BIOTERRORISM 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 ©2003 by ICON Group International, Inc. Copyright ©2003 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., 1960Bioterrorism: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References / James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary, and index. ISBN: 0-597-83768-6 1. Bioterrorism-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 bioterrorism. 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 BIOTERRORISM .......................................................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Bioterrorism .................................................................................. 4 E-Journals: PubMed Central ....................................................................................................... 52 The National Library of Medicine: PubMed ................................................................................ 54 CHAPTER 2. NUTRITION AND BIOTERRORISM ................................................................................ 97 Overview...................................................................................................................................... 97 Finding Nutrition Studies on Bioterrorism ................................................................................. 97 Federal Resources on Nutrition ................................................................................................... 98 Additional Web Resources ........................................................................................................... 99 CHAPTER 3. ALTERNATIVE MEDICINE AND BIOTERRORISM ........................................................ 101 Overview.................................................................................................................................... 101 National Center for Complementary and Alternative Medicine................................................ 101 Additional Web Resources ......................................................................................................... 104 General References ..................................................................................................................... 105 CHAPTER 4. DISSERTATIONS ON BIOTERRORISM .......................................................................... 107 Overview.................................................................................................................................... 107 Dissertations on Bioterrorism.................................................................................................... 107 Keeping Current ........................................................................................................................ 108 CHAPTER 5. PATENTS ON BIOTERRORISM ..................................................................................... 109 Overview.................................................................................................................................... 109 Patents on Bioterrorism ............................................................................................................. 109 Patent Applications on Bioterrorism ......................................................................................... 112 Keeping Current ........................................................................................................................ 121 CHAPTER 6. BOOKS ON BIOTERRORISM ........................................................................................ 123 Overview.................................................................................................................................... 123 Book Summaries: Federal Agencies............................................................................................ 123 Book Summaries: Online Booksellers......................................................................................... 124 The National Library of Medicine Book Index ........................................................................... 129 Chapters on Bioterrorism ........................................................................................................... 130 CHAPTER 7. MULTIMEDIA ON BIOTERRORISM .............................................................................. 131 Overview.................................................................................................................................... 131 Bibliography: Multimedia on Bioterrorism................................................................................ 131 CHAPTER 8. PERIODICALS AND NEWS ON BIOTERRORISM ........................................................... 133 Overview.................................................................................................................................... 133 News Services and Press Releases.............................................................................................. 133 Academic Periodicals covering Bioterrorism ............................................................................. 135 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 139 Overview.................................................................................................................................... 139 NIH Guidelines.......................................................................................................................... 139 NIH Databases........................................................................................................................... 141 Other Commercial Databases..................................................................................................... 143 APPENDIX B. PATIENT RESOURCES ............................................................................................... 145 Overview.................................................................................................................................... 145 Patient Guideline Sources.......................................................................................................... 145 Finding Associations.................................................................................................................. 156 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 159 Overview.................................................................................................................................... 159 Preparation................................................................................................................................. 159
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Finding a Local Medical Library................................................................................................ 159 Medical Libraries in the U.S. and Canada ................................................................................. 159 ONLINE GLOSSARIES................................................................................................................ 165 Online Dictionary Directories ................................................................................................... 167 BIOTERRORISM DICTIONARY............................................................................................... 169 INDEX .............................................................................................................................................. 217
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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 bioterrorism 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 bioterrorism, 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 bioterrorism, 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 bioterrorism. 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 bioterrorism, 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 bioterrorism. The Editors
1
From the NIH, National Cancer Institute (NCI): http://www.cancer.gov/cancerinfo/ten-things-to-know.
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CHAPTER 1. STUDIES ON BIOTERRORISM Overview In this chapter, we will show you how to locate peer-reviewed references and studies on bioterrorism.
The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and bioterrorism, 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 “bioterrorism” (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: •
Anthrax Source: Access. 15(10): 34-37. December 2001. Contact: Available from American Dental Hygienists' Association. 444 North Michigan Avenue, Chicago, IL 60611. Summary: With the recent exposures to and infections with anthrax, the public has become fearful of the risks associated with ordinary tasks such as opening the mail. The threat of bioterrorism has raised numerous questions concerning risk, course of infection, clinical manifestations, treatment, and prognosis. Health care providers, including oral health professionals, are in a unique position to provide their clients and community with accurate information about anthrax. This column reviews scientific information concerning this bacterial infection, highlights clinical manifestations of the
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disease, and discusses mechanisms for protection against infection. Topics include the pathogenesis of anthrax infections; symptoms of cutaneous, oropharyngeal, intestinal, inhalational, and septicemic anthrax, as well as anthrax meningitis; diagnostic strategies; treatment recommendations; the use of the anthrax vaccine; and prognosis for patients with anthrax. Patients with cutaneous anthrax have a good prognosis if treated early. The fatality rate for cutaneous anthrax is 20 percent without antibiotic treatment and less than 1 percent with antibiotic therapy. Unfortunately, the prognosis for the other forms of anthrax is poor. One sidebar summarizes recommended safe mail handling techniques. 20 references.
Federally Funded Research on Bioterrorism The U.S. Government supports a variety of research studies relating to bioterrorism. 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 bioterrorism. 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 bioterrorism. The following is typical of the type of information found when searching the CRISP database for bioterrorism: •
Project Title: A PORTABLE BIOSENSOR FOR FRANCISELLA TULARENSIS Principal Investigator & Institution: Edson, Clark M.; Radiation Monitoring Devices, Inc. 44 Hunt St Watertown, Ma 02472 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-MAR-2004 Summary: (provided by applicant): Radiation Monitoring Devices, Inc. proposes to design and build a portable bacteria sensor to identify Francisella tularensis, a CDC Category A agent of bioterrorism, in the field. The instrument will consist of a disposable microfluidic platform for carrying out the fluorescence labeling and immunocapture steps and a fluorescence detector utilizing our single-photon sensitive Geiger-mode micro avalanche photodiodes (muAPDs). muAPDs are rugged and can be battery-powered due to their low power requirements. The addition of appropriate collectors would permit detection and identification of bacteria in the air, soil, water and clinical material. The proposed Phase I studies include exploratory and optimization experiments in three areas: (1) fluorescent labeling of F. tularensis by non-specific DNA dyes or, if necessary, by fluorescent antibody; (2) selective immunocapture of the labeled bacteria by monoclonal antibody-coated magnetic beads; and (3) construction of a detector and analysis of the fluid flow of the labelled bacteria through poly(dimethylsiloxane) microchannels. Phase II studies will include development and
2
Healthcare projects are funded by the National Institutes of Health (NIH), Substance Abuse and Mental Health Services (SAMHSA), Health Resources and Services Administration (HRSA), Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDCP), Agency for Healthcare Research and Quality (AHRQ), and Office of Assistant Secretary of Health (OASH).
Studies
5
testing of prototype microfluidic devices, final design of the muAPD detection system, integration of the microfluidics platform with the detector, and evaluation of the ability of the integrated prototype instrument to detect and identify F. tularensis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: A SINDBIS VIRUS-BASED VACCINE AGAINST RVFV INFECTION Principal Investigator & Institution: Frolov, Ilya V.; Associate Professor; Microbiology and Immunology; University of Texas Medical Br Galveston 301 University Blvd Galveston, Tx 77555 Timing: Fiscal Year 2003; Project Start 15-APR-2003; Project End 31-MAR-2007 Summary: (provided by applicant): The Phlebovirus genus of the Bunyaviridae family is a group of arthropod-borne viruses, having mosquitoes and flies as the usual vectors and a wide variety of animals as primary hosts. Over fifty currently known members defining this group are widely distributed in both hemispheres. The Phlebovirus genus contains a spectrum of important pathogens that can cause fatal disease in humans and domestic animals. Our research plan focuses on creating a vaccine against the Rift Valley fever virus (RVFV). This virus can be transmitted by a wide variety of mosquitoes and spread to distant geographical sites to initiate epizootics. Most recently, RVFV caused a massive epidemic in sub-Saharan Africa in 1997-98 and spread across the Red Sea to Saudi Arabia and Yemen, causing devastating disease outbreaks in sheep and cattle. The RVFV has potential for use in bioterrorism, and its projected effect on U.S. agricultural interests would likely be immense. There is no treatment for humans or vaccine for the livestock that are such important amplifiers of the virus. An experimental vaccine exists for humans, but the number of doses is limited, and there are no prospects for future manufacture. We propose to develop a prototype recombinant vaccine against RVFV infection based on Sindbis virus replicons expressing structural proteins of RVFV. Replicons will be packaged into viral particles composed by structural proteins of Sindbis and other alpha viruses. Immunization by these particles will efficiently protect against RVFV infection, and it will be possible to manufacture this vaccine on an industrial scale. This vaccine will combine the efficiency of live attenuated vaccines and safety of the subunit vaccines. In this proposal we will identify i) the optimal strategy for expression of structural proteins of RVFV by recombinant Sindbis virus, ii) a system for delivery of recombinant genomes into antigen-presenting cells, and iii) the manufacturing procedure for large-scale production of the recombinant viruses. The study will be important for creating a general strategy for development of vaccines against emerging infections, vaccines that require fast design and large-scale production for immediate use. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: ALPHAVIRUS REPLICON VACCINES AGAINST MARBURG VIRUS Principal Investigator & Institution: Smith, Jonathan; Senior Vice President; Alphavax Human Vaccines, Inc. Box 110307, 2 Triangle Dr Research Triangle Park, Nc 27709 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-JUL-2007 Summary: (provided by applicant): The objectives of the proposed research are (1) to manufacture and perform phase 1 clinical testing of an alphavirus replicon particle vaccine previously shown to be effective for preventing disease and mortality after challenge with a homologous strain of Marburg virus in guinea pigs and nonhuman primates, (2) to evaluate in vitro immune assays as correlates of protective immunity, (3) to evaluate the effects of changes in the replicon particle surface coat on
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Bioterrorism
immunogenicity, (4) to design, construct and perform preclinical evaluations of bivalent alphavirus replicon particle vaccines using heterologous strains of Marburg virus, and (5) to manufacture and perform phase 1 clinical testing of a bivalent alphavirus replicon particle vaccine containing genes from two heterologous strains of Marburg virus. Marburg virus, a causative pathogen of viral hemorrhagic fever, is infectious by the aerosol route, can be grown to high titer, and can be stabilized by Iyophylization, making it an important biowarfare/bioterrorism agent. The glycoprotein gene from one strain of Marburg virus, which has been identified as a protective immunogen in both rodent and primate challenge models, will be inserted into self-replicating RNAs (replicons) derived from attenuated strains of Venezuelan equine encephalitis (VEE). The replicons will be packaged into single-cycle, propagation- defective, virus-Iike replicon particles (VRP) using a VEE glycoprotein coat that confers dendritic cell tropism. GMP manufacture and clinical testing in healthy volunteers will be performed using a study design based on previous experience with a VRP vaccine for HIV. To identify correlates of protective immunity, animals will be immunized with graded doses of Marburg VRP vaccines carrying different VEE glycoprotein surface coats, challenged with a lethal dose of Marburg virus, and protective efficacy after immunization will be correlated with pre-challenge immune responses (virus neutralization in vitro, ELISA, ADCC, ELISPOT). The same immunological assays will be performed with samples obtained during clinical trials. Bivalent VRP vaccines, expressing glycoprotein genes from two heterologous Marburg virus strains, will be constructed and used to immunize nonhuman primates. Immunogenicity and efficacy will be compared in animals immunized with bivalent or monovalent VRP vaccines. The most effective bivalent Marburg VRP vaccine strategy will be selected for GMP manufacture and clinical testing. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: AMPLIFYING FLUORESCENT POLYMER DETECTION OF BW AGENTS Principal Investigator & Institution: Deans, Robert; Nomadics, Inc. 1024 S Innovation Way Stillwater, Ok 74074 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2003 Summary: (provided by applicant): Nomadics will adapt amplifying fluorescent polymer (AFP) technology to nucleic acid detection. AFPs are a class of polymers that amplify optical signatures resulting from FRET or fluorescence quenching events. Combining this inherent signal amplification with the specificity exhibited by nucleic acid recognition events will enable a new generation of nucleic acid sensors that do not rely on target amplification or catalyzed reporter deposition. This AFP-based technology should make a significant contribution to the adaptation of nucleic acid diagnostics towards the demands of field operations in reducing size, weight, and power consumption. This will make the technology suitable for use in countering bioterrorism. The research will focus on nanoparticle AFP detection systems, as the particle format offers a number of advantages in the adaptation of AFP technology to PCR-less molecular analyses-principally, the ability to harness 3-dimensional signal amplification in the solid particle while retaining an optically clear fluid matrix. Particle systems can also minimize background and increase sensitivity through single-particle analyses. Further, variations in the AFP composition allow us to tune the emission color of the bead; this, in turn, will enable multiplex analyses to screen for multiple agents. In Phase I, Nomadics will demonstrate APP nanoparticle technology for the detection of nucleic acids. This will require fabrication and characterization of AFP nanoparticles and the
Studies
7
development of efficient coupling chemistries for the attachment of nucleic acid probes. This will enable hybridization studies to quantify the sensitivity and selectivity of APP nanoparticles. Experience in the handling and performance of AFP systems will enable design and fabrication of laboratory prototype systems. Studies will focus on anthrax. Synthesis and testing of a molecular beacon for a specific anthrax targets will only be performed in Phase II. Phase I will include selection of an appropriate anthrax target based on a complete literature search and design of a molecular beacon in silico. In order to test the concept using APP nanoparticles in Phase I, a probe that has already been designed, synthesized, and tested by Nomadics for another target will be used. The goal of Phase I will be to demonstrate highly specific nucleic acid detection in the low (<10) femtomole range. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: AN ORAL VACCINE AGAINST MULTIPLE BIOWARFARE AGENTS Principal Investigator & Institution: Klose, Karl E.; Associate Professor; Microbiology and Immunology; University of Texas Hlth Sci Ctr San Ant 7703 Floyd Curl Dr San Antonio, Tx 78229 Timing: Fiscal Year 2001; Project Start 01-AUG-2001; Project End 31-JUL-2005 Summary: (provided by applicant): Background: U.S. citizens, particularly military personnel, are vulnerable to the threat of exposure to biological warfare agents. Two such bacterial agents, Bacillus anthracis and Francisella tularensis, can be easily spread by aerosolization causing a high level of mortality, and are therefore considered to be candidate warfare agents. New vaccines against these and other potential warfare agents are needed which can be easily administered and provide high levels of protection against aerosolized bio-weapons. We have developed a Salmonella typhimurium strain (delta-glnA delta-glnH) with a number of attributes that make it an attractive candidate for a live attenuated multivalent vaccine. Our hypothesis is that this attenuated S. typhimurium strain can be used as a single oral vaccine to deliver multivalent antigens and provide both mucosal and systemic protective immunity against aerosolized biological warfare agents, specifically B. anthracis and F. tularensis. We will exploit specific S. typhimurium promoters (e.g., pmrH) to drive high-level expression of B. anthracis and F. tularensis antigens within the lymphoid tissue, and thus generate a sufficient immune response with a single dose. The Specific Aims of this project entail: (1) Construction of delta-glnA delta-glnH attenuated S. typhimurium vaccine strains with the pmrH promoter driving expression of B. anthracis. Protective Antigen (PA) and F. tularensis FopA and TUL4 proteins; (2) Evaluation of the efficacy of vaccine strains (Specific Aim 1) to express heterologous antigens within immune tissue and elicit an appropriate immune response; and (3) Challenge vaccinated animals with aerosolized B. anthracis and F. tularensis to determine efficacy of the vaccine strains. Our Study Design incorporates collaborative vaccine development at three different sites in San Antonio, based upon the expertise found at each site. The S. typhimurium vaccine strains expressing B. anthracis and F. tularensis antigens will be constructed and inoculated into animals in the laboratories of two S. typhimurium researchers, Drs. Karl Klose and John Gunn, at the University of Texas Health Science Center. The evaluation of levels of antigen expression within immune tissue will be carried out at the Brooks Air Force Base by Dr. Kenton Lohman. Aerosolized B. anthracis and F. tularensis challenge studies of vaccinated animals will take place in the Biosafety Level 4 (BSL-4) laboratory at the Southwest Foundation for Biomedical Research under the guidance of Dr. Jean Patterson. We will be taking advantage of this high-level biocontainment laboratory to perform the aerosol challenges necessary to prove the efficacy of this
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vaccine approach. Relevance: The development of a single oral vaccine that can simultaneously provide protection against multiple bio-warfare agents would be of tremendous benefit to the health of military personnel and other citizens exposed to these agents. If this vaccine strategy proves successful, additional antigens can be expressed from the same vaccine strain, offering an adaptive and protective health tool. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ANTIBODY-BIOCIDE CRYPTOSPORIDIUM
FUSIONS
TO
CONTROL
Principal Investigator & Institution: Imboden, Michael; Iogenetics, Llc Box 620128, 8137 Forsythia St Middleton, Wi 53562 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2005 Summary: (provided by applicant): The goal of this research is develop therapeutic products for Cryptosporidium parvum which can be made at a scale and cost which are feasible for delivery to large populations of patients or individuals at risk, as may be necessary in countering bioterrorism, or in protecting field-deployed armed forces. Our approach is to develop recombinant neutralizing monoclonal antibodies, and fusion proteins that genetically link monoclonal antibodies to parasiticidal proteins (biocides) which neutralize C. parvum sporozoites and merozoites. We will use a proprietary retrovector gene transfer technology to insert multicistronic gene constructs for the monoclonal fusion product candidates into cell culture. Following identification of products effective in vitro and in mouse models, we will scale up production in cell culture and by creation of transgenic cattle that express the monoclonal antibodies and fusion proteins in their milk and test anti-cryptosporidial efficacy in neonatal mice and pig models. Transgenic expression will enable manufacture of anti-cryptosporidial therapeutics economically and on a large scale. In addition to biodefense applications, the technology developed will also have important dual-use application in treatment of opportunistic infections with C. parvum and traveler's diarrhea, and in veterinary use to reduce the environmental reservoir of infection. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: APPLICATION OF IVIAT TO BACILLUS ANTHRACIS Principal Investigator & Institution: Ryan, Edward T.; Director, Immunization Center, Massachus; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2005 Summary: (provided by applicant): Bacillus anthracis is the cause of cutaneous, inhalation, and gastrointestinal anthrax. B. anthracis has also recently been used as an agent of bioterrorism. The identification of bacterial genes expressed uniquely in vivo during infection with B. anthracis would improve our understanding of the molecular bacterial events that occur during anthrax, and could lead to improved therapeutics and (less likely) an improved anthrax vaccine. One recently developed technique that permits identification of bacterial genes expressed uniquely in vivo is IVIAT (in vivo induced antigen technology). In this procedure, convalescent serum collected from humans or animals infected with a pathogen of interest is absorbed against bacteria grown in vitro. Absorbed serum is then used to probe a genomic DNA expression library of the pathogen of interest in an E. coli host system. Reactive clones express an antigen expressed uniquely in vivo, and reactive genes and their products can be further identified and analyzed. Our hypothesis is that B. anthracis contains genes that are expressed uniquely in vivo during anthrax, and that identification of such genes and
Studies
9
their products will lead to improved understanding of the pathogenic events that occur during anthrax. Our specific aim, therefore, is to apply IVIAT to B. anthracis using two sets of already collected convalescent sera: one from rhesus macaques that survived inhalational challenge with virulent Ames strain B. anthracis and cleared documented B. anthracis bacteremia as part of a fully approved anthrax study at the Centers for Disease Control and Prevention; the other from humans surviving naturally acquired cutaneous anthrax (collected as part of a fully approved collaborative study between Kazakhstani and CDC researchers). We designed our study to take into account the high lethality of anthrax and the presence of a B. anthracis capsule, and in our project, we will specifically not evaluate well characterized virulence factors of B. anthracis (such as exotoxin and capsule), but will focus our efforts on identifying previously unrecognized genes uniquely expressed in vivo. IVIAT is an established protocol in our laboratory, and this preliminary collaborative study should lay a foundation for subsequent analysis of identified B. anthracis genes and their products. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: AUTO SELECTION OF APTAMERS BINDING TO PX01 PROTEOME Principal Investigator & Institution: Ellington, Andrew D.; Wilson M & Kathryn Fraser Research Profe; Inst for Cell & Mol Biology; University of Texas Austin 101 E. 27Th/Po Box 7726 Austin, Tx 78712 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2005 Summary: (provided by investigator): As recent events have demonstrated, Bacillus anthracis can and has been used as a weapon of bioterrorism. The detection, tracking, and interdiction of various Bacillus anthracis strains is therefore of great concern, as is the treatment of anthrax infection, in order to generate molecular tools that can serve as resources in all of these venues, we propose to select nucleic acid binding species (aptamers) against the proteomes of one of the virulence plasmids associated with Bacillus anthracis, pXO1. These experiments will serve as a starting point for the immediate development of biosensors capable of identifying Bacillus anthracis, and will set the stage for future efforts in tracking, interdiction, and therapy. In particular, we plan to: 1. Increase the throughput of automated selection experiments. 2. Select aptamers against the pXO1 proteome. 3. Develop informatics methods for designing signaling aptamers. Overall, the significance of the proposed work can be succinctly summarized as follows: there are, no real-time or continuous methods for the detection of B. anthracis, primarily because there are no biopolymer reagents that can report molecular interactions without the need of immobilization or other processing steps (e.g., PCR, ELISA). The signaling aptamers we propose to develop will be unique in this respect. In addition, aptamers have a therapeutic potential that rivals that of monoclonal antibody or other protein drugs (see, for example, B.3). Therefore, we believe that the reagents developed during the execution of this application will be of great use to the entire biodefense community, and that investment in this work will have a significant multiplier effect. As a single example, based on our previous interactions with the military, we are poised to send any aptamers that are produced directly to the Critical Reagents Program of the Joint Program Office for Biotogicat Defense (JPOBD) for further assay and adaptation to military sensor systems. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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•
Project Title: AUTOMATED QUANTIFICATION
PCR
PATHOGEN
DETECTION
AND
Principal Investigator & Institution: Eyre, David J.; Idaho Technology 390 Wakara Way Salt Lake City, Ut 84108 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-MAY-2003 Summary: (provided by applicant): We will develop software for automated pathogen detection and quantification using data from PCR experiments. Automated pathogen detection using data from a PCR experiment requires software to determine whether DNA from the pathogen is present or absent in a sample. We will develop a patternmatching algorithm to mathematically analyze PCR amplification data. We will optimize the algorithm against a data set of at least 5000 PCR reactions (including a significant set of data gathered during the anthrax attack) to determine its efficacy and limitations. We expect the pathogen detection algorithms to distinguish positives samples from negative samples in more than 98% of the samples, to find inconclusive results in less than 1% of the samples, and to incorrectly classify less than 1% of the samples. We will also develop software to perform automated melting curve analysis of samples that our detection algorithm has determined to be positive or inconclusive. The melting profile of the probes is a property of the assay, and it can be used for secondary confirmation of a pathogen by comparing the profile of the unknown samples to the profile of the assay's positive controls. We will develop algorithms to automatically determine whether the melting profile of the sample and controls match. With melting analysis confirmation, the failure rate of the final detection algorithm should be less than 0.5%. Automated pathogen quantification requires software to determine the number of copies of a pathogen's DNA in a sample. We will develop discrete dynamical models of PCR for quantification. We will optimize these methods against a large data set of PCR reactions with dilution series. We will systematically determine the features of the models that provide information and the features that can be ignored. We will measure efficacy by comparing computed DNA copy numbers against the known concentrations (as specified by experimenters), and against each other. We will use the most effective model (or models) in the software we produce. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BIODEFENSE AGAINST AN AEROSOLIZED EBOLA THREAT Principal Investigator & Institution: Kagan, Elliott; Professor; Henry M. Jackson Fdn for the Adv Mil/Med Rockville, Md 20852 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2005 Summary: (provided by applicant): Ebola virus (EBOV) is an enveloped, nonsegmented, negative-strand RNA virus within the filovirus family, which can cause a lethal hemorrhagic febrile disease in humans and nonhuman primates, killing up to 90% of those, infected. There are currently no effective antiviral agents available for the treatment of EBOV infections nor have appropriate vaccines been developed for human disease prevention. The events of September 11, 2001 and the ensuing inhalation anthrax bioterrorism incidents have highlighted concerns that EBOV also might be used as a bioterrorism agent that could be disseminated via the aerosol route. However, little is known about the capacity of EBOV to colonize the human lower respiratory tract and to subsequently induce a systemic viral hemorrhagic fever syndrome. There are currently no published in vitro models for studying the effects of EBOV on human lung cells. Our preliminary data indicate that EBOV can replicate in NORMAL HUMAN BRONCHIAL EPITHELIAL CELLS (HBEC) maintained in air/liquid interface primary culture. In this
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R21 application, we propose that: inhaled EBOV aerosols are able to colonize the lungs by establishing a persistent infection in bronchial epithelium, leading to subsequent infection of alveolar macrophages. The SPECIFIC HYPOTHESIS is that EBOV entry into the bronchial epithelium is associated with plasma membrane-associated caveolae in these cells. Furthermore, once entry has occurred, viral replication within the bronchial epithelium (which requires the EBOV RNA-dependent RNA polymerase L and glycoprotein GP genes) induces up-regulation of interleukin-1 (IL-1), cyclooxygenase-2 (COX-2), and the inducible form of nitric oxide synthase (iNOS), which, in turn, facilitate further viral replication and inhibit bronchial epithelial apoptosis. To test this hypothesis both in vitro and in vivo, we propose the following four SPECIFIC AIMS: (1) to determine whether HBEC are permissive for EBOV entry and replication without inducing apoptosis and/or cytotoxicity; (2) to determine whether caveolae are required for cellular entry into HBEC; (3) to determine whether IL-1-mediated up-regulation of COX-2 and iNOS expression in HBEC prevent apoptosis and facilitate EBOV replication within HBEC; (4) to determine whether RNA interference (RNAi), by inducing posttranscriptional silencing of EBOV GP and L genes, can prevent or inhibit the replication and budding of virus within HBEC. These studies are expected to provide new information as to how the entry, replication, and budding of EBOV in HBEC could be modulated by multiple targeted biodefense approaches against aerosolized EBOV. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BIODEFENSE PROTEOMICS COLLABORATORY Principal Investigator & Institution: Gorenstein, David G.; Director of Nmr; Human Biol Chem and Genetics; University of Texas Medical Br Galveston 301 University Blvd Galveston, Tx 77555 Timing: Fiscal Year 2003; Project Start 15-APR-2003; Project End 31-MAR-2008 Summary: (provided by applicant): In vitro enzymatic combinatorial selection and splitsynthesis chemical combinatorial methods will be used to develop a "ThioAptamer Chip" (TACh) for proteomics - a diagnostic tool to identify and quantify the differential expression of key proteins in response to pathogens of concern for bioterrorism threat (BT). This new proteomics technology will utilize our proprietary thioselection and phosphorothioate-modified oligonucleotide "thioaptamers," combined with the surface enhanced laser desorption/ionization (SELDI) mass spectroscopy technology of our collaborating partner, Ciphergen, to target both rodent and human proteomes. In particular we will study the inflammatory response of cytokines and key transcription factors (e.g., NF-kappaB) challenged with BT agents. The five NF-?B/Rel family proteins can combine to form 15 homo- and heterodimers, each performing a specific signaling function upon translocation across the cell nuclear membrane and binding to a gene's promoter region. In partnership with Ciphergen, we will also develop new, massively parallel, thioaptamer bead-based screening of the proteome with SELDI massspectrometric methods to identify uncharacterized proteins involved in the immune response to BT viruses. Our results from the TACh/SELDI approaches will be validated by 2D gel mass spectrometric proteomic methods. We will also apply bioinformatic analyses to correlate changes in protein expression with available genomic data on changes in gene expression as a result of inflammation after viral infection or shock. Elucidating these protein expression changes will allow early diagnosis and enhanced prognosis of viral disease, and subsequent development of effective pharmacological and immunological interventions. Specific initial viral targets include arenaviruses, Pichinde and Lassa (the latter on both the NIH and CDC class A lists). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Bioterrorism
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Project Title: BIODEFENSE DEVELOPMENT
RESEARCH
TRAINING
AND
CAREER
Principal Investigator & Institution: Petri, William A.; Chief; Internal Medicine; University of Virginia Charlottesville Box 400195 Charlottesville, Va 22904 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2008 Summary: (provided by applicant): The Biodefense Research Training and Career Development Program is a new initiative of the University of Virginia, which is in response to the NIAID Blue Ribbon Panel on Bioterrorism and Its Implications for Biomedical Research. The program goal is to provide a rich interdisciplinary experience to prepare pre- and postdoctoral students for careers in biodefense. Research themes encompass the biology of and host response to microbes, vaccines, therapeutics and diagnostic technologies for infections by potential agents of bioterrorism. The training of predoctoral students, M.D., and Ph.D. postdoctoral fellows is enriched by special activities of the program, including a new graduate course in biodefense, an expanded two semester course in molecular mechanisms of microbial pathogenesis, advanced immunology courses and colloquia, a research-in-progress series and a journal club. The program is comprised of 31 faculty from eight departments and two research centers within a five minute walk to the School of Medicine. All of our faculty collaborate, and 46% have co-published papers in the last five years. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BIOINFORMATICS FOR IMMUNE RESPONSE BIOSIGNATURE ANALYSES Principal Investigator & Institution: Drake, Kenneth L.; Seralogix 8329 N Mopac Expressway Austin, Tx 78759 Timing: Fiscal Year 2003; Project Start 01-MAY-2003; Project End 31-OCT-2003 Summary: (provided by applicant): Our Fast Track Phase I objective is to define and prototype a new computational (bioinformatic) framework for innate immune response biosignature analyses of infectious diseases including biowarfare agents. The framework combines Dynamic Bayesian Network learning and modeling techniques with "Intelligent Software Agent" (ISA) technology to enable quantitative and qualitative analysis of over 100 time-course simultaneously measured biomarkers (biosignatures). We believe that infectious agents produce unique temporal biosignatures that can be observed by simultaneously measuring multiple circulating molecular biomarkers (cytokines, chemokines and others TBD) that are integral to the host's innate immune and inflammatory response mechanisms. A new computational methodology is essential for decoding molecular responses and the associated complexities of interacting processes that uniquely model and identify an infectious agent. Our methodology analyzes temporal patterns of change of circulating proteins during the initial onset of infection and its progression to reveal unique proteome-level "biosignatures." This new framework will substantially advance the industry's capability to analyze complex simultaneous protein interactions and time-course investigations of diseases at the proteomic level and not just for circulating proteins. Our Phase I milestone is to develop a prototype framework and demonstrate its concept and feasibility. We will refine our framework and continue development under Phase II efforts and validate our framework using in vivo mice models challenged by infectious agents. In Phase II, we will be integrating our platform to communicate with the Luminex LapMAP microbead flow cytometry immunoassay instrument. This instrument can measure up to 100 different cytokines/proteins/SNPs, simultaneously
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from a serum sample < 50 microliters. This is the core technology for Seralogix's web based point-of-care platform under commercial development being leveraged as in-kind contribution for this proposal. Our long-term objective is to commercialize a proteomicsbased point-of-care diagnostics platform for the presymptomatic detection of human infectious diseases, including BWAs. We envision the platform will have dual-use applications to supped the front-line physicians' therapeutics and diagnosis of emergent and bioterrorism infectious agents that are of great concern to public health and homeland security. The platform is intended to enable a National Counter-Bioterrorism Defense Platform critical to the Nation's preparedness against terrorist threats. The criticality of pre-symptomatic detection of any person suspected of BWA infection is obvious, not only for his or her own immediate treatment but also for the avoidance of a catastrophic national health disaster. A unique multidisciplinary team of industry and academia has been assembled for Phase I and Phase II. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BIOTHREAT DETECTION WITH IMPROVED BACKGROUND REJECTION Principal Investigator & Institution: Kebabian, Paul L.; Aerodyne Research, Inc. the Research Ctr at Manning Park Billerica, Ma 01821 Timing: Fiscal Year 2003; Project Start 01-MAY-2003; Project End 31-OCT-2003 Summary: (provided by applicant): The Quartz Crystal Microbalance (QCM) is a wellestablished technology for quantifying small changes in mass. The long-term objective of this program is to improve the QCM so that it is suitable for use as a field test for the common, foodborne bacteria. To do this, we will modify the standard quartz crystal (QC) used in the QCM so as to increase its background rejection capabilities. This will involve innovations to the design of the QC used as the detector to the electronics. We will utilize standard technology to deposit a uniform coating of antibody directed against E. coli onto the surface of the QC. We will use utilize commercially available preparations of E. coli and Pseudomonas to demonstrate that the innovations introduced to the QC design and the electronics of the QCM allow a single QC to serve as both the experimental and the reference detectors. Thus, the modified QCM can discriminate between specific and non-specific binding of mass to the QC. We will use a second antibody, labeled with horseradish peroxidase to generate an insoluble reaction product to further amplify the mass of bacteria attached to the QC. Furthermore, we will utilize glutaraldehyde to non-selectively bind bovine serum albumin to antibody on the surface of both the conventional and modified QCs. Only the modified QC will be able to discriminate between specific binding of E. coli to the antibody and the non-specific cross-linking of BSA to antibody. We believe that our innovations will be of particular value in field tests in which there will be relatively small amounts of pathogenic agent and relatively large amounts of nonhazardous materials. In Phase II of the project, we will apply the technology developed in Phase I to the detection of other common foodborne bacterial contaminants. We will also extend our working relationship with academic laboratories to further test the device. We will work with diagnostics companies to determine their willingness to commercialize this technology. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: BIOWARFARE APPLICATIONS OF A NEW IMMUNOREGULATOR Principal Investigator & Institution: Willeford, Kenneth O.; Genebact Biotechnologies, Inc. 713 Washington St Marietta, Oh 45750
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Bioterrorism
Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2004 Summary: (provided by applicant): If biological weapons were to be used by a terrorist organization, the public health system would be overwhelmed. The ease of use and delivery along with the apparent widespread availability of biological weapon grade agents could inflict mass civilian casualties anywhere in the world. The best way to combat and defend bioterrorism is to be prepared. Scientists at GeneBact Biotechnologies, Inc. have discovered a new class of Biological Response Modifiers from mammalian serum that we refer to as the Immune Cell Proliferation Factors ("ICPF"). ICPFs are novel lipoproteins that have been shown to have no direct antimicrobial activity, yet retain their ability to abate microbial pathogenesis as presented in a Salmonella typhimurium mouse model and a Pasteurella multocida avian model. ICPFs also show no direct virucidal activity, yet retain the ability to abate viral pathogenesis as presented in a West Nile Virus mouse model and a Parvovirus rat model. ICPFs were also shown to significantly increase levels of the circulating antibodies to Parvovirus in vaccinated rats when the vaccine was adjuvanted with ICPF as compared to a nonadjuvanted vaccine control. The primary objectives of this project are to (i) establish the safety and efficacy of an ICPF formulation for broad spectrum human use in the treatment of bacteremias and viremias, (ii) evaluate the efficacy of an ICPF formulation to provide prophylactic and therapeutic protection against both bacterial and viral infectious agents, and (iii) evaluate the efficacy of ICPF as and adjuvant in vaccines to amplify and expand existing stores of vaccines. The secondary objective of this project is to evaluate the "immunological memory" conferred upon infected patients treated with ICPF. Accomplishing the Tasks as outlined will provide specific benefits to address biowarfare issues in three major areas: 1. Provide a short-term prophylactic agent for use in high-risk populations such as military personnel entering a biological warfare theater of war. 2. Provide an effective therapeutic agent for personnel exposed to a biological warfare agent. 3. Provide an adjuvant to expand and amplify the existing stockpiles of vaccines. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BROADLY ACTIVE INHIBITORS OF HIGH PRIORITY PATHOGENS Principal Investigator & Institution: Gulnik, Sergei; Professor; Sequoia Pharmaceuticals, Inc. 401 Professional Dr, Ste 100 Gaithersburg, Md 20879 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2005 Summary: (provided by applicant): The recent anthrax attack of 2001 underscored the reality of large-scale aerosol bioweapons attack by terrorist groups. It also revealed that there is an urgent and pressing need to discover and develop novel and potent antimicrobials that can be used therapeutically and prophylactically for biodefense against new bioattacks. The NIH and CDC have identified a number of High Priority pathogens based on their likelihood of causing widespread contagious disease and/or death to the general population. The long range goal of this Phase I SBIR is to discover and develop potent, broad-spectrum, and mechanistically-novel antimicrobials suitable for treating and/or preventing outbreaks of diseases like anthrax, plague, cholera, gastroenteritis, multidrug-resistant tuberculosis (MDR TB), and for tackling the growing problem of antibiotic resistant bacteria strains. This Phase I application aims to generate novel inhibitors of a bacterial enzyme-3-dehydroquinate dehydratase (DHQase) using molecular target- and structure-based approaches. DHQase is a key enzyme in the shikimate pathway that is essential for the biosynthesis of aromatic amino acids in microorganisms, plants and fungi. Specific aims of the application include: 1) cloning, expression and purification of recombinant DHQases from Bacillus anthracis, Yersinia
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pestis, Campylobacter jejuni, Vibrio cholera and Mycobacteria tuberculosis; 2) establishing DHQase inhibitor assays using the recombinant enzymes; 3) identifying small molecule chemical leads using experimental and computational screening methods; and 4) validating binding modes of inhibitor leads using X-ray crystallography of inhibitor/enzyme complexes. High resolution crystal structures of DHQase, with and without inhibitors, are available from preliminary studies, and crystallization conditions are well established in the laboratory of the PI. The commercial goal of this SBIR is the invention of one or more patentable molecular entities with broad cross-reactivity against DHQases and the pathogens from which they are derived. Enzyme inhibitors identified in the Phase I portion of this work will serve as leads for launching into a Phase II study, the goal of which will be to translate potent and selective inhibitors of High Priority pathogens into safe and effective clinical drug candidates for use as biodefense agents. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BRUCELLA ABORTUS ALTERS TRAFFICKING IN HUMAN MONOCYTES Principal Investigator & Institution: Bellaire, Bryan H.; Microbiology and Immunology; Louisiana State Univ Hsc Shreveport P. O. Box 33932 Shreveport, La 71103 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2006 Summary: (provided by applicant): Brucella abortus is a highly infectious intracellular pathogen of humans that is classified as a Category B Bioterrorism agent. Virulence of this organism depends on its ability to survive and replicate within phagosomes of host monocytes. The experiments outlined in this proposal will characterize the maturation of the B. abortus phagosome that becomes acidified but does not fuse with lysosomes. Characterizing how B. abortus phagosomes interact with endosomes, phagosomes and lysosomes will give considerable insight into the host-pathogen relationship. Based on preliminary data and published reports, it is hypothesized that Brucella abortus establishes an intracellular niche within monocytes by interfering with host trafficking machinery to form a modified phagosome that does not fuse with lysosomes. The first set of experiments will use immunofluorescence microscopy and Western blot analysis on purified phagosomes containing live B. abortus to characterize these modified phagosomes. Phagosome maturation is a highly regulated process and key regulators of this pathway are the Rab GTPases Rab5 and Rab7. Altering the activity of these regulators contributes to the survival of other intracellular pathogens by preventing phagosome maturation and fusion with lysosomes. To determine if such a phenomenon is associated with the survival of intracellular B. abortus, phagosome maturation and bacterial survival will be examined in monocytes expressing the dominant-negative and constitutively active forms of Rab5 and Rab7. The goal of these studies is to identify which events in phagosome maturation B. abortus alters for intracellular survival and if Rab5 and Rab7 contribute to or antagonize the development of Brucella's modified phagosome. Completion of these studies will greatly increase our understanding of Brucella pathogenesis that will in turn aid the development a human vaccine and treatments for human brucellosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Bioterrorism
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Project Title: BURKHOLDERIA SP: IDENTIFICATION OF MAJOR CLONAL LINEAGES Principal Investigator & Institution: Lipuma, John J.; Associate Professor; Pediatrics & Communicable Dis; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2005 Summary: (provided by applicant): Certain bacterial species within the genus Burkholderia are capable of causing significant human infection. B. mallei and B. pseudomallei, the causative agents of glanders and melioidosis, respectively, have gained attention recently as agents of bioterrorism. Species within the B. cepacia complex (Bcc) are emerging nosocomial pathogens and are capable of causing lifethreatening infection in persons with chronic granulomatous disease (CGD) or cystic fibrosis (CF), the most common inherited lethal disorder in Caucasians. In CF, respiratory tract infection by Bcc is generally refractory to antimicrobial therapy and a significant proportion of patients succumbs to rapidly progressive pulmonary deterioration and sepsis. Recent work indicates that some Bcc species are much more frequently involved in infection in CF than others. Furthermore, at a subspecies level, certain strains or clones have been identified that infect multiple CF patients, suggesting that they have an enhanced ability to infect or to be transmitted within this population. The goals of the proposed research are to (i) identify major clonal lineages of human disease-causing Bcc by genotyping an extensive collection of isolates recovered from CF sputum culture, and (ii) identify genes specific to these major clones by using subtractive hybridization methodology. In the short term, the genotyping analysis will have an immediate impact on efforts to optimize current infection control strategies in CF. The genotyping data are also a prerequisite to future outcomes studies that will seek to correlate strain type and clinical course of Bcc infection. The identification of genes specific to major clones will provide an immediate avenue to investigate the potential roles of these genes as virulence determinants in Burkholderia. The long-term objectives of this work are to characterize the mechanisms whereby these virulence determinants enhance the pathogenicity and/or transmissibility of Bcc in human infection. This will enable the development of novel strategies to prevent and treat Bcc infections, and will also provide valuable insights to mechanisms involved in transmission of other respiratory pathogens. A better understanding of the pathogenicity of Bcc species is also likely to provide timely information regarding the mechanisms of virulence and personto-person transmission of the closely related species B. mallei and B. pseudomallei. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CELLULAR IMMUNITY TO CATEGORY A-C VIRUSES IN HUMANS Principal Investigator & Institution: Ennis, Francis A.; Professor; None; Univ of Massachusetts Med Sch Worcester Office of Research Funding Worcester, Ma 01655 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-MAR-2008 Summary: (provided by applicant): The proposed UMASS Center for Translational Research on Human Immunology and Biodefense is a comprehensive, interdepartmental collaboration to address, as its overall scientific theme, the role of human T lymphocyte responses in the immunopathogenesis of and protection from category A-C viral pathogens. The Center encompasses senior and junior investigators with significant prior expertise in human immunology and research on biodefense pathogens, including translation to clinical studies, and is organized around the following components: Project 1 (Poxviruses) will define immunodominant human T
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cell epitopes of vaccinia virus as markers of vaccine efficacy and advance knowledge toward the development of improved smallpox vaccines. Project 2 (Hantaviruses) will define human immune responses associated with immunopathogenesis of hemorrhagic fever with renal syndrome. Project 3 (Flaviviruses) will define protective and immunopathological cross-reactive human T cell responses to sequential virus infections. The Technical Development Component (TDC) will develop novel solidphase array and proteomics technologies for application in T cell epitope identification, detection and enumeration of virus-specific T cells, and identification of biomarkers of protective or pathological T cell responses. Core facilities will provide flow cytometry, MHC class I production, MHC class II production, and program administration services for use by the research projects and TDC. A Pilot Projects component will support pilot funding of promising novel research concepts proposed by UMMS faculty. An Education component will support short-term training of non-Center investigators. The proposed Center will address important NIAID research priorities related to these biodefense pathogens as well as career development for young investigators. The Center will facilitate synergistic interactions between the various investigators, to be assessed by periodic internal and external review that will greatly enhance the overall research productivity. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CHAPERONE/USHER PATHWAYS IN PLAGUE Principal Investigator & Institution: Hultgren, Scott J.; Professor; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2008 Summary: Yersinia pestis is the etiologic agent of the bubonic plague. Many historians consider the plague as the most devastating infectious disease in human history. Today, there are less than a dozen cases of the plague in the United States. But, after recent terrorist events, the CDC has identified Y. pestis as a serious biological weapons threat (1). Thus, an understanding of how Y. pestis causes disease will allow us to design appropriate therapies. Yersinia pestis secretes a capsule-like antigen called fraction (F1) 1 and very thin fibrillae known as pH 6 antigen. Both of these structures are assembled via the chaperone-usher system. We are the world's authorities on this pathway, as we have dissected the molecular details of chaperone-subunit interactions and function. The goal of this project will be to solve the crystal structures of F1 antigen (Caf1)-Caf1M complex and the pH 6 antigen (PsaA)-PsaB complex. From these structures, we will elucidate the details of chaperone-subunit interactions as well as predict the structural basis of F1 capsule and pH 6 antigen assembly. Using rational drug design, we will create novel antibacterials that will inhibit chaperone function and/or interfere with capsule/fibrillae assembly. Also, the complexes will be used as vaccines, in a strategy similar to that which we have used with the E. coLI FimC-FimH complex to protect against urinary tract infections. This work has the potential to lead to new vaccines to prevent plague, and new drugs to treat this deadly infection. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: COMBINATORIAL VACCINES AGAINST ANTHRAX AND PLAGUE Principal Investigator & Institution: Clements, John D.; Professor & Chairman; Microbiology and Immunology; Tulane University of Louisiana New Orleans, La 70118 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2005
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Bioterrorism
Summary: (provided by applicant): Until recently, anthrax was primarily a concern of individuals working in animal husbandry and military planners concerned about the potential use of anthrax spores as an agent of biological warfare. The use of anthrax as an agent of bioterrorism on civilian populations was a theoretical risk, heightened by the discovery that certain rogue nations (notably Iraq, Syria, and China) either had developed or were attempting to develop anthrax or other biologic agents as a weapon of mass destruction, The post- September 11 release of anthrax spores resulted in five civilian deaths, eighteen infections, and required that more than 30,000 individuals to undergo prophylactic antibiotic therapy. This event also highlighted the need for improved vaccines that would be appropriate for pre- or post- exposure immunization of civilian and military populations against potential bioterrorism agents, including anthrax and plague, Vaccines combining protective antigens from different microorganisms with potential for use against civilian or military populations as biological warfare/biological terrorism agents would be advantageous because they would both broaden the coverage of such vaccines and reduce the overall number of immunizations. The first logical combination to examine would be rPA from B. anthracis and F1-V from Y. pestis since they have individually been shown to induce protective responses. Combining vaccines to decrease the number of immunizations and to increase vaccine coverage is not a new concept in vaccine development and combination vaccines such as DTP and MMR have been used for many years. However, several examples of immunologic interference between individual components of combination vaccines have been observed both in clinical trials and in laboratory tests. We are therefore proposing to examine the potential of a combined vaccine consisting of rPA and F1-V with the specific objective of determining synergy or interference between the vaccine components. For this application, we propose to address a number of interrelated questions regarding immunization with a combined vaccine containing rPA and F1-V as immunogens to protect against anthrax and plague. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: COMPLETE GENOME SEQUENCE OF RICKETTSIA TYPHI Principal Investigator & Institution: Walker, David H.; Professor; Pathology; University of Texas Medical Br Galveston 301 University Blvd Galveston, Tx 77555 Timing: Fiscal Year 2001; Project Start 15-AUG-2000; Project End 31-JUL-2002 Summary: The complete DNA sequences of the genome of Rickettsia typhi will be determined and analyzed for putative coding regions and possible functions of the gene products. Under an addendum for potential bioterrorism agents of the Policy on Support of Large- Scale Genome Sequencing Projects, R. typhi has been designated as a priority bioterrorism agent. This application is prepared in response to this opportunity for support of large-scale genome sequencing of high priority pathogens as potential agents of bioterrorism. Rickettsia typhi is highly infectious, including via aerosol exposure, infection is deceptively difficult to diagnose clinically and causes a severe, incapacitating illness with 1 percent overall mortality. Knowledge of its genome would be most useful for comparison with that of the more virulent R. prowazekii and for investigation of virulence factors, targets of attenutation, and potential novel targets for antimicrobial therapy of strains that could be engineered to resistance to the only two effective agents, tetracyclines and chloramphenicol. Once the genomic sequences are determined and analyzed they will be made available to the research community through an online database with a number of tools to facilitate data retrieval. During the course of the project there will also be ongoing release of preliminary data. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CONJUGATE VACCINE FOR THE PREVENTION OF TULAREMIA Principal Investigator & Institution: Tzianabos, Arthur O.; Associate Professor of Medicine; Harvard University (Medical School) Medical School Campus Boston, Ma 02115 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2008 Summary: Francisella tularensis is a highly infectious bacterium that poses a serious threat as an agent of bioterrorism. A live whole cell vaccine is currently available for atrisk populations, but it is associated with incomplete immunity and side-effects. Studies of humans and mice vaccinated with this preparation indicate that humoral and cellmediated immune responses are required for complete protection in the infected host. Currently, little is known concerning the virulence factors associated with F. tularensis that contribute to its ability to cause lethal disease. However, previous studies have identified the capsule and LPS as principle determinants of its pathogenic potential. Our analysis of the recently released genome of F. tularensis Schu S4 has shown that it possesses a single polysaccharide biosynthetic locus responsible for expression of one surface polysaccharide. Based on these data, we hypothesize that the previously described capsule and O-antigen of this organism actually represents a single Oantigen/capsule that has the same repeating unit structure, but is expressed as a distinct large molecular-weight polymer and smaller molecular-weight Lipid A-linked polysaccharide. We predict that this structure has a central role in the pathogenesis of this organism and can be used as the basis for novel glycoconjugate vaccines that will elicit complete protection against experimental tularemia. To address the structural nature of this virulence factor and its role in the pathogenesis and immunity to F. tularensis, we propose to: 1) Characterize the structural and genetic nature of the Oantigen/capsule; 2) Determine the role of the O-antigen/capsule in virulence; 3) Determine the humoral and cell-mediated immune responses to the O-antigen/capsule and proteins of F. tularensis; and 4) Develop a conjugate vaccine for F. tularensis infections. These studies will employ a proteomics-based approach to identify new immunogenic proteins from F. tularensis that can be used as carriers in the development of novel acellular glycoconjugate vaccines. It is anticipated that these vaccines will activate both humoral and cell-mediated immune responses and elicit complete protection against tularemia. Glycoconjugate vaccines have been among the most effective biologics ever developed for the prevention of bacterial infections. It is expected that this approach can be applied successfully to the development of a vaccine that can ultimately be tested in clinical trials for the prevention of tularemia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CONTROL OF BACILLUS ANTHRACIS SPORE FORMATION Principal Investigator & Institution: Hanna, Philip C.; Assistant Professor; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2008 Summary: There is no text on file for this abstract. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CORE -- MONOCLONAL ANTIBODY AND BIOSENSOR Principal Investigator & Institution: Crowe, James E.; Associate Professor of Pediatrics; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2008
