CHOLERA A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R E FERENCES
J AMES N. P ARKER , M.D. AND P HILIP M. P ARKER , P H .D., E DITORS
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ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright 2003 by ICON Group International, Inc. Copyright 2003 by ICON Group International, Inc. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without written permission from the publisher. Printed in the United States of America. Last digit indicates print number: 10 9 8 7 6 4 5 3 2 1
Publisher, Health Care: Philip Parker, Ph.D. Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher's note: The ideas, procedures, and suggestions contained in this book are not intended for the diagnosis or treatment of a health problem. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960Cholera: 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: 0-597-83866-6 1. Cholera-Popular works. I. Title.
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Disclaimer This publication is not intended to be used for the diagnosis or treatment of a health problem. It is sold with the understanding that the publisher, editors, and authors are not engaging in the rendering of medical, psychological, financial, legal, or other professional services. References to any entity, product, service, or source of information that may be contained in this publication should not be considered an endorsement, either direct or implied, by the publisher, editors, or authors. ICON Group International, Inc., the editors, and the authors are not responsible for the content of any Web pages or publications referenced in this publication.
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Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this book which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which produce publications on cholera. Books in this series draw from various agencies and institutions associated with the United States Department of Health and Human Services, and in particular, the Office of the Secretary of Health and Human Services (OS), the Administration for Children and Families (ACF), the Administration on Aging (AOA), the Agency for Healthcare Research and Quality (AHRQ), the Agency for Toxic Substances and Disease Registry (ATSDR), the Centers for Disease Control and Prevention (CDC), the Food and Drug Administration (FDA), the Healthcare Financing Administration (HCFA), the Health Resources and Services Administration (HRSA), the Indian Health Service (IHS), the institutions of the National Institutes of Health (NIH), the Program Support Center (PSC), and the Substance Abuse and Mental Health Services Administration (SAMHSA). In addition to these sources, information gathered from the National Library of Medicine, the United States Patent Office, the European Union, and their related organizations has been invaluable in the creation of this book. Some of the work represented was financially supported by the Research and Development Committee at INSEAD. This support is gratefully acknowledged. Finally, special thanks are owed to Tiffany Freeman for her excellent editorial support.
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About the Editors James N. Parker, M.D. Dr. James N. Parker received his Bachelor of Science degree in Psychobiology from the University of California, Riverside and his M.D. from the University of California, San Diego. In addition to authoring numerous research publications, he has lectured at various academic institutions. Dr. Parker is the medical editor for health books by ICON Health Publications. Philip M. Parker, Ph.D. Philip M. Parker is the Eli Lilly Chair Professor of Innovation, Business and Society at INSEAD (Fontainebleau, France and Singapore). Dr. Parker has also been Professor at the University of California, San Diego and has taught courses at Harvard University, the Hong Kong University of Science and Technology, the Massachusetts Institute of Technology, Stanford University, and UCLA. Dr. Parker is the associate editor for ICON Health Publications.
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About ICON Health Publications To discover more about ICON Health Publications, simply check with your preferred online booksellers, including Barnes & Noble.com and Amazon.com which currently carry all of our titles. Or, feel free to contact us directly for bulk purchases or institutional discounts: ICON Group International, Inc. 4370 La Jolla Village Drive, Fourth Floor San Diego, CA 92122 USA Fax: 858-546-4341 Web site: www.icongrouponline.com/health
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Table of Contents FORWARD .......................................................................................................................................... 1 CHAPTER 1. STUDIES ON CHOLERA .................................................................................................. 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Cholera .......................................................................................... 4 E-Journals: PubMed Central ....................................................................................................... 60 The National Library of Medicine: PubMed ................................................................................ 89 CHAPTER 2. NUTRITION AND CHOLERA ...................................................................................... 135 Overview.................................................................................................................................... 135 Finding Nutrition Studies on Cholera....................................................................................... 135 Federal Resources on Nutrition ................................................................................................. 138 Additional Web Resources ......................................................................................................... 139 CHAPTER 3. ALTERNATIVE MEDICINE AND CHOLERA ................................................................ 141 Overview.................................................................................................................................... 141 National Center for Complementary and Alternative Medicine................................................ 141 Additional Web Resources ......................................................................................................... 152 General References ..................................................................................................................... 154 CHAPTER 4. DISSERTATIONS ON CHOLERA .................................................................................. 155 Overview.................................................................................................................................... 155 Dissertations on Cholera............................................................................................................ 155 Keeping Current ........................................................................................................................ 157 CHAPTER 5. PATENTS ON CHOLERA ............................................................................................. 159 Overview.................................................................................................................................... 159 Patents on Cholera ..................................................................................................................... 159 Patent Applications on Cholera ................................................................................................. 184 Keeping Current ........................................................................................................................ 195 CHAPTER 6. BOOKS ON CHOLERA ................................................................................................ 197 Overview.................................................................................................................................... 197 Book Summaries: Federal Agencies............................................................................................ 197 Book Summaries: Online Booksellers......................................................................................... 198 The National Library of Medicine Book Index ........................................................................... 202 Chapters on Cholera................................................................................................................... 204 CHAPTER 7. MULTIMEDIA ON CHOLERA...................................................................................... 207 Overview.................................................................................................................................... 207 Video Recordings ....................................................................................................................... 207 Bibliography: Multimedia on Cholera........................................................................................ 208 CHAPTER 8. PERIODICALS AND NEWS ON CHOLERA................................................................... 211 Overview.................................................................................................................................... 211 News Services and Press Releases.............................................................................................. 211 Academic Periodicals covering Cholera ..................................................................................... 216 CHAPTER 9. RESEARCHING MEDICATIONS .................................................................................. 217 Overview.................................................................................................................................... 217 U.S. Pharmacopeia..................................................................................................................... 217 Commercial Databases ............................................................................................................... 218 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 223 Overview.................................................................................................................................... 223 NIH Guidelines.......................................................................................................................... 223 NIH Databases........................................................................................................................... 225 Other Commercial Databases..................................................................................................... 228 APPENDIX B. PATIENT RESOURCES ............................................................................................... 229 Overview.................................................................................................................................... 229
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Patient Guideline Sources.......................................................................................................... 229 Finding Associations.................................................................................................................. 232 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 235 Overview.................................................................................................................................... 235 Preparation................................................................................................................................. 235 Finding a Local Medical Library................................................................................................ 235 Medical Libraries in the U.S. and Canada ................................................................................. 235 ONLINE GLOSSARIES................................................................................................................ 241 Online Dictionary Directories ................................................................................................... 244 CHOLERA DICTIONARY ........................................................................................................... 245 INDEX .............................................................................................................................................. 325
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FORWARD In March 2001, the National Institutes of Health issued the following warning: "The number of Web sites offering health-related resources grows every day. Many sites provide valuable information, while others may have information that is unreliable or misleading."1 Furthermore, because of the rapid increase in Internet-based information, many hours can be wasted searching, selecting, and printing. Since only the smallest fraction of information dealing with cholera 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 cholera, 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 cholera, 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 cholera. 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 cholera, 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 cholera. The Editors
1
From the NIH, National Cancer Institute (NCI): http://www.cancer.gov/cancerinfo/ten-things-to-know.
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CHAPTER 1. STUDIES ON CHOLERA Overview In this chapter, we will show you how to locate peer-reviewed references and studies on cholera.
The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and cholera, you will need to use the advanced search options. First, go to http://chid.nih.gov/index.html. From there, select the “Detailed Search” option (or go directly to that page with the following hyperlink: http://chid.nih.gov/detail/detail.html). The trick in extracting studies is found in the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Journal Article.” At the top of the search form, select the number of records you would like to see (we recommend 100) and check the box to display “whole records.” We recommend that you type “cholera” (or synonyms) into the “For these words:” box. Consider using the option “anywhere in record” to make your search as broad as possible. If you want to limit the search to only a particular field, such as the title of the journal, then select this option in the “Search in these fields” drop box. The following is what you can expect from this type of search: •
Hope in the Time of Cholera: How A Simple Solution is Rescuing Millions of Children From Cholera and Other Deadly Diarrheas Source: Harvard Public Health Review. 3(1): 20-27. Fall 1991-Winter 1992. Summary: This article focuses on the diarrheal diseases, including cholera, dysentery, and diarrhea caused by rotavirus, salmonella, and E. coli. The author reviews the differences in management of these diseases in the developed countries compared with the developing countries. Spread primarily through human and animal feces, diarrhea and dysentery are prevalent wherever waste disposal, water treatment, and personal and food hygiene practices are inadequate. The bulk of the article describes oral rehydration therapy (ORT), used to remedy the dehydrating effects of diarrhea. Topics include the principles of ORT, the magnitude of the problem, why ORT has not solved the morbidity and mortality caused by diarrhea, local and cultural obstacles to effective
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diarrhea management, public health education, the continuing overuse of antibiotics and antispasmodics in treating diarrhea, current research being performed by Harvard faculty members in this area, and the importance of training physicians and other health care workers about ORT.
Federally Funded Research on Cholera The U.S. Government supports a variety of research studies relating to cholera. 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 cholera. 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 cholera. The following is typical of the type of information found when searching the CRISP database for cholera: •
Project Title: A ROLE FOR INNATE IMMUNITY IN SALIVARY IGA RESPONSES Principal Investigator & Institution: Fujihashi, Kohtaro; Associate Professor; Oral Biology; University of Alabama at Birmingham Uab Station Birmingham, Al 35294 Timing: Fiscal Year 2002; Project Start 01-APR-1997; Project End 31-DEC-2006 Summary: The earlier FIRST award focused on elucidation of the underlying molecular and cellular mechanisms for the induction and regulation of antigen-specific secretory IgA (S-IgA) antibody (Ab) responses at mucosal surfaces with emphasis on the salivary glands. The earlier studies have produced important results indicating that a mucosal intranet consisting of alpha,beta-T cells, gammadelta T cells and epithelial cells played major roles in the induction and regulation of antigen-specific IgA Ab responses. Thus, nasal immunization with the weakly immunogenic protein ovalbumin (OVA) and the nonenterotoxic mutant cholera toxin (CT) as mucosal adjuvant induced Th2-type cytokine-mediated salivary S-IgA Ab responses. Interestingly, depletion of gammadelat T cells resulted in impaired mucosal IgA responses including those responses in saliva. Further, these findings showed that epithelial cells produced an important cytokine, i.e., interleukin (IL)-7 which is central to the development and differentiation of alphabeta T cells. These results clearly indicate that lymphocyte- epithelial cell interactions, representing innate and acquired immunity, are part of the mechanisms involved in the induction of antigen-specific IgA Ab responses. These findings suggest that the innate immune system may be a key element in bridging innate with acquired mucosal immunity as manifested by antigen-specific IgA responses. Recent studies have indeed shown that nasal application of defensins, or chemokines such as lymphotactin or RANTES with OVA induced OVA-specific mucosal IgA Ab responses, including those
2
Healthcare projects are funded by the National Institutes of Health (NIH), Substance Abuse and Mental Health Services (SAMHSA), Health Resources and Services Administration (HRSA), Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDCP), Agency for Healthcare Research and Quality (AHRQ), and Office of Assistant Secretary of Health (OASH).
Studies
5
associated with the salivary glands. Further, most recent findings through this grant effort showed that mRNA for these chemokines were expressed by intestinal and salivary gammadelta T cells as well as by epithelial cells. Thus, the overall hypothesis in this grant renewal application will be that the innate mucosal immune system plays an especially important role in acquired immunity for the induction and regulation of salivary gland IgA Ab responses. In order to understand the precise cellular and molecular mechanisms involved in innate immunity for mucosal IgA responses, the following Specific Aims are proposed. Specifically, there are plans to: 1) Characterize innate immunity in salivary glands of mice immunized with a hapten-LPS derivative of T-independent (TI) antigen; 2)Examine the roles for innate immunity-associated mucosal modulators for the induction of TI-antigen-specific immunity in the salivary gland; 3) The bridging mechanisms between immunity for the induction of antigenspecific immune responses in salivary glands induced by specific mucosal adjuvants and delivery systems; 4) Assess the roles of gammadelta T cells in the salivary intranet which bridge innate with acquired immunity; and 5) Determine how innate gammadelta T cells-CD4 about alphabeta T cells interact for IgA responses in the SMG. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ACCESSORY CHOLERA ENTEROTOXIN, ACE, MECHANISM OF ACTION Principal Investigator & Institution: Trucksis, Michele M.; Medicine; Univ of Massachusetts Med Sch Worcester Office of Research Funding Worcester, Ma 01655 Timing: Fiscal Year 2003; Project Start 15-SEP-1995; Project End 31-JAN-2007 Summary: (provided by applicant): Colonization of the small intestine by Vibrio cholerae causes the potentially lethal disease cholera due to massive salt and water secretion. Although the dehydrating diarrhea of cholera is attributed to secretion stimulated by cholera toxin, two other toxins of V. cholerae that alter short circuit current or resistance in Ussing chambers have been identified. V. cholerae ACE (accessory cholera enterotoxin) was initially described in 1993 as a toxin which increased short circuit current and potential difference in rabbit ileum mounted in Ussing chambers and caused fluid secretion in ligated rabbit ileal loops. We have investigated the mechanism of action of ACE utilizing monolayers of polarized intestinal epithelial cells (T84 cells) mounted in modified Ussing chambers. In these studies we identified novel physiology stimulated by ACE including that ACE is dependent on calcium as a second messenger; that although it is a calcium-dependent agonist it is unique in that it has a prolonged current response and acts synergistically with other calcium-dependent agonists; and finally, that it stimulates secretion that is equally dependent on chloride and bicarbonate ions (a newly emerging mechanism of secretion). We hypothesize that ACE interacts with the polarized intestinal epithelial cell, through a receptor present on the apical surface and that through this interaction it initiates signal transduction with calcium as a second messenger. We also hypothesize that ACE potentiates the Cl- secretory activity of carbachol by blocking the normal inhibitory pathway stimulated by carbachol. The Specific Aims are 1) Identify the ACE receptor; 2) Examine the signal transduction pathways stimulated by ACE; and 3) Examine the interaction of ACE with calcium-mediated inhibitory pathways. We will use molecular genetic, biochemical and cell physiology methods to examine the mechanism of action of ACE. The long term objectives of this proposal are to enhance our understanding of the role of ACE in cholera pathogenesis and to identify novel mechanisms of action of bacterial toxins. The utility of ACE in investigating the epithelial transport pathways in the intestine, and perhaps other tissue types lies in
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Cholera
ACE's novel physiology. The characterization of the ion channels activated by ACE may provide valuable information, which can be used to develop pharmacological modulators of chloride and bicarbonate secretion useful in the treatment of diarrheal diseases (excessive secretion) or cystic fibrosis (defective secretion). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ADJUVANTED DNA VACCINE FOR IMMUNOTHERAPY HIV INFECTION Principal Investigator & Institution: Haynes, Joel R.; Powderject Vaccines, Inc. 585 Science Dr Madison, Wi 53711 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 31-MAR-2004 Summary: The goal of this program is the optimization and evaluation of an adjuvanted therapeutic DNA vaccine strategy for AIDS using the rhesus monkey/SIV model system. In addition, a graduated clinical evaluation approach is planned to introduce this technology into the clinic in a stepwise manner. The DNA vaccine to be employed will encode the full length gag, pol, and env products of SIV as well as a series of defined CTL epitopes fused to an immunogenic carrier protein. The novelty of our approach centers on the inclusion of an adjuvant vector encoding the A and B subunits of cholera toxin (CT) or the E. coli heat labile enterotoxin (LT) to augment antigenspecific Th1 immunity and systemic and mucosal CTL responses. The adjuvanted DNA vaccine will be formulated onto microscopic gold particles and delivered to the skin as a therapeutic vaccine using a clinical "gene gun" device. Elucidation of the mechanism of adjuvant action will be assisted by the analysis of chemokine involvement and the activation and trafficking of dendritic cells. Justification of the proposed approach is based on three important findings from our laboratories: 1, Human clinical evaluation of a "gene gun"-based DNA vaccine for hepatitis B resulted in the induction of vigorous antigen-specific, Th1 and cytotoxic cellular immune responses in humans, confirming the clinical effectiveness of this means of DNA vaccine delivery. 2, The induction of SIVspecific CTL responses via gene gun-based DNA vaccination in the rhesus/SIV model provides measurable protection from challenge with pathogenic SIVdeltaB670. 3, The formulation of DNA vaccines with vectors encoding eith4r CT or LT results in marked and surprising enhancements of Th1 and CTL responses without any evidence of local or systemic toxicity in small and large animals. Clinical development of the adjuvanted DNA vaccine approach will take place in a graduated manner involving initial evaluation of a single HIV therapeutic DNA vaccine vector in a small phase I/II trial. A second clinical trial attempting to establish clinical proof of concept of the adjuvanted DNA vaccine approach will follow. The later trial will include the addition of a vector encoding CT or LT. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ADP PROLIFERATION
RIBOSYLATION
OF
A
POTENT
INDUCER
OF
Principal Investigator & Institution: Francis, Mark L.; Internal Medicine; Southern Illinois University Sch of Med Box 19616, 801 Rutledge St Springfield, Il 62794 Timing: Fiscal Year 2001; Project Start 01-JAN-1998; Project End 31-DEC-2002 Summary: (Adapted from Investigator's abstract): The broad goal of the proposed study is to improve understanding of signal transduction pathways involved in B cell activation. This knowledge will provide important understanding of both normal physiology and unregulated cell growth. Abnormalities of signal transduction proteins
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have been identified in both cancer and immunodeficiencies. Bacterial toxins have been useful tools to dissect the function of G proteins, a group of signal transduction proteins. Using NAD as a source, bacterial toxins add adenosine diphosphate ribose (ADP-ribose) to proteins, a process called ADP-ribosylation. This modification can alter the function of signal transduction proteins in a manner that mimics their physiologic function. Based on his previous work, the applicant hypothesizes that cholera toxin ADPribosylates a non-Gs protein that regulates B cell activation. The goals are to identify this protein and to determine its physiologic function. In Specific Aim 1, the ability of cholera toxin to ADP-ribosylate proteins in intact B cells will be used to block subsequent ADP-ribosylation of these proteins in vitro in the presence of [32P]NAD. While this reverse labeling technique has identified a single, non-Gs protein that is ADPribosylated by cholera toxin, other candidate proteins will be sought. Specific Aim 2 is designed to develop the necessary tools to study the physiologic function of the ADPribosylated proteins. Following microsequencing, the sequence information will be used to clone the corresponding cDNA. At each step, sequence information will be compared to known amino acid and nucleic acid data bases 1) to help identify the protein or any functional motifs and 2) to determine which proteins to pursue for further analysis. Finally, antibodies will be generated. Specific Aim 3 will begin to address the physiologic function of these proteins. Using antibodies, the investigator will determine whether and how these proteins are physiologically modulated by B cell stimulants, such as anti-Ig. In particular, he will determine whether these proteins are phosphorylated or dephosphorylated. If more than one candidate protein remains, these studies will establish which is the target protein. Conversely, selective activation of this protein by cholera toxin will permit him to explore the downstream effects that are specifically mediated by this protein. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ANTIGENS OF STREPTOCOCCUS MUTANS IN CARIES IMMUNITY Principal Investigator & Institution: Russell, Michael W.; Research Professor of Microbiology; Microbiology and Immunology; State University of New York at Buffalo Suite 211 Ub Commons Amherst, Ny 14228 Timing: Fiscal Year 2001; Project Start 01-JAN-1984; Project End 31-DEC-2003 Summary: This project is focused on three aspects in the development of novel genetically engineered mucosal immunogens constructed primarily from a salivabinding region (SBR) of surface protein AgI/II of Streptococcus mutans and a nontoxic component of cholera toxin (CT), the A2/B subunits, as potential candidates for inclusion in a vaccine against dental caries. Specific Aim 1 will address the mechanisms underlying immunological memory that maintains long-term and recallable salivary IgA antibody responses when SBR-CTA2/B is administered to mice by the intranasal route, which has previously been shown to be particularly effective for inducing these responses. The following will be investigated: the generation and characteristics of antigen-specific memory B and T cells, and the cytokines they produce, in the nasal lymphoid tissue and the cervical lymph nodes that drain it; the ability of these cells to serve as precursors of IgA antibody-secreting cells in salivary glands; and the uptake and retention of antigen by these tissues. Specific Aim 2 will develop and refine further mucosal immunogens based on the same technology, to improve the production and immunological properties of SBR-CTA2/B, to construct and evaluate immunogens from other segments of AgI/II that may be important for protection against dental caries, and to evaluate the use of similar immunogens constructed from S. mutans glucosyltransferase. The immunogens will be evaluated for their immunogenicity in
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Cholera
terms of the salivary IgA and serum antibodies induced in mice when administered by the intragastric and intranasal routes. Specific Aim 3 will determine the ability of SBRCTA2/B to induce salivary IgA and serum antibody responses to S. mutans AgI/II in adult human volunteers immunized orally or intranasally with this immunogen. This is planned as a small-scale, preclinical experiment, that takes advantage of the known safety and immunogenicity of CTB itself when administered to humans by these routes, and the previously demonstrated ability of CTB to serve as a carrier for other protein antigens coupled to it either chemically or genetically when these are administered to experimental animals by oral or intranasal routes. The information obtained will permit clinical trials to be proposed for the evaluation of these and similar immunogens are vaccines against dental caries, and demonstrate the utility of this technology for inducing mucosal immune responses that may be applicable against other human infections. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ARF BINDING IN THE ACTION OF CHOLERA AND E COLI TOXINS Principal Investigator & Institution: Kahn, Richard A.; Professor; Biochemistry; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2001; Project Start 01-DEC-1998; Project End 30-NOV-2002 Summary: (Adapted from the applicant's abstract): Cholera, and related diarrheal diseases, are the #3 cause of all deaths worldwide. Both cholera and the less virulent "travelers diarrhea" result from bacterial infections (by Vibrio cholerae and E. coli, respectively) and colonization of the gut where exotoxins are produced that cause all of the clinically important symptoms of the diseases. Cholera toxin (CT) and E. coli heat labile toxin (LT) are structurally (>80% identity), immunologically, and mechanistically very closely related. The key pathophysiological step in this process, the ADPribosylation of Gs, can be performed in vitro using purified components and requires a proteinaceous co-factor, termed the ADP-ribosylation factor or Arf. Arfs are ubiquitous, essential, GTP-binding regulators in eukaryotes of most (perhaps all) steps of vesicular membrane transport and are potent activators of phospholipase D. Entry of the CT/LT toxins occurs through a "reverse secretory" pathway from endosomes to Golgi to ER and back out to Golgi, where A and B subunits dissociate and the active A subunit presumably enters the cytosol. These surprising observations, that this regulator of membrane traffic, Arf, is required for ADP-ribosylation by the toxins in vitro and that the ADP-ribosylation toxins must transit the length of the secretory pathway before gaining access to the cytosol has prompted this detailed examination of the relationship between Arf and CT/LT. Another reason for doing so comes from the recent observations that CT/LT are very potent mucosal adjuvants, with potential applications against a host of human pathogens, including sexually transmitted viruses, e.g., herpes, papilloma, and HIV. The development of toxin based adjuvants has been limited by the toxicity of the toxins alone. The principal goal is to determine the importance of Arf binding to toxins in intact cells with respect to the activation of adenyl cyclase and to the mode of entry of toxins into cell cytosol. Finding mutants that retain adjuvant properties but reduced or absent cellular toxicities may prove essential to the development of these agents as adjuvants. This proposal has three specific aims: (1) Create and characterize point mutants of LTA that have partial or complete loss of the ability to bind and be activated by human Arf proteins. Results will begin to define the LTA-Arf binding surface. (2) Co-crystallize the Arf- GTP-LTA complex and solve the structure. Preliminary data make this a feasible approach and offer a rapid advance in our understanding of this protein interaction. (3) LT/CT mutants, defective in the ability to
Studies
9
interact productively with Arf, will be examined for their ability to activate adenyl cyclase, transit the "reverse secretory" pathway, localize to appropriate intracellular locales, and intoxicate mammalian cells. These studies will address for the first time the relevance of toxin-Arf interaction in live cells and provide important new mechanistic and structural information on this protein interaction that can either support or refute the potential use of loss-of-Arf-binding mutants of LT or CT as adjuvants, as antigens in vaccine development, or other uses. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ASSEMBLY AND STRUCTURE OF TYPE IV PILI Principal Investigator & Institution: Tainer, John A.; Professor; Scripps Research Institute 10550 N Torrey Pines Rd La Jolla, Ca 920371000 Timing: Fiscal Year 2001; Project Start 01-JUL-1985; Project End 31-JAN-2005 Summary: This renewal aims to characterize structure-function relationships for type IV pili fibers, which key virulence factors for pathogenic Gram-negative bacteria. Structural analyses for type IV pilin subunits will be integrated with electron microscopy (EM), fiber diffraction, and small angle x-ray scattering (SAXS) structures of native fibers via objective Fourier correlation methods. These proposed studies, which span atomic to subcellular resolutions, will focus upon type IV pili from Neisseria gonorrhoeae, the causative agent of gonorrhea. Successful methods and results on gonococcal pili will allow complementary structural and mutational studies on pili from Pseudomonas aeruginosa, the causative agent on deadly opportunistic nosocomial infections, and Vibrio cholerae, the causative agent of cholera, to define conserved and variable aspects of type IV pili. Key questions concerning pilus structure-function relationships will be addressed including whether the N. gonorrhoeae pilin fold is representative of all type IV pilins, how extreme antigenic variation avoids disrupting the pilin fold and fiber assembly, the nature and significance of post-translational modifications, structural changes associated with fiber formation, species-specific conservation of surface regions acting in target cell recognition and accessory protein binding, the structural chemistry controlling bundling, structural characteristics of immunodominant regions, and optimal approaches to the design of cross- species vaccines. Structural results and hypotheses will be experimentally tested by quantitative correlations among diffraction and electron microscopy results and by mutational analyses. The proposed integrated multi-disciplinary studies provide innovation in determining challenging fiber-forming protein structures and in bridging the huge resolution gap between protein crystal structures and EM image reconstructions of subcellular organelles. Overall, these structural and mutational results will promote integration of ongoing biochemical, immunobiological, genetic, and functional studies to decipher the structural chemistry governing pilus actions in pathogenicity: host cell surface attachment, twitching motility, bacteriophage absorption, modulation of transformation efficiency and toleration of extreme sequence variability while retaining structural integrity and flexibility. This understanding of pilus structure-function relationships has long-term potential applications for drug and vaccine design against major bacterial diseases now showing increasing antibiotic resistance and threats to public health. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: BACTERIAL PATHOGENESIS
ADENYLATE
CYCLASE
TOXINS:
ROLE
IN
Principal Investigator & Institution: Maynard, Jennifer A.; Microbiology and Immunology; Stanford University Stanford, Ca 94305
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Cholera
Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2005 Summary: (provided by applicant): Several high profile pathogens secrete virulence factors which manipulate host cAMP levels, including Vibrio cholera, Bordetella species, Bacillus anthracis, and Pseudomonas aeruginosa. These toxins contribute to pathogenesis by repressing aspects of innate and adaptive immunity in vitro, in particular phagocytosis, chemotaxis and the production of reactive oxygen species, thereby permitting bacteria to establish infection. In this proposal, we will identify functional differences between the three primary adenylate cyclase toxins (ACT) and pharmacological stimulation of cAMP on monocytes, using a series of purified ACT variants and chimeras, cell biology techniques and transcriptional profiling. In addition, using small molecule inhibitors and over-expression of regulatory subunits, we will define the host signaling events mediating immune suppression after intoxication. Experiments outlined in this proposal will lead to a better understanding of the role of bacterial adenylate cyclase toxins in pathogenesis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DETECTION
BACTERIAL
PATHOGEN
AMPLIFICATION
&
REAL-TIME
Principal Investigator & Institution: U'ren, Jack R.; Director of Research; Saigene Corporation 7126 180Th Ave Ne, Ste C-104 Redmond, Wa 98052 Timing: Fiscal Year 2003; Project Start 01-MAY-2003; Project End 30-NOV-2003 Summary: (provided by applicant): As we all know, bio-terrorism in America is a reality. However in addition to the Category A agents like anthrax, Yersinia pestis and smallpox, which are difficult to safely grow and disseminate, exist the Category B agents that could be used to infect our food or water supply. These organisms include bacterial pathogens, protozoa, and viruses. In addition to these natural pathogenic organisms they could also be genetically engineered to increase their virulence or to resist standard antibiotic treatments. Therefore new methods for rapid sensitive food and waterborne pathogen detection are greatly needed, especially if they can also be used to identify drug sensitivity within these organisms. Bio-terrorism using a food pathogen is not just a hypothetical threat to America. A religious cult in Dalles Oregon sickened at least 751 people by contaminating food in grocery stores and restaurants in the fall of 1984. The group simply grew cultures of the food pathogen Salmonella typhimurium that they obtained from their local scientific supply house and sprinkled the cultures on produce in the grocery stores and the restaurant salad bars. If the group had used a more deadly pathogen like Salmonella typhi that causes typhoid fever many people would certainly have died. The overall goal of this program is to develop an integrated isothermal DNA amplification and a probe array detection slide capable of rapidly identifying a variety of food and waterborne pathogens. All of the NIAID Biodefense Category B food and waterborne bacterial pathogens E. coli, Vibrio cholera, Shigella dysentery, Salmonella species, Listeria monocytogenes, Camphylobacter jejuni, and Yersinia enterocolitica will be detected in this program. A single integrated slide capable of isothermal amplifying and detecting all of these organisms in real-time in a closed sealed device is proposed. The program can also distinguish live organisms from dead organisms killed by the food or water sanitation process. Also, the test can be used to identify the antibiotic sensitivity of the pathogen to identify genetically altered organisms. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: BIOSYNTHESIS OF MEMBRANE PROTEINS(V2) Principal Investigator & Institution: Webster, Robert E.; Professor of Biochemistry; Biochemistry; Duke University Durham, Nc 27706 Timing: Fiscal Year 2001; Project Start 01-JAN-1978; Project End 31-MAR-2003 Summary: The long-term objective of this research is to gain a better understanding, at the molecular level, of how membrane associated protein structures interact to form specific functions in the bacteria. Two systems will be studied using genetic, biochemical and molecular biological techniques. The first system concerns the assembly of the filamentous bacteriophage, a process that occurs entirely at the bacterial membrane. The three capsid and three assembly proteins required for initiation and elongation of assembly will be systematically expressed in the presence or absence of the DNA packaging signal. Chemical and cysteine disulfide crosslinking methods will be used to see how the transmembrane regions of these proteins interact to initiate and elongate the assembling phage particle. The relevance of any identified interactions will be monitored by determining the effect that specific mutant phage proteins have on any observed interactions. Attempts will be made to specify the roles that the noncapsid gene I protein and its overlapping gene XI product play in the assembly process. Better knowledge of the filamentous phage assembly system will aid in our understanding of the apparent mechanistically similar export of many virulence factors from pathogenic bacteria as well as better understanding the production of the cholera toxin determining filamentous bacteriophage. This knowledge may also lead to better designed vectors for the combinational display of proteins on the bacteriophage surface. The second system studies the role of the membrane associated TolQRA and B proteins in maintaining the integrity of the outer membrane of gram negative bacteria as well as facilitating the uptake of the group A colicins. Genetics and affinity chromatography will be used to determine the cytoplasmic molecules that TolQ interacts with to allow the Tol system to function. Attempts will be made to determine if the long helical domain of TolA participates in coiled coil interactions for proper functioning. These studies should give a better understanding of how the outer membrane is maintained and perhaps help design systems for delivering macromolecules into gram negative bacteria. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: BROADLY ACTIVE INHIBITORS OF HIGH PRIORITY PATHOGENS Principal Investigator & Institution: Gulnik, Sergei; Professor; Sequoia Pharmaceuticals, Inc. 401 Professional Dr, Ste 100 Gaithersburg, Md 20879 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2005 Summary: (provided by applicant): The recent anthrax attack of 2001 underscored the reality of large-scale aerosol bioweapons attack by terrorist groups. It also revealed that there is an urgent and pressing need to discover and develop novel and potent antimicrobials that can be used therapeutically and prophylactically for biodefense against new bioattacks. The NIH and CDC have identified a number of High Priority pathogens based on their likelihood of causing widespread contagious disease and/or death to the general population. The long range goal of this Phase I SBIR is to discover and develop potent, broad-spectrum, and mechanistically-novel antimicrobials suitable for treating and/or preventing outbreaks of diseases like anthrax, plague, cholera, gastroenteritis, multidrug-resistant tuberculosis (MDR TB), and for tackling the growing problem of antibiotic resistant bacteria strains. This Phase I application aims to generate novel inhibitors of a bacterial enzyme-3-dehydroquinate dehydratase (DHQase) using molecular target- and structure-based approaches. DHQase is a key enzyme in the
12
Cholera
shikimate pathway that is essential for the biosynthesis of aromatic amino acids in microorganisms, plants and fungi. Specific aims of the application include: 1) cloning, expression and purification of recombinant DHQases from Bacillus anthracis, Yersinia pestis, Campylobacter jejuni, Vibrio cholera and Mycobacteria tuberculosis; 2) establishing DHQase inhibitor assays using the recombinant enzymes; 3) identifying small molecule chemical leads using experimental and computational screening methods; and 4) validating binding modes of inhibitor leads using X-ray crystallography of inhibitor/enzyme complexes. High resolution crystal structures of DHQase, with and without inhibitors, are available from preliminary studies, and crystallization conditions are well established in the laboratory of the PI. The commercial goal of this SBIR is the invention of one or more patentable molecular entities with broad cross-reactivity against DHQases and the pathogens from which they are derived. Enzyme inhibitors identified in the Phase I portion of this work will serve as leads for launching into a Phase II study, the goal of which will be to translate potent and selective inhibitors of High Priority pathogens into safe and effective clinical drug candidates for use as biodefense agents. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CAMPYLOBACTER Principal Investigator & Institution: Ruiz-Palacios, Guillermo; Eastern Virginia Medical School Norfolk, Va 23507 Timing: Fiscal Year 2003; Project Start 01-JUN-2003; Project End 31-MAR-2008 Summary: Campylobacter is among the most common causes of bacterial diarrhea in children worldwide. Infection by pathogenic Campylobacter is inhibited in vitro and in vivo by human milk oligosaccharides. The oligosaccharides responsible for this inhibition contain fucose linked by an alpha 1, 2 glycosidic bond. These linkages are produced by the 2-fucosyltransferase of milk that is the product of the secretor gene, FUT2. The purpose of this study is to determine whether these oligosaccharides also protect against related enteric pathogens, such as V. cholerae; to determine whether natural variation in maternal fucosyltransferases (differences in FUT2) is associated with differences in the risk of diarrhea in breast-fed infants; and to find the simplest alpha1, 2 linked fucosylooligosaccharides that protect infants from campylobacter and related causes of diarrhea. To achieve these goals, we propose the following specific aims: 1. Characterize the Campylobacter adhesin associated with binding to host cell receptors. 2. Define the molecular basis for affinity of Campylobacter and V. cholerae to alpha 1, 2linked histo-blood group antigen of epithelial cells, and for inhibition of such binding by human milk oligosaccharides. 3. Determine the genetic polymorphisms that underlie maternal and infant secretor and Lewis phenotypes and relate these to heterogeneity in human milk oligosaccharide expression and risk of bacterial diarrheal in breastfed infants. 4. Measure the safety, tolerance and efficacy of the human milk oligosaccharide 2'-fucosyllactose, and related compounds, to protect against Campylobacter and related pathogens in mice. The increased understanding of the pathophysiology of Campylobacter and related pathogens that would result from these studies would allow identification of infants and high risk for these pathogens, and would provide and novel prophylactic and/or therapeutic agents that would be used to prevent and/or treat infections with Campylobacter and related pathogens. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CANCER THERAPEUTICS THAT ANCHOR PROTEINS TO MEMBRANES Principal Investigator & Institution: Peterson, Blake R.; Chemistry; Pennsylvania State University-Univ Park 201 Old Main University Park, Pa 16802 Timing: Fiscal Year 2003; Project Start 01-JAN-2000; Project End 31-DEC-2007 Summary: (provided by applicant): Multidrug resistant (MDR) cancer remains the primary impediment to curative cancer chemotherapy. MDR cancer cells differ from typical tumor cells by dramatically upregulating production of several factors including the drug transporter P-glycoprotein, the cholesterol binding protein caveolin, and components of lipid raft microdomains of cellular plasma membranes. These raft domains are enriched in cholesterol and sphingolipids and play key roles in signal transduction processes. The distinct composition of plasma membranes of MDR cancers may enable selective chemotherapy targeting these cancers. During the last grant cycle, novel small molecules were synthesized that comprise cholesterylamine covalently linked to protein ligands such as biotin. These compounds bind lipid rafts in plasma membranes of cancer cells.Treatment of cancer cell lines with a synthetic biotincholesterylamine ligand (ligand #1) and the protein Streptavidin (SA) efficiently targets SA to lipid rafts, resulting in rapid clathrin-mediated endocytosis of this protein-ligand complex. This novel system mimics penetration of cells by Cholera toxin, which binds ganglioside GM1 in lipid rafts. This project is based on the hypothesis that ligand #1 will regulate endocytosis of SA linked to endosome-activated toxins daunorubicin and exotoxin in cancer cell lines. Since ligand #1 binds lipid rafts, selective delivery of SAlinked toxins to lipid raft-rich MDR cancer cells will be investigated in vitro and in vivo in murine cancer models. The effectiveness of ligand #1 at enhancing endocytosis of Satoxins fused to neuropeptide Y, which targets specific receptors on neuroblastoma cells, will also be evaluated. This novel approach directed at enhancing endocytosis of surface receptors by targeting to lipid rafts with small molecules could address the major problem in immunotherapy of non-internalized tumor antigens. The hypothesis that ligand-regulated delivery of SA to antigen presenting cells (APCs) will stimulate immune responses will also be tested. Novel immunostimulants will be investigated by fusing SA to the ovalbumin antigen, regulating endocytosis in APCs with ligand #1, and analyzing T-cell activation. This approach could control immunostimulation at the molecular level and yield novel tools for vaccine development. Recruitment of intracellular avidin fusion proteins to plasma membranes by ligand #1 will also be studied in an effort to conditionally regulate cellular growth and death Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CART AND THE HYPOTHALAMIC-PITUITARY-THYROID AXIS Principal Investigator & Institution: Lechan, Ronald M.; Professor of Medicine; New England Medical Center Hospitals 750 Washington St Boston, Ma 021111533 Timing: Fiscal Year 2001; Project Start 07-MAR-2001; Project End 31-JAN-2004 Summary: This collaborative study will be performed in Hungary as an extension of NIH grant #RO1 DK-37021, to define the anatomical relationships between cocaine and amphetamine-regulated transcript (CART) and hypophysiotropic TRH neurons in the hypothalamic paraventricular nucleus. It is proposed that in conjunction with the parent grant, these studies will elucidate the role of CART in the regulation of hypophysiotropic TRH and determine how CART is integrated into the central control system as a mediator for the action of leptin on the hypothalamic-pituitary-thyroid axis. The origin of CART-synthesizing neurons that project to TRH neurons in the
14
Cholera
paraventricular nucleus will be identified by a two-step procedure. First, regions of the brain that contain CART-synthesizing neurons and project to the paraventricular nucleus will be identified by a double-labeling immunofluorescent technique following the stereotaxic injection of the retrogradely transported marker substance, cholera toxin subunit B (CTB), into subdivisions of the paraventricular nucleus. Second, by confocal microscopy, it will be determined whether CART-producing neurons from each of the regions where CART-IR neurons accumulate CTB, project specifically to TRH neurons in the paraventricular nucleus. This will be accomplished by a triple-labeling fluorescent technique in which the anterogradely transported marker substance, PHAL and CART will be identified by immunofluorescence in axon terminals contacting proTRH mRNAcontaining neurons in the paraventricular nucleus, and proTRH mRNA will be identified by fluorescent, non-isotopic in situ hybridization histochemistry. Since CART is contained in the majority of TRH-producing neurons in the paraventricular nucleus, a double-labeling immunofluorescent technique will also be used to explore the possibility that the CART innervation to TRH neurons in the paraventricular nucleus may arise from an ultrashort feedback loop from hypophysiotropic neurons, itself. The subcellular organization of CART and TRH in these neurons will be examined by ultrastructural immunocytochemistry to determine whether both substances are packaged in the same vesicles, and whether their packaging is similarly affected by fasting. Finally, the effect of fasting and leptin administration to fasting animals on CART gene expression in hypophysitoropic TRH neurons and in CART-producing neurons that project to TRH-containing neurons in the paraventricular nucleus, will be studied using combined isotopic and non-isotopic techniques of in situ hybridization histochemistry and computerized image analysis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CHEMISTRY OF THE POLYSACCHARIDE OF V CHOLERAE 0139 Principal Investigator & Institution: Bush, C. Allen.; Professor; Chemistry and Biochemistry; University of Maryland Balt Co Campus Baltimore, Md 21250 Timing: Fiscal Year 2001; Project Start 01-JAN-1999; Project End 31-DEC-2002 Summary: (Adapted from abstract): Strain O139 of Vibrio cholerae, identified as a cause of epidemic cholera in Asia, is encapsulated, which raises serious public health concerns. This pathogen is antigenically distinct from O1 strains. The applicant has reported on the covalent chemical structure of the polysaccharide capsule and has initiated studies on the polysaccharide as a vaccine component. A working hypothesis concerning the polysaccharide is that based on analogy to similar epitopes found in Lewis blood group oligosaccharides, four of the six sugar residues in the repeating subunit, adopt a well defined fixed conformation with the linkages to the other two residues forming a flexible hinge. Tests of this idea will involve computer molecular modeling and NMR measurements involving isotope enrichment in 13C and 15N to facilitate approach to structural and dynamics issues. Long range carbon coupling constants, 3JHC and 3JCC, will be measured and correlated with glycosidic dihedral angles. Three-dimensional heteronuclear NMR spectroscopy will provide enhanced spectral resolution in NOESY experiments. Polysaccharide dynamics will be investigated by indirectly measured heteronuclear 13C and 15N relaxation rates, which will be interpreted using spectral density mapping methods as well as several forms of the model-free treatment augmented to include anisotropic tumbling and slower exchange processes. Oligosaccharide fragments will test the hypothesis of a conformational epitope that depends on molecular size. The oligosaccharides are to be
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used in development of chemically modified protein conjugates for vaccine development. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CLASS II MHC TRANSPORT AND FUNCTION Principal Investigator & Institution: Harding, Clifford V.; Professor; Pathology; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2001; Project Start 01-MAY-1994; Project End 31-JAN-2004 Summary: Our overall goal is to understand class II MHC(MHC-II) antigen processing mechanisms and how they may be modulated under different circumstances. In general terms, these studies will address: 1. Poorly understood aspects of the major MHC-II mechanisms. 2. Additional recently discovered processing mechanisms. 3. The means by which these various mechanisms are regulated under different pathophysiologic conditions, e.g. infection. The studies are relevent to understanding host-pathogen interactions (e.g with Mycobacterium tuberculosis), as well as mechanisms of vaccine efficacy (e.g with regard to targeting immunogens to specific antigen-processing pathways for enhancement of protective responses and understanding the mechanistic basis of adjuvant activity, cf NIH PA-97-101. Aim 1. Characterization of distinct endocytic antigen processing mechanisms used for different epitopes and the relative roles of early endosomes and late endocytic compartments in these mechanisms. We will further explore mechanistic differences between late endocytic antigen processing mechanisms and an early endocytic processing pathway that was discovered in experiments funded by this grant during the previous funding period. Aim 2. To characterize the mechanisms of phagocytic antigen processing. We will apply novel technological approaches to isolating and analyzing phagosomes for antigen processing function. Aim 3. To determine the mechanisms by which Mycobacterium tuberculosis inhibits antigen processing. This may be of importance to understanding the maintainance of latent infection by this organism. Aim 4. To characterize the mechanisms whereby cholera toxin (CT) and E. coli heat labile enterotoxin (LT) affect antigen processing. These toxins produce both inhibiting and enhancing effects at different stages of antigen processing and presentation. These studies will shed light on both antigen processing mechanisms and the effects of these adjuvants, which may be used in future human vaccines. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CRYSTALLOGRPHY ENTEROTOXINS
OF
CHOLERA
AND
HEAT
LABILE
Principal Investigator & Institution: Hol, Wim G.; Director; Biological Structure; University of Washington Seattle, Wa 98195 Timing: Fiscal Year 2001; Project Start 01-SEP-1993; Project End 31-AUG-2003 Summary: (Adapted from abstract): This project encompasses a range of structural studies on two secreted bacterial toxins, Escherichia coli heat labile enterotoxin (LT) and cholera toxin (CT). The severe diarrheal disease cause by cholera toxin may result in death within hours. The milder infectious diarrhea produced by LT is rarely lifethreatening in the developed world, but is a major cause of infant death in the third world. Specific aims of this proposal include x-ray crystallographic investigation of the fully active ADP-ribosylating A subunit to reveal catalytic mechanism and substrate binding modes, or engineered variants of the toxins, of the native toxins complexed with candidate inhibitors developed through structure-based drug design, and of hybrid
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Cholera
molecular assemblies which use the native toxin structure as a scaffold for vaccine design. Long-term goals of this project are: (1) to investigate fundamental biological questions including the catalytic mechanism of ADP- ribosylation, structural determinants of toxin assembly, and the structural basis for recognition of complex sacharides. (2) to guide design of drugs effective against enterotoxigenic disease by providing a structural explanation for the biological function and activity of these toxins. LT and CT are 80% identical in sequence, exhibit similar subunit assembly, are immunologically cross-reactive, bind specifically to the same cell surface receptor, and share a common catalytic activity. Three aspects targeted for structure-based drug design are toxin assembly, receptor binding, and catalytic activity. (3) to use the remarkable ability of LT and CT to stimulate the mucosal immune system by designing prototype vaccines which retain the desirable immunological properties of the toxin while minimizing or abolishing the toxic activity. This work comprises structural study of engineered variants of the native toxins and of hybrid protein assemblies which incorporate foreign epitopes into the toxin structure. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CTB AND AUTOANTIGENS--T1D PREVENTION AFTER ORAL FEEDING Principal Investigator & Institution: Von Herrath, Matthias G.; Associate Professor with Tenure; La Jolla Institute for Allergy/Immunolgy Allergy and Immunology San Diego, Ca 921211118 Timing: Fiscal Year 2001; Project Start 30-SEP-2001; Project End 30-AUG-2006 Summary: NO ABSTRACT AVAILABLE Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: DEVELOPMENT OF A LIVE ORAL CHOLERA VACCINE Principal Investigator & Institution: Kaper, James B.; Professor; Microbiology and Immunology; University of Maryland Balt Prof School Baltimore, Md 21201 Timing: Fiscal Year 2001; Project Start 01-JAN-1983; Project End 31-JAN-2006 Summary: (Adapted from the Applicant's Abstract): An ideal vaccine for the prevention of cholera is not yet available. Previous work in this project has resulted in the development of an attenuated live oral cholera vaccine, V. cholerae CVD 103-HgR. This vaccine confers strong protective immunity against experimental challenge with virulent V. cholerae O1 after a single dose. Although this vaccine is highly protective in North American volunteers and has been licensed in several highly developed countries for protection of travelers to cholera endemic countries, a recent field trial of this vaccine in Indonesia failed to show efficacy. The development of attenuated cholera vaccines has been plagued by the fact that V. cholerae strains deleted of the ctx genes encoding cholera toxin can still produce varying amounts of diarrhea and non-diarrheal symptoms such as headache, fever, abdominal cramps, and malaise in many individuals. Such symptoms are not seen with CVD 103-HgR, in all probability because this strain colonizes the human intestine at greatly reduced levels compared to the reactogenic, avidly colonizing ctx-negative strains. Although the reduced colonization of CVD 103-HgR was still sufficient to engender a protective immune response in North American volunteers whose small bowel intestinal flora is relatively sparse, it was not sufficient to induce a protective immune response in a cholera-endemic population with a heavy burden of small bowel intestinal flora which would compete against a live oral vaccine strain. The ability to construct a better-colonizing strain is hampered by the
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uncertainty as to what bacterial factor is responsible for the reactogenicity. Thus, the next period of support for this project will focus on characterizing the response of epithelial cells to adherent V. cholerae, establishing the role in reactogenicity of various cytolysins, proteases, other degradative enzymes, and other potential toxins revealed by the recently completed genome sequence of V. cholerae, and determining the V. cholerae genes that are specifically expressed during the course of human infection. These studies will use the broadest possible range of models to study host-pathogen interactions, including intestinal epithelial cell lines, freshly harvested human intestinal tissue, animal models, and human volunteer studies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DIFFERENTIATION OF SEXUAL BEHAVIOR Principal Investigator & Institution: Baum, Michael J.; Professor; Biology; Boston University Charles River Campus 881 Commonwealth Avenue Boston, Ma 02215 Timing: Fiscal Year 2001; Project Start 01-FEB-1980; Project End 31-AUG-2003 Summary: (adapted from applicant's abstract): The proposed research seeks to understand how sexually dimorphic aspects of forebrain structure control sexually dimorphic aspects of psychosexual and reproductive function in a carnivore, the ferret. The central hypothesis to be tested is that the processing of volatile odors, arising from sexually active conspecifics, by neurons located in different segments of the main olfactory projection to the hypothalamus, differs in males and in females. Studies are proposed to compare the effects of olfactory bulb deafferentation on sexual partner preference in male and female ferrets and to determine whether exposure to male odors augments the capacity of vaginal-cervical stimulation to activate mediobasal hypothalamic LHRH neurons in females. Additional studies will determine whether prenatal inhibition of estradiol biosynthesis in the male ferret brain results in a femalelike pattern of sexual partner preference in adulthood while attenuating the differentiation of a sexually dimorphic cluster of galanin neurons in the dorsal preoptic area/anterior hypothalamus (POA/AH). Other studies will assess the effects of infusing galanin or a galanin antagonist or of excitotoxic lesioning of the dorsomedial POA/AH on ferrets' odor and sexual partner preferences. The effects of these treatments on odorinduced expression of the immediate-early gene, c-fos, in neurons located at different stages of the main olfactory projection to the hypothalamus will also be compared in males and females. Finally, the density of projections from the medial amygdala to several hypothalamic regions will be compared in the two sexes using combined immunocytochemistry for the retrograde tracer, cholera toxin B, and Fos protein. Understanding how the male and female nervous systems process reproductive odors differently in a higher mammal like the ferret could provide new insights into sexually dimorphic brain-behavior relationships in man. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: DISRUPTION OF INTRACELLULAR TOXIN TRANSPORT Principal Investigator & Institution: Kirchhausen, Tomas L.; Cbr Investigator/ Professor; Harvard University (Medical School) Medical School Campus Boston, Ma 02115 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2008 Summary: Many toxins require the normal function of membrane traffic pathways to exert their toxic effects. We recently developed an imaging-based medium-throughput screen with intact cells to identify chemicals that affect different pathways of membrane traffic. From two different screens and using over 19,000 compounds, we identified two
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Cholera
chemicals, exo2 and secramine, with unique and specific effects on the function of cholera toxin and anthrax edema toxin. This suggests a potential novel route to therapeutics to mitigate the effects of these toxins, and possibly also those of ricin and shiga toxin, which, like cholera toxin, enter cells through endocytosis and require transport to the ER to exert their action. We now propose studies to determine the molecular basis for the biological activity of secramine on retrograde traffic from the TGN and the ER and to elucidate its molecular target. The results of these studies will ultimately allow us to design or discover a more potent analog of secramine. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DNA SUPERCOILING: LOCAL AND GLOBAL ASPECTS Principal Investigator & Institution: Schlick, Tamar; Professor; Chemistry; New York University 15 Washington Place New York, Ny 10003 Timing: Fiscal Year 2003; Project Start 01-SEP-1998; Project End 31-AUG-2007 Summary: (provided by applicant): Understanding chromosome organization and its control of gene expression represents one of the most fundamental open biological challenges. Genomic organization and expression are intimately related because the complex structure and dynamics of DNA and protein-bound DNA at a large range of spatial and temporal scales regulate basic processes of life, such as the movement of mobile genetic elements ("mobile DNA") like plasmids or transposons, and transcription initiation. Mobile DNAs are transferred among bacterial pathogens and can propagate bacterial pathogenicity (through virulence genes), as well as drug resistance. While the acquisition of mobile DNAs is only the first of many stages in the evolution of specialized pathogens such as plague, E. coli, cholera, and anthrax, it has been hypothesized that common mechanisms are responsible for regulating intercellular gene transfer in many pathogens. In eukaryotic transcription, the first step in protein synthesis, RNA synthesis can only proceed when the DNA is accessible: through a complex network of nucleosome modifications, variant histones, and remodeling, it is hypothesized that eukaryotic genomes alter states of folding and compaction of the chromatin fiber to control DNA access and, as such, orchestrate (recruit or repress) transcription as needed. Many details of mobile DNA transfer and chromatin organization are unknown. The goal of the proposed work is to elucidate structural/dynamical mechanisms associated with such regulatory control in the transfer of mobile DNAs within genomes and in chromatin organization following histone modifications. Our long-term goals are to integrate structural and dynamics aspects of chromatin organization and regulation with transcription initiation to delineate thermodynamic mechanisms involved. Both processes combine regulatory local protein/DNA interactions with global responses in large systems of protein-bound supercoiled DNA. Based on models and applications completed under prior support, we will integrate protein/DNA conformations at atomic resolution on the nanosecond scale with global aspects of site juxtaposition in supercoiled DNA on the millisecond scale through mesoscale models (which incorporate local details where needed and macroscopic features where possible). Our aims are to: 1) test/delineate the local conformational changes hypothesized to repress transposition in specific transposase monomer, dimer, and inhibitor complexes; 2) determine effects of plasmid superhelicity, DNA interwound conformations, and mobile DNA size on site synapsis times and juxtaposition mechanisms in very long DNA, and thereby estimate the probability of DNA transfer to complement traditional biochemical and genetic approaches to propagation of microbial virulence; and 3) delineate hypothesized crucial electrostatic effects of two sequence variants of histone H2 and modified tails of histones H3 and H4
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on chrornatin organization. Resulting insights can ultimately be exploited to design conditions that might limit mobile DNA propagation and hence microbial pathogen spread, or affect transcription initiation, such as enzymes that regulate DNA super coiling and nucleosome composition and pharmaceutical compounds that interfere with synaptic complexes and chromatin folding/unfolding rearrangements. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ER-LOCALIZED CHAPERONES IN TOXIN PATHOGENESIS Principal Investigator & Institution: Haslam, David B.; Professor; Pediatrics; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2002; Project Start 15-AUG-2002; Project End 31-JAN-2007 Summary: (provided by applicant): Shiga toxin follows a complex intracellular pathway in order to kill susceptible cells. After binding to cell surface glycolipids, the toxin is internalized and trafficked in retrograde fashion to the Golgi and endoplasmic reticulum (ER). From the ER lumen, the toxin must gain access to the cytoplasm, where it enzymatically inactivates the 28S ribosomal RNA, inhibiting protein synthesis. This recently discovered pathway from the endoplasmic reticulum lumen to the cytoplasm represents a cellular quality control mechanism responsible for degrading host proteins that misfold in the ER lumen (termed ER-associated degradation, or ERAD). Shiga toxin apparently "pretends" to be a misfolded host protein, and thereby utilizes the quality control pathway to gain access to ribosomes in the cytoplasm. In yeast, ERAD is known to require a pore called Sec61, as well as chaperones within the ER lumen. The host molecules involved in this pathway in higher eucaryotes are largely unknown. Recently, however, cholera toxin was found to be transported from the ER through Sec61. We devised a genetic screen for molecules involved in shiga toxin trafficking and isolated a cDNA encoding a novel chaperone. This chaperone, which we named HEDJ, was found to be localized to the ER lumen and to interact with Bip, a molecule known to be involved in protein translocation out of the ER. We demonstrate here that HEDJ interacts with shiga toxin in the ER lumen prior to toxin transport. We propose that STx, cholera and other toxins co-opt HEDJ and other chaperones for transport across the ER membrane. However, unlike host molecules transported in this manner, we propose that STx bypasses proteosomal degradation within the cytosol. Using in vitro assays developed in our laboratory, the experiments proposed here will address the role of HEDJ and other chaperones in toxin translocation to the cytoplasm. Sequential coimmunoprecipitation experiments will allow a detailed dissection of the ER-localized chaperones involved in toxin transport. Turning our attention to the toxin, structurefunction analyses will determine which portion(s) of STx enables the molecule to interact with chaperones and exit the ER. Additionally, we will determine whether STx avoids proteosomal degradation and will begin to examine the mechanism of proteosomal avoidance. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GASTRIN REGULATION OF PARIETAL CELL FUNCTION IN MICE Principal Investigator & Institution: Samuelson, Linda C.; Physiology; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2001; Project Start 01-JUN-2001; Project End 31-MAY-2005 Summary: (Applicant's Abstract): This proposal will examine the regulation of stomach acid secretion and the molecular mechanisms involved in the maturation of the acid secreting parietal cell. It takes advantage of a new gastrin-deficient mouse model
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produced in this laboratory by gene targeting in embryonic stem cells. With this model, regulatory mechanisms will be investigated in a novel manner since the investigators can control the maturation of the acid secretory system with the exogenous delivery of gastrin. Physiologic analysis of mouse strains that have been functionally altered by transgenic or gene knockout techniques is the basic experimental approach for this grant application. A re-examination of the central question of histamine's specific role in parietal cells stimulation and acid secretion will be tested as a significant component of this proposal. In addition, the applicant will examine the cellular and molecular changes in parietal cells, which take place during their functional maturation. Aim 1 will test the hypothesis that histamine is required for parietal cell maturation in the gastrin-deficient mice. The applicant will stimulate parietal cell maturation in gastrin-deficient mice under conditions where histamine H2 receptor signaling is blocked with a specific antagonist. Aim 2 will test the hypothesis that increased cyclic AMP in parietal cells is sufficient to induce acid secretion in gastrin-deficient mice. This will be achieved by using a newly developed transgenic mouse model designed to chronically upregulate cyclic AMP levels in parietal cells using the cholera toxin Al fragment. Aim 3 will focus on the molecular changes involved with parietal cell maturation. Parietal cells will be tested for CCK-B receptor and histamine H2 receptor function by analysis of intracellular signaling, morphological transformation and acid secretion. Finally, the applicant will use the differential display technique to identify mRNAs whose expression changes in response to gastrin-stimulated maturation of the acid secretory system. A better understanding of the basic biology of acid secretion and parietal cell function will be valuable for further insight into the pathology associated with acid secretion, which remains a significant health problem. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENE EXPRESSION IN RAT BRAIN Principal Investigator & Institution: Sutcliffe, J Gregor.; Professor; Scripps Research Institute 10550 N Torrey Pines Rd La Jolla, Ca 920371000 Timing: Fiscal Year 2002; Project Start 01-JUL-1983; Project End 30-NOV-2005 Summary: (provided by applicant): We propose to continue our studies on brain mRNAs so as to better our understanding of patterns of brain gene expression, to identify and solve the structures of novel brain proteins with spatially restricted expression within the brain, and to gain insights into their functional nature and their contribution to the behavioral and physiological operation of the organism. We will use the newly developed and automated TOGA technology to identify cDNA clones of mRNAs highly enriched in their expression in the hypothalamus, so as to identify those whose expression is restricted to discrete hypothalamic nuclei, or the striatum, so as to compile a complete dossier on the molecular nature of medium spiny neurons. Fulllength clones of novel ensemble members will be isolated and their sequences determined so as to team the identity of their encoded proteins. The sites of expression will be determined by in situ hybridization and unmunohistochemical methods using antisera to synthetic peptides corresponding to domains of the deduced protein sequences. We will use the acquired information to form hypotheses about function and test these by biochemical measurements on the recombinant protein expressed by bacteria or transfected manimalian cells and by gene inactivation studies. For hypocretin, an excitatory neoromodulatory peptide that is produced by a few thousand hypothalamic neurons, that has been implicated in multiple homeostatic systems, including sleep and feeding, and that is implicated in all human narcolepsies, and for cortistatin, a somatostatin-like sleep-promoting peptide of cortical inhibitory
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intemeurons, we will generate lines of transgenic mice that express the intracellular portions of either diphtheria toxin or cholera toxin and thus either ablate or hyperactivate the neurons that normally produce these peptides. The hypocretin-DT mice will serve as a model for HLA-linked narcolepsy, which is thought to be caused by autoimmune destruction of hypocretin neurons. We will isolate RNA from these several transgenic mouse lines and use TOGA to identify the entire ensemble of mRNAs that are selectively expressed in hypocretin and cortistatin neurons. We will characterize knockout mice with null alleles in the genes encoding: a) 5-HT7, a serotonin receptor expressed prominently in ventral hypothalamus, which is coupled to stimulation of adenylyl cyclase, and whose pharmacology we have shown to be uniquely consistent with that of the 5-HT receptor that mediates circadian phase shifts in hypothalamic slice preparations, and which is a target for the sleep-promoting effects of oleamide, b) RC3/neurogranin, a forebrain-specific calmodulin-binding phosphoprotein which has been implicated in determining the availability of calinodulin and the calcium set point in dendritic spines and possibly in the development of dendritic spines, and c) cortistatin, a neuropeptide of cortical intemeurons that antagonizes the desynchronizing effects of acetylcholine on paired pulse and EEG measurements and enhances slow wave sleep. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENE TRANSFER TO AIRWAY EPITHELIAL CELLS Principal Investigator & Institution: Cheng, Pi-Wan; Professor; Biochem and Molecular Biology; University of Nebraska Medical Center Omaha, Ne 681987835 Timing: Fiscal Year 2000; Project Start 01-JAN-1998; Project End 31-DEC-2003 Summary: (Applicant's abstract): Cystic Fibrosis (CF) is the most common lethal genetic disease among Caucasians. Lung diseases account for greater than 95 percent of the morbidity and mortality. Hence, CF lungs have been targeted for gene therapy. Current gene therapy vectors suffer from low transfection efficiency or induction of host immune response, which preclude them from being used for gene therapy in vivo and invite development of alternative vectors. We have developed a novel gene transfer vector composed of a receptor ligand and a cationic liposome, which yields high transfection efficiency in HeLa cells and immortalized tracheal epithelial cells of a cystic fibrosis patient (CFT1). The formation of liposome-transferrin-DNA complexes correlates with high transfection efficiency. The transfection vectors which contain transferrin, insulin, or cholera toxin could correct the cAMP-dependent chloride conductance defect in CFT1 cells. We propose to test the hypothesis that the liposomereceptor ligand-DNA complex by Sepharose gel chromatography and then characterize the physicochemical properties of the putative transfection complex by biochemical and transmission electron microscopic methods. We will examine if this complex alone or in combination with the receptor ligand and/or liposome yields high transfection efficiency in CFT1 cells, primary cultures of mouse and human airway epithelial cells, respiratory epithelial explants, and then in mouse airway epithelia in vivo. We will also characterize the kinetics of the receptor ligand-facilitated gene transfer using confocal microscopic, biochemical, molecular biological, and immunological techniques to identify the step(s) responsible for the enhancement of the transfection efficiency of liposome-mediated gene transfer. The efficacy of the gene therapy protocols employing a plasmid containing the cDNA encoding wild-type cystic fibrosis transmembrane conductance regulator will be examined in the primary cultures of airway epithelial cells and nasal and tracheal epithelia of CF mouse in vivo. The gene transfer vectors will be assessed for inflammatory and immune responses and cytopathology in normal and CF
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mouse. Correction of cAMP-dependent chloride conductance defect coupled with no immune response to the vectors in CF mouse should be the crucial information needed for planning future human gene therapy trials. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENETIC ANALYSIS OF CHOLERA TOXIN STRUCTURE AND FUNCTION Principal Investigator & Institution: Holmes, Randall K.; Professor and Chair; Microbiology; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, Co 800450508 Timing: Fiscal Year 2002; Project Start 01-FEB-1992; Project End 31-JAN-2007 Summary: (Adapted from the Applicant's Abstract): Approximately 1.5 billion cases of diarrhea cause 4 million deaths annually in children under 5 years old, and 5-7 million cases of cholera cause about100,000 deaths. Cholera toxin (CT) from Vibrio cholerae causes the massive watery diarrhea of cholera. Enterotoxigenic E. coli (ETEC) cause up to 20 percent of diarrheal disease in developing countries, and produce heat-labile enterotoxins called LTI and LTII that are closely related to CT in structure and function. The best current vaccines against cholera provide only moderate protection for short periods of time and are not licensed in the United States, and there are no vaccines for human use against ETEC. CT and related enterotoxins are potent immunogens and mucosal adjuvants, and they are also used widely as tools to investigate the role of heterotrimeric G proteins in signal transduction, the role of gangliosides in endocytosis and vesicular trafficking, the mapping and/or ablation of neural pathways, and many other cell functions. We study the structure and function of CT and use LTI and LTII in comparative studies to explore the molecular basis for functional differences between them. Our long term goals are to elucidate the molecular basis for biological activities of CT and related enterotoxins, and to use that knowledge to design novel structure-based vaccines and therapeutics to prevent or treat enterotoxic diarrheas. CT, LTI or LTII are also being studied widely as vaccine components, adjuvants or immunomodulators to prevent or treat diseases unrelated to enterotoxic diarrheas. Important issues concerning structure and function of CT that are not yet understood include identifying and characterizing: conformational changes that activate the catalytic capacity of CT-A1 after nicking and reduction of CT holotoxin; motifs on CT-A1 that determine its interactions with Gsalpha/beta/gamma as a substrate for ADP ribosylation and with ADPribosylation factors (ARFs) as stimulators of catalytic activity; features of CT-A and CTB that enable them to assemble spontaneously into CT holotoxin; mechanisms by which binding of enterotoxins to plasma membrane receptors determines their trafficking within target cells; and pathway(s) by which CT-A1 is translocated from the ER to the cytoplasm to reach its intracellular target and cause toxicity. During the next project period we will use a wide variety of novel methods from microbiology, genetics, biochemistry, cell biology and structural biology to investigate these important current issues concerning the structure and function of cholera toxin. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GENETIC AND BIOCHEMICAL STUDY OV V. CHOLERASE RTX TOXIN Principal Investigator & Institution: Fullner, Karla J.; Microbiology and Immunology; Northwestern University Office of Sponsored Programs Chicago, Il 60611 Timing: Fiscal Year 2003; Project Start 15-DEC-2002; Project End 30-NOV-2007
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Summary: (provided by applicant): Vibrio cholerae strains that do not produce cholera toxin induce a more inflammatory diarrhea than normal cholera disease, implicating other potent toxins in the pathogenesis of cholera. Several accessory toxins of V cholerae are purported to account for this reactogenic response. One of these factors is the newly discovered VcRtxA toxin of V cholerae. VcRtxA is a large protein toxin that is a unique member of the RTX family Production of this toxin has been evolutionarily conserved by Vibrio sp indicating that maintenance of this large toxin is essential for virulence or survival in the environment. Its cytotoxicity has been further shown to function by a novel mechanism This toxin causes depolymerization of actin stress fibers in both polarized and non-polarized cell lines by a unique pathway Concurrent with depolymerization, the actin molecules become covalently linked together into dimers, trimers, and higher order multimers This observation suggests that covalent crosslinking of actin by the toxin drives actin depolymerization This unusual reaction distinguishes VcRtxA from all other bacterial toxins that cause actin depolymerization. Research performed under this grant proposal will investigate further the novel biochemical properties of this important virulence factor The VcRtxA toxin is the largest single polypeptide protein toxin ever described, however, it is unclear whether the full 4545 amino acid protein is the toxic moiety The size of the toxic moiety and potential post-translational modifications will by identified by examining biochemical properties of the active form of purified toxin The catalytic activity will then be investigated and the role of a putative catalytic domain in this reaction will be assessed. It will then be established whether the toxin is active at the membrane or within the cytoplasm of the target cells, and the role of a putative actin-binding domain will be characterized. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENOMIC PROFILING OF NOVEL VIBRIO CHOLERAE VIRULENCE GENES Principal Investigator & Institution: Provenzano, Daniele; University of Texas at Brownsville 80 Fort Brown Brownsville, Tx 78520 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2007 Summary: Vibrio cholerae is a gram-negative enteric human pathogen that causes Asiatic cholera, a severe and often lethal form of diarrheal disease. V. cholerae is one of a select number of human pathogens that can cause pandemics, epidemics that span the entire globe. Virulent strains of V. cholerae are routinely isolated locally from brackish waters of the Gulf of Mexico and the Rio Grande River and represent a source of contamination to potable water in the event of an environmental catastrophe such as a hurricane or a bioterrorist attack. The leading cause of the dramatic diarrhea caused by V. cholerae infection is cholera toxin (CT) while the element critical for establishment of infection in the small intestine is a type IV pilus named toxin-coregulated pilus (TCP). Synthesis of CT and TCP is tightly regulated by a signal cascade governed by the transcriptional activators ToxR, TcpP, and ToxT. However, the signals encountered and sensed by V. cholerae leading to CT and TCP production in the small intestine remain unknown. The general aim of this proposal is the identification of yet-unknown virulence factors or signaling cascades contributing to colonization and pathogenesis of V. cholerae utilizing a genome-wide approach that exploits the inability of a defined set of colonization-deficient mutants to produce virulence factors in vitro. The utilization of a genome-wide technology is uniquely suited to V. cholerae because of the requirement of the ToxR/TcpP/ToxT virulence cascade for the production of virulence factors in vivo and in vitro and because the growth conditions that induce expression of virulence genes in the laboratory are known. The central hypothesis of this proposal is that among
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mRNA transcripts differentially expressed by wild type, virulent V. cholerae compared to colonization defective mutants, grown under in vitro conditions that induce expression of virulence factors, are those of genes contributing to colonization. The list of genes generated from this effort is expected to include open-reading frames whose functions are yet unknown. Coding sequences identified by this strategy will be targeted for in-frame deletions and new mutant strains will be constructed and tested for activation of virulence factors in vitro and colonization of the infant mouse small intestine. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GEOGRAPHICAL ANALYSIS IN VACCINE EFFICACY TRIALS Principal Investigator & Institution: Emch, Michael E.; Geography; Portland State University Box 751 Portland, or 97207 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2004 Summary: (provided by applicant): This study will develop and test spatial analytical methods for vaccine trials to control for spatially heterogeneous disease exposures (spatial effect modifiers) and spatial bias in disease outcomes (spatial confounders). In 1985, a community-based individually randomized oral cholera vaccine trial was conducted in Matlab, Bangladesh. The double-blind trial measured the efficacy of two vaccines, the B subunit-killed whole cell (BS-WC) and the killed whole cell only (WC) vaccine. Women over 15 and children aged 2 to 15 were the target group in the trial. To identify the cholera cases from the study area, the investigators conducted a passive surveillance at one hospital and two community-based treatment centers. Passive surveillance can introduce bias because access to treatment centers, which is usually a function of distance, influences health-seeking behavior. Also, efficacy might differ in different parts of the study area because socio-environmental circumstances and therefore disease exposure levels vary in space. This study will use a geographic information system (GIS) to determine: (1) how cholera vaccine efficacy varies spatially in the study area; (2) what ecological socio-environmental variables are related to cholera vaccine efficacy (i.e., which variables are effect modifiers); (3) how protective efficacy varies with access to treatment facilities (i.e., whether access is a spatial confounder); and (4) whether cholera incidence in the placebo group is related to vaccine coverage rates (i.e., is herd immunity important?). The study will use three data sets, previously collected by the investigators, including: (1) a large cholera vaccine trial database, (2) a comprehensive longitudinal demographic database of the rural population of approximately 200,000 from which the vaccine trial participants were selected, and (3) an accurate household-level spatial database of the same study area population. The results of this project can help with the design of all future vaccine trials. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: INTERFACES
GLYCOLIPID
TRANSFER--REGULATION
BY
MEMBRANE
Principal Investigator & Institution: Brown, Rhoderick E.; Professor; Hormel Institute; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2001; Project Start 01-MAY-1992; Project End 30-NOV-2001 Summary: The long-term goal of this project is to define the structural parameters of glycosphingolipids that promote formation of membrane domains and to determine the impact of glycosphingolipid membrane organization on the functional regulation of a
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protein that catalyzes the intermembrane transfer of glycolipids, i.e. glycolipid transfer protein. The ability of glycosphingolipids to organize into domains in biological membranes is postulated to be a key feature, not only in their own intracellular sorting and trafficking, but also in the sorting and trafficking of proteins with glycosylphosphatidylinositol covalent anchors. The processes by which glycosphingolipid-enriched domains are formed and maintained are not well understood and may involve specific proteins that can bind and transfer glycosphingolipids between membrane surfaces. By using model membrane systems that provide distinct yet complementary information about lipid-lipid and lipid- protein interactions, the following specific aims will be addressed: (1) to determine the structural features of glycolipids that modulate their mixing interactions with phospholipids and sterols, and to define the physical nature of the lamellar environment that is produced by glycolipid-lipid interactions using monolayer and calorimetric approaches; (2) to ascertain the role that glycolipid lateral organization plays in regulating the activity of glycolipid transfer protein by using monolayer and fluorescence techniques; and (3) to overexpress glycolipid transfer protein using molecular biological approaches and provide a foundation for future investigations of site- directed mutagenized forms of glycolipid transfer protein. Achieving these aims will be of fundamental importance in developing ways to control glycosphingolipid availability and accessibility at the cell surface. Such manipulations could be key to preventing infection by certain bacteria (N. gonorrhea, pathogenic E. coli, and cholera) and viruses (rotaviruses and HIV) as well as lead to better ways to target drugs to the surfaces of tumor cells that express oncogenically-related glycosphingolipids. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HETEROGENEITY OF CAVEOLAE IN INTESTINAL EPITHELIA Principal Investigator & Institution: Badizadegan, Kamran; Assistant Professor; Children's Hospital (Boston) Boston, Ma 021155737 Timing: Fiscal Year 2001; Project Start 01-SEP-2000; Project End 30-JUN-2005 Summary: (adapted from the application) The goal of the proposed studies is to begin to develop an understanding of the determinants of structural and functional heterogeneity in Detergent-Insoluble Glycosphingolipid-rich plasma membrane domains (DIGs) in the intestinal epithelia. DIGs, which include but are not limited to ultrastructurally characteristic caveolae, have been implicated in a variety of key cellular functions such as ligand-induced signal transduction, protein and lipid sorting, and vesicular trafficking. Biochemical preparations of DIGs typically consist of a mixture that include classical caveolae and non-caveolar membranes. Recent studies have suggested that classical caveolae may be biochemically or functionally distinct from the non-caveolar DIGS, and that membranes containing caveolin- I may be separated from other detergent-insoluble membranes. Heterogeneity in non-caveolar DIGs has not been formally addressed before. Our preliminary data suggest that in polarized intestinal epithelial T84 cells (which contain only rare caveolae), DIGs exhibit functional and structural heterogeneity. The observed heterogeneity has elements of epithelial cell polarity, and suggests a contribution of the cytoskeleton in establishment or expression of some of the observed differences. Proposed studies will define the patterns and determinants of heterogeneity of DIGs in polarized intestinal epithelial cells with a special emphasis on DIG/cytoskeleton interactions. These studies address the fundamental issue of cell polarity in epithelial cell biology, and may potentially identify a new aspect of intestinal epithelial cell polarity; namely, polarity in membrane microdomains. Furthermore, by using signal transduction by cholera toxin (CT) in
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intestinal epithelia as a classical model of DIG-mediated function, these studies extend our understanding of the pathogenesis of enterotoxicrenic secretory diarrhea. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HIV ENVELOPE PEPTIDE BASED VACCINE IN SHIV RHESUS MODEL Principal Investigator & Institution: Sastry, Jagannadha K.; Associate Professor; Veterinary Science; University of Texas Md Anderson Can Ctr Cancer Center Houston, Tx 77030 Timing: Fiscal Year 2001; Project Start 01-APR-2000; Project End 31-MAR-2003 Summary: (Adapted from Applicant's Abstract) We hypothesized earlier that an effective vaccination strategy against HIV-induced AIDS should focus on priming cellmediated immunity (CMI) by employing a cocktail of highly conserved epitopes identified to be reactive with multiple MHC haplotypes. Our long-term goal is to formulate a synthetic peptide-based vaccine against HIV because it offers the advantage of being defined, safe and economical. To achieve this goal, we proposed an innovative approach that included employing autologous dendritic cells (DC) for presenting the peptide cocktail and inducing efficient CMI responses for control of infection and pathology by SHIV in a rhesus monkey model. The vaccine consisted of a mixture of six synthetic peptides corresponding to highly conserved regions in the HIV envelope protein gpl60 that we identified in our previous studies, in a series of animal models (murine, rhesus and chimpanzee) and samples from HIV infected people (including long-term nonprogressors), to be capable of inducing HIV-specific CMI responses. The SHIV-rhesus model is best suited for testing the protective efficacy of the peptidecocktail because, SHIV, a chimeric virus comprised of HIV envelope and SIV core, induces AIDS-like disease in macaques, and thus provides the best alternative for testing HIV env-based vaccines and therapeutics. Our study design for the innovation HIV vaccine proposal involved immunizing rhesus monkeys initially with the peptides in Freund's adjuvant followed later by infusions of peptide-pulsed autologous DC that resulted in efficient induction of proliferative and CTL responses in the vaccinated animals. Importantly, upon challenge with SHIV KU -2, efficient clearance of virus infected cells in circulation and reduction in plasma infectivity were observed in all the vaccinated animals but not in the controls, despite uniform infection in all the monkeys initially. In one of the control monkeys this coincided with a precipitous drop in CD4+ cells to below 50 in three weeks, and signs of wasting by week 34, typical of AIDS. These results serve as proof of the principle for a peptide-based vaccine against HIV. Now, we propose to use the same six-peptide cocktail as a vaccine in combination with autologous DC, as sole adjuvant, for priming protective immunity in the SHIV-rhesus model. Additionally, we propose to adopt the SHIV-rhesus model to test the immunogenicity and efficacy of the six-conserved HIV env peptide cocktail for mucosal vaccination strategies employing adjuvants based on novel bacterial toxins that are modified to eliminate toxicity but retain adjuvant capacity. We obtained pilot data showing the effectiveness of mutated forms of cholera toxin and a hitherto untested cytotoxic enterotoxin from Aeromonos hydrophila, as model mucosal adjuvants for inducing HIV env-specific Th and CTL responses in mice. Finally, we propose to formulate a DNA vaccine, consisting of a cocktail of plasmids with mini-gene constructs encoding the six conserved HIV env peptides, and test immunogenicity and protective efficacy in the SHIV-rhesus model. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: HIV/SIV--MECHANISMS OF MUCOSAL TRANSMISSION & PROTECTION Principal Investigator & Institution: Neutra, Marian R.; Professor of Pediatrics; Children's Hospital (Boston) Boston, Ma 021155737 Timing: Fiscal Year 2001; Project Start 01-NOV-1993; Project End 31-OCT-2002 Summary: The goal of this Collaborative Mucosal Immunology Group is to provide basic information that will lead to design of mucosal vaccines that elicit anti-gpl2O secretory IgA (slgA) antibodies in rectal and cervical secretions of women, and that reduce the risk of sexual or vertical transmission of AIDS. Project l is focused on enhancing M cell uptake of gpl2O-containing vaccines administered orally or rectally, induction of anti-gpl2O IgA antibodies on rectal and female genital mucosal surfaces, and testing the protective potential of specific IgAs. The project has three aims: Aim I is to test novel methods for targeting of gpl2O proteins or peptides to M cells at intestinal and rectal inductive sites, and to evaluate resulting anti-HIV slgA in rectum, cervix and vagina. Selected recombinant gpl2O and polymeric gpl2O peptides (including cholera toxin conjugates provided by Project 2) will be delivered on M cell-targeted particulate carriers and liposomes by oral and rectal administration, and by direct application to follicle-associated epithelia. Alternative strategies will be evaluated by quantitating M cell adherence and transport, and by ELISA measurement of specific IgA levels in secretions retrieved with absorbent wicks from local mucosal surfaces. Aim II is to determine whether live, attenuated SIV particles are efficiency transported by rectal or intestinal M cells in mice and monkeys, and to assess the local mucosal immune response to this type of candidate vaccine. Triple-attenuated SIV will be applied to explants of monkey rectal mucosa in vitro, and mouse/rabbit Peyer's patch and rectal mucosa in vivo. M cell transport will be assessed by EM and immuno- cytochemistry. Monkeys and mice will be immunized rectally or vaginally with attenuated SIV, and local (rectal and cervical) anti-SIV IgA secretion will be measured by the ELISA/wick method. Aim III is to produce and characterize anti-gpl2O monoclonal IgA antibodies that recognize and precipitate intact HIV or SIV particles, and to test their abilities to prevent viral contact with epithelial and target cell surfaces. Using effective particulate vaccines identified in Aim I and attenuated SIV from Aim II, mice will be mucosallyimmunized, IgA hybridomas will be generated from Peyer's patch or rectal lymphocytes, and the epitope specificities of the anti-gpl2O monoclonal IgAs will be determined. IgAs will be tested for their capacity to precipitate HIV, to protect HIVsusceptible cells in vitro, and to prevent contact of virus, gpl2O-coated particles, or gpl2O-expressing cells with epithelial surfaces in vitro. The information gained in this project will clarify the potential role of mucosal immunity in prevention of AIDS, and will contribute to design of an effective mucosal vaccine against HIV. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: HORMONE REGULATED GTP BINDING PROTEINS Principal Investigator & Institution: Hildebrandt, John D.; Professor and Chair; Pharmacology; Medical University of South Carolina 171 Ashley Ave Charleston, Sc 29425 Timing: Fiscal Year 2001; Project Start 01-JUL-1991; Project End 30-JUN-2004 Summary: Heterotrimeric G proteins mediate signaling across the plasma membranes of cells for many hormones and neurotransmitters, as well as for a wide variety of other regulatory agents. They are known or likely sites for disease processes such as cholera and pertussis, and their role in cellular regulation makes them likely contributors to the
