic purposes. Hepatitis B virus (HBV) is an enveloped RNA virus that infects human liver and replicates via reverse-transcription of the pregenomic RNA. Infected patients develop acute hepatitis, which is often selflimiting, but may develop into chronic hepatitis with high risk of liver cirrhosis and primary liver carcinoma in roughly 10% of all cases. The World Health Organization estimates that there will be 400 million carriers Worldwide in year 2000. Effective vaccines exist, but anti viral drugs with good and long term efficacy are not available. Little is known about how HBV infects liver cells and the HBV cellular receptor(s) remain unknown. Many proteins have been identified which bind to the viral envelope associated proteins, HBsAg, or related proteins, but none are considered genuine HBV receptors (reviewed in De et al., 1997 and in references cited therein). Some of these binding proteins are found in serum and some in hepatocytes. None of these molecules have been convincingly tied to infectivity, disqualifying them as genuine HBV receptors. These molecules are of three types, S binding proteins, preS2 binding proteins, and preS1 binding proteins. A brief summary of the characteristics of the three groups is provided herein. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Hybrid or chimeric polynucleotides, proteins, and compositions comprising hepatitis B virus sequences Inventor(s): Firat, Huseyin; (Paris, FR), Langlade-Demoyen, Pierre; (Paris, FR), Lemonnier, Francois; (Bourg-la-Reine, FR), Michel, Marie-Louise; (Paris, FR), Suhrbier, Andreas A.; (Bunya, AU) Correspondence: Finnegan, Henderson, Farabow, Garrett & Dunner; Llp; 1300 I Street, NW; Washington; DC; 20005; US Patent Application Number: 20040018208 Date filed: March 14, 2003 Abstract: H-2 class I negative, HLA-A2.1 transgeniic HHD mice were used for a comparative evaluation of the immunogenicity of HLA-A2.1 restricted human tumorassociated CTL epitopes. A hierarchy was established among these epitopic peptides injected into mice in IFA which correlates globally with their capacity to bind and stabilize HLA-A2.1 molecules. Co-injection of a helper peptide enhanced most CTL responses. In contrast, classical HLA class I transgenic mice which still express their own class I molecules did not, in most cases, develop H.A.-A2.1-restricted CTL responses under the same experimental conditions. Different monoepitopic immunization strategies of acceptable clinical usage were compared in HHD mice. Recombinant Tyvirus-like particles, or DNA encoding epitopes fused to the hepatitis B virus middle envelope protein gave the best results. Using this latter approach and a melanomabased polyepitope construct, CTL responses against five distinct epitopes could be elicited simultaneously in a single animal. Thus, HHD mice provide a versatile animal model for preclinical evaluation of peptide-based cancer immunotherapy.
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Excerpt(s): This application depends on, and claims the benefit of, the filing date of U.S. Provisional Application Serial No. 60/156,945, filed Sep. 30, 2000, the entire disclosure of which is hereby incorporated herein by reference. This invention relates to polynucleotides and vectors, to compositions containing the polynucleotides and vectors, to polypeptides and polypeptide compositions, and to their use. CTL-mediated protection against tumors has been documented in mouse experimental models (1). In view of our refined comprehension of the molecular structures recognized by CTL, the search for human tumor-derived CTL epitopes has been undertaken in many laboratories, as best exemplified for melanomas (2). Subsequently, clinical trials using peptide-based immunization protocols provided encouraging results (3). However, the selection of peptide(s) and vaccine strategy remain difficult in view of the number of candidate peptides and variety of immunization strategies. An animal model allowing a controlled evaluation of the immunogenic potential of the epitopic peptides and of the immunization strategies would be of interest before human immunotherapeutic trials. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Identification of oligonucleotides for the capture, detection and quantitation of hepatitis B viral DNA Inventor(s): Shyamala, Venkatakrishna; (Oakland, CA) Correspondence: Chiron Corporation; Intellectual Property - R440; P.O. Box 8097; Emeryville; CA; 94662-8097; US Patent Application Number: 20030143527 Date filed: October 9, 2002 Abstract: Hepatitis B virus capture oligonucleotides, primers and probes derived from conserved regions of the hepatitis B virus genome are disclosed. Also disclosed are nucleic acid-based assays using the capture oligonucleotides, primers and probes. Excerpt(s): This application is related to provisional patent applications serial No. 60/328,492 filed Oct. 9, 2001, serial No. 60/368,823 filed Mar. 29, 2002, and serial No. 60/393,561 filed Jul. 2, 2002, from which priority is claimed under 35 USC.sctn.119(e)(1) and which applications are incorporated herein by reference in their entireties. The present invention pertains generally to viral diagnostics. In particular, the invention relates to nucleic acid-based assays for accurately diagnosing hepatitis B infection. Hepatitis B virus (HBV) is a member of a group of small DNA-containing viruses that cause persistent noncytopathic infections of the liver. HBV infection in humans can cause severe jaundice, liver degeneration and death. HBV enters predominantly by the parenteral route, has a characteristic incubation period of 60 to 160 days, and may persist in the blood for years in chronic carriers. It is estimated that about 6 to 7% of the human population is infected, with the level of infection being as high as 20% of the population in certain regions of Southeast Asia and sub-Sahara Africa. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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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 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
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Inhibitor of hepatitis B and HIV activity Inventor(s): Nagaoka, Hitoshi; (Abiko-shi, JP) Correspondence: Webb Ziesenheim Logsdon Orkin & Hanson, P.C.; 700 Koppers Building; 436 Seventh Avenue; Pittsburgh; PA; 15219; US Patent Application Number: 20040038330 Date filed: August 19, 2003 Abstract: The inhibitor of Hepatitis B virus and HIV activity according to the present invention comprises a Lentinus edodes mycelium extract obtained by the steps of inoculating Lentinus edodes fungus in a solid culture medium comprising bagasse, then disentangling the solid culture medium containing the proliferated mycelium, adding water and at least one enzyme selected from a group consisting of cellulase, protease and glucosidase to the disentangled solid culture medium with keeping the solid culture medium at 30 to 50.degree. C., grinding and milling the solid culture medium in the presence of the enzyme to obtain a Lentinus edodes mycelium extract, and then heating the extract to a temperature of not higher than 95.degree. C. to inactivate the enzyme and sterilize the extract. Excerpt(s): This application is a divisional of application Ser. No. 08/519,293, filed Aug. 25, 1995, which is a continuation of application Ser. No. 08/257,355, which, in turn, claims priority to Japanese application No. 5-317564, filed Dec. 17, 1993. The present
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invention relates to an inhibitor of Hepatitis B virus and HIV (human immunodeficiency virus) activity, and more particularly to an inhibitor of Hepatitis B and HIV activity which is therapeutically effective for these infectious diseases and hardly brings about side effects. It was reported that the first deceased by HIV-infection in the world was found in Africa in 1950, and in an instant, the HIV-infected persons spread all over the world. Recently, it has been reported that a great number of persons were infected with HIV and deceased. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Method and device for the rapid clinical diagnosis of hepatitis B virus (HBV) infection in biological samples Inventor(s): Kondiboyina, Venkata Ramana; (Mumbai, IN), Sharma, Vijay; (Mumbai, IN) Correspondence: Lackenbach Siegel; One Chase Road; Scarsdale; NY; 10583; US Patent Application Number: 20030157478 Date filed: January 3, 2002 Abstract: There is provided a method and kit for rapid clinical diagnosis of HBV in which the amplimers are transcripts of a pre-core or envelop region gene of HBV. The amplicons are hybridized to a specific oligonucleotide probe, which allows the amplicons to be detected. Excerpt(s): The present invention relates to methods and devices for the diagnosis of infections. In particular, the present invention relates to methods and kits for detection of Hepatitis B Virus Viremia (HBV). Hepatitis B virus (HBV) is an enveloped hepatotropic DNA virus. Acute and chronic HBV infection causes significant liver diseases and it is estimated that more than 300 million individuals world wide are chronically infected with HBV. The HBV genome is unique in the world of viruses due to its compact nature, use of overlapping reading frames, and dependence on a reversetranscriptional step, though the virion contains primarily DNA. The human hepatitis B virus is a member of the Hepadna Viridae family which includes duck hepatitis virus (DHBV), Ground squirrel hepatitis virus (GSHV), snow goose hepatitis B virus (sgHBV), woodchuck hepatitis virus (WHV) and wooly monkey hepatitis virus. Furthermore, persistent viral infection leads to chronic active hepatitis, liver cirrhosis and the development of hepatocellular carcinoma. It has recently been appreciated that individuals who recover from HBV infection have a broad based cellular immune response to HBV structural proteins. Indeed, cytotoxic lymphocyte activity (CTL) may be critical for promoting viral clearance from the liver and CTL activity has been detected many years after resolution of acute infection. The presence of CTL activity may be due to persistence of low level HBV infection in the liver that can be identified only by molecular techniques such as PCR. Thus, the concept has arisen that even if individuals serologically recover from HBV infection, the virus, in most instances is never completely irradicated from the liver. Hepatitis B is of great medical importance because Hepatocellular carcinomas(HCC), one of the most common cancers afflicting humans, is primarily caused by chronic HBV infection. In the last few decades, the correlation between HBV and the development of HCC has been well established. However, the mechanism by which HBV transforms hepatocytes remains elusive. It is noticed that before HBV can transform a cell, the virus first infects it. However, the mechanism through which HBV enters hepatocyte has not been resolved despite further understanding of the viral protein involved. Much more research is needed before it is fully understood by the scientist and the spread of this infectious agent is controlled.
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Method and kit for detecting hepatitis B virus Inventor(s): Lee, Tzong Hae; (San Francisco, CA) Correspondence: Stevens, Davis, Miller & Mosher, L.L.P.; 1615 L Street, N.W., Suite 850; P.O. Box 34387; Washington; DC; 20036; US Patent Application Number: 20030215790 Date filed: May 20, 2002 Abstract: A method for detecting Hepatitis B virus (HBV) in a sample includes the steps of (a) adding to the sample a thermostable polymerase, appropriate nucleoside triphosphates, a nucleic-acid-binding fluorescent entity, and a pair of primers substantially complementary to a target nucleic acid having the sequence shown in SEQ ID NO:1 or the complement of the target nucleic acid; (b) thermally cycling the sample between at least a denaturation temperature and an elongation temperature; (c) illuminating the sample with a selected wavelength of light that is absorbed by the fluorescent entity during the thermally cycling step; (d) determining the amount of fluorescence generated by the fluorescent entity; and (e) detecting the presence of the target nucleic acid by analyzing the amount of luminescence determined after at least one amplification cycle. The invention further provides kits for detection of HBV in samples. Excerpt(s): This invention relates to a method for detecting or quantifying Hepatitis B virus (HBV) in a sample. The disease known as hepatitis B is caused by the infectious Hepatitis B virus (HBV). It has been estimated by the World Health Organization (WHO) that HBV have infected over two billion people worldwide. This makes HBV one of the most common human pathogens. Approximately 500 million are chronic carriers. Hepatocellular carcinomas (HCC), one of the most common cancers afflicting humans, is primarily caused by chronic HBV infection. Transmission of HBV is primarily through blood and/or sexual contact, though other methods of transmission have been suggested. Before HBV can transform a cell, the virus must first infect it. However, the mechanism through which HBV enters hepatocytes has not been resolved despite further understanding of the viral proteins involved. Vaccines are available against HBV, but they may not be 100% effective against all variants of HBV. Furthermore, there is no cure for individuals already infected. Much more research is needed before we fully understand and control the spread of HBV. Currently, a sensitive, specific and rapid assay to detect HBV DNA is not available. Traditional PCR methods have been utilized in humans to measure viral load for diagnosis of hepatitis B. However, traditional PCR methods do not allow accurate quantitation as the product is monitored beyond the exponential phase of PCR reaction and require laborious postPCR processing. Moreover, methods such as southern blot analysis are not sensitive or quantitative enough to reliably monitor decrease in viral reduction during antiviral therapy. Accordingly, there exists a need in the art for a rapid and sensitive method for detecting or quantifying HBV in a sample. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Methods and reagents for the inhibition of hepatitis B virus replication Inventor(s): McSwiggen, James; (Boulder, CO), Morrissey, David; (Boulder, CO) Correspondence: Mcdonnell Boehnen Hulbert & Berghoff; 300 South Wacker Drive; Suite 3200; Chicago; IL; 60606; US Patent Application Number: 20030148985 Date filed: December 5, 2002 Abstract: The present invention relates to nucleic acid molecules that modulate Hepatitis B virus (HBV) gene expression and HBV replication, and methods thereof. Specifically, the present invention relates to nucleic acid decoy molecules and aptamers that bind to HBV reverse transcriptase and/or HBV reverse transcriptase primer sequences and methods for their use alone or in combination with other therapies. The present invention also relates to nucleic acid molecules that specifically bind the Enhancer I region of HBV DNA and methods for their use. Excerpt(s): The present invention concerns compounds, compositions, and methods for the study, diagnosis, and treatment of degenerative and disease states related to hepatitis B virus (HBV) infection, replication and gene expression. Specifically, the invention relates to nucleic acid molecules used to modulate expression of HBV. The following is a discussion of studies relating to hepatitis B virus (HBV). The discussion is not meant to be complete and is provided only for understanding of the invention that follows. The summary is not an admission that any of the work described below is prior art to the claimed invention. Chronic hepatitis B is caused by an enveloped virus, commonly known as the hepatitis B virus or HBV. HBV is transmitted via infected blood or other body fluids, especially saliva and semen, during delivery, sexual activity, or sharing of needles contaminated by infected blood. Individuals may be "carriers" and transmit the infection to others without ever having experienced symptoms of the disease. Persons at highest risk are those with multiple sex partners, those with a history of sexually transmitted diseases, parenteral drug users, infants born to infected mothers, "close" contacts or sexual partners of infected persons, and healthcare personnel or other service employees who have contact with blood. Transmission is also possible via tattooing, ear or body piercing, and acupuncture; the virus is also stable on razors, toothbrushes, baby bottles, eating utensils, and some hospital equipment such as respirators, scopes and instruments. There is no evidence that HBsAg positive food handlers pose a health risk in an occupational setting, nor should they be excluded from work. Hepatitis B has never been documented as being a food-borne disease. The average incubation period is 60 to 90 days, with a range of 45 to 180; the number of days appears to be related to the amount of virus to which the person was exposed. However, determining the length of incubation is difficult, since onset of symptoms is insidious. Approximately 50% of patients develop symptoms of acute hepatitis that last from 1 to 4 weeks. Two percent or less of these individuals develop fulminant hepatitis resulting in liver failure and death. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Methods for detecting and adjusting replication of hepatitis b virus and for preparing mutated virus strains with altered replication efficiency Inventor(s): Lin, Xu; (Shanghai, CN), Wen, Yumei; (Shanghai, CN), Yuan, Zhenghong; (Shanghai, CN) Correspondence: Dorsey & Whitney Llp; Intellectual Property Department; 50 South Sixth Street; Minneapolis; MN; 55402-1498; US Patent Application Number: 20040116368 Date filed: January 15, 2004 Abstract: The invention provides methods to assay and regulate the replication of hepatitis B virus (HBV), employing methods of generating HBV replication mutants. Based on the polymerase gene of HBV strains, various primers were designed, and by using restriction enzymes and polymerase chain reaction, fragments of the polymerase gene were substituted, and the replicative competency of the newly constructed recombinant polymerase gene was analyzed. This invention can be used to look for new functional domains in the polymerase and for designing anti-HBV replicating drugs and diagnostic reagents. Excerpt(s): The invention relates to virus genetic engineering, studies on the replicative competency of hepatitis B virus strains and their application. Hepatitis B virus (HBV) belongs to the hepadnaviridae, which has a unique genome structure and biological characteristics. The genome of this virus is double-stranded DNA but with a single stranded region. The genome consists of approximately 3,200 bp, but the length of the positive strand and the negative strand is not identical. The negative strand has a fixed length of around 3,200 bp, which comprises of four open reading frames, encoding the envelope (S/Pre-S), core (C/pre-C), polymerase (P) and X protein. The polymerase (P) gene is the longest, which covers approximately 80% of the whole genome, and overlaps with part or whole of other genes. Though the P gene overlaps with other genes, it has its own open reading frame. The clinical manifestations of HBV infections are variable, including asymptomatic carriers, acute hepatitis, chronic hepatitis, fulminant hepatitis and can result in cirrhosis of the liver and hepatocellular carcinoma. Currently, the variable clinical manifestations of HBV infections is considered not only associated with variations in host immune responses but also possibly associated with the structural and functional genomics of diverse virus strains. Among which, the virus replicative competency is one of the key factors of concern, because once virus replication is stopped, progression of disease can be under control. In duck hepatitis B virus (DHBV), Summers et al (Cell 1982; 29:403-415) first demonstrated that the replication cycle of this virus used RNA as an intermediate, and this unique form of replication was also confirmed in HBV. Thus scientists consider that the replication of HBV with certain similarities with retroviruses. The highly conserved regions in the HBV polymerase are similar to those of the RNA-dependent RNA polymerase, RNA-dependent DNA polymerase and RNaseH (Toh et al, Nature 1983;305:827). By comparing with human immunodeficiency virus (HIV) and other retroviruses, the polymerase of HBV can be divided into four regions: starting from the 5'-end, they are the terminal protein (TP)spacer (SP)-reverse transcriptase (RT/DNAP)-RNase H (Bartenschlagger and Schaller, 1988 EMBO J; 7:4185; Radziwill et al. 1990 J Virol; 64:613). Three of the four regions have functions, while the spacer has not been identified with functions. Among the various mutations detected in HBV polymerase, amino acid changes leading to resistance to the antiviral drug Lamivudine has raised the greatest concern. These mutations are at the 551-554 amino acids in the RT, when YMDD (Tyrosine-Methionine-Aspartic acidAspartic acid) was changed to YVDD (Tyrosine-Valine-Aspartic acid-Aspartic acid).
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Recently, resistance to another antiviral drug Famciclovir was found due to amino acid substitutions at the TP and RT regions. Compared to the RT domains in HIV, the domains of HBV RT can be divided into domains A (421-436), B (506-538), C (546-556), D (576-589), E (592-605) (Pock et al. 1989 EMBO J; 8:3867-3874; Gunther et al, 1999 J Hepatology; 30:749-754). The mutation of YMDD is in the C domain. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Methods for producing agrimonia extracts with improved activity against hepatitis b virus and pharmaceutical and food compositions containing said extracts Inventor(s): Ahn, Dong-Ho; (Gyeonggi-do, KR), Chang, Eun-Joo; (Daejeon, KR), Hong, Sa-Min; (Seoul, KR), Kwon, Hyok-Yun; (Daejeon, KR), Lee, Min-Kyung; (Gyeonggi-do, KR), Lee, Young-Sung; (Seoul, KR), Yoon, Seung-Kew; (Seoul, KR) Correspondence: Hunton & Williams Llp; 1601 Bryan Street; Energy Plaza - 30th Floor; Dallas; TX; 75201; US Patent Application Number: 20040091555 Date filed: December 31, 2003 Abstract: Disclosed are pharmaceutical and food compositions for preventing or treating hepatic disease, containing a pharmaceutically effective amount of an extract from a plant Agrimonia eupatoria L. Also, the present invention discloses a method of preparing a water-soluble extract from a plant of the genus Agrimonia, which which has improved efficacy in preventing or treating hepatic diseases, characterized by heating a mixture of a pulverized product of a plant of the genus Agrimonia and water at about 20.degree. C. to 30.degree. C. for about 7 days or more, and pharmaceutical and food compositions for preventing or treating a hepatic disease, containing a water-soluble extract prepared according to the method. Further, the present invention discloses a method of preparing an organic solvent-soluble extract from a plant of the genus Agrimonia, which has improved efficacy in preventing or treating hepatic diseases, comprising the steps of extracting a plant of the genus Agrimonia with an organic solvent, and removing an aqueous fraction and then obtaining an organic solventsoluble fraction, and pharmaceutical and food compositions for preventing or treating hepatic disease, containing an extract prepared according to the method. Excerpt(s): The present invention relates to methods of preparing extracts from plants belonging to the genus Agrimonia, which have improved activity against Hepatitis B virus. Also, the present invention is concerned with pharmaceutical and food compositions containing such extracts, which are useful for preventing and treating hepatic diseases. It is known that hepatitis B virus (HBV), which is a DNA virus, causes chronic hepatitis as well as acute hepatitis in humans, and is thus a major target of clinical research. When chronic hepatitis persists for a long period of time, liver cirrhosis and hepatocellular carcinoma can be induced (Peter J. Grob. Vaccine, 16:S11-S16 (1998)). Most hepatitis B viruses infect hosts via parenteral routes. In particular, infection of infants by HBV is a major global concern. If the mother has a chronic HBV infection, a fetus or a newborn infant is exposed to infection with HBV transmitted from the mother. Over two hundred million-people in the world suffer from HBV infection, and 3,500,000 people among those are in states of chronic infection which progress to liver cirrhosis and hepatocellular carcinoma, resulting in a high mortality rate (bavey S. State of the World's Vaccines and Immunization. Geneva: WHO, 1996:76-82). However, there is now no effective therapeutic agent for treatment of HBV infection. In this regard, a large number of research efforts for preventing or treating HBV infection are underway. As a
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result, the developed therapeutic agents are classified into immunomodulators, antiviral agents and nucleoside analogues, depending on their properties. The representative example of the immunomodulators is interferon, and examples of the antiviral agents include ribavirin, vidarabine, ara-AMP, acyclovir, suramin and zidovudine. Also, the nucleoside analogues include lamivudine, and adefovir having recently received approval from the Food and Drug Administration (FDA) in the USA for treatment of hepatitis B. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Methods for treating viral infection using IL-28 and IL-29 Inventor(s): Henderson, Katherine E.; (Seattle, WA), Kindsvogel, Wayne R.; (Seattle, WA), Klucher, Kevin M.; (Bellevue, WA), Sivakumar, Pallavur V.; (Seattle, WA) Correspondence: Deborah A. Sawislak; Zymogenetics, INC.; 1201 Eastlake Avenue East; Seattle; WA; 98102; US Patent Application Number: 20040138122 Date filed: October 23, 2003 Abstract: IL-28A, IL-28B, IL-29, and certain mutants thereof have been shown to have antiviral activity on a spectrum of viral species. Of particular interest is the antiviral activity demonstrated on viruses that infect liver, such as hepatitis B virus and hepatitis C virus. In addition, IL-28A, IL-28B, IL-29, and mutants thereof do not exhibit some of the antiproliferative activity on hematopoietic cells that is observed with interferon treatment. Without the immunosuppressive effects accompanying interferon treatment, IL-28A, IL-28B, and IL-29 will be useful in treating immunocompromised patients for viral infections. Excerpt(s): This application claims the benefit of U.S. Provisional Application Serial No. 60/420,714, filed Oct. 23, 2002, U.S. Provisional Application Serial No. 60/463,939, filed Apr. 18, 2003, U.S. Provisional Application Serial No. 60/420,713, filed Oct. 23, 2002, and U.S. Provisional Application Serial No. 60/463,982, filed Apr. 18, 2003, all of which are herein incorporated by reference. Strategies for treating infectious disease often focus on ways to enhance immunity. For instance, the most common method for treating viral infection involves prophylactic vaccines that induce immune-based memory responses. Another method for treating viral infection includes passive immunization via immunoglobulin therapy (Meissner, J. Pediatr. 124:S17-21, 1994). Administration of Interferon alpha (IFN-.alpha.) is another method for treating viral infections such as genital warts (Reichman et al., Ann. Intern. Med. 108:675-9, 1988) and chronic viral infections like hepatitis C virus (HCV) (Davis et al., New Engl. J. Med. 339:1493-9, 1998) and hepatitis B virus (HBV). For instance, IFN-.alpha. and IFN-.beta. are critical for inhibiting virus replication (reviewed by Vilcek et al., (Eds.), Interferons and other cytokines. In Fields Fundamental Virology., 3.sup.rd ed., Lippincott-Raven Publishers Philadelphia, Pa., 1996, pages 341-365). In response to viral infection, CD4+ T cells become activated and initiate a T-helper type I (TH1) response and the subsequent cascade required for cell-mediated immunity. That is, following their expansion by specific growth factors like the cytokine IL-2, T-helper cells stimulate antigen-specific CD8+ T-cells, macrophages, and NK cells to kill virally infected host cells. Although oftentimes efficacious, these methods have limitations in clinical use. For instance, many viral infections are not amenable to vaccine development, nor are they treatable with antibodies alone. In addition, IFN's are not extremely effective and they can cause significant toxicities; thus, there is a need for improved therapies. Not all viruses and
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viral diseases are treated identically because factors, such as whether an infection is acute or chronic and the patient's underlying health, influence the type of treatment that is recommended. Generally, treatment of acute infections in immunocompetent patients should reduce the disease's severity, decrease complications, and decrease the rate of transmission. Safety, cost, and convenience are essential considerations in recommending an acute antiviral agent. Treatments for chronic infections should prevent viral damage to organs such as liver, lungs, heart, central nervous system, and gastrointestinal sytem, making efficacy the primary consideration. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Methods of suppressing hepatitis virus infection using immunomodulatory polynucleotide sequences Inventor(s): Eiden, Joseph J. JR.; (Danville, CA), Van Nest, Gary; (Martinez, CA) Correspondence: Karen R. Zachow; Morrison & Foerster Llp; Suite 500; 3811 Valley Centre Drive; San Diego; CA; 92130-2332; US Patent Application Number: 20030216340 Date filed: February 3, 2003 Abstract: Methods are provided for the treatment of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections. A polynucleotide comprising an immunostimulatory sequence is administered to a individual who has been exposed to or infected by HBV and/or HCV. The polynucleotide is not administered with a HCV or HBV antigen. Administration of the polynucleotide results in amelioration of symptoms of HBV and/or HCV infection. Excerpt(s): This application claims the priority benefit of U.S. Provisional application 60/188,301, filed Mar. 10, 2000, which is hereby incorporated herein by reference in its entirety. This invention is in the field of immunomodulatory polynucleotides, more particularly their use in ameliorating or preventing hepatitis viral infection and/or symptoms of hepatitis virus infection. Hepatitis is a generic term for disease involving inflammation of the liver. A variety of agents can cause hepatitis, including viruses, drugs, toxins, and autoimmune disorders. Additionally, hepatitis can arise secondary to non liver-related disorders. Viral infection is the most common cause of hepatitis. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Modification of hepatitis b core antigen Inventor(s): Borisova, Galina; (Riga Latvia, GB), Li, Jin-Li; (Beckenham, GB), Page, Mark; (Derby, GB), Pumpens, Paul; (Riga Latvia, GB) Correspondence: Nixon & Vanderhye, PC; 1100 N Glebe Road; 8th Floor; Arlington; VA; 22201-4714; US Patent Application Number: 20040054139 Date filed: March 11, 2003 Abstract: A protein is provided comprising hepatitis B core antigen (HBcAg) wherein one or more of the four arginine repeats has been deleted, said protein comprising the C-terminal cysteine of HBcAg. The deleted region may be replaced by an epitope from a protein other than HBcAg, in which case the HBcAg acts as a carrier to present the
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epitope to the immune system. The chimeric protein is useful in prophylactic and therapeutic vaccination of a host, for example against hepatitis B virus. Excerpt(s): The invention relates to modified forms of the core antigen of hepatitis B virus (HBV) and to prophylactic and therapeutic vaccines containing the modified antigen. HBV remains a major healthcare problem throughout both the developed and developing world. Infection with the virus can result in an acute or chronic disease which in a proportion of cases may lead to hepatocellular carcinoma and death. The virus is double shelled, and its DNA is protected inside a protein structure called the core antigen (HBcAg). The core is surrounded by the envelope protein known as the surface or S antigen (HBsAg). HBcAg is an unusual antigen which can be used as a delivery vehicle for specific peptides to the immune system. The antigen has been used to present T-helper, B and cytotoxic lymphocyte (CTL) epitopes from a variety of viral and bacterial pathogens, including epitopes from the surface antigen of HBV, envelope proteins from hepatitis A and antigens from hepatitis C virus. For a review see Ulrich et al (1998) Advances in Virus Research 50 141-182. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Mouse model for inducing hepatocellular carcinoma by targeted integration of hepatitis B virus genes Inventor(s): Cui, Fang; (Beijing, CN), Huang, Cuifen; (Beijing, CN), Lu, Yaxin; (Beijing, CN), Wang, Youliang; (Beijing, CN), Yang, Xiao; (Beijing, CN) Correspondence: Darby & Darby P.C.; P. O. Box 5257; New York; NY; 10150-5257; US Patent Application Number: 20040016011 Date filed: May 14, 2003 Abstract: The invention provides a mouse model of hepatocellular carcinoma and a method for establishing an animal model comprising:a) inserting an exogenous gene of interest into a suitable vector having sequences homologous to a target site, to construct a recombinant targeting vector;b) transfecting ES cells of a studied animal using said targeting vector from step a), and screening targeted ES cells which have integrated the exogenous gene into a specific site;c) injecting targeted ES cells obtained from step b) into said animal's blastulas and culturing the blastulas in vitro, so that embryos containing targeted ES cells are generated; andd) implanting embryos generated from step c) into said animal's uterus, thereby progeny expressing the exogenous gene stably is developed.The invention further relates to the use of said transgenic mouse in research of hepatocellular carcinoma pathogenesis, its early stage diagnosis and therapy, and screening of anticancer drugs. Excerpt(s): The invention relates to a transgenic animal model and a method for establishing such model. Particularly, the invention relates to a method for integrating an exogenous gene of interest into an animal genome by an embryonic stem (ES) cell culture and homologous recombination to generate an animal model in which the exogenous gene is expressed stably. The invention also relates to an animal model obtained by the method. Hepatocellular carcinoma (HCC) is one of the leading malignancies worldwide, which especially distributes in Asia and Pacific regions including China. More than 1 million people develop into HCC each year (Bosch FX, Munoz N. Epidemiology of hepatocellular carcinoma. Bannsch P., Keppler D., eds. Liver cell carcinoma. Dordrecht: Kluwer Academic, 1989; 3-12). The five year survival rate of HCC is lower than 5%. A number of etiological factors, particularly hepatitis B virus
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(HBV) infection, are involved in the occurrence and progression of HCC. HBV is a DNA virus, which has a full length of approximately 3.2 kb containing a circular, partially double stranded DNA and replicating via an RNA intermediate. HBV can randomly integrate into a host genome. The host integrating HBV is referred to as a carrier. The carrier is in a state of chronic infection without any symptoms, but with the expression of hepatitis B surface antigen (HBsAg). It has been estimated that at least 350 million people worldwide are HBV chronic carriers (Zuckerman, A. J., More than third of world's population has been infected with hepatitis B. Br. Med. J 1213 (1999)), more than 75% being in Asia and Western Pacific (Gust, I. D., Epidemiology of hepatitis B infection in the Western Pacific and South East Asia, Gut 38 (suppl 2): s 18-s23 (1996)). Among these carriers, there are at least about 20% showing various degrees of chronic hepatitis and cirrhosis, and parts of them may develop into primary hepatocellular carcinoma. Clinical and epidemiological studies have shown that the risk of being afflicted with HCC reaches as high as 40 to 50% among HBV chronic carriers. For HCC, the best clinical approach is hepatocarcinoma resection at an early stage; thus, early stage diagnosis appears to be significantly important. However, no molecular marker in serum or liver that can be conveniently used to diagnose carriers who possibly develop into HCC with the least delay has been found yet. Further studies on pathology and molecular mechanisms responsible for HBV-induced HCC have great meaning for early stage diagnosis of such hepatocarcinoma. The induction and progression of hepatocellular carcinoma is a complex progress involving multiple factors, which relates to abnormal gene expression or mutation and interaction between them. After HBV infection, the interactions between HBV gene expression products and hepatocyte proteins or nucleic acids can interfere with normal gene expression and signal transduction, thus may trigger abnormal expression of proto-oncogenes, or functionally inactivate tumor suppressor genes, leading to abnormal growth and differentiation of hepatocyte, and finally to hepatocellular carcinoma. Up to now, however, the targets of HBV are unclear. Since HBV commonly infects neither cultured cells nor ordinary experimental animals (chimpanzee being the only sensitive experimental animal), this has limited the research on HBV pathogenesis to some degree. Transgenic animal techniques provide a new approach to investigate HBV pathogenesis. Chisari and Babinet et al. successfully established a number of HBV transgenic mouse models using transgenic techniques in 1985. Since then, studies on such mouse models have greatly promoted the understanding of pathology and molecular mechanisms of HBV-induced hepatocellular carcinoma. (Chisari F. V., Pinkert, C. A., et al. A transgenic mouse model of the chronic hepatitis B surface antigen carrier state. 230 Science 1157-1160 (1985); Babinet C., Farza, H., et al. Specific expression of hepatitis B surface antigen (HBsAg) in transgenic mice. 230 Science 1160-11(1985)). However, such transgenic mice are developed by traditional transgenic techniques, and the exogenous genes in them are randomly integrated into chromosomes. This often results in phenotype differences and to some degree makes phenotype analysis difficult. Thus, final conclusions regarding molecular mechanisms of HBV-induced HCC have not been made yet. Although domestic reports on transgenic mouse integrating an entire HBV genome have been published, there has been no report on successful transgenic mouse models for hepatocarcinoma up to now. Since the late eighties, on the basis of gene targeting techniques, a gene knock-in technique has been developed. The gene knock-in technique uses the technologies of homologous recombination and mouse ES cell culture to integrate an exogenous gene into a specific site on the mouse genome, obviating the blindness of traditional transgenic technology. Deng found that mice developed normally and that no abnormal phenotype existed in the liver after its p21 gene was removed. (Deng CX, Zhang P, et al. Mice lacking p21.sup.CIP/WAFI undergo normal development, but are defective in G1 checkpoint control. 82 Cell 675-684 (1995)).
