TULAREMIA
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
ii
ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright ©2004 by ICON Group International, Inc. Copyright ©2004 by ICON Group International, Inc. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without written permission from the publisher. Printed in the United States of America. Last digit indicates print number: 10 9 8 7 6 4 5 3 2 1
Publisher, Health Care: Philip Parker, Ph.D. Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher's note: The ideas, procedures, and suggestions contained in this book are not intended for the diagnosis or treatment of a health problem. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960Tularemia: 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: 0-597-84106-3
1. Tularemia-Popular works.I. Title.
iii
Disclaimer
This publication is not intended to be used for the diagnosis or treatment of a health problem. It is sold with the understanding that the publisher, editors, and authors are not engaging in the rendering of medical, psychological, financial, legal, or other professional services. References to any entity, product, service, or source of information that may be contained in this publication should not be considered an endorsement, either direct or implied, by the publisher, editors, or authors. ICON Group International, Inc., the editors, and the authors are not responsible for the content of any Web pages or publications referenced in this publication.
Copyright Notice If a physician wishes to copy limited passages from this book for patient use, this right is automatically granted without written permission from ICON Group International, Inc. (ICON Group). However, all of ICON Group publications have copyrights. With exception to the above, copying our publications in whole or in part, for whatever reason, is a violation of copyright laws and can lead to penalties and fines. Should you want to copy tables, graphs, or other materials, please contact us to request permission (E-mail:
[email protected]). ICON Group often grants permission for very limited reproduction of our publications for internal use, press releases, and academic research. Such reproduction requires confirmed permission from ICON Group International Inc. The disclaimer above must accompany all reproductions, in whole or in part, of this book.
iv
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 tularemia. 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.
v
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.
vi
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
vii
Table of Contents FORWARD .......................................................................................................................................... 1
CHAPTER 1. STUDIES ON TULAREMIA ............................................................................................... 3
Overview........................................................................................................................................ 3
Federally Funded Research on Tularemia ...................................................................................... 3
E-Journals: PubMed Central ....................................................................................................... 32
The National Library of Medicine: PubMed ................................................................................ 33
CHAPTER 2. NUTRITION AND TULAREMIA ..................................................................................... 69
Overview...................................................................................................................................... 69
Finding Nutrition Studies on Tularemia..................................................................................... 69
Federal Resources on Nutrition ................................................................................................... 70
Additional Web Resources ........................................................................................................... 71
CHAPTER 3. ALTERNATIVE MEDICINE AND TULAREMIA ............................................................... 73
Overview...................................................................................................................................... 73
National Center for Complementary and Alternative Medicine.................................................. 73
Additional Web Resources ........................................................................................................... 74
General References ....................................................................................................................... 74
CHAPTER 4. DISSERTATIONS ON TULAREMIA ................................................................................. 77
Overview...................................................................................................................................... 77
Dissertations on Tularemia.......................................................................................................... 77
Keeping Current .......................................................................................................................... 77
CHAPTER 5. BOOKS ON TULAREMIA ............................................................................................... 79
Overview...................................................................................................................................... 79
Book Summaries: Federal Agencies.............................................................................................. 79
Book Summaries: Online Booksellers........................................................................................... 80
The National Library of Medicine Book Index ............................................................................. 80
Chapters on Tularemia................................................................................................................. 81
CHAPTER 6. PERIODICALS AND NEWS ON TULAREMIA ................................................................. 83
Overview...................................................................................................................................... 83
News Services and Press Releases................................................................................................ 83
Academic Periodicals covering Tularemia ................................................................................... 85
CHAPTER 7. RESEARCHING MEDICATIONS ..................................................................................... 87
Overview...................................................................................................................................... 87
U.S. Pharmacopeia ....................................................................................................................... 87
Commercial Databases ................................................................................................................. 89
APPENDIX A. PHYSICIAN RESOURCES ............................................................................................ 93
Overview...................................................................................................................................... 93
NIH Guidelines............................................................................................................................ 93
NIH Databases ............................................................................................................................. 95
Other Commercial Databases....................................................................................................... 97
APPENDIX B. PATIENT RESOURCES ................................................................................................. 99
Overview...................................................................................................................................... 99
Patient Guideline Sources............................................................................................................ 99
Finding Associations.................................................................................................................. 106
APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 109
Overview.................................................................................................................................... 109
Preparation................................................................................................................................. 109
Finding a Local Medical Library................................................................................................ 109
Medical Libraries in the U.S. and Canada ................................................................................. 109
ONLINE GLOSSARIES................................................................................................................ 115
Online Dictionary Directories ................................................................................................... 120
viii Contents
TULAREMIA DICTIONARY ...................................................................................................... 121
INDEX .............................................................................................................................................. 159
1
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 tularemia 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 tularemia, 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 tularemia, 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 tularemia. 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 tularemia, 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 tularemia. The Editors
1
From the NIH, National Cancer Institute (NCI): http://www.cancer.gov/cancerinfo/ten-things-to-know.
3
CHAPTER 1. STUDIES ON TULAREMIA Overview In this chapter, we will show you how to locate peer-reviewed references and studies on tularemia.
Federally Funded Research on Tularemia The U.S. Government supports a variety of research studies relating to tularemia. 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 tularemia. 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 tularemia. The following is typical of the type of information found when searching the CRISP database for tularemia: •
Project Title: ACELLULAR VACCINES AGAINST FRANCISELLA TULARENSIS Principal Investigator & Institution: Conlan, Wayne; Senior Research Officer; National Research Council of Canada Ottawa Kiaor6, Canada Ottawa, Timing: Fiscal Year 2001; Project Start 15-JUN-2001; Project End 30-APR-2006 Summary: (Provided by Applicant): The facultative intracellular bacterial pathogen, Francisella tularensis, can cause severe pneumonia and death following the inhalation of
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).
4
Tularemia
very small numbers of infectious particles. For this reason, F. tularensis is considered a primary biological warfare agent. Acquired host immunity against this pathogen is predominantly T-cell-mediated rather than humoral. An attenuated strain of F. tularensis is an effective live vaccine against virulent strains of the pathogen. However, this strain retains its virulence for mice, and might cause disease if administered to immunocompromised individuals. Thus, for mass-vaccination purposes, a defined fastacting acellular vaccine would be preferable to the current live vaccine. Our institute has developed a novel vaccine delivery technology based on liposomes manufactured from the total polar lipids of various Archaebacteria. These liposomes termed, archaeosomes, generate robust cell-mediated immune responses to model antigens entrapped within them, without the aid of any additional immune stimulants. Recently, we showed that a short peptide antigen of another intracellular pathogen, Listeria monocytogenes, packaged in archaeosomes, provides a high level of protective immunity against this pathogen in a murine listeriosis model after only a single vaccination. Because multiple studies indicate that the same host defenses are needed to combat F. tularensis and L. monocytogenes, it is likely that appropriate antigens of the former pathogen encapsulated in archaeosomes will provide effective acellular vaccines. This proposal will explore this possibility. It is expected that the findings from the proposed studies will be applicable to the development of acellular vaccines against other intracellular respiratory pathogens such as Mycobacterium tuberculosis, and Chlamydia pneumoniae. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ADHESINS AND INVASINS OF FRANCISELLA TULARENSIS Principal Investigator & Institution: Mann, Barbara J.; Associate Professor; Internal Medicine; University of Virginia Charlottesville Box 400195 Charlottesville, Va 22904 Timing: Fiscal Year 2003; Project Start 15-SEP-2003; Project End 31-AUG-2005 Summary: (provided by applicant): Francisella tularensis causes a potentially lifethreatening disease called tularemia. This pathogen can be aerosolized, survive in the environment and has an infectious dose of as few as 10 organisms. This has led the CDC and NIAID to classify this organism as a category A select agent and a potential agent of biological warfare. F. tularensis is a gram-negative coccobacillus that can infect a wide variety of vertebrate and invertebrate hosts. In mammalian hosts it primarily lives and replicates inside macrophages. The mechanisms by which the organism colonizes, invades and survives inside the host cell are mostly unknown. We have chosen to focus this proposal on microbial adherence since for many pathogens this is a key step in pathogenicity. Our overall hypothesis is that adhesions are critical virulence factors that are required for pathogenicity. A search of the genomic sequences of the virulent strain F. tularensis Schu4 has identified several loci with homology to genes involved in type IV pili structure and biogenesis. In other bacteria, which have a similar type of pilus, these pili have been shown to be critical virulence factors. This has led to our specific hypothesis: Type IV pili mediate attachment to host cell macrophages and help to facilitate host cell invasion. In this proposal we will focus on identifying and characterizing the gene(s) encoding pilin, the structural subunit of type IV pili, and investigating the role of this pilus in adherence, invasion and twitching motility. Specifically we will verify the presence of type IV pili by microscopy and immune sera. We will isolate pili from F. tularensis and sequence the pilin subunit by mass spectrometry analysis. We will purify pili for antibody production. To explore the diversity of the pilin subunit we will also clone and sequence the pilin encoding genes from the live vaccine strain (LVS) and additional clinical isolates of F. tularensis. We will
Studies
5
develop an adherence and invasion assay using bacteria that express the gene encoding the green fluorescent protein. We will use pilin-specific antibody to try to block adherence and/or invasion. We will construct a pilin minus strain of F. tularensis and test its ability to adhere to and invade host cells and exhibit twitching motility. Understanding the basic mechanisms of pathogenicity will lead to a greater understanding of why this organism is such an effective pathogen, and the identification of new targets for therapies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: AIRWAY INFLAMMATION Principal Investigator & Institution: Skerrett, Shawn J.; Associate Professor; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2003; Project Start 04-SEP-2003; Project End 29-FEB-2008 Summary: The overall goal of this project is to define molecular pathways involved in the activation of innate immunity to airborne infection with gram negative bacteria that are potential biological weapons, including the agents of plague (Yersinia pestis), tularemia (Francisella tularensis) and melioidosis (Burkholderia pseudomallei). We will use aerosol challenge models in genetically modified mice to explore the roles of Tolllike receptors (TLRs) and cell populations in mediating inflammatory and immune responses to live bacteria and selected bacterial ligands. The central hypothesis is that TLR-mediated signaling is essential for the activation of innate immunity to Y. pestis and other Gram negative bacteria in the lungs. The specific aims are: Specific Aim 1. Determine the role of MyD88 in mediating innate immunity to aerosolized Y. pestis, F. tularensis, and B. pseudomallei. This aim will test the hypothesis that MyD88-deficient animals will fail to activate resident and recruited defenses, leading to accelerated bacterial replication in the lungs and early dissemination of infection in comparison with wild-type controls. Caspase 1 deficient animals also will be tested to evaluate the role of IL-1- and IL-18-mediated activation pathways that are signaled via MyD88 independently of TLRs. Specific Aim 2. Determine the role of TLR4 and TLR2 in mediating innate immunity to aerosolizcd Y. pestis. The first part of this aim will test the hypotheses that recognition of Y. pestis LPS is mediated by TLR4; that TLR4 has a role in activating host resistance to live Y pestis; that the LPS of Y. pestis grown at 37 degrees C is poorly recognized by human MD2/TLR4 in vivo; and that defective LPS recognition by human TLR4/MD2 contributes to blunted innate immune responses to aerosolized Y. pestis. The second part of this aim will test the hypotheses that the low calcium response virulence antigen (LcrV) of Y. pestis induces a TLR-2-dependent IL-10 response in vivo that suppresses innate immunity and permits accelerated bacterial replication and dissemination. Specific Aim 3. Determine the role of bone marrowderived cells and respiratory epithelial cells in the activation of innate immune responses to Y. pestis. This aim will use bone marrow chimeras of MyD88-deficient and wild type mice and transgenic mice expressing a dominant negative IkB under the surfactant protein C promoter to test the hypothesis that both marrow-derived and parenchymal cells are involved in the activation of innate resistance to Y. pestis in the lungs. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: ANIMALS Principal Investigator & Institution: Ellenberger, Mary; Animals; Boston Medical Center Gambro Bldg, 2Nd Fl, 660 Harrison Ave, Ste a Boston, Ma 02118
6
Tularemia
Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2008
Summary: The Animal Core will support research on F. tularensis in mice to develop a
vaccine candidate(s) to protect against inhalational tularemia. The work will include
active immunization with F. tularensis vaccine candidate antigens. The immune
response of female BALB/c mice will be determined by several in vitro tests and the
vaccine conditions that yield a high immune response will be used to vaccinate animals
prior to aerosol challenge with five F. tularensis strains. Protection from inhalational
tularemia will be assessed on the basis of survival and quantitative organ cultures. After
immunization of BALB/c and C57BL/6 mice, which differ in their major
histocompatibility complexes, with each of four different killed F. tularensis Schu4
preparations and with the F. tularensis live vaccine strain (LVS), the immune response
will be determined by several in vitro tests. The mouse strain and those conditions that
yielded the best in vitro immune response to F. tularensis will be used to produce F.
tularensis-specific polyclonal antibody expression libraries (PCALS). In addition,
monospecific polyclonal antibodies directed against vaccine candidate antigens will be
produced. Prophylactic and therapeutic efficacy of the PCALs to aerosol challenge with
virulent F. tularensis will be performed on BALB/c mice. Urine and respiratory
secretions from infected mice will be used to optimize the development of commercial
diagnostic assays.
Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: BACTERIAL DEVELOPMENT
ANTIGENS
AND
ANTHRAX
VACCINE
Principal Investigator & Institution: Hewlette, Erik; University of Maryland Balt Prof School Baltimore, Md 21201 Timing: Fiscal Year 2003; Project Start 04-SEP-2003; Project End 28-FEB-2008 Summary: The Middle Atlantic Region consortium proposes to establish a Regional Center of Excellence for Biodefense and Emerging Infectious Diseases Research (RCE), whose theme is "Defense against Bioterror and Emerging Infection Agents." The proposed Research Projects are: 1) Anthrax (new Bacillus anthracis antigens, tested in animal models; compounds to impede anthrax infection; mouse model for imaging germination and bacterial distribution; development of a mucosal live vector prime/parenteral boost anthrax vaccine); 2) Hemorrhagic Fever and other Emerging Viruses (identification/characterization of neutralizing human monoclonal antibodies reactive to functionally important determinants on Henipaviruses, Bunyaviruses, West Nile, Ebola and Marburg); 3) Poxviruses (subunit variola vaccine; identification of new targets of neutralizing antibody and of vaccinia immune globulin; and development of a mouse ectromelia virus model of smallpox pathogenesis/prevention); 4) Tularemia (conjugate tularemia vaccine; study possible therapy of F. tularensis infection using reagents already under clinical testing for sepsis; evaluate currently available bisphosphonate drugs as a first line of defense for individuals exposed to F. tularensis; attenuated, live-vector tularemia vaccine); 5) Low-Dose Enteric Pathogens (role of type 1 Cryptosporidium parvum candidate genes in pathogenesis/susceptibility to infection, as a prelude to vaccine development; Shigella dysenteriae 1 and EHEC vaccines; novel therapeutics for EHEC disease; diagnostics for detection of these pathogens in water, food, and environmental specimens); 6) Public Health Response Research (needle-free immunization and vaccine-adjuvanting strategies; immunogenetics of human immune response to smallpox vaccine; innovative diagnostic platforms for routine clinical use and in known or suspected bioterror events). Three Career Development Projects (to train the next generation of biodefense investigators) and 4 Developmental Projects
Studies
7
(high-risk projects on biodefense agents) will be funded per year. Training will include a Media Training Course; a short course in "GMP Production and Process Development" (in collaboration with Aventis Pasteur Vaccines and Merck Vaccines); a Category A Bioterror Agent Clinical Surveillance Course; a "hands-on" course on working in BSL-3 facilities; and travel awards for RCE scientists and trainees to visit other RCE labs to learn techniques or perform collaborative experiments. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BACTERIOLOGY/IMMUNOLOGY Principal Investigator & Institution: Shapiro, Daniel S.; Boston Medical Center Gambro Bldg, 2Nd Fl, 660 Harrison Ave, Ste a Boston, Ma 02118 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2008 Summary: The Bacteriology Core will support research on F. tularensis in mice to develop a vaccine candidate(s) to protect against inhalational tularemia. The work will include the growth under specified conditions to permit antigen extraction of several F. tularensis vaccine candidate antigens. Conditions will be optimized for reproducible aerosol challenge of mice with F. tularensis strains. Protection from inhalational tularemia will be assessed on the basis of survival and quantitative organ cultures. In all studies in which animals are infected with F. tularensis, the animals will be maintained under BSL-3 conditions. Stock specimens of several strains of F. tularensis will be frozen in a secure location in the BSL-3 facility. Additional support includes the growth and preparation of four different killed F. tularensis Schu4 preparations and growth of the F. tularensis live vaccine strain (LVS). This will support a study in which F. tularensis specific polyclonal antibody expression libraries (PCALS) are produced. Urine and respiratory secretions from infected mice will be used to optimize the development of commercial diagnostic assays by Binax, Inc. After extensive offsite research, development, and the manufacture of a prototype instrument designed to detect the presence of F. tularensis in the air, Radiation Monitoring Devices, Inc. will conduct studies of the device in the BUMC BSL-3 facility with the support of the Bacteriology Core. Boston University Bioinformatics (BUB) will work to identify additional candidate vaccine antigens in F. tularensis and will work with Gen-Probe, Inc. in efforts to design appropriate target sequences for the development of their diagnostic assays. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: CELL ENTRY INHIBITORS FOR SIN NOMBRE VIRUS Principal Investigator & Institution: Hjelle, Brian L.; Professor; Pathology; University of New Mexico Albuquerque Controller's Office Albuquerque, Nm 87131 Timing: Fiscal Year 2003; Project Start 15-SEP-2003; Project End 29-FEB-2008 Summary: (provided by applicant): Many of the pathogens that have properties that would be desirable to a would-be bioterrorist have been little-studied, in part because they cause a relatively limited toll in morbidity and mortality under natural circumstances. In other cases, such as for the North American hantaviruses, poor and medically underserved minority populations are disproportionately affected, making their toll even less visible. Two minority institutions in New Mexico, the University of New Mexico and New Mexico State University, have nevertheless devoted much attention to research on potential weapons of mass destruction (Sin Nombre virus or SNV, anthrax, tularemia, plague, etc) for years, with funding from at least four federal agencies. The hantavirus research portfolio at UNM, for example, has been funded at least $1 million direct/year essentially since its inception in 1994. The anthrax attacks of
8
Tularemia
2001 demonstrated the willingness and ability of terrorists to deploy bioweapons, which caused panic and severe economic damage. Countermeasures against WMD must be developed quickly to limit the damage exacted by future attacks. This application represents a concerted attack against SNV, a hantavirus that has killed over 100 Americans, including 26 New Mexicans, since its recognition in 1993. We have assembled an interdisciplinary team that pools its resources and skills in novel ways. We have developed interlocking, highly collaborative and cross-informing projects and cores involving project PIs who are genuine leaders in their fields, including several who have worked together productively in the past. The approaches that we have taken in this application will serve as a model that can be adapted successfully to a variety of pathogens other than hantaviruses. By pioneering new collaborative strategies using the SNV model, we will establish efficient, high-throughput methods that will work well against other agents. The core capabilities we describe herein will include highthroughput screening for antiviral effects of drugs, computer-assisted modeling that will be used to quickly refine and optimize lead compounds, and evaluation of the efficacy of drugs with sophisticated and quantitative animal model testing. The projects include (1) phage display to develop lead compounds that inhibit SNV entry into cells; (2) computational modeling of drugs; (3) development of RNA aptamer inhibitors of replication and/or packaging using SELEX; (4) development of potent human anti-SNV monoclonal antibodies; and (5) development of sophisticated mechanism-of-action assays to speed development of replicative inhibitors of SNV. Animal model, virology and structural analyses cores will each provide multiple projects with critical reagents or perform the molecular modeling services that are needed to improve lead compounds. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CHARACTERIZATION OF THE FRANCISELLA TULARENSIS PHAGOSOME Principal Investigator & Institution: Horwitz, Marcus A.; Medicine; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2002; Project Start 15-SEP-2002; Project End 31-AUG-2004 Summary: (provided by applicant): Francisella tularensis is a facultative intracellular bacterial pathogen that causes serious and potentially life threatening illness. Because the bacterium grows readily in broth culture, has extraordinarily high infectivity, causes serious morbidity and mortality, and is easily dispersed, it is also considered a potential agent of bioterrorism. While currently available antibiotics are effective in treating tularemia, F. tularensis can be engineered to carry antibiotic resistance genes. For these reasons, new approaches to treatment and prevention of tularemia are needed. However, devising such strategies requires an improved understanding of the cell biology of F. tularensis. At present, very little is known about the interactions between F. tularensis and its host cells or of the pathogenic mechanisms that allow F. tularensis to enter, survive, and multiply within host cells. The main objective of this application is to improve our understanding of the cell biology of F. tularensis. Specifically, our aims are: (a) to examine the adherence, uptake and growth of F. tularensis in human mononuclear phagocytes to confirm it as a model system for further study; (b) to examine the ultrastructural features of the F. tularensis compartment in human macrophages at sequential times after infection; and (c) to define the membrane trafficking interactions of the host cell and the F. tularensis compartment by immunofluorescence and immunoelectron microscopy and by examining the effect of overexpression of wild-type and mutant proteins involved in membrane trafficking. We shall combine techniques of cell biology, molecular biology, and immunoelectron microscopy to accomplish these
Studies
9
research objectives. An improved understanding the cell biology of F. tularensis is the first step in understanding its pathogenic mechanisms. Understanding how F. tularensis subverts the host cell membrane trafficking pathways and attains an intracellular compartment that is hospitable for its survival and growth will help guide new strategies for the prevention and treatment of tularemia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
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 at-
risk populations, but it is associated with incomplete immunity and side-effects. Studies
of humans and mice vaccinated with this preparation indicate that humoral and cell-
mediated 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 O-
antigen/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 O-
antigen/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
•
Project Title: DEFENSE AGAINST BIOWARFARE AND EMERGING INFECTION AGENTS Principal Investigator & Institution: Levine, Myron M.; Director, Ctr for Vaccine Development; Medicine; University of Maryland Balt Prof School Baltimore, Md 21201 Timing: Fiscal Year 2003; Project Start 04-SEP-2003; Project End 28-FEB-2008
10
Tularemia
Summary: (provided by applicant): The Middle Atlantic Region consortium proposes to establish a Regional Center of Excellence for Biodefense and Emerging Infectious Diseases Research (RCE) whose theme is "Defense Against Bioterror and Emerging Infection Agents." The proposed Research Projects are: 1) Anthrax (new Bacillus anthracis antigens tested in animal models; compounds to impede anthrax infection; mouse model for imaging germination and bacterial distribution; and development of a mucosal live vector prime/parenteral boost anthrax vaccine); 2) Hemorrhagic Fever and other Emerging Viruses (identification/characterization of neutralizing human monoclonal antibodies reactive to functionally important determinants on Henipaviruses, Bunyaviruses, West Nile, Ebola and Marburg viruses); 3) Poxviruses (subunit variola vaccine; identification of new targets of neutralizing antibody and of vaccinia immune globulin; and development of a mouse ectromelia virus model of smallpox pathogenesis/prevention); 4) Tularemia (conjugate tularemia vaccine; study possible therapy of Francisella tularensis infection using reagents already under clinical testing for sepsis; evaluate currently available bisphosphonate drugs as a first line of defense for individuals exposed to F. tularensis; and attenuated, live-vector tularemia vaccine); 5) Low-Dose Enteric Pathogens (role of type 1 Cryptosporidium parvum candidate genes in pathogenesis/susceptibility to infection as a prelude to vaccine development; Shigella dysenteriae 1 and EHEC vaccines; novel therapeutics for EHEC disease; and diagnostics for detection of these pathogens in water, food, and environmental specimens); and 6) Public Health Response Research (needle-free immunization and vaccine-adjuvanting strategies; immunogenetics of human immune response to smallpox vaccine; and innovative diagnostic platforms for routine clinical use and in known or suspected bioterror events). Three Career Development Projects (to train the next generation of biodefense investigators) and four Developmental Projects (high-risk projects on biodefense agents) will be funded per year. Training will include a Media Training Course; a short course in "GMP Production and Process Development" (in collaboration with Aventis Pasteur Vaccines and Merck Vaccines); a Category A Bioterror Agent Clinical Surveillance Course; a "hands-on" course on working in BSL-3 facilities; and travel awards for RCE scientists and trainees to visit other RCE labs to learn techniques or perform collaborative experiments. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DENDRITIC CELL RESPONSE TO CLASS A BIOTHREATS Principal Investigator & Institution: Lyons, C. Rick.; Associate Professor; Univ of New Mexico Hlth Sciences Ctr Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-AUG-2008 Summary: Project 2: Class A pathogens (Anthrax, Plague, Tularemia, Smallpox) resurface as bioterrorism agents or which potent countermeasures must be established urgently. Our basic understanding of the immunopathogenesis of human infectious diseases has always been hampered by the obvious limitation of our inability to directly challenge humans with most pathogens, access to organs that are targeted by the pathogens and the genetic variability within the human population. Therefore, development of new therapeutic antibiotics and vaccines was possible in the context of virus and/or bacteria with high natural incidence in the human population. However, the infectious agents associated with the new biothreats have a very low natural incidence in humans, particularly the inhaled route of these infections. This considerably limits the use of "high risk" populations for testing of therapeutic regimen efficacy. Moreover, this strategy is also becoming limited for a variety of emerging viruses. Therefore, new approaches are required in order to provide the highest level of
Studies
11
confidence that the new vaccines and immunomodulators are effective in humans. We now know that vaccines act through DCs and that many pathogens do indeed target DCs though very little information is available about Class A pathogens in that regard. We will thus determine how Class A pathogens alter human DCs in vitro and in vivo upon delivery into the lung. Aim 1 will determine the effect of category A biothreats on human myeloid DC subsets in vitro. Aim 2 will determine the effect of category A pathogens on human plasmacytoid DCs in vitro. Aim 3 will determine the effect of category A pathogens on human DCs in vivo in mice reconstituted with human CD34+HPCs (Humouse). Aim 4 will determine whether Humouse can generate primary and/or secondary immune response to category A pathogens. This project will also establish in vitro and in vivo biosignatures of Category A pathogens and thus complement the database of Category B-C pathogens generated in the Technical Development component. 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.