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pathology, if not etiology, of complex diseases such as diabetes, essential hypertension and cancer. Understanding how these proteins function in normal signaling events is essential to describing their role in disease states and to providing information about the future possible development of these proteins as targets for pharmacologic intervention. One of the two main hypotheses upon which this research is based is that the widespread involvement of these proteins in cell signaling depends upon the immense structural and functional diversity of the G protein subunits. A primary objective of the proposed studies is to define the role of subunit diversity in signaling by heterotrimeric G proteins. Thus, the first two Specific Aims are: (1) To determine the origin and nature of the structural diversity of the beta and gamma subunits of G proteins. These studies take advantage of protein chemistry and mass spectrometry expertise associated with this project. (2) To determine the functional differences between Gbetagamma dimers containing (a) different beta or gamma isoforms or (b) differently modified gamma subunit isoforms. These studies use primarily molecular biology approaches to apply the information generated under Specific Aim 1 to the biochemical characterization of the G protein subunits. An important functional step in the action of G proteins is the GTP-dependent dissociation of their a subunit from their associated betagamma dimer. This reaction has diverse implications for the cellular signaling processes mediated by G proteins, in large part due to their structural and functional diversity. We hypothesize that G protein subunit dissociation is a key step in signal transduction that can determine to what signals cells respond, as well as the nature of that response. To test this hypothesis the third Specific Aim is: (3) To determine the physiological role of subunit dissociation in intact membranes and intact cells. These studies will specifically test whether the G protein subunit diversity characterized under Specific Aims 1 and 2 is utilized by cells to generate changing patterns of G protein heterotrimers with varying signaling properties. The results of this project will define the potential range of functional diversity associated with these proteins, and in so doing define their diversity as potential drug targets. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: IMMUNE RESPONSE MODIFYING VACCINES FOR ASTHMA Principal Investigator & Institution: Levy, Shoshana; Professor; Medicine; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2001; Project Start 01-JUL-1999; Project End 30-JUN-2004 Summary: The long-term goals of this project are to develop novel immune responsemodifying vaccines for the treatment of asthma. Asthma is a major public health problem, and affects 15 million Americans, roughly 5-8 percent of the population. It has increased substantially in prevalence and in terms of mortality and morbidity over the past two decades, and this increase has occurred despite a substantial improvement in our understanding of asthma pathophysiology and the availability of improved medications for asthma. We propose to generate therapeutic fusion proteins and constructs for asthma by molecularly linking a prototypic allergen, ovalbumin (OVA), to an immune response polarizing cytokine, IL-18, and to a tolerogenic agent, cholera toxin, subunit B. We will use these immunotherapeutic agents in a murine model for asthma, and convert established, pathogenic Th2-dominated, allergic inflammatory responses into protective responses. The proposed studies are based on our previous results, which demonstrated that allergen immunotherapy improves allergic disease by correcting the underlying immune dysregulation, and that the efficacy of immunotherapy can be greatly improved by the use of antigen-cytokine fusion constructs. These constructs, by directing the activity of potent cytokines and other
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agents towards antigen-specific T cells, rectify the cytokine profile and activity of such pathogenic allergen-specific Th2 cells. Here we propose to produce and study more potent allergen-fusion proteins as well as cDNA plasmid vaccines containing OVA and IL-18 in established models of allergic inflammation and airway hyperreactivity. In addition, we will determine the role of allergen specific Th1 cells, other regulatory T cells (Th3, CD8, or gammadelta T cells), and of peripheral tolerance in down regulating allergic inflammation and asthma. These innovative studies will provide the basis for development of new disease-modifying strategies to treat and potentially cure patients with allergy and asthma. In addition, these studies will expand our understanding of the role of T cells that protect against these common disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: IMMUNE RESPONSES IN TUBULIN INDUCED HEARING LOSS IN MICE Principal Investigator & Institution: Yoo, Tai J.; Medicine; University of Tennessee Health Sci Ctr Health Science Center Memphis, Tn 38163 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2008 Summary: (provided by applicant): The long term objective of this project is to develop a new gene vaccination therapy for the autoimrnune hearing loss and Meniere's disease in humans. The immediate goal of this study is to induce autoimmune hearing loss induced by beta,-tubulin in mice to quantify immune responses and to modulate the hearing loss by immunologic methods. The specific aims are as follows. 1. To induce autoimmune hearing loss in mice strains -using varying concentrations of Tubulin. 2. To quantify the Immune response by analyzing Thl and Th2 cell functions. 3. To modulate tubulin-induced hearing loss by immunological means. 4. To determine if oral feeding of tubulin would prevent or improve hearing loss. This will eventually enable us to develop a new therapeutics: a naked DNA vaccine for hearing loss; Meniere's disease and autoimmune sensorineural hearing loss. These goals will be achieved as follows. 1. Mice w ill be immunized with varying concentration of tubulin to enhance the incidence of hearing loss. 2. The immune response will be quantified by a. By measuring IgG classes of immunoglobulin : circulating (by ELISA), and detect tubulin specific IgG classes of antibodies in the ear tissues by immunohistochemistry. b. By measuring cytokines IL-2, IFNg]amma, IL-4, IL-10, TGF-beta following tubulin immunization and induction of hearing loss. 3. Tubulin induced hearing loss will be modulated by following immunologic methods. a. By administering dendritic cells engineered to express tubulin (plasmid transfection) b. By administering plasmid DNA expressing IFN-gamma to enhance the disease severity. c. By administering plasmid DNA expressing TGF-beta, IL-10 or IL-4 to reduce the disease severity. 4. Oral tolerance study will be carried out by feeding (low dose, medium dose or high dose and cholera toxin B chain linked antigen) of tubulin in mice before or after immunization with tubulin to determine the efficacy of oral tolerance as either preventative measure or therapeutics. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: IMMUNE RESPONSES TO V. CHOLERAE INFECTION IN BANGLADESH Principal Investigator & Institution: Calderwood, Stephen B.; Physician/Chief; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2001; Project Start 05-SEP-2000; Project End 31-AUG-2005
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Summary: (adapted from application abstract): Vibrio cholerae causes a severe, dehydrating, and occasionally fatal diarrhea in humans. There are an estimated 5-7 million cases worldwide of cholera, with more than 100,000 deaths. Much of the impact of cholera occurs in developing areas of the world, particularly in South and Southeast Asia such as Bangladesh and India. Infection with V. cholerae induces long-lasting protective immunity to subsequent cholera, although the immune responses mediating protection are not fully understood. Many of the previous field studies of immune responses to V. cholerae infection were done in the 1970s, prior to the advent of more modern techniques for measuring mucosal immune responses, such as the use of antibody-secreting cell assays. More recent studies of V. cholerae infection in normal volunteers, many done in the United States, have provided important information on immune responses to infection with this pathogen, but these responses may differ substantially than those in patients in endemic areas, particularly as relates to the influence of age, morbidity, malnutrition and prior exposure to related antigens. Much work has been done recently on development of effective live, oral, attenuated V. cholerae vaccines, both for prevention of clinical cholera and as vectors for expressing heterologous antigens to protect against other infections at mucosal surfaces. This proposal would establish a long-term collaboration between scientists in the US and at the International Centre for Diarrhoeal Disease Research in Bangladesh to elucidate immune responses and protection from cholera infection in an endemic population. The Long-Term Goals of this project are to better understand mucosal immune responses after V. cholerae infection and vaccination, and to assess the effect of patient and microbial factors on these responses that may explain differences observed between patients from endemic areas and normal human volunteers. The Specific Aims of the proposal are: 1) determine the full range of immune responses, particularly mucosal antibody responses, in patients with cholera in Bangladesh, comparing vibriocidal and mucosal antibody responses and stratifying these responses by patient and microbial characteristics. We will test the hypothesis that the serum vibriocidal response represents a surrogate marker for a mucosal response to a relevant antigen or antigens that is actually protective: 2) correlate mucosal anti-V cholerae antibody levels on exposure to the organism with protection from subsequent clinical cholera. We will examine the hypothesis that pre-existing secretory immunity to LPS. CtxB, MSHA and/or TcpA at the time of colonization of V. cholerae protects against subsequent illness: 3) assess immune responses to CtxB at distant (non-intestinal) mucosal sites after clinical cholera, as a model for immune responses to heterologous antigens expressed by live, oral, attenuated V. cholerae vaccine vectors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: IMMUNOMODULATION IN INFECTIOUS DIARRHEA Principal Investigator & Institution: Klapproth, Jan-Michael A.; Medicine; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2008 Summary: (provided by applicant): The goal of the principal investigator is to continue to develop intellectual, technical, and analytical skills to become an independently funded physician-scientist investigator in microbial pathogenesis, examining the effect of bacterial products on the immune system. The program to achieve this goal will consist of additional didactic and laboratory training in basic immunology, lymphocyte signal transduction, and microbial and molecular genetics. Bacterial immunomodulatory products are of utmost importance in infectious diseases and their prevention. For example, C. difficile toxin A and B are implicated in the development of
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pseudomembranous enterocolitis, and cholera toxin functions as an adjuvant in oral immunization. In this proposal we will continue to characterize a novel toxin from Enteropathogenic E. coli (EPEC), resulting in marked inhibition of T cell activation. The inhibitory gene, lifA (lymphocyte inhibitory activity), encodes for a protein with the putative size of 366kDa. The lifA gene product, lymphostatin, bears significant similarity to the N-terminus of large Clostridial cytotoxins, encoding for a glucosyltransferase motif, which is critical for their specific activity. Similar immunosuppressive genes and biological activity have been identified in related bacteria, including other EPEC strains, Enterohemorrhagic E. coli, and the mouse pathogen C. rodentium. Our hypothesis is that the glucosyltransferase motif in lymphostatin is critical for the observed immunosuppression, leading to inhibition of defined lymphocyte subpopulations of the adaptive immune response and allowing firm establishment of enteric Gram negative infection. To test the hypothesis, we propose: Aim 1: To identify the co-substrate and target molecule(s) in lymphocytes exposed to lymphostatin. Aim 2: To investigate intracellular activation pathways in defined lymphocyte populations affected by lymphostatin, resulting in suppression of IL-2, IL-4, and IFN-gamma expression. Aim 3: To investigate whether lymphostatin suppresses the mucosal adaptive immune response and firmly establishes C. rodentium enteric infection in vivo. The proposed research project will contribute to the understanding of immune mechanisms involved in the pathogenesis of chronic infectious diarrhea and gastrointestinal inflammation as seen in Crohn's disease and ulcerative colitis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: IN VITRO AND IN VIVO EVALUATION OF GRANULYSIN DERIVATIVES Principal Investigator & Institution: Krensky, Alan M.; Shelagh Galligan Professor of Pediatrics; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2008 Summary: Granulysin is a 9 kD a-helical protein expressed by human natural killer cells and T lymphocytes. Recombinant granulysin lyses both mammalian cells and a broad spectrum of microbes. Synthetic peptides (10-30 residues) corresponding to the central region of granulysin recapitulate its lytic activity. In a subset of these peptides, replacement of cysteine or arginine residues, or introduction of D-amino acids to disrupt the a-helix, results in the loss of activity against mammalian cells with little or not effect on antimicrobial activity. The goal of this Project is to evaluate candidate immunotherapeutics based on the granulysin sequence for biodefense and for treatment of antibiotic resistant organisms. The specific aims are: 1) assay in vitro all first generation substituted peptides generated in Project 1 for activity against Vibrio cholerae, Salmonella typhimurium, Escherichia coli, Bacillus cereus, Pseudomonas aeruginosa, Staphlococcus aureus, Mycobacterium tuberculosis, human lymphocytes, and human erythrocytes; 2) assay in vitro all second generation derivative compounds produced in Project 1 on the same panel of microbes as well as on a panel of antibiotic resistant clinical isolates; and 3) evaluate the most promising compounds in vivo in three models: topical application in a murine wound model of infection; intragastric or intraintestinal application in the infant mouse and rabbit ileal loop models of cholera; and aerosol treatment of inhaled Mtb in a mouse model. The dose, kinetics, and synergy with conventional antibiotics will be assessed. Results from this Project should identify promising candidate compounds that can be advanced to clinical trials. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: INTESTINAL DISEASE: ENTEROCYTE/TOXIN INTERACTION Principal Investigator & Institution: Lencer, Wayne I.; Associate Professor; Children's Hospital (Boston) Boston, Ma 021155737 Timing: Fiscal Year 2001; Project Start 01-SEP-1993; Project End 31-MAY-2006 Summary: (Applicant's Abstract): Cholera toxin (CT) produced by Vibrio cholerae is the virulence factor responsible for the massive secretory diarrhea seen in Asiatic cholera. To induce disease, CT must bind ganglioside GM1 on the host cell apical membrane, enter the cell by endocytosis, and then somehow cross the cell to activate adenylyl cyclase on the cytoplasmic surface of the basolateral membrane. The investigator published data show that CT may move retrograde through Golgi and ER before arrival at the basolateral membrane, and that sorting into this pathway may depend on the lipid-based membrane anchor provided by the toxin's receptor GM1. GM1 concentrates CT in detergent-insoluble glycolipid-rich apical membrane microdomains (DIGs or "lipid rafts"). The applicant hypothesizes that GM1 endows CT with a lipid-based sorting motif that specifies association with DIGs and trafficking into the apical endosome, Golgi cisternae, ER, or transcytotic pathway. It is also not known how the toxin's enzymatic A-subunit enters the cytosol of host cells. Since CT must enter the ER for bioactivity, the investigator hypothesizes that C2 opportunistically utilizes the ER associated degradation system (ERAD) to unfold and cross the membrane via a protein translocase, possibly sec61p. To test these ideas, the applicant will define whether the ceramide domain of GM1 specifies the selective association with DIGs and toxin action in polarized T84 cells. The PI will use toxin variants deficient in clustering GM1 to test if cross-linking individual gangliosides is a prerequisite for association with DIGs or toxin function. The PI will examine raft dependence on membrane cholesterol by using betamethyl-cyclodextrin, heterogeneity in GM1 content by using a CT variant attenuated in binding GM1, and functional association with the cortical cytoskeleton by membrane fractionation, disruption of actin filaments, and depletion of cholesterol. To test whether GM1 specifies toxin sorting into Golgi and ER, as opposed to the endosome-lysosomal or direct transcytotic pathway, the intracellular itinerary of CT (that binds GM1) and the closely related E. coli toxin LTIIb (that binds ganglioside GD1a) will be systematically compared. Toxin entry into the Golgi or ER, will be defined by microscopy and by exploiting the trans-Golgi specific transfer of sulfate and the ER specific transfer of Nlinked oligosaccharides to label CT in these compartments. The mechanism of toxinunfolding and dislocation from the ER to cytosol will be examined in vitro using purified ER lumenal and membrane proteins, and in intact T84 cells through the use of selected toxin variants lacking sites for proteolytic nicking, ubiqitination and the cysl87199 disulfide bond in the toxin's enzymatic A-subunit. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: INTRACELLULAR TRAFFICKING OF IMMUNOTOXINS Principal Investigator & Institution: Press, Oliver W.; Professor of Medicine; Fred Hutchinson Cancer Research Center Box 19024, 1100 Fairview Ave N Seattle, Wa 98109 Timing: Fiscal Year 2001; Project Start 01-MAR-1992; Project End 31-DEC-2003 Summary: (Adapted from the applicant's abstract): Immunotoxins synthesized by conjugating cytotoxic plant proteins to monoclonal antibodies recognizing tumorassociated antigens have appeared promising in pre-clinical studies but have shown only modest efficacy so far in clinical trials. To kill target cells, immunotoxins must be internalized after binding to surface antigens and a commonly used plant protein, ricin A-chain must be delivered to cytosolic ribosomes where the 60S subunit is irreversibly
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inactivated. The overall objective of this project is to investigate methods of manipulating the intracellular routing of immunotoxins, so that the therapeutic index can be improved. Emphasis will be placed on facilitating translocation of toxins to the cytosol since this is the rate-limiting step in cell intoxication. Four specific goals are enunciated: First, the investigator will identify and characterize the membrane proteins normally involved in ricin A-chain translocation by a "nearest neighbor" cross-linking strategy. The importance of translocation-associated membranes identified by crosslinking will be verified by membrane glycoprotein depletion and reconstitution experiments. Second, the prevailing hypothesis will be tested that endoplasmic reticulum "translocon" pores are critical for toxin translocation by selective immunodepletion of the Sec 61p and TRAM proteins which are known to be essential structural and functional components of the ER translocon channels. Third, mutant ricin A-chain constructs will be genetically engineered which express in tandem amino acid sequences targeting the toxin to translocation-competent intracellular compartments (e.g., GOLGI, ER) followed by sequences possessing novel "pore-forming" domains (e.g., GALA) for membrane penetration. Fourth, the translocation efficiency of immunotoxins will be enhanced by chemical conjugation to polycarboxylic acids (e.g., polypropylacrylic acid) which undergo conformational changes upon transfer from the neutral extracellular compartment to the acidic environment of endosomal compartments. These conformational changes result in endosomal membrane disruption permitting rapid egress of ricin A-chain to the cytosome. It is believed in a more complete comprehension of the events involved in the intracellular trafficking and translocation of ricin A-chain should permit synthesis of more effective clinical reagents. Furthermore, the studies in this project are believed to be important independent of immunotoxin therapy since similar toxins mediate many important medical syndromes (diphtheria, Shigellosis, Cholera, Pseudomonas shock) and because the basic mechanisms underlying protein translocation across biological membranes remain poorly understood. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: INTRINSIC ANATOMY OF THE CIRCADIAN RHYTHM SYSTEM Principal Investigator & Institution: Morin, Lawrence P.; Professor; Psychiatry and Behavioral Scis; State University New York Stony Brook Stony Brook, Ny 11794 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2006 Summary: (provided by applicant): The clock governing such mammalian circadian rhythms as the sleep-wake or activity-rest cycles is located in the hypothalamic suprachiasmatic nucleus (SCN). Recently, several studies have demonstrated that areas within a single SCN oscillate out of phase with respect to one another. In order to properly understand the spatial issues relating to phasic activity at the cellular level in the SCN, it is necessary to have a careful description of the SCN itself. Despite the very large volume of literature on the topic, there has been no complete, three dimensional evaluation of the SCN intrinsic anatomy in any species. The vast majority of studies have used adjacent tissue sections to compare relative spatial locations of cell types within the nucleus; many fewer experiments have employed double label methods to determine whether individual cells contain two distinct neuromodulators. The proposed work will use immunohistofluorescence techniques to study combinations of three labels in order to determine their specific locations in the SCN. Importantly, all the work will be performed with animals pretreated with colchicine.Preliminary data show that all SCN neurons are darkly immunoreactive for GABA. This neuromodulator will serve to define the nucleus and anchor the locations of cells immunoreactive (IR) to other
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neuromodulators. There are neuron groups in the hamster SCN immunoreactive to GAGA, substance P, calbindin, calretinin, vasoactive intestinal polypeptide, vasopressin, cholecystokinin, and gastrin releasing peptide. The distribution of GABA cells encompasses the entire nucleus, vasopressin and cholecystokinin neurons occupy a dorsomedial location; substance P, gastrin releasing peptide, calbindin and calretinin cells are found in a central subnucleus; and vasoactive intestinal polypeptide neurons are found in a ventrally located area. There appears to be fairly extensive overlap among certain of the cell distributions. The exact locations of the cell types and their locations of overlap and co-localization of neuromodulator will be determined, and function will be assessed by evaluating co-localization of light-induced protein markers. In addition, the locations of the various cell types will be determined with respect to the terminal fields of the three main SCN-afferent projections, the NPY-IR geniculohypothalamic tract from the intergeniculate leaflet, the serotonin-lR projection from the median raphe nucleus and the retinohypothalamic projection identified by cholera toxin B fragment-IR following an eye injection. Presynaptic terminal identity will be confirmed by the presence of synaptophysin-IR. Work on the hamster will be extended to the mouse and we will determine which cell types exhibit light-induced gene expression in response to nocturnal light exposure. The results will provide the anatomical framework necessary for interpretation of future physiological and molecular experiments. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: JEOL JEM-1010 TRANSMISSION ELECTRON MICROSCOPE & CAMERA Principal Investigator & Institution: Compton, Duane A.; Associate Professor; Biochemistry; Dartmouth College 11 Rope Ferry Rd. #6210 Hanover, Nh 03755 Timing: Fiscal Year 2002; Project Start 01-JUN-2002; Project End 31-MAY-2003 Summary: (provided by applicant): This proposal is for the acquisition of a new transmission electron microscope and digital camera for use in NIH funded research and training, and other research, as well as undergraduate education. NIH-funded research on identification of proteins and characterization of molecular mechanisms involved in organizing microtubule minus ends at spindle poles in mammalian cells, interaction of Staphylococcus aureus with mammalian cells, and human colonization by the bacterium Vibrio cholera , all depend on high quality transmission electron microscopy for examination and evaluation of experiments. The transmission electron microscope (ThM) chosen is a JEOL USA, Inc. JEM-lOlO TEM, a 100KV microscope with 0.2 nm resolution, high tilt (+ or -60 degrees) pole piece, while the camera is a Gatan, Inc. Model 792 BioScan 1K by 1K wide angle CCD camera. The microscope and camera will be housed in the Rippel Electron Microscope Facility (REMF), an institutional resource, where it will be covered by service contract and a full time staff for training, research assistance and maintenance. The existing Faculty Advisory Committee will be extended to include the PIs for the purpose of ensuring access to the TEM. The TEM? to be replaced is 24 years old and has an anticipated life of no more than two years, despite having been continuously under service contract. The research of the principle investigators cannot be completed without continued availability of a transmission electron microscope. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: LIPOSOMAL S MUTANS DELIVERY SYSTEM FOR CARIES IMMUNITY Principal Investigator & Institution: Childers, Noel K.; Associate Professor; Pediatric Dentistry; University of Alabama at Birmingham Uab Station Birmingham, Al 35294 Timing: Fiscal Year 2001; Project Start 01-AUG-1992; Project End 30-JUN-2003 Summary: (Adapted from the Applicant's Abstract): Despite preventive measures that have been developed, dental caries persists as a major worldwide disease. Although not the most devastating, this infectious disease may be the most prevalent and costly disease in developing, as well as industrialized countries. Secretory IgA is a first line of defense against pathogens that invade through the oral cavity, including Streptococcus mutans (the bacterium associated with caries initiation). Despite extensive efforts on the development of a mucosal vaccine against microbial pathogens, (e.g., S. mutans), this route of immunization is only recently being recognized as the preferred route, compared to the conventional systemic route in inducing protective immunity. Recent preliminary human immunization studies have consistently found salivary S-IgA responses to S. mutans when liposomal antigens are given orally; however, the salivary responses were of low magnitude and short duration. In order to improve the magnitude and persistence of salivary responses to the mucosal liposomal vaccine, two new routes of immunization and adjuvants will be investigated in this proposal. Specifically, the proposed studies will determine the effectiveness of three liposome vaccines containing S. mutans glucosyltransferase (Cholera toxin B subunit [CTB]Liposomes, monophosphoryl lipid A [MPL]-Liposomes, Conventional Liposomes) to induce oral mucosal responses when administered by gastric, nasal, or topical routes in an experimental rat caries model. The results of the proposed animal studies, and those of previous clinical studies, are intended to provide supporting evidence and rationale for the design of human protocols aimed at inducing potential salivary immune responses to S. mutans vaccines by FDA Phase I studies. Following a dose response study, a double blind FDA Phase II clinical study (involving experimental and control groups of 100 subjects) is proposed to study the immunogenicity and efficacy of the identified optimal liposomal S. mutans vaccine and route. The objective of this proposal is to identify a "candidate" vaccine against S. mutans-induced dental caries. It is suggested that these studies will enhance the design and development of a dental caries vaccine, as well as liposomal-immunization strategies for use in inducing protective mucosal responses to various other pathogen-induced diseases. It is anticipated by the applicants that, pending favorable identification of an immunization route and delivery system, a candidate mucosal vaccine against dental caries will be ready for field trials (FDA Phase III studies) upon completion of these studies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: LIVE ATTENUATED SALMONELLA VACCINE FOR BOTULISM Principal Investigator & Institution: Galen, James E.; University of Maryland Balt Prof School Baltimore, Md 21201 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2008 Summary: Botulinum neurotoxin (BoNT) is the most toxic substance known to science. Recent advances in molecularly engineered vaccines have shown that multiple doses of recombinant C-terminal domains (Hc) of BoNT confer protection in animals challenged with 10(6) LD50. The goal of this Project is to develop a more efficient vaccination schedule: live vector-based multivalent botulinum vaccines will be developed to prime vaccinees such that they will mount responses that are faster, higher and stronger than
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without such priming. We will develop 2 "generations" of S. Typhi-based live vector vaccines. The first generation (Category 1) consists of live vectors expressing individual Hc domains from 4 serotypes; the second generation (Category 2), will yield single live vector strains expressing up to 4 different Hc serotypes. It is our intention to coadminister the final mutivalent product with a cholera-based vaccine (Project 4) against the remaining 3 serotypes. Products 1 - 4: The attenuated S. Typhi vaccine CVD 908htrA will be used as a live vector to individually express BoNT/A-Hc, BoNT/B-Hc BoNT/E-Hc. and BoNT/F-Hc from a genetically stabilized expression plasmid. The individual Hc serotypes will be targeted to the periplasmic space, the bacterial cell surface, or will be exported out of CVD 908-htrA into the extracellular environment. Products 5 - 7: Using the constructs and information generated in development of Products 1- 4, we will proceed to co-express subcellular location-optimized BoNT/AHc, B-Hc and F-Hc simultaneously from a single operon, encoded by a genetically stabilized expression plasmid in CVD 908-htrA (Product 5). Related to Product 5, Product 6 will co-express subcellular location-optimized BoNT/B-Hc, E-Hc, and F-Hc from a single operon encoded by a genetically stabilized expression plasmid. Product 7 will comprise CVD 908-htrA in which the four Hc serotypes are encoded by a single operon contained on a stabilized expression plasmid, on which transcriptional control of the operon has been optimized. These remaining 3 products will be ready for human testing by the end of the fifth year of this proposal. We expect that one or more of the second generation vaccines should result in excellent priming of the human immune system. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: M. TUBERCULOSIS INFECTION IN THE LUNG Principal Investigator & Institution: Boom, W Henry.; Professor of Medicine; Medicine; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2001; Project Start 30-SEP-1995; Project End 31-MAY-2006 Summary: (Adapted from the Applicant's Abstract): The lung is the major portal of entry for Mycobacterium tuberculosis, the cause of human tuberculosis. The lung is the site where immune responses to this bacterium are initiated, and where growth of the organism is controlled without complete eradication. Acquire immunity of T cells and macrophages controls infection in the majority of healthy individuals. The lung is not only the first site of infection, but also uniquely susceptible to M. tuberculosis. Mechanisms responsible for susceptibility of the lung to M. tuberculosis and the inability of acquired immunity to eradicate the bacteria are poorly understood. The murine model of aerogenic mycobacterial infection provides an excellent means to analyze the initiation and effector phases of acquired immunity to mycobacterial infection in the lung. This competitive renewal application for HL-55967 builds on the collaborative infrastructure developed during the last 4 years between Case Western Reserve University (CWRU) and Colorado State University (CSU) aimed at addressing immune mechanisms responsible for control of mycobacterial infection in the lung. The PI hypothesizes that mechanism(s) for the pulmonary susceptibility to M. Tuberculosis differ(s) according to stage and site of infection. Initially, M. Tuberculosis resists innate immune mechanisms in lung and uses alveolar and interstitial spaces as privileged sites. As acquired immunity develops, the ability of M. Tuberculosis to inhibit the function of antigen-processing cells becomes a dominant means to assure its survival within the lung. This hypothesis leads to the following specific aims: Aim1: To determine the mechanism(s) responsible for permissive mycobacterial growth in alveolar and interstitial lung macrophages and the role of chemokines and NK cells in control of
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mycobacterial growth during the innate phase of pulmonary M. Tuberculosis and M. bovis BCG infection. Aim2: To determine the ability of lung antigen presenting cells (alveolar macrophages, lung parenchymal macrophages and lung dendritic cells) to activate naive and memory T cells, and the mechanism(s) used by M. Tuberculosis to interfere with class II MHC antigen presenting cell function. Aim 3: To determine the ability of chemokines, CpG and cholera toxin to enhance innate and acquired immune defenses to M. bovis-BCG and M. Tuberculosis within lung. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MECHANISM ADJUVANTICITY
OF
CHOLERA
TOXIN
AND
E
COLI
LT
Principal Investigator & Institution: Clements, John D.; Professor & Chairman; Microbiology and Immunology; Tulane University of Louisiana New Orleans, La 70118 Timing: Fiscal Year 2001; Project Start 01-APR-1998; Project End 31-MAR-2003 Summary: The WHO report of Infectious Disease deaths for 1995 indicated that there were more than 13 million deaths world-wide during that year. The majority of those deaths were caused by organisms that first make contact with and then either colonize or cross mucosal surfaces to infect the host. A number of strategies have been developed to facilitate mucosal immunization to prevent these diseases, including addition of bacterial products with known adjuvant properties. The two bacterial products with the greatest potential to function as mucosal adjuvants are cholera toxin (T), produced by various strains of Vibrio cholerae, and the heat-labile enterotoxin (LT) produced by some enterotoxigenic strains of Escherichia coli. A number of mutants of CT and LT have been developed in an attempt to dissociate the desirable adjuvant properties of these molecules from their toxic effects. Both active-site and protease-site mutants have been constructed and evaluated in a variety of animal models with different antigens. Important questions regarding the adjuvanticity of CT and CT and mutants of these toxins remain to be answered. Some of these questions are practical and the answers will impact the immediate and short term use of these molecules in human vaccines. Other questions address the underlying mechanisms associated with adjuvanticity and the answers will have their greatest impact in the design of future adjuvants and vaccine strategies and in the development of a better understanding of vaccine induced immunity. The proposal includes a series of Specific Aims designed to directly address these issues. One of the most important aspects of the proposed study is a side-by-side comparison of CT, LT, active-site mutants, protease-site mutants, and recombinant Bsubunits for the ability to induce specific, targeted immunologic outcomes as a function of route of immunization and nature of the co-administered antigen. With the information obtained in the proposed studies, future vaccine strategies can be designed employing the optimum adjuvant/antigen formulation and route of administration for a variety of bacterial and viral pathogens. This proposal also examines the underlying cellular and intracellular signaling pathways activated by these different molecules to better understand the mechanisms of adjuvanticity at the cellular level. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MECHANISM OF CTX BACTERIOPHAGE INTEGRATION Principal Investigator & Institution: Mcleod, Sarah M.; Molecular Biol & Microbiology; Tufts University Boston Boston, Ma 02111 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2006
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Summary: (provided by applicant): The goal of this proposal is to understand the mechanism of CTXphi integration and its relationship to chromosome dimer resolution. CTXphi_ is a filamentous bacteriophage that carries the genes for cholera toxin, the primary virulence factor of Vibrio cholerae. CTXphi integrates site-specifically into the chromosome of v. cholerae and thereby renders non-pathogenic isolates toxigenic. Unlike other characterized phages and viruses, CTXphi depends on chromosomeencoded recombinases, XerC and XerD, to integrate its DNA. Integration occurs near the chromosome mid-point in close proximity to the d/f site, which is the XerC and XerD substrate for resolution of chromosome dimers. Thus, the specific aims of this proposal include: I) definition of DNA sequences required for CTXphi integration and recombination at d/f, II) characterization of recombination by XerC and XerD in vitro; 111) identification, via a genetic screen, of additional chromosomal genes required for CTXd_ integration; and IV) characterization of the phage encoded rstB gene and examination of its effect on CTXphi integral ion. Results from these studies will broaden our understanding of CTXphi biology and the evolution of V. cholerae pathogenicity and will clarify the mechanism of a novel means of phage integration. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MECHANISMS OF IMMUNE MODULATION AND PERIDONTAL DISEASE Principal Investigator & Institution: Katz, Jannet; Associate Professor; Oral Biology; University of Alabama at Birmingham Uab Station Birmingham, Al 35294 Timing: Fiscal Year 2001; Project Start 01-SEP-2001; Project End 30-JUN-2006 Summary: Periodontal disease is the result of the host response to periodontal pathogens such as Porphyromonas gingivalis. P. gingivalis is a black-pigmented, Gramnegative pathogen, which expresses various virulence factors implicated in disease. The overall goal of this project is to define the cellular mechanism(s) involved in the induction of host responses protective against P. gingivalis infection. The studies proposed will concentrate on delineating the mechanisms by which adjuvants modulate host responses to P. gingivalis antigens. Emphasis will be placed on the role of B7 costimulatory molecules in host responses and in infection by P. gingivalis, and on the involvement of cytokines, specific target cells, and other cell surface receptors. Specifically, there are plans to: 1) Determine the immunogenicity of the recombinant catalytic domain of the lysine-specific protease Kgp (rKgp-CAT) and the HagA repeat domain (rHArep) of P. gingivalis, and the effect of the B subunit of cholera toxin (CTB) and monophosphoryl lipid A (MPL) in modulating responses to these antigens following intranasal immunization, The level, isotype and IgG subclass of antibodies induced to HArep or Kgp-CAT in serum and external secretion$ will be measured by ELISA. The effects of CTB and MPL in enhancing/shifting responses will be further characterized by measuring antigen-specific proliferation and cytokine production. The effect of the responses, especially the nature of the antibodies, on protection will also be determined. 2) Determine the mechanisms by which the adjuvants CTB and MPL modulate the induction of the immune response. These studies will determine the involvement of the co-stimulatory B7 molecules in the immunoenhancing ability of the adjuvants and in P. gingivalis infection, the target cells affected by the adjuvants and the association between MPL, the Toll-like receptors and B7 co-stimulatory molecules. Groups of mice deficient in B7-l (B7-1-/-), B7-2 (B7-2j or both (B7-1/B7-2-/-) molecules and normal controls will be immunized with HArep or Kgp-CAT with and without CTB or MIPL. The levels of antibody and antibody-secreting cells will be assessed by ELISA and ELISPOT method. The effect of adjuvants on the expression of B7 molecules and of
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CD4OL will be analyzed by FACS. Differential regulation of cytokines induced and proliferative responses will also be assessed. The involvement of B7 co-stimulation in P. gingivalis infection will be assessed in B7 deficient mice. These studies will provide information on the mechanisms by which mucosal adjuvants modulate host immune responses, the target cells through which their adjuvanticity is exerted and the involvement of co-stimulatory signals provided by B7 molecules and of Toll-like receptors. An understanding of these processes is crucial for the development of means to interrupt/prevent periodontal disease pathogenesis by Porphyromonas gingivalis. Knowledge on the host effects induced by a potential periodontal vaccine will lead to the development of the therapeutic manipulation of effector function leading to the amelioration or prevention of periodontal disease and associated systemic diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: METHODS FOR EVALUATING VACCINE EFFICACY Principal Investigator & Institution: Halloran, M Elizabeth.; Professor; Biostatistics; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2001; Project Start 01-JAN-1992; Project End 31-MAR-2003 Summary: The overall objective of this research is to develop methods for estimating efficacy and effectiveness in the field and for characterizing complex and long-term properties of vaccines in individuals and populations. The specific aims are: (1) To develop methods for community trials of vaccines that estimate the indirect, total, and overall effects of vaccination strategies as well as the direct protective effects of vaccination, VE/S. (2) To continue development of methods for evaluating the vaccine efficacy for infectiousness, VE/1. In particular, we will develop the augmented vaccine trial design for acute and directly transmitted infectious diseases. (3) To develop methods for using exposure to infection data that may available on some individuals to improve estimation of vaccine efficacy for susceptibility, VE/5. (4) To develop designs and methods of analysis for using validation samples to correct for misclassified outcomes in vaccine studies. The goal is improved estimates of vaccine efficacy and of indirect, total, and overall effectiveness of vaccination strategies as well as designs for efficient, cost-effective studies. (5) To explore interpretation of the protective effects of vaccination, VE/5, when combining results across studies in different populations, taking into account different levels of baseline transmission and pre- existing immunity. Statistical approaches include likelihood inference, generalized estimating equations, semi-parametric methods for missing and mismeasured data, hierarchical models, and survival methods. The methods are motivated by studies of vaccines against influenza, cholera, rotavirus and tuberculosis, as well as other acute and childhood diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MODULATION OF BBB TO ENHANCE CNS CHEMOTHERAPY Principal Investigator & Institution: Eddington, Natalie D.; Professor and Chair; Pharmaceutical Sciences; University of Maryland Balt Prof School Baltimore, Md 21201 Timing: Fiscal Year 2001; Project Start 01-AUG-2001; Project End 31-JUL-2004 Summary: (provided by Applicant) This application is a request for a Mentored Research Scientist Development Award (KO1) to further Dr. Natalie Eddington's research in the area of anticancer drug delivery and pharmacokinetics. Dr. Eddington's long term goal is to enhance drug delivery of anticancer agents to the brain by modulating factors inherent in blood brain barrier physiology that serve to hinder drug transport. The main focus of her research has been to elucidate underlying
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pharmacokinetic related factors of drug distribution that are important in drug delivery and disposition. To that end, the goals of her research program are to better understand mechanistic activity at the blood brain barrier (BBB) that limit drug transport and modulate these factors to enhance drug delivery. Two factors that minimize drug transport across the BBB are: (1) the multidrug resistant protein, P-glycoprotein, which effectively ejects drugs out of the brain at the BBB, and (2) the presence of tight junctions in the BBB, which minimizes paracellular transport of drugs into the brain via the BBB. Modulation of the blood brain barrier by reducing P-glycoprotein mediated drug efflux or by reversibly opening tight junctions should theoretically enhance drug delivery to the brain. This proposal seeks training to pursue two research projects: One project seeks to examine the ability of a series of compounds, the enaminones, in reversing the P-gp mediated efflux of doxorubicin. The second project examines the ability of Zonula Occludens Toxin, a protein which can reversibly open the tight junctions, in enhancing drug delivery of a series of anticancer agents to the brain. A Mentored Research Scientist Award will allow Dr. Eddington to expand her expertise in the area of anticancer drug delivery and pharmacokinetics by focusing on the underlying mechanisms involved in drug delivery to the brain. In order to gain expertise in the areas mentioned, she will be mentored by Drs. Peter Melera and Yanto Lunardi-Iskandar. The training experience will involve gaining experience in optimizing cell culture techniques, Western Blot Analysis with quantitation, transfection techniques of P-gp into various cell lines, confocal microscopy to examine transport at the cellular level, and the development of a rodent glial tumor model. Experience in these areas will enhance her research skills and capabilities and will allow her to contribute to research in the area of anticancer drug delivery and pharmacokinetics. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MOLECULAR BIOLOGY AND VIRULENCE OF CTX PHAGE Principal Investigator & Institution: Waldor, Matthew K.; Scientist; New England Medical Center Hospitals 750 Washington St Boston, Ma 021111533 Timing: Fiscal Year 2001; Project Start 01-JAN-1998; Project End 31-DEC-2002 Summary: (Adapted from the applicant's abstract): Cholera toxin is the principal virulence factor of Vibrio cholerae, the Gram-negative bacterium that causes the severe diarrheal disease cholera. The investigators recently discovered that this potent enterotoxin is encoded by a novel filamentous bacteriophage designated CTX. The CTX phage is the first filamentous phage known to result in the lysogenic conversion of a host bacterium. The CTX phage can integrate into the V. cholerae chromosome and form stable lysogens or, after induction, excise from the chromosome and replicate as a plasmid. During this replicative stage of the phage life-cycle, cholera toxin can be expressed independently of the factors which were believed to be essential for its expression. Our demonstration of the induction of CTX phage from V. cholerae lysogens within the host gastrointestinal tract suggests the possibility that in vivo CTX phage induction plays a significant role in the virulence of V. cholerae. The objectives of the proposed studies are to understand the life-cycle of the CTX phage at the molecular level and to assess the significance of this bacteriophage in the pathogenesis of cholera. These studies will establish the molecular biology of a mechanism of horizontal transfer of virulence genes and thereby further our understanding of the emergence of pathogens. The study of the intraintestinal induction of CTX phage from lysogens, could establish a new paradigm for understanding the regulation of the expression of phage encoded virulence factors in a variety of bacterial pathogens that are lysogenized with
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converting phage. This work will also have important ramifications for the design of safer live attenuated V. cholerae vaccine strains. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MOLECULAR CHARACTERIZATION OF H2 RECEPTOR DUAL SIGNALING Principal Investigator & Institution: Delvalle, John; Professor; Internal Medicine; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2001; Project Start 30-SEP-1994; Project End 31-AUG-2002 Summary: (Adapted from applicant's abstract): This is a proposal to continue studies on signaling via histamine H2 receptors in gastric parietal cells. The Principal Investigator (PI) and his colleagues have characterized the molecular structure and function of the cloned H2 receptor and determined that it activates adenylate cyclase and phospholipase C (PLC) in a GTP-dependent, cholera toxin-sensitive manner. The mechanisms whereby the receptor couples to two effector systems remain to be determined. Furthermore, the PI has recently found that the receptor mediates cell proliferation and transcriptional activation of the early response gene, c-fos. In the current proposal the following will be examined. (1) Chimeric receptor constructs and site directed mutagenesis will be used to elucidate the structural components of the receptor linked to activation of adenylate cyclase and phospholipase C; (2) the G proteins involved in H2 receptor signaling in primary and transformed cells will be characterized using selective antibodies, immunoblotting, GTP-labeling and molecular techniques; and (3) the biological significance of dual signaling will be explored. H2 receptor/G protein targeted oligopeptides, antisera and antisense probes will be used to determine the relative importance of the two signaling pathways in cell proliferation and parietal cell secretory activity. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MULTIDENTATE HIGH AFFINITY LIGANDS FOR AB5 TOXINS Principal Investigator & Institution: Fan, Erkang; Biological Structure; University of Washington Seattle, Wa 98195 Timing: Fiscal Year 2001; Project Start 01-FEB-2000; Project End 31-JAN-2005 Summary: The goal of this proposal is to take advantage of the structural symmetry of multimeric proteins, a rarely explored property, to arrive eventually at structurally complementary multidentate protein ligands with ultra-high affinity and specificity. The long term objective is to illuminate an area of fundamental biological interest: the molecular recognition properties of multidentate protein ligands and the use of such ligands to control protein functions. Specifically, this proposal encompasses the design, synthesis and evaluation of multidentate ligands targeting a pair of ideal model systems: the heat-labile enterotoxin from E. coli (LT) and the closely related cholera toxin secreted by V. cholerae (CT), which are both AB5 heterohexamers. The biological mechanism of the actions of LT and CT includes a critical step of receptor recognition on the target cell by the B pentamer. The five-fold symmetry of the B subunits of LT and CT offers good opportunities to develop pentadentate ligands with overall structures complementary to the arrangement of toxin receptor binding sites. Such ligands will be created stepwise using a modular approach with each module providing opportunities for further optimization Building on the principles of molecular recognition, our proposed work will combine the powers of combinatorial chemistry and structure-based
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design to arrive at ultrahigh affinity pentadentate ligands. The affinity of the ligands obtained will be investigated with a variety of analytical tools. Detailed thermodynamics of ligand-protein interaction will be studied using a series of mono- to penta-dentate ligands. The proposed research has broad implications for the field of molecular recognition in general since it is at the frontiers of investigations focusing on multidentate ligands interacting with multimeric proteins. In addition, high affinity ligands derived from our work have potential health benefits, as they may lead to the development of agents useful for the detection, treatment, and prevention of AB5 toxinrelated enterotoxigenic diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MULTITARGETED LIGAND DESIGN FOR AB5 TOXINS Principal Investigator & Institution: Verlinde, Christophe; Biological Structure; University of Washington Seattle, Wa 98195 Timing: Fiscal Year 2001; Project Start 01-MAY-1997; Project End 31-MAR-2003 Summary: AB5 bacterial toxins are the major virulence factors in diseases that affect over a billion people in the world each year. The mode of action of these toxins is a multi-step process which involves toxin assembly, translocation and catalytic activity. None of the steps are fully understood, as cellular biology studies are limited by the lack of potent, stage-specific inhibitors. Therefore, the goal of this work is to design and discover such compounds. The known three-dimensional crystal structures of E.coli heat-labile enterotoxin, cholera toxin and of their complexes with carbohydrates are well-suited for a protein structure-based design cycle supported by complementary thermodynamical characterization to arrive at tightly binding ligands. Targets are the GM1 oligo-saccharide receptor binding site of the B subunits and the structural integrity of the AB5 holotoxins. Receptor antagonists and assembly inhibitors will be arrived at by: (1) screening of potential ligands generated by combinatorial oligosaccharide synthesis; (2) in computro docking experiments; and (3) de novo ligand design. All three strategies will be embedded in an integrated ligand discovery and design cycle. Experimental feedback at both the energetic and structural level, by calorimetry and Xray crystallography, will continuously validate the in computro approach and give insight in the binding process. The biological effect of potent inhibitors will be tested in cell culture systems. Whereas the immediate goal is to arrive at molecular tools for the study of the multi-step intoxication by AB5 toxins, the long-term goal is to provide leads and lay the foundation for the development of prophylactic drugs against the intoxication by all AB5 toxins. It is also anticipated that ligands developed for the oligosaccharide receptor binding B subunits may have therapeutic properties for the treatment of Guillaume-Barre syndrome, and may become molecular research tools for studying cell interactions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: NASALLY-DELIVERED MUCOSAL SUBUNIT VACCINE FOR PLAGUE Principal Investigator & Institution: Cramer, Carole L.; Professor; Biodefense Technologies, Inc. 610 N Main St, Ste 266 Blacksburg, Va 24060 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2004 Summary: (provided by applicant): We have developed a plant-based adjuvant/carrier:antigen fusion technology that offers significant advantages over conventional injectable vaccination regimes including: safety, mucosal efficacy, ease of
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delivery, rapid scalability, unlimited supply potential, and cost-savings. This technology has significant potential in contributing to biodefense strategies protecting both military and civilian populations currently threatened with biological weapons of mass destruction. Pneumonic plague is one of the most likely terrorist weapons for which no vaccine of proven efficacy is currently available. Since mucosal administration is considered the most effective route for conferring protection against a pneumonic form of the disease, the lack of an effective mucosal adjuvant acceptable for human use presents a significant hurdle. BioDefense Technologies, Inc. brings two new technologies to vaccine development that are significantly relevant for plague: 1) a new non-toxic mucosal adjuvant/carrier, MAC1, that functions to effectively deliver fused antigens to mucosal immune-responsive tissues and shows intranasal adjuvancy in mice equivalent to co-administered cholera toxin adjuvant and 2) transgenic plant-based bioproduction that addresses issues of safety, scale, and cost of recombinant subunit vaccines. A fusion of the Yersinia pestis protective antigens, F1 and V, appear the most promising for subunit vaccines. We propose to produce MAC1: F1:V fusion protein in transgenic tobacco. Purified MAC1:F1:V will be intranasally delivered to mice and mucosal and systemic responses will be used to assess vaccine efficacy. MAC1:F1:V adjuvancy in mice will be compared to that of co-administered F1:V and cholera toxin. These studies will provide the foundation for developing fusion proteins in transgenic plants, scale-up production protocols for MAC1:F1:V and conducting pneumonic plague challenges during Phase II. Our plant-based MAC1:antigen fusion technology is quite modular, easily purified and well suited for rapid development of new vaccines to counter genetically modified plague pathogens and newly emerging biowarfare agents. Furthermore, our MAC1:antigen technology has potential applications as a mucosal adjuvant/delivery molecule for developing non-defense related vaccines directed at HIV, cancer, and autoimmune diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NEW MECHANISMS FOR REGULATING VIRULENCE GENE EXPRESSION Principal Investigator & Institution: Skorupski, Karen A.; Anatomy-Cytology; Dartmouth College 11 Rope Ferry Rd. #6210 Hanover, Nh 03755 Timing: Fiscal Year 2002; Project Start 01-JUL-1997; Project End 31-JUL-2007 Summary: (provided by the applicant): Elucidating the mechanisms by which pathogenic bacteria regulate virulence gene expression in response to environmental stimuli is considerably important since this knowledge is central to understanding the molecular events that lead to the establishment of bacterial infections. Vibrio cholerae is the causative agent of epidemic cholera and possesses two distinct pathogenicity islands required for disease: the Vibrio pathogenicity island (VPI), which encodes an essential colonization factor, toxin-coregulated pilus (TCP), and the CTX element that carries the genes for cholera toxin (CT). We have recently identified two new activators, AphA and AphB, which function at what appears to be the initial regulatory step in the virulence transcriptional cascade. AphA and AphB function synergistically to activate the expression of the membrane bound transcriptional activators, TcpP and TcpH, which are encoded on the VPI. AphA appears to be a novel activator with no known homologs and AphB is a member of the LysR family. Interestingly, these two proteins are not encoded on either the VPI or CTX islands but are located in regions of the chromosome not previously associated with pathogenesis. Since activation of tcpPH expression by AphA and AphB occurs only under certain environmental conditions, these proteins may play a role in normal cellular physiology and function to couple physiological
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responses to virulence gene expression. The importance of AphA and AphB in pathogenesis is reflected by the dramatic attenuation in the infant mouse cholera model of mutants defective in either one of these genes. Furthermore, activation of tcpPH by AphA and AphB is responsible for the differential regulation of virulence genes between the two disease causing biotypes, classical and El Tor. The proposed research will allow us to gain a better understanding of the roles of AphA and AphB in pathogenesis. We propose: (1) to investigate the mechanism by which AphA and AphB differentially activate the expression of the classical and El Tor tcpPH promoters; (2) to determine the mechanism by which cAMP-CRP antagonizes AphA and AphB to negatively regulate tcpPH expression; (3) to elucidate the molecular mechanisms by which environmental stimuli influence the expression of the tcpPH promoter; and 4) to determine the importance of AphB-mediated differential activation of tcpPH expression for pathogenesis in vivo. These studies will enhance our understanding of the complex mechanisms utilized by pathogenic bacteria to regulate virulence gene expression in response to environmental stimuli so that better strategies can be developed to control and prevent bacterial infections. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NUCLEAR GM1 GANGLIOSIDE IN NEURONAL DIFFERENTIATION Principal Investigator & Institution: Ledeen, Robert W.; Professor; Neurology and Neurosciences; Univ of Med/Dent Nj Newark Newark, Nj 07103 Timing: Fiscal Year 2001; Project Start 22-APR-1996; Project End 31-JUL-2005 Summary: (Provided by the Applicant): The goal of this project is to elucidate the function of GM1 ganglioside in the nuclear membrane. The developmental expression of GM1 at this locus, which occurs during axon outgrowth, is different from that of teh plasma membrane and its functional role is different. Our study of neuroblastoma cells indicated a requirement for elevated intracellular calcium ( [CA2+]i ), and to support the physiological relevance of that finding we plan to study 2 primary neuronal cultures. The latter will also be used to test the developmental link between nuclear GM1 expression and axonal but dendrite-) outgrowth. Our primary hypothesis is that the function of nuclear GM1 is to facilitate calcium efflux from the nucleus by potentiating a sodium-calcium exchanger present in the nuclear envelope. That such an exchanger is present in this envelope is a new finding which we support with immunoblot analysis and immunoprecipitation; association of this exchanger with GM1 is indicated by Western blot analysis with cholera toxin B subunit and thin-layer chromatography. An effort will be made to isolate this exchanger protein and characterize its structure as well as its location in the inner vs outer nuclear membrane. The function of the exchanger will be investigated with a GM 1-null mutant of NG108-15 cells (NG-CR72); calcium signaling in these cless has been shown to differ significantly from wild type and the GM1- deficient cells undergo apoptosis on exposure to elevated [CA2+]i. Rescue with LIGA-20, a membrane permanent derivative of GM1 that enters the nuclear membrane, has been demonstrated and will now be applied to cerebellar granule neurons (CGN) from ganglioside knockout mice lacking GM2/GD2 synthase (GaINAc-T). The latter have been shown to resemble NG-CR72 cells in lacking calcium regulation when exposed to elevated K+, leading to apoptosis. CGN from the knockouts will be subjected to glutamate as an alternative means of elevating [CA2+]i. A stroke model will also be employed. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PERTUSSIS, DIPHTHERIA, CHOLERA TOXINS-INHIBITOR DESIGN Principal Investigator & Institution: Schramm, Vern L.; Professor; Biochemistry; Yeshiva University 500 W 185Th St New York, Ny 10033 Timing: Fiscal Year 2001; Project Start 01-JUL-1993; Project End 31-JAN-2004 Summary: This research program addresses two major and current problems in infectious disease using novel technology. Toxin-directed transition state inhibitors offer a new approach to prevent the damage of bacterial exotoxins to human tissues. Antibiotic resistance is a global problem in infectious disease. Tissue- protective toxin inhibitors could act as antibiotics which are not expected to elicit resistance in the causitive organisms. The experimental approach is to use the frontier method of enzymatic transition state analysis and to apply it to the action of bacterial exotoxins. ADP-ribosylating bacterial exotoxins catalyze the covalent modification of GTP-binding proteins. Cholera, diphtheria and pertussis toxins ADP-ribosylate Gsalpha, eukaryotic elongation factor 2, and Gialpha proteins, respectively. Transition state analysis of bacterial ADP-ribosylating exotoxins will be used to design transition state inhibitors against cholera, diphtheria, pertussis and related exotoxins. Transition-state inhibitors against bacterial exotoxins are expected to protect against the exotoxins and thus ameliorate the damage caused in these childhood and endemic diseases. Transition state structure is determined by measuring kinetic isotope effects with NAD+ substrate labeled in all of the atomic positions expected to undergo bonding changes as bonds are broken and made at the enzyme-stabilized transition state. The ADP- ribosylated Gprotein is analyzed for the isotopic discrimination of the incorporated ADP-ribose. The isotope effects are then corrected to reveal the full chemical expression of intrinsic isotope effects. An atomic model of all atoms at least two bonds from the reaction center is constructed which is constrained by the values of the kinetic isotope effects. Semiemperical and ab initio methods are used to complete the structure of the transition state molecules, with constraints at every step to comply with the experimental kinetic isotope effects. Transition state structures are mapped using the molecular electrostatic potential surface at the van der Waals radius and compared to that of the substrate. The relationship provides predictive value for transition state inhibitor design. Molecules with electronic similarity close to that of the transition state are synthesized and tested as transition state inhibitors. These procedures have resulted in the discovery of novel transition state inhibitors for several simple enzymatic reactions. The goal of this work is to extend transition state inhibitor design to the complex reactions catalyzed by bacterial ADP-ribosylating toxins. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PHAGES AND GENOMIC VARIATION IN V. CHOLERAE EVOLUTION Principal Investigator & Institution: Mekalanos, John J.; Professor; Microbiol & Molecular Genetics; Harvard University (Medical School) Medical School Campus Boston, Ma 02115 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-AUG-2007 Summary: (provided by applicant): The goal of this project is to characterize the mechanisms governing the evolution of Vibrio cholerae strains with epidemic potential within the context of a natural endemic environment. Emphasis will be placed on molecular genetic analysis of the role of vibriophages (bacterial viruses that grow on Vibrio species) in horizontal transfer of virulence-related genes, and in modulating V. cholerae population dynamics in the environment. Vibriophages will be isolated from 10
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environmental surveillance sites in Bangladesh and characterized with respect to their host range, environmental prevalence, and ability to package and transfer V. cholerae DNA encoding virulence-related genes. Any phage that correlates negatively or positively with the presence of specific subgroups of V. cholerae will be monitored more closely with specific PCR or nucleic acid probes. In this way we hope to assess the phages ability to modulate the prevalence of specific V. cholerae strains, thereby affecting the ability of these strains to cause outbreaks of cholera. Environmental and clinical V. cholerae strains will also be collected, analyzed by microarray, DNA sequencing, and genetic fingerprinting methods to establish the phylogenetic relationships among the strains. The virulence gene content of the collected strains will be determined, and variant alleles of certain genes will be tested for their ability to mediate virulence-related functions (e.g., intestinal colonization). Clinical isolates that do not possess known colonization factor genes will be subjected to genetic analysis in order to identify the novel determinants carried by these strains. V. cholerae present in cholera stools have been reported to show increased infectivity in infant mice. We will examine this phenomenon using a variety of approaches including physiology assays, expression profiling with V. cholerae microarrays and quantitative chemotaxis assays. The results of this project will not only provide a full understanding of the processes by which pathogenic V. cholerae strains emerge, evolve, and transmit, but will also guide the development of surveillance and preventive measures that can be used to combat cholera in a cholera endemic area. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: POPULATION BIOLOGY OF SURFACE POLYSACCHARIDES IN CHOLERA Principal Investigator & Institution: Morris, J G.; Epidemiology and Prev Medicine; University of Maryland Balt Prof School Baltimore, Md 21201 Timing: Fiscal Year 2001; Project Start 01-JUL-2000; Project End 30-JUN-2004 Summary: Cholera is an ancient disease in the midst of a modern resurgence, with cases reported to WHO by 65 member nations in Asia, Africa, the Americas, and Europe in 1997. With the appearance of V. cholerae 0139 Bengal and the recent identification of epidemic-associated 037 strains, there is increasing recognition that modifications in bacterial surface polysaccharides play a key role in the emergence of new, epidemicassociated strains. While the number of constituent sugars appears to be relatively small (less than 25), there are hundreds of O antigen/capsule types recognized among V. cholerae and other Vibrionaceae strains. Initial phylogenetic studies suggest that serotype and/or capsule type are independent of phylogeny. We hypothesize that there is frequent horizontal/sexual transfer and rearrangement of surface polysaccharide biosynthetic gene cassettes in V. cholerae, providing an opportunity for periodic emergence of new, pandemic cholera strains. Making use of our collection of Vibrionaceae (including the Smith Vibrio Reference Laboratory/serotype collection) and ongoing strain acquisition, we propose: 1) To describe and define the genetic relatedness of a 192-strain V. cholerae test collection, utilizing sequence analysis of conserved genetic elements (multilocus sequence typing) including genes used in multilocus enzyme electrophoresis/zymovar analysis. 2) To identify and characterize V. cholerae O antigen and capsular polysaccharides for stains within this collection, as a basis for assessing horizontal transfer of surface polysaccharide genes. This will include a) determination of sugar composition of O-antigen side chain and capsule; and b) identification and correlation of sugars with specific biosynthetic genes/gene combinations. 3) To assess the extent of genetic variability in surface polysaccharides
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plausibly available to V. cholerae, and, in particular, to V. cholerae strains with pandemic potential. For these latter studies we will a) correlate genetic relatedness (as determined above) with transfer/acceptance of specific polysaccharide genes; b) determine the placement and organization of biosynthesis genes for the sugars of the O side chain and capsule; and c) assess the nucleotide sequence divergence of the most commonly identified polysaccharide biosynthesis genes. Taken together, these studies will substantively expand our understanding of the evolutionary biology of V. cholerae, giving us a much better appreciation of the potential for changes in V. cholerae surface polysaccharides and, in turn, for the emergence of V. cholerae strains which can form the basis for new cholera pandemics. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: RAP 1B AS A MITOGENIC SIGNALING THYROID Principal Investigator & Institution: Altschuler, Daniel L.; Pharmacology; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 31-MAY-2007 Summary: (provided by applicant): cAMP stimulates proliferation of numerous cell types, particularly of differentiated endocrine origin, by acting synergistically with other growth factors. Thus, downstream targets of cAMP represent attractive candidates for new oncogenes. We have implicated the G-protein Rap1b as a critical target of cAMP mitogenic signaling by showing that Rap1b-expressing cells display enhanced DNA synthesis and are endowed with tumorigenic properties. Additionally, in thyroid follicular cells, which depends on increases in cellular cAMP by thyrotropin (TSH) for mitogenesis, DNA synthesis stimulated by TSH or cAMP requires Rap1b-GTP binding (activation) and its phosphorylation by the cAMP-dependent protein kinase PKA. Thus, we have proposed that Rap1b can be viewed as conditional oncogene--its role in cell proliferation is linked to the mitogenic signaling program elicited by cAMP. We now present new results showing that a GTPase-deficient (G12V) and phosphomimetic (S179D) Rap1b mutant, Rap1b-G12V-S179D, promotes mitogenesis independently of cAMP. Moreover, a dominant negative version of the Rap1b activator Epac, N-Epac, inhibits the mitogenic effect of cAMP but it has no effect on the mitogenic action of Rap1b-G12V-S179D. These results prove conditionality of the cAMP mitogenic signal on cAMP/Epac activation and cAMP/PKA phosphorylation of Rap1b, which is bypassed by Rap1b- G12V-S179D; they implicate activation and phosphorylation of Rab1b as the main biochemical events in the transduction of the cAMP mitogenic signal. However, it is necessary to verify whether Rap1b behaves as a conditional oncogene in vivo, linked to pathophysiological conditions with increased TSH levels. We have generated mice with thyroid-specific expression of an active Raplb mutant, "floxed" by LoxP sites, which, upon stimulation of CRE activity, will cease to express the active Rap1b mutant and produce a dominant negative Rap1b. This is the first example of a mouse model containing an "in vivo/in lession" built-in control system permitting the switch of expression of a stimulatory to an inhibitory G protein, encoded by a single gene. Mice expressing an active Rap1b mutant show no discernable alteration of thyroid morphology and function under physiological conditions, but, under pathologically sustained cAMP signaling, their thyroids are enlarged, display enhanced DNA synthesis, and present multiple adenomas, and, even carcinomas. These results suggest that Rap1b also behaves as a conditional oncogene in vivo. We propose to exploit these mice to understand the multi-step tumorigenic process in thyroid. The specific aims of this proposal are: 1: To establish whether thyroid-specific expression of Rap1b relays a cAMP-dependent mitogenic response. 2: To determine the effect of Rap1b in the
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establishment and/or progression of thyroid tumorigenesis. 3: To determine whether Rap1b action is required for cAMP-mediated hyperplasia. The long-term goal of this proposal is the identification of mitogenic signals relayed by Rap1b involved in cAMPdependent cell proliferation in endocrine systems. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: REAL TIME ANALYSIS OF TOXIN RECEPTOR INTERACTIONS FOR BIOSENSOR APPLICATIONS Principal Investigator & Institution: Nolan, John P.; Director; University of Calif-Los Alamos Nat Lab Ms G758 Los Alamos, Nm 87545 Timing: Fiscal Year 2001; Project Start 01-JUL-2001; Project End 30-JUN-2002 Summary: We will meet the need for a fundamentally new method of detection for biotoxin agents. Our strategy is based on using the cell surface receptor targeted by biological toxins or pathogens as the core of the sensor. Receptor-cell membrane mimics will be generated using self-assembly techniques where monolayers and bilayers are bound directly to an optical transducer surface. In addition, advanced transduction techniques that mimic the ability of natural systems to amplify signals will be developed. Our ultimate target is sensor arrays based on multiple receptor-cell membrane mimics that can serve as a "smart" sensing system capable of rapid identification and quantification of a wide range of biological toxins. Many toxins and pathogens enter cells through a general mechanism that begins with their binding of receptors on the animal cell surface. Most of the primary receptors have been identified for biological agent toxins, many of them have been identified f or bacterial pathogens, and some of them have been identified for viral pathogens. While cholera toxin was chosen for initial studies because of its experimental accessibility, ganglioside binding is a common feature of bacterial toxins. For example, the toxins from tetanus, botulinum, perfringens, and shiga and the toxin ricin all bind gangliosides before entering the cell. Thus, everything we learn about cholera toxin will be directly applicable to developing sensors for other important toxins such as botulinum and ricin. We have established two systems for detecting cholera toxin binding to its glycolipid receptor; one based on fluorescence detection by flow cytometry, and the other based on mass detection by surface plasmon resonance. In both cases the receptor is embedded in a biomimetic surface and toxin binding to the surface is detected. In flow cytometry (FC), the surface is a microsphere and the toxin is labeled with a fluorescent probe, whereas for surface plasmon reso nance (SPR), a gold-coated planar surface is used and toxin bnding is detected as a change in refractive index at the surface. These two systems represent our first generation of toxin sensors and will provide platforms with which we will optimize molecular recognition, the biomimetic substrate, and detection of binding. Systematic investigation of the receptor and toxin concentration dependence of these kinetics is in progress and will be interpreted in terms of a rigorous kinetic model to determine the individual rate constants (binding affinities) for the mixed, mono,-and multivalent binding events we envision. We will investigate the effect of receptor immobilization and of various biomimetic substrates on this interaction. These results will be used to guide the design of sensor surfaces with the desired sensitivity, specificity, reversibility, and stability. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: REGULATION OF IMMUNE RESPONSE IN THE ORAL CAVITY Principal Investigator & Institution: Michalek, Suzanne M.; Professor; Microbiology; University of Alabama at Birmingham Uab Station Birmingham, Al 35294
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Timing: Fiscal Year 2001; Project Start 01-JUN-1988; Project End 31-MAY-2004 Summary: Public awareness of emerging infectious diseases and that infectious diseases continue to be the leading cause of morbidity and mortality worldwide has fostered a need to develop better means for prevention and treatment. The evidence that most infectious agents cause disease by colonization of or penetration through mucosal surfaces has prompted novel vaccination strategies that would lead to increased protection of the mucosae as well as surfaces bathe by mucosal secretion, e.g., teeth. Secretory IgA antibodies in saliva are important in protection against oral diseases, including Streptococcus mutans-induced dental caries, and are induced following stimulation of the common mucosal immune system (CMIS). However, little information in known about the human CMIS, especially with respect to salivary IgA responses. The overall goals of this grant is to evaluate compartmentalization within the human CMIS, especially with respect to the salivary IgA response, and to develop a human caries vaccine. The purpose of the present studies is to establish the effectiveness of the intranasal (IN) route of immunization for inducing human salivary IgA responses protective against infection with S. mutans. Specifically, we will: 1) Determine the immunization regimen for the effective induction of human salivary IgA responses after IN immunization of S. mutans antigens and mucosal adjuvants. The recombinant (r) S. mutans antigens to be used are the saliva-binding region (SBR) of the adhesin AgI/II and the catalytic domain (CAT) and glucan-binding domain (GLU) of glucosyltransferase. The adjuvants to be used are the B subunit of cholera toxin (rCTB) and monophosphoryl lipid A (MPL). Adult volunteers will be used in this aspect of the study. The quality and quantity of antibody in saliva, nasal wash, and serum and of circulating antibody-secreting cells will be measured at various times up to 6 months after IN immunization with each antigen alone, antigen and an adjuvant, or a combination of antigens and an adjuvant. The oral microflora will be assessed for the number of S. mutans/total streptococci. These results should determine the effectiveness of IN immunization with S. mutans antigens in inducing salivary IgA responses, the usefulness of adjuvants in promoting the response, and whether the response was protective. 2) Determine the longevity of the human salivary IgA response after IN immunization and evaluate memory in the CMIS in terms of salivary IgA responses after subsequent IN immunization. The immune responses in serum and secretion from adult subjects used in aim 1) will be followed to evaluate the duration of the response. When the response wanes, these subjects will be boosted with the original vaccine and immunologic and microbiologic parameters will be measured to establish the effectiveness of the immunization regimen for inducing prolonged salivary responses and to learn more about memory in the human CMIS. 3) Determine the effect of age on human salivary IgA responses after IN immunization with S. mutans antigens and mucosal adjuvants. Since dental caries is a childhood disease, it is important to learn if the information we are obtaining in adults regarding the human CMIS also applies to children. In this portion of the study, children will be immunized by the IN route with antigen alone or antigen with an adjuvant. By analysis over time of antibody activity in saliva, nasal wash, and serum, we will be able to define similarities/differences in the CMIS of children and adults. By monitoring the oral microflora, we will be able to tell if the induced response was effective in reducing the level of S. mutans and in preventing the colonization by S. mutans of erupting molars. The results of this study should establish the effectiveness of the IN route of immunization, the suitability of the rSBR, rCAT and rGLU proteins of S. mutans for a combination vaccine, and the benefit of a mucosal adjuvant (CTB or MPL) for inducing a human salivary response which affords immune protection against S. mutans infection. This study will provide valuable
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information on the human CMIS which will help in the development of mucosal vaccines and bring us closer to establishing a human caries vaccine. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SMOOTH TO RUGOSE PHASE VARIATION IN VIBRIO CHOLERAE Principal Investigator & Institution: Yildiz, Havva F.; None; University of California Santa Cruz 1156 High St Santa Cruz, Ca 95064 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-JAN-2008 Summary: (provided by applicant): Cholera is a global disease; endemic to Bangladesh, regions of South America, Africa and Australia, and also the Gulf Coast of the United States with the potential for epidemics in all aquatic environments. It is estimated that 120,000 people worldwide die from cholera annually. V. cholerae causes periodic, seasonal outbreaks in regions where it is an established member of the indigenous aquatic flora and this capacity is linked to its survival under diverse environmental conditions. V. cholerae switches its colonial morphology from smooth and translucent type to wrinkled and opaque type termed rugose variant when exposed to environmental stresses. We hypothesize that the phase variation mediated changes in population composition of V. cholerae can increase aquatic survival chances of the organism. The long term goal of this project is to understand how V. cholerae survives between epidemics by focusing on the molecular mechanism of smooth to rugose phase variation, its physiological consequences and its effect on the aquatic survival of the organism. Towards this goal, we will focus on the following specific aims: 1) determine and characterize the molecular basis of the smooth to rugose phase variation, 2) characterize the transcriptional network governing rugose specific gene expression and characterize the physiological and behavioral changes in the organism resulting from phase variation 3) elucidate the effects of diverse environmental parameters on the aquatic survival properties of the smooth and rugose variants and on the frequency of phase variation. Understanding how the smooth to rugose phase variation is contributing to persistence and survival of V. cholerae O1 El Tor in environmental aquatic habitats, and elucidation of the genes and processes regulating the phase variation will further our understanding of the aquatic life cycle of an important human pathogen. Results obtained from this study should lead to the development of molecular tools that can be used to identify transcripts or proteins that are predicted to provide better environmental fitness to the organism in natural aquatic habitats. This information will prove useful in the prediction and/or control of cholera epidemics. Smooth to rugose phase variation presents another challenge in public heath since this process renders the organism resistant to oxidative stress and chlorine-mediated killing. Chlorination is used as a first line of defense against V. cholerae and many other waterborne pathogens. Understanding the mechanism and regulation of phase variation may aid in designing methods/inhibitors for modulating the frequency of phase variation and thus biocide resistance in V. cholerae and other aquatic pathogens. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: SRC REGULATION OF LUNG ENDOTHELIAL BARRIER FUNCTION Principal Investigator & Institution: Minshall, Richard D.; Biomedical & Therapeutic Sci; University of Illinois at Chicago 1737 West Polk Street Chicago, Il 60612 Timing: Fiscal Year 2003; Project Start 10-APR-2003; Project End 31-MAR-2007 Summary: (provided by applicant): Loss of endothelial barrier function is important in the development of Adult Respiratory Distress Syndrome. The transcellular transport of
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albumin and other macromolecules via endothelial caveolae is a factor regulating endothelial barrier function. Using pulmonary microvascular endothelial cells, we have identified specific interactions between caveolin-1 and Src-family tyrosine kinases that may regulate albumin uptake and its transport via caveolae. The primary objective of the proposed investigation is to address the roles of caveolin-1 and Src in endocytosis and regulation of endothelial barrier function. Caveolin-1 and Src knockout mice will be used to investigate (1) the function of caveolin-1 in internalization of caveolae and transendothelial transport in pulmonary microvascular endothelial cells and (2) the role of dynamin in mediating fission of caveolae from the membrane and transcellular albumin permeability in endothelial cells. Our hypothesis is that Src-dependent phosphorylation of caveolin-1 and dynamin is essential for formation of caveolae and their scission from the membrane. We will measure vessel wall albumin permeability in the mouse lung preparation from caveolin-1 knockout mice. Mutant caveolin-1, Src, and dynamin cDNA constructs will be used in cell culture experiments to examine the role of Src-dependent interactions in regulating caveolin-1 and dynamin functions. Cholera toxin subunit B and albumin endocytosis and transcellular transport will be determined by electron microscopy, confocal microscopy, and measurement of iodinated tracers in cultured cells. Molecular-genetic and biochemical strategies will be used to elucidate the domain-specific and phosphorylation-dependent interactions between caveolin-1, Src, and dynamin. Thus, these studies will elucidate the Src-dependent signaling mechanisms that regulate endocytosis and transport across the pulmonary vascular endothelial barrier. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: STRUCTURE OF TOXR/S AND TCPP/H: VIRULENCE REGULATORS Principal Investigator & Institution: Dirita, Victor J.; Professor; Laboratory Animal Medicine; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2005 Summary: (provided by applicant): This proposal seeks to develop methods for overexpressing, purifying and crystallizing membrane-localized transcription control proteins from Vibrio cholerae, the agent of human cholera disease. ToxR and TcpP are bi-topic membrane proteins with cytoplasmic DNA binding/activation domains. They control expression of important virulence factors by virtue of their ability to activate expression of toxT, the activator of genes encoding cholera toxin and toxin-coregulated pilus. The DNA binding/activation domains of ToxR and TcpP are homologous to the winged Helix-Turn-Helix (w-HTH) family of proteins. The structures of other w-HTH domains has been solved, but the unusual membrane topology of ToxR and TcpP, and significant preliminary data aimed at determining how they recognize DNA and activate toxT transcription, compel an interest in solving their crystal structures when bound to operator DNA. Upon completion, this study will enable us to discriminate between distinct hypotheses for how ToxR and TcpP function. Along with determining the structure of ToxR and TcpP, of interest also is overexpression, purification and crystallization of the structures of membrane effector proteins required for the activity of each: ToxS in the case of ToxR, and TcpH in the case of TcpP. The specific aims of the proposal are as follows: (i.) To purify a 6-His tagged version of full length ToxR for crystallization and structural determination with and without its toxT promoter binding site or its binding site in the ompU promoter (a promoter activated by ToxR independently of TcpP) (ii.) To purify a 6-His tagged version of full length TcpP for crystallization and structural determination with and without its toxT promoter-binding
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site (iii.) To obtain structural data on co-crystals of ToxR and TcpP on the toxT promoter (to determine whether protein-protein interactions affect DNA binding) (iv.) To purify FLAG epitope- tagged versions of ToxS and TcpH for crystallization and structural determination alone or in a co-crystal with ToxR or TcpP Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: STUDY OF TRANSMISSIBLE FORMS OF VIBRIO CHOLERAE Principal Investigator & Institution: Camilli, Andrew; Associate Professor; Molecular Biol & Microbiology; Tufts University Boston Boston, Ma 02111 Timing: Fiscal Year 2003; Project Start 15-MAY-2003; Project End 30-APR-2008 Summary: (provided by applicant): Vibrio cholerae, which lives in association with plankton in brackish, temperate waters the world over, is the causative agent of endemic and epidemic cholera. Hallmarks of the disease include prodigious watery diarrhea resulting from the action of secreted cholera toxin (CT), and infrequent but deadly explosive epidemics. The strong link between explosive epidemics and human crowding accompanied with untreated drinking water suggests a very efficient mode of fecal-oral transmission. We have discovered a heightened state of transmissibility of stool V. cholerae (referred to simply as "hyperinfectivity"), which persists even after shedding into water reservoirs. Knowledge of the molecular basis for this phenotype, and a general characterization of this transmissible form of V. cholerae, would contribute to the design of vaccines to prevent cholera at the initial stage of infection. Aim 1 of this proposal will use transcriptional profiling and proteomics to help define this transmissible form. Spotted DNA microarrays will be used to determine the transcriptome of stool V. cholerae incubated in pond water, and this will be compared to that of fresh stool V. cholerae to identify potential differences. The results will be validated by quantitatively assaying the steady state mRNA and protein levels from select genes. Microscopy and transcriptome data on stool V. cholerae predict a bacterial state of motility working in the absence of chemotactic signaling. This counterintuitive state is hypothesized to be responsible, at least in part, for the hyperinfective phenotype. In Aim 2 of this proposal, quantitative immunodetection using paralog-specific antisera will be used to test for reduced expression of all three CheW linker proteins and all three CheR methytransferases in fresh and pond water-incubated stool V. cholerae, as is predicted by current transcriptome data. In addition, capillary tube chemotaxis assays will be performed directly on V. cholerae from these samples to substantiate this hypothesis. Aim 2 will also test a second hypothesis, that ToxR regulated factors, which are essential for pathogenesis, are not playing a role in the hyperinfectious state. Finally, Aim 3 will use mutation and infectivity analyses to determine if other metabolic, physiologic or phenotypic properties of the bacteria contribute to the hyperinfective phenotype or, alternatively, to colonization of an environmental planktonic host, Anabaena variabilis. These studies will establish a basis for understanding the hyperinfective phenotype, and the properties in general, that are exhibited by fresh and pond water-incubated stool V. cholerae. In turn, this knowledge will enhance our understanding of transmission of this and perhaps other water-borne pathogens, it will aid in the development of new cholera vaccines that target the antigens of 'incoming' vibrios, and it may suggest new approaches for the prevention of the dissemination of this lethal organism. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: SYSTOLIC CARDIAC FUNCTION IN OBESITY AND EXERCISE Principal Investigator & Institution: Carroll, Joan F.; Integrative Physiology; University of North Texas Hlth Sci Ctr Fort Worth, Tx 761072699 Timing: Fiscal Year 2001; Project Start 01-JUL-2001; Project End 30-JUN-2005 Summary: (Applicant's abstract): The broad objectives of the proposed research are to determine mechanisms for reduced responsiveness to cardiac Beta-adrenergic stimulation in obesity and mechanisms whereby exercise training during the development of obesity may attenuate these effects. We hypothesize that obesity causes alterations in hemodynamics, cardiac hypertrophy, cardiac collagen, hormonal profile, and systolic function that are independent of hypertension. To test this hypothesis, we will compare lean rabbits with obese rabbits that develop hypertension along with obesity, and obese rabbits in which blood pressure will be controlled at pre-obese values using oral Hydralazine. We will use acute and chronic (telemetry) measurement of heart rate and blood pressure, as well as colored microspheres, to study hemodynamics. We will use western blotting techniques, blood sampling, wet and dry cardiac weights, and the Langendorff isolated heart preparation to analyze collagen, hormonal profile, cardiac hypertrophy, and systolic function. We also hypothesize that decreased cardiac responsiveness to Beta-adrenergic stimulation in obesity is due to abnormalities both at the cardiac Beta-receptor and in the G-coupled protein cascade leading to cAMP formation and calcium release from the sarcoplasmic reticulum. We will use appropriate assay and western blotting techniques to provide an analysis of the role of beta-receptor and post-receptor components such as Beta-receptor/Gs coupling, Gs stimulation of adenylate cyclase; formation of cAMP; activation of PKA, and sarcoplasmic reticulum calcium handling in contributing to cardiac abnormalities in obesity. We hypothesize that exercise training during development of obesity will 1) attenuate or prevent obesity-related hypertension, resting tachycardia, neurohumoral activation, and cardiac collagen formation and 2) attenuate obesity-related decreases in responsiveness to Betaadrenergic stimulation. Abnormalities occurring in sedentary obese rabbits will be compared with their reduction in obese rabbits that undergo 12 weeks of treadmill exercise. Comparisons will also be made with appropriate lean controls. Finally, we will determine mechanisms within the Beta-adrenergic signaling pathway responsible for exercise-mediated increased responsiveness to Beta-adrenergic stimulation in obesity, using appropriate assay and western blotting techniques as noted above. Insight into possible mechanisms whereby obesity causes increased risk for development of congestive heart failure may lead to important advances in therapeutics modalities for prevention and treatment of congestive heart failure in obese patients. Further, information on mechanisms whereby regular endurance exercise may improve cardiovascular risk profile and cardiac performance in obesity may help reduce risk development of cardiovascular disease. Because such a large segment of the American population is overweight or obese, knowledge and insight gained from these studies can have far-reaching effects. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: THE DIARY OF JOSEPH J MERSMAN, 1847-1864 Principal Investigator & Institution: Fisher, Linda A.; Individual Award--Fisher, Linda A. 4026 Woodland Rd Annandale, Va 22003 Timing: Fiscal Year 2001; Project Start 01-JUL-2001; Project End 30-JUN-2002 Summary: (provided by applicant): This project is to prepare for publication the test and annotation of a diary which gives new insight into mid-nineteenth century life and
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provides graphic accounts of two diseases which marked the era: cholera and syphilis. Written by Joseph J. Mersman (1924-1892), a German immigrant and capitalist, the diary begins in Cincinnati from 1847 to early 1849, and continues in St. Louis until September 1864. His is the story of a self-made member of the burgeoning middle class, with a taste for theater and an eye for women. Family members mentioned in the diary include the writer's sister, Agnes Mersman Lake, the circus star who later married James Butler 'Wild Bill' Hickok. Mostly in English the diary contains sections in French and German and describes many developments in business, social and health matters. The booming capitalist economy, the political climate of the country, and the social networks of immigrants are all part of Mersman's record. The diary includes details of cholera epidemics in 1849 and 1853. Mersman's description of premarital sexual encounters and one year of treatment for syphilis is unlike any other published pre-Civil War narrative. Other documents and textbooks written for and by health professionals, record medical treatments of the era. However, there are few reports of cholera and syphilis from the patient's perspective. The project will include transcribing the handwritten document, providing a critical introduction, extensive footnotes and illustrations. This project will fill a now unmet need for a primary document that illustrates important nineteenth century urban American issues. This diary vividly describes the state of public health in two western cities 150 years ago and provides a unique contribution to existing literature. Although many diaries and personal papers of ordinary people from the same period have been published, they generally focus on the Westward Expansion, the 1849 Gold Rush, or Civil War accounts. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TRANSCUTANEOUS IMMUNIZATION FOR ENTERIC VACCINE Principal Investigator & Institution: Kenney, Richard T.; Vice President; Iomai Corporation 20 Firstfield Rd, Ste 250 Gaithersburg, Md 20878 Timing: Fiscal Year 2002; Project Start 30-SEP-1999; Project End 31-AUG-2003 Summary: (provided by applicant): Having previously demonstrated immune responses in human subjects to heat labile enterotoxin of E coli and the colonization factor CS6, when administered via the transcutaneous route, this application proposes a clinical plan to determine if the observed immune responses are relevant, functional, and protective. First, a preliminary Phase 2 clinical study is proposed to firmly establish the antigen/adjuvant dose required to achieve a consistent and robust immune response. This will be followed by a second study in which volunteers will be challenged with a live E coli organism that expresses both LT and CS6. A successful demonstration of efficacy will lead to further development of an ETEC vaccine with broader coverage. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: TRANSCUTANEOUS IMMUNIZATION FOR TETANUS BOOSTER Principal Investigator & Institution: Glenn, Gregory M.; Iomai Corporation 20 Firstfield Rd, Ste 250 Gaithersburg, Md 20878 Timing: Fiscal Year 2002; Project Start 01-AUG-1999; Project End 30-JUN-2004 Summary: (Provided by Applicant) Based on extensive animal testing and limited human studies, transcutaneous immunization appears to be a viable and valuable technological improvement to traditional administration of vaccines. The aim of the proposed research plan is to continue commercialization of the technology through further clinical development of the lead tetanus booster product, administered by means of a simple skin patch. The critical activities in this program include: A Phase I human
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clinical study to further demonstrate safety and immunogenicity at lower adjuvant/antigen ratios. Product development in the area of formulation, analytical methodology, and patch design to yield a stable, commercially viable product design. A subsequent Phase I human study to evaluate the safety and efficacy of the proposed formulation(s) and patch design(s), at the appropriate dose of adjuvant and antigen. Specific outcomes of the work will be a product design that can advance to Phase II/III human studies required for regulatory licensure. Commercial opportunities for a tetanus booster product have been researched and identified, consisting primarily of developing world programs aimed at eliminating maternal and neonatal tetanus, and atrisk populations in developed countries, including those over 50 years of age and other specific at-risk groups. PROPOSED COMMERCIAL APPLICATION: The Transcutaneous tetanus booster is directed to 2 markets: 1. Maternal and neonatal tetanus elimination, primarily in developing countries; and, 2. Adult booster & at-risk population, including the over-50 population and other specific at-risk groups, such as agricultural workers. The commercial introduction of a tetanus vaccine delivered through a patch is expected to increase access to the vaccine and compliance with immunization protocols for the 2 focus markets, thus growing both markets. Additionally, the Transcutaneous booster will decrease the risk of needle-sticks and related disease, and reduce personnel and equipment requirements related to tetanus immunization. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TRANS-MEMBRANE WATER AND ION MEASUREMENT SYSTEM (TWIMS) Principal Investigator & Institution: Wong, Lid B.; Chief Scientific Officer; Biotechplex Corporation 755 Nicholas Blvd Elk Grove Village, Il 60007 Timing: Fiscal Year 2003; Project Start 30-SEP-2000; Project End 30-JUN-2005 Summary: (provided by applicant): BioTechPlex proposes to develop a Transmembrane Water and Ion Measurement System (TWIMS) to measure miniscule water fluxes across biological membranes in conjunction with their electro-physiological properties. BioTechPlex has accomplished all the objectives proposed in Phase I. A) Developed a novel light source and associated optics for fluorescence photon detection and analysis. B) Integrated the bench optics into a measurement system, tested the system and demonstrated its markedly increased sensitivity for the measurement of transmembrane water fluxes. In this Phase II project, BioTechPlex will integrate the principle and concepts of the electro-optics developed in this Phase I to build an 8-tissue chamber system. To develop a manufacturability prototype of the TWIMS, we will proceed with the development of further innovative technologies. These include: 1) fluorescence detection technology; 2) prototyping of the chambers and tissue holders to accommodate both native epithelia and confluent tissue cultures; and 3) a virtual instrumentation platform for the measurement of luminal to basolateral and basolateral to luminal waters fluxes, potential difference and short circuit current. This multichamber system will be designed to suit the needs of physiologists and pharmacologists, in academia, government and industry. It will be designed for scientific research experiments as well as for use in the drug discovery industry. BioTechPlex plans to market the TWIMS for scientific investigations and drug discovery in fields including but not limited to, 1) respiratory disease such as chronic bronchitis, asthma bronchiectasis and cystic fibrosis; 2) gastrointestinal disease such as diarrhea, cholera infection and severe dehydration; 3) kidney disease such as renal failure; and 4) eye diseases such as dry eye syndrome.