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Bioterrorism
Summary: There is no text on file for this abstract. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CORE -- NON-HUMAN PRIMATE ANIMAL MODEL CORE Principal Investigator & Institution: Lackner, Andrew A.; Professor & Director; Tulane University of Louisiana New Orleans, La 70118 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2008 Summary: There is no text on file for this abstract. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CORE -- PROTEIN EXPRESSION Principal Investigator & Institution: Liao, Hua-Xin X.; Duke University Durham, Nc 27706 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2008 Summary: There is no text on file for this abstract. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CORE--PROTEOMICS Principal Investigator & Institution: Brizuela, Leonardo; Harvard University (Medical School) Medical School Campus Boston, Ma 02115 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2008 Summary: This CORE will play an important role in the dynamics of this RCE by timely generation of comprehensive gene repositories and protein arrays of pathogens in NIAID Category A, B and C groups (with emphasis on category A). These deliverables will support and aid the Research and Development Projects within this RCE and throughout the New England region, as well as those supported by other NIAID initiatives. Likewise, this CORE will contribute to the training plans of the NERCE by allowing access to and dissemination of cutting edge technologies and instrumentation present in the facility. The unique and newly created repositories, and the genome-wide approaches they support, will certainly aid research in the areas of bacterial and viral pathogenesis as well as host response, and will have an impact on early drug discovery (target identification, assay development and screening), vaccine development, and development of new diagnostics and biosensors. This CORE is based on the existing infrastructure, experience, achievements and overall objectives of the Harvard Institute of Proteomics. The Institute was established three years ago and has developed and employed high-throughput technologies for the creation and exploitation of unique gene repositories, including those of several human pathogens. Objectives of the Proteomics CORE: i)To construct comprehensive, arrayed and sequence-verified gene repositories for pathogen organisms from NIAID Category A, B and C groups, using recombination-based cloning technology. ii) To produce high-density protein arrays using the clones from the newly created gene repositories. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CORE--SMALL MOLECULE SCREENING Principal Investigator & Institution: Lory, Stephen; Professor; Harvard University (Medical School) Medical School Campus Boston, Ma 02115 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2008
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Summary: The objective of the Small Molecule Screening Core within the RCE is to support biodefense-related research directed towards the development of new classes of therapeutic agents capable of interfering with the activities of biological weapons. A fully automated facility, capable of executing a number of small molecule screens, will be established. The Core will occupy newly remodeled space at Harvard Medical School, it will be equipped with the state of the art robotic equipment, and will assemble a number of synthetic compound libraries. These resources, together with the expertise of highly trained staff will be made available to individual investigators within the RCE, as well as to investigators with meritorious, biodefense related projects outside of the New England. The core will interact closely with the Institute of Chemistry and Cell Biology at Harvard, further expanding the core's capabilities. Based on the expertise of the Core's staff, a number of diverse, high-throughput screening platforms will be supported, including whole bacterial assays, protein enzyme assays, protein-protein or protein-ligand interaction assays, and a variety of cell-based assays using cultured mammalian cells. The Core will assist the investigators in follow-up analysis of compounds using computerized databases, and will help in the development of moreprecise screens. The long-term objectives of the Core are to promote the development of novel screening platforms to meet changing biodefense needs. Moreover, it will serve as a centralized resource for testing alternative natural or synthetic compound libraries as well as promote interactions between RCE investigators and medicinal chemists in the development of lead compounds to therapeutic products. Further development of promising compounds will be evaluated in consultation with MAID, interested industrial partners, and the NERCE Scientific Steering Committee. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CRYOGENIC SHIPPER FOR BIOMEDICINE AND BIODEFENSE Principal Investigator & Institution: Flynn, Thomas Murray.; Cryoco, Inc. 511 N Adams Ave Louisville, Co 800272241 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-MAR-2004 Summary: (provided by applicant): Progress in medical research worldwide is dependent on the safe, rapid, reliable and convenient exchange of biological specimens that are optimally preserved. Without the confidence that cryopreserved specimens being shipped among clinical sites, research laboratories and/or repositories will retain their integrity for the intended purposes - whether for in-vitro viability or functionality assays, or for in-vivo clinical or research purposes, the biomedical and biotechnological advances are seriously jeopardized. To date, the three-decade old safety innovation of the non-spill ("dry") vapor-phase liquid nitrogen (LN2, at-126 C, 77K) shipping tank, has only been applied to one commercial shipper possessing both a capacity for (up to 4) standard size freezer storage boxes and able to meet the IATA regulations for shipping cryopreserved infectious substances. A larger (6-12 freezer box) capacity, certified for both thousands of cryovialed specimens (biomedical research) and for infectious tissues or organs (disease control investigations; biodefense responses) can provide great flexibility while complying fully with IATA and US DOT regulations The earlier Phase I (see Introduction) simply showed that it was possible to use solid foams highly adsorbent of LN2 for greatly improved spill-proofing; and light-weight polymers having high strength at LN2 temperatures to replace aluminum for the body of the Dewar vessel. This current program will develop new data to optimize these components and to prove the feasibility of an innovative, low-cost; LN2 vapor-phase cooled Frozen Specimen Shipping Unit. Key innovations include: (1) proprietary nospill, faster-adsorbing material for the LN2 reservoir; (2) a lightweight polymer matedal
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(plastic) for the vessel ("Dewar") instead of aluminum; and (3) novel aerospace-type cryogenic insulation to extend holding time. Crucial to this Phase 1 program is optimizing a polymer for low temperature material strength and high vacuum service. In Summary, Phase I specific aims are: 1.Develop analytic techniques to compare polymers for Dewar vessel matedal to achieve high vacuum. 2. Select polymer and barrier techniques for enhanced cryogenic insulation. 3. Specify cryogenic insulation based on comparative properties (incl: holding time, cost, structural contribution to twopoint suspension, degradation of performance with time). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DESIGN OF ATTENUATED TULAREMIA VACCINE Principal Investigator & Institution: Cross, Andrew M.; University of Maryland Balt Prof School Baltimore, Md 21201 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2008 Summary: Its ease of transmission, history of having been weaponized and propensity to cause severe and fatal disease following inhalation, make Francisella tularensis (Ft) a Category A bioterrorism agent of concern. The only vaccine available for more than 40 years is efficacious, but its mode of attenuation is unknown and the FDA has not approved its general use. Development of new vaccines is limited by the paucity of information about the virulence determinants of Ft. This project will provide (1) measures to extend the disease-free interval until definitive therapy/vaccines are implemented; and (2) vaccines that induce humoral and cellular immunity to Ft. Project 1A will characterize mechanisms by which the unusual Ft LPS induces mediators responsible for the systemic inflammatory responses of tularemia, and determine if reagents already under clinical testing for sepsis are useful in the treatment of disseminated tularemia in a murine model. Upon stimulation, gamma-delta T cells rapidly produce inflammatory cytokines critical to both the initial innate immune response and organization of the adaptive responses. Activation of gamma-delta T cells is associated with convalescence from tularemia. Aminobisphosphonates drugs, widely used for bone disorders, stimulate gamma-delta T cells and might serve as initial therapy for individuals exposed to Ft (Project 1B). Project 2 will characterize the Ft capsule and develop a conjugate vaccine, using as carriers either the protective antigen of B. anthracis or proteins derived from plague or Ft. Adjuvants that also rapidly boost innate immunity (e.g. CpG) may accelerate a humoral response and provide early protection. Like the Vi vaccine for the intracellular pathogen, Salmonella Typhi, the Ft capsular conjugate vaccine is intended to prevent Ft from reaching its required intracellular niche. Durable immunity to Ft requires a cellular immune response. Based on our previous success in developing live attenuated strains of Salmonella, we will design an attenuated, easily administered Ft vaccine (Project 3A). Signature-tagged mutagenesis will define additional targets for attenuation and new virulence factors for further study (Project 3C). Activated T cells are sequestered in peripheral tissues. We will compare which immunization regimen optimally delivers primed effector/memory T cells to lung and liver, sites of Ft replication. These studies will provide public health officials short term and definitive treatment options in the event of a bioterror attack with Ft. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: DEVELOPMENT OF THERAPEUTIC INHIBITORS TO ANTHRAX TOXINS Principal Investigator & Institution: Peterson, Johnny W.; Professor and Vice Chair; 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-JUL-2007 Summary: (provided by applicant): Anthrax is a highly infectious disease caused by Bacillus anthracis, and aerosolization of the dried bacterial spores is a major biological warfare and bioterrorism threat. Two plasmid-encoded anthrax toxins are essential for bacterial virulence. Edema toxin (EdTx) is comprised of edema factor (EF) and protective antigen (PA), while lethal toxin (LeTx) is a molecular complex of lethal factor (LF) and PA. EF is a secreted calmodulin-dependent adenylyl cyclase enzyme that causes tissue edema, and LF is a uniquely selective Zn++-metalloprotease that inactivates important cell-signaling enzymes (mitogen-activated protein kinase kinases [MAPKKs]) in mammalian cells. PA is the receptor-binding component, which delivers the catalytic components into the cytosol of cells. Our hypothesis is that novel drugs (specific inhibitors of anthrax toxins) can be prepared to reduce the virulence of these bacteria for humans/animals and provide a new therapeutic adjunct to antibiotic therapy and vaccination. The proposal is based on our extensive preliminary studies of new heterocyclic compounds (e.g., prostaglandin E2-L-histidine) that specifically block the adenylyl cyclase activity of EF, and knowledge of metalloprotease inhibitors that block LF activity. Objective 1 will evaluate the capacity o PGE2-L-histidine and PGE2imidazole to reduce adenylyl cyclase activity of the EF toxin component using an in vitro enzyme assay. We will then use these data to design other inhibitors and dock them on the known crystal structures of EF and other adenylyl cyclases. Objective 2 will identify and characterize inhibitors that block the Zn++-metalloprotease activity of LF, and we will use these data in 3D-Quantitative structure activity relationship (QSAR) computations to optimize the enzyme inhibitors. Objective 3 will test the effectiveness of the EF and LF inhibitors in protecting cultured cells and mice challenged with toxins or B. anthracis. Objective 4 will evaluate the pharmacologic and toxicologic properties of these toxin inhibitors in experimental animals and establish their relative safety. Development of new drugs for anthrax by combining the inhibitors of EF and LF should reduce the virulence of B. anthracis, increase the efficacy of antibiotics, promote killing of the bacteria by phagocytes, and enhance vaccine-induced immunity. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: DIRECT INHIBITION OF ANTHRAX TOXIN ACTION Principal Investigator & Institution: Collier, R J.; Professor of Microbiology; Harvard University (Medical School) Medical School Campus Boston, Ma 02115 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2008 Summary: Besides exposing our general vulnerability to bioterrorism, the anthrax attacks of the fall of 2001 alerted the nation to the need to develop therapies and vaccines against Bacillus anthracis. B. anthracis produces two major virulence factors-an antiphagocytic poly-D-glutamic acid capsule and a tripartite toxin. Injection of the purified toxin causes rapid death of sensitive rodents and non-human primates, and immunization against the toxin protects against infection. Thus it is generally believed that death from anthrax infections results from the effects of the toxin. As a step towards developing new therapeutic interventions for anthrax, we propose to use a highthroughput screen to identify low molecular mass compounds that inhibit the action of
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anthrax toxin at the cellular level. We have developed a sensitive assay based on the effect of this toxin on mouse macrophages. Building on the experience of the Collier laboratory in studying anthrax toxin, we will characterize the most promising inhibitors found, to determine the specific step in toxin action that each inhibits. Lead compounds with low toxicity will be considered for testing in animal models of toxin action. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DISRUPTION OF INTRACELLULAR TOXIN TRANSPORT Principal Investigator & Institution: Kirchhausen, Tomas L.; Cbr Investigator/ Professor; Harvard University (Medical School) Medical School Campus Boston, Ma 02115 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2008 Summary: Many toxins require the normal function of membrane traffic pathways to exert their toxic effects. We recently developed an imaging-based medium-throughput screen with intact cells to identify chemicals that affect different pathways of membrane traffic. From two different screens and using over 19,000 compounds, we identified two chemicals, exo2 and secramine, with unique and specific effects on the function of cholera toxin and anthrax edema toxin. This suggests a potential novel route to therapeutics to mitigate the effects of these toxins, and possibly also those of ricin and shiga toxin, which, like cholera toxin, enter cells through endocytosis and require transport to the ER to exert their action. We now propose studies to determine the molecular basis for the biological activity of secramine on retrograde traffic from the TGN and the ER and to elucidate its molecular target. The results of these studies will ultimately allow us to design or discover a more potent analog of secramine. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: DYNAMIC NEUROTOXINS
DRUG
DESIGN
TARGETING
BOTULINUM
Principal Investigator & Institution: Briggs, James M.; Assistant Professor; Biology and Biochemistry; University of Houston 4800 Calhoun Rd Houston, Tx 77004 Timing: Fiscal Year 2003; Project Start 15-AUG-2003; Project End 31-JUL-2005 Summary: (provided by applicant): Botulinum neurotoxins (BoNTs) are a dangerous bioterrorism threat due to their extreme potency and lethality, as well as their ease of production and transport. If untreated, poisoning by the BoNTs can progress to flaccid paralysis and death due to respiratory failure. However, timely post-exposure intervention can limit the effects of the circulating toxin. Our overall, long-term research objective is to generate a novel class of therapeutics that can be administered to individuals who have been poisoned by BoNT. Each BoNT is composed of a catalytic light chain whose entry into neurons is mediated by the heavy chain. Our strategy is based on the model that botulism-related flaccid paralysis is a downstream consequence of the zinc-dependent endopeptidase activity elaborated by the BoNT light chain. One of the most powerful approaches to inactivate the endopeptidase function of the BoNT light chains is rational design of inhibitors targeting the active site. To achieve this, we wilt combine computational and experimental approaches to develop lead inhibitor templates. In Specific Aim 1, we will use a powerful computational approach called dynamic pharmacophore modeling to identify computational leads to block the endopeptidase activities of the BoNTs. In this approach, the conformational flexibility of the protein and active site are taken into account through molecular dynamics simulations and the generation of a consensus, or dynamic, pharmacophore model using an ensemble of molecular dynamics-generated protein conformations. The
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dynamic pharmacophore model is then used to search databases of commercially available small molecules to generate computational lead compounds. In Specific Aim 2, we will test each computational lead for inhibitory activity using enzyme assays and in vitro cellular assays. A milestone of this work will be the identification of one or more lead inhibitor templates that block the action of wild type toxin using in vitro model systems. The results from this research will establish the groundwork and justification for future development and in vivo testing of these novel inhibitors using established animal models. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: EARLY EVENTS IN THE PATHOGENESIS OF PNEUMONIA PLAGUE Principal Investigator & Institution: Goldman, William E.; Professor; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2008 Summary: Pneumonic plague is the deadliest form of disease caused by Yersinia pestis. The rapid progression of pneumonic plague, along with the ability to transmit it by an aersolized form make it a deadly bioterrorism threat. In this project, we will characterize the interaction between Yersinia pestis and airway epithelial cells using an in vitro model of infection. Primary cultures of rat pneumocytes will be infected with bacterIa, and we will characterize both the bacterial and host responses to infection using a variety of techniques, including microarray analyses. We will extend these studies to the hamster tracheal organ culture system developed by our laboratory and use these to study Y. pestis wild type organisms, as well as mutants of Yersinia lacking one or more of the three virulence plasmids. These studies will tell us more about how Yersinia interacts with host respiratory cells, and may provide new targets for therapeutics and plague vaccines. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: EBOLA VP35 MEDIATED VIRAL MECHANISMS Principal Investigator & Institution: He, Bin; Microbiology and Immunology; University of Illinois at Chicago 1737 West Polk Street Chicago, Il 60612 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2005 Summary: (provided by applicant): Ebola virus is a highly dangerous pathogen causing hemorrhagic fever in humans. Currently, there is no vaccine or effective treatment available for Ebola virus infection. While multiple factors contribute to the pathogenesis of Ebola virus infection, the ability of Ebola virus VP35 to abate the host interferon response is critical in determining the outcome of viral infection. VP35 is an essential component required for the Ebola virus RNA replication and nucleocapsid assembly. In addition, VP35 is implicated as an interferon antagonist. When expressed in mammalian cells, VP35 blocked interferon-beta expression and induction of interferon-stimulated response genes triggered by RNA or virus infection. These observations are consistent with previous findings that in cells infected with Ebola virus, production of interferon or expression of interferon-inducible genes is suppressed, for example, MHC class I, double-stranded RNA-dependent protein kinase, and interferon regulatory factor-1. Recent studies showed that mice lacking an interferon alpha/beta response resemble primates in their susceptibility to rapidly progressive, overwhelming Ebola virus infection. These studies suggest that VP35 is a viral factor that interferes with one or more components of the interferon pathways, therefore inhibiting host interferon response that results in rapid spread and dissemination of viruses. In this proposal, the
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biological functions of VP35 in interferon response will be investigated using mammalian cell lines and a surrogate infection system. Deletions or site-specific mutations will be used to define the functional modules of VP35. Furthermore, biochemical and genetic approaches will be employed to examine the nature of interactions between VP35 and the interferon pathways. Because of the potential of VP35 as a vaccine and antiviral target, the proposed studies should not only provide insight into the pathogenesis of Ebola virus infection but could also lead to the development of antiviral therapeutics. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ENTERIC PATHOGENS Principal Investigator & Institution: Guerrant, Richard L.; Professor; University of Maryland Balt Prof School Baltimore, Md 21201 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2008 Summary: Research Project V includes two Sub-Projects focused on key new aspects of the genomics, pathogenesis and vaccinology of the two leading Category B low-dose enteropathogens, and on their detection in clinical and environmental samples. These include the highly chlorine-resistant Cryptosporidium parvum, the most fearsome Shigella threat (S. dysenteriae 1) and the largely untreatable, Shiga toxin-producing enterohemorrhagic E. coli. These three pathogens all pose serious risks as low infectious dose agents of bioterrorism as well as major national and global health endemic and epidemic challenges. The team of investigators for this project has a very strong track record of working with these organisms. Led by experienced investigators with international reputations in enteric diseases, Richard L. Guerrant and James B. Kaper, this project builds upon highly productive expertise and upon longstanding and new cross-institutional synergies at UVa, UMd, VCU, VT, USUHS, UVt, and JHU. Our first Sub-Project V.1, on "Cryptosporidium genomics, pathogenesis and vaccinology" builds upon the near complete sequencing of the human (type 1) C. parvum genome by the VCU group, the published tissue culture, animal and field experience with Cryptosporidium by the UVa group, the plant-based production of mucosal vaccines at VT and on studies of the genetics of susceptibility at UVa, UVt, and JHU to identify and express type 1 (human) C. parvum candidate genes, define their roles in pathogenesis and immunity, express promising candidates and define genetic determinants of human susceptibility and thus optimal approaches to vaccine development. Sub-Project V.2 will engage UMd, USUHS and UVa colleagues to construct novel Shigella dysenteriae and enterohemorrhagic E. coli (EHEC) vaccines and develop novel therapeutics for EHEC disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: EPIDEMIOLOGY OF EMERGING INFECTIOUS DISEASES AND BIOTERR Principal Investigator & Institution: Tompkins, Lucy S.; Professor; Medicine; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2008 Summary: (provided by applicant): We propose to train MD, MD/PhD and pre-doctoral investigators in contemporary epidemiology of emerging infectious diseases and bioterrorism through instruction, practical application, and research in fundamental epidemiology, biostatistics and molecular epidemiology. For some trainees, additional training in bioinformatics or medical informatics will be offered. Trainees will be drawn
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from the pool of those accepted into the PhD graduate program in epidemiology at Stanford and from postdoctoral fellows in adult or pediatric infectious diseases. Trainee applicants will be evaluated by the Steering Committee and offered training grant slots on the basis of academic records, faculty interviews and demonstrated interest in epidemiology. Every effort will be made to attract minority candidates. The training program will be interdisciplinary, involving faculty from the Division of Epidemiology (Medicine (Infectious Diseases), and Pediatrics (Infectious Diseases) at Stanford and the School of Public Health, University of California/Berkeley. Predoctoral students will complete the requirements of the Stanford PhD program in epidemiology. MD or MD/PhD infectious diseases postdoctoral fellows may elect to obtain the MS degree in epidemiology, although this is not a requirement. The emphasis of the program is on research training in epidemiology of infectious diseases and bioterrorism. Trainees will conduct research under the mentorship of at least one training program faculty member; most will be co-mentored by two members of the training program. Thus, most research projects will be cross-disciplinary to take advantage of the strengths of the faculty. To promote interaction among trainees and faculty, research seminars conducted by trainees, weekly interdisciplinary seminars in infectious diseases epidemiology, weekly infectious diseases grand rounds, infectious diseases and bioterrorism lectures presented by faculty, and an annual 1-day research retreat will be held. Each trainee will be counseled and directed by a Research Committee comprised of the mentor(s) and several other scientists whose area of expertise is relevant to the project. The trainee will present his/her research progress to the committee at regular intervals. One PhD predoctoral and two MD (MD/PhD) post-doctoral trainees are to be supported by the Training Program each year. All trainees will be encouraged to apply for independent support. Trainees are expected to graduate to academic appointments or public health leadership positions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENETIC ANALYSIS OF LETHAL FACTOR SENSITIVITY Principal Investigator & Institution: Dietrich, William F.; Assistant Professor; Genetics; Harvard University (Medical School) Medical School Campus Boston, Ma 02115 Timing: Fiscal Year 2003; Project Start 01-JUN-1998; Project End 31-MAY-2008 Summary: (provided by applicant): Anthrax lethal toxin (LeTx) is an important component of the pathogenesis caused by Bacillus anthracis infections. We have recently identified mutations in a kinesin gene (Kif1 C) that increase susceptibility of mouse macrophages to the cytotoxic effects of LeTx. While it is well known that Kif1 C is a motor protein that mediates the intracellular transport of vesicles, the exact functions of Kif1 C in cells under normal and LeTx-intoxicated conditions are not well described. Accordingly, in the first 2 Aims, we propose experiments that exploit the different alleles of Kif1 C to try to unravel important aspects of its function. Specifically, we will test if the susceptibility-inducing mutations affect Kif1 C protein abundance, the susceptibility of Kif1 C to LF mediated proteolysis, the intracellular distribution or phosphorylation of Kif1 C, and the interactions of Kif1 C with likely cargo vesicles and proteins. The third Aim is designed to explore some essential unexplained questions about the functioning of the anthrax toxins during anthrax pathogenesis. We propose to investigate the possibility of an interaction between edema toxin and lethal toxin in the cytolysis of macrophages. We also propose to search for human macrophage variation in LeTx susceptibility as a means to better understand the pathogenesis of human anthrax and perhaps provide an explanation of variation in human susceptibility to anthrax.
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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HAND-HELD SYSTEM TO DETECT ANTHRAX SPORES IN BIODEFENSE Principal Investigator & Institution: Lemieux, Bertrand; R and D Group Leader; Iquum, Inc. 214 Lincoln St, Ste 300 Allston, Ma 02134 Timing: Fiscal Year 2003; Project Start 01-MAR-2003; Project End 31-OCT-2003 Summary: (provided by applicant): A recent government study on the accuracy of field tests for anthrax spores has cast serious doubt on the validity of these tests. This report clearly indicates the urgent need for a more rigorous selection of deoxyribonucleic (DNA) markers for anthrax testing. The proposed project aims to develop a more specific nucleic acid test for anthrax spores. PCR primers will be designed to amplify sequences in the anthrax bacterial chromosome and plasmids that can differentiate anthrax from related species. Rapid extraction of nucleic acids from anthrax spores is also a challenge for field tests. We will develop efficient spore disruption and nucleic acid extraction techniques by exploring a combination of approaches, including germination induction and mechanical disruption. The nucleic acid extraction and amplification protocols will then be incorporated into our proprietary lab-in-a-tube (Liat (TM)) platform to develop a handheld device that is suitable for field tests. The Liat system has been shown to be capable of performing rapid close-tube polymerase chain reaction (ct-PCR) DNA amplifications in 1/6 the time required by conventional thermal cyclers. Moreover, the system can be operated for 6 hours on battery power. Novel approaches to combine multiple tests in a single tube that will surpass the capability of other diagnostic technology platforms are also under development. A closed-tube assay will be safer to implement and the hand-held device will deliver results more quickly than most of the systems currently in operation. This fully automated "sample-toanswer" system will enable minimally trained operators to perform sophisticated nucleic acid tests in the field. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: HEMORRHAGIC FEVER Principal Investigator & Institution: Broder, Christopher C.; Associate Professor; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2008 Summary: Viral agents known to cause hemorrhagic fever disease with high morbidity and mortality in humans, such as the Bunyaviruses - Crimean-Congo hemorrhagic fever virus, Rift Valley fever virus, and Hantaan virus or the Filoviruses -Ebola and Marburg virus, are priority pathogens of biodefense concern. In addition, there have been several outbreaks of newly discovered and/or emerging viruses which have also resulted in significant numbers of human fatalities, and these include the Flavivirus West Nile virus and the Henipaviruses Nipah and Hendra virus. These emerging viruses have also been classified as agents of biodefense concern because they possess characteristics making them suitable for weaponization. For all of these viruses there are neither approved vaccines nor therapeutics for the prevention of infection or disease. As a potential gapfilling approach for the rapid development of safe and efficacious antiviral therapies for these agents, we propose to identify, isolate and characterize neutralizing human monoclonal antibodies (nhMAbs) reactive to the native forms of the envelope glycoproteins (Envs) of these viruses. The development of these nhMAbs would provide a valuable battery of post-exposure or post-infection therapeutics to combat disease
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caused by these agents. The antibodies will be obtained by screening human phage display libraries against the viral Envs. Our Research Project will be comprised of four Sub-Projects. The unifying strategy of these projects will be the development of recombinant-based assays for measuring virus entry along with the production of native viral Envs as antigens for phage panning procedures. Sub-Project 1 will develop the assays and Env antigens for the Henipaviruses and Bunyaviruses; Sub-Project 2 will focus on the Flaviviruses; Sub-Project 3 will employ the Ebola and Marburg virus systems; while Sub-Project 4 will develop a second-generation alphavirus-based replicon system as a vaccine platform utilizing one or more of the viral Envs derived from the other Sub-Projects. The overall objectives of the Research Project will be to develop a battery of potent nhMAbs capable of being used as passive immunotherapy against several important viral pathogens, and develop a vaccine platform capable of eliciting a humoral response which includes the antibody reactivities observed by those nhMAbs developed by the other Sub-Projects. The overall Research Project's Specific Aims will be 1) Develop high-throughput recombinant assays for virus entry and develop recombinant viral Envs; 2) identify and isolate Fabs and scFvs capable of blocking virus entry by using recombinant viral Envs and/or functional pseudotyped or virus-like particles as antigens for phage panning; and 3) develop and test a novel alphavirus-based vaccine platform. In summary, the short-term goals of this research Program will be the development of nhMAbs that could be used for passive immunotherapy, while the long-term objective is the creation of a vaccine platform capable of eliciting similar antibody responses in an animal host. Both of these research goals are priorities as immediate and long-term objectives for biodefense research on viral hemorrhagic fevers and emerging viruses. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HIGH THROUGH-PUT DETECTION OF FUNGAL PATHOGENS Principal Investigator & Institution: Fell, Jack W.; Marine Biology and Fisheries; University of Miami Coral Gables University Sta Coral Gables, Fl 33124 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-JUL-2005 Summary: (provided by applicant): Diagnoses of opportunistic fungal infections constitute an increasing clinical problem. Conventional diagnostic tests are time consuming and lack specificity and sensitivity for accurate and timely prognoses. The lack of precise and prompt diagnoses has undermined the health of patients and contributed to high mortality rates in immunocompromised individuals undergoing aggressive medical treatments. This condition has led to an increase in the emergence of new antifungal resistant strains and the need for rapid non-culture based methods for the detection of pathogens at species and strain levels. In cooperation with a unique team of researchers from government (USDA, Peoria, Ill), academia (University of Miami), two clinical laboratories (John Hopkins Medical Institute and Allogen Laboratories of the Cleveland Clinic) and industry (Luminex Corp, Austin, TX) we propose to develop a sensitive, fast and reliable high throughput DNA based method aimed at detection of such important fungal pathogens as species of Aspergillus, Candida, Cryptococcus and Trichosporon. The detection method will combine the specificity and reliability of nucleic acid hybridization analysis with the speed and sensitivity of LabMap, a new flow cytometric technique by Luminex Corp. The multiplexed assay analysis will consist of a combination of fluorescent microspheres covalently bound to species-specific fungal oligonucleotide probes, with the capability to simultaneously test as many as 100 different species-specific probes per tube/well at rates 0.47 min/well probes per minute. In the preliminary stages of this research, the
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system will be developed with extensive in-house databases and culture collections from USDA and UM and from clinical isolates from JHMI to produce a detection technique for cultured organisms. Validation of the assay with archived clinical specimens will be in conjunction with the Allogen Lab, which will lead to a detection system directly from clinical specimens. The fungal detection system will be expanded to include all known yeasts, including medical, foodborne and industrial species as well as other filamentous pathogens. We foresee that this multiplex testing fungal platform can be expanded to other microorganisms with important applications in areas of public health, bioterrorism, food safety and the environment. Resulting data will be disseminated via GenBank, publications in leading scientific journals and as an inexpensive commercial detection system. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HOST RESPONSES TO THE TULAREMIA AGENT Principal Investigator & Institution: Benach, Jorge L.; Professor, Molecular Genetics and Microb; Molecular Genetics & Microbiol; State University New York Stony Brook Stony Brook, Ny 11794 Timing: Fiscal Year 2001; Project Start 01-AUG-2000; Project End 31-JUL-2003 Summary: Human tularemia is a highly virulent bacterial zoonosis with endemic foci in the northern hemisphere. Its clinical manifestations depend on the route of infection. The ulceroglandular form is the most common presentation after handling sources contaminated with Francisella tularensis. When ingested, contaminated food or water can cause an oropharyngeal form. Pulmonary, typhoidal (the two more common forms reported in laboratory workers), glandular and ocular forms are other less frequent presentations. The disease occurs in outbreaks, usually associated with direct contact with infected game or contaminated water, or in a seasonal pattern in arthropod-borne tularemia. The severity of this infection, its initial nonspecific manifestations, and the ability of the agent to survive in the environment have led to the inclusion of F. tularensis in a list of bacterial pathogens that could be used for bioterrorism. The human and murine responses to F. tularensis have been studied with particular emphasis on the survival of the bacterium within macrophages and the cytokine responses resulting from intracellular infection. Less known are the interactions of this organism with cells that it must encounter to cause systemic infection. Thus, a very focused study of the interaction of F. tularensis with endothelium is proposed for this R03 application. Both the attenuated vaccine strain and the virulent American strain (F. tularensis tularensis) will be used for parallel experiments on infection of endothelium and its pro-inflammatory activation, as measured by upregulation of expression of adhesion molecules and chemokines. One feature of tularemia that has not been investigated is the manner of spread of this organism within the infected host. Tularemic lesions contain a marked mononuclear cell infiltrate, and the sequence of lesion formation is not known. Trafficking of the bacterium alone and of cells infected with the bacterium (neutrophils, monocytes) will be studied by assessing their ability to cross endothelium in vitro. Earlier studies have found that the lipopolysaccharide of F. tularensis does not activate mononuclear cells, so its effect on stimulation of endothelial cells is not clear, nor is there a certainty that there is a CD14-dependency of the response to the lipopolysaccharide or the whole organism. The proposed research is aimed at a greater understanding of the mechanisms used by F. tularensis to cause systemic infection. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: HUMAN DENDRITIC CELLS AND IN VIVO IMMUNITY TO BIOTHREAT Principal Investigator & Institution: Banchereau, Jacques F.; Director; Baylor Research Institute 3434 Live Oak St, Ste 125 Dallas, Tx 75204 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-MAR-2008 Summary: (provided by applicant): Vaccines and antibiotics permitted to combat many infectious diseases. While a wealth of vaccines has been developed, natural evolution and engineering for bioterrorism purposes creates a novel biothreat for which novel vaccines are needed. Dendritic cells (DCs) play a central role in the differentiation of immune effectors and thus are a major target for vaccination. Given the fact that distinct human DC subsets differentially control lymphocytes, it is important to understand how distinct DC subsets modulate vaccine immunity in vivo. Such knowledge will permit us to design targeted vaccines that will induce a desired type of immunity. Vaccines need to be tested in vivo but studies in mice often cannot be directly extrapolated to humans because of biological differences. Hence, the need for pre-clinical models of the human immune system for testing vaccine efficacy. With this in mind, The goal of the Center is to develop effective diagnostic, prognostic, and therapeutic measures against NIAID Category A-C pathogens through a focus on human dendritic cell subsets, which act as innate effectors as well as initiators and coordinators of adaptive immune responses. Objectives: 1. Develop our in vivo model of human immune responses based on mice reconstituted with a full human immune system. 2. Generate novel monoclonal antibodies identifying i) the various human DC subsets at their various stages of maturation, and ii) peptides derived from biothreat antigens presented by dendritic cells 3. Determine how Category A-C pathogens alter human dendritic cells in vitro and in vivo. 4. Determine the effects of Category A-C pathogens on the human immune system in vivo. 5. Identify the in vivo biosignatures of human Category A-C pathogens to allow rapid biothreat diagnosis, prediction of disease severity and initiation of biothreat specific treatment. 6. Test and identify in vivo novel human vaccines as biothreat countermeasures. The Program will include a Technical Development Component, four projects, 3 Core facilities: Administration, Microarray and Luminex multiplex analysis, and Education component. Two pilot projects are also proposed. Center will be based at the Baylor Institute for Immunology Research at Dallas and will include Investigators at Yale U., Rockefeller U., NIAID, U. of New Mexico and UT Southwestern. By harnessing human DC subsets in vivo we surmise that we will able to propose novel potent vaccines to protect humans against category A-C pathogens. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: IMMUNE EVASION MECHANISMS OF ECTROMELIA VIRUS Principal Investigator & Institution: Fremont, Daved H.; Assistant Professor of Pathology; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2008 Summary: Poxviruses are a family of large DNA viruses that encode up to 200 distinct open reading frames. The large size of the poxvirus genome is an important feature that has allowed them to acquire multiple immunomodulatory genes and thereby evolve unique strategies for evasion from host anti-viral responses. Ectromelia virus (EV) is a member of the orthopoxvirus family and is a highly virulent rodent pathogen that causes the disease mousepox. EV is similar to variola virus, the causative agent of human smallpox. Our primary hypothesis is that secreted and cell membrane associated proteins encoded by EV likely serve important roles in viral evasion of host mediated
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innate and adaptive immune responses. Using a bioinformatics approach coupled to the established literature, we have selected 28 target proteins from the EV Moscow strain genome that will be investigated by a combination of biochemical, functional, and crystallographic tools in a high-throughput, structural genomics style approach. Our primary targets of investigation include the seven known cytokine and chemokine decoy receptors encoded by the virus that are specific for TNF, CD30L, IL-18, IFN-alpha, IFN-gamma, IL-1beta, and CC-chemokines. We are also targeting three proteins with sequence similarity to natural killer receptors of the C-type lectin family. We have the following specific aims for the exploration of these potential agents of immune subterfuge: (1) Establish baculovirus and bacterial oxidative refolding expression systems for targeted EV encoded proteins to be used in functional and structural studies; (2) Identify and characterize the interactions between EV proteins and their host ligands and receptors; (3) Determine the structural basis of EV protein function by x-ray crystallography and structure-based mutagenesis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: IMMUNOSTIMULATORY DNA PRIMING OF LUNG INNATE IMMUNITY Principal Investigator & Institution: Coffman, Robert L.; Vice President and Chief Scientific Offi; Dynavax Technologies Corporation 717 Potter St, Ste 100 Berkeley, Ca 94710 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-MAR-2006 Summary: (provided by applicant): Synthetic oligonucleotides with immunostimulatory sequences (ISS) containing unmethylated CpG dinucleotides mimic the innate recognition of microbial DNA and show great promise as adjuvants and immune modulators in a wide variety of therapeutic settings. In addition to their ability to activate multiple components of innate immunity, ISS have shown the ability to "prime" the innate immune system to give enhanced innate and subsequent adaptive responses to a number of bacterial and viral pathogens (3). This can lead to enhanced resistance to both lethal and sublethal challenges. A single administration of ISS in animal models can provide measurable protection for two to four weeks and increased resistance can be maintained with periodic administration of ISS. Prophylactic vaccination through the innate immune system has significant potential as a first-line defense for populations threatened with exposure to bioterrorism/biowarfare agents or exotic or emerging infectious diseases. This proposal is for the development of an inhaled form of ISS as a prophylaxis for airborne infectious agents. We currently are developing 1018 ISS for treatment of asthma and have completed preclinical development and Phase I safety studies in man. The current studies would provide a set of proof-of-principle studies for its use as an inhaled prophylactic and would generate a set of surrogate assays that would be essential for clinical development for this indication. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: IMPACT OF ANTHRAX TOXIN ON EMBRYONIC DEVELOPMENT Principal Investigator & Institution: Ballard, Jimmy D.; Associate Professor; Botany and Microbiology; University of Oklahoma Norman Office of Research Services Norman, Ok 73019 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2005 Summary: (provided by applicant): Bacillus anthracis lethal toxin and edema toxin modify the physiology of cells by disrupting MAPKK signaling pathways and causing
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accumulation of cAMP respectively. Both MAPKK signaling and cAMP are important regulators of development and exposure of embryos to anthrax toxin could lead to defects. In recent DNA array studies we have found that Wnt signalling may also be disrupted by lethal toxin. Wnt signaling is a major part of development and aberrations in this pathway could also lead to defects in the developing embryo. In light of these observations we carried out pilot experiments on zebrafish embryos and found noticeable defects after treatment with anthrax toxin. These results strongly suggest a better understanding of anthrax toxin's impact on development is needed. In the case of a bioterrorist disseminating B. anthracis spores over a populated area, at least 1.5% of the human population will be pregnant and embryos could be exposed to the toxin. Therefore, in order to better understand the impact of anthrax toxin on embryonic development, we will address two specific aims. Specific Aim 1. We will determine the impact lethal toxin and edema toxin have on zebrafish embryo development. Specific Aim 2. We will determine the impact inactive anthrax toxin mutants have on zebrafish embryo development. Specific aim 2 will address the possibility that vaccine and therapeutic candidates might cause developmental defects. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: INNATE IMMUNITY HEMORRHAGIC FEVER VIRUSES Principal Investigator & Institution: Finberg, Robert W.; Professor of Medicine & Microbiology; Harvard University (Medical School) Medical School Campus Boston, Ma 02115 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2008 Summary: This project will examine the role of the innate immune system in the pathophysiology of the viral hemorrhagic fevers. Two viruses which are potential agents of bioterrorism, will be studied: 1) Ebola virus, a filovirus, which induces an acute illness characterized by fever, leucopenia, shock, and death, and 2) Lymphocytic Choriomeningitis Virus LCMV an arenavirus which causes an illness characterized by leucopenia and thrombocytopenia in mice and meningitis in humans. The high mortality rate associated with Ebola infection has been demonstrated to be directly associated with cytokine release which occurs after viral infection of macrophages. The mechanism by which Ebola induces this cytokine response will be defined and compounds will be screened for their ability to inhibit this activity. Preliminary data indicate a major role for Toll Like Receptor 2 (TLR-2) and CD14 in the cytokine response to LCMV. TLR-2 and CD14 are pattern recognition proteins whose role in bacterial sepsis has been recently defined. Both have also been associated with the immune responses to viruses. Using transfected cell lines and available knockout mice the mechanism by which these proteins affect both initial induction of cytokines as well as the subsequent immune responses to LCMV and Ebola virus will be defined. The specific TLRs (and other "pattern recognition proteins") involved in these responses as well as their interactions will be studied. The effect of these early recognition events on long-term Band T cell immunity will be investigated. These studies will result in a better understanding of the role that the innate immune system has in mediating the pathophysiology of hemorrhagic fever viruses and should lead to new therapeutic approaches to these diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: INTEGRATED IMMUNOASSAY/PCR TEST FOR BIOTERRORISM AGENTS Principal Investigator & Institution: Tang, Cha-Mei; President; Creatv Microtech, Inc. 11609 Lake Potomac Dr Potomac, Md 20854 Timing: Fiscal Year 2003; Project Start 04-AUG-2003; Project End 31-JUL-2005 Summary: (provided by investigator): This Small Business Innovation Research proposes to combine the best features of three different technologies: immunoassay, cell culture and real-time polymerase chain reaction (PCR), into one integrated test for environmental detection of the CDC Category A agents. Phase I will comprise development of the biosensor instrument, the test cartridge, reagents, and the assays. One bioterrorism agent, anthrax spores, will be used in Phase I. The proposed ThreeStep Biosensor will have the following properties: a rapid, sensitive immunoassay that detects pathogens within 20 minutes, a cell culture step that verifies the viability of the pathogens, a real-time PCR step that confirms positive immunoassay results, quantitation of the number of organisms or toxin molecules in the sample, a compact and self-contained disposable test cartridge that safely confines the environmental sample and all test by-products, automated sample preparation and data acquisition, and a portable instrument format for use in the field by first responders The integrated test will be simultaneously more sensitive and more specific than current methods, both for on-site rapid tests and laboratory applications. By selectively capturing pathogenic anthrax spores from environmental samples and purifying them from all other organisms in the sample, the biosensor can provide a spore-derived vegetative cell lysate free of inhibitors for subsequent PCR reactions. The test addresses the root causes of both false negatives (sensitivity, viability, inhibitors) and false positives (crossreaction, contamination) that affect other methods. Because it confirms organism viability, the test will enable real time monitoring of decontamination efforts, such as that recently performed at Washington DC postal facilities and government offices. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: INTERACTING MOTIFS OF ALPHAVIRUS ENVELOPE PROTEINS. Principal Investigator & Institution: Braun, Werner A.; Professor; Human Biol Chem and Genetics; University of Texas Medical Br Galveston 301 University Blvd Galveston, Tx 77555 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2005 Summary: (provided by applicant): The goal of this project is to obtain residue-specific characterization of the receptor binding sites and antigenic signatures on the envelope proteins of Venezuelan Equine Encephalitis virus (VEEV) and eventually for all alphaviruses. The Center for Disease Control and Prevention has classified VEEV as a bioterrorism agent, as it can be grown to high titers, and disseminated by aerosol. We will test the hypothesis that a comprehensive bioinformatics approach, combined with assays for cell binding, infection, and neutralization with monoclonal antibodies, will identify areas of the glycoproteins that determine antigenicity, fusion, and receptor interactions with host cells. We will establish a 3D-database of interacting regions of known complexes and new tools to locate areas with similar physical chemical properties in other proteins. The resulting trained neural networks or support vector machines will be used to identify areas of the envelope glycoproteins E1 and E2 of VEEV that are most likely to interact. As the 3D structures of E1 and E2 of VEEV have not been experimentally determined, we will model them on existing templates. We will map mutations of El and E2 that correlate with virulence on the models and analyze the
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structures of the surrounding areas. Mutants in selected areas will be assayed for their role in viral entry and fusion, using murine leukemia virus (MLV) pseudotypes that express the VEEV envelope proteins. This novel expression system permits study of the interacting sites of VEEV without the risks of dealing with infectious virus. Once the interacting areas of VEEV have been determined, our computational analysis will be extended to other pathogenic members of the alphavirus family. The resulting models can be used to design peptides mimicking the receptor recognition motifs, that may be the basis for the design of vaccines or inhibitors against alphaviruses. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: IRON TRANSPORT AND REGULATION IN YERSINIA PESTIS Principal Investigator & Institution: Perry, Robert D.; Professor; Microbiology Immunology, and Molecular Genetics; University of Kentucky 109 Kinkead Hall Lexington, Ky 40506 Timing: Fiscal Year 2003; Project Start 01-JUL-1993; Project End 31-MAR-2008 Summary: (provided by applicant): For over two thousand years Yersinia pestis, the causative agent of bubonic and pneumonic plague, has caused widespread loss of human life during recurrent pandemics. Modern, more contained epidemics are common in South America and Madagascar. In addition, Y. pestis is a category A bioterrorism agent with natural zoonotic foci as readily available sources of the organism on nearly every continent. The ability of pathogens to acquire iron from their hosts is one critical parameter in the outcome of the infectious process. Y. pestis encodes nine potential inorganic iron transport systems and two heme/hemoprotein transport systems. Of these, the siderophore-dependent yersiniabactin (Ybt) iron transport system and the Yfe ABC transporter are the most important systems for acquisition of inorganic iron. Ybt is essential in the early stages of bubonic plague and mutations in this system are avirulent in mice infected subcutaneously (SC). However, Ybt- mutants are fully virulent via an intravenous (IV) route of infection. Yfe plays an important role during the later stages of the infection - a Ybt-Yfe- mutant is completely avirulent in mice by IV injection. By SC injection, a Yfe- mutant is 75-fold less virulent than its Yfe+ parent suggesting that the Ybt system can partially compensate for a lack of the Yfe system but it is clearly not as effective in the later stages of disease. Expression of both systems is repressed by iron through the iron-responsive regulatory protein Fur. In addition, the Ybt system is activated by an AraC-type regulator, YbtA, possibly acting in concert with the Ybt siderophore. The Yfe system is also repressed by excess manganese through the Fur protein. In vivo repression by manganese and Fur is a unique regulatory mechanism. The specific aims of this proposal are to continue characterizing genetic and biochemical aspects of 1) the Ybt and 2) the Yfe transport systems and 3) to analyze the expression of these two systems in vivo and determine their roles in systemic spread of the disease. We will identify any remaining elements necessary for the function of these systems, examine the regulatory components controlling expression of these systems in vitro and in vivo, and determine the role of these systems in the infectious disease process of plague. An understanding of the components and functions of these twotransport system may lead to their use as protective antigens or as targets for new drugs. Our studies will also provide insights into the role of Ybt and Yfe in the pathogenesis of plague and other disease-causing organisms and into the general importance of iron acquisition in bacterial disease processes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MENTAL HEALTH CONSEQUENCES OF BIOTERRORISM Principal Investigator & Institution: North, Carol S.; Professor; Psychiatry; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2002; Project Start 01-JUN-2002; Project End 31-MAY-2004 Summary: The anthrax attacks subsequent to September 11, 2001 ushered in a new2 era of bioterrorism threat in the United States. This new area has arrived with no existing systematic database on the mental health effects of bioterrorism to guide our nation's response to it. In developing interventions to address psychological effects of bioterrorism, workers and policymakers can at best only extrapolate from information about other kinds of terrorism and other types of disasters, which may not fit the situation. In the special form of stealth terrorism that makes bioterrorism unique, victims often don't know their exposure status. This disarticulates psychological and behavior response from individuals' perceived exposure to the agent. As a result, mental health risks to individuals from bioterrorism are unpredictable because the risk follows unknown variables other than exposure that are not well understood. Our highly experienced disaster research team proposes to establish new research on the mental health effects of the recent bioterrorism attacks on Capitol Hill. We are unique positioned to respond to a narrow window of access to the exposed Capitol Hill population during the annual period of relative legislative quiet, when the affected population is most available to participate in research. This proposed one-year study will start by conducting focus groups with Capitol Hill office staff to identify the relevant issues for study. The information thus obtained will be used to develop interviews about the mental health effects of bioterrorism, to be administered to a random sample of 200 staff workers across Capitol Hill. This research will yield valuable information on mental health responses to bioterrorism and will provide an empirical basis for helping professionals responding to the mental health issues of the affected victims of this and future incidents. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PROGRAM
MRCE
CLINICAL/TRANSLATIONAL
RESEARCH
TRAINING
Principal Investigator & Institution: Polish, Louis; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2008 Summary: To provide an integrated training program for postdoctoral medical personnel, particularly, but not limited to, infectious disease fellows within Region VII in the epidemiology, recognition, and treatment of category A-C agents of bioterrorism as well as to provide course work in statistics and clinical research methods to equip new researchers with the tools necessary to pursue careers in biodefense research. This training program will serve as the necessary foundation for our overall mission of increasing the reservoir of clinical translational researchers in biodefense and emerging infectious diseases. We feel that translational researchers working in biodefense and emerging infectious diseases should be equipped with a core knowledge base and a set of research skills that will afford them the ability to lead the national biodefense mission into the future. Such a knowledge base and skill set will be centered around a detailed curriculum including all aspects of the class A-C agents of bioterrorism, didactic training in epidemiologic methods, biostatistics, clinical research design and grant writing as well as translational research opportunities with experienced, nationally and internationally known clinical investigators.