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Moreover, the implementation of human genome mapping marks the beginning of a post-genomic era in life science, and the research on proteomics is becoming an important tool in studying functional genomics. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Novel hepatitis B virus Inventor(s): Zheng, Jian; (Raritan, NJ) Correspondence: Audley A. Ciamporcero JR.; Johnson & Johnson; One Johnson & Johnson Plaza; New Brunswick; NJ; 08933-7003; US Patent Application Number: 20030165816 Date filed: March 30, 2001 Abstract: We isolated and characterized a new surface mutant of the hepatitis B virus surface antigen (HBsAg). The mutant was isolated from a symptomatic patient with Down's syndrome who was found to be persistently positive for both for HBsAg and anti-HBs Antibody (Ab) with an equally long-lasting anti-HB core (c) IgM Ab Excerpt(s): Hepatitis B virus (HBV), a small double stranded DNA virus, can cause a wide spectrum of clinical presentations: asymptomatic carrier state, acute self-limited hepatitis, fulminant hepatitis, and chronic liver diseases including chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. It has a circular genome of 3182 to 3221 base pairs (bp). Four major subtypes have been identified and can be differentiated by antibodies that recognize the different epitopes on the HBV surface. The HBsAg particles carry the common determinant, "a", as well as d or y and w or r subtype determinants, and are classified into the four major subtypes, i.e., adw, adr, ayw and ayr. Rare sera contain HBsAg particles with all four-subtype determinants (adywr). The antigenic determinants for the main HBV subtypes: adw, adr, ayw and ayr lie in the surface or "S" polypeptide. Two amino acid residues in particular, encoded by the S gene at codon positions 122 and 160, have been postulated to determine the different antigenic subtypes. While, the preC regions have frequently been reported to have mutations rendering HBe Ag negative. The virus has a high rate of mutation relative to other DNA viruses due to its mode of replication by reverse transcriptase of its pregenomic RNA. The importance of a novel mutant can be reflected in vaccine escape and HBsAg detection failure, implicating a public health problem. We have identified and characterized a new surface mutant of HBV. The mutant was isolated from a symptomatic patient with Down's syndrome who was found to be persistently positive for both for HBsAg and anti-HBs Antibody (Ab) with an equally long-lasting anti-HB core (c) IgM Ab. With a panel of six monoclonal antibodies (mAb(s)) to HBsAg, we evaluated the mutation influence on the major epitope of the "a" determinant antigenicity. A sample was taken from a 43-year-old white male patient with Down's syndrome who presented with jaundice to the American University of Beirut Medical Center in March 1999. The patient had no history of immunization to HBV, no transmissible risk factor including blood transfusion, IV drugs, homosexuality, family HBV infection or hemodialysis. During investigation, he was found to have elevated liver function tests (LFT): ALT 450 IU/L (range 10-35 IU/L), AST 250 IU/L (range 10-40 IU/L), gamma-GT 383 IU/L (range 10-50 IU/L), Bilirubin was 3.8/2.6 mg/dL (total/direct) (range, total: 0.1-1.2 IU/L and direct: 0.0-0.2 IU/L). More significantly, we noted incongruity in the HBV blood tests. The HBV markers test results using enzyme immunoassay (EIA) methodology were as follows: HBs Ag positive (>2/0.051), anti-HBs Ab positive (0.417/0.206), anti-HBc IgM Ab low positive (0.371/0.208), anti-HBc IgG Ab
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strong positive (>2/0.412), HBe Ag negative and anti-HBe Ab positive (0.197/0.830, a competitive assay). Both the anti-hepatitis A Ab and the anti-hepatitis C Ab were negative. Due to the discrepancy in the HBV markers, molecular methods were used to confirm the HBV antigen. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Novel steroid/thyroid hormone receptor-related gene, which is inappropriately expressed in human heptocellular carcinoma, and which is a retinoic acid receptor Inventor(s): Blaudin de The, Hugues; (Paris, FR), DeJean, Anne; (Paris, FR), Marchio, Agnes; (Paris, FR), Tiollais, Pierre; (Paris, FR) Correspondence: Finnegan, Henderson, Farabow, Garrett & Dunner; Llp; 1300 I Street, NW; Washington; DC; 20005; US Patent Application Number: 20030153740 Date filed: December 2, 2002 Abstract: A previously isolated hepatitis B virus (HBV) integration in a 147 bp cellular DNA fragment linked to hepatocellular carcinoma (HCC) was used as a probe to clone the corresponding complementary DNA from a human liver cDNA library. Nucleotide sequence analysis revealed that the overall structure of the cellular gene, which has been named hap, is similar to that of the DNA-binding hormone receptors. Six out of seven hepatoma and hepatoma-derived cell-lines express a 2.5 kb hap mRNA species which is undetectable in normal adult and fetal livers, but present in all non-hepatic tissues analyzed. Low stringency hybridization experiments revealed the existence of hap related genes in the human genome. The cloned DNA sequence is useful in the preparation of pure hap protein and as a probe in the detection and isolation of complementary DNA and RNA sequences. The hap protein is a retinoic acid (RA) receptor identified as RAR-.beta. Excerpt(s): This application is a continuation-in-part of application Ser. No. 209,009, filed Jun. 20, 1988, (Attorney Docket Past-059-B), which is a continuation-in-part of application Ser. No. 134,130, filed Dec. 17, 1987, (Attorney Docket PAST-059-A), which is a continuation-in-part of application Ser. No. 133,687, filed Dec. 16, 1987, (Attorney Docket PAST-059). The entire disclosure of each of these copending applications is relied upon and incorporated herein by reference. This invention relates to nucleotide sequences, polypeptides encoded by the nucleotide sequences, and to their use in diagnostic and pharmaceutical applications. Primary hepatocellular carcinoma (HCC) represents the most common cancer, especially in young men, in many parts of the world (as in China and in much of Asia and Africa) (reviewed in Tiollais et al., 1985). Its etiology was investigated mostly by epidemiological studies, which revealed that, beyond some minor potential agents such as aflatoxin and sex steroids, hormones, Hepatitis B virus (HBV) chronic infection could account for a large fraction of liver cancers (Beasley and Hwang, 1984). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Oral DNA composition for hepatitis B virus chronic infection Inventor(s): Ng, Mun-Hon; (Bagulo Villa, HK), Yuen, Kwok-Yung; (Baguio Villa, HK), Zheng, Bo-Jian; (Pokfulam Garden, HK) Correspondence: Sughrue Mion, Pllc; Suite 800; 2100 Pennsylvania AVE., N.W.; Washington; DC; 20037-3213; US Patent Application Number: 20030162741 Date filed: February 28, 2003 Abstract: The present invention provides an oral DNA composition for improving an impaired immunity associated with chronic infection of hepatitis B virus (HBV) and for suppressing transgene expression for a protrated period of time comprising an attenuated strain of bacterial cells which preferentially target phagocytic cells of the intestinal mucosa, and which serve as a vehicle for a plasmid vector carrying one or more genes or complementary DNA coding for at least a portion of a hepatitis B viral protein or peptide. Given orally, the DNA composition causes a transient and selflimiting infection of the intestinal tract through autolysis of the bacterial cells and release of the plasmid after gaining entry into infected host cells. A promotor contained within the plasmid allows for expression of the HBV gene(s) in the eurokaryotic environment, the viral products of which help to booster a cell-mediated immunity to clear the infection and reverse a state of immune tolerance characteristic of HBV chronic infection. Excerpt(s): The present invention relates to an oral DNA composition (ODV) for ameliorating an impaired immunity in individuals who are chronically infected with hepatitis B virus (HBV). The oral DNA composition serves to booster immunity against HBV, improve the immune deficits associated with the disease and clear the infection. The World Health Organization (WHO) estimated that there are 350 million people world wide, who are chronically infected with the hepatitis B virus (HBV) [1]. These individuals have a high risk of developing liver cirrhosis and liver cancer. In addition, being the only significant reservoir for HBV, these individuals also pose as a significant public health hazard. None of the treatments presently available for chronic HBV infection can clear the virus from these individuals and are only moderately effective in reducing virus replication [2-5]. The idea that HBV infection may be cleared through immune intervention is based on findings that acute self-limited HBV infection evokes vigorous, polyclonal T helper cell (Th) and cytotoxic T lymphocyte (CTL) responses against viral capsid and envelope antigens, leading to the clearance of the virus from the body. On the other hand, chronic HBV infection is associated with weak Th responses of a restricted spectrum of antiviral specificity and usually undetectable virus-specific CTL activity [6]. These findings suggested that an intact cell mediated immunity is the chief determinant of virus clearance and provided the rational basis for immune intervention of chronic HBV infection with the view to booster cell mediated immunity (CMI) against the virus in order to clear the infection [7]. The contention was further supported by findings from bone marrow transplantation showing that adoptive transfer of bone marrow cells from donors, who had acquired intact immunity against the virus from natural infection, can improve the immune deficits of the chronically infected recipients and thereby clear the infection [8]. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Peptides for inducing cytotoxic T lymphocyte responses to hepatitis B virus Inventor(s): Chisari, Francis V.; (Del Mar, CA) Correspondence: Townsend And Townsend And Crew, Llp; Two Embarcadero Center; Eighth Floor; San Francisco; CA; 94111-3834; US Patent Application Number: 20030171538 Date filed: February 5, 2003 Abstract: Peptides are used to define epitopes that stimulate HLA-restricted cytotoxic T lymphocyte activity against hepatitis B virus antigens. The peptides are derived from regions of HBV polymerase, and are particularly useful in treating or preventing HBV infection, including methods for stimulating the immune response of chronically infected individuals to respond to HBV antigens. Excerpt(s): The present application is a continuation-in-part application of U.S. Ser. No. 08/100,870, filed Aug. 2, 1993, which is a continuation-in-part of U.S. Ser. No. 07/935,898, which is a continuation-in-part of U.S. Ser. No. 07/749,540, the disclosures of which are incorporated herein by reference. Cytotoxic T lymphocytes (CTLs) play an essential role in fighting cells infected with viruses, intracellular bacteria and parasites, and tumor cells. They do so by direct cytotoxicity and by providing specific and nonspecific help to other immunocytes such as macrophages, B cells, and other T cells. Infected cells or tumor cells process antigen through intracellular events involving proteases. The processed antigen is presented on the cellular surface in the form of peptides bound to HLA class I molecules to T cell receptors on CTLs. MHC class I molecules can also bind exogenous peptides and present them to CTLs without intracellular processing. At the present time it is difficult to accurately predict from the sequence of an antigenic protein how the protein will be processed and which peptide portions will bind HLA class I molecules and be presented to CTLs. Binding motifs have been predicted for some HLA class I molecules based on sequence analysis of peptides eluted from these molecules (Falk et al., Nature 351:290 (1991)). Further, of the peptides that are processed and do bind to HLA class I, which ones will contain CTLrecognizable epitopes is not yet predictable. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Pre-S protein of hepatitis B virus (HBV) as an adjuvant and a component of HBV vaccine Inventor(s): Ahn, Byung-Cheol; (Seongnam-city, KR), Kim, Ki-Yong; (Seongnam-city, KR), Moon, Hong-Mo; (Kwangju-si, KR), Park, Ji-Hee; (Seoul, KR), Seomun, Young; (Seongnam-city, KR), Yi, Su-Young; (Seoul, KR), Yum, Jung-Sun; (Seongnam-city, KR) Correspondence: Alston & Bird Llp; Bank OF America Plaza; 101 South Tryon Street, Suite 4000; Charlotte; NC; 28280-4000; US Patent Application Number: 20040137016 Date filed: November 24, 2003 Abstract: The present invention relates to an adjuvant and vaccine composition containing pre-S of the hepatitis B virus, and more specifically to a modified recombinant pre-S that can enhance immunogenicity of a general vaccine antigen. The present invention also relates to an improved prophylactic Hepatitis B virus (HBV) vaccine and a therapeutic vaccine for the treatment of chronic HBV carriers.
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Excerpt(s): The present invention relates to the production of pre-S from a recombinant yeast clone, to an adjuvant activity of pre-S, and to the use of pre-S as an HBV vaccine component. More specifically, it relates to the invention of the function of pre-S in enhancing the immunogenicity of an HBV S antigen and to its use as a component of an improved prophylactic HBV vaccine and a therapeutic vaccine for the treatment of chronic HBV carriers. The hepatitis B virus (hereinafter referred to as "HBV") is transmitted primarily through activities that involve contact with blood or blood derived fluids, and then spreads to other liver cells through the blood. The majority of individuals who have HBV infection fully recover from the virus infection by the body's immune responses, but about 5% of them become chronic carriers. This becomes worse (over 90%) in the case when infants are infected through a chronic carrier mother or from other sources during the perinatal period. In addition, infection through organ transplantation leads to an almost 100% carrier state. Most patients maintain a carrier condition that shows no severe symptoms, but 10 to 30% of these patients experience chronic hepatitis, they slowly progress to liver cirrhosis, and then eventually develop a hepatocarcinoma. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
RNA interference mediated inhibition of hepatitis B virus (HBV) using short interfering nucleic acid (siNA) Inventor(s): Beigelman, Leonid; (Longmont, CO), McSwiggen, James A.; (Boulder, CO), Morrissey, David; (Boulder, CO) Correspondence: Mcdonnell Boehnen Hulbert & Berghoff; 300 South Wacker Drive; Suite 3200; Chicago; IL; 60606; US Patent Application Number: 20030206887 Date filed: September 16, 2002 Abstract: The present invention concerns methods and reagents useful in modulating hepatitis B virus (HBV) gene expression in a variety of applications, including use in therapeutic, diagnostic, target validation, and genomic discovery applications. Specifically, the invention relates to short interfering nucleic acid (siNA) or short interfering RNA (siRNA) molecules capable of mediating RNA interference (RNAi) against against hepatitis B virus (HBV). Excerpt(s): This application claims the benefit of U.S. application Ser. Nos. 60/358,580, filed Feb. 20, 2002, and 60/393,924, filed Jul. 3, 2002. This application also claims priority to PCT US02/09187, filed Mar. 26, 2002, which claims the benefit of U.S. application Ser. No. 60/296,876, filed Jun. 8, 2001. The present invention concerns methods and reagents useful in modulating hepatitis B virus (HBV) gene expression and activity in a variety of applications, including use in therapeutic, diagnostic, target validation, and genomic discovery applications. Specifically, the invention relates to short interfering nucleic acid (siNA) molecules capable of mediating RNA interference (RNAi) against HBV expression. The following is a discussion of relevant art pertaining to RNAi. The discussion is provided only for understanding of the invention that follows. The summary is not an admission that any of the work described below is prior art to the claimed invention. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Stabilized HBc chimer particles as therapeutic vaccine for chronic hepatitis Inventor(s): Friede, Martin; (Cardiff, CA), Page, Mark; (Allestree, GB) Correspondence: Welsh & Katz, Ltd; 120 S Riverside Plaza; 22nd Floor; Chicago; IL; 60606; US Patent Application Number: 20030198645 Date filed: February 21, 2003 Abstract: A method of treating chronic hepatitis B is disclosed that comprises administering a T cell-stimulating amount of a vaccine to a patient. The vaccine comprises an immunogenic amount of chimeric, carboxy-terminal truncated hepatitis B virus nucleocapsid (core) protein (HBc) that is engineered for both enhanced stability of self-assembled particles and the substantial absence of nucleic acid binding by those particles. The chimeric protein molecule can include one or more immunogenic epitopes peptide-bonded to one or more of the N-terminus, the immunogenic loop or the Cterminus of HBc. The enhanced stability of self-assembled particles is obtained by the presence of at least one heterologous cysteine residue near one or both of the aminoterminus and carboxy-terminus of the chimer molecule. Excerpt(s): This a continuation-in-part of application Ser. No. 10/080,299, filed Feb. 21, 2002 and Ser. No. 10/082,014 filed Feb. 22, 2002, 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 a chimeric hepatitis B virus (HBV) nucleocapsid protein that is useful as the immunogen in a vaccine for treating patients with chronic hepatitis by enhancing the immune response towards the hepatitis B virus and is engineered for enhanced stability of self-assembled particles via one or both of a C-terminal and an N-terminal cysteine residue. Over 350 million people worldwide are chronically infected carriers of hepatitis B (HBV). HBV is a virus that infects the liver and causes an increased risk of chronic hepatitis, cirrhosis of the liver, and hepatocellular carcinoma (cancer of the liver). Hepatitis B is the cause of over 80 percent of hepatocellular carcinomas, and claims the lives of 1-2 million people worldwide every year, representing an important public health challenge and a growing market for new therapeutics. 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 hepatitis B virus, 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 “hepatitis B virus” (or synonyms) into the “Term 1” box. After clicking on the search button, scroll down to see the various patents which have been granted to date on hepatitis B virus. You can also use this procedure to view pending patent applications concerning hepatitis B virus. 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 6. BOOKS ON HEPATITIS B VIRUS Overview This chapter provides bibliographic book references relating to hepatitis B virus. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on hepatitis B virus 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 “hepatitis B virus” (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 hepatitis B virus: •
Living with Hepatitis B: A Survivor's Guide Source: Long Island, NY: Hatherleigh Press. 2002. 303 p. Contact: Available from Hatherleigh Press. 5-22 46th Avenue Suite 200, Long Island City, NY 11101. (800) 528-2550. E-mail:
[email protected]. Website: http://store.yahoo.com/hatherleighpress/index.html. PRICE: $15.95 plus shipping and handling. ISBN: 1578260841. Summary: Chronic hepatitis B can lead to cirrhosis (liver scarring), liver cancer, and the need for liver transplantation. This book helps readers diagnosed with hepatitis B virus (HBV) infection educate themselves about the disease and its treatment. Topics include the nature of the disease and its effects on the body, how to recognize early warning symptoms, what steps to take after learning one has been infected, the HBV vaccine (including safety and effectiveness), coping with the emotional effects of hepatitis B,
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how to avoid infecting others, how to understand blood test results, nutrition tips for a healthier liver, children with hepatitis B, treatment options, cutting medical costs, and research trends. Much of the information is presented in outline format for ease of understanding. Throughout the book are quotes from real people living with HBV infection. The book concludes with an extensive list of references and a detailed subject index. •
Diseases of the Liver and Biliary System, Eleventh Edition Source: Malden, MA: Blackwell Science, Inc. 2002. 706 p. Contact: Available from Blackwell Science, Inc. 350 Main Street, Commerce Place, Malden, MA 02148. (800) 215-1000 or (617) 388-8250. Fax (617) 388-8270. E-mail:
[email protected]. Website: www.blackwell-science.com. PRICE: $178.95. ISBN: 0632055820. Summary: Designed to serve practicing physicians, surgeons and pathologists, as well as clinical students, this textbook presents a comprehensive and up-to-date account of diseases of the liver and biliary system. The text offers 38 chapters: anatomy and function; the assessment of liver function; biopsy of the liver; the hematology of liver disease; ultrasound, computed tomography (CT scan) and magnetic resonance imaging (MRI); hepatocellular failure; hepatic encephalopathy; acute liver failure; ascites (fluid accumulation); the portal venous system and portal hypertension; the hepatic artery and hepatic vein, and the liver in circulatory failure; jaundice; cholestasis; primary biliary cirrhosis (PBC); sclerosing cholangitis; viral hepatitis, including general features, hepatitis A, hepatitis E, and other viruses; hepatitis B virus and hepatitis Delta virus; hepatitis C virus; chronic hepatitis, its general features and autoimmune chronic disease; drugs and the liver; hepatic cirrhosis (scarring); alcohol and the liver; iron overload states; Wilson's disease; nutritional and metabolic liver diseases; the liver in infancy and childhood; the liver in pregnancy; the liver is systemic disease, granulomas, and hepatic trauma; the liver in infections; nodules and benign liver lesions; malignant liver tumors; the role of interventional radiology and endoscopy in imaging of the biliary tract; cysts and congenital biliary abnormalities; gallstones and inflammatory gallbladder diseases; benign stricture of the bile ducts; diseases of the ampulla of Vater and the pancreas; tumors of the gallbladder and bile ducts; and hepatic transplantation. The text includes full-color and black-and-white illustrations and photographs. A detailed subject index concludes the volume.
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The HIV/AIDS Training Curriculum Contact: Service Employees International Union, Education and Support Fund, 1313 L St NW, Washington, DC, 20005, (202) 898-3443, http://www.seiu.org. Summary: This curriculum helps unions educate their members about HIV/AIDS in the workplace. Divided into five modules, it opens with a section that provides information on preparing and conducting the training program. Module 1 covers basic HIV and AIDS information, and takes approximately 2-2 1/2 hours. In Module 2, which is the same length, the curriculum focuses on information for workers who have potential exposure to HIV or Hepatitis B virus (HBV) on the job. Module 3 addresses the issues that may confront unions and their members in the workplace, such as discrimination, benefits, catastrophic illness policies, reasonable accommodation, and mandatory testing. Modules 4 and 5 look at specific infection-control procedures for home health care and for nursing homes.
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Occupational Exposure to Bloodborne Pathogens Source: Federal Register; Vol. 56, no. 235. Contact: US Government Printing Office, PO Box 371954, Pittsburgh, PA, 15250-7954, (202) 512-1800, http://www.access.gpo.gov. Summary: This legislation/regulation, made available as part of the Federal Register, presents and discusses a new standard from the Occuapational Safety and Health Administration for preventing and controlling occupational exposure to bloodborne pathogens, such as the Hepatitis B virus (HBV) and the Human immunodeficiency virus (HIV). The standard applies to employees who are exposed to blood or other potentially infectious materials during the performance of their duties. It covers methods of HIV transmission and the epidemiology of the disease. Methods of prevention and infection control are given. The background of this standard, a summary and explanation through the presentation of case studies, as well as the full text of the regulation are included.
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HIV Prophylaxis Following Occupational Exposure Contact: New York Department of Health, AIDS Institute, Room 359, Corning Tower, Albany, NY, 12237, (518) 486-1383. Summary: This monograph presents guidelines for post-exposure prophylaxis (PEP) treatment of healthcare workers (HCWs) who have been exposed to the human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) on the job. It includes the following chapters: (1) Rationale for PEP, (2) Risk Factors Associated with HIV Transmission, (3) Recording Information Following Occupational Exposure, (4) General Management and Considerations, (5) Implementing PEP, (6) Recommended PEP Regimens, (7) Monitoring the HCW Following Occupational Exposure, (8) PEP for the Pregnant HCW, and (9) Occupational Exposure to Hepatitis B Virus and Hepatitis C Virus. The appendices include an Informed Consent Form, information on antiretroviral drugs and post-exposure management.
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Bloodborne Pathogens and Long - Term Care Workers Contact: US Department of Labor, Occupational Safety and Health Administration, 200 Constitution Ave NW, Rm N3101, Washington, DC, 20210, (202) 219-4667. Summary: This monograph provides an overview of the Occupational Safety and Health Administration's standard concerning bloodborne pathogens. The objective is to inform long-term health care workers of the risks of occupational exposure to bloodborne pathogens and how to reduce these risks. Who is covered by this standard, what an exposure control plan must include, who has occupational exposure, and communicating hazards to employees are addressed. Also discussed are preventive measures, methods of control, and how to handle an exposure incident. It also gives information about the OSHA requirements for recordkeeping by employers. A copy of the declination statement of hepatitis B virus (HBV) vaccine is provided in the appendix.
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A Patient-Expert Walks You Through Everything You Need to Learn and Do: The First Year: Hepatitis B: An Essential Guide for the Newly Diagnosed Contact: Publishers Group West Incorporated, 1700 4th St, Berkeley, CA, 94710-1711, (510) 528-1444, http://www.pgw.com.
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Summary: This monograph provides people who have hepatitis B virus (HBV) infection with up-to-date information on HBV so that they can take an active role in their treatment. The monograph takes the reader step-by-step through everything they need to do and learn each day of their first week after a diagnosis of HBV, each subsequent week of the first month, and the following 11 months of the first year. Each day, week, or month is divided into living and learning sections. The living section focuses on the problem of living with a chronic disease, and the learning section presents facts about the topic being discussed. The monograph begins with advice on coming to terms with the diagnosis. Subsequent chapters deal with discussing one's conditon with family, friends, and coworkers; selecting a medical team; managing fatigue and stress; making modifications to one's diet and in one's physical activity level; handling sexual and social relationships; becoming an HBV activist; having, raising, or adopting childen; and coping with depression. In addition, the monograph considers issues related to work and disability, alternative therapies, addictions, and complications. Throughout the monograph, sections focus on the emotional issues surrounding HBV and offer suggestions and personal advice from others who have HBV. •
Molecular Biology and Immunology in Hepatology: Advances in the Treatment of Intractable Liver Diseases Source: St. Louis, MO: Elsevier Science. 2002. 362 p. Contact: Available from Elsevier Science. Customer Service Department, 11830 Westline Industrial Drive, St. Louis, MO 63146. (800) 545-2522. Fax (800) 535-9935. Email:
[email protected]. Website: www.elsevierhealth.com. PRICE: $145.00. ISBN: 444506535. Summary: This text book offers 25 chapters on intractable liver diseases. Based on the editor's choice of important topics in hepatology, the book ranges from clinical research to basic research, including animal models. Topics include molecular biology and immunology; mechanisms of liver injury in hepatitis B virus (HBV) infection; genetic diversity and pathophysiology of HBV; immunopathogenesis of hepatitis C; interferon therapy for hepatitis C; new therapeutic strategies for chronic hepatitis C; transgenic mouse models for viral hepatitis and the role of hepatitis viruses in the development of liver cancer; gene therapy of viral hepatitis; the reversibility of liver cirrhosis; treatment of liver cancer (hepatocellular carcinoma); gene expression profiles in liver cancer; gene therapy for liver cancer; new immunological treatments for liver cancer; assessment of the reversibility and treatments of alcoholic liver disease; molecular mechanisms of autoimmune hepatitis; roles of hepatitis C virus (HCV) in autoimmune hepatitis; molecular mechanisms of T cell responses of autoimmune hepatitis; primary biliary cirrhosis; overlap syndrome; etiology and pathophysiology of fulminant hepatic failure; cytokines and fulminant hepatic failure; treatment and prognosis of fulminant hepatic failure; living related liver transplantation; viral cirrhosis and liver cancer in relation to living donor liver transplants. Each chapter concludes with references; the text concludes with a subject index.