12 Tularemia
Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DEVELOPMENT OF A MUCOSAL VACCINE AGAINST F. TULARENSIS Principal Investigator & Institution: Michalek, Suzanne M.; Professor; Microbiology; University of Alabama at Birmingham Uab Station Birmingham, Al 35294 Timing: Fiscal Year 2003; Project Start 15-SEP-2003; Project End 29-FEB-2008 Summary: (provided by applicant): Most infectious agents cause disease via our mucosal surfaces, which also applies to biological warfare agents. Therefore, in developing a vaccine against infectious/biological warfare agents, it is important to induce responses that would act at mucosal surfaces, as well as in the systemic compartment. Francisella tularensis is a gram-negative pathogen and cause of tularemia. This microorganism is a "category A pathogen and biological warfare agent". The overall goal of this project is to develop a safe mucosal vaccine effective in inducing protective responses against infection by F. tularensis. Specifically, we will 1) Determine the immunogenicity of heat shock proteins of F. tularensis and the effect of the saponin analog GPI-0100 and of ricin B in modulating host immune responses following systemic or intranasal immunization of mice. Serum and secretions will be collected and assayed for the nature and level of antigen-specific antibody activity by ELISA. Cells will be cultured and assessed for antigen-specific T cell proliferative responses and cytokine production (by ELISA). The effectiveness of the response on protection will be assessed following systemic or mucosal challenge with F. tularensis. 2) Determine the cellular mechanism(s) by which F. tularensis and its LPS, and the adjuvants modulate host responses. The role of Toll-like receptors (TLRs) and the B7 costimulatory system in mediating host responses and infection will be assessed in vitro and in vivo. Antigenpresenting cells from normal and TLR deficient mice will be stimulated in vitro and assessed for changes in the expression of MHC and B7 by flow cytometry and for cytokine production by ELISA. The cell signaling pathways involved in cell activation will also be determined. TLR- and B7-knockout mice will be used to determine the role of TLRs and B7 in responses to F. tularensis and its LPS. Humoral and cellular responses will be assessed as indicated above. Clearance of F. tularensis will be measured by microbiologic analysis. 3) Derive and characterize genetically defined attenuated strains of F. tularensis LVS with mutations in the shikimate and/or purine metabolic pathways for use as a live vaccine. Mutants will be derived and tested in mice for their safety, persistence in host tissue by microbiologic analysis, immunogenicity by inducing cellular (cell proliferation and cytokine production) and humoral (nature and level of antibody activity by ELISA) responses, and effectiveness in inducing protective immunity. These studies will define the role of the innate and adaptive immune systems in inducing protective responses to F. tularensis and will define a safe and efficacious vaccine against mucosal or systemic challenge with F. tularensis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: DEVELOPMENT OF GENETIC TOOLS FOR FRANCISELLA TULARENSIS Principal Investigator & Institution: Pavelka, Martin S.; Assistant Professor; Microbiology and Immunology; University of Rochester Orpa - Rc Box 270140 Rochester, Ny 14627 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2005
Studies
13
Summary: (provided by applicant): The Gram-negative bacterium Francisella tularensis subsp. tularensis, the causative agent of tularemia, is considered a potentially dangerous biological weapon. This is due to the organism's extreme infectivity via the aerosol route and the severity of the human disease it causes. The fastidious nature of the bacterium, the requirement that it be handled using biosafety level three (BSL3) containment, and the paucity of genetic tools have hindered research on this organism. Thus, compared to other pathogens, little is known about F. tularensis subsp. tularensis physiology, genetics, and pathogenesis. Previous studies have used the attenuated live vaccine strain (LVS) derived from F. tularensis subsp. palaearctica, or the rarely pathogenic F. tularensis subsp. novicida. The aim of this proposal is to develop genetic tools for the manipulation of virulent, pathogenic F. tularensis subsp. tularensis. These tools will then be used for the analysis of F. tularensis subsp. tularensis pathogenesis. Furthermore, the ability to genetically manipulate the organism will allow for the development of attenuated vaccine strains that could be administered to populations at risk from F. tularensis infection, either from natural sources or from a biological attack. The further development of Francisella genetics is timely, as the sequencing of the genome of the F. tularensis subsp. tularensis, strain Schu 4 is almost complete. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: FRANCISELLA TULARENSIS LIVE ATTENUATED VACCINES Principal Investigator & Institution: Klose, Karl E.; Associate Professor; University of Texas Hlth Sci Ctr San Ant 7703 Floyd Curl Dr San Antonio, Tx 78229 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-AUG-2008 Summary: Francisella tularensis is considered a Category A bioweapon due to the ease of transmission, the low infectious dose and high mortality associated with pneumonic tularemia, and the fact that it has been intensively studied and developed in bioweapons programs in several countries. There is currently no vaccine approved for general human use. A live vaccine strain (LVS) developed from F. tularensis subsp. holarctica has been shown to be very efficacious, however, the mechanism of attenuation in LVS is unknown, making it unlikely to be approved for general use. The focus of this research effort is to identify potential live vaccine candidates of F. tularensis subsp, holarctica that can protect against aerosol F. tularensis subsp, tularensis, and then thoroughly characterize their pathogenic potential and the immune response to them. This will dramatically increase our understanding of the virulence of F. tularensis and the immune response to it, and also identify live vaccine candidates and illuminate what constitutes protective immunity to tularemia. First, every gene of F. tularensis subsp. holarctica will be mutated and recombined back onto the chromosome. The viable mutant bacteria will be combined in pools and inoculated subcutaneously into mice, and those mutants that cannot survive within the host will be identified by a microarray-based technique. Next, the attenuated F. tularensis subsp, holarctica mutants will be used to vaccinate mice, which will then be challenged with aerosolized F. tularensis subsp, tularensis; strains that protect against subsp. tularensis aerosol challenge are potential live vaccine candidates. These strains will be tested for markers of virulence: ability for intramacrophage survival and growth, and resistance to antimicrobial compounds, including antimicrobial peptides, NO, and oxidative killing. The potential live vaccine strains will be inoculated into mice by various routes (intradermal, intravenous, inhalation) and the immune response thoroughly characterized, including analysis of immune markers (cytokines, chemokines, immune cells) within infected tissue, and the antibody and T-cell responses. Our research plan involves a multidisciplinary approach and utilizes multiple investigators at several
14 Tularemia
institutions in the region. This approach will allow us to propel the knowledge of F. tularensis pathogenesis and host response to a new level and identify novel vaccine candidates for the prevention of tularemia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TULAREMIA
FRANCISELLA
TULARENSIS
SECRETED
PROTEOME
IN
Principal Investigator & Institution: Mciver, Kevin S.; Assistant Professor; University of Texas Sw Med Ctr/Dallas Dallas, Tx 753909105 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2008 Summary: Gram-negative bacterial pathogens, including those that grow intracellularly, are known to secrete a variety of virulence molecules into the surrounding environment at specific points during infection. Such secreted proteins are important tools for Gramnegative pathogens to manipulate their host environment to allow growth in vivo and elude the host immune response. To date, there have been no secreted proteins of Francisella tularensis implicated in the pathogenesis of this important biothreat, nor have any studies directly addressed this question. Thus, this proposal will combine proteomic and genomic approaches as well as in situ and in vivo infection models to characterize the role of exoproteins expressed during F. tularensis infection. A broad and thorough analysis of proteins secreted by the highly virulent F. tularensis Schu4 into the extracellular milieu of may lead to a significant advancement in our understanding the pathogenesis of this pathogen. The Specific Aims of the project are: (1) To characterize the extracellular proteome of the virulent F. tularensis Schu4 strain grown under different conditions relevant to infection in vivo; (2) To identify the complete open reading frames (ORF's) encoding each secreted extracellular protein (Exp) characterized in Aim 1; (3) To determine the role of each F. tularensis Schu4 secreted extracellular protein (Exp) for in vitro growth in human macrophages and for virulence in murine models of tularemia; (4) To establish whether secreted extracellular proteins (Exp) of F. tularensis Schu4 represent targets for immunoprophylaxis or therapeutic treatment during early stages of tularemia. These aims will have strong relevance to the overall goals of the P01 application and close collaborations with the other five P01 investigators will markedly enhance the success of this project. These combined studies could lead to a better understand the pathogenesis of this organism, leading to the development of new diagnostic, vaccine, and intervention strategies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: IHALATION
FRANCISELLA
TULARENSIS:
INNATE
RESISTANCE
TO
Principal Investigator & Institution: Gregory, Stephen H.; Rhode Island Hospital (Providence, Ri) Providence, Ri 02903 Timing: Fiscal Year 2003; Project Start 15-SEP-2003; Project End 31-AUG-2005 Summary: (provided by applicant): Francisella tularensis is one of the most infectious pathogens known to man, as few as 10 organisms can cause disease. Aerosolized F. tularensis represents a potentially dangerous biological weapon. Alveolar macrophages (AM) constitute both the principal target for intracellular replication and a key effector for the elimination of F. tularensis deposited in the lungs. Infiltrating neutrophils are a prominent feature of pneumonic tularemia. Factors judged important in host defenses to F. tularensis are based largely upon studies involving mice inoculated intravenously. The role of specific defense mechanisms varies, however, dependent upon the route of
Studies
15
infection (i.e., inhalation vs. systemic) and primary site of invasion (lung vs. spleen or liver). Recent studies conducted in our laboratory indicate that the interaction between inflammatory neutrophils and resident tissue macrophages plays a critical role in host defenses to bacterial infections expressed in the liver. Similarly, it is speculated here that neutrophiI-AM interaction exerts a significant influence on innate resistance to F. tularensis in the lungs. The SPECIFIC AIMS of this proposal are to: I. Delineate the biological response of AM to aerosolized F. tularensis, i.e., IA. quantify phagocytosis of F. tularensis, apoptosis and the antimicrobial activity of AM, lB. quantify cytokine and chemokine production, IC. assess the intermediary role of AM in the infiltration and bactericidal activity of neutrophils, and ID. define the role of AM in down-regulating neutrophils sequestration and tissue injury. Il. Determine the effect of infiltrating neutrophils on proinflammatory cytokine and chemokine production by AM. Given the limited number of relevant studies to date, the results of the proposed experiments should dramatically increase our current understanding of the factors that effect innate host defenses to pulmonary F. tularensis infections. This, in turn, should enable the development of innovative strategies to improve treatment and prevent the fatal consequences that often occur in untreated cases of pneumonic tularemia. Moreover, our primary approach to studying cytokine gene expression by inflammatory cells (i.e., immuno-laser capture microdissection followed by GeneChip expression microarray analysis of mRNA) should afford considerable insight into the factors, pathways and underlying mechanisms that effect innate immunity to respiratory infections in general. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: RESISTANCE
GENETICS
OF
F
TULARENSIS
VIRULENCE
AND
DRUG
Principal Investigator & Institution: Rubin, Eric J.; Assistant Professor; Harvard University (Sch of Public Hlth) Public Health Campus Boston, Ma 02460 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2008 Summary: Francisella tularensis, the causative organism of tularemia, has long caused illness in animals and, occasionally, in humans. Recently this relatively uncommon human disease has gained new prominence as a potential agent of bioterrorism. Here we propose to study the genetics of F. tularensis to further understand how it grows, causes disease and resists killing by antibiotics. We will utilize methodology we have used to study another intracellular pathogen that causes pneumonia, Mycobacterium tuberculosis. To perform our experiments, we will first develop two new tools. We will construct a DNA microarray representing the predicted genes of F. tularensis and use a transposon to make a highly complex library of F. tularensis mutants. These tools will be combined to compare large pools of mutants simultaneously, allowing us to detect mutants that are unable to survive under specific growth conditions. We will apply this method to three different problems. First, we will search for those F. tularensis genes that are required for in vitro growth. This set of genes contains all of the possible targets for antibiotics. Second, we will identify those genes required for bacterial survival in experimental animals. Knowing these genes should help us understand the molecular mechanisms of F. tularensis pathogenesis. Third, we will define the genes used by F. tularensis to resist many commonly used antibiotics. This could lead to methods to enhance the ability of existing antibiotics to kill the pathogen. Altogether, these studies will help us devise new therapeutic and preventive strategies for tularemia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
16
Tularemia
•
Project Title: GENETICS OF VIRULENCE EXPRESSION BY F. TULARENSIS Principal Investigator & Institution: Sperandio, Vanessa; University of Texas Sw Med Ctr/Dallas Dallas, Tx 753909105 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2008 Summary: Francisella tularensis, a facultative intracellular gram-negative coccobacillus, is the etiological agent of tularemia, which can be a fatal disease in humans. One of the striking features of tularemia is the very low infectious dose and the high mortality rate associated with the pneumonic form of the disease usually acquired through aerosols. Taken together, these features make F. tularensis an attractive organism to be used in biological warfare, leading NIAID to include this organism as a class A bioterrorism agent. Very little is known about the pathogenesis mechanisms of F. tularensis, and the goal of this grant proposal is to identify F. tularensis Schu4 virulence genes. A better understanding of F. tularensis pathogenesis is essential for the design and development of a suitable vaccine. Bacterial pathogens express their virulence genes in concert within the host. Specific Aim 1 is designed to identify F. tularensis genes activated within macrophages using gene microarrays and differential fluorescence induction. In Specific Aim 2 we shall identify genes essential for disease in mice using signature tagged mutagenesis. The potential virulence genes identified through Specific Aims 1 and 2 will have their role in virulence directly assessed by generation of isogenic mutants and complemented strains. Therefore in Specific Aim 3 we will develop genetic systems to study the role of candidate F. tularensis Schu4 virulence genes. These combined studies will be germane to the identification of novel vaccine candidates and markers for F. tularensis detection. 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 proinflammatory activation, as measured by upregulation of expression of adhesion
Studies
17
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 •
Project Title: IDENTIFICATION OF F. TULARENSIS GENE PRODUCTS Principal Investigator & Institution: Hansen, Eric; Professor; University of Texas Sw Med Ctr/Dallas Dallas, Tx 753909105 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2008 Summary: Iron is an essential micronutrient for nearly all bacteria, and sequestration of iron by the mammalian host poses significant problems for an invading bacterial pathogen. Despite the central role of iron acquisition in bacterial growth, virtually nothing is known about how F. tularensis acquires this important cation and, to date, there have been no descriptions of F. tularensis gene products that are involved in this process. In other well-studied prokaryotic parasites, growth under iron-restricted conditions results in the expression of a myriad of bacterial gene products, some of which enhance the virulence potential of their respective pathogens. The Specific Aims of this proposal are designed to address this gap in our knowledge about this pathogen that represents a serious threat as a bioterrorism weapon. Identification of gene products involved in iron acquisition by the virulent F. tularensis Schu4 strain will be accomplished using a number of complementary approaches including both genomic and proteomic methodologies. The sources of iron that can be utilized by F. tularensis Schu4 and its possible production of a siderophore will be investigated in Specific Aim 1. We will use two-dimensional gel electrophoresis, DNA microarray analysis, and a GFP-based promoter trap in Specific Aim 2 to identify those F. tularensis Schu4 proteins whose expression is induced or up-regulated as a result of iron limitation. We will construct isogenic F. tularensis Schu4 mutants that lack the ability to express these proteins and determine whether these mutants have an altered ability to acquire iron, to survive and grow in human macrophages, or to cause disease in a murine model of pulmonary tularemia in Specific Aim 3. We will also determine whether iron-regulated outer membrane proteins (identified in Specific Aim 1) have the ability to induce protective immunity against aerosol challenge with F. tularensis Schu 4 in Specific Aim 4. These results will determine whether one or more of these iron-regulated proteins might have potential for vaccine development. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: TULAREMIA
IMMUNO-PROPHYLAXIS-THERAPY
&
DIAGNOSIS
OF
Principal Investigator & Institution: Rice, Peter A.; Professor & Chief; Boston Medical Center Gambro Bldg, 2Nd Fl, 660 Harrison Ave, Ste a Boston, Ma 02118 Timing: Fiscal Year 2003; Project Start 15-SEP-2003; Project End 29-FEB-2008
18
Tularemia
Summary: (provided by applicant): The major objectives of this Co-operative Research Program will be to: (1) develop a vaccine candidate(s) to protect against inhalational tularemia (caused by Francisella tularensis); (2) to develop a polyconal antibody library to be used for passive immunization to ameliorate or prevent acute illness from F. tularensis acquired by the inhalational route and (3) to develop diagnostic systems to detect F. tularensis in clinical specimens and in the environment using immunochemical and/or gene amplification methods. In Project 1, we will prepare and use as vaccine candidates in experimental systems, F. tularensis lipopolysaccharide derived Opolysaccharide and capsular polysaccharides. We will use conjugates and clinically relevant adjuvant and delivery systems to recruit T cell help to enhance immune responses. We will also create peptide surrogates (called mimics) of the two saccharide prototypes and use these for immunization. Mice will be immunized to assess vaccine efficacy against aerosol challenge with F. tularensis. In Project 2, we will design polyclonal antibody expression libraries against F. tularensis and examine the efficacy of passive administration in preventing and treating experimentally induced inhalational tularemia. We will use widely directed polyclonal antibodies to determine overall efficacy, use libraries depleted of putative subversive (blocking) antibodies and generate monospecific polyclonals directed against O-polysaccharides to passively immunize mice and assess protection from aerosol challenge with F. tularensis. In Project 3, we will develop three diagnostic systems, using gene amplification and immunochemical detection, to detect F. tularensis in clinical and environmental specimens. A transcription mediated amplification (TMA) assay will be developed to detect F. tularensis in respiratory secretions and an immunochemical test to detect Francisella antigens in respiratory secretions and urine and for monitoring environmental air samples. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: INNATE PATTERN RECOGNITION OF F. TULARENSIS Principal Investigator & Institution: Sellati, Timothy J.; Albany Medical Center Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2008 Summary: The overall objective of this subproject is to elucidate the molecular mechanism(s) whereby Francisella tularensis activates immune effector cells, a sentinel event in the early host response. Lipoproteins, beta-glucan, and LPS are the principle constituents of the F. tularensis cell wall. In other bacterial pathogens, these molecules are endowed with potent immunobiological properties many of which are mediated through interaction with pattern recognition receptors (PRR), such as CD14 and toll-like receptor 2 (TLR2), on the host cell surface. Very little is known, however, regarding the potential of francisellae cell wall constituents to activate immune effector cells and thus contribute to tularemia pathogenesis. Studies detailed herein will fill this critical gap in our understanding of the mechanism(s) whereby F. tularensis causes disease. Using the live vaccine strain of F. tularensis and CD14-deficient C3H/HeN mice we have begun to explore the possibility that francisellae stimulate host responses via binding to PRR. Based upon our findings, we hypothesize that F. tularensis lipoproteins/beta-glucans engage the CD14-TLR2 signaling pathway in innate immune cells thus triggering Th1 type host responses that engender the clinical manifestations of tularemia. This hypothesis will be tested through pursuit of the following Specific Aims: 1) compare the immunobiological activities of lipoproteins, beta-glucan, and lipopolysaccharide (LPS) isolated from F. tularensis, 2) determine the role of CD14 and TLR2 in macrophage activation by lipoproteins, beta-glucan, and LPS isolated from F. tularensis, and 3) determine the role of CD14 and TLR2 during primary pneumonic infection with F.
Studies
19
tularensis. It is our expectation that the experimental approach detailed herein will identify the F. tularensis component(s) responsible for immune cell activation and elucidate the molecular mechanism(s) by which this event occurs. The rationale underlying this work is the belief that defining immune mechanisms that engender clinical manifestations and disease resolution is an essential first step towards development of immunotherapeutic strategies and identification of appropriate vaccine targets. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: INTRACELLULAR TRAFFICKING OF THE F. TULARENSIS VACUOLE Principal Investigator & Institution: Daefler, Simon; University of Texas Sw Med Ctr/Dallas Dallas, Tx 753909105 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2008 Summary: The key feature for Francisella tularensis pathogenesis is its ability to survive inside the macrophage. Studies with other bacterial intracellular parasites have demonstrated that such a feat is usually accomplished by the mode of entry into the host cell and by bacterial virulence factors that specifically usurp host cell signaling pathways to position the bacterium-containing vacuole within protected coordinates unique to each bacterium within the host cell. Very few such factors have so far been defined in F. tularensis. This project proposes that F. tularensis steers its evolving phagosome to a defined and unique protected position within the macrophage through the elaboration of specific virulence factors that determine its mode of entry and target host cell signaling pathways. We will test this hypothesis by characterizing the F. tularensis-containing vacuole by biochemical and cell biology analyses to understand the trafficking and maturation of the phagosome. The F. tularensis Schu4 strain, which is virulent for humans, will be used in all studies. The factors that contribute to F. tularensis intracellular survival will be characterized by genetic and biochemical techniques. The entry pathway of the bacterium will be investigated by electron microscopy, manipulation of the entry pathway through selective host cell receptorblockade, and investigation of the cell signaling pathways activated via entry of F. tularensis. An understanding of the pathway of F. tularensis from the initial contact with the macrophage surface to its subcellular localization of protected replication within the macrophage and knowledge of the bacterial virulence factors involved are an important prerequisite for developing vaccines and novel antibacterial components. The investigations proposed here are within the overall goal of our laboratory to characterize the vesicle trafficking pathway within macrophages as it relates to invading intracellular microbes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: IRON TRANSPORT MECHANISMS OF FRANCISELLA TULARENSIS Principal Investigator & Institution: Ramakrishnan, Girija; Internal Medicine; University of Virginia Charlottesville Box 400195 Charlottesville, Va 22904 Timing: Fiscal Year 2003; Project Start 15-SEP-2003; Project End 31-AUG-2005 Summary: (provided by applicant): Francisella tularensis is a gram-negative bacterium and the causative agent of tularemia, a potentially deadly disease. It is a threat as an agent of bioterrorism because of the highly infectious nature of the airborne organism, with as few as 10 organisms being sufficient to cause disease. In the mammalian host, the bacterium is an intracellular pathogen, replicating within membrane-bound
20 Tularemia
phagosomes in macrophages and other cells. Iron is a scarce but essential nutrient for the invading pathogen, and iron acquisition systems are proving to be critical virulence determinants. The availability of iron was shown to be important for proliferation of F. tularensis within macrophages by Fortier et al. (Inf. Immun.63:1478, 1995). Iron acquisition mechanisms in this organism are however uncharacterized. The goal of this proposal is identification of systems for iron acquisition in F. tularensis with the hypothesis that iron acquisition is a key element in pathogenesis in the mammalian host. A variety of techniques including bioinformatics (based on the genome sequencing project currently underway), proteomic and genetic approaches will be taken to achieve this goal. Specific aim 1 of this project is the characterization of iron utilization in the organism. By analyzing growth of the bacteria under conditions of iron-limitation, characterizing uptake of ferrous versus ferric iron, and determining the various host sources of iron (transferrin, heme etc.) that can be utilized, the physiologically significant sources of iron for the invading pathogen may be identified. These studies will help define assay methods for studying specific transport mechanisms. Specific aim 2 is the identification of iron acquisition systems and characterizing their role in virulence. Identification of potential transport systems will involve bioinformatics-based and proteomic approaches followed by targeted mutagenesis. Mutants will be tested for their ability to proliferate in a macrophage infection assay as a first level determination of their role in virulence. The long-term goals with these studies are to explore potential new mechanisms for iron acquisition, to be able to harness them in therapeutic applications, and to test them as targets for a defined vaccine strain development. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MOLECULAR BASIS OF FRANCISELLA VIRULENCE AND IMMUNITY Principal Investigator & Institution: Kawula, Thomas H.; Associate Professor; Microbiology and Immunology; University of North Carolina Chapel Hill Office of Sponsored Research Chapel Hill, Nc 27599 Timing: Fiscal Year 2004; Project Start 15-DEC-2003; Project End 30-NOV-2005 Summary: (provided by applicant): Francisella tularensis is the etiologic agent of tularemia. This gram negative bacterium is a potential agent of bioterrorism because of its high mortality, extremely low infective dose, ability to survive for long periods of time outside of an animal host, and numerous transmission mechanisms including inhalation, ingestion, skin contact, mucous membrane contact, and insect vectors. Little is known about the mechanisms of F. tularensis pathogenesis and host resistance. F. tularensis will survive within macrophages, however macrophage-like cells infected with these organisms become apoptotic within 24 hours following inoculation. The first aim of this proposal is to examine the mechanism(s) by which F. tularensis provoke host cell death in macrophages. F. tularensis transposon insertion mutants that fail to induce macrophage apoptosis will be isolated and the mutations characterized to define bacterial products responsible for promoting host cell death. These mutant strains will be tested for potential attenuation in a mouse model of tularemia. The mechanism of apoptosis induction by F. tularensis will be determined using mouse gene chips possessing known pro- and anti- apoptotic gene sequences to compare macrophage mRNA levels from control and F. tularensis infected cells. The second aim is to isolate Francisella specific CD4 T cell hybrids and determine the differences in the epitopes recognized in C57B1/6 mice infected with live or heat killed bacteria. E. coli clones expressing the apoptosis inducing genes identified in the first aim will be created and used to isolate specific CD4 T cell hybrids. The ultimate aim will be to create T cell
Studies
21
clones of defined cytokine secretion (Thl or Th2) (by using the defined peptide epitopes) and determine the effect of the clones on pathogenesis and protection. These aims are directed towards examining the molecular basis for F. tularensis pathogenesis, combined with an approach to elucidate potential immune response targets that could lead to improved prophylaxis against tularemia 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: 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
22
Tularemia
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 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: MUTANT F. TULARENSIS INTERACTIONS WITH MACROPHAGES Principal Investigator & Institution: Banas, Jeffrey A.; Associate Professor; Albany Medical Center Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2008 Summary: Inhalation of as few as 10-50 F. tularensis organisms can lead to glandular tularemia as well as to acute and severe bronchiolitis, pneumonitis or pleuropneumonia. This extreme infectivity of F. tularensis, and the significant morbidity and mortality that can result in the absence of prompt antibiotic treatment, are reasons why F. tularensis has traditionally been considered to have potential as an agent of biological warfare. Little is known about the pathogenic mechanisms of F. tularensis, including the basis for its extraordinary infectivity. This infectivity may be at least partially explained by efficient uptake, survival and growth within host macrophages. The ability of F. tularensis to propagate intracellularly is enhanced by failure of lysosomes to fuse with the phagosome and the lack of stimulation of a respiratory burst. However, little has been described pertaining to the initial uptake of F. tularensis by macrophages early in infection. In general, macrophages can recognize intact bacteria via several different receptors; whether or not a respiratory burst is stimulated depends on which receptor(s) mediates uptake. We hypothesize that specific components on the surface of F. tularensis facilitate uptake by macrophages and that the identification of these interactions will lead to an understanding of why macrophages fail to undergo a respiratory burst. We further postulate that the identification of these surface components will suggest targets for modulating the immune response. In order to test this hypothesis we propose the following specific aims: 1) Generate and screen mutants
Studies
23
of F. tularensis that are deficient in being taken up by macrophages, 2) Generate and screen mutants of F. tularensis that become capable of stimulating the production of a respiratory burst or alter cytokine secretion in unstimulated macrophages, 3) Examine the mutants identified in Aims 1 and 2 in an animal model of infection noting changes in virulence, pathology, and immunity. The completion of these Aims will directly support at least two other subprojects, including the testing of vaccine candidates. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MWCE: TRANSMISSION/PATHOGENESIS OF BIOTERRORISM AGENTS Principal Investigator & Institution: Schlievert, Patrick M.; Professor; Microbiology; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2003; Project Start 04-SEP-2003; Project End 31-AUG-2005 Summary: (provided by applicant): This P-RCE brings together the strengths of 77 researchers, both basic and clinical and from both Universities and Industry, in the states of Minnesota, Illinois, Michigan, Indiana, and Ohio. Administrative infrastructure for this application includes leadership at each one of the institutions involved. Our research strengths are in Basic Biology of Category A agents of Bioterrorism, Inhalation Biology and Host Response to Category A organisms, Diagnostics and Experimental Therapeutics, and Vaccine Evaluation, the latter where we have two premier organizations committed to participate. We are particularly interested in moving basic research into clinical application. We submit two R01s and several concept projects in these areas. The first R01 seeks funding to study a novel two-component regulatory system in Bacillus anthracis that in other Gram-positive bacteria is essential to virulence. We have shown that the regulatory system homologue exists in B. anthracis and have initiated studies to clone and insertionally inactivate the system. Furthermore, we hypothesize that this regulatory system is the target of compounds that we have identified and inhibit production of exotoxins. The second R01 provides an example of our strength in Inhalation Biology with a project to study the mechanism underlying Francisella tularensis entry and trafficking into macrophages, and the role surfactant plays in these processes. Concept projects complement these studies and initiate research into Category A viral agents. We anticipate that in 1-2 years these grants will develop into 3-4 program projects. In addition, we have assembled a team of highlyskilled leaders to train both present and future researchers in the safe handling of Category A agents; we have a large collective number of BSL3 facilities to achieve this training, combined with a well-conceived plan. Finally, we have begun development of seamless interactions with first-line emergency responders in all Region V states, with our intent to serve as overflow "Bench Workers" if bioterrorism events occur. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: NEWLY IDENTIFIED ANTIGENS FOR GAMMA/DELTA T CELLS Principal Investigator & Institution: Bukowski, Jack F.; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2001; Project Start 01-AUG-1998; Project End 31-JUL-2002 Summary: (Adapted from Investigator's abstract): It is becoming evident that gamma/delta (gd) T cells play an important role in defense against bacterial and viral infections as well as in autoimmunity. gd T cells are expanded in humans with infectious diseases such as tuberculosis, salmonellosis, brucellosis, ehlichiosis, tularemia, malaria, leishmaniasis, mononucleosis, and in HIV (early stages). They are
24 Tularemia
expanded in the synovium of patients with sarcoidosis. In contrast to alpha/beta (ab) T cells, which recognize peptide antigens in the context of MHC molecules, the predominant subset of gd T cells in human peripheral blood, termed Vg2Vd2 T cells, having no homologue in rodents, recognize unprocessed nonpeptide phosphate antigens in the absence of professional APC or known antigen presenting molecules. Abundant data describing in detail the interactions of the ab TCR with MHC-bound peptide have deepened our understanding of their role in infectious disease and in autoimmunity. In contrast, there is little information regarding the nature of interaction between the gd TCRs and their ligands. In fact, the identities of most microbial and autoimmune antigens reactive with gd T cells is unknown. Preliminary evidence in the investigator's laboratory shows that the TCR g junctional region is of crucial importance for the recognition of phosphate antigens by Vg2Vd2 T cells, arguing against a superantigen-like recognition of such antigens. The laboratory recently has found that alkylamines, which are major products of certain bacteria that cause gingivitis and many other diseases and are also found in plant foods and human body fluids, cause proliferation of Vg2Vd2 T cells in a TCR-specific manner. Alkylamine antigens are the first phosphate-free antigens described for Vg2Vd2 T cells and thus represent a distinct chemical class of ligand for Vg2Vd2 T cells. The investigator proposes to 1) Define the structural characteristics necessary for bioactivity of alkylamine antigens by testing a panel of naturally occurring alkylamine antigens for reactivity to gd T cells; 2) Identify specific domains and residues in the gd TCR important for recognition of alkylamine and phosphate antigens; 3) Determine the requirements of alkylamine antigens for antigen presentation and processing; 4) Define the phenotypes and alkylamine antigen reactivities of gingival gd T cells from patients with chronic gingivitis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NOVEL ANTIBACTERIAL AGENTS FOR TREATMENT OF TULAREMIA Principal Investigator & Institution: Schmid, Molly B.; Senior Vice President; Affinium Pharmaceuticals, Inc. 100 University Ave, 12Th Fl, North Tower Toronto, Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-AUG-2005 Summary: (provided by applicant): A series of enoyI-ACP reductase (Fabl) inhibitors have been identified with potent, narrow spectrum in vitro antibacterial activity against the agent of Tularemia, Francisella tularensis, as well as excellent in vitro potency against Staphylococci. Lead compounds have shown good in vivo activity in treating Staphylococcus aureus infections in rats and have good oral bioavailability. We propose experiments to assess the in vivo safety of the lead compounds, the frequencies and mechanisms of resistance development, and the efficacy of the lead compounds in animal models of F. tularensis infection. The experiments in this application aim to complete the preclinical characterization of the lead compounds, identify additional compounds with improved characteristics that retain excellent potency against Staphylococci and Francisella, and produce sufficient cGMP material to initiate Phase I clinical studies. We will determine the high-resolution protein structures of the Staphylococcal and Francisella Fabl targets to guide the medicinal chemistry efforts. We aim to select a development candidate compound from this program that has excellent antimicrobial activity both in vitro and in vivo against Staphylococci and Francisella and that can be formulated for both IV and oral administration. Phase I and Phase II clinical trials are proposed in Years 4 and 5, as a narrow spectrum agent for the treatment of Staphylococcal infections. This funding will assure rapid progress of this new class of antibacterial agent through the last stages of discovery and preclinical studies and into
Studies
25
the initiation of clinical trials. The funding will also assure that there are sufficient F. tularensis microbiological data and animal model data to warrant inclusion of the information on the product label as a narrow spectrum agent that could be used in the event of a F. tularensis release. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: OUTER MEMBRANE PROTEINS & LIPOPROTEINS OF F. TULARENSIS Principal Investigator & Institution: Norgard, Michael V.; Professor; University of Texas Sw Med Ctr/Dallas Dallas, Tx 753909105 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2008 Summary: Outer membrane proteins (OMPs) and lipoproteins (LPs) of Gram-negative bacteria are of enormous importance as virulence factors, stabilizers of outer membrane integrity, protective immune targets (vaccines), and proinflammatory agonists that elicit innate immune responses. LPs, in particular, also tend to be superior serological test reagents given that they induce strong antibody responses via their intrinsic adjuvant properties. Virtually nothing is known about the OMPs and LPs of Francisella tularensis strains that are pathogenic for humans (e.g., F. tularensis Schu4). The substantial biohazard issues surrounding the laboratory manipulation of such virulent strains undoubtedly have contributed to this dearth of information. Consequently, given the potential importance of OMPs and LPs as candidate vaccines and diagnostic reagents for tularemia, the Specific Aims of this proposal are: (1) To identify and characterize the major OMPs of F. tularensis strain Schu4 (Schu4); (2) To identify the LPs of Schu4, with emphasis on characterizing those within the outer membrane; (3) To clone and express in E. coli Schu4 0MP and LP genes as fusion proteins for the generation of specific polyclonal and/or monoclonal antibodies (antibodies will be used in membrane topology and surface localization studies); and (4) To perform vaccine studies in the murine model of tularemia using candidate Schu4 0MPs and LPs identified in Specific Aims 1-3. The studies will include state-of-the-art experimental approaches for OMP and LP identification, combined with a F. tularensis pulmonary challenge model for vaccine experiments in mice. Interdigitation with the other four complementary projects of this P01 Program will markedly enhance the success of this project. The combined studies could lead to the discovery of new diagnostic reagents and acellular vaccines for tularemia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: POLYCLONAL ANTIBODY LIBRARIES FOR TULAREMIA Principal Investigator & Institution: Sharon, Jacqueline; Professor; Boston Medical Center Gambro Bldg, 2Nd Fl, 660 Harrison Ave, Ste a Boston, Ma 02118 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2008 Summary: The goal of this project is to generate recombinant polyclonal antibody libraries (PCALs) that could be used, alone or in part, for prophylactic or therapeutic treatment of tularemia, as well as for diagnosis or environmental detection. Francisella tularensis, the etiologic agent of tularemia, is a facultative intracellular bacterium that causes a debilitating, sometimes fatal disease. Despite successful treatment with antibiotics, the morbidity associated with infection and the threat of engineered multiple antibiotic-resistant strains for bioterrorism, suggest the need for additional strategies to combat tularemia. We have developed the PCAL technology to combine the advantages of serum-derived polyclonal antibodies and hybridoma-derived monoclonal antibodies.
26 Tularemia
Hence, PCALs are standardized mixtures of polyclonal antibodies for which the genes are available and therefore the antibodies can be amplified and modified as desired. Antibody gene repertoires are harvested from B cell-containing tissues by RT-PCR and cloned to produce Fab phage display libraries that can be positively and negatively selected for desired binding specificities. The selected libraries are then converted, by mass gene transfer, into mammalian expression vector libraries encoding full-length antibodies in which the same repertoire of antibody variable region genes can be connected to constant region genes of any isotype or species. PCALs are then produced by transfection into mammalian cells. The specific aims for the current proposal are: 1) Optimize the antibody response in mice to virulent strains of F. tularensis; 2) Produce F. tularensis-specific PCALs that are all-mouse, all-human, or chimeric, from mice optimally immunized with F. tularensis; 3) Determine the in vitro efficacy of the PCALs produced in Aim 2 in complement-mediated killing and opsonophagocytosis (with or without complement) assays and in blocking infection of macrophages in culture; 4) Determine the in vivo prophylactic and therapeutic efficacy of the PCALs produced in Aim 2 against different strains of F. tularensis in mouse models of inhalational infection. The PCALs generated in this proposal will be available for industrial scale-up for prophylactic/therapeutic use as well as for diagnostic and environmental detection devices. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: OUTBREAKS
PROXIMAL
DETERMINANTS
OF
RISK
FOR
TULAREMIA
Principal Investigator & Institution: Telford, Sam R.; Veterinary Biomedical Sciences; Tufts University Boston Boston, Ma 02111 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-AUG-2005 Summary: (provided by the applicant): Although much is known about the biology of Francisella tularensis, the factors that regulate its natural prevalence remain undescribed. We seek to test the 'rule of the incumbent' hypothesis: by analogy with politics, F. tularensis epizootics in the northeastern United States are limited by interactions with a 'ruling' endosymbiotic Francisella sp. (previously classified as Wolbachia sp.) common within tissues of dog ticks, Dermacentor variabilis. The recent outbreak of tularemia on Martha's Vineyard provides a unique opportunity for identifying factors that serve as the basis for increased transmission of this rare infection because sites there appear to be longstanding natural foci of this infection. However, testing this hypothesis requires identification of these natural foci, which may comprise small patches of vegetation; transmission is not homogeneously distributed over the entire 100,000-hectare island. Accordingly, we first seek to identify such natural foci by (1) determining whether striped skunks (Mephitis mephitis) serve as effective sentinels for F. tularensis transmission; and (2) complementing skunk-based predictions by enlisting landscapers and others who are occupationally exposed to tularemia and other tick borne infections to actively report, in real time, the presence of animal carcasses encountered during their work. Natural foci will be definitively confirmed by intensive longitudinal epizootiologic analyses (prevalence of F. tularensis infection in ticks and other potential vector arthropods; evidence of exposure in rodents and other animals). In this manner, we shall accumulate reliable study sites and the preliminary data required for a comprehensive test of the 'rule of the incumbent' hypothesis. In addition, our mapping of risky sites may serve as the basis for local public health measures. We anticipate that the epidemiologic and epizootiologic methods developed or validated during the proposed work may contribute towards enhanced investigations of
Studies
27
tularemia outbreaks; new prevention strategies for those at risk of natural or illicit tularemia exposure; enhanced detection of F. tularensis in the environment; and, ultimately, a better understanding of F. tularensis-host interactions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PULMONARY INNATE IMMUNE ACTIVATION FOR BIOTERROR DEFENSE Principal Investigator & Institution: Krieg, Arthur M.; Senior Vice President, R&D/Chief Scienti; Coley Pharmaceutical Group, Inc. 93 Worcester St, Ste 101 Wellesley, Ma 02481 Timing: Fiscal Year 2003; Project Start 15-SEP-2003; Project End 28-FEB-2006 Summary: (provided by applicant): Civilians in the US and other countries face a growing threat from bioterrorism. It is not feasible to develop effective vaccines or treatments for all possible biowarfare agents that may be encountered. Furthermore, the identity of the bioterror agent(s) employed in an attack may not be known in time to administer specific therapies. Therefore, it is highly desirable to develop broadspectrum nonspecific therapies that can protect against a wide range of pathogens. In theory, pre-activating the appropriate innate defenses should reduce morbidity and mortality, and improve the response to supportive therapy. Hundreds of millions of years of evolution have endowed humans with an extraordinary range of innate immune defenses against viruses, bacteria, fungi, and parasites. This innate immunity is thought to depend in large part on a family of molecules called "Toll like receptors" (TLRs), which bind molecules that are present in microbes, but not in normal host tissues. Recent studies show that ligands for TLR9, called CpG motifs, are particularly effective at activating broad-spectrum innate immune defenses, and can protect animals against a wide range of pathogens. Preclinical studies show that pretreatment with a synthetic CpG oligodeoxynucleotide (ODN) protects mice against a wide variety of viruses, bacteria, and intracellular parasites, including the Category A agents anthrax, tularemia, and Ebola. For protection against an inhaled pathogen, the optimal route of administration for the CpG ODN also appears to be inhaled. Three classes of CpG ODN have been identified, CpG-A, CpG-B, and CpG-C, with distinct immune profiles with human cells in vitro and in vivo in mice. Phase I/II human clinical trials in over 300 subjects administered a CpG-B ODN suggest strong enhancement of immune responses and an excellent safety profile. The overall goal of this proposal is to identify a CpG ODN that provides broad-spectrum defense against pathogens in animal challenge models, and to develop this CpG for protection of civilians against a bioterror agent. Based on studies of over 3000 ODN in the three classes, one optimized ODN from each class has been selected for comparison in this program: CpG-A 10108, CpG-B 10105, and CpG-C 10107. Our proposal is based on the hypothesis that the prophylactic activation of particular innate immune defenses with a CpG ODN will protect against a subsequent exposure to one or more bioterror agents. It is expected that pretreatment with CpG would reduce morbidity and mortality from bioterror and prolong the "golden hour" during which supportive therapy and specific countermeasures could be administered. If successful, the proposed studies would provide supportive data for human safety clinical trials and an eventual NDA submission. This goal will be accomplished through the following specific aims: Specific Aim 1. Determine the efficacy of different CpG classes in protecting mice against inhaled Category A pathogens. Specific Aim 2. Determine the efficacy of different CpG classes in protecting against other inhaled pathogens. Specific Aim 3. Determine the effect of inhaled CpG classes on respiratory tract immune function. Specific Aim 4. Identification of peripheral biomarkers for inhaled CpG ODN (mice, swine, sheep, primates). Specific Aim 5.