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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TULARENSIS
MUCOSAL
IMMUNOPATHOGENESIS
OF
FRANSCISELLA
Principal Investigator & Institution: Metzger, Dennis W.; Professor and Director; Ctr/Immunol/Microbial Disease; Albany Medical College of Union Univ Union University Albany, Ny 12208 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-MAR-2008 Summary: (provided by applicant): Francisella tularensis is considered a Category A agent by the NIAID because of its extreme infectivity, ease of dissemination, and substantial capacity to cause illness and death. The "characterization of innate and adaptive immune responses that occur after initial exposure to F. tularensis" has been identified as one of the priorities of NIAID's Counter-Bioterrorism Research Agenda. The pneumonic form of tularemia is the deadliest form of disease and the form most likely to be used by bioterrorists, yet the great majority of research against this organism has focused on systemic infection rather than pulmonary tularemia. The overriding hypothesis of the Program Project is that the pathogenesis of F. tularensis in the respiratory tract is unique and that distinct mechanisms of mucosal-specific immunity are required for protection against pneumonic tularemia. The Program Project brings together a diverse group of individuals with particular expertise in the fields of microbiology, cell biology, and mucosal immunology who will explore in an integrated fashion, the immune response to F. tularensis. The four subprojects will: 1) Define the immunobiology of F. tularensis-macrophage interactions and determine the influence of macrophage activation state on killing of the organism, antigen presentation, and elaboration of inflammatory cytokines. 2) Examine the role of F. tularensis pattern recognition by the innate immune system in fostering lung inflammation. 3) Determine the importance of mucosal immune mechanisms in protection against pneumonic tularemia and develop novel strategies for induction of protective respiratory immunity. 4) Develop F. tularensis mutants to investigate the pathogenic consequences of the organism's interactions with macrophages. The overall goal of the Project is to characterize the association of F. tularensis with macrophages, particularly alveolar macrophages, and develop approaches for effective protection at mucosal surfaces. The results of these studies will ultimately be used to evaluate new mucosal vaccination strategies and new vaccine candidates against human respiratory infection with F. tularensis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MULTIDISCIPLINARY BIODEFENSE TRAINING PROGRAM Principal Investigator & Institution: Huber, Brigitte T.; Professor; Pathology; Tufts University Boston Boston, Ma 02111 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2008 Summary: (provided by applicant): This is a new application to establish a biodefense training program to produce predoctoral trainees who will aid the nation in combating the new challenges of the bioterror threat. The program has a faculty of 19, drawn from the Genetics, Immunology and Molecular Microbiology Graduate Programs of the Sackler School of Graduate Biomedical Sciences of Tufts University School of Medicine and New England Medical Center Hospitals. Focused training in the pathogenesis and genetics of microorganisms that are relevant to biodefense will be integrated with training in understanding host responses to these microorganisms. In this way, our
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trainees will be prepared to attack biodefense-related problems with an in-depth understanding of pathogen-host interaction. A newly developed curriculum integrates courses offered by Genetics, Immunology and Molecular Microbiology. In addition, a newly-developed course presents the pathogenesis of the most potent biological agents together with scientific, medical, social, and political issues relevant to bioterrorism and biowarfare. The Biodefense Training Program also interfaces with the newly conceived Study Center for the Immunogenetics of Infectious Disease (SCIID), an organization that focuses on genetic, immunological and microbiological aspects of infectious disease. The SCIID will be located in the newly constructed Jaharis Family Center, and will provide an intellectual and physical home for our trainees. This Center will also give students the opportunity to work at the BL-3 level of containment, use gene array technology to study host and pathogen gene expression, and have access to BL-3-level cell sorting. Predoctoral students enrolled in the Genetics, Immunology or Molecular Microbiology Graduate Programs may apply to enter the Biodefense Training Program after their first year of graduate school. Selection for our program will be based on high achievement in lab rotations and coursework during the first year, selection of one of the Biodefense Training Program faculty as a thesis mentor, and commitment to work on a dissertation topic relevant to biodefense concerns. Three students will be selected for two years of support (six positions). Benefits of our program include: 1) students are already enrolled who are working on biodefense related issues; 2) a highly experienced training faculty is in place; 3) a strong curriculum already exists; and 4) development of the SCIID shows institutional commitment to this program and provides an outstanding training setting. PARTICIPATING FACULTY: The 19 training faculty include 11 professors, 3 associate professors, and 5 assistant professors. Six of the training faculty are women. Fourteen of the training faculty have primary appointments at Tufts University and five training faculty are located at the New England Medical Center Hospital. The primary areas of research include genetics, immunology and molecular microbiology. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MULTIPLEX PCR DETECTION OF CDC 'A' BIOTERRORISM AGENTS Principal Investigator & Institution: Henrickson, Kelly J.; Associate Professor; Pediatrics; Medical College of Wisconsin Po Box26509 Milwaukee, Wi 532264801 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2006 Summary: (provided by applicant): Anthrax and other agents of biological warfare have recently received intense publicity. These weapons are an increasingly fearsome danger to our civilization. Agents identified by the CDC (category "A") to pose the greatest threat include Variola major (smallpox), Bacillus anthracis (anthrax), Yersinia pestis (plague), Clostridium botulinum toxin (botulism), Francisella tularensis (tularemia), and a group of RNA viruses that cause hemorrhagic fevers (VHFs, e.g., Ebola). Accurate and efficient techniques to identify and diagnose these agents are severely limited. This lack of good diagnostic tests hampers the majority of goals set forth by the NIAID and CDC to prepare the U.S. to counter future bioterrorism attacks. Available older techniques have proven unreliable. Modern molecular tests like individual PCR assays have been developed for some agents. These offer increased speed and sensitivity but because there are so many bioterrorism agents it is prohibitive to run dozens of "singleplex" arrays on each specimen. Similarly, recently reported microchip (MAGI Chip) arrays and other microarrays suffer from either needing PCR amplification first, or from the high cost to make the arrays, and the need for sophisticated equipment. A single assay (or two) that could detect a large number of
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bioterrorism agents rapidly, sensitively, specifically, and cheaply would greatly enhance antiterrorism planning and biodefense. Our laboratory has pioneered a method of multiplex PCR that can accomplish this goal. This proprietary method (two U.S. patents) has been used commercially in the Hexaplex(r) Assay, which can detect seven common respiratory viruses in a single test. The Specific Aims of this project are: 1) To determine if a multiplex PCR-enzyme hybridization assay (EHA) can be made using our unique technology that will identify all of the CDC Category "A" Bioterrorism agents that are DNA based; 2) RNA based; and finally 3) a single combined multiplex (RNA/DNA) PCR assay with an analytical sensitivity equal to "singleplex" real time assays as developed by the CDC. Specific Aim 4: To determine if this multiplex assay is equivalent to these "singleplex" assays in a clinical trial. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NEUTRALIZING ANTIBODIES AGAINST ORTHOPOX VIRUSES Principal Investigator & Institution: Burton, Dennis R.; Professor; Scripps Research Institute 10550 N Torrey Pines Rd La Jolla, Ca 920371000 Timing: Fiscal Year 2002; Project Start 01-AUG-2000; Project End 31-MAY-2005 Summary: There is concern that variola virus, the causative agent of smallpox which was eradicated as a human pathogen more than two decades ago, forms a threat to humans once again, this time as an agent of bioterrorism. The use of variola virus in a bioterrorist attack would be met by the use of the licensed live vaccinia virus vaccine. This vaccine may cause serious side effects which can be successfully treated with vaccinia immune globulin (VIG) derived from hyperimmune individuals. VIG however is in short supply and future availability is uncertain, and in addition suffers from the general concerns of using human blood products for therapeutic applications. This proposal aims to prepare and characterize human monoclonal antibodies against vaccinia virus which, likely formulated as an antibody cocktail, will constitute a replacement for VIG. We will isolate neutralizing antibodies against both infectious forms of vaccinia virus, i.e. intracellular mature virus (IMV) and extracellular enveloped virus (EEV). We will place particular emphasis on isolating antibodies against EEV, as EEV mediates dissemination of infection and is the viral form against which protective immune responses are directed. Inactivation of vaccinia virus will be studied in vitro and in vivo, and will be aimed at designing an antibody cocktail that provides protection against vaccinia virus infection in pre-exposure and post- exposure immunopropylaxis. The antibody cocktail designed may provide a treatment for smallpox itself. To examine the impact of passive immunization in immunoprophylaxis and immunotherapy of a smallpox-like disease in a non-human primate model, we will use an experimental model of monkeypox virus infection Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: NOVEL ANTIVIRAL STRATEGY TO COMBAT ARENAVIRUSES Principal Investigator & Institution: De La Torre, Juan C.; Associate Professor; Scripps Research Institute 10550 N Torrey Pines Rd La Jolla, Ca 920371000 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2005 Summary: (provided by applicant): The prototypic Arenavirus lymphocytic choriomeningitis virus (LCMV) is an excellent model to study the molecular and cellular biology of hemorrhagic fever arenaviruses, including Lassa fever virus (LFV). These viruses cause severe human disease, and they pose a real threat as agents of bioterrorism. We have developed a reverse genetic system for LCMV. We can now
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probe the function of viral genes in cell entry, virus replication, assembly and budding. We have obtained evidence that Arenavirus Z protein is the main driving force of virus budding. Arenavirus Z proteins contain proline-rich motifs PPXY and PT/SAP, which have been identified as essential for budding of several viruses including HIV-1 and Ebola. Evidence indicates that many enveloped viruses are capable of hijacking the cellular multivesicular body (MVB) machinery to escape the cell. We hypothesize that budding of LFV is mediated by the interaction of Z proline-rich domains with specific host factors, including components of the MVB pathway. Understanding these interactions will facilitate targeting of these virally reprogrammed host cellular processes as a new strategy to combat arenaviruses. We propose two specific aims. First, to determine the role of PPPY and PTAPP motifs in LFV Z mediated budding. Z proteins with mutations in PPPY or PTAPP, or both, motifs will be evaluated for their competence to promote budding of virus like particles (VLPs). Second, to identify host factors required for Arenavirus budding. We will test the hypothesis that TSG101 and Nedd4 proteins, both members of the MVB pathway, interact with LFV Z and that these interactions are relevant in LFV Z mediated budding. We will use the tandem affinity purification (TAP) method combined with mass spectrometry procedures to identify other Z-interacting cellular proteins. We will use biochemical and cellular assays to characterize Z/host factor interactions. The functional significance of these host factors in Arenavirus budding will be investigated by quantifying budding of VLPs in cells where expression of the host protein of interest has been disrupted by RNA interference. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NOVEL IMMUNIZATION STRATEGIES AGAINST ANTHRAX Principal Investigator & Institution: Freytag, Lucia C.; Research Assistant Professor; Microbiology and Immunology; Tulane University of Louisiana New Orleans, La 70118 Timing: Fiscal Year 2003; Project Start 15-AUG-2003; Project End 31-JUL-2005 Summary: (provided by applicant): Anthrax is caused by the Gram-positive bacterium Bacillus anthracis. Disease in humans results from contact with infected animals, contaminated animal products or after exposure to accidentally or intentionally released spores of B. anthracis. The distribution of anthrax spores through the US mail has underscored the sense of urgency for the development of improved vaccines against this bacterial pathogen. The current human U.S. anthrax vaccine consists of aluminum hydroxide-adsorbed culture supernatant from a non-encapsulated strain of B. anthracis. This vaccine requires up to six intramuscular vaccine doses given over 18 months. In addition to Protective Antigen, the vaccine also contains a number of other bacterial and media-derived proteins which are likely responsible for the adverse effects experienced by some individuals and may reduce the efficacy of this vaccine. An ideal vaccine against anthrax should be safe, easy to deliver, provide long-lasting protection, require only one or a few doses, and be effective against different strains of B. anthracis. Recent advances in vaccine development have demonstrated that mucosal and transcutaneous immunization in the context of an appropriate adjuvant can produce both humoral and cellular antigen-specific immune responses in both the mucosal and systemic compartments of the host. Such needle-free immunizations are easy to deliver, costeffective, and suitable for mass immunization campaigns, such as would be necessary during a national emergency or for vaccines delivered to underdeveloped countries. In this application, we will test the hypothesis that mucosal or transcutaneous vaccination with anthrax antigens can induce strong, sustained, and effective immune responses associated with protection against infection or can prime effectively for the induction of these responses. Challenge studies will allow us to correlate immune responses with
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41
protective efficacy and determine the contribution of mucosal immune responses to protection against pulmonary anthrax The results obtained from these studies will contribute to our understanding of the host responses involved in protection against anthrax and to the formulation of improved anthrax vaccines. This information may also be valuable in the development of similar prevention strategies against other potential agents of biowarfare/bioterrorism. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ORTHOPOX IMMUNIZATION IN PATIENTS WITH CANCER OR ECZEMA Principal Investigator & Institution: Reinherz, Ellis L.; Chief; Dana-Farber Cancer Institute 44 Binney St Boston, Ma 02115 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-MAR-2008 Summary: (provided by applicant): While worldwide eradication of smallpox represents a major accomplishment of medicine in the 20th century, use of this virus as a bioterrorism agent against our largely disease-susceptible civilian population could result in unprecedented mortality. Individuals at risk for live-virus vaccine complications, including those with cancer and eczema, comprise a large percentage of the US population, mandating against massive large-scale vaccination. Recent developments in immunology, both with regard to mechanistic understanding of adaptive and innate immune responses now allow for evaluation of the cellular and humoral bases of protective immunity against orthopox and other classes of viruses. These advances include details of immune recognition at a structural level, antigen presentation, cell migration and T cell memory. Here, four groups of investigators will utilize their considerable talents in vaccinology, virology, immunology, cutaneous biology, structure and bioinformatics to identify critical orthopox epitopes affording protective human immunity. Project 1 will examine protective immunity to vaccinia virus in normal and high-risk patients elicited during virus vaccination trials based on parameters identified in Project 2. Project 2 will identify T cell epitopes shared by vaccinia, MVA and smallpox by genome-wide comparison using bioinformatics and position-specific scoring matrices, and confirmed by T cell functional assays and mass spectrometry. Antigen-specific T memory cells elicited through vaccination will be assessed by pMHC tetramers, conventional and new biomarkers of T cell memory and molecularly detailed T cell memory repertoires as examined by single cell PCR at different times post-vaccination. Likewise, targets and biophysical parameters of human neutralizing antibodies to vaccinia and variola, the latter in conjunction with CDC, will be identified using recombinant orthopox proteins, BIAcore, ELISA and neutralization studies. In Project 3, investigators from the Harvard Skin Disease Research Center will examine human skin elements of orthopox vaccinated normals or atopic dermatitis patients for productive viral infection, and compare and contrast the nature of central memory and skin homing effector T cells therein. Murine models using biologic response modifiers and transgenic mice will be exploited to examine how manipulation of the cutaneous environment alters vaccination efficacy. Project 4 will use contemporary molecular genetics to mutate vaccinia virus-Wyeth strain to lower virulence by deleting immune escape functions but maintaining host range, replication and immunogenicity. Pathogenicity and immunogenicity assessment will be in C57BL/6, transgenic or mutant mice using systematic, mucosal and dermal scarification infectious routes. An Educational Component, Pilot Project Component and Research Resource Technical Development Component are proposed for rapid dissemination of methods and reagents resulting from this Center's effort.
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Bioterrorism
Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ORTHOPOXVIRUS VACCINE DEVELOPMENT Principal Investigator & Institution: Feinberg, Mark A.; Associate Professor; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2008 Summary: There is no text on file for this abstract. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PERSONAL MONITOR TO DETECT EXPOSURE TO TOXIC AGENTS Principal Investigator & Institution: Cantor, Hal C.; President; Advanced Sensor Technologies, Inc. 39255 Country Club Dr, Ste B-12 Farmington Hills, Mi 48331 Timing: Fiscal Year 2003; Project Start 13-MAY-2002; Project End 31-JUL-2005 Summary: (provided by applicant): Advanced Sensor Technologies, Inc. (AST) proposes to continue its NIH funded Phase I efforts to develop a completely automated miniaturized device capable of monitoring different types of cholinesterases from a single drop of whole blood to determine the degree of exposure of an individual to organophosphate (OP) compounds or carbamates. This device will be amenable to mass screening of pesticide workers, persons in direct contact with OP compounds, as well as soldiers and civilians potentially exposed to chemical warfare agents. Towards these goals, AST has developed a passive first generation micro-electro-mechanical system (MEMS) based prototype with integrated fluid acquisition and external monitoring system, and has performed tests to prove its feasibility in monitoring cholinesterase activity. AST is requesting Phase II funding to improve the Phase I prototype and develop a commercially available, completely automated device, suitable for the general population. Cholinesterase activity in blood is affected by OP compounds and carbamates, with the level of exposure inversely proportional to the toxin concentration or activity. Different types of cholinesterases are located in plasma and red blood cells, and monitoring these blood enzymes automatically, in finger-prick samples of blood, by an untrained individual, will require miniaturization and integration of several different components. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: DETECTION
PHAGE
BINDING
FOR
CONTINUOUS
ANTHRAX
SPORE
Principal Investigator & Institution: Petrenko, Valery A.; Vet Pathobiology; Auburn University at Auburn Auburn University, Al 36849 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2005 Summary: (provided by investigator): Spores of Bacillus anthracis (BAS) poses a major bioterrorism threat because of their extreme potency and availability. There is an urgent need to rapidly detect BAS for efficient treatment of anthrax. The ultimate goal of this application is the development of a device that could be mounted to a SpinCon (air-toliquid) concentrator for the continuous monitoring, detection and alarm of the presence of airborne anthrax spores. Fluid from the SpinCon would be directed across the surface of the Auburn University-designed sensor, which could continuously monitor for the presence of anthrax spores. Detection would occur by the binding of the anthrax spores to phage-derived probes (BAS probes) specifically designed to target these spores. BASprobes will be selected from the billion-clone phage libraries expressing foreign random
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peptides on all 4,000 copies of the viral major coat protein (landscape libraries), and will be improved using mutagenesis and affinity maturation. The phage particles demonstrating best binding to BAS in Enzyme Linked Immuno Sorbent Assay (ELISA) will be remodeled to eliminate their Escherichia coil-binding domains, and will be immobilized onto the surface of either a miniaturized plasmon surface resonance or acoustic wave resonator to produce a signal indicating the detection of anthrax spores. Specificity and selectivity of detection of BAS will be studied using BAS mixed with unrelated spores, proteins and other biopolymers. Parallel experiments will also be conducted with antibody-derived probes for comparison evaluation of specificity, selectivity and longevity of the sensors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: POXVIRUS VACCINE RESEARCH Principal Investigator & Institution: Isaacs, Stuart N.; Assistant Professor; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2008 Summary: Bioterrorism with variola virus is of immense concern because (a) virtually the entire world population is susceptible since routine vaccination was discontinued; (b) there are no treatments; (c) the virus in aerosol form is stable; (d) the virus is transmissible person-to-person; and (e) infection results in high morbidity and mortality. Vaccination with vaccinia virus (VV) was a key factor in eradicating smallpox. The necessity to vaccinate an at-risk population with W is central to preparing for the potential threat of smallpox bioterrorism. However recognized complications of vaccinia vaccination, especially in immunocompromised hosts, pregnant women, and infants impose serious limitations of this strategy. In past vaccination efforts, such complications were treated in the U.S. with human vaccinia immune globulin (VIG) obtained from W immunized people. Current stocks of VIG are low, and while new stocks are being generated, there are still serious drawbacks to relying on a blood product. Consequently, there is a critical need to develop therapeutic interventions to counter complications from the current vaccine and to develop a safer vaccine. As part of the mid-Atlantic Regional Center of Excellence in Biodefense & Emerging Infectious Diseases, our poxvirus research project's hypothesis is that vaccine candidates and new therapies can be developed by understanding and targeting poxvirus proteins recognized by the humoral and innate immune system. To do this we will: 1. Develop a subunit vaccine against smallpox (variola) virus (Cohen/Eisenberg/Friedman, U. Penn) 2. Identify new targets of neutralizing antibody (Isaacs, U. Penn) 3. Identify the targets of VIG using a proteomics approach (Lambris, U. Penn) 4. Develop an ectromelia virus challenge system in the mouse as a model of smallpox pathogenesis and prevention (Braciale, U. Virginia) Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PROTECTIVE MECHANISMS AGAINST PANDEMIC RESPIRATORY VIRUS Principal Investigator & Institution: Arvin, Ann M.; Professor of Microbiology and Immunology; Pediatrics; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-MAR-2008 Summary: (provided by applicant): This Cooperative Center for Translational Research on Human Immunology and Biodefense is entitled 'Influenza Immunity: Protective Mechanisms against a Pandemic Respiratory Virus'. Our objective is to use vaccine-
44
Bioterrorism
induced and naturally acquired influenza A immunity as a model for comprehensive, integrated analyses of adaptive and innate immune mechanisms and antimicrobial protection of the respiratory tract in children and adults. Influenza immunology is relevant to biodefense because influenza A has significant potential to be modified genetically to create a bioterrorist agent. Further, influenza A causes natural pandemics, which can incapacitate a large fraction of the population, endangering preparedness. Influenza A has many characteristics of microbial pathogens that could become agents of civilian bioterrorism. Among these are: capacity to cause illness with high morbidity and mortality, highly efficient person-to-person transmission, high infectivity by aerosol, resulting in the capacity to cause large outbreaks, potential to cause anxiety in the public, and potential to be weaponized. While influenza vaccines exist, the immunologic mechanisms by which protection is induced in the respiratory tact are poorly understood in the human host. Genetically altered influenza A viruses that express unique hemagglutinin (HA) and neuraminidase (NA) proteins have the capacity to infect all age groups. In a biodefense context, the rapidity with which protection can be elicited in a non-immune population is critical. The influenza A model is expected to allow a better definition of specialized adaptive B cell and T cell immune mechanisms that control infections of the respiratory system. Our investigative approach also encompasses the study of innate, natural killer cell responses to influenza, in parallel with acquisition of adaptive immunity in children and adults. Comparing influenza vaccines will identify differences when the host responds to parenterally administered, inactivated antigens, versus live attenuated virus delivered via the respiratory route. At our Center, investigators leading the Research Resource Technical Development component and the Research Projects will undertake rapid translation of basic immunology methods into applications for analyzing innate and acquired influenza A immunity. These innovations will have broad relevance for for understanding human immunity against microbial pathogens of concern for biodefense. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PROTEOMIC ANALYSIS OF THE INNATE ANTIVIRAL RESPONSE Principal Investigator & Institution: Katze, Michael G.; Professor; Microbiology; University of Washington Seattle, Wa 98195 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2005 Summary: (provided by applicant): The innate immune response is the cell's first line of defense against virus infection. This response is typified by the induction of interferon, which in turn induces a cascade of gene expression resulting in the production of proteins that play various roles in eliminating the virus. Many viruses, including NIAID Category A, B, and C agents, are adept at counteracting this response, although the mechanisms by which this is accomplished are not well defined. To gain a better understanding of the signaling pathways involved in innate immunity, and the viral mechanisms used to subvert this response, we propose to identify the composition of protein complexes associated with viral proteins that have a demonstrated ability to act as interferon antagonists. These proteins will include the influenza virus NS 1 protein from the type A Texas/36/91 strain, the 1918 pandemic strain, and the avian Hong Kong strain, and the Ebola-Zaire, Ebola- Reston, and Marburg virus VP35 proteins. The NS 1 and VP35 proteins will be tagged using the tandem affinity purification (TAP) system and expressed by transient or stable transfection of appropriate cell lines (A549 human lung epithelial cells for NS1 and Huh7 human liver cells for VP35) in the presence or absence of infection with delNS 1 influenza virus. As an alternative approach, the tagged NS 1 gene will be introduced into a recombinant influenza virus in
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place of the wild-type gene. Tandem affinity purification will be used to purify protein complexes associated with the tagged proteins, and mass spectrometry and database search algorithms will be used to identify the individual components of the purified complexes. These studies will increase our understanding of the mechanisms used by viruses identified as potential bioterrorism and emerging infectious disease agents to evade the innate immune response and may suggest novel targets for therapeutic intervention. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: RAPID INTERACTIONS/DRUGS
SCREEN
FOR
EBOLA
VIRUS
MEMBRANE
Principal Investigator & Institution: Garry, Robert F.; Professor; Microbiology and Immunology; Tulane University of Louisiana New Orleans, La 70118 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2006 Summary: (provided by applicant): Similarities between the fusion proteins of Ebola virus (EboV) and those of other RNA viruses can be used to guide strategies of drug development against this important potential bioterrorism agent. Some fusion protein motifs, including the membrane-disruptive "fusion peptide" and a pair of extended alpha-helices, have been targeted, however, combinatorial design of drugs against membrane-interactive domains of the envelope protein of EboV could be facilitated with an effective screening assay. A visual microwell plate assay, which uses the lanthanide metal terbium(III) (Tb3+) entrapped in large unilamellar phospholipid vesicles (LUV) and the aromatic chelator dipicolinic acid (DPA) for rapid, high-throughput screening for membrane-disrupting molecules, was recently developed. Preliminary results indicate that synthetic peptides corresponding to several domains of the HIV- 1 transmembrane glycoprotein (TM) interact and disrupt vesicular membranes in the Tb3+/DPA:LUV microwell assay. In Specific Aim 1 we will extend these studies to determine whether synthetic peptides corresponding to similar, potential membraneinteractive motifs of the EboV glycoprotein 2 (GP2) also mediate vesicular lysis in this assay. Synthetic peptides based on representative strains of EboV will be tested. Analog peptides will also be tested to determine if they can interfere with membrane disruption by wild-type peptides. Structural features of membrane interactive peptides will be compared to inactive analogs by various biophysical techniques, including circular dichroism spectroscopy and a novel resonance energy transfer method. Studies proposed in Specific Aim 2 will determine whether synthetic peptides corresponding to various conserved motifs of EboV GP2 can block infectivity mediated by Ebola virus glycoproteins. Pseudotyped virions with membrane-bound EboV GP and the core of murine leukemia virus will be utilized to establish the feasibility of using the Tb3+/DPA:LUV microwell assay to screen for inhibitory peptides and non-peptide inhibitors of EboV membrane interactive domains. The proposed studies will provide proof-of-concept that combinatorial chemistry approaches may be useful for developing peptide and non-peptide drugs against Ebola virus, as well as a broad range of important human viral pathogens with similar fusion proteins. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: REPERTOIRE OF CD8+ T CELLS IN AGED MICE Principal Investigator & Institution: Judice, Stephen A.; Trudeau Institute, Inc. Saranac Lake, Ny 12983 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2006
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Bioterrorism
Summary: (provided by the applicant): Aged individuals suffer from infectious disease with increased frequency and severity. In particular, influenza viruses represent a major cause of illness among elderly individuals. Given that the protective efficacy of vaccination is greatly reduced in the elderly, it is critical that effective vaccination strategies for the elderly be developed for not only protection from natural yearly influenza infection epidemics, but also from potential bioterrorism attacks. An agerelated defect in the activation of naive CD4+ T-cells as well a diminished primary CD8+ T-cell response to influenza virus infection has been described, although there is less evidence of a functional defect in the aged CD8+ T-cells. It has been suggested that the defective cellular immune response in the aged is in part due to a loss of diversity in the CD8+ T-cell repertoire. The current research proposal will investigate the CD8+ Tcell deficit in a two pronged approach. First, we will compare the overall and functional diversity of the naive CD8+ repertoire in young aged mice via DNA spectratye analysis. Second, we will examine the diversity in the CD8+ cellular immune response of aged mice as compared to young mice in response to a primary influenza virus vaccination by DNA spectratype analysis. Together, these studies will determine whether an age associated loss of naive T-cell diversity affects immune function in the elderly. These results have relevance in determining the feasibility of some vaccination strategies for the elderly in which defined viral proteins or epitopes may be used as immunogens. Given that a significantly reduced repertoire diversity may result in 'holes' in the T-cell repertoire, these vaccination strategies may prove ineffective in an elderly population requiring alternate approaches. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CHELATES
SENSITIVE,
RAPID
BIOASSAY
USING
UPCONVERTING
Principal Investigator & Institution: Faris, Gregory W.; Senior Physicist; Sri International 333 Ravenswood Ave Menlo Park, Ca 94025 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2005 Summary: (provided by applicant): The long-term objective of this project is to develop appropriate diagnostic assays for bioterrorism attacks. A well coordinated and executed attack could kill hundreds of thousands to millions. Effective diagnostics will be crucial to minimizing morbidity and mortality from such an attack, as well as maintaining social order. These diagnostics must be rapid, easy to use, inexpensive, very sensitive, and very specific. Multiplexed tests (i.e., those that test for multiple targets) and low waste generation are also attractive capabilities for these diagnostics. Our near-term objective is to test the feasibility of a new diagnostic approach that should significantly outperform existing diagnostics in terms of speed, sensitivity, and simplicity of use. This assay is based on upconverting chelates in a homogeneous assay format. Upconverting chelates are a novel reporter SRI International (SRI) has invented that comprises a lanthanide (rare earth) ion in a chelating ligand. When excited with near infrared light, they upconvert, emitting light at visible wavelengths. These reporters have no autofluorescent background, do not photobleach, and have good properties for multiplexing. Because the assay is homogeneous, very little sample preparation is required, enabling rapid analysis. We propose a 2-year R21 project to prove the feasibility of this assay. As a test target we will use influenza virus strain PR8. Our specific aims in this work are to: (1) build a simple optical apparatus for detecting surface-enhanced upconverting chelate signals; (2) prove and optimize the homogeneous assay concept; (3) prove and optimize the assay for hemagglutinin
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protein; and (4) prove and optimize the assay for influenza virus. This work will combine the efforts of optical physicists, chemists, immunologists, and a virologist. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SINGLE CELL DNA FRAGMENT SIZING Principal Investigator & Institution: Keller, Richard A.; Laboratory Fellow; None; University of Calif-Los Alamos Nat Lab Ms G758 Los Alamos, Nm 87545 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 31-MAY-2006 Summary: (provided by applicant): We propose to develop a microscope-based imaging system for analysis of bacterial DNA fragments from single bacterial cells. Our approach eliminates the need for cell culturing common to other DNA fingerprinting methods, thereby reducing the analysis time from several days to hours. The proposed technique will allow DNA fragments, from a few hundred base pairs to millions of base pairs, originating from a single cell RFLP, to be sized. We envision many applications of this new capability in biomedicine to: more rapid diagnosis of infectious disease; determination of the source of an infectious disease outbreak; and measurement of the genotoxicity of drugs or environmental agents. In addition, this technique will impact biological research by providing a new measurement tool for single cell DNA analysis, as well as having immediate application to anti-bioterrorism, forensics, food safety, and agriculture. This technology will give researchers a powerful method for studying individual cells and organisms in the absence of averaging effects of ensemble measurements. Likewise, by making measurements on a number of single cells, information about the presence or extent of DNA heterogeneity will be established. The technique relies on performing all sample preparation reactions and analyses in an ultra-thin gel mounted on a microscope slide. Cell lysis, protein digestion, DNA restriction, and DNA staining, along with other reactions, will be carded out by diffusion of reagents into the gel. Staining conditions will be such that the fluorescence intensity is proportional to the fragment size. An electric field will be applied to the gel to electrophoretically separate the DNA fragments. Fluorescence from individual stained and separated fragments will then be detected and quantitated with a microscope-based, high sensitivity imaging system. The resulting DNA fragment size distribution histogram can be used as a fingerprint to identify individual organisms to the level of species and strain, detect damage in the DNA resulting from exposure to ionizing radiation or chemicals, or to monitor genetic variability. To demonstrate this technology we must complete the following specific aims: 1) assemble and characterize the apparatus and measurement approach; 2) develop and optimize the sample preparation chemistry; 3) demonstrate applicability to species and strain identification of representative bacteria. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: SMALL MOLECULES TO BLOCK FUSION BY ENVELOPE PROTEINS Principal Investigator & Institution: Harrison, Stephen C.; Professor; Harvard University (Medical School) Medical School Campus Boston, Ma 02115 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2008 Summary: Dengue and Ebola are both enveloped viruses that enter cells by membrane fusion. Aspects of the structures of their fusion proteins are known. Blocking membrane fusion by a viral envelope protein can prevent entry and infectivity, as shown by peptides such as T-20, an HIV antiviral now in clinical trials. In collaboration with the chemical screening core facility of the NERCE, we propose to develop structure-based
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Bioterrorism
screens for small molecules that will inhibit the Ebola and dengue fusion steps. In the case of Ebola, which has a Class 1 fusion protein, the strategy will follow one we have used successfully to discover small molecules that block envelope-dependent HIV fusion. In the case of dengue, which has a Class 2 fusion protein, our recently determined structure of the dengue envelope protein suggests a binding site for potential inhibitors; we will use this information to design our screen. Understanding the nature of the conformational change that leads to fusion is likely to provide additional avenues for structure-based inhibitor discovery. We therefore propose to determine the structure of the fusion-promoting ("low pH") conformation of the dengue envelope protein. To augment further our picture of flavivirus envelope structure, we propose to determine the arrangement of proteins on the surface of immature virions by three-dimensional image reconstruction from electron cryomicroscopy of inactivated, immature particles of tick-borne encephalitis virus. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SMALLPOX VIRULENCE AND COMPLEMENT REGULATORY PROTEINS Principal Investigator & Institution: Atkinson, John P.; Professor of Medicine & Molecular Biolog; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2008 Summary: Public health concems have emerged regarding use of smallpox as a bioterrorist weapon since most Americans are no longer immune. Poxviruses subvert the complement system via the expression of regulatory proteins. In variola, vaccinia and ectromelia, the proteins are called SPICE (for smallpox inhibitor of complement enzymes), VCP (vaccinia virus complement control protein) and EMICE (an uncharactedzed analog in ectromelia that we have labeled "ectromelia inhibitor of complement enzymes"). These secreted virulence factors down-regulate complement activation by mimicking the functional repertoire of a family of host proteins called the Regulators of Complement Activation (RCA). The viral proteins are also structurally related to their host counterparts. Specific Aims: 1. To characterize the complement inhibitory profile of SPICE compared to its human counterparts. We will identify the principal complement-evading activity of SPICE and this will become a target for neutralization. These assessments will take place with the native soluble protein as well as after it attaches to cells via either its heparin-binding site(s) or by addition of an anchor. 2. To determine the complement regulatory sites of SPICE. These experiments will take advantage of the functional profiles (defined in Aim 1) and the sequences of active sites of RCA proteins that are homologous to corresponding regions of SPICE, VCP, and EMICE. These two sets of data provide a logical strategy for a mutational analysis to locate the active sites. 3. To characterize the complement regulatory activity of EMICE. This mousepox protein has not been evaluated for its complement inhibitory (virulence) activity. It is about 90% identical to SPICE and VCP. We will first characterize its regulatory activity for human and mouse complement. Second, we will assess its role in vivo as a virulence factor by infecting sensitive and resistant mouse strains with the ectromelia virus deleted of its complement regulator. The proposed experiments should provide novel information relative to the pathogenesis of poxvirus infections of man and mouse. Additionally, these results will serve as a guide to produce a less toxic small pox vaccine and to identify a viral target for mAb treatment of variola infection. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: SUPERSENSITIVE DETECTION OF VIRAL BIOWARFARE AGENTS Principal Investigator & Institution: Drukier, Andrzej K.; Biotraces, Inc. 13455 Sunrise Valley Dr, Ste 200 Herndon, Va 20171 Timing: Fiscal Year 2003; Project Start 01-MAY-2003; Project End 31-OCT-2003 Summary: (provided by applicant): The ability to detect biological agents across a large number of diverse locations, all of which might be targets for terrorists, is currently limited by the restricted sensitivity and non-portability of available detection systems. BioTraces, Inc. has developed a new family of MPD systems that overcome these existing limitations. MPD has several advantages over existing assay methods: better than 1,000-fold improvement in sensitivity, enabling measurement of previously undetectable amounts of target substances; concurrent measurement of multiple samples, leading to higher throughput, and the ability to perform simultaneous assays for multiple targets in a single sample using portable, light weight instruments. The proposed applications of MPD for the detection of biological warfare agents can be divided into two synergistic sub-projects: * use of a panel of MPD enhanced immunoassays for detection of viral BW agents. * development of a universal biological warfare agent detector using supersensitive P-chips/MPD. Recent events in the US have shown the vulnerability of domestic institutions to terrorist activities. Over the next few years a significant market for means of detecting and preventing terrorist attacks will develop. Because of the superior sensitivity of MPD techniques, BioTraces is in a position to capture a significant share of the detection aspect of this emerging market. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: THE DESIGN OF INHIBITORS OF ANTHRAX TOXIN Principal Investigator & Institution: Kane, Ravi S.; Chemical Engineering; Rensselaer Polytechnic Institute 110 Eighth Street Troy, Ny 12180 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2005 Summary: (provided by applicant): Anthrax is caused by the spore-forming bacterium Bacillus anthracis. The ability to deliver the spores in an aerosol and the high mortality rate of inhalational anthrax have led to the use of the spores as a biological weapon. Antibiotic treatment of inhalational anthrax can be ineffective late in the infection because high levels of toxin in the blood cause death. Our research proposal is focused on the development of inhibitors of anthrax toxin, a combination of three proteins secreted by the bacterium. Protective antigen (PA) binds a receptor and is cleaved by a protease, allowing the heptamerization of the cell-associated PA63 fragment. Heptamerization allows binding of the enzymatic toxin components, edema factor (EF) and lethal factor (LF), and triggers endocytosis of these complexes. The acidic environment of the endosome leads to the translocation of the enzymatic proteins to the cytosol where they exert their toxic effects. EF is an adenylate cyclase that impairs the innate immune response by a variety of mechanisms. LF is a protease that causes lysis of macrophages, which results in shock-like symptoms and death. The recent identification of the anthrax toxin receptor (ATR) will facilitate the development of molecules that inhibit anthrax toxin action. We will use two approaches to isolate inhibitors of the PAATR interaction and test these inhibitors for the ability to block the intoxication process in vitro. In the first approach, we will select a peptide that binds ATR and then attach multiple copies of this peptide to a polymeric backbone. The resulting polyvalent compound is predicted to bind ATR with higher affinity than the peptide alone and prevent binding of PA to cells. The second approach is based on our previous observation that a soluble fragment of ATR can protect cells from toxin in vitro. We
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hypothesize that a mutant fragment that binds PA with higher than wild-type affinity will be a more effective inhibitor. We will isolate this mutant through sequential rounds of random mutagenesis, selection, and recombination. These compounds may extend the time during which a case of anthrax can be treated successfully. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: THE USE OF BIOFILMS TO COUNTER BIOTERRORISM Principal Investigator & Institution: James, Garth A.; Mse Technology Applications, Inc. Box 4078, 200 Technology Way Butte, Mt 59702 Timing: Fiscal Year 2001; Project Start 01-MAY-2001; Project End 31-OCT-2001 Summary: (Verbatim from Applicant's Abstract): The possibility that terrorists will contaminate public drinking water supplies with biological agents, such as bacteria, viruses, or toxins, becomes greater every day. Recent cases of intentional food contamination with bacteria emphasize our vulnerability to these attacks. An innovative approach to counteracting this threat is to use bacterial biofilms for trapping and rendering these pathogenic biological agents ineffective. The goal of this, and subsequent research, is to build a system that uses natural biofilms to remove pathogens from contaminated drinking water. During Phase I, we will quantify the extent of pathogen attachment to biofilms. Specifically, we will use a test apparatus capable of measuring the amount of bioterrorism agents that can be captured by bacterial biofilms. The data generated from this research will be used to create a preliminary design of a treatment system. There is a definite need for a system such as this to prevent contamination of public or military drinking water systems. The expertise of the assembled team at MSE, and our partner, the Center for Bioflim Engineering, is unsurpassed in the field of biofilm attachment phenomenon, especially as it relates to drinking water issues. Together we can effectively develop this technology and move it towards commercialization. PROPOSED COMMERCIAL APPLICATION: There is a definite need for systems that have the ability to effectively remove pathogenic substances from contaminated drinking water. A biofilm system will have many advantages over conventional systems because of its ability to trap and render ineffective a wide variety of pathogenic substances. Commercial applications for this system include the U.S. Military, hospitals, and water utilities. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: TRAINING IN EMERGING INFECTIOUS DISEASES Principal Investigator & Institution: Doms, Robert W.; Professor and Chair; Microbiology; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2008 Summary: (provided by applicant): In response to increased concern about emerging and re-emerging infectious diseases, particularly Class A-C agents that could be used as weapons of bioterrorism, the microbiology community at the University of Pennsylvania proposes to establish a Training Program in Emerging Infectious Diseases. The Training Program would initially support two Ph.D. and two M.D./Ph.D. or V.M.D./Ph.D. predoctoral fellows as well as three postdoctoral fellows, enabling them to work in any one of 14 laboratories directed by Principal Investigators who study important viral or parasitic pathogens that are classified as either emerging or reemerging threats to human health. The trainers associated with this T32 proposal have been selected because their research programs in these areas are well-established and are being supported by NIH grants and/or have published papers on this topic. The
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trainers study a number of important viral and parasitic pathogens. Six of the trainers on this grant study smallpox proteins or are developing anti-vaccinia agents, and currently hold one R01, two R21s and one U01 grants to support work in this area (Isaacs, Rosengard, Cohen, Eisenberg, Friedman, Ricciardi). Four trainers on this grant study Ebola virus, holding one R01 and two R21 grants and having published several papers in the last two years (Bates, DoTs, Shen, Harty). Collaborations with colleagues at USAMRIID make it possible to perform experiments with live Ebola virus. Other important emerging viral diseases that are subjects of significant research efforts by the trainers include West Nile virus and Dengue (DoTs, Bates). Emerging and re-emerging parasitic diseases are the focus of research efforts by the trainers and include Malaria, a major focus of the Roos laboratory which plays a major role in managing the Plasmodium genome project. Outbreaks of leishmaniasis (Scott) in Afghan refugee camps in Pakistan and other regions, have demonstrated increased incidence of old infections from a confluence of wars, population shifts, and development into little populated regions. Due to climactic changes and large-scale water resources development projects, there have been notable new outbreaks of schistosomiasis in previously unaffected areas (Pearce, Shen). Increased infections due to toxoplasma gondii have also been reported (Roos, Hunter). With time, we anticipate that other Penn investigators will join this training program as they shift their research focus to include emerging infectious diseases. The research opportunities provided by the trainers coupled with strong institutional commitment and an extensive and well-organized training program will provide excellent training in emerging infectious diseases to students and postdoctoral fellows. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TYPE IV PILINS AS VACCINES AGAINST BIOTERRORISM THREATS Principal Investigator & Institution: Donnenberg, Michael S.; Medicine; University of Maryland Balt Prof School Baltimore, Md 21201 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2005 Summary: (provided by applicant): Type IV pili are essential virulence factors for many Gram-negative bacterial pathogens and type IV pilin proteins have made effective vaccines for veterinary use. Burkholderia mallei and B. psuedomallei, the causative agents of glanders and melioidosis, respectively, represent significant biowarfare/bioterrorism threats. A search of the unfinished genomes of these microorganisms reveals that they contain identical genes for type IV pilin proteins. We plan to conduct pilot studies that will provide preliminary data for future studies of the use of the type IV pilin proteins of these organisms as vaccines. Our first specific aim is to purify soluble pilin protein, raise antisera, and test sera from animals sacrificed at various time periods after experimental glanders infection for antibody responses to pilin. Our second aim is to construct a strain of B. mallei that has a deletion in the pilin gene and test its ability to express pilin, pili and associated phenotypes in vitro. The data and reagents generated in these studies will be used for future studies to assess the role of the type IV pilus in experimental glanders infection and the protective efficacy of passive and active pilin immunization against glanders and melioidosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: USE INACTIVATION
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Principal Investigator & Institution: Biswas, Pratim; Professor and Director; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2008 Summary: ABSTRACT NOT PROVIDED Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: VACCINE INDUCED IMMUNITY IN THE YOUNG AND AGED Principal Investigator & Institution: Ahmed, Rafi; Director; Microbiology and Immunology; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-MAR-2008 Summary: (provided by applicant): The long-term goals of this U19 Application are three fold: One, to study the human immune response to a vaccine in it's entirety; starting from the innate responses, to the peak effector T and B cell responses, to the development and maintenance of immunological memory. Two, to understand how a successful vaccine works and to use this knowledge for designing strategies for enhancing vaccine efficacy. Three, to understand the cellular basis of immune senescence and develop strategies for improving responses of the elderly to vaccination. Also, a major emphasis of this proposal is on using genomics and proteomics to define the molecular signatures of innate and adaptive responses after vaccination. In fact, our overarching hypothesis is that there will clearly be molecular and cellular signatures of "good" and "bad" vaccines and that identifying these signatures will allow us to manipulate the immune response to either enhance immunity in the case of vaccines and immune therapy, or to decrease it for autoimmunity, transplantation and gene therapy. To achieve our goals we have put together a highly interactive and integrated Application consisting of three research projects: 1. Immunological memory to vaccination (Ahmed and Lanzavecchia); 2. Modulating vaccine responses with dendritic cells and TLRs (Pulendran); and 3. Immune senescence (Goronzy). These research projects are closely tied to the Technical Development Components that consist of: 1. Molecular signatures of immune responses to vaccination (Aderem); 2. Human monoclonal antibodies to category A pathogens (Mittler); and 3. Development of novel T cell assays (Altman). This overall research effort will be supported by an Administrative/Statistical Core (Ahmed and Manatunga) and a Clinical Research Core (Feinberg). In addition, there is a program for the education and training of scientists who wish to do research in human immunology (Ansari) and a Review Committee for evaluating and funding high risk/high impact projects in human immunology. 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
3
Adapted from the National Library of Medicine: http://www.pubmedcentral.nih.gov/about/intro.html.