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Viral Hepatitis: Diagnosis, Treatment, Prevention Source: New York, NY: Marcel Dekker, Inc. 1997. 532 p. Contact: Available from Marcel Dekker, Inc. 270 Madison Avenue, New York, NY 10016. (212) 696-9000. Fax (212) 685-4540. PRICE: $175.00. ISBN: 0824794168. Summary: This text familiarizes readers with current methods of diagnosis, treatment, and prevention of human viral hepatitis. Sixteen chapters cover: methods and
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applications of molecular diagnostic testing for viral hepatitis; the hepatitis A virus; the molecular biology and immunopathology of the hepatitis B virus; the prevention and therapy of clinical disease arising from the hepatitis B virus; the hepatitis C virus; the hepatitis D virus; the epidemiology and biology of the hepatitis E virus; other hepatitis viruses including the hepatitis G virus; the role of hepatitis viruses in acute liver failure; hepatocellular carcinoma and viral hepatitis; extrahepatic manifestations of chronic viral hepatitis; the overlap of chronic viral hepatitis and autoimmune hepatitis; liver transplantation and viral hepatitis B, D, and C; viral hepatitis in marrow and stem-cell transplant patients; viral hepatitis in the immunocompromised host; and the role of iron in chronic viral hepatitis. The authors evaluate diagnostic serological techniques such as ELISAs and PCRs; highlight nonhuman primate and transgenically created animal models used in disease transmission studies, virus isolation, and serological assays and vaccine development; review the management of fulminant hepatic failure and hepatitis in the immunocompromised patient; discuss how diagnosis may be complicated by predominant extrahepatic manifestations; assess various vaccines recent licensing and future prospects; and appraise the cost effectiveness of medical treatments with antiviral agents, the role of liver transplantation, and preventive measures. Each chapter includes extensive references, and a subject index concludes the volume.
Chapters on Hepatitis B Virus In order to find chapters that specifically relate to hepatitis B virus, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and hepatitis B virus 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 “hepatitis B virus” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on hepatitis B virus: •
Hepatitis B Virus and Hepatitis Delta Virus Source: in Sherlock, S.; Dooley, J. Diseases of the Liver and Biliary System. Malden, MA: Blackwell Science, Inc. 2002. p.285-303. Contact: Available from Blackwell Science, Inc. 350 Main Street, Commerce Place, Malden, MA 02148. (800) 215-1000 or (617) 388-8250. Fax (617) 388-8270. E-mail:
[email protected]. Website: www.blackwell-science.com. PRICE: $178.95. ISBN: 0632055820. Summary: This chapter on hepatitis B virus (HBV) and hepatitis Delta virus (HDV) is from a textbook that presents a comprehensive and up-to-date account of diseases of the liver and biliary system. The chapter includes three sections: acute HBV, chronic HBV, and HDV. Specific topics include epidemiology, the clinical course and features of each disease, prevention strategies for acute HBV, clinical relapse and reactivation of the hepatitis B virus, laboratory tests to monitor chronic HBV, needle liver biopsy, course and prognosis, treatment strategies, and screening for hepatocellular carcinoma (liver cancer). Each section offers a list of references for additional reading. 20 figures. 11 tables. 103 references.
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Screening for Hepatitis B Virus Infection Source: in U.S. Preventive Services Task Force (USPSTF). Guide to Clinical Preventive Services. 2nd ed. Germantown, MD: International Medical Publishing, Inc. 1996. p. 269276. Contact: Available from International Medical Publishing, Inc. Reiter's Scientific and Professional Books, 2021 K Street, NW, Washington, DC 20006. (800) 591-2713 or (202) 223-3327. Fax (202) 296-9103. PRICE: $24.00 plus shipping and handling. ISBN: 1883205131. Also available from the U.S. Government Printing Office. Superintendent of Documents, P.O. Box 371954, Pittsburgh, PA 15250-7954. (202) 512-1800. Fax (202) 5122250. Summary: This chapter on screening for hepatitis B virus (HBV) infection is from a guide to clinical preventive services published by the U.S. Preventive Services Task Force. Screening with hepatitis B surface antigen (HBsAg) to detect active (acute or chronic) HBV infection is recommended for all pregnant women at their first prenatal visit. The test may be repeated in the third trimester in women who are initially HBsAg negative but are at increased risk of HBV infection during pregnancy. Routine screening of the general population is not recommended. Certain persons at high risk may be screened to assess eligibility for vaccination. The chapter discusses the accuracy of screening tests, the effectiveness of early detection, and the recommendations of other groups. The chapter concludes with a summary of recommended clinical interventions. 56 references. (AA-M).
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CHAPTER 7. MULTIMEDIA ON HEPATITIS B VIRUS Overview In this chapter, we show you how to keep current on multimedia sources of information on hepatitis B virus. 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 hepatitis B virus is the Combined Health Information Database. You will need to limit your search to “Videorecording” and “hepatitis B virus” 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 “hepatitis B virus” (or synonyms) into the “For these words:” box. The following is a typical result when searching for video recordings on hepatitis B virus: •
Infection Control for Hemodialysis Source: Washington DC: Health Industry Manufacturers Association. 1991. Contact: Available from Health Sciences Consortium (HSC). 201 Silver Cedar Court, Chapel Hill, NC 27514-1517. (919) 942-8731. PRICE: $276.50 for HSC members; $395 for nonmembers. Order Number: R911-VI-039. Summary: The failure of staff to follow universal infection control measures in any part of the dialysis setting can lead to a vicious cycle of blood-borne infection transmission throughout the entire unit. This program focuses on preventing the transmission of hepatitis B virus (HBV) and human immunodeficiency virus (HIV) in the dialysis setting by adhering to universal precautions. (AA).
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And The Band Played On Contact: Home Box Office, Incorporated, 1100 Ave of the Americas, New York, NY, 10036, (212) 512-1000.
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Summary: This feature film chronicles the AIDS epidemic from the first reported cases in Europe to 1993. The story is told from the perspective of Dr. Don Francis, now retired researcher from the Centers for Disease Control and Prevention (CDC) who had worked on the hepatitis B virus among gay men and the ebola virus in Africa. The film uses a combination of real and fictional characters as well as actual news footage to record the series of decisions, discoveries, controversies, and progress from 1981 on. Researchers at the CDC were faced with the dilemma of having to prove that HIV was a virus before they could establish a blood test. This required the approval and funding of a case control study and appropriate laboratory equipment and support. HIV was first known as gay cancer and then Gay Related Immune Disorder (GRID). The concurrent reports of the condition causing the deaths of 19 people in 3 years in France, an outbreak among Haitian heterosexuals in Miami, and 11 cases among newborn babies brought the disease into the forefront. The film highlights the interaction and conflict between Dr. Don Francis, researchers at the Institute Pasteur, and Dr. Robert Gallo of the National Institutes of Health. The struggle to mandate testing and screening for all blood donors is also depicted. •
Someone You Know Source: Jenkintown, PA: Hepatitis B Foundation. 1997. (videocassette). Contact: Available from Hepatitis B Foundation. 101 Greenwood Avenue, Suite 570, Jenkintown, PA 19046. (215) 884-8786. Fax (215) 887-1931. E-mail:
[email protected]. Website: http://www.hepb.org. PRICE: $6.00 for shipping. Summary: This general health education videotape program educates viewers about the hepatitis B virus (HBV) and its present status as an 'epidemic' in the U.S. The program begins with a brief overview of liver functions (energy generation, detoxification of drugs and poisons, and making blood proteins and clotting factors) and the pathology caused by HBV infections. The program stresses that there is no cure for hepatitis B, although a preventive vaccine is available. Dr. Thomas London reviews the symptoms of acute illness, including nausea, vomiting, fever, jaundice, and extreme fatigue; and explains how the virus is transmitted through blood contact (including that from sharing toothbrushes or razors), through sexual contact, and from infected mother to her child during childbirth. Other topics covered include child care issues, the use of universal precautions, classroom supplies to prevent transmission, the percentages of infected persons who go on to chronic carrier status, the role of the World Health Organization, the long term complications of carrying HBV, and the costs of health care associated with HBV. The program includes an interview with Dr. Baruch Blumberg, the scientist who won the Nobel prize for developing the HBV vaccine. Another physician interviewed, Dr. Timothy Block, emphasizes the importance of universal immunization, the problems with assuming safety if one is not a member of a supposed 'high risk' group, and the need for chronic carriers to take very good care of their health and be screened twice per year to prevent morbidity and mortality. The program features numerous interviews with patients who are chronic carriers of HBV; they focus on the psychosocial aspects, including the stigma of having the disease, the long-term effects of constant fatigue, and worries about infecting their children and loved ones. The program concludes with a brief summary of the Hepatitis B Foundation.
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Hepatitis B: A Discovery Channel Program Source: Cedar Grove, NJ: Hepatitis Foundation International. 199x. (videocassette).
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Contact: Available from Hepatitis Foundation International. 30 Sunrise Terrace, Cedar Grove, NJ 07009. (800) 891-0707 or (201) 239-1035. Fax (201) 857-5044. PRICE: Free with membership; contact directly for current price for nonmembers. Summary: This video presents a health update on hepatitis B. After an introduction that reviews the anatomy and physiology of the liver, various health care providers (including two epidemiologists from the CDC) describe how all types of hepatitis affect the liver. The program continues with a discussion of hepatitis A, B, and C, and how each is transmitted and treated. The program then focuses on hepatitis B, covering details of transmission, symptoms, risk factors and behaviors, complications of hepatitis B virus (HBV) infection, including an increased risk of liver cancer, epidemiology, fulminant hepatitis, and the progression of HBV to chronic, carrier state. Additional sections describe the use of liver transplantation for people with hepatitis B and the psychosocial impact of chronic HBV infection. The program concludes with an interview with Thelma King Thiel, the founder and CEO of the Hepatitis Foundation International, an educational and support organization. •
Respect Yourself : Protect Yourself : Teens Talk to Teens About Liver Wellness Contact: Hepatitis Foundation International, 30 Sunrise Terr, Cedar Grove, NJ, 07009, (800) 857-0707. Summary: This video, designed for adolescents, discusses the hepatitis B virus (HBV) and the hepatitis C virus (HCV) and their effects on the liver. The video explains the functions of the liver and states that the liver is a 'non-complaining' organ, meaning that most disorders that affect it are asymptomatic. The video recommends vaccination to help prevent HBV. For HBV and HCV prevention, it advises the viewers to avoid sharing any items that might contain or carry blood such as razors or injection drug needles and other paraphernalia.
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Bloodborne Pathogens 2000 Contact: Long Island Productions, 106 Capitola Dr, Durham, NC, 27713-4471, (919) 5446663, http://www.lip-online.com. Summary: This videocassette provides information about bloodborne pathogens, including the human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS), the hepatitis B virus (HBV), and the hepatitis C virus (HCV), and how they can be prevented in the workplace. Occupational exposures to bloodborne pathogens usually occur when a worker comes into direct contact with infected bodily fluids and tissues. HIV is an infection that weakens the immune system and develops into AIDS, whereas HBV and HCV infect the liver. HBV is the most common occupational hazard among health professionals and can be prevented with a vaccine. The video lists the body fluids that can carry HIV, HBV, and HCV. Universal precautions can help to protect health and safety workers from occupational exposures to bloodborne pathogens and include measures such as the use of personal protective equipment (PPE), proper hygiene, and sanitation. Instructions are provided about how to wear and remove gloves and handle sharps containers as well as other biohazard disposal/storage materials. The video discusses the occupational risks for the transmission of a bloodborne pathogen and the procedures that should be followed immediately after an accidental exposure has occurred.
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AIDS in the Operating Room: A Guide to Universal Precautions Contact: First Step Medical, Incorporated, 25601 Centennial Trail, Golden, CO, 80401, (303) 526-2263. Summary: This videorecording depicts the universal precautions necessary to prevent transmission of the Human immunodeficiency virus (HIV) and the Hepatitis B virus (HBV) in the operating room. After opening with background information on Acquired immunodeficiency syndrome (AIDS), the videorecording advises viewers to treat all human blood and body fluids as if it were infected. It then graphically demonstrates those practices that the Occupational Safety and Health Administration (OSHA) mandates for the operating room. Techniques covered include sterilization of instruments, double-bagging and disposal of infectious wastes and sharp instruments, scrubbing, donning protective clothing, passing sharp instruments, coping with an occupational exposure to blood or body fluids, and cleaning the operating room.
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AIDS and Hepatitis B: What's Your Risk? Contact: Gulf Publishing Company, PO Box 2608, Houston, TX, 77252-2608, (713) 5294301. Summary: This videorecording discusses the guidelines necessary for all categories of health care workers to minimize their risk of exposure to Acquired immunodeficiency syndrome (AIDS) and Hepatitis B. The Human immunodeficiency virus (HIV) and the Hepatitis B virus are defined, and the routes of transmission discussed. The OSHAdefined risk categories based on level of contact to blood and body fluids are explained. The universal blood and body fluids guidelines are discussed. The importance of protective clothing and proper disposal, in relation to all employees in a health care setting, is emphasized.
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Universal Precautions: AIDS and Hepatitis B Prevention for the Medical Office Contact: Medcom Incorporated, PO Box 6003, Cypress, CA, (800) 541-0253. Summary: This videorecording focuses on prevention of exposure to HIV and Hepatitis B virus (HBV). What HIV and HBV are, and how they can be transmitted in an occupational setting, are discussed. Symptoms are described. The videorecording discusses the Occupational Safety and Health (OSHA) regulations on infectious bloodborne diseases and the universal precautions that have been established for healthcare workers to prevent occupational exposure. Safe work practices are illustrated, including the use of barrier methods of protection, and needle and sharps disposal. Standard equipment care, disinfection techniques, and biohazard waste disposal are explained.
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AIDS Prevention for Nursing Professionals Contact: Guidance Associates, Box 300, Mt. Kisco, NY, 10549, (914) 666-4100. Summary: This videorecording gives nurses working with hospital patients information on the use of universal precautions to prevent Human Immunodeficiency Virus (HIV) and Hepatitis B Virus (HBV) transmission. Nurses should also avoid occupational exposure to other diseases such as chicken pox and tuberculosis. Discussions center on which body fluids are infectious and which are not, high-risk situations for occupational exposure, and appropriate measures of infection control. Guidelines for handwashing; proper needle disposal after use; and the use of sterile gloves, gowns, and masks are emphasized. Sterilization procedures for body fluid spills and used medical equipment
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are outlined, and recent advances in equipment and devices are discussed. The difference between universal precautions and body substance isolation (BSI) is explained; post-exposure prophylaxis with azidothymidine (AZT) is discussed. The videorecording examines the controversial issues surrounding mandatory testing of health-care workers for HIV infection. It includes an extensive section on Occupational Safety and Health Administration (OSHA) guidelines. This updated version contains statistical information current at time of production. •
Emergency Medical Update: Bloodborne Pathogens Contact: Lockert - Jackson and Associates, PO Box 11380, Winslow, WA, 98110-5380, (206) 842-8454. Summary: This videorecording is designed to educate and train emergency medical technicians (EMT's) about the Occupational Safety and Health Administration's (OSHA's) bloodborne pathogen standards and guidelines. Bloodborne pathogens include hepatitis B virus, hepatitis C virus, HIV, and syphilis. Every time an individual treats a patient, risks are taken. It is important to review the agency's exposure-control plan, including specific information on personal protective equipment, disposal and decontamination, hepatitis B vaccinations, and warning signs used to identify contaminated materials. A post-exposure followup is also necessary. The videorecording includes three tracks titled, On the Run; Bloodborne Pathogen Exposure, On the Run: Exposure Control - A Part of Every Call, and Take Care: Post Exposure Follow Up.
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OSHA's Bloodborne Pathogens Standard for Laboratory and Healthcare Workers Contact: SAVANT Audiovisuals, Inc., PO Box 3670, Fullerton, CA, 92634, (714) 870-7880. Summary: This videorecording looks at the risks that laboratory workers face from the Human immunodeficiency virus (HIV) and the Hepatitis B virus (HBV). It analyzes the need for improved education in the workplace and workers' rights to legal protection. Occupational Safety and Health Administration (OSHA) regulations are studied. The videorecording then looks at needed precaution, including risk of infection in the workplace, the Centers for Disease Control (CDC) and Prevention universal blood and body fluid precaution guidelines, and OSHA recommendations on gloves, face protection, gowns and other protective clothing, resuscitative devices, handwashing, and protecting wounds. The videorecording also looks at OSHA standards for housekeeping activities, sanitation, and labeling. An accompanying teaching guide includes the script and self-tests.
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Principles of Infection Control Contact: Medcom Incorporated, PO Box 6003, Cypress, CA, (800) 541-0253. Summary: This videorecording presents health care workers with an overview of principles and guidelines related to infection control in the hospital environment. Under the universal blood and body fluid precautions recommended by the Centers for Disease Control and Prevention (CDC), all patients are to be considered potentially infectious for Human immunodeficiency virus (HIV), Hepatitis B virus, and other blood-borne pathogens. Protective barriers such as gloves, gowns, masks, and eyewear are demonstrated, along with basic health and work practices that protect the employee and reduce the risk of nosocomial and other infections in the hospital. In addition to a graphic representation of the chain of infection, cleaning, disinfection, and isolation
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procedures are reviewed in detail. The videorecording notes the small occupational risk presented to health care workers by Acquired immunodeficiency syndrome (AIDS). •
Workplace Precautions Against Bloodborne Pathogens Source: Washington, DC: Applied Science Associates, Inc. 1992. Contact: Available from Health Sciences Consortium. Distribution Department, 201 Silver Cedar Court, Chapel Hill, NC 27514-1517. (919) 942-8731. PRICE: $276.50 (HSC members); $395 (nonmembers). Summary: This videotape program is intended to provide general information about the Occupational Safety and Health Administration's (OSHA) Standards on Bloodborne Pathogens (effective March 1992), and to demonstrate the importance of taking universal precautions at the workplace. The program provides an overview of how the standards apply in different occupations, including law enforcement, fire fighting, emergency medical care, hospital laboratory, housekeeping, dentistry, and medical waste disposal. Vignettes of occupational applications of universal precautions are presented. The program includes a videotape and a viewing study guide. Specific topics include bloodborne pathogens, including HIV and hepatitis B virus; common risks of exposure for health care workers; universal precautions; and OSHA guidelines. The study guide concludes with a list of topics and questions for discussion.
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Dental Protective Measures Source: Evanston, IL: Altschul Group Corporation. 1996. (videocassette). Contact: Available from Altschul Group Corporation. 1560 Sherman Avenue, Suite 100, Evanston, IL 60201-9971. (800) 323-9084 or (828) 328-6700; Fax (847) 328-6706; E-mail:
[email protected]; http://www.agcmedia.com. PRICE: $179.00 plus shipping and handling. Order Number 8061. Summary: This videotape program presents an overview of dental protective measures. With the increased awareness of hepatitis B virus and HIV, the dental profession has adopted strict preventive measures including disinfection and sterilization techniques. The program demonstrates how protective clothing, masks, and gloves are also used to protect both patient and dental health professionals. The program is one in a series of self-health videos in which, by emphasizing lifestyle and environmental factors which increase the risk of illness, the prevention of disease is motivated. The programs also illustrate the impact of health problems on individuals and society. Each program in the series provides viewers with a better understanding of bodily functions and helps them to detect signs or symptoms of illness. This videotape is available in English or Spanish. (AA-M).
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CHAPTER 8. PERIODICALS AND NEWS ON HEPATITIS B VIRUS Overview In this chapter, we suggest a number of news sources and present various periodicals that cover hepatitis B virus.
News Services and Press Releases One of the simplest ways of tracking press releases on hepatitis B virus 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 “hepatitis B virus” (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 hepatitis B virus. 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 “hepatitis B virus” (or synonyms). The following was recently listed in this archive for hepatitis B virus: •
Occult hepatitis B virus infection still oncologic Source: Reuters Medical News Date: January 22, 2004
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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 “hepatitis B virus” (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 “hepatitis B virus” (or synonyms). If you know the name of a company that is relevant to hepatitis B virus, 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 “hepatitis B virus” (or synonyms).
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
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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 “hepatitis B virus” (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 hepatitis B virus: •
Labor and Delivery and Nursery Unit Guidelines to Prevent Hepatitis B Virus Transmission Source: Needle Tips and the Hepatitis B Coalition News. 12(1): 17. Summer 2002. Contact: Available from Hepatitis B Coalition. Immunization Action Coalition, 1573 Selby Avenue, Suite 229, St. Paul, MN 55104. (612) 647-9009. Fax (612) 647-9131. E-mail:
[email protected]. Website: www.winternet.com. Summary: These guidelines can be used to help a hospital establish standing orders for preventing perinatal hepatitis B virus (HBV) transmission in the labor and delivery and nursery units. The guidelines stress that procedures must already be in place to review the hepatitis B surface antigen (HBsAg) test results of all pregnant women at the time of hospital admission and to give immunoprophylaxis within 12 hours after birth to infants of HBsAg-positive mothers and infants of mothers who do not have documentation of HBsAg test results in their charts. Administration of hepatitis B (HepB) vaccine at birth to all infants is recommended by CDC's Advisory Committee on Immunization Practices, the American Academy of Pediatrics, the American Academy of Family Physicians, and the American College of Obstetricians and Gynecologists.
Academic Periodicals covering Hepatitis B Virus Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to hepatitis B virus. In addition to these sources, you can search for articles covering hepatitis B virus 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 9. 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 hepatitis B virus. 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 non-profit 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 hepatitis B virus. 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.).
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The following drugs have been mentioned in the Pharmacopeia and other sources as being potentially applicable to hepatitis B virus: Adefovir •
Systemic - U.S. Brands: Hepsera http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/500427.html
Antihemophilic Factor •
Systemic - U.S. Brands: Alphanate; Bioclate; Helixate; Helixate FS; Hemofil M; Humate-P; Hyate:C; Koate-HP; Kogenate; Kogenate FS; Monarc-M; Monoclate-P; Recombinate http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202671.html
Factor IX •
Systemic - U.S. Brands: AlphaNine SD; Bebulin VH; BeneFix; Konyne 80; Mononine; Profilnine SD; Proplex T http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202674.html
Hepatitis A Virus Vaccine Inactivated and Hepatitis B Virus Vaccine Recombinant •
Systemic - U.S. Brands: Twinrix http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/500307.html
Hepatitis B Immune Globulin (Human) •
Human - U.S. Brands: Nabi-HB http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/500325.html
Hepatitis B Vaccine Recombinant •
Systemic - U.S. Brands: Engerix-B; Recombivax HB; Recombivax HB Dialysis Formulation http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202281.html
Lamivudine •
Systemic - U.S. Brands: Epivir; Epivir-HBV http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202791.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.
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/.
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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.
Researching Orphan Drugs Although the list of orphan drugs is revised on a daily basis, you can quickly research orphan drugs that might be applicable to hepatitis B virus by using the database managed by the National Organization for Rare Disorders, Inc. (NORD), at http://www.rarediseases.org/. Scroll down the page, and on the left toolbar, click on “Orphan Drug Designation Database.” On this page (http://www.rarediseases.org/search/noddsearch.html), type “hepatitis B virus” (or synonyms) into the search box, and click “Submit Query.” When you receive your results, note that not all of the drugs may be relevant, as some may have been withdrawn from orphan status. Write down or print out the name of each drug and the relevant contact information. From there, visit the Pharmacopeia Web site and type the name of each orphan drug into the search box at http://www.nlm.nih.gov/medlineplus/druginformation.html. You may need to contact the sponsor or NORD for further information. NORD conducts “early access programs for investigational new drugs (IND) under the Food and Drug Administration’s (FDA’s) approval ‘Treatment INDs’ programs which allow for a limited number of individuals to receive investigational drugs before FDA marketing approval.” If the orphan product about which you are seeking information is approved for marketing, information on side effects can be found on the product’s label. If the product is not approved, you may need to contact the sponsor. The following is a list of orphan drugs currently listed in the NORD Orphan Drug Designation Database for hepatitis B virus: •
Hepatitis B immune globulin, intravenous (trade name: H-BIGIV) http://www.rarediseases.org/nord/search/nodd_full?code=735
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 Institute10: •
Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm
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National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/news/facts/
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National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html
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National Cancer Institute (NCI); guidelines available at http://www.cancer.gov/cancerinfo/list.aspx?viewid=5f35036e-5497-4d86-8c2c714a9f7c8d25
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National Eye Institute (NEI); guidelines available at http://www.nei.nih.gov/order/index.htm
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National Heart, Lung, and Blood Institute (NHLBI); guidelines available at http://www.nhlbi.nih.gov/guidelines/index.htm
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National Human Genome Research Institute (NHGRI); research available at http://www.genome.gov/page.cfm?pageID=10000375
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National Institute on Aging (NIA); guidelines available at http://www.nia.nih.gov/health/
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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
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National Institute of Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/
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National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm
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National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm
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National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/
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National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/
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National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm
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National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html
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National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm
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National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/practitioners/index.cfm
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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
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National Institute of Nursing Research (NINR); publications on selected illnesses at http://www.nih.gov/ninr/news-info/publications.html
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National Institute of Biomedical Imaging and Bioengineering; general information at http://grants.nih.gov/grants/becon/becon_info.htm
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Center for Information Technology (CIT); referrals to other agencies based on keyword searches available at http://kb.nih.gov/www_query_main.asp
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National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/
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National Center for Research Resources (NCRR); various information directories available at http://www.ncrr.nih.gov/publications.asp
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Office of Rare Diseases; various fact sheets available at http://rarediseases.info.nih.gov/html/resources/rep_pubs.html
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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.11 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:12 •
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
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HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html
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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
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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/
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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
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Cancer Information: Access to cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html
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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/
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Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html
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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
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Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html
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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
11
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). 12 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 NLM Gateway13 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.14 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “hepatitis B virus” (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 21651 115 607 484 67 22924
HSTAT15 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.16 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.17 Simply search by “hepatitis B virus” (or synonyms) at the following Web site: http://text.nlm.nih.gov.
13
Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.
14
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). 15 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 16 17
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.
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Coffee Break: Tutorials for Biologists18 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 staff.19 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.20 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/.
•
Medical World Search: Searches full text from thousands of selected medical sites on the Internet; see http://www.mwsearch.com/.
18 Adapted 19
from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html.
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. 20 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 hepatitis B virus 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 hepatitis B virus. 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 hepatitis B virus. 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 “hepatitis B virus”:
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Hepatitis http://www.nlm.nih.gov/medlineplus/hepatitis.html Hepatitis A http://www.nlm.nih.gov/medlineplus/hepatitisa.html Hepatitis B http://www.nlm.nih.gov/medlineplus/hepatitisb.html Hepatitis C http://www.nlm.nih.gov/medlineplus/hepatitisc.html Liver Diseases http://www.nlm.nih.gov/medlineplus/liverdiseases.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. 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 hepatitis B virus. 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: •
Genetic Diversity and Pathophysiology of Hepatitis B Virus Source: in Tsuji, T., et al, eds. Molecular Biology and Immunology in Hepatology. St. Louis, MO: Elsevier Science. 2002. p. 33-40. Contact: Available from Elsevier Science. Customer Service Department, 11830 Westline Industrial Drive, St. Louis, MO 63146. (800) 545-2522. Fax (800) 535-9935. Email:
[email protected]. Website: www.elsevierhealth.com. PRICE: $145.00. ISBN: 444506535. Summary: Hepatitis B virus (HBV) is a leading cause of chronic hepatitis, cirrhosis (liver scarring), and hepatocellular carcinoma (liver cancer). Viral and host factors, such as age, immunosuppression, and gender, contribute to the patient outcome. This chapter on the genetic diversity and pathophysiology of HBV is from a text book on the pathogenesis and treatment of intractable liver diseases. Topics include HBV DNA, mutations in the precore and core regions, and mutations in patients with HBV related fulminant hepatitis. The authors conclude that there is still a lack of reliable clinical markers that predict the outcome of acute hepatitis. The most important clinical findings of the data presented in this chapter is that clinicians may be able to predict the outcome of liver disease in patients with acute HBV infection by using PMA for HBV precore and core promoter analysis in patients without HBV genotype A. 2 figures. 28 references.
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Mechanisms of Liver Injury in Hepatitis B Virus Infection Source: in Tsuji, T., et al, eds. Molecular Biology and Immunology in Hepatology. St. Louis, MO: Elsevier Science. 2002. p. 25-32. Contact: Available from Elsevier Science. Customer Service Department, 11830 Westline Industrial Drive, St. Louis, MO 63146. (800) 545-2522. Fax (800) 535-9935. Email:
[email protected]. Website: www.elsevierhealth.com. PRICE: $145.00. ISBN: 444506535. Summary: Hepatitis B virus (HBV) is a noncytopathic virus with a circular double stranded DNA genome that causes acute and chronic necroinflammatory liver disease and hepatocellular carcinoma (liver cancer). Since the disease spectrum associated with HBV is extraordinarily variable, it is believed that the host immune response plays a critical role in the pathogenesis of the associated liver disease. This chapter on the mechanisms of liver injury in HBV infection is from a text book on the pathogenesis and treatment of intractable liver diseases. Topics include HBV immunopathogenesis and fulminant hepatitis in humans; CTL-mediated immunopathogenesis; pathogenetic potential of the CTL response to HBV (in mice); noncytopathic antiviral potential of the immune response to HBV; TH1-mediated immunopathogenesis; and factors responsible for disease exacerbation. 3 figures. 2 tables. 12 references.