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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TYPE II ENTEROTOXINS AS MUCOSAL IMMUNOMODULATORS Principal Investigator & Institution: Connell, Terry D.; Associate Professor; Microbiology; State University of New York at Buffalo Suite 211 Ub Commons Amherst, Ny 14228 Timing: Fiscal Year 2001; Project Start 15-APR-2001; Project End 31-MAR-2005 Summary: The objective of this application is to evaluate the mucosal adjuvant activities of the Escherichia coli Type II enterotoxins, LT-IIa and LT-IIb. Experiments in the laboratory of the applicant demonstrated that LT-IIa and LT-IIb induce different and distinctive patterns of enhanced immune responses, and that those patterns are profoundly different from those induced by cholera toxin (CT). For example, whereas CT used as an adjuvant induces predominantly a T helper 2-type response based on antibody isotype and cytokine patterns, Type II enterotoxins, particularly LT-IIb, induce both T helper 1 and T helper 2 responses. These data provide strong evidence that LTIIa, LT-IIb, and CT induce their adjuvant activities using different cellular and molecular mechanisms. As such, the Type II toxins provide an elegant set of tools for investigating the mechanisms of mucosal adjuvant induction. Although related in structure, LT-IIa, LT-IIb and CT bind to different sets of cell surface receptors. It is hypothesized that the distinctive adjuvant activities of the toxins are governed by their receptor-binding specificities. To test this hypothesis, the adjuvant activities of the Type II toxins will be analyzed in a mucosal mouse model using AgI/II of the oral pathogen Streptococcus mutans as a model antigen. Both antibody and cellular responses will be assessed. These studies will be facilitated by a collection of receptor-binding mutants, hybrid molecules, and chimeric toxins that are available in this laboratory. Immunization studies will be combined with immunohistological investigations of lymphoid tissue to begin to investigate the cellular component of toxin-induced adjuvant activity. Confocal microscopy will be used to identify the immunocompetent cells in the nasal lymphoid tissue and the draining lymph nodes that initially interact with the toxins after intranasal inoculation. As a further means to correlate adjuvant induction with toxin/cell interactions, immunocompetent cells taken from nasal lymphoid tissue will be classified for expression of toxin-specific surface receptors using flow cytometry analysis. Finally, the potential of non-toxic chimeric Type II proteins as adjuvant/antigen delivery vehicles will be evaluated. At the conclusion of these studies, the laboratory will be well positioned to evaluate the therapeutic potential of the Type II toxins as mucosal adjuvants in the subsequent production of new vaccines that will protect against pathogens that infect the oral, gastric and urogenital mucosae. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: V. PATHOGENESIS
CHOLERAE
IRON
TRANSPORT
MECHANISMS
AND
Principal Investigator & Institution: Payne, Shelley M.; Professor; Molecular Genetics & Microbiol0gy; University of Texas Austin 101 E. 27Th/Po Box 7726 Austin, Tx 78712 Timing: Fiscal Year 2002; Project Start 15-JAN-2002; Project End 31-DEC-2006 Summary: (provided by applicant): Most bacterial pathogens have an absolute requirement for iron. The low availability of iron in most environments has led to the evolution of high affinity iron transport systems. Although iron acquisition systems have been identified in several gram negative organisms, the sources of iron used and the relative contribution of the different systems in their growth and survival in the host
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and in different niches in the external environment are not understood. Vibrio cholerae, the causative agent of cholera, is responsible for considerable morbidity and mortality worldwide. This organism is amenable to genetic manipulation, and several iron acquisition systems have already been identified. However, genetic analysis indicates that there are additional high-affinity iron transport systems in V. cholerae. The recent completion of its genome sequence will allow us to identify the remaining iron acquisition systems and to rigorously examine the roles of the systems in different environments and during exposure to different environmental stresses. Our first Specific Aim is to complete our characterization of V. cholerae heme transport and utilization. Our genetic data indicate that this pathogen expresses multiple heme transport systems, and we will define which genes are required for heme transport. We will also continue characterization of genes that function in the utilization of heme after it has been transported into the cell. Our second Specific Aim is to identify the transport systems used for the uptake of two exogenous siderophores used by V. cholerae, enterobactin and schizokinen. The third Specific Aim is to use our mutant collection, together with other reagents, to determine which transport systems are used during specific environmental conditions, and during growth in the vertebrate host. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: VACCINIA VIRUS VACCINE FOR TYPE 1 DIABETES Principal Investigator & Institution: Langridge, William H.; Biochemistry; Loma Linda University Loma Linda, Ca 92350 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-JUL-2004 Summary: (provided by applicant): Type 1 diabetes is a Thl lymphocyte mediated autoimmune disease that is partially suppressed by oral administration of small amounts of insulin or other diabetes autoantigens. To strengthen this promising immunotolerization approach to diabetes prevention, new innovative strategies are needed. In response to RFA-DK-02-023, we propose to determine the feasibility of a recombinant vaccinia virus (rVV) mediated autoantigen delivery system for suppression of Type 1 diabetes. Genes encoding proinsulin (INS) and glutamate decarboxylase (GAD) autoantigens fused to a cholera toxin B subunit (CTB) receptor IJgand in an rVV expression vector will be expressed in intestinal epithelial cells inoculated with rVV. Following enterocyte apoptosis, autoantigen fusion proteins will be taken up by APCs of the subepithelium or released into the gut and targeted via the CTB ligand to intestinal M cells for indirect APC processing. Two specific aims will determine (1) rVV MOl's required to generate optimum autoantigen protein synthesis in enterocyte cells in culture. (2) The efficacy of rVV mediated tolerance for prevention of Type1 diabetes in vivo and the nature of the T cell response underlying diabetes prevention. Prediabetic NOD/LtJ mice will be orally inoculated with rVV encoding CTB-INS and CTB-GAD enterocyte targeted autoantigen fusion proteins to generate maximum levels of protection from diabetes as measured by levels of insulitis and hyperglycemia. Mechanisms of immunity underlying vaccinia mediated autoantigen suppression of diabetes will be investigated by measurement of T lymphocyte responses to mucosal immunization measured by ELISA quantification of IL-10, TGF-beta, IL-2 and IFNgamma cytokines secreted from salivary gland, spleen, pancreas and mesenteric lymphoid cells. CTL and T lymphocyte proliferation in response to vaccina mediated synthesis of INS and GAD will be quantified by flow cytometric analysis of spleen and mesenteric lymph node memory CD4+ and CD8+ lymphocytes. Specific CTL responses to vaccinia infection will be quantified by LDH assays for rVV, CTB, INS and GAD proteins. The results of these experiments will increase our understanding of the
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immunological mechanisms underlying vaccinia virus mediated immunotolerization against Type 1 diabetes for the long term goal of generating safer, more effective and inexpensive mucosal vaccines for protection against this devastating form of diabetes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: VIBRIO CHOLERAE 01 EPS--STRUCTURE, REGULATION & FUNCTION Principal Investigator & Institution: Schoolnik, Gary K.; Professor; Medicine; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2001; Project Start 01-JUL-1998; Project End 30-JUN-2003 Summary: (Adapted from the applicant's abstract): Epidemiological observations suggest that V. cholerae O1, that cause Asiatic cholera, exists as an indigenous member of the aquatic flora between outbreaks of human disease. Recently investigators in the Schoolnik lab have isolated a novel extracellular polysaccharide (EPS) from the rugose colonial variant of V. cholerae O1 El Tor. Chemical characterization of EPS shows that it is distinct from the O1 LPS and the O139 capsular polysaccharide and morphological studies suggest that it mediates biofilm formation by serving as an interbacterial matrix that causes bacteria to aggregate and attach to inanimate surfaces. Purified EPS also protects the smooth colonial variant of the same strain from the bactericidal effects of chlorine. Insertion mutagenesis of the rugose variant led to the identification of a heretofore unknown cluster of genes, designated vps, with sequences that share homology with polysaccharide biosynthetic genes from other species. Another class of mutants sustained insertions in genes homologous to two-component regulatory systems. These preliminary data have led to the hypothesis that EPS expression confers a survival advantage in environmental aquatic habitats. To test this hypothesis Dr. Schoolnik proposes to complete the structural characterization of EPS; characterize the vps gene cluster; prepare knockout mutants of selected vps genes and test these mutants for their capacity to survive in experimental microcosms that simulate natural aquatic habitats. Dr. Schoolnik's group will also identify physiologic factors that control EPS expression and study how these signals activate vps gene transcription. Finally, in collaborative studies conducted in Bangladesh, they will attempt to learn if V. cholerae O1 expresses EPS in naturally infected water sources. Taken together, these studies should shed some light on why this species continues to cause epidemics as a "reemerging" infectious agent. The grant proposal is divided into three specific aims:(1) Continue to examine the structure and biosynthesis of EPS by completing the physical/chemical structural characterization, and by identifying the genes of the vps gene cluster by mutational analysis and complementation on clones. (2) Study the regulation of vps gene expression using vps gene fusions to ascertain vps gene expression under different growth conditions, including biofilm formation, murine intestinal growth, and algal co-culture. Identify regulatory genes that mediate this regulation by the isolation of mutants with altered regulation. (3) Study the function of EPS by determining the effects of vps mutants on survival under various conditions, and ascertaining the relative abundance of EPS and O1 LPS present on V. cholerae found in biofilm layers in Bangladesh. Determine if there is a direct correlation between the rugose morphotype and EPS production. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: VIBRIO CHOLERAE PATHOGENICITY ISLAND Principal Investigator & Institution: Karaolis, David K R.; Epidemiology and Prev Medicine; University of Maryland Balt Prof School Baltimore, Md 21201
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Timing: Fiscal Year 2001; Project Start 15-JUN-1999; Project End 31-MAY-2004 Summary: (Adapted from the Applicant's Abstract): Cholera is an ancient disease that results in significant morbidity and mortality. The broad aim and focus of this project is to understand the pathogenesis of Vibrio cholera pathogenicity island phage (VPIphage) and its genes in the emergence, virulence, and spread of epidemic cholera. Cholera is traditionally caused by V. cholerae serogroup 01 strains which are divided into two biotypes, classical and El Tor. Although recent emergence of V. cholerae 0139 Bengal has demonstrated that virulent non-01 strains can occur, this strain appears to have evolved from an existing toxigenic 01 strain by substitution of 01 antigen genes to 0139. Thus, the factors involved in the emergence of virulent V. cholerae strains and the epidemic potential of non-01 serogroups are not well understood. Toxigenic V. cholerae appears to emerge via a multi-step process following the sequential infection of two bacteriophages, initially by VPIphage (whose genome represents a large pathogenicity island) then CTXphage (encoding cholera toxin) which uses VPIphage as its receptor. The VPIphage encodes genes which function as virulence factors, genes that regulate virulence factor expression, and a number of open reading frames (orfs) of unknown function. The VPIphage-encoded tcpA gene was thought to encode the major subunit of the toxin co-regulated pilus (TCP) "type IV" pilus, but it now appears that the VPIphage itself is the major V. cholerae colonization factor and that TcpA is the major structural coat protein of VPIphage. The central hypothesis of this proposal is that the VPIphage is critical for the emergence, pathogenesis, and spread of epidemic cholera as 1) the VPIphage is essential for colonization; 2) VPIphage encodes proteins which act as the CTXphage receptor; 3) VPIphage encodes genes which regulate virulence; d) VPIphage encodes genes for transfer of the VPIphage between strains. The specific aims of this proposal are to 1) test the virulence of the VPI in a non-pathogenic host background; 2) analyze the function of cryptic genes on the VPI; 3) to characterize the structure and regulation of a potential VPI-encoded regulon. It is hoped that the proposed experiments will increase the knowledge of the mechanisms leading to the emergence of epidemic strains of cholera and or the emergence of other pathogens that have pathogenicity islands and type IV pili. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: VIBRIO CHOLERAE TCP AND LPS SUBUNIT VACCINE, EPITOPES AN Principal Investigator & Institution: Wade, William F.; Associate Professor; Microbiology and Immunology; Dartmouth College 11 Rope Ferry Rd. #6210 Hanover, Nh 03755 Timing: Fiscal Year 2001; Project Start 01-APR-2000; Project End 31-MAR-2005 Summary: Cholera is an acute diarrheal disease caused by the gram-negative bacterium, Vibrio cholerae. Following ingestion of contaminated food or water, bacteria colonize the small intestine and secrete cholera toxin, which is responsible for the extensive loss of fluid and electrolytes from infected individuals. Cholera remains a worldwide problem. Although a number of live, attenuated or killed whole cell vaccine formulations have been tested, none have proven successful enough to result in their widespread use. This grant proposal focuses on new approaches to develop a cholera subunit vaccine formulation based on the current understanding of V. cholerae colonization, pathogenesis, and human immune responses to infection. The strategy will incorporate features of the highly successful Haemophilus influenzae type b and pertussis vaccines that utilize defined surface virulence determinants, colonization factors, and toxoids to achieve long-lasting protection. The present proposal will focus
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on formulations that include the toxin coregulated pilus (TCP) colonization factor, detoxified LPS, and the adjuvant cholerae toxin. The general goal for these studies is to define the most effective combination of TCP and LPS antigens that provide for protective humoral responses. We will characterize in detail the B cell epitopes for these antigens and determine which epitopes are minimally required for effective immunity. Studies will extend this information to human sera and demonstrate that the epitopes we have identified are operational in the field. Using a well- established mouse model, we will quickly be able to define the immunization regimen and immunogens that are likely candidates for extension into human trials. The proposed research formally brings together the expertise from two research groups at Dartmouth Medical School. Dr. William Wade is a molecular immunologist with training in structural and functional analyses of proteins as they relate to antigen presentation. His research focuses on methodologies to optimize the immunogenicity and delivery of antigens. Dr. Ronald Taylor's research focuses on the molecular basis of V. cholerae pathogenesis. He discovered TCP and his group has been instrumental in characterizing the tcpA gene and corresponding pilin protein as well as demonstrating that TCP is the major V. cholerae colonization factor and a protective antigen. Together, the expertise of these two research groups will provide a unique opportunity to develop and evaluate V: cholerae subunit vaccines using new approaches. 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 “cholera” (or synonyms) into the search box. This search gives you access to fulltext articles. The following is a sample of items found for cholera in the PubMed Central database: •
A cholera toxoid-insulin conjugate as an oral vaccine against spontaneous autoimmune diabetes. by Bergerot I, Ploix C, Petersen J, Moulin V, Rask C, Fabien N, Lindblad M, Mayer A, Czerkinsky C, Holmgren J, Thivolet C.; 1997 Apr 29; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=20771
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A classical strain of Vibrio cholerae with diminished ability to process the proteolytically sensitive site in the A subunit of cholera toxin. by Ichinose Y, Tsuji T, Kato M, Neves BC, Morita K, Ehara M, Hirayama T.; 1996 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=173887
3 4
Adapted from the National Library of Medicine: http://www.pubmedcentral.nih.gov/about/intro.html.
With PubMed Central, NCBI is taking the lead in preservation and maintenance of open access to electronic literature, just as NLM has done for decades with printed biomedical literature. PubMed Central aims to become a world-class library of the digital age. 5 The value of PubMed Central, in addition to its role as an archive, lies in the availability of data from diverse sources stored in a common format in a single repository. Many journals already have online publishing operations, and there is a growing tendency to publish material online only, to the exclusion of print.
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A Cytotoxin-Producing Strain of Vibrio cholerae Non-O1, Non-O139 as a Cause of Cholera and Bacteremia after Consumption of Raw Clams. by Namdari H, Klaips CR, Hughes JL.; 2000 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=87425
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A mutant cholera toxin B subunit that binds GM1- ganglioside but lacks immunomodulatory or toxic activity. by Aman AT, Fraser S, Merritt EA, Rodigherio C, Kenny M, Ahn M, Hol WG, Williams NA, Lencer WI, Hirst TR.; 2001 Jul 17; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=37471
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A new type of conjugative transposon encodes resistance to sulfamethoxazole, trimethoprim, and streptomycin in Vibrio cholerae O139. by Waldor MK, Tschape H, Mekalanos JJ.; 1996 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=178173
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A nontoxic cholera enterotoxin (CT) analog is chimeric with regard to both epitypes of CT-B subunits, CT-B-1 and CT-B-2. by Boesman-Finkelstein M, Peterson JW, Thai LS, Finkelstein RA.; 1996 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=173766
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A nontoxic mutant of cholera toxin elicits Th2-type responses for enhanced mucosal immunity. by Yamamoto S, Kiyono H, Yamamoto M, Imaoka K, Yamamoto M, Fujihashi K, Van Ginkel FW, Noda M, Takeda Y, McGhee JR.; 1997 May 13; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=24667
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A Recombinant Live Attenuated Strain of Vibrio cholerae Induces Immunity against Tetanus Toxin and Bordetella pertussis Tracheal Colonization Factor. by Chen I, Finn TM, Yanqing L, Guoming Q, Rappuoli R, Pizza M.; 1998 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=108100
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A Region of the Transmembrane Regulatory Protein ToxR That Tethers the Transcriptional Activation Domain to the Cytoplasmic Membrane Displays Wide Divergence among Vibrio Species. by Osorio CR, Klose KE.; 2000 Jan 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=94307
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A satellite phage-encoded antirepressor induces repressor aggregation and cholera toxin gene transfer. by Davis BM, Kimsey HH, Kane AV, Waldor MK.; 2002 Aug 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=126166
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A simple filtration method to remove plankton-associated Vibrio cholerae in raw water supplies in developing countries. by Huo A, Xu B, Chowdhury MA, Islam MS, Montilla R, Colwell RR.; 1996 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=168033
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A Survey of Stool Culturing Practices for Vibrio Species at Clinical Laboratories in Gulf Coast States. by Marano NN, Daniels NA, Easton AN, McShan A, Ray B, Wells JG, Griffin PM, Angulo FJ.; 2000 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=86778
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A Vibrio cholerae LysR Homolog, AphB, Cooperates with AphA at the tcpPH Promoter To Activate Expression of the ToxR Virulence Cascade. by Kovacikova G, Skorupski K.; 1999 Jul 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=93926
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A Vibrio cholerae pathogenicity island associated with epidemic and pandemic strains. by Karaolis DK, Johnson JA, Bailey CC, Boedeker EC, Kaper JB, Reeves PR.; 1998 Mar 17; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=19707
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Accessory Cholera Enterotoxin (Ace), the Third Toxin of a Vibrio cholerae Virulence Cassette. by Trucksis M, Galen JE, Michalski J, Fasano A, Kaper JB.; 1993 Jun 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=46697
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Accumulation of cholera toxin and GM1 ganglioside in the early endosome of Niemann --Pick C1-deficient cells. by Sugimoto Y, Ninomiya H, Ohsaki Y, Higaki K, Davies JP, Ioannou YA, Ohno K.; 2001 Oct 23; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=60064
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Active surveillance for Vibrio cholerae O1 and vibriophages in sewage water as a potential tool to predict cholera outbreaks. by Madico G, Checkley W, Gilman RH, Bravo N, Cabrera L, Calderon M, Ceballos A.; 1996 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229443
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Allelic Diversity and Population Structure in Vibrio cholerae O139 Bengal Based on Nucleotide Sequence Analysis. by Farfan M, Minana-Galbis D, Fuste MC, Loren JG.; 2002 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=134837
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Alterations in Vibrio cholerae motility phenotypes correlate with changes in virulence factor expression. by Gardel CL, Mekalanos JJ.; 1996 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=174063
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Alternative Mechanism of Cholera Toxin Acquisition by Vibrio cholerae: Generalized Transduction of CTX[Phi] by Bacteriophage CP-T1. by Fidelma Boyd E, Waldor MK.; 1999 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=96972
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Analysis of 16S-23S rRNA Intergenic Spacer Regions of Vibrio cholerae and Vibrio mimicus. by Chun J, Huq A, Colwell RR.; 1999 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=91317
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Analysis of an Autoregulatory Loop Controlling ToxT, Cholera Toxin, and ToxinCoregulated Pilus Production in Vibrio cholerae. by Yu RR, DiRita VJ.; 1999 Apr 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=93687
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Analysis of Clinical and Environmental Strains of Nontoxigenic Vibrio cholerae for Susceptibility to CTX[Phi]: Molecular Basis for Origination of New Strains with Epidemic Potential. by Faruque SM, Asadulghani, Saha MN, Alim AR, Albert MJ, Islam KM, Mekalanos JJ.; 1998 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=108736
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Analysis of Receptor for Vibrio cholerae El Tor Hemolysin with a Monoclonal Antibody That Recognizes Glycophorin B of Human Erythrocyte Membrane. by Zhang D, Takahashi J, Seno T, Tani Y, Honda T.; 1999 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=96888
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Antibiotic Resistance Conferred by a Conjugative Plasmid and a Class I Integron in Vibrio cholerae O1 El Tor Strains Isolated in Albania and Italy. by Falbo V, Carattoli A, Tosini F, Pezzella C, Dionisi AM, Luzzi I.; 1999 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89185
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Antibodies and Antibody-Secreting Cells in the Female Genital Tract after Vaginal or Intranasal Immunization with Cholera Toxin B Subunit or Conjugates. by Johansson EL, Rask C, Fredriksson M, Eriksson K, Czerkinsky C, Holmgren J.; 1998 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=107936
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Antibody against the capsule of Vibrio cholerae O139 protects against experimental challenge. by Sengupta DK, Boesman-Finkelstein M, Finkelstein RA.; 1996 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=173765
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Antibody Responses in the Lower Respiratory Tract and Male Urogenital Tract in Humans after Nasal and Oral Vaccination with Cholera Toxin B Subunit. by Rudin A, Riise GC, Holmgren J.; 1999 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=96596
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Anti-Class II Monoclonal Antibody-Targeted Vibrio cholerae TcpA Pilin: Modulation of Serologic Response, Epitope Specificity, and Isotype. by Wu JY, Taylor RK, Wade WF.; 2001 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98862
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Association of Protease Activity in Vibrio cholerae Vaccine Strains with Decreases in Transcellular Epithelial Resistance of Polarized T84 Intestinal Epithelial Cells. by Mel SF, Fullner KJ, Wimer-Mackin S, Lencer WI, Mekalanos JJ.; 2000 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=97739
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Attenuated live cholera vaccine strain CVD 103-HgR elicits significantly higher serum vibriocidal antibody titers in persons of blood group O. by Lagos R, Avendano A, Prado V, Horwitz I, Wasserman S, Losonsky G, Cryz S Jr, Kaper JB, Levine MM.; 1995 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=173056
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Bile affects production of virulence factors and motility of Vibrio cholerae. by Gupta S, Chowdhury R.; 1997 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=175102
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Biological and Biochemical Characterization of Variant A Subunits of Cholera Toxin Constructed by Site-Directed Mutagenesis. by Jobling MG, Holmes RK.; 2001 Jul 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=95286
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Cell Vacuolation Caused by Vibrio cholerae Hemolysin. by Figueroa-Arredondo P, Heuser JE, Akopyants NS, Morisaki JH, Giono-Cerezo S, Enriquez-Rincon F, Berg DE.; 2001 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98064
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Cell Vacuolation, a Manifestation of the El Tor Hemolysin of Vibrio cholerae. by Mitra R, Figueroa P, Mukhopadhyay AK, Shimada T, Takeda Y, Berg DE, Nair GB.; 2000 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=97368
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Changes in Human Ecology and Behavior in Relation to the Emergence of Diarrheal Diseases, Including Cholera. by Levine MM, Levine OS.; 1994 Mar 29; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=43377
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Characterization of a Toxigenic Vibrio cholerae O139 Strain Belonging to a New Ribotype and Isolated from a Diarrheal Patient. by Bhanumathi R, Sabeena F, Isac SR, Radhakutty G, Singh DV.; 2002 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=154604
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Characterization of Aeromonas trota strains that cross-react with Vibrio cholerae O139 Bengal. by Albert MJ, Ansaruzzaman M, Shimada T, Rahman A, Bhuiyan NA, Nahar S, Qadri F, Islam MS.; 1995 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=228656
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Characterization of the Major Control Region of Vibrio cholerae Bacteriophage K139: Immunity, Exclusion, and Integration. by Nesper J, Blass J, Fountoulakis M, Reidl J.; 1999 May 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=93736
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Characterization of the Role of the ToxR-Modulated Outer Membrane Porins OmpU and OmpT in Vibrio cholerae Virulence. by Provenzano D, Lauriano CM, Klose KE.; 2001 Jun 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=95243
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Characterization of the Vibrio cholerae El Tor lipase operon lipAB and a protease gene downstream of the hly region. by Ogierman MA, Fallarino A, Riess T, Williams SG, Attridge SR, Manning PA.; 1997 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=179649
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Characterization of Vibrio cgolerae non-O1 serogroups obtained from an outbreak of diarrhea in Lima, Peru. by Dalsgaard A, Albert MJ, Taylor DN, Shimada T, Meza R, Serichantalergs O, Echeverria P.; 1995 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=228562
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Characterization of Vibrio cholerae O1 El Tor galU and galE Mutants: Influence on Lipopolysaccharide Structure, Colonization, and Biofilm Formation. by Nesper J, Lauriano CM, Klose KE, Kapfhammer D, Kraiss A, Reidl J.; 2001 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=97901
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Characterization of VPI Pathogenicity Island and CTX[phi] Prophage in Environmental Strains of Vibrio cholerae. by Mukhopadhyay AK, Chakraborty S, Takeda Y, Nair GB, Berg DE.; 2001 Aug 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=99527
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Cholera from raw seaweed transported from the Philippines to California. by Vugia DJ, Shefer AM, Douglas J, Greene KD, Bryant RG, Werner SB.; 1997 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229558
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Cholera in Vietnam: Changes in Genotypes and Emergence of Class I Integrons Containing Aminoglycoside Resistance Gene Cassettes in Vibrio cholerae O1 Strains Isolated from 1979 to 1996. by Dalsgaard A, Forslund A, Tam NV, Vinh DX, Cam PD.; 1999 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=84539
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Cholera Toxin and Heat-Labile Enterotoxin Activate Human Monocyte-Derived Dendritic Cells and Dominantly Inhibit Cytokine Production through a Cyclic AMPDependent Pathway. by Bagley KC, Abdelwahab SF, Tuskan RG, Fouts TR, Lewis GK.; 2002 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=128358
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Cholera Toxin and Its B Subunit Promote Dendritic Cell Vaccination with Different Influences on Th1 and Th2 Development. by Eriksson K, Fredriksson M, Nordstrom I, Holmgren J.; 2003 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=152034
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Cholera toxin and Salmonella typhimurium induce different cytokine profiles in the gastrointestinal tract. by Klimpel GR, Asuncion M, Haithcoat J, Niesel DW.; 1995 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=173123
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Cholera Toxin B Subunit Activates Arachidonic Acid Metabolism. by Peterson JW, Finkelstein RA, Cantu J, Gessell DL, Chopra AK.; 1999 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=96388
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Cholera Toxin B Subunit as a Carrier Molecule Promotes Antigen Presentation and Increases CD40 and CD86 Expression on Antigen-Presenting Cells. by George-Chandy A, Eriksson K, Lebens M, Nordstrom I, Schon E, Holmgren J.; 2001 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98688
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Cholera Toxin B Subunit: An Efficient Transmucosal Carrier-Delivery System for Induction of Peripheral Immunological Tolerance. by Sun J, Holmgren J, Czerkinsky C.; 1994 Nov 8; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=45112
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Cholera Toxin Induces Migration of Dendritic Cells from the Subepithelial Dome Region to T- and B-Cell Areas of Peyer's Patches. by Shreedhar VK, Kelsall BL, Neutra MR.; 2003 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=143153
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Cholera toxin induces synthesis of phospholipase A2-activating protein. by Peterson JW, Saini SS, Dickey WD, Klimpel GR, Bomalaski JS, Clark MA, Xu XJ, Chopra AK.; 1996 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=174047
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Cholera. by Kaper JB, Morris JG Jr, Levine MM.; 1995 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=172849
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Class 1 Integron-Borne, Multiple-Antibiotic Resistance Encoded by a 150-Kilobase Conjugative Plasmid in Epidemic Vibrio cholerae O1 Strains Isolated in GuineaBissau. by Dalsgaard A, Forslund A, Petersen A, Brown DJ, Dias F, Monteiro S, Molbak K, Aaby P, Rodrigues A, Sandstrom A.; 2000 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=87474
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Classical and El Tor Biotypes of Vibrio cholerae Differ in Timing of Transcription of tcpPH during Growth in Inducing Conditions. by Murley YM, Behari J, Griffin R, Calderwood SB.; 2000 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=97520
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Climate and infectious disease: Use of remote sensing for detection of Vibrio cholerae by indirect measurement. by Lobitz B, Beck L, Huq A, Wood B, Fuchs G, Faruque AS, Colwell R.; 2000 Feb 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=26452
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Clinical and Environmental Isolates of Vibrio cholerae Serogroup O141 Carry the CTX Phage and the Genes Encoding the Toxin-Coregulated Pili. by Dalsgaard A, Serichantalergs O, Forslund A, Lin W, Mekalanos J, Mintz E, Shimada T, Wells JG.; 2001 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=88491
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Cloning and Characterization of Genes Encoding Homologues of the B Subunit of Cholera Toxin and the Escherichia coli Heat-Labile Enterotoxin from Clinical Isolates of Citrobacter freundii and E. coli. by Karasawa T, Ito H, Tsukamoto T, Yamasaki S, Kurazono H, Faruque SM, Nair GB, Nishibuchi M, Takeda Y.; 2002 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=133046
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Cloning and sequence of a region of Vibrio cholerae O139 Bengal and its use in PCRbased detection. by Falklind S, Stark M, Albert MJ, Uhlen M, Lundeberg J, Weintraub A.; 1996 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229431
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Cloning and Sequencing of the Genes Downstream of the wbf Gene Cluster of Vibrio cholerae Serogroup O139 and Analysis of the Junction Genes in Other Serogroups. by Sozhamannan S, Deng YK, Li M, Sulakvelidze A, Kaper JB, Johnson JA, Nair GB, Morris JG Jr.; 1999 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=96850
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Comparative and Genetic Analyses of the Putative Vibrio cholerae Lipopolysaccharide Core Oligosaccharide Biosynthesis (wav) Gene Cluster. by Nesper J, Kraiss A, Schild S, Bla[beta] J, Klose KE, Bockemuhl J, Reidl J.; 2002 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=127954
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Comparative Genomic Analyses of the Vibrio Pathogenicity Island and Cholera Toxin Prophage Regions in Nonepidemic Serogroup Strains of Vibrio cholerae. by Li M, Kotetishvili M, Chen Y, Sozhamannan S.; 2003 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=150053
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Comparative genomic analysis of Vibrio cholerae: Genes that correlate with cholera endemic and pandemic disease. by Dziejman M, Balon E, Boyd D, Fraser CM, Heidelberg JF, Mekalanos JJ.; 2002 Feb 5; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=122229
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Comparison of alternative buffers for use with a new live oral cholera vaccine, Peru15, in outpatient volunteers. by Sack DA, Shimko J, Sack RB, Gomes JG, MacLeod K, O'Sullivan D, Spriggs D.; 1997 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=175291
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Comparison of direct-plating and enrichment methods for isolation of Vibrio cholerae from diarrhea patients. by Lesmana M, Richie E, Subekti D, Simanjuntak C, Walz SE.; 1997 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229856
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Comparison of immune responses in patients infected with Vibrio cholerae O139 and O1. by Qadri F, Wenneras C, Albert MJ, Hossain J, Mannoor K, Begum YA, Mohi G, Salam MA, Sack RB, Svennerholm AM.; 1997 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=175508
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Comparison of the mechanisms of action of cholera toxin and the heat-stable enterotoxins of Escherichia coli. by Peterson JW, Whipp SC.; 1995 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=173174
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Comparison of the vibriocidal antibody response in cholera due to Vibrio cholerae O139 Bengal with the response in cholera due to Vibrio cholerae O1. by Qadri F, Mohi G, Hossain J, Azim T, Khan AM, Salam MA, Sack RB, Albert MJ, Svennerholm AM.; 1995 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=170220
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Comparison of Vibrio cholerae Pathogenicity Islands in Sixth and Seventh Pandemic Strains. by Karaolis DK, Lan R, Kaper JB, Reeves PR.; 2001 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98110
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Concomitant Infection of Enterotoxigenic Escherichia coli in an Outbreak of Cholera Caused by Vibrio cholerae O1 and O139 in Ahmedabad, India. by Chakraborty S, Deokule JS, Garg P, Bhattacharya SK, Nandy RK, Nair GB, Yamasaki S, Takeda Y, Ramamurthy T.; 2001 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=88325
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Construction and Characterization of a Nonproliferative El Tor Cholera Vaccine Candidate Derived from Strain 638. by Valle E, Ledon T, Cedre B, Campos J, Valmaseda T, Rodriguez B, Garcia L, Marrero K, Benitez J, Rodriguez S, Fando R.; 2000 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=97727
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Construction of a Vibrio cholerae Vaccine Candidate Using Transposon Delivery and FLP Recombinase-Mediated Excision. by Chiang SL, Mekalanos JJ.; 2000 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=97724
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Construction of nontoxic derivatives of cholera toxin and characterization of the immunological response against the A subunit. by Fontana MR, Manetti R, Giannelli V, Magagnoli C, Marchini A, Olivieri R, Domenighini M, Rappuoli R, Pizza M.; 1995 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=173311
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CP-96,345, a Substance P Antagonist, Inhibits Rat Intestinal Responses to Clostridium difficile Toxin A but not Cholera Toxin. by Pothoulakis C, Castagliuolo I, Lamont JT, Jaffer A, O'Keane JC, Snider RM, Leeman SE.; 1994 Feb 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=43070
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Crystal structure of an anti-carbohydrate antibody directed against Vibrio cholerae O1 in complex with antigen: Molecular basis for serotype specificity. by Villeneuve S, Souchon H, Riottot MM, Mazie JC, Lei PS, Glaudemans CP, Kovac P, Fournier JM, Alzari PM.; 2000 Jul 18; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=26965
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CTX Prophages in Classical Biotype Vibrio cholerae: Functional Phage Genes but Dysfunctional Phage Genomes. by Davis BM, Moyer KE, Boyd EF, Waldor MK.; 2000 Dec 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=94825
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CTX[phi] immunity: Application in the development of cholera vaccines. by Kimsey HH, Waldor MK.; 1998 Jun 9; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=22729
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CTX[phi] Infection of Vibrio cholerae Requires the tolQRA Gene Products. by Heilpern AJ, Waldor MK.; 2000 Mar 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=94473
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Cyclic AMP and its receptor protein negatively regulate the coordinate expression of cholera toxin and toxin-coregulated pilus in Vibrio cholerae. by Skorupski K, Taylor RK.; 1997 Jan 7; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=19310
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Delineation and Comparison of Ganglioside-Binding Epitopes for the Toxins of Vibrio cholerae, Escherichia coli, and Clostridium tetani: Evidence for Overlapping Epitopes. by Angstrom J, Teneberg S, Karlsson K.; 1994 Dec 6; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=45335
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Detection of RTX Toxin Gene in Vibrio cholerae by PCR. by Chow KH, Ng TK, Yuen KY, Yam WC.; 2001 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=88191
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Development and Evaluation of a Phage Typing Scheme for Vibrio cholerae O139. by Chakrabarti AK, Ghosh AN, Nair GB, Niyogi SK, Bhattacharya SK, Sarkar BL.; 2000 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=86014
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Development and testing of monoclonal antibody-based rapid immunodiagnostic test kits for direct detection of Vibrio cholerae O139 synonym Bengal. by Hasan JA, Huq A, Nair GB, Garg S, Mukhopadhyay AK, Loomis L, Bernstein D, Colwell RR.; 1995 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=228610
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Development of a [Delta]glnA Balanced Lethal Plasmid System for Expression of Heterologous Antigens by Attenuated Vaccine Vector Strains of Vibrio cholerae. by Ryan ET, Crean TI, Kochi SK, John M, Luciano AA, Killeen KP, Klose KE, Calderwood SB.; 2000 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=97124
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Development of a germfree mouse model of Vibrio cholerae infection. by Butterton JR, Ryan ET, Shahin RA, Calderwood SB.; 1996 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=174383
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Development of a Hexaplex PCR Assay for Rapid Detection of Virulence and Regulatory Genes in Vibrio cholerae and Vibrio mimicus. by Singh DV, Isac SR, Colwell RR.; 2002 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=139685
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Differential Activation of the tcpPH Promoter by AphB Determines Biotype Specificity of Virulence Gene Expression in Vibrio cholerae. by Kovacikova G, Skorupski K.; 2000 Jun 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=94511
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Differential Biological and Adjuvant Activities of Cholera Toxin and Escherichia coli Heat-Labile Enterotoxin Hybrids. by Bowman CC, Clements JD.; 2001 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98052
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Differential Interleukin-8 Response of Intestinal Epithelial Cell Line to Reactogenic and Nonreactogenic Candidate Vaccine Strains of Vibrio cholerae. by Rodriguez BL, Rojas A, Campos J, Ledon T, Valle E, Toledo W, Fando R.; 2001 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=97930
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Differential Regulation of Multiple Flagellins in Vibrio cholerae. by Klose KE, Mekalanos JJ.; 1998 Jan 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=106886
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Differential Transcription of the tcpPH Operon Confers Biotype-Specific Control of the Vibrio cholerae ToxR Virulence Regulon. by Murley YM, Carroll PA, Skorupski K, Taylor RK, Calderwood SB.; 1999 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=96860
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Differentiation of Environmental and Clinical Isolates of Vibrio mimicus from Vibrio cholerae by Multilocus Enzyme Electrophoresis. by Vieira VV, Teixeira LF, Vicente AC, Momen H, Salles CA.; 2001 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=92878
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Diminished Diarrheal Response to Vibrio cholerae Strains Carrying the Replicative Form of the CTX[Phi] Genome instead of CTX[Phi] Lysogens in Adult Rabbits. by Faruque SM, Rahman MM, Hasan AK, Nair GB, Mekalanos JJ, Sack DA.; 2001 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98737
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Direct Interaction of the EpsL and EpsM Proteins of the General Secretion Apparatus in Vibrio cholerae. by Sandkvist M, Hough LP, Bagdasarian MM, Bagdasarian M.; 1999 May 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=93768
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Directed polar secretion of protease from single cells of Vibrio cholerae via the type II secretion pathway. by Scott ME, Dossani ZY, Sandkvist M.; 2001 Nov 20; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=61152
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Distinct Cytokine Regulation by Cholera Toxin and Type II Heat-Labile Toxins Involves Differential Regulation of CD40 Ligand on CD4 + T Cells. by Martin M, Metzger DJ, Michalek SM, Connell TD, Russell MW.; 2001 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98523
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Distribution and Content of Class 1 Integrons in Different Vibrio cholerae OSerotype Strains Isolated in Thailand. by Dalsgaard A, Forslund A, Serichantalergs O, Sandvang D.; 2000 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89861
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DNA Adenine Methylase Is Essential for Viability and Plays a Role in the Pathogenesis of Yersinia pseudotuberculosis and Vibrio cholerae. by Julio SM, Heithoff DM, Provenzano D, Klose KE, Sinsheimer RL, Low DA, Mahan MJ.; 2001 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98854
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DNA fingerprinting of Vibrio cholerae strains with a novel insertion sequence element: a tool to identify epidemic strains. by Bik EM, Gouw RD, Mooi FR.; 1996 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229041
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Effect of Cholera Toxin on Intestinal Elimination of Ciprofloxacin in Rabbits. by Musafija A, Barzilai A, Ramon J, Rubinstein E.; 1998 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105441
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Effectiveness of Liposomes Possessing Surface-Linked Recombinant B Subunit of Cholera Toxin as an Oral Antigen Delivery System. by Harokopakis E, Hajishengallis G, Michalek SM.; 1998 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=108519
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Effects of changes in membrane sodium flux on virulence gene expression in Vibrio cholerae. by Hase CC, Mekalanos JJ.; 1999 Mar 16; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=15916
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Effects of Global Climate on Infectious Disease: the Cholera Model. by Lipp EK, Huq A, Colwell RR.; 2002 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=126864
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Effects of Oral Vaccination and Immunomodulation by Cholera Toxin on Experimental Helicobacter pylori Infection, Reinfection, and Gastritis. by Raghavan S, Svennerholm AM, Holmgren J.; 2002 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=128197
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Emergence of a new clone of toxigenic Vibrio cholerae O1 biotype El Tor displacing V. cholerae O139 Bengal in Bangladesh. by Faruque SM, Ahmed KM, Abdul Alim AR, Qadri F, Siddique AK, Albert MJ.; 1997 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229639
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Emergence of Fluoroquinolone Resistance in Strains of Vibrio cholerae Isolated from Hospitalized Patients with Acute Diarrhea in Calcutta, India. by Mukhopadhyay AK, Basu I, Bhattacharya SK, Bhattacharya MK, Balakrish Nair G.; 1998 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105486
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Emergence of Fluoroquinolone-Resistant Strains of Vibrio cholerae O1 Biotype El Tor among Hospitalized Patients with Cholera in Calcutta, India. by Garg P, Sinha S, Chakraborty R, Bhattacharya SK, Nair GB, Ramamurthy T.; 2001 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=90520
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Emergence of Vibrio cholerae O1 Biotype El Tor Serotype Inaba from the Prevailing O1 Ogawa Serotype Strains in India. by Garg P, Nandy RK, Chaudhury P, Chowdhury NR, De K, Ramamurthy T, Yamasaki S, Bhattacharya SK, Takeda Y, Nair GB.; 2000 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=87574
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Endemic and epidemic dynamics of cholera: the role of the aquatic reservoir. by Codeco CT.; 2001; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=29087
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Endochitinase Is Transported to the Extracellular Milieu by the eps-Encoded General Secretory Pathway of Vibrio cholerae. by Connell TD, Metzger DJ, Lynch J, Folster JP.; 1998 Nov 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=107616
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ENSO and cholera: A nonstationary link related to climate change? by Rodo X, Pascual M, Fuchs G, Faruque AS.; 2002 Oct 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=130557
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Enterobacterial repetitive intergenic consensus sequences and the PCR to generate fingerprints of genomic DNAs from Vibrio cholerae O1, O139, and non-O1 strains. by Rivera IG, Chowdhury MA, Huq A, Jacobs D, Martins MT, Colwell RR.; 1995 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=167567
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Environmental Signals Controlling Production of Hemagglutinin/Protease in Vibrio cholerae. by Benitez JA, Silva AJ, Finkelstein RA.; 2001 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98796
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Environmental Signals Modulate ToxT-Dependent Virulence Factor Expression in Vibrio cholerae. by Schuhmacher DA, Klose KE.; 1999 Mar 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=93540
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Epidemiology, Genetics, and Ecology of Toxigenic Vibrio cholerae. by Faruque SM, Albert MJ, Mekalanos JJ.; 1998 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98947
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Escalating Association of Vibrio cholerae O139 with Cholera Outbreaks in India. by Sinha S, Chakraborty R, De K, Khan A, Datta S, Ramamurthy T, Bhattacharya SK, Takeda Y, Nair GB.; 2002 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=120598
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Escherichia coli Heat-Labile Enterotoxin B Subunit Is a More Potent Mucosal Adjuvant than Its Closely Related Homologue, the B Subunit of Cholera Toxin. by Millar DG, Hirst TR, Snider DP.; 2001 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98315
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Evaluation of a bivalent (CVD 103-HgR/CVD 111) live oral cholera vaccine in adult volunteers from the United States and Peru. by Taylor DN, Tacket CO, Losonsky G, Castro O, Gutierrez J, Meza R, Nataro JP, Kaper JB, Wasserman SS, Edelman R, Levine MM, Cryz SJ.; 1997 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=175550
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Evaluation of Cholera Vaccines Formulated with Toxin-Coregulated Pilin Peptide Plus Polymer Adjuvant in Mice. by Wu JY, Wade WF, Taylor RK.; 2001 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98864
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Evaluation of the monoclonal antibody-based kit Bengal SMART for rapid detection of Vibrio cholerae O139 synonym Bengal in stool samples. by Qadri F, Hasan JA, Hossain J, Chowdhury A, Begum YA, Azim T, Loomis L, Sack RB, Albert MJ.; 1995 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=228023
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Evolutionary Relationships of Pathogenic Clones of Vibrio cholerae by Sequence Analysis of Four Housekeeping Genes. by Byun R, Elbourne LD, Lan R, Reeves PR.; 1999 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=96437
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Exogenous Cyclic AMP, Cholera Toxin, and Endotoxin Induce Expression of the Lipopolysaccharide Receptor CD14 in Murine Bone Marrow Cells: Role of Purinoreceptors. by Pedron T, Girard R, Chaby R.; 1999 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=95793
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Expanded Safety and Immunogenicity of a Bivalent, Oral, Attenuated Cholera Vaccine, CVD 103-HgR Plus CVD 111, in United States Military Personnel Stationed in Panama. by Taylor DN, Sanchez JL, Castro JM, Lebron C, Parrado CM, Johnson DE, Tacket CO, Losonsky GA, Wasserman SS, Levine MM, Cryz SJ.; 1999 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=96565
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Factors influencing secondary vibriocidal immune responses: relevance for understanding immunity to cholera. by Losonsky GA, Yunyongying J, Lim V, Reymann M, Lim YL, Wasserman SS, Levine MM.; 1996 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=173720
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Filamentous Bacteriophages of Vibrio parahaemolyticus as a Possible Clue to Genetic Transmission. by Chang B, Taniguchi H, Miyamoto H, Yoshida SI.; 1998 Oct 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=107544
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Genetic analysis of the interaction between Vibrio cholerae transcription activator ToxR and toxT promoter DNA. by Higgins DE, DiRita VJ.; 1996 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=177768
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Genetic and Transcriptional Analyses of the Vibrio cholerae Mannose-Sensitive Hemagglutinin Type 4 Pilus Gene Locus. by Marsh JW, Taylor RK.; 1999 Feb 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=93486
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Genetic Characterization of a New Type IV-A Pilus Gene Cluster Found in Both Classical and El Tor Biotypes of Vibrio cholerae. by Fullner KJ, Mekalanos JJ.; 1999 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=96473
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Genetic Diversity and Population Structure of Vibrio cholerae. by Beltran P, Delgado G, Navarro A, Trujillo F, Selander RK, Cravioto A.; 1999 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=84478
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Genetic Diversity of Clinical and Environmental Isolates of Vibrio cholerae Determined by Amplified Fragment Length Polymorphism Fingerprinting. by Jiang SC, Matte M, Matte G, Huq A, Colwell RR.; 2000 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=91798
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Genetic Diversity of Vibrio cholerae in Chesapeake Bay Determined by Amplified Fragment Length Polymorphism Fingerprinting. by Jiang SC, Louis V, Choopun N, Sharma A, Huq A, Colwell RR.; 2000 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=91797
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Genetic Diversity of Vibrio cholerae O1 in Argentina and Emergence of a New Variant. by Pichel M, Rivas M, Chinen I, Martin F, Ibarra C, Binsztein N.; 2003 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=149600
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Genomic Diversity of Clinical and Environmental Vibrio cholerae Strains Isolated in Brazil between 1991 and 2001 as Revealed by Fluorescent Amplified Fragment Length Polymorphism Analysis. by Thompson FL, Thompson CC, Vicente AC, Theophilo GN, Hofer E, Swings J.; 2003 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=154745
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Genomic profiles of clinical and environmental isolates of Vibrio cholerae O1 in cholera-endemic areas of Bangladesh. by Zo YG, Rivera IN, Russek-Cohen E, Islam MS, Siddique AK, Yunus M, Sack RB, Huq A, Colwell RR.; 2002 Sep 17; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=129458
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Genotypes Associated with Virulence in Environmental Isolates of Vibrio cholerae. by Rivera IN, Chun J, Huq A, Sack RB, Colwell RR.; 2001 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=92890
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Group B Streptococcus Capsular Polysaccharide-Cholera Toxin B Subunit Conjugate Vaccines Prepared by Different Methods for Intranasal Immunization. by Shen X, Lagergard T, Yang Y, Lindblad M, Fredriksson M, Holmgren J.; 2001 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=97884
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Heterologous antigen expression in Vibrio cholerae vector strains. by Butterton JR, Beattie DT, Gardel CL, Carroll PA, Hyman T, Killeen KP, Mekalanos JJ, Calderwood SB.; 1995 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=173360
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High-Resolution FRET Microscopy of Cholera Toxin B-Subunit and GPI-anchored Proteins in Cell Plasma Membranes. by Kenworthy AK, Petranova N, Edidin M.; 2000 May 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=14873
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Human Infection with Ascaris lumbricoides Is Associated with Suppression of the Interleukin-2 Response to Recombinant Cholera Toxin B Subunit following Vaccination with the Live Oral Cholera Vaccine CVD 103-HgR. by Cooper PJ, Chico M, Sandoval C, Espinel I, Guevara A, Levine MM, Griffin GE, Nutman TB.; 2001 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98058
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Identification and Strain Differentiation of Vibrio cholerae by Using Polyclonal Antibodies against Outer Membrane Proteins. by Martinez-Govea A, Ambrosio J, Gutierrez-Cogco L, Flisser A.; 2001 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=96140
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Identification in traditional herbal medications and confirmation by synthesis of factors that inhibit cholera toxin-induced fluid accumulation. by Oi H, Matsuura D, Miyake M, Ueno M, Takai I, Yamamoto T, Kubo M, Moss J, Noda M.; 2002 Mar 5; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=122469
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Identification of a Vibrio cholerae RTX toxin gene cluster that is tightly linked to the cholera toxin prophage. by Lin W, Fullner KJ, Clayton R, Sexton JA, Rogers MB, Calia KE, Calderwood SB, Fraser C, Mekalanos JJ.; 1999 Feb 2; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=15352
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Identification of motifs in cholera toxin A1 polypeptide that are required for its interaction with human ADP-ribosylation factor 6 in a bacterial two-hybrid system. by Jobling MG, Holmes RK.; 2000 Dec 19; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=18975
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Identification of Multiple [final sigma]54-Dependent Transcriptional Activators in Vibrio cholerae. by Klose KE, Novik V, Mekalanos JJ.; 1998 Oct 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=107568
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Identification of the Vibrio cholerae Enterobactin Receptors VctA and IrgA: IrgA Is Not Required for Virulence. by Mey AR, Wyckoff EE, Oglesby AG, Rab E, Taylor RK, Payne SM.; 2002 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=128051
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Immune mechanisms and protective antigens of Vibrio cholerae serogroup O139 as a basis for vaccine development. by Jonson G, Osek J, Svennerholm AM, Holmgren J.; 1996 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=174293
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Immune Response Genes Modulate Serologic Responses to Vibrio cholerae TcpA Pilin Peptides. by Meeks MD, Wade TK, Taylor RK, Wade WF.; 2001 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98863
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Immune Response Induced by Recombinant Mycobacterium bovis BCG Producing the Cholera Toxin B Subunit. by Biet F, Kremer L, Wolowczuk I, Delacre M, Locht C.; 2003 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=153234
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Immune response to the mannose-sensitive hemagglutinin in patients with cholera due to Vibrio cholerae O1 and O0139. by Qadri F, Jonson G, Begum YA, Wenneras C, Albert MJ, Salam MA, Svennerholm AM.; 1997 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=170545
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Immune Responses in Ileostomy Fluid and Serum after Oral Cholera Vaccination of Patients Colectomized because of Ulcerative Colitis. by Kilhamn J, Brevinge H, Svennerholm AM, Jertborn M.; 1998 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=108473
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Immunogenicity in Peruvian volunteers of a booster dose of oral cholera vaccine consisting of whole cells plus recombinant B subunit. by Begue RE, Castellares G, Cabezas C, Sanchez JL, Meza R, Watts DM, Taylor DN.; 1995 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=173519
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Immunologic characteristics of a Streptococcus mutans glucosyltransferase B sucrosebinding site peptide-cholera toxin B-subunit chimeric protein. by Laloi P, Munro CL, Jones KR, Macrina FL.; 1996 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=173723
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In Vitro and In Vivo Analyses of Constitutive and In Vivo-Induced Promoters in Attenuated Vaccine and Vector Strains of Vibrio cholerae. by John M, Crean TI, Calderwood SB, Ryan ET.; 2000 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=97263
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In Vivo Expression and Immunoadjuvancy of a Mutant of Heat-Labile Enterotoxin of Escherichia coli in Vaccine and Vector Strains of Vibrio cholerae. by Ryan ET, Crean TI, John M, Butterton JR, Clements JD, Calderwood SB.; 1999 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=96516
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Increased Levels of Inflammatory Mediators in Children and Adults Infected with Vibrio cholerae O1 and O139. by Qadri F, Raqib R, Ahmed F, Rahman T, Wenneras C, Kumar Das S, Alam NH, Mathan MM, Svennerholm AM.; 2002 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=119937
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Induction and Distribution of Intestinal Immune Responses after Administration of Recombinant Cholera Toxin B Subunit in the Ileal Pouches of Colectomized Patients. by Kilhamn J, Brevinge H, Quiding-Jarbrink M, Svennerholm AM, Jertborn M.; 2001 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98313
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Induction of Fimbriated Vibrio cholerae O139. by Ehara M, Iwami M, Ichinose Y, Hirayama T, Albert MJ, Sack RB, Shimodori S.; 1998 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=121393
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Induction of Systemic Antifimbria and Antitoxin Antibody Responses in Egyptian Children and Adults by an Oral, Killed Enterotoxigenic Escherichia coli plus Cholera Toxin B Subunit Vaccine. by Hall ER, Wierzba TF, Ahren C, Rao MR, Bassily S, Francis W, Girgis FY, Safwat M, Lee YJ, Svennerholm AM, Clemens JD, Savarino SJ.; 2001 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98234
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Induction of the Lysogenic Phage Encoding Cholera Toxin in Naturally Occurring Strains of Toxigenic Vibrio cholerae O1 and O139. by Faruque SM, Asadulghani, Abdul Alim AR, Albert MJ, Nasirul Islam KM, Mekalanos JJ.; 1998 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=108411
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Infectious CTX[Phi] and the Vibrio Pathogenicity Island Prophage in Vibrio mimicus: Evidence for Recent Horizontal Transfer between V. mimicus and V. cholerae. by Boyd EF, Moyer KE, Shi L, Waldor MK.; 2000 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=97308
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Inhibition of Endoplasmic Reticulum-Associated Degradation in CHO Cells Resistant to Cholera Toxin, Pseudomonas aeruginosa Exotoxin A, and Ricin. by Teter K, Holmes RK.; 2002 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=130429
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Inhibitors of COP-mediated Transport and Cholera Toxin Action Inhibit Simian Virus 40 Infection. by Richards AA, Stang E, Pepperkok R, Parton RG.; 2002 May 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=111141
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Initial studies of the structural signal for extracellular transport of cholera toxin and other proteins recognized by Vibrio cholerae. by Connell TD, Metzger DJ, Wang M, Jobling MG, Holmes RK.; 1995 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=173575
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Intracellular Signal Triggered by Cholera Toxin in Saccharomyces boulardii and Saccharomyces cerevisiae. by Brandao RL, Castro IM, Bambirra EA, Amaral SC, Fietto LG, Tropia MJ, Neves MJ, Dos Santos RG, Gomes NC, Nicoli JR.; 1998 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=106083
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Intranasal Immunization with Cytotoxic T-Lymphocyte Epitope Peptide and Mucosal Adjuvant Cholera Toxin: Selective Augmentation of Peptide-Presenting Dendritic Cells in Nasal Mucosa-Associated Lymphoid Tissue. by Porgador A, Staats HF, Itoh Y, Kelsall BL.; 1998 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=108744
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Intranasal Immunization with Recombinant Ascaris suum 14-Kilodalton Antigen Coupled with Cholera Toxin B Subunit Induces Protective Immunity to A. suum Infection in Mice. by Tsuji N, Suzuki K, Kasuga-Aoki H, Matsumoto Y, Arakawa T, Ishiwata K, Isobe T.; 2001 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98813
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Intranasal immunization with SAG1 protein of Toxoplasma gondii in association with cholera toxin dramatically reduces development of cerebral cysts after oral infection. by Debard N, Buzoni-Gatel D, Bout D.; 1996 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=174050
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Intranasal immunogenicity and adjuvanticity of site-directed mutant derivatives of cholera toxin. by Douce G, Fontana M, Pizza M, Rappuoli R, Dougan G.; 1997 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=175397
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Intranasal vaccination of humans with recombinant cholera toxin B subunit induces systemic and local antibody responses in the upper respiratory tract and the vagina. by Bergquist C, Johansson EL, Lagergard T, Holmgren J, Rudin A.; 1997 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=175378
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Intranasal Vaccination Using Interleukin-12 and Cholera Toxin Subunit B as Adjuvants To Enhance Mucosal and Systemic Immunity to Human Immunodeficiency Virus Type 1 Glycoproteins. by Albu DI, Jones-Trower A, Woron AM, Stellrecht K, Broder CC, Metzger DW.; 2003 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=154022
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Investigation of the Roles of Toxin-Coregulated Pili and Mannose-Sensitive Hemagglutinin Pili in the Pathogenesis of Vibrio cholerae O139 Infection. by Tacket CO, Taylor RK, Losonsky G, Lim Y, Nataro JP, Kaper JB, Levine MM.; 1998 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=107958
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Isolation and Characterization of Rugose Form of Vibrio cholerae O139 Strain MO10. by Mizunoe Y, Wai SN, Takade A, Yoshida SI.; 1999 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=96411
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Isolation of sucrose late-fermenting and nonfermenting variants of Vibrio cholerae O139 Bengal: implications for diagnosis of cholera. by Ansaruzzaman M, Rahman M, Kibriya AK, Bhuiyan NA, Islam MS, Albert MJ.; 1995 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=228158
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Kinetics of Local and Systemic Immune Responses to an Oral Cholera Vaccine Given Alone or Together with Acetylcysteine. by Kilhamn J, Jertborn M, Svennerholm AM.; 1998 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=121366
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Lessons to be learned from studying Vibrio cholerae in model systems. by Chaudhuri K.; 2001; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=138950
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Lipopolysaccharide- and Cholera Toxin-Specific Subclass Distribution of B-Cell Responses in Cholera. by Qadri F, Ahmed F, Karim MM, Wenneras C, Begum YA, Salam MA, Albert MJ, McGhee JR.; 1999 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=95781
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Local and systemic antibody responses to dextran-cholera toxin B subunit conjugates. by Bergquist C, Lagergard T, Lindblad M, Holmgren J.; 1995 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=173259
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Local and Systemic Immune Responses to Rectal Administration of Recombinant Cholera Toxin B Subunit in Humans. by Jertborn M, Nordstrom I, Kilander A, Czerkinsky C, Holmgren J.; 2001 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98479
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Lysogenic Conversion of Environmental Vibrio mimicus Strains by CTX[Phi]. by Faruque SM, Rahman MM, Asadulghani, Islam KM, Mekalanos JJ.; 1999 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=96947
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Mechanism of ToxT-Dependent Transcriptional Activation at the Vibrio cholerae tcpA Promoter. by Hulbert RR, Taylor RK.; 2002 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=139592
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Microtiter Assay for Detecting Campylobacter spp. and Helicobacter pylori with Surface Gangliosides Which Bind Cholera Toxin. by Sack DA, Lastovica AJ, Chang SH, Pazzaglia G.; 1998 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=104975
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Modulation of Expression of the ToxR Regulon in Vibrio cholerae by a Member of the Two-Component Family of Response Regulators. by Wong SM, Carroll PA, Rahme LG, Ausubel FM, Calderwood SB.; 1998 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=108741
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Molecular Analyses of a Putative CTX[phi] Precursor and Evidence for Independent Acquisition of Distinct CTX[phi]s by Toxigenic Vibrio cholerae. by Boyd EF, Heilpern AJ, Waldor MK.; 2000 Oct 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=110998
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Molecular Analysis of Non-O1, Non-O139 Vibrio cholerae Associated with an Unusual Upsurge in the Incidence of Cholera-Like Disease in Calcutta, India. by Sharma C, Thungapathra M, Ghosh A, Mukhopadhyay AK, Basu A, Mitra R, Basu I, Bhattacharya SK, Shimada T, Ramamurthy T, Takeda T, Yamasaki S, Takeda Y, Nair GB.; 1998 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=104621
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Molecular analysis of toxigenic Vibrio cholerae O139 Bengal strains isolated in Bangladesh between 1993 and 1996: evidence for emergence of a new clone of the Bengal vibrios. by Faruque SM, Ahmed KM, Siddique AK, Zaman K, Alim AR, Albert MJ.; 1997 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229958
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Molecular Analysis of Vibrio cholerae O1, O139, non-O1, and non-O139 Strains: Clonal Relationships between Clinical and Environmental Isolates. by Singh DV, Matte MH, Matte GR, Jiang S, Sabeena F, Shukla BN, Sanyal SC, Huq A, Colwell RR.; 2001 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=92666
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Molecular Characterization of a New Ribotype of Vibrio cholerae O139 Bengal Associated with an Outbreak of Cholera in Bangladesh. by Faruque SM, Siddique AK, Saha MN, Asadulghani, Rahman MM, Zaman K, Albert MJ, Sack DA, Sack RB.; 1999 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=84761
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Molecular characterization of Vibrio cholerae O1 strains isolated during cholera outbreaks in Guinea-Bissau. by Dalsgaard A, Mortensen HF, Molbak K, Dias F, Serichantalergs O, Echeverria P.; 1996 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=228980
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Molecular Characterization of Vibrio cholerae O139 Bengal Isolated from Water and the Aquatic Plant Eichhornia crassipes in the River Ganga, Varanasi, India. by Bhanumathi R, Sabeena F, Isac SR, Shukla BN, Singh DV.; 2003 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=154771
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Molecular Epidemiology of Reemergent Vibrio cholerae O139 Bengal in India. by Mukhopadhyay AK, Basu A, Garg P, Bag PK, Ghosh A, Bhattacharya SK, Takeda Y, Nair GB.; 1998 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105015
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Molecular epidemiology of toxigenic Vibrio cholerae in Bangladesh studied by numerical analysis of rRNA gene restriction patterns. by Faruque SM, Roy SK, Alim AR, Siddique AK, Albert MJ.; 1995 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=228589
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Molecular Evidence that a Distinct Vibrio cholerae O1 Biotype El Tor Strain in Calcutta May Have Spread to the African Continent. by Sharma C, Ghosh A, Dalsgaard A, Forslund A, Ghosh RK, Bhattacharya SK, Nair GB.; 1998 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=104642
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Molecular evolution of Vibrio cholerae O1 strains isolated in Lima, Peru, from 1991 to 1995. by Dalsgaard A, Skov MN, Serichantalergs O, Echeverria P, Meza R, Taylor DN.; 1997 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=232720
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Mucosal Immunization with a Genetically Engineered Pertussis Toxin S1 FragmentCholera Toxin Subunit B Chimeric Protein. by Lee SF, Halperin SA, Salloum DF, MacMillan A, Morris A.; 2003 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=152103
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Mucosal Immunization with Helicobacter, CpG DNA, and Cholera Toxin Is Protective. by Jiang W, Baker HJ, Smith BF.; 2003 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=143171
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Mucosal Immunogenicity of a Holotoxin-Like Molecule Containing the Serine-Rich Entamoeba histolytica Protein (SREHP) Fused to the A2 Domain of Cholera Toxin. by Sultan F, Jin LL, Jobling MG, Holmes RK, Stanley SL Jr.; 1998 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=107928
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Mucosal immunogenicity of a recombinant Salmonella typhimurium-cloned heterologous antigen in the absence or presence of coexpressed cholera toxin A2 and B subunits. by Harokopakis E, Hajishengallis G, Greenway TE, Russell MW, Michalek SM.; 1997 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=175152
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Multilocus Sequence Typing Has Better Discriminatory Ability for Typing Vibrio cholerae than Does Pulsed-Field Gel Electrophoresis and Provides a Measure of
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Phylogenetic Relatedness. by Kotetishvili M, Stine OC, Chen Y, Kreger A, Sulakvelidze A, Sozhamannan S, Morris, Jr. JG.; 2003 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=154734 •
Mutational Analysis of Ganglioside GM1-Binding Ability, Pentamer Formation, and Epitopes of Cholera Toxin B (CTB) Subunits and CTB/Heat-Labile Enterotoxin B Subunit Chimeras. by Jobling MG, Holmes RK.; 2002 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=127768
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Mutations in the Extracellular Protein Secretion Pathway Genes (eps) Interfere with Rugose Polysaccharide Production in and Motility of Vibrio cholerae. by Ali A, Johnson JA, Franco AA, Metzger DJ, Connell TD, Morris JG Jr, Sozhamannan S.; 2000 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=97374
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Mutations in toxR and toxS That Separate Transcriptional Activation from DNA Binding at the Cholera Toxin Gene Promoter. by Pfau JD, Taylor RK.; 1998 Sep 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=107489
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Native and Mutant Forms of Cholera Toxin and Heat-Labile Enterotoxin Effectively Enhance Protective Efficacy of Live Attenuated and Heat-Killed Shigella Vaccines. by Hartman AB, Van De Verg LL, Venkatesan MM.; 1999 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=96964
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New evidence for an inflammatory component in diarrhea caused by selected new, live attenuated cholera vaccines and by El Tor and Q139 Vibrio cholerae. by Silva TM, Schleupner MA, Tacket CO, Steiner TS, Kaper JB, Edelman R, Guerrant R.; 1996 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=174082
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New variant of Vibrio cholerae O1 from clinical isolates in Amazonia. by Coelho A, Andrade JR, Vicente AC, Salles CA.; 1995 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=227891
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New Variants of Vibrio cholerae O1 Biotype El Tor with Attributes of the Classical Biotype from Hospitalized Patients with Acute Diarrhea in Bangladesh. by Nair GB, Faruque SM, Bhuiyan NA, Kamruzzaman M, Siddique AK, Sack DA.; 2002 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=130785
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NhaA, an Na +/H + Antiporter Involved in Environmental Survival of Vibrio cholerae. by Vimont S, Berche P.; 2000 May 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=102005
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Nontoxigenic Vibrio cholerae 01 serotype Inaba biotype El Tor associated with a cluster of cases of cholera in southern India. by Saha PK, Koley H, Mukhopadhyay AK, Bhattacharya SK, Nair GB, Ramakrishnan BS, Krishnan S, Takeda T, Takeda Y.; 1996 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=228965
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Nucleotide Sequence and Spatiotemporal Expression of the Vibrio cholerae vieSAB Genes during Infection. by Lee SH, Angelichio MJ, Mekalanos JJ, Camilli A.; 1998 May 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=107168
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Optimizing the Germfree Mouse Model for In Vivo Evaluation of Oral Vibrio cholerae Vaccine and Vector Strains. by Crean TI, John M, Calderwood SB, Ryan ET.; 2000 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=97235
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Oral immunization of interleukin-4 (IL-4) knockout mice with a recombinant Salmonella strain or cholera toxin reveals that CD4+ Th2 cells producing IL-6 and IL10 are associated with mucosal immunoglobulin A responses. by Okahashi N, Yamamoto M, Vancott JL, Chatfield SN, Roberts M, Bluethmann H, Hiroi T, Kiyono H, McGhee JR.; 1996 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=173956
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Oral immunization with attenuated vaccine strains of Vibrio cholerae expressing a dodecapeptide repeat of the serine-rich Entamoeba histolytica protein fused to the cholera toxin B subunit induces systemic and mucosal antiamebic and anti-V. cholerae antibody responses in mice. by Ryan ET, Butterton JR, Zhang T, Baker MA, Stanley SL Jr, Calderwood SB.; 1997 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=175440
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Oral immunization with the dodecapeptide repeat of the serine-rich Entamoeba histolytica protein (SREHP) fused to the cholera toxin B subunit induces a mucosal and systemic anti-SREHP antibody response. by Zhang T, Li E, Stanley SL Jr.; 1995 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=173157
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Oral immunization with the saliva-binding region of Streptococcus mutans AgI/II genetically coupled to the cholera toxin B subunit elicits T-helper-cell responses in gut-associated lymphoid tissues. by Toida N, Hajishengallis G, Wu HY, Russell MW.; 1997 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=175068
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Ordered Cloned DNA Map of the Genome of Vibrio cholerae 569B and Localization of Genetic Markers. by Chatterjee S, Mondal AK, Begum NA, Roychoudhury S, Das J.; 1998 Feb 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=106970
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Pandemic Spread of Cholera: Genetic Diversity and Relationships within the Seventh Pandemic Clone of Vibrio cholerae Determined by Amplified Fragment Length Polymorphism. by Lan R, Reeves PR.; 2002 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=120103
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Pathogenic Potential of Environmental Vibrio cholerae Strains Carrying Genetic Variants of the Toxin-Coregulated Pilus Pathogenicity Island. by Faruque SM, Kamruzzaman M, Meraj IM, Chowdhury N, Nair GB, Sack RB, Colwell RR, Sack DA.; 2003 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=145385
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pepA, a Gene Mediating pH Regulation of Virulence Genes in Vibrio cholerae. by Behari J, Stagon L, Calderwood SB.; 2001 Jan 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=94864
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Persistence of serum and salivary antibody responses after oral immunization with a bacterial protein antigen genetically linked to the A2/B subunits of cholera toxin. by Hajishengallis G, Michalek SM, Russell MW.; 1996 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=173818
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Phage specific for Vibrio cholerae O139 Bengal. by Albert MJ, Bhuiyan NA, Rahman A, Ghosh AN, Hultenby K, Weintraub A, Nahar S, Kibriya AK, Ansaruzzaman M, Shimada T.; 1996 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229133
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Phagocytic Cell Killing Mediated by Secreted Cytotoxic Factors of Vibrio cholerae. by Punj V, Zaborina O, Dhiman N, Falzari K, Bagdasarian M, Chakrabarty AM.; 2000 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=101703
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Phase 1 Evaluation of Vibrio cholerae O1, Serotype Inaba, Polysaccharide-Cholera Toxin Conjugates in Adult Volunteers. by Gupta RK, Taylor DN, Bryla DA, Robbins JB, Szu SC.; 1998 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=108318
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Phenotypic and genotypic changes in Vibrio cholerae O139 Bengal. by Albert MJ, Bhuiyan NA, Talukder KA, Faruque AS, Nahar S, Faruque SM, Ansaruzzaman M, Rahman M.; 1997 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=230015
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Phylogeny of Vibrio cholerae Based on recA Sequence. by Stine OC, Sozhamannan S, Gou Q, Zheng S, Morris JG Jr, Johnson JA.; 2000 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=97837
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pIIICTX, a Predicted CTX[phi] Minor Coat Protein, Can Expand the Host Range of Coliphage fd To Include Vibrio cholerae. by Heilpern AJ, Waldor MK.; 2003 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=142820
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Plasmid Vectors Encoding Cholera Toxin or the Heat-Labile Enterotoxin from Escherichia coli Are Strong Adjuvants for DNA Vaccines. by Arrington J, Braun RP, Dong L, Fuller DH, Macklin MD, Umlauf SW, Wagner SJ, Wu MS, Payne LG, Haynes JR.; 2002 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=155070
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Plasmidic Extended-Spectrum [beta]-Lactamases in Vibrio cholerae O1 El Tor Isolates in Argentina. by Petroni A, Corso A, Melano R, Cacace ML, Bru AM, Rossi A, Galas M.; 2002 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=127142
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Preliminary Assessment of the Safety and Immunogenicity of a New CTX[Phi]Negative, Hemagglutinin/Protease-Defective El Tor Strain as a Cholera Vaccine Candidate. by Benitez JA, Garcia L, Silva A, Garcia H, Fando R, Cedre B, Perez A, Campos J, Rodriguez BL, Perez JL, Valmaseda T, Perez O, Perez A, Ramirez M, Ledon T, Jidy MD, Lastre M, Bravo L, Sierra G.; 1999 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=96352
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Preparation, Immunogenicity, and Protective Efficacy, in a Murine Model, of a Conjugate Vaccine Composed of the Polysaccharide Moiety of the Lipopolysaccharide of Vibrio cholerae O139 Bound to Tetanus Toxoid. by Boutonnier A, Villeneuve S, Nato F, Dassy B, Fournier JM.; 2001 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98317
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Production of Vibrio cholerae accessory cholera enterotoxin (Ace) in the yeast Pichia pastoris. by Trucksis M, Conn TL, Fasano A, Kaper JB.; 1997 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=175719