28 Tularemia
Characterize the toxicity of inhaled CpG ODN. Specific Aim 6. Characterize the absorption, distribution, metabolism, and excretion of inhaled CpG ODN. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: RAPID IDENTIFICATION OF SECRETED OF F TULARENSIS ANTIGEN Principal Investigator & Institution: Heffron, Fred L.; Professor; Molecular Microbiology and Immunology; Oregon Health & Science University Portland, or 972393098 Timing: Fiscal Year 2002; Project Start 10-SEP-2002; Project End 31-AUG-2004 Summary: (provided by applicant): Intracellular bacterial pathogens secrete proteins after infection that function to alter the normal structural and metabolic machinery of the host cell thus facilitating their survival and avoidance of host immune surveillance. Recent discoveries of the molecular mechanisms that intracellular bacterial pathogens use for evasion or subversion of the immune system of the host will greatly facilitate the development of antibacterial vaccines and diagnostic tools. Much like many other intracellular facultative pathogens such as Salmonella typhimurium, Mycobacterium tuberculosis and Legionella pneumophila, F. tularensis shares a predilection for macrophages as its preferred host cell. However, in contrast to other intracellular bacterial pathogens, little is known about virulence factors used by F. tularensis internally within its host cell. We have designed and tested a system that enables us to identify Class I Accessible Proteins (CAPs) in Salmonella typhimurium and propose to utilize a similar approach for the study of F. tularensis. Due to their susceptibility to the host' s processing and presentation pathways, CAPs represent a potentially important resource for the design and construction of effective vaccines against F. tularensis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: REGION VI CENTER FOR BIODEFENCE AND EMERGING INFECTIONS Principal Investigator & Institution: Walker, David H.; Professor; Pathology; University of Texas Medical Br Galveston 301 University Blvd Galveston, Tx 77555 Timing: Fiscal Year 2003; Project Start 04-SEP-2003; Project End 29-FEB-2008 Summary: (provided by applicant): In response to NIAID's call for the creation of strong infrastructure and multifaceted research and development activities applying the best basic, translational, and clinical science to the generation of new diagnostic, therapeutic and vaccine countermeasures for Category A, B, and C pathogens posing threats as agents of bioterrorism, 22 institutions in Texas, New Mexico, Oklahoma, Arkansas, and Louisiana have combined their energy, creativity, and resources to propose creation of the Region Vl Center of Excellence for Biodefense and Emerging Infectious Diseases (Region Vl RCE). Nine scientific cores will provide access to state-of-the-art proteomics, genomics, standardized small animal and non-human primate models of infectious diseases, BSL-4 laboratory facilities, and GLP scale-up production, as well as crosscutting functions in computational biology and a streamlined process for translational development of vaccines and drugs leading to FDA approval. A wealth of scientific expertise on biothreat agents and contemporary biomedical technology will be applied to establishing the scientific basis and translating it through 11 major research projects, 3 developmental research projects, and 4 career development projects to the development of vaccines against Rift Valley fever, tularemia, smallpox, Venezuelan, eastern, and western equine encephalitis, brucellosis, and typhus; new therapeutic agents against Bacillus anthracis (including the spore), arenaviruses, filoviruses,
Studies
29
alphaviruses, flaviviruses, and poxviruses, as well as novel approaches to synthesis of chemical libraries that will promote future drug discovery; and advanced diagnostic methods for Q fever and typhus as well as computational analysis of all host response biosignatures observed within the RCE for the construction of diagnostic and prognostic algorithms and analysis of host responses to infection and immunization. A consistently strong spirit of cooperation among traditionally competing institutions has established an interlocking network of projects, cores, and administration that will strengthen and flourish as the Center is implemented. The guidance of this network of interactive research projects and core resource facilities will be executed under a comprehensive administrative plan to contribute substantially to the nation's biodefense mission by fulfilling a carefully crafted scientific strategy on a common theme; Collaborations for host-pathogen biology based development of novel vaccines, diagnostics, and therapeutics against biothreat agents. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SCREENING FOR INHIBITORS OF F. TULARENSIS VIRULENCE Principal Investigator & Institution: Pierini, Lynda M.; Surgery; Weill Medical College of Cornell Univ New York, Ny 10021 Timing: Fiscal Year 2003; Project Start 15-JUL-2003; Project End 30-JUN-2005 Summary: (provided by applicant): The gram-negative zoonotic bacteria, F tularensis is the causative agent of tularemia, a severe and sometimes fatal illness that can be caused by inoculation or inhalation of as few as 10 organisms. The extreme infectivity, ease of dissemination and capacity for disease and death, make the potential use of F tularensis as a biological weapon a serious concern. Despite this, there has been little basic science research on this pathogen. It is known that the macrophage is central for both the pathology and resolution of F tularensis infections. Accordingly, a molecular understanding of F tularensis interactions with macrophages is crucial if we hope to modify the course of disease with therapeutics. Chemical genetics provides a way to rapidly advance both fundamental and applied research on this genetically intractable microbe and we propose to use this approach, coupled with high resolution quantitative fluorescence microscopy to address the following two questions: First, how does F tularensis infect host cells? There is conflicting evidence regarding the entry mechanism used by this organism. It remains to be determined if F tularensis invades cells by phagocytosis, endocytosis or an active invasion mechanism. We will use fluorescence microscopy and pharmacological and molecular inhibitors to investigate the entry mechanisms, and we will use automated fluorescence imaging to screen a small molecule library for compounds that block macrophage infection. Knowledge of viral entry mechanisms is currently providing the basis for development of new therapeutics for HIV, so analogous information may be similarly helpful for protecting against F tularensis. Second, what are the properties of the intracellular niche occupied by F tularensis? Vacuoles inhabited by Mycobacteria, for example, are slightly acidic and this fact is being exploited for targeted delivery of antibiotics. There is scant data about the nature of the F tularensis vacuole. We will measure the pH of F tularensis-containing vacuoles using ratiometric fluorescence imaging, determine if vacuoles can fuse with early endosomes and/or lysosomes, and characterize the protein constituents of the vacuole. We will then use a fluorescence imaging-based screen to identify cellpermeable molecules that alter the intracellular fate of F tularensis. Small molecule modulators of F tularensis-macrophage interactions will be used in future experiments to identify virulence factors, and may provide leads for post-attack prophylaxes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
30
Tularemia
•
Project Title: SYSTEMIC LYMPH NODE SPECIFIC AGENTS Principal Investigator & Institution: Papisov, Mikhail I.; Associate Chemist; Nanopharma, Corporation C/O Puretech Ventures Boston, Ma 02116 Timing: Fiscal Year 2003; Project Start 15-APR-2003; Project End 14-APR-2004 Summary: (provided by applicant): This is an amended application 1 R41 AI052921-01. The overall goal of this project is to develop new targeted formulations of antibiotics for prevention and treatment of diseases caused by Category A pathogens, in particular Bacillus anthracis (anthrax), Yersinia pestis (plague), and Francisella tularensis (tularemia). These preparations will specifically accumulate inside and or in the near vicinity of cells harboring such pathogens after exposure to weaponized (aerosolized) biological agents. Availability of such preparations will provide new strategies of disease prevention for those at risk of exposure, and novel effective treatments for those already infected. The proposed new formulations will be based on lymph node-specific nanocarriers developed at Massachusetts General Hospital. These carriers are capable of transporting various drug substances to lymph node phagocytes (primary pathogenharboring cells) after systemic administration. It is expected that delivery of antibiotics by such carriers will result in much higher drug levels in the infected lymph node tissue than conventional preparations of the same antibiotics. Thus, the primary site of germination and development of weaponized biological agents will be sufficiently saturated with drugs to prevent or stop disease development at the very early stage (before the onset of symptoms). The objective of this project is to test feasibility of previously established nanocarrier technology for loading lymph node phagocytes with two model antibiotics (one of Fluoroquinolone and one of Tetracycline families), and to develop two respective prototype preparations for further characterization and optimization. The specific aims are: (1) develop two prototype lymph node specific preparations (of Ciprofloxacin and Tetracycline); (2) investigate, in a rodent model, the degree of drug accumulation inside and in the near vicinity of target cells, and (3) evaluate efficacy in infected cells. If successful, this project will result in the development of a new class of preparations and a new strategy for prophylactic and early post-exposure treatment of bacterial diseases of Category A. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: TULAREMIA AND LUNG INNATE IMMUNITY Principal Investigator & Institution: Schlesinger, Larry S.; Associate Professor; Ohio State University Research Fdn Columbus, Oh 43210 Timing: Fiscal Year 2003; Project Start 04-SEP-2003; Project End 31-AUG-2005 Summary: Francisella tularensis, the causative agent of Tularemia, is a highly virulent intracellular pathogen of macrophages. When used as an agent of bioterrorism, the bacterium would be presented as an aerosol As such, the first interaction between F. tularensis and the human host occurs in the lung where it would encounter the unique alveolar macrophage (AM). AMs are bathed in surfactant, components of which regulate macrophage function and microbe-cell interactions [i.e. surfactant protein A (SP-A) and surfactant protein D (SP-D)]. Thus, interactions between F. tularensis and AM are particularly important in understanding disease pathogenesis and the host response. Much of the work on F. tularensis has used the live vaccine strain (LVS), a strain that is avirulent in humans but is fully virulent and lethal in mice. In vitro, the bacterium enters murine macrophages and proliferates in a phagosome that does not fuse with lysosomes. The details of the phagocytic pathway and the nature of the phagosome are poorly understood. For other intracellular pathogens of macrophages
Studies
31
that reside in unique phagosomes with limited lysosomal fusion such as pathogenic mycobacteria; complement receptors, esp. CR3, and the mannose receptor (MR) play major roles in phagocytosis. Our laboratory has identified the important role for CR3 and the MR in the phagocytosis of M. tuberculosis by human monocyte-derived macrophages (MDMs) and alveolar macrophages (AMs). We have determined that the nature of the receptor-ligand interaction(s) impacts on the immediate host cell response. Further, our studies provide evidence that SP-A and SP-D play important, but distinct roles in the lung innate immune response to M. tuberculosis. The goal of this proposal is to identify the microbial and macrophage factors that mediate phagocytosis of F. tularensis by human macrophages, including AMs, and to determine whether the phagocytic pathway influences the formation of the F. tularensis phagosome shortly following entry. Once the pathway is further elucidated, we will determine whether components of surfactant, i.e. SP-A and SP-D, alter it in order to gain insight into the unique interaction between F. tularensis and the lung innate immune system. We will utilize our expertise in macrophage biology and immunologic and molecular techniques to address these issues in order to identify the molecular determinants involved. Such determinants will be targets for the development of new therapeutic and vaccine interventions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TULAREMIA VACCINE DEVELOPMENT Principal Investigator & Institution: Wetzler, Lee M.; Associate Professor; Boston Medical Center Gambro Bldg, 2Nd Fl, 660 Harrison Ave, Ste a Boston, Ma 02118 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2008 Summary: Francisella tularensis, a facultative intracellular pathogen, causes significant disease including classic ulceroglandular tularemic infection and the more deadly pulmonary tularemic infection with dissemination and tularemia. Immunity to this potential bioterrorist agent is unclearbut it appears both humoral and cell mediated immunity play a role. The purpose of this project is to investigate the potential protective efficacy of anti-Francisella vaccines consisting of Francisella capsular polysaccharide or LPS derived oligosaccharides. As these antigens are classic T-cell independent antigens, the humoral immune response towards these antigens shall be optimized by inducing a T-cell dependent response by 1) either combining these antigens with the vaccine adjuvant, meningococcal porin PorB, or conjugating the antigens to the classic vaccine carrier, tetanus toxoid or 2) convert the epitopes of F-CPS or F-OS to protein based peptide mimotopes. Both these methods are state of the art and have proven to be effective in increasing the efficacy of polysaccharide based vaccines. Most, if not all, effective anti-bacterial vaccines consist of bacterial capsular polysaccharides and this approach has great potential in inducing protection. The aims of this proposal are 1) Preparation of the Francisella capsular polysaccharide (F-CPS) and Francisella LPS derived oligosaccharide (F-OS) vaccine immunogens (combined with various adjuvants), immunization of mice and determination of anti-Francisella IgG levels, 2) Development of F-CPS and F-OS protein mimotpes and optimization of vaccine preparations based on the peptide mimotopes consensus sequences and measurement of IgG antibodies induced by this method that recognize native antigen and intact organism and 3) Determination of the potential protective efficacy of both set of vaccine preparations in Aims 1 and 2 by examining the functional activity of the vaccine induced sera in bactericidal assays, opsonophagocytic assays and prevention of macrophage invasion and measuring the protective effect of vaccination in the murine inhalation model of tularemia.
32 Tularemia
Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TULARENSIS
VIRULENCE
GENES
IDENTIFICATION
IN
FRANCISELLA
Principal Investigator & Institution: Escuyer, Vincent E.; Research Scientist; Southern Research Institute Birmingham, Al 35205 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-AUG-2005 Summary: (provided by applicant): F. tularensis, is a facultative intracellular bacterial pathogen considered as a major biological warfare agent, mainly because it is very infectious and can cause life threatening illness in humans. Without treatment, the mortality rate has been as high as 30 to 60% for the pulmonary form of tularemia, which is the most likely form in case of an act of bioterrorism. Treatment of human tularemia relies upon antibiotic therapies but relapse is frequent. Also, it is possible to engineer multiresistant strains. A live attenuated vaccine is available but confers incomplete protection, particularly if administered after exposure. Therefore, there is a crucial need for new treatments and vaccines against tularemia. However, understanding of the mechanisms of virulence in F. tularensis is currently too limited to address this problem efficiently. This is partly due to the lack of genetic tools, particularly a simple method of general mutagenesis. Transposable elements have become valuable mutagenic tools for genetic and molecular analysis in many different bacteria. However, no direct transposition has been observed so far in F. tularensis. The main goals of this proposal are as follows: first, to develop a simple and reproducible method of transposon mutagenesis in F. tularensis, by using a fully functional Tn5 transposition system (EZ::TN TM TransposomeTM), reconstituted in vitro. Our preliminary work has shown strong evidence for direct transposition in F. tularensis with this system; second, to perform transposon signature-tagged mutagenesis to isolate mutants attenuated in their virulence, in the mouse model. This pilot study should provide important informations on the genes involved in the virulence of F. tularensis and a better understanding of the pathogenicity of this microorganism. Some of the virulence genes will be used as potential targets for new approaches in drug design and vaccine development. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
E-Journals: PubMed Central3 PubMed Central (PMC) is a digital archive of life sciences journal literature developed and managed by the National Center for Biotechnology Information (NCBI) at the U.S. National Library of Medicine (NLM).4 Access to this growing archive of e-journals is free and unrestricted.5 To search, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Pmc, and type “tularemia” (or synonyms) into the search box. This search gives you access to fulltext articles. The following is a sample of items found for tularemia in the PubMed Central database:
3 4
Adapted from the National Library of Medicine: http://www.pubmedcentral.nih.gov/about/intro.html.
With PubMed Central, NCBI is taking the lead in preservation and maintenance of open access to electronic
literature, just as NLM has done for decades with printed biomedical literature. PubMed Central aims to become a
world-class library of the digital age.
5 The value of PubMed Central, in addition to its role as an archive, lies in the availability of data from diverse
sources stored in a common format in a single repository. Many journals already have online publishing operations,
and there is a growing tendency to publish material online only, to the exclusion of print.
Studies
33
•
Comparative Analysis of PCR versus Culture for Diagnosis of Ulceroglandular Tularemia. by Johansson A, Berglund L, Eriksson U, Goransson I, Wollin R, Forsman M, Tarnvik A, Sjostedt A.; 2000 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=86009
•
Cytokine expression in the liver during the early phase of murine tularemia. by Golovliov I, Sandstrom G, Ericsson M, Sjostedt A, Tarnvik A.; 1995 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=173028
•
Detection of Francisella tularensis in ulcers of patients with tularemia by PCR. by Sjostedt A, Eriksson U, Berglund L, Tarnvik A.; 1997 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=232700
•
Expansion of V[gamma]9V[delta]2 T Cells Is Triggered by Francisella tularensisDerived Phosphoantigens in Tularemia but Not after Tularemia Vaccination. by Poquet Y, Kroca M, Halary F, Stenmark S, Peyrat MA, Bonneville M, Fournie JJ, Sjostedt A.; 1998 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=108170
•
Rapid Local Expression of Interleukin-12, Tumor Necrosis Factor Alpha, and Gamma Interferon after Cutaneous Francisella tularensis Infection in Tularemia-Immune Mice. by Stenmark S, Sunnemark D, Bucht A, Sjostedt A.; 1999 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=96529
•
Seroepidemiologic study of three zoonoses (leptospirosis, Q fever, and tularemia) among trappers in Quebec, Canada. by Levesque B, De Serres G, Higgins R, D'Halewyn MA, Artsob H, Grondin J, Major M, Garvie M, Duval B.; 1995 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=170188
•
Tularemia. by Ellis J, Oyston PC, Green M, Titball RW.; 2002 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=126859
•
Tularemia. by Levin W.; 1940 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=233540
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.
6
PubMed was developed by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM) at the National Institutes of Health (NIH). The PubMed database was developed in conjunction with publishers of biomedical literature as a search tool for accessing literature citations and linking to full-text journal articles at Web sites of participating publishers. Publishers that participate in PubMed supply NLM with their citations electronically prior to or at the time of publication.
34 Tularemia
To generate your own bibliography of studies dealing with tularemia, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “tularemia” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for tularemia (hyperlinks lead to article summaries): •
“Muskrat fever”: two outbreaks of tularemia near Montreal. Author(s): Ford-Jones L, Delage G, Powell KR, Ahronheim GA, Rousseau E, Gosselin F. Source: Can Med Assoc J. 1982 August 15; 127(4): 298-9. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7046897&dopt=Abstract
•
A case of insect borne tularemia above the tree line. Author(s): Silverman M, Law B, Carson J.
Source: Arctic Med Res. 1991; Suppl: 377-9.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=1365160&dopt=Abstract
•
A case of tularemia meningitis in Sweden. Author(s): Hill B, Sandstrom G, Schroder S, Franzen C, Tarnvik A.
Source: Scandinavian Journal of Infectious Diseases. 1990; 22(1): 95-9.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=2320968&dopt=Abstract
•
A family outbreak of tularemia. Author(s): Greco D, Ninu E.
Source: European Journal of Epidemiology. 1985 September; 1(3): 232-3.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=3842118&dopt=Abstract
•
A five-year evaluation of tularemia in Arkansas. Author(s): McChesney TC, Narain J.
Source: J Ark Med Soc. 1983 November; 80(6): 257-62. No Abstract Available.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=6227605&dopt=Abstract
•
A procedure for differentiating between the intentional release of biological warfare agents and natural outbreaks of disease: its use in analyzing the tularemia outbreak in Kosovo in 1999 and 2000. Author(s): Grunow R, Finke EJ.
Source: Clinical Microbiology and Infection : the Official Publication of the European
Society of Clinical Microbiology and Infectious Diseases. 2002 August; 8(8): 510-21.
Review.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=12197873&dopt=Abstract
•
A skin test survey of tularemia in a Montana sheep-raising county. Author(s): Casper EA, Philip RN.
Source: Public Health Reports (Washington, D.C. : 1974). 1969 July; 84(7): 611-5.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=4980174&dopt=Abstract
Studies
35
•
A tale of tularemia. Author(s): Coffey JD Jr.
Source: Pediatr Infect Dis. 1984 January-February; 3(1): 89-90. No Abstract Available.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=6701107&dopt=Abstract
•
A waterborne tularemia outbreak. Author(s): Greco D, Allegrini G, Tizzi T, Ninu E, Lamanna A, Luzi S.
Source: European Journal of Epidemiology. 1987 March; 3(1): 35-8.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=3582597&dopt=Abstract
•
A whole-blood lymphocyte stimulation test for the diagnosis of human tularemia. Author(s): Syrjala H, Herva E, Ilonen J, Saukkonen K, Salminen A.
Source: The Journal of Infectious Diseases. 1984 December; 150(6): 912-5.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=6501932&dopt=Abstract
•
Acute glaucoma and acute corneal oedema in association with tularemia. Author(s): Parssinen O, Rummukainen M.
Source: Acta Ophthalmologica Scandinavica. 1997 December; 75(6): 732-4.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=9527343&dopt=Abstract
•
Adrenocortical responses during tularemia in human subjects. Author(s): Beisel WR, Bruton J, Anderson KD, Sawyer WD.
Source: The Journal of Clinical Endocrinology and Metabolism. 1967 January; 27(1): 61-9.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=4225306&dopt=Abstract
•
Adult respiratory distress syndrome secondary to tularemia pneumonia. Author(s): Sunderrajan EV, Hutton J, Marienfeld RD.
Source: Archives of Internal Medicine. 1985 August; 145(8): 1435-7.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=4026475&dopt=Abstract
•
Aerogenic immunization of man with live Tularemia vaccine. Author(s): Hornick RB, Eigelsbach HT.
Source: Bacteriol Rev. 1966 September; 30(3): 532-8. No Abstract Available.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=5917334&dopt=Abstract
•
Agglutination and ELISA methods in the diagnosis of tularemia in different clinical forms and severities of the disease. Author(s): Syrjala H, Koskela P, Ripatti T, Salminen A, Herva E.
Source: The Journal of Infectious Diseases. 1986 January; 153(1): 142-5.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=3941279&dopt=Abstract
36 Tularemia
•
Agglutinins and antibodies to Francisella tularensis outer membrane antigens in the early diagnosis of disease during an outbreak of tularemia. Author(s): Bevanger L, Maeland JA, Naess AI.
Source: Journal of Clinical Microbiology. 1988 March; 26(3): 433-7.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=3356786&dopt=Abstract
•
Airborne transmission of tularemia in farmers. Author(s): Syrjala H, Kujala P, Myllyla V, Salminen A.
Source: Scandinavian Journal of Infectious Diseases. 1985; 17(4): 371-5.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=4089543&dopt=Abstract
•
Airborne tularemia in Sweden. Author(s): Dahlstrand S, Ringertz O, Zetterberg B.
Source: Scandinavian Journal of Infectious Diseases. 1971; 3(1): 7-16.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=5099427&dopt=Abstract
•
An epidemic of tularemia in Sweden during the summer of 1967. Author(s): Myrback KE, Ringertz O, Dahlstrand S.
Source: Acta Pathol Microbiol Scand. 1968; 72(3): 463-4. No Abstract Available.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=4385092&dopt=Abstract
•
An outbreak of human tularemia associated with the American dog tick, Dermacentor variabilis. Author(s): Saliba GS, Harmston FC, Diamond BE, Zymet CL, Goldenberg MI, Chin TD. Source: The American Journal of Tropical Medicine and Hygiene. 1966 July; 15(4): 531-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5949558&dopt=Abstract
•
An outbreak of primary pneumonic tularemia on Martha's Vineyard. Author(s): Feldman KA, Enscore RE, Lathrop SL, Matyas BT, McGuill M, Schriefer ME,
Stiles-Enos D, Dennis DT, Petersen LR, Hayes EB.
Source: The New England Journal of Medicine. 2001 November 29; 345(22): 1601-6.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=11757506&dopt=Abstract
•
An outbreak of primary pneumonic tularemia. Author(s): Perez-Castrillon J, Bachiller-Luque P, Mena-Martin FJ.
Source: The New England Journal of Medicine. 2002 March 28; 346(13): 1027-9; Author
Reply 1027-9.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=11924660&dopt=Abstract
Studies
37
•
An outbreak of primary pneumonic tularemia. Author(s): Stralin K, Eliasson H, Back E.
Source: The New England Journal of Medicine. 2002 March 28; 346(13): 1027-9; Author
Reply 1027-9.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=11919317&dopt=Abstract
•
An outbreak of tularemia in the northern part of central Sweden. Author(s): Christenson B.
Source: Scandinavian Journal of Infectious Diseases. 1984; 16(3): 285-90.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=6149615&dopt=Abstract
•
Analysis of 106 cases of tularemia. Author(s): Sanders CV, Hahn R.
Source: J La State Med Soc. 1968 September; 120(9): 391-3. No Abstract Available.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=5693258&dopt=Abstract
•
Anthrax, botulism and tularemia in Italy. Author(s): Serraino D, Puro V, Bidoli E, Piselli P, Girardi E, Ippolito G.
Source: Infection. 2003 March; 31(2): 128-9.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=12749299&dopt=Abstract
•
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
•
Antibiotic prophylaxis and therapy of airborne tularemia. Author(s): Sawyer WD, Dangerfield HG, Hogge AL, Crozier D.
Source: Bacteriol Rev. 1966 September; 30(3): 542-50. No Abstract Available.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=4958341&dopt=Abstract
•
Arthropod-borne tularemia in Japan: clinical analysis of 1,374 cases observed between 1924 and 1996. Author(s): Ohara Y, Sato T, Homma M.
Source: Journal of Medical Entomology. 1998 July; 35(4): 471-3.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=9701929&dopt=Abstract
38 Tularemia
•
Bacteriological study of a natural focus of tularemia in the Lake Reserve of Srebrna, the Silistra region, Bulgaria. Author(s): Dinev T, Zlatanov Z.
Source: J Hyg Epidemiol Microbiol Immunol. 1972; 16(3): 341-5. No Abstract Available.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=4673074&dopt=Abstract
•
Behavioral effects of tularemia and sandfly fever in man. Author(s): Alluisi EA, Beisel WR, Bartelloni PJ, Coates GD.
Source: The Journal of Infectious Diseases. 1973 December; 128(6): 710-7.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=4203075&dopt=Abstract
•
Bronchial changes in airborne tularemia. Author(s): Syrjala H, Sutinen S, Jokinen K, Nieminen P, Tuuponen T, Salminen A. Source: The Journal of Laryngology and Otology. 1986 October; 100(10): 1169-76. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3772243&dopt=Abstract
•
Bubonic plague misdiagnosed as tularemia. Retrospective serologic diagnosis. Author(s): Sites VR, Poland JD, Hudson BW.
Source: Jama : the Journal of the American Medical Association. 1972 December 25;
222(13): 1642-3.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=4678367&dopt=Abstract
•
Case report of tularemia. Author(s): Pace SA.
Source: American Family Physician. 1980 June; 21(6): 23.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=7377083&dopt=Abstract
•
Case report. Tularemia in Ohio: report of two cases and clinical review. Author(s): Myers JP, Baird IM.
Source: The American Journal of the Medical Sciences. 1981 November-December;
282(3): 148-52.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=7315867&dopt=Abstract
•
Case report. Tularemia presenting as unresponsive pneumonia: diagnosis and therapy with gentamicin. Author(s): Jackson RT, Lester JP.
Source: J Tenn Med Assoc. 1978 March; 71(3): 189-91. No Abstract Available.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=661292&dopt=Abstract
Studies
39
•
Cat scratch induced tularemia. Author(s): Cooper WR, Ewell NM Jr.
Source: Va Med Mon (1918). 1973 July; 100(7): 640-2. No Abstract Available.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=4736842&dopt=Abstract
•
Cat-bite tularemia in a seventeen-year-old girl treated with ciprofloxacin. Author(s): Arav-Boger R.
Source: The Pediatric Infectious Disease Journal. 2000 June; 19(6): 583-4.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=10877184&dopt=Abstract
•
Cat-bite tularemia. Author(s): Quenzer RW, Mostow SR, Emerson JK.
Source: Jama : the Journal of the American Medical Association. 1977 October 24;
238(17): 1845.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=578542&dopt=Abstract
•
Cavitary pneumonia associated with tularemia. Author(s): Kozak AJ, Hall WH, Gerding DN.
Source: Chest. 1978 March; 73(3): 426-7.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=630947&dopt=Abstract
•
Changes of the epidemiology and the clinical picture of tularemia in Southern Moravia (the Czech Republic) during the period 1936-1999. Author(s): Cerny Z.
Source: European Journal of Epidemiology. 2001; 17(7): 637-42.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=12086077&dopt=Abstract
•
Ciprofloxacin for treatment of tularemia in children. Author(s): Johansson A, Berglund L, Gothefors L, Sjostedt A, Tarnvik A.
Source: The Pediatric Infectious Disease Journal. 2000 May; 19(5): 449-53.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=10819342&dopt=Abstract
•
Ciprofloxacin for treatment of tularemia. Author(s): Johansson A, Berglund L, Sjostedt A, Tarnvik A.
Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases
Society of America. 2001 July 15; 33(2): 267-8.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=11418893&dopt=Abstract
40 Tularemia
•
Clinical manifestations of tularemia in Japan--analysis of 1,355 cases observed between 1924 and 1987. Author(s): Ohara Y, Sato T, Fujita H, Ueno T, Homma M.
Source: Infection. 1991 January-February; 19(1): 14-7.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=2013502&dopt=Abstract
•
Clinically mild tularemia associated with tick-borne Francisella tularensis. Author(s): Schmid GP, Kornblatt AN, Connors CA, Patton C, Carney J, Hobbs J,
Kaufmann AF.
Source: The Journal of Infectious Diseases. 1983 July; 148(1): 63-7.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=6886487&dopt=Abstract
•
Comparative analysis of antibodies to Francisella tularensis antigens during the acute phase of tularemia and eight years later. Author(s): Bevanger L, Maeland JA, Kvan AI.
Source: Clinical and Diagnostic Laboratory Immunology. 1994 March; 1(2): 238-40.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=7496953&dopt=Abstract
•
Comparative analysis of PCR versus culture for diagnosis of ulceroglandular tularemia. Author(s): Johansson A, Berglund L, Eriksson U, Goransson I, Wollin R, Forsman M,
Tarnvik A, Sjostedt A.
Source: Journal of Clinical Microbiology. 2000 January; 38(1): 22-6.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=10618057&dopt=Abstract
•
Competitive enzyme immunoassay for antibodies to a 43,000-molecular-weight Francisella tularensis outer membrane protein for the diagnosis of tularemia. Author(s): Bevanger L, Maeland JA, Naess AI.
Source: Journal of Clinical Microbiology. 1989 May; 27(5): 922-6.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=2745701&dopt=Abstract
•
Culture of P. tularensis in the 1966-67 outbreaks of tularemia in Sweden. Laboratory methods and precautions against laboratory infections. Author(s): Ringertz O, Dahlstrand S.
Source: Acta Pathol Microbiol Scand. 1968; 72(3): 464. No Abstract Available.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=5689988&dopt=Abstract
•
Detection of antigen in urine of a patient with tularemia. Author(s): Tarnvik A, Lofgren S, Ohlund L, Sandstrom G.
Source: European Journal of Clinical Microbiology. 1987 June; 6(3): 318-9.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=3622500&dopt=Abstract
Studies
41
•
Detection of Francisella tularensis in ulcers of patients with tularemia by PCR. Author(s): Sjostedt A, Eriksson U, Berglund L, Tarnvik A.
Source: Journal of Clinical Microbiology. 1997 May; 35(5): 1045-8.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=9114378&dopt=Abstract
•
Development of Francisella tularensis antigen responses measured as T-lymphocyte proliferation and cytokine production (tumor necrosis factor alpha, gamma interferon, and interleukin-2 and -4) during human tularemia. Author(s): Surcel HM, Syrjala H, Karttunen R, Tapaninaho S, Herva E.
Source: Infection and Immunity. 1991 June; 59(6): 1948-53.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=1674737&dopt=Abstract
•
Dual infection: tularemia and Lyme borreliosis acquired by single tick bite in northwest Croatia. Author(s): Golubic D, Zember S.
Source: Acta Med Croatica. 2001; 55(4-5): 207-9.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=12398025&dopt=Abstract
•
Ecological features of the tularemia natural focus in central Posavina (Croatia). Author(s): Borcic B, Hrabar A, Dulic B, Tvrtkovic N, Bilic V, Mikacic D.
Source: Folia Parasitol (Praha). 1976; 23(3): 257-65.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=795754&dopt=Abstract
•
Ecological research as a base of epidemiological forecasting (in a natural focus of tularemia). Author(s): Borcic B, Hrabar A, Tvrtkovic N, Bilic V, Mikacic D, Dulic B.
Source: Revue D'epidemiologie Et De Sante Publique. 1978 March 15; 25(5-6): 437-9.
English, French.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=370926&dopt=Abstract
•
Enzyme-linked immunosorbent assay for immunological diagnosis of human tularemia. Author(s): Carlsson HE, Lindberg AA, Lindberg G, Hederstedt B, Karlsson KA, Agell
BO.
Source: Journal of Clinical Microbiology. 1979 November; 10(5): 615-21.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=120873&dopt=Abstract
•
Epidemiologic characteristics of human tularemia in the southwest-central states, 1981-1987. Author(s): Taylor JP, Istre GR, McChesney TC, Satalowich FT, Parker RL, McFarland
LM.
Source: American Journal of Epidemiology. 1991 May 15; 133(10): 1032-8.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=2035503&dopt=Abstract
42 Tularemia
•
Epidemiologic study of human tularemia reported in Missouri, 1949-65. Author(s): Assal N, Blenden DC, Price ER.
Source: Public Health Reports (Washington, D.C. : 1974). 1967 July; 82(7): 627-32.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=4961434&dopt=Abstract
•
Epidemiologic study on reported human tularemia in Oklahoma, 1944-65. Author(s): Assal NR, Lindeman RD, Carpenter RL.
Source: J Okla State Med Assoc. 1968 March; 61(3): 120-4. No Abstract Available.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=5641655&dopt=Abstract
•
Epidemiological analysis of tularemia in Japan (yato-byo). Author(s): Ohara Y, Sato T, Homma M.
Source: Fems Immunology and Medical Microbiology. 1996 March; 13(3): 185-9. Review.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=8861026&dopt=Abstract
•
Epidemiological analysis of tularemia in Sweden 1931-1993. Author(s): Tarnvik A, Sandstrom G, Sjostedt A.
Source: Fems Immunology and Medical Microbiology. 1996 March; 13(3): 201-4.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=8861029&dopt=Abstract
•
Epidemiology and clinical characteristics of tularemia in Oklahoma, 1979 to 1985. Author(s): Rohrbach BW, Westerman E, Istre GR.
Source: Southern Medical Journal. 1991 September; 84(9): 1091-6.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=1891728&dopt=Abstract
•
Erythema nodosum revealing oculoglandular tularemia. Author(s): Peter R, Banyai T.
Source: Dermatology (Basel, Switzerland). 2001; 202(1): 79-80.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=11244242&dopt=Abstract
•
Expansion of Vgamma9 Vdelta2 T cells is triggered by Francisella tularensis-derived phosphoantigens in tularemia but not after tularemia vaccination. Author(s): Poquet Y, Kroca M, Halary F, Stenmark S, Peyrat MA, Bonneville M, Fournie
JJ, Sjostedt A.
Source: Infection and Immunity. 1998 May; 66(5): 2107-14.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=9573096&dopt=Abstract
•
Factors associated with a poor outcome in tularemia. Author(s): Penn RL, Kinasewitz GT.
Source: Archives of Internal Medicine. 1987 February; 147(2): 265-8.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=3813743&dopt=Abstract
Studies
43
•
Fatal-cat trasmitted tularemia: demonstration of the organism in tissue. Author(s): Gallivan MV, Davis WA 2nd, Garagusi VF, Paris AL, Lack EE.