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Universal Precautions for the Prevention of Human Immunodeficiency Virus, Hepatitis B Virus and Other Blood - Borne Diseases in the Medical Center Contact: US Department of Veterans Affairs, Central Texas Veterans Health Care System, Thomas T Connally Integrated Clinical Facility, 1016 Ward St, Marlin, TX, 76661, (254) 883-3511, http://www.va.gov/facilities. Summary: This fact sheet details the Veterans Administration Medical Center in Marlin, TX, policy on implementing universal precautions to prevent the transmission of the Human immunodeficiency virus (HIV), the Hepatitis B virus (HBV), and other bloodborne illnesses. The fact sheet outlines the policy of the center, and the responsibilities of the medical center director and medical center employees.
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STD Facts: Hepatitis: Type B (Caused by the Hepatitis B Virus) Contact: Minnesota Department of Health, Infectious Disease Epidemiology Prevention and Control Division, PO Box 9441, Minneapolis, MN, 55440-9441, (612) 676-5414, http://www.health.state.mn.us/divs/dpc/idepc.html. Summary: This information sheet presents an overview of hepatitis B, including information on signs and symptoms, routes of transmission, complications and consequences such as chronic liver disease and cirrhosis, and recommendations for prevention. It explains that hepatitis B immune globulin injection is the recommended treatment strategy following exposure. Sources for additional information are provided. 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:
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Hepatitis B Immunization Coverage Among Vietnamese-American Children 3 to 18 Years Old Summary: Persons with chronic hepatitis B virus (HBV) infection are at increased risk of chronic hepatitis, cirrhosis, and liver cancer. Source: American Academy of Pediatrics http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=7366
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Hepatitis B Virus (HBV) Summary: Written for clinicians, this hepatitis B virus (HBV) fact sheet presents basic information about the disorder that includes diagnosis, epidemiology, disease management guidelines, data on risk groups, Source: Educational Institution--Follow the Resource URL for More Information http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=5319
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If You Have Chronic Hepatitis B Virus (HBV) Infection. Source: Immunization Action Coalition http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=3382 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 hepatitis B virus. 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
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Family Village: http://www.familyvillage.wisc.edu/specific.htm
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Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/
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Med Help International: http://www.medhelp.org/HealthTopics/A.html
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Open Directory Project: http://dmoz.org/Health/Conditions_and_Diseases/
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Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/
Patient Resources
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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 hepatitis B virus. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with hepatitis B virus. 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 hepatitis B virus. 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 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 “hepatitis B virus” (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 “hepatitis B virus”. 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 “hepatitis B virus” (or synonyms) into the “For these words:” box. You should check back periodically with this database since it is updated every three months.
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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 “hepatitis B virus” (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.21
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
21
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)22: •
Alabama: Health InfoNet of Jefferson County (Jefferson County Library Cooperative, Lister Hill Library of the Health Sciences), http://www.uab.edu/infonet/
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Alabama: Richard M. Scrushy Library (American Sports Medicine Institute)
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Arizona: Samaritan Regional Medical Center: The Learning Center (Samaritan Health System, Phoenix, Arizona), http://www.samaritan.edu/library/bannerlibs.htm
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California: Kris Kelly Health Information Center (St. Joseph Health System, Humboldt), http://www.humboldt1.com/~kkhic/index.html
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California: Community Health Library of Los Gatos, http://www.healthlib.org/orgresources.html
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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
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California: Gateway Health Library (Sutter Gould Medical Foundation)
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California: Health Library (Stanford University Medical Center), http://wwwmed.stanford.edu/healthlibrary/
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California: Patient Education Resource Center - Health Information and Resources (University of California, San Francisco), http://sfghdean.ucsf.edu/barnett/PERC/default.asp
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California: Redwood Health Library (Petaluma Health Care District), http://www.phcd.org/rdwdlib.html
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California: Los Gatos PlaneTree Health Library, http://planetreesanjose.org/
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California: Sutter Resource Library (Sutter Hospitals Foundation, Sacramento), http://suttermedicalcenter.org/library/
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California: Health Sciences Libraries (University of California, Davis), http://www.lib.ucdavis.edu/healthsci/
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California: ValleyCare Health Library & Ryan Comer Cancer Resource Center (ValleyCare Health System, Pleasanton), http://gaelnet.stmarysca.edu/other.libs/gbal/east/vchl.html
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California: Washington Community Health Resource Library (Fremont), http://www.healthlibrary.org/
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Colorado: William V. Gervasini Memorial Library (Exempla Healthcare), http://www.saintjosephdenver.org/yourhealth/libraries/
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Connecticut: Hartford Hospital Health Science Libraries (Hartford Hospital), http://www.harthosp.org/library/
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Connecticut: Healthnet: Connecticut Consumer Health Information Center (University of Connecticut Health Center, Lyman Maynard Stowe Library), http://library.uchc.edu/departm/hnet/
22
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
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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
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Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine, Wilmington), http://www.delamed.org/chls.html
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Georgia: Family Resource Library (Medical College of Georgia, Augusta), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm
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Georgia: Health Resource Center (Medical Center of Central Georgia, Macon), http://www.mccg.org/hrc/hrchome.asp
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Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library, Honolulu), http://hml.org/CHIS/
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Idaho: DeArmond Consumer Health Library (Kootenai Medical Center, Coeur d’Alene), http://www.nicon.org/DeArmond/index.htm
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Illinois: Health Learning Center of Northwestern Memorial Hospital (Chicago), http://www.nmh.org/health_info/hlc.html
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Illinois: Medical Library (OSF Saint Francis Medical Center, Peoria), http://www.osfsaintfrancis.org/general/library/
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Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital, Lexington), http://www.centralbap.com/education/community/library.cfm
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Kentucky: University of Kentucky - Health Information Library (Chandler Medical Center, Lexington), http://www.mc.uky.edu/PatientEd/
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Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation, New Orleans), http://www.ochsner.org/library/
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Louisiana: Louisiana State University Health Sciences Center Medical LibraryShreveport, http://lib-sh.lsuhsc.edu/
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Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital, Farmington), http://www.fchn.org/fmh/lib.htm
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Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center, Lewiston), http://www.cmmc.org/library/library.html
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Maine: Hadley Parrot Health Science Library (Eastern Maine Healthcare, Bangor), http://www.emh.org/hll/hpl/guide.htm
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Maine: Maine Medical Center Library (Maine Medical Center, Portland), http://www.mmc.org/library/
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Maine: Parkview Hospital (Brunswick), http://www.parkviewhospital.org/
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Maine: Southern Maine Medical Center Health Sciences Library (Southern Maine Medical Center, Biddeford), http://www.smmc.org/services/service.php3?choice=10
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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
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Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre, Winnipeg), http://www.deerlodge.mb.ca/crane_library/about.asp
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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
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Massachusetts: Baystate Medical Center Library (Baystate Health System), http://www.baystatehealth.com/1024/
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Massachusetts: Boston University Medical Center Alumni Medical Library (Boston University Medical Center), http://med-libwww.bu.edu/library/lib.html
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Massachusetts: Lowell General Hospital Health Sciences Library (Lowell General Hospital, Lowell), http://www.lowellgeneral.org/library/HomePageLinks/WWW.htm
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Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital, Boston), http://www.nebh.org/health_lib.asp
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Massachusetts: St. Luke’s Hospital Health Sciences Library (St. Luke’s Hospital, Southcoast Health System, New Bedford), http://www.southcoast.org/library/
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Massachusetts: Treadwell Library Consumer Health Reference Center (Massachusetts General Hospital), http://www.mgh.harvard.edu/library/chrcindex.html
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Massachusetts: UMass HealthNet (University of Massachusetts Medical School, Worchester), http://healthnet.umassmed.edu/
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Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm
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Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/
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Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html
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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
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Michigan: Sladen Library & Center for Health Information Resources - Consumer Health Information (Detroit), http://www.henryford.com/body.cfm?id=39330
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Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center, Missoula)
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National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html
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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/
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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
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New Hampshire: Dartmouth Biomedical Libraries (Dartmouth College Library, Hanover), http://www.dartmouth.edu/~biomed/resources.htmld/conshealth.htmld/
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New Jersey: Consumer Health Library (Rahway Hospital, Rahway), http://www.rahwayhospital.com/library.htm
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New Jersey: Dr. Walter Phillips Health Sciences Library (Englewood Hospital and Medical Center, Englewood), http://www.englewoodhospital.com/links/index.htm
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New Jersey: Meland Foundation (Englewood Hospital and Medical Center, Englewood), http://www.geocities.com/ResearchTriangle/9360/
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New York: Choices in Health Information (New York Public Library) - NLM Consumer Pilot Project participant, http://www.nypl.org/branch/health/links.html
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New York: Health Information Center (Upstate Medical University, State University of New York, Syracuse), http://www.upstate.edu/library/hic/
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New York: Health Sciences Library (Long Island Jewish Medical Center, New Hyde Park), http://www.lij.edu/library/library.html
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New York: ViaHealth Medical Library (Rochester General Hospital), http://www.nyam.org/library/
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Ohio: Consumer Health Library (Akron General Medical Center, Medical & Consumer Health Library), http://www.akrongeneral.org/hwlibrary.htm
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Oklahoma: The Health Information Center at Saint Francis Hospital (Saint Francis Health System, Tulsa), http://www.sfh-tulsa.com/services/healthinfo.asp
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Oregon: Planetree Health Resource Center (Mid-Columbia Medical Center, The Dalles), http://www.mcmc.net/phrc/
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Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center, Hershey), http://www.hmc.psu.edu/commhealth/
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Pennsylvania: Community Health Resource Library (Geisinger Medical Center, Danville), http://www.geisinger.edu/education/commlib.shtml
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Pennsylvania: HealthInfo Library (Moses Taylor Hospital, Scranton), http://www.mth.org/healthwellness.html
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Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System, Pittsburgh), http://www.hsls.pitt.edu/guides/chi/hopwood/index_html
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Pennsylvania: Koop Community Health Information Center (College of Physicians of Philadelphia), http://www.collphyphil.org/kooppg1.shtml
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Pennsylvania: Learning Resources Center - Medical Library (Susquehanna Health System, Williamsport), http://www.shscares.org/services/lrc/index.asp
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Pennsylvania: Medical Library (UPMC Health System, Pittsburgh), http://www.upmc.edu/passavant/library.htm
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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
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Texas: Houston HealthWays (Houston Academy of Medicine-Texas Medical Center Library), http://hhw.library.tmc.edu/
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Washington: Community Health Library (Kittitas Valley Community Hospital), http://www.kvch.com/
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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
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Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/
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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
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On-line Medical Dictionary (CancerWEB): http://cancerweb.ncl.ac.uk/omd/
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Rare Diseases Terms (Office of Rare Diseases): http://ord.aspensys.com/asp/diseases/diseases.asp
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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).
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
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MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html
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Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/
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Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine
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HEPATITIS B VIRUS DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. 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] Aberrant: Wandering or deviating from the usual or normal course. [EU] Academic Medical Centers: Medical complexes consisting of medical school, hospitals, clinics, libraries, administrative facilities, etc. [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] Accommodation: Adjustment, especially that of the eye for various distances. [EU] Acetaminophen: Analgesic antipyretic derivative of acetanilide. It has weak antiinflammatory properties and is used as a common analgesic, but may cause liver, blood cell, and kidney damage. [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] 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 myelogenous leukemia: AML. A quickly progressing disease in which too many immature blood-forming cells are found in the blood and bone marrow. Also called acute myeloid leukemia or acute nonlymphocytic leukemia. [NIH] Acute myeloid leukemia: AML. A quickly progressing disease in which too many immature blood-forming cells are found in the blood and bone marrow. Also called acute myelogenous leukemia or acute nonlymphocytic leukemia. [NIH] Acute nonlymphocytic leukemia: A quickly progressing disease in which too many immature blood-forming cells are found in the blood and bone marrow. Also called acute myeloid leukemia or acute myelogenous leukemia. [NIH] Acute renal: A condition in which the kidneys suddenly stop working. In most cases, kidneys can recover from almost complete loss of function. [NIH] Acyclovir: Functional analog of the nucleoside guanosine. It acts as an antimetabolite, especially in viruses. It is used as an antiviral agent, especially in herpes infections. [NIH] Adaptability: Ability to develop some form of tolerance to conditions extremely different
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from those under which a living organism evolved. [NIH] Adduct: Complex formed when a carcinogen combines with DNA or a protein. [NIH] Adenine: A purine base and a fundamental unit of adenine nucleotides. [NIH] Adenocarcinoma: A malignant epithelial tumor with a glandular organization. [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] 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] 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] 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] Aflatoxin B1: A potent hepatotoxic and hepatocarcinogenic mycotoxin produced by the Aspergillus flavus group of fungi. It is also mutagenic, teratogenic, and causes immunosuppression in animals. It is found as a contaminant in peanuts, cottonseed meal, corn, and other grains. The mycotoxin requires epoxidation to aflatoxin B1 2,3-oxide for activation. Microsomal monooxygenases biotransform the toxin to the less toxic metabolites aflatoxin M1 and Q1. [NIH] Aflatoxins: A group of closely related toxic metabolites that are designated mycotoxins. They are produced by Aspergillus flavus and A. parasiticus. Members of the group include aflatoxin B1, aflatoxin B2, aflatoxin G1, aflatoxin G2, aflatoxin M1, and aflatoxin M2. [NIH] Agar: A complex sulfated polymer of galactose units, extracted from Gelidium cartilagineum, Gracilaria confervoides, and related red algae. It is used as a gel in the preparation of solid culture media for microorganisms, as a bulk laxative, in making emulsions, and as a supporting medium for immunodiffusion and immunoelectrophoresis. [NIH]
Age-Adjusted: Summary measures of rates of morbidity or mortality in a population using statistical procedures to remove the effect of age differences in populations that are being compared. Age is probably the most important and the most common variable in determining the risk of morbidity and mortality. [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,
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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] 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] Alleles: Mutually exclusive forms of the same gene, occupying the same locus on homologous chromosomes, and governing the same biochemical and developmental process. [NIH] Allogeneic: Taken from different individuals of the same species. [NIH] Allograft: An organ or tissue transplant between two humans. [NIH] Alpha-fetoprotein: AFP. A protein normally produced by a developing fetus. AFP levels are usually undetectable in the blood of healthy nonpregnant adults. An elevated level of AFP suggests the presence of either a primary liver cancer or germ cell tumor. [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] Ameliorating: A changeable condition which prevents the consequence of a failure or accident from becoming as bad as it otherwise would. [NIH] Amino acid: Any organic compound containing an amino (-NH2 and a carboxyl (- COOH) group. The 20 a-amino acids listed in the accompanying table are the amino acids from which proteins are synthesized by formation of peptide bonds during ribosomal translation of messenger RNA; all except glycine, which is not optically active, have the L configuration. Other amino acids occurring in proteins, such as hydroxyproline in collagen, are formed by posttranslational enzymatic modification of amino acids residues in polypeptide chains. There are also several important amino acids, such as the neurotransmitter y-aminobutyric acid, that have no relation to proteins. Abbreviated AA. [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-terminal: The end of a protein or polypeptide chain that contains a free amino group (-NH2). [NIH] Amplification: The production of additional copies of a chromosomal DNA sequence, found as either intrachromosomal or extrachromosomal DNA. [NIH] Ampulla: A sac-like enlargement of a canal or duct. [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] 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] 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] 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] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Angiogenesis: Blood vessel formation. Tumor angiogenesis is the growth of blood vessels from surrounding tissue to a solid tumor. This is caused by the release of chemicals by the tumor. [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] Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis. [NIH] Annealing: The spontaneous alignment of two single DNA strands to form a double helix. [NIH]
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 substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this
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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] Anticarcinogenic: Pertaining to something that prevents or delays the development of cancer. [NIH] 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] Anti-inflammatory: Having to do with reducing 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] 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] Antiproliferative: Counteracting a process of proliferation. [EU] Antiviral: Destroying viruses or suppressing their replication. [EU] 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] Anus: The opening of the rectum to the outside of the body. [NIH] Aphidicolin: An antiviral antibiotic produced by Cephalosporium aphidicola and other fungi. It inhibits the growth of eukaryotic cells and certain animal viruses by selectively inhibiting the cellular replication of DNA polymerase II or the viral-induced DNA polymerases. The drug may be useful for controlling excessive cell proliferation in patients with cancer, psoriasis or other dermatitis with little or no adverse effect upon nonmultiplying cells. [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
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which the proteins are bound have been removed. They play an important role in lipid transport and metabolism. [NIH] Apoptosis: One of the two mechanisms by which cell death occurs (the other being the pathological process of necrosis). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA (DNA fragmentation) at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. [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] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Artery: Vessel-carrying blood from the heart to various parts of the body. [NIH] Ascites: Accumulation or retention of free fluid within the peritoneal cavity. [NIH] Aseptic: Free from infection or septic material; sterile. [EU] Aspartic: The naturally occurring substance is L-aspartic acid. One of the acidic-amino-acids is obtained by the hydrolysis of proteins. [NIH] Aspartic Acid: One of the non-essential amino acids commonly occurring in the L-form. It is found in animals and plants, especially in sugar cane and sugar beets. It may be a neurotransmitter. [NIH] Aspiration: The act of inhaling. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Asymptomatic: Having no signs or symptoms of disease. [NIH] Atrophy: Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. [NIH] Attenuated: Strain with weakened or reduced virulence. [NIH] Autoimmune Hepatitis: A liver disease caused when the body's immune system destroys liver cells for no known reason. [NIH] Autolysis: The spontaneous disintegration of tissues or cells by the action of their own autogenous enzymes. [NIH] Autopsy: Postmortem examination of the body. [NIH] Avian: A plasmodial infection in birds. [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
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bacillary, and spiral or spirochetal. [NIH] Bactericidal: Substance lethal to bacteria; substance capable of killing bacteria. [NIH] Bacteriophage: A virus whose host is a bacterial cell; A virus that exclusively infects 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] Bacterium: Microscopic organism which may have a spherical, rod-like, or spiral unicellular or non-cellular body. Bacteria usually reproduce through asexual processes. [NIH] Base Sequence: The sequence of purines and pyrimidines in nucleic acids and polynucleotides. It is also called nucleotide or nucleoside sequence. [NIH] Basophils: Granular leukocytes characterized by a relatively pale-staining, lobate nucleus and cytoplasm containing coarse dark-staining granules of variable size and stainable by basic dyes. [NIH] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]
Beta-glucans: Polysaccharides made by several types of mushrooms. Beta-glucans have been used to treat patients with gastric cancer and colorectal cancer. They may be able to stimulate the immune system. [NIH] Bilateral: Affecting both the right and left side of body. [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 the treatment of gallstones. [NIH] Bile duct: A tube through which bile passes in and out of the liver. [NIH] Bile Pigments: Pigments that give a characteristic color to bile including: bilirubin, biliverdine, and bilicyanin. [NIH] Biliary: Having to do with the liver, bile ducts, and/or gallbladder. [NIH] Biliary Tract: The gallbladder and its ducts. [NIH] Bilirubin: A bile pigment that is a degradation product of heme. [NIH] Binding Sites: The reactive parts of a macromolecule that directly participate in its specific combination with another molecule. [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 therapy: Treatment to stimulate or restore the ability of the immune system to fight infection and disease. Also used to lessen side effects that may be caused by some cancer treatments. Also known as immunotherapy, biotherapy, or biological response modifier (BRM) therapy. [NIH] Bioluminescence: The emission of light by living organisms such as the firefly, certain
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mollusks, beetles, fish, bacteria, fungi and protozoa. [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] Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body. [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] Biotransformation: The chemical alteration of an exogenous substance by or in a biological system. The alteration may inactivate the compound or it may result in the production of an active metabolite of an inactive parent compound. The alteration may be either nonsynthetic (oxidation-reduction, hydrolysis) or synthetic (glucuronide formation, sulfate conjugation, acetylation, methylation). This also includes metabolic detoxication and clearance. [NIH] Bladder: The organ that stores urine. [NIH] Blast phase: The phase of chronic myelogenous leukemia in which the number of immature, abnormal white blood cells in the bone marrow and blood is extremely high. Also called blast crisis. [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 transfusion: The administration of blood or blood products into a blood vessel. [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-Borne Pathogens: Infectious organisms in the blood, of which the predominant medical interest is their contamination of blood-soiled linens, towels, gowns, bandages, other items from individuals in risk categories, needles and other sharp objects, and medical and dental waste, all of which health workers are exposed to. This concept is differentiated from the clinical conditions of bacteremia, viremia, and fungemia where the organism is present in the blood of a patient as the result of a natural infectious process. [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 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
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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] Bone Marrow Transplantation: The transference of bone marrow from one human or animal to another. [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] Broad-spectrum: Effective against a wide range of microorganisms; said of an antibiotic. [EU] Buccal: Pertaining to or directed toward the cheek. In dental anatomy, used to refer to the buccal surface of a tooth. [EU] Buffers: A chemical system that functions to control the levels of specific ions in solution. When the level of hydrogen ion in solution is controlled the system is called a pH buffer. [NIH]
Calcium: A basic element found in nearly all organized tissues. It is a member of the 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] Capsid: The outer protein protective shell of a virus, which protects the viral nucleic acid. [NIH]
Capsular: Cataract which is initiated by an opacification at the surface of the lens. [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] Carboxy: Cannabinoid. [NIH] Carboxy-terminal: The end of any polypeptide or protein that bears a free carboxyl group. [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] Carcinogenicity: The ability to cause cancer. [NIH] 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] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Carotene: The general name for a group of pigments found in green, yellow, and leafy vegetables, and yellow fruits. The pigments are fat-soluble, unsaturated aliphatic hydrocarbons functioning as provitamins and are converted to vitamin A through enzymatic processes in the intestinal wall. [NIH] Carotenoids: Substance found in yellow and orange fruits and vegetables and in dark green, leafy vegetables. May reduce the risk of developing cancer. [NIH]
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Carrier State: The condition of harboring an infective organism without manifesting symptoms of infection. The organism must be readily transmissable to another susceptible host. [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] Catastrophic Illness: An acute or prolonged illness usually considered to be life-threatening or with the threat of serious residual disability. Treatment may be radical and is frequently costly. [NIH] Cations: Postively charged atoms, radicals or groups of atoms which travel to the cathode or negative pole during electrolysis. [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 Artery: The arterial trunk that arises from the abdominal aorta and after a short course divides into the left gastric, common hepatic and splenic arteries. [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 Cycle: The complex series of phenomena, occurring between the end of one cell division and the end of the next, by which cellular material is divided between daughter cells. [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 Division: The fission of a cell. [NIH] Cell proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH] Cell Respiration: The metabolic process of all living cells (animal and plant) in which oxygen is used to provide a source of energy for the cell. [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] Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. [NIH] Cell Transplantation: Transference of cells within an individual, between individuals of the same species, or between individuals of different species. [NIH] Cellulase: An enzyme isolated from fungi and bacteria. It catalyzes the endohydrolysis of 1,4-beta-glucosidic linkages in cellulose, lichenin, and cereal beta-glucans. EC 3.2.1.4. [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] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Centrifugation: A method of separating organelles or large molecules that relies upon
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differential sedimentation through a preformed density gradient under the influence of a gravitational field generated in a centrifuge. [NIH] Cerebrospinal: Pertaining to the brain and spinal cord. [EU] Cerebrospinal fluid: CSF. The fluid flowing around the brain and spinal cord. Cerebrospinal fluid is produced in the ventricles in the brain. [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] Chemical Warfare: Tactical warfare using incendiary mixtures, smokes, or irritant, burning, or asphyxiating gases. [NIH] Chemical Warfare Agents: Chemicals that are used to cause the disturbance, disease, or death of humans during war. [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] Chemoprevention: The use of drugs, vitamins, or other agents to try to reduce the risk of, or delay the development or recurrence of, cancer. [NIH] Chemopreventive: Natural or synthetic compound used to intervene in the early precancerous stages of carcinogenesis. [NIH] Chemoprotective: A quality of some drugs used in cancer treatment. Chemoprotective agents protect healthy tissue from the toxic effects of anticancer drugs. [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] Child Care: Care of children in the home or institution. [NIH] Chimeras: Organism that contains a mixture of genetically different cells. [NIH] Chin: The anatomical frontal portion of the mandible, also known as the mentum, that contains the line of fusion of the two separate halves of the mandible (symphysis menti). This line of fusion divides inferiorly to enclose a triangular area called the mental protuberance. On each side, inferior to the second premolar tooth, is the mental foramen for the passage of blood vessels and a nerve. [NIH] Chloroform: A commonly used laboratory solvent. It was previously used as an anesthetic, but was banned from use in the U.S. due to its suspected carcinogenecity. [NIH] Chlorophyll: Porphyrin derivatives containing magnesium that act to convert light energy in photosynthetic organisms. [NIH] Cholangitis: Inflammation of a bile duct. [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] Cholestasis: Impairment of biliary flow at any level from the hepatocyte to Vater's ampulla. [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]
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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] Chorioretinitis: Inflammation of the choroid in which the sensory retina becomes edematous and opaque. The inflammatory cells and exudate may burst through the sensory retina to cloud the vitreous body. [NIH] Choroid: The thin, highly vascular membrane covering most of the posterior of the eye between the retina and sclera. [NIH] Chromatin: The material of chromosomes. It is a complex of DNA, histones, and nonhistone proteins (chromosomal proteins, non-histone) found within the nucleus of a cell. [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 lymphocytic leukemia: A slowly progressing disease in which too many white blood cells (called lymphocytes) are found in the body. [NIH] Chronic myelogenous leukemia: CML. A slowly progressing disease in which too many white blood cells are made in the bone marrow. Also called chronic myeloid leukemia or chronic granulocytic leukemia. [NIH] Chronic phase: Refers to the early stages of chronic myelogenous leukemia or chronic lymphocytic leukemia. The number of mature and immature abnormal white blood cells in the bone marrow and blood is higher than normal, but lower than in the accelerated or blast phase. [NIH] Chronic renal: Slow and progressive loss of kidney function over several years, often resulting in end-stage renal disease. People with end-stage renal disease need dialysis or transplantation to replace the work of the kidneys. [NIH] Chylomicrons: A class of lipoproteins that carry dietary cholesterol and triglycerides from the small intestines to the tissues. [NIH] Cirrhosis: A type of chronic, progressive liver disease. [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] Cleave: A double-stranded cut in DNA with a restriction endonuclease. [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] Clone: The term "clone" has acquired a new meaning. It is applied specifically to the bits of inserted foreign DNA in the hybrid molecules of the population. Each inserted segment originally resided in the DNA of a complex genome amid millions of other DNA segment. [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