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Promoter activities in Vibrio cholerae ctx phi prophage. by Fando R, Perez JL, Rodriguez BL, Campos J, Robert A, Garcia L, Silva A, Benitez JA.; 1997 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=175171
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Pulsed-Field Gel Electrophoresis-Based Molecular Comparison of Vibrio cholerae O1 Isolates from Domestic and Imported Cases of Cholera in Japan. by Arakawa E, Murase T, Matsushita S, Shimada T, Yamai S, Ito T, Watanabe H.; 2000 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=88740
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Purification and characterization of a Chinese hamster ovary cell elongation factor of Vibrio hollisae. by Kothary MH, Claverie EF, Miliotis MD, Madden JM, Richardson SH.; 1995 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=173323
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Purification and Characterization of a Cytotonic Protein Expressed In Vitro by the Live Cholera Vaccine Candidate CVD 103-HgR. by Sathyamoorthy V, Hall RH, McCardell BA, Kothary MH, Ahn SJ, Ratnayake S.; 2000 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=101575
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Purification and Characterization of Novel Toxin Produced by Vibrio cholerae O1. by Walia K, Ghosh S, Singh H, Nair GB, Ghosh A, Sahni G, Vohra H, Ganguly NK.; 1999 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=96873
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Quorum-sensing regulators control virulence gene expression in Vibrio cholerae. by Zhu J, Miller MB, Vance RE, Dziejman M, Bassler BL, Mekalanos JJ.; 2002 Mar 5; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=122484
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Random Amplified Polymorphic DNA and Amplified Fragment Length Polymorphism Analyses of Pasteurella multocida Isolates from Fatal Fowl Cholera Infections. by Huber BS, Allred DV, Carmen JC, Frame DD, Whiting DG, Cryan JR, Olson TR, Jackson PJ, Hill K, Laker MT, Robison RA.; 2002 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=130706
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Randomized, Controlled Human Challenge Study of the Safety, Immunogenicity, and Protective Efficacy of a Single Dose of Peru-15, a Live Attenuated Oral Cholera Vaccine. by Cohen MB, Giannella RA, Bean J, Taylor DN, Parker S, Hoeper A, Wowk S, Hawkins J, Kochi SK, Schiff G, Killeen KP.; 2002 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=127885
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Randomized, double-blind placebo-controlled trial to evaluate the safety and immunogenicity of combined Salmonella typhi Ty21a and Vibrio cholerae CVD 103HgR live oral vaccines. by Kollaritsch H, Furer E, Herzog C, Wiedermann G, Que JU, Cryz SJ Jr.; 1996 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=173943
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Randomized, Double-Blind, Placebo-Controlled, Multicentered Trial of the Efficacy of a Single Dose of Live Oral Cholera Vaccine CVD 103-HgR in Preventing Cholera following Challenge with Vibrio cholerae O1 El Tor Inaba Three Months after Vaccination. by Tacket CO, Cohen MB, Wasserman SS, Losonsky G, Livio S, Kotloff K, Edelman R, Kaper JB, Cryz SJ, Giannella RA, Schiff G, Levine MM.; 1999 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=97039
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Rapid detection of Vibrio cholerae O139 Bengal from stool specimens by PCR. by Albert MJ, Islam D, Nahar S, Qadri F, Falklind S, Weintraub A.; 1997 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229809
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Rapid Diagnosis of Cholera Caused by Vibrio cholerae O139. by Chaicumpa W, Srimanote P, Sakolvaree Y, Kalampaheti T, Chongsa-Nguan M, Tapchaisri P, Eampokalap B, Moolasart P, Nair GB, Echeverria P.; 1998 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105246
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Rapid Method for Species-Specific Identification of Vibrio cholerae Using Primers Targeted to the Gene of Outer Membrane Protein OmpW. by Nandi B, Nandy RK, Mukhopadhyay S, Nair GB, Shimada T, Ghose AC.; 2000 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=87555
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Rapid screening method for identification of cholera toxin-producing Vibrio cholerae O1 and O139. by Osawa R, Okitsu T, Sata S, Yamai S.; 1997 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229707
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Relative significance of mannose-sensitive hemagglutinin and toxin-coregulated pili in colonization of infant mice by Vibrio cholerae El Tor. by Attridge SR, Manning PA, Holmgren J, Jonson G.; 1996 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=174231
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Resurgent Vibrio cholerae O139: Rearrangement of Cholera Toxin Genetic Elements and Amplification of rrn Operon. by Khetawat G, Bhadra RK, Nandi S, Das J.; 1999 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=96290
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rfb Mutations in Vibrio cholerae Do Not Affect Surface Production of ToxinCoregulated Pili but Still Inhibit Intestinal Colonization. by Chiang SL, Mekalanos JJ.; 1999 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=96415
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Role of Active Efflux in Association with Target Gene Mutations in Fluoroquinolone Resistance in Clinical Isolates of Vibrio cholerae. by Baranwal S, Dey K, Ramamurthy T, Nair GB, Kundu M.; 2002 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=127385
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Role of DnaK in In Vitro and In Vivo Expression of Virulence Factors of Vibrio cholerae. by Chakrabarti S, Sengupta N, Chowdhury R.; 1999 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=96425
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Role of Platelet Activating Factor in the Intestinal Epithelial Secretory and Chinese Hamster Ovary Cell Cytoskeletal Responses to Cholera Toxin. by Guerrant RL, Fang GD, Thielman NM, Fonteles MC.; 1994 Sep 27; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=44872
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Role of Vibrio cholerae O139 Surface Polysaccharides in Intestinal Colonization. by Nesper J, Schild S, Lauriano CM, Kraiss A, Klose KE, Reidl J.; 2002 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=130371
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Rotavirus 2/6 Virus-Like Particles Administered Intranasally in Mice, with or without the Mucosal Adjuvants Cholera Toxin and Escherichia coli Heat-Labile Toxin, Induce a Th1/Th2-Like Immune Response. by Fromantin C, Jamot B, Cohen J, Piroth L, Pothier P, Kohli E.; 2001 Nov 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=114681
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Rotavirus 2/6 Viruslike Particles Administered Intranasally with Cholera Toxin, Escherichia coli Heat-Labile Toxin (LT), and LT-R192G Induce Protection from Rotavirus Challenge. by O'Neal CM, Clements JD, Estes MK, Conner ME.; 1998 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=109829
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Safety and immunogenicity of a live oral bivalent typhoid fever (Salmonella typhi Ty21a)-cholera (Vibrio cholerae CVD 103-HgR) vaccine in healthy adults. by Cryz SJ Jr, Que JU, Levine MM, Wiedermann G, Kollaritsch H.; 1995 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=173155
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Safety and Immunogenicity of Two Different Lots of the Oral, Killed Enterotoxigenic Escherichia coli-Cholera Toxin B Subunit Vaccine in Israeli Young Adults. by Cohen D, Orr N, Haim M, Ashkenazi S, Robin G, Green MS, Ephros M, Sela T, Slepon R, Ashkenazi I, Taylor DN, Svennerholm AM, Eldad A, Shemer J.; 2000 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98356
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Salivary, nasal, genital, and systemic antibody responses in monkeys immunized intranasally with a bacterial protein antigen and the Cholera toxin B subunit. by Russell MW, Moldoveanu Z, White PL, Sibert GJ, Mestecky J, Michalek S M.; 1996 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=173915
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Selected Bacterial Strains Protect Artemia spp. from the Pathogenic Effects of Vibrio proteolyticus CW8T2. by Verschuere L, Heang H, Criel G, Sorgeloos P, Verstraete W.; 2000 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=91954
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Selective Amplification of an mRNA and Related Pseudogene for a Human ADPRibosylation Factor, a Guanine Nucleotide-Dependent Protein Activator of Cholera Toxin. by Monaco L, Murtagh JJ, Newman KB, Tsai S, Moss J, Vaughan M.; 1990 Mar 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=53655
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Sensitive Microplate Assay for Detection of Bactericidal Antibodies to Vibrio cholerae O139. by Attridge SR, Johansson C, Trach DD, Qadri F, Svennerholm AM.; 2002 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=119965
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Specific Detection of Pasteurella multocida in Chickens with Fowl Cholera and in Pig Lung Tissues Using Fluorescent rRNA In Situ Hybridization. by Mbuthia PG, Christensen H, Boye M, Petersen KM, Bisgaard M, Nyaga PN, Olsen JE.; 2001 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=88196
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Structural and Functional Characterization of IS1358 from Vibrio cholerae. by Dumontier S, Trieu-Cuot P, Berche P.; 1998 Dec 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=107693
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Sunlight-Induced Propagation of the Lysogenic Phage Encoding Cholera Toxin. by Faruque SM, Asadulghani, Rahman MM, Waldor MK, Sack DA.; 2000 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98441
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Surface display of the cholera toxin B subunit on Staphylococcus xylosus and Staphylococcus carnosus. by Liljeqvist S, Samuelson P, Hansson M, Nguyen TN, Binz H, Stahl S.; 1997 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=168546
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Susceptibility of Vibrio cholerae O139 to Antibody-Dependent, ComplementMediated Bacteriolysis. by Attridge SR, Qadri F, Albert MJ, Manning PA.; 2000 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=95892
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Synthesis of hybrid molecules between heat-labile enterotoxin and cholera toxin B subunits: potential for use in a broad-spectrum vaccine. by Lebens M, Shahabi V, Backstrom M, Houze T, Lindblad N, Holmgren J.; 1996 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=174048
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Systemic and Mucosal Immune Responses in Mice after Mucosal Immunization with Group B Streptococcus Type III Capsular Polysaccharide-Cholera Toxin B Subunit Conjugate Vaccine. by Shen X, Lagergard T, Yang Y, Lindblad M, Fredriksson M, Holmgren J.; 2000 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=101533
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TaqMan PCR for Detection of Vibrio cholerae O1, O139, Non-O1, and Non-O139 in Pure Cultures, Raw Oysters, and Synthetic Seawater. by Lyon WJ.; 2001 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=93220
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Thapsigargin-Induced Transport of Cholera Toxin to the Endoplasmic Reticulum. by Sandvig K, Garred O, Deurs BV.; 1996 Oct 29; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=37992
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The Alternative Sigma Factor [sigma]E Plays an Important Role in Intestinal Survival and Virulence in Vibrio cholerae. by Kovacikova G, Skorupski K.; 2002 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=128310
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The complete genome sequence of Vibrio cholerae: a tale of two chromosomes and of two lifestyles. by Schoolnik GK, Yildiz FH.; 2000; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=138858
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The first epidemic of Vibrio cholerae O139. by John TJ, Jesudason MV.; 1995 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=228318
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The Mannose-Sensitive Hemagglutinin of Vibrio cholerae Promotes Adherence to Zooplankton. by Chiavelli DA, Marsh JW, Taylor RK.; 2001 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=93004
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The OmpU outer membrane protein, a potential adherence factor of Vibrio cholerae. by Sperandio V, Giron JA, Silveira WD, Kaper JB.; 1995 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=173631
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The sixth and seventh cholera pandemics are due to independent clones separately derived from environmental, nontoxigenic, non-O1 Vibrio cholerae. by Karaolis DK, Lan R, Reeves PR.; 1995 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=177010
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The toxR Gene of Vibrio (Listonella) anguillarum Controls Expression of the Major Outer Membrane Proteins but Not Virulence in a Natural Host Model. by Okuda J, Nakai T, Chang PS, Oh T, Nishino T, Koitabashi T, Nishibuchi M.; 2001 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98738
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The ToxR-Mediated Organic Acid Tolerance Response of Vibrio cholerae Requires OmpU. by Merrell DS, Bailey C, Kaper JB, Camilli A.; 2001 May 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=99489
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The Vibrio cholerae Mannose-Sensitive Hemagglutinin Is the Receptor for a Filamentous Bacteriophage from V. cholerae O139. by Jouravleva EA, McDonald GA, Marsh JW, Taylor RK, Boesman-Finkelstein M, Finkelstein RA.; 1998 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=108235
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The Vibrio cholerae O139 Calcutta Bacteriophage CTX[phi] Is Infectious and Encodes a Novel Repressor. by Davis BM, Kimsey HH, Chang W, Waldor MK.; 1999 Nov 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=94144
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The Vibrio cholerae vieSAB Locus Encodes a Pathway Contributing to Cholera Toxin Production. by Tischler AD, Lee SH, Camilli A.; 2002 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=135224
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The Vibrio Pathogenicity Island-Encoded Mop Protein Modulates the Pathogenesis and Reactogenicity of Epidemic Vibrio cholerae. by Zhang D, Xu Z, Sun W, Karaolis DK.; 2003 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=143176
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The Virulence Regulatory Protein ToxR Mediates Enhanced Bile Resistance in Vibrio cholerae and Other Pathogenic Vibrio Species. by Provenzano D, Schuhmacher DA, Barker JL, Klose KE.; 2000 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=97306
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Thiazolidinone CFTR inhibitor identified by high-throughput screening blocks cholera toxin --induced intestinal fluid secretion. by Ma T, Thiagarajah JR, Yang H, Sonawane ND, Folli C, Galietta LJ, Verkman AS.; 2002 Dec 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=151633
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Toxin-coregulated pilus, but not mannose-sensitive hemagglutinin, is required for colonization by Vibrio cholerae O1 El Tor biotype and O139 strains. by Thelin KH, Taylor RK.; 1996 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=174155
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ToxR-Independent Expression of Cholera Toxin from the Replicative Form of CTX[phi]. by Lazar S, Waldor MK.; 1998 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=107917
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Transcytosis of Cholera Toxin Subunits Across Model Human Intestinal Epithelia. by Lencer WI, Moe S, Rufo PA, Madara JL.; 1995 Oct 24; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=40742
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Transfer of the Cholera Toxin A1 Polypeptide from the Endoplasmic Reticulum to the Cytosol Is a Rapid Process Facilitated by the Endoplasmic Reticulum-Associated Degradation Pathway. by Teter K, Allyn RL, Jobling MG, Holmes RK.; 2002 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=130427
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Transient Transcriptional Activation of the Vibrio cholerae El Tor Virulence Regulator ToxT in Response to Culture Conditions. by Medrano AI, DiRita VJ, Castillo G, Sanchez J.; 1999 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=115955
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Treatment of Experimental Autoimmune Encephalomyelitis by Feeding Myelin Basic Protein Conjugated to Cholera Toxin B Subunit. by Sun J, Rask C, Olsson T, Holmgren J, Czerkinsky C.; 1996 Jul 9; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=38959
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Unique organization of the CTX genetic element in Vibrio cholerae O139 strains which reemerged in Calcutta, India, in September 1996. by Sharma C, Maiti S, Mukhopadhyay AK, Basu A, Basu I, Nair GB, Mukhopadhyaya R, Das B, Kar S, Ghosh RK, Ghosh A.; 1997 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=230184
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Uptake and retention of Vibrio cholerae O1 in the Eastern oyster, Crassostrea virginica. by Murphree RL, Tamplin ML.; 1995 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=167666
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Use of RNA Arbitrarily Primed-PCR Fingerprinting To Identify Vibrio cholerae Genes Differentially Expressed in the Host following Infection. by Chakrabortty A, Das S, Majumdar S, Mukhopadhyay K, Roychoudhury S, Chaudhuri K.; 2000 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=101662
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Utility of rapid monoclonal antibody-based coagglutination test for direct detection of Vibrio cholerae O1 and/or O139 in stool samples. by Arya SC.; 1995 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=227981
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Validation and Characterization of a Human Volunteer Challenge Model for Cholera by Using Frozen Bacteria of the New Vibrio cholerae Epidemic Serotype, O139. by Cohen MB, Giannella RA, Losonsky GA, Lang DR, Parker S, Hawkins JA, Gunther C, Schiff GA.; 1999 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=97040
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Validation of a Volunteer Model of Cholera with Frozen Bacteria as the Challenge. by Sack DA, Tacket CO, Cohen MB, Sack RB, Losonsky GA, Shimko J, Nataro JP, Edelman R, Levine MM, Giannella RA, Schiff G, Lang D.; 1998 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=108151
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Vibrio cholerae Hcp, a secreted protein coregulated with HlyA. by Williams SG, Varcoe LT, Attridge SR, Manning PA.; 1996 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=173757
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Vibrio cholerae Hemagglutinin/Protease Inactivates CTX[phi]. by Kimsey HH, Waldor MK.; 1998 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=108480
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Vibrio cholerae H-NS Silences Virulence Gene Expression at Multiple Steps in the ToxR Regulatory Cascade. by Nye MB, Pfau JD, Skorupski K, Taylor RK.; 2000 Aug 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=101945
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Vibrio cholerae Intestinal Population Dynamics in the Suckling Mouse Model of Infection. by Angelichio MJ, Spector J, Waldor MK, Camilli A.; 1999 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=96647
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Vibrio cholerae O139 Bengal: Combined Physical and Genetic Map and Comparative Analysis with the Genome of V. cholerae O1. by Khetawat G, Bhadra RK, Kar S, Das J.; 1998 Sep 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=107462
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Vibrio cholerae O139 Conjugate Vaccines: Synthesis and Immunogenicity of V. cholerae O139 Capsular Polysaccharide Conjugates with Recombinant Diphtheria Toxin Mutant in Mice. by Kossaczka Z, Shiloach J, Johnson V, Taylor DN, Finkelstein RA, Robbins JB, Szu SC.; 2000 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=101731
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Vibrio cholerae Produces a Second Enterotoxin, which Affects Intestinal Tight Junctions. by Fasano A, Baudry B, Pumplin DW, Wasserman SS, Tall BD, Ketley JM.; 1991 Jun 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=51848
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Vibrio cholerae tolC Is Required for Bile Resistance and Colonization. by Bina JE, Mekalanos JJ.; 2001 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98549
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Vibrio cholerae-Induced Cellular Responses of Polarized T84 Intestinal Epithelial Cells Are Dependent on Production of Cholera Toxin and the RTX Toxin. by Fullner KJ, Lencer WI, Mekalanos JJ.; 2001 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98766
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Vibrio fischeri Genes hvnA and hvnB Encode Secreted NAD +-Glycohydrolases. by Stabb EV, Reich KA, Ruby EG.; 2001 Jan 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=94880
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Vibrio Pathogenicity Island and Cholera Toxin Genetic Element-Associated Virulence Genes and Their Expression in Non-O1 Non-O139 Strains of Vibrio cholerae. by Sarkar A, Nandy RK, Nair GB, Ghose AC.; 2002 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=128188
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Vibrio vulnificus Has the Transmembrane Transcription Activator ToxRS Stimulating the Expression of the Hemolysin Gene vvhA. by Lee SE, Shin SH, Kim SY, Kim YR, Shin DH, Chung SS, Lee ZH, Lee JY, Jeong KC, Choi SH, Rhee JH.; 2000 Jun 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=101907
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Vibriocidal antibody responses in North American volunteers exposed to wild-type or vaccine Vibrio cholerae O139: specificity and relevance to immunity. by Losonsky
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GA, Lim Y, Motamedi P, Comstock LE, Johnson JA, Morris JG Jr, Tacket CO, Kaper JB, Levine MM.; 1997 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=170516 •
Virulence Genes in Environmental Strains of Vibrio cholerae. by Chakraborty S, Mukhopadhyay AK, Bhadra RK, Ghosh AN, Mitra R, Shimada T, Yamasaki S, Faruque SM, Takeda Y, Colwell RR, Nair GB.; 2000 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=92254
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Vitek system antimicrobial susceptibility testing of O1, O139, and non-O1 Vibrio cholerae. by Sciortino CV, Johnson JA, Hamad A.; 1996 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=228913
The National Library of Medicine: PubMed One of the quickest and most comprehensive ways to find academic studies in both English and other languages is to use PubMed, maintained by the National Library of Medicine.6 The advantage of PubMed over previously mentioned sources is that it covers a greater number of domestic and foreign references. It is also free to use. If the publisher has a Web site that offers full text of its journals, PubMed will provide links to that site, as well as to sites offering other related data. User registration, a subscription fee, or some other type of fee may be required to access the full text of articles in some journals. To generate your own bibliography of studies dealing with cholera, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “cholera” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for cholera (hyperlinks lead to article summaries): •
A 4-year study of the epidemiology of Vibrio cholerae in four rural areas of Bangladesh. Author(s): Sack RB, Siddique AK, Longini IM Jr, Nizam A, Yunus M, Islam MS, Morris JG Jr, Ali A, Huq A, Nair GB, Qadri F, Faruque SM, Sack DA, Colwell RR. Source: The Journal of Infectious Diseases. 2003 January 1; 187(1): 96-101. Epub 2002 December 13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12508151&dopt=Abstract
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A cholera toxin B-subunit variant that binds ganglioside G(M1) but fails to induce toxicity. Author(s): Rodighiero C, Fujinaga Y, Hirst TR, Lencer WI. Source: The Journal of Biological Chemistry. 2001 October 5; 276(40): 36939-45. Epub 2001 July 30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11479294&dopt=Abstract
6
PubMed was developed by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM) at the National Institutes of Health (NIH). The PubMed database was developed in conjunction with publishers of biomedical literature as a search tool for accessing literature citations and linking to full-text journal articles at Web sites of participating publishers. Publishers that participate in PubMed supply NLM with their citations electronically prior to or at the time of publication.
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A cytotoxin-producing strain of Vibrio cholerae non-O1, non-O139 as a cause of cholera and bacteremia after consumption of raw clams. Author(s): Namdari H, Klaips CR, Hughes JL. Source: Journal of Clinical Microbiology. 2000 September; 38(9): 3518-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10970422&dopt=Abstract
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A human volunteer challenge model using frozen bacteria of the new epidemic serotype, V. cholerae O139 in Thai volunteers. Author(s): Pitisuttithum P, Cohen MB, Phonrat B, Suthisarnsuntorn U, Bussaratid V, Desakorn V, Phumratanaprapin W, Singhasivanon P, Looareesuwan S, Schiff GM, Ivanoff B, Lang D. Source: Vaccine. 2001 December 12; 20(5-6): 920-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11738758&dopt=Abstract
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A legacy in 20th-century medicine: Robert Allan Phillips and the taming of cholera. Author(s): Savarino SJ. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2002 September 15; 35(6): 713-20. Epub 2002 August 23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12203169&dopt=Abstract
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A localised outbreak of Vibrio cholerae O139 in Kolkata, West Bengal. Author(s): Sur D, Sengupta PG, Mondal SK, Dutta P, Gupta DN, Ghosh S, Pandey A, Ramamurthy T, Bhattacharya SK. Source: The Indian Journal of Medical Research. 2002 April; 115: 149-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12239837&dopt=Abstract
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A molecular and phenotypic study of Vibrio cholerae in Iran. Author(s): Pourshafie M, Grimont F, Kohestani S, Grimont PA. Source: Journal of Medical Microbiology. 2002 May; 51(5): 392-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11990491&dopt=Abstract
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A proposal for safety standards for human use of cholera toxin (or Escherichia coli heat-labile enterotoxin) derivatives as an adjuvant of nasal inactivated influenza vaccine. Author(s): Tamura SI, Kurata T. Source: Japanese Journal of Infectious Diseases. 2000 June; 53(3): 98-106. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10957706&dopt=Abstract
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A voyage of discovery: cholera, climate and complexity. Author(s): Colwell RR. Source: Environmental Microbiology. 2002 February; 4(2): 67-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11972615&dopt=Abstract
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Acute secretory traveller's diarrhoea caused by Vibrio cholerae which does not belong to the O1 or O139 serogroup. Author(s): Bhattacharya MK, Dutta D, Deb A, Garg P, Chakraborty S, Mukhopadhyay AK, Bhattacharya SK, Moitra A. Source: Natl Med J India. 1998 September-October; 11(5): 248-9. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10997178&dopt=Abstract
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Albendazole treatment of children with ascariasis enhances the vibriocidal antibody response to the live attenuated oral cholera vaccine CVD 103-HgR. Author(s): Cooper PJ, Chico ME, Losonsky G, Sandoval C, Espinel I, Sridhara R, Aguilar M, Guevara A, Guderian RH, Levine MM, Griffin GE, Nutman TB. Source: The Journal of Infectious Diseases. 2000 October; 182(4): 1199-206. Epub 2000 September 08. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10979918&dopt=Abstract
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Allelic diversity and population structure in Vibrio cholerae O139 Bengal based on nucleotide sequence analysis. Author(s): Farfan M, Minana-Galbis D, Fuste MC, Loren JG. Source: Journal of Bacteriology. 2002 March; 184(5): 1304-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11844759&dopt=Abstract
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Amylase-resistant starch plus oral rehydration solution for cholera. Author(s): Pierce NF, Fontaine O, Sack RB. Source: The New England Journal of Medicine. 2000 June 29; 342(26): 1995-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10877651&dopt=Abstract
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An evaluation of current cholera treatment. Author(s): Bhattacharya SK. Source: Expert Opinion on Pharmacotherapy. 2003 February; 4(2): 141-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12562304&dopt=Abstract
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An outbreak of Eltor cholera in Aizwal town of Mizoram, India. Author(s): Sengupta PG, Niyogi SK, Bhattacharya SK. Source: J Commun Dis. 2000 September; 32(3): 207-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11407007&dopt=Abstract
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Antagonism against Vibrio cholerae by diffusible substances produced by bacterial components of the human faecal microbiota. Author(s): Silva SH, Vieira EC, Dias RS, Nicoli JR. Source: Journal of Medical Microbiology. 2001 February; 50(2): 161-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11211223&dopt=Abstract
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Antigen-specific immunoglobulin A antibodies secreted from circulating B cells are an effective marker for recent local immune responses in patients with cholera: comparison to antibody-secreting cell responses and other immunological markers. Author(s): Qadri F, Ryan ET, Faruque AS, Ahmed F, Khan AI, Islam MM, Akramuzzaman SM, Sack DA, Calderwood SB. Source: Infection and Immunity. 2003 August; 71(8): 4808-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12874365&dopt=Abstract
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Antimicrobial susceptibility pattern of Vibrio cholerae O1 strains during two cholera outbreaks in Dar es Salaam, Tanzania. Author(s): Urassa WK, Mhando YB, Mhalu FS, Mjonga SJ. Source: East Afr Med J. 2000 July; 77(7): 350-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12862151&dopt=Abstract
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Are the environmental niches of Vibrio cholerae O139 different from those of Vibrio cholerae O1 El Tor? Author(s): Ali M, Emch M, Yunus M, Sack RB. Source: International Journal of Infectious Diseases : Ijid : Official Publication of the International Society for Infectious Diseases. 2001; 5(4): 214-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11953220&dopt=Abstract
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Azithromycin in the treatment of cholera in children. Author(s): Bhattacharya MK, Dutta D, Ramamurthy T, Sarkar D, Singharoy A, Bhattacharya SK. Source: Acta Paediatrica (Oslo, Norway : 1992). 2003 June; 92(6): 676-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12856976&dopt=Abstract
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Bacterial diarrhea in Laos, a region where cholera was endemic. Author(s): Midorikawa Y, Nakamura S, Iwade Y, Sugiyama A, Sisavath L, Phakhounthong R. Source: Southeast Asian J Trop Med Public Health. 1996 December; 27(4): 724-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9253874&dopt=Abstract
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Bacteriological profile of cholera in Tamil Nadu (1980-2001). Author(s): Sundaram SP, Revathi J, Sarkar BL, Bhattacharya SK. Source: The Indian Journal of Medical Research. 2002 December; 116: 258-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12807153&dopt=Abstract
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Bacteriophage and the evolution of epidemic cholera. Author(s): Miller JF. Source: Infection and Immunity. 2003 June; 71(6): 2981-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12761073&dopt=Abstract
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Bivalent cholera and typhoid vaccine. Author(s): Foster RH, Noble S. Source: Drugs. 1999 July; 58(1): 91-6; Discussion 97-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10439932&dopt=Abstract
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Calibrated serological techniques demonstrate significant different serum response rates to an oral killed cholera vaccine between Swedish and Nicaraguan children. Author(s): Hallander HO, Paniagua M, Espinoza F, Askelof P, Corrales E, Ringman M, Storsaeter J. Source: Vaccine. 2002 November 22; 21(1-2): 138-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12443672&dopt=Abstract
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Characterization of a clinical Vibrio cholerae O139 isolate from Mexico. Author(s): Parveen S, Farrah SR, Gonzalez-Bonilla C, Zamudio AV, Tamplin ML. Source: Canadian Journal of Microbiology. 2003 January; 49(1): 65-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12674350&dopt=Abstract
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Characterization of a novel Vibrio pathogenicity island (VPI-2) encoding neuraminidase (nanH) among toxigenic Vibrio cholerae isolates. Author(s): Jermyn WS, Boyd EF. Source: Microbiology (Reading, England). 2002 November; 148(Pt 11): 3681-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12427958&dopt=Abstract
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Characterization of a toxigenic Vibrio cholerae O139 strain belonging to a new ribotype and isolated from a diarrheal patient. Author(s): Bhanumathi R, Sabeena F, Isac SR, Radhakutty G, Singh DV. Source: Journal of Clinical Microbiology. 2002 December; 40(12): 4779-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12454195&dopt=Abstract
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Cholera and climate--the evidence grows. Author(s): Sharp D. Source: Lancet. 2002 December 14; 360(9349): 1902. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12493254&dopt=Abstract
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Cholera and other types of vibriosis: a story of human pandemics and oysters on the half shell. Author(s): Morris JG Jr. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2003 July 15; 37(2): 272-80. Epub 2003 Jul 03. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12856219&dopt=Abstract
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Cholera epidemic in and around Loni a rural area in western Maharashtra. Author(s): Gujrathi UP, Sivarajan K, Kulkarni SG. Source: Indian J Pathol Microbiol. 2000 January; 43(1): 101-2. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12583433&dopt=Abstract
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Cholera toxin internalization and intoxication. Author(s): Fishman PH, Orlandi PA. Source: Journal of Cell Science. 2003 February 1; 116(Pt 3): 431-2; Author Reply 432-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12508102&dopt=Abstract
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Cholera, diarrhea, and oral rehydration therapy: triumph and indictment. Author(s): Guerrant RL, Carneiro-Filho BA, Dillingham RA. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2003 August 1; 37(3): 398-405. Epub 2003 July 22. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12884165&dopt=Abstract
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Class I integrons and SXT elements in El Tor strains isolated before and after 1992 Vibrio cholerae O139 outbreak, Calcutta, India. Author(s): Amita, Chowdhury SR, Thungapathra M, Ramamurthy T, Nair GB, Ghosh A. Source: Emerging Infectious Diseases. 2003 April; 9(4): 500-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12702236&dopt=Abstract
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Cloning and characterization of genes encoding homologues of the B subunit of cholera toxin and the Escherichia coli heat-labile enterotoxin from clinical isolates of Citrobacter freundii and E. coli. Author(s): Karasawa T, Ito H, Tsukamoto T, Yamasaki S, Kurazono H, Faruque SM, Nair GB, Nishibuchi M, Takeda Y. Source: Infection and Immunity. 2002 December; 70(12): 7153-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12438400&dopt=Abstract
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Coleridge's choleras: cholera morbus, Asiatic cholera, and dysentery in early nineteenth-century England. Author(s): Rousseau GS, Haycock DB. Source: Bulletin of the History of Medicine. 2003 Summer; 77(2): 298-331. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12955962&dopt=Abstract
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Commentary: Behind the Broad Street pump: aetiology, epidemiology and prevention of cholera in mid-19th century Britain. Author(s): Smith GD. Source: International Journal of Epidemiology. 2002 October; 31(5): 920-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12435761&dopt=Abstract
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Commentary: Dr John Sutherland, Vibrio cholerae and 'predisposing causes'. Author(s): Halliday S. Source: International Journal of Epidemiology. 2002 October; 31(5): 912-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12435759&dopt=Abstract
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Commentary: Sutherland, Snow and water: the transmission of cholera in the nineteenth century. Author(s): Snow SJ. Source: International Journal of Epidemiology. 2002 October; 31(5): 908-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12435758&dopt=Abstract
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Comparative genomic analyses of the vibrio pathogenicity island and cholera toxin prophage regions in nonepidemic serogroup strains of Vibrio cholerae. Author(s): Li M, Kotetishvili M, Chen Y, Sozhamannan S. Source: Applied and Environmental Microbiology. 2003 March; 69(3): 1728-38. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12620865&dopt=Abstract
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Comparison of single-dose azithromycin and 12-dose, 3-day erythromycin for childhood cholera: a randomised, double-blind trial. Author(s): Khan WA, Saha D, Rahman A, Salam MA, Bogaerts J, Bennish ML. Source: Lancet. 2002 November 30; 360(9347): 1722-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12480424&dopt=Abstract
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Concurrent infection with S.typhi and V. cholerae--a case report”. Author(s): Tankhiwale SS, Dani VS, Jalgaonkar SV, Kiratkar R, Kamlakar UP. Source: Indian Journal of Medical Sciences. 2003 February; 57(2): 64-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14514270&dopt=Abstract
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Conformation of the hexasaccharide repeating subunit from the Vibrio cholerae O139 capsular polysaccharide. Author(s): Adeyeye J, Azurmendi HF, Stroop CJ, Sozhamannan S, Williams AL, Adetumbi AM, Johnson JA, Bush CA. Source: Biochemistry. 2003 April 8; 42(13): 3979-88. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12667089&dopt=Abstract
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Coupling of oral human or porcine insulin to the B subunit of cholera toxin (CTB) overcomes critical antigenic differences for prevention of type I diabetes. Author(s): Petersen JS, Bregenholt S, Apostolopolous V, Homann D, Wolfe T, Hughes A, De Jongh K, Wang M, Dyrberg T, Von Herrath MG. Source: Clinical and Experimental Immunology. 2003 October; 134(1): 38-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12974752&dopt=Abstract
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Detection and molecular characterization of the zot gene in Vibrio cholerae and V. alginolyticus isolates. Author(s): Raja N, Shamsudin MN, Somarny W, Rosli R, Rahim RA, Radu S. Source: Southeast Asian J Trop Med Public Health. 2001 March; 32(1): 100-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11485069&dopt=Abstract
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Detection of anti-lipopolysaccharide antibodies to Vibrio cholerae O1 and O139 using a novel microtiter limulus amebocyte lysate (LAL) assay. Author(s): Chang HS, Sack DA. Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. 2001 October; 312(1-2): 49-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11580909&dopt=Abstract
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Detection of faecal leucocytes & erythrocytes from stools of cholera patients suggesting an evidence of an inflammatory response in cholera. Author(s): Saha DR, Niyogi SK, Nair GB, Manna B, Bhattacharya SK. Source: The Indian Journal of Medical Research. 2000 July; 112: 5-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11006654&dopt=Abstract
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Detection of RTX toxin gene in Vibrio cholerae by PCR. Author(s): Chow KH, Ng TK, Yuen KY, Yam WC. Source: Journal of Clinical Microbiology. 2001 July; 39(7): 2594-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11427575&dopt=Abstract
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Detection of virulence associated genes, haemolysin and protease amongst Vibrio cholerae isolated in Malaysia. Author(s): Iyer L, Vadivelu J, Puthucheary SD. Source: Epidemiology and Infection. 2000 August; 125(1): 27-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11057956&dopt=Abstract
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Development and evaluation of a phage typing scheme for Vibrio cholerae O139. Author(s): Chakrabarti AK, Ghosh AN, Nair GB, Niyogi SK, Bhattacharya SK, Sarkar BL. Source: Journal of Clinical Microbiology. 2000 January; 38(1): 44-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10618061&dopt=Abstract
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Development of a hexaplex PCR assay for rapid detection of virulence and regulatory genes in Vibrio cholerae and Vibrio mimicus. Author(s): Singh DV, Isac SR, Colwell RR. Source: Journal of Clinical Microbiology. 2002 November; 40(11): 4321-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12409420&dopt=Abstract
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D-glucose and NaCl enhance the expression of aquaporin-1: inhibition of both by cholera toxin. Author(s): Jenq W, Ramirez G, Peguero A, Cooper DR, Vesely DL. Source: Nephron. 2002 October; 92(2): 279-86. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12218304&dopt=Abstract
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Diarrheagenicity evaluation of attenuated Vibrio cholerae O1 and O139 strains in the human intestine ex vivo. Author(s): Burgos JM, Perez JL, Garcia L, Gonzalez GS, Benitez JA, Galindo F, Silberstein C, Ibarra C. Source: Vaccine. 1999 February 26; 17(7-8): 949-56. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10067702&dopt=Abstract
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Differential biological and adjuvant activities of cholera toxin and Escherichia coli heat-labile enterotoxin hybrids. Author(s): Bowman CC, Clements JD. Source: Infection and Immunity. 2001 March; 69(3): 1528-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11179323&dopt=Abstract
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Differential effect of cholera toxin on CD45RA+ and CD45RO+ T cells: specific inhibition of cytokine production but not proliferation of human naive T cells. Author(s): Eriksson K, Nordstrom I, Czerkinsky C, Holmgren J. Source: Clinical and Experimental Immunology. 2000 August; 121(2): 283-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10931143&dopt=Abstract
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Differential interleukin-8 response of intestinal epithelial cell line to reactogenic and nonreactogenic candidate vaccine strains of Vibrio cholerae. Author(s): Rodriguez BL, Rojas A, Campos J, Ledon T, Valle E, Toledo W, Fando R. Source: Infection and Immunity. 2001 January; 69(1): 613-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11119564&dopt=Abstract
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Differentiation of environmental and clinical isolates of Vibrio mimicus from Vibrio cholerae by multilocus enzyme electrophoresis. Author(s): Vieira VV, Teixeira LF, Vicente AC, Momen H, Salles CA. Source: Applied and Environmental Microbiology. 2001 May; 67(5): 2360-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11319123&dopt=Abstract
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Dirty water and cholera. Author(s): Drusin LM. Source: Pharos Alpha Omega Alpha Honor Med Soc. 1999 Summer; 62(3): 52-3. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10509121&dopt=Abstract
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Distinct cytokine regulation by cholera toxin and type II heat-labile toxins involves differential regulation of CD40 ligand on CD4(+) T cells. Author(s): Martin M, Metzger DJ, Michalek SM, Connell TD, Russell MW. Source: Infection and Immunity. 2001 July; 69(7): 4486-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11401990&dopt=Abstract
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Distribution of phage type of Vibrio cholerae O1 biotype ElTor in Indian scenario (1991-98). Author(s): Sarkar BL, Roy MK, Chakrabarti AK, Niyogi SK. Source: The Indian Journal of Medical Research. 1999 June; 109: 204-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10491911&dopt=Abstract
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Diversity in the arrangement of the CTX prophages in classical strains of Vibrio cholerae O1. Author(s): Basu A, Mukhopadhyay AK, Garg P, Chakraborty S, Ramamurthy T, Yamasaki S, Takeda Y, Nair GB. Source: Fems Microbiology Letters. 2000 January 1; 182(1): 35-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10612727&dopt=Abstract
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DNA sequence of both chromosomes of the cholera pathogen Vibrio cholerae. Author(s): Heidelberg JF, Eisen JA, Nelson WC, Clayton RA, Gwinn ML, Dodson RJ, Haft DH, Hickey EK, Peterson JD, Umayam L, Gill SR, Nelson KE, Read TD, Tettelin H, Richardson D, Ermolaeva MD, Vamathevan J, Bass S, Qin H, Dragoi I, Sellers P, McDonald L, Utterback T, Fleishmann RD, Nierman WC, White O. Source: Nature. 2000 August 3; 406(6795): 477-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10952301&dopt=Abstract
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Domestic cholera in Germany associated with fresh fish imported from Nigeria. Author(s): Schurmann D, Ebert N, Kampf D, Baumann B, Frei U, Suttorp N. Source: European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology. 2002 November; 21(11): 827-8. Epub 2002 November 07. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12461596&dopt=Abstract
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Drug sensitivity pattern of cholera in children. Author(s): Memon IA, Murtaza G. Source: J Pak Med Assoc. 2002 August; 52(8): 347-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12481672&dopt=Abstract
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Effects of global climate on infectious disease: the cholera model. Author(s): Lipp EK, Huq A, Colwell RR. Source: Clinical Microbiology Reviews. 2002 October; 15(4): 757-70. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12364378&dopt=Abstract
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Effects of the adjuvant cholera toxin on dendritic cells: stimulatory and inhibitory signals that result in the amplification of immune responses. Author(s): Gagliardi MC, Sallusto F, Marinaro M, Vendetti S, Riccomi A, De Magistris MT. Source: International Journal of Medical Microbiology : Ijmm. 2002 February; 291(6-7): 571-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11892684&dopt=Abstract
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Efficacy of a packaged rice oral rehydration solution among children with cholera and cholera-like illness. Author(s): Zaman K, Yunus M, Rahman A, Chowdhury HR, Sack DA. Source: Acta Paediatrica (Oslo, Norway : 1992). 2001 May; 90(5): 505-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11430708&dopt=Abstract
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Efficacy of atovaquone/proguanil for malaria prophylaxis in children and its effect on the immunogenicity of live oral typhoid and cholera vaccines. Author(s): Faucher JF, Binder R, Missinou MA, Matsiegui PB, Gruss H, Neubauer R, Lell B, Que JU, Miller GB, Kremsner PG. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2002 November 15; 35(10): 1147-54. Epub 2002 October 25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12410473&dopt=Abstract
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Emergence and evolution of Vibrio cholerae O139. Author(s): Faruque SM, Sack DA, Sack RB, Colwell RR, Takeda Y, Nair GB. Source: Proceedings of the National Academy of Sciences of the United States of America. 2003 February 4; 100(3): 1304-9. Epub 2003 January 21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12538850&dopt=Abstract
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Emergence and rapid spread of tetracycline-resistant Vibrio cholerae strains, Madagascar. Author(s): Dromigny JA, Rakoto-Alson O, Rajaonatahina D, Migliani R, Ranjalahy J, Mauclere P. Source: Emerging Infectious Diseases. 2002 March; 8(3): 336-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11927038&dopt=Abstract
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Emergence and re-emergence of Vibrio cholerae 0139: an epidemiological study during 1993-2002 at Nagpur, Central India. Author(s): Agrawal G, Jalgaonkar SV, Jagtap PM, Kamlakar UP, Deogade NG. Source: Indian Journal of Medical Sciences. 2003 April; 57(4): 155-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14510347&dopt=Abstract
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Emergence of fluoroquinolone-resistant strains of Vibrio cholerae O1 biotype El Tor among hospitalized patients with cholera in Calcutta, India. Author(s): Garg P, Sinha S, Chakraborty R, Bhattacharya SK, Nair GB, Ramamurthy T, Takeda Y. Source: Antimicrobial Agents and Chemotherapy. 2001 May; 45(5): 1605-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11372642&dopt=Abstract
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Emergence of Vibrio cholerae 0139 in Manipal-coastal Karnataka-South India. Author(s): Ballal M, Nandanan B, Shivananda PG. Source: Indian J Pathol Microbiol. 2001 April; 44(2): 177. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11883141&dopt=Abstract
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Endemic and epidemic dynamics of cholera: the role of the aquatic reservoir. Author(s): Codeco CT. Source: Bmc Infectious Diseases [electronic Resource]. 2001; 1(1): 1. Epub 2001 February 02. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11208258&dopt=Abstract
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Enlightening cholera bug reveals new virulence system. Author(s): Flores G. Source: Drug Discovery Today. 2002 October 1; 7(19): 984-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12546909&dopt=Abstract
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ENSO and cholera: a nonstationary link related to climate change? Author(s): Rodo X, Pascual M, Fuchs G, Faruque AS. Source: Proceedings of the National Academy of Sciences of the United States of America. 2002 October 1; 99(20): 12901-6. Epub 2002 September 12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12228724&dopt=Abstract
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Epidemic and endemic cholera trends over a 33-year period in Bangladesh. Author(s): Longini IM Jr, Yunus M, Zaman K, Siddique AK, Sack RB, Nizam A. Source: The Journal of Infectious Diseases. 2002 July 15; 186(2): 246-51. Epub 2002 June 17. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12134262&dopt=Abstract
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Epidemic of Vibrio cholerae serogroup O139 in Berhampur, Orissa. Author(s): Samal B, Ghosh SK, Mohanty SK, Patnaik K. Source: The Indian Journal of Medical Research. 2001 July; 114: 10-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11762200&dopt=Abstract
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Epidemiological investigation of a fatal case of cholera in Japan by phenotypic techniques and pulsed-field gel electrophoresis. Author(s): Matsumoto M, Suzuki M, Hiramatsu R, Yamazaki M, Matsui H, Sakae K, Suzuki Y, Miyazaki Y. Source: Journal of Medical Microbiology. 2002 March; 51(3): 264-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11871621&dopt=Abstract
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Epidemiology of cholera outbreak in Kampala, Uganda. Author(s): Legros D, McCormick M, Mugero C, Skinnider M, Bek'Obita DD, Okware SI. Source: East Afr Med J. 2000 July; 77(7): 347-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12862150&dopt=Abstract
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Epidemiology of cholera--a five year study. Author(s): Bajaj JK, Baradker VP, Joshi SG, Damle AS, Kayararte RP, Deshmukh AB. Source: J Commun Dis. 2001 December; 33(4): 282-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12561506&dopt=Abstract
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Escalating association of Vibrio cholerae O139 with cholera outbreaks in India. Author(s): Sinha S, Chakraborty R, De K, Khan A, Datta S, Ramamurthy T, Bhattacharya SK, Takeda Y, Nair GB. Source: Journal of Clinical Microbiology. 2002 July; 40(7): 2635-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12089294&dopt=Abstract
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Expression of Vibrio cholerae virulence genes in response to environmental signals. Author(s): Peterson KM. Source: Curr Issues Intest Microbiol. 2002 September; 3(2): 29-38. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12400636&dopt=Abstract
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EXTRACTS from appendix (A) to the Report of the General Board of Health on the Epidemic Cholera of 1848 & 1849(a). Author(s): Sutherland J. Source: International Journal of Epidemiology. 2002 October; 31(5): 900-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12435757&dopt=Abstract
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Faecal excretion of Vibrio cholerae during convalescence of cholera patients in Calabar, Nigeria. Author(s): Utsalo SJ, Eko FO, Umoh F, Asindi AA. Source: European Journal of Epidemiology. 1999 April; 15(4): 379-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10414380&dopt=Abstract
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Fear and frustration--the Liverpool cholera riots of 1832. Author(s): Gill G, Burrell S, Brown J. Source: Lancet. 2001 July 21; 358(9277): 233-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11476860&dopt=Abstract
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Features of the 1996 cholera epidemic among Nigerian children in Ibadan, Nigeria. Author(s): Falade AG, Lawoyin T. Source: Journal of Tropical Pediatrics. 1999 February; 45(1): 59-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10191599&dopt=Abstract
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Field trial of a locally produced, killed, oral cholera vaccine in Vietnam. Author(s): Trach DD, Clemens JD, Ke NT, Thuy HT, Son ND, Canh DG, Hang PV, Rao MR. Source: Lancet. 1997 January 25; 349(9047): 231-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9014909&dopt=Abstract
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Field trial of oral cholera vaccine in Vietnam. Author(s): Nagaraj K, Babu BV. Source: Lancet. 1997 April 26; 349(9060): 1253-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9130971&dopt=Abstract
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Filipin-dependent inhibition of cholera toxin: evidence for toxin internalization and activation through caveolae-like domains. Author(s): Orlandi PA, Fishman PH. Source: The Journal of Cell Biology. 1998 May 18; 141(4): 905-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9585410&dopt=Abstract
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First do no harm: making oral rehydration solution safer in a cholera epidemic. Author(s): Daniels NA, Simons SL, Rodrigues A, Gunnlaugsson G, Forster TS, Wells JG, Hutwagner L, Tauxe RV, Mintz ED. Source: The American Journal of Tropical Medicine and Hygiene. 1999 June; 60(6): 10515. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10403342&dopt=Abstract
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Floating cholera toxin into epithelial cells: functional association with caveolae-like detergent-insoluble membrane microdomains. Author(s): Badizadegan K, Wolf AA, Rodighiero C, Jobling M, Hirst TR, Holmes RK, Lencer WI. Source: International Journal of Medical Microbiology : Ijmm. 2000 October; 290(4-5): 403-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11111918&dopt=Abstract
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Food as a vehicle of transmission of cholera. Author(s): Rabbani GH, Greenough WB 3rd. Source: J Diarrhoeal Dis Res. 1999 March; 17(1): 1-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10892490&dopt=Abstract
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Fowl cholera. Author(s): Christensen JP, Bisgaard M. Source: Rev Sci Tech. 2000 August; 19(2): 626-37. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10935284&dopt=Abstract
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From the history of cholera epidemics in Kyiv in 1847. Author(s): Zhukovsky L. Source: Agapit. 1996; (4): 70-1. English, Ukrainian. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11620504&dopt=Abstract
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Funerals during the 1994 cholera epidemic in Guinea-Bissau, West Africa: the need for disinfection of bodies of persons dying of cholera. Author(s): Gunnlaugsson G, Einarsdottir J, Angulo FJ, Mentambanar SA, Passa A, Tauxe RV. Source: Epidemiology and Infection. 1998 February; 120(1): 7-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9528812&dopt=Abstract
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Further molecular characterization and stability of the live oral attenuated cholera vaccine strain CVD103-HgR. Author(s): Favre D, Struck MM, Cryz SJ Jr, Viret JF. Source: Vaccine. 1996 April; 14(6): 526-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8782351&dopt=Abstract
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Fusions to the cholera toxin B subunit: influence on pentamerization and GM1 binding. Author(s): Liljeqvist S, Stahl S, Andreoni C, Binz H, Uhlen M, Murby M. Source: Journal of Immunological Methods. 1997 December 29; 210(2): 125-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9520296&dopt=Abstract
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Ganglioside structure dictates signal transduction by cholera toxin and association with caveolae-like membrane domains in polarized epithelia. Author(s): Wolf AA, Jobling MG, Wimer-Mackin S, Ferguson-Maltzman M, Madara JL, Holmes RK, Lencer WI. Source: The Journal of Cell Biology. 1998 May 18; 141(4): 917-27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9585411&dopt=Abstract
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Gastroenteritis due to Vibrio cholerae El-Tor Ogawa in Dhule. Author(s): Nitsure S, Dravid M, Jaffari LA, Anvikar AR. Source: Indian Journal of Medical Sciences. 1997 November; 51(11): 417-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9567501&dopt=Abstract
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Gene capture in Vibrio cholerae. Author(s): Manning PA, Clark CA, Focareta T. Source: Trends in Microbiology. 1999 March; 7(3): 93-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10203830&dopt=Abstract
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Genesis of variants of Vibrio cholerae O1 biotype El Tor: role of the CTXphi array and its position in the genome. Author(s): Nandi S, Maiti D, Saha A, Bhadra RK. Source: Microbiology (Reading, England). 2003 January; 149(Pt 1): 89-97. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12576583&dopt=Abstract
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Genetic diversity and population structure of Vibrio cholerae. Author(s): Beltran P, Delgado G, Navarro A, Trujillo F, Selander RK, Cravioto A. Source: Journal of Clinical Microbiology. 1999 March; 37(3): 581-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9986816&dopt=Abstract
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Genetic diversity of clinical and environmental isolates of Vibrio cholerae determined by amplified fragment length polymorphism fingerprinting. Author(s): Jiang SC, Matte M, Matte G, Huq A, Colwell RR. Source: Applied and Environmental Microbiology. 2000 January; 66(1): 148-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10618216&dopt=Abstract
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Genetic diversity of Vibrio cholerae O1 in Argentina and emergence of a new variant. Author(s): Pichel M, Rivas M, Chinen I, Martin F, Ibarra C, Binsztein N. Source: Journal of Clinical Microbiology. 2003 January; 41(1): 124-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12517837&dopt=Abstract
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Genetic relationships between clinical and environmental Vibrio cholerae isolates based on multilocus enzyme electrophoresis. Author(s): Farfan M, Minana D, Fuste MC, Loren JG. Source: Microbiology (Reading, England). 2000 October; 146 ( Pt 10): 2613-26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11021936&dopt=Abstract
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Genome sequence of Vibrio parahaemolyticus: a pathogenic mechanism distinct from that of V cholerae. Author(s): Makino K, Oshima K, Kurokawa K, Yokoyama K, Uda T, Tagomori K, Iijima Y, Najima M, Nakano M, Yamashita A, Kubota Y, Kimura S, Yasunaga T, Honda T, Shinagawa H, Hattori M, Iida T. Source: Lancet. 2003 March 1; 361(9359): 743-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12620739&dopt=Abstract
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Genomic and biochemical relatedness between Vibrio cholerae serovar O139 and serovar O1 eltor strains. Author(s): Prager R, Beer W, Voigt W, Claus H, Seltmann G, Stephan R, Bockemuhl J, Tschape H. Source: Zentralbl Bakteriol. 1995 November; 283(1): 14-28. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9810642&dopt=Abstract
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Genomic diversity among Vibrio cholerae O139 strains isolated in Bangladesh and India between 1992 and 1998. Author(s): Faruque SM, Saha MN, Asadulghani, Bag PK, Bhadra RK, Bhattacharya SK, Sack RB, Takeda Y, Nair GB. Source: Fems Microbiology Letters. 2000 March 15; 184(2): 279-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10713434&dopt=Abstract
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Genomic diversity of clinical and environmental Vibrio cholerae strains isolated in Brazil between 1991 and 2001 as revealed by fluorescent amplified fragment length polymorphism analysis. Author(s): Thompson FL, Thompson CC, Vicente AC, Theophilo GN, Hofer E, Swings J. Source: Journal of Clinical Microbiology. 2003 May; 41(5): 1946-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12734232&dopt=Abstract
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Genomic profiles of clinical and environmental isolates of Vibrio cholerae O1 in cholera-endemic areas of Bangladesh. Author(s): Zo YG, Rivera IN, Russek-Cohen E, Islam MS, Siddique AK, Yunus M, Sack RB, Huq A, Colwell RR. Source: Proceedings of the National Academy of Sciences of the United States of America. 2002 September 17; 99(19): 12409-14. Epub 2002 August 30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12205294&dopt=Abstract
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Geographical patterns of cholera in Mexico, 1991-1996. Author(s): Borroto RJ, Martinez-Piedra R. Source: International Journal of Epidemiology. 2000 August; 29(4): 764-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10922357&dopt=Abstract
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George Leith Roupell FRS (1797-1854): significant contributions to the early nineteenth-century understanding of cholera and typhus. Author(s): Cook GC. Source: J Med Biogr. 2000 February; 8(1): 1-7. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10994040&dopt=Abstract
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Global climate and infectious disease: the cholera paradigm. Author(s): Colwell RR. Source: Science. 1996 December 20; 274(5295): 2025-31. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8953025&dopt=Abstract
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Glucose-stimulated sodium transport by the human intestine during experimental cholera. Author(s): Schiller LR, Santa Ana CA, Porter J, Fordtran JS. Source: Gastroenterology. 1997 May; 112(5): 1529-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9136831&dopt=Abstract
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Haemagglutinin/protease expression and mucin gel penetration in El Tor biotype Vibrio cholerae. Author(s): Silva AJ, Pham K, Benitez JA. Source: Microbiology (Reading, England). 2003 July; 149(Pt 7): 1883-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12855739&dopt=Abstract
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Haemolysin produced by Vibrio cholerae non-O1 is not enterotoxic. Author(s): Singh DV, Shukla BN, Sanyal SC. Source: Journal of Medical Microbiology. 1996 July; 45(1): 35-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8667410&dopt=Abstract
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Hand infections due to non-cholera Vibrio after injuries from St Peter's fish (Tilapia zillii). Author(s): Said R, Volpin G, Grimberg B, Friedenstrom SR, Lefler E, Stahl S. Source: Journal of Hand Surgery (Edinburgh, Lothian). 1998 December; 23(6): 808-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9888689&dopt=Abstract
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Health education and cholera in rural Guinea-bissau. Author(s): Einarsdottir J, Passa A, Gunnlaugsson G. Source: International Journal of Infectious Diseases : Ijid : Official Publication of the International Society for Infectious Diseases. 2001; 5(3): 133-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11724669&dopt=Abstract
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Health impairments arising from drinking water resources contaminated with Vibrio cholerae. Author(s): Ramamurthy T, Chakraborty S, Nair GB, Bhattacharya SK. Source: Schriftenr Ver Wasser Boden Lufthyg. 2000; 105: 29-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10842790&dopt=Abstract
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Helicobacter pylori and epidemic Vibrio cholerae O1 infection in Peru. Author(s): Shahinian ML, Passaro DJ, Swerdlow DL, Mintz ED, Rodriguez M, Parsonnel J. Source: Lancet. 2000 January 29; 355(9201): 377-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10665561&dopt=Abstract
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Heterogeneity in the organization of the CTX genetic element in strains of Vibrio cholerae O139 Bengal isolated from Calcutta, India and Dhaka, Bangladesh and its possible link to the dissimilar incidence of O139 cholera in the two locales. Author(s): Basu A, Mukhopadhyay AK, Sharma C, Jyot J, Gupta N, Ghosh A, Bhattacharya SK, Takeda Y, Faruque AS, Albert MJ, Balakrish Nair G. Source: Microbial Pathogenesis. 1998 March; 24(3): 175-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9514639&dopt=Abstract
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High-resolution FRET microscopy of cholera toxin B-subunit and GPI-anchored proteins in cell plasma membranes. Author(s): Kenworthy AK, Petranova N, Edidin M. Source: Molecular Biology of the Cell. 2000 May; 11(5): 1645-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10793141&dopt=Abstract
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Home-grown Vietnamese cholera vaccine “completely safe”. Author(s): Quirk M. Source: The Lancet Infectious Diseases. 2002 April; 2(4): 198. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11937407&dopt=Abstract
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Host-induced epidemic spread of the cholera bacterium. Author(s): Merrell DS, Butler SM, Qadri F, Dolganov NA, Alam A, Cohen MB, Calderwood SB, Schoolnik GK, Camilli A. Source: Nature. 2002 June 6; 417(6889): 642-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12050664&dopt=Abstract
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Host-pathogen interactions in emerging and re-emerging infectious diseases: a genomic perspective of tuberculosis, malaria, human immunodeficiency virus infection, hepatitis B, and cholera. Author(s): McNicholl JM, Downer MV, Udhayakumar V, Alper CA, Swerdlow DL. Source: Annual Review of Public Health. 2000; 21: 15-46. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10884944&dopt=Abstract
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Human infection with Ascaris lumbricoides is associated with suppression of the interleukin-2 response to recombinant cholera toxin B subunit following vaccination with the live oral cholera vaccine CVD 103-HgR. Author(s): Cooper PJ, Chico M, Sandoval C, Espinel I, Guevara A, Levine MM, Griffin GE, Nutman TB. Source: Infection and Immunity. 2001 March; 69(3): 1574-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11179329&dopt=Abstract
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Identification and strain differentiation of Vibrio cholerae by using polyclonal antibodies against outer membrane proteins. Author(s): Martinez-Govea A, Ambrosio J, Gutierrez-Cogco L, Flisser A. Source: Clinical and Diagnostic Laboratory Immunology. 2001 July; 8(4): 768-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11427424&dopt=Abstract
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Identification of motifs in cholera toxin A1 polypeptide that are required for its interaction with human ADP-ribosylation factor 6 in a bacterial two-hybrid system. Author(s): Jobling MG, Holmes RK. Source: Proceedings of the National Academy of Sciences of the United States of America. 2000 December 19; 97(26): 14662-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11106366&dopt=Abstract
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Identifying environmental risk factors for endemic cholera: a raster GIS approach. Author(s): Ali M, Emch M, Donnay JP, Yunus M, Sack RB. Source: Health & Place. 2002 September; 8(3): 201-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12135643&dopt=Abstract
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Immune response to the mannose-sensitive hemagglutinin in patients with cholera due to Vibrio cholerae O1 and O0139. Author(s): Qadri F, Jonson G, Begum YA, Wenneras C, Albert MJ, Salam MA, Svennerholm AM. Source: Clinical and Diagnostic Laboratory Immunology. 1997 July; 4(4): 429-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9220159&dopt=Abstract
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In vitro susceptibility of Vibrio cholerae O1 biotype El Tor strains associated with an outbreak of cholera in Kerala, Southern India. Author(s): Sabeena F, Thirivikramji G, Radhakutty G, Indu P, Singh DV. Source: The Journal of Antimicrobial Chemotherapy. 2001 March; 47(3): 361-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11222575&dopt=Abstract
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In vivo covalent cross-linking of cellular actin by the Vibrio cholerae RTX toxin. Author(s): Fullner KJ, Mekalanos JJ. Source: The Embo Journal. 2000 October 16; 19(20): 5315-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11032799&dopt=Abstract
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Incidence and molecular analysis of Vibrio cholerae associated with cholera outbreak subsequent to the super cyclone in Orissa, India. Author(s): Chhotray GP, Pal BB, Khuntia HK, Chowdhury NR, Chakraborty S, Yamasaki S, Ramamurthy T, Takeda Y, Bhattacharya SK, Nair GB. Source: Epidemiology and Infection. 2002 April; 128(2): 131-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12002529&dopt=Abstract
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Incidence of Vibrio cholerae in different age groups and sex in Aurangabad Province isolated during January 1994 to December 1994. Author(s): Slathia P, Bansal MP. Source: Indian Journal of Medical Sciences. 1999 August; 53(8): 349-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10776515&dopt=Abstract
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Increased levels of inflammatory mediators in children and adults infected with Vibrio cholerae O1 and O139. Author(s): Qadri F, Raqib R, Ahmed F, Rahman T, Wenneras C, Das SK, Alam NH, Mathan MM, Svennerholm AM. Source: Clinical and Diagnostic Laboratory Immunology. 2002 March; 9(2): 221-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11874856&dopt=Abstract
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Increased nitrite and nitrate concentrations in sera and urine of patients with cholera or shigellosis. Author(s): Rabbani GH, Islam S, Chowdhury AK, Mitra AK, Miller MJ, Fuchs G. Source: The American Journal of Gastroenterology. 2001 February; 96(2): 467-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11232692&dopt=Abstract
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Independent prognostic factors for fatality in patients with invasive vibrio cholerae non-O1 infections. Author(s): Ou TY, Liu JW, Leu HS. Source: J Microbiol Immunol Infect. 2003 June; 36(2): 117-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12886963&dopt=Abstract
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Induction and distribution of intestinal immune responses after administration of recombinant cholera toxin B subunit in the ileal pouches of colectomized patients. Author(s): Kilhamn J, Brevinge H, Quiding-Jarbrink M, Svennerholm AM, Jertborn M. Source: Infection and Immunity. 2001 May; 69(5): 3466-71. Erratum In: Infect Immun 2001 October; 69(10): 6564. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11292777&dopt=Abstract
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Induction of systemic antifimbria and antitoxin antibody responses in Egyptian children and adults by an oral, killed enterotoxigenic Escherichia coli plus cholera toxin B subunit vaccine. Author(s): Hall ER, Wierzba TF, Ahren C, Rao MR, Bassily S, Francis W, Girgis FY, Safwat M, Lee YJ, Svennerholm AM, Clemens JD, Savarino SJ. Source: Infection and Immunity. 2001 May; 69(5): 2853-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11292698&dopt=Abstract
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Infectious disease. Cholera strengthened by trip through gut. Author(s): Pennisi E. Source: Science. 2002 June 7; 296(5574): 1783-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12052928&dopt=Abstract
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Internalization of cholera toxin by different endocytic mechanisms. Author(s): Torgersen ML, Skretting G, van Deurs B, Sandvig K. Source: Journal of Cell Science. 2001 October; 114(Pt 20): 3737-47. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11707525&dopt=Abstract
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Intestinal and systemic immune responses to an oral cholera toxoid B subunit wholecell vaccine administered during zinc supplementation. Author(s): Karlsen TH, Sommerfelt H, Klomstad S, Andersen PK, Strand TA, Ulvik RJ, Ahren C, Grewal HM. Source: Infection and Immunity. 2003 July; 71(7): 3909-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12819076&dopt=Abstract
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Intestinal coinfection with numerous Giardia trophozoites and Vibrio cholerae in hospitalized children with watery diarrhea. Author(s): Zerpa R, Huicho L. Source: Wilderness Environ Med. 1995 May; 6(2): 167-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11995904&dopt=Abstract
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Introductory evaluation of an oral, killed whole cell enterotoxigenic Escherichia coli plus cholera toxin B subunit vaccine in Egyptian infants. Author(s): Savarino SJ, Hall ER, Bassily S, Wierzba TF, Youssef FG, Peruski LF Jr, AbuElyazeed R, Rao M, Francis WM, El Mohamady H, Safwat M, Naficy AB, Svennerholm AM, Jertborn M, Lee YJ, Clemens JD; Pride Study Group. Source: The Pediatric Infectious Disease Journal. 2002 April; 21(4): 322-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12075764&dopt=Abstract
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Investigations into the safety and immunogenicity of a killed oral cholera vaccine developed in Viet Nam. Author(s): Trach DD, Cam PD, Ke NT, Rao MR, Dinh D, Hang PV, Hung NV, Canh DG, Thiem VD, Naficy A, Ivanoff B, Svennerholm AM, Holmgren J, Clemens JD. Source: Bulletin of the World Health Organization. 2002; 80(1): 2-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11884967&dopt=Abstract
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Is starch the answer for cholera? Author(s): Bhatnagar S. Source: Natl Med J India. 2000 September-October; 13(5): 252-3. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11190054&dopt=Abstract
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Kinetics of local and systemic immune responses to an oral cholera vaccine given alone or together with acetylcysteine. Author(s): Kilhamn J, Jertborn M, Svennerholm AM. Source: Clinical and Diagnostic Laboratory Immunology. 1998 March; 5(2): 247-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9521151&dopt=Abstract
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KZN 'on the mend' from cholera. Author(s): Bateman C. Source: South African Medical Journal. Suid-Afrikaanse Tydskrif Vir Geneeskunde. 2000 December; 90(12): 1166-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11234638&dopt=Abstract
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Lack of polymorphism in a Vibrio cholerae O139-specific DNA region encoding the somatic antigen in strains isolated during 1993-1998. Author(s): Falklind-Jerkerus S, Albert MJ, Weintraub A. Source: International Journal of Medical Microbiology : Ijmm. 2003 February; 292(7-8): 505-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12635933&dopt=Abstract
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Learning from cholera: medical and social responses to the first great Paris epidemic in 1832. Author(s): Kudlick CJ. Source: Microbes and Infection / Institut Pasteur. 1999 October; 1(12): 1051-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10617936&dopt=Abstract
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Lessons to be learned from studying Vibrio cholerae in model systems. Author(s): Chaudhuri K. Source: Genome Biology. 2001; 2(8): Interactions1003. Epub 2001 July 31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11532208&dopt=Abstract
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Lipopolysaccharide- and cholera toxin-specific subclass distribution of B-cell responses in cholera. Author(s): Qadri F, Ahmed F, Karim MM, Wenneras C, Begum YA, Abdus Salam M, Albert MJ, McGhee JR. Source: Clinical and Diagnostic Laboratory Immunology. 1999 November; 6(6): 812-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10548569&dopt=Abstract
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Literature and medicine: Garcia Marquez' Love in the time of cholera. Author(s): Jones AH. Source: Lancet. 1997 October 18; 350(9085): 1169-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9379818&dopt=Abstract
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Live oral cholera vaccine. Author(s): Herzog C, Wegmuller B, Cryz SJ. Source: Lancet. 1997 June 14; 349(9067): 1772-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9193404&dopt=Abstract
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Local and systemic immune responses to combined vibrio cholerae CVD103-HgR and salmonella typhi ty21a live oral vaccines after primary immunization and reimmunization. Author(s): Kollaritsch H, Cryz SJ Jr, Lang AB, Herzog C, Que JU, Wiedermann G. Source: Vaccine. 2000 July 1; 18(26): 3031-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10825607&dopt=Abstract
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Local and systemic immune responses to rectal administration of recombinant cholera toxin B subunit in humans. Author(s): Jertborn M, Nordstrom I, Kilander A, Czerkinsky C, Holmgren J. Source: Infection and Immunity. 2001 June; 69(6): 4125-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11349086&dopt=Abstract
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Local production of anti-vibrio cholerae mucosal antibody in reproductive tract tissues after cholera. Author(s): Ryan ET, Bridges EA, Crean TI, Gausia K, Hamadani JD, Aziz A, Hawkes S, Begum M, Bogaerts J, Faruque SM, Salam MA, Fuchs GJ, Calderwood SB. Source: The Journal of Infectious Diseases. 2001 September 1; 184(5): 643-7. Epub 2001 August 09. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11494170&dopt=Abstract
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Loss of biological activity due to Glu-->Arg mutation at residue 11 of the B subunit of cholera toxin. Author(s): Yamaoka J, Yamasaki S, Kurazono H, Imamura S, Noda M, Miyai K, Takeda Y. Source: Microbial Pathogenesis. 1997 November; 23(5): 297-302. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9405207&dopt=Abstract
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Lowering of the electric potential on the membrane as a possible signal modulating the expression of virulence factors in Vibrio cholerae. Author(s): Dibrov P. Source: Molecular Microbiology. 2000 January; 35(2): 473-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10652109&dopt=Abstract
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Luteinizing hormone/choriogonadotropin-dependent, cholera toxin-catalyzed adenosine 5'-diphosphate (ADP)-ribosylation of the long and short forms of Gs alpha and pertussis toxin-catalyzed ADP-ribosylation of Gi alpha*. Author(s): Rajagopalan-Gupta RM, Rasenick MM, Hunzicker-Dunn M. Source: Molecular Endocrinology (Baltimore, Md.). 1997 May; 11(5): 538-49. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9139798&dopt=Abstract
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Maturation of human dendritic cells induced by the adjuvant cholera toxin: role of cAMP on chemokine receptor expression. Author(s): Gagliardi MC, De Magistris MT. Source: Vaccine. 2003 February 14; 21(9-10): 856-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12547594&dopt=Abstract
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Microbes and microbial Toxins: paradigms for microbial-mucosal toxins. V. Cholera: invasion of the intestinal epithelial barrier by a stably folded protein toxin. Author(s): Lencer WI. Source: American Journal of Physiology. Gastrointestinal and Liver Physiology. 2001 May; 280(5): G781-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11292584&dopt=Abstract
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Misleading negative findings in a field trial of killed, oral cholera vaccine in Peru. Author(s): Clemens JD, Sack DA, Ivanoff B. Source: The Journal of Infectious Diseases. 2001 April 15; 183(8): 1306-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11262221&dopt=Abstract
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Modification of the multiplex PCR for unambiguous differentiation of the El Tor & classical biotypes of Vibrio cholerae O1. Author(s): De K, Ramamurthy T, Ghose AC, Islam MS, Takeda Y, Nair GB, Nandy RK. Source: The Indian Journal of Medical Research. 2001 September; 114: 77-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11873401&dopt=Abstract
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Molecular analyses of a putative CTXphi precursor and evidence for independent acquisition of distinct CTX(phi)s by toxigenic Vibrio cholerae. Author(s): Boyd EF, Heilpern AJ, Waldor MK. Source: Journal of Bacteriology. 2000 October; 182(19): 5530-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10986258&dopt=Abstract
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Molecular analysis of Vibrio cholerae O1, O139, non-O1, and non-O139 strains: clonal relationships between clinical and environmental isolates. Author(s): Singh DV, Matte MH, Matte GR, Jiang S, Sabeena F, Shukla BN, Sanyal SC, Huq A, Colwell RR. Source: Applied and Environmental Microbiology. 2001 February; 67(2): 910-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11157262&dopt=Abstract
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Molecular characterisation of rough variants of Vibrio cholerae isolated from hospitalised patients with diarrhoea. Author(s): Mitra RK, Nandy RK, Ramamurthy T, Bhattacharya SK, Yamasaki S, Shimada T, Takeda Y, Nair GB. Source: Journal of Medical Microbiology. 2001 March; 50(3): 268-76. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11232774&dopt=Abstract
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Molecular characterization of Vibrio cholerae O1 outbreak strains in Miri, Sarawak (Malaysia). Author(s): Radu S, Vincent M, Apun K, Abdul-Rahim R, Benjamin PG, Yuherman, Rusul G. Source: Acta Tropica. 2002 August; 83(2): 169-76. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12088858&dopt=Abstract
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Molecular characterization of Vibrio cholerae O139 bengal isolated from water and the aquatic plant Eichhornia crassipes in the River Ganga, Varanasi, India. Author(s): Bhanumathi R, Sabeena F, Isac SR, Shukla BN, Singh DV. Source: Applied and Environmental Microbiology. 2003 April; 69(4): 2389-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12676727&dopt=Abstract
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Molecular comparison of toxigenic clinical & non-toxigenic environmental strains of Vibrio cholerae O1 Ogawa isolated during an outbreak of cholera in south India. Author(s): Sinha S, Chowdhury P, Chowdhury NR, Kamruzzaman M, Faruque SM, Ramamurthy T, Bhattacharya SK, Yamasaki S, Takeda Y, Nair GB. Source: The Indian Journal of Medical Research. 2001 September; 114: 83-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11873402&dopt=Abstract
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Molecular ecology of toxigenic Vibrio cholerae. Author(s): Faruque SM, Nair GB. Source: Microbiology and Immunology. 2002; 46(2): 59-66. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11939579&dopt=Abstract
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Molecular epidemiologic analysis of Vibrio cholerae O1 isolated during the 1997-8 cholera epidemic in southern Thailand. Author(s): Kondo S, Kongmuang U, Kalnauwakul S, Matsumoto C, Chen CH, Nishibuchi M. Source: Epidemiology and Infection. 2001 August; 127(1): 7-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11561977&dopt=Abstract