Source: Southern Medical Journal. 1980 February; 73(2): 240-2.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=6153473&dopt=Abstract
•
Field investigations of tularemia in Norway. Author(s): Berdal BP, Mehl R, Meidell NK, Lorentzen-Styr AM, Scheel O.
Source: Fems Immunology and Medical Microbiology. 1996 March; 13(3): 191-5.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=8861027&dopt=Abstract
•
Focus of tularemia in the Pisz district. Author(s): Dominowska C, Malottke R.
Source: Biul Inst Med Morsk Gdansk. 1972; 23(1): 95-100. No Abstract Available.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=4505628&dopt=Abstract
•
Francisella tularensis-induced in vitro gamma interferon, tumor necrosis factor alpha, and interleukin 2 responses appear within 2 weeks of tularemia vaccination in human beings. Author(s): Karttunen R, Surcel HM, Andersson G, Ekre HP, Herva E.
Source: Journal of Clinical Microbiology. 1991 April; 29(4): 753-6.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=1909711&dopt=Abstract
•
Further studies on tularemia in Alaska: human tularemia. Author(s): Miller LG.
Source: Canadian Journal of Microbiology. 1974 November; 20(11): 1539-44.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=4434260&dopt=Abstract
•
Further studies on tularemia in Alaska: virulence and biochemical characteristics of indigenous strains. Author(s): Miller LG.
Source: Canadian Journal of Microbiology. 1974 November; 20(11): 1585-90.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=4434261&dopt=Abstract
•
Glandular tularemia with typhoidal features in a Manitoba child. Author(s): Jacobs H.
Source: Cmaj : Canadian Medical Association Journal = Journal De L'association
Medicale Canadienne. 1992 November 1; 147(9): 1313.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=1483231&dopt=Abstract
44 Tularemia
•
Glandular tularemia with typhoidal features in a Manitoba child. Author(s): Plourde PJ, Embree J, Friesen F, Lindsay G, Williams T.
Source: Cmaj : Canadian Medical Association Journal = Journal De L'association
Medicale Canadienne. 1992 June 1; 146(11): 1953-5.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=1596844&dopt=Abstract
•
Guillain-Barre syndrome and tularemia pleuritis with high adenosine deaminase activity in pleural fluid. Author(s): Syrjala H, Koskela P, Kujala P, Myllyla V.
Source: Infection. 1989 May-June; 17(3): 152-3.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=2737756&dopt=Abstract
•
Head and neck manifestations of tularemia. Author(s): Wills PI, Gedosh EA, Nichols DR.
Source: The Laryngoscope. 1982 July; 92(7 Pt 1): 770-3.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=7087646&dopt=Abstract
•
Hepatic abscess complicating ulceroglandular tularemia. Author(s): Gourdeau M, Lamothe F, Ishak M, Cote J, Breton G, Villeneuve JP, D'Amico P.
Source: Can Med Assoc J. 1983 December 15; 129(12): 1286-8.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=6652596&dopt=Abstract
•
Hepatic porphyrias simulating typhoidal tularemia. Author(s): Loftin EB 3rd.
Source: American Family Physician. 1982 July; 26(1): 45, 48.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=7090965&dopt=Abstract
•
Histopathology of human lymph node tularemia caused by Francisella tularensis var palaearctica. Author(s): Sutinen S, Syrjala H.
Source: Archives of Pathology & Laboratory Medicine. 1986 January; 110(1): 42-6.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=3753568&dopt=Abstract
•
Human tularemia at an urban zoo. Author(s): Preiksaitis JK, Crawshaw GJ, Nayar GS, Stiver HG.
Source: Can Med Assoc J. 1979 October 20; 121(8): 1097-9. No Abstract Available.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=120758&dopt=Abstract
Studies
45
•
Hydatid disease, epidemic nephritis, and tularemia in northern Sweden. Author(s): Soderhjelm L.
Source: Archives of Environmental Health. 1969 January; 18(1): 127-32.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=5812430&dopt=Abstract
•
Immunization against tularemia: analysis of the effectiveness of live Francisella tularensis vaccine in prevention of laboratory-acquired tularemia. Author(s): Burke DS.
Source: The Journal of Infectious Diseases. 1977 January; 135(1): 55-60.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=833449&dopt=Abstract
•
Importance of surveillance of tularemia natural foci in the known endemic area of Central Europe, 1991-1997. Author(s): Gurycova D, Vyrostekova V, Khanakah G, Kocianova E, Stanek G.
Source: Wiener Klinische Wochenschrift. 2001 June 15; 113(11-12): 433-8.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=11467089&dopt=Abstract
•
Index of suspicion. Case 2. Diagnosis: ulceroglandular tularemia. Author(s): Fisher RG.
Source: Pediatrics in Review / American Academy of Pediatrics. 1996 June; 17(6): 221-3.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=8992473&dopt=Abstract
•
Influence of intermittent 98 percent oxygen and 380 mm. hg total pressure on susceptibility to tularemia. SAM-TR-67-9. Author(s): Schmidt JP, Cordaro JT, Busch LF Jr, Ball RJ.
Source: Tech Rep Sam-Tr. 1966 November; : 1-3. No Abstract Available.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=5298108&dopt=Abstract
•
Infraspecific taxonomy of tularemia agent Francisella tularensis McCoy et Chapin. Author(s): Olsufjev NG, Meshcheryakova IS.
Source: J Hyg Epidemiol Microbiol Immunol. 1982; 26(3): 291-9.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=7142690&dopt=Abstract
•
Insulin response during tularemia in man. Author(s): Shambaugh GE 3rd, Beisel WR.
Source: Diabetes. 1967 June; 16(6): 369-76.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=6025263&dopt=Abstract
46 Tularemia
•
Interleukin 2 and gamma interferon production, interleukin 2 receptor expression, and DNA synthesis induced by tularemia antigen in vitro after natural infection or vaccination. Author(s): Karttunen R, Andersson G, Ekre HP, Juutinen K, Surcel HM, Syrjala H,
Herva E.
Source: Journal of Clinical Microbiology. 1987 June; 25(6): 1074-8.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=3110207&dopt=Abstract
•
Investigations of mammals in the surroundings of Akhtopol (Bulgaria) on the incidence of tularemia. Author(s): Pavlov P, Hubalek Z, Daniel M, Rosicky B.
Source: Folia Parasitol (Praha). 1978; 25(1): 87-9. No Abstract Available.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=640529&dopt=Abstract
•
Landmark article April 25, 1925: Tularemia. By Edward Francis. Author(s): Francis E.
Source: Jama : the Journal of the American Medical Association. 1983 December 16;
250(23): 3216-24.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=6358564&dopt=Abstract
•
Landmark perspective: Tularemia. Author(s): Sanford JP.
Source: Jama : the Journal of the American Medical Association. 1983 December 16;
250(23): 3225-6.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=6358566&dopt=Abstract
•
Lawnmower tularemia. Author(s): McCarthy VP, Murphy MD.
Source: The Pediatric Infectious Disease Journal. 1990 April; 9(4): 298-300.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=2336320&dopt=Abstract
•
Massive adenopathy in oropharyngeal tularemia; C.T. demonstration. Author(s): Umlas SL, Jaramillo D.
Source: Pediatric Radiology. 1990; 20(6): 483-4.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=2392370&dopt=Abstract
•
Membrane proteins of Francisella tularensis LVS differ in ability to induce proliferation of lymphocytes from tularemia-vaccinated individuals. Author(s): Surcel HM, Sarvas M, Helander IM, Herva E.
Source: Microbial Pathogenesis. 1989 December; 7(6): 411-9.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=2622330&dopt=Abstract
Studies
47
•
Microagglutination test for early and specific serodiagnosis of tularemia. Author(s): Sato T, Fujita H, Ohara Y, Homma M.
Source: Journal of Clinical Microbiology. 1990 October; 28(10): 2372-4.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=2229367&dopt=Abstract
•
Multiform skin eruptions with photodistribution in patients with tularemia. Author(s): Vaatainen N, Mattila R, Fraki JE.
Source: Photodermatol. 1985 April; 2(2): 122-3. No Abstract Available.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=4034420&dopt=Abstract
•
Neutrophile alkaline phosphatase changes in tularemia, sandfly fever, Q fever and noninfectious fevers. Author(s): Beisel WR.
Source: Blood. 1967 February; 29(2): 257-68.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=4960539&dopt=Abstract
•
Oculoglandular tularemia - a case report. Author(s): Chappell CW, Brainard J, Shock JP.
Source: J Ark Med Soc. 1981 August; 78(3): 128-30. No Abstract Available.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=6456257&dopt=Abstract
•
Oculoglandular tularemia in an inner city child. Author(s): Bloom ME, Shearer WT, Barton LL.
Source: Pediatrics. 1973 March; 51(3): 564-6.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=4575107&dopt=Abstract
•
Oculoglandular tularemia. Author(s): Steinemann TL, Sheikholeslami MR, Brown HH, Bradsher RW.
Source: Archives of Ophthalmology. 1999 January; 117(1): 132-3.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=9930180&dopt=Abstract
•
Oculoglandular tularemia: a case report. Author(s): Anderson RA.
Source: J Iowa Med Soc. 1970 January; 60(1): 21-6. No Abstract Available.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=5411798&dopt=Abstract
•
One-half century of tularemia in Florida. Author(s): Hoff GL, Bigler WJ, Prather EC.
Source: J Fla Med Assoc. 1975 September; 62(9): 35-7. No Abstract Available.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=1099166&dopt=Abstract
48 Tularemia
•
Oral tularemia vaccine in man. Author(s): Hornick RB, Dawkins AT, Eigelsbach HT, Tulis JJ.
Source: Antimicrobial Agents Chemother. 1966; 6: 11-4. No Abstract Available.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=4860768&dopt=Abstract
•
Oropharyngeal tularemia. Author(s): Everett ED, Templer JW.
Source: Arch Otolaryngol. 1980 April; 106(4): 237-8.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=6928749&dopt=Abstract
•
Oropharyngeal tularemia. Author(s): Caruso VG, Caruso AP, Panebianco RJ.
Source: N Y State J Med. 1983 February; 83(2): 226-7. No Abstract Available.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=6572814&dopt=Abstract
•
Oropharyngeal tularemia. With a note on the differential diagnosis of nonstreptococcal pharyngitis. Author(s): Fulginiti VA, Hoyle C.
Source: Rocky Mt Med J. 1966 February; 63(2): 41-2 Passim. No Abstract Available.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=5901542&dopt=Abstract
•
Oropharyngeal tularemia: an uncommon cause of pharyngitis, fever, and adenopathy. Author(s): Raitiere CR.
Source: The Journal of Family Practice. 1981 August; 13(2): 281-2.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=7252456&dopt=Abstract
•
Otolaryngological manifestations of tularemia. Author(s): Mair IW, Natvig K, Johannessen TA.
Source: Arch Otolaryngol. 1973 September; 98(3): 156-8. No Abstract Available.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=4742420&dopt=Abstract
•
Passive protection of mice against lethal Francisella tularensis (live tularemia vaccine strain) infection by the sera of human recipients of the live tularemia vaccine. Author(s): Drabick JJ, Narayanan RB, Williams JC, Leduc JW, Nacy CA.
Source: The American Journal of the Medical Sciences. 1994 August; 308(2): 83-7.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=8042659&dopt=Abstract
•
Peripheral blood leukocyte counts, erythrocyte sedimentation rate and C-reactive protein in tularemia caused by the type B strain of Francisella tularensis. Author(s): Syrjala H.
Source: Infection. 1986 March-April; 14(2): 51-4.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=3710592&dopt=Abstract
Studies
49
•
Photo quiz. Diagnosis: tularemia. Author(s): Jassal DS, Targownik L, Thottingal P, Embil JM.
Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases
Society of America. 1999 August; 29(2): 275; 420-1.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=10476724&dopt=Abstract
•
Plague and tularemia. Author(s): Craven RB, Barnes AM.
Source: Infectious Disease Clinics of North America. 1991 March; 5(1): 165-75. Review.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=2051013&dopt=Abstract
•
Plague and tularemia. Author(s): Butler T.
Source: Pediatric Clinics of North America. 1979 May; 26(2): 355-66. Review.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=379779&dopt=Abstract
•
Pleuropulmonary tularemia. A review of 29 patients. Author(s): Miller RP, Bates JH.
Source: Am Rev Respir Dis. 1969 January; 99(1): 31-41. No Abstract Available.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=5762111&dopt=Abstract
•
Pleuropulmonary tularemia: successful treatment with erythromycin. Author(s): Harrell RE Jr, Simmons HF.
Source: Southern Medical Journal. 1990 November; 83(11): 1363-4.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=2237578&dopt=Abstract
•
Pneumonic tularemia following the shearing of a dog. Author(s): Rumble CT.
Source: J Med Assoc Ga. 1972 October; 61(10): 355. No Abstract Available.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=4672882&dopt=Abstract
•
Pneumonic tularemia in a patient with chronic granulomatous disease. Author(s): Maranan MC, Schiff D, Johnson DC, Abrahams C, Wylam M, Gerber SI. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 1997 September; 25(3): 630-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9314451&dopt=Abstract
•
Pneumonic tularemia on Martha's Vineyard. Author(s): Teutsch SM, Martone WJ, Brink EW, Potter ME, Eliot G, Hoxsie R, Craven
RB, Kaufmann AF.
Source: The New England Journal of Medicine. 1979 October 11; 301(15): 826-8.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=481515&dopt=Abstract
50 Tularemia
•
Predominant expansion of V gamma 9/V delta 2 T cells in a tularemia patient. Author(s): Sumida T, Maeda T, Takahashi H, Yoshida S, Yonaha F, Sakamoto A,
Tomioka H, Koike T, Yoshida S.
Source: Infection and Immunity. 1992 June; 60(6): 2554-8.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=1534075&dopt=Abstract
•
Prevalence of ticks infected with Francisella tularensis in natural foci of tularemia in western Slovakia. Author(s): Gurycova D, Kocianova E, Vyrostekova V, Rehacek J.
Source: European Journal of Epidemiology. 1995 August; 11(4): 469-74.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=8549717&dopt=Abstract
•
Pulmonary tularemia. A report of five cases and consideration of pathogenesis and terminology. Author(s): Avery FW, Barnett TB.
Source: Am Rev Respir Dis. 1967 April; 95(4): 584-91. No Abstract Available.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=6021119&dopt=Abstract
•
Radiographic spectrum of pleuropulmonary tularemia. Author(s): Rubin SA.
Source: Ajr. American Journal of Roentgenology. 1978 August; 131(2): 277-81.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=98007&dopt=Abstract
•
Rapid laboratory diagnosis of ulceroglandular tularemia with polymerase chain reaction. Author(s): Karhukorpi EK, Karhukorpi J.
Source: Scandinavian Journal of Infectious Diseases. 2001; 33(5): 383-5.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=11440227&dopt=Abstract
•
Recent studies on live tularemia vaccine. Author(s): Eigelsbach HT, Hornick RB, Tulis JJ.
Source: Med Ann Dist Columbia. 1967 May; 36(5): 282-6. No Abstract Available.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=4962955&dopt=Abstract
•
Recent trends in the epidemiology of tularemia in the United States. Author(s): Boyce JM.
Source: The Journal of Infectious Diseases. 1975 February; 131(2): 197-9.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=1167886&dopt=Abstract
Studies
51
•
Relapse of tularemia after aminoglycoside therapy: case report and discussion of therapeutic options. Author(s): Risi GF, Pombo DJ.
Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases
Society of America. 1995 January; 20(1): 174-5. Review.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=7727647&dopt=Abstract
•
Role of lipopolysaccharide and a major outer membrane protein from Francisella tularensis in the induction of immunity against tularemia. Author(s): Fulop M, Manchee R, Titball R.
Source: Vaccine. 1995 September; 13(13): 1220-5.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=8578807&dopt=Abstract
•
Seroepidemiologic study of three zoonoses (leptospirosis, Q fever, and tularemia) among trappers in Quebec, Canada. Author(s): Levesque B, De Serres G, Higgins R, D'Halewyn MA, Artsob H, Grondin J,
Major M, Garvie M, Duval B.
Source: Clinical and Diagnostic Laboratory Immunology. 1995 July; 2(4): 496-8.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=7583933&dopt=Abstract
•
Serological investigations on tularemia in the Koszalin province in 1979-1981. Author(s): Dabrowski J, Kowalska B.
Source: Bull Inst Marit Trop Med Gdynia. 1983; 34(1-2): 95-100. No Abstract Available.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=6679471&dopt=Abstract
•
Similar pleural fluid findings in pleuropulmonary tularemia and tuberculous pleurisy. Author(s): Pettersson T, Nyberg P, Nordstrom D, Riska H.
Source: Chest. 1996 February; 109(2): 572-5.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=8620743&dopt=Abstract
•
Skin manifestations of tularemia. Author(s): Cerny Z.
Source: International Journal of Dermatology. 1994 July; 33(7): 468-70. Review.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=7928027&dopt=Abstract
•
Skin manifestations of tularemia: a study of 88 cases in northern Finland during 16 years (1967-1983). Author(s): Syrjala H, Karvonen J, Salminen A.
Source: Acta Dermato-Venereologica. 1984; 64(6): 513-6.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=6084923&dopt=Abstract
52 Tularemia
•
Streptomycin and alternative agents for the treatment of tularemia: review of the literature. Author(s): Enderlin G, Morales L, Jacobs RF, Cross JT.
Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases
Society of America. 1994 July; 19(1): 42-7. Review.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=7948556&dopt=Abstract
•
Suppurative inflammatory eruption occurring in septicemia tularemia. Author(s): Lewis JE.
Source: Cutis; Cutaneous Medicine for the Practitioner. 1982 July; 30(1): 92, 96-7, 100.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=7116928&dopt=Abstract
•
The 2000 tularemia outbreak: a case-control study of risk factors in disease-endemic and emergent areas, Sweden. Author(s): Eliasson H, Lindback J, Nuorti JP, Arneborn M, Giesecke J, Tegnell A. Source: Emerging Infectious Diseases. 2002 September; 8(9): 956-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12194773&dopt=Abstract
•
The ecology of tularemia. Author(s): Hopla CE.
Source: Adv Vet Sci Comp Med. 1974; 18(0): 25-53. No Abstract Available.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=4419176&dopt=Abstract
•
The laboratory diagnosis of tularemia. Author(s): Brown M.
Source: Va Med Mon (1918). 1970 June; 97(6): 388-90. No Abstract Available.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=5528117&dopt=Abstract
•
The role of endotoxin during typhoid fever and tularemia in man. IV. The integrity of the endotoxin tolerance mechanisms during infection. Author(s): Greisman SE, Hornick RB, Wagner HN Jr, Woodward WE, Woodward TE. Source: The Journal of Clinical Investigation. 1969 April; 48(4): 613-29. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4886645&dopt=Abstract
•
The skin test in an epidemiologic study of tularemia in Montana trappers. Author(s): Philip RN, Casper EA, Lackman DB.
Source: The Journal of Infectious Diseases. 1967 December; 117(5): 393-402.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=6078219&dopt=Abstract
Studies
53
•
The spider as a possible source of tularemia. Author(s): Rowland MD, Griffiths DW.
Source: Jama : the Journal of the American Medical Association. 1988 July 1; 260(1): 33.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=3379719&dopt=Abstract
•
The tularemia skin test. 325 skin tests in 210 persons: serologic correlation and review of the literature. Author(s): Buchanan TM, Brooks GF, Brachman PS.
Source: Annals of Internal Medicine. 1971 March; 74(3): 336-43.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=5552107&dopt=Abstract
•
The unusual presentations of tularemia. Bacteremia, pneumonia, and rhabdomyolysis. Author(s): Klotz SA, Penn RL, Provenza JM.
Source: Archives of Internal Medicine. 1987 February; 147(2): 214.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=3813735&dopt=Abstract
•
Tickborne oculoglandular tularemia: case report and review of seasonal and vectorial associations in 106 cases. Author(s): Guerrant RL, Humphries MK Jr, Butler JE, Jackson RS.
Source: Archives of Internal Medicine. 1976 July; 136(7): 811-3.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=938174&dopt=Abstract
•
Tick-borne tularemia presenting as ulcerative lymphadenitis. Author(s): Speert DP, Britt WJ, Kaplan EL.
Source: Clinical Pediatrics. 1979 April; 18(4): 239-41.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=428180&dopt=Abstract
•
Tick-borne tularemia. An outbreak of lymphadenopathy in children. Author(s): Markowitz LE, Hynes NA, de la Cruz P, Campos E, Barbaree JM, Plikaytis
BD, Mosier D, Kaufmann AF.
Source: Jama : the Journal of the American Medical Association. 1985 November 22-29;
254(20): 2922-5.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=4057512&dopt=Abstract
•
Tick-borne ulceroglandular tularemia. Author(s): Leggiadro RJ, Kenigsberg K, Annunziato D.
Source: N Y State J Med. 1983 July-September; 83(8-10): 1053-4. No Abstract Available.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=6579402&dopt=Abstract
54
Tularemia
•
Time of lymphocyte response after onset of tularemia and after tularemia vaccination. Author(s): Tarnvik A, Sandstrom G, Lofgren S.
Source: Journal of Clinical Microbiology. 1979 December; 10(6): 854-60.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=521485&dopt=Abstract
•
Tonsillopharyngeal tularemia: a reminder. Author(s): Parkhurst JB, San Joaquin VH.
Source: Am J Dis Child. 1990 October; 144(10): 1070-1. No Abstract Available.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=2403080&dopt=Abstract
•
Treatment of tularemia with ciprofloxacin. Author(s): Chocarro A, Gonzalez A, Garcia I.
Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases
Society of America. 2000 August; 31(2): 623.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=10987739&dopt=Abstract
•
Treatment of tularemia with ciprofloxacin. Author(s): Scheel O, Reiersen R, Hoel T.
Source: European Journal of Clinical Microbiology & Infectious Diseases : Official
Publication of the European Society of Clinical Microbiology. 1992 May; 11(5): 447-8.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=1425715&dopt=Abstract
•
Treatment of tularemia with fluoroquinolones: two cases and review. Author(s): Limaye AP, Hooper CJ.
Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases
Society of America. 1999 October; 29(4): 922-4. Review.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=10589911&dopt=Abstract
•
Treatment of tularemia with gentamicin in pediatric patients. Author(s): Cross JT Jr, Schutze GE, Jacobs RF.
Source: The Pediatric Infectious Disease Journal. 1995 February; 14(2): 151-2.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=7746700&dopt=Abstract
•
Treatment of tularemia with imipenem/cilastatin sodium. Author(s): Lee HC, Horowitz E, Linder W.
Source: Southern Medical Journal. 1991 October; 84(10): 1277-8.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=1925735&dopt=Abstract
Studies
55
•
Treatment of tularemia with levofloxacin. Author(s): Aranda EA.
Source: Clinical Microbiology and Infection : the Official Publication of the European
Society of Clinical Microbiology and Infectious Diseases. 2001 March; 7(3): 167-8.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=11318818&dopt=Abstract
•
Treatment of tularemia, including pulmonary tularemia, with gentamicin. Author(s): Mason WL, Eigelsbach HT, Little SF, Bates JH.
Source: Am Rev Respir Dis. 1980 January; 121(1): 39-45.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=7352712&dopt=Abstract
•
Tularemia and atypical lymphocytosis. Author(s): Gelfand MS, Mehra N, Simmons BP.
Source: J Tenn Med Assoc. 1989 August; 82(8): 417-8. No Abstract Available.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=2761249&dopt=Abstract
•
Tularemia and Q fever. Author(s): Choi E.
Source: The Medical Clinics of North America. 2002 March; 86(2): 393-416. Review.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=11982309&dopt=Abstract
•
Tularemia and report of a case by Jerome A. Murphy. N. Y. State J. Med. 1928. Author(s): Murphy JA.
Source: N Y State J Med. 1983 July-September; 83(8-10): 1062. No Abstract Available.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=6355929&dopt=Abstract
•
Tularemia and rhabdomyolysis. Author(s): Kaiser AB, Rieves D, Price AH, Gelfand MR, Parrish RE, Decker MD, Evans
ME.
Source: Jama : the Journal of the American Medical Association. 1985 January 11; 253(2):
241-3.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=3965776&dopt=Abstract
•
Tularemia and the tomcat. Author(s): Evans ME, McGee ZA, Hunter PT, Schaffner W.
Source: Jama : the Journal of the American Medical Association. 1981 September 18;
246(12): 1343.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=7196465&dopt=Abstract
56 Tularemia
•
Tularemia as a biological weapon: medical and public health management. Author(s): Dennis DT, Inglesby TV, Henderson DA, Bartlett JG, Ascher MS, Eitzen E,
Fine AD, Friedlander AM, Hauer J, Layton M, Lillibridge SR, McDade JE, Osterholm
MT, O'Toole T, Parker G, Perl TM, Russell PK, Tonat K; Working Group on Civilian
Biodefense.
Source: Jama : the Journal of the American Medical Association. 2001 June 6; 285(21):
2763-73. Review.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=11386933&dopt=Abstract
•
Tularemia complicated by acute renal failure. Author(s): Tilley WS, Garman RW, Stone WJ.
Source: Southern Medical Journal. 1983 February; 76(2): 273-4.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=6823614&dopt=Abstract
•
Tularemia epidemia: Vermont, 1968. Forty-seven cases linked to contact with muskrats. Author(s): Young LS, Bickness DS, Archer BG, Clinton JM, Leavens LJ, Feeley JC,
Brachman PS.
Source: The New England Journal of Medicine. 1969 June 5; 280(23): 1253-60.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=4891088&dopt=Abstract
•
Tularemia epidemic associated with the deerfly. Author(s): Klock LE, Olsen PF, Fukushima T.
Source: Jama : the Journal of the American Medical Association. 1973 October 8; 226(2):
149-52.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=4740907&dopt=Abstract
•
Tularemia epidemic in northwestern Spain: clinical description and therapeutic response. Author(s): Perez-Castrillon JL, Bachiller-Luque P, Martin-Luquero M, Mena-Martin FJ,
Herreros V.
Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases
Society of America. 2001 August 15; 33(4): 573-6. Epub 2001 July 06.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=11462198&dopt=Abstract
•
Tularemia epidemic--Vermont, 1968. Author(s): Hornick RB, Eigelsbach HT.
Source: The New England Journal of Medicine. 1969 December 4; 281(23): 1310.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=5349815&dopt=Abstract
Studies
57
•
Tularemia fatality. Author(s): Garrett CL.
Source: N C Med J. 1995 October; 56(10): 476. No Abstract Available.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=7477450&dopt=Abstract
•
Tularemia from a cat bite: case report and review of feline-associated tularemia. Author(s): Capellan J, Fong IW.
Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases
Society of America. 1993 April; 16(4): 472-5. Review.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=8513049&dopt=Abstract
•
Tularemia from domestic cats. Author(s): Liles WC, Burger RJ.
Source: The Western Journal of Medicine. 1993 June; 158(6): 619-22.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=8337864&dopt=Abstract
•
Tularemia immunization in early pregnancy. Author(s): Albrecht RC, Cefalo RC, O'Brien WF.
Source: American Journal of Obstetrics and Gynecology. 1980 December 15; 138(8): 1226
7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7446636&dopt=Abstract
•
Tularemia in a Wisconsin resident--a reminder. Author(s): Franson TR, Rose HD.
Source: Wis Med J. 1982 October; 81(10): 27-8. No Abstract Available.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=7180020&dopt=Abstract
•
Tularemia in adults and children: a changing presentation. Author(s): Jacobs RF, Condrey YM, Yamauchi T.
Source: Pediatrics. 1985 November; 76(5): 818-22.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=4058993&dopt=Abstract
•
Tularemia in an inner city child. Author(s): Szalay GC.
Source: Clinical Pediatrics. 1974 April; 13(4): 375-6.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=4821824&dopt=Abstract
•
Tularemia in Bursa, Turkey: 205 cases in ten years. Author(s): Helvaci S, Gedikoglu S, Akalin H, Oral HB.
Source: European Journal of Epidemiology. 2000 March; 16(3): 271-6.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=10870943&dopt=Abstract
58
Tularemia
•
Tularemia in Canada with a focus on Saskatchewan. Author(s): Martin T, Holmes IH, Wobeser GA, Anthony RF, Greefkes I.
Source: Can Med Assoc J. 1982 August 15; 127(4): 279-82. Review. No Abstract
Available.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=7046896&dopt=Abstract
•
Tularemia in children caused by Francisella tularensis biovar palaearctica. Author(s): Uhari M, Syrjala H, Salminen A.
Source: The Pediatric Infectious Disease Journal. 1990 February; 9(2): 80-3. Review.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=2179844&dopt=Abstract
•
Tularemia in children. Author(s): Jacobs RF, Narain JP.
Source: Pediatr Infect Dis. 1983 November-December; 2(6): 487-91. Review. No Abstract
Available.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=6361709&dopt=Abstract
•
Tularemia in Delaware: forgotten but not gone. Author(s): Eppes SC.
Source: Del Med J. 2003 April; 75(4): 137-41. No Abstract Available.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=12774546&dopt=Abstract
•
Tularemia in Florida: Sylvilagus palustris as a source of human infection. Author(s): Hoff GL, Bigler WJ, Hemmert W.
Source: J Wildl Dis. 1975 October; 11(4): 560-1.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=1195503&dopt=Abstract
•
Tularemia in hamster hunters. Author(s): Szekelyfoldi J.
Source: Del Med J. 1970 November; 42(11): 305-6. No Abstract Available.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=5529760&dopt=Abstract
•
Tularemia in Huron County, Ontario, 1968. Author(s): Evans GP.
Source: Canadian Journal of Public Health. Revue Canadienne De Sante Publique. 1969
November; 60(11): 447-9.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=5389771&dopt=Abstract
•
Tularemia in metropolitan New York. Author(s): Nussbaum M, Shenker IR, Kaplan E.
Source: N Y State J Med. 1978 November; 78(13): 2093-4. No Abstract Available.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=280774&dopt=Abstract
Studies
59
•
Tularemia in North Carolina, 1965-1990. Author(s): Langley R, Campbell R.
Source: N C Med J. 1995 July; 56(7): 314-7. No Abstract Available.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=7643926&dopt=Abstract
•
Tularemia in North Carolina. Author(s): Avery FW.
Source: N C Med J. 1995 September; 56(9): 412. No Abstract Available.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=7477462&dopt=Abstract
•
Tularemia in otolaryngologic practice. An analysis of 127 cases. Author(s): Luotonen J, Syrjala H, Jokinen K, Sutinen S, Salminen A.
Source: Archives of Otolaryngology--Head & Neck Surgery. 1986 January; 112(1): 77-80.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=2866760&dopt=Abstract
•
Tularemia in the United States: epidemiologic aspects in the 1960s and follow-up of the outbreak of tularemia in Vermont. Author(s): Brooks GF, Buchanan TM.
Source: The Journal of Infectious Diseases. 1970 March; 121(3): 357-9.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=5415053&dopt=Abstract
•
Tularemia in the United States: recent trends and a major epidemic in 1968. Author(s): Young LS, Sherman IL.
Source: The Journal of Infectious Diseases. 1969 January; 119(1): 109-10.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=5812725&dopt=Abstract
•
Tularemia infection of the eye. Author(s): Hanna C, Lyford JH.
Source: Ann Ophthalmol. 1971 December; 3(12): 1321 Passim. No Abstract Available.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=5138221&dopt=Abstract
•
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
•
Tularemia of the middle ear. Author(s): Luotonen L, Tapiainen T, Kallioinen M, Luotonen J.
Source: The Pediatric Infectious Disease Journal. 2002 March; 21(3): 264-5.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=12005098&dopt=Abstract
60 Tularemia
•
Tularemia on Martha's Vineyard: seroprevalence and occupational risk. Author(s): Feldman KA, Stiles-Enos D, Julian K, Matyas BT, Telford SR 3rd, Chu MC,
Petersen LR, Hayes EB.
Source: Emerging Infectious Diseases. 2003 March; 9(3): 350-4.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=12643831&dopt=Abstract
•
Tularemia outbreak investigation in Kosovo: case control and environmental studies. Author(s): Reintjes R, Dedushaj I, Gjini A, Jorgensen TR, Cotter B, Lieftucht A, D'Ancona F, Dennis DT, Kosoy MA, Mulliqi-Osmani G, Grunow R, Kalaveshi A, Gashi L, Humolli I.
Source: Emerging Infectious Diseases. 2002 January; 8(1): 69-73.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=11749751&dopt=Abstract
•
Tularemia pneumonia in Oklahoma, 1982-1987. Author(s): Scofield RH, Lopez EJ, McNabb SJ.
Source: J Okla State Med Assoc. 1992 April; 85(4): 165-70.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=1593309&dopt=Abstract
•
Tularemia pneumonia in urban children. Author(s): Halsted CC, Kulasinghe HP.
Source: Pediatrics. 1978 April; 61(4): 660-2.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=566417&dopt=Abstract
•
Tularemia pneumonia in Washington, DC. A report of three cases with possible common-source exposures. Author(s): Martone WJ, Marshall LW, Kaufmann AF, Hobbs JH, Levy ME.
Source: Jama : the Journal of the American Medical Association. 1979 November 23;
242(21): 2315-7.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=573806&dopt=Abstract
•
Tularemia pneumonia mimicking legionnaires' disease: isolation of organism on CYE agar and successful treatment with erythromycin. Author(s): Westerman EL, McDonald J.
Source: Southern Medical Journal. 1983 September; 76(9): 1169-70.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=6612398&dopt=Abstract
•
Tularemia pneumonia. Author(s): Gill V, Cunha BA.
Source: Seminars in Respiratory Infections. 1997 March; 12(1): 61-7. Review.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=9097380&dopt=Abstract
Studies
61
•
Tularemia presenting as a lymphoma. Author(s): Sibert NS.
Source: J Med Soc N J. 1976 November; 73(11): 943-4. No Abstract Available.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=1068305&dopt=Abstract
•
Tularemia presenting as an isolated pleural effusion. Author(s): Funk LM, Simpson SQ, Mertz G, Boyd J.
Source: The Western Journal of Medicine. 1992 April; 156(4): 415-7.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=1574890&dopt=Abstract
•
Tularemia presenting as community-acquired pneumonia. Implications in the era of managed care. Author(s): Fredricks DN, Remington JS.
Source: Archives of Internal Medicine. 1996 October 14; 156(18): 2137-40.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=8862107&dopt=Abstract
•
Tularemia presenting with ataxia. Author(s): LeDoux MS.
Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases
Society of America. 2000 January; 30(1): 211-2.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=10619760&dopt=Abstract
•
Tularemia presenting with splenic nodules. Author(s): Garver MK, St Geme JW 3rd, Siegel MJ.
Source: The Pediatric Infectious Disease Journal. 1994 September; 13(9): 830-2.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=7808857&dopt=Abstract
•
Tularemia revisited. Author(s): Hornick R.
Source: The New England Journal of Medicine. 2001 November 29; 345(22): 1637-9.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=11757513&dopt=Abstract
•
Tularemia simulating acute myocardial infarction. Author(s): Loftin EB 3rd.
Source: Jama : the Journal of the American Medical Association. 1981 November 27;
246(21): 2429-30.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=7299963&dopt=Abstract
•
Tularemia transmitted by a squirrel bite. Author(s): Magee JS, Steele RW, Kelly NR, Jacobs RF.
Source: The Pediatric Infectious Disease Journal. 1989 February; 8(2): 123-5.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=2704604&dopt=Abstract
62
Tularemia
•
Tularemia treated successfully with gentamicin. Author(s): Alford RH, John JT, Bryant RE.
Source: Am Rev Respir Dis. 1972 August; 106(2): 265-8. No Abstract Available.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=5049658&dopt=Abstract
•
Tularemia with unusual laboratory characteristics in South Dakota children. Author(s): Larson BW, Jacobson HJ.
Source: S D J Med. 1984 June; 37(6): 5-10. No Abstract Available.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=6589779&dopt=Abstract
•
Tularemia, an analysis of 25 cases. Author(s): Cox SK, Everett ED.
Source: Mo Med. 1981 February; 78(2): 70-4. No Abstract Available.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=7219406&dopt=Abstract
•
Tularemia, biological warfare, and the battle for Stalingrad (1942-1943). Author(s): Croddy E, Krcalova S.
Source: Military Medicine. 2001 October; 166(10): 837-8.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=11603230&dopt=Abstract
•
Tularemia. Author(s): Jensen WA, Kirsch CM.
Source: Seminars in Respiratory Infections. 2003 September; 18(3): 146-58.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=14505277&dopt=Abstract
•
Tularemia. Author(s): Feldman KA.
Source: J Am Vet Med Assoc. 2003 March 15; 222(6): 725-30. Review.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=12675294&dopt=Abstract
•
Tularemia. Author(s): Machado LJ.
Source: J Okla State Med Assoc. 2002 October; 95(10): 671-3. No Abstract Available.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=12420417&dopt=Abstract
•
Tularemia. Author(s): Ellis J, Oyston PC, Green M, Titball RW.
Source: Clinical Microbiology Reviews. 2002 October; 15(4): 631-46. Review.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=12364373&dopt=Abstract
Studies
63
•
Tularemia. Author(s): Rohrbach BW.
Source: J Am Vet Med Assoc. 1988 August 15; 193(4): 428-32. No Abstract Available.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=3170317&dopt=Abstract
•
Tularemia. Author(s): Jacobs RF.
Source: Adv Pediatr Infect Dis. 1996; 12: 55-69. Review. No Abstract Available.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=9033975&dopt=Abstract
•
Tularemia. Author(s): Kodama BF, Fitzpatrick JE, Gentry RH.
Source: Cutis; Cutaneous Medicine for the Practitioner. 1994 October; 54(4): 279-80.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=7805415&dopt=Abstract
•
Tularemia. Author(s): Burnett JW.
Source: Cutis; Cutaneous Medicine for the Practitioner. 1994 August; 54(2): 77-8.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=7956338&dopt=Abstract
•
Tularemia. Author(s): Feldman RA, Koehler RE.
Source: Jama : the Journal of the American Medical Association. 1973 October 8; 226(2):
189.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=4740911&dopt=Abstract
•
Tularemia. Author(s): Evans GP.
Source: Can Med Assoc J. 1970 December 19; 103(13): 1394. No Abstract Available.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=5531169&dopt=Abstract
•
Tularemia. A pathogen in nature and a biological weapon. Author(s): Altman GB.
Source: Aaohn Journal : Official Journal of the American Association of Occupational
Health Nurses. 2002 August; 50(8): 373-7; Quiz 378-9. Review.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=12227212&dopt=Abstract
•
Tularemia. A review. Author(s): Finley CR, Hamilton BW, Hamilton TR.
Source: Mo Med. 1986 November; 83(11): 741-3. Review. No Abstract Available.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=3334069&dopt=Abstract
64 Tularemia
•
Tularemia. Two manifestations in an urban man. Author(s): Nohinek B, Marr JJ.
Source: Mo Med. 1983 November; 80(11): 687-9, 698. No Abstract Available.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=6646107&dopt=Abstract
•
Tularemia: a 30-year experience with 88 cases. Author(s): Evans ME, Gregory DW, Schaffner W, McGee ZA.
Source: Medicine; Analytical Reviews of General Medicine, Neurology, Psychiatry,
Dermatology, and Pediatrics. 1985 July; 64(4): 251-69. Review.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=3892222&dopt=Abstract
•
Tularemia: a case transmitted from a sheep. Author(s): Senol M, Ozcan A, Karincaoglu Y, Aydin A, Ozerol IH.
Source: Cutis; Cutaneous Medicine for the Practitioner. 1999 January; 63(1): 49-51.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=10328679&dopt=Abstract
•
Tularemia: a differential diagnosis in oto-rhino-laryngology. Author(s): Nordahl SH, Hoel T, Scheel O, Olofsson J.
Source: The Journal of Laryngology and Otology. 1993 February; 107(2): 127-9.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=8496644&dopt=Abstract
•
Tularemia: a practical guide to management in the event of a tick bite or terrorist attack. Author(s): Coleman EA.
Source: The American Journal of Nursing. 2002 June; 102(6): 65-6, 66.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=12394080&dopt=Abstract
•
Tularemia: an unappreciated cause of exudative pharyngitis. Author(s): Tyson HK.
Source: Pediatrics. 1976 December; 58(6): 864-6.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=995514&dopt=Abstract
•
Tularemia: association with hunting and farming. Author(s): Stewart SJ.
Source: Fems Immunology and Medical Microbiology. 1996 March; 13(3): 197-99.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=8861028&dopt=Abstract
•
Tularemia: atypical presentation. Author(s): Vento AO, Oung BY.
Source: Md State Med J. 1984 May; 33(5): 395-6. No Abstract Available.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=6738121&dopt=Abstract
Studies
65
•
Tularemia: Dr. Edward Francis and his first 23 isolates of Francisella tularensis. Author(s): Jellison WL.
Source: Bulletin of the History of Medicine. 1972 September-October; 46(5): 477-85.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=4570449&dopt=Abstract
•
Tularemia: emergency department presentation of an infrequently recognized disease. Author(s): Harrell RE Jr, Whitaker GR.
Source: The American Journal of Emergency Medicine. 1985 September; 3(5): 415-8.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=4041193&dopt=Abstract
•
Tularemia: experience in the Hamilton area. Author(s): Walker WJ, Moore CA.
Source: Can Med Assoc J. 1971 August 21; 105(4): 390-3 Passim. No Abstract Available.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=5162327&dopt=Abstract
•
Tularemia: lymphadenitis with a twist. Author(s): Bryant KA.
Source: Pediatric Annals. 2002 March; 31(3): 187-90. Review.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=11905292&dopt=Abstract
•
Tularemia: review of eight cases of tick-borne infection and the epidemiology of the disease in Georgia. Author(s): Lopez CE, Kornblatt AN, Sikes RK, Hanes OE.
Source: Southern Medical Journal. 1982 April; 75(4): 405-7.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=7071635&dopt=Abstract
•
Tularemia: treatment failures with outpatient use of ceftriaxone. Author(s): Cross JT, Jacobs RF.
Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases
Society of America. 1993 December; 17(6): 976-80.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=8110955&dopt=Abstract
•
Tularemia--an unusual cause of a solitary pulmonary nodule in the post-transplant setting. Author(s): Naughton M, Brown R, Adkins D, DiPersio J.
Source: Bone Marrow Transplantation. 1999 July; 24(2): 197-9.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=10455349&dopt=Abstract
66 Tularemia
•
Typhoidal tularemia in a human immunodeficiency virus-infected adolescent. Author(s): Gries DM, Fairchok MP.
Source: The Pediatric Infectious Disease Journal. 1996 September; 15(9): 838-40.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=8878235&dopt=Abstract
•
Typhoidal tularemia presenting as enteritis with leukopenia. Author(s): Hoyt RE.
Source: Va Med. 1988 August; 115(8): 388-9. No Abstract Available.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=3176624&dopt=Abstract
•
Typhoidal tularemia. Author(s): Marcus DM, Frederick AR Jr, Hodges T, Allan JD, Albert DM.
Source: Archives of Ophthalmology. 1990 January; 108(1): 118-9.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=2297319&dopt=Abstract
•
Ulceroglandular and pulmonary tularemia: a case resulting from a cat bite to the hand. Author(s): von Schroeder HP, McDougall EP.
Source: The Journal of Hand Surgery. 1993 January; 18(1): 132-4.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=8423298&dopt=Abstract
•
Ulceroglandular tularemia: a typical case of relapse. Author(s): Miller SD, Snyder MB, Kleerekoper M, Grossman CH.
Source: Henry Ford Hosp Med J. 1989; 37(2): 73-5.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=2606733&dopt=Abstract
•
Use of RNA hybridization in the diagnosis of a case of ulceroglandular tularemia. Author(s): Forsman M, Kuoppa K, Sjostedt A, Tarnvik A.
Source: European Journal of Clinical Microbiology & Infectious Diseases : Official
Publication of the European Society of Clinical Microbiology. 1990 October; 9(10): 784-5.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=1702055&dopt=Abstract
•
Water related tularemia cases in Illinois. Author(s): Stahl LW, Schnurrenberger PR, Martin RJ.
Source: Imj Ill Med J. 1969 September; 136(3): 276-309 Passim. No Abstract Available.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=4390713&dopt=Abstract
Studies
•
67
Waterborne outbreak of tularemia associated with crayfish fishing. Author(s): Anda P, Segura del Pozo J, Diaz Garcia JM, Escudero R, Garcia Pena FJ,
Lopez Velasco MC, Sellek RE, Jimenez Chillaron MR, Sanchez Serrano LP, Martinez
Navarro JF.
Source: Emerging Infectious Diseases. 2001; 7(3 Suppl): 575-82.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=11485678&dopt=Abstract
69
CHAPTER 2. NUTRITION AND TULAREMIA Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and tularemia.
Finding Nutrition Studies on Tularemia 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 “tularemia” (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.
70 Tularemia
The following information is typical of that found when using the “Full IBIDS Database” to search for “tularemia” (or a synonym): •
Acute glaucoma and acute corneal oedema in association with tularemia. Author(s): Department of Ophthalmology, Central Hospital of Central Finland.
Source: Parssinen, O Rummukainen, M Acta-Ophthalmol-Scand. 1997 December; 75(6):
732-4 1395-3907
•
Clinical manifestations of tularemia in Japan--analysis of 1,355 cases observed between 1924 and 1987. Author(s): Dept. of Neurological Sciences, Tohoku University School of Medicine,
Sendai, Japan.
Source: Ohara, Y Sato, T Fujita, H Ueno, T Homma, M Infection. 1991 Jan-February;
19(1): 14-7 0300-8126
•
Treatment of tularemia with imipenem/cilastatin sodium. Author(s): Department of Medicine, Creighton University Medical Center, Omaha, Neb.
68131.
Source: Lee, H C Horowitz, E Linder, W South-Med-J. 1991 October; 84(10): 1277-8 0038
4348
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
•
The United States Department of Agriculture’s Web site dedicated to nutrition information: www.nutrition.gov
•
The Food and Drug Administration’s Web site for federal food safety information: www.foodsafety.gov
•
The National Action Plan on Overweight and Obesity sponsored by the United States Surgeon General: http://www.surgeongeneral.gov/topics/obesity/
•
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/
•
Center for Nutrition Policy and Promotion sponsored by the United States Department of Agriculture: http://www.usda.gov/cnpp/
•
Food and Nutrition Information Center, National Agricultural Library sponsored by the United States Department of Agriculture: http://www.nal.usda.gov/fnic/
•
Food and Nutrition Service sponsored by the United States Department of Agriculture: http://www.fns.usda.gov/fns/
Nutrition
71
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
•
Family Village: http://www.familyvillage.wisc.edu/med_nutrition.html
•
Google: http://directory.google.com/Top/Health/Nutrition/
•
Healthnotes: http://www.healthnotes.com/
•
Open Directory Project: http://dmoz.org/Health/Nutrition/
•
Yahoo.com: http://dir.yahoo.com/Health/Nutrition/
•
WebMD®Health: http://my.webmd.com/nutrition
•
WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html
73
CHAPTER 3. ALTERNATIVE MEDICINE AND TULAREMIA Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to tularemia. 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 tularemia 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 “tularemia” (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 tularemia: •
Bacteria as agents of biowarfare. How to proceed when the worst is suspected. Author(s): Tjaden JA, Lazarus AA, Martin GJ. Source: Postgraduate Medicine. 2002 August; 112(2): 57-60, 63-4, 67-70. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12198754&dopt=Abstract
•
Behavioral effects of infectious diseases: respiratory Pasteurella tularensis in man. Author(s): Alluisi EA, Thurmond JB, Coates GD. Source: Percept Mot Skills. 1971 April; 32(2): 647-68. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5089099&dopt=Abstract
•
Behavioral effects of tularemia and sandfly fever in man. Author(s): Alluisi EA, Beisel WR, Bartelloni PJ, Coates GD.
74
Tularemia
Source: The Journal of Infectious Diseases. 1973 December; 128(6): 710-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4203075&dopt=Abstract •
Do homeopathic nosodes protect against infection? An experimental test. Author(s): Jonas WB.
Source: Alternative Therapies in Health and Medicine. 1999 September; 5(5): 36-40.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=10484829&dopt=Abstract
•
Plague pneumonia disease caused by Yersinia pestis. Author(s): Cleri DJ, Vernaleo JR, Lombardi LJ, Rabbat MS, Mathew A, Marton R, Reyelt
MC.
Source: Seminars in Respiratory Infections. 1997 March; 12(1): 12-23. Review.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_
uids=9097371&dopt=Abstract
Additional Web Resources A number of additional Web sites offer encyclopedic information covering CAM and related topics. The following is a representative sample: •
Alternative Medicine Foundation, Inc.: http://www.herbmed.org/
•
AOL: http://search.aol.com/cat.adp?id=169&layer=&from=subcats
•
Chinese Medicine: http://www.newcenturynutrition.com/
•
drkoop.com®: http://www.drkoop.com/InteractiveMedicine/IndexC.html
•
Family Village: http://www.familyvillage.wisc.edu/med_altn.htm
•
Google: http://directory.google.com/Top/Health/Alternative/
•
Healthnotes: http://www.healthnotes.com/
•
MedWebPlus: http://medwebplus.com/subject/Alternative_and_Complementary_Medicine
•
Open Directory Project: http://dmoz.org/Health/Alternative/
•
HealthGate: http://www.tnp.com/
•
WebMD®Health: http://my.webmd.com/drugs_and_herbs
•
WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html
•
Yahoo.com: http://dir.yahoo.com/Health/Alternative_Medicine/
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.
Alternative Medicine 75
This Web site provides a general overview of various topics and can lead to a number of general sources.
77
CHAPTER 4. DISSERTATIONS ON TULAREMIA Overview In this chapter, we will give you a bibliography on recent dissertations relating to tularemia. 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 “tularemia” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on tularemia, we have not necessarily excluded non-medical dissertations in this bibliography.
Dissertations on Tularemia 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 tularemia. 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: •
Cellular Resistance in Experimental Murine Tularemia by Anthony, L. S. D; PhD from McGill University (Canada), 1987 http://wwwlib.umi.com/dissertations/fullcit/NL44282
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.
79
CHAPTER 5. BOOKS ON TULAREMIA Overview This chapter provides bibliographic book references relating to tularemia. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on tularemia 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 “tularemia” (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 tularemia: •
Everything You Need To Know About Lyme Disease and Other Tick-Borne Disorders Source: Somerset, NJ: John Wiley and Sons, Inc. 1997. 256 p. Contact: Available from John Wiley and Sons, Inc. Distribution Center, 1 Wiley Drive, Somerset, NJ 08875-1272. (800) 225-5945 or (732) 469-4400. Fax (732) 302-2300. E-mail:
[email protected]. Website: catalog.wiley.com. PRICE: $14.95 plus shipping and handling. Also available from Lyme Disease Foundation. 1 Financial Plaza, 18th Floor, Hartford, CT 06103. (800)886-LYME or (860) 525-2000. Fax (860) 525-TICK. E-mail:
[email protected]. Website: www.lyme.org. PRICE: $18.00; bulk orders available at cost. Summary: This book provides the general public and people who have Lyme disease with comprehensive information about this tick-borne illness. The book begins with a chapter on the public health threat posed by Lyme disease. This chapter provides an overview of progression, diagnosis, and treatment; an explanation of the science of Lyme disease; and a description of other tick-borne disorders. Chapter two discusses
80 Tularemia
ticks' life cycle and method of feeding. Other topics include the forces that have converged to increase the threat of ticks, factors influencing the likelihood of becoming ill from a tick bite, and types of ticks. The next chapter presents significant events in the history of Lyme disease. Chapter four presents the signs and symptoms of localized and disseminated Lyme disease. The fifth chapter discusses the diagnosis of Lyme disease in terms of getting a diagnosis and undergoing antibody tests to detect Borrelia burgdorferi, as well as types of antibody and direct detection tests. Chapter six addresses treatment, focusing on choosing health professionals, taking antibiotics, persuading an insurer to pay for treatment, and obtaining emotional support. This is followed by a chapter that describes other tick-borne disorders, including babesiosis, ehrlichiosis, Rocky Mountain spotted fever, Colorado tick fever, tularemia, relapsing fever, Powassan encephalitis, and tick paralysis. Subsequent chapters provide guidelines on using proper equipment to remove a tick, protecting oneself and family members from ticks, and modifying property to create tick-free zones. Final chapters report on the promise of a vaccine for Lyme disease and discuss the risks of tick bites to animals. 6 appendixes, 28 figures, 1 table, and numerous references.
Book Summaries: Online Booksellers Commercial Internet-based booksellers, such as Amazon.com and Barnes&Noble.com, offer summaries which have been supplied by each title’s publisher. Some summaries also include customer reviews. Your local bookseller may have access to in-house and commercial databases that index all published books (e.g. Books in Print®). IMPORTANT NOTE: Online booksellers typically produce search results for medical and non-medical books. When searching for “tularemia” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “tularemia” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “tularemia” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •
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; ISBN: 1932634797; http://www.amazon.com/exec/obidos/ASIN/1932634797/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 “tularemia” (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:8 8 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.
Books
81
•
Bibliography on tularemia. Author: United States. Army. Chemical Corps. Technical Library.; Year: 1963; Frederick, Md., 1958
•
Contamination of natural waters and mud with Pasteurella tularensis and tularemia in beavers and muskrats in the northwestern United States, by R. R. Parker [and others] From the National Institutes of Health Rocky Mountain Laboratory, Hamilton, Montana. Author: Parker, Ralph Robinson,; Year: 1951; Washington, U. S. Govt. Print. Off., 1951
•
Questions in the epidemiology and prophylaxis of tularemia [under the editorship of. professor N. G. Olsuf'yev et al.]. Author: Olsuf'ev, N. G. (Nikolai Grigor'evich); Year: 1970; Fort Detrick, Frederick, Md., United States Army Biological Laboratories, 1964
•
Review of Russian papers on tularemia. Author: Pollitzer, R. (Robert),; Year: 1967; Bethesda, Md., 1958
•
Some questions and answers on tularemia. Author: Gibson, John M. (John Mendinghall),; Year: 1953; [Montgomery, Ala., 1953]
•
Tularemia [by] John W. McDowell [et al.]. Author: McDowell, John W.; Year: 1955; Atlanta, Communicable Disease Center, Training Branch, 1964
•
Tularemia in North America, 1930-1974. Author: William L. Jellison; Year: 1974
•
Tularemia in sheep and in sheep industry workers in western United States [by] William L. Jellison [and] Glen M. Kohls. Author: Jellison, William L. (William Livingston),; Year: 1955; [Washington, 1955]
•
Tularemia in the USSR. Author: United States. Foreign Broadcast Information Service.; Year: 1953; Arlington, Va.: Foreign Broadcast Information Service; Springfield, Va.: National Technical Information Service [distributor], [1982]
•
Tularemia, weather, and rabbit populations [by] Ralph E. Yeatter [and] David H. Thompson. Author: Yeatter, Ralph E.; Year: 1964; Urbana, Ill., 1952
•
Tularemia. Author: Eugeniusz Skrodzki; Year: 1978
•
Tularemia; history, pathology, diagnosis and treatment. Author: Simpson, Walter Malcolm, 1895-; Year: 1929
Chapters on Tularemia In order to find chapters that specifically relate to tularemia, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and tularemia 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 “tularemia” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on tularemia: •
Oral Bacterial Infections Source: in Eisen, D. and Lynch, D.P. Mouth: Diagnosis and Treatment. St. Louis, MO: Mosby, Inc. 1998. p. 92-107.
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.
82
Tularemia
Contact: Available from Harcourt Health Sciences. Book Order Fulfillment Department, 11830 Westline Industrial Drive, St. Louis, MO 63146-9988. Website: www.mosby.com. PRICE: $79.95 plus shipping and handling. ISBN: 0815131054. Summary: More than 300 different bacteria, including Staphylococcus aureus, coliform bacteria, Kelsiella, and Pseudomonas, reside in the oral cavity and comprise what is regarded as normal oral flora. When a species of bacteria increases in number or when the host defense threshold is exceeded, disease arises. Two of the most common bacterial diseases that afflict humans are dental caries and periodontal disease. This chapter on oral bacterial infections is from a textbook on the mouth that offers information to primary care physicians and to many specialists in medicine and dentistry. Topics include gingivitis and periodontitis, necrotizing gingivostomatitis, tuberculosis, oral cutaneous fistulas, gonorrhea, syphilis, actinomycosis, parulis, and miscellaneous infections, including scarlet fever, diphtheria, tularemia, granuloma inguinale, leprosy, suppurative infection of the salivary glands, and noma. For each condition, the authors describe symptoms, identification, complications, and treatment. The chapter is illustrated with numerous full color photographs of the conditions under discussion. 19 figures. 46 references. •
Bacterial Diseases Source: in Bork, K., et al. Diseases of the Oral Mucosa and the Lips. Orlando, FL: W.B. Saunders Company. 1993. p. 123-151. Contact: Available from W.B. Saunders Company. Order Fulfillment, 6277 Sea Harbor Drive, Orlando, FL 32887-4430. (800) 545-2522 (individuals) or (800) 782-4479 (schools); Fax (800) 874-6418 or (407) 352-3445; http://www.wbsaunders.com. PRICE: $99.00 plus shipping and handling. ISBN: 0721640397. Summary: This lengthy chapter, from a textbook on diseases of the oral mucosa and the lips, discusses the etiology, clinical features, histopathology, diagnosis, and differential diagnosis for a variety of bacterial diseases that demonstrate oral manifestations. Diseases covered include impetigo, furuncle and carbuncle (deep staphylococcal infections of the hair follicle), acute bacterial cheilitis with ectropion, chancriform pyoderma, erysipelas, periodontal disease, simple gingivitis, hyperplastic or chronic gingivitis, acute necrotizing ulcerative gingivostomatitis (ANUG), noma (cancrum oris), chronic periodontitis, juvenile periodontitis, periodontal abscess, parodontal pseudocysts, dental sinus tracts, dental infection as a cause of other diseases, nonodontogenic oral abscesses, scarlet fever, diphtheria, cat-scratch disease, gonorrhea, chancroid, syphilis, congenital syphilis, yaws, tuberculosis (including lupus vulcagis), leprosy, actinomycosis, and miscellaneous bacterial infections, including anthrax, brucellosis, listeriosis, glanders, meningococcemia, granuloma inguinale, pertussis, and tularemia. Full-color photographs illustrate the chapter; references are provided for each section. 57 figures. 100 references. (AA-M).
83
CHAPTER 6. PERIODICALS AND NEWS ON TULAREMIA Overview In this chapter, we suggest a number of news sources and present various periodicals that cover tularemia.
News Services and Press Releases One of the simplest ways of tracking press releases on tularemia 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 “tularemia” (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 tularemia. 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 “tularemia” (or synonyms). The following was recently listed in this archive for tularemia: •
Tularemia detected in prairie dogs to be sold as pets, CDC warns Source: Reuters Medical News Date: August 06, 2002
•
Tularemia incidence tracked for bioterrorism preparedness Source: Reuters Medical News Date: March 07, 2002
84
Tularemia
•
Lawn mowing implicated as risk factor in tularemia outbreak Source: Reuters Medical News Date: November 28, 2001 The NIH
Within MEDLINEplus, the NIH has made an agreement with the New York Times Syndicate, the AP News Service, and Reuters to deliver news that can be browsed by the public. Search news releases at http://www.nlm.nih.gov/medlineplus/alphanews_a.html. MEDLINEplus allows you to browse across an alphabetical index. Or you can search by date at the following Web page: http://www.nlm.nih.gov/medlineplus/newsbydate.html. Often, news items are indexed by MEDLINEplus within its search engine. Business Wire Business Wire is similar to PR Newswire. To access this archive, simply go to http://www.businesswire.com/. You can scan the news by industry category or company name. Market Wire Market Wire is more focused on technology than the other wires. To browse the latest press releases by topic, such as alternative medicine, biotechnology, fitness, healthcare, legal, nutrition, and pharmaceuticals, access Market Wire’s Medical/Health channel at http://www.marketwire.com/mw/release_index?channel=MedicalHealth. Or simply go to Market Wire’s home page at http://www.marketwire.com/mw/home, type “tularemia” (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 “tularemia” (or synonyms). If you know the name of a company that is relevant to tularemia, 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 “tularemia” (or synonyms).
Periodicals and News
85
Academic Periodicals covering Tularemia Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to tularemia. In addition to these sources, you can search for articles covering tularemia that have been published by any of the periodicals listed in previous chapters. To find the latest studies published, go to http://www.ncbi.nlm.nih.gov/pubmed, type the name of the periodical into the search box, and click “Go.” If you want complete details about the historical contents of a journal, you can also visit the following Web site: http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi. Here, type in the name of the journal or its abbreviation, and you will receive an index of published articles. At http://locatorplus.gov/, you can retrieve more indexing information on medical periodicals (e.g. the name of the publisher). Select the button “Search LOCATORplus.” Then type in the name of the journal and select the advanced search option “Journal Title Search.”
87
CHAPTER 7. RESEARCHING MEDICATIONS Overview While a number of hard copy or CD-ROM resources are available for researching medications, a more flexible method is to use Internet-based databases. Broadly speaking, there are two sources of information on approved medications: public sources and private sources. We will emphasize free-to-use public sources.
U.S. Pharmacopeia Because of historical investments by various organizations and the emergence of the Internet, it has become rather simple to learn about the medications recommended for tularemia. One such source is the United States Pharmacopeia. In 1820, eleven physicians met in Washington, D.C. to establish the first compendium of standard drugs for the United States. They called this compendium the U.S. Pharmacopeia (USP). Today, the USP is a non profit organization consisting of 800 volunteer scientists, eleven elected officials, and 400 representatives of state associations and colleges of medicine and pharmacy. The USP is located in Rockville, Maryland, and its home page is located at http://www.usp.org/. The USP currently provides standards for over 3,700 medications. The resulting USP DI® Advice for the Patient® can be accessed through the National Library of Medicine of the National Institutes of Health. The database is partially derived from lists of federally approved medications in the Food and Drug Administration’s (FDA) Drug Approvals database, located at http://www.fda.gov/cder/da/da.htm. While the FDA database is rather large and difficult to navigate, the Phamacopeia is both user-friendly and free to use. It covers more than 9,000 prescription and over-the-counter medications. To access this database, simply type the following hyperlink into your Web browser: http://www.nlm.nih.gov/medlineplus/druginformation.html. To view examples of a given medication (brand names, category, description, preparation, proper use, precautions, side effects, etc.), simply follow the hyperlinks indicated within the United States Pharmacopeia (USP). Below, we have compiled a list of medications associated with tularemia. If you would like more information on a particular medication, the provided hyperlinks will direct you to ample documentation (e.g. typical dosage, side effects, drug-interaction risks, etc.). The
88 Tularemia
following drugs have been mentioned in the Pharmacopeia and other sources as being potentially applicable to tularemia: Cephalosporins •
Systemic - U.S. Brands: Ancef; Ceclor; Ceclor CD; Cedax; Cefadyl; Cefizox; Cefobid; Cefotan; Ceftin; Cefzil; Ceptaz; Claforan; Duricef; Fortaz; Keflex 20; Keftab 20; Kefurox; Kefzol; Mandol; Maxipime; Mefoxin; Monocid; Omnicef; Rocephin; Suprax; Tazicef; Tazidime; Vantin; Velo http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202119.html
Chloramphenicol •
Systemic http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202119.html
•
Systemic - U.S. Brands: Chloromycetin http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202127.html
Diphtheria and Tetanus Toxoids •
Systemic http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202127.html
Diphtheria and Tetanus Toxoids and Pertussis Vaccine Adsorbed •
Systemic - U.S. Brands: Acel-Imune; Certiva; Infanrix; Tripedia http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202201.html
Diphtheria and Tetanus Toxoids and Pertussis Vaccine Adsorbed and Haemophilus B Conjugate Vaccine •
Systemic - U.S. Brands: Tetramune http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202911.html
Diphtheria Antitoxin •
Systemic http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202911.html
Gentamicin •
Ophthalmic http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202604.html
•
Ophthalmic - U.S. Brands: Garamycin; Gentacidin; Gentafair; Gentak; OcuMycin; Spectro-Genta http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202604.html
•
Topical - U.S. Brands: Garamycin; Gentamar; G-Myticin http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202258.html
Plague Vaccine •
Topical http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202258.html
Researching Medications
89
Commercial Databases In addition to the medications listed in the USP above, a number of commercial sites are available by subscription to physicians and their institutions. Or, you may be able to access these sources from your local medical library.
Mosby’s Drug Consult™ Mosby’s Drug Consult™ database (also available on CD-ROM and book format) covers 45,000 drug products including generics and international brands. It provides prescribing information, drug interactions, and patient information. Subscription information is available at the following hyperlink: http://www.mosbysdrugconsult.com/.
PDRhealth The PDRhealth database is a free-to-use, drug information search engine that has been written for the public in layman’s terms. It contains FDA-approved drug information adapted from the Physicians’ Desk Reference (PDR) database. PDRhealth can be searched by brand name, generic name, or indication. It features multiple drug interactions reports. Search PDRhealth at http://www.pdrhealth.com/drug_info/index.html. Other Web Sites Drugs.com (www.drugs.com) reproduces the information in the Pharmacopeia as well as commercial information. You may also want to consider the Web site of the Medical Letter, Inc. (http://www.medletter.com/) which allows users to download articles on various drugs and therapeutics for a nominal fee. If you have any questions about a medical treatment, the FDA may have an office near you. Look for their number in the blue pages of the phone book. You can also contact the FDA through its toll-free number, 1-888-INFO-FDA (1-888-463-6332), or on the World Wide Web at www.fda.gov.
91
APPENDICES
93
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 Institute9: •
Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm
•
National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/news/facts/
•
National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html
•
National Cancer Institute (NCI); guidelines available at http://www.cancer.gov/cancerinfo/list.aspx?viewid=5f35036e-5497-4d86-8c2c714a9f7c8d25
•
National Eye Institute (NEI); guidelines available at http://www.nei.nih.gov/order/index.htm
•
National Heart, Lung, and Blood Institute (NHLBI); guidelines available at http://www.nhlbi.nih.gov/guidelines/index.htm
•
National Human Genome Research Institute (NHGRI); research available at http://www.genome.gov/page.cfm?pageID=10000375
•
National Institute on Aging (NIA); guidelines available at http://www.nia.nih.gov/health/
9
These publications are typically written by one or more of the various NIH Institutes.
94 Tularemia
•
National Institute on Alcohol Abuse and Alcoholism (NIAAA); guidelines available at http://www.niaaa.nih.gov/publications/publications.htm
•
National Institute of Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/
•
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm
•
National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm
•
National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/
•
National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/
•
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm
•
National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html
•
National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm
•
National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/practitioners/index.cfm
•
National Institute of Neurological Disorders and Stroke (NINDS); neurological disorder information pages available at http://www.ninds.nih.gov/health_and_medical/disorder_index.htm
•
National Institute of Nursing Research (NINR); publications on selected illnesses at http://www.nih.gov/ninr/news-info/publications.html
•
National Institute of Biomedical Imaging and Bioengineering; general information at http://grants.nih.gov/grants/becon/becon_info.htm
•
Center for Information Technology (CIT); referrals to other agencies based on keyword searches available at http://kb.nih.gov/www_query_main.asp
•
National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/
•
National Center for Research Resources (NCRR); various information directories available at http://www.ncrr.nih.gov/publications.asp
•
Office of Rare Diseases; various fact sheets available at http://rarediseases.info.nih.gov/html/resources/rep_pubs.html
•
Centers for Disease Control and Prevention; various fact sheets on infectious diseases available at http://www.cdc.gov/publications.htm
Physician Resources
95
NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.10 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:11 •
Bioethics: Access to published literature on the ethical, legal, and public policy issues surrounding healthcare and biomedical research. This information is provided in conjunction with the Kennedy Institute of Ethics located at Georgetown University, Washington, D.C.: http://www.nlm.nih.gov/databases/databases_bioethics.html
•
HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html
•
NLM Online Exhibitions: Describes “Exhibitions in the History of Medicine”: http://www.nlm.nih.gov/exhibition/exhibition.html. Additional resources for historical scholarship in medicine: http://www.nlm.nih.gov/hmd/hmd.html
•
Biotechnology Information: Access to public databases. The National Center for Biotechnology Information conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information for the better understanding of molecular processes affecting human health and disease: http://www.ncbi.nlm.nih.gov/
•
Population Information: The National Library of Medicine provides access to worldwide coverage of population, family planning, and related health issues, including family planning technology and programs, fertility, and population law and policy: http://www.nlm.nih.gov/databases/databases_population.html
•
Cancer Information: Access to cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html
•
Profiles in Science: Offering the archival collections of prominent twentieth-century biomedical scientists to the public through modern digital technology: http://www.profiles.nlm.nih.gov/
•
Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html
•
Clinical Alerts: Reports the release of findings from the NIH-funded clinical trials where such release could significantly affect morbidity and mortality: http://www.nlm.nih.gov/databases/alerts/clinical_alerts.html
•
Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html
•
MEDLINE: Bibliographic database covering the fields of medicine, nursing, dentistry, veterinary medicine, the healthcare system, and the pre-clinical sciences: http://www.nlm.nih.gov/databases/databases_medline.html
10
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). 11 See http://www.nlm.nih.gov/databases/databases.html.