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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 “bioterrorism” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for bioterrorism in the PubMed Central database: •
Anthrax: of bison and bioterrorism. by Weir E.; 2000 Sep 5; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=80494
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Bioterrorism becoming too dominant on public health agenda? by Cassels A.; 2002 Nov 26; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=134156
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Bioterrorism planning continues at frantic pace. by Kondro W.; 2002 Jan 8; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=99248
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Bioterrorism: guidelines for medical and public health management. by Beaulieu MA.; 2003 Jan 21; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=140432
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Bioterrorism: Implications for the Clinical Microbiologist. by Klietmann WF, Ruoff KL.; 2001 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=88979
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Canada stocks up on smallpox vaccine, pushes bioterrorism training. by Kondro W.; 2001 Nov 13; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=81639
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Experts warn of cracks in European response to bioterrorism threats. by Orellana C.; 2001 Nov 27; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=81682
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Exposure of Laboratory Workers to Francisella tularensis despite a Bioterrorism Procedure. by Shapiro DS, Schwartz DR.; 2002 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=130659
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MD critic challenges US over bioterrorism, Iraq. by Silversides A.; 2003 Nov 11; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=236245
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Preparing for bioterrorism. by OReilly M.; 2002 May 28; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=111239
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Role of the Hospital-Based Microbiology Laboratory in Preparation for and Response to a Bioterrorism Event. by Snyder JW.; 2003 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=149646
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Tularemia. by Ellis J, Oyston PC, Green M, Titball RW.; 2002 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=126859
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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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Winter, plague and pestilence. by Petsko GA.; 2001; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=138975
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 bioterrorism, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “bioterrorism” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for bioterrorism (hyperlinks lead to article summaries): •
A European centre to respond to threats of bioterrorism and major epidemics. Author(s): Tibayrenc M. Source: Bulletin of the World Health Organization. 2001; 79(12): 1094. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11799439&dopt=Abstract
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A national laboratory network for bioterrorism: evolution from a prototype network of laboratories performing routine surveillance. Author(s): Gilchrist MJ. Source: Military Medicine. 2000 July; 165(7 Suppl 2): 28-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10920634&dopt=Abstract
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A novel about bioterrorism. Author(s): Akbar R. Source: Jama : the Journal of the American Medical Association. 2001 June 27; 285(24): 3091-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11427134&dopt=Abstract
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A pediatrician's view. Skin manifestations of bioterrorism. Author(s): Cross JT Jr, Altemeier WA 3rd. Source: Pediatric Annals. 2000 January; 29(1): 7-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10941763&dopt=Abstract
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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 physician's notes for community education in bioterrorism. Author(s): Samadani AM. Source: Wmj. 2002; 101(2): 10-1, 36. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12085489&dopt=Abstract
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A risk analysis approach to selecting respiratory protection against airborne pathogens used for bioterrorism. Author(s): Nicas M, Hubbard A. Source: Aiha Journal : a Journal for the Science of Occupational and Environmental Health and Safety. 2003 January-February; 64(1): 95-101. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12570401&dopt=Abstract
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A Swedish/European view of bioterrorism. Author(s): Sandstrom G. Source: Annals of the New York Academy of Sciences. 2000; 916: 112-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11193610&dopt=Abstract
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Acute psychological effects of suspected bioterrorism. Author(s): Mason BW, Lyons RA. Source: Journal of Epidemiology and Community Health. 2003 May; 57(5): 353-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12700219&dopt=Abstract
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Addressing bioterrorism. What ethical issues and questions surround potential responses to bioterrorist attacks? Author(s): Haas JM. Source: Healthcare Executive. 2003 May-June; 18(3): 76-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12737102&dopt=Abstract
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Agents of bioterrorism. Preparing for bioterrorism at the community health care level. Author(s): Miller JM. Source: Infectious Disease Clinics of North America. 2001 December; 15(4): 1127-56. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11780270&dopt=Abstract
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An epidemiologist's view of bioterrorism. Eddy A. Bresnitz, MD, MS, discusses state initiatives and preparedness. Interview by Leah Z. Ziskin. Author(s): Bresnitz EA. Source: N J Med. 2003 April; 100(4): 12-9; Quiz 19-22. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12703333&dopt=Abstract
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An overview on the use of a viral pathogen as a bioterrorism agent: why smallpox? Author(s): Mahy BW. Source: Antiviral Research. 2003 January; 57(1-2): 1-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12615297&dopt=Abstract
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Anthrax bioterrorism: lessons learned and future directions. Author(s): Hughes JM, Gerberding JL. Source: Emerging Infectious Diseases. 2002 October; 8(10): 1013-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12396907&dopt=Abstract
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Anthrax in Europe: its epidemiology, clinical characteristics, and role in bioterrorism. Author(s): Schmid G, Kaufmann A. Source: Clinical Microbiology and Infection : the Official Publication of the European Society of Clinical Microbiology and Infectious Diseases. 2002 August; 8(8): 479-88. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12197870&dopt=Abstract
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Anthrax scare in Buncombe County. A lesson in the basics of bioterrorism preparedness. Author(s): Bond GF Jr. Source: N C Med J. 2002 September-October; 63(5): 271-3. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12970972&dopt=Abstract
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Anthrax, bioterrorism fears stimulate immune, other research. Author(s): James JS. Source: Aids Treat News. 2001 October 26; (373): 7-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11768882&dopt=Abstract
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Anthrax, tularemia, plague, ebola or smallpox as agents of bioterrorism: recognition in the emergency room. Author(s): Cunha BA. Source: Clinical Microbiology and Infection : the Official Publication of the European Society of Clinical Microbiology and Infectious Diseases. 2002 August; 8(8): 489-503. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12197871&dopt=Abstract
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Anthrax. An old disease returns as a bioterrorism weapon. Author(s): Morgan MF. Source: N J Med. 2000 September; 97(9): 35-41. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11011551&dopt=Abstract
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Anthrax: of bison and bioterrorism. Author(s): Weir E. Source: Cmaj : Canadian Medical Association Journal = Journal De L'association Medicale Canadienne. 2000 September 5; 163(5): 608. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11006776&dopt=Abstract
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Anthrax: U.S. bioterrorism affecting Missourians. Author(s): Miller D. Source: Mo Med. 2001 December; 98(12): 546-7. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11778308&dopt=Abstract
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Are water supplies safe from bioterrorism? Author(s): Homler H. Source: Postgraduate Medicine. 2001 January; 109(1): 18. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11198253&dopt=Abstract
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Assessing the threat of bioterrorism: are we ready? Author(s): Keenan PS, Kline J. Source: Issue Brief (Commonw Fund). 2002 April; (535): 1-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11993502&dopt=Abstract
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Attacks heighten US concern about threat of bioterrorism. Author(s): McCarthy M. Source: Lancet. 2001 September 29; 358(9287): 1071. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11589945&dopt=Abstract
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Automated laboratory reporting of infectious diseases in a climate of bioterrorism. Author(s): M'ikantha NM, Southwell B, Lautenbach E. Source: Emerging Infectious Diseases. 2003 September; 9(9): 1053-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14519239&dopt=Abstract
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Bacterial pathogens as biological weapons and agents of bioterrorism. Author(s): Greenfield RA, Drevets DA, Machado LJ, Voskuhl GW, Cornea P, Bronze MS. Source: The American Journal of the Medical Sciences. 2002 June; 323(6): 299-315. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12074485&dopt=Abstract
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Biological toxins as potential agents of bioterrorism. Author(s): Slater LN, Greenfield RA. Source: J Okla State Med Assoc. 2003 February; 96(2): 73-6. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12674908&dopt=Abstract
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Biotechnology to fight bioterrorism. While the fight against terrorism is helping to revitalize the biotech market, academic scientists are starting to worry about limitations on research. Author(s): Brower V. Source: Embo Reports. 2003 March; 4(3): 227-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12634833&dopt=Abstract
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Bioterrorism & pregnant women. Promoting access to care in times of crisis. Author(s): Adkins-Bley K, Greenhill LM. Source: Awhonn Lifelines / Association of Women's Health, Obstetric and Neonatal Nurses. 2002 June-July; 6(3): 209-11. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12078566&dopt=Abstract
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Bioterrorism and biological warfare: not only a respiratory affair. Author(s): Fasano A. Source: Journal of Pediatric Gastroenterology and Nutrition. 2003 March; 36(3): 305-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12669708&dopt=Abstract
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Bioterrorism and catastrophe response: a quick-reference guide to resources. Author(s): Han SZ, Alfano MC, Psoter WJ, Rekow ED. Source: The Journal of the American Dental Association. 2003 June; 134(6): 745-52. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12839411&dopt=Abstract
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Bioterrorism and critical care. Author(s): Karwa M, Bronzert P, Kvetan V. Source: Critical Care Clinics. 2003 April; 19(2): 279-313. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12699324&dopt=Abstract
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Bioterrorism and the Biological Weapons Convention--the wider context. Author(s): Holdstock D. Source: Medicine, Conflict, and Survival. 2002 April-June; 18(2): 107-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12044021&dopt=Abstract
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Bioterrorism and water security. Author(s): Luthy RG. Source: Environmental Science & Technology. 2002 April 1; 36(7): 123A. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11999032&dopt=Abstract
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Bioterrorism defense priorities. Author(s): May T, Silverman R. Source: Science. 2003 July 4; 301(5629): 17. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12843359&dopt=Abstract
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Bioterrorism in Australia. Author(s): Smallwood RA, Merianos A, Mathews JD. Source: The Medical Journal of Australia. 2002 March 18; 176(6): 251-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11999254&dopt=Abstract
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Bioterrorism law and policy: critical choices in public health. Author(s): Hodge JG Jr. Source: The Journal of Law, Medicine & Ethics : a Journal of the American Society of Law, Medicine & Ethics. 2002 Summer; 30(2): 254-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12066602&dopt=Abstract
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Bioterrorism meets privacy: an analysis of the Model State Emergency Health Powers Act and the HIPAA privacy rule. Author(s): Bruce J. Source: Ann Health Law. 2003; 12(1): 75-120, Table of Contents. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12705205&dopt=Abstract
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Bioterrorism preparedness for the public health and medical communities. Author(s): Meyer RF, Morse SA. Source: Mayo Clinic Proceedings. 2002 July; 77(7): 619-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12108597&dopt=Abstract
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Bioterrorism preparedness. Author(s): Jacobs LM, Burns K, Lane V, Ross J. Source: Conn Med. 2003 February; 67(2): 95-101. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12664837&dopt=Abstract
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Bioterrorism preparedness: answers for the health-system pharmacist. Author(s): Teeter DS. Source: American Journal of Health-System Pharmacy : Ajhp : Official Journal of the American Society of Health-System Pharmacists. 2002 May 15; 59(10): 928-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12040731&dopt=Abstract
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Bioterrorism response. Author(s): Alfano MC. Source: The Journal of the American Dental Association. 2003 March; 134(3): 278, 280. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12699041&dopt=Abstract
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Bioterrorism threat makes preparation essential. Author(s): Parvin K. Source: Wmj. 2002; 101(2): 14-6. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12085491&dopt=Abstract
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Bioterrorism today. Author(s): Snell N. Source: Biologist (London, England). 2002 June; 49(3): 140. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12097718&dopt=Abstract
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Bioterrorism watch. APIC: smallpox plan uses outdated infection control. Author(s): Evans G. Source: Ed Manag. 2002 June; 14(6): Suppl 3-4. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12046240&dopt=Abstract
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Bioterrorism watch. They don't call it bioterror for nothing: fear is the foe when anthrax spores are found within hospital walls. Author(s): Evans G. Source: Ed Manag. 2002 June; 14(6): Suppl 1-3. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12046239&dopt=Abstract
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Bioterrorism watch. Traumatized health care providers may need stress counseling in horrific aftermath of bioterror attack. Author(s): Evans G. Source: Hosp Peer Rev. 2002 May; 27(5): Suppl 1-3. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12001563&dopt=Abstract
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Bioterrorism web site resources for infectious disease clinicians and epidemiologists. Author(s): Ferguson NE, Steele L, Crawford CY, Huebner NL, Fonseka JC, Bonander JC, Kuehnert MJ. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2003 June 1; 36(11): 1458-73. Epub 2003 May 22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12766842&dopt=Abstract
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Bioterrorism, embryonic stem cells, and Frankenstein. Author(s): Guinan P. Source: Journal of Religion and Health. 2002 Summer; 41(2): 305-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12728944&dopt=Abstract
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Bioterrorism, the public's health, and the law. Author(s): Moore J. Source: N C Med J. 2002 September-October; 63(5): 268-70. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12970971&dopt=Abstract
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Bioterrorism. Author(s): Manning ML, Henretig FM. Source: Journal for Specialists in Pediatric Nursing : Jspn. 2002 April-June; 7(2): 49-50, 84-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12061492&dopt=Abstract
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Bioterrorism. Author(s): Cieslak TJ, Henretig FM. Source: Pediatric Annals. 2003 March; 32(3): 154-65. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12661490&dopt=Abstract
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Bioterrorism. Author(s): Fish D. Source: Vector Borne and Zoonotic Diseases (Larchmont, N.Y.). 2001 Fall; 1(3): 179. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12653145&dopt=Abstract
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Bioterrorism. Author(s): Shahi SK, Ranga S, Gupta P. Source: Indian J Pathol Microbiol. 2001 October; 44(4): 391-2. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12035346&dopt=Abstract
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Bioterrorism. Clinical recognition and primary management. Author(s): Branda JA, Ruoff K. Source: American Journal of Clinical Pathology. 2002 June; 117 Suppl: S116-23. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14569808&dopt=Abstract
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Bioterrorism. How devastating would a smallpox attack really be? Author(s): Enserink M. Source: Science. 2002 May 31; 296(5573): 1592-5. Erratum In: Science 2002 July 26; 297(5581): 522. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12040157&dopt=Abstract
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Bioterrorism. In search of a kinder, gentler vaccine. Author(s): Enserink M. Source: Science. 2002 May 31; 296(5573): 1594. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12040158&dopt=Abstract
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Bioterrorism: an update with a focus on anthrax. Author(s): Brachman PS. Source: American Journal of Epidemiology. 2002 June 1; 155(11): 981-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12034576&dopt=Abstract
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Bioterrorism: are we prepared? Author(s): Sawyer PP. Source: Home Healthcare Nurse. 2003 April; 21(4): 220-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12695693&dopt=Abstract
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Bioterrorism: better safe than sorry. Author(s): Gilbert N. Source: Provider. 2002 June; 28(6): 43-4. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12068488&dopt=Abstract
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Bioterrorism: defining a research agenda. Author(s): Fauci AS. Source: Food Drug Law J. 2002; 57(3): 413-21. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12703508&dopt=Abstract
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Bioterrorism: responding to an emerging threat. Author(s): Hamburg MA. Source: Trends in Biotechnology. 2002 July; 20(7): 296-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12062974&dopt=Abstract
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Bioterrorism: what is and what may never be. Part 1. Author(s): Emmons W. Source: Del Med J. 2002 May; 74(5): 219-25. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12063832&dopt=Abstract
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Bioterrorism: What? Why? and Who? Author(s): Campbell J. Source: Clin Lab Sci. 2002 Winter; 15(1): 6-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12778948&dopt=Abstract
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Bioterrorism-related inhalational anthrax in an elderly woman, Connecticut, 2001. Author(s): Griffith KS, Mead P, Armstrong GL, Painter J, Kelley KA, Hoffmaster AR, Mayo D, Barden D, Ridzon R, Parashar U, Teshale EH, Williams J, Noviello S, Perz JF, Mast EE, Swerdlow DL, Hadler JL. Source: Emerging Infectious Diseases. 2003 June; 9(6): 681-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12781007&dopt=Abstract
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Calls about anthrax to the Texas Poison Center Network in relation to the anthrax bioterrorism attack in 2001. Author(s): Forrester MB, Stanley SK. Source: Vet Hum Toxicol. 2003 October; 45(5): 247-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14513892&dopt=Abstract
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Call-tracking data and the public health response to bioterrorism-related anthrax. Author(s): Mott JA, Treadwell TA, Hennessy TW, Rosenberg PA, Wolfe MI, Brown CM, Butler JC. Source: Emerging Infectious Diseases. 2002 October; 8(10): 1088-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12396921&dopt=Abstract
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CDC: be alert to symptoms associated with bioterrorism. Author(s): Levenson D. Source: Rep Med Guidel Outcomes Res. 2001 November 1; 12(21): 1-2, 5. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12382635&dopt=Abstract
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CDC's strategic plan for bioterrorism preparedness and response. Author(s): Koplan J. Source: Public Health Reports (Washington, D.C. : 1974). 2001; 116 Suppl 2: 9-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11880662&dopt=Abstract
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Citywide pharmaceutical preparation for bioterrorism. Author(s): Terriff CM, Tee AM. Source: American Journal of Health-System Pharmacy : Ajhp : Official Journal of the American Society of Health-System Pharmacists. 2001 February 1; 58(3): 233-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11217178&dopt=Abstract
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Climate change: the new bioterrorism. Author(s): Stott P. Source: Lancet. 2002 June 15; 359(9323): 2119. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12086798&dopt=Abstract
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Clinical presentation of inhalational anthrax following bioterrorism exposure: report of 2 surviving patients. Author(s): Mayer TA, Bersoff-Matcha S, Murphy C, Earls J, Harper S, Pauze D, Nguyen M, Rosenthal J, Cerva D Jr, Druckenbrod G, Hanfling D, Fatteh N, Napoli A, Nayyar A, Berman EL. Source: Jama : the Journal of the American Medical Association. 2001 November 28; 286(20): 2549-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11722268&dopt=Abstract
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Clinicians must be voice of reason, reassurance now that bioterrorism battle has been joined. Author(s): Evans G. Source: Hosp Case Manag. 2001 December; 9(12): Suppl 1-3. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11763593&dopt=Abstract
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Coccidioides immitis as a Select Agent of bioterrorism. Author(s): Dixon DM. Source: Journal of Applied Microbiology. 2001 October; 91(4): 602-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11576294&dopt=Abstract
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Combating bioterrorism with bioengineering. Author(s): Laxminarayan S, Kun LG. Source: Ieee Engineering in Medicine and Biology Magazine : the Quarterly Magazine of the Engineering in Medicine & Biology Society. 2002 September-October; 21(5): 21, 23-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12405054&dopt=Abstract
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Combating bioterrorism. The Brentwood Project. Author(s): Smith SM, Smith LG. Source: N J Med. 2002 November; 99(11): 39. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12455464&dopt=Abstract
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Community reaction to bioterrorism: prospective study of simulated outbreak. Author(s): DiGiovanni C Jr, Reynolds B, Harwell R, Stonecipher EB, Burkle FM Jr. Source: Emerging Infectious Diseases. 2003 June; 9(6): 708-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12781011&dopt=Abstract
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Comparative genomics tools applied to bioterrorism defence. Author(s): Slezak T, Kuczmarski T, Ott L, Torres C, Medeiros D, Smith J, Truitt B, Mulakken N, Lam M, Vitalis E, Zemla A, Zhou CE, Gardner S. Source: Briefings in Bioinformatics. 2003 June; 4(2): 133-49. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12846395&dopt=Abstract
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Confronting bioterrorism: physicians on the front line. Author(s): Varkey P, Poland GA, Cockerill FR 3rd, Smith TF, Hagen PT. Source: Mayo Clinic Proceedings. 2002 July; 77(7): 661-72. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12108604&dopt=Abstract
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Confusion over leadership of US bioterrorism research. Author(s): Dove A. Source: Nature Medicine. 2002 August; 8(8): 770-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12152020&dopt=Abstract
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Congress approves bioterrorism bill. Author(s): Van Koevering M. Source: Healthplan. 2002 July-August; 43(4): 8-10, 12. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12221782&dopt=Abstract
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Containing and combatting bioterrorism. Author(s): Spencer RC, Lightfoot NF. Source: Hosp Med. 2002 September; 63(9): 516-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12357849&dopt=Abstract
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Critical biological agents: disease reporting as a tool for determining bioterrorism preparedness. Author(s): Horton HH, Misrahi JJ, Matthews GW, Kocher PL. Source: The Journal of Law, Medicine & Ethics : a Journal of the American Society of Law, Medicine & Ethics. 2002 Summer; 30(2): 262-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12066603&dopt=Abstract
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Death due to bioterrorism-related inhalational anthrax: report of 2 patients. Author(s): Borio L, Frank D, Mani V, Chiriboga C, Pollanen M, Ripple M, Ali S, DiAngelo C, Lee J, Arden J, Titus J, Fowler D, O'Toole T, Masur H, Bartlett J, Inglesby T. Source: Jama : the Journal of the American Medical Association. 2001 November 28; 286(20): 2554-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11722269&dopt=Abstract
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Dentistry's response to bioterrorism: a report of a consensus workshop. Author(s): Guay AH. Source: The Journal of the American Dental Association. 2002 September; 133(9): 1181-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12356249&dopt=Abstract
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Department of Health report. Bioterrorism: a public health issue. Author(s): Moore WL. Source: Tenn Med. 2000 April; 93(4): 142-3. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10754806&dopt=Abstract
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Detection of vaccinia virus, herpes simplex virus, varicella-zoster virus, and Bacillus anthracis DNA by LightCycler polymerase chain reaction after autoclaving: implications for biosafety of bioterrorism agents. Author(s): Espy MJ, Uhl JR, Sloan LM, Rosenblatt JE, Cockerill FR 3rd, Smith TF. Source: Mayo Clinic Proceedings. 2002 July; 77(7): 624-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12108599&dopt=Abstract
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Diagnosis and management of suspected cases of bioterrorism: a pediatric perspective. Author(s): Patt HA, Feigin RD. Source: Pediatrics. 2002 April; 109(4): 685-92. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11927716&dopt=Abstract
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Disasters and bioterrorism: does management training develop readiness? Author(s): Orton S, Umble K, Davis MV, Porter JE. Source: Public Health Reports (Washington, D.C. : 1974). 2002 November-December; 117(6): 596-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12576540&dopt=Abstract
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Don't suffer the consequences. Prepare your office for bioterrorism response. Author(s): Wolper LF, Gans DN, Peterson TP. Source: Mgma Connexion / Medical Group Management Association. 2003 April; 3(4): 56-60, 1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12701366&dopt=Abstract
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Duration of immunity after smallpox vaccination: a study on vaccination policy against smallpox bioterrorism in Japan. Author(s): Arita I. Source: Japanese Journal of Infectious Diseases. 2002 August; 55(4): 112-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12403907&dopt=Abstract
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Effective public health assessment, prevention, response, and training for emerging and re-emerging infectious diseases, including bioterrorism. Author(s): American Public Health Association. Source: American Journal of Public Health. 2001 March; 91(3): 500-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11236439&dopt=Abstract
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Emergency mental health management in bioterrorism events. Author(s): Benedek DM, Holloway HC, Becker SM. Source: Emergency Medicine Clinics of North America. 2002 May; 20(2): 393-407. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12120485&dopt=Abstract
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Emergency: Bioterrorism. Author(s): Hagstad D. Source: The American Journal of Nursing. 2000 December; 100(12): 33-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11202782&dopt=Abstract
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Emerging illness and bioterrorism: implications for public health. Author(s): O'Toole T. Source: Journal of Urban Health : Bulletin of the New York Academy of Medicine. 2001 June; 78(2): 396-402. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11419591&dopt=Abstract
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Emerging infections and bioterrorism raise profile of schools of public health. Author(s): Lovinger SP. Source: Jama : the Journal of the American Medical Association. 2003 September 10; 290(10): 1306-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12966108&dopt=Abstract
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Endemic, notifiable bioterrorism-related diseases, United States, 1992-1999. Author(s): Chang MH, Glynn MK, Groseclose SL. Source: Emerging Infectious Diseases. 2003 May; 9(5): 556-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12737739&dopt=Abstract
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Epidemiologic clues to bioterrorism. Author(s): Treadwell TA, Koo D, Kuker K, Khan AS. Source: Public Health Reports (Washington, D.C. : 1974). 2003 March-April; 118(2): 92-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12690063&dopt=Abstract
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Epidemiologic investigations of bioterrorism-related anthrax, New Jersey, 2001. Author(s): Greene CM, Reefhuis J, Tan C, Fiore AE, Goldstein S, Beach MJ, Redd SC, Valiante D, Burr G, Buehler J, Pinner RW, Bresnitz E, Bell BP; CDC New Jersey Anthrax Investigation Team. Centers for Desease Control and Prevention. Source: Emerging Infectious Diseases. 2002 October; 8(10): 1048-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12396914&dopt=Abstract
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Europe needs “urgent focus” on bioterrorism. Author(s): Watson R. Source: Bmj (Clinical Research Ed.). 2001 November 10; 323(7321): 1086. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11701566&dopt=Abstract
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Expanding disaster preparedness to include bioterrorism. Author(s): Poe BM. Source: American Journal of Health-System Pharmacy : Ajhp : Official Journal of the American Society of Health-System Pharmacists. 2002 May 15; 59(10): 926-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12040730&dopt=Abstract
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Experts focus on infective agents of bioterrorism. Author(s): Stephenson J. Source: Jama : the Journal of the American Medical Association. 2002 February 6; 287(5): 575-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11829676&dopt=Abstract
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Exposure of laboratory workers to Francisella tularensis despite a bioterrorism procedure. Author(s): Shapiro DS, Schwartz DR. Source: Journal of Clinical Microbiology. 2002 June; 40(6): 2278-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12037110&dopt=Abstract
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Fear of bioterrorism and implications for public health preparedness. Author(s): Dworkin MS, Ma X, Golash RG. Source: Emerging Infectious Diseases. 2003 April; 9(4): 503-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12702237&dopt=Abstract
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First case of bioterrorism-related inhalational anthrax in the United States, Palm Beach County, Florida, 2001. Author(s): Traeger MS, Wiersma ST, Rosenstein NE, Malecki JM, Shepard CW, Raghunathan PL, Pillai SP, Popovic T, Quinn CP, Meyer RF, Zaki SR, Kumar S, Bruce SM, Sejvar JJ, Dull PM, Tierney BC, Jones JD, Perkins BA; Florida Investigation Team. Source: Emerging Infectious Diseases. 2002 October; 8(10): 1029-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12396910&dopt=Abstract
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First case of bioterrorism-related inhalational anthrax, Florida, 2001: North Carolina investigation. Author(s): Maillard JM, Fischer M, McKee KT Jr, Turner LF, Cline JS. Source: Emerging Infectious Diseases. 2002 October; 8(10): 1035-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12396911&dopt=Abstract
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FirstWatch: bioterrorism alert system for EMS. Author(s): Garza MA. Source: J Emerg Med Serv Jems. 2002 December; 27(12): 90. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12493998&dopt=Abstract
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Flash detection/identification of pathogens, bacterial spores and bioterrorism agent biomarkers from clinical and environmental matrices. Author(s): White DC, Lytle CA, Gan YD, Piceno YM, Wimpee MH, Peacock AD, Smith CA. Source: Journal of Microbiological Methods. 2002 February; 48(2-3): 139-47. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11777564&dopt=Abstract
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Food and safety. Bioterrorism and our food supply. Author(s): Theis M. Source: Health Care Food & Nutrition Focus. 2002 September; 19(1): 5-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12233229&dopt=Abstract
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From the Centers for Disease Control and Prevention. Investigation of bioterrorismrelated anthrax and interim guidelines for clinical evaluation of persons with possible anthrax. Author(s): Centers for Disease Control and Prevention. Source: Jama : the Journal of the American Medical Association. 2001 November 21; 286(19): 2392-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11759667&dopt=Abstract
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Future challenges in preparing for and responding to bioterrorism events. Author(s): Jones J, Terndrup TE, Franz DR, Eitzen EM Jr. Source: Emergency Medicine Clinics of North America. 2002 May; 20(2): 501-24. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12120489&dopt=Abstract
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Good intentions and the road to bioterrorism preparedness. Author(s): Sidel VW, Cohen HW, Gould RM. Source: American Journal of Public Health. 2001 May; 91(5): 716-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11344877&dopt=Abstract
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Has bioterrorism preparedness improved public health? Author(s): Staiti AB, Katz A, Hoadley JF. Source: Issue Brief Cent Stud Health Syst Change. 2003 July; (65): 1-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12901394&dopt=Abstract
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Health plans mobilize national bioterrorism response. Author(s): Rehm B, Bocchino C. Source: Healthplan. 2002 May-June; 43(3): 38-42. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12068730&dopt=Abstract
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Health services in the detection of and defence against bioterrorism. Author(s): Nicoll A. Source: Hosp Med. 2002 September; 63(9): 519. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12357850&dopt=Abstract
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Hospital preparedness for acts of bioterrorism: an assessment of emergency preparedness plans of hospitals in Rhode Island. Author(s): Boni CE, Earls EA. Source: Medicine and Health, Rhode Island. 2001 June; 84(6): 199. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11434149&dopt=Abstract
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Hospital preparedness for bioterrorism. Author(s): Bentley JD. Source: Public Health Reports (Washington, D.C. : 1974). 2001; 116 Suppl 2: 36-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11880669&dopt=Abstract
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Hospitals and country are 'woefully unprepared' for bioterrorism attacks. Author(s): Johnson DE. Source: Health Care Strategic Management. 2001 October; 19(10): 14-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11683056&dopt=Abstract
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Hospitals are more ready for bioterrorism. Author(s): Johnson DE. Source: Health Care Strategic Management. 2001 November; 19(11): 2-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11729606&dopt=Abstract
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Hospitals create new models as they gird for bioterrorism. Council on Public Health Preparedness says past year has brought improvements, but gaps remain. Author(s): Tieman J. Source: Modern Healthcare. 2002 September 2; 32(35): 8, 16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12298359&dopt=Abstract
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How bioterrorism became an HIM issue. Author(s): Rode D. Source: J Ahima. 2002 January; 73(1): 14, 16-7. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12580203&dopt=Abstract
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How do labs report bioterrorism agents? Author(s): Harty-Golder B. Source: Mlo: Medical Laboratory Observer. 2002 October; 34(10): 19. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12385172&dopt=Abstract
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How much is enough? AHA, lawmakers debate federal funding for bioterrorism preparation. Author(s): Lovern E. Source: Modern Healthcare. 2001 November 19; 31(47): 4-5, 16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11761733&dopt=Abstract
Studies
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Identifying bacterial agents of bioterrorism: the pivotal role of the laboratory response network.2. Author(s): Vanner CL, Combs WS Jr, Bertrand T, Bandy U. Source: Medicine and Health, Rhode Island. 2001 May; 84(5): 178-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11392961&dopt=Abstract
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Imaging characteristics of bioterrorism: signs of our times. Author(s): Rogers LF. Source: Ajr. American Journal of Roentgenology. 2003 March; 180(3): 563. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12591654&dopt=Abstract
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Implementing a bioterrorism response plan in your pharmacy. Author(s): Teeter D, Terriff C. Source: Journal of the American Pharmaceutical Association (Washington,D.C. : 1996). 2002 September-October; 42(5 Suppl 1): S52-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12296555&dopt=Abstract
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Implications of pandemic influenza for bioterrorism response. Author(s): Schoch-Spana M. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2000 December; 31(6): 1409-13. Epub 2000 November 17. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11096011&dopt=Abstract
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Index case of fatal inhalational anthrax due to bioterrorism in the United States. Author(s): Bush LM, Abrams BH, Beall A, Johnson CC. Source: The New England Journal of Medicine. 2001 November 29; 345(22): 1607-10. Epub 2001 Nov 08. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11704685&dopt=Abstract
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India wakes up to threat of bioterrorism. Author(s): Sharma R. Source: Bmj (Clinical Research Ed.). 2001 September 29; 323(7315): 714. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11576976&dopt=Abstract
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Infection control practitioners' perceptions and educational needs regarding bioterrorism: results from a national needs assessment survey. Author(s): Shadel BN, Rebmann T, Clements B, Chen JJ, Evans RG. Source: American Journal of Infection Control. 2003 May; 31(3): 129-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12734517&dopt=Abstract
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Influenza virus: natural disease and bioterrorism threat. Author(s): Lutz BD, Bronze MS, Greenfield RA. Source: J Okla State Med Assoc. 2003 January; 96(1): 27-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12632850&dopt=Abstract
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Inhalational anthrax after bioterrorism exposure: spectrum of imaging findings in two surviving patients. Author(s): Earls JP, Cerva D Jr, Berman E, Rosenthal J, Fatteh N, Wolfe PP, Clayton R, Murphy C, Pauze D, Mayer T, Bersoff-Matcha S, Urban B. Source: Radiology. 2002 February; 222(2): 305-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11818592&dopt=Abstract
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Inhalational anthrax and bioterrorism. Author(s): Quintiliani R Jr, Quintiliani R. Source: Current Opinion in Pulmonary Medicine. 2003 May; 9(3): 221-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12682568&dopt=Abstract
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Inhalational anthrax due to bioterrorism: would current Centers for Disease Control and Prevention guidelines have identified the 11 patients with inhalational anthrax from October through November 2001? Author(s): Mayer TA, Morrison A, Bersoff-Matcha S, Druckenbrod G, Murphy C, Howell J, Hanfling D, Cates R, Pauze D, Earls J. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2003 May 15; 36(10): 1275-83. Epub 2003 May 09. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12746773&dopt=Abstract
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Innovative surveillance methods for rapid detection of disease outbreaks and bioterrorism: results of an interagency workshop on health indicator surveillance. Author(s): Pavlin JA, Mostashari F, Kortepeter MG, Hynes NA, Chotani RA, Mikol YB, Ryan MA, Neville JS, Gantz DT, Writer JV, Florance JE, Culpepper RC, Henretig FM, Kelley PW. Source: American Journal of Public Health. 2003 August; 93(8): 1230-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12893601&dopt=Abstract
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Internet technology and bioterrorism. Author(s): Goldstein D. Source: Manag Care Interface. 2002 March; 15(3): 50-1. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11925678&dopt=Abstract
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Investigation of bioterrorism-related anthrax, United States, 2001: epidemiologic findings. Author(s): Jernigan DB, Raghunathan PL, Bell BP, Brechner R, Bresnitz EA, Butler JC, Cetron M, Cohen M, Doyle T, Fischer M, Greene C, Griffith KS, Guarner J, Hadler JL, Hayslett JA, Meyer R, Petersen LR, Phillips M, Pinner R, Popovic T, Quinn CP, Reefhuis J, Reissman D, Rosenstein N, Schuchat A, Shieh WJ, Siegal L, Swerdlow DL, Tenover FC, Traeger M, Ward JW, Weisfuse I, Wiersma S, Yeskey K, Zaki S, Ashford DA, Perkins BA, Ostroff S, Hughes J, Fleming D, Koplan JP, Gerberding JL; National Anthrax Epidemiologic Investigation Team. Source: Emerging Infectious Diseases. 2002 October; 8(10): 1019-28. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12396909&dopt=Abstract
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Is the U.S. public health system ready for bioterrorism? An assessment of the U.S. public health infrastructure and its capacity for infectious disease surveillance. Author(s): Baxter RJ, Steinberg CR, Shapiro JR. Source: Yale J Health Policy Law Ethics. 2001 Autumn; 2(1): 1-21. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12664935&dopt=Abstract
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Is your laboratory prepared for a bioterrorism attack? Author(s): Szabo J. Source: Mlo: Medical Laboratory Observer. 2001 December; 33(12): 10-6; Quiz 20-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11799622&dopt=Abstract
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Isolated case of bioterrorism-related inhalational anthrax, New York City, 2001. Author(s): Holtz TH, Ackelsberg J, Kool JL, Rosselli R, Marfin A, Matte T, Beatrice ST, Heller MB, Hewett D, Moskin LC, Bunning ML, Layton M. Source: Emerging Infectious Diseases. 2003 June; 9(6): 689-96. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12781008&dopt=Abstract
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Kentucky Bioterrorism Advisory Committee--update. Author(s): Kentucky Bioterrorism Advisory Committee. Source: Ky Nurse. 2002 October-December; 50(4): 7. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12430342&dopt=Abstract
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Knowledge-based bioterrorism surveillance. Author(s): Buckeridge DL, Graham J, O'Connor MJ, Choy MK, Tu SW, Musen MA. Source: Proceedings / Amia. Annual Symposium. Amia Symposium. 2002; : 76-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12463790&dopt=Abstract
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Laboratory aspects of bioterrorism-related anthrax--from identification to molecular subtyping to microbial forensics. Author(s): Popovic T, Glass M. Source: Croatian Medical Journal. 2003 June; 44(3): 336-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12808729&dopt=Abstract
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Laboratory safety practices associated with potential agents of biocrime or bioterrorism. Author(s): Sewell DL. Source: Journal of Clinical Microbiology. 2003 July; 41(7): 2801-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12843004&dopt=Abstract
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Legal preparedness for bioterrorism. Author(s): Matthews GW, Benjamin G, Mills SP, Parmet W, Misrahi JJ. Source: The Journal of Law, Medicine & Ethics : a Journal of the American Society of Law, Medicine & Ethics. 2002 Fall; 30(3 Suppl): 52-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12508503&dopt=Abstract
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Lessons from the West Nile viral encephalitis outbreak in New York City, 1999: implications for bioterrorism preparedness. Author(s): Fine A, Layton M. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2001 January 15; 32(2): 277-82. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11170918&dopt=Abstract
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Lessons learned from a full-scale bioterrorism exercise. Author(s): Hoffman RE, Norton JE. Source: Emerging Infectious Diseases. 2000 November-December; 6(6): 652-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11203432&dopt=Abstract
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Leveraging the nation's anti-bioterrorism investments: foundation efforts to ensure a revitalized public health system. Author(s): Hearne SA, Segal LM. Source: Health Aff (Millwood). 2003 July-August; 22(4): 230-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12889772&dopt=Abstract
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Managing terror. Public health officials learn lessons from bioterrorism attacks. Author(s): Benjamin GC. Source: Physician Executive. 2002 March-April; 28(2): 80-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11957420&dopt=Abstract
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Medical counterbioterrorism: the response to provide anthrax prophylaxis to New York City US Postal Service employees. Author(s): Partridge R, Alexander J, Lawrence T, Suner S. Source: Annals of Emergency Medicine. 2003 April; 41(4): 441-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12658240&dopt=Abstract
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Medical examiners and bioterrorism. Author(s): Nolte KB. Source: The American Journal of Forensic Medicine and Pathology : Official Publication of the National Association of Medical Examiners. 2000 December; 21(4): 419-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11111810&dopt=Abstract
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Medical examiners, coroners, and bioterrorism. Author(s): Nolte KB, Yoon SS, Pertowski C. Source: Emerging Infectious Diseases. 2000 September-October; 6(5): 559-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10998392&dopt=Abstract
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Medical management of the suspected victim of bioterrorism: an algorithmic approach to the undifferentiated patient. Author(s): Henretig FM, Cieslak TJ, Kortepeter MG, Fleisher GR. Source: Emergency Medicine Clinics of North America. 2002 May; 20(2): 351-64. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12120483&dopt=Abstract
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Medical management of vulnerable populations and co-morbid conditions of victims of bioterrorism. Author(s): White SR, Henretig FM, Dukes RG. Source: Emergency Medicine Clinics of North America. 2002 May; 20(2): 365-92, Xi. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12120484&dopt=Abstract
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Medical response to bioterrorism: are we prepared? Author(s): Haines JD, Pitts K, Crutcher JM. Source: J Okla State Med Assoc. 2000 May; 93(5): 187-96. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10826225&dopt=Abstract
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Meeting the challenge of bioterrorism: lessons learned from West Nile virus and anthrax. Author(s): Crupi RS, Asnis DS, Lee CC, Santucci T, Marino MJ, Flanz BJ. Source: The American Journal of Emergency Medicine. 2003 January; 21(1): 77-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12563588&dopt=Abstract
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Mental health consequences of bioterrorism. Author(s): Kron S, Mendlovic S. Source: Isr Med Assoc J. 2002 July; 4(7): 524-7. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12120464&dopt=Abstract
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Michael Osterholm--medical detective to fighting bioterrorism. Interview by Pam Das. Author(s): Osterholm M. Source: The Lancet Infectious Diseases. 2002 August; 2(8): 502-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12150850&dopt=Abstract
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Modeling the consequences of bioterrorism response. Author(s): Giovachino M, Carey N. Source: Military Medicine. 2001 November; 166(11): 925-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11725318&dopt=Abstract
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Modeling the public health response to bioterrorism: using discrete event simulation to design antibiotic distribution centers. Author(s): Hupert N, Mushlin AI, Callahan MA. Source: Medical Decision Making : an International Journal of the Society for Medical Decision Making. 2002 September-October; 22(5 Suppl): S17-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12369227&dopt=Abstract
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Molecular subtyping of Bacillus anthracis and the 2001 bioterrorism-associated anthrax outbreak, United States. Author(s): Hoffmaster AR, Fitzgerald CC, Ribot E, Mayer LW, Popovic T. Source: Emerging Infectious Diseases. 2002 October; 8(10): 1111-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12396925&dopt=Abstract
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More bioterrorism. Author(s): Shulman ST. Source: Pediatric Annals. 2003 April; 32(4): 213. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12723114&dopt=Abstract
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More bioterrorism. Author(s): Madariaga MG. Source: Pediatrics. 2002 December; 110(6): 1257-8; Author Reply 1257-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12456930&dopt=Abstract
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National leadership in confronting bioterrorism: 1. Author(s): Hamre JJ. Source: Public Health Reports (Washington, D.C. : 1974). 2001; 116 Suppl 2: 112-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11880683&dopt=Abstract
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National leadership in confronting bioterrorism: 2. Author(s): Kennedy EM. Source: Public Health Reports (Washington, D.C. : 1974). 2001; 116 Suppl 2: 116-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11880684&dopt=Abstract
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National preparedness for biological warfare and bioterrorism: smallpox and the ophthalmologist. Author(s): Maki DG. Source: Archives of Ophthalmology. 2003 May; 121(5): 710-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12742850&dopt=Abstract
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Need for physicians trained in preventive medicine and public health: implications for a bioterrorism response. Author(s): Malecki J, Brumback CL. Source: Journal of Public Health Management and Practice : Jphmp. 2003 March-April; 9(2): 89-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12629910&dopt=Abstract
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New law funds nursing's role in bioterrorism response. The ANA establishes the National Nurses Response Team. Author(s): Donnellan C. Source: The American Journal of Nursing. 2002 August; 102(8): 23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12394032&dopt=Abstract
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New leader, new mission. Heightened focus on bioterrorism poses unique challenges for CDC's new chief. Author(s): Piotrowski J. Source: Modern Healthcare. 2002 August 5; 32(31): 16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12224356&dopt=Abstract
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Nipah virus--a potential agent of bioterrorism? Author(s): Lam SK. Source: Antiviral Research. 2003 January; 57(1-2): 113-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12615307&dopt=Abstract
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NSUCOM establishes bioterrorism preparedness center. Author(s): Silvagni AJ. Source: J Am Osteopath Assoc. 2003 May; 103(5): 215. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12776761&dopt=Abstract
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Olympics 2000: preparing to respond to bioterrorism. Author(s): Hauer J. Source: Public Health Reports (Washington, D.C. : 1974). 2001; 116 Suppl 2: 19-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11880664&dopt=Abstract
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On the front lines: family physicians' preparedness for bioterrorism. Author(s): Chen FM, Hickner J, Fink KS, Galliher JM, Burstin H. Source: The Journal of Family Practice. 2002 September; 51(9): 745-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12366891&dopt=Abstract
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Other bacterial diseases as a potential consequence of bioterrorism: Q fever, brucellosis, glanders, and melioidosis. Author(s): Voskuhl GW, Cornea P, Bronze MS, Greenfield RA. Source: J Okla State Med Assoc. 2003 May; 96(5): 214-7. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12833721&dopt=Abstract
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Our first line of defense against bioterrorism part 2. Author(s): Simpson RL. Source: Nursing Management. 2002 May; 33(5): 10, 11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12006878&dopt=Abstract
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Our first line of defense against bioterrorism. Part 1. Author(s): Simpson RL. Source: Nursing Management. 2002 March; 33(3): 10-3. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11923974&dopt=Abstract
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Overview: cause and prevention in biowarfare and bioterrorism. Author(s): Hilleman MR. Source: Vaccine. 2002 August 19; 20(25-26): 3055-67. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12163257&dopt=Abstract
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Pathogenic rickettsiae as bioterrorism agents. Author(s): Azad AF, Radulovic S. Source: Annals of the New York Academy of Sciences. 2003 June; 990: 734-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12860715&dopt=Abstract
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Pathology and pathogenesis of bioterrorism-related inhalational anthrax. Author(s): Guarner J, Jernigan JA, Shieh WJ, Tatti K, Flannagan LM, Stephens DS, Popovic T, Ashford DA, Perkins BA, Zaki SR; Inhalational Anthrax Pathology Working Group. Source: American Journal of Pathology. 2003 August; 163(2): 701-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12875989&dopt=Abstract
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Pediatric implications in bioterrorism part I: physiologic and psychosocial differences. Author(s): Bernardo LM. Source: International Journal of Trauma Nursing. 2001 January-March; 7(1): 14-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11174764&dopt=Abstract
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Pediatric implications in bioterrorism part II: postexposure diagnosis and treatment. Author(s): Rosenfield RL, Bernardo LM. Source: International Journal of Trauma Nursing. 2001 October-December; 7(4): 133-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11707769&dopt=Abstract
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Pediatric implications in bioterrorism: education for healthcare providers. Author(s): Bernardo LM, Kapsar P. Source: Disaster Management & Response : Dmr : an Official Publication of the Emergency Nurses Association. 2003 April-June; 1(2): 52-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12704321&dopt=Abstract
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Perceptions of state public health officers and state veterinarians regarding risks of bioterrorism in the United States. Author(s): Tharratt RS, Case JT, Hird DW. Source: J Am Vet Med Assoc. 2002 June 15; 220(12): 1782-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12092950&dopt=Abstract
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Practical guidelines for acute care of victims of bioterrorism: conventional injuries and concomitant nerve agent intoxication. Author(s): Ben Abraham R, Rudick V, Weinbroum AA; Department of Anesthesiology and Critical Care Medicine, Tel Aviv Sourasky Medical Center and the Sackler Faculty of Medicine. Source: Anesthesiology. 2002 October; 97(4): 989-1004. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12357169&dopt=Abstract
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Preparedness and response to bioterrorism. Author(s): Spencer RC, Lightfoot NF. Source: The Journal of Infection. 2001 August; 43(2): 104-10. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11676515&dopt=Abstract
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Preparedness for bioterrorism? Author(s): Cohen HW, Sidel VW, Gould RM. Source: The New England Journal of Medicine. 2001 November 8; 345(19): 1423-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11794178&dopt=Abstract
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Preparing for bioterrorism in North Carolina. Author(s): Cline JS. Source: N C Med J. 2002 September-October; 63(5): 257-64. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12970969&dopt=Abstract
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Preparing for bioterrorism. Author(s): Farrell PM, Mejicano G. Source: Wmj. 2002; 101(2): 35-6. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12085495&dopt=Abstract
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Preparing for bioterrorism. Author(s): Thompson TG. Source: Anesthesiology. 2002 October; 97(4): 776-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12357139&dopt=Abstract
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Preparing for bioterrorism. Author(s): Persell DJ, Arangie P, Young C, Stokes EN, Payne WC, Skorga P, GilbertPalmer D. Source: Nursing. 2002 February; 32(2): 36-43; Quiz 44-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11924164&dopt=Abstract
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Preparing for bioterrorism: category A agents. Author(s): Persell DJ, Arangie P, Young C, Stokes EN, Payne WC, Skorga P, GilbertPalmer D. Source: The Nurse Practitioner. 2001 December; 26(12): 12-5, 19-24, 27; Quiz 28-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11809039&dopt=Abstract
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Preparing for expected bioterrorism attacks. Author(s): Moser R Jr, White GL, Lewis-Younger CR, Garrett LC. Source: Military Medicine. 2001 May; 166(5): 369-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11370195&dopt=Abstract
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Prescriptions on bioterrorism have it backwards. Author(s): Cohen HW, Sidel VW, Gould RM. Source: Bmj (Clinical Research Ed.). 2000 April 29; 320(7243): 1211. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10784560&dopt=Abstract
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Preventive and therapeutic approaches to viral agents of bioterrorism. Author(s): Bronze MS, Greenfield RA. Source: Drug Discovery Today. 2003 August 15; 8(16): 740-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12944096&dopt=Abstract
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Protecting the public's health in an era of bioterrorism: the Model State Emergency Health Powers Act. Author(s): Hodge JG Jr. Source: Accountability in Research. 2003 April-June; 10(2): 91-107. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14577422&dopt=Abstract
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Public health and civil liberties in an era of bioterrorism. Author(s): Gostin LO. Source: Criminal Justice Ethics. 2002 Summer; 21(2): 2, 74-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12956132&dopt=Abstract
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Public health and the media: the challenge now faced by bioterrorism. Author(s): Mullin S. Source: Journal of Urban Health : Bulletin of the New York Academy of Medicine. 2002 March; 79(1): 12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11937610&dopt=Abstract
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Public Health Grand Rounds addresses bioterrorism preparedness. Author(s): Roper WL, Davis DE. Source: Journal of Public Health Management and Practice : Jphmp. 2000 July; 6(4): 70-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10977617&dopt=Abstract
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Public health in the time of bioterrorism. Author(s): Perkins BA, Popovic T, Yeskey K. Source: Emerging Infectious Diseases. 2002 October; 8(10): 1015-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12396908&dopt=Abstract
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Public health preparedness for bioterrorism. Author(s): Wetterhall SF. Source: J Med Assoc Ga. 2002 Summer; 91(2): 8-11. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12189966&dopt=Abstract
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Ready or not--preparedness for bioterrorism. Author(s): Khan AS, Ashford DA. Source: The New England Journal of Medicine. 2001 July 26; 345(4): 287-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11474670&dopt=Abstract
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Readying for bioterrorism. Senators question nation's preparedness, propose big spending increase. Author(s): Lovern E. Source: Modern Healthcare. 2001 October 8; 31(41): 9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11668841&dopt=Abstract
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Recognition and management of bioterrorism infections. Author(s): O'Brien KK, Higdon ML, Halverson JJ. Source: American Family Physician. 2003 May 1; 67(9): 1927-34. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12751654&dopt=Abstract
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Report of the “Bioterrorism Workshop.” Duke University Thomas Center on April 24, 2002, organized by US Army Research Office. Author(s): Fox A. Source: Journal of Microbiological Methods. 2002 November; 51(3): 247-54. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12223285&dopt=Abstract
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Resources in the war against bioterrorism. Author(s): Gourlay M, Siwek J. Source: American Family Physician. 2001 November 15; 64(10): 1676, 1678. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11759075&dopt=Abstract
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Responding to bioterrorism and psychological toxicity: an introduction to the concept of shielding. Author(s): Everly GS Jr. Source: Int J Emerg Ment Health. 2002 Fall; 4(4): 231-3. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12629839&dopt=Abstract
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Responding to bioterrorism. Author(s): Breithaupt H. Source: Embo Reports. 2001 December; 2(12): 1053. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11743010&dopt=Abstract
Studies
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Responding to the threat of bioterrorism: a microbial ecology perspective--the case of anthrax. Author(s): Atlas RM. Source: International Microbiology : the Official Journal of the Spanish Society for Microbiology. 2002 December; 5(4): 161-7. Epub 2002 August 20. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12497181&dopt=Abstract
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Responding to the threat of bioterrorism: practical resources and references, and the importance of preparation. Author(s): Stopford BM. Source: Journal of Emergency Nursing: Jen : Official Publication of the Emergency Department Nurses Association. 2001 October; 27(5): 471-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11577287&dopt=Abstract
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Response to “bioterrorism” editorial. Author(s): Sudia WD. Source: Vector Borne and Zoonotic Diseases (Larchmont, N.Y.). 2002 Summer; 2(2): 51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12653297&dopt=Abstract
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Response to bioterrorism. Anthrax issue underlines need for infection specialists trained at bedside. Author(s): Green S. Source: Bmj (Clinical Research Ed.). 2002 February 9; 324(7333): 364. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11858182&dopt=Abstract
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Response to bioterrorism. Countermeasures against weapons of mass destruction must be assessed now. Author(s): Barach P. Source: Bmj (Clinical Research Ed.). 2002 February 9; 324(7333): 363-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11858181&dopt=Abstract
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Response to bioterrorism. Screening for agents of bioterrorism increases terror. Author(s): Temte J. Source: Bmj (Clinical Research Ed.). 2002 February 9; 324(7333): 363. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11858180&dopt=Abstract
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Response to bioterrorism. Terror weapons are regarded as weapons of mass destruction. Author(s): Lim MK. Source: Bmj (Clinical Research Ed.). 2002 February 9; 324(7333): 362-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11858178&dopt=Abstract
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Response to bioterrorism. US anthrax incidents led to scares in Scotland. Author(s): Bree M, Stevenson J. Source: Bmj (Clinical Research Ed.). 2002 February 9; 324(7333): 363. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11858179&dopt=Abstract
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Restricting genome data won't stop bioterrorism. Author(s): Read TD, Parkhill J. Source: Nature. 2002 May 23; 417(6887): 379. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12024189&dopt=Abstract
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Ring-a-ring-a-roses: bioterrorism and its peculiar relevance to pediatrics. Author(s): Cieslak TJ, Henretig FM. Source: Current Opinion in Pediatrics. 2003 February; 15(1): 107-11. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12544281&dopt=Abstract
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Risk communication, the West Nile virus epidemic, and bioterrorism: responding to the communication challenges posed by the intentional or unintentional release of a pathogen in an urban setting. Author(s): Covello VT, Peters RG, Wojtecki JG, Hyde RC. Source: Journal of Urban Health : Bulletin of the New York Academy of Medicine. 2001 June; 78(2): 382-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11419589&dopt=Abstract
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Role of the hospital-based microbiology laboratory in preparation for and response to a bioterrorism event. Author(s): Snyder JW. Source: Journal of Clinical Microbiology. 2003 January; 41(1): 1-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12517818&dopt=Abstract
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Roundtable on bioterrorism detection: information system-based surveillance. Author(s): Lober WB, Karras BT, Wagner MM, Overhage JM, Davidson AJ, Fraser H, Trigg LJ, Mandl KD, Espino JU, Tsui FC. Source: Journal of the American Medical Informatics Association : Jamia. 2002 MarchApril; 9(2): 105-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11861622&dopt=Abstract
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Rural bioterrorism: are we exempt? Author(s): Rosenthal TC. Source: The Journal of Rural Health : Official Journal of the American Rural Health Association and the National Rural Health Care Association. 2003 Winter; 19(1): 5-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12585767&dopt=Abstract
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Science and the fight against bioterrorism. Author(s): Rieff HI. Source: The Faseb Journal : Official Publication of the Federation of American Societies for Experimental Biology. 2002 January; 16(1): 1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11772930&dopt=Abstract
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Sentinel bioterrorism responders: are hospital labs ready? Author(s): York M. Source: Mlo: Medical Laboratory Observer. 2003 August; 35(8): 12-7, 19; Quiz 22-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12942658&dopt=Abstract
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Serious adverse events among participants in the Centers for Disease Control and Prevention's Anthrax Vaccine and Antimicrobial Availability Program for persons at risk for bioterrorism-related inhalational anthrax. Author(s): Tierney BC, Martin SW, Franzke LH, Marano N, Reissman DB, Louchart RD, Goff JA, Rosenstein NE, Sever JL, McNeil MM; Centers for Disease Control and Prevention's Anthrax Vaccine and Antimicrobial Availability Program. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2003 October 1; 37(7): 905-11. Epub 2003 September 12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13130401&dopt=Abstract
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Sixth annual conference on infectious diseases focuses on bioterrorism, as well as more familiar problems. Monday, Dec 3, to Wednesday, Dec 5, 2001. Author(s): Dawes BS. Source: Aorn Journal. 2002 February; 75(2): 272-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11855223&dopt=Abstract
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Smallpox and bioterrorism. Author(s): Huff DM. Source: Cleve Clin J Med. 2002 May; 69(5): 360; Author Reply 360-1. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12022377&dopt=Abstract
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Smallpox and bioterrorism. Author(s): Drazen JM. Source: The New England Journal of Medicine. 2002 April 25; 346(17): 1262-3. Epub 2002 March 28. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11923485&dopt=Abstract
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Smallpox vaccination after a bioterrorism-based exposure. Author(s): Bicknell WJ, James K. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2003 August 1; 37(3): 467. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12884184&dopt=Abstract
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Smallpox vaccination to combat bioterrorism. Author(s): Arya SC. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2003 July 1; 37(1): 150-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12830424&dopt=Abstract
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Smallpox, bioterrorism, and the neurologist. Author(s): Cleri DJ, Villota FJ, Porwancher RB. Source: Archives of Neurology. 2003 April; 60(4): 489-94. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12707060&dopt=Abstract
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Smallpox: a potential agent of bioterrorism. Author(s): Whitley RJ. Source: Antiviral Research. 2003 January; 57(1-2): 7-12. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12615298&dopt=Abstract
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State epidemiologist, Eddy Bresnitz, MD, MS, on bioterrorism. Author(s): Porwancher R. Source: N J Med. 2003 July-August; 100(7-8): 47; Author Reply 47. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12955807&dopt=Abstract
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Surveillance for early detection and monitoring of infectious disease outbreaks associated with bioterrorism. Author(s): Green MS, Kaufman Z. Source: Isr Med Assoc J. 2002 July; 4(7): 503-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12120460&dopt=Abstract
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Syndromic analysis of computerized emergency department patients' chief complaints: an opportunity for bioterrorism and influenza surveillance. Author(s): Irvin CB, Nouhan PP, Rice K. Source: Annals of Emergency Medicine. 2003 April; 41(4): 447-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12658241&dopt=Abstract
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Syndromic surveillance using minimum transfer of identifiable data: the example of the National Bioterrorism Syndromic Surveillance Demonstration Program. Author(s): Platt R, Bocchino C, Caldwell B, Harmon R, Kleinman K, Lazarus R, Nelson AF, Nordin JD, Ritzwoller DP. Source: Journal of Urban Health : Bulletin of the New York Academy of Medicine. 2003 June; 80(2 Suppl 1): I25-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12791776&dopt=Abstract
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Testing a symptom-based surveillance system at high-profile gatherings as a preparatory measure for bioterrorism. Author(s): Osaka K, Takahashi H, Ohyama T. Source: Epidemiology and Infection. 2002 December; 129(3): 429-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12558324&dopt=Abstract
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The anthrax team: a novel teaching approach to increase anthrax and bioterrorism awareness. Author(s): Brooks KL, Dauenhauer SA. Source: American Journal of Infection Control. 2003 May; 31(3): 176-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12734524&dopt=Abstract
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The application of ultraviolet germicidal irradiation to control transmission of airborne disease: bioterrorism countermeasure. Author(s): Brickner PW, Vincent RL, First M, Nardell E, Murray M, Kaufman W. Source: Public Health Reports (Washington, D.C. : 1974). 2003 March-April; 118(2): 99114. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12690064&dopt=Abstract
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The bioterrorism preparedness and response Early Aberration Reporting System (EARS). Author(s): Hutwagner L, Thompson W, Seeman GM, Treadwell T. Source: Journal of Urban Health : Bulletin of the New York Academy of Medicine. 2003 June; 80(2 Suppl 1): I89-96. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12791783&dopt=Abstract
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The Center for the Study of Bioterrorism and Emerging Infections: training the public health workforce for the future. Author(s): Evans RG, Shadel BN, Clements B. Source: Public Health Reports (Washington, D.C. : 1974). 2001 May-June; 116(3): 276-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12034919&dopt=Abstract
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The challenge of training a public health workforce in bioterrorism preparedness. Author(s): Ryder RW. Source: N C Med J. 2002 September-October; 63(5): 265-7. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12970970&dopt=Abstract
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The contributions of biomedical informatics to the fight against bioterrorism. Author(s): Kohane IS. Source: Journal of the American Medical Informatics Association : Jamia. 2002 MarchApril; 9(2): 116-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11861623&dopt=Abstract
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The critical role of hospitals involved in national bioterrorism preparedness. Author(s): Ridge T. Source: J Healthc Prot Manage. 2002 Summer; 18(2): 39-48. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12371247&dopt=Abstract
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The cyber response to bioterrorism. Author(s): Clark AD; Greene County Medical Society. Source: Mo Med. 2001 November; 98(11): 481. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11732345&dopt=Abstract
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The difference between biological warfare and bioterrorism: Australia finally makes a start towards real preparedness for bioterrorism. Author(s): Grayson ML. Source: Internal Medicine Journal. 2003 May-June; 33(5-6): 213-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12752887&dopt=Abstract
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The epidemiologic pyramid of bioterrorism. Author(s): Huerta M, Leventhal A. Source: Isr Med Assoc J. 2002 July; 4(7): 498-502. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12120459&dopt=Abstract
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The Laboratory Response Network for bioterrorism. Author(s): Heatherley SS. Source: Clin Lab Sci. 2002 Summer; 15(3): 177-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12778964&dopt=Abstract
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The malevolent use of microbes and the rule of law: legal challenges presented by bioterrorism. Author(s): Fidler DP. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2001 September 1; 33(5): 686-9. Epub 2001 July 30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11486291&dopt=Abstract
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The microbiology laboratory's role in response to bioterrorism. Author(s): Robinson-Dunn B. Source: Archives of Pathology & Laboratory Medicine. 2002 March; 126(3): 291-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11860302&dopt=Abstract
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The Model State Emergency Health Powers Act: planning for and response to bioterrorism and naturally occurring infectious diseases. Author(s): Gostin LO, Sapsin JW, Teret SP, Burris S, Mair JS, Hodge JG Jr, Vernick JS. Source: Jama : the Journal of the American Medical Association. 2002 August 7; 288(5): 622-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12150674&dopt=Abstract
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The plain lawyer's guide to bioterrorism. Author(s): Richmond C. Source: Med Leg J. 2001; 69(Pt 4): 182-3. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11887760&dopt=Abstract
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The potential role of viral pathogens as agents of bioterrorism. Author(s): Bronze MS, Voskuhl GW, Machado LJ, Greenfield RA. Source: J Okla State Med Assoc. 2003 January; 96(1): 29-33. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12632851&dopt=Abstract
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The potential use of influenza virus as an agent for bioterrorism. Author(s): Krug RM. Source: Antiviral Research. 2003 January; 57(1-2): 147-50. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12615310&dopt=Abstract
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The reality of the modern bioterrorism response. Author(s): Barbera JA, Macintyre AG. Source: Lancet. 2002 December; 360 Suppl: S33-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12504495&dopt=Abstract
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The role of primary care in bioterrorism, epidemics and other major emergencies: failing to plan is planning to fail. Author(s): Hodgkin P, Perrett K. Source: The British Journal of General Practice : the Journal of the Royal College of General Practitioners. 2003 January; 53(486): 5-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12564269&dopt=Abstract
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The role of risk analysis in understanding bioterrorism. Author(s): Haas CN. Source: Risk Analysis : an Official Publication of the Society for Risk Analysis. 2002 August; 22(4): 671-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12224741&dopt=Abstract
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The threat of bioterrorism. Author(s): Place MD. Source: Health Progress (Saint Louis, Mo.). 2002 March-April; 83(2): 6-7, 52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11924264&dopt=Abstract
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The threat of bioterrorism. Author(s): Berger DS. Source: Posit Aware. 2003 March-April; 14(2): 40-1. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12693375&dopt=Abstract
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The USA preparing for bioterrorism: the role of Fort Detrick since 1970. Author(s): Proctor RA. Source: Wmj. 2002; 101(2): 20-4. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12085492&dopt=Abstract
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Therapeutic challenges posed by bacterial bioterrorism threats. Author(s): Gilligan PH. Source: Current Opinion in Microbiology. 2002 October; 5(5): 489-95. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12354556&dopt=Abstract
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Therapeutic options for diseases due to potential viral agents of bioterrorism. Author(s): Bronze MS, Greenfield RA. Source: Curr Opin Investig Drugs. 2003 February; 4(2): 172-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12669378&dopt=Abstract
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Though better prepared after 9/11, America still vulnerable to bioterrorism. Author(s): Nolen RS. Source: J Am Vet Med Assoc. 2003 July 15; 223(2): 163-4. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12875435&dopt=Abstract
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Threats in bioterrorism. I: CDC category A agents. Author(s): Darling RG, Catlett CL, Huebner KD, Jarrett DG. Source: Emergency Medicine Clinics of North America. 2002 May; 20(2): 273-309. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12120480&dopt=Abstract
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Threats in bioterrorism. II: CDC category B and C agents. Author(s): Moran GJ. Source: Emergency Medicine Clinics of North America. 2002 May; 20(2): 311-30. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12120481&dopt=Abstract
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Towards an internet civil defence against bioterrorism. Author(s): LaPorte RE, Sauer F, Dearwater S, Sekikawa A, Sa ER, Aaron D, Shubnikov E. Source: The Lancet Infectious Diseases. 2001 September; 1(2): 125-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11871463&dopt=Abstract
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Training requirements and opportunities in planning responses to bioterrorism. Author(s): Downs KE. Source: American Journal of Health-System Pharmacy : Ajhp : Official Journal of the American Society of Health-System Pharmacists. 2002 July 15; 59(14): 1331-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12132558&dopt=Abstract
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Tularemia of the head and neck: a possible sign of bioterrorism. Author(s): Stupak HD, Scheuller MC, Schindler DN, Ellison DE. Source: Ear, Nose, & Throat Journal. 2003 April; 82(4): 263-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12735158&dopt=Abstract
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U.S. hospitals, physicians playing “catch-up” on bioterrorism. Author(s): Coile RC Jr. Source: Russ Coile's Health Trends. 2001 December; 14(2): 2-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11765713&dopt=Abstract
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Update: Investigation of bioterrorism-related anthrax and interim guidelines for clinical evaluation of persons with possible anthrax. Author(s): Centers for Disease Control and Prevention. Source: Mmwr. Morbidity and Mortality Weekly Report. 2001 November 2; 50(43): 9418. Erratum In: Mmwr Morb Mortal Wkly Rep 2001 Nov 9; 50(44): 991. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11708591&dopt=Abstract
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Update: Investigation of bioterrorism-related anthrax and interim guidelines for exposure management and antimicrobial therapy, October 2001. Author(s): Centers for Disease Control and Prevention. Source: Mmwr. Morbidity and Mortality Weekly Report. 2001 October 26; 50(42): 909-19. Erratum In: Mmwr Morb Mortal Wkly Rep 2001 November 2; 50(43): 962. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11699843&dopt=Abstract
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US agriculture is vulnerable to bioterrorism. Author(s): Moon HW, Kirk-Baer C, Ascher M, Cook RJ, Franz DR, Hoy M, Husnik DF, Jensen HH, Keller KH, Lederberg J, Madden LV, Powers LS, Steinberg AD, Strating A, Smith RE, Kuzma J, Grossblatt N, Holliday L, Sweatt D, Strongin S. Source: J Vet Med Educ. 2003 Summer; 30(2): 96-104. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12970850&dopt=Abstract
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US anthrax scares prompt action on bioterrorism. Author(s): Greenberg DS. Source: Lancet. 2001 October 27; 358(9291): 1435. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11705502&dopt=Abstract
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US fear of bioterrorism spreads as anthrax cases increase. Author(s): Josefson D. Source: Bmj (Clinical Research Ed.). 2001 October 20; 323(7318): 883. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11668122&dopt=Abstract
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US federal bureaucracy hampers progress in countering bioterrorism. Author(s): Fox JL. Source: Nature Biotechnology. 2002 June; 20(6): 530. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12042838&dopt=Abstract
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US health bodies reap funds for bioterrorism. Author(s): Greenberg DS. Source: Lancet. 2002 March 2; 359(9308): 771. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11888599&dopt=Abstract
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US plans drugs stockpile to counter bioterrorism threat. Author(s): Charatan F. Source: Bmj (Clinical Research Ed.). 2000 May 6; 320(7244): 1225. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10797021&dopt=Abstract
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Usage of a web-based decision support tool for bioterrorism detection. Author(s): Shannon M, Burstein J, Mandl K, Fleisher G. Source: The American Journal of Emergency Medicine. 2002 July; 20(4): 384-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12098202&dopt=Abstract
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Use of automated ambulatory-care encounter records for detection of acute illness clusters, including potential bioterrorism events. Author(s): Lazarus R, Kleinman K, Dashevsky I, Adams C, Kludt P, DeMaria A Jr, Platt R. Source: Emerging Infectious Diseases. 2002 August; 8(8): 753-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12141958&dopt=Abstract
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Vaccines and bioterrorism: smallpox and anthrax. Author(s): Kimmel SR, Mahoney MC, Zimmerman RK. Source: The Journal of Family Practice. 2003 January; 52(1 Suppl): S56-61. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12556279&dopt=Abstract
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Vaccines, biological warfare, and bioterrorism. Author(s): Polgreen PM, Helms C. Source: Primary Care. 2001 December; 28(4): 807-21, Vii. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11739031&dopt=Abstract
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VA's role in bioterrorism preparations. Author(s): Teeter DS, Koenig KL. Source: American Journal of Infection Control. 2000 August; 28(4): 321. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10926711&dopt=Abstract
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Veterinarians key to bioterrorism preparedness initiatives. Author(s): Kuehn BM. Source: J Am Vet Med Assoc. 2002 September 15; 221(6): 757-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12322902&dopt=Abstract
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Veterinarians take a lead role in agency responses to bioterrorism. Author(s): Demert A. Source: J Am Vet Med Assoc. 2002 March 15; 220(6): 730. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11918257&dopt=Abstract
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Vigilance against bioterrorism. Author(s): Scudamore JM. Source: The Veterinary Record. 2001 December 15; 149(24): 751. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11808660&dopt=Abstract
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Vigilance against bioterrorism. Author(s): Storrar JA, Kirby C. Source: The Veterinary Record. 2001 November 10; 149(19): 599-600. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11730172&dopt=Abstract
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Viral agents as biological weapons and agents of bioterrorism. Author(s): Bronze MS, Huycke MM, Machado LJ, Voskuhl GW, Greenfield RA. Source: The American Journal of the Medical Sciences. 2002 June; 323(6): 316-25. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12074486&dopt=Abstract
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Viruses of the Bunya- and Togaviridae families: potential as bioterrorism agents and means of control. Author(s): Sidwell RW, Smee DF. Source: Antiviral Research. 2003 January; 57(1-2): 101-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12615306&dopt=Abstract
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Wake-up call: a bioterrorism exercise. Author(s): Tyre TE. Source: Military Medicine. 2001 December; 166(12 Suppl): 90-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11778452&dopt=Abstract
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War, bioterrorism, and the political landscape. Author(s): Greenberg DS. Source: Lancet. 2001 December 22-29; 358(9299): 2137. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11784639&dopt=Abstract
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Waterborne infections in the era of bioterrorism. Author(s): Tramarin A, Fabris P, Bishai D, Selle V, De Lalla F. Source: Lancet. 2002 November 23; 360(9346): 1699. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12457828&dopt=Abstract
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WHA takes on bioterrorism and poverty. Author(s): Kapp C. Source: The Lancet Infectious Diseases. 2002 July; 2(7): 389. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12127342&dopt=Abstract
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What we need to know about bioterrorism preparedness: results from focus groups conducted at APIC 2000. Author(s): Shadel BN, Clements B, Arndt B, Rebmann T, Evans RG. Source: American Journal of Infection Control. 2001 December; 29(6): 347-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11743480&dopt=Abstract
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What's our pharmacologic readiness against a bioterrorism attack? Author(s): Bucci KK, Briscoe-Dwyer L. Source: Jaapa. 2002 April; 15(4): 10, 13. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12012583&dopt=Abstract
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WHO addresses poverty and bioterrorism. Author(s): Walt G, Brugha R, Starling M. Source: Lancet. 2002 February 2; 359(9304): 448. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11844554&dopt=Abstract
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WHO executive board addresses poverty and bioterrorism. Author(s): Kapp C. Source: Lancet. 2002 January 19; 359(9302): 239. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11812575&dopt=Abstract
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Why should dentists be involved in bioterrorism? Author(s): Miller DJ. Source: The New York State Dental Journal. 2003 May; 69(5): 10-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12875132&dopt=Abstract
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Will the nation be ready for the next bioterrorism attack? Mending gaps in the public health infrastructure. Author(s): Salinsky E. Source: Nhpf Issue Brief. 2002 June 12; (776): 1-19. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12083160&dopt=Abstract
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CHAPTER 2. NUTRITION AND BIOTERRORISM Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and bioterrorism.