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Molecular epidemiological study of Vibrio cholerae isolates from infected patients in Teheran, Iran. Author(s): Pourshafie MR, Grimont F, Saifi M, Grimont PA. Source: Journal of Medical Microbiology. 2000 December; 49(12): 1085-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11129720&dopt=Abstract
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Molecular epidemiology of O139 Vibrio cholerae: mutation, lateral gene transfer, and founder flush. Author(s): Garg P, Aydanian A, Smith D, J Glenn M Jr, Nair GB, Stine OC. Source: Emerging Infectious Diseases. 2003 July; 9(7): 810-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12890320&dopt=Abstract
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Molecular epidemiology of Vibrio cholerae O139 in China: polymorphism of ribotypes and CTX elements. Author(s): Qu M, Xu J, Ding Y, Wang R, Liu P, Kan B, Qi G, Liu Y, Gao S. Source: Journal of Clinical Microbiology. 2003 June; 41(6): 2306-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12791841&dopt=Abstract
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Molecular identification of pathogenicity genes and ERIC types in Vibrio cholerae O1 epidemic strains from Mozambique. Author(s): Folgosa E, Mastrandrea S, Cappuccinelli P, Uzzau S, Rappelli P, Brian MJ, Colombo MM. Source: Epidemiology and Infection. 2001 August; 127(1): 17-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11561970&dopt=Abstract
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Mortality, morbidity, and microbiology of endemic cholera among hospitalized patients in Dhaka, Bangladesh. Author(s): Ryan ET, Dhar U, Khan WA, Salam MA, Faruque AS, Fuchs GJ, Calderwood SB, Bennish ML. Source: The American Journal of Tropical Medicine and Hygiene. 2000 July-August; 63(1-2): 12-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11357989&dopt=Abstract
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Mozambique cholera will affect region. Author(s): Bateman C. Source: South African Medical Journal. Suid-Afrikaanse Tydskrif Vir Geneeskunde. 2002 February; 92(2): 104-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11894638&dopt=Abstract
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Mucosal adjuvants and anti-infection and anti-immunopathology vaccines based on cholera toxin, cholera toxin B subunit and CpG DNA. Author(s): Holmgren J, Harandi AM, Czerkinsky C. Source: Expert Rev Vaccines. 2003 April; 2(2): 205-17. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12899572&dopt=Abstract
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Multilocus sequence typing has better discriminatory ability for typing Vibrio cholerae than does pulsed-field gel electrophoresis and provides a measure of phylogenetic relatedness. Author(s): Kotetishvili M, Stine OC, Chen Y, Kreger A, Sulakvelidze A, Sozhamannan S, Morris JG Jr. Source: Journal of Clinical Microbiology. 2003 May; 41(5): 2191-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12734277&dopt=Abstract
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Nasal administration of cholera toxin (CT) suppresses clinical signs of experimental autoimmune encephalomyelitis (EAE). Author(s): Yura M, Takahashi I, Terawaki S, Hiroi T, Kweon MN, Yuki Y, Kiyono H. Source: Vaccine. 2001 October 12; 20(1-2): 134-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11567757&dopt=Abstract
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National Institute of Cholera and Enteric Diseases. Author(s): National Institute of Cholera and Enteric Diseases. Source: Journal of Postgraduate Medicine. 2000 July-September; 46(3): 231-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11298480&dopt=Abstract
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Neonatal diarrhea caused by Vibrio cholerae 0139 Bengal. Author(s): Khan AM, Bhattacharya MK, Albert MJ. Source: Diagnostic Microbiology and Infectious Disease. 1995 December; 23(4): 155-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9407221&dopt=Abstract
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New developments in the understanding of cholera. Author(s): Butler T. Source: Current Gastroenterology Reports. 2001 August; 3(4): 315-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11470000&dopt=Abstract
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New evidence for an inflammatory component in diarrhea caused by selected new, live attenuated cholera vaccines and by El Tor and Q139 Vibrio cholerae. Author(s): Silva TM, Schleupner MA, Tacket CO, Steiner TS, Kaper JB, Edelman R, Guerrant R. Source: Infection and Immunity. 1996 June; 64(6): 2362-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8675353&dopt=Abstract
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New insights on the emergence of cholera in Latin America during 1991: the Peruvian experience. Author(s): Seas C, Miranda J, Gil AI, Leon-Barua R, Patz J, Huq A, Colwell RR, Sack RB. Source: The American Journal of Tropical Medicine and Hygiene. 2000 April; 62(4): 5137. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11220769&dopt=Abstract
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New variants of Vibrio cholerae O1 biotype El Tor with attributes of the classical biotype from hospitalized patients with acute diarrhea in Bangladesh. Author(s): Nair GB, Faruque SM, Bhuiyan NA, Kamruzzaman M, Siddique AK, Sack DA. Source: Journal of Clinical Microbiology. 2002 September; 40(9): 3296-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12202569&dopt=Abstract
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NhaA, an Na(+)/H(+) antiporter involved in environmental survival of Vibrio cholerae. Author(s): Vimont S, Berche P. Source: Journal of Bacteriology. 2000 May; 182(10): 2937-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10781565&dopt=Abstract
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Nitric oxide production during Vibrio cholerae infection. Author(s): Janoff EN, Hayakawa H, Taylor DN, Fasching CE, Kenner JR, Jaimes E, Raij L. Source: The American Journal of Physiology. 1997 November; 273(5 Pt 1): G1160-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9374715&dopt=Abstract
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Non-0:1 Vibrio cholerae septicemia in thalassemia patients. Author(s): Laosombat V, Pruekprasert P, Wongchanchailert M. Source: Southeast Asian J Trop Med Public Health. 1996 June; 27(2): 411-3. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9280014&dopt=Abstract
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Non-O1 Vibrio cholerae bacteraemia without diarrhoea. Author(s): Fernandez-Natal I, Alcoba-Leza M. Source: Lancet. 1996 July 6; 348(9019): 67. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8691963&dopt=Abstract
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Non-O1 Vibrio cholerae: a fatal cause of sepsis in northern Australia. Author(s): Heath CH, Garrow SC, Golledge CL. Source: The Medical Journal of Australia. 2001 May 7; 174(9): 480-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11386599&dopt=Abstract
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Non-serogroup O:1 Vibrio cholerae bacteremia and cerebritis. Author(s): Suankratay C, Phantumchinda K, Tachawiboonsak W, Wilde H. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2001 April 1; 32(7): E117-9. Epub 2001 March 20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11264049&dopt=Abstract
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Nontoxigenic Vibrio cholerae 01 serotype Inaba biotype El Tor associated with a cluster of cases of cholera in southern India. Author(s): Saha PK, Koley H, Mukhopadhyay AK, Bhattacharya SK, Nair GB, Ramakrishnan BS, Krishnan S, Takeda T, Takeda Y. Source: Journal of Clinical Microbiology. 1996 May; 34(5): 1114-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8727886&dopt=Abstract
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Nontoxigenic vibrio Cholerae O1 bacteremia: case report and review. Author(s): Ninin E, Caroff N, El Kouri D, Espaze E, Richet H, Quilici ML, Fournier JM. Source: European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology. 2000 June; 19(6): 489-91. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10947231&dopt=Abstract
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Norfloxacin monodose use in patients with cholera in Salta Argentina. Author(s): Seijo AC, Fernandez M, Campos C, Cernigoi BE, Nogueras M, San Juan J, Torres MF, Martino OA. Source: Revista Do Instituto De Medicina Tropical De Sao Paulo. 1996 May-June; 38(3): 217-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9163987&dopt=Abstract
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Nosocomial infection due to Vibrio cholerae in two referral hospitals in Guatemala. Author(s): Hernandez JE, Mejia CR, Cazali IL, Arathoon EG. Source: Infection Control and Hospital Epidemiology : the Official Journal of the Society of Hospital Epidemiologists of America. 1996 June; 17(6): 371-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8805070&dopt=Abstract
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Novel carbohydrate binding site recognizing blood group A and B determinants in a hybrid of cholera toxin and Escherichia coli heat-labile enterotoxin B-subunits. Author(s): Angstrom J, Backstrom M, Berntsson A, Karlsson N, Holmgren J, Karlsson KA, Lebens M, Teneberg S. Source: The Journal of Biological Chemistry. 2000 February 4; 275(5): 3231-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10652309&dopt=Abstract
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Oceanography and the seventh cholera pandemic. Author(s): Mourino-Perez RR. Source: Epidemiology (Cambridge, Mass.). 1998 May; 9(3): 355-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9583431&dopt=Abstract
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Oral administration of cholera toxin B-insulin conjugates protects NOD mice from autoimmune diabetes by inducing CD4+ regulatory T-cells. Author(s): Ploix C, Bergerot I, Durand A, Czerkinsky C, Holmgren J, Thivolet C. Source: Diabetes. 1999 November; 48(11): 2150-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10535448&dopt=Abstract
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Oral fluid therapy of cholera among Bangladesh refugees. 1973. Author(s): Mahalanabis D, Choudhuri AB, Bagchi NG, Bhattacharya AK, Simpson TW. Source: Bulletin of the World Health Organization. 2001; 79(5): 473-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11421245&dopt=Abstract
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Oral immunisation of chickens using cholera toxin B subunit and Softigen as adjuvants results in high antibody titre in the egg yolk. Author(s): Hedlund GP, Hau J. Source: In Vivo. 2001 September-October; 15(5): 381-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11695233&dopt=Abstract
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Oral vaccines against cholera: lessons from Vietnam and elsewhere. Author(s): Levine MM. Source: Lancet. 1997 January 25; 349(9047): 220-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9014902&dopt=Abstract
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Oral vaccines for cholera control. Author(s): Chaturvedi S, Chaturvedi S. Source: Natl Med J India. 1997 January-February; 10(1): 17-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9069701&dopt=Abstract
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Oral, inactivated, whole cell enterotoxigenic Escherichia coli plus cholera toxin B subunit vaccine: results of the initial evaluation in children. PRIDE Study Group. Author(s): Savarino SJ, Hall ER, Bassily S, Brown FM, Youssef F, Wierzba TF, Peruski L, El-Masry NA, Safwat M, Rao M, El Mohamady H, Abu-Elyazeed R, Naficy A, Svennerholm AM, Jertborn M, Lee YJ, Clemens JD. Source: The Journal of Infectious Diseases. 1999 January; 179(1): 107-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9841829&dopt=Abstract
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Orogastric vaccination of guinea pigs with Helicobacter pylori sonicate and a high dose of cholera toxin lowers the burden of infection. Author(s): Durrani Z, Rijpkema S. Source: Fems Immunology and Medical Microbiology. 2003 May 25; 36(3): 169-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12738387&dopt=Abstract
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Outbreak of cholera caused by Vibrio cholerae 01 intermediately resistant to norfloxacin at Malda, West Bengal. Author(s): Bhattacharya MK, Ghosh S, Mukhopadhyay AK, Deb A, Bhattacharya SK. Source: J Indian Med Assoc. 2000 July; 98(7): 389-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11143861&dopt=Abstract
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Outbreak of cholera in arid zone of Bikaner. Author(s): Gupta A, Jain S, Mahawal BS. Source: The Indian Journal of Medical Research. 1999 October; 110: 126-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10645099&dopt=Abstract
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Outbreak of cholera in Ibadan, Nigeria. Author(s): Lawoyin TO, Ogunbodede NA, Olumide EA, Onadeko MO. Source: European Journal of Epidemiology. 1999 April; 15(4): 367-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10414378&dopt=Abstract
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Outbreaks of cholera in Kathmandu Valley in Nepal. Author(s): Ise T, Pokharel BM, Rawal S, Shrestha RS, Dhakhwa JR. Source: Journal of Tropical Pediatrics. 1996 October; 42(5): 305-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8936965&dopt=Abstract
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Outbreaks of cholera in Nepal. Author(s): Pokhrel BM, Kubo T. Source: Southeast Asian J Trop Med Public Health. 1996 September; 27(3): 574-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9185273&dopt=Abstract
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Pandemic spread of cholera: genetic diversity and relationships within the seventh pandemic clone of Vibrio cholerae determined by amplified fragment length polymorphism. Author(s): Lan R, Reeves PR. Source: Journal of Clinical Microbiology. 2002 January; 40(1): 172-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11773113&dopt=Abstract
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Passive protection of serum from volunteers inoculated with attenuated strain 638 of Vibrio cholerae O1 in animal models. Author(s): Perez JL, Garcia L, Talavera A, Oliva R, Valmaseda T, Ano G, Perez O, Sierra G. Source: Vaccine. 2000 September 15; 19(2-3): 376-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10930693&dopt=Abstract
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Peak occurrences of ciguatera fish poisoning precede cholera outbreaks in Hong Kong. Author(s): Kwan LC, Cheung DK, Kam KM. Source: Epidemiology and Infection. 2003 August; 131(1): 621-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12948360&dopt=Abstract
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pepA, a gene mediating pH regulation of virulence genes in Vibrio cholerae. Author(s): Behari J, Stagon L, Calderwood SB. Source: Journal of Bacteriology. 2001 January; 183(1): 178-88. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11114915&dopt=Abstract
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Peroral immunization of microencapsulated human VP8 in combination with cholera toxin induces intestinal antibody responses. Author(s): Kang DK, Kim PH, Ko EJ, Seo JY, Seong SY, Kim YH, Kwon IC, Jeong SY, Yang JM. Source: Molecules and Cells. 1999 December 31; 9(6): 609-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10672927&dopt=Abstract
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Phosphorylation of the flagellar regulatory protein FlrC is necessary for Vibrio cholerae motility and enhanced colonization. Author(s): Correa NE, Lauriano CM, McGee R, Klose KE. Source: Molecular Microbiology. 2000 February; 35(4): 743-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10692152&dopt=Abstract
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Plasmid vectors encoding cholera toxin or the heat-labile enterotoxin from Escherichia coli are strong adjuvants for DNA vaccines. Author(s): Arrington J, Braun RP, Dong L, Fuller DH, Macklin MD, Umlauf SW, Wagner SJ, Wu MS, Payne LG, Haynes JR. Source: Journal of Virology. 2002 May; 76(9): 4536-46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11932419&dopt=Abstract
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Plasmidic extended-spectrum beta-lactamases in Vibrio cholerae O1 El Tor isolates in Argentina. Author(s): Petroni A, Corso A, Melano R, Cacace ML, Bru AM, Rossi A, Galas M. Source: Antimicrobial Agents and Chemotherapy. 2002 May; 46(5): 1462-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11959583&dopt=Abstract
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Pneumonia, cholera, and dysentery feared after earthquake. Author(s): Sharma R. Source: Bmj (Clinical Research Ed.). 2001 February 10; 322(7282): 317. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11159649&dopt=Abstract
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Positive and negative regulation of water channel aquaporins in human small intestine by cholera toxin. Author(s): Hamabata T, Liu C, Takeda Y. Source: Microbial Pathogenesis. 2002 June; 32(6): 273-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12137754&dopt=Abstract
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Possibility of public health hazards by contamination of toxin producing Vibrio cholerae through fishes reared in sewage fed fishery. Author(s): Saha MK, Dutta P, De SP. Source: Indian J Public Health. 1999 April-June; 43(2): 71-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11243070&dopt=Abstract
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Predictability of Vibrio cholerae in Chesapeake Bay. Author(s): Louis VR, Russek-Cohen E, Choopun N, Rivera IN, Gangle B, Jiang SC, Rubin A, Patz JA, Huq A, Colwell RR. Source: Applied and Environmental Microbiology. 2003 May; 69(5): 2773-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12732548&dopt=Abstract
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Preferential association of the heat-stable enterotoxin gene (stn) with environmental strains of Vibrio cholerae belonging to the O14 serogroup. Author(s): Sarkar B, Bhattacharya T, Ramamurthy T, Shimada T, Takeda Y, Balakrish Nair G. Source: Epidemiology and Infection. 2002 October; 129(2): 245-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12403100&dopt=Abstract
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Preparation and preclinical evaluation of experimental group B streptococcus type III polysaccharide-cholera toxin B subunit conjugate vaccine for intranasal immunization. Author(s): Shen X, Lagergard T, Yang Y, Lindblad M, Fredriksson M, Holmgren J. Source: Vaccine. 2000 November 22; 19(7-8): 850-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11115709&dopt=Abstract
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Preparation of a subcellular conjugate with the lipopolysaccharide from Vibrio cholerae 01 using beta-D-glucan as matrix. Author(s): Machova E, Bystricky S, Galikova A, Kogan G. Source: European Journal of Medicinal Chemistry. 2002 August; 37(8): 681-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12161065&dopt=Abstract
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Prevalence of virulence-associated genes in clinical and environmental Vibrio cholerae strains isolated in Brazil between 1991 and 1999. Author(s): Vital Brazil JM, Alves RM, Rivera IN, Rodrigues DP, Karaolis DK, Campos LC. Source: Fems Microbiology Letters. 2002 September 24; 215(1): 15-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12393195&dopt=Abstract
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Prevention fails to halt South Africa's well-treated cholera epidemic. Author(s): Morris K. Source: Lancet. 2001 January 27; 357(9252): 290. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11214139&dopt=Abstract
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Protection from cholera by adding lime juice to food - results from community and laboratory studies in Guinea-Bissau, West Africa. Author(s): Rodrigues A, Sandstrom A, Ca T, Steinsland H, Jensen H, Aaby P. Source: Tropical Medicine & International Health : Tm & Ih. 2000 June; 5(6): 418-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10929141&dopt=Abstract
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Protective efficacy of rotavirus 2/6-virus-like particles combined with CT-E29H, a detoxified cholera toxin adjuvant. Author(s): Siadat-Pajouh M, Cai L. Source: Viral Immunology. 2001; 14(1): 31-47. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11270595&dopt=Abstract
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Pulsed-field gel electrophoresis-based molecular comparison of vibrio cholerae O1 isolates from domestic and imported cases of cholera in Japan. Author(s): Arakawa E, Murase T, Matsushita S, Shimada T, Yamai S, Ito T, Watanabe H. Source: Journal of Clinical Microbiology. 2000 January; 38(1): 424-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10618132&dopt=Abstract
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Quinolone susceptibility of Vibrio cholerae O1 & O139 isolates from Vellore. Author(s): Jesudason MV, Balaji V, Thomson CJ. Source: The Indian Journal of Medical Research. 2002 September; 116: 96-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12619447&dopt=Abstract
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Quorum-sensing regulators control virulence gene expression in Vibrio cholerae. Author(s): Zhu J, Miller MB, Vance RE, Dziejman M, Bassler BL, Mekalanos JJ. Source: Proceedings of the National Academy of Sciences of the United States of America. 2002 March 5; 99(5): 3129-34. Epub 2002 February 19. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11854465&dopt=Abstract
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Randomized, controlled human challenge study of the safety, immunogenicity, and protective efficacy of a single dose of Peru-15, a live attenuated oral cholera vaccine. Author(s): Cohen MB, Giannella RA, Bean J, Taylor DN, Parker S, Hoeper A, Wowk S, Hawkins J, Kochi SK, Schiff G, Killeen KP. Source: Infection and Immunity. 2002 April; 70(4): 1965-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11895960&dopt=Abstract
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Randomized, double-blind, placebo-controlled, multicentered trial of the efficacy of a single dose of live oral cholera vaccine CVD 103-HgR in preventing cholera following challenge with Vibrio cholerae O1 El tor inaba three months after vaccination. Author(s): Tacket CO, Cohen MB, Wasserman SS, Losonsky G, Livio S, Kotloff K, Edelman R, Kaper JB, Cryz SJ, Giannella RA, Schiff G, Levine MM. Source: Infection and Immunity. 1999 December; 67(12): 6341-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10569747&dopt=Abstract
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Rapid detection of Vibrio cholerae O1 in west Africa. Author(s): Lowenhaupt E, Huq A, Colwell RR, Adingra A, Epstein PR. Source: Lancet. 1998 January 3; 351(9095): 34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9433429&dopt=Abstract
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Rapid diagnosis of cholera by coagglutination test. Author(s): Hanumanthappa AR, Rajagopal V. Source: Indian J Pathol Microbiol. 2001 April; 44(2): 123-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11883125&dopt=Abstract
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Rapid method for species-specific identification of Vibrio cholerae using primers targeted to the gene of outer membrane protein OmpW. Author(s): Nandi B, Nandy RK, Mukhopadhyay S, Nair GB, Shimada T, Ghose AC. Source: Journal of Clinical Microbiology. 2000 November; 38(11): 4145-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11060082&dopt=Abstract
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Rapid spread of the new clone of Vibrio cholerae O1 biotype El Tor in cholera endemic areas in India. Author(s): Bag PK, Maiti S, Sharma C, Ghosh A, Basu A, Mitra R, Bhattacharya SK, Nakamura S, Yamasaki S, Takeda Y, Balakrish Nair G. Source: Epidemiology and Infection. 1998 October; 121(2): 245-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9825773&dopt=Abstract
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Readers respond to “Cholera in Paris”. Author(s): Frerichs RR. Source: American Journal of Public Health. 2001 August; 91(8): 1170. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11499092&dopt=Abstract
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Readers respond to “Cholera in Paris”. Author(s): Birden H. Source: American Journal of Public Health. 2001 August; 91(8): 1170. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11499091&dopt=Abstract
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Reappearance of Vibrio cholerae serogroup 0139 in Yavatmal during June-August1998. Author(s): Ambhore NA, Ingole KV, Fule RP. Source: Indian Journal of Medical Sciences. 2000 February; 54(2): 63-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11271727&dopt=Abstract
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Rearrangements in the genomes of Vibrio cholerae strains belonging to different serovars and biovars. Author(s): Nandi S, Khetawat G, Sengupta S, Majumder R, Kar S, Bhadra RK, Roychoudhury S, Das J. Source: International Journal of Systematic Bacteriology. 1997 July; 47(3): 858-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9272984&dopt=Abstract
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Recent developments in cholera. Author(s): Shears P. Source: Current Opinion in Infectious Diseases. 2001 October; 14(5): 553-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11964875&dopt=Abstract
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Recombination between rRNA operons created most of the ribotype variation observed in the seventh pandemic clone of Vibrio cholerae. Author(s): Lan R, Reeves PR. Source: Microbiology (Reading, England). 1998 May; 144 ( Pt 5): 1213-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9611796&dopt=Abstract
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Reduction of cholera in Bangladeshi villages by simple filtration. Author(s): Colwell RR, Huq A, Islam MS, Aziz KM, Yunus M, Khan NH, Mahmud A, Sack RB, Nair GB, Chakraborty J, Sack DA, Russek-Cohen E. Source: Proceedings of the National Academy of Sciences of the United States of America. 2003 February 4; 100(3): 1051-5. Epub 2003 January 14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12529505&dopt=Abstract
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Reemergence of epidemic Vibrio cholerae O139, Bangladesh. Author(s): Faruque SM, Chowdhury N, Kamruzzaman M, Ahmad QS, Faruque AS, Salam MA, Ramamurthy T, Nair GB, Weintraub A, Sack DA. Source: Emerging Infectious Diseases. 2003 September; 9(9): 1116-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14519249&dopt=Abstract
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Regulation of gene expression in Vibrio cholerae by ToxT involves both antirepression and RNA polymerase stimulation. Author(s): Yu RR, DiRita VJ. Source: Molecular Microbiology. 2002 January; 43(1): 119-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11849541&dopt=Abstract
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Regulation of virulence in Vibrio cholerae. Author(s): Klose KE. Source: International Journal of Medical Microbiology : Ijmm. 2001 May; 291(2): 81-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11437342&dopt=Abstract
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Role of active efflux in association with target gene mutations in fluoroquinolone resistance in clinical isolates of Vibrio cholerae. Author(s): Baranwal S, Dey K, Ramamurthy T, Nair GB, Kundu M. Source: Antimicrobial Agents and Chemotherapy. 2002 August; 46(8): 2676-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12121955&dopt=Abstract
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Role of sodium bioenergetics in Vibrio cholerae. Author(s): Hase CC, Barquera B. Source: Biochimica Et Biophysica Acta. 2001 May 1; 1505(1): 169-78. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11248198&dopt=Abstract
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Roles of NhaA, NhaB, and NhaD Na+/H+ antiporters in survival of Vibrio cholerae in a saline environment. Author(s): Herz K, Vimont S, Padan E, Berche P. Source: Journal of Bacteriology. 2003 February; 185(4): 1236-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12562793&dopt=Abstract
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Rotavirus 2/6 viruslike particles administered intranasally with cholera toxin, Escherichia coli heat-labile toxin (LT), and LT-R192G induce protection from rotavirus challenge. Author(s): O'Neal CM, Clements JD, Estes MK, Conner ME. Source: Journal of Virology. 1998 April; 72(4): 3390-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9525668&dopt=Abstract
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Safety and immunogenicity of two different lots of the oral, killed enterotoxigenic escherichia coli-cholera toxin B subunit vaccine in Israeli young adults. Author(s): Cohen D, Orr N, Haim M, Ashkenazi S, Robin G, Green MS, Ephros M, Sela T, Slepon R, Ashkenazi I, Taylor DN, Svennerholm AM, Eldad A, Shemer J. Source: Infection and Immunity. 2000 August; 68(8): 4492-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10899847&dopt=Abstract
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Seasonal, nontoxigenic Vibrio cholerae O1 Ogawa infections in the Eastern Region of Saudi Arabia. Author(s): Bubshait SA, Al-Turki K, Qadri MH, Fontaine RE, Cameron D. Source: International Journal of Infectious Diseases : Ijid : Official Publication of the International Society for Infectious Diseases. 2000; 4(4): 198-202. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11231182&dopt=Abstract
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Selection of a WEHI-3B leukemia cell subclone resistant to inhibition by cholera toxin. Author(s): Pessina A, Giuliani A, Croera C, Foti P, Mascolo L, Gagliardi G, Neri MG. Source: Molecular and Cellular Biochemistry. 2002 April; 233(1-2): 19-26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12083375&dopt=Abstract
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Sensitive microplate assay for detection of bactericidal antibodies to Vibrio cholerae O139. Author(s): Attridge SR, Johansson C, Trach DD, Qadri F, Svennerholm AM. Source: Clinical and Diagnostic Laboratory Immunology. 2002 March; 9(2): 383-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11874883&dopt=Abstract
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Serotypes and phage types of Vibrio cholerae in Mysore. Author(s): Hanumanthappa AR, Rajagopal V. Source: J Commun Dis. 2000 December; 32(4): 313-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11668944&dopt=Abstract
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Severe cholera outbreak following floods in a northern district of West Bengal. Author(s): Sur D, Dutta P, Nair GB, Bhattacharya SK. Source: The Indian Journal of Medical Research. 2000 November; 112: 178-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12452126&dopt=Abstract
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Sharp eyes on cholera flashpoints. Author(s): Bateman C. Source: South African Medical Journal. Suid-Afrikaanse Tydskrif Vir Geneeskunde. 2001 April; 91(4): 278-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11402891&dopt=Abstract
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Solar disinfection of drinking water protects against cholera in children under 6 years of age. Author(s): Conroy RM, Meegan ME, Joyce T, McGuigan K, Barnes J. Source: Archives of Disease in Childhood. 2001 October; 85(4): 293-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11567937&dopt=Abstract
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Splenic abscess with Vibrio cholerae masking pancreatic cancer. Author(s): Cavuoti D, Fogli M, Quinton R, Gander RM, Southern PM. Source: Diagnostic Microbiology and Infectious Disease. 2002 August; 43(4): 311-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12151192&dopt=Abstract
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Structural studies of receptor binding by cholera toxin mutants. Author(s): Merritt EA, Sarfaty S, Jobling MG, Chang T, Holmes RK, Hirst TR, Hol WG. Source: Protein Science : a Publication of the Protein Society. 1997 July; 6(7): 1516-28. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9232653&dopt=Abstract
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Study of the physical meaning of the binding parameters involved in effector-target conjugation using monoclonal antibodies against adhesion molecules and cholera toxin. Author(s): Garcia-Penarrubia P, Lorenzo N, Galvez J, Campos A, Ferez X, Rubio G. Source: Cellular Immunology. 2002 February; 215(2): 141-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12202151&dopt=Abstract
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Supplementation with zinc, but not vitamin A, improves seroconversion to vibriocidal antibody in children given an oral cholera vaccine. Author(s): Albert MJ, Qadri F, Wahed MA, Ahmed T, Rahman AS, Ahmed F, Bhuiyan NA, Zaman K, Baqui AH, Clemens JD, Black RE. Source: The Journal of Infectious Diseases. 2003 March 15; 187(6): 909-13. Epub 2003 Mar 06. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12660937&dopt=Abstract
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Survival in a cruel world: how Vibrio cholerae and Salmonella respond to an unwilling host. Author(s): Slauch J, Taylor R, Maloy S. Source: Genes & Development. 1997 July 15; 11(14): 1761-74. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9242485&dopt=Abstract
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Susceptibility of Vibrio cholerae O139 to antibody-dependent, complement-mediated bacteriolysis. Author(s): Attridge SR, Qadri F, Albert MJ, Manning PA. Source: Clinical and Diagnostic Laboratory Immunology. 2000 May; 7(3): 444-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10799459&dopt=Abstract
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Susceptibility to rifaximin of Vibrio cholerae strains from different geographical areas. Author(s): Scrascia M, Forcillo M, Maimone F, Pazzani C. Source: The Journal of Antimicrobial Chemotherapy. 2003 August; 52(2): 303-5. Epub 2003 July 01. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12837732&dopt=Abstract
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Tetracycline in the treatment of cholera caused by Vibrio cholerae O1 resistant to the drug in vitro. Author(s): Khan AM, von Gierke U, Hossain MS, Fuchs GJ. Source: J Health Popul Nutr. 2003 March; 21(1): 76-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12751678&dopt=Abstract
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The cholera toxin B subunit is a mucosal adjuvant for oral tolerance induction in type 1 diabetes. Author(s): Bregenholt S, Wang M, Wolfe T, Hughes A, Baerentzen L, Dyrberg T, von Herrath MG, Petersen JS. Source: Scandinavian Journal of Immunology. 2003 May; 57(5): 432-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12753499&dopt=Abstract
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The global regulator ArcA modulates expression of virulence factors in Vibrio cholerae. Author(s): Sengupta N, Paul K, Chowdhury R. Source: Infection and Immunity. 2003 October; 71(10): 5583-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14500477&dopt=Abstract
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The spatial epidemiology of cholera in an endemic area of Bangladesh. Author(s): Ali M, Emch M, Donnay JP, Yunus M, Sack RB. Source: Social Science & Medicine (1982). 2002 September; 55(6): 1015-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12220086&dopt=Abstract
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The vibrio pathogenicity island-encoded mop protein modulates the pathogenesis and reactogenicity of epidemic vibrio cholerae. Author(s): Zhang D, Xu Z, Sun W, Karaolis DK. Source: Infection and Immunity. 2003 January; 71(1): 510-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12496202&dopt=Abstract
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Thiazolidinone CFTR inhibitor identified by high-throughput screening blocks cholera toxin-induced intestinal fluid secretion. Author(s): Ma T, Thiagarajah JR, Yang H, Sonawane ND, Folli C, Galietta LJ, Verkman AS. Source: The Journal of Clinical Investigation. 2002 December; 110(11): 1651-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12464670&dopt=Abstract
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Toxigenic Vibrio cholerae serogroup O141-associated cholera-like diarrhea and bloodstream infection in the United States. Author(s): Crump JA, Bopp CA, Greene KD, Kubota KA, Middendorf RL, Wells JG, Mintz ED. Source: The Journal of Infectious Diseases. 2003 March 1; 187(5): 866-8. Epub 2003 February 18. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12599062&dopt=Abstract
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ToxR regulon of Vibrio cholerae and its expression in vibrios shed by cholera patients. Author(s): Bina J, Zhu J, Dziejman M, Faruque S, Calderwood S, Mekalanos J. Source: Proceedings of the National Academy of Sciences of the United States of America. 2003 March 4; 100(5): 2801-6. Epub 2003 February 24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12601157&dopt=Abstract
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Transport of protein toxins into cells: pathways used by ricin, cholera toxin and Shiga toxin. Author(s): Sandvig K, van Deurs B. Source: Febs Letters. 2002 October 2; 529(1): 49-53. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12354612&dopt=Abstract
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Tropical enteritis: nutritional consequences and connections with the riddle of cholera. Author(s): Rosenberg IH. Source: The Journal of Nutrition. 2003 January; 133(1): 333S-335S. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12514321&dopt=Abstract
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Uncoupling of the cholera toxin-G(M1) ganglioside receptor complex from endocytosis, retrograde Golgi trafficking, and downstream signal transduction by depletion of membrane cholesterol. Author(s): Wolf AA, Fujinaga Y, Lencer WI. Source: The Journal of Biological Chemistry. 2002 May 3; 277(18): 16249-56. Epub 2002 February 21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11859071&dopt=Abstract
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Uneasy bedfellows: science and politics in the refutation of Koch's bacterial theory of cholera. Author(s): Ogawa M. Source: Bulletin of the History of Medicine. 2000 Winter; 74(4): 671-707. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11201262&dopt=Abstract
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Unexpected carbohydrate cross-binding by Escherichia coli heat-labile enterotoxin. Recognition of human and rabbit target cell glycoconjugates in comparison with cholera toxin. Author(s): Karlsson KA, Teneberg S, Angstrom J, Kjellberg A, Hirst TR, Berstrom J, Miller-Podraza H. Source: Bioorganic & Medicinal Chemistry. 1996 November; 4(11): 1919-28. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9007276&dopt=Abstract
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Unique organization of the CTX genetic element in Vibrio cholerae O139 strains which reemerged in Calcutta, India, in September 1996. Author(s): Sharma C, Maiti S, Mukhopadhyay AK, Basu A, Basu I, Nair GB, Mukhopadhyaya R, Das B, Kar S, Ghosh RK, Ghosh A. Source: Journal of Clinical Microbiology. 1997 December; 35(12): 3348-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9399556&dopt=Abstract
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Unusual occurrence of cholera in Delhi during January 1994: epidemiological investigations. Author(s): Singh J, Khanna KK, Dhariwal AC, Bhattacharjee J, Singh M, Jain DC, Datta KK. Source: J Diarrhoeal Dis Res. 1996 June; 14(2): 107-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8870404&dopt=Abstract
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Use of dipsticks for rapid diagnosis of cholera caused by Vibrio cholerae O1 and O139 from rectal swabs. Author(s): Bhuiyan NA, Qadri F, Faruque AS, Malek MA, Salam MA, Nato F, Fournier JM, Chanteau S, Sack DA, Balakrish Nair G. Source: Journal of Clinical Microbiology. 2003 August; 41(8): 3939-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12904424&dopt=Abstract
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Use of in vivo-induced antigen technology (IVIAT) to identify genes uniquely expressed during human infection with Vibrio cholerae. Author(s): Hang L, John M, Asaduzzaman M, Bridges EA, Vanderspurt C, Kirn TJ, Taylor RK, Hillman JD, Progulske-Fox A, Handfield M, Ryan ET, Calderwood SB. Source: Proceedings of the National Academy of Sciences of the United States of America. 2003 July 8; 100(14): 8508-13. Epub 2003 June 25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12826608&dopt=Abstract
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Use of RNA arbitrarily primed-PCR fingerprinting to identify Vibrio cholerae genes differentially expressed in the host following infection. Author(s): Chakrabortty A, Das S, Majumdar S, Mukhopadhyay K, Roychoudhury S, Chaudhuri K. Source: Infection and Immunity. 2000 July; 68(7): 3878-87. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10858198&dopt=Abstract
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Use of telemedicine in evading cholera outbreak in Mahakumbh Mela, Prayag, UP, India: an encouraging experience. Author(s): Ayyagari A, Bhargava A, Agarwal R, Mishra SK, Mishra AK, Das SR, Shah R, Singh SK, Pandey A. Source: Telemedicine Journal and E-Health : the Official Journal of the American Telemedicine Association. 2003 Spring; 9(1): 89-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12699612&dopt=Abstract
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Using a knowledge, attitudes and practices survey to supplement findings of an outbreak investigation: cholera prevention measures during the 1991 epidemic in Peru. Author(s): Quick RE, Gerber ML, Palacios AM, Beingolea L, Vargas R, Mujica O, Moreno D, Seminario L, Smithwick EB, Tauxe RV. Source: International Journal of Epidemiology. 1996 August; 25(4): 872-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8921469&dopt=Abstract
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Vaba, Haiza, Kholera, Foklune or Cholera: in any language still the disease of seven pandemics. Author(s): Stewart-Tull DE. Source: Journal of Applied Microbiology. 2001 October; 91(4): 580-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11576291&dopt=Abstract
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Vascular changes in duodenal mucosa in shigellosis and cholera. Author(s): Koshi R, Chandy G, Mathan M, Mathan VI. Source: Clinical Anatomy (New York, N.Y.). 2003 July; 16(4): 317-27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12794915&dopt=Abstract
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Vibrio cholerae 01 strain resistant to vibriostatic compound 0/129 isolated from cholera cases in Kilifi, Kenya. Author(s): Khamala JK, Mwarumba S, Lewa P, Lowe B. Source: East Afr Med J. 2002 October; 79(10): 560. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12635766&dopt=Abstract
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Vibrio cholerae bacteremia in a neutropenic patient with non-small-cell lung carcinoma. Author(s): Berghmans T, Crokaert F, Sculier JP. Source: European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology. 2002 September; 21(9): 676-8. Epub 2002 September 03. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12373501&dopt=Abstract
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Vibrio cholerae diarrhoea in a three-day-old breastfed neonate. Author(s): Sethi NK, Sethi SK. Source: Indian J Pediatr. 2001 August; 68(8): 791-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11563260&dopt=Abstract
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Vibrio cholerae hemagglutinin/protease degrades chironomid egg masses. Author(s): Halpern M, Gancz H, Broza M, Kashi Y. Source: Applied and Environmental Microbiology. 2003 July; 69(7): 4200-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12839800&dopt=Abstract
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Vibrio cholerae O1 outbreak isolates in Mozambique and South Africa in 1998 are multiple-drug resistant, contain the SXT element and the aadA2 gene located on class 1 integrons. Author(s): Dalsgaard A, Forslund A, Sandvang D, Arntzen L, Keddy K. Source: The Journal of Antimicrobial Chemotherapy. 2001 December; 48(6): 827-38. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11733467&dopt=Abstract
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Vibrio cholerae O139 Bengal: odyssey of a fortuitous variant. Author(s): Ramamurthy T, Yamasaki S, Takeda Y, Nair GB. Source: Microbes and Infection / Institut Pasteur. 2003 April; 5(4): 329-44. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12706446&dopt=Abstract
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Vibrio cholerae-induced cellular responses of polarized T84 intestinal epithelial cells are dependent on production of cholera toxin and the RTX toxin. Author(s): Fullner KJ, Lencer WI, Mekalanos JJ. Source: Infection and Immunity. 2001 October; 69(10): 6310-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11553575&dopt=Abstract
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Vulnerability to coastal cholera ecology. Author(s): Collins AE. Source: Social Science & Medicine (1982). 2003 October; 57(8): 1397-407. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12927470&dopt=Abstract
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What makes a Vibrio cholerae pandemic? Author(s): Bradbury J. Source: The Lancet Infectious Diseases. 2002 March; 2(3): 132. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11944178&dopt=Abstract
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CHAPTER 2. NUTRITION AND CHOLERA Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and cholera.
Finding Nutrition Studies on Cholera 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 “cholera” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.
7
Adapted from http://ods.od.nih.gov. IBIDS is produced by the Office of Dietary Supplements (ODS) at the National Institutes of Health to assist the public, healthcare providers, educators, and researchers in locating credible, scientific information on dietary supplements. IBIDS was developed and will be maintained through an interagency partnership with the Food and Nutrition Information Center of the National Agricultural Library, U.S. Department of Agriculture.
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The following information is typical of that found when using the “Full IBIDS Database” to search for “cholera” (or a synonym): •
A new method for simultaneous demonstration of anterograde and retrograde connections in the brain: co-injections of biotinylated dextran amine and the beta subunit of cholera toxin. Author(s): Department of Cell Biology, University of Cincinnati, OH 45267, USA.
[email protected] Source: Coolen, L M Jansen, H T Goodman, R L Wood, R I Lehman, M N J-NeurosciMethods. 1999 September 15; 91(1-2): 1-8 0165-0270
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ADP-ribosylation of thylakoid membrane polypeptides by cholera toxin is correlated with inhibition of thylakoid GTPase activity and protein phosphorylation. Author(s): Department of Biochemistry, University of Leeds, U.K. Source: Millner, P A Robinson, P S Cell-Signal. 1989; 1(5): 421-33 0898-6568
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An outbreak of El Tor cholera in an institution for the mentally retarded in Nonthaburi, June-July 1987. Author(s): Department of Community and Social Medicine, Mae Sot General Hospital, Tak. Source: Swaddiwudhipong, W Limpakarnjanarat, K J-Med-Assoc-Thai. 1991 June; 74(6): 306-10 0125-2208
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Anchor-based design of improved cholera toxin and E. coli heat-labile enterotoxin receptor binding antagonists that display multiple binding modes. Author(s): Department of Biological Structure, Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195, USA. Source: Pickens, Jason C Merritt, Ethan A Ahn, Misol Verlinde, Christophe L M J Hol, Wim G J Fan, Erkang Chem-Biol. 2002 February; 9(2): 215-24 1074-5521
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Cholera associated with imported frozen coconut milk--Maryland, 1991. Source: Anonymous MMWR-Morb-Mortal-Wkly-Repage 1991 December 13; 40(49): 8445 0149-2195
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Cholera toxin as a mucosal adjuvant: III. Antibody responses to nontarget dietary antigens are not increased. Author(s): Institute of Pathology, Case Western Reserve University, Cleveland, OH 44106. Source: Nedrud, J G Sigmund, N Reg-Immunol. 1990-91; 3(5): 217-22 0896-0623
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Cholera toxin increases intracellular pH in B lymphoma cells and decreases their antigen-presenting ability. Author(s): Department of Immunology, Toho University School of Medicine, Tokyo, Japan. Source: Tanaka, Y Nakano, H Ishikawa, F Yoshida, M Gyotoku, Y Kakiuchi, T Eur-JImmunol. 1999 May; 29(5): 1561-70 0014-2980
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Cholera toxin induces tumor necrosis factor alpha production in human monocytes. Author(s): Chemistry Department, Georgetown University, Washington, DC 20056, USA.
[email protected] Source: Yan, Z Yang, D C Jett, M Mol-Cell-Biol-Res-Commun. 1999 August; 2(2): 124-30 1522-4724
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Cholera toxin-induced ADP-ribosylation of a 46 kDa protein is decreased in brains of ethanol-fed mice. Author(s): Division of Intramural Clinical and Biological Research, National Institute on Alcohol Abuse and Alcoholism, Rockville, MD 20852.
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Source: Nhamburo, P T Hoffman, P L Tabakoff, B Adv-Alcohol-Subst-Abuse. 1988; 7(34): 103-5 0270-3106 •
Culture media for the isolation and enumeration of pathogenic Vibrio species in foods and environmental samples. Source: Donovan, T.J. Van Netten, P. Culture media for food microbiology /. Amsterdam; New York : Elsevier, 1995. page 203-217. ISBN: 0444814981
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Effects of Hange-shashin-to on cholera toxin-induced fluid secretion in the small intestine of rats. Author(s): Central Research Laboratories, Tsumura and Co., Ibaraki, Japan. Source: Kase, Y Saitoh, K Yuzurihara, M Ishige, A Komatsu, Y Biol-Pharm-Bull. 1998 February; 21(2): 117-20 0918-6158
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Efficacy of atovaquone/proguanil for malaria prophylaxis in children and its effect on the immunogenicity of live oral typhoid and cholera vaccines. Author(s): Medical Research Unit, Albert Schweitzer Hospital, Lambarene, Gabon. Source: Faucher, J F Binder, R Missinou, M A Matsiegui, P B Gruss, H Neubauer, R Lell, B Que, J U Miller, G B Kremsner, P G Clin-Infect-Dis. 2002 November 15; 35(10): 1147-54 1537-6591
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Enhancement of respiratory immunity to Pasteurella multocida by cholera toxin in rabbits. Source: Suckow, M.A. Bowersock, T.L. Nielsen, K. Grigdesby, C.F. Lab-anim. London : Royal Society of Medicine Press Ltd. April 1996. volume 30 (2) page 120-126. 0023-6772
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Immunosuppressive effect of cholera toxin B on allergic conjunctivitis model in guinea pig. Author(s): Department of Ophthalmology, Nihon University School of Medicine, Itabashi-ku, Tokyo, Japan. Source: Saito, K Shoji, J Inada, N Iwasaki, Y Sawa, M Jpn-J-Ophthalmol. 2001 Jul-August; 45(4): 332-8 0021-5155
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Impaired cholera toxin relaxation with age in rat aorta. Author(s): Portland VA Medical Center, OR 97207-1035, USA. Source: Chapman, J Schutzer, W E Watts, V J Mader, S L J-Gerontol-A-Biol-Sci-Med-Sci. 1999 April; 54(4): B154-9 1079-5006
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Interaction of the B subunit of cholera toxin with endogenous ganglioside GM1 causes changes in membrane potential of rat thymocytes. Author(s): Division of Nutrition, Food and Drug Administration, Washington, D.C. 20204. Source: Mulhern, S A Fishman, P H Spiegel, S J-Membr-Biol. 1989 July; 109(1): 21-8 00222631
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Internalization of cholera toxin by different endocytic mechanisms. Author(s): Institute for Cancer Research, the Norwegian Radium Hospital, Montebello, 0310 Oslo, Norway. Source: Torgersen, M L Skretting, G van Deurs, B Sandvig, K J-Cell-Sci. 2001 October; 114(Pt 20): 3737-47 0021-9533
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Peripheral nerve lesion-induced uptake and transport of choleragenoid by capsaicinsensitive c-fibre spinal ganglion neurons. Author(s): Department of Physiology, University of Szeged, Hungary.
[email protected] Source: Jancso, G Santha, P Gecse, K Acta-Biol-Hung. 2002; 53(1-2): 77-84 0236-5383
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Pretreatment with cholera or pertussis toxin differentially modulates morphine- and beta-endorphin-induced antinociception in the mouse formalin test. Author(s): Department of Pharmacology, Institute of Natural Medicine, Hallym University, Kangwon-do, South Korea. Source: Chung, K M Suh, H W Neuropeptides. 2001 Oct-December; 35(5-6): 197-203 0143-4179
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Rat kidney proximal tubule cells in defined medium: the roles of cholera toxin, extracellular calcium and serum in cell growth and expression of gammaglutamyltransferase. Author(s): W. Alton Jones Cell Science Center, Lake Placid, New York 12946. Source: Hatzinger, P B Stevens, J L In-Vitro-Cell-Dev-Biol. 1989 February; 25(2): 205-12 0883-8364
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Somatic nerve stimulation and cholera-induced net fluid secretion in the small intestine of the rat: evidence for an opioid effect. Author(s): Institute of Physiology and Pharmacology, Department of Physiology, University of Goteborg, Sweden.
[email protected] Source: Jonsdottir, I H Sjoqvist, A Lundgren, O Thoren, P J-Auton-Nerv-Syst. 1999 October 8; 78(1): 18-23 0165-1838
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Suppressive versus stimulatory effects of allergen/cholera toxoid (CTB) conjugates depending on the nature of the allergen in a murine model of type I allergy. Author(s): Division of Immunopathology, Institute of General and Experimental Pathology, University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria. Source: Wiedermann, U Jahn Schmid, B Lindblad, M Rask, C Holmgren, J Kraft, D Ebner, C Int-Immunol. 1999 October; 11(10): 1717-24 0953-8178
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The mucosal adjuvant effects of cholera toxin and immune-stimulating complexes differ in their requirement for IL-12, indicating different pathways of action. Author(s): Department of Medical Microbiology and Immunology, University of Goteborg, Sweden. Source: Grdic, D Smith, R Donachie, A Kjerrulf, M Hornquist, E Mowat, A Lycke, N EurJ-Immunol. 1999 June; 29(6): 1774-84 0014-2980
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Ultrastructural changes in the nephron and renal protein cleaving function in suckling rabbits with experimental cholera. Author(s): Laboratory of Pathomorphology and Pathophysiology, Plague Control Institute, Rostov-on-Don, Russia. Source: Bardakhch'yan, E A Kharlanova, N G Lomov, Y M Sayamov, S R Tkacheva, T I Bull-Exp-Biol-Med. 2001 February; 131(2): 186-90 0007-4888
Federal Resources on Nutrition In addition to the IBIDS, the United States Department of Health and Human Services (HHS) and the United States Department of Agriculture (USDA) provide many sources of information on general nutrition and health. Recommended resources include: •
healthfinder®, HHS’s gateway to health information, including diet and nutrition: http://www.healthfinder.gov/scripts/SearchContext.asp?topic=238&page=0
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The United States Department of Agriculture’s Web site dedicated to nutrition information: www.nutrition.gov
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The Food and Drug Administration’s Web site for federal food safety information: www.foodsafety.gov
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The National Action Plan on Overweight and Obesity sponsored by the United States Surgeon General: http://www.surgeongeneral.gov/topics/obesity/
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The Center for Food Safety and Applied Nutrition has an Internet site sponsored by the Food and Drug Administration and the Department of Health and Human Services: http://vm.cfsan.fda.gov/
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Center for Nutrition Policy and Promotion sponsored by the United States Department of Agriculture: http://www.usda.gov/cnpp/
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Food and Nutrition Information Center, National Agricultural Library sponsored by the United States Department of Agriculture: http://www.nal.usda.gov/fnic/
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Food and Nutrition Service sponsored by the United States Department of Agriculture: http://www.fns.usda.gov/fns/
Additional Web Resources A number of additional Web sites offer encyclopedic information covering food and nutrition. The following is a representative sample: •
AOL: http://search.aol.com/cat.adp?id=174&layer=&from=subcats
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Family Village: http://www.familyvillage.wisc.edu/med_nutrition.html
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Google: http://directory.google.com/Top/Health/Nutrition/
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Healthnotes: http://www.healthnotes.com/
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Open Directory Project: http://dmoz.org/Health/Nutrition/
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Yahoo.com: http://dir.yahoo.com/Health/Nutrition/
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WebMDHealth: http://my.webmd.com/nutrition
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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html
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CHAPTER 3. ALTERNATIVE MEDICINE AND CHOLERA Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to cholera. 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 cholera 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 “cholera” (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 cholera: •
“I'm not dog, no!”: cries of resistance against cholera control campaigns. Author(s): Nations MK, Monte CM. Source: Social Science & Medicine (1982). 1996 September; 43(6): 1007-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8888470&dopt=Abstract
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A note on the basis of differentiation of cholera and eltor vibrios. Author(s): Chatterjee SN, Adhikari PC, Das J, Maiti M, Roychaudhuri C, Sur P, Datta MC. Source: Bull Calcutta Sch Trop Med. 1971 October; 19(4): 96-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5005625&dopt=Abstract
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A second guanyl nucleotide-binding site associated with adenylate cyclase. Distinct nucleotides activate adenylate cyclase and permit ADP-ribosylation by cholera toxin. Author(s): Gill DM, Meren R.
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Source: The Journal of Biological Chemistry. 1983 October 10; 258(19): 11908-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6311828&dopt=Abstract •
Absence of concurrent permeability changes of intestinal mucosa in association with cholera toxin-induced secretion. Author(s): Scherer RW, Harper DT, Banwell JG, Hendrix TR. Source: Johns Hopkins Med J. 1974 March; 134(3): 156-67. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4206092&dopt=Abstract
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ADP-ribosylation of thylakoid membrane polypeptides by cholera toxin is correlated with inhibition of thylakoid GTPase activity and protein phosphorylation. Author(s): Millner PA, Robinson PS. Source: Cellular Signalling. 1989; 1(5): 421-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2561911&dopt=Abstract
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Amylase-resistant starch plus oral rehydration solution for cholera. Author(s): Pierce NF, Fontaine O, Sack RB. Source: The New England Journal of Medicine. 2000 June 29; 342(26): 1995-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10877651&dopt=Abstract
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Amylase-resistant starch plus oral rehydration solution for cholera. Author(s): Ramakrishna BS, Venkataraman S, Srinivasan P, Dash P, Young GP, Binder HJ. Source: The New England Journal of Medicine. 2000 February 3; 342(5): 308-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10655529&dopt=Abstract
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An epidemic of Vibrio cholerae el tor Inaba resistant to several antibiotics with a conjugative group C plasmid coding for type II dihydrofolate reductase in Thailand. Author(s): Tabtieng R, Wattanasri S, Echeverria P, Seriwatana J, Bodhidatta L, Chatkaeomorakot A, Rowe B. Source: The American Journal of Tropical Medicine and Hygiene. 1989 December; 41(6): 680-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2641646&dopt=Abstract
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Biochemical characterization of extracellular proteases from Vibrio cholerae. Author(s): Young DB, Broadbent DA. Source: Infection and Immunity. 1982 September; 37(3): 875-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6752027&dopt=Abstract
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Cholera in Mali and popular reactions to its first appearance. Author(s): Imperato PJ.
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Cholera toxin activation of adenylate cyclase. Roles of nucleoside triphosphates and a macromolecular factor in the ADP ribosylation of the GTP-dependent regulatory component. Author(s): Enomoto K, Gill DM. Source: The Journal of Biological Chemistry. 1980 February 25; 255(4): 1252-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6766444&dopt=Abstract
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Cholera toxin and its B subunit do not change cytosolic free calcium concentration. Author(s): Astashkin EI, Surin AM, Mikhna MG, Nikolaeva IS, Lazarev AV, Gukovskaya AS. Source: Cell Calcium. 1990 June-July; 11(6): 419-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2393900&dopt=Abstract
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Cholera toxin as a mucosal adjuvant: III. Antibody responses to nontarget dietary antigens are not increased. Author(s): Nedrud JG, Sigmund N. Source: Reg Immunol. 1990-91; 3(5): 217-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1966580&dopt=Abstract
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Cholera toxin B-gold, a retrograde tracer that can be used in light and electron microscopic immunocytochemical studies. Author(s): Llewellyn-Smith IJ, Minson JB, Wright AP, Hodgson AJ. Source: The Journal of Comparative Neurology. 1990 April 8; 294(2): 179-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1692043&dopt=Abstract
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Cholera toxin, a potent inducer of epidermal hyperplasia but with no tumor promoting activity in mouse skin carcinogenesis. Author(s): Kuroki T, Chida K, Munakata K, Murakami Y. Source: Biochemical and Biophysical Research Communications. 1986 May 29; 137(1): 486-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3013191&dopt=Abstract
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Cholera, the flickering flame. Author(s): Bryceson AD. Source: Proc R Soc Med. 1977 May; 70(5): 363-5. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=327482&dopt=Abstract
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Coca chewing and cholera. Author(s): Feldmeier H, Krantz I.
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Source: Lancet. 1991 June 1; 337(8753): 1342. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1674310&dopt=Abstract •
Comparative study of the effect of cholera toxin and sodium deoxycholate on the paracellular permeability and on net fluid and electrolyte transfer in the rat colon. Author(s): Goerg KJ, Gross M, Nell G, Rummel W, Schulz L. Source: Naunyn-Schmiedeberg's Archives of Pharmacology. 1980 May; 312(1): 91-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6771659&dopt=Abstract
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Composition and immunochemical properties of the cell surface proteins of Vibrio cholerae. Author(s): Kabir S. Source: J Gen Microbiol. 1986 August; 132 ( Pt 8): 2235-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3794649&dopt=Abstract
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Congruences in Chinese and Western medicine from 1830-1911: smallpox, plague and cholera. Author(s): Summers WC. Source: Yale J Biol Med. 1994 January-April; 67(1-2): 23-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7544052&dopt=Abstract
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Corpses and the spread of cholera. Author(s): Sack RB, Siddique AK. Source: Lancet. 1998 November 14; 352(9140): 1570. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9843100&dopt=Abstract
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Cutting edge: the mucosal adjuvant cholera toxin redirects vaccine proteins into olfactory tissues. Author(s): van Ginkel FW, Jackson RJ, Yuki Y, McGhee JR. Source: Journal of Immunology (Baltimore, Md. : 1950). 2000 November 1; 165(9): 477882. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11045998&dopt=Abstract
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Effect of cholera toxin on passive transepithelial transport of 51Crethylenediaminetetraacetic acid and 14C-mannitol in rat jejunum. Author(s): Fihn BM, Sjoqvist A, Jodal M. Source: Acta Physiologica Scandinavica. 2001 February; 171(2): 153-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11350275&dopt=Abstract
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Effect of ethylenediamine tetra-acetic acid (EDTA) on cholera and el tor vibrios. Author(s): Adhikary P, Chatterjee SN.
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Source: Bull Calcutta Sch Trop Med. 1969 January; 17(1): 6-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4990154&dopt=Abstract •
Effect of oral pancreatic enzymes on the course of cholera in protein-deficient vervet monkeys. Author(s): Gyr K, Felsenfeld O, Zimmerli-Ning M. Source: Gastroenterology. 1978 March; 74(3): 511-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=415928&dopt=Abstract
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Effects of Hange-shashin-to on cholera toxin-induced fluid secretion in the small intestine of rats. Author(s): Kase Y, Saitoh K, Yuzurihara M, Ishige A, Komatsu Y. Source: Biological & Pharmaceutical Bulletin. 1998 February; 21(2): 117-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9514604&dopt=Abstract
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Efficacy of oral hyposmolar glucose-based and rice-based oral rehydration salt solutions in the treatment of cholera in adults. Author(s): Bhattacharya MK, Bhattacharya SK, Dutta D, Deb AK, Deb M, Dutta A, Saha Choudhury A, Nair GB, Mahalanabis D. Source: Scandinavian Journal of Gastroenterology. 1998 February; 33(2): 159-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9517526&dopt=Abstract
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Epidemic cholera in Burundi: patterns of transmission in the Great Rift Valley Lake region. Author(s): Birmingham ME, Lee LA, Ndayimirije N, Nkurikiye S, Hersh BS, Wells JG, Deming MS. Source: Lancet. 1997 April 5; 349(9057): 981-5. Erratum In: Lancet 1997 June 14; 349(9067): 1776. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9100624&dopt=Abstract
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Epidemiology of eltor cholera in rural Bangladesh: importance of surface water in transmission. Author(s): Hughes JM, Boyce JM, Levine RJ, Khan M, Aziz KM, Huq MI, Curlin GT. Source: Bulletin of the World Health Organization. 1982; 60(3): 395-404. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6982775&dopt=Abstract
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Evaluation of oral hypo-osmolar glucose-based and rice-based oral rehydration solutions in the treatment of cholera in children. Author(s): Dutta D, Bhattacharya MK, Deb AK, Sarkar D, Chatterjee A, Biswas AB, Chatterjee K, Nair GB, Bhattacharya SK. Source: Acta Paediatrica (Oslo, Norway : 1992). 2000 July; 89(7): 787-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10943958&dopt=Abstract
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Experimental parameters differentially affect the humoral response of the choleratoxin-based murine model of food allergy. Author(s): Kroghsbo S, Christensen HR, Frokiaer H. Source: International Archives of Allergy and Immunology. 2003 August; 131(4): 256-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12915768&dopt=Abstract
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Extinction of Vibrio cholerae in acidic substrata: contaminated cabbage and lettuce treated with lime juice. Author(s): Mata L, Vargas C, Saborio D, Vives M. Source: Rev Biol Trop. 1994 December; 42(3): 487-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7501870&dopt=Abstract
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Extinction of Vibrio cholerae in acidic substrata: contaminated fish marinated with lime juice (ceviche). Author(s): Mata L, Vives M, Vicente G. Source: Rev Biol Trop. 1994 December; 42(3): 479-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7501869&dopt=Abstract
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His chastening rod: cholera epidemics and the Mormons. Author(s): Divett RT. Source: Dialogue. 1979; 12(3): 6-15. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11614400&dopt=Abstract
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His chastening rod: cholera epidemics and the Mormons. Author(s): Divett RT. Source: Dialogue. 1979 Fall; 12(3): 6-15. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11614397&dopt=Abstract
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Identification in traditional herbal medications and confirmation by synthesis of factors that inhibit cholera toxin-induced fluid accumulation. Author(s): Oi H, Matsuura D, Miyake M, Ueno M, Takai I, Yamamoto T, Kubo M, Moss J, Noda M. Source: Proceedings of the National Academy of Sciences of the United States of America. 2002 March 5; 99(5): 3042-6. Epub 2002 February 19. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11854470&dopt=Abstract
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Identification of a CHO cell-elongating factor produced by Vibrio cholerae O1. Author(s): McCardell BA, Kothary MH, Hall RH, Sathyamoorthy V. Source: Microbial Pathogenesis. 2000 July; 29(1): 1-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10873485&dopt=Abstract
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Immigrants, cholera and the Saint John Sisters of Charity, 1854-64. Author(s): Kennedy E.
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Source: Study Sess Can Cathol Hist Assoc. 1977; 44: 25-44. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11615183&dopt=Abstract •
Indicator dilution studies in the small bowel of patients with cholera diarrhea. II. Comparisons of absorbable and “poorly absorbable” substances. Author(s): Brigham KL, Banwell JG, Pierce NF, Mitra RC, Fedson DS, Mondal A. Source: Johns Hopkins Med J. 1970 August; 127(2): 107-18. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4990568&dopt=Abstract
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Internalization of cholera toxin by different endocytic mechanisms. Author(s): Torgersen ML, Skretting G, van Deurs B, Sandvig K. Source: Journal of Cell Science. 2001 October; 114(Pt 20): 3737-47. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11707525&dopt=Abstract
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Intestinal and systemic immune responses to an oral cholera toxoid B subunit wholecell vaccine administered during zinc supplementation. Author(s): Karlsen TH, Sommerfelt H, Klomstad S, Andersen PK, Strand TA, Ulvik RJ, Ahren C, Grewal HM. Source: Infection and Immunity. 2003 July; 71(7): 3909-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12819076&dopt=Abstract
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Is starch the answer for cholera? Author(s): Bhatnagar S. Source: Natl Med J India. 2000 September-October; 13(5): 252-3. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11190054&dopt=Abstract
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Letter: Palmerston on cholera. Author(s): Don G. Source: British Medical Journal. 1973 November 10; 4(5888): 359. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4586040&dopt=Abstract
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Localization of the GM1 ganglioside in the vestibular system using cholera toxin. Author(s): Mancini P, Santi PA. Source: Hearing Research. 1993 January; 64(2): 151-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8432686&dopt=Abstract
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Microtubule assembly in cultivated Greene melanoma cells is stimulated by dibutyryl adenosine 3':5'-cyclic monophosphate or cholera toxin. Author(s): DiPasquale AM, McGuire J, Moellmann G, Wasserman SJ. Source: The Journal of Cell Biology. 1976 December; 71(3): 735-48. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=186462&dopt=Abstract
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Plasma membrane-associated component(s) that confer(s) cholera toxin sensitivity to adenylate cyclase. Author(s): Pinkett MO, Anderson WB. Source: Biochimica Et Biophysica Acta. 1982 February 2; 714(2): 337-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7055618&dopt=Abstract
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Properties of the cholera phage PL 163/10. Author(s): Chanda PK, Chatterjee SN. Source: Acta Virol. 1975 May; 19(3): 197-203. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=239574&dopt=Abstract
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Protection from cholera by adding lime juice to food - results from community and laboratory studies in Guinea-Bissau, West Africa. Author(s): Rodrigues A, Sandstrom A, Ca T, Steinsland H, Jensen H, Aaby P. Source: Tropical Medicine & International Health : Tm & Ih. 2000 June; 5(6): 418-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10929141&dopt=Abstract
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Providence, prayer and cholera: the English general fast of 1832. Author(s): Janet RJ. Source: Hist Mag Protestant Episcop Church. 1982; 51(3): 297-317. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11620183&dopt=Abstract
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Rapid detection of Vibrio cholerae with a new selective enrichment medium and polymerase chain reaction. Author(s): Kida N, Suzuki S, Taguchi F. Source: Kansenshogaku Zasshi. 1995 July; 69(7): 826-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7561254&dopt=Abstract
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Regulation of follicle-stimulating hormone binding to receptors on bovine calf testis membranes by cholera toxin-sensitive guanine nucleotide binding protein. Author(s): Zhang SB, Dattatreyamurty B, Reichert LE Jr. Source: Molecular Endocrinology (Baltimore, Md.). 1988 February; 2(2): 148-58. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2840571&dopt=Abstract
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Religion and medicine: the cholera pamphlets of Oxford, 1832, 1849 and 1854. Author(s): Morris RJ. Source: Medical History. 1975 July; 19(3): 256-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1095865&dopt=Abstract
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Risk factors for cholera infection in the initial phase of an epidemic in GuineaBissau: protection by lime juice. Author(s): Rodrigues A, Brun H, Sandstrom A.
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Source: The American Journal of Tropical Medicine and Hygiene. 1997 November; 57(5): 601-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9392602&dopt=Abstract •
Sensitivity to injected cholera toxin of the sodium efflux in single barnacle muscle fibers. Author(s): Bittar EE, Nwoga J. Source: Comp Biochem Physiol C. 1984; 78(1): 89-98. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6146489&dopt=Abstract
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Socio-cultural aspects of a cholera epidemic in Trengganu, Malaysia. Author(s): Chen PC. Source: Trop Geogr Med. 1971 September; 23(3): 296-303. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5099001&dopt=Abstract
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Somatic nerve stimulation and cholera-induced net fluid secretion in the small intestine of the rat: evidence for an opioid effect. Author(s): Jonsdottir IH, Sjoqvist A, Lundgren O, Thoren P. Source: Journal of the Autonomic Nervous System. 1999 October 8; 78(1): 18-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10589819&dopt=Abstract
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Supplementation with zinc, but not vitamin A, improves seroconversion to vibriocidal antibody in children given an oral cholera vaccine. Author(s): Albert MJ, Qadri F, Wahed MA, Ahmed T, Rahman AS, Ahmed F, Bhuiyan NA, Zaman K, Baqui AH, Clemens JD, Black RE. Source: The Journal of Infectious Diseases. 2003 March 15; 187(6): 909-13. Epub 2003 Mar 06. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12660937&dopt=Abstract
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The “blessed turf”: cholera and popular panic in Ireland, June 1832. Author(s): Connolly SJ. Source: Ir Hist Stud. 1983; 23(9): 214-32. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11614660&dopt=Abstract
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The 1904 epidemic of cholera in Persia: some aspects of Qajar society. Author(s): Burrell RM. Source: Bull Sch Orient Afr Stud. 1988; 51(2): 258-70. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11616738&dopt=Abstract
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The aggregational status of cholera enterotoxin fragment A following biochemical fractionation. Author(s): Knoop FC.
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Source: Biochem Exp Biol. 1978; 14(2): 125-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=753371&dopt=Abstract •
The effect of needle stimulation of acupuncture loci Tienshu (St-25) Chung-Wan (CV12) on the immune response in sensitized mice against experimental cholera. Author(s): Kuan TK, Lee SP, Lin JG, Shen M. Source: The American Journal of Chinese Medicine. 1986; 14(1-2): 73-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3962918&dopt=Abstract
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The effect of stimulating somatic afferents on cholera secretion in the rat small intestine. Author(s): Cassuto J, Larsson P, Yao T, Jodal M, Thoren P, Andersson S, Lundgren O. Source: Acta Physiologica Scandinavica. 1982 December; 116(4): 443-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7171003&dopt=Abstract
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The erratic evolution of cholera therapy: from folklore to science. Author(s): Carpenter CC. Source: Clinical Therapeutics. 1990; 12 Suppl A: 22-7; Discussion 28. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2187609&dopt=Abstract
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The homoeopathic treatment of cholera; a historical study. Author(s): Raj N. Source: Bull Indian Inst Hist Med Hyderabad. 1978; 8(1-4): 39-43. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11613634&dopt=Abstract
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The homoepathic management of cholera in the nineteenty century with special reference to the epidemic in London, 1854. Author(s): Leary B. Source: Med Ges Gesch. 1997; 16: 125-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11623647&dopt=Abstract
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The lysis of cholera and El Tor Vibrios. Author(s): Adhikari PC, Raychaudhuri C, Chatterjee SN. Source: J Gen Microbiol. 1969 November; 59(1): 91-5. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4983467&dopt=Abstract
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The protective activity of tea against infection by Vibrio cholerae O1. Author(s): Toda M, Okubo S, Ikigai H, Suzuki T, Suzuki Y, Shimamura T. Source: The Journal of Applied Bacteriology. 1991 February; 70(2): 109-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2019547&dopt=Abstract
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The search for a better oral rehydration solution for cholera. Author(s): Rabbani GH. Source: The New England Journal of Medicine. 2000 February 3; 342(5): 345-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10655535&dopt=Abstract
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The serological properties of the cell surface proteins of Vibrio cholerae. Author(s): Kabir S. Source: J Gen Microbiol. 1983 July; 129 (Pt 7): 2199-206. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6415227&dopt=Abstract
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The study of intestinal immunity against V. cholerae: purification of V. cholerae El Tor haemagglutinin and the protective role of its antibody in experimental cholera. Author(s): Chaicumpa W, Atthasishtha N. Source: Southeast Asian J Trop Med Public Health. 1979 March; 10(1): 73-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=483020&dopt=Abstract
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Tracer-toxins: cholera toxin B-saporin as a model. Author(s): Llewellyn-Smith IJ, Martin CL, Arnolda LF, Minson JB. Source: Journal of Neuroscience Methods. 2000 November 15; 103(1): 83-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11074098&dopt=Abstract
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Transcellular fluid secretion induced by cholera toxin and vasoactive intestinal polypeptide in the small intestine of the rat. Author(s): Sjoqvist A, Fihn BM. Source: Acta Physiologica Scandinavica. 1993 August; 148(4): 393-401. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8213194&dopt=Abstract
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Unique properties of the follicle-stimulating hormone- and cholera toxin-sensitive adenylyl cyclase of immature granulosa cells. Author(s): Hunzicker-Dunn M, LaBarbera AR. Source: Endocrinology. 1986 January; 118(1): 302-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3000740&dopt=Abstract
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Usefulness of a medicinal plant (Bragantia wallichi) in experimental cholera. Author(s): Panse MV, Nayak KP. Source: The Indian Journal of Medical Research. 1971 August; 59(8): 1190-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4943617&dopt=Abstract
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Vibrio cholerae soluble hemagglutinin/protease is a metalloenzyme. Author(s): Booth BA, Boesman-Finkelstein M, Finkelstein RA.
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Why cholera still takes lives in rural Bangladesh. Study of an epidemic. Author(s): Siddique AK, Akram K, Islam Q. Source: Trop Doct. 1988 January; 18(1): 40-2. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3341090&dopt=Abstract
Additional Web Resources A number of additional Web sites offer encyclopedic information covering CAM and related topics. The following is a representative sample: •
Alternative Medicine Foundation, Inc.: http://www.herbmed.org/
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AOL: http://search.aol.com/cat.adp?id=169&layer=&from=subcats
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Chinese Medicine: http://www.newcenturynutrition.com/
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drkoop.com: http://www.drkoop.com/InteractiveMedicine/IndexC.html
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Family Village: http://www.familyvillage.wisc.edu/med_altn.htm
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Google: http://directory.google.com/Top/Health/Alternative/
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Healthnotes: http://www.healthnotes.com/
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MedWebPlus: http://medwebplus.com/subject/Alternative_and_Complementary_Medicine
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Open Directory Project: http://dmoz.org/Health/Alternative/
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HealthGate: http://www.tnp.com/
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WebMDHealth: http://my.webmd.com/drugs_and_herbs
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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html
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Yahoo.com: http://dir.yahoo.com/Health/Alternative_Medicine/
The following is a specific Web list relating to cholera; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: •
General Overview Diarrhea Source: Healthnotes, Inc.; www.healthnotes.com Food Poisoning Source: Integrative Medicine Communications; www.drkoop.com
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Herbs and Supplements Barberry Alternative names: Berberis vulgaris Source: Healthnotes, Inc.; www.healthnotes.com Berberis Alternative names: Barberry; Berberis sp. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Doxycycline Source: Healthnotes, Inc.; www.healthnotes.com Eleuthero Alternative names: Siberian Ginseng, Eleuthero; Acanthopanax/Eleutherococcus senticosus Rupr. & Maxim. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Ginger Source: Prima Communications, Inc.www.personalhealthzone.com Goldenseal Alternative names: Hydrastis canadensis Source: Integrative Medicine Communications; www.drkoop.com Hydrastis Canadensis Source: Integrative Medicine Communications; www.drkoop.com L. Acidophilus Source: Integrative Medicine Communications; www.drkoop.com Lactobacillus Acidophilus Source: Integrative Medicine Communications; www.drkoop.com Oregon Grape Alternative names: Berberis aquifolium Source: Healthnotes, Inc.; www.healthnotes.com Prickly Ash Alternative names: Zanthoxylum clava-herculis, Zanthoxylum americanum Source: Healthnotes, Inc.; www.healthnotes.com Sanguinaria Alternative names: Bloodroot; Sanguinaria canadensis L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Terminalia Alternative names: Myrobalans; Terminalia arjuna Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Tetracycline Source: Healthnotes, Inc.; www.healthnotes.com
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Zingiber Alternative names: Ginger; Zingiber officinale Roscoe Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org
General References A good place to find general background information on CAM is the National Library of Medicine. It has prepared within the MEDLINEplus system an information topic page dedicated to complementary and alternative medicine. To access this page, go to the MEDLINEplus site at http://www.nlm.nih.gov/medlineplus/alternativemedicine.html. This Web site provides a general overview of various topics and can lead to a number of general sources.