96 Tularemia
•
Toxicology and Environmental Health Information (TOXNET): Databases covering toxicology and environmental health: http://sis.nlm.nih.gov/Tox/ToxMain.html
•
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 Gateway12 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.13 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “tularemia” (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 1915 63 424 0 0 2402
HSTAT14 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.15 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.16 Simply search by “tularemia” (or synonyms) at the following Web site: http://text.nlm.nih.gov.
12
Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.
13
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).
14 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html.
15 16
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.
Physician Resources
97
Coffee Break: Tutorials for Biologists17 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.18 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.19 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/.
17 Adapted 18
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.
19 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.
99
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 tularemia 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 tularemia. 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 tularemia. 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 “tularemia”:
100 Tularemia
•
Other guides Bacterial Infections http://www.nlm.nih.gov/medlineplus/bacterialinfections.html Biodefense and Bioterrorism http://www.nlm.nih.gov/medlineplus/biodefenseandbioterrorism.html Insect Bites and Stings http://www.nlm.nih.gov/medlineplus/insectbitesandstings.html Lyme Disease http://www.nlm.nih.gov/medlineplus/lymedisease.html Tick Bites http://www.nlm.nih.gov/medlineplus/tickbites.html
Within the health topic page dedicated to tularemia, 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
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
Patient Resources
101
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
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/648.xml
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
102 Tularemia
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
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 Customs Agents Will Do Food Terror Checks Source: 12/03/2003, United Press International http://www.nlm.nih.gov//www.nlm.nih.gov/medlineplus/news/fullstory_14961 .html
Patient Resources
103
FDA and CPB Bolster Safeguards on Imported Food Source: 12/03/2003, Food and Drug Administration
http://www.fda.gov/bbs/topics/NEWS/2003/NEW00988.html
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/ 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
104 Tularemia
•
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 tularemia. 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: •
Guide to Tick-Borne Disorders Source: Hartford, CT: Lyme Disease Foundation. 1997. 8 p. Contact: Available from Lyme Disease Foundation. 1 Financial Plaza, 18th Floor, Hartford, CT 06103. (800)886-LYME or (860) 525-2000. Fax (860) 525-TICK. E-mail:
[email protected]. Website: www.lyme.org. PRICE: $1.00; bulk orders available at cost. Summary: This pamphlet provides the general public with information about tick-borne illnesses including babesiosis, Colorado tick fever, ehrlichiosis, Lyme disease, relapsing fever, Rocky Mountain spotted fever, tick paralysis, and tularemia, and their symptoms. The pamphlet offers tips on reducing the chances of getting a tick bite, removing a tick, and reducing the number of ticks around a home. In addition, the pamphlet provides information on the Lyme Disease Foundation and lists many of the free services it offers. 6 figures.
•
Tick ID Wallet Card To Protect Your Family Source: Hartford, CT: Lyme Disease Foundation. 1998. 2 p. Contact: Available from Lyme Disease Foundation. 1 Financial Plaza, 18th Floor, Hartford, CT 06103. (800)886-LYME or (860) 525-2000. Fax (860) 525-TICK. E-mail:
[email protected]. Website: www.lyme.org. PRICE: $1.00; bulk orders available at cost. Summary: This wallet card provides the general public with information about tick protection and removal. The card highlights the symptoms of various tick-borne illnesses, including Lyme disease, relapsing fever, Rocky Mountain spotted fever, tick paralysis, tularemia, babesiosis, Colorado tick fever, and ehrlichiosis, and provides pictures of the ticks that cause these illnesses. In addition, it offers suggestions on reducing the chances of getting a tick bite and provides guidelines on properly removing a tick.
Patient Resources
105
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 “tularemia” (or synonyms). The following was recently posted: •
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=tularemia 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: •
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 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 tularemia. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html. Additional Web Sources A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •
AOL: http://search.aol.com/cat.adp?id=168&layer=&from=subcats
•
Family Village: http://www.familyvillage.wisc.edu/specific.htm
106 Tularemia
•
Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/
•
Med Help International: http://www.medhelp.org/HealthTopics/A.html
•
Open Directory Project: http://dmoz.org/Health/Conditions_and_Diseases/
•
Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/
•
WebMD®Health: http://my.webmd.com/health_topics
Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to tularemia. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with tularemia. 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 tularemia. 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 “tularemia” (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 “tularemia”. Type the following hyperlink into your
Patient Resources
107
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 “tularemia” (or synonyms) into the “For these words:” box. You should check back periodically with this database since it is updated every three months. The National Organization for Rare Disorders, Inc. The National Organization for Rare Disorders, Inc. has prepared a Web site that provides, at no charge, lists of associations organized by health topic. You can access this database at the following Web site: http://www.rarediseases.org/search/orgsearch.html. Type “tularemia” (or a synonym) into the search box, and click “Submit Query.”
109
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.20
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
20
Adapted from the NLM: http://www.nlm.nih.gov/psd/cas/interlibrary.html.
110 Tularemia
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)21: •
Alabama: Health InfoNet of Jefferson County (Jefferson County Library Cooperative, Lister Hill Library of the Health Sciences), http://www.uab.edu/infonet/
•
Alabama: Richard M. Scrushy Library (American Sports Medicine Institute)
•
Arizona: Samaritan Regional Medical Center: The Learning Center (Samaritan Health System, Phoenix, Arizona), http://www.samaritan.edu/library/bannerlibs.htm
•
California: Kris Kelly Health Information Center (St. Joseph Health System, Humboldt), http://www.humboldt1.com/~kkhic/index.html
•
California: Community Health Library of Los Gatos, http://www.healthlib.org/orgresources.html
•
California: Consumer Health Program and Services (CHIPS) (County of Los Angeles Public Library, Los Angeles County Harbor-UCLA Medical Center Library) - Carson, CA, http://www.colapublib.org/services/chips.html
•
California: Gateway Health Library (Sutter Gould Medical Foundation)
•
California: Health Library (Stanford University Medical Center), http://wwwmed.stanford.edu/healthlibrary/
•
California: Patient Education Resource Center - Health Information and Resources (University of California, San Francisco), http://sfghdean.ucsf.edu/barnett/PERC/default.asp
•
California: Redwood Health Library (Petaluma Health Care District), http://www.phcd.org/rdwdlib.html
•
California: Los Gatos PlaneTree Health Library, http://planetreesanjose.org/
•
California: Sutter Resource Library (Sutter Hospitals Foundation, Sacramento), http://suttermedicalcenter.org/library/
•
California: Health Sciences Libraries (University of California, Davis), http://www.lib.ucdavis.edu/healthsci/
•
California: ValleyCare Health Library & Ryan Comer Cancer Resource Center (ValleyCare Health System, Pleasanton), http://gaelnet.stmarysca.edu/other.libs/gbal/east/vchl.html
•
California: Washington Community Health Resource Library (Fremont), http://www.healthlibrary.org/
•
Colorado: William V. Gervasini Memorial Library (Exempla Healthcare), http://www.saintjosephdenver.org/yourhealth/libraries/
•
Connecticut: Hartford Hospital Health Science Libraries (Hartford Hospital), http://www.harthosp.org/library/
•
Connecticut: Healthnet: Connecticut Consumer Health Information Center (University of Connecticut Health Center, Lyman Maynard Stowe Library), http://library.uchc.edu/departm/hnet/
21
Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.
Finding Medical Libraries
111
•
Connecticut: Waterbury Hospital Health Center Library (Waterbury Hospital, Waterbury), http://www.waterburyhospital.com/library/consumer.shtml
•
Delaware: Consumer Health Library (Christiana Care Health System, Eugene du Pont Preventive Medicine & Rehabilitation Institute, Wilmington), http://www.christianacare.org/health_guide/health_guide_pmri_health_info.cfm
•
Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine, Wilmington), http://www.delamed.org/chls.html
•
Georgia: Family Resource Library (Medical College of Georgia, Augusta), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm
•
Georgia: Health Resource Center (Medical Center of Central Georgia, Macon), http://www.mccg.org/hrc/hrchome.asp
•
Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library, Honolulu), http://hml.org/CHIS/
•
Idaho: DeArmond Consumer Health Library (Kootenai Medical Center, Coeur d’Alene), http://www.nicon.org/DeArmond/index.htm
•
Illinois: Health Learning Center of Northwestern Memorial Hospital (Chicago), http://www.nmh.org/health_info/hlc.html
•
Illinois: Medical Library (OSF Saint Francis Medical Center, Peoria), http://www.osfsaintfrancis.org/general/library/
•
Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital, Lexington), http://www.centralbap.com/education/community/library.cfm
•
Kentucky: University of Kentucky - Health Information Library (Chandler Medical Center, Lexington), http://www.mc.uky.edu/PatientEd/
•
Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation, New Orleans), http://www.ochsner.org/library/
•
Louisiana: Louisiana State University Health Sciences Center Medical LibraryShreveport, http://lib-sh.lsuhsc.edu/
•
Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital, Farmington), http://www.fchn.org/fmh/lib.htm
•
Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center, Lewiston), http://www.cmmc.org/library/library.html
•
Maine: Hadley Parrot Health Science Library (Eastern Maine Healthcare, Bangor), http://www.emh.org/hll/hpl/guide.htm
•
Maine: Maine Medical Center Library (Maine Medical Center, Portland), http://www.mmc.org/library/
•
Maine: Parkview Hospital (Brunswick), http://www.parkviewhospital.org/
•
Maine: Southern Maine Medical Center Health Sciences Library (Southern Maine Medical Center, Biddeford), http://www.smmc.org/services/service.php3?choice=10
•
Maine: Stephens Memorial Hospital’s Health Information Library (Western Maine Health, Norway), http://www.wmhcc.org/Library/
112 Tularemia
•
Manitoba, Canada: Consumer & Patient Health Information Service (University of Manitoba Libraries), http://www.umanitoba.ca/libraries/units/health/reference/chis.html
•
Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre, Winnipeg), http://www.deerlodge.mb.ca/crane_library/about.asp
•
Maryland: Health Information Center at the Wheaton Regional Library (Montgomery County, Dept. of Public Libraries, Wheaton Regional Library), http://www.mont.lib.md.us/healthinfo/hic.asp
•
Massachusetts: Baystate Medical Center Library (Baystate Health System), http://www.baystatehealth.com/1024/
•
Massachusetts: Boston University Medical Center Alumni Medical Library (Boston University Medical Center), http://med-libwww.bu.edu/library/lib.html
•
Massachusetts: Lowell General Hospital Health Sciences Library (Lowell General Hospital, Lowell), http://www.lowellgeneral.org/library/HomePageLinks/WWW.htm
•
Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital, Boston), http://www.nebh.org/health_lib.asp
•
Massachusetts: St. Luke’s Hospital Health Sciences Library (St. Luke’s Hospital, Southcoast Health System, New Bedford), http://www.southcoast.org/library/
•
Massachusetts: Treadwell Library Consumer Health Reference Center (Massachusetts General Hospital), http://www.mgh.harvard.edu/library/chrcindex.html
•
Massachusetts: UMass HealthNet (University of Massachusetts Medical School, Worchester), http://healthnet.umassmed.edu/
•
Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm
•
Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/
•
Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html
•
Michigan: Patient Education Resouce Center - University of Michigan Cancer Center (University of Michigan Comprehensive Cancer Center, Ann Arbor), http://www.cancer.med.umich.edu/learn/leares.htm
•
Michigan: Sladen Library & Center for Health Information Resources - Consumer Health Information (Detroit), http://www.henryford.com/body.cfm?id=39330
•
Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center, Missoula)
•
National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html
•
National: National Network of Libraries of Medicine (National Library of Medicine) provides library services for health professionals in the United States who do not have access to a medical library, http://nnlm.gov/
•
National: NN/LM List of Libraries Serving the Public (National Network of Libraries of Medicine), http://nnlm.gov/members/
Finding Medical Libraries
113
•
Nevada: Health Science Library, West Charleston Library (Las Vegas-Clark County Library District, Las Vegas), http://www.lvccld.org/special_collections/medical/index.htm
•
New Hampshire: Dartmouth Biomedical Libraries (Dartmouth College Library, Hanover), http://www.dartmouth.edu/~biomed/resources.htmld/conshealth.htmld/
•
New Jersey: Consumer Health Library (Rahway Hospital, Rahway), http://www.rahwayhospital.com/library.htm
•
New Jersey: Dr. Walter Phillips Health Sciences Library (Englewood Hospital and Medical Center, Englewood), http://www.englewoodhospital.com/links/index.htm
•
New Jersey: Meland Foundation (Englewood Hospital and Medical Center, Englewood), http://www.geocities.com/ResearchTriangle/9360/
•
New York: Choices in Health Information (New York Public Library) - NLM Consumer Pilot Project participant, http://www.nypl.org/branch/health/links.html
•
New York: Health Information Center (Upstate Medical University, State University of New York, Syracuse), http://www.upstate.edu/library/hic/
•
New York: Health Sciences Library (Long Island Jewish Medical Center, New Hyde Park), http://www.lij.edu/library/library.html
•
New York: ViaHealth Medical Library (Rochester General Hospital), http://www.nyam.org/library/
•
Ohio: Consumer Health Library (Akron General Medical Center, Medical & Consumer Health Library), http://www.akrongeneral.org/hwlibrary.htm
•
Oklahoma: The Health Information Center at Saint Francis Hospital (Saint Francis Health System, Tulsa), http://www.sfh-tulsa.com/services/healthinfo.asp
•
Oregon: Planetree Health Resource Center (Mid-Columbia Medical Center, The Dalles), http://www.mcmc.net/phrc/
•
Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center, Hershey), http://www.hmc.psu.edu/commhealth/
•
Pennsylvania: Community Health Resource Library (Geisinger Medical Center, Danville), http://www.geisinger.edu/education/commlib.shtml
•
Pennsylvania: HealthInfo Library (Moses Taylor Hospital, Scranton), http://www.mth.org/healthwellness.html
•
Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System, Pittsburgh), http://www.hsls.pitt.edu/guides/chi/hopwood/index_html
•
Pennsylvania: Koop Community Health Information Center (College of Physicians of Philadelphia), http://www.collphyphil.org/kooppg1.shtml
•
Pennsylvania: Learning Resources Center - Medical Library (Susquehanna Health System, Williamsport), http://www.shscares.org/services/lrc/index.asp
•
Pennsylvania: Medical Library (UPMC Health System, Pittsburgh), http://www.upmc.edu/passavant/library.htm
•
Quebec, Canada: Medical Library (Montreal General Hospital), http://www.mghlib.mcgill.ca/
114 Tularemia
•
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
115
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 tularemia: •
Basic Guidelines for Tularemia Anthrax Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001325.htm Brucellosis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000597.htm Chancroid Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000635.htm Diphtheria Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001608.htm Encephalitis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001415.htm Endocarditis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001098.htm
116 Tularemia
Hepatitis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001154.htm Herpes simplex Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001324.htm Lymphogranuloma venereum Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000634.htm Malaria Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000621.htm Osteomyelitis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000437.htm Plague Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000596.htm Pleural effusion Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000086.htm Psittacosis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000088.htm Qfever Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001337.htm Rat-bite fever Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001348.htm Renal failure Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000501.htm Rhabdomyolysis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000473.htm Sporotrichosis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001338.htm Streptococcal pharyngitis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000639.htm Syphilis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001327.htm Toxoplasmosis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000637.htm Tularemia Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000856.htm
Online Glossaries 117
Typhoid fever Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001332.htm •
Signs & Symptoms for Tularemia Chest pain Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003079.htm Chills Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003091.htm Cough Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003072.htm Diarrhea Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003126.htm Enlarged lymph nodes Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003097.htm Erythema Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003220.htm Fatigue Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003088.htm Fever Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003090.htm Headache Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003024.htm Hemoptysis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003073.htm Hepatomegaly Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003275.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 Myalgia Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003178.htm Papule Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003233.htm
118 Tularemia
Rales Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003323.htm Shortness of breath Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003075.htm Skin lesion Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003220.htm Skin rash Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003220.htm Sore throat Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003053.htm Splenomegaly Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003276.htm Sweating Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003218.htm Vomiting Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003117.htm Weight loss Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003107.htm •
Diagnostics and Tests for Tularemia ALT Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003473.htm Antibody titer Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003333.htm Biopsy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003416.htm Blood culture Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003744.htm CBC Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003642.htm Chest X-ray Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003804.htm CO2 Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003469.htm CPK Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003503.htm
Online Glossaries 119
Creatinine Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003475.htm ELISA Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003332.htm ESR Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003638.htm Febrile/cold agglutinins Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003549.htm Fibrin split products Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003655.htm Fibrinogen Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003650.htm Liver function tests Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003436.htm Serology Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003511.htm Serology for tularemia Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003523.htm Thoracentesis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003420.htm X-ray Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003337.htm •
Background Topics for Tularemia Abdominal discomfort Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002228.htm Anthrax Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002235.htm Cardiovascular Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002310.htm Endemic Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002362.htm Incidence Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002387.htm Renal Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002289.htm
120 Tularemia
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
121
TULAREMIA DICTIONARY
The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. Abscess: A localized, circumscribed collection of pus. [NIH] Actinomycosis: Infections with bacteria of the genus Actinomyces. [NIH] Acute renal: A condition in which the kidneys suddenly stop working. In most cases, kidneys can recover from almost complete loss of function. [NIH] Adaptability: Ability to develop some form of tolerance to conditions extremely different from those under which a living organism evolved. [NIH] Adenine: A purine base and a fundamental unit of adenine nucleotides. [NIH] Adenopathy: Large or swollen lymph glands. [NIH] 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] Adenosine Deaminase: An enzyme that catalyzes the hydrolysis of adenosine to inosine with the elimination of ammonia. Since there are wide tissue and species variations in the enzyme, it has been used as a tool in the study of human and animal genetics and in medical diagnosis. EC 3.5.4.4. [NIH] Adhesions: Pathological processes consisting of the union of the opposing surfaces of a wound. [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] 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] 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] Agar: A complex sulfated polymer of galactose units, extracted from Gelidium cartilagineum, Gracilaria confervoides, and related red algae. It is used as a gel in the preparation of solid culture media for microorganisms, as a bulk laxative, in making emulsions, and as a supporting medium for immunodiffusion and immunoelectrophoresis. [NIH]
122 Tularemia
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] Agonists: Drugs that trigger an action from a cell or another drug. [NIH] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alimentary: Pertaining to food or nutritive material, or to the organs of digestion. [EU] Alkaline: Having the reactions of an alkali. [EU] Alkaline Phosphatase: An enzyme that catalyzes the conversion of an orthophosphoric monoester and water to an alcohol and orthophosphate. EC 3.1.3.1. [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] Amber: A yellowish fossil resin, the gum of several species of coniferous trees, found in the alluvial deposits of northeastern Germany. It is used in molecular biology in the analysis of organic matter fossilized in amber. [NIH] Amino Acid Motifs: Commonly observed structural components of proteins formed by simple combinations of adjacent secondary structures. A commonly observed structure may be composed of a conserved sequence which can be represented by a consensus sequence. [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 ( 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] Ammonia: A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. [NIH] Amplification: The production of additional copies of a chromosomal DNA sequence, found as either intrachromosomal or extrachromosomal DNA. [NIH] Anaerobic: 1. Lacking molecular oxygen. 2. Growing, living, or occurring in the absence of molecular oxygen; pertaining to an anaerobe. [EU] Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Analog: In chemistry, a substance that is similar, but not identical, to another. [NIH] Analogous: Resembling or similar in some respects, as in function or appearance, but not in origin or development;. [EU] Anaphylatoxins: The family of peptides C3a, C4a, C5a, and C5a des-arginine produced in the serum during complement activation. They produce smooth muscle contraction, mast cell histamine release, affect platelet aggregation, and act as mediators of the local
Dictionary 123
inflammatory process. The order of anaphylatoxin activity from strongest to weakest is C5a, C3a, C4a, and C5a des-arginine. The latter is the so-called "classical" anaphylatoxin but shows no spasmogenic activity though it contains some chemotactic ability. [NIH] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH]
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]
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]
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]
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]
Antimicrobial: Killing microorganisms, or suppressing their multiplication or growth. [EU]
Antiviral: Destroying viruses or suppressing their replication. [EU]
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]
124 Tularemia
Apoptosis: One of the two mechanisms by which cell death occurs (the other being the
pathological process of necrosis). Apoptosis is the mechanism responsible for the
physiological deletion of cells and appears to be intrinsically programmed. It is
characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin
cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA (DNA
fragmentation) at internucleosomal sites. This mode of cell death serves as a balance to
mitosis in regulating the size of animal tissues and in mediating pathologic processes
associated with tumor growth. [NIH]
Aqueous: Having to do with water. [NIH]
Arterial: Pertaining to an artery or to the arteries. [EU]
Arteries: The vessels carrying blood away from the heart. [NIH]
Ascites: Accumulation or retention of free fluid within the peritoneal cavity. [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]
Ataxia: Impairment of the ability to perform smoothly coordinated voluntary movements.
This condition may affect the limbs, trunk, eyes, pharnyx, larnyx, and other structures.
Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from
posterior column injury or peripheral nerve diseases. Motor ataxia may be associated with
cerebellar diseases; cerebral cortex diseases; thalamic diseases; basal ganglia diseases; injury
to the red nucleus; and other conditions. [NIH]
Attenuated: Strain with weakened or reduced virulence. [NIH]
Attenuation: Reduction of transmitted sound energy or its electrical equivalent. [NIH]
Atypical: Irregular; not conformable to the type; in microbiology, applied specifically to
strains of unusual type. [EU] 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]
Babesiosis: A group of tick-borne diseases of mammals including zoonoses in humans.
They are caused by protozoans of the genus babesia, which parasitize erythrocytes,
producing hemolysis. In the U.S., the organism's natural host is mice and transmission is by
the deer tick ixodes scapularis. [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 Vaccines: Suspensions of attenuated or killed bacteria administered for the
prevention or treatment of infectious bacterial disease. [NIH]
Bactericidal: Substance lethal to bacteria; substance capable of killing bacteria. [NIH]
Dictionary 125
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] Bacteriostatic: 1. Inhibiting the growth or multiplication of bacteria. 2. An agent that inhibits the growth or multiplication of bacteria. [EU]
Bacterium: Microscopic organism which may have a spherical, rod-like, or spiral unicellular
or non-cellular body. Bacteria usually reproduce through asexual processes. [NIH]
Basal Ganglia: Large subcortical nuclear masses derived from the telencephalon and located in the basal regions of the cerebral hemispheres. [NIH] Basal Ganglia Diseases: Diseases of the basal ganglia including the putamen; globus pallidus; claustrum; amygdala; and caudate nucleus. Dyskinesias (most notably involuntary movements and alterations of the rate of movement) represent the primary clinical manifestations of these disorders. Common etiologies include cerebrovascular disease; neurodegenerative diseases; and craniocerebral trauma. [NIH] Base: In chemistry, the nonacid part of a salt; a substance that combines with acids to form salts; a substance that dissociates to give hydroxide ions in aqueous solutions; a substance whose molecule or ion can combine with a proton (hydrogen ion); a substance capable of donating a pair of electrons (to an acid) for the formation of a coordinate covalent bond. [EU] Beta-glucans: Polysaccharides made by several types of mushrooms. Beta-glucans have been used to treat patients with gastric cancer and colorectal cancer. They may be able to stimulate the immune system. [NIH] Beta-Lactamases: Enzymes found in many bacteria which catalyze the hydrolysis of the amide bond in the beta-lactam ring. Well known antibiotics destroyed by these enzymes are penicillins and cephalosporins. EC 3.5.2.6. [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] Bioavailability: The degree to which a drug or other substance becomes available to the target tissue after administration. [EU]
Biochemical: Relating to biochemistry; characterized by, produced by, or involving
chemical reactions in living organisms. [EU]
Biogenesis: The origin of life. It includes studies of the potential basis for life in organic
compounds but excludes studies of the development of altered forms of life through
mutation and natural selection, which is evolution. [NIH]
Biological response modifier: BRM. A substance that stimulates the body's response to infection and disease. [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]
Biomedical Technology: The application of technology to the solution of medical problems.
[NIH]
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
126 Tularemia
clinically useful. Alteration of biologic function at the molecular level (i.e., genetic
engineering) is a central focus; laboratory methods used include transfection and cloning
technologies, sequence and structure analysis algorithms, computer databases, and gene and
protein structure function analysis and prediction. [NIH]
Bioterrorism: The use of biological agents in terrorism. This includes the malevolent use of
bacteria, viruses, or toxins against people, animals, or plants. [NIH]
Bladder: The organ that stores urine. [NIH]
Blood Coagulation: The process of the interaction of blood coagulation factors that results in
an insoluble fibrin clot. [NIH]
Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber.
Unless there is reference to another location, such as the pulmonary artery or one of the
heart chambers, it refers to the pressure in the systemic arteries, as measured, for example,
in the forearm. [NIH]
Blood vessel: A tube in the body through which blood circulates. Blood vessels include a
network of arteries, arterioles, capillaries, venules, and veins. [NIH]
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]
Branch: Most commonly used for branches of nerves, but applied also to other structures.
[NIH]
Broad-spectrum: Effective against a wide range of microorganisms; said of an antibiotic. [EU]
Bronchioles: The tiny branches of air tubes in the lungs. [NIH]
Bronchiolitis: Inflammation of the bronchioles. [NIH]
Bronchiseptica: A small, gram-negative, motile bacillus. A normal inhabitant of the
respiratory tract in man, dogs, and pigs, but is also associated with canine infectious
tracheobronchitis and atrophic rhinitis in pigs. [NIH]
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]
Buccal: Pertaining to or directed toward the cheek. In dental anatomy, used to refer to the
buccal surface of a tooth. [EU]
Calcium: A basic element found in nearly all organized tissues. It is a member of the
alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic
weight 40. Calcium is the most abundant mineral in the body and combines with
phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal
functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in
many enzymatic processes. [NIH]
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-, poly-
Dictionary 127
and heterosaccharides. [EU]
Carbuncle: An infection of cutaneous and subcutaneous tissue that consists of a cluster of
boils. Commonly, the causative agent is Staphylococcus aureus. Carbuncles produce fever,
leukocytosis, extreme pain, and prostration. [NIH]
Carcinogenic: Producing carcinoma. [EU]
Case report: A detailed report of the diagnosis, treatment, and follow-up of an individual
patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin). [NIH]
Castor Oil: Oil obtained from seeds of Ricinus communis that is used as a cathartic and as a
plasticizer. [NIH]
Cat-Scratch Disease: A self-limiting bacterial infection of the regional lymph nodes caused
by Afipia felis, a gram-negative bacterium recently identified by the Centers for Disease
Control and Prevention and by Bartonella henselae. It usually arises one or more weeks
following a feline scratch, with raised inflammatory nodules at the site of the scratch being
the primary symptom. [NIH]
Ceftriaxone: Broad-spectrum cephalosporin antibiotic with a very long half-life and high
penetrability to usually inaccessible infections, including those involving the meninges,
eyes, inner ears, and urinary tract. [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 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 proliferation: An increase in the number of cells as a result of cell growth and cell
division. [NIH] Cell Size: The physical dimensions of a cell. It refers mainly to changes in dimensions
correlated with physiological or pathological changes in cells. [NIH]
Cerebellar: Pertaining to the cerebellum. [EU]
Cerebral: Of or pertaining of the cerebrum or the brain. [EU]
Chancroid: Acute, localized autoinoculable infectious disease usually acquired through
sexual contact. Caused by Haemophilus ducreyi, it occurs endemically almost worldwide,
especially in tropical and subtropical countries and more commonly in seaports and urban
areas than in rural areas. [NIH]
Cheilitis: Inflammation of the lips. It is of various etiologies and degrees of pathology. [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]
128 Tularemia
Chimeras: Organism that contains a mixture of genetically different 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] Cilastatin: A renal dehydropeptidase-I and leukotriene D4 dipeptidase inhibitor. Since the antibiotic, imipenem, is hydrolyzed by dehydropeptidase-I, which resides in the brush border of the renal tubule, cilastatin is administered with imipenem to increase its effectiveness. The drug also inhibits the metabolism of leukotriene D4 to leukeotriene E4. [NIH]
Ciprofloxacin: A carboxyfluoroquinoline antimicrobial agent that is effective against a wide range of microorganisms. It has been successfully and safely used in the treatment of resistant respiratory, skin, bone, joint, gastrointestinal, urinary, and genital infections. [NIH] Civilization: The distinctly human attributes and attainments of a particular society. [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] 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] Colloidal: Of the nature of a colloid. [EU] Colorectal: Having to do with the colon or the rectum. [NIH] Colorectal Cancer: Cancer that occurs in the colon (large intestine) or the rectum (the end of the large intestine). A number of digestive diseases may increase a person's risk of colorectal cancer, including polyposis and Zollinger-Ellison Syndrome. [NIH] 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
Dictionary 129
attached at the spina recti lateralis. [NIH]
Complement: A term originally used to refer to the heat-labile factor in serum that causes
immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire
functionally related system comprising at least 20 distinct serum proteins that is the effector
not only of immune cytolysis but also of other biologic functions. Complement activation
occurs by two different sequences, the classic and alternative pathways. The proteins of the
classic pathway are termed 'components of complement' and are designated by the symbols
C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and
C1s. The proteins of the alternative pathway (collectively referred to as the properdin
system) and complement regulatory proteins are known by semisystematic or trivial names.
Fragments resulting from proteolytic cleavage of complement proteins are designated with
lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix
'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a
bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1
to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1,
IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative
pathway can be activated by IgA immune complexes and also by nonimmunologic materials
including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the
classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the
alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in
the cleavage of C5 and the formation of the membrane attack complex. Complement
activation also results in the formation of many biologically active complement fragments
that act as anaphylatoxins, opsonins, or chemotactic factors. [EU]
Complementary and alternative medicine: CAM. Forms of treatment that are used in
addition to (complementary) or instead of (alternative) standard treatments. These practices
are not considered standard medical approaches. CAM includes dietary supplements,
megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy,
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]
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]
Consensus Sequence: A theoretical representative nucleotide or amino acid sequence in
which each nucleotide or amino acid is the one which occurs most frequently at that site in
the different sequences which occur in nature. The phrase also refers to an actual sequence
which approximates the theoretical consensus. A known conserved sequence set is
represented by a consensus sequence. Commonly observed supersecondary protein
structures (amino acid motifs) are often formed by conserved sequences. [NIH]
Conserved Sequence: A sequence of amino acids in a polypeptide or of nucleotides in DNA
130 Tularemia
or RNA that is similar across multiple species. A known set of conserved sequences is
represented by a consensus sequence. Amino acid motifs are often composed of conserved
sequences. [NIH]
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]
Convalescence: The period of recovery following an illness. [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]
Cortex: The outer layer of an organ or other body structure, as distinguished from the
internal substance. [EU]
Culture Media: Any liquid or solid preparation made specifically for the growth, storage, or
transport of microorganisms or other types of cells. The variety of media that exist allow for
the culturing of specific microorganisms and cell types, such as differential media, selective
media, test media, and defined media. Solid media consist of liquid media that have been
solidified with an agent such as agar or gelatin. [NIH]
Curative: Tending to overcome disease and promote recovery. [EU]
Cutaneous: Having to do with the skin. [NIH]
Cutaneous Fistula: An abnormal passage or communication leading from an internal organ
to the surface of the body. [NIH]
Cysteine: A thiol-containing non-essential amino acid that is oxidized to form cystine. [NIH]
Cytochrome: Any electron transfer hemoprotein having a mode of action in which the
transfer of a single electron is effected by a reversible valence change of the central iron atom
of the heme prosthetic group between the +2 and +3 oxidation states; classified as
cytochromes a in which the heme contains a formyl side chain, cytochromes b, which
contain protoheme or a closely similar heme that is not covalently bound to the protein,
cytochromes c in which protoheme or other heme is covalently bound to the protein, and
cytochromes d in which the iron-tetrapyrrole has fewer conjugated double bonds than the
hemes have. Well-known cytochromes have been numbered consecutively within groups
and are designated by subscripts (beginning with no subscript), e.g. cytochromes c, c1, C2, .