Finding Nutrition Studies on Bioterrorism 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 “bioterrorism” (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 “bioterrorism” (or a synonym): •
Bioterrorism syndromes. Source: Anonymous WMJ. 2002; 101(2): 13
•
Diagnosis and management of suspected cases of bioterrorism: a pediatric perspective. Author(s): Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030, USA. Source: Patt, Hanoch A Feigin, Ralph D Pediatrics. 2002 April; 109(4): 685-92 1098-4275
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Directions for research in complementary medicine and bioterrorism. Author(s): Samueli Institute for Information Biology in Corona del Mar, Calif, USA. Source: Jonas, Wayne B Altern-Ther-Health-Med. 2002 Mar-April; 8(2): 30-1 1078-6791
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Mitogen therapy for biological warfare/terrorist attacks and viral hemorrhagic fever control. Source: Wimer, B M Cancer-Biother-Radiopharm. 2002 February; 17(1): 19-28 1084-9785
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Straus testifies on CAM and bioterrorism, research progress update released. Source: Muscat, Michael Altern-Ther-Health-Med. 2002 Jan-February; 8(1): 28-30 10786791
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/
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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 bioterrorism; 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 Iodine Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,888,00.html
•
Food and Diet Garlic Alternative names: Allium sativum Source: Integrative Medicine Communications; www.drkoop.com Guava Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,139,00.html
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CHAPTER 3. ALTERNATIVE MEDICINE AND BIOTERRORISM Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to bioterrorism. 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 bioterrorism 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 “bioterrorism” (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 bioterrorism: •
2002: something old, something new. Author(s): Puckett RP. Source: Health Care Food & Nutrition Focus. 2002 January; 18(5): 1-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11794905&dopt=Abstract
•
Agroterrorism. Author(s): Lutz BD, Greenfield RA. Source: J Okla State Med Assoc. 2003 June; 96(6): 259-63. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12858816&dopt=Abstract
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Bioterrorism. Experts call fungus threat poppycock. Author(s): Stone R.
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Source: Science. 2000 October 13; 290(5490): 246. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11183368&dopt=Abstract •
Bioweapons, bioterrorism and biodiversity: potential impacts of biological weapons attacks on agricultural and biological diversity. Author(s): Dudley JP, Woodford MH. Source: Rev Sci Tech. 2002 April; 21(1): 125-37. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11974624&dopt=Abstract
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Curricular and pedagogic questions raised by recent medical education efforts on bioterrorism. Author(s): Heun LR. Source: J Am Osteopath Assoc. 2002 December; 102(12): 662-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12501984&dopt=Abstract
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Directions for research in complementary medicine and bioterrorism. Author(s): Jonas WB. Source: Alternative Therapies in Health and Medicine. 2002 March-April; 8(2): 30-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11890382&dopt=Abstract
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Educating health professionals, first responders, and the community about bioterrorism and weapons of mass destruction. Author(s): Silvagni AJ, Levy LA, McFee RB; NOVA Southeastern University-College of Osteopathic Medicine Task Force on Bioterrorism and Weapons of Mass Destruction. Source: J Am Osteopath Assoc. 2002 September; 102(9): 491-9. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12361182&dopt=Abstract
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Food safety and global security. Author(s): Crawford L. Source: J Vet Med Educ. 2003 Summer; 30(2): 110-1. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12970852&dopt=Abstract
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How to deal with anxiety. Author(s): Lemonick M. Source: Time. 2001 October 29; 158(19): 91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11699136&dopt=Abstract
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Marine natural products and their potential applications as anti-infective agents. Author(s): Donia M, Hamann MT. Source: The Lancet Infectious Diseases. 2003 June; 3(6): 338-48. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12781505&dopt=Abstract
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Plague, policy, saints and terrorists: a historical survey. Author(s): Lippi D, Conti AA. Source: The Journal of Infection. 2002 May; 44(4): 226-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12099728&dopt=Abstract
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Plague: a veterinary perspective. Author(s): Orloski KA, Lathrop SL. Source: J Am Vet Med Assoc. 2003 February 15; 222(4): 444-8. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12597416&dopt=Abstract
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Q fever. Author(s): McQuiston JH, Childs JE, Thompson HA. Source: J Am Vet Med Assoc. 2002 September 15; 221(6): 796-9. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12322916&dopt=Abstract
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Straus testifies on CAM and bioterrorism, research progress update released. Author(s): Muscat M. Source: Alternative Therapies in Health and Medicine. 2002 January-February; 8(1): 2830. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11795619&dopt=Abstract
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Survey of chief livestock officials regarding bioterrorism preparedness in the United States. Author(s): Fitzpatrick AM, Bender JB. Source: J Am Vet Med Assoc. 2000 November 1; 217(9): 1315-7. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11061382&dopt=Abstract
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The current state of veterinary vaccines: is there hope for the future? Author(s): Carter PB. Source: J Vet Med Educ. 2003 Summer; 30(2): 152-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12970862&dopt=Abstract
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Veterinary participation in emergency response plans is vital. Author(s): Lovern C. Source: J Am Vet Med Assoc. 2003 January 1; 222(1): 11. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12523471&dopt=Abstract
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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/
The following is a specific Web list relating to bioterrorism; 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: •
Alternative Therapy Meditation Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,717,00.html
•
Herbs and Supplements Allium Sativum Source: Integrative Medicine Communications; www.drkoop.com Barberry Alternative names: Berberis vulgaris, Berberry Source: Integrative Medicine Communications; www.drkoop.com Berberis Vulgaris Source: Integrative Medicine Communications; www.drkoop.com Berberry Source: Integrative Medicine Communications; www.drkoop.com
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Rosemary Alternative names: Rosmarinus officinalis Source: Healthnotes, Inc.; www.healthnotes.com Verbascum Alternative names: Mullein; Verbascum thapsus L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org
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 BIOTERRORISM Overview In this chapter, we will give you a bibliography on recent dissertations relating to bioterrorism. 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 “bioterrorism” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on bioterrorism, we have not necessarily excluded nonmedical dissertations in this bibliography.
Dissertations on Bioterrorism 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 bioterrorism. 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: •
Identification of Barriers to the Use of Department of Defense Medical Assets in Support of Federal, State, and Local Authorities to Mitigate the Consequences of Domestic Bioterrorism by Barbisch, Donna Feigley; Dha from Medical University of South Carolina - College of Health Professions, 2000, 156 pages http://wwwlib.umi.com/dissertations/fullcit/9969058
•
Terror in the Air: Biological Weapons, Terrorism, and Asymmetric Threats to United States National Security in the Twenty-first Century by Calfano, Brian Robert; Ma from Regent University, 2002, 158 pages http://wwwlib.umi.com/dissertations/fullcit/1410852
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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 BIOTERRORISM 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 “bioterrorism” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on bioterrorism, we have not necessarily excluded nonmedical patents in this bibliography.
Patents on Bioterrorism By performing a patent search focusing on bioterrorism, 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. The following is an 8Adapted
from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.
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example of the type of information that you can expect to obtain from a patent search on bioterrorism: •
Biological warfare agent sensor system employing ruthenium-terminated oligonucleotides complementary to target live agent DNA sequences Inventor(s): Megerle; Clifford A. (Thousand Oaks, CA) Assignee(s): Raytheon Company (El Segundo, CA) Patent Number: 5,874,046 Date filed: October 30, 1996 Abstract: A sensor system and method are provided that are capable of the real-time detection of target live microorganisms, such as biological warfare agents. The sensor system includes a highly-sensitive, highly-selective sensor cell that comprises a singlestranded oligonucleic acid sequence that is complementary to a portion of the DNA of a target live microorganism, the oligonucleic acid having been modified with the covalent attachment of electron donor and acceptor moieties. In the presence of the targeted microorganism, hybridization occurs between the modified oligonucleic acid and the microorganism's DNA, such that the electron conductance between the electron transfer moieties greatly increases, thereby providing a means of detecting the presence of the target live microorganism. Aside from the sensor cell, the sensor system also includes an inlet port in the sensor cell wall by which to introduce a sample from the fluid environment into the sensor cell; a cell wall disrupter to release the nucleic acid of the fluid sample into the sensor cell; an electron transfer rate measuring system to gauge the electron transfer rate between the electron transfer moieties of the modified oligonucleic acid; a power source; a microcontroller to analyze the measured electron transfer rate for evidence of hybridization; and a communication system for relaying information regarding the presence or absence of the target live microorganism to the user of the sensor system. It is contemplated that the sensor system, exclusive of a battery and pump pack, will be only slightly larger than a pack of cigarettes and light enough to be comfortably worn and carried by personnel. Excerpt(s): The present invention relates generally to sensors for specific nucleic acid sequences. More particularly, the present invention relates to a real-time sensor system for the detection of target live agent deoxyribonucleic acid, such as would be useful in the detection of biological warfare agents. The detection of bacteria and viruses that pose a threat to human populations is an invaluable capability. With early detection of a harmful microorganism, persons located in the vicinity of an infected area may be notified so that they might take necessary precautions for their protection, such as fleeing to a safe haven, consuming appropriate antibiotics, or donning protective gear. While the proliferation of harmful air-borne or water-borne microorganisms in an area might be a natural occurrence or, at least, an unintended result of human interference (e.g., the contamination of bodies of water by raw sewage), the potential for rogue governments and terrorists to employ biological warfare agents (BWA's) against troops and civilian populations is an increasing concern that makes the need for sensor systems for harmful microorganisms all the more urgent. The sheer variety of BWA's that might be employed requires that a sensor system should be highly sensitive and highly selective with regard to target live agents. Examples of potential BWA's include anthrax, typhoid fever, smallpox, and valley fever. Given the speed with which BWA's might adversely affect a population, it would be highly desirable that the sensor system offer real-time detection.
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Web site: http://www.delphion.com/details?pn=US05874046__ •
Biological warfare mask Inventor(s): Hutchinson; Richard W. (Whiteford, MD), Jones; Van Roger (Havre de Grace, MD) Assignee(s): The United States of America as represented by the Secretary of the Army (Washington, DC) Patent Number: 5,957,131 Date filed: July 31, 1997 Abstract: A respiratory filtration mask that offers protection from hazardous particulate aerosols, vapors, and the like and which is particularly useful for providing respiratory protection from biological warfare agents. The mask provides a military level of protection against biological agents in a half mask configuration, thereby avoiding the disadvantages of a full face mask such as restricted vision, heat buildup, weight, and feeling of enclosure. The mask has a housing enclosing a filter compartment and a gas transfer compartment and an air inlet which allows unfiltered air into the filter compartment. There is a filter medium in the filter compartment which removes contaminants from the unfiltered air and provides filtered air substantially free of contaminants to the gas transfer compartment. A one way air valve regulates air flow between the filter compartment and the gas transfer compartment. Both a mouthpiece and a nasal insert extend outwardly from the housing and allow for the inhalation of filtered air from the gas transfer compartment and the receipt of exhaled air from the mouth and nose of a user. An air exit valve regulates the removal of exhaled air from the gas transfer compartment. Excerpt(s): The present invention pertains to respiratory masks, and more specifically relates to respiratory filtration masks that offer protection from hazardous particulate aerosols, vapors, and the like. Specifically, the invention addresses respiratory protection from biological warfare agents in a half-mask configuration. Respiratory protection masks have been used by the military and police forces as protection against the inhalation of hazardous particulate matter, such as smoke and toxic gas. In the field of respiratory protection, one of the factors by which the level of protection provided by a mask is measured is its fit. The standard United States military mask achieves a fit providing adequate protection against biological as well as chemical warfare agents. However, these military masks seal around the periphery of the face and are referred to as "full face masks". Although such masks provide a high level of protection, they also burden the user to a significant degree. For example, vision is restricted and the use of sights and lenses is made difficult. In addition, full face masks create a heat and weight burden for the user and a feeling of enclosure. Commercial versions of respiratory protection masks, used to protect the wearer from paint fumes, particulate, and other vapors, are "half masks" that seal around the wearer's nose and mouth. The fit of half masks is generally regarded as inadequate to meet the military standard for protection against biological agents. Commercial evacuation or escape masks utilize a snorkel type mouthpiece and a nose clamp to provide protection while the wearer leaves an area of hazardous vapors. Despite these developments in respiratory protection masks, there has been no protection made which meets the military standard for protection against biological agents in a half-mask form and provides for respiration through the nose as well as the mouth. Web site: http://www.delphion.com/details?pn=US05957131__
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Patent Applications on Bioterrorism 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 bioterrorism: •
Chemical and biological warfare decontaminating solution using bleach activators Inventor(s): Brown, Jerry S.; (Woodford, VA) Correspondence: James B. Bechtel; Office of Counsel (Patents) Code XDC1; Naval Surface Warfare Center; Dahlgren Division; Dahlgren; VA; 22448-5100; US Patent Application Number: 20030045767 Date filed: February 1, 2002 Abstract: A chemical and biological warfare agent decontaminating solution having a peroxygen compound and bleach activator. The peroxygen compound and bleach activator are mixed in a surfactant system to generate a peroxycarboylic acid in-situ to detoxify warfare agents. Excerpt(s): The invention described herein may be manufactured and used by or for the government of the United States of America for governmental purposes without the payment of any royalties thereon or therefor. The present invention relates to a chemical warfare agent decontamination solution. More particularly, the decontamination solution includes a peroxygen component and bleach activator to generate a peroxycarboxylic acid in-situ. Most particularly, the decontaminating solution contains a microemulsion for applying a formed peroxycarboxylic acid. The decontaminating solution is useful in neutralizing chemical and biological warfare agents. Methods for decontamination of chemical warfare agents, which include a variety of organophosphorus and organosulfur compounds, are known in the art. However, these known methods use compositions which have certain undesirable properties, including corrosiveness, flammability and toxicity. For example, hypochlorite formulations are very corrosive and toxic. Additionally, application of the hypochlorite decontaminant often requires substantial scrubbing for removal and destruction of the chemical warfare agent, a procedure which limits its use. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Conductimetric biosensor device, method and system Inventor(s): Alocilja, Evangelyn C.; (East Lansing, MI), Muhammad-Tahir, Zarini; (East Lansing, MI) Correspondence: MCLEOD & MOYNE, P.C.; 2190 COMMONS PARKWAY; OKEMOS; MI; 48864; US Patent Application Number: 20030153094 Date filed: February 13, 2002 Abstract: A multi-array membrane strip biosensor device (10, 20) using a fluid mobile conductive polymer as reporter is described. The biosensor device (20) is designed to detect multiple analytes at low concentrations in near real-time with an electronic data
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This has been a common practice outside the United States prior to December 2000.
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collection system. The biosensor device can be small. The device can be used to detect pathogens, proteins, and other biological materials of interest in food, water, and environmental samples. The device can also be used for on-site diagnosis and against potential bioterrorism. Potential users include food processing plants, meat packaging facilities, fruit and vegetable packers, restaurants, food and water safety inspectors, food wholesalers and retailers, farms, homes, medical profession, import border crossing personnel, and the police force, military, space habitation and national security. Excerpt(s): Not Applicable. The present invention relates to a biosensor device which is conductimetric, wherein conductance or resistance is measured. In particular, the present invention relates to a biosensor device which uses a fluid mobile electrically conductive polymer bound to or as a moiety of a capture reagent (such as an antibody) which captures an analyte in a fluid sample and then migrates to a capture zone where the complexed analyte is captured by another capture reagent (such as a monoclonal or polyclonal antibody) bound to (immobilized on) a substrate. The conductance or resistance is then measured. Bacteria are particularly detected by the biosensor device. Multiple detections can be accomplished simultaneously in different parallel arrays on the biosensor device. Assays based upon conductivity or resistance are well known. Illustrative patents are U.S. Pat. Nos. 5,312,762 to Guiseppi-Elie and 5,670,031 to Hintsche et al. Illustrative published art is Kim et al., Biosensor & Bioelectrics 14 907, 915 (published in February of 2000). In this art, conductive polymers are used as sensors of analytes ('762 patent and Kim et al) and microsized test devices (Hirtsche et al) are used to detect an analyte. In Kim et al, a conductive polymer is bonded to conductive gold particles, which also serve as a visually detectable reagent, for a conductimetric assay. None of the prior art uses a capture reagent labeled with a conductive polymer in a sandwich type assay in the absence of conductive metal particles. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Decontamination of surface exposed to biological warfare agents Inventor(s): Marsden, James L.; (Manhattan, KS) Correspondence: Mark Rogers; Speed & Rogers; 1701 Centerview; Suite 125; Little Rock; AR; 72211; US Patent Application Number: 20030165403 Date filed: March 12, 2003 Abstract: A system is disclosed in which a surface exposed to, suspected of being exposed to, or in imminent danger of being exposed to a biological warfare agent is treated with an effective amount of a quaternary ammonium compound to inactivate the biological warfare agent. The quaternary ammonium compound is preferably selected from the group consisting of an alkylpyridinium salt, a tetra-alkyl ammonium salt, and an alkylalicyclic ammonium salt. The quaternary ammonium salt is more preferably an alkylpyridinium salt and is most preferably cetylpyridinium chloride ("CPC"). The compound is preferably present in solution in a weight percent that is substantially within a range of from approximately 0.5% to approximately 5.0% and is more preferably present in solution in a weight percent of approximately 1%. The compound may be applied as a mist, spray, or fog. Air or other gases that have been exposed to or that are suspected of being exposed to a biological warfare agent may also be treated by passing the air or gas through a filter impregnated with an effective amount of a quaternary ammonium compound to inactivate the biological warfare agent.
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Excerpt(s): This invention relates to a system for decontaminating surfaces exposed to biological warfare agents, and more particularly, to a system for treating such surfaces with a compound that inactivates a broad spectrum of biological warfare agents. 5) treatment of infected personnel after an attack. Each of these steps or activities serves an important function and offers advantages. Still, none of these steps accomplishes a thorough decontamination of environments, equipment, personnel, animals, or food in the event of an attack. Decontamination is an important part of reducing the impact of an attack using a biological warfare agent. For example, Bacillus anthracis is a sporeforming human and animal pathogen that causes anthrax. This organism is feared as a biological warfare agent and poses considerable difficulty in decontamination because of its sporeforming nature. Unless effective decontamination steps are taken, this organism can withstand high heat, UV light, chemical disinfectants, and drying conditions to persist in the environment for extended periods of time. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Effective monitoring system for anthrax smallpox, or other pathogens Inventor(s): Byerly, Joseph; (Pebble Beach, CA), Lu, Peter S.; (Mountain View, CA), Sherlock, Thomas M.; (Los Altos, CA) Correspondence: David Garman; 772 Lucerne Drive; Sunnyvale; CA; 94085; US Patent Application Number: 20030153021 Date filed: December 6, 2002 Abstract: A device and method for detecting anthrax or other pathogens are disclosed. Individual self-contained monitoring devices of a monitoring system can be portable or stationary (e.g. installed in air ducts or plumbing of buildings) and can be part of a network of devices. Monitoring devices may be used for the detection of a variety of airborne or surface pathogens, including but not limited to anthrax, smallpox, and Salmonella. Bioamplification-coupled proteomics assays provide rapid and reliable detection of pathogens, with self-checking capabilities reducing or eliminating false positives and false negatives. Sample preservation capability allows pathogen samples to be preserved after detection for further testing. The device of the invention can be remotely operated by minimally trained technicians or security personnel. The pathogen monitoring device of the invention provides a more compact, accurate, rapid, and costeffective alternative to other anthrax detectors, and an effective weapon against bioterrorism. Excerpt(s): The rapid detection of microorganisms, particularly highly virulent pathogens, is required for the timely treatment of serious infections. Contamination of air or water by pathogenic microorganisms can occur naturally, can be the result of unintended human interference, or can occur as a result of intentional use of biological warfare agents against military and civilian populations. Because of the ability of pathogens to disseminate and infect human populations rapidly, a detection system requires speed, versatility and, preferably, portability. Early detection and identification of pathogens in patients allows a health care worker to diagnose and appropriately treat a patient. Remote sampling and detection of microorganisms can limit exposure to biological agents through the identification of contaminated areas. These areas can then be quarantined and decontaminated by appropriately trained individuals. However, in spite of the need for rapid detection of pathogens, detection equipment in current use has significant shortcomings. Manipulating and interpreting pathogen detection devices in the field is a hazardous duty, and can be made more difficult by cumbersome
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protective clothing worn by health care or military personnel. Thus, remote and automated sensing is required to address both safety and efficiency concerns. To be truly effective as a monitoring system, it also must be widely distributed, such that detection of bioterrorism induced or natural outbreaks can be rapidly identified and controlled. In turn, the need for a widespread early warning network demands that any detection device be accurate, automated and relatively inexpensive. There are several methods commonly used to detect pathogens in collected samples, but not all of these methods are rapid, readily automatable or of low cost. These include (i) amplification of pathogen-specific nucleic acid sequences, including methods for amplifying pathogenspecific nucleic acid sequences requiring numerous time-consuming steps that are difficult to automate and often produce false positives or false negatives; (ii) culture of pathogens on appropriate growth media, followed by isolation and either timeconsuming biochemical or histological assays; (iii) mass spectrometer-based detection of pathogen-specific components, in which each detection unit is expensive to produce; and (iv) serological-based assays, which have limited sample size and can only detect pathogens in an infected individual. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Method and apparatus for control of chemical or biological warfare agents Inventor(s): Jones, David A.; (Manhattan, KS), Lanz, Bret E.; (Manhattan, KS), Mulukutla, Ravichandra S.; (Manhattan, KS), Rhule, Jeffrey T.; (Franklin, OH), Sigel, Michael W.; (Marion, KS) Correspondence: HOVEY WILLIAMS LLP; 2405 GRAND BLVD., SUITE 400; KANSAS CITY; MO; 64108; US Patent Application Number: 20030215355 Date filed: May 14, 2002 Abstract: Metal oxide area decontamination apparatus (10) is provided which is designed for rapid, emergency situation decontamination of areas contaminated with potentially harmful or lethal chemical and/or biological warfare agents or other hazardous substances. The apparatus (10) preferably includes a pressurizable metallic container (12) equipped with a valve-type delivery nozzle assembly (16), so that upon a manipulation of the assembly (16), a spray of metal oxide and/or metal hydroxide particles is generated; the particles are selected and sized in order to destroy or chemisorb the contaminating agents. The preferred decontamination agent is MgO aggregated to an average aggregate size of from about 50 nm-10 microns. The particles are mixed with a gaseous or liquid propellant within the container (12) allowing rapid and thorough particle cleanout when the nozzle assembly (16) is actuated. Excerpt(s): The present invention is broadly concerned with apparatus and methods for area decontamination and is of particular utility for emergency situations where a given area must be at least partially and rapidly decontaminated. More particularly, the invention is concerned with such devices and methods which include a container that is or can be pressurized containing sprayable mixture therein including reactive metal oxide and/or metal hydroxide particles (e.g., MgO) and having a selectively operable spray nozzle assembly coupled with the container. The invention finds particular utility for destroying or chemisorbing a variety of chemical, biological and/or hazardous agents, especially chemical/biological warfare agents. Governments around the world have become increasingly concerned about the effects of chemical and/or biological warfare agents and other types of hazardous substances, particularly in light of the
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recent rise in terrorism. The potentially catastrophic results which could ensue in high density population centers subjected to such agents are well known to disaster experts. While a number of proposals have been adopted for dealing with warfare agents and similar substances, in general these deal with massive decontamination or cleanup efforts. However, it is contemplated that, in many instances, there will be a need for immediate, at least partial decontamination over restricted areas in order to minimize the risk to affected populations. There are currently two general types of decontamination methods for biological agents, namely chemical disinfection and physical decontamination. Chemical disinfectants such as hypochlorite solutions are useful but are corrosive to most metals and fabrics, and to human skin. Liquid-like foam disinfectants have also been used, and generally require water and pressurized gases for efficient application. Physical decontamination usually involves dry heat up to 160.degree. C. for 2 hours or steam or super-heated steam for about 20 minutes. Sometimes UV light can be used effectively, but it is difficult to implement in actual practice. Techniques used for decontamination of areas subjected to chemical warfare agents are more varied, and depend principally upon the nature of the agent in question. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Method and system for early detection of infectious diseases or symptoms of bioterrorism attacks Inventor(s): Mault, James R.; (Evergreen, CO) Correspondence: GIFFORD, KRASS, GROH, SPRINKLE; ANDERSON & CITKOWSKI, PC; 280 N OLD WOODARD AVE; SUITE 400; BIRMINGHAM; MI; 48009; US Patent Application Number: 20030129578 Date filed: June 4, 2002 Abstract: A method and system for the early detection of infectious diseases, or the symptoms of bioterrorism attacks in a population, includes a plurality of local input devices located with a plurality of individuals geographically dispersed with a population, the local input devices being capable of recording information relating to certain physiological conditions of the respective individuals, and transmitting the information to a central computer via a communication network; and a central computer capable of receiving the transmitted information, of statistically analyzing the information based on a comparison of such information to information transmitted at previous times, to detect patterns of infectious diseases or symptoms of terrorism attacks, and of utilizing the statistical analysis to produce outputs relating to actions to be taken. Excerpt(s): The present application is based on Provisional Application No. 60/344,493, filed Oct. 26, 2001, the contents of which are incorporated herein by reference, and the priority date of which application is claimed herein. The present invention relates to a method, and also a system, for the early detection of infectious diseases, or the symptoms of bioterrorism attacks, in a population. The difficulties encountered in recognizing the existence of a bioterrorism attack, highlighted by the actual distribution of anthrax spores through the U.S. mails, has established the importance of the early detection of infectious diseases and the need for a system for the immediate reporting of symptoms to a central analysis center to allow patterns of infection to be recognized. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Method of detecting biological weapon use by monitoring a monolayer Inventor(s): O'Brien, Robert Neville; (Victoria, CA) Correspondence: Robert N. O'Brien; 2614 Queenswood Dr.; Victoria; BC; V8N 1X5; CA Patent Application Number: 20030203424 Date filed: April 30, 2002 Abstract: For a method of detecting biological weapon use, the disclosure suggests to apply known technology relating to interfacial films of monolayer-forming substances having molecules that when spread at an air/water interface will immerse into the water a hydrophilic terminal group for each molecule, with a long-chain carboncontaining hydrophobic group extending vertically upward away from the water. Such monolayers manifest monitorable properties which are susceptible using known instrumentation means to measurement of changes induced by biological contaminants thus making it possible to determine by appropriate testing what a bioattack signature change would be. Given siting of a monolayer coated aqueous body in a reservoir where a biological attack may occur, monitoring the monolayer properties for the signature change can detect whether and when such an attack does occur. One example of enacting the method involves a lake-sized water reservoir coated by a mixed monolayer which changes respecting color absorbance when bacteria and a biocide in the monolayer interact. Another example uses an instrumented film balance, ie., Langmuir trough as the reservoir, which is small enough for siting anywhere needed, eg., inside postal stations or other important buildings. Excerpt(s): This invention relates to a method of detecting clandestine release at an attacked site of pathogenic bacteria used as a biological weapon. As described hereinafter, the method of detecting such an attack will involve a process of monitoring properties of an interfacial film known in surface chemistry as a `monomolecular film` or `monolayer`, which is proposed to be formed on the surface of an aqueous body located anywhere deemed likely to be targeted for intentional contamination by release of pathogenic bacteria. What the monitoring specifically looks for shall be termed, in lexicography of the inventor, a `bioattack signature change`, meaning a technologically insensible change in hereinafter discussed monitorable monolayer properties that can be inferred with likelihood of correctness to occur as a result of intrusion of a non-naturally occuring quantity of pathogenic bacteria to the site of the aqueous body coated by the monolayer. Need for a method of detecting clandestine releases of pathogenic bacteria is especially apparent from the several anthrax fatalities that occurred in the United States late in 2001, establishing the dreadful fact that unauthorized individuals can somehow acquire sufficient quantities of anthrax (Baccillus anthracis) to produce lethal biological weapons. Adoption of a universal anthrax immunization program like that instituted for military personnel during the Gulf War but terminated in 1998 seems unlikely thus far, and defense of civilian facilities against biological attacks is difficult because actual acts of releasing pathogenic bacteria will more often than not escape being witnessed directly. Obtaining verification that such an attack has occurred has tended to be postponed until after undue passage of time that increases lethality of infection. It is essential to administer antibiotics and anti-toxins to victims as soon as possible after the bacterial exposure event infecting them. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Non-lethal chemical weapons Inventor(s): Bahary, William S.; (Pearl River, NY) Correspondence: DR. WILLIAM S. BAHARY; 291 N. MIDDLETOWN RD; PEARL RIVER; NY; 10965; US Patent Application Number: 20030170180 Date filed: November 12, 2002 Abstract: The invention relates to compositions of non-lethal chemical weapons for riot and crowd control. The compositions can also be used to clear areas and facilities for extended periods without collateral damage. Specifically, this invention discloses "dial an effect" non-lethal weapons for crowd control, from moderate to near lethal strength. The composition contains three unique active ingredients comprising an odoriferous substance, a hot substance, and a tear gas agent, A method is disclosed to prepare the compositions with solvents, carriers, pressurizers, and optional ingredients, as well as a method to apply them. Excerpt(s): The invention relates to non-lethal weapons. Specifically, the purpose of the invention is to disclose compositions and methods of using the compositions for crowd control. Further, the objective is to ward off enemies and specifically terrorists by making them move out of locations in proximity to civilians, and of their hiding places. The compositions range from the non-lethal to near lethal ones, with the non-lethal compositions sufficiently objectionable to make the whereabout places of objectionable subjects uninhabitable. In the 21.sup.st century, combat with terrorists is of prime concern. Because of the terrorists elusive and destructive towards the military as well as civilians, the availability of an array of non-lethal weapons is an important option in combination with lethal weapons. Terrorists are necrophiles and appear to be instinctively compelled to death and destruction. Many countries and nations experience serious problems with terrorists. For example, in Afghanistan, the terrorists can hide in caves and tunnels to avoid detection. In the 18.sup.th century, the British could not conquer the Afghani's. More recently, in the 20.sup.th century, the Russians could not conquer Afghanistan. After many years of fighting, the Russians were forced to withdraw from their positions in Afghanistan. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Public health surveillance system Inventor(s): Brown, Stephen J.; (Woodside, CA), Cherry, Julie C.; (Milpitas, CA), Clapp, Geoffrey J.; (Los Altos, CA), Gunabushanam, Gowthaman; (Hyderabad, IN) Correspondence: BLACK LOWE & GRAHAM; 816 SECOND AVE.; SEATTLE; WA; 98104; US Patent Application Number: 20030163351 Date filed: October 23, 2002 Abstract: A networked system for identifying whether an individual or a plurality of individuals has been exposed to a disease-causing infectious agent associated with a bioterrorism event. Excerpt(s): This application is a Continuation-In-Part of application U.S. Ser. No. 10/233,296 filed Aug. 30, 2002 which is a Continuation-In-Part of application U.S. Ser. No. 09/713,922 filed Nov. 15, 2000 which is a Continuation-In-Part of application U.S.
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Ser. No. 08/975,774 filed Nov. 21, 1997, herein incorporated by reference. This invention relates generally to remote health monitoring systems, as applied to the field of public health surveillance. In particular, it relates to a multi-user remote health monitoring system that is capable of reliably identifying healthcare providers and collecting data from frontline healthcare providers, laboratory and hospital information systems, and individual patients in a number of ways, with a view to aid in the field of public health. The system can also be used to query both healthcare providers, and the patients regarding specifics pertaining to the health of the patients, and for patient tracking, monitoring, and the collection of patient data. Critical gaps exist in our nation's ability to anticipate, detect and respond to epidemics that may be `natural` or that which may be attributed to bioterrorism due to ineffective disease surveillance and fragmented information systems. Federal, state, and local agencies urgently need (i) surveillance capabilities to accelerate time-to-detection and monitor preparedness at the local level, and (ii) integrated information solutions that enable rapid statistical analyses and facilitate investigations. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Safe mailbox Inventor(s): Wang, Jian Chun; (North Potomac, MD), Wang, Xu Cong; (North Potomac, MD) Correspondence: JIAN CHUN WANG; 14001 Saddle River Dr.; North Potomac; MD; 20878; US Patent Application Number: 20030103866 Date filed: December 4, 2001 Abstract: Biological weapons are any infectious agent such as a bacteria or virus when used intentionally to inflict harm upon others. This definition is often expanded to include biologically-derived toxins and poisons. Biological warfare agents include both living microorganisms (bacteria, protozoa, rickettsia, viruses, and fungi), and toxins (chemicals) produced by microorganisms, plants, or animals. Ultraviolet (UV) light, which at select wavelengths of energy, is immensely germicidal. Chemicals also denature proteins and nucleic acids of all bacterial and virus. Set UV light and chemicals as disinfection's tool which against bacterial and viruses in inside of Mailbox to secure mails and posters which delivered by outside will be disinfected. The Safe Mailbox is a very important tool that protect innocent people from bioterrorism at individual family level. Excerpt(s): The threat of bioterrorism has heightened over the past few years. Biological weapons are any infectious agent such as a bacteria or virus when used intentionally to inflict harm upon others. This definition is often expanded to include biologicallyderived toxins and poisons. Biological warfare agents include both living microorganisms (bacteria, protozoa, rickettsia, viruses, and fungi), and toxins (chemicals) produced by microorganisms, plants, or animals. It is became very important issues that protect innocent people from bioterrorism. At individual family level, the mailbox is a most danger place to keep the mail or poster which been contaminated by the bacterial or virus from outside of family by post office or commercial companies. Ultraviolet (UV) light, which at select wavelengths of energy, is immensely germicidal. It can kill all bacterial and viral particles. Disinfection refers to the reduction of pathogens (disease causing organisms) while sanitation refers to the quality of cleanliness. Reducing the load of pathogens in the environment of your flock
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will decrease the risk of disease. Disinfectants are chemical agents that can kill pathogens on contact. The use of UV disinfection tool and chemical disinfection tools to make a safer mailbox carrier become more important way to protect individual family from bioterrorism attack in the future. Ultraviolet light is the portion of the spectrum with wavelengths of 100-400 nm. The UV spectrum is further divided into three different types according to wavelength. UVA extends from 320 to 400 nm. UVB extends from 290 to 320 nm, whereas UVC from 100 to 290 nm. UV light damages living cells by directly and indirectly altering nucleic acids, particularly DNA. It cross-link DNA forming pyrimidine. The damage effects of UV on nucleic acids include photodimerizations between adjacent pyrimidine bases, photohydration of cytosine, and, at much lower frequencies, inter- and intra-strand cross-links, protein-DNA crosslinks, and rare base adducts. Indirect effects result when reactive oxygen species (ROS) are generated. They also react with DNA, damaging bases, breaking strands, and crosslinking DNA and proteins. The wavelength dependence for the induction of direct DNA damage by UV light corresponds to the DNA absorbance spectrum. DNA absorbance is maximal and fairly constant across the UVC (100-290 nm) range, then falls through more than three orders of magnitude in the UVB (290-320 nm) and reaches near-negligible levels in the UVA. UVB is responsible for both direct and indirect DNA damage, while UVA produces only indirect damage in microorganisms exposed to sunlight. UVC has most strong effect for directly damaging DNA. Chemicals also denature proteins and nucleic acids of all bacterial and virus. Some are gaseous (e.g. ethylene oxide) and some are effective as aqueous solutions (e.g. bleach). Some may be used in both forms (e.g. formaldehyde). They inactivate vegetative bacteria, fungi, lipid and non-lipid viruses, HBV, TB, Coxiella burnetii, and bacterial spores. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
System for preventing unauthorized access to products in retail system Inventor(s): Razumov, Sergey N.; (Moscow, RU) Correspondence: McDERMOTT, WILL & EMERY; 600 13th Street, N.W.; Washington; DC; 20005-3096; US Patent Application Number: 20020095353 Date filed: January 16, 2002 Abstract: A novel system for preventing unauthorized access to products is provided in a retail system in order to prevent exposure of the products to contamination caused by bioterrorism. The system for preventing unauthorized access comprises an orderprocessing system for receiving a purchase order from a customer, and a tracking system for tracking the ordered product until the product is received by the customer. In particular, the system for preventing unauthorized access is suitable for preventing exposure of food products handled in a retail system to contamination by unwanted or dangerous substances. Excerpt(s): The present application is a continuation-in-part of the U.S. patent application No. b 09/745,420 filed on Dec. 26, 2000, entitled "RETAIL SYSTEM WITH PURCHASE ORDERING" and incorporated herewith by reference. The present invention relates to retail systems, and more specifically, to prevention of unauthorized access to products in a retail system having a mechanism that enables customers to place a purchase order. In the aftermath of recent events relating to terrorists' activity, there is increasing public concern over bioterrorism and its impact on the food supply. All segments of the food-related industry, including production, processing, handling,
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distribution and retail sectors, as well as suppliers to the industry such as companies supplying packaging materials, chemicals, etc. are affected by the increased threat. 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 bioterrorism, 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 “bioterrorism” (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 bioterrorism. You can also use this procedure to view pending patent applications concerning bioterrorism. 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 BIOTERRORISM Overview This chapter provides bibliographic book references relating to bioterrorism. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on bioterrorism 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 “bioterrorism” (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 bioterrorism: •
Preventing Emerging Infectious Diseases: A Strategy for the 21st Century Source: Atlanta, GA: U.S. Department of Health and Human Services. Centers for Disease Control and Prevention. 1998. 75 p. Contact: Available from Office of Health Communication, National Center for Infectious Diseases, Centers for Disease Control and Prevention. Mailstop C-14, 1600 Clifton Road, Atlanta, GA 30333. Fax (404) 639-4194. PRICE: Single copy free. Summary: This document describes the plan of the Centers for Disease Control and Prevention (CDC) for combating infectious diseases over the next 5 years. The plan is organized under four goals: surveillance and response, applied research, infrastructure and training, and prevention and control. For goal one, objectives call for strengthening surveillance and response in the United States and internationally, as well as improving methods for gathering and evaluating surveillance data on infectious diseases. They also emphasize that surveillance data are critical not only for detecting outbreaks, but also
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for improving public health practice and medical treatment. For goal two, objectives include improving tools for identifying and understanding emerging infectious diseases; determining risk factors for infectious diseases, as well as infectious risk factors for chronic diseases; and conducting research to develop and evaluate prevention and control strategies. The public health infrastructure is the underlying foundation that supports the planning, delivery, and evaluation of public health activities and practices. For goal three, objectives and activities focus on enhancing epidemiologic and laboratory capacity in the United States and internationally. In the United States, this requires CDC to improve its ability to communicate electronically with its partners and to strengthen its capacity to serve as a reference center for diagnosing infectious diseases and testing drug resistance. Objectives and activities also address the need to enhance the Nation's capacity to respond to outbreaks, including those caused by bioterrorism, and to provide training opportunities to ensure that today's workers and future generations are able to respond to emerging threats. All of CDC's efforts are ultimately directed toward the fourth goal: prevention and control. CDC will work with many partners to implement, support, and evaluate disease prevention in the United States and internationally. As part of this effort, CDC will conduct demonstration programs and will develop, evaluate, and promote strategies to help health care providers and others change behaviors that facilitate disease transmission. Target areas for all four goals include developing and using vaccines and preventing emerging infectious diseases, antimicrobial resistance, food-and waterborne diseases, vectorborne and zoonotic diseases, diseases transmitted through blood transfusions or products, chronic diseases caused by infectious agents, diseases of people with impaired host defenses, diseases of pregnant women and newborns, and diseases of travelers, immigrants, and refugees. The document includes specific strategies in each goal area, anticipated outcomes, and the immediate past history (1994-1997) in these areas. Also included are references, tables, figures, sidebars (in boxes), a list of acronyms, and a subject index. 45 boxes. 94 references. •
Strengthening the public health system for a healthier future Source: Washington, DC: Grantmakers in Health. 2003. 48 pp. Contact: Available from Grantmakers In Health, 1100 Connecticut Avenue, N.W., Suite 1200, Washington, DC 20036. Telephone: (202) 452-8331 / fax: (202) 452-8340 / e-mail:
[email protected] / Web site: http://www.gih.org. Available from the Web site at no charge. Summary: This issue brief synthesizes key points from an expert dialog held November 6, 2002 to examine the status of national and local efforts to maintain the public health system and prepare for the possibility of bioterrorism. Topics include an examination of the role and weaknesses of the nation's public health infrastructure; organizational, workforce and competency capacity; information and data systems; and emergency preparedness in the public health infrastructure. Sections on conclusions and references are also included.