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molecules. [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] 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] 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] Colon: The long, coiled, tubelike organ that removes water from digested food. The remaining material, solid waste called stool, moves through the colon to the rectum and leaves the body through the anus. [NIH] Colorectal: Having to do with the colon or the rectum. [NIH] Colorectal Cancer: Cancer that occurs in the colon (large intestine) or the rectum (the end of the large intestine). A number of digestive diseases may increase a person's risk of colorectal cancer, including polyposis and Zollinger-Ellison Syndrome. [NIH] Communicable disease: A disease that can be transmitted by contact between persons. [NIH] Competency: The capacity of the bacterium to take up DNA from its surroundings. [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
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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, 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] Complementation: The production of a wild-type phenotype when two different mutations are combined in a diploid or a heterokaryon and tested in trans-configuration. [NIH] Compliance: Distensibility measure of a chamber such as the lungs (lung compliance) or bladder. Compliance is expressed as a change in volume per unit change in pressure. [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] Computed tomography: CT scan. A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized tomography and computerized axial tomography (CAT) scan. [NIH] Computerized axial tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called CAT scan, computed tomography (CT scan), or computerized tomography. [NIH] Computerized tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized axial tomography (CAT) scan and computed tomography (CT scan). [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] Cones: One type of specialized light-sensitive cells (photoreceptors) in the retina that provide sharp central vision and color vision. [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
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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] Constitutional: 1. Affecting the whole constitution of the body; not local. 2. Pertaining to the constitution. [EU] Constriction: The act of constricting. [NIH] Contamination: The soiling or pollution by inferior material, as by the introduction of organisms into a wound, or sewage into a stream. [EU] 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] 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] Convalescence: The period of recovery following an illness. [NIH] Cooperative group: A group of physicians, hospitals, or both formed to treat a large number of persons in the same way so that new treatment can be evaluated quickly. Clinical trials of new cancer treatments often require many more people than a single physician or hospital can care for. [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 Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Cortisol: A steroid hormone secreted by the adrenal cortex as part of the body's response to stress. [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] 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] Cryoelectron Microscopy: Electron microscopy involving rapid freezing of the samples. The
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imaging of frozen-hydrated molecules and organelles permits the best possible resolution closest to the living state, free of chemical fixatives or stains. [NIH] Culture Media: Any liquid or solid preparation made specifically for the growth, storage, or transport of microorganisms or other types of cells. The variety of media that exist allow for the culturing of specific microorganisms and cell types, such as differential media, selective media, test media, and defined media. Solid media consist of liquid media that have been solidified with an agent such as agar or gelatin. [NIH] 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] Cyclin: Molecule that regulates the cell cycle. [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]
Cytochrome: Any electron transfer hemoprotein having a mode of action in which the transfer of a single electron is effected by a reversible valence change of the central iron atom of the heme prosthetic group between the +2 and +3 oxidation states; classified as cytochromes a in which the heme contains a formyl side chain, cytochromes b, which contain protoheme or a closely similar heme that is not covalently bound to the protein, cytochromes c in which protoheme or other heme is covalently bound to the protein, and cytochromes d in which the iron-tetrapyrrole has fewer conjugated double bonds than the hemes have. Well-known cytochromes have been numbered consecutively within groups and are designated by subscripts (beginning with no subscript), e.g. cytochromes c, c1, C2, . New cytochromes are named according to the wavelength in nanometres of the absorption maximum of the a-band of the iron (II) form in pyridine, e.g., c-555. [EU] Cytogenetics: A branch of genetics which deals with the cytological and molecular behavior of genes and chromosomes during cell division. [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] Cytomegalovirus Infections: Infection with Cytomegalovirus, characterized by enlarged cells bearing intranuclear inclusions. Infection may be in almost any organ, but the salivary glands are the most common site in children, as are the lungs in adults. [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] Cytosine: A pyrimidine base that is a fundamental unit of nucleic acids. [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
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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] Deamination: The removal of an amino group (NH2) from a chemical compound. [NIH] Death Certificates: Official records of individual deaths including the cause of death certified by a physician, and any other required identifying information. [NIH] Decompensation: Failure of compensation; cardiac decompensation is marked by dyspnea, venous engorgement, and edema. [EU] Decontamination: The removal of contaminating material, such as radioactive materials, biological materials, or chemical warfare agents, from a person or object. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] 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] 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] Dental Waste: Any waste product generated by a dental office, surgery, clinic, or laboratory including amalgams, saliva, and rinse water. [NIH] Deoxyglucose: 2-Deoxy-D-arabino-hexose. An antimetabolite of glucose with antiviral activity. [NIH] Deoxyguanosine: A nucleoside consisting of the base guanine and the sugar deoxyribose. [NIH]
Dermatitis: Any inflammation of the skin. [NIH] Desensitization: The prevention or reduction of immediate hypersensitivity reactions by administration of graded doses of allergen; called also hyposensitization and immunotherapy. [EU] Detoxification: Treatment designed to free an addict from his drug habit. [EU] Developed Countries: Countries that have reached a level of economic achievement through an increase of production, per capita income and consumption, and utilization of natural and human resources. [NIH] Developing Countries: Countries in the process of change directed toward economic
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growth, that is, an increase in production, per capita consumption, and income. The process of economic growth involves better utilization of natural and human resources, which results in a change in the social, political, and economic structures. [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] 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] Didanosine: A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by a hydrogen. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. Didanosine is a potent inhibitor of HIV replication, acting as a chain-terminator of viral DNA by binding to reverse transcriptase; ddI is then metabolized to dideoxyadenosine triphosphate, its putative active metabolite. [NIH] Dideoxyadenosine: A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by a hydrogen. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. The compound is an inhibitor of HIV replication, acting as a chain-terminator of viral DNA by binding to reverse transcriptase. Its principal side effect is nephrotoxicity. In vivo, dideoxyadenosine is rapidly metabolized to didanosine (ddI) by enzymatic deamination; ddI is then converted to dideoxyinosine monophosphate and ultimately to dideoxyadenosine triphosphate, the putative active metabolite. [NIH] Dideoxynucleosides: Nucleosides that have two hydroxy groups removed from the sugar moiety. The majority of these compounds have broad-spectrum antiretroviral activity due to their action as antimetabolites. The nucleosides are phosphorylated intracellularly to their 5'triphosphates and act as chain-terminating inhibitors of viral reverse transcription. [NIH] Diethylcarbamazine: An anthelmintic used primarily as the citrate in the treatment of filariasis, particularly infestations with Wucheria bancrofti or Loa loa. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [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] Dimerization: The process by which two molecules of the same chemical composition form a condensation product or polymer. [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] Discrete: Made up of separate parts or characterized by lesions which do not become blended; not running together; separate. [NIH] Discrimination: The act of qualitative and/or quantitative differentiation between two or more stimuli. [NIH] Disease Transmission: The transmission of infectious disease or pathogens. When transmission is within the same species, the mode can be horizontal (disease transmission, horizontal) or vertical (disease transmission, vertical). [NIH]
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Disease Transmission, Horizontal: The transmission of infectious disease or pathogens from one individual to another in the same generation. [NIH] Disease Transmission, Vertical: The transmission of infectious disease or pathogens from one generation to another. It includes transmission in utero or intrapartum by exposure to blood and secretions, and postpartum exposure via breastfeeding. [NIH] Disinfectant: An agent that disinfects; applied particularly to agents used on inanimate objects. [EU] Disinfection: Rendering pathogens harmless through the use of heat, antiseptics, antibacterial agents, etc. [NIH] Disposition: A tendency either physical or mental toward certain diseases. [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] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU] 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] Double-blind: Pertaining to a clinical trial or other experiment in which neither the subject nor the person administering treatment knows which treatment any particular subject is receiving. [EU] 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] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Drug Resistance: Diminished or failed response of an organism, disease or tissue to the intended effectiveness of a chemical or drug. It should be differentiated from drug tolerance which is the progressive diminution of the susceptibility of a human or animal to the effects of a drug, as a result of continued administration. [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] Duct: A tube through which body fluids pass. [NIH] Duodenum: The first part of the small intestine. [NIH] Dyslipidemia: Disorders in the lipoprotein metabolism; classified as hypercholesterolemia, hypertriglyceridemia, combined hyperlipidemia, and low levels of high-density lipoprotein (HDL) cholesterol. All of the dyslipidemias can be primary or secondary. Both elevated levels of low-density lipoprotein (LDL) cholesterol and low levels of HDL cholesterol predispose to premature atherosclerosis. [NIH]
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Dysplasia: Cells that look abnormal under a microscope but are not cancer. [NIH] Dyspnea: Difficult or labored breathing. [NIH] Ebola Virus: A species of filovirus which causes a form of African viral hemorrhagic fever first reported from an outbreak in the Yambuku area of (what was then) Zaire in 1976. [NIH] Edema: Excessive amount of watery fluid accumulated in the intercellular spaces, most commonly present in subcutaneous tissue. [NIH] Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [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] Ejaculation: The release of semen through the penis during orgasm. [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] Electrolytes: Substances that break up into ions (electrically charged particles) when they are dissolved in body fluids or water. Some examples are sodium, potassium, chloride, and calcium. Electrolytes are primarily responsible for the movement of nutrients into cells, and the movement of wastes out of cells. [NIH] 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] Elementary Particles: Individual components of atoms, usually subatomic; subnuclear particles are usually detected only when the atomic nucleus decays and then only transiently, as most of them are unstable, often yielding pure energy without substance, i.e., radiation. [NIH] Emaciation: Clinical manifestation of excessive leanness usually caused by disease or a lack of nutrition. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Emergency Medical Technicians: Paramedical personnel trained to provide basic emergency care and life support under the supervision of physicians and/or nurses. These services may be carried out at the site of the emergency, in the ambulance, or in a health care institution. [NIH] Emulsions: Colloids of two immiscible liquids where either phase may be either fatty or aqueous; lipid-in-water emulsions are usually liquid, like milk or lotion and water-in-lipid emulsions tend to be creams. [NIH] 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] Encephalomyelitis: A general term indicating inflammation of the brain and spinal cord, often used to indicate an infectious process, but also applicable to a variety of autoimmune and toxic-metabolic conditions. There is significant overlap regarding the usage of this term
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and encephalitis in the literature. [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] Endocrinology: A subspecialty of internal medicine concerned with the metabolism, physiology, and disorders of the endocrine system. [NIH] Endoderm: The inner of the three germ layers of the embryo. [NIH] Endogenous: Produced inside an organism or cell. The opposite is external (exogenous) production. [NIH] Endopeptidases: A subclass of peptide hydrolases. They are classified primarily by their catalytic mechanism. Specificity is used only for identification of individual enzymes. They comprise the serine endopeptidases, EC 3.4.21; cysteine endopeptidases, EC 3.4.22; aspartic endopeptidases, EC 3.4.23, metalloendopeptidases, EC 3.4.24; and a group of enzymes yet to be assigned to any of the above sub-classes, EC 3.4.99. EC 3.4.-. [NIH] Endoscopy: Endoscopic examination, therapy or surgery performed on interior parts of the body. [NIH] Endotoxins: Toxins closely associated with the living cytoplasm or cell wall of certain microorganisms, which do not readily diffuse into the culture medium, but are released upon lysis of the cells. [NIH] End-stage renal: Total chronic kidney failure. When the kidneys fail, the body retains fluid and harmful wastes build up. A person with ESRD needs treatment to replace the work of the failed kidneys. [NIH] Enhancer: Transcriptional element in the virus genome. [NIH] Enteropeptidase: A specialized proteolytic enzyme secreted by intestinal cells. It converts trypsinogen into its active form trypsin by removing the N-terminal peptide. EC 3.4.21.9. [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] Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. [NIH] Eosinophil: A polymorphonuclear leucocyte with large eosinophilic granules in its cytoplasm, which plays a role in hypersensitivity reactions. [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] Epidermal: Pertaining to or resembling epidermis. Called also epidermic or epidermoid. [EU]
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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] Epidermoid carcinoma: A type of cancer in which the cells are flat and look like fish scales. Also called squamous cell carcinoma. [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] 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]
Equine Infectious Anemia: Viral disease of horses caused by the equine infectious anemia virus (EIAV). It is characterized by intermittent fever, weakness, and anemia. Chronic infection consists of acute episodes with remissions. [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] Ethidium: A trypanocidal agent and possible antiviral agent that is widely used in experimental cell biology and biochemistry. Ethidium has several experimentally useful properties including binding to nucleic acids, noncompetitive inhibition of nicotinic acetylcholine receptors, and fluorescence among others. It is most commonly used as the bromide. [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] Ethoxyquin: Antioxidant; also a post-harvest dip to prevent scald on apples and pears. [NIH] Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH] Excipient: Any more or less inert substance added to a prescription in order to confer a suitable consistency or form to the drug; a vehicle. [EU] 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]
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Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Extracellular: Outside a cell or cells. [EU] Extraction: The process or act of pulling or drawing out. [EU] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Fat: Total lipids including phospholipids. [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]
Fetoprotein: Transabdominal aspiration of fluid from the amniotic sac with a view to detecting increases of alpha-fetoprotein in maternal blood during pregnancy, as this is an important indicator of open neural tube defects in the 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] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Filovirus: A genus of the family Filoviridae containing two species: Ebola virus and Marburg virus. Both were originally associated with African monkeys but are capable of causing severe hemorrhagic disease in humans. The natural host of either virus is unknown. Transmission is by close personal contact. [NIH] 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] 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 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] Fludarabine: An anticancer drug that belongs to the family of drugs called antimetabolites. [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]
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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] Fractionation: Dividing the total dose of radiation therapy into several smaller, equal doses delivered over a period of several days. [NIH] Frameshift: A type of mutation which causes out-of-phase transcription of the base sequence; such mutations arise from the addition or delection of nucleotide(s) in numbers other than 3 or multiples of 3. [NIH] Frameshift Mutation: A type of mutation in which a number of nucleotides not divisible by three is deleted from or inserted into a coding sequence, thereby causing an alteration in the reading frame of the entire sequence downstream of the mutation. These mutations may be induced by certain types of mutagens or may occur spontaneously. [NIH] Free Radicals: Highly reactive molecules with an unsatisfied electron valence pair. Free radicals are produced in both normal and pathological processes. They are proven or suspected agents of tissue damage in a wide variety of circumstances including radiation, damage from environment chemicals, and aging. Natural and pharmacological prevention of free radical damage is being actively investigated. [NIH] Fulminant Hepatic Failure: Liver failure that occurs suddenly in a previously healthy person. The most common causes of FHF are acute hepatitis, acetaminophen overdose, and liver damage from prescription drugs. [NIH] Fungemia: The presence of fungi circulating in the blood. Opportunistic fungal sepsis is seen most often in immunosuppressed patients with severe neutropenia or in postoperative patients with intravenous catheters and usually follows prolonged antibiotic therapy. [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] Ganciclovir: Acyclovir analog that is a potent inhibitor of the Herpesvirus family including cytomegalovirus. Ganciclovir is used to treat complications from AIDS-associated cytomegalovirus infections. [NIH] 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] Gastric: Having to do with the stomach. [NIH] Gastric Mucosa: Surface epithelium in the stomach that invaginates into the lamina propria, forming gastric pits. Tubular glands, characteristic of each region of the stomach (cardiac,
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gastric, and pyloric), empty into the gastric pits. The gastric mucosa is made up of several different kinds of cells. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]
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 Targeting: The integration of exogenous DNA into the genome of an organism at sites where its expression can be suitably controlled. This integration occurs as a result of homologous recombination. [NIH] Gene Therapy: The introduction of new genes into cells for the purpose of treating disease by restoring or adding gene expression. Techniques include insertion of retroviral vectors, transfection, homologous recombination, and injection of new genes into the nuclei of single cell embryos. The entire gene therapy process may consist of multiple steps. The new genes may be introduced into proliferating cells in vivo (e.g., bone marrow) or in vitro (e.g., fibroblast cultures) and the modified cells transferred to the site where the gene expression is required. Gene therapy may be particularly useful for treating enzyme deficiency diseases, hemoglobinopathies, and leukemias and may also prove useful in restoring drug sensitivity, particularly for leukemia. [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 testing: Analyzing DNA to look for a genetic alteration that may indicate an increased risk for developing a specific disease or disorder. [NIH] Genetic transcription: The process by which the genetic information encoded in the gene, represented as a linear sequence of deoxyribonucleotides, is copied into an exactly complementary sequence of ribonucleotides known as messenger RNA. [NIH] Genital: Pertaining to the genitalia. [EU] Genomics: The systematic study of the complete DNA sequences (genome) of organisms. [NIH]
Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Geographic Locations: All of the continents and every country situated within, the United States and each of the constituent states arranged by region, Canada and each of its provinces, Australia and each of its states, the major bodies of water and major islands on both hemispheres, and selected major cities. Although the geographic locations are not printed in index medicus as main headings, in indexing they are significant in epidemiologic
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studies and historical articles and for locating administrative units in education and the delivery of health care. [NIH] Germ Cells: The reproductive cells in multicellular organisms. [NIH] Gestation: The period of development of the young in viviparous animals, from the time of fertilization of the ovum until birth. [EU] 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] 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] Glucocorticoid: A compound that belongs to the family of compounds called corticosteroids (steroids). Glucocorticoids affect metabolism and have anti-inflammatory and immunosuppressive effects. They may be naturally produced (hormones) or synthetic (drugs). [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] Glucosidases: Enzymes that hydrolyze O-glucosyl-compounds. (Enzyme Nomenclature, 1992) EC 3.2.1.-. [NIH] Glucosinolates: Substituted thioglucosides. They are found in rapeseed (Brassica campestris) products and related Cruciferae. They are metabolized to a variety of toxic products which are most likely the cause of hepatocytic necrosis in animals and humans. [NIH]
Glutathione Peroxidase: An enzyme catalyzing the oxidation of 2 moles of glutathione in the presence of hydrogen peroxide to yield oxidized glutathione and water. EC 1.11.1.9. [NIH]
Glycine: A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter. [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] Gonadal: Pertaining to a gonad. [EU] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [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]
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Granule: A small pill made from sucrose. [EU] Granulocyte: A type of white blood cell that fights bacterial infection. Neutrophils, eosinophils, and basophils are granulocytes. [NIH] Granulocyte-Macrophage Colony-Stimulating Factor: An acidic glycoprotein of MW 23 kDa with internal disulfide bonds. The protein is produced in response to a number of inflammatory mediators by mesenchymal cells present in the hemopoietic environment and at peripheral sites of inflammation. GM-CSF is able to stimulate the production of neutrophilic granulocytes, macrophages, and mixed granulocyte-macrophage colonies from bone marrow cells and can stimulate the formation of eosinophil colonies from fetal liver progenitor cells. GM-CSF can also stimulate some functional activities in mature granulocytes and macrophages. [NIH] Granulocytopenia: A deficiency in the number of granulocytes, a type of white blood cell. [NIH]
Granulomas: Small lumps in tissues caused by inflammation. [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] Guanine: One of the four DNA bases. [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]
Gynecology: A medical-surgical specialty concerned with the physiology and disorders primarily of the female genital tract, as well as female endocrinology and reproductive physiology. [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] Health Behavior: Behaviors expressed by individuals to protect, maintain or promote their health status. For example, proper diet, and appropriate exercise are activities perceived to influence health status. Life style is closely associated with health behavior and factors influencing life style are socioeconomic, educational, and cultural. [NIH] Health Education: Education that increases the awareness and favorably influences the attitudes and knowledge relating to the improvement of health on a personal or community basis. [NIH] Health Services: Services for the diagnosis and treatment of disease and the maintenance of health. [NIH] Health Status: The level of health of the individual, group, or population as subjectively
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assessed by the individual or by more objective measures. [NIH] Hematology: A subspecialty of internal medicine concerned with morphology, physiology, and pathology of the blood and blood-forming tissues. [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] Hemoglobinopathies: A group of inherited disorders characterized by structural alterations within the hemoglobin molecule. [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] Hepatic: Refers to the liver. [NIH] Hepatic Artery: A branch of the celiac artery that distributes to the stomach, pancreas, duodenum, liver, gallbladder, and greater omentum. [NIH] Hepatic Encephalopathy: A condition that may cause loss of consciousness and coma. It is usually the result of advanced liver disease. Also called hepatic coma. [NIH] Hepatitis: Inflammation of the liver and liver disease involving degenerative or necrotic alterations of hepatocytes. [NIH] Hepatitis A: Hepatitis caused by hepatovirus. It can be transmitted through fecal contamination of food or water. [NIH] Hepatitis B: Hepatitis caused by hepatitis B virus. It may be transmitted by transfusion of contaminated blood or blood products. [NIH] Hepatitis C: A form of hepatitis, similar to type B post-transfusion hepatitis, but caused by a virus which is serologically distinct from the agents of hepatitis A, B, and E, and which may persist in the blood of chronic asymptomatic carriers. Hepatitis C is parenterally transmitted and associated with transfusions and drug abuse. [NIH] Hepatitis D: Hepatitis caused by the hepatitis delta virus in association with hepatitis B. It is endemic in some European countries and is seen in drug users, hemophiliacs, and
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polytransfused persons. [NIH] Hepatitis Delta Virus: A defective virus, containing particles of RNA nucleoprotein in virion-like form, present in patients with acute hepatitis B and chronic hepatitis. Officially this is classified as a subviral satellite RNA. [NIH] Hepatitis Viruses: Any of the viruses that cause inflammation of the liver. They include both DNA and RNA viruses as well viruses from humans and animals. [NIH] Hepatitis, Chronic: A collective term for a clinical and pathological syndrome which has several causes and is characterized by varying degrees of hepatocellular necrosis and inflammation. Specific forms of chronic hepatitis include autoimmune hepatitis, chronic hepatitis B, chronic hepatitis C, chronic hepatitis D, indeterminate chronic viral hepatitis, cryptogenic chronic hepatitis, and drug-related chronic hepatitis. [NIH] Hepatoblastoma: A type of liver tumor that occurs in infants and children. [NIH] Hepatocellular: Pertaining to or affecting liver cells. [EU] Hepatocellular carcinoma: A type of adenocarcinoma, the most common type of liver tumor. [NIH] Hepatocyte: A liver cell. [NIH] Hepatology: The field of medicine concerned with the functions and disorders of the liver. [NIH]
Hepatoma: A liver tumor. [NIH] Hepatotoxic: Toxic to liver cells. [EU] Hepatotoxicity: How much damage a medicine or other substance does to the liver. [NIH] Hepatovirus: A genus of Picornaviridae causing infectious hepatitis naturally in humans and experimentally in other primates. It is transmitted through fecal contamination of food or water. [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] Heterodimer: Zippered pair of nonidentical proteins. [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]
Heterogenic: Derived from a different source or species. Also called heterogenous. [NIH] Heterogenous: Derived from a different source or species. Also called heterogenic. [NIH] Histocompatibility: The degree of antigenic similarity between the tissues of different individuals, which determines the acceptance or rejection of allografts. [NIH] Histology: The study of tissues and cells under a microscope. [NIH] Histones: Small chromosomal proteins (approx 12-20 kD) possessing an open, unfolded structure and attached to the DNA in cell nuclei by ionic linkages. Classification into the various types (designated histone I, histone II, etc.) is based on the relative amounts of arginine and lysine in each. [NIH]
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Homeless Persons: Persons who have no permanent residence. The concept excludes nomadic peoples. [NIH] Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable. [NIH] 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] Homosexuality: Sexual attraction or relationship between members of the same sex. [NIH] Hormonal: Pertaining to or of the nature of a hormone. [EU] Hormonal therapy: Treatment of cancer by removing, blocking, or adding hormones. Also called hormone therapy or endocrine therapy. [NIH] 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 therapy: Treatment of cancer by removing, blocking, or adding hormones. Also called endocrine therapy. [NIH] Host-cell: A cell whose metabolism is used for the growth and reproduction of a virus. [NIH] Housekeeping: The care and management of property. [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] Hybridoma: A hybrid cell resulting from the fusion of a specific antibody-producing spleen cell with a myeloma cell. [NIH] Hydration: Combining with water. [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] Hydrophobic: Not readily absorbing water, or being adversely affected by water, as a hydrophobic colloid. [EU] 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]
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Hypercholesterolemia: Abnormally high levels of cholesterol in the blood. [NIH] Hyperlipidemia: An excess of lipids in the blood. [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] Hypertriglyceridemia: Condition of elevated triglyceride concentration in the blood; an inherited form occurs in familial hyperlipoproteinemia IIb and hyperlipoproteinemia type IV. It has been linked to higher risk of heart disease and arteriosclerosis. [NIH] Hypoxia: Reduction of oxygen supply to tissue below physiological levels despite adequate perfusion of the tissue by blood. [EU] Immune adjuvant: A drug that stimulates the immune system to respond to disease. [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] Immune Tolerance: The specific failure of a normally responsive individual to make an immune response to a known antigen. It results from previous contact with the antigen by an immunologically immature individual (fetus or neonate) or by an adult exposed to extreme high-dose or low-dose antigen, or by exposure to radiation, antimetabolites, antilymphocytic serum, etc. [NIH] 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] Immunochemistry: Field of chemistry that pertains to immunological phenomena and the study of chemical reactions related to antigen stimulation of tissues. It includes physicochemical interactions between antigens and antibodies. [NIH] Immunocompromised: Having a weakened immune system caused by certain diseases or treatments. [NIH] Immunocompromised Host: A human or animal whose immunologic mechanism is deficient because of an immunodeficiency disorder or other disease or as the result of the administration of immunosuppressive drugs or radiation. [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]
Immunodiffusion: Technique involving the diffusion of antigen or antibody through a
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semisolid medium, usually agar or agarose gel, with the result being a precipitin reaction. [NIH]
Immunodominant Epitopes: Subunits of the antigenic determinant that are most easily recognized by the immune system and thus most influence the specificity of the induced antibody. [NIH] Immunoelectrophoresis: A technique that combines protein electrophoresis and double immunodiffusion. In this procedure proteins are first separated by gel electrophoresis (usually agarose), then made visible by immunodiffusion of specific antibodies. A distinct elliptical precipitin arc results for each protein detectable by the antisera. [NIH] Immunogen: A substance that is capable of causing antibody formation. [NIH] Immunogenic: Producing immunity; evoking an immune response. [EU] Immunoglobulin: A protein that acts as an antibody. [NIH] Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents. [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] Immunology: The study of the body's immune system. [NIH] Immunosuppressant: An agent capable of suppressing immune responses. [EU] Immunosuppression: Deliberate prevention or diminution of the host's immune response. It may be nonspecific as in the administration of immunosuppressive agents (drugs or radiation) or by lymphocyte depletion or may be specific as in desensitization or the simultaneous administration of antigen and immunosuppressive drugs. [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] In situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU] In Situ Hybridization: A technique that localizes specific nucleic acid sequences within intact chromosomes, eukaryotic cells, or bacterial cells through the use of specific nucleic acid-labeled probes. [NIH] 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]
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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] Indolent: A type of cancer that grows slowly. [NIH] 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] Infantile: Pertaining to an infant or to infancy. [EU] 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]
Infection Control: Programs of disease surveillance, generally within health care facilities, designed to investigate, prevent, and control the spread of infections and their causative microorganisms. [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] 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] Inorganic: Pertaining to substances not of organic origin. [EU] Insertional: A technique in which foreign DNA is cloned into a restriction site which occupies a position within the coding sequence of a gene in the cloning vector molecule.