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CHAPTER 4. DISSERTATIONS ON CHOLERA Overview In this chapter, we will give you a bibliography on recent dissertations relating to cholera. 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 “cholera” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on cholera, we have not necessarily excluded non-medical dissertations in this bibliography.
Dissertations on Cholera 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 cholera. 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: •
Cholera in the Large Towns of the West and East Ridings, 1848-1893 (west Riding, East Riding, England, Yorkshire) by Sigsworth, Michael, Phd from Council for National Academic Awards (united Kingdom), 1991, 420 pages http://wwwlib.umi.com/dissertations/fullcit/DX98080
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Communicating Cholera: News and Health Information for Andean Peasants (quichua, Ecuador) by Mullen, Joel Pink, Phd from The University of Utah, 1996, 226 pages http://wwwlib.umi.com/dissertations/fullcit/9627130
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Disease, Public Health and Urban Social Relations: Perceptions of Cholera and the Paris Environment, 1830-1850 by Kudlick, Catherine Jean, Phd from University of California, Berkeley, 1988, 279 pages http://wwwlib.umi.com/dissertations/fullcit/8902168
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Ecology and Pathogenesis of Fowl Cholera in Turkeys by Pabs-garnon, Leonard F; Advdeg from University of Guelph (canada), 1970 http://wwwlib.umi.com/dissertations/fullcit/NK07177
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Epidemic Proportions: Cholera in the British West Indies, 1850-1855 by Higgins, Brian Thomas, Phd from Bowling Green State University, 1993, 362 pages http://wwwlib.umi.com/dissertations/fullcit/9334554
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From Yellow Fever to Cholera: a Study of French Government Policy, Medical Professionalism and Popular Movements in the Epidemic Crises of the Restoration and the July Monarchy by Sussman, George David, Phd from Yale University, 1971, 388 pages http://wwwlib.umi.com/dissertations/fullcit/7131018
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Identification and Characterization of Essential Genes in Vibrio Cholerae by Judson, Nicholas Matthew Freeland; Phd from Harvard University, 2002, 207 pages http://wwwlib.umi.com/dissertations/fullcit/3051200
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International Cooperation and Pandemic Diseases: Regimes and the Role of Epistemic Communities in Combating Cholera, Smallpox and Aids (immune Deficiency) by Mcfadden, David Fancher, Phd from The Claremont Graduate University, 1995, 273 pages http://wwwlib.umi.com/dissertations/fullcit/9612315
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International Health Statecraft: the Case of Peru's 1991 Cholera Epidemic (health Diplomacy Initiative) by Panisset, Ulysses B., Phd from The Johns Hopkins University, 1996, 81 pages http://wwwlib.umi.com/dissertations/fullcit/9629488
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Organizing for an Epidemic: Cholera in Guatemala by Alvarado, Felix Manuel, Phd from State University of New York at Albany, 1995, 222 pages http://wwwlib.umi.com/dissertations/fullcit/9540343
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Russian Apocalypse, 1891-1917: Popular Perceptions of Events from the Year of Famine and Cholera to the Fall of the Tsar by Heretz, Leonid, Phd from Harvard University, 1993, 437 pages http://wwwlib.umi.com/dissertations/fullcit/9412350
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Structural and Functional Analysis of the Extracellular Transport Signal of Chitinase a of Vibrio Cholerae by Folster, Jason Patrick; Phd from State University of New York at Buffalo, 2003, 156 pages http://wwwlib.umi.com/dissertations/fullcit/3076479
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The Analysis of Gene Expression Alterations of Human Lymphoid Cells in Response to Cholera Toxin by Royaee, Atabak Reza; Phd from Georgetown University, 2002, 266 pages http://wwwlib.umi.com/dissertations/fullcit/3080083
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The Enigma of Hog Cholera: Controversies, Cause, and Control, 1833-1917 by Tang, Ho Yin, Phd from University of Minnesota, 1986, 192 pages http://wwwlib.umi.com/dissertations/fullcit/8627050
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The Prussian Administrative Response to the First Cholera Epidemic in Prussia in 1831 (epidemic) by Ross, Richard Sadler, Phd from Boston College, 1991, 296 pages http://wwwlib.umi.com/dissertations/fullcit/9211806
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The Upper Canadian Legal Response to the Cholera Epidemics of 1832 and 1834 (ontario) by Atkinson, Joseph Logan; Lld from University of Ottawa (canada), 2000, 418 pages http://wwwlib.umi.com/dissertations/fullcit/NQ58262
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The Viable but Non-culturable State in Vibrio Cholerae O1 and O139 by Chaiyanan, Sitthipan; Phd from University of Maryland College Park, 2002, 181 pages http://wwwlib.umi.com/dissertations/fullcit/3078210
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The Western Cholera Trail: Studies in the Urban Response to Epidemic Disease in the Trans-mississippi West, 1848-1850 (louisiana, Missouri, California) by Roth, Mitchel Philip, Phd from University of California, Santa Barbara, 1993, 470 pages http://wwwlib.umi.com/dissertations/fullcit/9419105
Keeping Current Ask the medical librarian at your library if it has full and unlimited access to the ProQuest Digital Dissertations database. From the library, you should be able to do more complete searches via http://wwwlib.umi.com/dissertations.
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CHAPTER 5. PATENTS ON CHOLERA Overview Patents can be physical innovations (e.g. chemicals, pharmaceuticals, medical equipment) or processes (e.g. treatments or diagnostic procedures). The United States Patent and Trademark Office defines a patent as a grant of a property right to the inventor, issued by the Patent and Trademark Office.8 Patents, therefore, are intellectual property. For the United States, the term of a new patent is 20 years from the date when the patent application was filed. If the inventor wishes to receive economic benefits, it is likely that the invention will become commercially available within 20 years of the initial filing. It is important to understand, therefore, that an inventor’s patent does not indicate that a product or service is or will be commercially available. The patent implies only that the inventor has “the right to exclude others from making, using, offering for sale, or selling” the invention in the United States. While this relates to U.S. patents, similar rules govern foreign patents. In this chapter, we show you how to locate information on patents and their inventors. If you find a patent that is particularly interesting to you, contact the inventor or the assignee for further information. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical patents that use the generic term “cholera” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on cholera, we have not necessarily excluded non-medical patents in this bibliography.
Patents on Cholera By performing a patent search focusing on cholera, you can obtain information such as the title of the invention, the names of the inventor(s), the assignee(s) or the company that owns or controls the patent, a short abstract that summarizes the patent, and a few excerpts from the description of the patent. The abstract of a patent tends to be more technical in nature, while the description is often written for the public. Full patent descriptions contain much more information than is presented here (e.g. claims, references, figures, diagrams, etc.). We
8Adapted
from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.
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will tell you how to obtain this information later in the chapter. The following is an example of the type of information that you can expect to obtain from a patent search on cholera: •
1-galactose derivatives Inventor(s): Hindsgaul; Ole (Edmonton, CA) Assignee(s): Synsorb Biotech, Inc. (Calgary, CA) Patent Number: 5,932,554 Date filed: November 14, 1997 Abstract: Disclosed are novel 1-galactose derivatives which inhibit binding of toxins, such as heat-labile enterotoxin or cholera toxin, to their receptors either in vitro or in vivo. Additionally, disclosed are compounds which inhibit binding of enterovirulent organisms (e.g., bacteria, virus, fungi, and the like), such as Vibrio cholerae and enterotoxigenic strains of Escherichia coli, to their cell surface receptors. Excerpt(s): This invention relates to novel 1-galactose derivatives which inhibit binding of toxins, such as heat-labile enterotoxin (LT) or cholera toxin (CT), to their receptors either in vitro or in vivo. Additionally, the compounds of this invention inhibit binding of enterovirulent organisms (e.g., bacteria, virus, fungi, and the like), such as Vibrio cholerae and enterotoxigenic strains of Escherichia coli, to their cell surface receptors.sup.1 Spangler, B. D., "Structure and Function of Cholera Toxin and Related Escherichia coli Heat-Labile Enterotoxin", Microbiological Reviews, 56(4):622-647 (1992).sup.2 Hol, W. G. J., et al., "Structure and Function of E. coli Heat-Labile Enterotoxin and Cholera Toxin B Pentamer", Bacterial Toxins and Virulence Factors in Disease, Ed. by J. Moss et al., Marcel Dekker, Inc. (1995). Web site: http://www.delphion.com/details?pn=US05932554__
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1-thiogalactose derivatives Inventor(s): Hindsgaul; Ole (Edmonton, CA) Assignee(s): Synsorb Biotech, Inc. (Calgary, CA) Patent Number: 5,968,907 Date filed: November 14, 1997 Abstract: Disclosed are novel 1-thiogalactose derivatives which inhibit binding of toxins, such as heat-labile enterotoxin or cholera toxin, to their receptors either in vitro or in vivo. Additionally, disclosed are compounds which inhibit binding of organisms (e.g., bacteria, virus, fungi, and the like), such as Vibrio cholerae and enterotoxigenic strains of Escherichia coli, to their cell surface receptors. Excerpt(s): This invention relates to novel 1-thiogalactose derivatives which inhibit binding of toxins, such as heat-labile enterotoxin (LT) or cholera toxin (CT), to their receptors either in vitro or in vivo. Additionally, the compounds of this invention inhibit binding of organisms (e.g., bacteria, virus, fungi, and the like), such as Vibrio cholerae and enterotoxigenic strains of Escherichia coli, to their cell surface receptors. 1 Spangler, B. D., "Structure and Function of Cholera Toxin and Related Escherichia coli Heat-Labile Enterotoxin", Microbiological Reviews, 56(4): 622-647 (1992). 2 Hol, W. G. J., et al., "Structure and Function of E. coli Heat-Labile Enterotoxin and Cholera Toxin B
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Pentamer", Bacterial Toxins and Virulence Factors in Disease, Ed. by J. Moss et al., Marcel Dekker, Inc. (1995). Web site: http://www.delphion.com/details?pn=US05968907__ •
Deletion mutants of cholera vaccines expressing heterologous antigens Inventor(s): Mekalanos; John J. (Cambridge, MA) Assignee(s): President and Fellows of Harvard College (Cambridge, MA) Patent Number: 5,874,088 Date filed: January 5, 1995 Abstract: The invention features a nontoxigenic genetically stable mutant strain of V. cholerae which lacks any functional attRS1 sequences is useful as a live, oral vaccine for inducing immunological protection against cholera and a method for making same. The invention also features a killed, oral cholera vaccine comprising at least a first and a second V. cholerae strain, wherein at least one of the strains is a different serotype, and the vaccine also contains cholera toxin B subunit, produced by at least one of the serotypes. Excerpt(s): The field of invention is Vibrio cholerae vaccines. After more than 100 years of research on cholera, there remains a need for an effective cholera vaccine. There have been six pandemics of this disease caused by strains of V. cholera belonging to the "Classical" biotype. The etiological agents of the current (seventh) pandemic belong to the "El Tor" biotype (Finkelstein, Crit. Rev. Microbiol 2:553-623, 1973, Wachsmuth et al., The Lancet 337:1097-1098, 1991). Recently the seventh pandemic has extended to a new locale, that of South America. Beginning in January of 1991, an epidemic of cholera resulted in greater than 250,000 cases and over 2,000 deaths in Peru, Ecuador, Columbia, and Chile. Before this epidemic it was estimated that over 200,000 cases of cholera occurred per year mainly in India, Bangladesh, Africa and Western Asia (Tacket et al., Cholera Vaccines. In Vaccines: New Approaches to Immunological Problems, Ellis, R. W., editor, Butterworth-Heinemann, Boston, 1992). In November of 1992, an antigenically distinct, non-01 form of V. cholerae emerged in India and Bangladesh and within eight months caused an estimated 500,000 cases and 6,000 deaths. The pandemic potential of this new strain, designated serogroup 0139 synonym "Bengal", seems assured and is a new cause of concern throughout the developing world. These recent experiences underline the need for effective cholera vaccines against disease due to both El Tor 01 and Bengal 0139 serotypes of V. cholerae. Because natural infection by and recovery from cholera induces immunity lasting at least 3 years (Tacket et al., Supra; Levine et al., J. Infect. Dis. 143:818-820, 1981; Cash et al., J. Infect. Dis. 130:325-333, 1974), much effort has been made to produce live, attenuated cholera vaccines that when administered orally would mimic the disease in its immunization properties but would not cause adverse symptoms or reactions in the immunized individual (i.e., display low reactogenicity). Vaccines of this type involve deletion mutations that inactivate the gene encoding the A subunit of cholera toxin, a protein which is responsible for most of the diarrhea seen in this disease (Mekalanos et al., Proc. Natl. Acad. Sci. U.S.A. 79:151-155, 1982; Mekalanos et al., Nature 306:551-557, 1983; Kaper et al., Nature 308:655-658, 1984; Kaper et al., Biotechnology 2:345, 1984; Pierce et al., Infect. Immun. 55:477-481, 1987; Taylor et al., Vaccine 6:151-154, 1988; Levine et al., Infn. Immun. 56:161-167, 1988; Herrington et al. J. Exper. Med. 168:1487-1492, 1988; Levine et al., Lancet ii:467-470, 1988; Kaper et al., Res. Microbiol. 141:901-906, 1990; Pearson et al., Res. Microbiol. 141:893-899, 1990). See also Mekalanos, U.S. Pat. Nos. 5,098,998 and 4,882,278, and Kaper et al., U.S.
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Pat. No. 4,935,364, hereby incorporated by reference. While both oral, killed whole cell vaccines and several live, attenuated cholera vaccine have been developed, the most promising of these provide little protection against the El Tor biotype of V. cholerae and probably no protection against the 0139 serotype. The major issues associated with cholera vaccines are safety, stability and their degree of antigenicity. Web site: http://www.delphion.com/details?pn=US05874088__ •
Heterologous antigens in live cell V. cholerae strains Inventor(s): Calderwood; Stephen B. (Wellesley, MA), Ryan; Edward T. (Quincy, MA) Assignee(s): The General Hospital Corporation (Boston, MA) Patent Number: 6,036,953 Date filed: November 25, 1997 Abstract: Disclosed is a V. cholerae cell containing a DNA encoding a fusion polypeptide that includes a heterologous antigenic polypeptide sequence such as a portion of C. difficile toxin A. The fusion polypeptide also includes one of the following: (i) an E. coli hemolysin A subunit (wich is coexpressed with sequences encoding hemolysin B and D subunits); (ii) a secretion signal sequence and cholera toxin A2 subunit (which is coexpressed with cholera toxin B subunit); or (iii) cholera toxin B subunit. Excerpt(s): The field of the invention is genetically engineered live V. cholerae vaccine strains. Microbial pathogens that infect mammals via mucosal surfaces have caused significant morbidity and mortality in the developing world. Of particular concern are pathogens that infect the gastrointestinal, respiratory, and genitourinary systems. Many proposed, conventional systemic immunization methods have been ineffective in protecting against infections that occur via such mucosal surfaces. The immune system is thought to be functionally separated into systemic and mucosal immune compartments (Czerkinsky et al., Cellular and Molecular, 1994, 1:37-44). The mucosal immune system represents the largest immunological organ in the body. Luminal antigens are processed via M (microfold) cells, which are specialized epithelial cells found in the gastrointestinal tract and are involved in the induction of a mucosal immune response (Neutra et al., Johnson LR, ed. Physiology of the Gastrointestinal Tract, Third Edition, 1994, 685-708). Antigen processing and presentation are followed by proliferation and differentiation of IgA-committed, antigen-specific B lymphocytes that circulate via the bloodstream and populate the lamina propria of the upper respiratory, intestinal, and genitourinary tracts, as well as the salivary and mammary glands. In these effector sites, plasma cells produce antigen-specific IgA, which is then secreted across epithelial cells, acquiring secretory component in the process (Neutra et al., Johnson LR, ed., Physiology of the Gastrointestinal Tract, Third Edition, 1994, 685708). Secretory component enhances resistance of these antibodies to proteolysis. The circulation of antigen-specific cells from one inductive site to multiple effector sites has led to the concept of a common mucosal immune system. Web site: http://www.delphion.com/details?pn=US06036953__
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Hog cholera virus vaccine and diagnostic Inventor(s): Meyers; Gregor (Stuttgart, DE), Rumenapf; Tillmann (Pasadena, CA), Thiel; Heinz-Jurgen (Tubingen, DE) Assignee(s): Akzo Nobel N.V. (Arnhem, NL) Patent Number: 5,811,103 Date filed: June 12, 1997 Abstract: The present invention is concerned with a hog cholera virus vaccine comprising a polypeptide characteristic of hog cholera virus. Vector vaccines capable to express a nucleic acid sequence encoding such a polypeptide also form part of the present invention. Said polypeptide and nucleic acid sequence can also be used for the detection of hog cholera virus infection. Excerpt(s): The present invention is concerned with a nucleic acid sequence, a recombinant nucleic acid molecule comprising such a nucleic acid sequence, a recombinant expression system comprising such a recombinant nucleic acid molecule, a polypeptide characteristic of the hog cholera virus, a vaccine comprising such a polypeptide or recombinant expression system as well as a method for the preparation of such vaccines. Classical swine fever or hog cholera (HC) represents an economically important disease of swine in many countries worldwide. Under natural conditions, the pig is the only animal known to be susceptible to HC. Hog cholera is a highly contagious disease which causes degeneration in the walls of capillaries, resulting in hemorrhages and necrosis of the internal organs. In the first instance hog cholera is characterized by fever, anorexia, vomiting and diarrhea which can be followed by a chronic course of the disease characterized by infertility, abortion and weak offsprings of sows. However, nearly all pigs die within 2 weeks after the first symptoms appear. The causative agent, the hog cholera virus (HCV) has been shown to be structurally and serologically related to bovine viral diarrhea virus (BVDV) of cattle and to border disease virus (BDV) of sheep. These viruses are grouped together into the genus pestivirus within the family togaviridae. The nature of the genetic material of pestiviruses has long been known to be RNA, i.e. positive-strand RNA which lacks significant polyadenylation. The HCV probably comprises 3-5 structural proteins of which two are possibly glycosylated. The number of non-structural viral proteins is unknown. Web site: http://www.delphion.com/details?pn=US05811103__
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Human breast epithelial cell type with stem cell and luminal epithelial cell characteristics Inventor(s): Chang; Chia-Cheng (Okemos, MI), Trosko; James E. (Okemos, MI) Assignee(s): Michigan State University (East Lansing, MI) Patent Number: 5,814,511 Date filed: November 16, 1995 Abstract: Described is a substantially purified human breast epithelial cell (Type I HBEC) displaying the following characteristics: variable cell shape; smooth cell colony boundary; deficiency in gap junctional intercellular communication; positive expression of epithelial membrane antigen and keratin 18; negative expression of keratin 14,.alpha.6 integrin and gap junction genes for connexins (Cx26, Cx32 and Cx43); growth promotion
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by fetal bovine serum; induction by cholera toxin to differentiate into Type II HBEC (prior art); and acquisition anchorage independent growth by Semian virus 40 transfection. Also described is a method of obtaining the above-identified epithelial cells comprising the steps of: a) development of a mixture of human breast epithelial cells from reduction mammoplasty tissues using the MSU-1 medium; b) eliminating stromal fibroblasts by a trypsin (0.002%) and ethylenediamine tetraacetic acid (0.02%) solution; c) separating Type I HBEC from Type II HBEC which attach on culture dishes earlier by collecting Type I HBEC that remain in suspension after trypsinization and prolonged incubation; d) the continuing culture of these cells in MSU-1 medium supplemented with fetal bovine serum, which inhibits the growth of Type II HBEC while promoting the growth of Type I HBEC, gives rise to Type I HBEC. Described also is a new defined medium (the MSU-1 medium) which supports the growth of both Type I and Type II human breast epithelial cells. Excerpt(s): The invention is directed toward epithelial cells and, in particular, human breast epithelial cells having stem cell characteristics. The human breast contains a variety of cell types including luminal and basal epithelial cells that form the ductal tree. These two types of epithelial cells are immunocytochemically distinguishable in tissue sections (1) or in enzymatically dissociated single-cell suspensions (2). Antigenic markers that can distinguish these two cell types would include the epithelial membrane antigen (EMA) and keratin 18 which are predominantly expressed in luminal epithelial cells (1,2) and keratin 14 and.alpha.6 integrin which are specifically expressed in basal epithelial cells (1,3). When the expression of these antigenic markers were examined in primary human breast carcinomas, it was found that the carcinoma cells were similar to the luminal epithelial cells in their expression of antigens (1,3,4). This evidence can be interpreted as indicating that breast carcinomas are primarily derived from luminal epithelial cells or their precursor cells with similar phenotypes. Most normal human breast epithelial cell cultures were derived either from lactational fluids, which contained cells primarily of luminal origin, or were derived from reduction mammoplasty. Cells from reduction mammoplasty, cultured in the commonly used MCDB 170 (Department of Molecular, Cellular and Developmental Biology, University of Colorado) (5) or DFCI-1 (Dana-Farber Cancer Institute) (6) media, exhibit predominantly basal epithelial cell phenotypes (1,4). Web site: http://www.delphion.com/details?pn=US05814511__ •
Hybrid molecules between heat-labile enterotoxin and cholera toxin B subunits Inventor(s): Holmgren; Jan (Korvettgatan 1 D, VastraFrolunda, SE), Lebens; Michael R. (S-413 22 Drive Belfrages Vag 20, Goborg, SE) Assignee(s): none reported Patent Number: 6,019,973 Date filed: January 5, 1998 Abstract: Hybrid molecules between heat-labile enterotoxin B subunit (LTB) and cholera toxin B subunit (CTB) are disclosed. Such a hybrid molecule comprises an amino-acid sequence which is composed of the amino-acid sequence of mature CTB in which such amino-acid residues are substituted with the corresponding amino-acid residues of mature LTB which impart LTB-specific epitope characteristics to said immunogenic mature CTB, or vice versa. In addition, a structural gene coding for such a hybrid molecule, a plasmid containing such a structural gene, and an immunogenic protein comprising such a hybrid molecule and optionally an immunoreactive amino-acid
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sequence of a prokaryotic or eukaryotic cell or a virus, are disclosed. Disclosed is also a vaccine, e.g. against enterotoxin-induced illness, comprising such an immunogenic protein, and a method of preventing or treating enterotoxin-induced illness in an individual. Excerpt(s): This application is filed as a.sctn. 371 application of PCT/SE96/00570, filed May 2, 1996 with a priority claim to national application 9501682-0, filed May 5, 1995 in Sweden. The present invention relates to hybrid molecules between heat-labile enterotoxin B subunit (LTB) and cholera toxin B subunit (CTB). Immunogenic proteins comprising such hybrid molecules, optionally fused to immunoreactive amino-acid sequences of or from cells or viruses, may be used as immunogenic components in vaccines, e.g. in a broad spectrum vaccine against enterotoxin-induced diarrhoea. Cholera remains an important cause of illness in many developing countries and has been estimated to result in more than 200,000 deaths each year. Infection with enterotoxigenic E. coli (ETEC) is the most frequent cause of diarrhoea in the developing world and amongst travellers; it is responsible for more than one billion diarrhoeal episodes and one million deaths annually. Infection with ETEC is also an important cause of disease in animals For both cholera and ETEC infections there is a great need for effective vaccines. Web site: http://www.delphion.com/details?pn=US06019973__ •
Hydrophilic composition containing protease produced by Vibrio Inventor(s): Durham; Donald Richard (Gaithersburg, MD), Fortney; Donald Zane (Westminster, MD), Yang; Kang (Chalfont, PA) Assignee(s): Conn. / Teva Pharmaceuticals USA, Inc. (Kulpsville, PA), W. R. Grace & Co. (New York, NY) Patent Number: 6,017,531 Date filed: June 2, 1997 Abstract: Hydrophillic compositions and methods of use are provided for debriding and wound healing applications. The compositions contain certain proteases produced by microorganisms of the genus Vibrio. Excerpt(s): The present invention relates to hydrophilic pharmaceutical compositions containing enzymes, particularly proteases. The composition is capable of maintaining enzyme activity at room temperature storage. More specifically, the present invention relates to hydrophilic compositions containing a protease produced by microorganisms of the genus Vibrio. The compositions are useful for debridement and/or wound healing. The present invention further relates to the usage of these pharmaceutical compositions for debridement and/or as wound healing agents. The healing of wounds is a complex process which is often further complicated by the presence of non-viable, necrotic tissue in the wound area. Debridement is the process of removing the nonviable tissue from a wound to prevent infection and facilitate healing. Considerable efforts have been made to discover materials capable of distinguishing between viable and non-viable tissue. The discovery of materials which would digest devitalized tissue while not attacking viable tissue would make it possible to remove the devitalized tissue without surgery. It would be a beneficial therapeutic agent in virtually all disease processes or injuries where topically devitalized tissue needs to be removed from the wound area such as burns, cutaneous ulcers, pressure necroses, incisional, traumatic and pyogenic wounds, and ulcers secondary to peripheral vascular disease.
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Web site: http://www.delphion.com/details?pn=US06017531__ •
Immunogenic detoxified mutants of cholera toxin and of the toxin LT, their preparation and their use for the preparation of vaccines Inventor(s): Domenighini; Mario (Quercegrossa, IT), Hol; Wim (Seattle, WA), Pizza; Mariagrazia (Siena, IT), Rappuoli; Rino (Quercegrossa, IT) Assignee(s): Biocine S.p.A. (Siena, IT) Patent Number: 6,149,919 Date filed: March 25, 1997 Abstract: An immunogenic detoxified protein comprising the amino acid sequence of subunit A of cholera toxin (CT-A) or subunit A of an Escherichia coli heat labile toxin (LT-A) or a fragment thereof wherein one or more amino acids at, or in positions corresponding to Val-53, Ser-63, Val-97, Tyr-104 or Pro-106 are replaced with another amino acid or deleted. Examples of specific replacements include Val-53-Asp, Val-53Glu, Val-53-Tyr, Ser-63-Lys, Val-97-Lys, Val-97-Tyr, Tyr-104-Lys, Tyr-104-Asp, Tyr-104Ser, Pro-106-Ser. The immunogenic detoxified protein is useful as vaccine for Vibrio cholerae or an enterotoxigenic strain of Escherichia coli and is produced by recombinant DNA means by site-directed mutagenesis. Excerpt(s): The present invention relates to immunogenic detoxified proteins of cholera toxins (CT), or of heat labile toxins (LT) produced by the enterotoxigenic strains of Escherichia coli (E. coli) having substitutions at one or more of amino acids Val-53, Ser63, Val-97, Tyr-104 or Pro-106 and to their use in vaccines which are useful for the prevention or treatment of cholera or enterotoxigenic E. coli infections. The proteins can be suitably produced using recombinant DNA techniques by site-directed mutagenesis of DNA encoding the wild type toxins. Cholera is a contagious disease widely distributed in the world, in particular in the Third World, where, in certain areas, it is endemic. The serious disorders which develop in the intestinal system prove fatal in a high percentage of the recorded cases of the disease. The etiological agent of cholera is the Gram-negative microorganism Vibrio cholerae (V. cholerae). This colonises the intestinal tract of individuals who have come into contact with it through ingestion of contaminated food or water, and multiplies to very high concentrations. The principal symptom is severe diarrhoea as a result of which the patient can lose as much as 10-15 liters of liquids per day via the faeces. As a result of the severe dehydration and loss of electrolytes, the patient does not withstand the infection in 50-60% of cases, and dies. The diarrhoea caused by V. cholerae is due to the secretion of cholera toxin, CT, which acts by stimulating the activity of the adenylate cyclase enzyme so as to induce disturbances at cell level. Web site: http://www.delphion.com/details?pn=US06149919__
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Intestinal function using leptin Inventor(s): O'Connor; Darlise (Newark, DE), Schwartz; Marshall (Bryn Mawr, PA) Assignee(s): The Nemours Foundation (Wilmington, DE) Patent Number: 6,630,444 Date filed: October 23, 2000
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Abstract: A method for treating a patient that has inadequate intestinal function is described. Administering leptin to a subject increases the intestinal function beyond that for a normal intestine and beyond that of a normal adaptive response. Further, administering leptin to a subject results in an increase in amino acid absorption, sugar absorption, mucosal mass, transport mechanisms for amino acids, or transport mechanisms for sugars. The method may be used for treating subjects have conditions such as short bowel syndrome, inflammation of the bowel, necrotizing enterocolitis, intestinal atresia, midgut volvulus, severe acute gastroenteritis, chronic gastroenteritis, cholera, chronic infections of the bowel, immunologic disorders affecting the small intestine, and inflammatory bowel disease such as, chronic ulcerative colitis and Crohn's Disease. Excerpt(s): The present invention relates broadly to enhancing the functions of the small intestine and the treatment of inflammatory bowel diseases in a patient by the administration of leptin. Short bowel syndrome ("SBS") is a devastating clinical disorder resulting from massive small bowel resection. SBS affects many infants and children and threatens normal growth and development. The remnant intestine naturally adapts to resection, however, this adaptation process is often inadequate to meet the patients fluid and nutritional goals. There is no effective treatment and current management includes total parenteral nutrition ("TPN"), which itself is a source of significant morbidity and mortality. Accordingly, there is a need for an alternative method of management for short bowel syndrome. Other disorders of the small intestine can render the bowel nonfunctional for a prolonged period of time such as severe infection and inflammatory bowel disease. It is an object of the present invention to provide an alternative method for management for short bowel syndrome and other disorders of the intestine. Web site: http://www.delphion.com/details?pn=US06630444__ •
Ionene polymers as microbicides Inventor(s): Hollis; C. George (Germantown, TN), Jaquess; Percy A. (Tigrett, TN) Assignee(s): Buckman Laboratories International, Inc. (Memphis, TN) Patent Number: 5,681,862 Date filed: March 5, 1993 Abstract: A method for controlling the growth of at least one microorganism in an aqueous system susceptible to the growth of said microorganism and in recognized need of said control comprising the step of adding to said aqueous system an ionene polymer in an amount effective to inhibit the growth at least one microorganism selected from Campylobacter spp., Mycobacterium spp., Shigella spp., ribrio spp., Yersinia spp., Entamoeba spp., and poliovirus. The aqueous system is selected from potable water, sewage, and other nonmarine surface water. Methods for controlling the spread of the diseases cholera and polio are also disclosed. Excerpt(s): This invention relates to methods for the microbicidal control of microorganisms in aqueous systems by treating the system with an effective amount of an ionene polymer. Particularly, it relates to methods for controlling the growth of species (ssp.) within the bacterial genera Campylobacter, Shigella, Vibrio and Yersinia, and protozoa within the genus Entamoeba in aqueous systems such as potable water, sewage and other nonmarine surface water. This invention also relates to methods for controlling the growth of the bacteria Mycobacterium boris, Salmonella typhi, and the fungus Candida albicans in these nonmarine aqueous systems. This invention further
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relates to methods for controlling poliovirus in potable water, sewage, and other nonmarine surface water. Methods for controlling the spread of the diseases cholera and polio are also disclosed. Cholera is endemic in regions of India and Bangladesh, and has spread to other regions of the globe in a series of pandemics. Recent cholera pandemics from the 1960s through the 1980s have involved Africa, the Philippines, Western Europe and Southeast Asia. In the United States, the number of cases of cholera has increased during the past fifteen years. Zinsser Microbiology 566-73 (W. K. Joklik, H. P. Willett, D. B. Amos, C. A. Wilfert, eds., 20th ed., 1992). Cholera struck recently in Latin America, where the epidemic has affected more than half a million people, resulting in the death of tens of thousands of Latin Americans. The cholera epidemic that currently plagues Latin America began in Peru in 1990, and has spread at least as far as Brazil, Guatemala, Mexico, and Nicaragua. The Pan American Health Organization acknowledged that "once cholera arrives on a continent, it's likely to remain endemic until we make vast improvements in water and sanitation." Christine Tierney, Central America Suffers Summertime Cholera Surge, Reuter Newswire, Sep. 4, 1992. Vibrio cholerae is the species of the bacterial genus Vibrio, which causes epidemic cholera, and is among the leading causes of other gastrointestinal infections. V. parahaemolyticus is another Vibrio that causes gastrointestinal infection, and is prevalent in the United States. Other Vibrio ssp. may cause human illnesses that include diarrhea, bloody diarrhea, vomiting, cramps, sepsis and soft tissue infections. For example, V. vulnificus may produce infection in a preexisting wound or ulcer, or may cause primary sepsis that may be accompanied by shock that may be fatal. V. alginolyticus may also infect wounds, cause middle ear infections (otitis media), or cause bacteremia. S. M. Finegold, W. J. Martin, Diagnostic Microbiology 86-87, 240-46 (6th ed. 1982). Vibrio ssp. also cause disease in fishes, eels, frogs, other vertebrates and invertebrates as well. See 1 Bergey's Manual of Systematic Bacteriology 518-38 (N. R. Krieg and J. G. Bolt eds. 1984). Web site: http://www.delphion.com/details?pn=US05681862__ •
Marine bacterial strain of the genus vibrio, water-soluble polysaccharides produced by said strain and their uses Inventor(s): Guezennec; Jean (Plouzane, FR), Pignet; Patricia (Brest, FR), Raguenes; Gerard (Brest, FR), Rougeaux; Helene (Brest, FR) Assignee(s): Instit Francais de Recherche pour l'Exploitation de la Mer (Issy les Moulineaux, FR) Patent Number: 6,436,680 Date filed: November 19, 1999 Abstract: The invention concerns a hydrothermal bacterial strain of marine origin, belonging to the genus Vibrio, and an exopolysaccharide produced by said strain. Said exopolysaccharide is useful in particular for preparing medicines. Excerpt(s): The present invention relates to a new bacterial strain of the genus Vibrio, to the exopolysaccharides produced by the said strain and to their uses. Some microorganisms obtained from the deep submarine hydrothermal medium produce biomolecules whose particular structure and composition confer on them properties of great potential industrial interest; among these biomolecules are a wide variety of polysaccharides some of which have already been the subject of studies intended to determine their structures and their properties. The studies mentioned below have related more specifically to the exopolysaccharides (EPS) excreted by bacteria of the
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genus Alteromonas which are cultured under laboratory conditions, and in particular on glucose-enriched medium. Web site: http://www.delphion.com/details?pn=US06436680__ •
Method for purifying cholera toxin Inventor(s): Dertzbaugh; Mark (Fairfield, PA) Assignee(s): The United States of America as represented by the Secretary of the Army (Washington, DC) Patent Number: 6,008,329 Date filed: March 6, 1998 Abstract: The invention relates to a method of purifying cholera toxin using a matrix with at least one ion chosen from among matrix with Ni.sup.+2, Co.sup.+2, Cd.sup.2 or Zn.sup.+2 immobilized thereon. It is possible thereby to selectively elute the B subunit for cholera toxin from the matrix. Excerpt(s): This invention relates to affinity matrix with the Ni.sup.+2, Co.sup.+2, Cd.sup.+2 or Zn.sup.+2 ion immobilized thereon which binds cholera toxin. The matrix may be used in purification of cholera toxin and for performing separation of the B subunit from the A subunit when the linkage between the units has been broken. Cholera toxin (CT) is composed of two subunits: a toxigenic A subunit (CTA), and a binding B subunit (CTB). The latter mediates binding of CTA to the surface of eukaryotic cells via its interaction with the monosialoganglioside GM1. The type I heatlabile enterotoxin of Escherichia coli (LT) is closely related to CT. It has an identical subunit structure and function, and shares 80% amino acid homology with CT. Although LT is very similar to CT in structure and function, it binds to a broader array of ligands than CT, including glycolipids and glycoproteins. The 3-D crystal structure has been determined for both CT and LT. In addition, the crystal structure of CTB complexed with the GM1-pentasaccharide has also been determined. The crystal structure of this complex has revealed all interactions between the GM1 head group and the receptor binding site of CTB without any indication of the presence of a divalent ion binding site. Also, no biochemical evidence indicating that cations mediate ganglioside binding has previously been reported. However, some of the receptors for these enterotoxins have only been recently identified. Thus, it is possible that there are additional receptors for CT and LT that are still unknown. Web site: http://www.delphion.com/details?pn=US06008329__
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Method of inhibiting secretory effects caused by Cholera Inventor(s): Fang; Guodong D. (Charlottesville, VA), Fonteles; Manasses C. (Porangabussu, BR), Guerrant; Richard L. (Charlottesville, VA) Assignee(s): UVA Patent Foundation (Charlottesville, VA) Patent Number: 5,929,095 Date filed: June 17, 1997 Abstract: The administration of the PAF antagonists BN 52021 and SR 27417, in combination with cyclooxygenase antagonist indomethacin are disclosed as effective in inhibiting the secretory effects caused by Cholera toxin.
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Excerpt(s): The invention relates to the treatment of antibiotic associated colitis, typically due to Clostridium difficile using Platelet Activating Factor antagonists, such as WEB 2170, SR 27417 or BN 52021, or the cyclooxygenase antagonists, such as indomethacin. The PAF antagonists BN 52021 and SR 27417 and the cyclooxygenase antagonist indomethacin were effective in inhibiting the secretory effects caused by C. difficle Toxin A and even by Cholera toxin. Clostridium difficile is one of the most frequently recognized bacterial causes of diarrheal disease in hospitalized adults in industrialized countries. The microorganism can be acquired nosocomially and is present in environmental sources. Antibiotic associated colitis and pseudomembranous colitis are frequently associated with cytotoxigenic Clostridium difficile. The frequency of Clostridium difficile toxin associated with antibiotic associated colitis is 50-80% and with pseudomembranous colitis is 90-100%. Despite available treatment for antibiotic associated colitis and pseudomembranous colitis, relapses occur in 20-25% of patients. Vancomycin and metronidazole can be effective, but are subject to relapse after the use of the drugs may occur. Clostridium difficile produces two toxins, A (enterotoxic) and B (cytopathic), the former (Toxin A) being implicated in the pathogenesis of pseudomembranous colitis. Toxin A causes hemorrhagic fluid accumulation associated with mucosal damage and a cytopathic effect in tissue culture cells. In experimental animals such as rabbits, toxin A causes hemorrhagic fluid secretion and cell damage in ligated intestinal segments of loops, and is considered to be the cause of antibioticassociated colitis in experimental hamsters and in people. Web site: http://www.delphion.com/details?pn=US05929095__ •
Modified cholera toxin based on mutagenized subunit A Inventor(s): Burnette; W. Neal (Thousand Oaks, CA), Kaslow; Harvey R. (Los Angeles, CA) Assignee(s): Amgen Inc. (Thousand Oaks, CA), University of Southern California (Los Angeles, CA) Patent Number: 5,770,203 Date filed: May 24, 1995 Abstract: The development of subunits and subunit analogs of the cholera exotoxin by recombinant DNA techniques provides vaccine products that can retain their biological activity and immunogenicity, and can confer protection against disease challenge. Genetically-engineered modifications of the subunits result in products that retain immunogenicity, yet are reduced in, or are essentially free of, enzymatic activity associated with toxin reactogenicity. Excerpt(s): The present invention relates to the recombinant expression of analog subunits of cholera exotoxin, and to vaccines based on such analogs. More particularly, genetically engineered modifications of the exotoxin provide analogs of cholera toxin having the capability to elicit a protective response with reduced or essentially no catalytic activity which can contribute to the reactogenicity of cholera vaccines. The term "cholera" refers to the disease caused by infection with the etiologic agent Vibrio cholerae, most commonly occurring in geographical areas where poor hygienic conditions prevail. Cholera remains a major cause of morbidity and mortality in many parts of the world(1,2). Experience has shown that contraction of the disease usually confers long-lasting protection against subsequent exposure to the etiologic agent(3). Consequently, considerable effort has been devoted to the development of a vaccine that would be similarly protective. A parenteral whole cell cholera vaccine has been
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produced, but some no longer regard it as useful, particularly for young children who are at greatest risk from the disease(1). As for many other infectious diseases, a biological exotoxin (in this case, "cholera toxin" or "CTX") encoded by the genome of the infectious agent and secreted by it, contributes significantly to the ability of the microorganism to colonize the infected host(4). Moreover, exposure to the toxin causes severe diarrhea and vomiting which result in dehydration, a life-threatening condition of the disease(3,5). These experiences suggest that a vaccine which elicits an immunologic response (e.g., antibodies) sufficient to neutralize the toxin would thus significantly help to prevent or reduce bacterial colonization and attendant symptoms such as diarrhea and vomiting. Thus, substantial effort has been applied toward developing a vaccine containing a non-toxic analog of the toxin, i.e., a "toxoid"(1,3-13). It is known that cholera toxin is a multi-subunit macromolecule consisting of a subunit termed "A", containing a catalytic region called "A1" which ADP-ribosylates G-proteins in target cells, and a "B" oligomer which binds the holotoxin to the target cells(6). Nontoxic analogs of cholera toxin have been produced for purposes of vaccine development by various means. These methods include chemical treatment of the holotoxin or toxin subunits, deletion of the A subunit and use of the remaining B oligomer, and synthesis or isolation of peptide fragments of toxin subunits(l,3-13). Web site: http://www.delphion.com/details?pn=US05770203__ •
Mucosal administration of pneumococcal antigens Inventor(s): Briles; David E. (Birmingham, AL), Wu; Hong-Yin (Birmingham, AL) Assignee(s): UAB Research Foundation (Birmingham, AL) Patent Number: 6,027,734 Date filed: September 30, 1994 Abstract: Mucosal administration, particularly intranasally, of killed whole pneumococci, lysate of pneumococci and isolated and purified PspA, as well as immunogenic fragments thereof, particularly when administered with cholera toxin B subunit, provides protection in animals against pneumococcal colonization and systemic infection. The ability to elicit protection against pneumococcal colonization in a host prevents carriage among immunized individuals, which can lead to elimination of disease from the population as a whole. Excerpt(s): This invention relates to mucosal immunization of animals with pneumococcal antigens to provide protection against pneumococcal colonization and systemic infection. Streptococcus pneumoniae causes more fatal infections world-wide than almost any other pathogen (refs. 1, 2,--a list of the references appears at the end of the disclosure). In the U.S.A., deaths caused by S. pneumoniae exceed in numbers those caused by AIDS (ref. 1). In the U.S.A., most fatal pneumococcal infections occur in individuals over 65 years of age, in whom S. pneumoniae is the most common cause of community-acquired pneumonia. In the developed world, most pneumococcal deaths occur in the elderly, or in immunodeficient patents including those with sickle cell disease. In the less-developed areas of the world, pneumococcal infection is one of the largest causes of death among children less than 5 years of age (refs. 3, 4, 5, 6). The increase in the frequency of multiple antibiotic resistance among pneumococci and the prohibitive cost of drug treatment in poor countries make the present prospects for control of pneumococcal disease problematical (refs. 7, 8, 9). Humans acquire pneumococci through aerosols or by direct contact. Pneumococci first colonize the upper airways and can remain in nasal mucosa for weeks or months, As many as 50% or
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more of young children and the elderly are colonized. In most cases, this colonization results in no apparent infection (refs. 10, 11, 12). Studies of outbreak strains have suggested that even highly virulent strains, can colonize without causing disease (refs. 13, 14, 15, 16). These expectations have been recently confirmed using molecular probes to fingerprint individual clones (M. J. Crain, personal communication to one of the inventors). In some individuals, however, the organism carried in the nasopharynx can give rise to symptomatic sinusitis or middle ear infections. If pneumococci are aspirated into the lung, especially with food particles or mucus, they can cause pneumonia. Infections at these sites generally shed some pneumococci into the blood where they can lead to sepsis, especially if they continue to be shed into the blood in in large numbers. Pneumococci in the blood can reach the brain where they can cause meningitis. Although pneumococcal meningitis is less common than other infections caused by these bacteria, it is particularly devastating; some 10% of patients die and greater than 50% of the remainder have life-long neurological sequelae (refs. 17, 18). Web site: http://www.delphion.com/details?pn=US06027734__ •
Mucosal immunogens for novel vaccines Inventor(s): Hajishengallis; Georgios (Birmingham, AL), Hollingshead; Susan K. (Birmingham, AL), Michalek; Suzanne Mary (Birmingham, AL), Russell; Michael William (Birmingham, AL), Wu; Hong-Yin (Hoover, AL) Assignee(s): UAB Research Foundation (Birmingham, AL) Patent Number: 6,030,624 Date filed: August 15, 1997 Abstract: The present invention provides chimeric proteins such as Salivary Binding Protein (SBR) coupled to the B subunit of cholera toxin. Such a chimeric protein, when expressed in attenuated Salmonella typhymurium produces significant increases in serum IgG and salivary IgA antibody levels after oral immunization. In another embodiment of the present invention, the recombinant plasmid contains a salivary binding protein-cholera toxin A2/B chimeric protein expressed in E. coli. Intragastric immunization of SBR coupled to CTB in this chimeric protein form leads to increased antigen responsive T cells. In another embodiment of the present invention, the recombinant plasmid contains a salivary binding protein-cholera toxin.sup.DELTA.A1 chimeric protein expressed in Salmonella typhimurium. Oral immunization using this recombinant plasmid results in increased serum IgG responses to antigen. Oral immunization using this recombinant plasmid also resulted in increased salivary IgA antibody responses to antigen. Excerpt(s): The present invention relates generally to the fields of molecular immunology and protein chemistry. More specifically, the present invention relates to a novel mucosal immunogens for use in novel vaccines. An oral immunization strategy is when the desired mucosal immunogen is genetically fused to the A2 subunit of cholera toxin (CT) that mediates association with the B subunit of CT, a potent immunoenhancing agent. An antigen selected for evaluating the oral immunogenicity of such non-toxic CTA2/B-based constructs is the saliva-binding region (SBR) of the AgI/II adhesin from the oral bacterium Streptococcus mutans. The SBR genetically linked to CTA2/B, designated SBR-CT.sup.DELTA.A1, was found to be immunogenic by the oral route and elicited high levels of secretory immunoglobulin A (S-IgA) and serum IgG antibodies to AgI/II. Despite its great importance for mucosal defense, the SIgA antibody response is often of relatively short duration, lasting from a few weeks in
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experimental animals to a few months in humans. Moreover, whether the secretory immune system is capable of anamnestic immune responses has been debated, but recent studies in mice and humans have addressed the concept of immunological memory at the mucosal surfaces. Immunological memory can be manifested as a longlasting immune response or as a faster and more vigorous anamnestic response to reencounter with an antigen. A desirable vaccine characteristic is the induction of prolonged immune responses, especially when the pathogenic organism is frequently encountered at mucosal surfaces, in which case a continuing level of immunity may be necessary. Web site: http://www.delphion.com/details?pn=US06030624__ •
Non-viable total keratinocyte lysate for promoting wound healing Inventor(s): Van Bossuyt; Hans (Relegem, BE) Assignee(s): N.V Innogentics S.A. (Ghent, BE) Patent Number: 5,866,167 Date filed: January 2, 1997 Abstract: Cultures of keratinocyte cells are provided which are free from nonautologous fibroblasts and organ extracts, and which have a high speed of cell amplification for a minimum seeding density. Preferably, a culture contains no more than about 10% autologous non-keratinocyte cells such as star-shaped, non-keratinocyte cells and no more than about 1% autologous fibroblasts. The cultures can be cryopreserved in a buffered isotonic medium containing serum and a cryoprotectant. The cultures are produced by a process that does not involve the use of a feeder layer and organ extracts. A culture medium used contains Medium 199, serum, epidermal growth factor, cholera toxin and/or hydrocortisone, and optionally insulin. A substance for wound healing and for cosmetic applications is derived from cultured human keratinocytes. Lyophilized keratinocyte cell cultures or an extract therefrom is used to provide a pharmaceutical composition. Confluent and cohesive keratinocyte sheets are prepared for use in wound healing. A non-viable total keratinocyte lysate for use in promoting wound healing is produced by growing keratinocyte cells on a support, detaching the cells from the support, and lysing the detached cells to obtain the lysate. The lysate may be frozen and lyophilized. The detached cells may be frozen to produce the lysate without lysis before freezing. Excerpt(s): The invention relates to new cultures of keratinocytes. The invention also relates to a process for preparing the same. The invention also relates to the use of new cultures of keratinocytes as wound healing substances. Web site: http://www.delphion.com/details?pn=US05866167__
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Oligonucleotides used for detecting vibrio parahaemolyticus and method of detection therewith Inventor(s): Doumoto; Nobuhiko (Tokyo, JP), Venkateswaran; Kasthuri (San Gabriel, CA) Assignee(s): Nippon Suisan Kaisha, Ltd. (Tokyo, JP) Patent Number: 6,048,697 Date filed: January 6, 1999 Abstract: An oligonucleotide is provided which has a nucleotide sequence derived from SEQ ID NO:1, characterized in that it contains at least one site capable of amplifying a nucleotide sequence characteristic of Vibrio parahaemolyticus. The oligonucleotide may have a nucleotide sequence not derived from SEQ ID NO:3, or incapable of amplifying nucleotide sequences originating in Vibrio alginolyticus and Vibrio harveyi, and may be represented by SEQ ID NO:5 or SEQ ID NO:6. A method of detecting Vibrio parahaemolyticus in a specimen is also provided which comprises preparing a primer set comprising two of the above oligonucleotides, selectively amplifying therewith a DNA gyrase subunit B gene sequence contained in the specimen as a target, and determining whether or not there is a gyrB unit specific for Vibrio parahaemolyticus in the specimen. Also provided is a primer which reacts specifically with a gyrB gene of Vibrio parahaemolyticus to thereby differentiate and identify the same among other Vibrios and strains other than the genus Vibrio. The Vibrio parahaemolyticus-specific primer serves to detect 285-bp gyrB gene fragments specific for this Vibrio by the PCR method without the necessity for DNA extraction or like operations from bacterial cells. Excerpt(s): This invention relates to oligonucleotide primers for amplification of the target nucleotide sequence characteristic of Vibrio parahaemolyticus (abbreviated as "VP" somewhere hereinafter). This invention relates to the method for detecting Vibrio parahaemolyticus based on the polymerase chain reaction (PCR) using a primer specific for the DNA gyrase sub-unit B gene (Nucleotide sequence of DNA gyrase B subunit, abbreviated as "gyrB" hereinafter). Vibrio parahaemolyticus is known to cause food poisoning in many countries. It is found not only in the intestine but also in other organs and in the postoperative wound. Vibrio parahaemolyticus is a Gram negative, polymorphic, bacilliform, halophilic, facultative anaerobe, which ferments carbohydrate to generate gas. It forms green colonies on thiosulfate-citrate-bile-sucrose (TCBS) agar. For detection of Vibrio parahaemolyticus, is used usually a method where the specimen is cultivated in an enrichment medium followed by isolation by the selective plate culture. The conventional method of detection requires one week, and therefore a more rapid method has been desired. Web site: http://www.delphion.com/details?pn=US06048697__
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Oral dosage composition comprising zonnula occludens toxin and a therapeutic agent for intestinal delivery Inventor(s): Fasano; Alessio (Ellicott City, MD) Assignee(s): University of Maryland at Baltimore (Baltimore, MD) Patent Number: 5,827,534 Date filed: May 24, 1995
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Abstract: An oral dosage composition for intestinal delivery of a therapeutic agent comprising:(A) a therapeutic agent selected from the group consisting of a drug compound, a biologically active peptide and a vaccine; and(B) an intestinal absorption enhancing effective amount of purified Vibrio cholera zonula occludens toxin. Excerpt(s): The development of the present invention was supported by the University of Maryland, Baltimore, Md. The present invention relates to an oral dosage composition for intestinal delivery comprising (A) a biologically active ingredient; and (B) an intestinal absorption enhancing effective amount of zonula occludens toxin, as well as a method for the use of the same. The intestinal absorption of a large number of compounds routinely used for the treatment of common diseases is significantly limited by their chemical-physical characteristics. Thus, in recent years, the development of intestinal delivery systems has been one of the most challenging areas of research for pharmaceutical companies. Web site: http://www.delphion.com/details?pn=US05827534__ •
Process for the isolation of a nontoxinogenic vibrio cholerae strain and a process for preparing cholera vaccine from said vibrio cholerae strain Inventor(s): Ghosh; Amit (Union Territory, IN), Ghosh; Ranajit Kumar (Calcutta, IN), Gupta; Naveen (Union Territory, IN), Kole; Hemanta (Calcutta, IN), Mukhopadhyay; Asish (Calcutta, IN), Muthukumarappa; Thungapathra (Union Territory, IN), Nair; Gopinath Balakrish (Calcutta, IN), Sharma; Charu (Union Territory, IN) Assignee(s): Council of Scientific & Industrial Research (New Delhi, IN), Department of Biotechnology (New Delhi, IN), National Institute of Cholera and Enteric Diseases (Calcutta, IN) Patent Number: 6,106,843 Date filed: February 3, 1999 Abstract: A process for the isolation of nontoxinogenic V. cholerae strain and a process for preparing a cholera vaccine from said V. cholerae strain, said process comprising (a) isolating V. cholerae from the stool of a patient suffering from cholera by spreading the stool on a selector medium specific for V. cholerae, (b) separating the non-toxinogenic V. cholerae strain from the population of the V. cholerae strains isolated in step (a), and (c) incorporating immunogenic cholera toxin (ctx) B subunit gene into the chromosome of the strain by conventional methods to produce the vaccine. Excerpt(s): The present invention relates to a process for the isolation of a nontoxinogenic Vibro cholerae strain and its use in the preparation of cholera vaccine. The present invention also, particularly, relates to a process for the preparation of cholera vaccine using V. cholerae strain having ATCC Accession No. 202010. The vaccine prepared by the process of the invention has proved efficacious in animal trials. If proved successful in human trials, it can be used to control the disease cholera, since an effective and safe cholera vaccine is still not available. The present invention specifically relates to a process for the preparation of cholera vaccine using V. cholerae strain having the ATCC Accession No. 202010 as a parent strain. Annealing refers to the process in which single strands of deoxyribonucleic acid (DNA) having complementary base sequences become paired to form a double stranded molecule. Clone refers to a large number of cells or plasmid molecules derived from a single ancestral cell or plasmid molecule and a colony refers to a visible cluster of cells formed on a solid growth medium by repeated division of a single parental cell.
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Web site: http://www.delphion.com/details?pn=US06106843__ •
Recombinant DNAS encoding three-part hybrid proteins Inventor(s): Murphy; John R. (Wayland, MA) Assignee(s): Seragen, Inc. (Hopkinton, MA) Patent Number: 5,965,406 Date filed: June 7, 1995 Abstract: Disclosed is a recombinant DNA molecule encoding a hybrid protein comprising a first part, a second part, and a third part,(a) wherein said first part comprises a portion of the binding domain of a cell-binding polypeptide ligand effective to cause said hybrid protein to bind to a cell of an animal;(b) wherein said second part comprises a portion of a translocation domain of naturally occurring protein selected from the group consisting of diphtheria toxin, botulinum neurotoxin, ricin, cholera toxin, LT toxin, C3 toxin, Shiga toxin, Shiga-like toxin, pertussis toxin and tetanus toxin, which translocates said third part across the cytoplasmic membrane into the cytosol of the cell; and(c) wherein said third part comprises a polypeptide entity to be introduced into the cell, wherein said third part is non-native with respect to said naturally occurring protein of (b). Excerpt(s): This invention relates to hybrid molecules having a cell-binding part and a translocation part. The literature contains many examples of fused genes which code for hybrid proteins. For example, Villa-Komaroff et al., Proc. Natl. Acad. Sci. U.S.A. 75: 3727-3731, 1978, describes a fused gene made up of a eukaryotic structural gene fused to a non-cytoplasmic bacterial gene. The fused gene codes for a hybrid protein which is transported out of the cytoplasm. Hybrid proteins also have been made by other methods (e.g., the coupling of two different protein molecules) which do not involve recombinant DNA techniques. For example, it has been proposed to form, by coupling, therapeutic hybrid proteins consisting of portions of toxin molecules coupled to a ligand capable of binding specifically to a selected class of cells. One attempt to make such a hybrid protein, reported in Chang et al., J. Biol. Chem. 252:1515-1522, 1977, resulted in a hybrid consisting of the diphtheria toxin A chain coupled to human placental lactogen hormone by cross-linking through a disulfide bond. The hybrid protein, although it bound to cells containing lactogen receptors, did not inhibit protein synthesis in those cells. Web site: http://www.delphion.com/details?pn=US05965406__
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Recombinant flagellin vaccines Inventor(s): Majarian; William R. (Mt. Royal, NJ), Newton; Salete M. C. (Mountain View, CA), Stocker; Bruce A. D. (Palo Alto, CA) Assignee(s): American Cyanamid Company (Madison, NJ), The Board of Trustees of the Leland Stanford Junior University (Stanford, CA) Patent Number: 6,130,082 Date filed: February 14, 1992 Abstract: The present invention is directed to recombinant genes and their encoded proteins which are recombinant flagellin fusion proteins. Such fusion proteins comprise
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amino acid sequences specifying an epitope encoded by a flagellin structural gene and an epitope of a heterologous organism which is immunogenic upon introduction of the fusion protein into a vertebrate host. The recombinant genes and proteins of the present invention can be used in vaccine formulations, to provide protection against infection by the heterologous organism, or to provide protection against conditions or disorders caused by an antigen of the organism. In a specific embodiment, attenuated invasive bacteria expressing the recombinant flagellin genes of the invention can be used in live vaccine formulations. The invention is illustrated by way of examples in which epitopes of malaria circumsporozoite antigens, the B subunit of Cholera toxin, surface and presurface antigens of Hepatitis B. VP7 polypeptide of rotavirus, envelope glycoprotein of HIV, and M protein of Streptococcus, are expressed in recombinant flagellin fusion proteins which assemble into functional flagella, and which provoke an immune response directed against the heterologous epitope, in a vertebrate host. Excerpt(s): Recombinant DNA technology involves insertion of specific DNA sequences into a DNA vehicle (vector) to form a recombinant DNA molecule which is capable of replication in a host cell. Generally, the inserted DNA sequence is foreign to the recipient DNA vehicle, i.e., the inserted DNA sequence and the DNA vector are derived from organisms which do not exchange genetic information in nature, or the inserted DNA sequence may be wholly or partially synthetically made. Several general methods have been developed which enable construction of recombinant DNA molecules. Regardless of the method used for construction, the recombinant DNA molecule must be compatible with the host cell, i.e., capable of autonomous replication in the host cell or stably integrated into one or more of the host cell's chromosomes or plasmids. The recombinant DNA molecule should preferably also have a marker function which allows the selection of the desired recombinant DNA molecule(s). In addition, if all of the proper replication, transcription, and translation signals are correctly arranged on the recombinant vector, the foreign gene will be properly expressed in, e.g., the transformed bacterial cells, in the case of bacterial expression plasmids, or in permissive cell lines or hosts infected with a recombinant virus or carrying a recombinant plasmid having the appropriate origin of replication. Different genetic signals and processing events control levels of gene expression such as DNA transcription and messenger RNA (mRNA) translation. Transcription of DNA is dependent upon the presence of a promoter, which is a DNA sequence that directs the binding of RNA polymerase and thereby promotes mRNA synthesis. The DNA sequences of eucaryotic promoters differ from those of procaryotic promoters. Furthermore, eucaryotic promoters and accompanying genetic signals may not be recognized in or may not function in a procaryotic system, and furthermore, procaryotic promoters are not recognized and do not function in eucaryotic cells. Web site: http://www.delphion.com/details?pn=US06130082__ •
Recombinant systems for expression of cholera B-subunit with the aid of foreign promoters and/or leader peptides Inventor(s): Holmgren; Jan (Vastra Frolunda, SE), Sanches Castillo; Joaquin (Privada Xejc, MX) Assignee(s): Vitec Aktiebolag (SE) Patent Number: 5,834,246 Date filed: January 21, 1997
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Abstract: Disclosed herein are procedures whereby with the aid of recombinant DNA methods, the expression of the binding subunit protein of cholera toxin (CTB) or derivatives thereof including hybrid gene fusion proteins to CTB has been brought under the control of a foreign (non-cholera toxin) promoter and/or the CTB protein or its derivatives being synthesized with a foreign rather than the natural leader peptide to facilitate translocation across cell membranes. Excerpt(s): Vibrio cholerae of serogroup O1 may induce severe diarrhoeal disease when miultiplying in the gut of infected individuals by releasing cholera toxin (CT) which induces active electrolyte and water secretion from the intestinal epithelium. By analogous mechanisms several other bacteria, for instance Escherichia coli, may also cause diarrhoea by releasing other enterotoxins that may be related or unrelated to CT. CT is the prototype bacterial enterotoxin. It is a protein built from two types of subunits: a single A subunit of molecular weight 28,000 and five B subunits, each with a molecular weight of 11,600. The B subunits are aggregated in a ring by tight noncovalent bonds; the A subunit is linked to and probably partially inserted in the B pentamer ring through weaker noncovalent interactions. The two types of subunits have different roles in the intoxication process: the B subunits are responsible for cell binding and the A subunit for the direct toxic activity. The molecular aspects of toxin binding to intestinal and other mammalian cells and of the subsequent events leading to activation of adenylate cyclase through the intracellular action of the A subunit (and its A1 fragment) have been clarified in considerable detail (see J Holmgren, Nature 292:413-417, 1981). More recently information has also become available on the genetics and biochemistry of cholera toxin synthesis, assembly and secretion by V. cholerae bacteria. CT is encoded by chromosomal structural genes for the A and B subunits, respectively. These genes have been cloned from several strains, and their nucleotide sequences have been determined The genes for the A and B subunits of CT are arranged in a single transcriptional unit with the A cistron (ctxA) preceeding the B cistron (ctxB). Studies on the organization of CT genes in V. cholerae strains of classical and El Tor biotypes have suggested that there are two copies of CT genes in classical biotype strains while there is only one copy in most El Tor strains (J J Mekalanos et al, Nature 306:551-557, 1983). The synthesis of CT is positively regulated by a gene, toxR that increases ctx expression manifold (V L Miller and J J Mekalanos, Proc Natl Acad Sci USA, 81:3471-3475, 1984). ToxR acts at the transcriptional level, and is present in strains of both classical and El Tor biotypes. ToxR probably increases ctx transcription by encoding a regulatory protein that interacts positively with the ctx promoter region. Studies on heat-labile enterotoxin (LT) in Escherichia coli (the subunit structure and function of LT is closely similar but not identical to CT) have shown that the A and B subunits are initially synthesized as precursors with a leader peptide preceeding the mature subunit proteins. These precursors are rapidly processed (i.e. the leader peptide is being removed) and translocated across the inner membrane into the periplasm, where unassembled monomeric B subunits pentamerize and associate with A subunit with a half-time of 1-2 min. The pathway of toxin assembly appears to proceed via A subunit association with B monomers or small oligomers. Once the complete toxin has assembled, in V. cholerae (in contrast to E. coli where the toxin remains in the periplasm the toxin is being translocated (secreted) across the V. cholerae O1 outer membrane through some sort of interaction of B subunit domains with the outer membrane (T R Hirst & J Holmgren, Proc Natl Acad Sci USA, 84:7418-7422, 1987; S J S Hardy et al, ibid, in press, 1988). If the B subunits of CT or LT are being expressed in the absence of any A subunit (several such strains have been prepared by chemical mutagenesis or deletions by recombinant DNA methods in the ctxA or eltA cistrons) the B subunits form pentamers which are then secreted from V. cholerae via the same pathway as for the intact toxin except for an
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apparently slightly slower assembly process in the periplasm (T R Hirst et al, Proc Natl Acad Sci USA 81:2645-2649, 1984; S J S Hardy et al, ibid, in press, 1988). Because vaccination against cholera by parenteral injection has yielded only modest and shortterm protection (usually less than 50% protection for less than 6 months), attention has turned to development of oral vaccines that stimulate intestinal immunity more efficiently. Special attention has been drawn to CTB pentamers as one component of such oral cholera vaccines (J Holmgren et al., Nature 269:602-604, 1977). CTB is an effective oral immunizing agent which in a large field trial has been shown to afford protection against both cholera and diarrhoea caused by LT enterotoxigenic E. coli (J Clemens et al., Lancet ii:124-127, 1986; J Infect Dis, in press, 1988). The separation of B subunit from A excludes any risk of reversion to toxicity, and CTB has been administered orally to more than 25,000 people without any side effects. These features have made CTB an important component, together with killed whole cholera vibrios, of a new oral cholera vaccine. Moreover, CTB has attracted much interest recently as an immunogenic carrier for various other peptide or carbohydrate antigens and has also been used as a receptor-blocking and receptor-modulating agent for short-term prophylaxis of cholera and E. coli diarrhoea (R I Glass et al, J Infect Dis 149:495-500, 1984; S T Donta et al, ibid 157:557-564, 1988; S J McKenzie and J F Halsey, J Immunol 133:1818-1824, 1984; A-M Svennerholm et al J Clin Microbiol 24:585-590, 1986). These findings have emphasized a need to increase the yield of CTB for large-scale production, ideally avoiding at the same time the drawback in currently used preparation methods (see J L Tayot et al, Eur J Biochem 113:249-258, 1981) of having to purify the CTB protein from active toxin. Therefore, with the aid of strategies and procedures described in this application we have constructed overexpression systems for CTB and CTB fusion proteins in which the CTB gene (or the gene for the hybrid fusion protein) is under control of strong foreign (non-cholera toxin) promoters. Our success in this regard contrasts with previous attempts by different procedures by J J Mekalanos et al (Nature 306:551-557, 1983) to attain this goal using one of the promoters (tacP) described in one of our examples, as these attempts were reported to fail since they resulted in expression of less CTB than achieved with the natural ctx promoter. Web site: http://www.delphion.com/details?pn=US05834246__ •
Saccharide derivatives Inventor(s): Hindsgaul; Ole (Edmonton, CA) Assignee(s): Synsorb Biotech, Inc. (Calgary, CA) Patent Number: 6,087,339 Date filed: November 14, 1997 Abstract: Disclosed are novel saccharide derivatives which inhibit binding of toxins, such as heat-labile enterotoxin or cholera toxin, to their receptors either in vitro or in vivo. Additionally, disclosed are compounds which inhibit binding of enterovirulent organisms (e.g., bacteria, virus, fungi, and the like), such as Vibrio cholerae and enterotoxigenic strains of Escherichia coli, to their cell surface receptors. Excerpt(s): This invention relates to novel saccharide derivatives which inhibit binding of toxins, such as heat-labile enterotoxin (LT or cholera toxin (CT), to their receptors either in vitro or in vivo. Additionally, the compounds of this invention inhibit binding of organisms (e.g., bacteria, virus, fungi, and the like), such as Vibrio cholerae and enterotoxigenic strains of Escherichia coli, to their cell surface receptors. All of the above publications, patents and patent applications are herein incorporated by reference in
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their entirety to the same extent as if each individual publication, patent or patent application was specifically and individually indicated to be incorporated by reference in its entirety. Heat-labile enterotoxin and cholera toxin are known to bind to oligosaccharide receptors on host cells as an initial step in the pathological development of the associated disease condition.sup.2 Specifically, both LT and CT are known to bind to ganglioside G.sub.M1, a glycosphingolipid situated in the outer leaflet of the host cell membrane.sup.2 G.sub.M1 has a characteristic pentasaccharide structure, i.e., Gal(.beta.1.fwdarw.3)GalNAc(.beta.1.fwdarw.4){NeuAc(.alpha.2.fwdarw.3)}Gal (.beta.1.fwdarw.4)Glc, on its surface which serves as a receptor for LT and CT. LT is also known to bind to other gangliosides, such as ganglioside G.sub.D1b. Web site: http://www.delphion.com/details?pn=US06087339__ •
Species-specific DNA probes for Vibrio vulnificus and Vibrio cholerae, methods and kits Inventor(s): Bennison; Brenda W. (Tallahassee, FL), LaRock; Paul A. (Baton Rouge, LA), Reeves; Robert H. (Tallahassee, FL) Assignee(s): Florida State University (Tallahassee, FL) Patent Number: 6,312,891 Date filed: April 21, 1997 Abstract: The present invention relates to species-specific DNA probes specific for Vibrio vulnificus and Vibrio cholerae. The DNA probes of the present invention specifically detects Vibrio vulnificus or Vibrio cholerae in a mixed bacterial sample based on unique ribosomal RNA nucleotide sequences. When the DNA probes of the present invention are tagged with a labeled molecule such as a fluorescent label, it affords direct and immediate visualization of individual bacterial cells, and a rapid method of detection of bacterial infection in humans and shellfish without culturing. Excerpt(s): The present invention relates to species-specific oligonucleotide probes for binding specifically to ribosomal RNA of bacterium Vibrio Vulnificus or Vibrio cholerae. The present invention further relates to methods and kits for identifying the bacteria Vibrio vulnificus or Vibrio cholerae with such probes in a single day, without the need for culturing the bacteria. Vibrio vulnificus and Vibrio cholerae are small organisms called bacteria that live in the marine environment. Vibrio cholerae can also survive in fresh water. By drinking water, eating fruits and vegetables, fish or shellfish that are contaminated with this bacterium (one bacteria), a person can become very ill or may even die from the disease cholera which causes severe diarrhea and dehydration. Vibrio vulnificus can cause serious illness and even death within three days in people who eat raw or improperly cooked fish or shellfish that are infected with this microorganism. There are many types of bacteria, both good and bad, in food and water. To find out whether water or food contains these harmful Vibrio bacteria, or if a person is infected with them, laboratory tests must be performed. The first step is to culture, or grow, the bacteria in a special liquid. Then a series of tests are done to identify the bacteria based on whether or not they use certain sugars and other compounds in order to grow. It may take as long as one week to do these tests and by that time a person may die if not given the proper medicine. What is needed is a rapid and easy way to detect and identify Vibrio cholerae and Vibrio vulnificus. Web site: http://www.delphion.com/details?pn=US06312891__
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Treatment of bacterial infections Inventor(s): Armstrong; Glen (Edmonton, CA), Bundle; David R. (Edmonton, CA), Kitov; Pavel (Edmonton, CA), Ling; Hong (Edmonton, CA), Read; Randy J. (Cambridge, GB) Assignee(s): Governors of the University of Alberta (Edmonton, CA) Patent Number: 6,310,043 Date filed: May 24, 1999 Abstract: Compounds which bind to toxins associated with enteric bacterial infection, compositions including the compounds, methods for the neutralization of toxins in a patient, and methods for the diagnosis of bacterial and viral infections are disclosed. Toxins which can be bound by the compounds include pentameric toxins, for example SLTs, such as those from salmonella, camylobacter and other bacteria, verotoxins from E. coli, cholera toxin, clostridium difficile toxins A and B, bacterial pili from enteropathogenic E. coli (EPEC) and enterotoxigenic E. coli (ETEC) and viral lectins such as viral hemagglutinins. The compounds include a core molecule bound to a plurality of linker arms, which in turn are bound to a plurality of bridging moieties, which in turn are bound to at least one, and preferably, two or more ligands which bind to the toxin. The presence of a plurality of bridged dimers of the ligands is responsible for the increased binding affinity of the compounds relative to the ligands themselves. In one embodiment, the compounds, when administered in a timely fashion to a patient suffering from enteric E. coli infection, inhibit progression of this infection into hemolytic uremic syndrome (HUS). Excerpt(s): This invention relates to the treatment of toxins, in particular, toxins generated by bacteria. The following references are cited in the application as numbers in brackets ([ ]) at the relevant portion of the application. 1. Karmali, M. A. et al., J Clin. Microbiol. 22:614-619 (1985). Web site: http://www.delphion.com/details?pn=US06310043__
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Treatment of cholera Inventor(s): Armstrong; Glen D. (Edmonton, CA), Heerze; Louis D. (Edmonton, CA) Assignee(s): Synsorb Biotech, Inc. (Calgary, CA) Patent Number: 5,661,131 Date filed: June 5, 1995 Abstract: This invention relates to treatment of cholera and related conditions using oligosaccharide compositions which bind V. cholerae toxin and/or one or more serotypes of the organism V. cholerae. More specifically, the invention concerns neutralization and removal of V. cholerae toxin and/or organisms from the intestinal tract. Excerpt(s): This invention relates to treatment of cholera. More specifically, the invention concerns neutralization and elimination of cholera toxin. This invention also relates to binding and removal of Vibrio cholerae, the causative agent of cholera from the intestinal tract. The following references are cited in the application as numbers in brackets ([ ]) at the relevant portion of the application. 1. Merritt, Ethan A., et al., "Crystal structure of cholera toxin B-pentamer bound to receptor G.sub.M1 pentasaccharide", Protein Science, 3: 166-175 (1994).