New cytochromes are named according to the wavelength in nanometres of the absorption
maximum of the a-band of the iron (II) form in pyridine, e.g., c-555. [EU]
Cytochrome b: Cytochromes (electron-transporting proteins) with protoheme or a related
heme as the prosthetic group. The prosthetic group is not covalently bound to the protein
moiety. [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] Databases, Bibliographic: Extensive collections, reputedly complete, of references and citations to books, articles, publications, etc., generally on a single subject or specialized
Dictionary 131
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] Defense Mechanisms: Unconscious process used by an individual or a group of individuals in order to cope with impulses, feelings or ideas which are not acceptable at their conscious level; various types include reaction formation, projection and self reversal. [NIH] 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] Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] Dental Caries: Localized destruction of the tooth surface initiated by decalcification of the enamel followed by enzymatic lysis of organic structures and leading to cavity formation. If left unchecked, the cavity may penetrate the enamel and dentin and reach the pulp. The three most prominent theories used to explain the etiology of the disase are that acids produced by bacteria lead to decalcification; that micro-organisms destroy the enamel protein; or that keratolytic micro-organisms produce chelates that lead to decalcification. [NIH]
Diagnostic procedure: A method used to identify a disease. [NIH] Diaphragm: The musculofibrous partition that separates the thoracic cavity from the abdominal cavity. Contraction of the diaphragm increases the volume of the thoracic cavity aiding inspiration. [NIH] 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] Dihydrotestosterone: Anabolic agent. [NIH] Diphtheria: A localized infection of mucous membranes or skin caused by toxigenic strains of Corynebacterium diphtheriae. It is characterized by the presence of a pseudomembrane at the site of infection. Diphtheria toxin, produced by C. diphtheriae, can cause myocarditis, polyneuritis, and other systemic toxic effects. [NIH] 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] Drug Design: The molecular designing of drugs for specific purposes (such as DNAbinding, enzyme inhibition, anti-cancer efficacy, etc.) based on knowledge of molecular properties such as activity of functional groups, molecular geometry, and electronic structure, and also on information cataloged on analogous molecules. Drug design is generally computer-assisted molecular modeling and does not include pharmacokinetics, dosage analysis, or drug administration analysis. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Drug Tolerance: Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from drug resistance wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from maximum tolerated
132 Tularemia
dose and no-observed-adverse-effect level. [NIH] Duct: A tube through which body fluids pass. [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] Dyspnea: Difficult or labored breathing. [NIH] Ectromelia: Gross hypo- or aplasia of one or more long bones of one or more limbs. The 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] 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] Effector cell: A cell that performs a specific function in response to a stimulus; usually used to describe cells in the immune system. [NIH] Efficacy: The extent to which a specific intervention, procedure, regimen, or service produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is based on the results of a randomized control trial. [NIH] Effusion: The escape of fluid into a part or tissue, as an exudation or a transudation. [EU] Ehrlichiosis: A tick-borne disease characterized by fever, headache, myalgias, anorexia, and occasionally rash. In humans the disease is caused by Ehrlichia chaffeensis, in dogs it is caused by E. canis, and in horses, E. equi. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electrons: Stable elementary particles having the smallest known negative charge, present in all elements; also called negatrons. Positively charged electrons are called positrons. The numbers, energies and arrangement of electrons around atomic nuclei determine the chemical identities of elements. Beams of electrons are called cathode rays or beta rays, the latter being a high-energy biproduct of nuclear decay. [NIH] Electrophoresis: An electrochemical process in which macromolecules or colloidal particles with a net electric charge migrate in a solution under the influence of an electric current. [NIH]
Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Emulsions: Colloids of two immiscible liquids where either phase may be either fatty or aqueous; lipid-in-water emulsions are usually liquid, like milk or lotion and water-in-lipid emulsions tend to be creams. [NIH] Enamel: A very hard whitish substance which covers the dentine of the anatomical crown of a tooth. [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
Dictionary 133
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 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] Endotoxin: Toxin from cell walls of bacteria. [NIH] Enteritis: Inflammation of the intestine, applied chiefly to inflammation of the small intestine; see also enterocolitis. [EU] Enterocolitis: Inflammation of the intestinal mucosa of the small and large bowel. [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] 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] Epidemiological: Relating to, or involving epidemiology. [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] Epitopes: Sites on an antigen that interact with specific antibodies. [NIH] Erysipelas: An acute infection of the skin caused by species of streptococcus. This disease most frequently affects infants, young children, and the elderly. Characteristics include pink-to-red lesions that spread rapidly and are warm to the touch. The commonest site of
134 Tularemia
involvement is the face. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks
containing hemoglobin whose function is to transport oxygen. [NIH]
Erythromycin: A bacteriostatic antibiotic substance produced by Streptomyces erythreus.
Erythromycin A is considered its major active component. In sensitive organisms, it inhibits
protein synthesis by binding to 50S ribosomal subunits. This binding process inhibits
peptidyl transferase activity and interferes with translocation of amino acids during
translation and assembly of proteins. [NIH]
Excitation: An act of irritation or stimulation or of responding to a stimulus; the addition of
energy, as the excitation of a molecule by absorption of photons. [EU]
Exhaustion: The feeling of weariness of mind and body. [NIH]
Exotoxins: Toxins produced, especially by bacterial or fungal cells, and released into the
culture medium or environment. [NIH]
Extracellular: Outside a cell or cells. [EU]
Extraction: The process or act of pulling or drawing out. [EU]
Exudate: Material, such as fluid, cells, or cellular debris, which has escaped from blood
vessels and has been deposited in tissues or on tissue surfaces, usually as a result of
inflammation. An exudate, in contrast to a transudate, is characterized by a high content of
protein, cells, or solid materials derived from cells. [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]
Fibrin: A protein derived from fibrinogen in the presence of thrombin, which forms part of
the blood clot. [NIH]
Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [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] 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]
Dictionary 135
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] Gastric: Having to do with the stomach. [NIH] 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 Amplification: A selective increase in the number of copies of a gene coding for a specific protein without a proportional increase in other genes. It occurs naturally via the excision of a copy of the repeating sequence from the chromosome and its extrachromosomal replication in a plasmid, or via the production of an RNA transcript of the entire repeating sequence of ribosomal RNA followed by the reverse transcription of the molecule to produce an additional copy of the original DNA sequence. Laboratory techniques have been introduced for inducing disproportional replication by unequal crossing over, uptake of DNA from lysed cells, or generation of extrachromosomal sequences from rolling circle replication. [NIH] Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [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] Genital: Pertaining to the genitalia. [EU] Genomics: The systematic study of the complete DNA sequences (genome) of organisms. [NIH]
Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Giant Cells: Multinucleated masses produced by the fusion of many cells; often associated with viral infections. In AIDS, they are induced when the envelope glycoprotein of the HIV virus binds to the CD4 antigen of uninfected neighboring T4 cells. The resulting syncytium leads to cell death and thus may account for the cytopathic effect of the virus. [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] Glomerulus: A tiny set of looping blood vessels in the nephron where blood is filtered in the kidney. [NIH] Glottis: The vocal apparatus of the larynx, consisting of the true vocal cords (plica vocalis) and the opening between them (rima glottidis). [NIH] Glucans: Polysaccharides composed of repeating glucose units. They can consist of
136 Tularemia
branched or unbranched chains in any linkages. [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] Gonorrhea: Acute infectious disease characterized by primary invasion of the urogenital tract. The etiologic agent, Neisseria gonorrhoeae, was isolated by Neisser in 1879. [NIH] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to replace diseased or injured tissue removed from another part of the body. [NIH] Gram-negative: Losing the stain or decolorized by alcohol in Gram's method of staining, a primary characteristic of bacteria having a cell wall composed of a thin layer of peptidoglycan covered by an outer membrane of lipoprotein and lipopolysaccharide. [EU] Gram-positive: Retaining the stain or resisting decolorization by alcohol in Gram's method of staining, a primary characteristic of bacteria whose cell wall is composed of a thick layer of peptidologlycan with attached teichoic acids. [EU] Granuloma: A relatively small nodular inflammatory lesion containing grouped mononuclear phagocytes, caused by infectious and noninfectious agents. [NIH] Granuloma Inguinale: Anogenital ulcers caused by Calymmatobacterium granulomatis as distinguished from lymphogranuloma inguinale (see lymphogranuloma venereum) caused by Chlamydia trachomatis. Diagnosis is made by demonstration of typical intracellular Donovan bodies in crushed-tissue smears. [NIH] Granulomatous Disease, Chronic: A recessive X-linked defect of leukocyte function in which phagocytic cells ingest but fail to digest bacteria, resulting in recurring bacterial infections with granuloma formation. [NIH] Growth: The progressive development of a living being or part of an organism from its earliest stage to maturity. [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]
Half-Life: The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity. [NIH] Hantavirus: A genus of the family Bunyaviridae causing Hantavirus infections, first identified during the Korean war. Infection is found primarily in rodents and humans. Transmission does not appear to involve arthropods. The genus has one recognized group (Hantaan group) consisting of several species including Dobrava-Belgrade virus, Seoul virus, Prospect Hill virus, Puumala virus, Thottapalayam virus, and Hantaan virus, the type species. [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] Heart failure: Loss of pumping ability by the heart, often accompanied by fatigue, breathlessness, and excess fluid accumulation in body tissues. [NIH]
Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the
prosthetic group in many hemeproteins. [NIH]
Dictionary 137
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] Hemolysis: The destruction of erythrocytes by many different causal agents such as antibodies, bacteria, chemicals, temperature, and changes in tonicity. [NIH]
Hemolytic: A disease that affects the blood and blood vessels. It destroys red blood cells,
cells that cause the blood to clot, and the lining of blood vessels. HUS is often caused by the
Escherichia coli bacterium in contaminated food. People with HUS may develop acute renal
failure. [NIH]
Hemorrhage: Bleeding or escape of blood from a vessel. [NIH]
Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring.
2. The genetic constitution of an individual. [EU] Heterotrophic: Pertaining to organisms that are consumers and dependent on other
organisms for their source of energy (food). [NIH]
Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin
help in breaking down food. Some hormones come from cells in the stomach and small
intestine. [NIH]
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] Hybridoma: A hybrid cell resulting from the fusion of a specific antibody-producing spleen cell with a myeloma cell. [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]
Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH]
Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions
upon subsequent exposure to that particular antigen. [NIH]
Id: The part of the personality structure which harbors the unconscious instinctive desires
138 Tularemia
and strivings of the individual. [NIH] Idiopathic: Describes a disease of unknown cause. [NIH] Imipenem: Semisynthetic thienamycin that has a wide spectrum of antibacterial activity against gram-negative and gram-positive aerobic and anaerobic bacteria, including many multiresistant strains. It is stable to beta-lactamases. Clinical studies have demonstrated high efficacy in the treatment of infections of various body systems. Its effectiveness is enhanced when it is administered in combination with cilastatin, a renal dipeptidase inhibitor. [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] Immunodeficiency: The decreased ability of the body to fight infection and disease. [NIH] Immunodiffusion: Technique involving the diffusion of antigen or antibody through a semisolid medium, usually agar or agarose gel, with the result being a precipitin reaction. [NIH]
Immunoelectrophoresis: A technique that combines protein electrophoresis and double immunodiffusion. In this procedure proteins are first separated by gel electrophoresis (usually agarose), then made visible by immunodiffusion of specific antibodies. A distinct elliptical precipitin arc results for each protein detectable by the antisera. [NIH] 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] Immunogenetics: A branch of genetics which deals with the genetic basis of the immune response. [NIH] Immunogenic: Producing immunity; evoking an immune response. [EU] Immunoglobulin: A protein that acts as an antibody. [NIH] Immunologic: The ability of the antibody-forming system to recall a previous experience with an antigen and to respond to a second exposure with the prompt production of large amounts of antibody. [NIH] Immunology: The study of the body's immune system. [NIH] Impetigo: A common superficial bacterial infection caused by staphylococcus aureus or
Dictionary 139
group A beta-hemolytic streptococci. Characteristics include pustular lesions that rupture and discharge a thin, amber-colored fluid that dries and forms a crust. This condition is commonly located on the face, especially about the mouth and nose. [NIH] In situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incubation: The development of an infectious disease from the entrance of the pathogen to the appearance of clinical symptoms. [EU] Incubation period: The period of time likely to elapse between exposure to the agent of the disease and the onset of clinical symptoms. [NIH] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU] 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] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]
Infectious Mononucleosis: A common, acute infection usually caused by the Epstein-Barr virus (Human herpesvirus 4). There is an increase in mononuclear white blood cells and other atypical lymphocytes, generalized lymphadenopathy, splenomegaly, and occasionally hepatomegaly with hepatitis. [NIH] Infiltration: The diffusion or accumulation in a tissue or cells of substances not normal to it or in amounts of the normal. Also, the material so accumulated. [EU] Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH] Ingestion: Taking into the body by mouth [NIH] Inhalation: The drawing of air or other substances into the lungs. [EU] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Inner ear: The labyrinth, comprising the vestibule, cochlea, and semicircular canals. [NIH] Insect Vectors: Insects that transmit infective organisms from one host to another or from an inanimate reservoir to an animate host. [NIH] Insight: The capacity to understand one's own motives, to be aware of one's own psychodynamics, to appreciate the meaning of symbolic behavior. [NIH] Interferon: A biological response modifier (a substance that can improve the body's natural
140 Tularemia
response to disease). Interferons interfere with the division of cancer cells and can slow
tumor growth. There are several types of interferons, including interferon-alpha, -beta, and
gamma. These substances are normally produced by the body. They are also made in the
laboratory for use in treating cancer and other diseases. [NIH]
Interferon-alpha: One of the type I interferons produced by peripheral blood leukocytes or
lymphoblastoid cells when exposed to live or inactivated virus, double-stranded RNA, or
bacterial products. It is the major interferon produced by virus-induced leukocyte cultures
and, in addition to its pronounced antiviral activity, it causes activation of NK cells. [NIH]
Interleukin-2: Chemical mediator produced by activated T lymphocytes and which
regulates the proliferation of T cells, as well as playing a role in the regulation of NK cell
activity. [NIH]
Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU]
Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU]
Intestine: A long, tube-shaped organ in the abdomen that completes the process of
digestion. There is both a large intestine and a small intestine. Also called the bowel. [NIH]
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]
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]
Ixodes: A large, widely distributed genus of ticks consisting of approximately 245 species.
Many infest man and other mammals and several are vectors of diseases such as Lyme
disease, tick-borne encephalitis (encephalitis, tick-borne), and Kyasanur forest disease. [NIH]
Joint: The point of contact between elements of an animal skeleton with the parts that
surround and support it. [NIH]
Kb: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA
fragments are up to 50 kilobases long. [NIH]
Keratolytic: An agent that promotes keratolysis. [EU]
Labile: 1. Gliding; moving from point to point over the surface; unstable; fluctuating. 2.
Chemically unstable. [EU]
Laboratory Infection: Accidentally acquired infection in laboratory workers. [NIH]
Laceration: 1. The act of tearing. 2. A torn, ragged, mangled wound. [EU]
Laxative: An agent that acts to promote evacuation of the bowel; a cathartic or purgative.
[EU]
Lectin: A complex molecule that has both protein and sugars. Lectins are able to bind to the
outside of a cell and cause biochemical changes in it. Lectins are made by both animals and
plants. [NIH]
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
Dictionary 141
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]
Leprosy: A chronic granulomatous infection caused by Mycobacterium leprae. The
granulomatous lesions are manifested in the skin, the mucous membranes, and the
peripheral nerves. Two polar or principal types are lepromatous and tuberculoid. [NIH]
Leptospirosis: Infections with bacteria of the genus Leptospira. [NIH]
Lesion: An area of abnormal tissue change. [NIH]
Lethal: Deadly, fatal. [EU]
Leukocyte Count: A count of the number of white blood cells per unit volume in venous
blood. A differential leukocyte count measures the relative numbers of the different types of
white cells. [NIH]
Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils,
and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [NIH]
Leukocytosis: A transient increase in the number of leukocytes in a body fluid. [NIH]
Leukopenia: A condition in which the number of leukocytes (white blood cells) in the blood
is reduced. [NIH]
Levofloxacin: A substance used to treat bacterial infections. It belongs to the family of drugs
called quinolone antibiotics. [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]
Lipid: Fat. [NIH]
Lipopolysaccharide: Substance consisting of polysaccaride and lipid. [NIH]
Lipoprotein: Any of the lipid-protein complexes in which lipids are transported in the
blood; lipoprotein particles consist of a spherical hydrophobic core of triglycerides or
cholesterol esters surrounded by an amphipathic monolayer of phospholipids, cholesterol,
and apolipoproteins; the four principal classes are high-density, low-density, and very-low-
density lipoproteins and chylomicrons. [EU]
Liposomes: Artificial, single or multilaminar vesicles (made from lecithins or other lipids)
that are used for the delivery of a variety of biological molecules or molecular complexes to
cells, for example, drug delivery and gene transfer. They are also used to study membranes
and membrane proteins. [NIH]
Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Localization: The process of determining or marking the location or site of a lesion or disease. May also refer to the process of keeping a lesion or disease in a specific location or site. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Lupus: A form of cutaneous tuberculosis. It is seen predominantly in women and typically
involves the nasal, buccal, and conjunctival mucosa. [NIH]
Lymph: The almost colorless fluid that travels through the lymphatic system and carries
cells that help fight infection and disease. [NIH]
142 Tularemia
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]
Lymphadenitis: Inflammation of the lymph nodes. [NIH] Lymphadenopathy: Disease or swelling of the lymph nodes. [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] Lymphocytosis: Excess of normal lymphocytes in the blood or in any effusion. [NIH] Lymphogranuloma Venereum: Subacute inflammation of the inguinal lymph glands caused by certain immunotypes of Chlamydia trachomatis. It is a sexually transmitted disease in the U.S. but is more widespread in developing countries. It is distinguished from granuloma venereum (granuloma inguinale), which is caused by Calymmatobacterium granulomatis. [NIH]
Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Lymphokines: Soluble protein factors generated by activated lymphocytes that affect other cells, primarily those involved in cellular immunity. [NIH] Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue. [NIH] 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] Major Histocompatibility Complex: The genetic region which contains the loci of genes which determine the structure of the serologically defined (SD) and lymphocyte-defined (LD) transplantation antigens, genes which control the structure of the immune responseassociated (Ia) antigens, the immune response (Ir) genes which control the ability of an animal to respond immunologically to antigenic stimuli, and genes which determine the structure and/or level of the first four components of complement. [NIH] Malaise: A vague feeling of bodily discomfort. [EU] Malaria: A protozoan disease caused in humans by four species of the genus Plasmodium (P. falciparum (malaria, falciparum), P. vivax (malaria, vivax), P. ovale, and P. malariae) and transmitted by the bite of an infected female mosquito of the genus Anopheles. Malaria is endemic in parts of Asia, Africa, Central and South America, Oceania, and certain Caribbean
Dictionary 143
islands. It is characterized by extreme exhaustion associated with paroxysms of high fever,
sweating, shaking chills, and anemia. Malaria in animals is caused by other species of
plasmodia. [NIH]
Malaria, Falciparum: Malaria caused by Plasmodium falciparum. This is the severest form
of malaria and is associated with the highest levels of parasites in the blood. This disease is
characterized by irregularly recurring febrile paroxysms that in extreme cases occur with
acute cerebral, renal, or gastrointestinal manifestations. [NIH]
Malaria, Vivax: Malaria caused by Plasmodium vivax. This form of malaria is less severe
than malaria, falciparum, but there is a higher probability for relapses to occur. Febrile
paroxysms often occur every other day. [NIH]
Mediate: Indirect; accomplished by the aid of an intervening medium. [EU]
Mediator: An object or substance by which something is mediated, such as (1) a structure of
the nervous system that transmits impulses eliciting a specific response; (2) a chemical
substance (transmitter substance) that induces activity in an excitable tissue, such as nerve
or muscle; or (3) a substance released from cells as the result of the interaction of antigen
with antibody or by the action of antigen with a sensitized lymphocyte. [EU]
MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical
Literature Analysis and Retrieval System of the National Library of Medicine. [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 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]
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,
144 Tularemia
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] Micro-organism: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microscopy: The application of microscope magnification to the study of materials that cannot be properly seen by the unaided eye. [NIH] Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [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] 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] 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] Monocyte: A type of white blood cell. [NIH] Mononuclear: A cell with one nucleus. [NIH] Mononucleosis: The presence of an abnormally large number of mononuclear leucocytes (monocytes) in the blood. The term is often used alone to refer to infectious mononucleosis. [EU]
Morphology: The science of the form and structure of organisms (plants, animals, and other forms of life). [NIH] Motility: The ability to move spontaneously. [EU] Mucocutaneous: Pertaining to or affecting the mucous membrane and the skin. [EU] Mucosa: A mucous membrane, or tunica mucosa. [EU] Mutagenesis: Process of generating genetic mutations. It may occur spontaneously or be induced by mutagens. [NIH] Mutagenic: Inducing genetic mutation. [EU] Mutagens: Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes. [NIH]
Dictionary 145
Myeloma: Cancer that arises in plasma cells, a type of white blood cell. [NIH]
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]
Myocarditis: Inflammation of the myocardium; inflammation of the muscular walls of the
heart. [EU] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle
known as cardiac muscle. [NIH]
Natural selection: A part of the evolutionary process resulting in the survival and
reproduction of the best adapted individuals. [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] Neoplastic: Pertaining to or like a neoplasm (= any new and abnormal growth); pertaining
to neoplasia (= the formation of a neoplasm). [EU]
Nephritis: Inflammation of the kidney; a focal or diffuse proliferative or destructive process
which may involve the glomerulus, tubule, or interstitial renal tissue. [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]
Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis,
as the neutral arch. [EU]
Neurologic: Having to do with nerves or the nervous system. [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] 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] 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] Oedema: The presence of abnormally large amounts of fluid in the intercellular tissue spaces of the body; usually applied to demonstrable accumulation of excessive fluid in the subcutaneous tissues. Edema may be localized, due to venous or lymphatic obstruction or to increased vascular permeability, or it may be systemic due to heart failure or renal disease. Collections of edema fluid are designated according to the site, e.g. ascites (peritoneal cavity), hydrothorax (pleural cavity), and hydropericardium (pericardial sac). Massive
146 Tularemia
generalized edema is called anasarca. [EU]
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]
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]
Oral Manifestations: Disorders of the mouth attendant upon non-oral disease or injury.
[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]
Orthopoxvirus: A genus of the family Poxviridae, subfamily Chordopoxvirninae,
comprising many species infecting mammals. Viruses of this genus cause generalized
infections and a rash in some hosts. The type species is Vaccinia virus. [NIH]
Outpatient: A patient who is not an inmate of a hospital but receives diagnosis or treatment
in a clinic or dispensary connected with the hospital. [NIH]
Ovum: A female germ cell extruded from the ovary at ovulation. [NIH]
Pachymeningitis: Inflammation of the dura mater of the brain, the spinal cord or the optic
nerve. [NIH]
Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU]
Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior
abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is
comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar
gland that secretes digestive enzymes. [NIH]
Pancreatic: Having to do with the pancreas. [NIH]
Panic: A state of extreme acute, intense anxiety and unreasoning fear accompanied by
disorganization of personality function. [NIH]
Parenteral: Not through the alimentary canal but rather by injection through some other
route, as subcutaneous, intramuscular, intraorbital, intracapsular, intraspinal, intrasternal,
intravenous, etc. [EU]
Parietal: 1. Of or pertaining to the walls of a cavity. 2. Pertaining to or located near the
parietal bone, as the parietal lobe. [EU] Parotid: The space that contains the parotid gland, the facial nerve, the external carotid
artery, and the retromandibular vein. [NIH]
Paroxysmal: Recurring in paroxysms (= spasms or seizures). [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]
Patient Education: The teaching or training of patients concerning their own health needs.
Dictionary 147
[NIH]
Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Periodontal Abscess: Localized circumscribed purulent area of inflammation in the periodontal tissue. It is a derivative of marginal periodontitis and commonly associated with suprabony and infrabony pockets and interradicular involvements, in contrast to periapical abscess which is attributable to pulp necrosis. [NIH] Periodontal disease: Disease involving the supporting structures of the teeth (as the gums and periodontal membranes). [NIH] Periodontitis: Inflammation of the periodontal membrane; also called periodontitis simplex. [NIH]
Peripheral blood: Blood circulating throughout the body. [NIH] Peripheral Nerves: The nerves outside of the brain and spinal cord, including the autonomic, cranial, and spinal nerves. Peripheral nerves contain non-neuronal cells and connective tissue as well as axons. The connective tissue layers include, from the outside to the inside, the epineurium, the perineurium, and the endoneurium. [NIH] Peritoneal: Having to do with the peritoneum (the tissue that lines the abdominal wall and covers most of the organs in the abdomen). [NIH] Peritoneal Cavity: The space enclosed by the peritoneum. It is divided into two portions, the greater sac and the lesser sac or omental bursa, which lies behind the stomach. The two sacs are connected by the foramen of Winslow, or epiploic foramen. [NIH] Pertussis: An acute, highly contagious infection of the respiratory tract, most frequently affecting young children, usually caused by Bordetella pertussis; a similar illness has been associated with infection by B. parapertussis and B. bronchiseptica. It is characterized by a catarrhal stage, beginning after an incubation period of about two weeks, with slight fever, sneezing, running at the nose, and a dry cough. In a week or two the paroxysmal stage begins, with the characteristic paroxysmal cough, consisting of a deep inspiration, followed by a series of quick, short coughs, continuing until the air is expelled from the lungs; the close of the paroxysm is marked by a long-drawn, shrill, whooping inspiration, due to spasmodic closure of the glottis. This stage lasts three to four weeks, after which the convalescent stage begins, in which paroxysms grow less frequent and less violent, and finally cease. Called also whooping cough. [EU] Phagocytosis: The engulfing of microorganisms, other cells, and foreign particles by phagocytic cells. [NIH] 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] 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] Pharyngitis: Inflammation of the throat. [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
148 Tularemia
teeth, and is a component of adenosine triphosphate (ATP; the primary energy source for the body's cells.) [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 study: The initial study examining a new method or treatment. [NIH] Plague: An acute infectious disease caused by Yersinia pestis that affects humans, wild rodents, and their ectoparasites. This condition persists due to its firm entrenchment in sylvatic rodent-flea ecosystems throughout the world. Bubonic plague is the most common form. [NIH] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] Plasmid: An autonomously replicating, extra-chromosomal DNA molecule found in many bacteria. Plasmids are widely used as carriers of cloned genes. [NIH] Pleura: The thin serous membrane enveloping the lungs and lining the thoracic cavity. [NIH] Pleural: A circumscribed area of hyaline whorled fibrous tissue which appears on the surface of the parietal pleura, on the fibrous part of the diaphragm or on the pleura in the interlobar fissures. [NIH] Pleural cavity: A space enclosed by the pleura (thin tissue covering the lungs and lining the interior wall of the chest cavity). It is bound by thin membranes. [NIH] Pleural Effusion: Presence of fluid in the pleural cavity resulting from excessive transudation or exudation from the pleural surfaces. It is a sign of disease and not a diagnosis in itself. [NIH] Pleurisy: Inflammation of the pleura, with exudation into its cavity and upon its surface. It may occur as either an acute or a chronic process. In acute pleurisy the pleura becomes reddened, then covered with an exudate of lymph, fibrin, and cellular elements (the dry stage); the disease may progress to the second stage, in which a copious exudation of serum occurs (stage of liquid effusion). The inflamed surfaces of the pleura tend to become united by adhesions, which are usually permanent. The symptoms are a stitch in the side, a chill, followed by fever and a dry cough. As effusion occurs there is an onset of dyspnea and a diminution of pain. The patient lies on the affected side. [EU] Pneumonitis: A disease caused by inhaling a wide variety of substances such as dusts and molds. Also called "farmer's disease". [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
Dictionary 149
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] Polypeptide: A peptide which on hydrolysis yields more than two amino acids; called tripeptides, tetrapeptides, etc. according to the number of amino acids contained. [EU] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together
chemically. [NIH]
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]
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] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or
severity. [EU]
Projection: A defense mechanism, operating unconsciously, whereby that which is
emotionally unacceptable in the self is rejected and attributed (projected) to others. [NIH]
Promoter: A chemical substance that increases the activity of a carcinogenic process. [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]
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]
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 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
150 Tularemia
recurrent venous and arterial thrombosis. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] Proteolytic: 1. Pertaining to, characterized by, or promoting proteolysis. 2. An enzyme that promotes proteolysis (= the splitting of proteins by hydrolysis of the peptide bonds with formation of smaller polypeptides). [EU] 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] Pseudocysts: A collection of enzyme-rich pancreatic fluid and tissue debris arising within areas of necrosis or an obstructed smaller duct. [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] Purulent: Consisting of or containing pus; associated with the formation of or caused by pus. [EU] Pustular: Pertaining to or of the nature of a pustule; consisting of pustules (= a visible collection of pus within or beneath the epidermis). [EU] Pyoderma: Any purulent skin disease (Dorland, 27th ed). [NIH] 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] 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] Radioactive: Giving off radiation. [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] 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] Red Nucleus: A pinkish-yellow portion of the midbrain situated in the rostral mesencephalic tegmentum. It receives a large projection from the contralateral half of the cerebellum via the superior cerebellar peduncle and a projection from the ipsilateral motor cortex. [NIH] Reductase: Enzyme converting testosterone to dihydrotestosterone. [NIH]
Dictionary 151
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]
Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of
treatment. [NIH] Regional lymph node: In oncology, a lymph node that drains lymph from the region
around a tumor. [NIH]
Relapse: The return of signs and symptoms of cancer after a period of improvement. [NIH]
Respiratory Burst: A large increase in oxygen uptake by neutrophils and most types of
tissue macrophages through activation of an NADPH-cytochrome b-dependent oxidase that
reduces oxygen to a superoxide. Individuals with an inherited defect in which the oxidase
that reduces oxygen to superoxide is decreased or absent (granulomatous disease, chronic)
often die as a result of recurrent bacterial infections. [NIH]
Respiratory distress syndrome: A lung disease that occurs primarily in premature infants;
the newborn must struggle for each breath and blueing of its skin reflects the baby's inability
to get enough oxygen. [NIH]
Respiratory Mucosa: The mucous membrane lining the respiratory tract. [NIH] Reversion: A return to the original condition, e. g. the reappearance of the normal or wild
type in previously mutated cells, tissues, or organisms. [NIH]
Rhabdomyolysis: Necrosis or disintegration of skeletal muscle often followed by
myoglobinuria. [NIH]
Ribose: A pentose active in biological systems usually in its D-form. [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]
Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of
developing a disease. [NIH]
Rod: A reception for vision, located in the retina. [NIH] Saliva: The clear, viscous fluid secreted by the salivary glands and mucous glands of the
mouth. It contains mucins, water, organic salts, and ptylin. [NIH]
Salivary: The duct that convey saliva to the mouth. [NIH]
Salivary glands: Glands in the mouth that produce saliva. [NIH]
Salmonellosis: Infection by salmonellae. [NIH]
Saponin: A substance found in soybeans and many other plants. Saponins may help lower
cholesterol and may have anticancer effects. [NIH]
Sarcoidosis: An idiopathic systemic inflammatory granulomatous disorder comprised of
epithelioid and multinucleated giant cells with little necrosis. It usually invades the lungs
with fibrosis and may also involve lymph nodes, skin, liver, spleen, eyes, phalangeal bones,
and parotid glands. [NIH]
Scarlet Fever: Infection with group A streptococci that is characterized by tonsillitis and
pharyngitis. An erythematous rash is commonly present. [NIH]
Screening: Checking for disease when there are no symptoms. [NIH]
Secretion: 1. The process of elaborating a specific product as a result of the activity of a
gland; this activity may range from separating a specific substance of the blood to the
elaboration of a new chemical substance. 2. Any substance produced by secretion. [EU]
152 Tularemia
Sepsis: The presence of bacteria in the bloodstream. [NIH] Septicemia: Systemic disease associated with the presence and persistence of pathogenic microorganisms or their toxins in the blood. Called also blood poisoning. [EU] Sequencing: The determination of the order of nucleotides in a DNA or RNA chain. [NIH] Serologic: Analysis of a person's serum, especially specific immune or lytic serums. [NIH] 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] Shock: The general bodily disturbance following a severe injury; an emotional or moral upset occasioned by some disturbing or unexpected experience; disruption of the circulation, which can upset all body functions: sometimes referred to as circulatory shock. [NIH]
Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the one sought to be benefited by its administration. [EU] Signs and Symptoms: Clinical manifestations that can be either objective when observed by a physician, or subjective when perceived by the patient. [NIH] Skeletal: Having to do with the skeleton (boney part of the body). [NIH] Skin Tests: Epicutaneous or intradermal application of a sensitizer for demonstration of either delayed or immediate hypersensitivity. Used in diagnosis of hypersensitivity or as a test for cellular immunity. [NIH] Skunks: Omnivorous New World mammals of the family Mustelidae, showing typical warning coloration of patterned black and white and able to eject a malodorous secretion when the animal is startled or in danger. [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] Sneezing: Sudden, forceful, involuntary expulsion of air from the nose and mouth caused by irritation to the mucous membranes of the upper respiratory tract. [NIH] Sodium: An element that is a member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23. With a valence of 1, it has a strong affinity for oxygen and other nonmetallic elements. Sodium provides the chief cation of the extracellular body fluids. Its salts are the most widely used in medicine. (From Dorland, 27th ed) Physiologically the sodium ion plays a major role in blood pressure regulation, maintenance of fluid volume, and electrolyte balance. [NIH] Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] Spasmodic: Of the nature of a spasm. [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
Dictionary 153
Latinized adjective or noun. [EU]
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]
Spleen: An organ that is part of the lymphatic system. The spleen produces lymphocytes,
filters the blood, stores blood cells, and destroys old blood cells. It is located on the left side
of the abdomen near the stomach. [NIH]
Staphylococcal Infections: Infections with bacteria of the genus Staphylococcus. [NIH]
Staphylococcus: A genus of gram-positive, facultatively anaerobic, coccoid bacteria. Its
organisms occur singly, in pairs, and in tetrads and characteristically divide in more than
one plane to form irregular clusters. Natural populations of Staphylococcus are membranes
of warm-blooded animals. Some species are opportunistic pathogens of humans and
animals. [NIH]
Staphylococcus aureus: Potentially pathogenic bacteria found in nasal membranes, skin,
hair follicles, and perineum of warm-blooded animals. They may cause a wide range of
infections and intoxications. [NIH]
Stimulants: Any drug or agent which causes stimulation. [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] 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]
Streptococcal: Caused by infection due to any species of streptococcus. [NIH]
Streptococci: A genus of spherical Gram-positive bacteria occurring in chains or pairs. They
are widely distributed in nature, being important pathogens but often found as normal commensals in the mouth, skin, and intestine of humans and other animals. [NIH]
Streptococcus: A genus of gram-positive, coccoid bacteria whose organisms occur in pairs
or chains. No endospores are produced. Many species exist as commensals or parasites on
man or animals with some being highly pathogenic. A few species are saprophytes and
occur in the natural environment. [NIH]
Subacute: Somewhat acute; between acute and chronic. [EU]
Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other
disease or abnormality before symptoms and signs become apparent or detectable by
clinical examination or laboratory tests, or of a very mild form of an infection or other
disease or abnormality. [EU]
Subcutaneous: Beneath the skin. [NIH]
Subspecies: A category intermediate in rank between species and variety, based on a
smaller number of correlated characters than are used to differentiate species and generally conditioned by geographical and/or ecological occurrence. [NIH] Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of pain, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses.