Book Summaries: Online Booksellers Commercial Internet-based booksellers, such as Amazon.com and Barnes&Noble.com, offer summaries which have been supplied by each title’s publisher. Some summaries also include customer reviews. Your local bookseller may have access to in-house and commercial databases that index all published books (e.g. Books in Print®). IMPORTANT
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NOTE: Online booksellers typically produce search results for medical and non-medical books. When searching for “bioterrorism” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “bioterrorism” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “bioterrorism” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •
A Plague upon Humanity : The Secret Genocide of Axis Japan's Germ Warfare Operation by Daniel Barenblatt (Author) (2004); ISBN: 0060186259; http://www.amazon.com/exec/obidos/ASIN/0060186259/icongroupinterna
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Battling Bioterrorism: Why Time Information-Sharing Between Local, State and Federal Governments Is the Key to Protecting Public Health: Hear by United States (2003); ISBN: 0160695155; http://www.amazon.com/exec/obidos/ASIN/0160695155/icongroupinterna
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Biological Weapons Defense: Principles and Mechanisms for Infectious Diseases Counter-Bioterrorism (Infectious Disease) by Luther, Md. Lindler (Editor), et al (2004); ISBN: 1588291847; http://www.amazon.com/exec/obidos/ASIN/1588291847/icongroupinterna
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Bioterrorism by Prentice Hall (2003); ISBN: 0131458701; http://www.amazon.com/exec/obidos/ASIN/0131458701/icongroupinterna
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Bioterrorism : Psychological and Public Health Interventions by Robert J. Ursano (Editor), et al (2004); ISBN: 0521814723; http://www.amazon.com/exec/obidos/ASIN/0521814723/icongroupinterna
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Bioterrorism and Biocrimes: The Illicit Use of Biological Agents Since 1900 by W. Seth Carus, et al (2002); ISBN: 1410100235; http://www.amazon.com/exec/obidos/ASIN/1410100235/icongroupinterna
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Bioterrorism and Biology of Botulism Clostridium Botulinum: Index of New Information and Guide-Book for Consumers, Reference and Research by John C., Dr Bartone (2001); ISBN: 0788327100; http://www.amazon.com/exec/obidos/ASIN/0788327100/icongroupinterna
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Bioterrorism and Political Violence: Web Resources by M. Sandra Wood (Editor), Andrew Sandra Easton (2002); ISBN: 0789019647; http://www.amazon.com/exec/obidos/ASIN/0789019647/icongroupinterna
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Bioterrorism and Proposals to Combat Bioterrorism: Hearing Before the Committee on Energy and Commerce, U.S. House of Representatives by W. J. Tauzin (2003); ISBN: 075672872X; http://www.amazon.com/exec/obidos/ASIN/075672872X/icongroupinterna
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Bioterrorism and Public Health: An Internet Resource Guide by John G., M.D. Bartlett (Editor), et al (2002); ISBN: 1563634279; http://www.amazon.com/exec/obidos/ASIN/1563634279/icongroupinterna
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Bioterrorism Anthrax Manual and CD: For Healthcare Workers and Public Officers (Allied Health, Nurses, Doctors, Public Health workers, EMS workers, other emergency, safety, fire, police, and disaster planning and response personnel) and the Public, Detailed Introduction on the Infection and Treatment by Daniel Farb (2003); ISBN: 1932634738; http://www.amazon.com/exec/obidos/ASIN/1932634738/icongroupinterna
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Bioterrorism Botulinum Manual and CD: For Healthcare Workers and Public Officers (Allied Health, Nurses, Doctors, Public Health workers, EMS workers, other
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emergency, safety, fire, police, and disaster planning and response personnel) and the Public, Detailed Introduction on Infection, Toxin, and Treatment by Daniel Farb (2003); ISBN: 1932634746; http://www.amazon.com/exec/obidos/ASIN/1932634746/icongroupinterna •
Bioterrorism Certificate Program Manual and CD, For Healthcare Workers and Public Officers (Allied Health, Nurses, Doctors, Public Health workers, EMS workers, other emergency, safety, fire, police, and disaster planning and response personnel) and the Public, Detailed Introduction to the Most Dangerous Forms of Bioterrorism, Including Anthrax, Botulinum, Hemorrhagic Viruses, Plague, Radiation, Smallpox, and Tularemia by Daniel Farb, Bruce Gordon (2003); ISBN: 1932634606; http://www.amazon.com/exec/obidos/ASIN/1932634606/icongroupinterna
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Bioterrorism Hemorrhagic Viruses Manual and CD: For Healthcare Workers and Public Officers (Allied Health, Nurses, Doctors, Public Health workers, EMS workers, other emergency, safety, fire, police, and disaster planning and response personnel) and the Public, Detailed Introduction on Infection and Treatment by Daniel Farb (2003); ISBN: 1932634754; http://www.amazon.com/exec/obidos/ASIN/1932634754/icongroupinterna
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Bioterrorism of Plague Yersenia Infections: Index of New Information and GuideBook for Consumers, Reference and Research by John C., Dr Bartone (2001); ISBN: 0788326317; http://www.amazon.com/exec/obidos/ASIN/0788326317/icongroupinterna
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Bioterrorism Plague Manual and CD: For Healthcare Workers and Public Officers (Allied Health, Nurses, Doctors, Public Health workers, EMS workers, other emergency, safety, fire, police, and disaster planning and response personnel) and the Public, Detailed Introduction on Infection and Treatment by Daniel Farb (2003); ISBN: 1932634762; http://www.amazon.com/exec/obidos/ASIN/1932634762/icongroupinterna
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Bioterrorism Radiation Manual and CD: For Healthcare Workers and Public Officers (Allied Health, Nurses, Doctors, Public Health workers, EMS workers, other emergency, safety, fire, police, and disaster planning and response personnel) and the Public, Detailed Introduction by Daniel Farb, Bruce Gordon (2003); ISBN: 1932634770; http://www.amazon.com/exec/obidos/ASIN/1932634770/icongroupinterna
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Bioterrorism Reader by Arthur P. Rogers (Editor), Steven P. Bianci (2003); ISBN: 1590335686; http://www.amazon.com/exec/obidos/ASIN/1590335686/icongroupinterna
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Bioterrorism Readiness and Response by American Health Consultants (2003); ISBN: 1931107408; http://www.amazon.com/exec/obidos/ASIN/1931107408/icongroupinterna
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Bioterrorism Smallpox Manual and CD: For Healthcare Workers and Public Officers (Allied Health, Nurses, Doctors, Public Health workers, EMS workers, other emergency, safety, fire, police, and disaster planning and response personnel) and the Public, Detailed Introduction on Infection and Treatment by Daniel Farb (2003); ISBN: 1932634789; http://www.amazon.com/exec/obidos/ASIN/1932634789/icongroupinterna
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Bioterrorism Tularemia Manual and CD: For Healthcare Workers and Public Officers (Allied Health, Nurses, Doctors, Public Health workers, EMS workers, other emergency, safety, fire, police, and disaster planning and response personnel) and the Public, Detailed Introduction on Infection and Treatment by Daniel Farb (2003); ISBN:
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1932634797; http://www.amazon.com/exec/obidos/ASIN/1932634797/icongroupinterna •
Bioterrorism, Threats and Biology of Toxins: Index of New Information and GuideBook for Consumers, Reference and Research by John C., Dr Bartone (2001); ISBN: 0788326996; http://www.amazon.com/exec/obidos/ASIN/0788326996/icongroupinterna
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Bioterrorism: Federal Research and Preparedness Activities, Coordination and Preparedness, and Public Health Preparedness Programs by Janet Heinrich (2003); ISBN: 0756718600; http://www.amazon.com/exec/obidos/ASIN/0756718600/icongroupinterna
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Bioterrorism: Field Guide to Disease Identification and Initial Patient Management by Dag K. J. E. Von Lubitz (2003); ISBN: 0849320305; http://www.amazon.com/exec/obidos/ASIN/0849320305/icongroupinterna
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Bioterrorism: Mathematical Modeling Applications in Homeland Security (Frontiers in Applied Mathematics (Unnumbered).) by H. Thomas Banks (Editor), Carlos CastilloChavez (Editor) (2003); ISBN: 0898715490; http://www.amazon.com/exec/obidos/ASIN/0898715490/icongroupinterna
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Bioterrorism: You Can Survive by Wesley Shankland II (2002); ISBN: 0972053204; http://www.amazon.com/exec/obidos/ASIN/0972053204/icongroupinterna
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Bioterrorism-Related Anthrax: Emerging Infectious Diseases (Emerging Infectious Diseases, Vol. 8, No. 10, October 2002) by D. Peter Drotman (Editor) (2003); ISBN: 0756727677; http://www.amazon.com/exec/obidos/ASIN/0756727677/icongroupinterna
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Comprehensive Medical Care for Bioterrorism Exposure: Are We Making EvidencedBased Decisions?: What Are the Research Needs: Hearing Before the Commit by United States (2002); ISBN: 0160670055; http://www.amazon.com/exec/obidos/ASIN/0160670055/icongroupinterna
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Countering Bioterrorism: The Role of Science and Technology (2002); ISBN: 0309086078; http://www.amazon.com/exec/obidos/ASIN/0309086078/icongroupinterna
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Crab Wars: A Tale of Horseshoe Crabs, Bioterrorism, and Human Health by William Sargent (2002); ISBN: 1584651687; http://www.amazon.com/exec/obidos/ASIN/1584651687/icongroupinterna
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Effective Responses to the Threat of Bioterrorism: Hearing Before the Subcommittee on Public Health of the Committee on Health, Education, Labor, and by United States (2002); ISBN: 0160684536; http://www.amazon.com/exec/obidos/ASIN/0160684536/icongroupinterna
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Federal Efforts to Coordinate and Prepare the United States for Bioterrorism: Are They Ready?: Joint Hearing Before the Governmental Affairs Committee by United States (2002); ISBN: 0160687829; http://www.amazon.com/exec/obidos/ASIN/0160687829/icongroupinterna
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Fema's Role in Managing Bioterrorist Attacks and the Impact of Public Health Concerns on Bioterrorism Preparedness: Hearing Before the International Security, Proliferation and Federal Services Subcommittee of the Committee on Governmental Affairs United States sena by Daniel K. Akaka (Editor) (2003); ISBN: 0756726069; http://www.amazon.com/exec/obidos/ASIN/0756726069/icongroupinterna
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Fighting Bioterrorism (At Issue) by Lisa Yount (Editor) (2004); ISBN: 0737716118; http://www.amazon.com/exec/obidos/ASIN/0737716118/icongroupinterna
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Germ Warriors : Stories of the Men and Women Who Fight the World's Worst Plagues from Tuberculosis to Smallpox by Clint Willis (Editor) (2004); ISBN: 1560255609; http://www.amazon.com/exec/obidos/ASIN/1560255609/icongroupinterna
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Germs, Biological Warfare, Vaccinations: What You Need to Know by James Feast, Gary, Ph.D. Null (2003); ISBN: 1583225188; http://www.amazon.com/exec/obidos/ASIN/1583225188/icongroupinterna
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Handbook of Viral Bioterrorism and Biodefense by Erik De Clercq (Editor), Earl R. Kern (Editor) (2003); ISBN: 0444513264; http://www.amazon.com/exec/obidos/ASIN/0444513264/icongroupinterna
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Law and Bioterrorism (Carolina Academic Press Law Casebook Series) by Victoria Sutton (2003); ISBN: 0890890714; http://www.amazon.com/exec/obidos/ASIN/0890890714/icongroupinterna
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Legislative Hearing on Bioterrorism, H.R. 3253 and H.R. 3254: Hearing Before the Subcommittee on Health of the Committee on Veterans' Affairs, House o by United States (2003); ISBN: 0160700930; http://www.amazon.com/exec/obidos/ASIN/0160700930/icongroupinterna
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Lessons from the Anthrax Attacks: Implications for U.S. Bioterrorism Preparedness: A Report on a National Forum on Biodefense (Csis Report) by David Heyman, et al (2002); ISBN: 0892064145; http://www.amazon.com/exec/obidos/ASIN/0892064145/icongroupinterna
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National Symposium on Medical and Public Health Response to Bioterrorism by Joseph E. McDade (Editor) (1999); ISBN: 0788185314; http://www.amazon.com/exec/obidos/ASIN/0788185314/icongroupinterna
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Preparedness for Epidemics and Bioterrorism: Hearing Before a Subcommittee of the Committee on Appropriations United States Senate, One Hundred Fifth Congress, Second Session, Special Hearing by Lauch Faircloth (2001); ISBN: 0756704960; http://www.amazon.com/exec/obidos/ASIN/0756704960/icongroupinterna
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Public Health Security and Bioterrorism Preparedness and Response Act of 2002: Congressional Conference Report to Accompany H.R. 3448 by E. J. Tauzin (Editor) (2003); ISBN: 075673245X; http://www.amazon.com/exec/obidos/ASIN/075673245X/icongroupinterna
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Review of Federal Bioterrorism Preparedness Program: Building an Early Warning Public Health Surveillance System: Hearing Before the Committee on Energy and Commerce, U.S. House of Representatives by James C. Greenwood (Editor) (2003); ISBN: 0756728711; http://www.amazon.com/exec/obidos/ASIN/0756728711/icongroupinterna
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Science of Bioterrorism: Is the Federal Government Prepared?: Hearing Before the Committee on Science, House of Representatives, One Hundred Se by United States (2002); ISBN: 0160686792; http://www.amazon.com/exec/obidos/ASIN/0160686792/icongroupinterna
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The Boobonic Plague (An American Epidemic) by Timothy P. Buchanan (2001); ISBN: 1588510867; http://www.amazon.com/exec/obidos/ASIN/1588510867/icongroupinterna
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The Official Patient's Sourcebook on Plague: A Revised and Updated Directory for the Internet Age by Icon Health Publications (2002); ISBN: 0597833060; http://www.amazon.com/exec/obidos/ASIN/0597833060/icongroupinterna
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The Plague Cycle: How Resurging Diseases Will Change Our Civilization by Joe M. D. Duarte (2003); ISBN: 0761520058; http://www.amazon.com/exec/obidos/ASIN/0761520058/icongroupinterna
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Threat of Bioterrorism and the Spread of Infectious Diseases: Hearing Before the Committee on Foreign Relations, U.S. Senate by Joseph R, Jr. Biden (Editor) (2003); ISBN: 0756726255; http://www.amazon.com/exec/obidos/ASIN/0756726255/icongroupinterna
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Threat of Bioterrorism in America: Assessing the Adequacy of the Federal Law Relating to Dangerous Biological Agents by Fred Upton (Editor) (1999); ISBN: 0756716098; http://www.amazon.com/exec/obidos/ASIN/0756716098/icongroupinterna
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Training of Clinicians for Public Health Events Relevant to Bioterrorism Preparedness by Monika S. Schmid (2002); ISBN: 1587630729; http://www.amazon.com/exec/obidos/ASIN/1587630729/icongroupinterna
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When Every Moment Counts: What You Need to Know About Bioterrorism from the Senate's Only Doctor by William H. Frist (2002); ISBN: 0742522458; http://www.amazon.com/exec/obidos/ASIN/0742522458/icongroupinterna
The National Library of Medicine Book Index The National Library of Medicine at the National Institutes of Health has a massive database of books published on healthcare and biomedicine. Go to the following Internet site, http://locatorplus.gov/, and then select “Search LOCATORplus.” Once you are in the search area, simply type “bioterrorism” (or synonyms) into the search box, and select “books only.” From there, results can be sorted by publication date, author, or relevance. The following was recently catalogued by the National Library of Medicine:10 •
Americans speak out on bioterrorism and U.S. preparedness to address risk Author: Robert Wood Johnson Foundation.; Year: 2002; [Washington, DC?]: Lake, Snell, Perry; Associates, [2002]
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Biological and chemical weapons Author: Haugen, David M.,; Year: 2001; San Diego, Calif.: Greenhaven Press, c2001; ISBN: 0737705558 http://www.amazon.com/exec/obidos/ASIN/0737705558/icongroupinterna
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Biological warfare and disarmament: new problems Author: Wright, Susan,; Year: 2002; Lanham: Rowan; Littlefield Publishers, c2002; ISBN: 074252468X http://www.amazon.com/exec/obidos/ASIN/074252468X/icongroupinterna
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In addition to LOCATORPlus, in collaboration with authors and publishers, the National Center for Biotechnology Information (NCBI) is currently adapting biomedical books for the Web. The books may be accessed in two ways: (1) by searching directly using any search term or phrase (in the same way as the bibliographic database PubMed), or (2) by following the links to PubMed abstracts. Each PubMed abstract has a "Books" button that displays a facsimile of the abstract in which some phrases are hypertext links. These phrases are also found in the books available at NCBI. Click on hyperlinked results in the list of books in which the phrase is found. Currently, the majority of the links are between the books and PubMed. In the future, more links will be created between the books and other types of information, such as gene and protein sequences and macromolecular structures. See http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Books.
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Bioterrorism: information technology strategy could strengthen federal agencies' abilities to respond to public health emergencies: report to congressional requesters. Author: United States. General Accounting Office.; Year: 2003; Washington, D.C.: United States General Accounting Office, [2003]
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Bioterrorism: public health response to anthrax incidents of 2001: report to the Honorable Bill Frist, Majority Leader, U.S. Senate. Author: Frist, William H.; Year: 2003; Washington, D.C.: United States General Accounting Office, [2003]
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Contagious disease dynamics for biological warfare and bioterrorism casualty assessments Author: Bombardt, John N.; Year: 2001; Alexandria, Va.: Institute for Defense Analyses, c2000
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Hospital preparedness: most urban hospitals have emergency plans but lack certain capacities for bioterrorism response: report to congressional committees. Author: United States. General Accounting Office.; Year: 2003; Washington, D.C.: United States General Accounting Office, [2003]
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Infectious disease outbreaks: bioterrorism preparedness efforts have improved public health response capacity, but gaps remain: testimony before the Committee on Government Reform, House of Representatives Author: Heinrich, Janet.; Year: 2003; Washington, D.C.: United States General Accounting Office, [2003]
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Laboratory safety, management, and diagnosis of biological agents associated with bioterrorism Author: Gilchrist, Mary J. R.; Year: 2000; Washington, DC: ASM Press, c2000
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Planning for bioterrorism: behavioral & mental health responses to weapons of mass destruction & mass disruption Author: Ursano, Robert J.,; Year: 2000; Bethesda, Md.: Center for the Study of Traumatic Stress, Dept. of Psychiatry, Uniformed Services University of the Health Sciences, c2000
Chapters on Bioterrorism In order to find chapters that specifically relate to bioterrorism, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and bioterrorism 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 “bioterrorism” (or synonyms) into the “For these words:” box.
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CHAPTER 7. MULTIMEDIA ON BIOTERRORISM Overview In this chapter, we show you how to keep current on multimedia sources of information on bioterrorism. 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.
Bibliography: Multimedia on Bioterrorism The National Library of Medicine is a rich source of information on healthcare-related multimedia productions including slides, computer software, and databases. To access the multimedia database, go to the following Web site: http://locatorplus.gov/. Select “Search LOCATORplus.” Once in the search area, simply type in bioterrorism (or synonyms). Then, in the option box provided below the search box, select “Audiovisuals and Computer Files.” From there, you can choose to sort results by publication date, author, or relevance. The following multimedia has been indexed on bioterrorism: •
Battling bioterrorism [electronic resource]: why time [i.e. timely] information-sharing between local, state and federal governments is the key to protecting public health: hearing before the Subcommittee on Technology and Procurement Policy of the Commitee on Government Reform, House of Representatives, One Hundred Seventh Congress, first session, December 14, 2001. Source: United States. Congress. House. Committee on Government Reform. Subcommittee on Technology and Procurement Policy; Year: 2003; Format: Electronic resource; Washington: U.S. G.P.O.: For sale by the Supt. of Docs., U.S. G.P.O. [Congressional Sales Office], 2003
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Bioterrorism [videorecording]: implications for clinical practice Source: a coproduction of Multimedia Communications and Physician Education and Development; Year: 2001; Format: Videorecording; Oakland, CA: Kaiser Foundation Health Plan, c2001
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Bioterrorism [videorecording]: implications for public health Source: CDC, UNC School of Public Health; Year: 1999; Format: Videorecording; [Atlanta, Ga.]: Public Health Training Network, [1999]
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Bioterrorism [videorecording]; Take a closer look: alcohol and drug abuse in the elderly Source: HSTN, Health & Sciences Television Network; Year: 2001; Format: Videorecording; Carrollton, TX: PRIMEDIA Workplace Learning, c2001
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Bioterrorism and the healthcare epidemiology Source: infection control team / produced by Public Health Training Network, Division of Professional Development and Evaluation, Public Health Practice Program Office, Centers for Disease Control & Pr; Year: 2001; Format: Videorecording; [Atlanta, Ga.]: U.S. Dept. of Health & Human Services, Public Health Service, Centers for Disease Control and Prevention, [2001]
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Bioterrorism for healthcare [videorecording]: essential disaster planning Source: Medfilms Inc; Year: 2002; Format: Videorecording; Tucson, AZ: Medfilms, c2002
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Clinical manifestations of bioterrorism [videorecording] Source: a co-production of Multimedia Communications and Physician Education and Development; Year: 2001; Format: Videorecording; Oakland, CA: Kaiser Foundation Health Plan, c2001
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Coping with bioterrorism [videorecording]: the role of the laboratorian Source: presented by the Centers for Disease Control and Prevention, Public Health Training Network; Year: 2001; Format: Videorecording; Atlanta, GA: Centers for Disease Control, 2001
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National Symposium on Medical and Public Health Response to Bioterrorism [electronic resource]: the foundation for coordinating a strategic response, February 16-17, 1999, Arlington, Virginia Source: presented by the Johns Hopkins Center for Civilian Biodefens; Year: 1999; Format: Electronic resource; [Baltimore, Md.]: Johns Hopkins University, c1999
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Post traumatic stress disorder [videorecording]; Laboratory detection of bioterrorism agents. Year: 2002; Format: Videorecording; Carrollton, TX: HSTN, c2002
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Risk communication and bioterrorism [videorecording] Source: U.S. Public Health Service, CDC, Centers for Disease Control and Prevention, Public Health Training Network; produced for Office of the Director, Centers for Disease Control and Prevention; produced; Year: 2001; Format: Videorecording; [Atlanta, Ga.]: Centers for Disease Control and Prevention, [2001]
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The counter-bioterrorism research agenda of the National Institute of Allergy and Infectious Diseases (NIAID) for CDC category A agents [electronic resource]: responding through research. Year: 2002; Format: Electronic resource; [Bethesda, Md.]: The Institute, [2002]
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CHAPTER 8. PERIODICALS AND NEWS ON BIOTERRORISM Overview In this chapter, we suggest a number of news sources and present various periodicals that cover bioterrorism.
News Services and Press Releases One of the simplest ways of tracking press releases on bioterrorism 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 “bioterrorism” (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 bioterrorism. 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 “bioterrorism” (or synonyms). The following was recently listed in this archive for bioterrorism: •
U.S. House passes bill to boost bioterrorism research Source: Reuters Health eLine Date: July 17, 2003
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U.S. House Committee approves bioterrorism bill Source: Reuters Health eLine Date: May 15, 2003
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ID Biomedical vaccine effective against plague in preclinical study Source: Reuters Industry Breifing Date: May 05, 2003
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Co. wins US contract for plague, anthrax vaccine Source: Reuters Health eLine Date: January 22, 2003
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Avant wins government contract for oral vaccine against plague, anthrax Source: Reuters Industry Breifing Date: January 22, 2003
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Simple test found to quickly spot plague infection Source: Reuters Health eLine Date: January 17, 2003
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Simple test can quickly detect plague bacteria Source: Reuters Industry Breifing Date: January 17, 2003
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Texas professor arrested in plague scare Source: Reuters Medical News Date: January 16, 2003
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Hollis-Eden to supply immune hormone drugs to bioterrorism effort Source: Reuters Industry Breifing Date: January 14, 2003
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Germ warfare nothing new, Tartar bioterror shows Source: Reuters Health eLine Date: November 06, 2002
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US Army extends plague vaccine work with ID Biomedical Source: Reuters Industry Breifing Date: October 10, 2002
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Cubist wins SBIR grant for bioterrorism research Source: Reuters Industry Breifing Date: July 30, 2002
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US panel recommends broad bioterrorism agenda Source: Reuters Health eLine Date: June 25, 2002
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Broad bioterrorism agenda recommended by US panel Source: Reuters Medical News Date: June 25, 2002 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.
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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 “bioterrorism” (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 “bioterrorism” (or synonyms). If you know the name of a company that is relevant to bioterrorism, 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 “bioterrorism” (or synonyms).
Academic Periodicals covering Bioterrorism Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to bioterrorism. In addition to these sources, you can search for articles covering bioterrorism 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
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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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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 Institute11: •
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/
11
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.12 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:13 •
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
12
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). 13 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 Gateway14 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.15 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “bioterrorism” (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 2018 173 17 5 17 2230
HSTAT16 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.17 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.18 Simply search by “bioterrorism” (or synonyms) at the following Web site: http://text.nlm.nih.gov.
14
Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.
15
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). 16 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 17 18
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 Biologists19 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.20 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.21 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/.
19 Adapted 20
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. 21 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 bioterrorism 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 bioterrorism. 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 bioterrorism. 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 “bioterrorism”:
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Other guides Anthrax http://www.nlm.nih.gov/medlineplus/anthrax.html Bacterial Infections http://www.nlm.nih.gov/medlineplus/bacterialinfections.html Biodefense and Bioterrorism http://www.nlm.nih.gov/medlineplus/biodefenseandbioterrorism.html Chemical Weapons http://www.nlm.nih.gov/medlineplus/chemicalweapons.html Disasters and Emergency Preparedness http://www.nlm.nih.gov/medlineplus/disastersandemergencypreparedness.html Environmental Health http://www.nlm.nih.gov/medlineplus/environmentalhealth.html Food Safety http://www.nlm.nih.gov/medlineplus/foodsafety.html Hantavirus Infections http://www.nlm.nih.gov/medlineplus/hantavirusinfections.html Insect Bites and Stings http://www.nlm.nih.gov/medlineplus/insectbitesandstings.html Lyme Disease http://www.nlm.nih.gov/medlineplus/lymedisease.html Monkeypox Virus Infections http://www.nlm.nih.gov/medlineplus/monkeypoxvirusinfections.html Pets and Pet Health http://www.nlm.nih.gov/medlineplus/petsandpethealth.html Plague http://www.nlm.nih.gov/medlineplus/plague.html Radiation Exposure http://www.nlm.nih.gov/medlineplus/radiationexposure.html Smallpox http://www.nlm.nih.gov/medlineplus/smallpox.html Tick Bites http://www.nlm.nih.gov/medlineplus/tickbites.html
Within the health topic page dedicated to bioterrorism, the following was listed: •
General/Overviews Biological Diseases/Agents Source: Centers for Disease Control and Prevention http://www.bt.cdc.gov/Agent/Agentlist.asp Biological Warfare: Questions and Answers Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=MH00018
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Biological, Chemical Weapons: Arm Yourself with Information Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=MH00027 •
Treatment National Pharmaceutical Stockpile Source: Centers for Disease Control and Prevention http://www.bt.cdc.gov/stockpile/ Offers to Treat Biological Threats: What You Need to Know Source: Federal Trade Commission http://www.ftc.gov/bcp/conline/pubs/alerts/bioalrt.htm
•
Alternative Therapy Bioterrorism and CAM (Complementary and Alternative Medicine): What the Public Needs to Know Source: National Center for Complementary and Alternative Medicine http://nccam.nih.gov/health/alerts/bioterrorism/
•
Coping Coping with Anxiety During High Risk Terrorist Alerts Source: American Psychiatric Association http://www.psych.org/news_room/press_releases/copingwithanxietyduringhigh alerts021203.pdf Handbook for Coping After Terrorism Source: Dept. of Justice, Office for Victims of Crime http://www.ojp.usdoj.gov/ovc/publications/infores/cat_hndbk/welcome.html Mental Health Aspects of Terrorism Source: Center for Mental Health Services http://www.mentalhealth.org/publications/allpubs/KEN-01-0095/default.asp
•
Specific Conditions/Aspects Biological Threat Source: Dept. of Homeland Security http://www.ready.gov/biological.html Biothreats -- Are Claims to Treat Really Just a Trick? Source: Federal Trade Commission http://www.ftc.gov/bcp/conline/pubs/alerts/biothrtalrt.htm Brucellosis Source: National Center for Infectious Diseases, Division of Bacterial and Mycotic Diseases http://www.cdc.gov/ncidod/dbmd/diseaseinfo/brucellosis_g.htm Explosions Source: Dept. of Homeland Security http://www.ready.gov/explosions.html
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Frequently Asked Consumer Questions about Food Safety and Terrorism Source: Food and Drug Administration http://www.cfsan.fda.gov/%7Edms/fsterrqa.html Frequently Asked Questions (FAQ) about Tularemia Source: Centers for Disease Control and Prevention http://www.bt.cdc.gov/agent/tularemia/faq.asp Glanders Source: National Center for Infectious Diseases, Division of Bacterial and Mycotic Diseases http://www.cdc.gov/ncidod/dbmd/diseaseinfo/glanders_g.htm Homeland Security Advisory System Source: Dept. of Homeland Security http://www.dhs.gov/dhspublic/display?theme=29 Mass Psychogenic Illness Source: American Academy of Family Physicians http://familydoctor.org/handouts/648.html Melioidosis Source: National Center for Infectious Diseases, Division of Bacterial and Mycotic Diseases http://www.cdc.gov/ncidod/dbmd/diseaseinfo/melioidosis_g.htm Q Fever Source: Centers for Disease Control and Prevention http://www.cdc.gov/ncidod/dvrd/qfever/index.htm Respirator Fact Sheet: What You Should Know in Deciding Whether to Buy Escape Hoods, Gas Masks, or Other Respirators for Preparedness at Home and Work Source: National Institute for Occupational Safety and Health http://www.cdc.gov/niosh/npptl/npptlrespfact.html Risks of Stockpiling Antibiotics to Counter Bioterrorism Source: Alliance for the Prudent Use of Antibiotics http://www.tufts.edu/med/apua/News/Articles/risksOfStockpiling.html Tularemia Source: National Institute of Allergy and Infectious Diseases http://www.niaid.nih.gov/factsheets/tularemia.htm •
Children Anthrax/Bioterrorism Q and A Source: American Academy of Pediatrics http://www.aap.org/advocacy/releases/anthraxqa.htm Homeland Security Advisory System Source: Federal Emergency Management Agency http://www.fema.gov/kids/nse/homeland.htm National Security Emergencies: Things to Know Source: Federal Emergency Management Agency http://www.fema.gov/kids/nse/things_know.htm
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Talking to Children about Terrorism and War Source: American Academy of Child and Adolescent Psychiatry http://www.aacap.org/publications/factsFam/87.htm Talking to Children about War and Terrorism: Tips for Parents and Teachers Source: American Psychiatric Association http://www.psych.org/news_room/press_releases/talkingtochildrenrewarterror.p df What to Do If There Is a Chemical and Biological Attack Source: Federal Emergency Management Agency http://www.fema.gov/kids/nse/biological.htm What You Might Feel in a Disaster Source: Federal Emergency Management Agency http://www.fema.gov/kids/feel.htm Youngest Victims: Disaster Preparedness to Meet Children's Needs Source: American Academy of Pediatrics http://www.aap.org/advocacy/releases/disaster_preparedness.htm •
Latest News FDA Introduces New Technology to Improve Food Security Source: 10/16/2003, Food and Drug Administration http://www.fda.gov/bbs/topics/NEWS/2003/NEW00960.html NIAID Reports 'Tremendous Progress' in Biodefense Research Source: 09/29/2003, National Institute of Allergy and Infectious Diseases http://www.nih.gov/news/pr/sep2003/niaid-29.htm U.S. Germ Detection System Active in 31 Cities Source: 11/14/2003, Reuters Health http://www.nlm.nih.gov//www.nlm.nih.gov/medlineplus/news/fullstory_14682 .html
•
Law and Policy Bioterrorism Act of 2002 Source: Food and Drug Administration http://www.fda.gov/oc/bioterrorism/bioact.html FDA Issues Final Two Proposed Food Safety Regulations Source: Food and Drug Administration http://www.fda.gov/bbs/topics/NEWS/2003/NEW00902.html FDA Issues New Security Guidance as Part of Operation Liberty Shield to Protect the Food Supply Source: Food and Drug Administration http://www.fda.gov/bbs/topics/NEWS/2003/NEW00881.html
•
Organizations Dept. of Homeland Security http://www.dhs.gov/dhspublic/
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Public Health Emergency Preparedness and Response Program Source: Centers for Disease Control and Prevention http://www.bt.cdc.gov/ U.S. Army Medical Research Institute of Infectious Diseases http://www.usamriid.army.mil/ •
Prevention/Screening Are You Ready? A Guide to Citizen Preparedness http://www.fema.gov/areyouready/ Facts about Sheltering in Place Source: Centers for Disease Control and Prevention http://www.bt.cdc.gov/planning/shelteringfacts.asp President Details Project BioShield Source: White House http://www.whitehouse.gov/news/releases/2003/02/20030203.html
•
Research NIAID Reports 'Tremendous Progress' in Biodefense Research Source: National Institute of Allergy and Infectious Diseases http://www.nih.gov/news/pr/sep2003/niaid-29.htm
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 bioterrorism. 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: •
Bioterrorism and CAM: What the Public Needs To Know Source: Gaithersburg, MD: National Center for Complementary and Alternative Medicine. 2001. 2 p. Contact: Available from National Center for Complementary and Alternative Medicine Clearinghouse. P.O. Box 7923, Gaithersburg, MD 20898. (888) 644-6226; INTERNATIONAL PHONE: (301) 519-3153; TTY: (866) 464-3615; FAX: (866) 464-3616; EMAIL:
[email protected]. PRICE: Free. Publication Number: D151.