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Insertion interrupts the gene's sequence such that its original function is no longer expressed. [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] 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] Insulin-like: Muscular growth factor. [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]
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-10: Factor that is a coregulator of mast cell growth. It is produced by T-cells and B-cells and shows extensive homology with the Epstein-Barr virus BCRFI gene. [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] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Intestinal: Having to do with the intestines. [NIH] Intestinal Mucosa: The surface lining of the intestines where the cells absorb nutrients. [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] Intrahepatic: Within the liver. [NIH] Intramuscular: IM. Within or into muscle. [NIH] Intravenous: IV. Into a vein. [NIH]
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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]
Invertebrates: Animals that have no spinal column. [NIH] Involuntary: Reaction occurring without intention or volition. [NIH] Ionizing: Radiation comprising charged particles, e. g. electrons, protons, alpha-particles, etc., having sufficient kinetic energy to produce ionization by collision. [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] 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]
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] Kidney Transplantation: The transference of a kidney from one human or animal to another. [NIH] Kinetics: The study of rate dynamics in chemical or physical systems. [NIH] Labile: 1. Gliding; moving from point to point over the surface; unstable; fluctuating. 2. Chemically unstable. [EU] Lamivudine: A reverse transcriptase inhibitor and zalcitabine analog in which a sulfur atom replaces the 3' carbon of the pentose ring. It is used to treat HIV disease. [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] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH] Laxative: An agent that acts to promote evacuation of the bowel; a cathartic or purgative. [EU]
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] Lens: The transparent, double convex (outward curve on both sides) structure suspended between the aqueous and vitreous; helps to focus light on the retina. [NIH] Lesion: An area of abnormal tissue change. [NIH] Lethal: Deadly, fatal. [EU] Leucine: An essential branched-chain amino acid important for hemoglobin formation. [NIH] 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] Leukoencephalopathy: A condition with spongy holes in the brain's white matter. [NIH] Leukopenia: A condition in which the number of leukocytes (white blood cells) in the blood is reduced. [NIH]
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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] Life Expectancy: A figure representing the number of years, based on known statistics, to which any person of a given age may reasonably expect to live. [NIH] Ligands: A RNA simulation method developed by the MIT. [NIH] Linkage: 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] Lip: Either of the two fleshy, full-blooded margins of the mouth. [NIH] Lipid: Fat. [NIH] Lipid Peroxidation: Peroxidase catalyzed oxidation of lipids using hydrogen peroxide as an electron acceptor. [NIH] Lipid Peroxides: Peroxides produced in the presence of a free radical by the oxidation of unsaturated fatty acids in the cell in the presence of molecular oxygen. The formation of lipid peroxides results in the destruction of the original lipid leading to the loss of integrity of the membranes. They therefore cause a variety of toxic effects in vivo and their formation is considered a pathological process in biological systems. Their formation can be inhibited by antioxidants, such as vitamin E, structural separation or low oxygen tension. [NIH] Lipopolysaccharides: 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] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Liver cancer: A disease in which malignant (cancer) cells are found in the tissues of the liver. [NIH]
Liver Cirrhosis: Liver disease in which the normal microcirculation, the gross vascular anatomy, and the hepatic architecture have been variably destroyed and altered with fibrous septa surrounding regenerated or regenerating parenchymal nodules. [NIH] Liver Transplantation: The transference of a part of or an entire liver from one human or animal to another. [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] Longitudinal study: Also referred to as a "cohort study" or "prospective study"; the analytic method of epidemiologic study in which subsets of a defined population can be identified who are, have been, or in the future may be exposed or not exposed, or exposed in different degrees, to a factor or factors hypothesized to influence the probability of occurrence of a given disease or other outcome. The main feature of this type of study is to observe large numbers of subjects over an extended time, with comparisons of incidence rates in groups that differ in exposure levels. [NIH]
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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] 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] Luminescence: The property of giving off light without emitting a corresponding degree of heat. It includes the luminescence of inorganic matter or the bioluminescence of human matter, invertebrates and other living organisms. For the luminescence of bacteria, bacterial luminescence is available. [NIH] Lung Transplantation: The transference of either one or both of the lungs from one human or animal to another. [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] 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 Depletion: Immunosuppression by reduction of circulating lymphocytes or by T-cell depletion of bone marrow. The former may be accomplished in vivo by thoracic duct drainage or administration of antilymphocyte serum. The latter is performed ex vivo on bone marrow before its transplantation. [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] Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue. [NIH] Lysine: An essential amino acid. It is often added to animal feed. [NIH] Lysogeny: The phenomenon by which a temperate phage incorporates itself into the DNA
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of a bacterial host, establishing a kind of symbiotic relation between prophage and bacterium which results in the perpetuation of the prophage in all the descendants of the bacterium until induction by various agents, such as ultraviolet radiation, releases the phage, which then becomes virulent and lyses the bacterium. [NIH] 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] Magnetic Resonance Imaging: Non-invasive method of demonstrating internal anatomy based on the principle that atomic nuclei in a strong magnetic field absorb pulses of radiofrequency energy and emit them as radiowaves which can be reconstructed into computerized images. The concept includes proton spin tomographic techniques. [NIH] Magnetic Resonance Spectroscopy: Spectroscopic method of measuring the magnetic moment of elementary particles such as atomic nuclei, protons or electrons. It is employed in clinical applications such as NMR Tomography (magnetic resonance imaging). [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] 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, 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]
Mandatory Testing: Testing or screening required by federal, state, or local law or other agencies for the diagnosis of specified conditions. It is usually limited to specific populations such as categories of health care providers, members of the military, and prisoners or to specific situations such as premarital examinations or donor screening. [NIH] Man-made: Ionizing radiation emitted by artificial or concentrated natural, radioactive material or resulting from the operation of high voltage apparatus, such as X-ray apparatus or particle accelerators, of nuclear reactors, or from nuclear explosions. [NIH]
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Mannans: Polysaccharides consisting of mannose units. [NIH] Mastitis: Inflammatory disease of the breast, or mammary gland. [NIH] Measles Virus: The type species of morbillivirus and the cause of the highly infectious human disease measles, which affects mostly children. [NIH] 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] Medical Waste: Blood, mucus, tissue removed at surgery or autopsy, soiled surgical dressings, and other materials requiring special disposal procedures. [NIH] 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] 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] Menopause: Permanent cessation of menstruation. [NIH] Menstruation: The normal physiologic discharge through the vagina of blood and mucosal tissues from the nonpregnant uterus. [NIH] Mental: Pertaining to the mind; psychic. 2. (L. mentum chin) pertaining to the chin. [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] Mentors: Senior professionals who provide guidance, direction and support to those persons desirous of improvement in academic positions, administrative positions or other career development situations. [NIH] Mercury: A silver metallic element that exists as a liquid at room temperature. It has the atomic symbol Hg (from hydrargyrum, liquid silver), atomic number 80, and atomic weight
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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] Mesenchymal: Refers to cells that develop into connective tissue, blood vessels, and lymphatic tissue. [NIH] Mesoderm: The middle germ layer of the embryo. [NIH] Meta-Analysis: A quantitative method of combining the results of independent studies (usually drawn from the published literature) and synthesizing summaries and conclusions which may be used to evaluate therapeutic effectiveness, plan new studies, etc., with application chiefly in the areas of research and medicine. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] Metastasis: The spread of cancer from one part of the body to another. Tumors formed from cells that have spread are called "secondary tumors" and contain cells that are like those in the original (primary) tumor. The plural is metastases. [NIH] Methionine: A sulfur containing essential amino acid that is important in many body functions. It is a chelating agent for heavy metals. [NIH] Methotrexate: An antineoplastic antimetabolite with immunosuppressant properties. It is an inhibitor of dihydrofolate reductase and prevents the formation of tetrahydrofolate, necessary for synthesis of thymidylate, an essential component of DNA. [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] Mice Minute Virus: The type species of parvovirus prevalent in mouse colonies and found as a contaminant of many transplanted tumors or leukemias. [NIH] Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microcirculation: The vascular network lying between the arterioles and venules; includes capillaries, metarterioles and arteriovenous anastomoses. Also, the flow of blood through this network. [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, Electron: Visual and photographic microscopy in which electron beams with wavelengths thousands of times shorter than visible light are used in place of light, thereby allowing much greater magnification. [NIH] Mitochondria: Parts of a cell where aerobic production (also known as cell respiration) takes place. [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] Mitogen-Activated Protein Kinase Kinases: A serine-threonine protein kinase family whose members are components in protein kinase cascades activated by diverse stimuli. These MAPK kinases phosphorylate mitogen-activated protein kinases and are themselves phosphorylated by MAP kinase kinase kinases. JNK kinases (also known as SAPK kinases) are a subfamily. EC 2.7.10.- [NIH]
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Mitogen-Activated Protein Kinases: A superfamily of protein-serine-threonine kinases that are activated by diverse stimuli via protein kinase cascades. They are the final components of the cascades, activated by phosphorylation by mitogen-activated protein kinase kinases which in turn are activated by mitogen-activated protein kinase kinase kinases (MAP kinase kinase kinases). Families of these mitogen-activated protein kinases (MAPKs) include extracellular signal-regulated kinases (ERKs), stress-activated protein kinases (SAPKs) (also known as c-jun terminal kinases (JNKs)), and p38-mitogen-activated protein kinases. EC 2,7,1.- [NIH] Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH] Mobility: Capability of movement, of being moved, or of flowing freely. [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] Molecular Structure: The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds. [NIH] 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] 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] Mononuclear: A cell with one nucleus. [NIH] Monophosphate: So called second messenger for neurotransmitters and hormones. [NIH] Monotherapy: A therapy which uses only one drug. [EU] 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]
Morphological: Relating to the configuration or the structure of live organs. [NIH] Morphology: The science of the form and structure of organisms (plants, animals, and other forms of life). [NIH]
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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] 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] 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] Muscle Fibers: Large single cells, either cylindrical or prismatic in shape, that form the basic unit of muscle tissue. They consist of a soft contractile substance enclosed in a tubular sheath. [NIH] Mutagenesis: Process of generating genetic mutations. It may occur spontaneously or be induced by mutagens. [NIH] Mutagenic: Inducing genetic mutation. [EU] 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] Mycotoxins: Toxins derived from bacteria or fungi. [NIH] Myelogenous: Produced by, or originating in, the bone marrow. [NIH] Myeloma: Cancer that arises in plasma cells, a type of white blood cell. [NIH] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myosin: Chief protein in muscle and the main constituent of the thick filaments of muscle fibers. In conjunction with actin, it is responsible for the contraction and relaxation of muscles. [NIH] Nasal Mucosa: The mucous membrane lining the nasal cavity. [NIH] Natural selection: A part of the evolutionary process resulting in the survival and reproduction of the best adapted individuals. [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] Neonatal: Pertaining to the first four weeks after birth. [EU] Neoplasm: A new growth of benign or malignant tissue. [NIH]
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Neoplastic: Pertaining to or like a neoplasm (= any new and abnormal growth); pertaining to neoplasia (= the formation of a neoplasm). [EU] 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] Networks: Pertaining to a nerve or to the nerves, a meshlike structure of interlocking fibers or strands. [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] Neural tube defects: These defects include problems stemming from fetal development of the spinal cord, spine, brain, and skull, and include birth defects such as spina bifida, anencephaly, and encephalocele. Neural tube defects occur early in pregnancy at about 4 to 6 weeks, usually before a woman knows she is pregnant. Many babies with neural tube defects have difficulty walking and with bladder and bowel control. [NIH] Neurologic: Having to do with nerves or the nervous system. [NIH] Neurology: A medical specialty concerned with the study of the structures, functions, and diseases 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, 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] Neuroretinitis: Inflammation of the optic nerve head and adjacent retina. [NIH] Neurotoxic: Poisonous or destructive to nerve tissue. [EU] Neurotoxicity: The tendency of some treatments to cause damage to the nervous system. [NIH]
Neurotoxins: Toxic substances from microorganisms, plants or animals that interfere with the functions of the nervous system. Most venoms contain neurotoxic substances. Myotoxins are included in this concept. [NIH] Neurotransmitter: Any of a group of substances that are released on excitation from the axon terminal of a presynaptic neuron of the central or peripheral nervous system and travel across the synaptic cleft to either excite or inhibit the target cell. Among the many substances that have the properties of a neurotransmitter are acetylcholine, norepinephrine, epinephrine, dopamine, glycine, y-aminobutyrate, glutamic acid, substance P, enkephalins, endorphins, and serotonin. [EU] Neutralization: An act or process of neutralizing. [EU] Night Blindness: Anomaly of vision in which there is a pronounced inadequacy or complete absence of dark-adaptation. [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] Nosocomial: Pertaining to or originating in the hospital, said of an infection not present or
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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] Nucleolus: A small dense body (sub organelle) within the nucleus of eukaryotic cells, visible by phase contrast and interference microscopy in live cells throughout interphase. Contains RNA and protein and is the site of synthesis of ribosomal RNA. [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] Occult: Obscure; concealed from observation, difficult to understand. [EU] Occupational Exposure: The exposure to potentially harmful chemical, physical, or biological agents that occurs as a result of one's occupation. [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] 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] Oltipraz: A drug used in cancer prevention. [NIH] Omentum: A fold of the peritoneum (the thin tissue that lines the abdomen) that surrounds the stomach and other organs in the abdomen. [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 environmental exposure to carcinogens. [NIH] Oncogenic: Chemical, viral, radioactive or other agent that causes cancer; carcinogenic. [NIH] Oocytes: Female germ cells in stages between the prophase of the first maturation division and the completion of the second maturation division. [NIH] Opacity: Degree of density (area most dense taken for reading). [NIH] Open Reading Frames: Reading frames where successive nucleotide triplets can be read as codons specifying amino acids and where the sequence of these triplets is not interrupted by
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stop codons. [NIH] Operon: The genetic unit consisting of a feedback system under the control of an operator gene, in which a structural gene transcribes its message in the form of mRNA upon blockade of a repressor produced by a regulator gene. Included here is the attenuator site of bacterial operons where transcription termination is regulated. [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] Opportunistic Infections: An infection caused by an organism which becomes pathogenic under certain conditions, e.g., during immunosuppression. [NIH] Opsin: A protein formed, together with retinene, by the chemical breakdown of metarhodopsin. [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] 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] Ori region: The point or region (origin) at which DNA replication begins in a bacterium or virus. Plasmids used in rec DNA research always contain an ori region, which gives very efficient initiation of replication. [NIH] Orthohepadnavirus: A genus of Hepadnaviridae causing hepatitis in humans, woodchucks, and ground squirrels. It is also associated with human hepatocellular carcinoma. Hepatitis B virus is the type species. [NIH] Osmotic: Pertaining to or of the nature of osmosis (= the passage of pure solvent from a solution of lesser to one of greater solute concentration when the two solutions are separated by a membrane which selectively prevents the passage of solute molecules, but is permeable to the solvent). [EU] Osteosarcoma: A cancer of the bone that affects primarily children and adolescents. Also called osteogenic sarcoma. [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] Overdose: An accidental or deliberate dose of a medication or street drug that is in excess of what is normally used. [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
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molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]
Oxidation-Reduction: A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471). [NIH] Oxidative Stress: A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi). [NIH] P53 gene: A tumor suppressor gene that normally inhibits the growth of tumors. This gene is altered in many types of cancer. [NIH] 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] Pancreatic: Having to do with the pancreas. [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] Paralysis: Loss of ability to move all or part of the body. [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] Parenteral: Not through the alimentary canal but rather by injection through some other route, as subcutaneous, intramuscular, intraorbital, intracapsular, intraspinal, intrasternal, intravenous, etc. [EU] Partial remission: The shrinking, but not complete disappearance, of a tumor in response to therapy. Also called partial response. [NIH] Particle: A tiny mass of material. [EU] Particle Accelerators: Devices which accelerate electrically charged atomic or subatomic particles, such as electrons, protons or ions, to high velocities so they have high kinetic energy. [NIH] Parvovirus: A genus of the family Parvoviridae, subfamily Parvovirinae, infecting a variety of vertebrates including humans. Parvoviruses are responsible for a number of important diseases but also can be non-pathogenic in certain hosts. The type species is mice minute virus. [NIH] Pathogen: Any disease-producing microorganism. [EU] Pathogenesis: The cellular events and reactions that occur in the development of disease.
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[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] Pathologic Processes: The abnormal mechanisms and forms involved in the dysfunctions of tissues and organs. [NIH] Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Patient Education: The teaching or training of patients concerning their own health needs. [NIH]
Pediatrics: A medical specialty concerned with maintaining health and providing medical care to children from birth to adolescence. [NIH] Pelvis: The lower part of the abdomen, located between the hip bones. [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] Perceived risk: Estimate or evaluation of risk as observed through personal experience or personal study, and personal evaluation of consequences. [NIH] Percutaneous: Performed through the skin, as injection of radiopacque material in radiological examination, or the removal of tissue for biopsy accomplished by a needle. [EU] Perfusion: Bathing an organ or tissue with a fluid. In regional perfusion, a specific area of the body (usually an arm or a leg) receives high doses of anticancer drugs through a blood vessel. Such a procedure is performed to treat cancer that has not spread. [NIH] Perinatal: Pertaining to or occurring in the period shortly before and after birth; variously defined as beginning with completion of the twentieth to twenty-eighth week of gestation and ending 7 to 28 days after birth. [EU] Peripheral blood: Blood circulating throughout the body. [NIH] Peripheral Neuropathy: Nerve damage, usually affecting the feet and legs; causing pain, numbness, or a tingling feeling. Also called "somatic neuropathy" or "distal sensory polyneuropathy." [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] Pharmacodynamic: Is concerned with the response of living tissues to chemical stimuli, that is, the action of drugs on the living organism in the absence of disease. [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
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of melanin, dopamine, noradrenalin, and thyroxine. [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] Phosphorylated: Attached to a phosphate group. [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] Physicochemical: Pertaining to physics and chemistry. [EU] 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] Picornavirus: Any of a group of tiny RNA-containing viruses including the enteroviruses and rhinoviruses. [NIH] Pigment: A substance that gives color to tissue. Pigments are responsible for the color of skin, eyes, and hair. [NIH] Pilot study: The initial study examining a new method or treatment. [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] Plasma protein: One of the hundreds of different proteins present in blood plasma, including carrier proteins ( such albumin, transferrin, and haptoglobin), fibrinogen and other coagulation factors, complement components, immunoglobulins, enzyme inhibitors, precursors of substances such as angiotension and bradykinin, and many other types of proteins. [EU] 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]
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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] 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]
Pneumonia: Inflammation of the lungs. [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] Poliomyelitis: An acute viral disease, occurring sporadically and in epidemics, and characterized clinically by fever, sore throat, headache, and vomiting, often with stiffness of the neck and back. In the minor illness these may be the only symptoms. The major illness, which may or may not be preceded by the minor illness, is characterized by involvement of the central nervous system, stiff neck, pleocytosis in the spinal fluid, and perhaps paralysis. There may be subsequent atrophy of groups of muscles, ending in contraction and permanent deformity. The major illness is called acute anterior p., infantile paralysis and Heine-Medin disease. The disease is now largely controlled by vaccines. [EU] Polyarteritis Nodosa: A form of necrotizing vasculitis involving small- and medium-sized arteries. The signs and symptoms result from infarction and scarring of the affected organ system. [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] Polymorphic: Occurring in several or many forms; appearing in different forms at different stages of development. [EU] Polymorphism: The occurrence together of two or more distinct forms in the same population. [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] Polyposis: The development of numerous polyps (growths that protrude from a mucous membrane). [NIH] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] Polyvalent: Having more than one valence. [EU] Population Dynamics: The pattern of any process, or the interrelationship of phenomena,
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which affects growth or change within a population. [NIH] Portal Hypertension: High blood pressure in the portal vein. This vein carries blood into the liver. Portal hypertension is caused by a blood clot. This is a common complication of cirrhosis. [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] Postnatal: Occurring after birth, with reference to the newborn. [EU] Potentiate: 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] Precancerous: A term used to describe a condition that may (or is likely to) become cancer. Also called premalignant. [NIH] Preclinical: Before a disease becomes clinically recognizable. [EU] 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] Predictive factor: A situation or condition that may increase a person's risk of developing a certain disease or disorder. [NIH] 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] Primary Biliary Cirrhosis: A chronic liver disease. Slowly destroys the bile ducts in the liver. This prevents release of bile. Long-term irritation of the liver may cause scarring and cirrhosis in later stages of the disease. [NIH] Probe: An instrument used in exploring cavities, or in the detection and dilatation of strictures, or in demonstrating the potency of channels; an elongated instrument for exploring or sounding body cavities. [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] Progesterone: Pregn-4-ene-3,20-dione. The principal progestational hormone of the body, secreted by the corpus luteum, adrenal cortex, and placenta. Its chief function is to prepare the uterus for the reception and development of the fertilized ovum. It acts as an antiovulatory agent when administered on days 5-25 of the menstrual cycle. [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]
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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] Prone: Having the front portion of the body downwards. [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] 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] 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] Prostitution: The practice of indulging in promiscuous sexual relations for money. [NIH] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Protease Inhibitors: Compounds which inhibit or antagonize biosynthesis or actions of proteases (endopeptidases). [NIH] Protective Agents: Synthetic or natural substances which are given to prevent a disease or disorder or are used in the process of treating a disease or injury due to a poisonous agent. [NIH]
Protective Clothing: Clothing designed to protect the individual against possible exposure to known hazards. [NIH] 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 Kinase C: An enzyme that phosphorylates proteins on serine or threonine residues in the presence of physiological concentrations of calcium and membrane phospholipids. The additional presence of diacylglycerols markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by phorbol esters and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters. EC 2.7.1.-. [NIH] Protein p53: Nuclear phosphoprotein encoded by the p53 gene whose normal function is to
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control cell proliferation. A mutant or absent p53 protein has been found in leukemia, osteosarcoma, lung cancer, and colorectal cancer. [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] Protein-Serine-Threonine Kinases: A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors. EC 2.7.10. [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] Proto-Oncogenes: Normal cellular genes homologous to viral oncogenes. The products of proto-oncogenes are important regulators of biological processes and appear to be involved in the events that serve to maintain the ordered procession through the cell cycle. Protooncogenes have names of the form c-onc. [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] Protozoal: Having to do with the simplest organisms in the animal kingdom. Protozoa are single-cell organisms, such as ameba, and are different from bacteria, which are not members of the animal kingdom. Some protozoa can be seen without a microscope. [NIH] Protozoan: 1. Any individual of the protozoa; protozoon. 2. Of or pertaining to the protozoa; protozoal. [EU] Provirus: Virus that is integrated into the chromosome of a host cell and is transmitted in that form from one host cell generation to another without leading to the lysis of the host cells. [NIH] Psoriasis: A common genetically determined, chronic, inflammatory skin disease characterized by rounded erythematous, dry, scaling patches. The lesions have a predilection for nails, scalp, genitalia, extensor surfaces, and the lumbosacral region. Accelerated epidermopoiesis is considered to be the fundamental pathologic feature in psoriasis. [NIH] Psychic: Pertaining to the psyche or to the mind; mental. [EU] Psychoactive: Those drugs which alter sensation, mood, consciousness or other psychological or behavioral functions. [NIH] 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]
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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] Public Sector: The area of a nation's economy that is tax-supported and under government control. [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] 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]
Purifying: Respiratory equipment whose function is to remove contaminants from otherwise wholesome air. [NIH] Purpura: Purplish or brownish red discoloration, easily visible through the epidermis, caused by hemorrhage into the tissues. [NIH] Pyrimidines: A family of 6-membered heterocyclic compounds occurring in nature in a wide variety of forms. They include several nucleic acid constituents (cytosine, thymine, and uracil) and form the basic structure of the barbiturates. [NIH] Quality of Health Care: The levels of excellence which characterize the health service or health care provided based on accepted standards of quality. [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] Quiescent: Marked by a state of inactivity or repose. [EU] 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] Radioisotope: An unstable element that releases radiation as it breaks down. Radioisotopes can be used in imaging tests or as a treatment for cancer. [NIH] Radiological: Pertaining to radiodiagnostic and radiotherapeutic procedures, and interventional radiology or other planning and guiding medical radiology. [NIH] Radiology: A specialty concerned with the use of x-ray and other forms of radiant energy in the diagnosis and treatment of disease. [NIH] Randomized: Describes an experiment or clinical trial in which animal or human subjects
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are assigned by chance to separate groups that compare different treatments. [NIH] Reactivation: The restoration of activity to something that has been inactivated. [EU] Reactive Oxygen Species: Reactive intermediate oxygen species including both radicals and non-radicals. These substances are constantly formed in the human body and have been shown to kill bacteria and inactivate proteins, and have been implicated in a number of diseases. Scientific data exist that link the reactive oxygen species produced by inflammatory phagocytes to cancer development. [NIH] Reading Frames: The sequence of codons by which translation may occur. A segment of mRNA 5'AUCCGA3' could be translated in three reading frames, 5'AUC. or 5'UCC. or 5'CCG., depending on the location of the start codon. [NIH] Reagent: A substance employed to produce a chemical reaction so as to detect, measure, produce, etc., other substances. [EU] 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] 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] Reductase: Enzyme converting testosterone to dihydrotestosterone. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Reflective: Capable of throwing back light, images, sound waves : reflecting. [EU] Reflex: An involuntary movement or exercise of function in a part, excited in response to a stimulus applied to the periphery and transmitted to the brain or spinal cord. [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] Reinfection: A second infection by the same pathogenic agent, or a second infection of an organ such as the kidney by a different pathogenic agent. [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
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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] Reminder Systems: Systems used to prompt or aid the memory. The systems can be computerized reminders, color coding, telephone calls, or devices such as letters and postcards. [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] Replication Origin: The point or region (origin) at which DNA replication begins in a bacterium or virus. Plasmids used in rec DNA research always contain an ori region, which gives very efficient initiation of replication. [NIH] Resection: Removal of tissue or part or all of an organ by surgery. [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] Respirators: These enable the wearer to breathe in atmospheres polluted by dust, poisonous vapors, smoke, etc., and are therefore used in certain industries or in warfare; they consist essentially of a mask, a metal frame with outlet and inlet valves, and a socket. [NIH] Reticulate: An area of the cell wall involved in the coalescence of two vessel elements having multiple perforations that are netlike. [NIH] Retina: The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outer-most layer is pigmented, whereas the inner nine layers are transparent. [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] Retinitis: Inflammation of the retina. It is rarely limited to the retina, but is commonly associated with diseases of the choroid (chorioretinitis) and of the optic nerve (neuroretinitis). The disease may be confined to one eye, but since it is generally dependent on a constitutional factor, it is almost always bilateral. It may be acute in course, but as a rule it lasts many weeks or even several months. [NIH] Retinitis Pigmentosa: Hereditary, progressive degeneration of the neuroepithelium of the retina characterized by night blindness and progressive contraction of the visual field. [NIH] Retinoid: Vitamin A or a vitamin A-like compound. [NIH] Retinol: Vitamin A. It is essential for proper vision and healthy skin and mucous membranes. Retinol is being studied for cancer prevention; it belongs to the family of drugs called retinoids. [NIH]
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Retreatment: The therapy of the same disease in a patient, with the same agent or procedure repeated after initial treatment, or with an additional or alternate measure or follow-up. It does not include therapy which requires more than one administration of a therapeutic agent or regimen. Retreatment is often used with reference to a different modality when the original one was inadequate, harmful, or unsuccessful. [NIH] Retroviral vector: RNA from a virus that is used to insert genetic material into cells. [NIH] Reversion: A return to the original condition, e. g. the reappearance of the normal or wild type in previously mutated cells, tissues, or organisms. [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] Rhodopsin: A photoreceptor protein found in retinal rods. It is a complex formed by the binding of retinal, the oxidized form of retinol, to the protein opsin and undergoes a series of complex reactions in response to visible light resulting in the transmission of nerve impulses to the brain. [NIH] 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] Ribose: A pentose active in biological systems usually in its D-form. [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] Rickettsiae: One of a group of obligate intracellular parasitic microorganisms, once regarded as intermediate in their properties between bacteria and viruses but now classified as bacteria in the order Rickettsiales, which includes 17 genera and 3 families: Rickettsiace. [NIH]
Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Rituximab: A type of monoclonal antibody used in cancer detection or therapy. Monoclonal antibodies are laboratory-produced substances that can locate and bind to cancer cells. [NIH] Rods: One type of specialized light-sensitive cells (photoreceptors) in the retina that provide side vision and the ability to see objects in dim light (night vision). [NIH] Saccharomyces: A genus of ascomycetous fungi of the family Saccharomycetaceae, order saccharomycetales. [NIH] Saccharomyces cerevisiae: A species of the genus Saccharomyces, family Saccharomycetaceae, order Saccharomycetales, known as "baker's" or "brewer's" yeast. The dried form is used as a dietary supplement. [NIH] Saccharomycetales: An order of fungi in the phylum Ascomycota that multiply by budding. They include the telomorphic ascomycetous yeasts which are found in a very wide range of habitats. [NIH] 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]
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Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [NIH] Salvage Therapy: A therapeutic approach, involving chemotherapy, radiation therapy, or surgery, after initial regimens have failed to lead to improvement in a patient's condition. Salvage therapy is most often used for neoplastic diseases. [NIH] Sanitation: The development and establishment of environmental conditions favorable to the health of the public. [NIH] Saponins: Sapogenin glycosides. A type of glycoside widely distributed in plants. Each consists of a sapogenin as the aglycon moiety, and a sugar. The sapogenin may be a steroid or a triterpene and the sugar may be glucose, galactose, a pentose, or a methylpentose. Sapogenins are poisonous towards the lower forms of life and are powerful hemolytics when injected into the blood stream able to dissolve red blood cells at even extreme dilutions. [NIH] Sarcoma: A connective tissue neoplasm formed by proliferation of mesodermal cells; it is usually highly malignant. [NIH] Satellite: Applied to a vein which closely accompanies an artery for some distance; in cytogenetics, a chromosomal agent separated by a secondary constriction from the main body of the chromosome. [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] Screening: Checking for disease when there are no symptoms. [NIH] Secondary tumor: Cancer that has spread from the organ in which it first appeared to another organ. For example, breast cancer cells may spread (metastasize) to the lungs and cause the growth of a new tumor. When this happens, the disease is called metastatic breast cancer, and the tumor in the lungs is called a secondary tumor. Also called secondary cancer. [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] Sedimentation: The act of causing the deposit of sediment, especially by the use of a centrifugal machine. [EU] Segregation: The separation in meiotic cell division of homologous chromosome pairs and their contained allelomorphic gene pairs. [NIH] Selenium: An element with the atomic symbol Se, atomic number 34, and atomic weight 78.96. It is an essential micronutrient for mammals and other animals but is toxic in large amounts. Selenium protects intracellular structures against oxidative damage. It is an essential component of glutathione peroxidase. [NIH]
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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] 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] 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] 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] Sequencing: The determination of the order of nucleotides in a DNA or RNA chain. [NIH] Serine: A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from glycine or threonine. It is involved in the biosynthesis of purines, pyrimidines, and other amino acids. [NIH] Seroconversion: The change of a serologic test from negative to positive, indicating the development of antibodies in response to infection or immunization. [EU] 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] 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] Sexual Partners: Married or single individuals who share sexual relations. [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]
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] Signs and Symptoms: Clinical manifestations that can be either objective when observed by a physician, or subjective when perceived by the patient. [NIH] Sizofiran: A beta-D-glucan obtained from the Aphyllophoral fungus Schizophyllum commune. It is used as an immunoadjuvant in the treatment of neoplasms, especially tumors found in the stomach. [NIH] Skin test: A test for an immune response to a compound by placing it on or under the skin. [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]
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Social Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [NIH] Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] Solid tumor: Cancer of body tissues other than blood, bone marrow, or the lymphatic system. [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] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] Sound wave: An alteration of properties of an elastic medium, such as pressure, particle displacement, or density, that propagates through the medium, or a superposition of such alterations. [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] 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] Spermatozoa: Mature male germ cells that develop in the seminiferous tubules of the testes. Each consists of a head, a body, and a tail that provides propulsion. The head consists mainly of chromatin. [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] 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] Spores: The reproductive elements of lower organisms, such as protozoa, fungi, and cryptogamic plants. [NIH] Squamous: Scaly, or platelike. [EU] Squamous cell carcinoma: Cancer that begins in squamous cells, which are thin, flat cells resembling fish scales. Squamous cells are found in the tissue that forms the surface of the skin, the lining of the hollow organs of the body, and the passages of the respiratory and digestive tracts. Also called epidermoid carcinoma. [NIH] Squamous cell carcinoma: Cancer that begins in squamous cells, which are thin, flat cells resembling fish scales. Squamous cells are found in the tissue that forms the surface of the skin, the lining of the hollow organs of the body, and the passages of the respiratory and
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digestive tracts. Also called epidermoid carcinoma. [NIH] Squamous cells: Flat cells that look like fish scales under a microscope. These cells cover internal and external surfaces of the body. [NIH] State Government: The level of governmental organization and function below that of the national or country-wide government. [NIH] Stem cell transplantation: A method of replacing immature blood-forming cells that were destroyed by cancer treatment. The stem cells are given to the person after treatment to help the bone marrow recover and continue producing healthy blood cells. [NIH] Stem Cells: Relatively undifferentiated cells of the same lineage (family type) that retain the ability to divide and cycle throughout postnatal life to provide cells that can become specialized and take the place of those that die or are lost. [NIH] Stenosis: Narrowing or stricture of a duct or canal. [EU] Sterile: Unable to produce children. [NIH] 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]
Strand: DNA normally exists in the bacterial nucleus in a helix, in which two strands are coiled together. [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] Stricture: The abnormal narrowing of a body opening. Also called stenosis. [NIH] Stringency: Experimental conditions (e. g. temperature, salt concentration) used during the hybridization of nucleic acids. [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] 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] Structure-Activity Relationship: The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size,
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stereochemical arrangement, and distribution of functional groups. Other factors contributing to structure-activity relationship include chemical reactivity, electronic effects, resonance, and inductive effects. [NIH] Subacute: Somewhat acute; between acute and chronic. [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] 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] 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] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Suramin: A polyanionic compound with an unknown mechanism of action. It is used parenterally in the treatment of African trypanosomiasis and it has been used clinically with diethylcarbamazine to kill the adult Onchocerca. (From AMA Drug Evaluations Annual, 1992, p1643) It has also been shown to have potent antineoplastic properties. [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] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] 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] Systemic disease: Disease that affects the whole body. [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] Teratogenic: Tending to produce anomalies of formation, or teratism (= anomaly of formation or development : condition of a monster). [EU] Therapeutics: The branch of medicine which is concerned with the treatment of diseases,
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palliative or curative. [NIH] Thermal: Pertaining to or characterized by heat. [EU] 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] 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] Thymidine: A chemical compound found in DNA. Also used as treatment for mucositis. [NIH]
Thymidine Phosphorylase: The enzyme catalyzing the transfer of 2-deoxy-D-ribose from thymidine to orthophosphate, thereby liberating thymidine. EC 2.4.2.4. [NIH] Thymosin: A family of heat-stable, polypeptide hormones secreted by the thymus gland. Their biological activities include lymphocytopoiesis, restoration of immunological competence and enhancement of expression of T-cell characteristics and function. They have therapeutic potential in patients having primary or secondary immunodeficiency diseases, cancer or diseases related to aging. [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] Thymus Gland: A single, unpaired primary lymphoid organ situated in the mediastinum, extending superiorly into the neck to the lower edge of the thyroid gland and inferiorly to the fourth costal cartilage. It is necessary for normal development of immunologic function early in life. By puberty, it begins to involute and much of the tissue is replaced by fat. [NIH] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH] Thyroxine: An amino acid of the thyroid gland which exerts a stimulating effect on thyroid metabolism. [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] Tomography: Imaging methods that result in sharp images of objects located on a chosen plane and blurred images located above or below the plane. [NIH] Topical: On the surface of the body. [NIH]
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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] Toxin: A poison; frequently used to refer specifically to a protein produced by some higher plants, certain animals, and pathogenic bacteria, which is highly toxic for other living organisms. Such substances are differentiated from the simple chemical poisons and the vegetable alkaloids by their high molecular weight and antigenicity. [EU] Trachea: The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi. [NIH] 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] Transfusion: The infusion of components of blood or whole blood into the bloodstream. The blood may be donated from another person, or it may have been taken from the person earlier and stored until needed. [NIH] Translating: Conversion from one language to another language. [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 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] 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] Treatment Failure: A measure of the quality of health care by assessment of unsuccessful results of management and procedures used in combating disease, in individual cases or series. [NIH]
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Hepatitis B Virus
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] Trypanosomiasis: Infection with protozoa of the genus Trypanosoma. [NIH] Trypsin: A serine endopeptidase that is formed from trypsinogen in the pancreas. It is converted into its active form by enteropeptidase in the small intestine. It catalyzes hydrolysis of the carboxyl group of either arginine or lysine. EC 3.4.21.4. [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] Tumor Necrosis Factor: Serum glycoprotein produced by activated macrophages and other mammalian mononuclear leukocytes which has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. It mimics the action of endotoxin but differs from it. It has a molecular weight of less than 70,000 kDa. [NIH] Tumor suppressor gene: Genes in the body that can suppress or block the development of cancer. [NIH] Tumor-derived: Taken from an individual's own tumor tissue; may be used in the development of a vaccine that enhances the body's ability to build an immune response to the tumor. [NIH] Tupaia: A genus of tree shrews of the family Tupaiidae which consists of about 12 species. One of the most frequently encountered species is T. glis. Members of this genus inhabit rain forests and secondary growth areas in southeast Asia. [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] Universal Precautions: Prudent standard preventive measures to be taken by professional and other health personnel in contact with persons afflicted with a communicable disease, to avoid contracting the disease by contagion or infection. Precautions are especially applicable in the diagnosis and care of AIDS patients. [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [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] Urokinase: A drug that dissolves blood clots or prevents them from forming. [NIH] 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 adjuvant: A substance added to a vaccine to improve the immune response so that less vaccine is needed. [NIH] Vaccines: Suspensions of killed or attenuated microorganisms (bacteria, viruses, fungi, protozoa, or rickettsiae), antigenic proteins derived from them, or synthetic constructs, administered for the prevention, amelioration, or treatment of infectious and other diseases.