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Web site: http://www.delphion.com/details?pn=US05661131__ •
Vaccine composition comprising autologous epidermal growth factor or a fragment or a derivative thereof having anti-tumor activity and use thereof in the therapy of malignant diseases Inventor(s): Davila; Augustin Bienvenido Lage (Habana, CU), Delgado; Irene Beausoleil (Habana, CU), Gandolf; Gilda Nurez (Habana, CU), Marinello; Gisela Gonzalez (Habana, CU), Peztana; Eduardo Suarez (Habana, CU), Ramirez; Belinda Sanchez (Habana, CU) Assignee(s): Centro De Immunologia Molecular (Havana, CU) Patent Number: 5,894,018 Date filed: February 21, 1996 Abstract: The invention provides novel uses of EGF and vaccine compositions comprising EGF. In particular, autologous EGF, or a fragment or a derivative thereof, is used as an active immunization against the proliferation of EGF-dependent tumors, or other EGF-dependent diseases. Autologous EGF is preferably coupled to a carrier protein, such as tetanus toxoid or Cholera toxin B chain. The vaccine compositions according to the invention will usually comprise an adjuvant such as aluminum hydroxide. Excerpt(s): This invention relates to the field of immunology, in particular to vaccine compositions able to produce an autoimmune reaction against autologous (self) Epidermal Growth Factor (EGF). An important object of this invention is to obtain a vaccine composition for the active immunotherapy of EGF dependent malignant tumors (e.g. epidermoid carcinoma of lung, glioblastoma multiforme and head and neck epidermoid carcinomas), which can inhibit the proliferation of those tumors, and which therefore are useful for the treatment of malignant neoplasms and of other EGF related diseases. Thus, the invention is also related to the field of cancer therapy. Epidermal Growth Factor, a polypeptide that stimulates epithelial cell proliferation, has been considered to be one of the growth factors involved in malignant transformations. Its action is mainly performed via its membrane receptors. Web site: http://www.delphion.com/details?pn=US05894018__
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Vaccine compositions including chitosan for intranasal administration and use thereof Inventor(s): Chatfield; Steven Neville (Berkshire, GB), Illum; Lisbeth (Nottingham, GB) Assignee(s): West Pharmaceutical Services Drug Delivery & Clinical Research Centre (Nottingham, GB) Patent Number: 6,391,318 Date filed: June 1, 1998 Abstract: A variety of different types of nasal vaccine systems have been described including cholera toxin, microspheres, nanoparticles, liposomes, attenuated virus, and outer membrane proteins (proteosomes). The present invention is directed toward a novel nasal vaccine composition that utilizes the cationic polysaccharide, chitosan, as a delivery system. Chitosan is a polysaccharide comprising copolymers of glucosamine
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and N-acetylglucosamine. The term chitosan encompasses a series of chitosan polymers with different molecular weights (50 kDa-2,000 kDa) and degree of acetylation (40%98%). Several vaccine animal studies were carried out employing influenza or pertussis antigens in combination with chitosan. Nasal administration of chitosan-antigen nasal vaccines induced significant serum IgG responses and secretory IgA levels. Animals vaccinated via the nasal route with various chitosan-antigen vaccines were also found to be protected against the appropriate challenge. Excerpt(s): The invention is generally in the field of vaccine compositions, and specifically those for intranasal administration. Vaccines are preparations of antigenic materials, administered to recipients with a view to enhancing resistance to infection by inducing active immunity to specific microorganisms, for example bacteria or viruses. Vaccines, which may be as single or mixed component vaccines, are presented in a variety of forms. For example, current influenza vaccines consist of either inactivated whole virus, disrupted virus (split vaccines) or purified preparations of antigenic proteins. Web site: http://www.delphion.com/details?pn=US06391318__ •
Vibrio cholerae 01 (CVD111) and non-01 (CVD112 and CVD112RM) serogroup vaccine strains, methods of making same and products thereof Inventor(s): Kaper; James B. (Columbia, MD), Levine; Myron M. (Columbia, MD) Assignee(s): The University of Maryland System (Baltimore, MD) Patent Number: 5,882,653 Date filed: July 29, 1996 Abstract: Avirulent Vibrio cholerae strains of O1 (CVD111) and non-O1 (CVD112 and CVD112RM) serogroups having the DNA of the cholera toxin core and the RS1 sequences of the cholera toxin locus deleted, and further having a DNA encoding a resistance to mercury, and a DNA encoding the cholera toxin B subunit, or a part thereof sufficient to confer immunogenicity, re-inserted in the chromosome. Methods of making the avirulent V. cholerae O1 and non-O1 strains of the invention, and cholera vaccines using these strains. Excerpt(s): Vibrio cholerae (V. cholerae) is a non-invasive enteropathogen of the small bowel that does not penetrate the mucosal surface. Local Siga mediated immunity at the mucosal surface is therefore implicated as a protective mechanism. Pathogenic V. cholerae 01 elaborate a protein enterotoxin (also know as cholera enterotoxin, or choleragen, or cholera toxin) which is responsible for induction of copious secretion by the intestine resulting in watery diarrhea, the clinical consequence of cholera infection. The genes responsible for cholera enterotoxin are the ctx genes (also known as the tox genes). Cholera diarrhea can be extraordinarily severe and result in loss of so much body water and salts that dehydration, acidosis, shock, and death ensue without prompt therapy. There is known in the region of the V. cholerae chromosome containing the ctx genes that multiples copies of a 2700 base pair sequence called RS1 (for repetitive sequence) can be found. Mekalanos, Cell 35, 253-263 (1983). Applicants have also discovered that a second enterotoxin is produced by V. cholerae which has been named zonula occludens toxin, reported in Fasano et al, Vibrio cholerae Produces a Second enterotoxin Which Affects Intestinal Tight Junctions, Proc. Nat. Acad. Sci. (USA) 88, 5242-5246 (1991). The cholera vaccines that have been developed can be broadly divided into two categories; those aiming to stimulate antitoxic immunity and those intending to
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induce antibacterial immunity. Experiments with animal models support a protective role for either or both antitoxic and antibacterial immunity. It has been suggested that when both types of immunity work in unison, there is a synergistic effect. ›Holmgren, J. et al. J. Infect. Dis. 136 Suppl., S105-S1122 (1977); Peterson, J. W. Infect. Immun. 26, 594 (1979); Resnick, I. G. et al. Infect. Immun. 13, 375 (1980); Svennerholm, A.-M. et al. Infect. Immun. 13, 735 (1976)!. However, it appears that protective immunity in humans can be conferred without such synergistic effect, that is by either antitoxic immunity or antibacterial immunity ›Eubanks, E. R. et al. Infect. Immun. 15, 533 (1977); Fujita, K. et al. J. Infect. Dis. 125, 647 (1972); Holmgren, J., J. Infect. Dis., supra; Lange, S. et al. Acta Path. Microbiol. Scand Sect. C 86, 145 (1978); Peterson, J. W., supra (1979); Pierce, N. F. et al. Infect Immun. 37, 687 (1982); Pierce, N. F. et al. Infect. Immun. 21, 185 (1978); Pierce, N. F. et al. J. Infect. Dis. 135, 888 (1977); Resnick, I. G. et al., supra; Svennerholm, A.-M. et al, supra!. Web site: http://www.delphion.com/details?pn=US05882653__ •
Zonula occludens toxin receptors Inventor(s): Fasano; Alessio (Ellicott City, MD) Assignee(s): University of Maryland, Baltimore (Baltimore, MD) Patent Number: 5,912,323 Date filed: February 17, 1998 Abstract: Receptors for the zonula occludens toxin of Vibrio cholera, as well as methods involving the use of the same are disclosed. Excerpt(s): The development of the present invention was supported by the University of Maryland, Baltimore, Md. The present invention relates to receptors for the zonula occludens toxin of Vibrio cholera, as well as methods involving the use of the same. The tight junctions (hereinafter "tj") or zonula occludens (hereinafter "ZO") are one of the hallmarks of absorptive and secretory epithelia (Madara, J. Clin. Invest., 83:1089-1094 (1989); and Madara, Textbook of Secretory Diarrhea Eds. Lebenthal et al, Chapter 11, pages 125-138 (1990)). As a barrier between apical and basolateral compartments, they selectively regulate the passive diffusion of ions and water-soluble solutes through the paracellular pathway (Gumbiner, Am. J. Physiol., 253 (Cell Physiol. 22):C749-C758 (1987)). This barrier maintains any gradient generated by the activity of pathways associated with the transcellular route (Diamond, Physiologist, 20:10-18 (1977)). Web site: http://www.delphion.com/details?pn=US05912323__
Patent Applications on Cholera As of December 2000, U.S. patent applications are open to public viewing.9 Applications are patent requests which have yet to be granted. (The process to achieve a patent can take several years.) The following patent applications have been filed since December 2000 relating to cholera:
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This has been a common practice outside the United States prior to December 2000.
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Bovine viral diarrhea virus serum antigen capture Inventor(s): Dubovi, Edward Joseph; (Ithaca, NY), Huchzermeier, Roy; (Fayetteville, NY) Correspondence: Michael L. Goldman; Nixon Peabody Llp; Clinton Square; P. O. Box 31051; Rochester; NY; 14603; US Patent Application Number: 20010051332 Date filed: December 1, 2000 Abstract: The invention disclosed herein presents an antigen-capture immunoassay that utilizes serum, plasma, milk, urine, saliva, or other bodily fluid samples to identify cattle infected with the Bovine Viral Diarrhea Virus (BVDV). The results of this assay allow an effective, reliable, quick, and cost efficient way to identify, and thereby remove, infected cattle and/or other ruminants from otherwise uninfected herds. The BVD virus causes an acute enteric disease with a variety of clinical manifestations, and is closely related to sheep border disease virus (BDV) and hog cholera virus (HCV). The traditional method of detecting infected animals, including persistently infected (PI) carriers, has been through the use of virus isolation procedures. While this older test methodology can detect infected animals, the virus isolation test can only be performed by highly trained technicians in a highly specialized laboratory facility. The kit disclosed herein uses ELISA methodology, employs the BVDV antigen specific monoclonal antibody 15.c.5, and requires at least 100.mu.l of sample per assay. Excerpt(s): The invention pertains to the field of immunoassay tests for viral infection. More particularly, the invention pertains to the development of an antigen-capture immunoassay which can use serum, plasma, milk, mucosal fluid, or urine samples to identify animals infected with the bovine viral diarrhea virus. Bovine viral diarrhea virus ("BVDV") currently represents a major threat to the cattle industry. First described over fifty years ago, this pathogen has been found to be both highly virulent and easily spread. Considered a primary pathogen of the bovine enteric, respiratory, reproductive, and immune systems, BVDV continues to cause significant economic losses to the cattle industry worldwide. Recent outbreaks have occurred in Canada, the US, and throughout the world. To help combat these problems, a simpler, more cost effective method of BVDV detection, capable of yielding results in a timely fashion, is needed to better control the spread of the BVDV virus within the cattle population. Such a diagnostic tool is particularly important in light of the ineffectiveness of currently available BVDV vaccines. Classified as a member of the genus Pestivirus and Flaviniridae family, BVDV is closely related to sheep border disease virus (BDV), and hog cholera virus (HCV), both of which are serologically related pestiviruses. Entire or partial genomic sequencing of pestivirus isolates has allowed the determination that a high degree of sequence conservation is present among the pestiviruses. More recently, antigenic variants of BVDV have been identified, and BVDV strains have been divided into two distinct genotypes, type 1 and type 2, which have been further subdivided, based upon cytopathogenicity. Molecular cloning, and Polymerase Chain Reaction (PCR) technology have determined that the general structure of BVDV consists of a capsid protein and three envelope glycoproteins. The genome of BVDV is a 12.3 kb RNA consisting of a single open reading frame ("ORF"). The BVD virus is itself a small, enveloped RNA virus with positive strand polarity. This positive strand aspect of the viral genome allows the RNA to be infectious, even in the absence of virion proteins. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Chimeric antigen-enterotoxin mucosal immunogens Inventor(s): Connell, Terry D.; (Williamsville, NY), Russell, Michael W.; (East Amherst, NY) Correspondence: Benjamin Aaron Adler; Adler & Associates; 8011 Candle Lane; Houston; TX; 77071; US Patent Application Number: 20020004238 Date filed: April 3, 2001 Abstract: The present invention provides methods of inducing immune responses by recombinant antigen-enterotoxin chimeric mucosal immunogens that contain the A2/B subunits of cholera toxin or heat-labile type II toxins. These chimeric immunogens differentially enhance antibody secretion, cytokine production, as well as B7-dependent co-stimulation of T cells and CD40L expression on CD4.sup.+ T cells. Excerpt(s): This non-provisional patent application claims benefit of provisional patent application U.S. Ser. No. 60/194,498, filed Apr. 3, 2000, now abandoned. The present invention relates generally to the field of immunology. More specifically, the present invention relates to chimeric antigen-enterotoxin mucosal immunogens that differentially enhance immune responses. Cholera toxin (CT) produced by Vibrio cholerae and the labile toxins (LT) from Escherichia coli are structurally related heatlabile enterotoxins (HLE) that have been employed as mucosal adjuvants to augment mucosal immune responses to co-administered antigens (Ag) (1, 2). These enterotoxins consist of an ADP-ribosylating A1 subunit non-covalently coupled with a pentameric ring of five identical B subunits through the A2 subunit, which is the C-terminal end of the A polypeptide (3). Initial studies using heat-labile enterotoxins as adjuvants in animal models led to the conclusion that their adjuvanticity was due to their toxic enzyme activity (4). ADP-ribosylation of the Gs.alpha. subunit of adenylate cyclase results in abnormally high levels of intracellular cAMP (3, 5), and subsequent chloride ion efflux into the lumen of the gut that is ultimately responsible for the characteristic watery diarrhea. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Hybrid lt-a/ct-b holotoxin for use as an adjuvant Inventor(s): Clements, John D; (New Orleans, LA) Correspondence: Pennie And Edmonds; 1155 Avenue OF The Americas; New York; NY; 100362711 Patent Application Number: 20030113345 Date filed: November 19, 2002 Abstract: The present invention provides a novel composition which is a hybrid heat labile enterotoxin comprising the A-subunit of the heat labile toxin of Escherichia coli (LT-A) and the B-subunit of the cholera enterotoxin of Vibrio cholerae (CT-B). The hybrid toxin is designated LT-A/CT-B. The LT-A subunit, the CT-B subunit, or both subunits of the hybrid toxin may be mutant subunits, e.g., differing from wild-type subunits by amino acid substitutions, deletions or additions. Also provided are methods of using the novel LT-A/CT-B comprising compositions of the invention as adjuvants for vaccines, methods of making the LT-A/CT-B hybrid holotoxin, and kits.
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Excerpt(s): The present invention is directed towards a novel composition which is a hybrid heat labile enterotoxin holotoxin comprising the A-subunit of the heat labile toxin of Escherichia coli (LT-A) and the B-subunit of the cholera enterotoxin of Vibrio cholerae (CT-B). The hybrid toxin is designated LT-A/CT-B. The LT-A subunit, the CT-B subunit, or both subunits of the hybrid holotoxin may be mutant subunits, e.g., differing from wild-type subunits by one or more amino acid substitutions, deletions or additions. Each year, infectious diseases kill more than 17 million people, including 9 million children. In the United States, deaths due to infectious diseases increased 58 percent from 1982 to 1992 and are now third in the leading causes of death. In addition to suffering and death, infectious diseases impose an enormous financial burden on society. The majority of those infections and deaths are caused by organisms that first make contact with and then either colonize or cross mucosal surfaces to infect the host. While vaccination is the most cost-effective means of controlling infectious disease morbidity and mortality, traditional vaccine strategies that involve parenteral immunization (via needle) with inactivated viruses or bacteria or subunits of relevant virulence determinants of those pathogens do not prevent those interactions. In fact, traditional vaccine strategies do not prevent infection but instead resolve infection before disease ensues. In some cases, HIV for example, once the virus crosses the mucosal surface and enters the host cell, be that a dendritic cell, an epithelial cell, or a Tcell, the host-parasite relationship is moved decidedly in favor of the parasite (HIV). In that case, as in many others, a vaccine strategy that does not prevent the initial infection of the host is unlikely to succeed. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Hybrid proteins for autoimmune disease Inventor(s): Udaka, Shigezo; (Ashiya-shi, JP), Yuki, Yoshikazu; (Kobe-shi, JP) Correspondence: Pillsury Winthrop Llp; Intellectual Property Group; 11682 EL Camino Real; Suite 200; San Diego; CA; 94105; US Patent Application Number: 20030049797 Date filed: April 16, 2001 Abstract: Autoantigen-tolerogen fusion polypeptides, polynucleotides, expression vectors and host cells useful in inducing tolerance to autoantigens are provided. Preferred autoantigen fusion polypeptides contain a peptide encompassing proteolipid protein amino acids 139-151 fused to cholera toxin B-subunit. A Bacillus brevis expression-secretion system and methods for making autoantigen fusion polypeptides are also disclosed. The invention also includes methods for inducing tolerance to autoantigens, as well as treating and ameliorating the symptoms of neurodegenerative disease. Excerpt(s): The present invention generally relates to autoantigen-tolerogen fusion polypeptides useful for treatment of autoimmune disease, polynucleotides encoding fusion polypeptides, expression vectors and methods of producing autoantigen fusion polypeptides, particularly expression in Bacillus brevis. Also provided are methods of using autoantigen fusion polypeptides for inducing tolerance to autoantigens and treating neurodegenerative disease. An estimated four percent of the population is currently affected by autoimmune diseases including forms of multiple sclerosis, diabetes, arthritis and lupus. Autoimmunity results when the cells of the immune system recognize and attack so called "self" antigens or autoantigens that are normally present in and indeed produced by the body itself. As immune responses are in general
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destructive, i.e. meant to destroy invasive foreign antigens, autoimmune responses can cause destruction of the body's own tissue. Steroid treatment is the most common therapy for autoimmune disease. However, steroids non-specifically repress a wide variety of both desirable and undesirable immune functions, may be only partially effective, and are associated with significant adverse physiological and psychological side effects. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Immunogenic detoxified mutants of cholera toxin Inventor(s): Fontana, Maria Rita; (Siena, IT), Giannelli, Valentina; (Monteroni d'Arbia, IT), Pizza, Mariagrazia; (Siena, IT), Rappuoli, Rino; (Castelnuovo Berardenga, IT) Correspondence: Alisa A. Harbin, ESQ.; Chiron Corporation; Intellectual Property; P.O. Box 8097; Emeryville; CA; 94662-8097; US Patent Application Number: 20020044939 Date filed: March 28, 2001 Abstract: An immunogenic detoxified protein comprising the amino acid sequence of subunit A of a cholera toxin (CT-A) or a fragment thereof or the amino acid sequence of subunit A of an Escherichia coli heat labile toxin (LT-A) or a fragment thereof wherein the amino acids at, or in positions corresponding to Ser-63 and Arg-192 are replaced with another amino acid. The immunogenic detoxified protein is useful as vaccine for Vibrio cholerae or an enterotoxigenic strain of Escherichia coli and is produced by recombinant DNA means by site-directed mutagenesis. Excerpt(s): The present invention relates to immunogenic detoxified proteins of cholera toxins (CT), or of heat labile toxins (LT) produced by the enterotoxigenic strains of Escherichia coli (E. coli) wherein the amino acids at, or in positions corresponding to, Ser-63 and Arg-192 are replaced with another amino acid and to their use in vaccines which are useful for the prevention or treatment of cholera or enterotoxigenic E. coli infections and as mucosal adjuvants for other immunogenic proteins. The detoxified immunogenic proteins can be suitably produced using recombinant DNA techniques by site-directed mutagenesis of DNA encoding the wild type toxins. Cholera is a contagious disease widely distributed in the world, in particular in the Third World, where, in certain areas, it is endemic. The serious disorders which develop in the intestinal system prove fatal in a high percentage of the recorded cases of the disease. The etiological agent of cholera is the Gram-negative microorganism Vibrio cholerae (V. cholerae). This colonises the intestinal tract of individuals who have come into contact with it through ingestion of contaminated food or water, and multiplies to very high concentrations. The principal symptom is severe diarrhoea as a result of which the patient can lose as much as 10-15 liters of liquids per day via the faeces. As a result of the severe dehydration and loss of electrolytes, the patient does not withstand the infection in 50-60% of cases, and dies. The diarrhoea caused by V. cholerae is due to the secretion of cholera toxin, CT, which acts by stimulating the activity of the adenylate cyclase enzyme so as to induce disturbances at cell level. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Intranasal delivery of pneumococcal polysaccharide vaccines Inventor(s): Jonsdottir, Ingileif; (Reykjavik, IS) Correspondence: Michael S. Greenfield; Mcdonnell Boehnen Hulbert & Berghoff; 32nd Floor; 300 S. Wacker Drive; Chicago; IL; 60606; US Patent Application Number: 20020094338 Date filed: September 10, 2001 Abstract: The invention relates to a method for preventing against diseases induced by Streptococcus pneumoniae infections, which comprises mucosally administering to a patient in need of a S. pneunmoniae capsular polysaccharide. This latter may be conjugated or not and is preferably mixed with a mucosal adjuvant such as cholera toxin, E. coli heatlabile toxin or Rhinovax.TM. A preferred route of administration is the intranasal route. Excerpt(s): The invention relates to a method for preventing mammals against Streptococcus pneumoniae infections which comprises mucosally administering to a patient in need, a S. pneumoniae capsular polysaccharide. The mucosal surfaces of respiratory, genitourinary and gastrointestinal tracts are covered by a specialized epithelium, which creates an efficient physical barrier against environmental pathogens. However, a majority of bacterial and viral infections directly affect or enter the body through mucosal surfaces and colonization at these sites is often the first step in pathogenesis. S. pneumoniae is a major pathogen, which enters the body through the respiratory mucosa and may cause serious infections such as pneumonia, bacteremia and meningitis, especially in elderly people with a variety of chronic diseases, and in young children. It is also a common cause of mucosal infections like otitis media and sinusitis. The pneumococcus is surrounded by capsular polysaccharides, which are the main virulence factors and protect the pneumococci from defense mechanisms of the host which largely depends on opsonophagocytosis mediated by antibodies and complement (phagocytosis of bacteria opsonized by type-specific IgG antibodies and complement). Capsular polysaccharides can induce antibody production in the absence of T-cell help and are therefore classified as thymus-independent antigens type 2 (TI-2). It is thought that the TI-2 antigens only activate mature B cells, which may be one reason why infants respond poorly to polysaccharide antigens. Conjugation of polysaccharides to proteins makes them immunogenic in infants. The immunogenicity of such pneumococcal polysaccharide conjugate vaccines is assumed to be related to their thymus-dependent-like character, although the mechanism is not known in detail. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Method for clearing color and debris from or adding adjuvants or reactants to a selected portion of a chromatographic strip alone or in combination with a cell lysing step Inventor(s): Hudak, Robert; (Carlsbad, CA), Piasio, Roger N.; (Cumberland Foreside, ME) Correspondence: The M.H. Sears Law Firm, Chartered; 910 Seventeenth Street N.W.; Washington; DC; 20006; US Patent Application Number: 20030186463 Date filed: March 18, 2002
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Abstract: In an improved method for clearing a field of observation or treatment of unwanted color or other extraneous material, a chromatographic strip of paper, plastic, glass or like material, with or without simultaneous deposit of adjuvant or reactants on the cleared field, the strip is immersed to a level just barely above the juncture of the zone to be cleared with the preceding zone of the strip in a chase liquid, such as water containing adjuvant if desired. Where red blood cells containing parasitic pathogens such as cholera parasites are to be assayed, a lysing step is performed on the same strip prior to the clearing strip. Excerpt(s): The present invention relates to an improved method for clearing a field of observation or treatment of unwanted color and other extraneous material that is rapid and exceptionally efficacious. The method is applicable to a wide variety of assays and to other laboratory operations including chemical, biochemical and biological reactions that lend themselves to being conducted, at least for purposes of removing color or other unwanted materials that may obscure a background field of vision, on a chromatographic test strip comprised at least in part of paper, nitrocellulose, nylon, polyester, glass or like materials. The invention is also useful in depositing adjuvants or reactants on a field on which clearance of unwanted color or debris is being, or has been, effected. Many parasitic pathogens that commonly infect humans and other mammals preferentially invade red blood cells, making it necessary to design assays for detecting their presence in a blood sample by means of an assay process that includes a lysing step which breaks open these cells and exposes any parasitic agent contained therein to the action of reagents needed to identify it or to treat it experimentally. Among parasitic diseases are many of those indigenous to tropical areas, such as cholera, dengue fever, filariasis, Ebola fever, Marburg fever, etc. These diseases, which affect humans, are severe and the development of more rapid and reliable tests for early diagnosis of each is an ongoing effort. A parasitically caused disease that tends to affect dogs and related mammals is canine heartworm. In all such situations, the ability to lyse red blood cells (i.e., split them open) and thereafter immediately and rapidly clear the field of vision and further reaction of irrelevant debris and the intense red color of hemoglobin is important. In addition to red blood cells, other types of cells that may need to be lysed, followed by rapid clearing of biological debris in order to permit detection of an infective organism on a rapid and accurate basis include white cells, virions, phages, micelles, liposomes and other structures similar in that they each have an internal and an external region separated by a rupturable boundary. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Oligonucleotides for detection of vibrio parahaemolyticus and detection method for vibrio parahaemolyticus using the same oligonucleotides Inventor(s): Ishiguro, Takahiko; (Yokohama-shi, JP), Ishizuka, Tetsuya; (Yokohama-shi, JP), Saitoh, Juichi; (Yamato-shi, JP) Correspondence: Jeffrey I. Auerbach; Liniak, Berenato, Longacre & White; Suite 240; 6550 Rock Spring Drive; Bethesda; MD; 20817; US Patent Application Number: 20010031471 Date filed: March 15, 2001 Abstract: An oligonucleotide for detection or amplification of a gene selected from the group consisting of Vibrio parahaemolyticus thermostable direct hemolysin-related hemolysin genes (trh1 and trh2) and Vibrio parahaemolyticus thermostable direct
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hemolysin gene (tdh2) or RNA derived therefrom is provided. Further, method for detecting trh1, trh2 or tdh2 using said oligonucleotide is provided. Excerpt(s): The present invention relates to oligonucleotides for detection of Vibrio parahaemolyticus for clinical examination, public hygiene, food evaluation or food poisoning evaluation, and to detection methods for Vibrio parahaemolyticus. Vibrio parahaemolyticus is known as a common infectious food poisoning bacteria. Over 95% of Vibrio parahaemolyticus isolated from gastroenteritis patients are Kanagawa phenomenon-positive bacteria exhibiting hemolytic activity in Wagatsuma agar medium, whereas 99% of these bacteria isolated from fish and water are Kanagawa phenomenon-negative bacteria. This had suggested a strong relationship between pathogenic Vibrio parahaemolyticus and the Kanagawa phenomenon, and later investigation revealed that the Kanagawa phenomenon is a phenomenon that occurs due to extracellular release of Vibrio parahaemolyticus thermostable direct hemolysin (TDH). As a result, TDH has come to notice as a pathogenic factor of Vibrio parahaemolyticus. More recently, certain pathogenic strains even among the Kanagawa phenomenon-negative strains have been confirmed to have a base sequence similar to that of TDH, and produce a hemolysin (TDH-related hemolysin: TRH) with partially common antigenicity. Detection and identification of Vibrio parahaemolyticus has hitherto been complicated and time-consuming as it involves enrichment culturing and isolation culturing followed by determination of the Kanagawa phenomenon. Recently, detection and identification of Vibrio parahaemolyticus has been accomplished by the hybridization method using genetic probes specific to sequences in the TDH or TRH genes, but it has been difficult to obtain sufficient detection sensitivity for food evaluation and the like. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Orally immunogenic bacterial enterotoxins expressed in transgenic plants Inventor(s): Arntzen, Charles J.; (Superstition Mountain, AZ), Mason, Hugh S.; (Phoenix, AZ) Correspondence: Palmer & Dodge, Llp; Kathleen M. Williams; 111 Huntington Avenue; Boston; MA; 02199; US Patent Application Number: 20030176653 Date filed: December 30, 2002 Abstract: The invention provides mutant Escherichia coli heat labile (LT) and Vibrio cholerae toxin (CT) polypeptides and the polynucleotides that encode them. The mutant LT and CT polypeptides can be readily produced in plants and can be used to treat or prevent diseases caused by E. coli and V. cholera. The polypeptides are also useful as adjuvants. Excerpt(s): This application claims the benefit of U.S. application Ser. No. 60/113,507; which is incorporated in its entirety by reference. The present invention is related to genetic engineering of plants and the transformation of plants using recombinant DNA techniques to produce edible vaccines. More particularly, the invention relates to the production of oral vaccines and adjuvants in transgenic plants using polynucleotides encoding E. coli heat-labile toxin subunits LT-A and LT-B, cholera toxin subunits CT-A and CT-B, and mutants of thereof. Vaccines are administered to humans and animals to induce an immune response against viruses, bacteria, and other types of pathogenic organisms. In the economically advanced countries of the world, vaccines have brought
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many diseases under control. However, many vaccines for such diseases as poliomyelitis, measles, mumps, rabies, foot and mouth are too expensive for use in lesser developed countries. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Pharmaceutical proteins, human therapeutics, human serum albumin, insulin, native cholera toxic b submitted on transgenic plastids Inventor(s): Daniell, Henry; (Winter Park, FL) Correspondence: Schnader Harrison Segal & Lewis; IP Department 36th Floor; 1600 Market Street; Philadelphia; PA; 19103; US Patent Application Number: 20030204864 Date filed: April 18, 2001 Abstract: Transgenic chloroplast technology could provide a viable solution to the production of Insulin-like Growth Factor I (IGF-I), Human Serum Albumin (HSA), or interferons (IFN) because of hyper-expression capabilities, ability to fold and process eukaryotic proteins with disulfide bridges (thereby eliminating the need for expensive post-purification processing). Tobacco is an ideal choice because of its large biomass, ease of scale-up (million seeds per plant), genetic manipulation and impending need to explore alternate uses for this hazardous crop. Therefore, all three human proteins will be expressed as follows: a) Develop recombinant DNA vectors for enhanced expression via tobacco chloroplast genomes b) generate transgenic plants c) characterize transgenic expression of proteins or fusion proteins using molecular and biochemical methods d) large scale purification of therapeutic proteins from transgenic tobacco and comparison of current purification/processing methods in E. coli or yeast e) Characterization and comparison of therapeutic proteins (yield, purity, functionality) produced in yeast or E. coli with transgenic tobacco f) animal testing and pre-clinical trials for effectiveness of the therapeutic proteins.Mass production of affordable vaccines can be achieved by genetically engineering plants to produce recombinant proteins that are candidate vaccine antigens. The B subunits of Enteroxigenic E. coli (LTB) and cholera toxin of Vibrio cholerae (CTB) are examples of such antigens. When the native LTB gene was expressed via the tobacco nuclear genome, LTB accumulated at levels less than 0.01% of the total soluble leaf protein. Production of effective levels of LTB in plants, required extensive codon modification. Amplification of an unmodified CTB coding sequence in chloroplasts, up to 10,000 copies per cell, resulted in the accumulation of up to 4.1% of total soluble tobacco leaf protein as oligomers (about 410 fold higher expression levels than that of the unmodified LTB gene). PCR and Southern blot analyses confirmed stable integration of the CTB gene into the chloroplast genome. Western blot analysis showed that chloroplast synthesized CTB assembled into oligomers and was antigenically identical to purified native CTB. Also, GM.sub.1,-ganglioside binding assays confirmed that chloroplast synthesized CTB binds to the intestinal membrane receptor of cholera toxin, indicating correct folding and disulfide bond formation within the chloroplast. In contrast to stunted nuclear transgenic plants, chloroplast transgenic plants were morphologically indistinguishable from untransformed plants, when CTB was constitutively expressed. The introduced gene was stably inherited in the subsequent generation as confirmed by PCR and Southern blot analyses. Incrased production of an efficient transmucosal carrier molecule and delivery system, like CTB, in transgenic chloroplasts makes plant based oral vaccines and fusion proteins with CTB needing oral administration a much more practical approach.
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Excerpt(s): (60/115,987) Research efforts have been made to synthesize high value pharmacologically active recombinant proteins in plants. Recombinant proteins such as vaccines, monoclonal antibodies, hormones, growth factors, neuropeptides, cytotoxins, serum proteins and enzymes have been expressed in nuclear transgenic plants (May et al., 1996). It has been estimated that one tobacco plant should be able to produce more recombinant protein than a 300-liter fermenter of E. coli. In addition, a tobacco plant produces a million seeds, thereby facilitating large-scale production. Tobacco is also an ideal choice because of its relative ease of genetic manipulation and an impending need to explore alternate uses for this hazardous crop. (60/185,987) A primary reason for the high cost of production via fermentation is the cost of carbon source co-substances as well as maintenance of a large fermentation facility. In contrast, most estimates of plant production are a thousand-fold less expensive than fermentation. Tissue specific expression of high value proteins in leaves can enable the use of crop plants as renewable resources. Harvesting the cobs, tubers, seeds or fruits for food and feed and leaves for value added products should result in further economy with no additional investment. (60/185,987) However, one of the major limitations in producing pharmaceutical proteins in plants is their low level of foreign protein expression, despite reports of higher level expression of enzymes and certain proteins. May et al. (1998) discuss this problem using the following examples. Although plant derived recombinant hepatitis B surface antigen was as effective as a commercial recombinant vaccine, the levels of expression in transgenic tobacco were low (0.01% of total soluble protein). Even though Norwalk virus capsid protein expressed in potatoes caused oral immunization when consumed as food (edible vaccine), expression levels were low (0.3% of total soluble protein). A synthetic gene coding for the human epidermal growth factor was expressed only up to 0.001% of total soluble protein in transgenic tobacco. Human serum albumin has been expressed only up to 0.02% of the total soluble protein in transgenic plants. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Protease obtained from Vibrio metschnikovii variants and detergent compositions comprising the above protease Inventor(s): Jhon, Sung-Hoo; (Seoul, KR), Jin, Ghee-Hong; (Seoul, KR), Lee, HyunHwan; (Yongin Si, KR), Rho, Hyune-Mo; (Seoul, KR) Correspondence: Jacobson Holman Pllc; 400 Seventh Street N.W.; Suite 600; Washington; DC; 20004; US Patent Application Number: 20030096723 Date filed: August 27, 2002 Excerpt(s): The present invention relates to a Vibrio metscnikovii variants, more particularly to a biochemical characteristics of protease which is obtained from Vibrio metscnikovii variant strains such as Vibrio metschnikovii KS1, Vibrio metschnikovii KS1 transformed with pDSBCm, Vibrio metschnikovii KS1 transformed with pSBCm and Vibrio metschnikovii RH530 N-4-8 strain which is the mother strain of Vibrio metschnikovii and to a detergent compositions including the protease. Up to now, an enzyme for a detergent has been exploited to remove contaminants by protein, fat, starch, etc. effectively with being added to a powder-type or liquid-type detergents. Recently, the amount of enzyme for a detergent increases to reinforce a declined washing power that is resulted from reducing amount of phosphate or toxic surfactant provoking a water pollution. The enzyme for a detergent is classified into a protease, a
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lipase and a cellulase by decomposing cellulose which results in preventing decoloration of cloths. Presently, the protease among these is used as a main enzyme world-widely. The enzymes mentioned above are also utilized as a detergent by being added into an automatic dish washer to reinforce a washing power. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Transgenic plant-based vaccines Inventor(s): Arakawa, Takeshi; (Okinawa, JP), Langridge, William H.R.; (Loma Linda, CA), Yu, Jie; (Redlands, CA) Correspondence: Sheldon & Mak; C/o David A. Farah, M.D.; 9th Floor; 225 South Lake Avenue; Pasadena; CA; 91101; US Patent Application Number: 20030021803 Date filed: September 16, 2002 Abstract: A DNA construct that encodes, upon expression in a plant cell, a fusion protein comprising a multimeric cholera toxin B subunit and a first immunogenic antigen from a causal factor of a mammalian disease. A DNA construct that encodes, upon expression in a plant cell, a fusion protein comprising a cholera toxin A2 subunit, a multimeric cholera toxin B subunit, a first immunogenic antigen from a causal factor of a mammalian disease, and a first immunogenic antigen from a causal factor of a mammalian disease. A method of inducing partial or complete immunity to an infectious disease in a mammal comprising providing to the mammal for oral consumption an effective amount of the plant transformed with a construct according to the present invention Excerpt(s): The present Application is a divisional of U.S. patent application Ser. No. 09/771,536, filed Jan. 29, 2001, entitled "Transgenic Plant-Based Vaccines," which claims the benefit of U.S. provisional patent application No. 60/178,403, filed Jan. 27, 2001, entitled "Production of a Cholera Toxic B Subunit-Rotavirus NSP4 Enterotoxin Fusion Protein in Potato"; and the present application claims the benefit of PCT/US01/02663, filed Jan. 29, 2001 entitled "Transgenic Plant-Based Vaccines," the contents of which is incorporated herein by reference in their entirety. Acute infectious enteric diseases, such as acute gastroenteritis, are second only to acute respiratory diseases as a cause of human death worldwide. Cholera, rotavirus and enterotoxigenic E. coli are the three major causative agents of acute gastroenteritis. Human rotavirus, for example, is the most important cause of infantile gastroenteritis worldwide. This virus has a tremendous public health impact worldwide, infecting nearly every child in the first few years of life. Rotavirus infection is responsible for approximately 1 million deaths each year and an estimated 18 million hospitalizations. 20% to 40% of the hospitalizations are for childhood diarrhea, which makes the rotavirus the most important single cause of diarrheal mortality among children. Treatment for acute gastroenteritis includes antibiotics and metabolic support. However, adequate treatment is often not available, particularly in lesser developed areas where the incidence of acute gastroenteritis is highest. Prevention of acute gastroenteritis would be preferable to treatment. However, preventative measures, such as the provision of safe drinking water, are often inadequate or unavailable. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Keeping Current In order to stay informed about patents and patent applications dealing with cholera, you can access the U.S. Patent Office archive via the Internet at the following Web address: http://www.uspto.gov/patft/index.html. You will see two broad options: (1) Issued Patent, and (2) Published Applications. To see a list of issued patents, perform the following steps: Under “Issued Patents,” click “Quick Search.” Then, type “cholera” (or synonyms) into the “Term 1” box. After clicking on the search button, scroll down to see the various patents which have been granted to date on cholera. You can also use this procedure to view pending patent applications concerning cholera. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.
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CHAPTER 6. BOOKS ON CHOLERA Overview This chapter provides bibliographic book references relating to cholera. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on cholera 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 “cholera” (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 cholera: •
Rational Use of Drugs in the Management of Acute Diarrhoea in Children Source: Geneva, Switzerland: World Health Organization. 1990. 75 p. Contact: Available from WHO Publications Center USA. 49 Sheridan Avenue, Albany, NY 12210. (518) 436-9686. Fax (518) 436-7433. PRICE: $12.60. ISBN: 9241561424. Order number 1150355. Summary: This book provides information about the rational use of drugs in the management of acute diarrhea in infants and young children, and tackles the problems posed by the prescribing of clinically useless and potentially dangerous drugs. The authors argue against the widespread use of medicines that have no established clinical benefits, are frequently harmful, and may delay or replace effective treatment measures. A table of drugs judged effective lists four first-choice antimicrobials, and six alternatives, useful in the management of cholera, shigella dysentery, amoebiasis, and giardiasis. Apart from these cases of specific etiology, readers are informed that
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antidiarrheal drugs and antiemetic should never be used for children, as none has any proven practical value and some are frankly dangerous. This statement is substantiated through a thorough review of data on eleven antidiarrheal drugs widely used in paediatric practice. The book concludes that none of these preparations has any documented benefits, some actually prolong diarrhoea, and others have been shown to produce severe and sometimes fatal side-effects. Specific compounds covered include diphenoxylate hydrochloride, loperamide, streptomycin and dihydrostreptomycin, neomycin, hydroxyquinolines, nonabsorbable sulfonamides, kaolin and pectin, activated charcoal, and attapulgite and smectite. Each chapter includes numerous references. (AA-M). •
Health in the Americas Source: Washington, DC: Pan American Health Organization. 1998. 2v., [890 p.]. Contact: Available from Pan American Health Organization, Sales and Distribution Center. P.O. Box 27, Annapolis Junction, MD 20701-0027. (301) 617-7806. Fax (301) 2069789. E-mail:
[email protected]. Website: www.paho.org. PRICE: $60.00 in the United States; $44.00 in Latin America and the Caribbean; plus shipping and handling. ISBN: 9275115699 for English version; 9275315698 for Spanish version. Summary: This two-volume reference set offers information on health indicators and trends affecting the 800 million inhabitants of the Americas and the Caribbean. The set includes the most recent data on socioeconomic conditions, demographic characteristics, existing and emerging diseases, environmental issues, and the health sector's response. Volume I explores the health situation regionwide. The regional analysis examines public health trends, the health status of various population groups, major diseases and health problems, the health sector's response to these conditions, and the status of external technical and financial cooperation destined for health. Volume II contains country reports that present the most current data for each of the region's 45 countries and territories from the perspective of each country's socioeconomic and demographic context and then sketches health prospects for the immediate future. The country reports all cover the general health situation and trends (including socioeconomic perspectives, mortality, and morbidity), specific health problems (including analysis by population groups, diseases and health impairments, and risk factors), and the response of the health systems (including health policies and programs, health research and technology, and costs and financing of services). The set offers statistical presentations of the major diseases and health impairments, mortality and morbidity trends, and health services, as well as the impact of environmental factors and economic conditions on health. The digestive system diseases discussed are hepatitis, cholera, schistosomiasis, malaria, nutritional diseases, and diseases of metabolism. Each chapter offers extensive charts, tables, figures, and 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 “cholera” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “cholera” (or a synonym) in their titles. The
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following is indicative of the results you might find when searching for “cholera” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •
Advances in Research on Cholera and Related Diarrheas: Proceedings of the 18th Joint Conference on by S. Kuwahara (Editor), N. F. Pierce (Editor) (1985); ISBN: 0898386802; http://www.amazon.com/exec/obidos/ASIN/0898386802/icongroupinterna
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Cars, Cholera and Cows: Virtual Risk and the Management of Uncertainty by John Adams; ISBN: 0853361355; http://www.amazon.com/exec/obidos/ASIN/0853361355/icongroupinterna
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Cholera by William Coleman, et al (2003); ISBN: 0791073033; http://www.amazon.com/exec/obidos/ASIN/0791073033/icongroupinterna
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Cholera by William B. Greenough (Editor), D. Barua (Editor) (1992); ISBN: 0306440776; http://www.amazon.com/exec/obidos/ASIN/0306440776/icongroupinterna
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Cholera (Epidemics) by Chris Hayhurst (2001); ISBN: 0823933458; http://www.amazon.com/exec/obidos/ASIN/0823933458/icongroupinterna
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Cholera 1832 : the social response to an epidemic by R. J. Morris; ISBN: 0856643777; http://www.amazon.com/exec/obidos/ASIN/0856643777/icongroupinterna
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Cholera 1849: Reported Deaths in the Coventry Herald by Beverly Wishart (1997); ISBN: 1900372185; http://www.amazon.com/exec/obidos/ASIN/1900372185/icongroupinterna
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Cholera and Famine in British India, 1870-1930 by Maureen Sibbons (1995); ISBN: 0906250307; http://www.amazon.com/exec/obidos/ASIN/0906250307/icongroupinterna
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Cholera and Public Health (History in Depth) by Neil Tonge, Michael Quincey; ISBN: 0333350804; http://www.amazon.com/exec/obidos/ASIN/0333350804/icongroupinterna
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Cholera and Related Diarrheas: Molecular Aspects of a Global Health Problem: (Proceedings of The) 43rd Nobel Symposium, Stockholm, August 6-11, 1978 by J. Holmgren (Editor), et al (1980); ISBN: 3805530609; http://www.amazon.com/exec/obidos/ASIN/3805530609/icongroupinterna
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Cholera Bulletin by Association of Physicians, introduction by Professor Charles E. Rosenberg Association of Physicians; ISBN: 0405039425; http://www.amazon.com/exec/obidos/ASIN/0405039425/icongroupinterna
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Cholera in Africa : diffusion of the disease 1970-1975, with particular emphasis on West Africa by Robert F. Stock; ISBN: 0853020507; http://www.amazon.com/exec/obidos/ASIN/0853020507/icongroupinterna
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Cholera in Post-Revolutionary Paris: A Cultural History (Studies on the History of Society and Culture, 25) by Catherine J. Kudlick (1996); ISBN: 0520202732; http://www.amazon.com/exec/obidos/ASIN/0520202732/icongroupinterna
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Cholera morbus : epidemie, medicina e pregiudizi nel Salento dell'Ottocento by Ennio De Simone; ISBN: 8872610923; http://www.amazon.com/exec/obidos/ASIN/8872610923/icongroupinterna
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Cholera on the American Continents by A. F. De Castro (Editor), W. F. Almeida (Editor) (1993); ISBN: 094439812X; http://www.amazon.com/exec/obidos/ASIN/094439812X/icongroupinterna
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Cholera Problem by Oscar Felsenfeld (1967); ISBN: 0875270085; http://www.amazon.com/exec/obidos/ASIN/0875270085/icongroupinterna
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Cholera Years by Rosenberg; ISBN: 0226726789; http://www.amazon.com/exec/obidos/ASIN/0226726789/icongroupinterna
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Cholera, Chloroform and the Science of Medicine: A Life of John Snow by Peter Vinten-Johansen, et al (2003); ISBN: 019513544X; http://www.amazon.com/exec/obidos/ASIN/019513544X/icongroupinterna
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Cholera, Fever & English Medicine 1825-65 by Margaret Pelling (1989); ISBN: 0198218729; http://www.amazon.com/exec/obidos/ASIN/0198218729/icongroupinterna
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Cholera. by Saunders, 1974.Rc Philadelphia; ISBN: 0721615430; http://www.amazon.com/exec/obidos/ASIN/0721615430/icongroupinterna
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Cholera: The American Scientific Experience, 1947-1980 by John R. Seal, W. E. Van Heyningen; ISBN: 0865314004; http://www.amazon.com/exec/obidos/ASIN/0865314004/icongroupinterna
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Confronting Cholera: The Development of a Hemispheric Response to the Epidemic by Henry Hamman (Editor) (1991); ISBN: 0935501398; http://www.amazon.com/exec/obidos/ASIN/0935501398/icongroupinterna
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Cytokines, Cholera and the Gut by G. T. Keusch (Editor), Masanobu Kawakami (Editor); ISBN: 905199298X; http://www.amazon.com/exec/obidos/ASIN/905199298X/icongroupinterna
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Darkened House: Cholera in Nineteenth Century Canada: 1832-1871 (Social History of Canada, No. 31) by Geoffrey Bilson; ISBN: 0802064027; http://www.amazon.com/exec/obidos/ASIN/0802064027/icongroupinterna
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Death in Hamburg: Society and Politics in the Cholera Years, 1830-1910 by Richard J. Evans; ISBN: 014012473X; http://www.amazon.com/exec/obidos/ASIN/014012473X/icongroupinterna
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Disease and Civilization : The Cholera in Paris, 1832 by François Delaporte (Author), Arthur Goldhammer (Translator); ISBN: 026254055X; http://www.amazon.com/exec/obidos/ASIN/026254055X/icongroupinterna
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Epidemics: Deadly Diseases Throughout History: The Plague, AIDS, Tuberculosis, Cholera, Small Pox, Polio, Influenza, Malaria (Epidemics: Deadly Diseases Throughout History Series) by Holly Cefrey, et al; ISBN: 0823992020; http://www.amazon.com/exec/obidos/ASIN/0823992020/icongroupinterna
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Eradication of hog cholera and African swine fever : report of the FAO/EEC Expert Consultation, held in Hanover, Federal Republic of Germany, 8-10 September, 1976; ISBN: 9251001820; http://www.amazon.com/exec/obidos/ASIN/9251001820/icongroupinterna
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Guidelines for Cholera Control by World Health Organization (1993); ISBN: 924154449X; http://www.amazon.com/exec/obidos/ASIN/924154449X/icongroupinterna
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Guidelines for the laboratory diagnosis of cholera; ISBN: 9241540346; http://www.amazon.com/exec/obidos/ASIN/9241540346/icongroupinterna
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Latin America in the Time of Cholera: Electoral Politics, Market Economics, and Permanent Crisis by James Petras, Morris Morley; ISBN: 0415905362; http://www.amazon.com/exec/obidos/ASIN/0415905362/icongroupinterna
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Pointers to the Common Remedies: Stomach and Digestive Disorders, Constipation, Acute Diarrhoea, Acute Intestinal Conditions and Colic, Epidemic Diarrhoea of Children, Acute Dysentery, Cholera by M.L. Tyler (1981); ISBN: 0946717311; http://www.amazon.com/exec/obidos/ASIN/0946717311/icongroupinterna
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Russia and the cholera, 1823-1832 by Roderick Erle McGrew (Author); ISBN: B00005XTYP; http://www.amazon.com/exec/obidos/ASIN/B00005XTYP/icongroupinterna
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Russia and the Cholera, Eighteen Twenty-Three-Eighteen Thirty-Two by Roderick E. McGrew; ISBN: 029903710X; http://www.amazon.com/exec/obidos/ASIN/029903710X/icongroupinterna
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Smallpox: Cholera by Vasile Tudor; ISBN: 0856260924; http://www.amazon.com/exec/obidos/ASIN/0856260924/icongroupinterna
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Stories in the Time of Cholera: Racial Profiling during a Medical Nightmare by Charles L. Briggs, Clara Mantini-Briggs; ISBN: 0520230310; http://www.amazon.com/exec/obidos/ASIN/0520230310/icongroupinterna
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The Cholera Crisis (Child to Child Readers) by D Bailey; ISBN: 0582245346; http://www.amazon.com/exec/obidos/ASIN/0582245346/icongroupinterna
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The cholera epidemic in Latin America : hearing before the Subcommittee on Western Hemisphere Affairs of the Committee on Foreign Affairs, House of Representatives, One Hundred Second Congress, first session, May 1, 1991; ISBN: 0160353947; http://www.amazon.com/exec/obidos/ASIN/0160353947/icongroupinterna
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The Cholera Years: The United States in 1832, 1849, and 1866 by Charles E. Rosenberg (1987); ISBN: 0226726770; http://www.amazon.com/exec/obidos/ASIN/0226726770/icongroupinterna
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The first spasmodic cholera epidemic in York, 1832 by Michael Durey; ISBN: 0900701390; http://www.amazon.com/exec/obidos/ASIN/0900701390/icongroupinterna
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The history of the cholera in Exeter in 1832 by Thomas Shapter; ISBN: 0854096744; http://www.amazon.com/exec/obidos/ASIN/0854096744/icongroupinterna
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The Imported Food and Feedingstuffs (Safeguards Against Cholera) Regulations (Northern Ireland) 1992: European Communities679.00:0/01 (Statutory Rule: 1992: 434) (1993); ISBN: 0337903344; http://www.amazon.com/exec/obidos/ASIN/0337903344/icongroupinterna
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The Official Patient's Sourcebook on Cholera: A Revised and Updated Directory for the Internet Age by Icon Health Publications (2002); ISBN: 0597832927; http://www.amazon.com/exec/obidos/ASIN/0597832927/icongroupinterna
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The return of the plague : British society and the cholera, 1831-2 by Michael Durey; ISBN: 0391010387; http://www.amazon.com/exec/obidos/ASIN/0391010387/icongroupinterna
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The Sewer Sleuth: a Tale of Victorian Cholera (Sparks) by Julia Jarman; ISBN: 0749625902; http://www.amazon.com/exec/obidos/ASIN/0749625902/icongroupinterna
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The Vibrios by A. L. Furniss; ISBN: 0118871021; http://www.amazon.com/exec/obidos/ASIN/0118871021/icongroupinterna
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Understanding Global Issues - Pack: Water & Health: Cholera's Grim Warning; ISBN: 0850489873; http://www.amazon.com/exec/obidos/ASIN/0850489873/icongroupinterna
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Water and Health: Cholera's Grim Warning by Ric Buckley (1992); ISBN: 085048927X; http://www.amazon.com/exec/obidos/ASIN/085048927X/icongroupinterna
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Women & children of Bangladesh as experimental animals : military objectives of cholera research & violation of biomedical ethics in the research on human subjects; ISBN: 9844670500; http://www.amazon.com/exec/obidos/ASIN/9844670500/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 “cholera” (or synonyms) into the search box, and select “books only.” From there, results can be sorted by publication date, author, or relevance. The following was recently catalogued by the National Library of Medicine:10 •
[Abstracts of papers prepared in advance of the Symposium on Cholera Research, to be held at the East-West Center in Honolulu, Hawaii, January 24-29, 1965.; Year: 1958; Honolulu, 1965]
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A dissertation upon the cholera infantum: to which are added, rules and regulations, as preventive means of the autumnal diseases of children: which gained the Boylstonian prize, for the year 1803 Author: Mann, James,; Year: 1974; Boston: Printed for Young; Minns, printers., 1804
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A letter on the cholera as it occurred in Cincinnati, Ohio, in October 1832: addressed to Dr. Short of Lexington, Ky. Author: Henry, J. (John),; Year: 1966; [Lexington Ky.: s.n., 1832]
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An interim report of the cholera epidemic, December 20, 1963-April 30, 1964, Vietnam. Author: United States. Agency for International Development. Public Health Division.; Year: 1964; [Saigon, 1964]
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An outline of the diagnosis and treatment of cholera. Author: Indian Council of Medical Research.; Year: 1866; New Delhi, 1966
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Antibodies in blood eight months after inoculation with supersonic wave-treated cholera vaccine. Author: Japan. Army Medical College, Tokyo. Epidemiology Laboratory.; Year: 1948; [Tokyo] 1940
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In addition to LOCATORPlus, in collaboration with authors and publishers, the National Center for Biotechnology Information (NCBI) is currently adapting biomedical books for the Web. The books may be accessed in two ways: (1) by searching directly using any search term or phrase (in the same way as the bibliographic database PubMed), or (2) by following the links to PubMed abstracts. Each PubMed abstract has a "Books" button that displays a facsimile of the abstract in which some phrases are hypertext links. These phrases are also found in the books available at NCBI. Click on hyperlinked results in the list of books in which the phrase is found. Currently, the majority of the links are between the books and PubMed. In the future, more links will be created between the books and other types of information, such as gene and protein sequences and macromolecular structures. See http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Books.
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Cholera [by] R. Pollitzer. With a chapter on world incidence written in collaboration with S. Swaroop and a chapter on problems in immunology and an annex written in collaboration with W. Burrows. Author: Pollitzer, R. (Robert),; Year: 1962; Geneva, World Health Organization, 1959
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Cholera epidemics in Japan. With a monograph on the influence of the habits and customs of races on the prevalence of cholera. Author: Simmons, Duane B.,; Year: 1974; Shanghai, 1880
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Cholera research in India, 1934-1940; a review, under the Indian Research Fund Association. Author: Taylor, John,; Year: 1969; Cawnpore, Job Press, 1941
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Cholera, its prevention and cure. Author: DeMonte, A. J. H.; Year: 1973; Calcutta, Thacker, Spink [1940?]
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Cholera; its causes, prevention, and treatment. Author: Marston, Charles Henry.; Year: 1849; Devizes: C. Gillman, 1866
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Cholera; the work of the Pakistan-SEATO Cholera Research Laboratory. Author: SEATO.; Year: 1831; Bangkok] 1967
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Experimental research on toxic fractions of U. S. W. cholera vaccine. Author: Japan. Army Medical College, Tokyo. Epidemiology Laboratory.; Year: 1973; [Tokyo] 1940
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Guidelines for the laboratory diagnosis of cholera. Author: World Health Organization. Bacterial Diseases Unit.; Year: 1967; Geneva, 1974; ISBN: 0924154034
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King Cholera; the biography of a disease. Author: Longmate, Norman.; Year: 1969; London, Hamilton [c1966]
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Observations on cholera as it appeared at Port Glasgow during the months of July and August, 1831; illustrated by numerous cases. Author: Marshall, John,; Year: 1865; Edinburgh: Waugh; Innes, 1831
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Paupers, criminals and cholera at Dorchester in 1854 [being letters from the Rev. Henry Moule, Vicar of Fordington St. George, to H. R. H. the Prince Consort during the cholera of 1854]. Author: Moule, Henry,; Year: 1855; Guernsey, C. I., Toucan, 1968
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Proceedings of the Cholera Research Symposium, January 24-29, 1965, Honolulu, Hawaii. Convened at the East-West Center of the University of Hawaii. Sponsored by the University of Hawaii's Pacific Biomedical Research Center and the Centerfor Cultural and Technical Interchange between East and West. Author: East-West Center.; Year: 1965; Washington, 1965
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Report of the commissioners appointed to inquire into the causes which have led to, or have aggravated the late outbreak of cholera in the towns of Newcastle-upon-Tyne, Gateshead, and Tynemouth. London, H. M. Stationery Off., 1854. Author: Great Britain. Cholera Inquiry Commission.; Year: 1968
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Report of the outbreak of cholera in the sub-districts of Berwick Street, Golden Square, and St. Anne's Author: Fraser, D.; Year: 1881; London: George E. Eyre and William Spottiswoode, 1855
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Report on the capabilities of the metropolitan workhouses for the reception and treatment of cholera cases. London, H. M. Stationery Off., 1848. Author: Great Britain. Poor Law Board.; Year: 1967
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Requirements for biological substances. 3. Requirements for yellow fever vaccine. 4. Requirements for cholera vaccine. Report. Author: World Health Organization. Study Group on Requirements for Yellow Fever Vaccine, and Requirements for Cholera Vaccine.; Year: 1966; Geneva, 1959
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Research on cholera vaccines treated with supersonic waves; effects of formalin on antigenic properties. Author: Japan. Army Medical College, Tokyo. Epidemiology Laboratory.; Year: 1941; [Tokyo] 1939
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Russia and the cholera, 1823-1832. Author: McGrew, Roderick E. (Roderick Erle); Year: 1965; Madison, Univ. of Wisconsin Press, 1965
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Serological studies on supersonic wave-treated polyvalent cholera vaccine. Author: Japan. Army Medical College, Tokyo. Epidemiology Laboratory.; Year: 1973; [Tokyo] 1942
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The cholera problem. Author: Felsenfeld, Oscar.; Year: 1967; St. Louis, Green [c1967]
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The cholera. Brief hints for the prevention of cholera, with a plain account of its symptoms, the proper preventive measures, and the management of its early stages. Sanctioned by the Medical Faculty of Lowell. Author: Mason, Augustus,; Year: 1964; Lowell: B. H. Penhallow, 1849
Chapters on Cholera In order to find chapters that specifically relate to cholera, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and cholera 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 “cholera” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on cholera: •
Secretory Diarrhea Source: in Brandt, L., et al., eds. Clinical Practice of Gastroenterology. Volume One. Philadelphia, PA: Current Medicine. 1999. p. 615-625. Contact: Available from W.B. Saunders Company. Order Fulfillment, 6277 Sea Harbor Drive, Orlando, FL 32887. (800) 545-2522. Fax (800) 874-6418 or (407) 352-3445. Website: www.wbsaunders.com. PRICE: $235.00 plus shipping and handling. ISBN: 0443065209 (two volume set); 0443065217 (volume 1); 0443065225 (volume 2). Summary: Clinical investigators broadly categorize diarrhea as secretory or osmotic, by measuring electrolytes and the osmolality of fecal fluid. In secretory diarrheas, analysis of the fecal fluid reveals that sodium, potassium, and accompanying anions account entirely for the observed osmolarity. This chapter on secretory diarrhea is from a lengthy textbook that brings practitioners up to date on the complexities of gastroenterology practice, focusing on the essentials of patient care. The author of this chapter reassesses the clinical and basic models of secretory diarrheas and considers how relevant they may be to the realities of clinical practice. Acute diarrheas may have a secretory component, but in Western countries, they are generally transient and rarely life threatening conditions, except perhaps in infants. Despite the vast array of diagnostic studies that can be used to evaluate a complaint of chronic diarrhea, making a specific diagnosis is often difficult. The basic and clinical models of secretory diarrhea in use have been shaped by the medical understanding of cholera. A focused and orderly workup of the patient can assist in understanding the pathophysiology, and then one can begin appropriate treatment. However, the symptoms of diarrhea can often be controlled adequately without altering the primary pathophysiologic abnormality.
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Patients can be placed on a therapeutic trial with loperamide or diphenoxylate. Although patients often take these drugs sporadically with some success, a regular dosing schedule may provide significant amelioration of symptoms. 5 figures. 5 tables. 36 references. •
Infectious Diarrhea and Bacterial Food Poisoning Source: in Feldman, M.; Friedman, L.S.; Sleisenger, M.H. Sleisenger and Fordtran's Gastrointestinal and Liver Disease: Pathophysiology/Diagnosis/Management. 7th ed. [2-volume set]. St. Louis, MO: Saunders. 2002. p. 1864-1913. Contact: Available from Elsevier. 11830 Westline Industrial Drive, St. Louis, MO 63146. (800) 545-2522. Fax (800) 568-5136. Website: www.us.elsevierhealth.com. PRICE: $229.00 plus shipping and handling. ISBN: 0721689736. Summary: This chapter on infectious diarrhea and bacterial food poisoning is from a comprehensive and authoritative textbook that covers disorders of the gastrointestinal tract, biliary tree, pancreas, and liver, as well as the related topics of nutrition and peritoneal disorders. Topics include changes in normal flora caused by diarrhea; classification of bacterial diarrhea; toxigenic diarrheas, including cholera, other vibrios, Aeromonas, Plesiomonas shigelloides, and Escherichia coli; invasive pathogens, including Shigella, nontyphoidal Salmonellosis, typhoid fever, Campylobacter, and Yersinia; viral diarrhea, including that due to rotavirus, calicivirus, enteric andenovirus, astrovirus, and torovirus; traveler's diarrhea, including microbiology, epidemiology, clinical features, and prevention; diarrhea in the elderly; diagnosis of infectious diarrheal disease; treatment of infectious diarrhea, including with fluid therapy, diet, antimicrobial drugs, and nonspecific therapy; tuberculosis of the gastrointestinal tract; and bacterial food poisoning, including that from Clostridium perfringers, Saphylococcus auerus, Listeria, Bacillus cereus, botulism, and Bacillus anthracis. The chapter includes a mini-outline with page citations, illustrations, and extensive references. 8 figures. 16 tables. 329 references.
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Socioeconomic, Ethnic and Geographical Health Issues Source: in Scully, C. and Cawson, R.A. Medical Problems in Dentistry. 4th ed. Woburn, MA: Butterworth-Heinemann. 1998. p. 529-547. Contact: Available from Butterworth-Heinemann. 225 Wildwood Avenue, Woburn, MA 01801-2041. (800) 366-2665 or (781) 904-2500. Fax (800) 446-6520 or (781) 933-6333. E-mail:
[email protected]. Website: www.bh.com. PRICE: $110.00. ISBN: 0723610568. Summary: This chapter on socioeconomic, ethnic, and geographical health issues is from a text that covers the general medical and surgical conditions relevant to the oral health care sciences. The authors discuss mainly the relevant imported diseases, problems related to social deprivation, and those which religious or ethnic groups may present during oral health care. Topics include infections, including typhoid, paratyphoid, cholera, nonvenereal treponematoses, yaws (framboesia), granuloma inguinale (donovanosis), lymphogranuloma vereneum, blood-borne viruses, arboviruses, arenaviruses, rhabdoviruses (Ebola, rabies), systemic mycoses, Aspergillosis, blastomycosis, coccidioidomycosis, cryptococcosis, histoplasmosis, mucormycosis, rhinosporidiosis, sporotrichosis, systemic candidosis, parasitic infestations, scabies, lice, fleas, malaria, toxoplasmosis, leishmaniasis, trichinosis, echinococcosis, cysticercosis, myiasis, larva migrans, filariasis, trichuriasis, gnathostomiasis, and oral submucous fibrosis. For each condition, the authors discuss general aspects, diagnosis and
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management issues, dental aspects, and patient care strategies. The chapter includes a summary of the points covered. 9 tables. 45 references. •
Routes of Transmission of Pathogenic Microorganisms Source: in Joneja, J.M. and Bielory, L. Understanding Allergy, Sensitivity, and Immunity: A Comprehensive Guide. New Brunswick, NJ: Rutgers University Press. 1990. p. 20-25. Contact: Available from Rutgers University Press. 109 Church Street, New Brunswick, NJ 08901. (201) 932-7037. PRICE: $35 (cloth) or $13.95 (paperback). ISBN: 0813515203 (cloth) or 0813515211 (paperback). Summary: This chapter, from a comprehensive guide to understanding allergy, sensitivity, and immunity, discusses the routes of transmission of pathogenic microorganisms, notably the digestive route. Microorganisms in food, water, and other beverages are introduced into the digestive tract during eating and drinking. They may cause infections of the alimentary system alone or in other organ systems after dissemination from the initial infection site. Cholera, typhoid fever, and shigellosis are intestinal infections caused by bacteria that can be transmitted in contaminated water supplies. Hepatitis A virus can be transmitted in the same manner. Escherichia coli, a normal inhabitant of the healthy intestinal tract, but which can cause gastroenteritis, is commonly present in water contaminated with feces. The authors also discuss the variety of ways that food can be contaminated.
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Toxigenic Diarrheas, Congenital Diarrheas, and Cystic Fibrosis: Disorders of Intestinal Ion Transport Source: in Hoffman, J.F. and De Weer, P., eds. Annual Review of Physiology. Palo Alto, CA: Annual Reviews Inc. 1993. Volume 55: 631-655. Contact: Available from Annual Reviews Inc. 4139 El Camino Way, P.O. Box 10139, Palo Alto, CA 94303-0139. (800) 523-8635. Fax (415) 424-0910. E-mail:
[email protected]. PRICE: $46.00. ISBN: 0824303555. ISSN: 00664278. Individual chapter reprints available from Annual Reviews Preprints and Reprints. (800) 347-8007 or (415) 259-5017. Base price $13.50 per article. Summary: This entry from the Annual Review of Physiology discusses the pathophysiology of enterotoxic diarrheas, congenital diarrheas, and cystic fibrosis (CF). The authors begin with a brief summary of the ion transport properties of the intestine as they relate to the active secretion of electrolytes. Other topics include Vibrio Cholerae enterotoxins, including the cholera toxin and the enteric nervous system; heat-stable Escherichia Coli enterotoxin and guanylin; congenital defects of intestinal electrolyte transport; and directions for future research. 3 figures. 128 references.
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CHAPTER 7. MULTIMEDIA ON CHOLERA Overview In this chapter, we show you how to keep current on multimedia sources of information on cholera. We start with sources that have been summarized by federal agencies, and then show you how to find bibliographic information catalogued by the National Library of Medicine.
Video Recordings An excellent source of multimedia information on cholera is the Combined Health Information Database. You will need to limit your search to “Videorecording” and “cholera” using the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find video productions, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Videorecording (videotape, videocassette, etc.).” Type “cholera” (or synonyms) into the “For these words:” box. The following is a typical result when searching for video recordings on cholera: •
Plagued Contact: Filmakers Library, Incorporated, 124 East 40th St, New York, NY, 10016, (212) 808-4980. Summary: This videorecording is a four-part series that documents historic information on the occurrence and origins of epidemics and pandemics worldwide, not only as infectious diseases, but as products of societal, political, and economic forces that encourage the spread of disease. It draws the parallel with the rise in the incidence of HIV and AIDS, and asserts that AIDS will continue to be an increasing problem unless societies learn the lessons of history. Part 1, "The Origins of Disease," investigates how new diseases arise. It profiles Korean hemorrhagic fever, well-documented during the Korean War. This disease is now infecting rats on the Baltimore docks. The second segment, "Epidemics," takes up the theme that epidemics are the products of progress, and that despite medical advances, individuals are still vulnerable to old diseases that still exist. It focuses on the incidence of plague, which is endemic in the rodent population of the Western United States, and cholera, found in the Chesapeake Bay and
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coastal waters off Alabama. The third segment, "Invisible Armies," examines the epidemic of measles in the Hispanic population of Los Angeles. It explores the connections between the immune system and history, and the genetic reasons that Africa and Jamaica have primarily Black populations, while the United States and Australia are predominantly European. The last segment poses the question "Will We Ever Learn?" and draws together the themes from the first three segments to illustrate that unless society learns from the epidemics of the past, new diseases will continue to arise, and old diseases will re-emerge. It examines the incidence of congenital syphilis in New York, and that of sexually transmitted diseases (STDs) in general. •
The Health Century, Episode One: The Fight Against Infectious Disease; From Yellow Fever to AIDS Contact: Maryland Public Television, Public Broadcasting System Video, 11767 Owings Mills Blvd, Owings Mills, MD, 21117, (301) 356-5600. Summary: This videorecording, part of a series broadcast on Maryland Public Television, examines the history of infectious diseases up through the current epidemic of Acquired immunodeficiency syndrome (AIDS). Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases (NIAID), and Cecil Fox, a senior scientist at the National Institutes of Health (NIH), appear in an opening segment that discusses AIDS and the work being done on developing a vaccine. NIH's work in funding research programs is discussed. After pointing out that AIDS research is also feeding results back into other fields, the videorecording turns to the history of NIH, which goes back to the cholera epidemic of 1878, when a one-man staff began work in a New York City laboratory. Moving on through history, the videorecording looks at epidemics of pellagra, influenza, and polio, examining the research that went into developing penicillin and the massive efforts that went into producing the polio vaccine. During the last 15 minutes of the program, Dr. Michael Clement of San Francisco General Hospital talks about azidothymidine (AZT) and treating persons with Human immunodeficiency virus (HIV) infection, and Dr. Robert Gallo, co-discoverer of HIV, talks about research methods.
Bibliography: Multimedia on Cholera The National Library of Medicine is a rich source of information on healthcare-related multimedia productions including slides, computer software, and databases. To access the multimedia database, go to the following Web site: http://locatorplus.gov/. Select “Search LOCATORplus.” Once in the search area, simply type in cholera (or synonyms). Then, in the option box provided below the search box, select “Audiovisuals and Computer Files.” From there, you can choose to sort results by publication date, author, or relevance. The following multimedia has been indexed on cholera: •
Cholera "a problem": water & salt [slide] Source: McMaster University, Health Sciences; Year: 1978; Format: Slide; [Hamilton, Ont.]: The University, c1978
•
Cholera [filmstrip] Source: presented by Trainex Corporation; Year: 1980; Format: Filmstrip; Garden Grove, Calif.: Trainex, c1980
•
Cholera [slide] Source: Instructional Systems Division, Center for Disease Control; Year: 1974; Format: Slide; [Atlanta]: The Center, [1974?]
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•
Cholera [videorecording] Source: a presentation of Films for the Humanities & Sciences; Year: 1996; Format: Videorecording; Princeton, N.J: Films for the Humanities & Sciences, c1996
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Cholera can be conquered [motion picture] Source: [Byron; presented by] the United States Navy; Year: 1946; Format: Motion picture; United States: Byron, c1946
•
Cholera today [motion picture]: bedside evaluation and treatment Source: Southeast Asia Treaty Organization Cholera Research Program of the National Institutes of Health and the Agency for International Development; produced by Public HealthService Audiovisua; Year: 1971; Format: Motion picture; Atlanta: National Medical Audiovisual Center, [1971]
•
Cholera today [motion picture]. Part II: Practical laboratory diagnosis Source: Agency for International Development and National Institutes of Health; produced by National Medical Audiovisual Center; Year: 1966; Format: Motion picture; [Atlanta]: National Medical Audiovisual Center, [1966]
•
Laboratory methods for the diagnosis of epidemic dysentery and cholera [electronic resource] Source: [CDC, Centers for Disease Control and Prevention, NCID, National Center for Infectious Diseases]; Year: 1999; Format: Electronic resource; Atlanta, Ga.: Centers for Disease Control and Prevention, 1999
•
Technical guidelines, cholera [electronic resource] Source: [prepared by the Data for Decision Making Project of the Division of International Health/Epidemiology Program Office of the Centers for Disease Control and Prevention]; Year: 2001; Format: Electronic resource; Atlanta, Ga.: The Project, [2001?]
•
Traveller's diarrhea, Campylobacter gastroenteritis and cholera in the U.S.A. [videorecording] Source: presented by Department of Medicine, Emory University, School of Medicine; Year: 1982; Format: Videorecording; Atlanta, Ga.: Emory Medical Television Network, 1982
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CHAPTER 8. PERIODICALS AND NEWS ON CHOLERA Overview In this chapter, we suggest a number of news sources and present various periodicals that cover cholera.
News Services and Press Releases One of the simplest ways of tracking press releases on cholera 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 “cholera” (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 cholera. 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 “cholera” (or synonyms). The following was recently listed in this archive for cholera: •
Cholera outbreak sweeps along Niger River in Mali Source: Reuters Health eLine Date: November 19, 2003
•
Live, oral toxin-deficient cholera vaccine resists reversion to toxigenic strain Source: Reuters Industry Breifing Date: October 28, 2003
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•
Djibouti refugee camp gets aid to fight cholera Source: Reuters Health eLine Date: September 30, 2003
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Ominous increase in cholera cases in Iraq's Basra Source: Reuters Health eLine Date: May 29, 2003
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Cholera outbreak confirmed in Iraqi city of Basra Source: Reuters Health eLine Date: May 14, 2003
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Basra hospital struggles with cholera scare Source: Reuters Health eLine Date: May 09, 2003
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Cholera outbreak kills 12 in flood-hit Mozambique Source: Reuters Health eLine Date: January 27, 2003
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Household filtration method controls cholera in Bangladesh Source: Reuters Medical News Date: January 15, 2003
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Household cloth can be used to cut cholera risk Source: Reuters Health eLine Date: January 13, 2003
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Avant's cholera vaccine enters phase II in Bangladesh Source: Reuters Industry Breifing Date: December 12, 2002
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Single-dose azithromycin effective against cholera in children Source: Reuters Industry Breifing Date: November 28, 2002
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Nigeria: Cholera outbreak responsible for 10 deaths Source: Reuters Health eLine Date: November 07, 2002
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Cholera outbreak responsible for 10 deaths in northeastern Nigeria village Source: Reuters Medical News Date: November 07, 2002
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Sri Lanka cholera outbreak under control Source: Reuters Health eLine Date: September 30, 2002
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Study suggests cholera will worsen as globe warms Source: Reuters Health eLine Date: August 26, 2002
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Cholera kills 1,000 Malawians in 9 months Source: Reuters Health eLine Date: August 23, 2002
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Human gut helps cholera epidemics to take off Source: Reuters Health eLine Date: June 05, 2002
Periodicals and News
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Changes in gene expression during infection increase infectivity of V. cholerae Source: Reuters Medical News Date: June 05, 2002
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Cholera kills over 900 in Malawi, Africa Source: Reuters Health eLine Date: April 23, 2002
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Cholera kills more than 900 in Malawi Source: Reuters Medical News Date: April 23, 2002
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Oral cholera vaccine protective against challenge in normal volunteers Source: Reuters Industry Breifing Date: April 08, 2002
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Oral cholera vaccine effective in human tests Source: Reuters Health eLine Date: April 08, 2002
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Cholera death toll in Congo nears 600 - UN Source: Reuters Health eLine Date: March 22, 2002
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Cholera death toll in Congo nears 600 Source: Reuters Medical News Date: March 22, 2002
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Congo says cholera outbreak under control Source: Reuters Health eLine Date: March 08, 2002
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At least 28 people dead in Malawi cholera outbreak Source: Reuters Health eLine Date: January 04, 2002
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Cholera outbreak kills 81 in Mozambique Source: Reuters Health eLine Date: December 12, 2001
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Cholera kills 200 in north Nigeria, medics say Source: Reuters Health eLine Date: November 13, 2001
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Cholera kills 40 in Nigerian state Source: Reuters Health eLine Date: October 26, 2001
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Solar water disinfection could help thwart cholera Source: Reuters Health eLine Date: September 26, 2001
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Russia says cholera outbreak not spreading Source: Reuters Health eLine Date: August 07, 2001
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Russia battles cholera outbreak, 200 in hospital Source: Reuters Health eLine Date: August 01, 2001
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Cholera breaks out in central Russia Source: Reuters Health eLine Date: July 31, 2001
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Afghan opposition seeks aid against cholera Source: Reuters Health eLine Date: July 23, 2001
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Avant achieves promising phase IIb data for oral cholera vaccine Source: Reuters Industry Breifing Date: May 09, 2001
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Cuba seeks cholera and AIDS vaccines Source: Reuters Medical News Date: April 05, 2001
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Acambis in typhoid, cholera vaccine alliance with Berna Source: Reuters Industry Breifing Date: March 16, 2001
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Southern Africa to meet on cholera epidemic Source: Reuters Health eLine Date: February 06, 2001
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Three more die in South African Cholera epidemic Source: Reuters Health eLine Date: January 31, 2001
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South Africa cholera death toll rises, more infected Source: Reuters Medical News Date: January 24, 2001
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SGI, MSI map cholera genome Source: Reuters Industry Breifing Date: January 24, 2001
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South African cholera outbreak spreads to city Source: Reuters Health eLine Date: January 19, 2001
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Southern Africa fights cholera as summer rains fall Source: Reuters Health eLine Date: January 09, 2001
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WHO team arrives in South Africa to help with cholera epidemic Source: Reuters Medical News Date: January 08, 2001
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S. Africa cholera epidemic affects 12,000 Source: Reuters Health eLine Date: January 02, 2001
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Nonproliferative cholera vaccine is effective in animal models Source: Reuters Industry Breifing Date: December 15, 2000
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Cholera kills 33, infects thousands in S. Africa Source: Reuters Health eLine Date: November 13, 2000
Periodicals and News
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Cholera has killed 33 in South African province this year Source: Reuters Medical News Date: November 13, 2000
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S. Africa cholera outbreak kills 31, thousands at risk Source: Reuters Health eLine Date: October 30, 2000
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S. Africa cholera outbreak kills 30, thousands at risk Source: Reuters Health eLine Date: October 23, 2000
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The NIH Within MEDLINEplus, the NIH has made an agreement with the New York Times Syndicate, the AP News Service, and Reuters to deliver news that can be browsed by the public. Search news releases at http://www.nlm.nih.gov/medlineplus/alphanews_a.html. MEDLINEplus allows you to browse across an alphabetical index. Or you can search by date at the following Web page: http://www.nlm.nih.gov/medlineplus/newsbydate.html. Often, news items are indexed by MEDLINEplus within its search engine. Business Wire Business Wire is similar to PR Newswire. To access this archive, simply go to http://www.businesswire.com/. You can scan the news by industry category or company name. Market Wire Market Wire is more focused on technology than the other wires. To browse the latest press releases by topic, such as alternative medicine, biotechnology, fitness, healthcare, legal, nutrition, and pharmaceuticals, access Market Wire’s Medical/Health channel at http://www.marketwire.com/mw/release_index?channel=MedicalHealth. Or simply go to Market Wire’s home page at http://www.marketwire.com/mw/home, type “cholera” (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 “cholera” (or synonyms). If you know the name of a company that is relevant to cholera, 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/.
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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 “cholera” (or synonyms).
Academic Periodicals covering Cholera Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to cholera. In addition to these sources, you can search for articles covering cholera that have been published by any of the periodicals listed in previous chapters. To find the latest studies published, go to http://www.ncbi.nlm.nih.gov/pubmed, type the name of the periodical into the search box, and click “Go.” If you want complete details about the historical contents of a journal, you can also visit the following Web site: http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi. Here, type in the name of the journal or its abbreviation, and you will receive an index of published articles. At http://locatorplus.gov/, you can retrieve more indexing information on medical periodicals (e.g. the name of the publisher). Select the button “Search LOCATORplus.” Then type in the name of the journal and select the advanced search option “Journal Title Search.”
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CHAPTER 9. RESEARCHING MEDICATIONS Overview While a number of hard copy or CD-ROM resources are available for researching medications, a more flexible method is to use Internet-based databases. Broadly speaking, there are two sources of information on approved medications: public sources and private sources. We will emphasize free-to-use public sources.