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Summary: This document was developed by the National Center for Complementary and Alternative Medicine (NCCAM) for use in response to inquiries they receive. It discusses what NCCAM's recommendations are regarding CAM and bioterrorism, why CAM is not appropriate for diseases such as anthrax or smallpox, and whether NCCAM is studying CAM for use against bioterrorism. This document is available electronically and it provides a hyperlink to the NCCAM Director's full testimony before Congress in November 2001. The National Guideline Clearinghouse™ The National Guideline Clearinghouse™ offers hundreds of evidence-based clinical practice guidelines published in the United States and other countries. You can search this site located at http://www.guideline.gov/ by using the keyword “bioterrorism” (or synonyms). The following was recently posted: •
(1) Botulinum toxin as a biological weapon: medical and public health management. (2) Botulinum toxin as a biological weapon. (Addendum) Source: Center for Civilian Biodefense Strategies, School of Medicine, Johns Hopkins University - Academic Institution; 2001 February 28 (addendum published 2002); 15 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3619&nbr=2845&a mp;string=bioterrorism
•
(1) Smallpox as a biological weapon: medical and public health management. (2) Smallpox as a biological weapon. (Addendum) Source: Center for Civilian Biodefense Strategies, School of Medicine, Johns Hopkins University - Academic Institution; 1999 June 9 (addendum published 2002); 22 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3612&nbr=2838&a mp;string=bioterrorism
•
Anthrax as a biological weapon, 2002: updated recommendations for management Source: Center for Civilian Biodefense Strategies, School of Medicine, Johns Hopkins University - Academic Institution; 1999 May 12 (updated 2002 May 1); 17 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3220&nbr=2446&a mp;string=bioterrorism
•
Hemorrhagic fever viruses as biological weapons: medical and public health management Source: Center for Civilian Biodefense Strategies, School of Medicine, Johns Hopkins University - Academic Institution; 2002 May 8; 15 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3224&nbr=2450&a mp;string=bioterrorism
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Plague as a biological weapon. Medical and public health management Source: Center for Civilian Biodefense Strategies, School of Medicine, Johns Hopkins University - Academic Institution; 2000 October 4; 10 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2983&nbr=2209&a mp;string=bioterrorism
•
Tularemia as a biological weapon. Medical and public health management Source: Center for Civilian Biodefense Strategies, School of Medicine, Johns Hopkins University - Academic Institution; 2001 June 6; 11 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2981&nbr=2207&a mp;string=bioterrorism 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: •
Anthrax Interactive Health Tutorial Summary: Audio-based format walks users through an introduction to anthrax, its definition, types, symptoms, diagnosis, treatment, and vaccination. A section on bioterrorism is included. Source: National Library of Medicine, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6384
•
Biodefense and Bioterrorism Summary: This biological and chemical weapons page from the National Library of Medicine's MEDLINEplus features sections such as latest news, overviews, prevention and screening, specific conditions, and Source: National Library of Medicine, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6340
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Bioterrorism: U.S. Food and Drug Administration Summary: This bioterrorism page from the FDA provides general information about anthrax, smallpox, botulism and other biological agents. Source: U.S. Food and Drug Administration http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6375
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CDC Plague Home Page Summary: This CDC plague home page provides a brief overview of plague and the risks of infection. Source: National Center for Infectious Diseases, Centers for Disease Control and Prevention http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6347
•
Children and Anthrax: A Fact Sheet for Clinicians Summary: This CDC fact sheet dealing with bioterrorism describes inhalational, cutaneous, and gastrointestinal anthrax. It provides recommendations for pediatric postexposure prevention and treatment. Source: Centers for Disease Control and Prevention, U.S. Department of Health and Human Services http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6372
•
Children and Anthrax: A Fact Sheet for Parents Summary: This CDC fact sheet related to bioterrorism describes inhalational, cutaneous, and gastrointestinal anthrax and provides tips on what parents should know and how to reduce fears. Source: Centers for Disease Control and Prevention, U.S. Department of Health and Human Services http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6373
•
Epidemiologic Information on Bioterrorism Summary: This site provides educational information on possible biological weapons, considered in an epidemiologic and public health context. Source: UCLA Department of Epidemiology http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6446
•
HHS Initiative Prepares for Possible Bioterrorism Threat Summary: This fact sheet details HHS' efforts to prevent and respond to bioterrorism. Source: U.S. Department of Health and Human Services http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6317
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•
Information About Anthrax and Bioterrorism: Morbidity and Mortality Weekly Report Summary: This document is a compilation of current and previous Morbidity and Mortality Weekly Reports covering anthrax, bioterrorism, and other biological agents such as smallpox. Source: Centers for Disease Control and Prevention, U.S. Department of Health and Human Services http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6374
•
JAMA Consensus Statement: Anthrax As a Biological Weapon Summary: This JAMA consensus statement describes the history of the current threat of anthrax, its microbiology, clinical manifestations, epidemiology, diagnosis, prophylaxis, and therapy. Source: American Medical Association http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6369
•
JAMA Consensus Statement: Botulinum Toxin As a Biological Weapon Summary: This JAMA consensus statement describes the history of the current threat of botulinum toxin, its microbiology and virulence, clinical manifestations, epidemiology, diagnosis, prophylaxis, and Source: American Medical Association http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6343
•
JAMA Consensus Statement: Plague As a Biological Weapon Summary: This JAMA consensus statement describes the history of the current threat of plague, its microbiology and virulence, clinical manifestations, epidemiology, diagnosis, prophylaxis, and treatment. Source: American Medical Association http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6346
•
JAMA Consensus Statement: Smallpox As a Biological Weapon Summary: This JAMA consensus statement describes the history of the current threat of smallpox, its microbiology and virulence, clinical manifestations, epidemiology, diagnosis, prophylaxis, and treatment. Source: American Medical Association http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6388
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JAMA Consensus Statement: Tularemia As a Biological Weapon Summary: This JAMA consensus statement describes the history of the current threat of tularemia, its microbiology and virulence, clinical manifestations, epidemiology, diagnosis, prophylaxis, and treatment. Source: American Medical Association http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6345
•
United States Postal Service: Safety and Security of the Mail Summary: Breaking news about bioterrorism issues. Source: U.S. Postal Service http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6352
•
Webcasts: Anthrax and Bioterrorism Summary: Archived videos featuring experts from the Centers for Disease Control and Prevention and the National Institutes of Health providing information about anthrax and bioterrorism. Source: Centers for Disease Control and Prevention, U.S. Department of Health and Human Services http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6353 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 bioterrorism. 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/
•
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 bioterrorism. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with bioterrorism. 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 bioterrorism. 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 “bioterrorism” (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 “bioterrorism”. 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 “bioterrorism” (or synonyms) into the “For
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these words:” box. You should check back periodically with this database since it is updated every three months. The National Organization for Rare Disorders, Inc. The National Organization for Rare Disorders, Inc. has prepared a Web site that provides, at no charge, lists of associations organized by health topic. You can access this database at the following Web site: http://www.rarediseases.org/search/orgsearch.html. Type “bioterrorism” (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.22
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
22
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)23: •
Alabama: Health InfoNet of Jefferson County (Jefferson County Library Cooperative, Lister Hill Library of the Health Sciences), http://www.uab.edu/infonet/
•
Alabama: Richard M. Scrushy Library (American Sports Medicine Institute)
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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/
•
Connecticut: Healthnet: Connecticut Consumer Health Information Center (University of Connecticut Health Center, Lyman Maynard Stowe Library), http://library.uchc.edu/departm/hnet/
23
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/
•
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
•
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/
•
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
•
New York: Health Information Center (Upstate Medical University, State University of New York, Syracuse), http://www.upstate.edu/library/hic/
•
New York: Health Sciences Library (Long Island Jewish Medical Center, New Hyde Park), http://www.lij.edu/library/library.html
•
New York: ViaHealth Medical Library (Rochester General Hospital), http://www.nyam.org/library/
•
Ohio: Consumer Health Library (Akron General Medical Center, Medical & Consumer Health Library), http://www.akrongeneral.org/hwlibrary.htm
•
Oklahoma: The Health Information Center at Saint Francis Hospital (Saint Francis Health System, Tulsa), http://www.sfh-tulsa.com/services/healthinfo.asp
•
Oregon: Planetree Health Resource Center (Mid-Columbia Medical Center, The Dalles), http://www.mcmc.net/phrc/
•
Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center, Hershey), http://www.hmc.psu.edu/commhealth/
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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
•
Quebec, Canada: Medical Library (Montreal General Hospital), http://www.mghlib.mcgill.ca/
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•
South Dakota: Rapid City Regional Hospital Medical Library (Rapid City Regional Hospital), http://www.rcrh.org/Services/Library/Default.asp
•
Texas: Houston HealthWays (Houston Academy of Medicine-Texas Medical Center Library), http://hhw.library.tmc.edu/
•
Washington: Community Health Library (Kittitas Valley Community Hospital), http://www.kvch.com/
•
Washington: Southwest Washington Medical Center Library (Southwest Washington Medical Center, Vancouver), http://www.swmedicalcenter.com/body.cfm?id=72
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ONLINE GLOSSARIES The Internet provides access to a number of free-to-use medical dictionaries. The National Library of Medicine has compiled the following list of online dictionaries: •
ADAM Medical Encyclopedia (A.D.A.M., Inc.), comprehensive medical reference: http://www.nlm.nih.gov/medlineplus/encyclopedia.html
•
MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp
•
Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/
•
Multilingual Glossary of Technical and Popular Medical Terms in Eight European Languages (European Commission) - Danish, Dutch, English, French, German, Italian, Portuguese, and Spanish: http://allserv.rug.ac.be/~rvdstich/eugloss/welcome.html
•
On-line Medical Dictionary (CancerWEB): http://cancerweb.ncl.ac.uk/omd/
•
Rare Diseases Terms (Office of Rare Diseases): http://ord.aspensys.com/asp/diseases/diseases.asp
•
Technology Glossary (National Library of Medicine) - Health Care Technology: http://www.nlm.nih.gov/nichsr/ta101/ta10108.htm
Beyond these, MEDLINEplus contains a very patient-friendly encyclopedia covering every aspect of medicine (licensed from A.D.A.M., Inc.). The ADAM Medical Encyclopedia can be accessed at http://www.nlm.nih.gov/medlineplus/encyclopedia.html. ADAM is also available on commercial Web sites such as drkoop.com (http://www.drkoop.com/) and Web MD (http://my.webmd.com/adam/asset/adam_disease_articles/a_to_z/a). The NIH suggests the following Web sites in the ADAM Medical Encyclopedia when searching for information on bioterrorism: •
Basic Guidelines for Bioterrorism Plague Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000596.htm Tularemia Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000856.htm
•
Signs & Symptoms for Bioterrorism Bloody sputum Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003073.htm Cough Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003072.htm Coughing Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003072.htm
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Difficulty breathing Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003075.htm Enlarged lymph nodes Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003097.htm Fever Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003090.htm Headache Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003024.htm Joint stiffness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003261.htm Malaise Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003089.htm Muscle pains Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003178.htm Muscular pains Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003178.htm Seizures Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003200.htm Shortness of breath Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003075.htm Sweating Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003218.htm Swollen lymph glands Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003097.htm Weight loss Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003107.htm •
Diagnostics and Tests for Bioterrorism Blood culture Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003744.htm Culture of sputum Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003723.htm Febrile/cold agglutinins Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003549.htm Lymph node culture Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003737.htm
Online Glossaries 167
Serology for tularemia Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003523.htm •
Background Topics for Bioterrorism Endemic Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002362.htm Flea bite Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000033.htm Incidence Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002387.htm Intravenous Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002383.htm Respiratory Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002290.htm Tick Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002856.htm Tick bite Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000033.htm Ticks Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002856.htm
Online Dictionary Directories The following are additional online directories compiled by the National Library of Medicine, including a number of specialized medical dictionaries: •
Medical Dictionaries: Medical & Biological (World Health Organization): http://www.who.int/hlt/virtuallibrary/English/diction.htm#Medical
•
MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html
•
Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/
•
Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine
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BIOTERRORISM DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. 3-dimensional: 3-D. A graphic display of depth, width, and height. Three-dimensional radiation therapy uses computers to create a 3-dimensional picture of the tumor. This allows doctors to give the highest possible dose of radiation to the tumor, while sparing the normal tissue as much as possible. [NIH] Abdomen: That portion of the body that lies between the thorax and the pelvis. [NIH] Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Acceptor: A substance which, while normally not oxidized by oxygen or reduced by hydrogen, can be oxidized or reduced in presence of a substance which is itself undergoing oxidation or reduction. [NIH] Acetylcholine: A neurotransmitter. Acetylcholine in vertebrates is the major transmitter at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. It is generally not used as an administered drug because it is broken down very rapidly by cholinesterases, but it is useful in some ophthalmological applications. [NIH] Acoustic: Having to do with sound or hearing. [NIH] Adaptation: 1. The adjustment of an organism to its environment, or the process by which it enhances such fitness. 2. The normal ability of the eye to adjust itself to variations in the intensity of light; the adjustment to such variations. 3. The decline in the frequency of firing of a neuron, particularly of a receptor, under conditions of constant stimulation. 4. In dentistry, (a) the proper fitting of a denture, (b) the degree of proximity and interlocking of restorative material to a tooth preparation, (c) the exact adjustment of bands to teeth. 5. In microbiology, the adjustment of bacterial physiology to a new environment. [EU] Adenosine: A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. [NIH] Adenylate Cyclase: An enzyme of the lyase class that catalyzes the formation of cyclic AMP and pyrophosphate from ATP. EC 4.6.1.1. [NIH] Adjustment: The dynamic process wherein the thoughts, feelings, behavior, and biophysiological mechanisms of the individual continually change to adjust to the environment. [NIH] Adjuvant: A substance which aids another, such as an auxiliary remedy; in immunology, nonspecific stimulator (e.g., BCG vaccine) of the immune response. [EU] Adolescence: The period of life beginning with the appearance of secondary sex characteristics and terminating with the cessation of somatic growth. The years usually referred to as adolescence lie between 13 and 18 years of age. [NIH] 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]
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Aerosol: A solution of a drug which can be atomized into a fine mist for inhalation therapy. [EU]
Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among simple, uniform antigenic determinants such as haptens. Expressed as the association constant (K litres mole -1), which, owing to the heterogeneity of affinities in a population of antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU] Age Groups: Persons classified by age from birth (infant, newborn) to octogenarians and older (aged, 80 and over). [NIH] Aged, 80 and Over: A person 80 years of age and older. [NIH] Agglutinins: Substances, usually of biological origin, that cause cells or other organic particles to aggregate and stick to each other. They also include those antibodies which cause aggregation or agglutination of a particulate or insoluble antigen. [NIH] Airway: A device for securing unobstructed passage of air into and out of the lungs during general anesthesia. [NIH] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alleles: Mutually exclusive forms of the same gene, occupying the same locus on homologous chromosomes, and governing the same biochemical and developmental process. [NIH] Alpha Particles: Positively charged particles composed of two protons and two neutrons, i.e., helium nuclei, emitted during disintegration of very heavy isotopes; a beam of alpha particles or an alpha ray has very strong ionizing power, but weak penetrability. [NIH] Alpha-helices: One of the secondary element of protein. [NIH] Alphavirus: A genus of Togaviridae, also known as Group A arboviruses, serologically related to each other but not to other Togaviridae. The viruses are transmitted by mosquitoes. The type species is the sindbis virus. [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] Aluminum: A metallic element that has the atomic number 13, atomic symbol Al, and atomic weight 26.98. [NIH] Aluminum Hydroxide: Hydrated aluminum. A compound with many biomedical applications: as a gastric antacid, an antiperspirant, in dentifrices, as an emulsifier, as an adjuvant in bacterins and vaccines, in water purification, etc. [NIH] 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 Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (-
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COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amplification: The production of additional copies of a chromosomal DNA sequence, found as either intrachromosomal or extrachromosomal DNA. [NIH] 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] Analytes: A component of a test sample the presence of which has to be demonstrated. The term "analyte" includes where appropriate formed from the analyte during the analyses. [NIH]
Anaphylatoxins: The family of peptides C3a, C4a, C5a, and C5a des-arginine produced in the serum during complement activation. They produce smooth muscle contraction, mast cell histamine release, affect platelet aggregation, and act as mediators of the local inflammatory process. The order of anaphylatoxin activity from strongest to weakest is C5a, C3a, C4a, and C5a des-arginine. The latter is the so-called "classical" anaphylatoxin but shows no spasmogenic activity though it contains some chemotactic ability. [NIH] Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH] Animal Husbandry: The science of breeding, feeding, and care of domestic animals; includes housing and nutrition. [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]
Anorexia: Lack or loss of appetite for food. Appetite is psychologic, dependent on memory and associations. Anorexia can be brought about by unattractive food, surroundings, or company. [NIH] Anthrax: An acute bacterial infection caused by ingestion of bacillus organisms. Carnivores may become infected from ingestion of infected carcasses. It is transmitted to humans by contact with infected animals or contaminated animal products. The most common form in humans is cutaneous anthrax. [NIH] 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]
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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 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] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] Antifungal: Destructive to fungi, or suppressing their reproduction or growth; effective against fungal infections. [EU] 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-infective: An agent that so acts. [EU] Anti-Infective Agents: Substances that prevent infectious agents or organisms from spreading or kill infectious agents in order to prevent the spread of infection. [NIH] Antimicrobial: Killing microorganisms, or suppressing their multiplication or growth. [EU] Antiproliferative: Counteracting a process of proliferation. [EU] Antiseptic: A substance that inhibits the growth and development of microorganisms without necessarily killing them. [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] Anxiety: Persistent feeling of dread, apprehension, and impending disaster. [NIH] Aplasia: Lack of development of an organ or tissue, or of the cellular products from an organ or tissue. [EU] 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
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mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. [NIH] Applicability: A list of the commodities to which the candidate method can be applied as presented or with minor modifications. [NIH] Aqueous: Having to do with water. [NIH] Arachidonic Acid: An unsaturated, essential fatty acid. It is found in animal and human fat as well as in the liver, brain, and glandular organs, and is a constituent of animal phosphatides. It is formed by the synthesis from dietary linoleic acid and is a precursor in the biosynthesis of prostaglandins, thromboxanes, and leukotrienes. [NIH] Arenavirus: The only genus in the family Arenaviridae. It contains two groups LCM-Lassa complex viruses and Tacaribe complex viruses, which are distinguished by antigenic relationships and geographic distribution. [NIH] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Aromatic: Having a spicy odour. [EU] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Aseptic: Free from infection or septic material; sterile. [EU] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Atopic: Pertaining to an atopen or to atopy; allergic. [EU] Attenuated: Strain with weakened or reduced virulence. [NIH] Attenuation: Reduction of transmitted sound energy or its electrical equivalent. [NIH] Autoimmune disease: A condition in which the body recognizes its own tissues as foreign and directs an immune response against them. [NIH] Autoimmunity: Process whereby the immune system reacts against the body's own tissues. Autoimmunity may produce or be caused by autoimmune diseases. [NIH] Avian: A plasmodial infection in birds. [NIH] Bacillus: A genus of Bacillaceae that are spore-forming, rod-shaped cells. Most species are saprophytic soil forms with only a few species being pathogenic. [NIH] Bacteremia: The presence of viable bacteria circulating in the blood. Fever, chills, tachycardia, and tachypnea are common acute manifestations of bacteremia. The majority of cases are seen in already hospitalized patients, most of whom have underlying diseases or procedures which render their bloodstreams susceptible to invasion. [NIH] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Bacterial Infections: Infections by bacteria, general or unspecified. [NIH] Bacterial Physiology: Physiological processes and activities of bacteria. [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
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or non-cellular body. Bacteria usually reproduce through asexual processes. [NIH] Base: In chemistry, the nonacid part of a salt; a substance that combines with acids to form salts; a substance that dissociates to give hydroxide ions in aqueous solutions; a substance whose molecule or ion can combine with a proton (hydrogen ion); a substance capable of donating a pair of electrons (to an acid) for the formation of a coordinate covalent bond. [EU] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the 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] Binding Sites: The reactive parts of a macromolecule that directly participate in its specific combination with another molecule. [NIH] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Bioengineering: The application of engineering principles to the solution of biological problems, for example, remote-handling devices, life-support systems, controls, and displays. [NIH] Biofilms: Films of bacteria or other microbial organisms, usually embedded in extracellular polymers such as implanted medical devices, which adhere to surfaces submerged in, or subjected to, aquatic environments (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed). Biofilms consist of multilayers of microbial cells glued together to form microbial communities which are highly resistant to both phagocytes and antibiotics. [NIH] Biological response modifier: BRM. A substance that stimulates the body's response to infection and disease. [NIH] Biological Transport: The movement of materials (including biochemical substances and drugs) across cell membranes and epithelial layers, usually by passive diffusion. [NIH] Biological Warfare: Warfare involving the use of living organisms or their products as disease etiologic agents against people, animals, or plants. [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] Biopolymers: Polymers, such as proteins, DNA, RNA, or polysaccharides formed by any living organism. [NIH] Biosynthesis: The building up of a chemical compound in the physiologic processes of a living organism. [EU] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Bioterrorism: The use of biological agents in terrorism. This includes the malevolent use of bacteria, viruses, or toxins against people, animals, or plants. [NIH] Biotin: Hexahydro-2-oxo-1H-thieno(3,4-d)imidazole-4-pentanoic acid. Growth factor present in minute amounts in every living cell. It occurs mainly bound to proteins or
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polypeptides and is abundant in liver, kidney, pancreas, yeast, and milk.The biotin content of cancerous tissue is higher than that of normal tissue. [NIH] Bivalent: Pertaining to a group of 2 homologous or partly homologous chromosomes during the zygotene stage of prophase to the first metaphase in meiosis. [NIH] Bladder: The organ that stores urine. [NIH] Blood Platelets: Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation. [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] 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 of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bowel: The long tube-shaped organ in the abdomen that completes the process of digestion. There is both a small and a large bowel. Also called the intestine. [NIH] Brachytherapy: A collective term for interstitial, intracavity, and surface radiotherapy. It uses small sealed or partly-sealed sources that may be placed on or near the body surface or within a natural body cavity or implanted directly into the tissues. [NIH] Bradykinin: A nonapeptide messenger that is enzymatically produced from kallidin in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from mast cells during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter. [NIH] Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]
Breakdown: A physical, metal, or nervous collapse. [NIH] Breeding: The science or art of changing the constitution of a population of plants or animals through sexual reproduction. [NIH] Broad-spectrum: Effective against a wide range of microorganisms; said of an antibiotic. [EU] Bronchi: The larger air passages of the lungs arising from the terminal bifurcation of the trachea. [NIH] Bronchial: Pertaining to one or more bronchi. [EU] Brucellosis: Infection caused by bacteria of the genus Brucella mainly involving the reticuloendothelial system. This condition is characterized by fever, weakness, malaise, and weight loss. [NIH] Calcium: A basic element found in nearly all organized tissues. It is a member of the
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alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. [NIH] Calmodulin: A heat-stable, low-molecular-weight activator protein found mainly in the brain and heart. The binding of calcium ions to this protein allows this protein to bind to cyclic nucleotide phosphodiesterases and to adenyl cyclase with subsequent activation. Thereby this protein modulates cyclic AMP and cyclic GMP levels. [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] Carbon Dioxide: A colorless, odorless gas that can be formed by the body and is necessary for the respiration cycle of plants and animals. [NIH] Carcinogenic: Producing carcinoma. [EU] Castor Oil: Oil obtained from seeds of Ricinus communis that is used as a cathartic and as a plasticizer. [NIH] Caveolae: Endocytic/exocytic cell membrane structures rich in glycosphingolipids, cholesterol, and lipid-anchored membrane proteins that function in endocytosis (potocytosis), transcytosis, and signal transduction. Caveolae assume various shapes from open pits to closed vesicles. Caveolar coats are composed of caveolins. [NIH] Caveolins: The main structural proteins of caveolae. Several distinct genes for caveolins have been identified. [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 membrane: Cell membrane = plasma membrane. The structure enveloping a cell, enclosing the cytoplasm, and forming a selective permeability barrier; it consists of lipids, proteins, and some carbohydrates, the lipids thought to form a bilayer in which integral proteins are embedded to varying degrees. [EU] Cell Membrane Structures: Structures which are part of the cell membrane or have cell membrane as a major part of their structure. [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]
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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] Cetylpyridinium: Cationic bactericidal surfactant used as a topical antiseptic for skin, wounds, mucous membranes, instruments, etc.; and also as a component in mouthwash and lozenges. [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] 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] Chlorine: A greenish-yellow, diatomic gas that is a member of the halogen family of elements. It has the atomic symbol Cl, atomic number 17, and atomic weight 70.906. It is a powerful irritant that can cause fatal pulmonary edema. Chlorine is used in manufacturing, as a reagent in synthetic chemistry, for water purification, and in the production of chlorinated lime, which is used in fabric bleaching. [NIH] Chlorophyll: Porphyrin derivatives containing magnesium that act to convert light energy in photosynthetic organisms. [NIH] Cholera: An acute diarrheal disease endemic in India and Southeast Asia whose causative agent is vibrio cholerae. This condition can lead to severe dehydration in a matter of hours unless quickly treated. [NIH] Cholera Toxin: The enterotoxin from Vibrio cholerae. It is a protein that consists of two major components, the heavy (H) or A peptide and the light (L) or B peptide or choleragenoid. The B peptide anchors the protein to intestinal epithelial cells, while the A peptide, enters the cytoplasm, and activates adenylate cyclase, and production of cAMP. Increased levels of cAMP are thought to modulate release of fluid and electrolytes from intestinal crypt cells. [NIH] Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. [NIH] 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]
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Civilization: The distinctly human attributes and attainments of a particular society. [NIH] Clamp: A u-shaped steel rod used with a pin or wire for skeletal traction in the treatment of certain fractures. [NIH] Clathrin: The main structural coat protein of coated vesicles which play a key role in the intracellular transport between membranous organelles. Clathrin also interacts with cytoskeletal proteins. [NIH] Clear cell carcinoma: A rare type of tumor of the female genital tract in which the inside of the cells looks clear when viewed under a microscope. [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 molecules. [NIH] Coated Vesicles: Vesicles formed when cell-membrane coated pits invaginate and pinch off. The outer surface of these vesicles are covered with a lattice-like network of coat proteins, such as clathrin, coat protein complex proteins, or caveolins. [NIH] Codons: Any triplet of nucleotides (coding unit) in DNA or RNA (if RNA is the carrier of primary genetic information as in some viruses) that codes for particular amino acid or signals the beginning or end of the message. [NIH] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline, hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [NIH] Colloidal: Of the nature of a colloid. [EU] Combinatorial: A cut-and-paste process that churns out thousands of potentially valuable compounds at once. [NIH] Communis: Common tendon of the rectus group of muscles that surrounds the optic foramen and a portion of the superior orbital fissure, to the anterior margin of which it is attached at the spina recti lateralis. [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
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C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complement Activation: The sequential activation of serum components C1 through C9, initiated by an erythrocyte-antibody complex or by microbial polysaccharides and properdin, and producing an inflammatory response. [NIH] 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] 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] Concomitant: Accompanying; accessory; joined with another. [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] Consultation: A deliberation between two or more physicians concerning the diagnosis and the proper method of treatment in a case. [NIH] Consumption: Pulmonary tuberculosis. [NIH] Contamination: The soiling or pollution by inferior material, as by the introduction of organisms into a wound, or sewage into a stream. [EU] 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]
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Convalescence: The period of recovery following an illness. [NIH] Cornea: The transparent part of the eye that covers the iris and the pupil and allows light to enter the inside. [NIH] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [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] Critical Care: Health care provided to a critically ill patient during a medical emergency or crisis. [NIH] Crossing-over: The exchange of corresponding segments between chromatids of homologous chromosomes during meiosia, forming a chiasma. [NIH] Crystallization: The formation of crystals; conversion to a crystalline form. [EU] Cultured cells: Animal or human cells that are grown in the laboratory. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Cutaneous: Having to do with the skin. [NIH] Cyclic: Pertaining to or occurring in a cycle or cycles; the term is applied to chemical compounds that contain a ring of atoms in the nucleus. [EU] Cysteine: A thiol-containing non-essential amino acid that is oxidized to form cystine. [NIH] Cytokine: Small but highly potent protein that modulates the activity of many cell types, including T and B cells. [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] Cytoplasmic Vesicles: Membrane-limited structures derived from the plasma membrane or various intracellular membranes which function in storage, transport or metabolism. [NIH] Cytosine: A pyrimidine base that is a fundamental unit of nucleic acids. [NIH] Cytotoxic: Cell-killing. [NIH] Cytotoxicity: Quality of being capable of producing a specific toxic action upon cells of special organs. [NIH] Data Collection: Systematic gathering of data for a particular purpose from various sources, including questionnaires, interviews, observation, existing records, and electronic devices. The process is usually preliminary to statistical analysis of the data. [NIH] Databases, Bibliographic: Extensive collections, reputedly complete, of references and citations to books, articles, publications, etc., generally on a single subject or specialized subject area. Databases can operate through automated files, libraries, or computer disks. The concept should be differentiated from factual databases which is used for collections of data and facts apart from bibliographic references to them. [NIH] Decontamination: The removal of contaminating material, such as radioactive materials, biological materials, or chemical warfare agents, from a person or object. [NIH]
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Dehydration: The condition that results from excessive loss of body water. [NIH] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [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] Dentifrices: Any preparations used for cleansing teeth; they usually contain an abrasive, detergent, binder and flavoring agent and may exist in the form of liquid, paste or powder; may also contain medicaments and caries preventives. [NIH] Dentists: Individuals licensed to practice dentistry. [NIH] Deoxyribonucleic: A polymer of subunits called deoxyribonucleotides which is the primary genetic material of a cell, the material equivalent to genetic information. [NIH] Deoxyribonucleic acid: A polymer of subunits called deoxyribonucleotides which is the primary genetic material of a cell, the material equivalent to genetic information. [NIH] Deoxyribonucleotides: A purine or pyrimidine base bonded to a deoxyribose containing a bond to a phosphate group. [NIH] Dermal: Pertaining to or coming from the skin. [NIH] Dermatitis: Any inflammation of the skin. [NIH] DES: Diethylstilbestrol. A synthetic hormone that was prescribed from the early 1940s until 1971 to help women with complications of pregnancy. DES has been linked to an increased risk of clear cell carcinoma of the vagina in daughters of women who used DES. DES may also increase the risk of breast cancer in women who used DES. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Diarrhea: Passage of excessively liquid or excessively frequent stools. [NIH] Diarrhoea: Abnormal frequency and liquidity of faecal discharges. [EU] Diffusion: The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself throughout the available space; a major mechanism of biological transport. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Dilatation: The act of dilating. [NIH] Dilution: A diluted or attenuated medicine; in homeopathy, the diffusion of a given quantity of a medicinal agent in ten or one hundred times the same quantity of water. [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] Disaster Planning: Procedures outlined for the care of casualties and the maintenance of services in disasters. [NIH] Disease Outbreaks: Sudden increase in the incidence of a disease. The concept includes epidemics. [NIH]
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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] 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] Disinfection: Rendering pathogens harmless through the use of heat, antiseptics, antibacterial agents, etc. [NIH] 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] Domesticated: Species in which the evolutionary process has been influenced by humans to meet their needs. [NIH] Drive: A state of internal activity of an organism that is a necessary condition before a given stimulus will elicit a class of responses; e.g., a certain level of hunger (drive) must be present before food will elicit an eating response. [NIH] Drug Design: The molecular designing of drugs for specific purposes (such as DNAbinding, enzyme inhibition, anti-cancer efficacy, etc.) based on knowledge of molecular properties such as activity of functional groups, molecular geometry, and electronic structure, and also on information cataloged on analogous molecules. Drug design is generally computer-assisted molecular modeling and does not include pharmacokinetics, dosage analysis, or drug administration analysis. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Drug 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] Dura mater: The outermost, toughest, and most fibrous of the three membranes (meninges) covering the brain and spinal cord; called also pachymeninx. [EU] Dyes: Chemical substances that are used to stain and color other materials. The coloring may or may not be permanent. Dyes can also be used as therapeutic agents and test reagents in medicine and scientific research. [NIH] Ectromelia: Gross hypo- or aplasia of one or more long bones of one or more limbs. The
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concept includes amelia, hemimelia, and phocomelia. [NIH] Ectromelia Virus: A species of orthopoxvirus infecting mice and causing a disease that involves internal organs and produces characteristic skin lesions. [NIH] Eczema: A pruritic papulovesicular dermatitis occurring as a reaction to many endogenous and exogenous agents (Dorland, 27th ed). [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] 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] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Empirical: A treatment based on an assumed diagnosis, prior to receiving confirmatory laboratory test results. [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] Encephalitis, Viral: Inflammation of brain parenchymal tissue as a result of viral infection. Encephalitis may occur as primary or secondary manifestation of Togaviridae infections; Herpesviridae infections; Adenoviridae infections; Flaviviridae infections; Bunyaviridae infections; Picornaviridae infections; Paramyxoviridae infections; Orthomyxoviridae infections; Retroviridae infections; and Arenaviridae infections. [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] Endocytosis: Cellular uptake of extracellular materials within membrane-limited vacuoles or microvesicles. Endosomes play a central role in endocytosis. [NIH] Endosomes: Cytoplasmic vesicles formed when coated vesicles shed their clathrin coat. Endosomes internalize macromolecules bound by receptors on the cell surface. [NIH] Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart. [NIH] Endothelium: A layer of epithelium that lines the heart, blood vessels (endothelium, vascular), lymph vessels (endothelium, lymphatic), and the serous cavities of the body. [NIH] Endothelium, Lymphatic: Unbroken cellular lining (intima) of the lymph vessels (e.g., the
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high endothelial lymphatic venules). It is more permeable than vascular endothelium, lacking selective absorption and functioning mainly to remove plasma proteins that have filtered through the capillaries into the tissue spaces. [NIH] Endothelium, Vascular: Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components from interstitium to lumen; this function has been most intensively studied in the blood capillaries. [NIH] Endothelium-derived: Small molecule that diffuses to the adjacent muscle layer and relaxes it. [NIH] Endotoxic: Of, relating to, or acting as an endotoxin (= a heat-stable toxin, associated with the outer membranes of certain gram-negative bacteria. Endotoxins are not secreted and are released only when the cells are disrupted). [EU] 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] 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] 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] Epithelial: Refers to the cells that line the internal and external surfaces of the body. [NIH] Epithelial Cells: Cells that line the inner and outer surfaces of the body. [NIH] Epithelium: One or more layers of epithelial cells, supported by the basal lamina, which covers the inner or outer surfaces of the body. [NIH] Epitope: A molecule or portion of a molecule capable of binding to the combining site of an antibody. For every given antigenic determinant, the body can construct a variety of antibody-combining sites, some of which fit almost perfectly, and others which barely fit. [NIH]
Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Evacuation: An emptying, as of the bowels. [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] Excitatory: When cortical neurons are excited, their output increases and each new input they receive while they are still excited raises their output markedly. [NIH] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Exotoxin: Toxic substance excreted by living bacterial cells. [NIH] Expiration: The act of breathing out, or expelling air from the lungs. [EU] External-beam radiation: Radiation therapy that uses a machine to aim high-energy rays at the cancer. Also called external radiation. [NIH]
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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] Fatty acids: A major component of fats that are used by the body for energy and tissue development. [NIH] Febrile: Pertaining to or characterized by fever. [EU] Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [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] Filtration: The passage of a liquid through a filter, accomplished by gravity, pressure, or vacuum (suction). [EU] Flaccid: Weak, lax and soft. [EU] Flatus: Gas passed through the rectum. [NIH] Flavivirus: A genus of Flaviviridae, also known as Group B arbovirus, containing several subgroups and species. Most are arboviruses transmitted by mosquitoes or ticks. The type species is yellow fever virus. [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] Fluorescence: The property of emitting radiation while being irradiated. The radiation emitted is usually of longer wavelength than that incident or absorbed, e.g., a substance can be irradiated with invisible radiation and emit visible light. X-ray fluorescence is used in diagnosis. [NIH] Fluorescent Dyes: Dyes that emit light when exposed to light. The wave length of the emitted light is usually longer than that of the incident light. Fluorochromes are substances that cause fluorescence in other substances, i.e., dyes used to mark or label other compounds with fluorescent tags. They are used as markers in biochemistry and immunology. [NIH] Focus Groups: A method of data collection and a qualitative research tool in which a small group of individuals are brought together and allowed to interact in a discussion of their opinions about topics, issues, or questions. [NIH] Fold: A plication or doubling of various parts of the body. [NIH] Food Contamination: The presence in food of harmful, unpalatable, or otherwise objectionable foreign substances, e.g. chemicals, microorganisms or diluents, before, during,
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or after processing or storage. [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] 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] Ganglion: 1. A knot, or knotlike mass. 2. A general term for a group of nerve cell bodies located outside the central nervous system; occasionally applied to certain nuclear groups within the brain or spinal cord, e.g. basal ganglia. 3. A benign cystic tumour occurring on a aponeurosis or tendon, as in the wrist or dorsum of the foot; it consists of a thin fibrous capsule enclosing a clear mucinous fluid. [EU] Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] Gas exchange: Primary function of the lungs; transfer of oxygen from inhaled air into the blood and of carbon dioxide from the blood into the lungs. [NIH] Gastric: Having to do with the stomach. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]
Gastroenteritis: An acute inflammation of the lining of the stomach and intestines, characterized by anorexia, nausea, diarrhoea, abdominal pain, and weakness, which has various causes, including food poisoning due to infection with such organisms as Escherichia coli, Staphylococcus aureus, and Salmonella species; consumption of irritating food or drink; or psychological factors such as anger, stress, and fear. Called also enterogastritis. [EU] Gastrointestinal: Refers to the stomach and intestines. [NIH] 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] 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]
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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] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] 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] 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] Glanders: A contagious disease of horses that can be transmitted to humans. It is caused by Pseudomonas mallei and characterized by ulceration of the respiratory mucosa and an eruption of nodules on the skin. [NIH] Glucuronic Acid: Derivatives of uronic acid found throughout the plant and animal kingdoms. They detoxify drugs and toxins by conjugating with them to form glucuronides in the liver which are more water-soluble metabolites that can be easily eliminated from the body. [NIH] Glutamate: Excitatory neurotransmitter of the brain. [NIH] Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid (glutamate) is the most common excitatory neurotransmitter in the central nervous system. [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] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Gp120: 120-kD HIV envelope glycoprotein which is involved in the binding of the virus to its membrane receptor, the CD4 molecule, found on the surface of certain cells in the body. [NIH]
Grade: The grade of a tumor depends on how abnormal the cancer cells look under a microscope and how quickly the tumor is likely to grow and spread. Grading systems are different for each type of cancer. [NIH] Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to replace diseased or injured tissue removed from another part of the body. [NIH] Graft Rejection: An immune response with both cellular and humoral components, directed against an allogeneic transplant, whose tissue antigens are not compatible with those of the recipient. [NIH] Gram-negative: Losing the stain or decolorized by alcohol in Gram's method of staining, a primary characteristic of bacteria having a cell wall composed of a thin layer of peptidoglycan covered by an outer membrane of lipoprotein and lipopolysaccharide. [EU] Growth: The progressive development of a living being or part of an organism from its earliest stage to maturity. [NIH] Guanylate Cyclase: An enzyme that catalyzes the conversion of GTP to 3',5'-cyclic GMP and
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pyrophosphate. It also acts on ITP and dGTP. (From Enzyme Nomenclature, 1992) EC 4.6.1.2. [NIH] Guinea Pigs: A common name used for the family Caviidae. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research. [NIH]
Habitat: An area considered in terms of its environment, particularly as this determines the type and quality of the vegetation the area can carry. [NIH] Hair follicles: Shafts or openings on the surface of the skin through which hair grows. [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] Hazardous Substances: Substances which, upon release into the atmosphere, water, or soil, or which, in direct contact with the skin, eyes, or mucous membranes, or as additives to food, cause health risks to humans or animals through absorption, inhalation, or ingestion. The concept includes safe handling, transportation, and storage of these substances. [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] Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. [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] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hemorrhagic Fever with Renal Syndrome: An acute febrile disease occurring predominately in Asia. It is characterized by fever, prostration, vomiting, hemorrhagic phenonema, shock, and renal failure. It is caused by any one of several closely related species of the genus Hantavirus. The most severe form is caused by Hantaan virus whose natural host is the rodent Apodemus agrarius. A milder form is caused by Seoul virus and related species and transmitted by the rodents Rattus rattus and R. norvegicus. [NIH] Heparin: Heparinic acid. A highly acidic mucopolysaccharide formed of equal parts of sulfated D-glucosamine and D-glucuronic acid with sulfaminic bridges. The molecular weight ranges from six to twenty thousand. Heparin occurs in and is obtained from liver, lung, mast cells, etc., of vertebrates. Its function is unknown, but it is used to prevent blood clotting in vivo and vitro, in the form of many different salts. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU]
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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 Zoster: Acute vesicular inflammation. [NIH] Heterodimers: 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]
Heterotrophic: Pertaining to organisms that are consumers and dependent on other organisms for their source of energy (food). [NIH] Histamine: 1H-Imidazole-4-ethanamine. A depressor amine derived by enzymatic decarboxylation of histidine. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter. [NIH] Histidine: An essential amino acid important in a number of metabolic processes. It is required for the production of histamine. [NIH] Homogeneous: Consisting of or composed of similar elements or ingredients; of a uniform quality throughout. [EU] Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] 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] Horseradish Peroxidase: An enzyme isolated from horseradish which is able to act as an antigen. It is frequently used as a histochemical tracer for light and electron microscopy. Its antigenicity has permitted its use as a combined antigen and marker in experimental immunology. [NIH] Hospital Information Systems: Integrated, computer-assisted systems designed to store, manipulate, and retrieve information concerned with the administrative and clinical aspects of providing medical services within the hospital. [NIH] Host: Any animal that receives a transplanted graft. [NIH] Humoral: Of, relating to, proceeding from, or involving a bodily humour - now often used of endocrine factors as opposed to neural or somatic. [EU] Humour: 1. A normal functioning fluid or semifluid of the body (as the blood, lymph or bile) especially of vertebrates. 2. A secretion that is itself an excitant of activity (as certain hormones). [EU] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [NIH] Hybridization: The genetic process of crossbreeding to produce a hybrid. Hybrid nucleic acids can be formed by nucleic acid hybridization of DNA and RNA molecules. Protein hybridization allows for hybrid proteins to be formed from polypeptide chains. [NIH] 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 Bonding: A low-energy attractive force between hydrogen and another element.
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It plays a major role in determining the properties of water, proteins, and other compounds. [NIH]
Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hydrophilic: Readily absorbing moisture; hygroscopic; having strongly polar groups that readily interact with water. [EU] Hydrophobic: Not readily absorbing water, or being adversely affected by water, as a hydrophobic colloid. [EU] Id: The part of the personality structure which harbors the unconscious instinctive desires and strivings of the individual. [NIH] Imidazole: C3H4N2. The ring is present in polybenzimidazoles. [NIH] Immune function: Production and action of cells that fight disease or infection. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]
Immune Sera: Serum that contains antibodies. It is obtained from an animal that has been immunized either by antigen injection or infection with microorganisms containing the antigen. [NIH] Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] Immunity: Nonsusceptibility to the invasive or pathogenic microorganisms or to the toxic effect of antigenic substances. [NIH]
effects
of
foreign
Immunization: Deliberate stimulation of the host's immune response. Active immunization involves administration of antigens or immunologic adjuvants. Passive immunization involves administration of immune sera or lymphocytes or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow). [NIH] 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] 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] Immunofluorescence: A technique for identifying molecules present on the surfaces of cells or in tissues using a highly fluorescent substance coupled to a specific antibody. [NIH] 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] 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] Immunosuppressive: Describes the ability to lower immune system responses. [NIH]
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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] Implant radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called [NIH] In 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] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU] 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] Infant, Newborn: An infant during the first month after birth. [NIH] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]
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] Information Science: The field of knowledge, theory, and technology dealing with the collection of facts and figures, and the processes and methods involved in their manipulation, storage, dissemination, publication, and retrieval. It includes the fields of communication, publishing, library science and informatics. [NIH] Information Systems: Integrated set of files, procedures, and equipment for the storage, manipulation, and retrieval of information. [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
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step in a carcinogenic process. [NIH] Inorganic: Pertaining to substances not of organic origin. [EU] 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] 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] Interferon-beta: One of the type I interferons produced by fibroblasts in response to stimulation by live or inactivated virus or by double-stranded RNA. It is a cytokine with antiviral, antiproliferative, and immunomodulating activity. [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-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] Internal radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called brachytherapy, implant radiation, or interstitial radiation therapy. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intestinal: Having to do with the intestines. [NIH] Intestines: The section of the alimentary canal from the stomach to the anus. It includes the large intestine and small intestine. [NIH] Intoxication: Poisoning, the state of being poisoned. [EU] Intracellular: Inside a cell. [NIH] Intracellular Membranes: Membranes of subcellular structures. [NIH] Intramuscular: IM. Within or into muscle. [NIH] Intravenous: IV. Into a vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]
Ionization: 1. Any process by which a neutral atom gains or loses electrons, thus acquiring a net charge, as the dissociation of a substance in solution into ions or ion production by the passage of radioactive particles. 2. Iontophoresis. [EU] Ionizing: Radiation comprising charged particles, e. g. electrons, protons, alpha-particles, etc., having sufficient kinetic energy to produce ionization by collision. [NIH]
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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] Irradiation: The use of high-energy radiation from x-rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Irradiation is also called radiation therapy, radiotherapy, and x-ray therapy. [NIH] 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] Kinesin: A microtubule-associated mechanical adenosine triphosphatase, that uses the energy of ATP hydrolysis to move organelles along microtubules toward the plus end of the microtubule. The protein is found in squid axoplasm, optic lobes, and in bovine brain. Bovine kinesin is a heterotetramer composed of two heavy (120 kDa) and two light (62 kDa) chains. EC 3.6.1.-. [NIH] Kinetic: Pertaining to or producing motion. [EU] Labile: 1. Gliding; moving from point to point over the surface; unstable; fluctuating. 2. Chemically unstable. [EU] 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] Leishmaniasis: A disease caused by any of a number of species of protozoa in the genus Leishmania. There are four major clinical types of this infection: cutaneous (Old and New World), diffuse cutaneous, mucocutaneous, and visceral leishmaniasis. [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] 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] Library Services: Services offered to the library user. They include reference and circulation. [NIH]
Life cycle: The successive stages through which an organism passes from fertilized ovum or spore to the fertilized ovum or spore of the next generation. [NIH] Ligands: A RNA simulation method developed by the MIT. [NIH] Linkages: The tendency of two or more genes in the same chromosome to remain together from one generation to the next more frequently than expected according to the law of independent assortment. [NIH] Lipid: Fat. [NIH] Lipid A: Lipid A is the biologically active component of lipopolysaccharides. It shows strong endotoxic activity and exhibits immunogenic properties. [NIH] Lipopolysaccharide: Substance consisting of polysaccaride and lipid. [NIH]