Dictionary 317
[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] 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] Vascular endothelial growth factor: VEGF. A substance made by cells that stimulates new blood vessel formation. [NIH] Vasculitis: Inflammation of a blood vessel. [NIH] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [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] Venoms: Poisonous animal secretions forming fluid mixtures of many different enzymes, toxins, and other substances. These substances are produced in specialized glands and secreted through specialized delivery systems (nematocysts, spines, fangs, etc.) for disabling prey or predator. [NIH] 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] Vesicular: 1. Composed of or relating to small, saclike bodies. 2. Pertaining to or made up of vesicles on the skin. [EU] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [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] Viraemia: The presence of virus in blood or blood plasma. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] 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 Proteins: Proteins found in any species of virus. [NIH] Viral Regulatory Proteins: Proteins which regulate the rate of transcription of viral structural genes. [NIH]
318
Hepatitis B Virus
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 be used to carry genes that can change cancer cells back to normal cells. [NIH] Viremia: The presence of viruses in the blood. [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] 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] 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 Activation: The mechanism by which latent viruses, such as genetically transmitted tumor viruses or prophages of lysogenic bacteria, are induced to replicate and are released as infectious viruses. It may be effected by various endogenous and exogenous stimuli, including B-cell lipopolysaccharides, glucocorticoid hormones, halogenated pyrimidines, ionizing radiation, ultraviolet light, and superinfecting viruses. [NIH] Virus Diseases: A general term for diseases produced by viruses. [NIH] Virus Integration: Insertion of viral DNA into host-cell DNA. This includes integration of phage DNA into bacterial DNA (lysogeny) to form a prophage or integration of retroviral DNA into cellular DNA to form a provirus. [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] Visual field: The entire area that can be seen when the eye is forward, including peripheral vision. [NIH] Vitelline Membrane: The plasma membrane of the egg. [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] Warts: Benign epidermal proliferations or tumors; some are viral in origin. [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]
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]
Dictionary 319
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] 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] Yolk Sac: An embryonic membrane formed from endoderm and mesoderm. In reptiles and birds it incorporates the yolk into the digestive tract for nourishing the embryo. In placental mammals its nutritional function is vestigial; however, it is the source of most of the intestinal mucosa and the site of formation of the germ cells. It is sometimes called the vitelline sac, which should not be confused with the vitelline membrane of the egg. [NIH] Zalcitabine: A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by a hydrogen. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. The compound is a potent inhibitor of HIV replication at low concentrations, acting as a chainterminator of viral DNA by binding to reverse transcriptase. Its principal toxic side effect is axonal degeneration resulting in peripheral neuropathy. [NIH] Zidovudine: A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by an azido group. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. The compound is a potent inhibitor of HIV replication, acting as a chain-terminator of viral DNA during reverse transcription. It improves immunologic function, partially reverses the HIVinduced neurological dysfunction, and improves certain other clinical abnormalities associated with AIDS. Its principal toxic effect is dose-dependent suppression of bone marrow, resulting in anemia and leukopenia. [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] 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]
321
INDEX A Abdominal, 171, 175, 176, 187, 253, 262, 298, 299 Abdominal Pain, 171, 175, 176, 187, 253 Aberrant, 65, 83, 253 Academic Medical Centers, 12, 253 Acceptor, 62, 253, 288, 297, 315 Accommodation, 212, 253 Acetaminophen, 253, 276 Acetylcholine, 253, 274, 295 Acquired Immunodeficiency Syndrome, 176, 253 Actin, 253, 294 Acute myelogenous leukemia, 111, 253 Acute myeloid leukemia, 253 Acute nonlymphocytic leukemia, 253 Acute renal, 253, 280 Acyclovir, 200, 253, 276 Adaptability, 253, 262 Adduct, 49, 254 Adenine, 81, 159, 182, 254 Adenocarcinoma, 254, 281 Adjuvant, 32, 40, 151, 169, 181, 207, 208, 254, 277 Adolescence, 254, 299 Adoptive Transfer, 28, 206, 254 Adverse Effect, 36, 254, 257, 310 Aerobic, 254, 292 Affinity, 68, 89, 114, 168, 191, 254 Aflatoxin B1, 146, 254 Aflatoxins, 48, 58, 254 Agar, 55, 254, 268, 284 Age-Adjusted, 22, 254 Alanine, 9, 254 Albumin, 23, 48, 255, 300 Algorithms, 255, 260 Alimentary, 255, 298 Alkaline, 179, 255, 261 Alleles, 139, 255 Allogeneic, 125, 255, 278 Allograft, 7, 53, 140, 255 Alpha-fetoprotein, 255, 275 Alternative medicine, 224, 255 Alum, 40, 255 Aluminum, 255 Ameliorating, 201, 206, 255 Amino Acid Sequence, 174, 175, 181, 184, 255, 256, 277
Amino Acid Substitution, 115, 170, 199, 255 Amino-terminal, 39, 256 Amplification, 54, 67, 68, 71, 73, 89, 133, 134, 170, 188, 196, 256 Ampulla, 212, 256, 263 Anaemia, 256, 257 Anaesthesia, 256, 285 Anal, 14, 20, 256, 273, 288 Analog, 53, 74, 253, 256, 276, 287 Analogous, 60, 256, 315 Anaphylatoxins, 256, 266 Anemia, 256, 274, 290, 319 Angiogenesis, 104, 256 Animal model, 29, 38, 48, 49, 58, 60, 192, 193, 202, 214, 215, 256 Anions, 255, 256, 287 Annealing, 256, 301 Antibacterial, 256, 271, 311 Antibiotic, 256, 257, 261, 276, 311, 317 Anticarcinogenic, 48, 257 Anticoagulant, 257, 270, 303 Antigen-Antibody Complex, 257, 265 Antigen-presenting cell, 257, 269 Anti-inflammatory, 253, 257, 278 Antimetabolite, 253, 257, 269, 292, 308 Antineoplastic, 257, 292, 313, 317 Antioxidant, 35, 257, 274, 298 Antiproliferative, 200, 257 Antiviral Agents, 29, 51, 53, 60, 153, 164, 165, 175, 200, 215, 257 Anus, 256, 257, 265 Aphidicolin, 147, 257 Aplastic anaemia, 136, 257 Apolipoproteins, 257, 288 Apoptosis, 14, 34, 51, 59, 62, 83, 90, 122, 143, 258 Aqueous, 199, 258, 268, 272, 282, 287 Arenavirus, 258, 289 Arginine, 182, 201, 256, 258, 281, 316 Arterial, 258, 262, 264, 283, 304 Arteries, 258, 260, 262, 267, 289, 292, 301 Artery, 258, 260, 267, 305, 309, 317 Ascites, 212, 258 Aseptic, 258, 289, 297 Aspartic, 88, 198, 258, 273 Aspartic Acid, 88, 258 Aspiration, 258, 275
322
Hepatitis B Virus
Asymptomatic, 4, 25, 102, 113, 146, 152, 165, 167, 171, 184, 198, 204, 219, 258, 280 Atrophy, 258, 301 Attenuated, 45, 52, 206, 258, 316 Autoimmune Hepatitis, 214, 215, 258, 281 Autolysis, 206, 258 Autopsy, 112, 258, 291 Avian, 57, 69, 77, 148, 194, 258 B Bacteremia, 258, 260 Bactericidal, 259, 274 Bacteriophage, 259, 315 Bacterium, 259, 265, 266, 280, 290, 297, 307 Base Sequence, 259, 276, 277 Basophils, 259, 279, 287 Benign, 25, 212, 259, 279, 289, 294, 298, 318 Beta-glucans, 259, 262 Bilateral, 259, 307 Bile, 212, 259, 263, 276, 282, 287, 288, 302, 312 Bile Acids, 259, 312 Bile Acids and Salts, 259 Bile duct, 212, 259, 263, 302 Bile Pigments, 259, 287 Biliary, 146, 147, 212, 215, 259, 263 Biliary Tract, 212, 259 Bilirubin, 204, 255, 259, 282 Binding Sites, 177, 259 Bioavailability, 14, 259 Biological therapy, 259, 279 Bioluminescence, 259, 289 Biomarkers, 21, 48, 62, 64, 260 Biopsy, 212, 215, 260, 299 Biosynthesis, 69, 90, 260, 303, 310 Biotechnology, 66, 97, 188, 224, 235, 260 Biotransformation, 58, 260 Bladder, 260, 266, 295, 303, 316 Blast phase, 260, 264 Blood Coagulation, 260, 261, 314 Blood pressure, 260, 283, 293, 302 Blood transfusion, 165, 178, 204, 260 Blood vessel, 256, 260, 261, 263, 280, 289, 292, 299, 311, 312, 314, 317 Blood-Borne Pathogens, 3, 221, 260 Blot, 18, 196, 260 Body Fluids, 103, 178, 197, 219, 220, 260, 271, 272, 316 Bone Marrow Cells, 80, 206, 261, 279, 291 Bone Marrow Transplantation, 125, 132, 206, 261 Bowel, 256, 261, 286, 287, 295 Broad-spectrum, 261, 270
Buccal, 261, 312 Buffers, 32, 261 C Calcium, 59, 68, 187, 261, 265, 272, 303 Capsid, 64, 70, 72, 82, 84, 92, 96, 100, 173, 181, 189, 206, 261, 296, 318 Capsular, 52, 261 Carbohydrate, 166, 261, 278, 301, 310 Carboxy, 194, 209, 261 Carboxy-terminal, 194, 209, 261 Carcinogen, 48, 49, 58, 62, 254, 261 Carcinogenesis, 49, 58, 120, 261, 263 Carcinogenic, 58, 261, 285, 296, 303, 312 Carcinogenicity, 49, 261 Cardiac, 17, 261, 269, 274, 276, 294, 312 Cardiovascular, 108, 261 Carotene, 261, 307 Carotenoids, 22, 261 Carrier State, 167, 171, 191, 203, 204, 208, 219, 262 Case report, 112, 113, 262 Catalyse, 189, 262 Catastrophic Illness, 212, 262 Cations, 262, 287 Causal, 262, 273, 310 Cause of Death, 21, 171, 262, 269 Celiac Artery, 262, 280 Cell Cycle, 18, 34, 57, 262, 268, 304 Cell Death, 34, 51, 59, 167, 258, 262, 294 Cell Division, 30, 258, 262, 268, 279, 291, 293, 300, 303, 309 Cell proliferation, 86, 257, 262, 304 Cell Respiration, 262, 292, 307 Cell Size, 262, 275 Cell Survival, 262, 279 Cell Transplantation, 262 Cellulase, 194, 262 Cellulose, 262, 276, 300 Central Nervous System, 16, 26, 38, 201, 253, 255, 262, 279, 297, 301 Centrifugation, 166, 179, 262 Cerebrospinal, 13, 263 Cerebrospinal fluid, 13, 263 Character, 263, 269 Chemical Warfare, 263, 269 Chemical Warfare Agents, 263, 269 Chemokines, 54, 263 Chemoprevention, 49, 263 Chemopreventive, 48, 263 Chemoprotective, 49, 263 Chemotactic Factors, 263, 266
323
Chemotherapy, 113, 114, 119, 123, 124, 148, 152, 157, 158, 263, 309 Child Care, 218, 263 Chimeras, 77, 263 Chin, 80, 147, 154, 155, 263, 291 Chloroform, 71, 263 Chlorophyll, 263, 276 Cholangitis, 212, 263 Cholera, 263, 310 Cholestasis, 212, 263 Cholesterol, 259, 263, 264, 271, 283, 288, 289, 312 Cholesterol Esters, 264, 288 Chorioretinitis, 264, 307 Choroid, 264, 307 Chromatin, 61, 258, 264, 311 Chromosomal, 256, 264, 281, 300, 309 Chromosome, 264, 266, 279, 288, 304, 309 Chronic Disease, 36, 202, 212, 214, 264 Chronic lymphocytic leukemia, 264 Chronic myelogenous leukemia, 260, 264 Chronic phase, 51, 264 Chronic renal, 10, 264 Chylomicrons, 264, 288 CIS, 66, 70, 98, 102, 138, 264, 307 Cleave, 33, 70, 182, 264 Clinical Medicine, 264, 302 Clinical trial, 4, 11, 12, 13, 15, 16, 17, 20, 26, 42, 50, 53, 63, 124, 193, 235, 264, 267, 271, 304, 305 Clone, 51, 183, 205, 208, 264 Cloning, 8, 71, 103, 173, 179, 260, 264, 285 Codon, 33, 38, 94, 136, 204, 265, 277, 306 Cofactor, 34, 61, 131, 265, 304, 314 Cohort Studies, 11, 37, 265, 273 Collagen, 255, 265, 277 Colloidal, 255, 265 Colon, 6, 265, 287 Colorectal, 21, 259, 265, 304 Colorectal Cancer, 21, 259, 265, 304 Communicable disease, 265, 316 Competency, 198, 265 Complement, 38, 196, 256, 265, 266, 277, 290, 300 Complementary and alternative medicine, 151, 160, 266 Complementary medicine, 151, 266 Complementation, 18, 266 Compliance, 14, 40, 42, 103, 266 Computational Biology, 235, 266 Computed tomography, 212, 266 Computerized axial tomography, 266
Computerized tomography, 266 Conception, 266, 275 Concomitant, 59, 266 Cones, 266, 307 Conjugated, 259, 266, 268 Conjugation, 260, 266 Conjunctiva, 267, 285 Connective Tissue, 261, 265, 267, 275, 277, 289, 292, 308, 309, 312 Consciousness, 267, 269, 271, 280, 304 Constitutional, 267, 307 Constriction, 267, 309 Contamination, 260, 267, 280, 281 Contraindications, ii, 267 Control group, 35, 267 Convalescence, 180, 267 Cooperative group, 12, 267 Coronary, 267, 292 Coronary Thrombosis, 267, 292 Cortisol, 255, 267 Cowpox, 267, 317 Cowpox Virus, 267, 317 Crossing-over, 267, 306 Cross-Sectional Studies, 267, 273 Cryoelectron Microscopy, 84, 267 Culture Media, 254, 268 Cultured cells, 203, 268 Curative, 187, 268, 314 Cutaneous, 268, 317 Cyclic, 189, 268 Cyclin, 128, 268 Cysteine, 62, 85, 90, 201, 209, 263, 268, 273, 313 Cystine, 268 Cytochrome, 49, 268 Cytogenetics, 268, 309 Cytokine, 29, 52, 72, 143, 200, 268 Cytomegalovirus, 13, 15, 81, 108, 268, 276 Cytomegalovirus Infections, 81, 268, 276 Cytoplasm, 60, 258, 259, 268, 273, 293, 308 Cytosine, 66, 268, 305 Cytotoxic chemotherapy, 104, 111, 124, 132, 268 Cytotoxicity, 153, 207, 268 D Data Collection, 23, 56, 269, 276 Deamination, 269, 270 Death Certificates, 21, 269 Decompensation, 7, 8, 269 Decontamination, 221, 269 Degenerative, 197, 269, 280 Deletion, 67, 77, 98, 134, 258, 269
324
Hepatitis B Virus
Delivery of Health Care, 269, 278 Dementia, 13, 14, 16, 17, 47, 253, 269 Denaturation, 196, 269, 301 Dendrites, 269, 295 Dendritic, 47, 59, 136, 269, 291 Dendritic cell, 47, 59, 136, 269 Density, 61, 179, 263, 269, 271, 275, 288, 296, 311 Dental Waste, 260, 269 Deoxyglucose, 125, 269 Deoxyguanosine, 35, 48, 74, 82, 269 Dermatitis, 257, 269 Desensitization, 269, 284 Detoxification, 58, 218, 269 Developed Countries, 27, 269 Developing Countries, 27, 175, 176, 269 Dextran Sulfate, 191, 270 Diagnostic procedure, 163, 224, 270 Dialyzer, 270, 280 Didanosine, 270 Dideoxyadenosine, 175, 270 Dideoxynucleosides, 51, 270 Diethylcarbamazine, 270, 313 Digestion, 255, 259, 261, 270, 286, 288, 312 Digestive tract, 270, 310, 311, 312, 319 Dimerization, 61, 270 Diploid, 266, 270, 300 Direct, iii, 9, 19, 21, 23, 39, 46, 49, 73, 92, 106, 146, 204, 207, 219, 227, 264, 270, 303, 306 Discrete, 40, 168, 270, 319 Discrimination, 212, 270 Disease Transmission, 215, 270, 271 Disease Transmission, Horizontal, 270, 271 Disease Transmission, Vertical, 270, 271 Disinfectant, 271, 274 Disinfection, 220, 221, 222, 271 Disposition, 63, 271 Dissociation, 254, 271 Distal, 271, 299 Dose-dependent, 271, 319 Double-blind, 32, 271 Drive, ii, vi, 4, 10, 14, 15, 18, 41, 145, 174, 214, 240, 241, 271 Drug Interactions, 13, 14, 63, 228, 229, 271 Drug Resistance, 18, 25, 85, 94, 271 Drug Tolerance, 271, 314 Duct, 256, 271, 274, 289, 309, 312 Duodenum, 259, 271, 280, 312 Dyslipidemia, 102, 271 Dysplasia, 14, 272
Dyspnea, 269, 272 E Ebola Virus, 218, 272 Edema, 269, 272 Effector, 38, 52, 54, 253, 265, 272 Efficacy, 6, 19, 22, 45, 49, 50, 53, 58, 60, 67, 74, 87, 108, 126, 147, 154, 190, 192, 199, 201, 272 Ejaculation, 272, 310 Elective, 91, 136, 272 Electrolytes, 259, 272 Electrons, 257, 272, 287, 290, 298, 305 Elementary Particles, 272, 290, 304 Emaciation, 253, 272 Embryo, 272, 273, 285, 292, 319 Emergency Medical Technicians, 221, 272 Emulsions, 254, 272 Encapsulated, 186, 272 Encephalitis, 171, 272, 273 Encephalomyelitis, 38, 272 Endemic, 6, 37, 62, 65, 78, 83, 263, 273, 280, 290 Endocrinology, 273, 279 Endoderm, 273, 319 Endogenous, 179, 273, 315, 318 Endopeptidases, 273, 303 Endoscopy, 132, 212, 273 Endotoxins, 265, 273 End-stage renal, 264, 273 Enhancer, 29, 68, 75, 77, 79, 82, 83, 85, 88, 90, 93, 94, 113, 157, 197, 273 Enteropeptidase, 273, 316 Environmental Exposure, 62, 273, 296 Environmental Health, 48, 234, 236, 273 Enzymatic, 55, 75, 187, 255, 261, 265, 270, 273, 301, 307 Enzyme Inhibitors, 189, 273, 300 Eosinophil, 273, 279 Epidemic, 5, 17, 20, 36, 56, 75, 175, 176, 186, 218, 273 Epidemiologic Studies, 65, 273, 278 Epidemiological, 8, 53, 58, 109, 123, 129, 183, 203, 205, 273 Epidermal, 273, 291, 318 Epidermis, 273, 274, 305 Epidermoid carcinoma, 274, 311, 312 Epigastric, 274, 298 Epinephrine, 274, 295, 316 Epithelial, 254, 274, 298 Epithelium, 274, 276, 298, 319 Epitope, 29, 70, 72, 74, 86, 143, 168, 170, 175, 180, 184, 194, 201, 204, 274
325
Equine Infectious Anemia, 83, 148, 274 Erythrocytes, 256, 260, 274, 306 Esophagus, 270, 274, 299, 312 Ethanol, 28, 29, 35, 274 Ethidium, 179, 274 Ethnic Groups, 16, 274 Ethoxyquin, 58, 274 Eukaryotic Cells, 257, 274, 284, 296, 297 Excipient, 40, 181, 274 Excitation, 274, 275, 295 Exhaustion, 38, 59, 274, 290 Exocrine, 274, 298 Exogenous, 33, 202, 207, 260, 273, 275, 277, 318 Extracellular, 267, 275, 293 Extraction, 71, 75, 108, 133, 157, 275 F Family Planning, 235, 275 Fat, 259, 260, 261, 275, 288, 308, 311, 314 Fatigue, 175, 176, 214, 218, 275 Fetoprotein, 65, 93, 275 Fetus, 199, 255, 275, 283, 302, 316 Fibrinogen, 275, 300, 314 Fibrosis, 7, 165, 275 Filovirus, 272, 275 Fixatives, 268, 275 Flow Cytometry, 46, 275 Fludarabine, 119, 275 Fluorescence, 30, 134, 196, 274, 275 Fluorescent Dyes, 275 Focus Groups, 43, 276 Fold, 22, 25, 276, 296 Fractionation, 46, 64, 276 Frameshift, 33, 276 Frameshift Mutation, 33, 276 Free Radicals, 257, 271, 276 Fulminant Hepatic Failure, 214, 215, 276 Fungemia, 260, 276 Fungi, 254, 257, 260, 262, 266, 276, 292, 294, 308, 311, 316, 319 Fungus, 194, 276, 310 G Gallbladder, 212, 253, 259, 276, 280 Ganciclovir, 131, 276 Gangrenous, 276, 310 Gas, 276, 282, 295 Gastric, 22, 110, 259, 262, 276 Gastric Mucosa, 110, 276 Gastrin, 277, 282 Gastrointestinal, 34, 63, 201, 274, 277, 290, 313, 316 Gastrointestinal tract, 63, 274, 277, 316
Gelatin, 268, 277, 278, 314 Gene Targeting, 203, 277 Gene Therapy, 100, 137, 214, 277 Genetic Code, 277, 296 Genetic Engineering, 8, 60, 176, 198, 260, 264, 277 Genetic testing, 277, 301 Genetic transcription, 277, 303, 315 Genital, 200, 277, 279 Genomics, 198, 204, 277 Geographic Locations, 38, 277 Germ Cells, 278, 291, 296, 311, 319 Gestation, 278, 299 Gland, 278, 289, 291, 298, 303, 309, 312, 314 Glomerular, 278 Glomeruli, 278 Glomerulonephritis, 139, 278 Glucocorticoid, 43, 278, 318 Glucose, 262, 269, 270, 278, 280, 286, 309 Glucosidases, 50, 61, 278 Glucosinolates, 58, 278 Glutathione Peroxidase, 35, 278, 309 Glycine, 56, 255, 259, 278, 295, 310 Glycoprotein, 61, 63, 181, 275, 278, 279, 314, 316 Glycosidic, 278, 296 Glycosylation, 61, 90, 156, 278 Gonadal, 278, 312 Governing Board, 278, 302 Graft, 7, 278, 284 Graft Rejection, 278, 284 Granule, 279, 308 Granulocyte, 6, 108, 279 Granulocyte-Macrophage ColonyStimulating Factor, 108, 279 Granulocytopenia, 257, 279 Granulomas, 212, 279 Growth factors, 200, 279 Guanine, 269, 279 Guinea Pigs, 279, 289 Gynecology, 15, 42, 279 H Handwashing, 220, 221, 279 Haploid, 279, 300 Haptens, 254, 279 Headache, 279, 285, 301 Health Behavior, 41, 279 Health Education, 218, 279 Health Services, 31, 36, 269, 279 Health Status, 279 Hematology, 212, 280
326
Hepatitis B Virus
Heme, 259, 268, 280 Hemodialysis, 115, 204, 217, 270, 280 Hemoglobin, 256, 274, 280, 287 Hemoglobinopathies, 277, 280 Hemolytic, 71, 280 Hemorrhage, 279, 280, 305, 312 Hepadnaviridae, 165, 194, 198, 280, 297 Hepatic Artery, 212, 280 Hepatic Encephalopathy, 212, 280 Hepatitis, Chronic, 198, 281 Hepatoblastoma, 80, 86, 88, 114, 129, 281 Hepatocellular, 4, 5, 6, 7, 8, 10, 18, 19, 21, 22, 25, 27, 28, 30, 34, 37, 39, 40, 46, 47, 49, 51, 54, 56, 64, 67, 73, 75, 77, 85, 98, 100, 101, 104, 105, 114, 115, 117, 119, 120, 122, 125, 127, 131, 138, 155, 156, 166, 167, 168, 171, 173, 174, 175, 176, 183, 184, 191, 195, 196, 198, 199, 202, 204, 205, 209, 212, 214, 215, 240, 241, 281, 297 Hepatocyte, 23, 34, 54, 72, 78, 84, 86, 89, 175, 181, 186, 195, 203, 263, 281 Hepatoma, 38, 64, 70, 73, 74, 80, 88, 92, 104, 122, 125, 152, 156, 171, 183, 205, 281 Hepatotoxic, 254, 281 Hepatotoxicity, 35, 44, 281 Hepatovirus, 280, 281 Heredity, 277, 281 Herpes, 15, 24, 38, 77, 137, 253, 281, 317 Herpes virus, 15, 24, 38, 281, 317 Herpes Zoster, 281 Heterodimer, 59, 281 Heterogeneity, 114, 254, 281 Heterogenic, 281 Heterogenous, 186, 281 Histocompatibility, 168, 281 Histology, 6, 130, 281 Histones, 264, 281 Homeless Persons, 28, 282 Homeostasis, 27, 282 Homologous, 60, 84, 95, 169, 191, 202, 255, 267, 277, 282, 294, 304, 309 Homosexuality, 204, 282 Hormonal, 26, 258, 282 Hormonal therapy, 26, 282 Hormone, 84, 90, 95, 148, 183, 205, 267, 274, 277, 282, 286, 302, 308, 314 Hormone therapy, 282 Host-cell, 282, 318 Housekeeping, 3, 221, 222, 282 Human papillomavirus, 64, 282 Humoral, 29, 38, 45, 70, 168, 171, 278, 282