154 Tularemia
[NIH]
Superoxide: Derivative of molecular oxygen that can damage cells. [NIH] Suppurative: Consisting of, containing, associated with, or identified by the formation of pus. [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]
Syphilis: A contagious venereal disease caused by the spirochete Treponema pallidum. [NIH]
Syphilis, Congenital: Syphilis acquired in utero and manifested by any of several characteristic tooth (Hutchinson's teeth) or bone malformations and by active mucocutaneous syphilis at birth or shortly thereafter. Ocular and neurologic changes may also occur. [NIH] Systemic: Affecting the entire body. [NIH] Testosterone: A hormone that promotes the development and maintenance of male sex characteristics. [NIH] Tetani: Causal agent of tetanus. [NIH] Tetanic: Having the characteristics of, or relating to tetanus. [NIH] Tetanus: A disease caused by tetanospasmin, a powerful protein toxin produced by Clostridium tetani. Tetanus usually occurs after an acute injury, such as a puncture wound or laceration. Generalized tetanus, the most common form, is characterized by tetanic muscular contractions and hyperreflexia. Localized tetanus presents itself as a mild condition with manifestations restricted to muscles near the wound. It may progress to the generalized form. [NIH] Thalamic: Cell that reaches the lateral nucleus of amygdala. [NIH] Thalamic Diseases: Disorders of the centrally located thalamus, which integrates a wide range of cortical and subcortical information. Manifestations include sensory loss, movement disorders; ataxia, pain syndromes, visual disorders, a variety of neuropsychological conditions, and coma. Relatively common etiologies include cerebrovascular disorders; craniocerebral trauma; brain neoplasms; brain hypoxia; intracranial hemorrhages; and infectious processes. [NIH] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thermal: Pertaining to or characterized by heat. [EU] Threshold: For a specified sensory modality (e. g. light, sound, vibration), the lowest level (absolute threshold) or smallest difference (difference threshold, difference limen) or intensity of the stimulus discernible in prescribed conditions of stimulation. [NIH] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] 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] 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] Tick Paralysis: Paralysis caused by a neurotropic toxin secreted by the salivary glands of
Dictionary 155
ticks. [NIH]
Tick-Borne Diseases: Bacterial, viral, or parasitic diseases transmitted to humans and
animals by the bite of infected ticks. The families Ixodidae and Argasidae contain many
bloodsucking species that are important pests of man and domestic birds and mammals and
probably exceed all other arthropods in the number and variety of disease agents they
transmit. Many of the tick-borne diseases are zoonotic. [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]
Tolerance: 1. The ability to endure unusually large doses of a drug or toxin. 2. Acquired
drug tolerance; a decreasing response to repeated constant doses of a drug or the need for
increasing doses to maintain a constant response. [EU]
Tonsillitis: Inflammation of the tonsils, especially the palatine tonsils. It is often caused by a
bacterium. Tonsillitis may be acute, chronic, or recurrent. [NIH] Toxic: Having to do with poison or something harmful to the body. Toxic substances
usually cause unwanted side effects. [NIH]
Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic
microbe or of a poison. [EU]
Toxicology: The science concerned with the detection, chemical composition, and
pharmacologic action of toxic substances or poisons and the treatment and prevention of
toxic manifestations. [NIH]
Toxins: Specific, characterizable, poisonous chemicals, often proteins, with specific
biological properties, including immunogenicity, produced by microbes, higher plants, or animals. [NIH]
Toxoid: The material resulting from the treatment of toxin in such a way that the toxic
properties are inactivated whilst the antigenic potency remains intact. [NIH]
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]
Translating: Conversion from one language to another language. [NIH]
Translation: The process whereby the genetic information present in the linear sequence of
ribonucleotides in mRNA is converted into a corresponding sequence of amino acids in a
protein. It occurs on the ribosome and is unidirectional. [NIH]
Translational: The cleavage of signal sequence that directs the passage of the protein
through a cell or organelle membrane. [NIH]
Translocation: The movement of material in solution inside the body of the plant. [NIH]
Transplantation: Transference of a tissue or organ, alive or dead, within an individual,
between individuals of the same species, or between individuals of different species. [NIH]
Treatment Failure: A measure of the quality of health care by assessment of unsuccessful
results of management and procedures used in combating disease, in individual cases or
series. [NIH]
Tuberculosis: Any of the infectious diseases of man and other animals caused by species of
Mycobacterium. [NIH]
Tuberculosis, Oral: Tuberculosis of the mouth, tongue, and salivary glands. [NIH]
156 Tularemia
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] Tumor Necrosis Factor: Serum glycoprotein produced by activated macrophages and other mammalian mononuclear leukocytes which has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. It mimics the action of endotoxin but differs from it. It has a molecular weight of less than 70,000 kDa. [NIH] 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]
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]
Urine: Fluid containing water and waste products. Urine is made by the kidneys, stored in
the bladder, and leaves the body through the urethra. [NIH]
Urogenital: Pertaining to the urinary and genital apparatus; genitourinary. [EU]
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]
Vaccine adjuvant: A substance added to a vaccine to improve the immune response so that
less vaccine is needed. [NIH]
Vaccinia: The cutaneous and occasional systemic reactions associated with vaccination
using smallpox (variola) vaccine. [NIH]
Vacuole: A fluid-filled cavity within the cytoplasm of a cell. [NIH]
Variola: A generalized virus infection with a vesicular rash. [NIH]
Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU]
Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in
nature or in recombinant DNA technology. [NIH]
Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH]
Venereal: Pertaining or related to or transmitted by sexual contact. [EU]
Dictionary 157
Venous: Of or pertaining to the veins. [EU] Venous blood: Blood that has given up its oxygen to the tissues and carries carbon dioxide
back for gas exchange. [NIH]
Vesicular: 1. Composed of or relating to small, saclike bodies. 2. Pertaining to or made up of
vesicles on the skin. [EU] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and
treatment of diseases in animals. [NIH]
Viral: Pertaining to, caused by, or of the nature of virus. [EU]
Virulence: The degree of pathogenicity within a group or species of microorganisms or
viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [NIH]
Virulent: A virus or bacteriophage capable only of lytic growth, as opposed to temperate
phages establishing the lysogenic response. [NIH]
Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some
viruses may be made into vaccines that help the body build an immune response to, and
kill, tumor cells. [NIH]
Visceral: , from viscus a viscus) pertaining to a viscus. [EU]
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]
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]
Whooping Cough: A respiratory infection caused by Bordetella pertussis and characterized
by paroxysmal coughing ending in a prolonged crowing intake of breath. [NIH]
Whooping Cough: A respiratory infection caused by Bordetella pertussis and characterized
by paroxysmal coughing ending in a prolonged crowing intake of breath. [NIH]
Xenograft: The cells of one species transplanted to another species. [NIH]
Yaws: A systemic non-venereal infection of the tropics caused by Treponema pallidum
subspecies pertenue. [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]
Zoonoses: Diseases of non-human animals that may be transmitted to man or may be
transmitted from man to non-human animals. [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]
Zymogen: Inactive form of an enzyme which can then be converted to the active form,
usually by excision of a polypeptide, e. g. trypsinogen is the zymogen of trypsin. [NIH]
159
INDEX
A Abscess, 44, 121, 147 Actinomycosis, 82, 121 Acute renal, 56, 121, 137 Adaptability, 121, 127 Adenine, 121 Adenopathy, 46, 48, 121 Adenosine, 44, 121, 148 Adenosine Deaminase, 44, 121 Adhesions, 4, 121, 148 Adjuvant, 18, 25, 121 Adverse Effect, 121, 152 Aerobic, 121, 138 Aerosol, 5, 6, 7, 13, 17, 18, 30, 121 Affinity, 121, 152 Agar, 60, 121, 130, 138 Agglutinins, 36, 119, 122 Agonists, 25, 122 Algorithms, 29, 122, 126 Alimentary, 122, 146 Alkaline, 47, 122, 126 Alkaline Phosphatase, 47, 122 Alternative medicine, 84, 122 Amber, 122, 139 Amino Acid Motifs, 122, 129 Amino Acid Sequence, 122, 123, 129 Amino Acids, 122, 129, 134, 146, 147, 149, 150, 155 Ammonia, 121, 122 Amplification, 18, 22, 122 Anaerobic, 122, 138, 153 Anaesthesia, 122, 139 Analog, 12, 122 Analogous, 29, 122, 131, 155 Anaphylatoxins, 122, 129 Anemia, 123, 143 Animal model, 6, 8, 10, 23, 24, 123 Annealing, 123, 149 Anorexia, 123, 132 Anthrax, 6, 7, 10, 21, 27, 30, 37, 82, 102, 115, 119, 123 Antibacterial, 19, 24, 28, 123, 138, 153 Antibiotic, 8, 22, 25, 32, 37, 123, 126, 127, 128, 134, 153 Antibodies, 6, 18, 25, 31, 36, 40, 122, 123, 133, 137, 138, 142, 144, 148 Antibody, 4, 6, 7, 10, 12, 13, 18, 25, 80, 118, 121, 123, 129, 137, 138, 139, 143, 144
Anticoagulant, 123, 149 Antigen-Antibody Complex, 123, 129 Antimicrobial, 13, 15, 24, 48, 123, 128 Antiviral, 8, 123, 140 Anxiety, 100, 123, 146 Aplasia, 123, 132 Apoptosis, 15, 20, 124 Aqueous, 124, 125, 130, 132, 141 Arterial, 124, 150 Arteries, 124, 126, 130, 143, 145 Ascites, 124, 145 Aseptic, 124, 146 Assay, 5, 18, 20, 22, 41, 124, 138, 156 Ataxia, 61, 124, 154 Attenuated, 4, 6, 10, 11, 12, 13, 16, 32, 124 Attenuation, 11, 13, 20, 124 Atypical, 55, 64, 124, 139 Autoimmune disease, 124 Autoimmunity, 23, 124 B Babesiosis, 80, 104, 124 Bacillus, 6, 10, 22, 23, 28, 30, 123, 124, 126 Bacteremia, 53, 124, 143 Bacterial Infections, 9, 15, 81, 82, 100, 124, 136, 141, 151 Bacterial Vaccines, 31, 124 Bactericidal, 15, 31, 124 Bacteriophage, 125, 157 Bacteriostatic, 125, 134 Bacterium, 8, 9, 13, 16, 19, 20, 25, 30, 125, 127, 137, 155 Basal Ganglia, 124, 125 Basal Ganglia Diseases, 124, 125 Base, 41, 121, 125, 131, 134, 140, 156 Beta-glucans, 18, 125 Beta-Lactamases, 125, 138 Bile, 125, 137, 141 Bioavailability, 24, 125 Biochemical, 19, 43, 125, 134, 140 Biogenesis, 4, 125 Biological response modifier, 125, 139 Biological Warfare, 4, 12, 16, 21, 22, 32, 34, 62, 100, 125 Biomarkers, 27, 125 Biomedical Technology, 28, 125 Biotechnology, 32, 33, 80, 84, 95, 125 Bladder, 126, 149, 156 Blood Coagulation, 126, 154
160 Tularemia
Blood pressure, 126, 152 Blood vessel, 126, 133, 134, 135, 137, 142, 152, 154, 156 Body Fluids, 24, 125, 126, 132, 152, 156 Bone Marrow, 5, 65, 126, 138, 142 Branch, 81, 113, 126, 138, 142, 146, 150, 152, 154 Broad-spectrum, 27, 126, 127 Bronchioles, 126 Bronchiolitis, 22, 126 Bronchiseptica, 126, 147 Brucellosis, 23, 28, 82, 101, 115, 126 Buccal, 126, 141 C Calcium, 5, 126, 129 Capsular, 11, 18, 31, 126 Carbohydrate, 126, 149 Carbuncle, 82, 127 Carcinogenic, 127, 139, 149 Case report, 38, 47, 51, 53, 57, 127 Castor Oil, 127, 151 Cat-Scratch Disease, 82, 127 Ceftriaxone, 65, 127 Cell Death, 20, 124, 127, 135, 145 Cell Division, 124, 127, 144, 148 Cell membrane, 9, 127 Cell proliferation, 12, 127 Cell Size, 127, 134 Cerebellar, 124, 127, 150 Cerebral, 124, 125, 127, 143 Chancroid, 82, 115, 127 Cheilitis, 82, 127 Chemokines, 13, 17, 127 Chemotactic Factors, 127, 129 Chimeras, 5, 128 Cholesterol, 125, 128, 141, 151 Chromatin, 124, 128, 145 Chromosomal, 122, 128, 148 Chromosome, 13, 128, 135 Chronic, 24, 49, 82, 128, 139, 141, 148, 153, 155 Cilastatin, 54, 70, 128, 138 Ciprofloxacin, 30, 39, 54, 128 Civilization, 22, 128 Clathrin, 128, 133 Clinical trial, 3, 9, 22, 24, 27, 95, 128, 150 Clone, 4, 23, 25, 128 Cloning, 126, 128 Coated Vesicles, 128, 133 Codons, 128, 146 Cofactor, 128, 149, 154 Colloidal, 128, 132
Colorectal, 125, 128 Colorectal Cancer, 125, 128 Communis, 127, 128, 151 Complement, 11, 23, 26, 31, 122, 129, 142 Complementary and alternative medicine, 73, 74, 129 Complementary medicine, 73, 129 Computational Biology, 28, 95, 129 Connective Tissue, 126, 129, 134, 142, 147 Consensus Sequence, 31, 122, 129, 130 Conserved Sequence, 122, 129 Contraindications, ii, 130 Convalescence, 11, 130 Coronary, 130, 143, 145 Coronary Thrombosis, 130, 143, 145 Cortex, 124, 130, 150 Culture Media, 121, 130 Curative, 130, 154 Cutaneous, 33, 52, 63, 64, 82, 123, 127, 130, 140, 141, 156 Cutaneous Fistula, 82, 130 Cysteine, 127, 130 Cytochrome, 130, 151 Cytochrome b, 130, 151 Cytokine, 12, 15, 16, 21, 23, 33, 41, 130 Cytoplasm, 124, 127, 130, 145, 156 Cytoplasmic Vesicles, 130, 147 D Databases, Bibliographic, 95, 130 Defense Mechanisms, 14, 131 Deletion, 124, 131 Denaturation, 131, 149 Density, 131, 134, 141 Dental Caries, 82, 131 Diagnostic procedure, 84, 131 Diaphragm, 131, 148 Diffusion, 131, 138, 139 Digestion, 122, 125, 131, 140, 141, 153 Dihydrotestosterone, 131, 150 Diphtheria, 82, 88, 115, 131 Direct, iii, 7, 16, 32, 80, 87, 131, 151 Disaster Planning, 80, 131 Drug Design, 32, 131 Drug Interactions, 89, 131 Drug Tolerance, 131, 155 Duct, 132, 150, 151 Dura mater, 132, 143, 146 Dyes, 132, 134, 145 Dyspnea, 132, 148 E Ectromelia, 6, 10, 132 Ectromelia Virus, 6, 10, 132
Index 161
Edema, 132, 145 Effector, 11, 14, 18, 129, 132 Effector cell, 18, 132 Efficacy, 6, 8, 10, 18, 24, 26, 27, 30, 31, 131, 132, 138 Effusion, 116, 132, 142, 148 Ehrlichiosis, 80, 104, 132 Electrolyte, 132, 152 Electrons, 125, 132, 140, 150 Electrophoresis, 17, 132, 138 Embryo, 132, 139 Emulsions, 121, 132 Enamel, 131, 132 Encapsulated, 4, 132 Encephalitis, 28, 80, 115, 132, 133, 140 Encephalitis, Viral, 132, 133 Endemic, 16, 45, 52, 119, 133, 142 Endocytosis, 29, 133 Endosomes, 29, 133 Endothelial cell, 17, 133, 154 Endothelium, 16, 133 Endothelium, Lymphatic, 133 Endothelium, Vascular, 133 Endotoxin, 52, 133, 156 Enteritis, 66, 133 Enterocolitis, 133 Environmental Health, 45, 94, 96, 133 Enzymatic, 126, 129, 131, 133, 149 Enzyme, 22, 40, 41, 121, 122, 131, 132, 133, 148, 150, 154, 157 Epidemic, 36, 45, 56, 59, 133 Epidemiological, 41, 42, 133 Epithelial, 5, 133 Epithelial Cells, 5, 133 Epithelium, 133 Epitopes, 20, 31, 133 Erysipelas, 82, 133 Erythrocytes, 123, 124, 126, 134, 137 Erythromycin, 49, 60, 134 Excitation, 134 Exhaustion, 134, 143 Exotoxins, 23, 134 Extracellular, 14, 129, 133, 134, 152 Extraction, 7, 134 Exudate, 134, 148 F Family Planning, 95, 134 Fat, 126, 134, 141, 152, 154 Fibrin, 119, 126, 134, 148, 154 Fibrosis, 134, 151 Flow Cytometry, 12, 134 Fluorescence, 16, 29, 134
Fluorescent Dyes, 134 Frameshift, 134, 135, 156 Frameshift Mutation, 135, 156 Fungi, 27, 135, 143, 144, 157 G Gastric, 125, 135 Gastrointestinal, 128, 135, 143, 153, 156 Gene, 4, 13, 15, 16, 17, 18, 20, 26, 80, 126, 135, 141 Gene Amplification, 18, 135 Gene Expression, 15, 135 Genetic testing, 135, 149 Genetics, 13, 15, 16, 29, 121, 135, 138 Genital, 128, 135, 156 Genomics, 28, 135 Genotype, 135, 147 Giant Cells, 135, 151 Gland, 135, 142, 146, 149, 151, 153 Glanders, 82, 101, 135, 143 Glomerulus, 135, 145 Glottis, 135, 147 Glucans, 125, 135 Glycoprotein, 135, 136, 154, 156 Glycosidic, 136, 146 Gonorrhea, 82, 136 Governing Board, 136, 149 Graft, 136, 137 Gram-negative, 4, 12, 13, 14, 16, 19, 25, 29, 126, 127, 136, 138 Gram-positive, 23, 136, 138, 153 Granuloma, 82, 136, 142 Granuloma Inguinale, 82, 136, 142 Granulomatous Disease, Chronic, 136, 151 Growth, 7, 8, 13, 14, 15, 17, 20, 22, 123, 124, 125, 127, 130, 136, 140, 145, 146, 148, 157 H Habitat, 136, 145 Half-Life, 127, 136 Hantavirus, 7, 136 Headache, 117, 132, 136, 156 Heart failure, 136, 145 Heme, 20, 130, 136 Hemoglobin, 123, 134, 136, 137 Hemolysis, 124, 137 Hemolytic, 137, 139 Hemorrhage, 136, 137, 151 Heredity, 135, 137 Heterotrophic, 135, 137 Hormone, 137, 143, 154 Humoral, 4, 9, 11, 12, 31, 137 Humour, 137 Hybrid, 128, 137
162 Tularemia
Hybridization, 22, 66, 137 Hybridoma, 25, 137 Hydrogen, 125, 126, 131, 137, 144, 145 Hydrolysis, 121, 125, 137, 149, 150 Hypersensitivity, 137, 152 I Id, 71, 74, 100, 105, 112, 114, 137 Idiopathic, 138, 151 Imipenem, 54, 70, 128, 138 Immune function, 27, 138 Immune Sera, 4, 138 Immune system, 12, 21, 28, 31, 124, 125, 132, 138, 142, 156, 157 Immunity, 4, 5, 9, 11, 12, 13, 15, 17, 21, 23, 27, 31, 41, 42, 50, 51, 138, 142, 152, 155 Immunization, 6, 10, 11, 12, 18, 29, 31, 35, 45, 57, 138 Immunoassay, 40, 138 Immunocompromised, 4, 138 Immunodeficiency, 66, 138 Immunodiffusion, 121, 138 Immunoelectrophoresis, 121, 138 Immunofluorescence, 8, 138 Immunogenetics, 6, 10, 138 Immunogenic, 9, 138 Immunoglobulin, 123, 138, 144 Immunologic, 31, 127, 138, 142 Immunology, 12, 20, 21, 28, 40, 42, 43, 51, 64, 121, 134, 138 Impetigo, 82, 138 In situ, 14, 139 In vitro, 6, 11, 12, 14, 15, 17, 24, 26, 27, 30, 32, 43, 46, 139, 149 In vivo, 5, 11, 12, 14, 24, 26, 27, 139 Incubation, 139, 147 Incubation period, 139, 147 Indicative, 80, 139, 146, 156 Induction, 16, 20, 21, 51, 139 Infarction, 139 Infectious Mononucleosis, 139, 144 Infiltration, 15, 139 Inflammation, 21, 126, 127, 132, 133, 134, 139, 142, 143, 145, 146, 147, 148, 151, 155 Ingestion, 20, 123, 139, 148 Inhalation, 3, 11, 13, 15, 20, 22, 23, 29, 31, 121, 139, 148 Initiation, 25, 139 Inner ear, 127, 139 Insect Vectors, 20, 139 Insight, 15, 31, 139 Interferon, 33, 41, 43, 46, 139, 140 Interferon-alpha, 140
Interleukin-2, 41, 140 Intermittent, 45, 140 Interstitial, 140, 145 Intestine, 128, 133, 140, 152, 153 Intracellular, 3, 8, 11, 14, 15, 16, 19, 25, 27, 28, 29, 30, 31, 32, 128, 130, 136, 139, 140, 143 Intracellular Membranes, 130, 140, 143 Intramuscular, 140, 146 Intravenous, 13, 140, 146 Intrinsic, 25, 121, 140 Invasive, 138, 140 Ions, 125, 132, 137, 140 Ixodes, 124, 140 J Joint, 117, 128, 140 K Kb, 94, 140 Keratolytic, 131, 140 L Labile, 129, 140 Laboratory Infection, 40, 140 Laceration, 140, 154 Laxative, 121, 140 Lectin, 140, 143 Leishmaniasis, 23, 140 Lens, 126, 141 Leprosy, 82, 141 Leptospirosis, 33, 51, 141 Lesion, 17, 118, 136, 141 Lethal, 9, 30, 48, 124, 141, 151 Leukocyte Count, 48, 141 Leukocytes, 126, 127, 140, 141, 145, 156 Leukocytosis, 127, 141 Leukopenia, 66, 141 Levofloxacin, 55, 141 Library Services, 112, 141 Life cycle, 80, 135, 141 Ligands, 5, 24, 27, 141 Lipid, 9, 132, 141 Lipopolysaccharide, 17, 18, 51, 136, 141 Lipoprotein, 136, 141 Liposomes, 4, 141 Liver, 11, 15, 33, 119, 125, 141, 151 Localization, 19, 25, 141 Localized, 80, 121, 127, 131, 132, 139, 141, 145, 147, 148, 154 Lupus, 82, 141 Lymph, 30, 44, 53, 117, 121, 133, 137, 139, 141, 142, 148, 151 Lymph node, 30, 44, 117, 142, 151 Lymphadenitis, 53, 65, 142
Index 163
Lymphadenopathy, 53, 139, 142 Lymphatic, 133, 139, 141, 142, 145, 153, 154 Lymphatic system, 141, 142, 153, 154 Lymphocyte, 35, 41, 54, 123, 142, 143 Lymphocytosis, 55, 142 Lymphogranuloma Venereum, 136, 142 Lymphoid, 123, 142 Lymphokines, 142 Lymphoma, 61, 142 Lysosome, 142, 147 Lytic, 142, 152, 157 M Macrophage, 18, 19, 20, 21, 29, 30, 31, 142 Macrophage Activation, 18, 21, 142 Major Histocompatibility Complex, 6, 142 Malaise, 117, 126, 142 Malaria, 23, 116, 142, 143 Malaria, Falciparum, 142, 143 Malaria, Vivax, 142, 143 Mediate, 4, 31, 143 Mediator, 140, 143 MEDLINE, 95, 143 Melioidosis, 5, 101, 143 Membrane Proteins, 17, 25, 141, 143 Memory, 11, 123, 143 Meninges, 127, 132, 143 Meningitis, 34, 143 Mental Health, iv, 3, 94, 96, 101, 143, 150 Mercury, 134, 143 MI, 36, 120, 143 Microbe, 29, 30, 143, 155 Microbiological, 25, 143 Microbiology, 12, 20, 21, 23, 28, 34, 36, 37, 40, 41, 42, 43, 46, 47, 54, 55, 62, 64, 66, 105, 124, 143, 144 Microorganism, 12, 32, 128, 144, 146, 157 Micro-organism, 131, 144 Microscopy, 4, 8, 19, 29, 144 Migration, 142, 144 Mitosis, 124, 144 Modeling, 8, 131, 144 Molecule, 29, 123, 125, 129, 132, 134, 135, 136, 137, 140, 144, 145, 148, 150, 156 Monoclonal, 6, 8, 10, 25, 144 Monoclonal antibodies, 6, 8, 10, 25, 144 Monocyte, 31, 144 Mononuclear, 8, 17, 136, 139, 144, 156 Mononucleosis, 23, 144 Morphology, 142, 144 Motility, 4, 144 Mucocutaneous, 141, 144, 154
Mucosa, 82, 133, 141, 144 Mutagenesis, 11, 16, 20, 32, 144 Mutagenic, 32, 144 Mutagens, 135, 144 Myeloma, 137, 145 Myocardial infarction, 61, 130, 143, 145 Myocarditis, 131, 145 Myocardium, 143, 145 N Natural selection, 125, 145 Necrosis, 124, 139, 143, 145, 147, 150, 151 Need, 22, 25, 32, 79, 81, 100, 106, 121, 142, 145, 155 Neoplastic, 142, 145 Nephritis, 45, 145 Nerve, 124, 143, 145, 146, 153 Neural, 137, 145 Neurologic, 145, 154 Neutrophils, 14, 17, 141, 145, 151 Niche, 11, 29, 145 Nucleic acid, 137, 144, 145 Nucleic Acid Hybridization, 137, 145 Nucleus, 124, 125, 128, 130, 144, 145, 153, 154 O Ocular, 16, 145, 154 Oedema, 35, 70, 145 Oligosaccharides, 31, 146 Open Reading Frames, 14, 146 Oral Manifestations, 82, 146 Organ Culture, 6, 7, 146 Orthopoxvirus, 132, 146 Outpatient, 65, 146 Ovum, 141, 146 P Pachymeningitis, 143, 146 Palliative, 146, 154 Pancreas, 125, 146, 156 Pancreatic, 146, 150 Panic, 8, 146 Parenteral, 6, 10, 146 Parietal, 146, 148 Parotid, 146, 151 Paroxysmal, 146, 147, 157 Pathogen, 3, 4, 8, 11, 12, 14, 15, 17, 19, 27, 29, 30, 31, 32, 63, 139, 146 Pathogenesis, 6, 9, 10, 13, 14, 15, 16, 18, 19, 20, 21, 30, 46, 50, 146 Pathologic, 124, 130, 137, 146 Pathologic Processes, 124, 146 Patient Education, 104, 110, 112, 120, 146 Peptide, 4, 18, 21, 24, 31, 147, 149, 150
164 Tularemia
Periodontal Abscess, 82, 147 Periodontal disease, 82, 147 Periodontitis, 82, 147 Peripheral blood, 24, 48, 140, 147 Peripheral Nerves, 141, 147 Peritoneal, 124, 145, 147 Peritoneal Cavity, 124, 145, 147 Pertussis, 82, 88, 147, 157 Phagocytosis, 15, 29, 31, 147 Phagosomes, 20, 31, 147 Pharmacokinetics, 131, 147 Pharmacologic, 136, 147, 155 Pharyngitis, 48, 64, 116, 147, 151 Phenotypes, 24, 147 Phocomelia, 132, 147 Phosphorus, 126, 147 Physiologic, 136, 148, 150 Physiology, 13, 148 Phytotoxin, 148, 151 Pilot study, 32, 148 Plague, 5, 7, 10, 11, 22, 30, 37, 38, 49, 74, 88, 116, 148, 156 Plants, 125, 126, 140, 144, 148, 151, 155 Plasma, 123, 127, 130, 133, 137, 145, 148 Plasma cells, 123, 145, 148 Plasmid, 135, 148, 156 Pleura, 148 Pleural, 44, 51, 61, 116, 145, 148 Pleural cavity, 145, 148 Pleural Effusion, 61, 148 Pleurisy, 51, 148 Pneumonitis, 22, 148 Poisoning, 143, 148, 152 Polymerase, 50, 148, 149 Polymerase Chain Reaction, 50, 149 Polypeptide, 122, 129, 137, 149, 157 Polysaccharide, 9, 18, 31, 123, 149 Posterior, 124, 146, 149 Practice Guidelines, 96, 105, 149 Preclinical, 24, 27, 149 Precursor, 132, 133, 149 Prevalence, 26, 50, 149 Progression, 79, 123, 149 Progressive, 131, 136, 145, 149 Projection, 131, 149, 150 Promoter, 5, 17, 149 Prophylaxis, 21, 37, 81, 105, 149, 156 Proportional, 135, 149 Prostate, 125, 149, 156 Protein C, 29, 122, 125, 128, 141, 149 Protein S, 24, 80, 126, 129, 134, 149 Proteolytic, 129, 150, 151
Protozoa, 140, 144, 150 Pseudocysts, 82, 150 Public Health, 6, 10, 11, 15, 26, 34, 42, 56, 58, 79, 80, 96, 103, 105, 150 Public Policy, 95, 150 Publishing, 32, 150 Pulmonary, 15, 16, 17, 21, 25, 31, 32, 50, 55, 65, 66, 126, 150, 154 Purulent, 147, 150 Pustular, 139, 150 Pyoderma, 82, 150 R Rabies, 150, 157 Radiation, 7, 134, 150 Radioactive, 136, 137, 144, 150 Randomized, 132, 150 Receptor, 18, 19, 22, 31, 46, 123, 150 Recombinant, 25, 150, 156 Red Nucleus, 124, 150 Reductase, 24, 150 Refer, 1, 126, 129, 135, 141, 144, 151 Refraction, 151, 153 Regimen, 10, 11, 132, 151 Regional lymph node, 127, 151 Relapse, 32, 51, 66, 151 Respiratory Burst, 22, 151 Respiratory distress syndrome, 35, 151 Respiratory Mucosa, 135, 151 Reversion, 151, 156 Rhabdomyolysis, 53, 55, 116, 151 Ribose, 121, 151 Ricin, 12, 151 Risk factor, 52, 84, 151 Rod, 124, 125, 151 S Saliva, 151 Salivary, 82, 151, 154, 155 Salivary glands, 82, 151, 154, 155 Salmonellosis, 23, 151 Saponin, 12, 151 Sarcoidosis, 24, 151 Scarlet Fever, 82, 151 Screening, 8, 128, 151 Secretion, 21, 23, 137, 151, 152 Sepsis, 6, 10, 11, 152 Septicemia, 52, 152 Sequencing, 13, 20, 149, 152 Serologic, 38, 53, 138, 152 Serous, 133, 148, 152 Serum, 12, 25, 122, 129, 138, 148, 152, 156 Shock, 12, 47, 152 Side effect, 87, 121, 152, 155
Index 165
Signs and Symptoms, 80, 151, 152 Skeletal, 151, 152 Skin Tests, 53, 152 Skunks, 26, 152 Small intestine, 133, 137, 140, 152 Smallpox, 6, 10, 22, 28, 37, 152, 156 Sneezing, 147, 152 Sodium, 54, 70, 152 Soft tissue, 126, 152 Somatic, 137, 144, 152 Spasmodic, 147, 152 Specialist, 106, 152 Spectrum, 24, 27, 50, 138, 153 Sperm, 128, 153 Spirochete, 153, 154 Spleen, 15, 137, 142, 151, 153 Staphylococcal Infections, 82, 153 Staphylococcus, 24, 82, 127, 138, 153 Staphylococcus aureus, 24, 82, 127, 138, 153 Stimulants, 4, 153 Stimulus, 132, 134, 153, 154 Stomach, 135, 137, 147, 152, 153 Strand, 148, 153 Streptococcal, 48, 116, 153 Streptococci, 139, 151, 153 Streptococcus, 133, 153 Subacute, 139, 142, 153 Subclinical, 139, 153 Subcutaneous, 127, 132, 145, 146, 153 Subspecies, 152, 153, 157 Substance P, 134, 151, 153 Superoxide, 151, 154 Suppurative, 52, 82, 154 Surfactant, 5, 23, 30, 154 Syphilis, 82, 116, 154 Syphilis, Congenital, 82, 154 Systemic, 11, 12, 15, 16, 21, 30, 88, 126, 131, 139, 145, 151, 152, 154, 155, 156, 157 T Testosterone, 150, 154 Tetani, 154 Tetanic, 154 Tetanus, 31, 88, 154 Thalamic, 124, 154 Thalamic Diseases, 124, 154 Therapeutics, 6, 10, 23, 29, 89, 154 Thermal, 149, 154 Threshold, 82, 154 Thrombin, 134, 149, 154 Thrombomodulin, 149, 154 Thrombosis, 150, 154
Thymus, 138, 142, 154 Tick Paralysis, 80, 104, 154 Tick-Borne Diseases, 124, 155 Ticks, 26, 50, 80, 104, 120, 140, 155 Tolerance, 52, 121, 155 Tonsillitis, 151, 155 Toxic, iv, 131, 138, 147, 148, 155 Toxicity, 28, 131, 143, 155 Toxicology, 96, 155 Toxins, 123, 126, 132, 134, 139, 144, 152, 155 Toxoid, 31, 155 Transfection, 26, 126, 155 Transfer Factor, 138, 155 Translating, 28, 155 Translation, 134, 155 Translational, 28, 155 Translocation, 134, 155 Transplantation, 65, 138, 142, 155 Treatment Failure, 65, 155 Tuberculosis, 4, 15, 23, 28, 31, 82, 141, 155 Tuberculosis, Oral, 82, 155 Tumor marker, 125, 156 Tumor Necrosis Factor, 33, 41, 43, 156 Typhimurium, 28, 156 Typhoid fever, 52, 117, 156 U Ulceration, 135, 156 Unconscious, 131, 137, 156 Urethra, 149, 156 Urinary, 127, 128, 156 Urinary tract, 127, 156 Urine, 6, 7, 18, 40, 126, 156 Urogenital, 136, 156 V Vaccination, 4, 21, 31, 33, 42, 43, 46, 54, 156 Vaccine adjuvant, 31, 156 Vaccinia, 6, 10, 146, 156 Vacuole, 19, 29, 156 Variola, 6, 10, 22, 156 Vascular, 133, 139, 145, 156 Vector, 6, 10, 26, 156 Vein, 140, 146, 156 Venereal, 154, 156, 157 Venous, 141, 145, 150, 157 Venous blood, 141, 157 Vesicular, 152, 156, 157 Veterinary Medicine, 95, 157 Viral, 23, 29, 132, 133, 135, 150, 155, 157 Virulence, 4, 5, 9, 11, 13, 14, 16, 17, 19, 20, 23, 25, 28, 29, 32, 43, 105, 124, 155, 157
166 Tularemia
Virulent, 4, 6, 13, 14, 16, 17, 19, 25, 26, 30, 157 Virus, 7, 10, 66, 125, 135, 136, 139, 140, 146, 152, 156, 157 Visceral, 141, 157 Vitro, 6, 11, 12, 24, 157 Vivo, 5, 11, 14, 24, 157 W War, 102, 136, 157 White blood cell, 123, 139, 141, 142, 144, 145, 148, 157
Whole cell vaccine, 9, 157 Whooping Cough, 147, 157 X Xenograft, 123, 157 Y Yaws, 82, 157 Yeasts, 135, 157 Z Zoonoses, 33, 51, 124, 150, 157 Zoonosis, 16, 157 Zymogen, 149, 157
Index 167
168 Tularemia