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Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [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] 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] Lymphocytic: Referring to lymphocytes, a type of white blood cell. [NIH] Lymphocytic Choriomeningitis Virus: The type species of arenavirus, part of the LCMLassa complex viruses, producing an inapparent infection in house and laboratory mice. In humans, infection with LCMV can be inapparent, or can present with an influenza-like illness, a benign aseptic meningitis, or a severe meningoencephalomyelitis. The virus can also infect monkeys, dogs, field mice, guinea pigs, and hamsters, the latter an epidemiologically important host. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Lymphokines: Soluble protein factors generated by activated lymphocytes that affect other cells, primarily those involved in cellular immunity. [NIH] Lysosome: A sac-like compartment inside a cell that has enzymes that can break down cellular components that need to be destroyed. [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] Macrophage Activation: The process of altering the morphology and functional activity of macrophages so that they become avidly phagocytic. It is initiated by lymphokines, such as the macrophage activation factor (MAF) and the macrophage migration-inhibitory factor (MMIF), immune complexes, C3b, and various peptides, polysaccharides, and immunologic adjuvants. [NIH] Malaise: A vague feeling of bodily discomfort. [EU] Manifest: Being the part or aspect of a phenomenon that is directly observable : concretely expressed in behaviour. [EU] Mannans: Polysaccharides consisting of mannose units. [NIH] Mass Screening: Organized periodic procedures performed on large groups of people for
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the purpose of detecting disease. [NIH] Meat: The edible portions of any animal used for food including domestic mammals (the major ones being cattle, swine, and sheep) along with poultry, fish, shellfish, and game. [NIH]
Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] Medical Informatics: The field of information science concerned with the analysis and dissemination of medical data through the application of computers to various aspects of health care and medicine. [NIH] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [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] Melioidosis: A disease of humans and animals that resembles glanders. It is caused by Burkholderia pseudomallei and may range from a dormant infection to a condition that causes multiple abscesses, pneumonia, and bacteremia. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Membrane Fusion: The adherence of cell membranes, intracellular membranes, or artifical membrane models of either to each other or to viruses, parasites, or interstitial particles through a variety of chemical and physical processes. [NIH] Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors. [NIH] Memory: Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. [NIH] Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] Meningitis: Inflammation of the meninges. When it affects the dura mater, the disease is termed pachymeningitis; when the arachnoid and pia mater are involved, it is called leptomeningitis, or meningitis proper. [EU] Mental Health: The state wherein the person is well adjusted. [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 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] Metaphase: The second phase of cell division, in which the chromosomes line up across the equatorial plane of the spindle prior to separation. [NIH] MI: Myocardial infarction. Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microbiological: Pertaining to microbiology : the science that deals with microorganisms,
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including algae, bacteria, fungi, protozoa and viruses. [EU] Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [NIH] Microorganism: An organism that can be seen only through a microscope. Microorganisms include bacteria, protozoa, algae, and fungi. Although viruses are not considered living organisms, they are sometimes classified as microorganisms. [NIH] Microscopy: The application of microscope magnification to the study of materials that cannot be properly seen by the unaided eye. [NIH] Microspheres: Small uniformly-sized spherical particles frequently radioisotopes or various reagents acting as tags or markers. [NIH]
labeled
with
Microtubules: Slender, cylindrical filaments found in the cytoskeleton of plant and animal cells. They are composed of the protein tubulin. [NIH] Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [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] 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] Modeling: A treatment procedure whereby the therapist presents the target behavior which the learner is to imitate and make part of his repertoire. [NIH] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecular mass: The sum of the atomic masses of all atoms in a molecule, based on a scale in which the atomic masses of hydrogen, carbon, nitrogen, and oxygen are 1, 12, 14, and 16, respectively. For example, the molecular mass of water, which has two atoms of hydrogen and one atom of oxygen, is 18 (i.e., 2 + 16). [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] Monkeypox Virus: A species of orthopoxvirus causing an epidemic disease among captive primates. [NIH]
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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] 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] Mucocutaneous: Pertaining to or affecting the mucous membrane and the skin. [EU] 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] Mutagenesis: Process of generating genetic mutations. It may occur spontaneously or be induced by mutagens. [NIH] Mutagens: Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes. [NIH] Mutate: To change the genetic material of a cell. Then changes (mutations) can be harmful, beneficial, or have no effect. [NIH] Myalgia: Pain in a muscle or muscles. [EU] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Naive: Used to describe an individual who has never taken a certain drug or class of drugs (e. g., AZT-naive, antiretroviral-naive), or to refer to an undifferentiated immune system cell. [NIH] Nasal Mucosa: The mucous membrane lining the nasal cavity. [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] Necrosis: A pathological process caused by the progressive degradative action of enzymes that is generally associated with severe cellular trauma. It is characterized by mitochondrial swelling, nuclear flocculation, uncontrolled cell lysis, and ultimately cell death. [NIH] Need: A state of tension or dissatisfaction felt by an individual that impels him to action toward a goal he believes will satisfy the impulse. [NIH] Needs Assessment: Systematic identification of a population's needs or the assessment of individuals to determine the proper level of services needed. [NIH] Neonatal: Pertaining to the first four weeks after birth. [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
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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] Neuraminidase: An enzyme that catalyzes the hydrolysis of alpha-2,3, alpha-2,6-, and alpha-2,8-glycosidic linkages (at a decreasing rate, respectively) of terminal sialic residues in oligosaccharides, glycoproteins, glycolipids, colominic acid, and synthetic substrate. (From Enzyme Nomenclature, 1992) EC 3.2.1.18. [NIH] Neurologist: A doctor who specializes in the diagnosis and treatment of disorders of the nervous system. [NIH] 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] Neurotoxic: Poisonous or destructive to nerve tissue. [EU] 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] Neutralization: An act or process of neutralizing. [EU] Neutrons: Electrically neutral elementary particles found in all atomic nuclei except light hydrogen; the mass is equal to that of the proton and electron combined and they are unstable when isolated from the nucleus, undergoing beta decay. Slow, thermal, epithermal, and fast neutrons refer to the energy levels with which the neutrons are ejected from heavier nuclei during their decay. [NIH] Neutrophils: Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes. [NIH] Niche: The ultimate unit of the habitat, i. e. the specific spot occupied by an individual organism; by extension, the more or less specialized relationships existing between an organism, individual or synusia(e), and its environment. [NIH] Nitric Oxide: A free radical gas produced endogenously by a variety of mammalian cells. It is synthesized from arginine by a complex reaction, catalyzed by nitric oxide synthase. Nitric oxide is endothelium-derived relaxing factor. It is released by the vascular endothelium and mediates the relaxation induced by some vasodilators such as acetylcholine and bradykinin. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic guanylate cyclase and thus elevates intracellular levels of cyclic GMP. [NIH]
Nitrogen: An element with the atomic symbol N, atomic number 7, and atomic weight 14. Nitrogen exists as a diatomic gas and makes up about 78% of the earth's atmosphere by volume. It is a constituent of proteins and nucleic acids and found in all living cells. [NIH] Nosocomial: Pertaining to or originating in the hospital, said of an infection not present or incubating prior to admittance to the hospital, but generally occurring 72 hours after admittance; the term is usually used to refer to patient disease, but hospital personnel may also acquire nosocomial infection. [EU] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through
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the kidneys. [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] Nucleic Acid Hybridization: The process whereby two single-stranded polynucleotides form a double-stranded molecule, with hydrogen bonding between the complementary bases in the two strains. [NIH] Nucleic Acid Probes: Nucleic acid which complements a specific mRNA or DNA molecule, or fragment thereof; used for hybridization studies in order to identify microorganisms and for genetic studies. [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] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Ocular: 1. Of, pertaining to, or affecting the eye. 2. Eyepiece. [EU] Odour: A volatile emanation that is perceived by the sense of smell. [EU] Oligonucleotide Probes: Synthetic or natural oligonucleotides used in hybridization studies in order to identify and study specific nucleic acid fragments, e.g., DNA segments near or within a specific gene locus or gene. The probe hybridizes with a specific mRNA, if present. Conventional techniques used for testing for the hybridization product include dot blot assays, Southern blot assays, and DNA:RNA hybrid-specific antibody tests. Conventional labels for the probe include the radioisotope labels 32P and 125I and the chemical label biotin. [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] 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 stop codons. [NIH] Ophthalmologist: A medical doctor specializing in the diagnosis and medical or surgical treatment of visual disorders and eye disease. [NIH] Opportunistic Infections: An infection caused by an organism which becomes pathogenic under certain conditions, e.g., during immunosuppression. [NIH] Oral Health: The optimal state of the mouth and normal functioning of the organs of the mouth without evidence of disease. [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] 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] Orthopoxvirus: A genus of the family Poxviridae, subfamily Chordopoxvirninae, comprising many species infecting mammals. Viruses of this genus cause generalized
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infections and a rash in some hosts. The type species is Vaccinia virus. [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] Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]
Oxygen Consumption: The oxygen consumption is determined by calculating the difference between the amount of oxygen inhaled and exhaled. [NIH] Pachymeningitis: Inflammation of the dura mater of the brain, the spinal cord or the optic nerve. [NIH] Palladium: A chemical element having an atomic weight of 106.4, atomic number of 46, and the symbol Pd. It is a white, ductile metal resembling platinum, and following it in abundance and importance of applications. It is used in dentistry in the form of gold, silver, and copper alloys. [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] 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] Parasitic Diseases: Infections or infestations with parasitic organisms. They are often contracted through contact with an intermediate vector, but may occur as the result of direct exposure. [NIH] Particle: A tiny mass of material. [EU] Pathogen: Any disease-producing microorganism. [EU] Pathogenesis: The cellular events and reactions that occur in the development of disease. [NIH]
Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] 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]
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Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Peptide Elongation Factors: Protein factors uniquely required during the elongation phase of protein synthesis. [NIH] Peptide T: N-(N-(N(2)-(N-(N-(N-(N-D-Alanyl L-seryl)-L-threonyl)-L-threonyl) L-threonyl)L-asparaginyl)-L-tyrosyl) L-threonine. Octapeptide sharing sequence homology with HIV envelope protein gp120. It is potentially useful as antiviral agent in AIDS therapy. The core pentapeptide sequence, TTNYT, consisting of amino acids 4-8 in peptide T, is the HIV envelope sequence required for attachment to the CD4 receptor. [NIH] PH: The symbol relating the hydrogen ion (H+) concentration or activity of a solution to that of a given standard solution. Numerically the pH is approximately equal to the negative logarithm of H+ concentration expressed in molarity. pH 7 is neutral; above it alkalinity increases and below it acidity increases. [EU] Phagosomes: Membrane-bound cytoplasmic vesicles formed by invagination of phagocytized material. They fuse with lysosomes to form phagolysosomes in which the hydrolytic enzymes of the lysosome digest the phagocytized material. [NIH] Pharmacist: A person trained to prepare and distribute medicines and to give information about them. [NIH] Pharmacokinetics: Dynamic and kinetic mechanisms of exogenous chemical and drug absorption, biotransformation, distribution, release, transport, uptake, and elimination as a function of dosage, and extent and rate of metabolic processes. It includes toxicokinetics, the pharmacokinetic mechanism of the toxic effects of a substance. [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] Phenotypes: An organism as observed, i. e. as judged by its visually perceptible characters resulting from the interaction of its genotype with the environment. [NIH] Phocomelia: Congenital deformity that leaves the child without legs. [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] Phosphorylate: Attached to a phosphate group. [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] 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] Phytotoxin: A substance which is toxic for plants. [NIH] Pilot Projects: Small-scale tests of methods and procedures to be used on a larger scale if the pilot study demonstrates that these methods and procedures can work. [NIH] Pilot study: The initial study examining a new method or treatment. [NIH] Plague: An acute infectious disease caused by Yersinia pestis that affects humans, wild
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rodents, and their ectoparasites. This condition persists due to its firm entrenchment in sylvatic rodent-flea ecosystems throughout the world. Bubonic plague is the most common form. [NIH] Plague Vaccine: A suspension of killed Yersinia pestis used for immunizing people in enzootic plague areas. [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] Platelet Aggregation: The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin, collagen) and is part of the mechanism leading to the formation of a thrombus. [NIH] Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Platinum: Platinum. A heavy, soft, whitish metal, resembling tin, atomic number 78, atomic weight 195.09, symbol Pt. (From Dorland, 28th ed) It is used in manufacturing equipment for laboratory and industrial use. It occurs as a black powder (platinum black) and as a spongy substance (spongy platinum) and may have been known in Pliny's time as "alutiae". [NIH]
Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [NIH] Polymerase: An enzyme which catalyses the synthesis of DNA using a single DNA strand as a template. The polymerase copies the template in the 5'-3'direction provided that sufficient quantities of free nucleotides, dATP and dTTP are present. [NIH] Polymerase Chain Reaction: In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships. [NIH] Polymers: Compounds formed by the joining of smaller, usually repeating, units linked by covalent bonds. These compounds often form large macromolecules (e.g., polypeptides, proteins, plastics). [NIH] Polypeptide: A peptide which on hydrolysis yields more than two amino acids; called
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tripeptides, tetrapeptides, etc. according to the number of amino acids contained. [EU] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] Polyvalent: Having more than one valence. [EU] Port: An implanted device through which blood may be withdrawn and drugs may be infused without repeated needle sticks. Also called a port-a-cath. [NIH] Port-a-cath: An implanted device through which blood may be withdrawn and drugs may be infused without repeated needle sticks. Also called a port. [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] Potentiates: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [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] 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] Prenatal: Existing or occurring before birth, with reference to the fetus. [EU] Preventive Medicine: A medical specialty primarily concerned with prevention of disease and the promotion and preservation of health in the individual. [NIH] Probe: An instrument used in exploring cavities, or in the detection and dilatation of strictures, or in demonstrating the potency of channels; an elongated instrument for exploring or sounding body cavities. [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] Proline: A non-essential amino acid that is synthesized from glutamic acid. It is an essential component of collagen and is important for proper functioning of joints and tendons. [NIH] Promoter: A chemical substance that increases the activity of a carcinogenic process. [NIH] 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] Proportional: Being in proportion : corresponding in size, degree, or intensity, having the same or a constant ratio; of, relating to, or used in determining proportions. [EU] Prospective study: An epidemiologic study in which a group of individuals (a cohort), all free of a particular disease and varying in their exposure to a possible risk factor, is followed over a specific amount of time to determine the incidence rates of the disease in the exposed and unexposed groups. [NIH]
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Prostaglandin: Any of a group of components derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway that are extremely potent mediators of a diverse group of physiologic processes. The abbreviation for prostaglandin is PG; specific compounds are designated by adding one of the letters A through I to indicate the type of substituents found on the hydrocarbon skeleton and a subscript (1, 2 or 3) to indicate the number of double bonds in the hydrocarbon skeleton e.g., PGE2. The predominant naturally occurring prostaglandins all have two double bonds and are synthesized from arachidonic acid (5,8,11,14-eicosatetraenoic acid) by the pathway shown in the illustration. The 1 series and 3 series are produced by the same pathway with fatty acids having one fewer double bond (8,11,14-eicosatrienoic acid or one more double bond (5,8,11,14,17-eicosapentaenoic acid) than arachidonic acid. The subscript a or ß indicates the configuration at C-9 (a denotes a substituent below the plane of the ring, ß, above the plane). The naturally occurring PGF's have the a configuration, e.g., PGF2a. All of the prostaglandins act by binding to specific cell-surface receptors causing an increase in the level of the intracellular second messenger cyclic AMP (and in some cases cyclic GMP also). The effect produced by the cyclic AMP increase depends on the specific cell type. In some cases there is also a positive feedback effect. Increased cyclic AMP increases prostaglandin synthesis leading to further increases in cyclic AMP. [EU] Prostaglandins A: (13E,15S)-15-Hydroxy-9-oxoprosta-10,13-dien-1-oic acid (PGA(1)); (5Z,13E,15S)-15-hydroxy-9-oxoprosta-5,10,13-trien-1-oic acid (PGA(2)); (5Z,13E,15S,17Z)-15hydroxy-9-oxoprosta-5,10,13,17-tetraen-1-oic acid (PGA(3)). A group of naturally occurring secondary prostaglandins derived from PGE. PGA(1) and PGA(2) as well as their 19hydroxy derivatives are found in many organs and tissues. [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] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] 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 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 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]
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Proteolytic: 1. Pertaining to, characterized by, or promoting proteolysis. 2. An enzyme that promotes proteolysis (= the splitting of proteins by hydrolysis of the peptide bonds with formation of smaller polypeptides). [EU] Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or vaccine dosages, length of study, routes of administration, who may participate, and other aspects of trial design. [NIH] Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] Protozoa: A subkingdom consisting of unicellular organisms that are the simplest in the animal kingdom. Most are free living. They range in size from submicroscopic to macroscopic. Protozoa are divided into seven phyla: Sarcomastigophora, Labyrinthomorpha, Apicomplexa, Microspora, Ascetospora, Myxozoa, and Ciliophora. [NIH] Pruritic: Pertaining to or characterized by pruritus. [EU] Psychotherapy: A generic term for the treatment of mental illness or emotional disturbances primarily by verbal or nonverbal communication. [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] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] Publishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing. [NIH]
Pulmonary: Relating to the lungs. [NIH] Pulmonary Edema: An accumulation of an excessive amount of watery fluid in the lungs, may be caused by acute exposure to dangerous concentrations of irritant gasses. [NIH] Pulmonary Ventilation: The total volume of gas per minute inspired or expired measured in liters per minute. [NIH] Pulse: The rhythmical expansion and contraction of an artery produced by waves of pressure caused by the ejection of blood from the left ventricle of the heart as it contracts. [NIH]
Purifying: Respiratory equipment whose function is to remove contaminants from otherwise wholesome air. [NIH] Quaternary: 1. Fourth in order. 2. Containing four elements or groups. [EU] Rabies: A highly fatal viral infection of the nervous system which affects all warm-blooded animal species. It is one of the most important of the zoonoses because of the inevitably fatal outcome for the infected human. [NIH] 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,
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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] Radiolabeled: Any compound that has been joined with a radioactive substance. [NIH] Radiotherapy: The use of ionizing radiation to treat malignant neoplasms and other benign conditions. The most common forms of ionizing radiation used as therapy are x-rays, gamma rays, and electrons. A special form of radiotherapy, targeted radiotherapy, links a cytotoxic radionuclide to a molecule that targets the tumor. When this molecule is an antibody or other immunologic molecule, the technique is called radioimmunotherapy. [NIH] Randomized: Describes an experiment or clinical trial in which animal or human subjects are assigned by chance to separate groups that compare different treatments. [NIH] 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] Reagent: A substance employed to produce a chemical reaction so as to detect, measure, produce, etc., other substances. [EU] Reassurance: A procedure in psychotherapy that seeks to give the client confidence in a favorable outcome. It makes use of suggestion, of the prestige of the therapist. [NIH] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] 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] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Red blood cells: RBCs. Cells that carry oxygen to all parts of the body. Also called erythrocytes. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH] Refractory: Not readily yielding to treatment. [EU] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Reliability: Used technically, in a statistical sense, of consistency of a test with itself, i. e. the extent to which we can assume that it will yield the same result if repeated a second time. [NIH]
Renal failure: Progressive renal insufficiency and uremia, due to irreversible and
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progressive renal glomerular tubular or interstitial disease. [NIH] Replicon: In order to be replicated, DNA molecules must contain an origin of duplication and in bacteria and viruses there is usually only one per genome. Such molecules are called replicons. [NIH] Research Design: A plan for collecting and utilizing data so that desired information can be obtained with sufficient precision or so that an hypothesis can be tested properly. [NIH] Respiration: The act of breathing with the lungs, consisting of inspiration, or the taking into the lungs of the ambient air, and of expiration, or the expelling of the modified air which contains more carbon dioxide than the air taken in (Blakiston's Gould Medical Dictionary, 4th ed.). This does not include tissue respiration (= oxygen consumption) or cell respiration (= cell respiration). [NIH] Respiratory failure: Inability of the lungs to conduct gas exchange. [NIH] Respiratory Mucosa: The mucous membrane lining the respiratory tract. [NIH] Respiratory System: The tubular and cavernous organs and structures, by means of which pulmonary ventilation and gas exchange between ambient air and the blood are brought about. [NIH] Retrograde: 1. Moving backward or against the usual direction of flow. 2. Degenerating, deteriorating, or catabolic. [EU] 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] 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] Ricin: A protein phytotoxin from the seeds of Ricinus communis, the castor oil plant. It agglutinates cells, is proteolytic, and causes lethal inflammation and hemorrhage if taken internally. [NIH] Rickettsia: A genus of gram-negative, aerobic, rod-shaped bacteria often surrounded by a protein microcapsular layer and slime layer. The natural cycle of its organisms generally involves a vertebrate and an invertebrate host. Species of the genus are the etiological agents of human diseases, such as typhus. [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]
Rigidity: Stiffness or inflexibility, chiefly that which is abnormal or morbid; rigor. [EU] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Risk patient: Patient who is at risk, because of his/her behaviour or because of the type of person he/she is. [EU] Rod: A reception for vision, located in the retina. [NIH] Ruthenium: A hard, brittle, grayish-white rare earth metal with an atomic symbol Ru, atomic number 44, and atomic weight 101.07. It is used as a catalyst and hardener for platinum and palladium. [NIH] Sanatorium: This category applies to all those institutions partially or wholly devoted to the diagnosis and treatment of tuberculosis. [NIH] Sanitation: The development and establishment of environmental conditions favorable to
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the health of the public. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Sebaceous: Gland that secretes sebum. [NIH] Segregation: The separation in meiotic cell division of homologous chromosome pairs and their contained allelomorphic gene pairs. [NIH] Senescence: The bodily and mental state associated with advancing age. [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] Sepsis: The presence of bacteria in the bloodstream. [NIH] Sequence Homology: The degree of similarity between sequences. Studies of amino acid and nucleotide sequences provide useful information about the genetic relatedness of certain species. [NIH] Sequencing: The determination of the order of nucleotides in a DNA or RNA chain. [NIH] 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] Serologic: Analysis of a person's serum, especially specific immune or lytic serums. [NIH] Serous: Having to do with serum, the clear liquid part of blood. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Serum Albumin: A major plasma protein that serves in maintaining the plasma colloidal osmotic pressure and transporting large organic anions. [NIH] Sexually Transmitted Diseases: Diseases due to or propagated by sexual contact. [NIH] Shiga Toxin: A toxin produced by Shigella dysenteriae. It is the protype of class of toxins that inhibit protein synthesis by blocking the interaction of ribosomal RNA with peptide elongation factors. [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] Signal Transduction: The intercellular or intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GABA-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptormediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet
Dictionary 209
activation signal pathway. [NIH] Sindbis Virus: The type species of alphavirus normally transmitted to birds by Culex mosquitoes in Egypt, South Africa, India, Malaya, the Philippines, and Australia. It may be associated with fever in humans. [NIH] Skeletal: Having to do with the skeleton (boney part of the body). [NIH] Skeleton: The framework that supports the soft tissues of vertebrate animals and protects many of their internal organs. The skeletons of vertebrates are made of bone and/or cartilage. [NIH] 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] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] 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] Spectrometer: An apparatus for determining spectra; measures quantities such as wavelengths and relative amplitudes of components. [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] Spirochete: Lyme disease. [NIH] Spores: The reproductive elements of lower organisms, such as protozoa, fungi, and cryptogamic plants. [NIH] Sputum: The material expelled from the respiratory passages by coughing or clearing the throat. [NIH] Steel: A tough, malleable, iron-based alloy containing up to, but no more than, two percent carbon and often other metals. It is used in medicine and dentistry in implants and instrumentation. [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] Sterile: Unable to produce children. [NIH] 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]
210 Bioterrorism
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] 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] 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] Substrate: A substance upon which an enzyme acts. [EU] Suction: The removal of secretions, gas or fluid from hollow or tubular organs or cavities by means of a tube and a device that acts on negative pressure. [NIH] Surfactant: A fat-containing protein in the respiratory passages which reduces the surface tension of pulmonary fluids and contributes to the elastic properties of pulmonary tissue. [NIH]
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] Tachycardia: Excessive rapidity in the action of the heart, usually with a heart rate above 100 beats per minute. [NIH] Tachypnea: Rapid breathing. [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] Terbium: Terbium. An element of the rare earth family of metals. It has the atomic symbol Tb, atomic number 65, and atomic weight 158.92. [NIH] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thermal: Pertaining to or characterized by heat. [EU] 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] 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]
Dictionary 211
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] Ticks: Blood-sucking arachnids of the order Acarina. [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] Tooth Preparation: Procedures carried out with regard to the teeth or tooth structures preparatory to specified dental therapeutic and surgical measures. [NIH] Topical: On the surface of the body. [NIH] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicologic: Pertaining to toxicology. [EU] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxins: Specific, characterizable, poisonous chemicals, often proteins, with specific biological properties, including immunogenicity, produced by microbes, higher plants, or animals. [NIH] Toxoplasma: A genus of protozoa parasitic to birds and mammals. T. gondii is one of the most common infectious pathogenic animal parasites of man. [NIH] Tracer: A substance (such as a radioisotope) used in imaging procedures. [NIH] Traction: The act of pulling. [NIH] Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process. [NIH] Transcutaneous: Transdermal. [EU] 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] 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] 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]
212 Bioterrorism
Tropism: Directed movements and orientations found in plants, such as the turning of the sunflower to face the sun. [NIH] Tubercle: A rounded elevation on a bone or other structure. [NIH] Tuberculin: A sterile liquid containing the growth products of, or specific substances extracted from, the tubercle bacillus; used in various forms in the diagnosis of tuberculosis. [NIH]
Tuberculosis: Any of the infectious diseases of man and other animals caused by species of Mycobacterium. [NIH] Tularemia: A plague-like disease of rodents, transmissible to man. It is caused by Francisella tularensis and is characterized by fever, chills, headache, backache, and weakness. [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] TYPHI: The bacterium that gives rise to typhoid fever. [NIH] Typhimurium: Microbial assay which measures his-his+ reversion by chemicals which cause base substitutions or frameshift mutations in the genome of this organism. [NIH] Typhoid fever: The most important member of the enteric group of fevers which also includes the paratyphoids. [NIH] Typhoid fever: The most important member of the enteric group of fevers which also includes the paratyphoids. [NIH] Ulceration: 1. The formation or development of an ulcer. 2. An ulcer. [EU] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Ureters: Tubes that carry urine from the kidneys to the bladder. [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]
Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] Urinary tract: The organs of the body that produce and discharge urine. These include the kidneys, ureters, bladder, and urethra. [NIH] Urinary tract infection: An illness caused by harmful bacteria growing in the urinary tract. [NIH]
Urine: Fluid containing water and waste products. Urine is made by the kidneys, stored in the bladder, and leaves the body through the urethra. [NIH] Vaccination: Administration of vaccines to stimulate the host's immune response. This includes any preparation intended for active immunological prophylaxis. [NIH] Vaccine: A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. [NIH] Vaccinia: The cutaneous and occasional systemic reactions associated with vaccination using smallpox (variola) vaccine. [NIH] Vaccinia Virus: The type species of Orthopoxvirus, related to cowpox virus, but whose true origin is unknown. It has been used as a live vaccine against smallpox. It is also used as a vector for inserting foreign DNA into animals. Rabbitpox virus is a subspecies of vaccinia
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virus. [NIH] Vacuoles: Any spaces or cavities within a cell. They may function in digestion, storage, secretion, or excretion. [NIH] Vagina: The muscular canal extending from the uterus to the exterior of the body. Also called the birth canal. [NIH] Varicella: Chicken pox. [EU] Variola: A generalized virus infection with a vesicular rash. [NIH] Variola Virus: A species of Orthopoxvirus causing infections in humans. No infections have been reported since 1977 and the virus is now believed to be virtually extinct. [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vasodilators: Any nerve or agent which induces dilatation of the blood vessels. [NIH] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH] Vegetative: 1. Concerned with growth and with nutrition. 2. Functioning involuntarily or unconsciously, as the vegetative nervous system. 3. Resting; denoting the portion of a cell cycle during which the cell is not involved in replication. 4. Of, pertaining to, or characteristic of plants. [EU] 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] Vesicular: 1. Composed of or relating to small, saclike bodies. 2. Pertaining to or made up of vesicles on the skin. [EU] Veterinarians: Individuals with a degree in veterinary medicine that provides them with training and qualifications to treat diseases and injuries of animals. [NIH] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Vibrio: A genus of Vibrionaceae, made up of short, slightly curved, motile, gram-negative rods. Various species produce cholera and other gastrointestinal disorders as well as abortion in sheep and cattle. [NIH] Vibrio cholerae: The etiologic agent of cholera. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Virion: The infective system of a virus, composed of the viral genome, a protein core, and a protein coat called a capsid, which may be naked or enclosed in a lipoprotein envelope called the peplos. [NIH] Virologist: A specialist of the study of viruses and viral disease. [NIH] Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [NIH] Virulent: A virus or bacteriophage capable only of lytic growth, as opposed to temperate phages establishing the lysogenic response. [NIH]
214 Bioterrorism
Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH] Virus Diseases: A general term for diseases produced by viruses. [NIH] Virus Replication: The process of intracellular viral multiplication, consisting of the synthesis of proteins, nucleic acids, and sometimes lipids, and their assembly into a new infectious particle. [NIH] Visceral: , from viscus a viscus) pertaining to a viscus. [EU] Visual Acuity: Acuteness or clearness of vision, especially of form vision, which is dependent mainly on the sharpness of the retinal focus. [NIH] Vitro: Descriptive of an event or enzyme reaction under experimental investigation occurring outside a living organism. Parts of an organism or microorganism are used together with artificial substrates and/or conditions. [NIH] Vivo: Outside of or removed from the body of a living organism. [NIH] Vulgaris: An affection of the skin, especially of the face, the back and the chest, due to chronic inflammation of the sebaceous glands and the hair follicles. [NIH] War: Hostile conflict between organized groups of people. [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]
Whole cell vaccine: Vaccine made from whole tumor cells that have been changed in the laboratory. [NIH] Xenograft: The cells of one species transplanted to another species. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH] X-ray therapy: The use of high-energy radiation from x-rays to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. X-ray therapy is also called radiation therapy, radiotherapy, and irradiation. [NIH] Yeasts: A general term for single-celled rounded fungi that reproduce by budding. Brewers' and bakers' yeasts are Saccharomyces cerevisiae; therapeutic dried yeast is dried yeast. [NIH] Yellow Fever: An acute infectious disease primarily of the tropics, caused by a virus and transmitted to man by mosquitoes of the genera Aedes and Haemagogus. [NIH] Yellow Fever Virus: The type species of the Flavivirus genus. Principal vector transmission to humans is by Aedes spp. mosquitoes. [NIH] Zoonosis: Disease of animals, e. g. rabies, that can be transmitted to humans. A risk in major disasters; any disease and/or infection which is likely to be naturally transmitted from animals to man; disease caused by animal parasites. [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,
Dictionary 215
usually by excision of a polypeptide, e. g. trypsinogen is the zymogen of trypsin. [NIH]
217
INDEX 3 3-dimensional, 6, 169, 204 A Abdomen, 169, 175, 194, 210 Abdominal, 169, 186, 200 Acceptor, 110, 169, 200 Acetylcholine, 169, 198 Acoustic, 43, 169 Adaptation, 6, 9, 169 Adenosine, 169, 193, 201 Adenylate Cyclase, 49, 169, 177 Adjustment, 169 Adjuvant, 14, 40, 169, 170 Adolescence, 169, 200 Adverse Effect, 40, 169, 208 Aerobic, 169, 207 Aerosol, 6, 7, 10, 14, 18, 34, 43, 44, 49, 170 Affinity, 40, 43, 44, 49, 170 Age Groups, 44, 170 Aged, 80 and Over, 170 Agglutinins, 166, 170 Airway, 25, 170 Algorithms, 10, 45, 170, 174 Alleles, 27, 170 Alpha Particles, 170, 205 Alpha-helices, 45, 170 Alphavirus, 5, 29, 35, 170, 209 Alternative medicine, 135, 170 Aluminum, 21, 40, 170 Aluminum Hydroxide, 40, 170 Amino Acid Sequence, 170, 172, 186 Amino Acids, 14, 170, 171, 186, 199, 201, 202, 204, 207, 208, 211 Amplification, 6, 10, 28, 38, 115, 171 Anaesthesia, 171, 191 Anal, 22, 171 Analog, 24, 45, 48, 171 Analogous, 171, 182, 211 Analytes, 112, 113, 171 Anaphylatoxins, 171, 179 Anesthesia, 170, 171 Animal Husbandry, 18, 171 Animal model, 24, 25, 32, 171 Anions, 171, 193, 208 Annealing, 171, 202 Anorexia, 171, 186 Antibacterial, 171, 182, 209
Antibiotic, 4, 14, 18, 23, 49, 76, 171, 175, 209 Antibodies, 8, 14, 29, 39, 41, 170, 172, 188, 190, 194, 197, 202 Anticoagulant, 172, 204 Antifungal, 29, 172 Antigen, 5, 7, 8, 17, 19, 22, 23, 37, 40, 41, 49, 170, 172, 179, 181, 189, 190, 191 Antigen-Antibody Complex, 172, 179 Antigen-presenting cell, 5, 172, 181 Anti-infective, 102, 172 Anti-Infective Agents, 102, 172 Antimicrobial, 14, 16, 18, 44, 85, 92, 124, 172 Antiproliferative, 172, 192 Antiseptic, 172, 177 Antiviral, 10, 26, 28, 47, 56, 77, 86, 89, 94, 172, 192, 201 Antiviral Agents, 10, 172 Anus, 171, 172, 192 Anxiety, 44, 102, 147, 172 Aplasia, 172, 182 Apoptosis, 11, 172 Applicability, 47, 173 Aqueous, 117, 120, 173, 174, 180, 193 Arachidonic Acid, 173, 204 Arenavirus, 33, 39, 173, 194 Arginine, 171, 173, 198 Aromatic, 14, 45, 173 Arterial, 173, 204 Arteries, 173, 175, 180, 195 Aseptic, 173, 194, 199 Assay, 9, 10, 20, 23, 24, 28, 29, 38, 43, 45, 46, 49, 113, 173, 190, 212 Atopic, 41, 173 Attenuated, 5, 6, 7, 22, 30, 44, 173, 181 Attenuation, 22, 173 Autoimmune disease, 173 Autoimmunity, 52, 173 Avian, 14, 44, 173 B Bacillus, 7, 8, 9, 14, 23, 27, 32, 38, 40, 42, 49, 65, 76, 114, 171, 173, 212 Bacteremia, 9, 173, 195 Bacterial Infections, 19, 146, 173 Bacterial Physiology, 169, 173 Bactericidal, 173, 177 Bacteriophage, 173, 213
218 Bioterrorism
Bacterium, 19, 30, 40, 49, 173, 178, 212 Base, 7, 36, 47, 120, 174, 180, 181, 186, 193, 210, 212 Benign, 174, 186, 188, 194, 206 Bile, 174, 189, 194 Binding Sites, 34, 174 Biochemical, 26, 32, 35, 40, 115, 170, 174, 185, 193 Bioengineering, 64, 140, 174 Biofilms, 50, 174 Biological response modifier, 174, 192 Biological Transport, 174, 181 Biomarkers, 12, 17, 41, 68, 174 Biopolymers, 43, 174 Biosynthesis, 14, 173, 174, 208 Biotechnology, 52, 54, 58, 62, 92, 129, 135, 141, 174 Biotin, 174, 199 Bivalent, 6, 175 Bladder, 175, 204, 212 Blood Platelets, 175, 210 Blood pressure, 175, 196 Blood transfusion, 124, 175 Blood vessel, 175, 183, 194, 210, 213 Blot, 15, 175, 199 Body Fluids, 174, 175, 183, 212 Bone Marrow, 175, 190, 194, 197 Bowel, 171, 175 Brachytherapy, 175, 192, 193, 206, 214 Bradykinin, 175, 198, 202 Branch, 163, 175, 194, 200, 205, 209, 210 Breakdown, 175, 181, 186 Breeding, 171, 175 Broad-spectrum, 14, 175 Bronchi, 175 Bronchial, 11, 175, 189 Brucellosis, 15, 78, 147, 175 C Calcium, 175, 176, 178, 183, 204, 208 Calmodulin, 23, 176 Capsid, 176, 199, 213 Capsular, 22, 176 Carbohydrate, 176, 203 Carbon Dioxide, 176, 186, 207 Carcinogenic, 176, 192, 203 Castor Oil, 176, 207 Caveolae, 11, 176 Caveolins, 176, 178 Cell Cycle, 176, 213 Cell Death, 172, 176, 197 Cell Division, 173, 176, 195, 196, 202, 203, 208
Cell membrane, 31, 174, 176, 195 Cell Membrane Structures, 176 Cell Respiration, 176, 207 Cell Size, 176, 185 Cellulose, 177, 186, 202 Central Nervous System, 169, 177, 186, 187, 188 Cetylpyridinium, 113, 177 Chemical Warfare, 42, 111, 112, 116, 177, 180 Chemical Warfare Agents, 42, 111, 112, 116, 177, 180 Chemokines, 12, 30, 32, 177 Chemotactic Factors, 177, 179 Chlorine, 26, 177 Chlorophyll, 177, 186 Cholera, 14, 24, 177, 213 Cholera Toxin, 24, 177 Cholesterol, 174, 176, 177 Chromatin, 172, 177, 198 Chromosomal, 171, 177, 202 Chromosome, 28, 177, 188, 193, 208 Chronic, 16, 124, 177, 191, 210, 214 Chronic Disease, 124, 177 Civilization, 38, 129, 178 Clamp, 111, 178 Clathrin, 178, 183 Clear cell carcinoma, 178, 181 Clinical trial, 4, 6, 18, 19, 39, 47, 141, 178, 205, 206 Clone, 42, 178 Cloning, 14, 20, 174, 178 Coated Vesicles, 178, 183 Codons, 178, 186, 199 Cofactor, 178, 204, 210 Collagen, 178, 185, 202, 203 Colloidal, 178, 208 Combinatorial, 11, 45, 178 Communis, 176, 178, 207 Competency, 124, 178 Complement, 48, 171, 178, 179, 187, 202 Complement Activation, 48, 171, 179 Complementary and alternative medicine, 101, 105, 179 Complementary medicine, 98, 101, 102, 179 Computational Biology, 141, 179 Concomitant, 79, 179 Conjunctiva, 179, 191 Connective Tissue, 175, 178, 179, 185, 194 Consultation, 21, 179 Consumption, 6, 179, 186, 200
Index 219
Contamination, 34, 50, 110, 114, 117, 120, 179 Contraindications, ii, 179 Convalescence, 22, 180 Cornea, 57, 78, 180, 214 Coronary, 180, 195 Coronary Thrombosis, 180, 195 Cowpox, 180, 212 Cowpox Virus, 180, 212 Critical Care, 58, 79, 180 Crossing-over, 180, 206 Crystallization, 15, 180 Cultured cells, 23, 180 Curative, 180, 210 Cutaneous, 4, 8, 41, 153, 171, 180, 193, 212 Cyclic, 169, 176, 180, 187, 198, 204 Cysteine, 177, 180 Cytokine, 30, 32, 33, 180, 192 Cytoplasm, 172, 176, 177, 180, 184, 197, 198, 207 Cytoplasmic Vesicles, 180, 201 Cytosine, 120, 180 Cytotoxic, 27, 180, 206, 208 Cytotoxicity, 11, 180 D Data Collection, 113, 180, 185 Databases, Bibliographic, 141, 180 Decontamination, 34, 112, 113, 114, 115, 180 Dehydration, 177, 181 Deletion, 51, 172, 181 Denaturation, 181, 202 Dendrites, 181, 198 Dendritic, 6, 31, 52, 181 Dendritic cell, 6, 31, 52, 181 Density, 20, 116, 181, 185, 199 Dentifrices, 170, 181 Dentists, 95, 181 Deoxyribonucleic, 28, 110, 181 Deoxyribonucleic acid, 110, 181 Deoxyribonucleotides, 181 Dermal, 41, 181 Dermatitis, 41, 181, 183 DES, 11, 171, 181 Diagnostic procedure, 109, 135, 181 Diarrhea, 8, 181 Diarrhoea, 181, 186 Diffusion, 47, 174, 181, 191 Digestion, 47, 174, 175, 181, 194, 210, 213 Dilatation, 181, 203, 213 Dilution, 10, 181 Diploid, 181, 202
Direct, iii, 14, 30, 42, 120, 181, 188, 200, 206 Disaster Planning, 125, 126, 132, 181 Disease Outbreaks, 5, 72, 86, 130, 181 Disease Transmission, 124, 182 Disease Transmission, Horizontal, 182 Disease Transmission, Vertical, 182 Disinfection, 116, 119, 182 Dissociation, 170, 182, 192 Domesticated, 182, 188 Drive, ii, vi, 7, 97, 114, 182 Drug Design, 17, 182 Drug Interactions, 182 Drug Resistance, 124, 182 Drug Tolerance, 182 Dura mater, 182, 195, 200 Dyes, 4, 182, 185, 198 E Ectromelia, 31, 43, 48, 182, 183 Ectromelia Virus, 43, 48, 183 Eczema, 41, 183 Edema, 23, 24, 27, 32, 49, 183 Effector, 22, 41, 52, 169, 178, 183 Efficacy, 6, 7, 8, 10, 14, 17, 23, 31, 40, 41, 46, 51, 52, 182, 183 Electrolytes, 174, 177, 183 Electrons, 174, 183, 192, 193, 200, 205, 206 Embryo, 33, 183, 191 Empirical, 36, 183 Encapsulated, 40, 183 Encephalitis, 6, 34, 48, 74, 183 Encephalitis, Viral, 183 Endemic, 26, 30, 67, 167, 177, 183 Endocytosis, 24, 49, 176, 183 Endosomes, 15, 183 Endothelial cell, 30, 183, 210 Endothelium, 30, 183, 184, 198 Endothelium, Lymphatic, 183 Endothelium, Vascular, 183, 184 Endothelium-derived, 184, 198 Endotoxic, 184, 193 Endotoxins, 179, 184 Environmental Health, 55, 140, 142, 146, 184 Enzymatic, 11, 49, 176, 179, 184, 189, 202 Enzyme Inhibitors, 23, 184, 202 Epidemic, 5, 26, 84, 128, 184, 196 Epithelial, 11, 25, 44, 174, 177, 184 Epithelial Cells, 25, 44, 177, 184 Epithelium, 11, 183, 184, 214 Epitope, 17, 184 Erythrocytes, 175, 184, 206 Evacuation, 111, 184
220 Bioterrorism
Excitation, 184, 185 Excitatory, 184, 187 Exogenous, 183, 184, 201 Exotoxin, 9, 184 Expiration, 184, 207 External-beam radiation, 184, 193, 206, 214 Extracellular, 39, 174, 179, 183, 185, 196 Extraction, 28, 185 F Family Planning, 141, 185 Fat, 173, 175, 185, 193, 210 Fatty acids, 185, 204 Febrile, 10, 166, 185, 188 Fibroblasts, 185, 192 Fibrosis, 16, 185 Filovirus, 10, 33, 185 Filtration, 111, 185 Flaccid, 24, 185 Flatus, 185, 186 Flavivirus, 28, 48, 185, 214 Flow Cytometry, 12, 17, 185 Fluorescence, 4, 6, 47, 185 Fluorescent Dyes, 185 Focus Groups, 36, 94, 185 Fold, 35, 49, 52, 185 Food Contamination, 50, 185 Frameshift, 186, 212 Frameshift Mutation, 186, 212 Fungi, 14, 119, 172, 186, 195, 196, 209, 214 Fungus, 101, 186 G Ganglion, 186, 214 Gas, 111, 113, 118, 148, 176, 177, 181, 185, 186, 189, 198, 205, 207, 210 Gas exchange, 186, 207 Gastric, 170, 186, 189 Gastrin, 186, 189 Gastroenteritis, 14, 186 Gastrointestinal, 8, 153, 175, 186, 212, 213 Gene, 6, 8, 11, 18, 20, 27, 38, 44, 51, 52, 129, 170, 174, 186, 187, 199, 208 Gene Expression, 11, 38, 44, 186 Genetic Code, 186, 199 Genetic Engineering, 174, 178, 187 Genetic testing, 187, 202 Genetics, 11, 26, 27, 30, 34, 35, 37, 41, 187 Genomics, 26, 32, 52, 64, 187 Genotype, 187, 201 Gland, 187, 194, 200, 204, 208, 209 Glanders, 16, 51, 78, 148, 187, 195 Glucuronic Acid, 187, 188
Glutamate, 187 Glutamic Acid, 23, 187, 203 Glycoprotein, 6, 11, 45, 187, 210 Glycosidic, 187, 198, 199 Governing Board, 187, 203 Gp120, 187, 201 Grade, 14, 187 Graft, 187, 189, 191 Graft Rejection, 187, 191 Gram-negative, 51, 184, 187, 207, 213 Growth, 115, 169, 171, 172, 173, 174, 176, 187, 192, 199, 202, 212, 213 Guanylate Cyclase, 187, 198 Guinea Pigs, 5, 188, 194 H Habitat, 188, 198 Hair follicles, 188, 214 Haploid, 188, 202 Haptens, 170, 188 Hazardous Substances, 115, 188 Headache, 166, 188, 191, 212 Heme, 35, 188 Hemoglobin, 184, 188 Hemorrhage, 188, 207 Hemorrhagic Fever with Renal Syndrome, 17, 188 Heparin, 48, 188 Heredity, 186, 187, 188 Herpes, 65, 189 Herpes Zoster, 189 Heterodimers, 11, 189 Heterogeneity, 47, 170, 189 Heterotrophic, 186, 189 Histamine, 171, 189 Histidine, 23, 189 Homogeneous, 46, 189 Homologous, 5, 48, 170, 175, 180, 189, 197, 208 Hormone, 134, 181, 186, 189, 195, 208 Horseradish Peroxidase, 13, 189 Hospital Information Systems, 119, 189 Humoral, 19, 22, 29, 40, 41, 43, 187, 189 Humour, 189 Hybrid, 178, 189, 199 Hybridization, 7, 16, 39, 110, 189, 199 Hydrogen, 169, 174, 176, 181, 189, 196, 198, 199, 200, 201, 205 Hydrogen Bonding, 189, 199 Hydrolysis, 190, 193, 198, 202, 205 Hydrophilic, 117, 190 Hydrophobic, 117, 190
Index 221
I Id, 99, 104, 146, 147, 151, 152, 155, 162, 164, 190 Imidazole, 23, 174, 189, 190 Immune function, 46, 190 Immune Sera, 190 Immune system, 31, 32, 33, 37, 43, 172, 173, 190, 191, 194, 197, 212, 214 Immunity, 5, 7, 19, 22, 23, 26, 31, 32, 33, 37, 41, 43, 44, 52, 66, 190, 194, 211 Immunization, 5, 6, 8, 18, 22, 23, 39, 40, 51, 117, 190, 191 Immunoassay, 12, 34, 190 Immunocompromised, 29, 43, 190 Immunocompromised Host, 43, 190 Immunodeficiency, 190 Immunofluorescence, 15, 190 Immunogen, 6, 190 Immunogenic, 19, 190, 193 Immunoglobulin, 172, 190, 197 Immunologic, 18, 44, 177, 190, 194, 206 Immunology, 5, 7, 12, 15, 16, 17, 23, 25, 31, 35, 37, 40, 41, 43, 45, 52, 169, 170, 185, 189, 190 Immunosuppressive, 190, 191 Immunosuppressive therapy, 191 Immunotherapy, 29, 39, 191 Implant radiation, 191, 192, 193, 206, 214 In vitro, 5, 8, 10, 11, 23, 25, 30, 31, 35, 39, 49, 51, 191, 202, 211 In vivo, 8, 11, 12, 25, 31, 35, 39, 48, 188, 191 Indicative, 125, 191, 200, 213 Induction, 25, 28, 33, 37, 40, 44, 120, 191 Infant, Newborn, 170, 191 Infarction, 180, 191, 195 Infection, 3, 5, 8, 9, 11, 12, 16, 17, 18, 23, 25, 28, 30, 33, 34, 35, 37, 39, 40, 41, 43, 44, 46, 48, 49, 51, 56, 60, 71, 80, 83, 87, 93, 94, 103, 116, 117, 125, 126, 132, 134, 153, 171, 172, 173, 174, 175, 177, 180, 183, 186, 190, 191, 193, 194, 195, 198, 199, 205, 209, 210, 213, 214 Infection Control, 16, 60, 71, 87, 93, 94, 132, 191 Infiltration, 191, 214 Inflammation, 11, 37, 181, 183, 185, 186, 189, 191, 195, 200, 207, 214 Influenza, 43, 44, 46, 71, 72, 86, 89, 191, 194 Information Science, 191, 195 Information Systems, 119, 191 Ingestion, 171, 188, 191, 202
Inhalation, 8, 10, 22, 111, 170, 188, 191, 202 Initiation, 31, 191, 211 Inorganic, 35, 192 Insight, 15, 26, 192 Interferon, 25, 44, 192 Interferon-alpha, 192 Interferon-beta, 25, 192 Interleukin-1, 11, 192 Interleukin-2, 192 Internal radiation, 192, 193, 206, 214 Interstitial, 175, 192, 193, 195, 207, 214 Intestinal, 4, 177, 192 Intestines, 169, 186, 192 Intoxication, 49, 79, 192 Intracellular, 15, 22, 27, 30, 39, 178, 180, 191, 192, 195, 198, 204, 207, 208, 214 Intracellular Membranes, 180, 192, 195 Intramuscular, 40, 192 Intravenous, 35, 167, 192 Intrinsic, 170, 192 Invasive, 190, 192 Ionization, 11, 192 Ionizing, 47, 170, 192, 206 Ions, 174, 176, 182, 183, 189, 192, 193 Irradiation, 87, 193, 214 K Kb, 140, 193 Kinesin, 27, 193 Kinetic, 192, 193, 201 L Labile, 178, 193 Lectin, 32, 193, 195 Leishmaniasis, 51, 193 Lens, 176, 193 Lesion, 30, 193 Lethal, 6, 10, 16, 19, 23, 27, 32, 49, 115, 117, 118, 173, 193, 207 Leukemia, 35, 45, 193 Leukocytes, 175, 177, 192, 193, 197, 198 Library Services, 162, 193 Life cycle, 186, 193 Ligands, 32, 193 Linkages, 188, 193, 198 Lipid, 19, 120, 176, 193 Lipid A, 19, 120, 193 Lipopolysaccharide, 30, 187, 193 Liver, 22, 44, 169, 173, 174, 175, 187, 188, 194 Localized, 183, 191, 194, 202 Locomotion, 194, 202 Lymph, 166, 183, 189, 194 Lymph node, 166, 194
222 Bioterrorism
Lymphatic, 184, 191, 194, 211 Lymphatic system, 194, 211 Lymphocyte, 16, 172, 194 Lymphocytic, 33, 39, 194 Lymphocytic Choriomeningitis Virus, 33, 39, 194 Lymphoid, 7, 172, 194 Lymphokines, 194 Lysosome, 194, 201 Lytic, 194, 208, 213 M Macrophage, 27, 37, 192, 194 Macrophage Activation, 37, 194 Malaise, 166, 175, 194 Manifest, 117, 194 Mannans, 186, 194 Mass Screening, 42, 194 Meat, 113, 195 Mediate, 45, 195 Medical Informatics, 26, 84, 88, 195 MEDLINE, 141, 195 Meiosis, 175, 195, 197 Melioidosis, 16, 51, 78, 148, 195 Membrane Fusion, 47, 195 Membrane Proteins, 176, 195 Memory, 14, 22, 41, 52, 171, 195 Meninges, 177, 182, 195 Meningitis, 4, 33, 194, 195 Mental Health, iv, 4, 36, 66, 130, 140, 142, 147, 195, 205 Mercury, 185, 195 Metaphase, 175, 195 MI, 63, 112, 116, 167, 195 Microbe, 195, 211 Microbiological, 38, 68, 82, 195 Microorganism, 110, 178, 196, 200, 214 Microscopy, 15, 189, 196 Microspheres, 29, 196 Microtubules, 193, 196 Migration, 41, 194, 196 Mitogen-Activated Protein Kinase Kinases, 23, 196 Mitogen-Activated Protein Kinases, 196 Mitosis, 173, 196 Modeling, 12, 24, 76, 127, 182, 196 Molecular mass, 23, 196 Monitor, 42, 47, 119, 196, 198 Monkeypox Virus, 39, 146, 196 Monoclonal, 4, 8, 9, 28, 31, 34, 39, 52, 113, 193, 197, 206, 214 Monoclonal antibodies, 8, 28, 31, 34, 39, 52, 197
Monocytes, 15, 30, 192, 193, 197 Mononuclear, 30, 197 Morphological, 183, 186, 197 Morphology, 194, 197 Mucocutaneous, 193, 197 Multivalent, 7, 197 Mutagenesis, 22, 32, 43, 50, 197 Mutagens, 186, 197 Mutate, 41, 197 Myalgia, 191, 197 Myocardium, 195, 197 N Naive, 46, 197 Nasal Mucosa, 191, 197 Nausea, 186, 197 Necrosis, 172, 191, 195, 197 Needs Assessment, 71, 197 Neonatal, 8, 58, 197 Nerve, 79, 171, 181, 186, 197, 198, 200, 209, 213, 214 Nervous System, 177, 197, 198, 205, 213 Networks, 34, 198 Neural, 34, 189, 198 Neuraminidase, 44, 198 Neurologist, 86, 198 Neurons, 24, 181, 184, 198 Neurotoxic, 198 Neurotoxins, 24, 198 Neutralization, 6, 34, 41, 48, 198 Neutrons, 170, 193, 198, 205 Neutrophils, 30, 193, 198 Niche, 15, 22, 198 Nitric Oxide, 11, 198 Nitrogen, 21, 196, 198 Nosocomial, 16, 198 Nuclear, 11, 183, 186, 197, 198 Nucleic acid, 6, 9, 28, 29, 110, 115, 119, 120, 176, 180, 186, 189, 197, 198, 199, 214 Nucleic Acid Hybridization, 29, 189, 199 Nucleic Acid Probes, 7, 199 Nucleocapsid, 25, 199 Nucleus, 172, 177, 180, 195, 197, 198, 199, 203, 205, 210 O Ocular, 30, 199 Odour, 173, 199 Oligonucleotide Probes, 29, 199 Oligosaccharides, 198, 199 Opacity, 181, 199 Open Reading Frames, 31, 199 Ophthalmologist, 77, 199 Opportunistic Infections, 8, 199
Index 223
Oral Health, 3, 199 Organ Culture, 25, 199, 211 Organelles, 178, 180, 193, 197, 199 Orthopoxvirus, 31, 180, 183, 196, 199, 212, 213 Osmotic, 200, 208 Oxidation, 169, 200 Oxygen Consumption, 200, 207 P Pachymeningitis, 195, 200 Palladium, 200, 207 Palliative, 200, 210 Pancreas, 169, 174, 175, 200, 212 Paralysis, 24, 200 Parasite, 200 Parasitic, 50, 200, 207, 211 Parasitic Diseases, 51, 200 Particle, 5, 6, 115, 200, 214 Pathogen, 6, 8, 10, 15, 20, 22, 25, 31, 38, 39, 40, 50, 56, 84, 114, 200 Pathogenesis, 4, 12, 14, 15, 19, 20, 25, 26, 27, 35, 37, 43, 48, 79, 200 Pathologic, 173, 180, 200 Pathologic Processes, 173, 200 Pathophysiology, 33, 200 Patient Education, 150, 160, 162, 167, 200 Pediatrics, 16, 19, 27, 38, 43, 66, 76, 84, 98, 148, 149, 200 Peptide, 45, 49, 177, 201, 202, 204, 205, 208 Peptide Elongation Factors, 201, 208 Peptide T, 49, 201 PH, 4, 90, 201 Phagosomes, 15, 201 Pharmacist, 59, 201 Pharmacokinetics, 182, 201 Pharmacologic, 23, 95, 171, 201, 211 Pharynx, 191, 201 Phenotypes, 51, 201 Phocomelia, 183, 201 Phosphorus, 176, 201 Phosphorylate, 196, 201 Phosphorylated, 196, 201 Phosphorylation, 27, 196, 201 Physiologic, 79, 174, 201, 204, 206 Physiology, 32, 201 Phytotoxin, 201, 207 Pilot Projects, 17, 31, 201 Pilot study, 201 Plague Vaccine, 25, 134, 202 Plants, 14, 113, 119, 174, 175, 176, 193, 197, 198, 201, 202, 209, 211, 212, 213
Plasma, 11, 42, 172, 176, 180, 184, 188, 202, 208 Plasma cells, 172, 202 Plasma protein, 184, 202, 208 Plasmid, 23, 202, 213 Platelet Aggregation, 171, 198, 202 Platelets, 198, 202 Platinum, 200, 202, 207 Poisoning, 24, 186, 192, 195, 197, 202 Polymerase, 11, 28, 34, 65, 172, 202 Polymerase Chain Reaction, 28, 34, 65, 202 Polymers, 6, 21, 113, 174, 202, 204 Polypeptide, 170, 178, 189, 202, 204, 215 Polysaccharide, 19, 172, 177, 203 Polyvalent, 49, 203 Port, 110, 203 Port-a-cath, 203 Posterior, 171, 200, 203 Postnatal, 203, 209 Potentiates, 192, 203 Practice Guidelines, 142, 151, 203 Preclinical, 6, 32, 134, 203 Precursor, 173, 183, 184, 203 Prenatal, 183, 203 Preventive Medicine, 77, 161, 203 Probe, 7, 8, 40, 199, 203 Progression, 12, 25, 171, 203 Progressive, 16, 25, 182, 187, 197, 203, 206 Proline, 40, 178, 203 Promoter, 7, 11, 203 Prophase, 175, 197, 203 Prophylaxis, 32, 75, 154, 155, 172, 203, 212 Proportional, 42, 47, 203 Prospective study, 64, 203 Prostaglandin, 23, 204 Prostaglandins A, 204 Prostate, 174, 204, 212 Protease, 49, 204 Protective Clothing, 115, 204 Protein C, 24, 44, 47, 170, 173, 178, 204, 213 Protein Conformation, 24, 170, 204 Protein Kinase C, 196, 204 Protein S, 48, 129, 172, 174, 186, 201, 204, 207, 208 Proteolytic, 179, 205, 207 Protocol, 9, 205 Protons, 170, 189, 192, 205 Protozoa, 119, 193, 196, 205, 209, 211 Pruritic, 183, 205 Psychotherapy, 205, 206 Public Policy, 141, 205 Publishing, 53, 191, 205
224 Bioterrorism
Pulmonary, 16, 30, 37, 41, 72, 175, 177, 179, 205, 207, 210 Pulmonary Edema, 177, 205 Pulmonary Ventilation, 205, 207 Pulse, 196, 205 Purifying, 34, 205 Q Quaternary, 113, 204, 205 R Rabies, 205, 214 Race, 196, 205 Radiation, 4, 47, 126, 146, 169, 184, 185, 190, 192, 193, 205, 206, 214 Radiation therapy, 169, 184, 192, 193, 205, 214 Radioactive, 180, 189, 191, 192, 193, 197, 198, 206, 214 Radioisotope, 199, 206, 211 Radiolabeled, 193, 206, 214 Radiotherapy, 175, 193, 206, 214 Randomized, 183, 206 Reactive Oxygen Species, 120, 206 Reagent, 113, 177, 206 Reassurance, 64, 206 Receptor, 23, 33, 34, 49, 169, 172, 187, 201, 204, 206, 208 Recombinant, 5, 8, 14, 29, 41, 44, 206, 213 Recombination, 20, 50, 206 Rectum, 172, 185, 186, 204, 206 Red blood cells, 42, 184, 206 Refer, 1, 14, 178, 186, 189, 194, 197, 198, 206 Refraction, 206, 209 Refractory, 16, 206 Regimen, 22, 183, 206 Reliability, 29, 206 Renal failure, 188, 206 Replicon, 5, 29, 207 Research Design, 36, 207 Respiration, 111, 176, 196, 207 Respiratory failure, 24, 207 Respiratory Mucosa, 187, 207 Respiratory System, 44, 207 Retrograde, 24, 207 Reversion, 207, 212 Ribosome, 207, 211 Ricin, 24, 207 Rickettsia, 18, 119, 207 Rickettsiae, 78, 207 Rigidity, 202, 207 Risk factor, 124, 203, 207 Risk patient, 41, 207
Rod, 173, 178, 207 Ruthenium, 110, 207 S Sanatorium, 207 Sanitation, 119, 207 Screening, 11, 15, 20, 21, 29, 45, 47, 83, 152, 178, 208 Sebaceous, 208, 214 Segregation, 206, 208 Senescence, 52, 208 Sensor, 4, 9, 42, 110, 208 Sepsis, 16, 22, 33, 208 Sequence Homology, 201, 208 Sequencing, 18, 26, 202, 208 Serine, 196, 204, 208 Serologic, 190, 208 Serous, 183, 208 Serum, 8, 13, 14, 171, 178, 179, 190, 208 Serum Albumin, 13, 208 Sexually Transmitted Diseases, 208 Shiga Toxin, 24, 208 Shock, 11, 33, 49, 188, 208 Side effect, 39, 169, 208, 211 Signal Transduction, 176, 208 Sindbis Virus, 170, 209 Skeletal, 178, 209 Skeleton, 204, 209 Skull, 209, 210 Small intestine, 189, 192, 209 Somatic, 169, 189, 195, 196, 209 Specialist, 156, 209, 213 Specificity, 6, 29, 43, 170, 209 Spectrometer, 115, 209 Spectrum, 5, 14, 72, 114, 120, 209 Sperm, 177, 209 Spirochete, 209, 210 Spores, 18, 23, 28, 33, 34, 40, 42, 49, 60, 68, 116, 120, 209 Sputum, 16, 165, 166, 209 Steel, 178, 209 Stem Cells, 60, 209 Sterile, 173, 209, 212 Stimulus, 182, 184, 209 Stomach, 169, 186, 189, 192, 197, 201, 209, 210 Strand, 10, 120, 202, 210 Stress, 60, 130, 132, 186, 196, 197, 210 Subacute, 191, 210 Subclinical, 191, 210 Subcutaneous, 183, 210 Subspecies, 16, 209, 210, 212 Substrate, 113, 184, 198, 210
Index 225
Suction, 185, 210 Surfactant, 112, 177, 210 Symptomatic, 13, 210 Synergistic, 17, 49, 210 Syphilis, 210 Systemic, 7, 10, 22, 30, 35, 37, 40, 175, 191, 193, 206, 210, 211, 212, 214 T Tachycardia, 173, 210 Tachypnea, 173, 210 Temporal, 12, 210 Terbium, 45, 210 Therapeutics, 8, 12, 13, 24, 25, 26, 28, 210 Thermal, 28, 182, 198, 202, 210 Threonine, 196, 201, 204, 208, 210 Thrombin, 202, 204, 210 Thrombocytopenia, 33, 210 Thrombomodulin, 204, 210 Thrombosis, 204, 210 Thymus, 190, 194, 211 Ticks, 167, 185, 211 Tissue Culture, 26, 211 Tooth Preparation, 169, 211 Topical, 177, 211 Toxic, iv, 24, 48, 49, 111, 112, 180, 184, 190, 198, 201, 211 Toxicity, 24, 82, 112, 182, 195, 211 Toxicologic, 23, 211 Toxicology, 142, 211 Toxins, 23, 24, 27, 50, 57, 117, 119, 127, 172, 174, 183, 184, 187, 191, 197, 208, 211, 213 Toxoplasma, 51, 211 Tracer, 189, 211 Traction, 178, 211 Transcription Factors, 11, 211 Transcutaneous, 40, 211 Transfection, 44, 174, 211 Transfer Factor, 190, 211 Transfusion, 211 Translation, 16, 44, 211 Translational, 16, 36, 43, 211 Translocation, 11, 49, 211 Transplantation, 52, 190, 211 Tropism, 6, 212 Tubercle, 212 Tuberculin, 212 Tuberculosis, 14, 128, 179, 207, 212 Tularemia, 19, 22, 30, 37, 38, 53, 56, 91, 126, 148, 152, 155, 165, 167, 212 Tumor marker, 174, 212 TYPHI, 18, 212
Typhimurium, 7, 14, 212 Typhoid fever, 110, 212 U Ulceration, 187, 212 Unconscious, 190, 212 Ureters, 212 Urethra, 204, 212 Urinary, 17, 212 Urinary tract, 17, 212 Urinary tract infection, 17, 212 Urine, 175, 212 V Vaccination, 23, 31, 32, 37, 40, 41, 43, 46, 52, 66, 86, 152, 212 Vaccinia, 17, 39, 41, 43, 48, 51, 65, 200, 212 Vaccinia Virus, 17, 39, 41, 43, 48, 65, 212 Vacuoles, 183, 199, 213 Vagina, 181, 213 Varicella, 65, 213 Variola, 31, 38, 39, 41, 43, 48, 212, 213 Variola Virus, 31, 39, 43, 213 Vascular, 184, 191, 198, 213 Vasodilators, 198, 213 Vector, 34, 61, 83, 200, 212, 213, 214 Vegetative, 34, 120, 213 Vein, 192, 198, 213 Venereal, 210, 213 Venoms, 198, 213 Venous, 204, 213 Vesicular, 45, 189, 209, 213 Veterinarians, 79, 93, 213 Veterinary Medicine, 141, 213 Vibrio, 15, 177, 213 Vibrio cholerae, 177, 213 Virion, 199, 213 Virologist, 47, 213 Virulence, 9, 15, 16, 18, 19, 22, 23, 25, 34, 41, 48, 51, 154, 155, 173, 211, 213 Virulent, 9, 18, 30, 31, 35, 114, 213 Virus Diseases, 172, 214 Virus Replication, 40, 214 Visceral, 193, 214 Visual Acuity, 214 Vitro, 6, 11, 21, 25, 49, 188, 214 Vivo, 8, 21, 31, 35, 214 Vulgaris, 104, 214 W War, 14, 82, 94, 117, 149, 177, 214 White blood cell, 172, 193, 194, 202, 214 Whole cell vaccine, 19, 214 X Xenograft, 171, 214
226 Bioterrorism
X-ray, 15, 32, 185, 193, 198, 205, 206, 214 X-ray therapy, 193, 214 Y Yeasts, 30, 186, 214 Yellow Fever, 185, 214
Yellow Fever Virus, 185, 214 Z Zoonosis, 30, 214 Zoster, 65, 214 Zymogen, 204, 214
Index 227
228 Bioterrorism