Humour, 282 Hybrid, 71, 79, 179, 181, 190, 192, 264, 282 Hybridoma, 168, 282 Hydration, 40, 282 Hydrogen, 253, 261, 269, 270, 278, 282, 288, 293, 297, 304, 319 Hydrogen Peroxide, 278, 282, 288 Hydrolysis, 258, 260, 282, 299, 301, 304, 316 Hydrophobic, 282, 288 Hydroxyproline, 255, 265, 282 Hyperbilirubinemia, 282, 287 Hypercholesterolemia, 271, 283 Hyperlipidemia, 271, 283 Hypersensitivity, 269, 273, 283, 308 Hypertension, 279, 283, 302 Hypertriglyceridemia, 271, 283 Hypoxia, 156, 283 I Immune adjuvant, 255, 283 Immune Sera, 283 Immune system, 24, 184, 190, 202, 219, 257, 258, 259, 283, 284, 289, 290, 318 Immune Tolerance, 32, 185, 206, 283 Immunization Schedule, 11, 283 Immunoassay, 22, 69, 75, 86, 89, 91, 128, 204, 283 Immunochemistry, 147, 173, 283 Immunocompromised, 10, 49, 87, 200, 215, 283 Immunocompromised Host, 215, 283 Immunodeficiency syndrome, 220, 222, 283 Immunodiffusion, 254, 283, 284 Immunodominant Epitopes, 168, 284 Immunoelectrophoresis, 254, 284 Immunogen, 189, 190, 194, 209, 284 Immunogenic, 177, 189, 190, 193, 194, 209, 284 Immunoglobulin, 126, 200, 256, 284, 293 Immunohistochemistry, 105, 284 Immunologic, 12, 13, 14, 16, 36, 46, 254, 263, 283, 284, 314, 319 Immunosuppressant, 284, 292 Immunosuppression, 240, 254, 284, 289, 297, 313 Immunosuppressive, 136, 200, 278, 283, 284 Immunosuppressive Agents, 284 Immunosuppressive therapy, 136, 284 Immunotherapy, 51, 80, 126, 192, 254, 259, 269, 284
327
Impairment, 263, 284, 291 In situ, 117, 147, 179, 186, 284 In Situ Hybridization, 147, 284 Incision, 284, 287 Incubated, 180, 285 Incubation, 52, 166, 175, 176, 180, 187, 188, 193, 197, 285 Incubation period, 52, 166, 175, 176, 187, 188, 193, 197, 285 Indolent, 119, 285 Induction, 27, 45, 49, 57, 58, 59, 68, 83, 91, 168, 203, 285, 290 Infancy, 212, 285 Infantile, 285, 301 Infarction, 267, 285, 292, 301 Infection Control, 103, 138, 213, 217, 220, 221, 285 Infiltration, 278, 285, 319 Influenza, 189, 194, 285, 289 Infusion, 285, 315 Ingestion, 21, 285, 301 Inhalation, 178, 285, 301 Initiation, 19, 33, 44, 45, 67, 76, 77, 82, 96, 136, 285, 297, 303, 307, 315 Inorganic, 285, 289, 294 Insertional, 26, 285 Insight, 34, 39, 40, 54, 286 Insulin, 114, 286 Insulin-dependent diabetes mellitus, 286 Insulin-like, 114, 286 Intensive Care, 103, 286 Interferon-alpha, 105, 114, 152, 286 Interleukin-1, 82, 117, 286 Interleukin-10, 117, 286 Interleukin-2, 80, 83, 286 Intermittent, 6, 274, 286, 289 Intestinal, 14, 206, 261, 273, 286, 319 Intestinal Mucosa, 206, 286, 319 Intestine, 259, 261, 265, 286, 287 Intoxication, 286, 318 Intracellular, 13, 15, 64, 83, 85, 96, 123, 141, 171, 187, 207, 285, 286, 308, 309, 318 Intrahepatic, 44, 52, 54, 81, 83, 133, 186, 286 Intramuscular, 286, 298 Intravenous, 15, 65, 78, 130, 229, 276, 285, 286, 298 Intrinsic, 254, 287 Invasive, 66, 287, 290 Invertebrates, 287, 289 Involuntary, 287, 294, 306 Ionizing, 273, 287, 290, 318
Ions, 30, 33, 261, 271, 272, 282, 287, 293, 298 J Jaundice, 166, 171, 175, 176, 187, 193, 204, 212, 218, 282, 287 K Kb, 18, 166, 183, 203, 205, 234, 287 Kidney Transplantation, 7, 287 Kinetics, 30, 47, 52, 123, 287 L Labile, 265, 287 Large Intestine, 265, 270, 286, 287, 306, 310 Latent, 42, 43, 125, 287, 318 Laxative, 254, 287 Lectin, 62, 287 Lens, 261, 287 Lesion, 287, 288 Lethal, 23, 259, 287 Leucine, 61, 287 Leukemia, 61, 119, 187, 264, 277, 287, 304 Leukocytes, 259, 260, 263, 286, 287, 293, 316 Leukoencephalopathy, 16, 287 Leukopenia, 287, 319 Life cycle, 34, 56, 60, 276, 288 Life Expectancy, 16, 288 Ligands, 189, 288 Linkage, 20, 62, 288 Lip, 219, 288 Lipid, 35, 166, 167, 258, 272, 286, 288, 298 Lipid Peroxidation, 35, 288, 298 Lipid Peroxides, 35, 288 Lipopolysaccharides, 288, 318 Lipoprotein, 17, 173, 188, 271, 288, 289, 318 Liver Cirrhosis, 4, 35, 56, 98, 111, 125, 164, 192, 195, 199, 204, 206, 208, 214, 288 Liver Transplantation, 10, 53, 65, 111, 113, 116, 126, 131, 133, 137, 211, 214, 215, 219, 288 Localization, 18, 43, 64, 84, 147, 284, 288 Localized, 272, 285, 288, 300 Locomotion, 288, 300 Longitudinal study, 23, 35, 132, 288 Long-Term Care, 20, 289 Loop, 39, 68, 83, 92, 93, 175, 194, 209, 289 Low-density lipoprotein, 271, 288, 289 Luminescence, 196, 289 Lung Transplantation, 141, 289 Lymph, 59, 282, 289 Lymph node, 59, 289 Lymphatic, 285, 289, 292, 311, 314
328
Hepatitis B Virus
Lymphatic system, 289, 311, 314 Lymphocyte, 46, 51, 72, 83, 87, 153, 167, 181, 195, 202, 206, 207, 253, 257, 284, 289, 290, 291 Lymphocyte Count, 253, 289 Lymphocyte Depletion, 284, 289 Lymphocytic, 168, 181, 289 Lymphocytic Choriomeningitis Virus, 168, 181, 289 Lymphoid, 13, 47, 52, 59, 157, 256, 289, 314 Lymphoma, 113, 119, 135, 148, 152, 158, 289 Lysine, 182, 281, 289, 316 Lysogeny, 289, 318 Lytic, 43, 290, 310 M Macrophage, 6, 279, 286, 290 Magnetic Resonance Imaging, 212, 290 Magnetic Resonance Spectroscopy, 13, 290 Major Histocompatibility Complex, 24, 86, 94, 168, 290 Malaria, 24, 52, 290 Malaria, Falciparum, 290 Malaria, Vivax, 290 Malignancy, 166, 290, 298 Malignant, 25, 65, 152, 212, 253, 254, 257, 288, 290, 294, 309 Malnutrition, 35, 255, 258, 290 Mandatory Testing, 212, 221, 290 Man-made, 18, 290 Mannans, 276, 291 Mastitis, 291, 310 Measles Virus, 45, 291 Mediator, 286, 291 Medical Waste, 222, 291 MEDLINE, 235, 291 Megakaryocytes, 261, 291 Meiosis, 291, 294 Melanin, 291, 300, 316 Melanocytes, 291 Melanoma, 192, 193, 291 Memory, 200, 269, 291, 307 Meninges, 262, 291 Meningitis, 289, 291 Menopause, 26, 291 Menstruation, 291 Mental, iv, 11, 31, 234, 236, 263, 269, 271, 275, 291, 304, 309 Mental Disorders, 31, 291 Mental Health, iv, 11, 234, 236, 291, 304 Mentors, 20, 291
Mercury, 275, 291 Mesenchymal, 279, 292 Mesoderm, 292, 319 Meta-Analysis, 124, 292 Metabolite, 260, 270, 292, 302 Metastasis, 59, 101, 292 Methionine, 174, 198, 292, 313 Methotrexate, 113, 292 MI, 78, 83, 96, 114, 115, 123, 251, 292 Mice Minute Virus, 292, 298 Microbe, 292, 315 Microcirculation, 288, 292, 301 Microorganism, 265, 292, 298, 318 Microscopy, Electron, 64, 292 Mitochondria, 27, 292, 297 Mitochondrial Swelling, 292, 294 Mitogen-Activated Protein Kinase Kinases, 292, 293 Mitogen-Activated Protein Kinases, 148, 292, 293 Mitosis, 258, 293 Mobility, 59, 293 Modeling, 42, 47, 49, 85, 293, 303 Modification, 201, 255, 270, 277, 293, 305, 319 Molecular Structure, 193, 293 Monitor, 10, 13, 22, 56, 69, 105, 185, 186, 196, 215, 293, 296 Monoclonal, 88, 89, 168, 184, 204, 293, 305, 308 Monoclonal antibodies, 168, 204, 293, 308 Monocytes, 117, 286, 287, 293 Mononuclear, 72, 108, 148, 293, 316 Monophosphate, 182, 270, 293 Monotherapy, 6, 50, 111, 293 Morbillivirus, 291, 293 Morphological, 166, 272, 276, 291, 293 Morphology, 92, 280, 293 Motion Sickness, 294 Mucins, 294, 308 Mucosa, 277, 294, 312 Mucositis, 294, 314 Mucus, 291, 294 Multivalent, 190, 294 Muscle Fibers, 173, 294 Mutagenesis, 26, 31, 46, 48, 51, 69, 294, 303 Mutagenic, 30, 254, 294 Mutagens, 276, 294 Myalgia, 285, 294 Mycotoxins, 58, 254, 294 Myelogenous, 294 Myeloma, 282, 294
329
Myocardium, 292, 294 Myosin, 59, 294 N Nasal Mucosa, 285, 294 Natural selection, 24, 294 Nausea, 218, 294 NCI, 1, 233, 264, 294 Necrosis, 40, 96, 167, 171, 173, 258, 278, 281, 285, 292, 294 Neonatal, 155, 294 Neoplasm, 294, 295, 298, 309 Neoplastic, 289, 295, 309 Nephropathy, 108, 159, 295 Nerve, 263, 269, 291, 295, 297, 299, 308, 312, 319 Nervous System, 262, 291, 295, 313 Networks, 12, 36, 56, 295 Neural, 275, 282, 295 Neural tube defects, 275, 295 Neurologic, 13, 15, 17, 47, 295 Neurology, 15, 38, 42, 295 Neuronal, 13, 295 Neurons, 269, 295 Neuropathy, 295, 299 Neuroretinitis, 295, 307 Neurotoxic, 295 Neurotoxicity, 182, 295 Neurotoxins, 13, 295 Neurotransmitter, 253, 255, 258, 278, 295, 313 Neutralization, 88, 121, 295 Night Blindness, 295, 307 Nitrogen, 119, 295 Nosocomial, 5, 221, 295 Nuclei, 60, 267, 272, 277, 281, 290, 293, 296, 297, 304 Nucleocapsid, 72, 77, 79, 89, 90, 92, 148, 166, 167, 168, 171, 172, 190, 194, 209, 296 Nucleolus, 296, 308 Nucleoprotein, 168, 181, 281, 296 Nucleus, 18, 43, 57, 186, 187, 258, 259, 264, 268, 272, 274, 291, 293, 296, 303, 304, 312 O Occult, 5, 86, 103, 112, 124, 130, 131, 223, 296 Occupational Exposure, 103, 213, 219, 220, 296 Odds Ratio, 296, 307 Oligosaccharides, 61, 64, 296 Oltipraz, 49, 58, 296 Omentum, 280, 296 Oncogene, 141, 149, 159, 175, 296
Oncogenic, 55, 296 Oocytes, 70, 296 Opacity, 269, 296 Open Reading Frames, 198, 296 Operon, 297, 303 Ophthalmology, 15, 42, 297 Opportunistic Infections, 13, 15, 17, 253, 297 Opsin, 297, 307, 308 Optic Nerve, 295, 297, 307 Organ Culture, 297, 314 Organ Transplantation, 10, 208, 297 Organelles, 262, 268, 291, 293, 297 Ori region, 297, 307 Orthohepadnavirus, 280, 297 Osmotic, 255, 292, 297 Osteosarcoma, 297, 304 Outpatient, 22, 297 Overdose, 276, 297 Ovum, 278, 288, 297, 302, 318 Oxidation, 253, 257, 260, 268, 278, 288, 297, 298 Oxidation-Reduction, 260, 298 Oxidative Stress, 35, 48, 49, 84, 298 P P53 gene, 298, 303 Palate, 298, 312 Palliative, 298, 314 Pancreas, 212, 253, 260, 280, 286, 298, 316 Pancreatic, 182, 298 Papilloma, 24, 298 Papillomavirus, 298 Paralysis, 298, 301 Parasite, 62, 298 Parasitic, 24, 298, 308 Parenteral, 166, 172, 178, 193, 197, 199, 298 Partial remission, 298, 307 Particle, 70, 78, 166, 173, 179, 180, 186, 188, 190, 290, 298, 311, 315, 318 Particle Accelerators, 290, 298 Parvovirus, 181, 292, 298 Pathogen, 33, 45, 63, 165, 174, 184, 188, 219, 221, 285, 298, 313 Pathologic, 184, 258, 260, 267, 275, 282, 283, 299, 304 Pathologic Processes, 258, 299 Pathophysiology, 214, 240, 299 Patient Education, 240, 246, 248, 251, 299 Pediatrics, 20, 41, 50, 65, 138, 146, 225, 242, 299 Pelvis, 299, 316
330
Hepatitis B Virus
Peptide, 24, 33, 67, 84, 109, 120, 137, 142, 167, 168, 170, 171, 181, 184, 189, 190, 192, 193, 206, 207, 209, 255, 273, 299, 301, 303, 304 Peptide Fragments, 171, 299 Perceived risk, 41, 299 Percutaneous, 23, 299 Perfusion, 283, 299 Perinatal, 9, 10, 32, 125, 208, 225, 299 Peripheral blood, 13, 108, 117, 119, 125, 148, 168, 257, 286, 299 Peripheral Neuropathy, 47, 299, 319 Peritoneal, 258, 299 Peritoneal Cavity, 258, 299 Pharmacodynamic, 14, 299 Pharmacokinetic, 13, 14, 299 Pharmacologic, 12, 13, 299, 315 Pharynx, 285, 299 Phenotype, 29, 38, 52, 66, 94, 203, 266, 299 Phenylalanine, 299, 316 Phospholipids, 275, 288, 300, 303 Phosphorus, 261, 300 Phosphorylated, 93, 270, 292, 300 Phosphorylation, 18, 43, 57, 59, 77, 87, 293, 300, 304 Physicochemical, 283, 300 Physiologic, 11, 31, 260, 291, 300, 306 Physiology, 24, 219, 273, 279, 280, 300, 313 Picornavirus, 45, 300 Pigment, 259, 291, 300 Pilot study, 65, 131, 300 Plants, 32, 199, 258, 278, 287, 293, 295, 300, 309, 311, 315, 316 Plasma, 13, 46, 64, 73, 89, 107, 137, 157, 173, 179, 254, 255, 256, 264, 275, 277, 280, 294, 300, 306, 310, 317, 318 Plasma cells, 256, 294, 300 Plasma protein, 255, 300 Plasmid, 177, 206, 300, 317 Plasmin, 300, 301 Plasminogen, 49, 300, 301 Plasminogen Activators, 300, 301 Platinum, 289, 301 Pneumonia, 267, 301 Point Mutation, 33, 129, 301 Poisoning, 286, 292, 294, 301 Poliomyelitis, 189, 301 Polyarteritis Nodosa, 137, 301 Polymerase Chain Reaction, 8, 37, 68, 73, 78, 129, 134, 158, 198, 301 Polymorphic, 24, 301 Polymorphism, 24, 100, 102, 132, 301
Polyposis, 265, 301 Polysaccharide, 153, 257, 262, 301 Polyvalent, 190, 301 Population Dynamics, 47, 301 Portal Hypertension, 212, 302 Posterior, 256, 264, 298, 302 Postnatal, 302, 312 Potentiate, 32, 169, 302 Potentiation, 169, 302 Practice Guidelines, 236, 302 Precancerous, 263, 302 Preclinical, 19, 192, 302 Precursor, 29, 179, 272, 273, 299, 300, 302, 316 Predictive factor, 134, 302 Prenatal, 117, 216, 272, 302 Prevalence, 5, 9, 10, 21, 22, 23, 27, 31, 34, 36, 49, 65, 78, 119, 133, 166, 296, 302 Primary Biliary Cirrhosis, 212, 214, 302 Probe, 71, 98, 109, 128, 146, 147, 179, 183, 191, 195, 205, 302 Prodrug, 175, 176, 302 Progeny, 25, 60, 87, 202, 266, 302 Progesterone, 302, 312 Progression, 9, 12, 13, 35, 44, 46, 57, 62, 113, 137, 198, 203, 219, 256, 302, 317 Progressive, 38, 165, 175, 176, 187, 264, 269, 271, 294, 302, 307 Promotor, 9, 206, 303 Prone, 167, 303 Prophase, 294, 296, 303 Prophylaxis, 12, 14, 16, 53, 110, 119, 124, 133, 155, 157, 182, 213, 221, 257, 303, 316 Prospective study, 11, 98, 288, 303 Prostate, 260, 303, 316 Prostitution, 27, 303 Protease, 13, 14, 47, 63, 69, 88, 194, 303 Protease Inhibitors, 13, 14, 63, 303 Protective Agents, 49, 303 Protective Clothing, 220, 221, 222, 303 Protein C, 25, 51, 84, 93, 148, 159, 177, 179, 181, 190, 201, 255, 257, 259, 265, 288, 303, 318 Protein Conformation, 255, 303 Protein Engineering, 194, 209, 303 Protein Kinase C, 292, 293, 303 Protein p53, 59, 303 Protein S, 30, 64, 202, 257, 260, 277, 303, 304, 308 Protein-Serine-Threonine Kinases, 293, 304 Proteolytic, 33, 265, 273, 275, 300, 301, 304
331
Protocol, 14, 15, 17, 46, 304 Protons, 282, 287, 290, 298, 304, 305 Proto-Oncogenes, 175, 203, 304 Protozoa, 260, 266, 292, 304, 311, 316 Protozoal, 304 Protozoan, 62, 290, 304 Provirus, 304, 318 Psoriasis, 257, 304 Psychic, 291, 304 Psychoactive, 304, 318 Public Health, 21, 24, 56, 58, 118, 124, 204, 206, 209, 236, 304 Public Policy, 235, 305 Public Sector, 9, 305 Publishing, 66, 216, 220, 305 Pulmonary, 171, 260, 305, 317 Pulse, 40, 293, 305 Purifying, 191, 305 Purpura, 142, 305 Pyrimidines, 259, 305, 310, 318 Q Quality of Health Care, 305, 315 Quality of Life, 17, 42, 52, 305 Quaternary, 94, 303, 305 Quiescent, 25, 305 R Race, 36, 135, 305 Radiation, 272, 273, 275, 276, 283, 284, 287, 290, 305, 309, 318, 319 Radiation therapy, 276, 305, 309 Radioactive, 146, 269, 282, 290, 293, 296, 305 Radioisotope, 180, 305 Radiological, 299, 305 Radiology, 212, 305 Randomized, 6, 11, 28, 41, 43, 53, 65, 272, 305 Reactivation, 7, 38, 104, 111, 113, 119, 124, 135, 136, 137, 152, 157, 158, 215, 306 Reactive Oxygen Species, 27, 35, 47, 306 Reading Frames, 24, 195, 306 Reagent, 270, 306 Recombinant Proteins, 180, 306 Recombination, 76, 93, 202, 266, 277, 306 Reconstitution, 12, 46, 57, 306 Rectum, 257, 265, 270, 276, 287, 303, 306 Recurrence, 53, 111, 125, 140, 263, 306 Red blood cells, 274, 280, 306, 309 Reductase, 292, 306 Refer, 1, 261, 265, 276, 281, 288, 296, 306, 315 Reflective, 12, 306
Reflex, 27, 306 Refraction, 306, 311 Regeneration, 25, 30, 172, 186, 306 Regimen, 44, 184, 272, 306, 308 Reinfection, 53, 133, 306 Relapse, 6, 44, 56, 134, 185, 215, 306 Relative risk, 39, 306 Reminder Systems, 65, 307 Remission, 10, 135, 306, 307 Replication Origin, 66, 89, 307 Resection, 203, 307 Respiration, 293, 307 Respirators, 197, 307 Reticulate, 142, 307 Retina, 264, 266, 287, 295, 297, 307, 308 Retinal, 43, 297, 307, 308 Retinitis, 42, 43, 307 Retinitis Pigmentosa, 43, 307 Retinoid, 90, 146, 307 Retinol, 307, 308 Retreatment, 157, 308 Retroviral vector, 70, 277, 308 Reversion, 96, 140, 308 Rheumatism, 137, 308 Rheumatoid, 113, 308 Rheumatoid arthritis, 113, 308 Rhinitis, 308, 310 Rhodopsin, 297, 307, 308 Ribavirin, 130, 200, 308 Ribose, 308, 314 Ribosome, 30, 308, 315 Rickettsiae, 308, 316 Risk factor, 17, 21, 22, 27, 31, 34, 90, 104, 118, 204, 219, 273, 303, 306, 308 Rituximab, 111, 113, 119, 308 Rods, 307, 308 S Saccharomyces, 64, 76, 147, 308, 319 Saccharomyces cerevisiae, 64, 76, 147, 308, 319 Saccharomycetales, 308 Saliva, 197, 269, 308, 309 Salivary, 66, 268, 308, 309 Salivary glands, 268, 308, 309 Salvage Therapy, 14, 309 Sanitation, 219, 221, 309 Saponins, 309, 312 Sarcoma, 47, 297, 309 Satellite, 15, 281, 309 Schizoid, 309, 318 Schizophrenia, 309, 318 Schizotypal Personality Disorder, 309, 318
332
Hepatitis B Virus
Secondary tumor, 292, 309 Secretory, 33, 94, 95, 309 Sediment, 309 Sedimentation, 179, 263, 309 Segregation, 306, 309 Selenium, 35, 150, 309 Semen, 47, 197, 272, 303, 310 Sensor, 22, 61, 310 Septicaemia, 310 Sequence Analysis, 71, 72, 183, 191, 205, 207, 310 Sequencing, 46, 64, 128, 173, 301, 310 Serine, 87, 273, 292, 303, 304, 310, 316 Seroconversion, 4, 7, 8, 11, 19, 23, 32, 124, 134, 310 Serologic, 66, 123, 283, 310 Serology, 21, 31, 108, 310 Serotypes, 52, 310 Sexual Partners, 197, 310 Sexually Transmitted Diseases, 9, 197, 310 Shock, 122, 162, 310, 315 Side effect, 19, 195, 227, 229, 254, 259, 270, 310, 315, 319 Signs and Symptoms, 3, 241, 301, 306, 307, 310 Sizofiran, 153, 310 Skin test, 21, 310 Skull, 295, 310, 313 Small intestine, 264, 271, 282, 286, 310, 316 Smallpox, 310, 317 Social Environment, 305, 311 Soft tissue, 260, 311 Solid tumor, 256, 311 Solvent, 199, 263, 274, 297, 311 Somatic, 254, 282, 291, 293, 299, 311 Sound wave, 306, 311 Specialist, 243, 311 Specificity, 26, 61, 80, 168, 178, 184, 206, 254, 273, 284, 311 Spectrum, 5, 119, 146, 200, 204, 206, 241, 311, 317 Sperm, 191, 264, 311 Spermatozoa, 310, 311 Spinal cord, 262, 263, 272, 291, 295, 306, 311 Spirochete, 311, 313 Spleen, 268, 282, 289, 311 Spores, 19, 311 Squamous, 138, 274, 311, 312 Squamous cell carcinoma, 138, 274, 311 Squamous cells, 311, 312 State Government, 26, 312
Stem cell transplantation, 125, 312 Stem Cells, 31, 312 Stenosis, 312 Sterile, 220, 258, 312 Sterilization, 220, 222, 312 Steroid, 158, 182, 183, 205, 259, 267, 309, 312 Stimulant, 29, 312 Stimulus, 271, 274, 306, 312 Stomach, 21, 32, 253, 270, 274, 276, 277, 280, 282, 294, 296, 299, 310, 311, 312 Stomatitis, 62, 312 Strand, 31, 39, 66, 76, 92, 98, 138, 148, 162, 166, 179, 186, 198, 301, 312 Stress, 3, 8, 35, 51, 62, 68, 106, 214, 225, 267, 293, 294, 298, 308, 312 Stricture, 212, 312 Stringency, 183, 205, 312 Stroke, 21, 234, 312 Stromal, 261, 312 Stromal Cells, 261, 312 Structure-Activity Relationship, 49, 312 Subacute, 285, 313 Subclinical, 5, 137, 165, 285, 313 Subcutaneous, 272, 276, 298, 313 Subspecies, 311, 313, 317 Substance P, 292, 306, 309, 313 Substrate, 62, 180, 187, 273, 313 Sulfur, 270, 287, 292, 313 Superinfection, 96, 99, 107, 120, 162, 313 Suppression, 14, 16, 44, 53, 84, 88, 92, 313, 319 Suramin, 200, 313 Survival Rate, 7, 202, 313 Symptomatic, 204, 313 Synergistic, 35, 157, 313 Syphilis, 9, 221, 313 Systemic, 29, 32, 169, 212, 228, 260, 274, 285, 305, 312, 313, 315, 317 Systemic disease, 212, 313 T Temporal, 80, 313 Teratogenic, 254, 313 Therapeutics, 13, 33, 63, 99, 209, 229, 313 Thermal, 271, 301, 314 Threonine, 174, 292, 303, 304, 310, 314 Thrombin, 275, 303, 314 Thrombocytopenia, 257, 314 Thrombolytic, 300, 314 Thrombomodulin, 303, 314 Thrombosis, 304, 312, 314 Thymidine, 60, 314
333
Thymidine Phosphorylase, 60, 314 Thymosin, 10, 149, 165, 184, 314 Thymus, 283, 289, 314 Thymus Gland, 314 Thyroid, 183, 205, 314, 316 Thyroxine, 255, 300, 314 Tissue Culture, 38, 50, 81, 92, 314 Titre, 7, 314 Tolerance, 172, 253, 314 Tomography, 125, 290, 314 Topical, 274, 282, 314 Toxic, iv, 254, 263, 267, 268, 272, 273, 278, 281, 288, 295, 309, 315, 319 Toxicity, 36, 49, 50, 60, 271, 292, 315 Toxicology, 54, 236, 315 Toxin, 184, 254, 314, 315 Trachea, 299, 314, 315 Transcription Factors, 27, 79, 82, 84, 135, 157, 315 Transduction, 55, 57, 143, 203, 315 Transfection, 60, 190, 260, 277, 315 Transfer Factor, 283, 315 Transferases, 58, 278, 315 Transfusion, 7, 26, 119, 131, 158, 280, 315 Translating, 170, 315 Translation, 30, 33, 43, 60, 87, 96, 136, 191, 255, 306, 315 Translational, 33, 315 Translocation, 39, 172, 315 Trauma, 212, 279, 294, 315 Treatment Failure, 12, 315 Trivalent, 33, 316 Tropism, 25, 38, 85, 95, 316 Trypanosomiasis, 313, 316 Trypsin, 34, 273, 316, 319 Tuberculosis, 21, 42, 52, 220, 316 Tumor marker, 260, 316 Tumor Necrosis Factor, 37, 83, 96, 100, 316 Tumor suppressor gene, 62, 203, 298, 316 Tumor-derived, 193, 316 Tupaia, 49, 316 Tyrosine, 57, 68, 198, 316 U Universal Precautions, 217, 218, 220, 222, 241, 316 Urethra, 303, 316 Urine, 21, 48, 63, 85, 140, 191, 260, 316 Urokinase, 49, 316 Uterus, 202, 291, 302, 316 V Vaccine adjuvant, 108, 316 Vaccinia, 77, 91, 317
Vaccinia Virus, 77, 91, 317 Valves, 307, 317 Varicella, 317 Variola, 317 Vascular, 104, 264, 285, 288, 292, 301, 317 Vascular endothelial growth factor, 104, 317 Vasculitis, 135, 137, 301, 317 Vector, 52, 82, 121, 172, 173, 174, 177, 179, 202, 206, 285, 315, 317 Vein, 212, 286, 296, 302, 309, 317 Venereal, 313, 317 Venoms, 295, 317 Venous, 212, 269, 304, 317 Ventricle, 305, 317 Vesicular, 32, 62, 281, 310, 317 Veterinary Medicine, 149, 235, 317 Vidarabine, 200, 317 Viraemia, 10, 317 Viral Load, 6, 23, 35, 196, 317 Viral Proteins, 196, 317 Viral Regulatory Proteins, 61, 317 Viral vector, 60, 318 Viremia, 22, 37, 68, 185, 195, 260, 318 Virion, 38, 63, 64, 67, 78, 83, 84, 91, 104, 115, 166, 186, 195, 281, 296, 318 Virulence, 30, 62, 258, 313, 315, 318 Virus Activation, 113, 318 Virus Diseases, 257, 318 Virus Integration, 72, 95, 318 Virus Replication, 34, 38, 55, 59, 64, 66, 67, 68, 74, 75, 77, 78, 80, 81, 82, 84, 86, 87, 89, 91, 94, 96, 98, 122, 129, 137, 138, 146, 153, 197, 198, 200, 206, 318 Visual field, 307, 318 Vitelline Membrane, 318, 319 Vitro, 14, 18, 25, 27, 38, 39, 48, 50, 54, 55, 58, 61, 67, 68, 74, 76, 77, 80, 81, 84, 87, 88, 93, 100, 110, 121, 123, 125, 127, 138, 154, 156, 157, 168, 170, 178, 179, 202, 277, 284, 301, 310, 313, 314, 318 Vivo, 15, 25, 29, 30, 34, 40, 47, 50, 54, 60, 61, 72, 77, 78, 80, 83, 84, 86, 93, 94, 97, 110, 121, 127, 146, 147, 148, 153, 154, 168, 181, 270, 277, 284, 288, 289, 318 W Warts, 200, 282, 318 White blood cell, 256, 260, 264, 279, 285, 287, 289, 290, 294, 300, 318 Windpipe, 299, 314, 318 Withdrawal, 19, 113, 182, 318 Womb, 316, 318
334
Hepatitis B Virus
X Xenograft, 256, 319 X-ray, 266, 275, 290, 296, 305, 319 Y Yeasts, 62, 180, 276, 299, 308, 319 Yolk Sac, 74, 319
Z Zalcitabine, 287, 319 Zidovudine, 200, 319 Zoster, 317, 319 Zymogen, 303, 319
335
336
Hepatitis B Virus