U.S. Pharmacopeia Because of historical investments by various organizations and the emergence of the Internet, it has become rather simple to learn about the medications recommended for cholera. One such source is the United States Pharmacopeia. In 1820, eleven physicians met in Washington, D.C. to establish the first compendium of standard drugs for the United States. They called this compendium the U.S. Pharmacopeia (USP). Today, the USP is a nonprofit organization consisting of 800 volunteer scientists, eleven elected officials, and 400 representatives of state associations and colleges of medicine and pharmacy. The USP is located in Rockville, Maryland, and its home page is located at http://www.usp.org/. The USP currently provides standards for over 3,700 medications. The resulting USP DI Advice for the Patient can be accessed through the National Library of Medicine of the National Institutes of Health. The database is partially derived from lists of federally approved medications in the Food and Drug Administration’s (FDA) Drug Approvals database, located at http://www.fda.gov/cder/da/da.htm. While the FDA database is rather large and difficult to navigate, the Phamacopeia is both user-friendly and free to use. It covers more than 9,000 prescription and over-the-counter medications. To access this database, simply type the following hyperlink into your Web browser: http://www.nlm.nih.gov/medlineplus/druginformation.html. To view examples of a given medication (brand names, category, description, preparation, proper use, precautions, side effects, etc.), simply follow the hyperlinks indicated within the United States Pharmacopeia (USP). Below, we have compiled a list of medications associated with cholera. If you would like more information on a particular medication, the provided hyperlinks will direct you to ample documentation (e.g. typical dosage, side effects, drug-interaction risks, etc.). The
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following drugs have been mentioned in the Pharmacopeia and other sources as being potentially applicable to cholera: Doxycycline •
Dental - U.S. Brands: Atridox http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203716.html
Furazolidone •
Oral - U.S. Brands: Furoxone http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202252.html
Trimethoprim •
Systemic - U.S. Brands: Proloprim; Trimpex http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202579.html
Yellow Fever Vaccine •
Systemic - U.S. Brands: YF-Vax http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202689.html
Commercial Databases In addition to the medications listed in the USP above, a number of commercial sites are available by subscription to physicians and their institutions. Or, you may be able to access these sources from your local medical library.
Mosby’s Drug Consult Mosby’s Drug Consult database (also available on CD-ROM and book format) covers 45,000 drug products including generics and international brands. It provides prescribing information, drug interactions, and patient information. Subscription information is available at the following hyperlink: http://www.mosbysdrugconsult.com/.
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.
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If you have any questions about a medical treatment, the FDA may have an office near you. Look for their number in the blue pages of the phone book. You can also contact the FDA through its toll-free number, 1-888-INFO-FDA (1-888-463-6332), or on the World Wide Web at www.fda.gov.
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APPENDICES
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APPENDIX A. PHYSICIAN RESOURCES Overview In this chapter, we focus on databases and Internet-based guidelines and information resources created or written for a professional audience.
NIH Guidelines Commonly referred to as “clinical” or “professional” guidelines, the National Institutes of Health publish physician guidelines for the most common diseases. Publications are available at the following by relevant Institute11: •
Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm
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National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/news/facts/
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National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html
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National Cancer Institute (NCI); guidelines available at http://www.cancer.gov/cancerinfo/list.aspx?viewid=5f35036e-5497-4d86-8c2c714a9f7c8d25
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National Eye Institute (NEI); guidelines available at http://www.nei.nih.gov/order/index.htm
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National Heart, Lung, and Blood Institute (NHLBI); guidelines available at http://www.nhlbi.nih.gov/guidelines/index.htm
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National Human Genome Research Institute (NHGRI); research available at http://www.genome.gov/page.cfm?pageID=10000375
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National Institute on Aging (NIA); guidelines available at http://www.nia.nih.gov/health/
11
These publications are typically written by one or more of the various NIH Institutes.
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•
National Institute on Alcohol Abuse and Alcoholism (NIAAA); guidelines available at http://www.niaaa.nih.gov/publications/publications.htm
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National Institute of Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/
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National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm
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National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm
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National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/
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National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/
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National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm
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National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html
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National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm
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National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/practitioners/index.cfm
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National Institute of Neurological Disorders and Stroke (NINDS); neurological disorder information pages available at http://www.ninds.nih.gov/health_and_medical/disorder_index.htm
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National Institute of Nursing Research (NINR); publications on selected illnesses at http://www.nih.gov/ninr/news-info/publications.html
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National Institute of Biomedical Imaging and Bioengineering; general information at http://grants.nih.gov/grants/becon/becon_info.htm
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Center for Information Technology (CIT); referrals to other agencies based on keyword searches available at http://kb.nih.gov/www_query_main.asp
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National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/
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National Center for Research Resources (NCRR); various information directories available at http://www.ncrr.nih.gov/publications.asp
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Office of Rare Diseases; various fact sheets available at http://rarediseases.info.nih.gov/html/resources/rep_pubs.html
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Centers for Disease Control and Prevention; various fact sheets on infectious diseases available at http://www.cdc.gov/publications.htm
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NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.12 Physician-oriented resources provide a wide variety of information related to the biomedical and health sciences, both past and present. The format of these resources varies. Searchable databases, bibliographic citations, full-text articles (when available), archival collections, and images are all available. The following are referenced by the National Library of Medicine:13 •
Bioethics: Access to published literature on the ethical, legal, and public policy issues surrounding healthcare and biomedical research. This information is provided in conjunction with the Kennedy Institute of Ethics located at Georgetown University, Washington, D.C.: http://www.nlm.nih.gov/databases/databases_bioethics.html
•
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/
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Population Information: The National Library of Medicine provides access to worldwide coverage of population, family planning, and related health issues, including family planning technology and programs, fertility, and population law and policy: http://www.nlm.nih.gov/databases/databases_population.html
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Cancer Information: Access to cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html
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Profiles in Science: Offering the archival collections of prominent twentieth-century biomedical scientists to the public through modern digital technology: http://www.profiles.nlm.nih.gov/
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Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html
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Clinical Alerts: Reports the release of findings from the NIH-funded clinical trials where such release could significantly affect morbidity and mortality: http://www.nlm.nih.gov/databases/alerts/clinical_alerts.html
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Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html
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MEDLINE: Bibliographic database covering the fields of medicine, nursing, dentistry, veterinary medicine, the healthcare system, and the pre-clinical sciences: http://www.nlm.nih.gov/databases/databases_medline.html
12
Remember, for the general public, the National Library of Medicine recommends the databases referenced in MEDLINEplus (http://medlineplus.gov/ or http://www.nlm.nih.gov/medlineplus/databases.html). 13 See http://www.nlm.nih.gov/databases/databases.html.
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•
Toxicology and Environmental Health Information (TOXNET): Databases covering toxicology and environmental health: http://sis.nlm.nih.gov/Tox/ToxMain.html
•
Visible Human Interface: Anatomically detailed, three-dimensional representations of normal male and female human bodies: http://www.nlm.nih.gov/research/visible/visible_human.html The Combined Health Information Database
A comprehensive source of information on clinical guidelines written for professionals is the Combined Health Information Database. You will need to limit your search to one of the following: Brochure/Pamphlet, Fact Sheet, or Information Package, and “cholera” using the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find associations, use the drop boxes at the bottom of the search page where “You may refine your search by.” For the publication date, select “All Years.” Select your preferred language and the format option “Fact Sheet.” Type “cholera” (or synonyms) into the “For these words:” box. The following is a sample result: •
1997 Red Book: Report of the Committee on Infectious Diseases. 24th ed Source: Elk Grove Village, IL: American Academy of Pediatrics. 1997. 764 p. Contact: Available from American Academy of Pediatrics. Publications, P.O. Box 747, Elk Grove Village, IL 60009-0747. (800) 433-9016 or (847) 228-5005. Fax (847) 228-1281. Email:
[email protected]. PRICE: Single copy free to members, with additional copies $74.95 each; $79.95 for nonmembers. ISBN: 091076185x. Publication number MA0001. Summary: This monograph contains the 24th edition of the report of the Committee on Infectious Diseases, the group responsible for formulating and revising guidelines of the American Academy of Pediatrics for the control of infectious diseases in children. Five sections present guidelines in the areas of active and passive immunization; recommendations for the care of children in special circumstances, including children in day care, infection control for hospitalized children, and medical evaluation of internationally adopted children; summaries of infectious diseases; antimicrobial prophylaxis; and antimicrobials and related therapy. Infectious diseases that can affect the digestive system include amebiasis, campylobacter infections, cholera, Escherichia coli, diarrhea, giardia lamblia, helicobacter pylori, hepatitis, HIV, malaria, parasitic diseases, salmonellosis, schistosomiasis, shigellosis, vibrio infections, and yersinia infections. A summary of major changes in the 1997 edition is provided; changes include the addition of recent information on Escherichia coli diarrhea (E coli 0157:H7 infection) and its complication of hemolytic-uremic syndrome, and expanded information about Hepatitis A, B, and C. A subject index concludes the volume. 9 appendices.
The NLM Gateway14 The NLM (National Library of Medicine) Gateway is a Web-based system that lets users search simultaneously in multiple retrieval systems at the U.S. National Library of Medicine (NLM). It allows users of NLM services to initiate searches from one Web interface,
14
Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.
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providing one-stop searching for many of NLM’s information resources or databases.15 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “cholera” (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 16594 2780 15 49 0 19438
HSTAT16 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.17 These documents include clinical practice guidelines, quickreference guides for clinicians, consumer health brochures, evidence reports and technology assessments from the Agency for Healthcare Research and Quality (AHRQ), as well as AHRQ’s Put Prevention Into Practice.18 Simply search by “cholera” (or synonyms) at the following Web site: http://text.nlm.nih.gov.
Coffee Break: Tutorials for Biologists19 Coffee Break is a general healthcare site that takes a scientific view of the news and covers recent breakthroughs in biology that may one day assist physicians in developing treatments. Here you will find a collection of short reports on recent biological discoveries. Each report incorporates interactive tutorials that demonstrate how bioinformatics tools are used as a part of the research process. Currently, all Coffee Breaks are written by NCBI staff.20 Each report is about 400 words and is usually based on a discovery reported in one or more articles from recently published, peer-reviewed literature.21 This site has new articles 15 The NLM Gateway is currently being developed by the Lister Hill National Center for Biomedical Communications (LHNCBC) at the National Library of Medicine (NLM) of the National Institutes of Health (NIH). 16 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 17
The HSTAT URL is http://hstat.nlm.nih.gov/.
18
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. 19 Adapted from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html. 20
The figure that accompanies each article is frequently supplied by an expert external to NCBI, in which case the source of the figure is cited. The result is an interactive tutorial that tells a biological story. 21 After a brief introduction that sets the work described into a broader context, the report focuses on how a molecular understanding can provide explanations of observed biology and lead to therapies for diseases. Each
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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/.
vignette is accompanied by a figure and hypertext links that lead to a series of pages that interactively show how NCBI tools and resources are used in the research process.
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APPENDIX B. PATIENT RESOURCES Overview Official agencies, as well as federally funded institutions supported by national grants, frequently publish a variety of guidelines written with the patient in mind. These are typically called “Fact Sheets” or “Guidelines.” They can take the form of a brochure, information kit, pamphlet, or flyer. Often they are only a few pages in length. Since new guidelines on cholera 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 cholera. 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 cholera. 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 “cholera”:
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•
Other guides Bacterial Infections http://www.nlm.nih.gov/medlineplus/bacterialinfections.html Biodefense and Bioterrorism http://www.nlm.nih.gov/medlineplus/biodefenseandbioterrorism.html E. Coli Infections http://www.nlm.nih.gov/medlineplus/ecoliinfections.html Food Contamination/Poisoning http://www.nlm.nih.gov/medlineplus/foodcontaminationpoisoning.html Food Safety http://www.nlm.nih.gov/medlineplus/foodsafety.html Gastroenteritis http://www.nlm.nih.gov/medlineplus/gastroenteritis.html Infection Control http://www.nlm.nih.gov/medlineplus/infectioncontrol.html Water Safety http://www.nlm.nih.gov/medlineplus/watersafetyrecreational.html
You may also choose to use the search utility provided by MEDLINEplus at the following Web address: http://www.nlm.nih.gov/medlineplus/. Simply type a keyword into the search box and click “Search.” This utility is similar to the NIH search utility, with the exception that it only includes materials that are linked within the MEDLINEplus system (mostly patient-oriented information). It also has the disadvantage of generating unstructured results. We recommend, therefore, that you use this method only if you have a very targeted search. The Combined Health Information Database (CHID) CHID Online is a reference tool that maintains a database directory of thousands of journal articles and patient education guidelines on cholera. 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: •
Cholera Prevention Source: Atlanta, GA: Centers for Disease Control. National Center for Infectious Disease. May 1992. 4 p. Contact: Available from Division of Bacterial and Mycotic Diseases, National Center for Infectious Diseases, Centers for Disease control, Mailstop C09, 1600 Clifton Road, Atlanta, GA 30333. (404) 488-4605. PRICE: Single copy free. Summary: Cholera is an acute, diarrheal illness caused by infection of the intestine with the bacterium Vibrio cholerae. This brochure reviews the problem of cholera and how it can be prevented. Written in a question and answer format, the brochure covers topics including a definition of the disease; how a person gets cholera; the risk for cholera in
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the United States; what travelers should do to avoid getting cholera; the use of a vaccine to prevent cholera; how cholera is treated; the current cholera epidemics in Latin America and Africa; U.S. government activities aimed at combatting cholera; and how to get more information about cholera. One sidebar summarizes recommendations for travelers to help them avoid contracting cholera. 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: •
FAQ - About Cholera Source: National Center for Infectious Diseases, Centers for Disease Control and Prevention http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6250 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 cholera. 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. NORD (The National Organization of Rare Disorders, Inc.) NORD provides an invaluable service to the public by publishing short yet comprehensive guidelines on over 1,000 diseases. NORD primarily focuses on rare diseases that might not be covered by the previously listed sources. NORD’s Web address is http://www.rarediseases.org/. A complete guide on cholera can be purchased from NORD for a nominal fee. Additional Web Sources A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •
AOL: http://search.aol.com/cat.adp?id=168&layer=&from=subcats
•
Family Village: http://www.familyvillage.wisc.edu/specific.htm
•
Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/
232 Cholera
•
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/
•
WebMDHealth: 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 cholera. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with cholera. 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 cholera. 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 “cholera” (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 “cholera”. Type the following hyperlink into your Web browser: http://chid.nih.gov/detail/detail.html. To find associations, use the drop boxes at the bottom of the search page where “You may refine your search by.” For publication date,
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select “All Years.” Then, select your preferred language and the format option “Organization Resource Sheet.” Type “cholera” (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 “cholera” (or a synonym) into the search box, and click “Submit Query.”
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APPENDIX C. FINDING MEDICAL LIBRARIES Overview In this Appendix, we show you how to quickly find a medical library in your area.
Preparation Your local public library and medical libraries have interlibrary loan programs with the National Library of Medicine (NLM), one of the largest medical collections in the world. According to the NLM, most of the literature in the general and historical collections of the National Library of Medicine is available on interlibrary loan to any library. If you would like to access NLM medical literature, then visit a library in your area that can request the publications for you.22
Finding a Local Medical Library The quickest method to locate medical libraries is to use the Internet-based directory published by the National Network of Libraries of Medicine (NN/LM). This network includes 4626 members and affiliates that provide many services to librarians, health professionals, and the public. To find a library in your area, simply visit http://nnlm.gov/members/adv.html or call 1-800-338-7657.
Medical Libraries in the U.S. and Canada In addition to the NN/LM, the National Library of Medicine (NLM) lists a number of libraries with reference facilities that are open to the public. The following is the NLM’s list and includes hyperlinks to each library’s Web site. These Web pages can provide information on hours of operation and other restrictions. The list below is a small sample of
22
Adapted from the NLM: http://www.nlm.nih.gov/psd/cas/interlibrary.html.
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libraries recommended by the National Library of Medicine (sorted alphabetically by name of the U.S. state or Canadian province where the library is located)23: •
Alabama: Health InfoNet of Jefferson County (Jefferson County Library Cooperative, Lister Hill Library of the Health Sciences), http://www.uab.edu/infonet/
•
Alabama: Richard M. Scrushy Library (American Sports Medicine Institute)
•
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/
23
Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.
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•
Connecticut: Waterbury Hospital Health Center Library (Waterbury Hospital, Waterbury), http://www.waterburyhospital.com/library/consumer.shtml
•
Delaware: Consumer Health Library (Christiana Care Health System, Eugene du Pont Preventive Medicine & Rehabilitation Institute, Wilmington), http://www.christianacare.org/health_guide/health_guide_pmri_health_info.cfm
•
Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine, Wilmington), http://www.delamed.org/chls.html
•
Georgia: Family Resource Library (Medical College of Georgia, Augusta), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm
•
Georgia: Health Resource Center (Medical Center of Central Georgia, Macon), http://www.mccg.org/hrc/hrchome.asp
•
Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library, Honolulu), http://hml.org/CHIS/
•
Idaho: DeArmond Consumer Health Library (Kootenai Medical Center, Coeur d’Alene), http://www.nicon.org/DeArmond/index.htm
•
Illinois: Health Learning Center of Northwestern Memorial Hospital (Chicago), http://www.nmh.org/health_info/hlc.html
•
Illinois: Medical Library (OSF Saint Francis Medical Center, Peoria), http://www.osfsaintfrancis.org/general/library/
•
Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital, Lexington), http://www.centralbap.com/education/community/library.cfm
•
Kentucky: University of Kentucky - Health Information Library (Chandler Medical Center, Lexington), http://www.mc.uky.edu/PatientEd/
•
Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation, New Orleans), http://www.ochsner.org/library/
•
Louisiana: Louisiana State University Health Sciences Center Medical LibraryShreveport, http://lib-sh.lsuhsc.edu/
•
Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital, Farmington), http://www.fchn.org/fmh/lib.htm
•
Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center, Lewiston), http://www.cmmc.org/library/library.html
•
Maine: Hadley Parrot Health Science Library (Eastern Maine Healthcare, Bangor), http://www.emh.org/hll/hpl/guide.htm
•
Maine: Maine Medical Center Library (Maine Medical Center, Portland), http://www.mmc.org/library/
•
Maine: Parkview Hospital (Brunswick), http://www.parkviewhospital.org/
•
Maine: Southern Maine Medical Center Health Sciences Library (Southern Maine Medical Center, Biddeford), http://www.smmc.org/services/service.php3?choice=10
•
Maine: Stephens Memorial Hospital’s Health Information Library (Western Maine Health, Norway), http://www.wmhcc.org/Library/
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•
Manitoba, Canada: Consumer & Patient Health Information Service (University of Manitoba Libraries), http://www.umanitoba.ca/libraries/units/health/reference/chis.html
•
Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre, Winnipeg), http://www.deerlodge.mb.ca/crane_library/about.asp
•
Maryland: Health Information Center at the Wheaton Regional Library (Montgomery County, Dept. of Public Libraries, Wheaton Regional Library), http://www.mont.lib.md.us/healthinfo/hic.asp
•
Massachusetts: Baystate Medical Center Library (Baystate Health System), http://www.baystatehealth.com/1024/
•
Massachusetts: Boston University Medical Center Alumni Medical Library (Boston University Medical Center), http://med-libwww.bu.edu/library/lib.html
•
Massachusetts: Lowell General Hospital Health Sciences Library (Lowell General Hospital, Lowell), http://www.lowellgeneral.org/library/HomePageLinks/WWW.htm
•
Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital, Boston), http://www.nebh.org/health_lib.asp
•
Massachusetts: St. Luke’s Hospital Health Sciences Library (St. Luke’s Hospital, Southcoast Health System, New Bedford), http://www.southcoast.org/library/
•
Massachusetts: Treadwell Library Consumer Health Reference Center (Massachusetts General Hospital), http://www.mgh.harvard.edu/library/chrcindex.html
•
Massachusetts: UMass HealthNet (University of Massachusetts Medical School, Worchester), http://healthnet.umassmed.edu/
•
Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm
•
Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/
•
Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html
•
Michigan: Patient Education Resouce Center - University of Michigan Cancer Center (University of Michigan Comprehensive Cancer Center, Ann Arbor), http://www.cancer.med.umich.edu/learn/leares.htm
•
Michigan: Sladen Library & Center for Health Information Resources - Consumer Health Information (Detroit), http://www.henryford.com/body.cfm?id=39330
•
Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center, Missoula)
•
National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html
•
National: National Network of Libraries of Medicine (National Library of Medicine) provides library services for health professionals in the United States who do not have access to a medical library, http://nnlm.gov/
•
National: NN/LM List of Libraries Serving the Public (National Network of Libraries of Medicine), http://nnlm.gov/members/
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•
Nevada: Health Science Library, West Charleston Library (Las Vegas-Clark County Library District, Las Vegas), http://www.lvccld.org/special_collections/medical/index.htm
•
New Hampshire: Dartmouth Biomedical Libraries (Dartmouth College Library, Hanover), http://www.dartmouth.edu/~biomed/resources.htmld/conshealth.htmld/
•
New Jersey: Consumer Health Library (Rahway Hospital, Rahway), http://www.rahwayhospital.com/library.htm
•
New Jersey: Dr. Walter Phillips Health Sciences Library (Englewood Hospital and Medical Center, Englewood), http://www.englewoodhospital.com/links/index.htm
•
New Jersey: Meland Foundation (Englewood Hospital and Medical Center, Englewood), http://www.geocities.com/ResearchTriangle/9360/
•
New York: Choices in Health Information (New York Public Library) - NLM Consumer Pilot Project participant, http://www.nypl.org/branch/health/links.html
•
New York: Health Information Center (Upstate Medical University, State University of New York, Syracuse), http://www.upstate.edu/library/hic/
•
New York: Health Sciences Library (Long Island Jewish Medical Center, New Hyde Park), http://www.lij.edu/library/library.html
•
New York: ViaHealth Medical Library (Rochester General Hospital), http://www.nyam.org/library/
•
Ohio: Consumer Health Library (Akron General Medical Center, Medical & Consumer Health Library), http://www.akrongeneral.org/hwlibrary.htm
•
Oklahoma: The Health Information Center at Saint Francis Hospital (Saint Francis Health System, Tulsa), http://www.sfh-tulsa.com/services/healthinfo.asp
•
Oregon: Planetree Health Resource Center (Mid-Columbia Medical Center, The Dalles), http://www.mcmc.net/phrc/
•
Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center, Hershey), http://www.hmc.psu.edu/commhealth/
•
Pennsylvania: Community Health Resource Library (Geisinger Medical Center, Danville), http://www.geisinger.edu/education/commlib.shtml
•
Pennsylvania: HealthInfo Library (Moses Taylor Hospital, Scranton), http://www.mth.org/healthwellness.html
•
Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System, Pittsburgh), http://www.hsls.pitt.edu/guides/chi/hopwood/index_html
•
Pennsylvania: Koop Community Health Information Center (College of Physicians of Philadelphia), http://www.collphyphil.org/kooppg1.shtml
•
Pennsylvania: Learning Resources Center - Medical Library (Susquehanna Health System, Williamsport), http://www.shscares.org/services/lrc/index.asp
•
Pennsylvania: Medical Library (UPMC Health System, Pittsburgh), http://www.upmc.edu/passavant/library.htm
•
Quebec, Canada: Medical Library (Montreal General Hospital), http://www.mghlib.mcgill.ca/
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•
South Dakota: Rapid City Regional Hospital Medical Library (Rapid City Regional Hospital), http://www.rcrh.org/Services/Library/Default.asp
•
Texas: Houston HealthWays (Houston Academy of Medicine-Texas Medical Center Library), http://hhw.library.tmc.edu/
•
Washington: Community Health Library (Kittitas Valley Community Hospital), http://www.kvch.com/
•
Washington: Southwest Washington Medical Center Library (Southwest Washington Medical Center, Vancouver), http://www.swmedicalcenter.com/body.cfm?id=72
241
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 cholera: •
Basic Guidelines for Cholera Cholera Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000303.htm Vibrio Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000303.htm
•
Signs & Symptoms for Cholera Abdominal cramps Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003120.htm Bowel sounds Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003137.htm Cyanosis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003215.htm
242 Cholera
Decreased skin turgor Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003281.htm Diarrhea Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003126.htm Dry mucus membranes Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003250.htm Dry skin Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003250.htm Fever Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003090.htm Heart sounds Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003266.htm Hypotension Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003083.htm Lethargy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003088.htm Low urine output Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003147.htm Malaise Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003089.htm Nausea Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003117.htm Oliguria Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003147.htm Rapid pulse Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003077.htm Seizures Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003200.htm Skin turgor Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003281.htm Sleepiness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003208.htm Tachycardia Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003077.htm
Online Glossaries 243
Thirst Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003085.htm Thirst, excessive Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003085.htm Tiredness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003088.htm Vomiting Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003117.htm Weakness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003174.htm •
Diagnostics and Tests for Cholera ADH Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003702.htm Blood culture Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003744.htm BUN Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003474.htm Creatinine Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003475.htm Heart rate Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003399.htm Hgb Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003645.htm Hyperplasia Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003441.htm Stool culture Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003758.htm WBC count Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003643.htm X-ray Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003337.htm
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Background Topics for Cholera Acute Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002215.htm
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Asymptomatic Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002217.htm Electrolytes Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002350.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 Intravenous Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002383.htm Shellfish Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002851.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
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MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html
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Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/
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Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine
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CHOLERA DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Abdominal Cramps: Abdominal pain due to spasmodic contractions of the bowel. [NIH] Abdominal Pain: Sensation of discomfort, distress, or agony in the abdominal region. [NIH] Ablate: In surgery, is to remove. [NIH] Ablation: The removal of an organ by surgery. [NIH] Abscess: Accumulation of purulent material in tissues, organs, or circumscribed spaces, usually associated with signs of infection. [NIH] Acceptor: A substance which, while normally not oxidized by oxygen or reduced by hydrogen, can be oxidized or reduced in presence of a substance which is itself undergoing oxidation or reduction. [NIH] Acetylcholine: A neurotransmitter. Acetylcholine in vertebrates is the major transmitter at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. It is generally not used as an administered drug because it is broken down very rapidly by cholinesterases, but it is useful in some ophthalmological applications. [NIH] Acetylcysteine: The N-acetyl derivative of cysteine. It is used as a mucolytic agent to reduce the viscosity of mucous secretions. It has also been shown to have antiviral effects in patients with HIV due to inhibition of viral stimulation by reactive oxygen intermediates. [NIH] Acetylglucosamine: The N-acetyl derivative of glucosamine. [NIH] Acidosis: A pathologic condition resulting from accumulation of acid or depletion of the alkaline reserve (bicarbonate content) in the blood and body tissues, and characterized by an increase in hydrogen ion concentration. [EU] Actin: Essential component of the cell skeleton. [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] Adaptation: 1. The adjustment of an organism to its environment, or the process by which it enhances such fitness. 2. The normal ability of the eye to adjust itself to variations in the intensity of light; the adjustment to such variations. 3. The decline in the frequency of firing of a neuron, particularly of a receptor, under conditions of constant stimulation. 4. In dentistry, (a) the proper fitting of a denture, (b) the degree of proximity and interlocking of restorative material to a tooth preparation, (c) the exact adjustment of bands to teeth. 5. In microbiology, the adjustment of bacterial physiology to a new environment. [EU] Adenine: A purine base and a fundamental unit of adenine nucleotides. [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 Diphosphate: Adenosine 5'-(trihydrogen diphosphate). An adenine nucleotide
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containing two phosphate groups esterified to the sugar moiety at the 5'-position. [NIH] Adenosine Diphosphate Ribose: An ester formed between the aldehydic carbon of ribose and the terminal phosphate of adenosine diphosphate. Serves as a ribose carrier. [NIH] Adenylate Cyclase: An enzyme of the lyase class that catalyzes the formation of cyclic AMP and pyrophosphate from ATP. EC 4.6.1.1. [NIH] Adhesions: Pathological processes consisting of the union of the opposing surfaces of a wound. [NIH] Adipocytes: Fat-storing cells found mostly in the abdominal cavity and subcutaneous tissue. Fat is usually stored in the form of tryglycerides. [NIH] Adjustment: The dynamic process wherein the thoughts, feelings, behavior, and biophysiological mechanisms of the individual continually change to adjust to the environment. [NIH] Adjuvant: A substance which aids another, such as an auxiliary remedy; in immunology, nonspecific stimulator (e.g., BCG vaccine) of the immune response. [EU] Adrenal Cortex: The outer layer of the adrenal gland. It secretes mineralocorticoids, androgens, and glucocorticoids. [NIH] Adrenergic: Activated by, characteristic of, or secreting epinephrine or substances with similar activity; the term is applied to those nerve fibres that liberate norepinephrine at a synapse when a nerve impulse passes, i.e., the sympathetic fibres. [EU] Adverse Effect: An unwanted side effect of treatment. [NIH] Aerosol: A solution of a drug which can be atomized into a fine mist for inhalation therapy. [EU]
Aetiology: Study of the causes of disease. [EU] Afferent: Concerned with the transmission of neural impulse toward the central part of the nervous system. [NIH] Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among simple, uniform antigenic determinants such as haptens. Expressed as the association constant (K litres mole -1), which, owing to the heterogeneity of affinities in a population of antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU] Affinity Chromatography: In affinity chromatography, a ligand attached to a column binds specifically to the molecule to be purified. [NIH] Agar: A complex sulfated polymer of galactose units, extracted from Gelidium cartilagineum, Gracilaria confervoides, and related red algae. It is used as a gel in the preparation of solid culture media for microorganisms, as a bulk laxative, in making emulsions, and as a supporting medium for immunodiffusion and immunoelectrophoresis. [NIH]
Age Groups: Persons classified by age from birth (infant, newborn) to octogenarians and older (aged, 80 and over). [NIH] Aged, 80 and Over: A person 80 years of age and older. [NIH]
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Agglutinins: Substances, usually of biological origin, that cause cells or other organic particles to aggregate and stick to each other. They also include those antibodies which cause aggregation or agglutination of a particulate or insoluble antigen. [NIH] Agonist: In anatomy, a prime mover. In pharmacology, a drug that has affinity for and stimulates physiologic activity at cell receptors normally stimulated by naturally occurring substances. [EU] Airway: A device for securing unobstructed passage of air into and out of the lungs during general anesthesia. [NIH] Albumin: 1. Any protein that is soluble in water and moderately concentrated salt solutions and is coagulable by heat. 2. Serum albumin; the major plasma protein (approximately 60 per cent of the total), which is responsible for much of the plasma colloidal osmotic pressure and serves as a transport protein carrying large organic anions, such as fatty acids, bilirubin, and many drugs, and also carrying certain hormones, such as cortisol and thyroxine, when their specific binding globulins are saturated. Albumin is synthesized in the liver. Low serum levels occur in protein malnutrition, active inflammation and serious hepatic and renal disease. [EU] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alimentary: Pertaining to food or nutritive material, or to the organs of digestion. [EU] Alkaline: Having the reactions of an alkali. [EU] Alkaloid: A member of a large group of chemicals that are made by plants and have nitrogen in them. Some alkaloids have been shown to work against cancer. [NIH] Alleles: Mutually exclusive forms of the same gene, occupying the same locus on homologous chromosomes, and governing the same biochemical and developmental process. [NIH] Allergen: An antigenic substance capable of producing immediate-type hypersensitivity (allergy). [EU] Allylamine: Possesses an unusual and selective cytotoxicity for vascular smooth muscle cells in dogs and rats. Useful for experiments dealing with arterial injury, myocardial fibrosis or cardiac decompensation. [NIH] Alpha-Defensins: Defensins found in azurophilic granules of neutrophils and in the secretory granules of intestinal paneth cells. [NIH] Alpha-helix: One of the secondary element of protein. [NIH] Alternative medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used instead of standard treatments. Alternative medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Aluminum: A metallic element that has the atomic number 13, atomic symbol Al, and atomic weight 26.98. [NIH] Aluminum Hydroxide: Hydrated aluminum. A compound with many biomedical applications: as a gastric antacid, an antiperspirant, in dentifrices, as an emulsifier, as an adjuvant in bacterins and vaccines, in water purification, etc. [NIH] Amebiasis: Infection with any of various amebae. It is an asymptomatic carrier state in most individuals, but diseases ranging from chronic, mild diarrhea to fulminant dysentery may occur. [NIH]
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Ameliorating: A changeable condition which prevents the consequence of a failure or accident from becoming as bad as it otherwise would. [NIH] Amine: An organic compound containing nitrogen; any member of a group of chemical compounds formed from ammonia by replacement of one or more of the hydrogen atoms by organic (hydrocarbon) radicals. The amines are distinguished as primary, secondary, and tertiary, according to whether one, two, or three hydrogen atoms are replaced. The amines include allylamine, amylamine, ethylamine, methylamine, phenylamine, propylamine, and many other compounds. [EU] Amino Acid 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 Acid Substitution: The naturally occurring or experimentally induced replacement of one or more amino acids in a protein with another. If a functionally equivalent amino acid is substituted, the protein may retain wild-type activity. Substitution may also diminish or eliminate protein function. Experimentally induced substitution is often used to study enzyme activities and binding site properties. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] 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] Amphetamine: A powerful central nervous system stimulant and sympathomimetic. Amphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulation of release of monamines, and inhibiting monoamine oxidase. Amphetamine is also a drug of abuse and a psychotomimetic. The l- and the d,l-forms are included here. The l-form has less central nervous system activity but stronger cardiovascular effects. The d-form is dextroamphetamine. [NIH] Amplification: The production of additional copies of a chromosomal DNA sequence, found as either intrachromosomal or extrachromosomal DNA. [NIH] Amygdala: Almond-shaped group of basal nuclei anterior to the inferior horn of the lateral ventricle of the brain, within the temporal lobe. The amygdala is part of the limbic system. [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] Analgesic: An agent that alleviates pain without causing loss of consciousness. [EU] Analog: In chemistry, a substance that is similar, but not identical, to another. [NIH] Analogous: Resembling or similar in some respects, as in function or appearance, but not in
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origin or development;. [EU] Analytes: A component of a test sample the presence of which has to be demonstrated. The term "analyte" includes where appropriate formed from the analyte during the analyses. [NIH]
Anaphylatoxins: The family of peptides C3a, C4a, C5a, and C5a des-arginine produced in the serum during complement activation. They produce smooth muscle contraction, mast cell histamine release, affect platelet aggregation, and act as mediators of the local inflammatory process. The order of anaphylatoxin activity from strongest to weakest is C5a, C3a, C4a, and C5a des-arginine. The latter is the so-called "classical" anaphylatoxin but shows no spasmogenic activity though it contains some chemotactic ability. [NIH] Anaplasia: Loss of structural differentiation and useful function of neoplastic cells. [NIH] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH] Animal model: An animal with a disease either the same as or like a disease in humans. Animal models are used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis. [NIH] Annealing: The spontaneous alignment of two single DNA strands to form a double helix. [NIH]
Anode: Electrode held at a positive potential with respect to a cathode. [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] Anterograde: Moving or extending forward; called also antegrade. [EU] Anthracycline: A member of a family of anticancer drugs that are also antibiotics. [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
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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] Antiemetic: An agent that prevents or alleviates nausea and vomiting. Also antinauseant. [EU]
Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Antigen-Antibody Complex: The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes immune complex diseases. [NIH] Antigen-presenting cell: APC. A cell that shows antigen on its surface to other cells of the immune system. This is an important part of an immune response. [NIH] Anti-infective: An agent that so acts. [EU] Anti-Infective Agents: Substances that prevent infectious agents or organisms from spreading or kill infectious agents in order to prevent the spread of infection. [NIH] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Antimicrobial: Killing microorganisms, or suppressing their multiplication or growth. [EU] Antioxidant: A substance that prevents damage caused by free radicals. Free radicals are highly reactive chemicals that often contain oxygen. They are produced when molecules are split to give products that have unpaired electrons. This process is called oxidation. [NIH] Antiporters: Membrane glycoproteins that transport substrates across the membrane in a tightly coupled stoichiometric manner. The stoichiometry of influx of one substrate and the efflux of another is fixed by a single transport catalytic cycle; that is, the membrane is not freely permeable to either substrate. Antiporters mediate secondary active transport, using the electrochemical energy of a primary gradient (mostly for sodium) that is built up by an ATP-consuming transporter (mostly sodium, potassium ATPase) to maintain transmembrane gradients for other electrolytes or metabolic substrates. [NIH] Antiserum: The blood serum obtained from an animal after it has been immunized with a particular antigen. It will contain antibodies which are specific for that antigen as well as antibodies specific for any other antigen with which the animal has previously been immunized. [NIH] Antispasmodics: Medicines that help reduce or stop muscle spasms in the intestines. Examples are dicyclomine (dy-SY-klo-meen) (Bentyl) and atropine (AH-tro-peen) (Donnatal). [NIH] Antitoxin: A purified antiserum from animals (usually horses) immunized by injections of a toxin or toxoid, administered as a passive immunizing agent to neutralize a specific bacterial toxin, e.g., botulinus, tetanus or diphtheria. [EU] Antiviral: Destroying viruses or suppressing their replication. [EU] Anus: The opening of the rectum to the outside of the body. [NIH] Anxiety: Persistent feeling of dread, apprehension, and impending disaster. [NIH] Aorta: The main trunk of the systemic arteries. [NIH]
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Aponeurosis: Tendinous expansion consisting of a fibrous or membranous sheath which serves as a fascia to enclose or bind a group of muscles. [NIH] Apoptosis: One of the two mechanisms by which cell death occurs (the other being the pathological process of necrosis). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA (DNA fragmentation) at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. [NIH] Aquaporins: Membrane proteins which facilitate the passage of water. They are members of the family of membrane channel proteins which includes the lens major intrinsic protein and bacterial glycerol transporters. [NIH] Aqueous: Having to do with water. [NIH] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Aromatic: Having a spicy odour. [EU] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Ascariasis: Infection by nematodes of the genus Ascaris. Ingestion of infective eggs causes diarrhea and pneumonitis. Its distribution is more prevalent in areas of poor sanitation and where human feces are used for fertilizer. [NIH] Aspartate: A synthetic amino acid. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Astringents: Agents, usually topical, that cause the contraction of tissues for the control of bleeding or secretions. [NIH] Astrocytoma: A tumor that begins in the brain or spinal cord in small, star-shaped cells called astrocytes. [NIH] Astrovirus: A genus of small, circular RNA viruses in the family Astroviridae. They cause gastroenteritis and are found in the stools of several vertebrates including humans. Transmission is by the fecal-oral route. There are at least seven human serotypes and the type species is human astrovirus 1. [NIH] Asymptomatic: Having no signs or symptoms of disease. [NIH] Atresia: Lack of a normal opening from the esophagus, intestines, or anus. [NIH] Atropine: A toxic alkaloid, originally from Atropa belladonna, but found in other plants, mainly Solanaceae. [NIH] Attenuated: Strain with weakened or reduced virulence. [NIH] Attenuation: Reduction of transmitted sound energy or its electrical equivalent. [NIH] Autacoids: A chemically diverse group of substances produced by various tissues in the body that cause slow contraction of smooth muscle; they have other intense but varied pharmacologic activities. [NIH] Autoantibodies: Antibodies that react with self-antigens (autoantigens) of the organism that produced them. [NIH]
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Autoantigens: Endogenous tissue constituents that have the ability to interact with autoantibodies and cause an immune response. [NIH] Autoimmune disease: A condition in which the body recognizes its own tissues as foreign and directs an immune response against them. [NIH] Autologous: Taken from an individual's own tissues, cells, or DNA. [NIH] Autonomic: Self-controlling; functionally independent. [EU] Avidin: A specific protein in egg albumin that interacts with biotin to render it unavailable to mammals, thereby producing biotin deficiency. [NIH] Axonal: Condition associated with metabolic derangement of the entire neuron and is manifest by degeneration of the distal portion of the nerve fiber. [NIH] Azithromycin: A semi-synthetic macrolide antibiotic structurally related to erythromycin. It has been used in the treatment of Mycobacterium avium intracellulare infections, toxoplasmosis, and cryptosporidiosis. [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] Bacteraemia: The presence of bacteria in the blood. [EU] Bacteremia: The presence of viable bacteria circulating in the blood. Fever, chills, tachycardia, and tachypnea are common acute manifestations of bacteremia. The majority of cases are seen in already hospitalized patients, most of whom have underlying diseases or procedures which render their bloodstreams susceptible to invasion. [NIH] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Bacterial Infections: Infections by bacteria, general or unspecified. [NIH] Bacterial Physiology: Physiological processes and activities of bacteria. [NIH] Bacterial toxin: A toxic substance, made by bacteria, that can be modified to kill specific tumor cells without harming normal cells. [NIH] Bactericidal: Substance lethal to bacteria; substance capable of killing bacteria. [NIH] Bacteriolysis: Rupture of bacterial cells due to mechanical force, chemical action, or the lytic growth of bacteriophages. [NIH] Bacteriophage: A virus whose host is a bacterial cell; A virus that exclusively infects bacteria. It generally has a protein coat surrounding the genome (DNA or RNA). One of the coliphages most extensively studied is the lambda phage, which is also one of the most important. [NIH] 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] Base: In chemistry, the nonacid part of a salt; a substance that combines with acids to form salts; a substance that dissociates to give hydroxide ions in aqueous solutions; a substance whose molecule or ion can combine with a proton (hydrogen ion); a substance capable of donating a pair of electrons (to an acid) for the formation of a coordinate covalent bond. [EU] Base Sequence: The sequence of purines and pyrimidines in nucleic acids and
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polynucleotides. It is also called nucleotide or nucleoside sequence. [NIH] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]
Beta-Defensins: Defensins found mainly in epithelial cells. [NIH] Beta-Endorphin: A peptide consisting of amino acid sequence 61-91 of the endogenous pituitary hormone beta-lipotropin. The first four amino acids show a common tetrapeptide sequence with methionine- and leucine enkephalin. The compound shows opiate-like activity. Injection of beta-endorphin induces a profound analgesia of the whole body for several hours. This action is reversed after administration of naloxone. [NIH] Beta-glucans: Polysaccharides made by several types of mushrooms. Beta-glucans have been used to treat patients with gastric cancer and colorectal cancer. They may be able to stimulate the immune system. [NIH] 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] Beta-Thromboglobulin: A platelet-specific protein which is released when platelets aggregate. Elevated plasma levels have been reported after deep venous thrombosis, preeclampsia, myocardial infarction with mural thrombosis, and myeloproliferative disorders. Measurement of beta-thromboglobulin in biological fluids by radioimmunoassay is used for the diagnosis and assessment of progress of thromboembolic disorders. [NIH] Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Bile Acids: Acids made by the liver that work with bile to break down fats. [NIH] Bile Acids and Salts: Steroid acids and salts. The primary bile acids are derived from cholesterol in the liver and usually conjugated with glycine or taurine. The secondary bile acids are further modified by bacteria in the intestine. They play an important role in the digestion and absorption of fat. They have also been used pharmacologically, especially in the treatment of gallstones. [NIH] Bile Ducts: Tubes that carry bile from the liver to the gallbladder for storage and to the small intestine for use in digestion. [NIH] Biliary: Having to do with the liver, bile ducts, and/or gallbladder. [NIH] Bilirubin: A bile pigment that is a degradation product of heme. [NIH] Binding Sites: The reactive parts of a macromolecule that directly participate in its specific combination with another molecule. [NIH] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biological therapy: Treatment to stimulate or restore the ability of the immune system to fight infection and disease. Also used to lessen side effects that may be caused by some cancer treatments. Also known as immunotherapy, biotherapy, or biological response modifier (BRM) therapy. [NIH] Biological Transport: The movement of materials (including biochemical substances and drugs) across cell membranes and epithelial layers, usually by passive diffusion. [NIH] Biomass: Total mass of all the organisms of a given type and/or in a given area. (From Concise Dictionary of Biology, 1990) It includes the yield of vegetative mass produced from any given crop. [NIH]
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Biomolecular: A scientific field at the interface between advanced computing and biotechnology. [NIH] Biosynthesis: The building up of a chemical compound in the physiologic processes of a living organism. [EU] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Biotin: Hexahydro-2-oxo-1H-thieno(3,4-d)imidazole-4-pentanoic acid. Growth factor present in minute amounts in every living cell. It occurs mainly bound to proteins or polypeptides and is abundant in liver, kidney, pancreas, yeast, and milk.The biotin content of cancerous tissue is higher than that of normal tissue. [NIH] Biotype: A group of individuals having the same genotype. [NIH] Bivalent: Pertaining to a group of 2 homologous or partly homologous chromosomes during the zygotene stage of prophase to the first metaphase in meiosis. [NIH] Bladder: The organ that stores urine. [NIH] Blastomycosis: A fungal infection that may appear in two forms: 1) a primary lesion characterized by the formation of a small cutaneous nodule and small nodules along the lymphatics that may heal within several months; and 2) chronic granulomatous lesions characterized by thick crusts, warty growths, and unusual vascularity and infection in the middle or upper lobes of the lung. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood Glucose: Glucose in blood. [NIH] Blood Platelets: Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood transfusion: The administration of blood or blood products into a blood vessel. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Blot: To transfer DNA, RNA, or proteins to an immobilizing matrix such as nitrocellulose. [NIH]
Blotting, Western: Identification of proteins or peptides that have been electrophoretically separated by blotting and transferred to strips of nitrocellulose paper. The blots are then detected by radiolabeled antibody probes. [NIH] Body Fluids: Liquid components of living organisms. [NIH] Body Mass Index: One of the anthropometric measures of body mass; it has the highest correlation with skinfold thickness or body density. [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
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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] Border Disease: Congenital disorder of lambs caused by a virus closely related to or identical with certain strains of bovine viral diarrhea virus. [NIH] Border Disease Virus: A species of Pestivirus causing a congenital sheep disease characterized by an abnormally hairy birth-coat, tremors, and poor growth. [NIH] Bowel: The long tube-shaped organ in the abdomen that completes the process of digestion. There is both a small and a large bowel. Also called the intestine. [NIH] Bowel Movement: Body wastes passed through the rectum and anus. [NIH] Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]
Breakdown: A physical, metal, or nervous collapse. [NIH] Broad-spectrum: Effective against a wide range of microorganisms; said of an antibiotic. [EU] Bronchi: The larger air passages of the lungs arising from the terminal bifurcation of the trachea. [NIH] Bronchial: Pertaining to one or more bronchi. [EU] Bronchiectasis: Persistent abnormal dilatation of the bronchi. [NIH] Bronchiseptica: A small, gram-negative, motile bacillus. A normal inhabitant of the respiratory tract in man, dogs, and pigs, but is also associated with canine infectious tracheobronchitis and atrophic rhinitis in pigs. [NIH] Bronchitis: Inflammation (swelling and reddening) of the bronchi. [NIH] Buccal: Pertaining to or directed toward the cheek. In dental anatomy, used to refer to the buccal surface of a tooth. [EU] Buffers: A chemical system that functions to control the levels of specific ions in solution. When the level of hydrogen ion in solution is controlled the system is called a pH buffer. [NIH]
Burns: Injuries to tissues caused by contact with heat, steam, chemicals (burns, chemical), electricity (burns, electric), or the like. [NIH] Burns, Electric: Burns produced by contact with electric current or from a sudden discharge of electricity. [NIH] Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. [NIH] Calcium Signaling: Signal transduction mechanisms whereby calcium mobilization (from outside the cell or from intracellular storage pools) to the cytoplasm is triggered by external stimuli. Calcium signals are often seen to propagate as waves, oscillations, spikes or puffs. The calcium acts as an intracellular messenger by activating calcium-responsive proteins. [NIH]
Calicivirus: A genus in the family Caliciviridae containing many species including feline calicivirus , vesicular exanthema of swine virus, and San Miguel sea lion viruses. [NIH] Calmodulin: A heat-stable, low-molecular-weight activator protein found mainly in the brain and heart. The binding of calcium ions to this protein allows this protein to bind to
256 Cholera
cyclic nucleotide phosphodiesterases and to adenyl cyclase with subsequent activation. Thereby this protein modulates cyclic AMP and cyclic GMP levels. [NIH] Campylobacter: A genus of bacteria found in the reproductive organs, intestinal tract, and oral cavity of animals and man. Some species are pathogenic. [NIH] Campylobacter Infections: Infections with bacteria of the genus Campylobacter. [NIH] Candidosis: An infection caused by an opportunistic yeasts that tends to proliferate and become pathologic when the environment is favorable and the host resistance is weakened. [NIH]
Capillary: Any one of the minute vessels that connect the arterioles and venules, forming a network in nearly all parts of the body. Their walls act as semipermeable membranes for the interchange of various substances, including fluids, between the blood and tissue fluid; called also vas capillare. [EU] Capsaicin: Cytotoxic alkaloid from various species of Capsicum (pepper, paprika), of the Solanaceae. [NIH] Capsid: The outer protein protective shell of a virus, which protects the viral nucleic acid. [NIH]
Capsular: Cataract which is initiated by an opacification at the surface of the lens. [NIH] Carbachol: A slowly hydrolyzed cholinergic agonist that acts at both muscarinic and nicotinic receptors. [NIH] Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen are usually in the proportion to form water, (CH2O)n. The most important carbohydrates are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, polyand heterosaccharides. [EU] Carbon Dioxide: A colorless, odorless gas that can be formed by the body and is necessary for the respiration cycle of plants and animals. [NIH] Carcinogen: Any substance that causes cancer. [NIH] Carcinogenesis: The process by which normal cells are transformed into cancer cells. [NIH] Carcinogenic: Producing carcinoma. [EU] Carcinoma: Cancer that begins in the skin or in tissues that line or cover internal organs. [NIH]
Cardiac: Having to do with the heart. [NIH] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Cardiovascular disease: Any abnormal condition characterized by dysfunction of the heart and blood vessels. CVD includes atherosclerosis (especially coronary heart disease, which can lead to heart attacks), cerebrovascular disease (e.g., stroke), and hypertension (high blood pressure). [NIH] Carrier State: The condition of harboring an infective organism without manifesting symptoms of infection. The organism must be readily transmissable to another susceptible host. [NIH] Case report: A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin). [NIH] Case series: A group or series of case reports involving patients who were given similar treatment. Reports of case series usually contain detailed information about the individual patients. This includes demographic information (for example, age, gender, ethnic origin)
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and information on diagnosis, treatment, response to treatment, and follow-up after treatment. [NIH] Castor Oil: Oil obtained from seeds of Ricinus communis that is used as a cathartic and as a plasticizer. [NIH] Catalytic Domain: The region of an enzyme that interacts with its substrate to cause the enzymatic reaction. [NIH] Cathode: An electrode, usually an incandescent filament of tungsten, which emits electrons in an X-ray tube. [NIH] Cations: Postively charged atoms, radicals or groups of atoms which travel to the cathode or negative pole during electrolysis. [NIH] Caudal: Denoting a position more toward the cauda, or tail, than some specified point of reference; same as inferior, in human anatomy. [EU] Causal: Pertaining to a cause; directed against a cause. [EU] Caveolae: Endocytic/exocytic cell membrane structures rich in glycosphingolipids, cholesterol, and lipid-anchored membrane proteins that function in endocytosis (potocytosis), transcytosis, and signal transduction. Caveolae assume various shapes from open pits to closed vesicles. Caveolar coats are composed of caveolins. [NIH] Caveolins: The main structural proteins of caveolae. Several distinct genes for caveolins have been identified. [NIH] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function which takes place during the development of the embryo and leads to the formation of specialized cells, tissues, and organs. [NIH] Cell Division: The fission of a cell. [NIH] Cell membrane: Cell membrane = plasma membrane. The structure enveloping a cell, enclosing the cytoplasm, and forming a selective permeability barrier; it consists of lipids, proteins, and some carbohydrates, the lipids thought to form a bilayer in which integral proteins are embedded to varying degrees. [EU] Cell Membrane Structures: Structures which are part of the cell membrane or have cell membrane as a major part of their structure. [NIH] Cell Physiology: Characteristics and physiological processes of cells from cell division to cell death. [NIH] Cell Polarity: Orientation of intracellular structures especially with respect to the apical and basolateral domains of the plasma membrane. Polarized cells must direct proteins from the Golgi apparatus to the appropriate domain since tight junctions prevent proteins from diffusing between the two domains. [NIH] Cell proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH] Cell Size: The physical dimensions of a cell. It refers mainly to changes in dimensions correlated with physiological or pathological changes in cells. [NIH] Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. [NIH]
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Cellobiose: A disaccharide consisting of two glucose units in beta (1-4) glycosidic linkage. Obtained from the partial hydrolysis of cellulose. [NIH] Cellular Structures: Components of a cell. [NIH] Cellulase: An enzyme isolated from fungi and bacteria. It catalyzes the endohydrolysis of 1,4-beta-glucosidic linkages in cellulose, lichenin, and cereal beta-glucans. EC 3.2.1.4. [NIH] Cellulose: A polysaccharide with glucose units linked as in cellobiose. It is the chief constituent of plant fibers, cotton being the purest natural form of the substance. As a raw material, it forms the basis for many derivatives used in chromatography, ion exchange materials, explosives manufacturing, and pharmaceutical preparations. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Central Nervous System Infections: Pathogenic infections of the brain, spinal cord, and meninges. DNA virus infections; RNA virus infections; bacterial infections; mycoplasma infections; Spirochaetales infections; fungal infections; protozoan infections; helminthiasis; and prion diseases may involve the central nervous system as a primary or secondary process. [NIH] Cephalosporins: A group of broad-spectrum antibiotics first isolated from the Mediterranean fungus Acremonium (Cephalosporium acremonium). They contain the betalactam moiety thia-azabicyclo-octenecarboxylic acid also called 7-aminocephalosporanic acid. [NIH] Ceramide: A type of fat produced in the body. It may cause some types of cells to die, and is being studied in cancer treatment. [NIH] Cerebellar: Pertaining to the cerebellum. [EU] Cerebellum: Part of the metencephalon that lies in the posterior cranial fossa behind the brain stem. It is concerned with the coordination of movement. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebral hemispheres: The two halves of the cerebrum, the part of the brain that controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. The right hemisphere controls muscle movement on the left side of the body, and the left hemisphere controls muscle movement on the right side of the body. [NIH] Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU] Cerebrum: The largest part of the brain. It is divided into two hemispheres, or halves, called the cerebral hemispheres. The cerebrum controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. [NIH] Cervical: Relating to the neck, or to the neck of any organ or structure. Cervical lymph nodes are located in the neck; cervical cancer refers to cancer of the uterine cervix, which is the lower, narrow end (the "neck") of the uterus. [NIH] Cervix: The lower, narrow end of the uterus that forms a canal between the uterus and vagina. [NIH] Character: In current usage, approximately equivalent to personality. The sum of the relatively fixed personality traits and habitual modes of response of an individual. [NIH] Chemokines: Class of pro-inflammatory cytokines that have the ability to attract and activate leukocytes. They can be divided into at least three structural branches: C (chemokines, C), CC (chemokines, CC), and CXC (chemokines, CXC), according to variations in a shared cysteine motif. [NIH] Chemotactic Factors: Chemical substances that attract or repel cells or organisms. The
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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] Chemotaxis: The movement of cells or organisms toward or away from a substance in response to its concentration gradient. [NIH] Chemotherapy: Treatment with anticancer drugs. [NIH] Chimeras: Organism that contains a mixture of genetically different cells. [NIH] Chimeric Proteins: Proteins in individuals that are derived from genetically different zygotes. [NIH] Chlorine: A greenish-yellow, diatomic gas that is a member of the halogen family of elements. It has the atomic symbol Cl, atomic number 17, and atomic weight 70.906. It is a powerful irritant that can cause fatal pulmonary edema. Chlorine is used in manufacturing, as a reagent in synthetic chemistry, for water purification, and in the production of chlorinated lime, which is used in fabric bleaching. [NIH] Chlorophyll: Porphyrin derivatives containing magnesium that act to convert light energy in photosynthetic organisms. [NIH] Chloroplasts: Plant cell inclusion bodies that contain the photosynthetic pigment chlorophyll, which is associated with the membrane of thylakoids. Chloroplasts occur in cells of leaves and young stems of higher plants. [NIH] Cholecystokinin: A 33-amino acid peptide secreted by the upper intestinal mucosa and also found in the central nervous system. It causes gallbladder contraction, release of pancreatic exocrine (or digestive) enzymes, and affects other gastrointestinal functions. Cholecystokinin may be the mediator of satiety. [NIH] Cholera: An acute diarrheal disease endemic in India and Southeast Asia whose causative agent is vibrio cholerae. This condition can lead to severe dehydration in a matter of hours unless quickly treated. [NIH] Cholera Toxin: The enterotoxin from Vibrio cholerae. It is a protein that consists of two major components, the heavy (H) or A peptide and the light (L) or B peptide or choleragenoid. The B peptide anchors the protein to intestinal epithelial cells, while the A peptide, enters the cytoplasm, and activates adenylate cyclase, and production of cAMP. Increased levels of cAMP are thought to modulate release of fluid and electrolytes from intestinal crypt cells. [NIH] Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. [NIH] Cholinergic: Resembling acetylcholine in pharmacological action; stimulated by or releasing acetylcholine or a related compound. [EU] Chromaffin System: The cells of the body which stain with chromium salts. They occur along the sympathetic nerves, in the adrenal gland, and in various other organs. [NIH] Chromatin: The material of chromosomes. It is a complex of DNA, histones, and nonhistone proteins (chromosomal proteins, non-histone) found within the nucleus of a cell. [NIH] Chromosomal: Pertaining to chromosomes. [EU] Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chronic Disease: Disease or ailment of long duration. [NIH] Circadian: Repeated more or less daily, i. e. on a 23- to 25-hour cycle. [NIH]
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Circadian Rhythm: The regular recurrence, in cycles of about 24 hours, of biological processes or activities, such as sensitivity to drugs and stimuli, hormone secretion, sleeping, feeding, etc. This rhythm seems to be set by a 'biological clock' which seems to be set by recurring daylight and darkness. [NIH] Circulatory system: The system that contains the heart and the blood vessels and moves blood throughout the body. This system helps tissues get enough oxygen and nutrients, and it helps them get rid of waste products. The lymph system, which connects with the blood system, is often considered part of the circulatory system. [NIH] Clathrin: The main structural coat protein of coated vesicles which play a key role in the intracellular transport between membranous organelles. Clathrin also interacts with cytoskeletal proteins. [NIH] Clear cell carcinoma: A rare type of tumor of the female genital tract in which the inside of the cells looks clear when viewed under a microscope. [NIH] Clinical Medicine: The study and practice of medicine by direct examination of the patient. [NIH]
Clinical study: A research study in which patients receive treatment in a clinic or other medical facility. Reports of clinical studies can contain results for single patients (case reports) or many patients (case series or clinical trials). [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] Clostridium: A genus of motile or nonmotile gram-positive bacteria of the family Bacillaceae. Many species have been identified with some being pathogenic. They occur in water, soil, and in the intestinal tract of humans and lower animals. [NIH] Clostridium difficile: A common inhabitant of the colon flora in human infants and sometimes in adults. It produces a toxin that causes pseudomembranous enterocolitis in patients receiving antibiotic therapy. [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] Coca: Any of several South American shrubs of the Erythroxylon genus (and family) that yield cocaine; the leaves are chewed with alum for CNS stimulation. [NIH] Cocaine: An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake. [NIH] Coccidioidomycosis: An infectious disease caused by a fungus, Coccidioides immitis, that is prevalent in the western United States and is acquired by inhalation of dust containing the spores. [NIH]
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Codon: A set of three nucleotides in a protein coding sequence that specifies individual amino acids or a termination signal (codon, terminator). Most codons are universal, but some organisms do not produce the transfer RNAs (RNA, transfer) complementary to all codons. These codons are referred to as unassigned codons (codons, nonsense). [NIH] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] Colchicine: A major alkaloid from Colchicum autumnale L. and found also in other Colchicum species. Its primary therapeutic use is in the treatment of gout, but it has been used also in the therapy of familial Mediterranean fever (periodic disease). [NIH] Colicins: Bacteriocins elaborated by strains of Escherichia coli and related species. They are proteins or protein-lipopolysaccharide complexes lethal to other strains of the same species. [NIH]
Coliphages: Viruses whose host is Escherichia coli. [NIH] Colitis: Inflammation of the colon. [NIH] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline, hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [NIH] Collagen disease: A term previously used to describe chronic diseases of the connective tissue (e.g., rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis), but now is thought to be more appropriate for diseases associated with defects in collagen, which is a component of the connective tissue. [NIH] Colloidal: Of the nature of a colloid. [EU] Combinatorial: A cut-and-paste process that churns out thousands of potentially valuable compounds at once. [NIH] Communis: Common tendon of the rectus group of muscles that surrounds the optic foramen and a portion of the superior orbital fissure, to the anterior margin of which it is attached at the spina recti lateralis. [NIH] 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
262 Cholera
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] Complementation: The production of a wild-type phenotype when two different mutations are combined in a diploid or a heterokaryon and tested in trans-configuration. [NIH] 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] Confounder: A factor of confusion which blurs a specific connection between a disease and a probable causal factor which is being studied. [NIH] Confusion: A mental state characterized by bewilderment, emotional disturbance, lack of clear thinking, and perceptual disorientation. [NIH] Congestive heart failure: Weakness of the heart muscle that leads to a buildup of fluid in body tissues. [NIH] Conjugated: Acting or operating as if joined; simultaneous. [EU] Conjugation: 1. The act of joining together or the state of being conjugated. 2. A sexual process seen in bacteria, ciliate protozoa, and certain fungi in which nuclear material is exchanged during the temporary fusion of two cells (conjugants). In bacterial genetics a form of sexual reproduction in which a donor bacterium (male) contributes some, or all, of its DNA (in the form of a replicated set) to a recipient (female) which then incorporates differing genetic information into its own chromosome by recombination and passes the recombined set on to its progeny by replication. In ciliate protozoa, two conjugants of separate mating types exchange micronuclear material and then separate, each now being a fertilized cell. In certain fungi, the process involves fusion of two gametes, resulting in union of their nuclei and formation of a zygote. 3. In chemistry, the joining together of two compounds to produce another compound, such as the combination of a toxic product with some substance in the body to form a detoxified product, which is then eliminated. [EU] Conjunctiva: The mucous membrane that lines the inner surface of the eyelids and the anterior part of the sclera. [NIH] Conjunctivitis: Inflammation of the conjunctiva, generally consisting of conjunctival hyperaemia associated with a discharge. [EU] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH]
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Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connexins: A group of homologous proteins which form the intermembrane channels of gap junctions. The connexins are the products of an identified gene family which has both highly conserved and highly divergent regions. The variety contributes to the wide range of functional properties of gap junctions. [NIH] Consciousness: Sense of awareness of self and of the environment. [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 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] Constriction: The act of constricting. [NIH] Consumption: Pulmonary tuberculosis. [NIH] Contamination: The soiling or pollution by inferior material, as by the introduction of organisms into a wound, or sewage into a stream. [EU] Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] Control group: In a clinical trial, the group that does not receive the new treatment being studied. This group is compared to the group that receives the new treatment, to see if the new treatment works. [NIH] Convalescence: The period of recovery following an illness. [NIH] Convulsions: A general term referring to sudden and often violent motor activity of cerebral or brainstem origin. Convulsions may also occur in the absence of an electrical cerebral discharge (e.g., in response to hypotension). [NIH] Coordination: Muscular or motor regulation or the harmonious cooperation of muscles or groups of muscles, in a complex action or series of actions. [NIH] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary heart disease: A type of heart disease caused by narrowing of the coronary arteries that feed the heart, which needs a constant supply of oxygen and nutrients carried by the blood in the coronary arteries. When the coronary arteries become narrowed or clogged by fat and cholesterol deposits and cannot supply enough blood to the heart, CHD results. [NIH] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [EU] Cortical: Pertaining to or of the nature of a cortex or bark. [EU] Cortisol: A steroid hormone secreted by the adrenal cortex as part of the body's response to
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stress. [NIH] Cowpox: A mild, eruptive skin disease of milk cows caused by cowpox virus, with lesions occurring principally on the udder and teats. Human infection may occur while milking an infected animal. [NIH] Cowpox Virus: A species of orthopoxvirus that is the etiologic agent of cowpox. It is closely related to but antigenically different from vaccina virus. [NIH] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU] Craniocerebral Trauma: Traumatic injuries involving the cranium and intracranial structures (i.e., brain; cranial nerves; meninges; and other structures). Injuries may be classified by whether or not the skull is penetrated (i.e., penetrating vs. nonpenetrating) or whether there is an associated hemorrhage. [NIH] Cribriform: Pierced with small holes as in a sieve. Refers to the appearance of a tumor when viewed under a microscope. The tumor appears to have open spaces or small holes inside. [NIH]
Crossing-over: The exchange of corresponding segments between chromatids of homologous chromosomes during meiosia, forming a chiasma. [NIH] Crowding: Behavior with respect to an excessive number of individuals, human or animal, in relation to available space. [NIH] Cryptococcosis: Infection with a fungus of the species Cryptococcus neoformans. [NIH] Cryptosporidiosis: Parasitic intestinal infection with severe diarrhea caused by a protozoan, Cryptosporidium. It occurs in both animals and humans. [NIH] Crystallization: The formation of crystals; conversion to a crystalline form. [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] Cultured cells: Animal or human cells that are grown in the laboratory. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Cutaneous: Having to do with the skin. [NIH] Cyclic: Pertaining to or occurring in a cycle or cycles; the term is applied to chemical compounds that contain a ring of atoms in the nucleus. [EU] Cysteine: A thiol-containing non-essential amino acid that is oxidized to form cystine. [NIH] Cystine: A covalently linked dimeric nonessential amino acid formed by the oxidation of cysteine. Two molecules of cysteine are joined together by a disulfide bridge to form cystine. [NIH]
Cytogenetics: A branch of genetics which deals with the cytological and molecular behavior of genes and chromosomes during cell division. [NIH] Cytokine: Small but highly potent protein that modulates the activity of many cell types, including T and B cells. [NIH] 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
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various intracellular membranes which function in storage, transport or metabolism. [NIH] Cytoskeletal Proteins: Major constituent of the cytoskeleton found in the cytoplasm of eukaryotic cells. They form a flexible framework for the cell, provide attachment points for organelles and formed bodies, and make communication between parts of the cell possible. [NIH]
Cytoskeleton: The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm. [NIH] Cytotoxic: Cell-killing. [NIH] Cytotoxicity: Quality of being capable of producing a specific toxic action upon cells of special organs. [NIH] Cytotoxins: Substances elaborated by microorganisms, plants or animals that are specifically toxic to individual cells; they may be involved in immunity or may be contained in venoms. [NIH]
Databases, Bibliographic: Extensive collections, reputedly complete, of references and citations to books, articles, publications, etc., generally on a single subject or specialized subject area. Databases can operate through automated files, libraries, or computer disks. The concept should be differentiated from factual databases which is used for collections of data and facts apart from bibliographic references to them. [NIH] Daunorubicin: Very toxic anthracycline aminoglycoside antibiotic isolated from Streptomyces peucetius and others, used in treatment of leukemias and other neoplasms. [NIH]
Day Care: Institutional health care of patients during the day. The patients return home at night. [NIH] De novo: In cancer, the first occurrence of cancer in the body. [NIH] Decarboxylation: The removal of a carboxyl group, usually in the form of carbon dioxide, from a chemical compound. [NIH] Defense Mechanisms: Unconscious process used by an individual or a group of individuals in order to cope with impulses, feelings or ideas which are not acceptable at their conscious level; various types include reaction formation, projection and self reversal. [NIH] Defensins: Family of antimicrobial peptides that have been identified in humans, animals, and plants. They are thought to play a role in host defenses against infections, inflammation, wound repair, and acquired immunity. Based on the disulfide pairing of their characteristic six cysteine residues, they are divided into alpha-defensins and beta-defensins. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Dehydration: The condition that results from excessive loss of body water. [NIH] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Denaturation: Rupture of the hydrogen bonds by heating a DNA solution and then cooling it rapidly causes the two complementary strands to separate. [NIH] Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other neurons. [NIH] Dendritic: 1. Branched like a tree. 2. Pertaining to or possessing dendrites. [EU] Dendritic cell: A special type of antigen-presenting cell (APC) that activates T lymphocytes. [NIH]
Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH]
266 Cholera
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]
Dentifrices: Any preparations used for cleansing teeth; they usually contain an abrasive, detergent, binder and flavoring agent and may exist in the form of liquid, paste or powder; may also contain medicaments and caries preventives. [NIH] Deoxyribonucleic: A polymer of subunits called deoxyribonucleotides which is the primary genetic material of a cell, the material equivalent to genetic information. [NIH] Deoxyribonucleic acid: A polymer of subunits called deoxyribonucleotides which is the primary genetic material of a cell, the material equivalent to genetic information. [NIH] Deoxyribonucleotides: A purine or pyrimidine base bonded to a deoxyribose containing a bond to a phosphate group. [NIH] Depolarization: The process or act of neutralizing polarity. In neurophysiology, the reversal of the resting potential in excitable cell membranes when stimulated, i.e., the tendency of the cell membrane potential to become positive with respect to the potential outside the cell. [EU] Deprivation: Loss or absence of parts, organs, powers, or things that are needed. [EU] Dermatosis: Any skin disease, especially one not characterized by inflammation. [EU] DES: Diethylstilbestrol. A synthetic hormone that was prescribed from the early 1940s until 1971 to help women with complications of pregnancy. DES has been linked to an increased risk of clear cell carcinoma of the vagina in daughters of women who used DES. DES may also increase the risk of breast cancer in women who used DES. [NIH] Detergents: Purifying or cleansing agents, usually salts of long-chain aliphatic bases or acids, that exert cleansing (oil-dissolving) and antimicrobial effects through a surface action that depends on possessing both hydrophilic and hydrophobic properties. [NIH] Developed Countries: Countries that have reached a level of economic achievement through an increase of production, per capita income and consumption, and utilization of natural and human resources. [NIH] Developing Countries: Countries in the process of change directed toward economic growth, that is, an increase in production, per capita consumption, and income. The process of economic growth involves better utilization of natural and human resources, which results in a change in the social, political, and economic structures. [NIH] Dextroamphetamine: The d-form of amphetamine. It is a central nervous system stimulant and a sympathomimetic. It has also been used in the treatment of narcolepsy and of attention deficit disorders and hyperactivity in children. Dextroamphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulating release of monamines, and inhibiting monoamine oxidase. It is also a drug of abuse and a psychotomimetic. [NIH] Diabetes Mellitus: A heterogeneous group of disorders that share glucose intolerance in common. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Diagnostic Services: Organized services for the purpose of providing diagnosis to promote and maintain health. [NIH] Diarrhea: Passage of excessively liquid or excessively frequent stools. [NIH]
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Diarrhoea: Abnormal frequency and liquidity of faecal discharges. [EU] Diastolic: Of or pertaining to the diastole. [EU] Dicyclomine: A muscarinic antagonist used as an antispasmodic and in urinary incontinence. It has little effect on glandular secretion or the cardiovascular system. It does have some local anesthetic properties and is used in gastrointestinal, biliary, and urinary tract spasms. [NIH] Diencephalon: The paired caudal parts of the prosencephalon from which the thalamus, hypothalamus, epithalamus, and subthalamus are derived. [NIH] Dietary Fats: Fats present in food, especially in animal products such as meat, meat products, butter, ghee. They are present in lower amounts in nuts, seeds, and avocados. [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] Digestive system: The organs that take in food and turn it into products that the body can use to stay healthy. Waste products the body cannot use leave the body through bowel movements. The digestive system includes the salivary glands, mouth, esophagus, stomach, liver, pancreas, gallbladder, small and large intestines, and rectum. [NIH] Digestive tract: The organs through which food passes when food is eaten. These organs are the mouth, esophagus, stomach, small and large intestines, and rectum. [NIH] Dihydrotestosterone: Anabolic agent. [NIH] Dihydroxy: AMPA/Kainate antagonist. [NIH] Dilatation: The act of dilating. [NIH] Dilution: A diluted or attenuated medicine; in homeopathy, the diffusion of a given quantity of a medicinal agent in ten or one hundred times the same quantity of water. [NIH] Dimethyl: A volatile metabolite of the amino acid methionine. [NIH] Diphenoxylate: A meperidine congener used as an antidiarrheal, usually in combination with atropine. At high doses, it acts like morphine. Its unesterified metabolite difenoxin has similar properties and is used similarly. It has little or no analgesic activity. [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] Diphtheria Toxin: A 60 kD single chain protein elaborated by Corynebacterium diphtheriae that causes the sign and symptoms of diphtheria; it can be broken into two unequal fragments, the smaller (A fragment) inhibits protein synthesis and is the lethal moiety that needs the larger (B fragment) for entry into cells. [NIH] Diploid: Having two sets of chromosomes. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Discrimination: The act of qualitative and/or quantitative differentiation between two or more stimuli. [NIH] Disinfectant: An agent that disinfects; applied particularly to agents used on inanimate objects. [EU]
268 Cholera
Disinfection: Rendering pathogens harmless through the use of heat, antiseptics, antibacterial agents, etc. [NIH] Dislocation: The displacement of any part, more especially of a bone. Called also luxation. [EU]
Disposition: A tendency either physical or mental toward certain diseases. [EU] Dissection: Cutting up of an organism for study. [NIH] Dissociation: 1. The act of separating or state of being separated. 2. The separation of a molecule into two or more fragments (atoms, molecules, ions, or free radicals) produced by the absorption of light or thermal energy or by solvation. 3. In psychology, a defense mechanism in which a group of mental processes are segregated from the rest of a person's mental activity in order to avoid emotional distress, as in the dissociative disorders (q.v.), or in which an idea or object is segregated from its emotional significance; in the first sense it is roughly equivalent to splitting, in the second, to isolation. 4. A defect of mental integration in which one or more groups of mental processes become separated off from normal consciousness and, thus separated, function as a unitary whole. [EU] Dissociative Disorders: Sudden temporary alterations in the normally integrative functions of consciousness. [NIH] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU] Diuretic: A drug that increases the production of urine. [NIH] Domesticated: Species in which the evolutionary process has been influenced by humans to meet their needs. [NIH] Dopamine: An endogenous catecholamine and prominent neurotransmitter in several systems of the brain. In the synthesis of catecholamines from tyrosine, it is the immediate precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of dopaminergic receptor subtypes mediate its action. Dopamine is used pharmacologically for its direct (beta adrenergic agonist) and indirect (adrenergic releasing) sympathomimetic effects including its actions as an inotropic agent and as a renal vasodilator. [NIH] Dorsal: 1. Pertaining to the back or to any dorsum. 2. Denoting a position more toward the back surface than some other object of reference; same as posterior in human anatomy; superior in the anatomy of quadrupeds. [EU] Dorsum: A plate of bone which forms the posterior boundary of the sella turcica. [NIH] Doxorubicin: Antineoplastic antibiotic obtained from Streptomyces peucetics. It is a hydroxy derivative of daunorubicin and is used in treatment of both leukemia and solid tumors. [NIH] Drive: A state of internal activity of an organism that is a necessary condition before a given stimulus will elicit a class of responses; e.g., a certain level of hunger (drive) must be present before food will elicit an eating response. [NIH] Drug Design: The molecular designing of drugs for specific purposes (such as DNAbinding, enzyme inhibition, anti-cancer efficacy, etc.) based on knowledge of molecular properties such as activity of functional groups, molecular geometry, and electronic structure, and also on information cataloged on analogous molecules. Drug design is generally computer-assisted molecular modeling and does not include pharmacokinetics, dosage analysis, or drug administration analysis. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH]
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Drug Resistance: Diminished or failed response of an organism, disease or tissue to the intended effectiveness of a chemical or drug. It should be differentiated from drug tolerance which is the progressive diminution of the susceptibility of a human or animal to the effects of a drug, as a result of continued administration. [NIH] Drug Tolerance: Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from drug resistance wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from maximum tolerated dose and no-observed-adverse-effect level. [NIH] Dry Eye Syndrome: A common condition that occurs when the eyes do not produce enough tears to keep the eye moist and comfortable. Common symptoms of dry eye include pain, stinging, burning, scratchiness, and intermittent blurring of vision. [NIH] Duct: A tube through which body fluids pass. [NIH] Duodenum: The first part of the small intestine. [NIH] Dura mater: The outermost, toughest, and most fibrous of the three membranes (meninges) covering the brain and spinal cord; called also pachymeninx. [EU] Dysentery: Any of various disorders marked by inflammation of the intestines, especially of the colon, and attended by pain in the abdomen, tenesmus, and frequent stools containing blood and mucus. Causes include chemical irritants, bacteria, protozoa, or parasitic worms. [EU]
Echinococcosis: An infection caused by the infestation of the larval form of tapeworms of the genus Echinococcus. The liver, lungs, and kidney are the most common areas of infestation. [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] Egg Yolk: Cytoplasm stored in an egg that contains nutritional reserves for the developing embryo. It is rich in polysaccharides, lipids, and proteins. [NIH] Elastin: The protein that gives flexibility to tissues. [NIH] Elective: Subject to the choice or decision of the patient or physician; applied to procedures that are advantageous to the patient but not urgent. [EU] Electrolysis: Destruction by passage of a galvanic electric current, as in disintegration of a chemical compound in solution. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electron microscope: A microscope (device used to magnify small objects) that uses electrons (instead of light) to produce an enlarged image. An electron microscopes shows tiny details better than any other type of microscope. [NIH] Electrons: Stable elementary particles having the smallest known negative charge, present in all elements; also called negatrons. Positively charged electrons are called positrons. The
270 Cholera
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 this condition. [NIH] Encephalomyelitis: A general term indicating inflammation of the brain and spinal cord, often used to indicate an infectious process, but also applicable to a variety of autoimmune and toxic-metabolic conditions. There is significant overlap regarding the usage of this term and encephalitis in the literature. [NIH] Endemic: Present or usually prevalent in a population or geographical area at all times; said of a disease or agent. Called also endemial. [EU] Endocrine Glands: Ductless glands that secrete substances which are released directly into the circulation and which influence metabolism and other body functions. [NIH] Endocrine System: The system of glands that release their secretions (hormones) directly into the circulatory system. In addition to the endocrine glands, included are the chromaffin system and the neurosecretory systems. [NIH] Endocytosis: Cellular uptake of extracellular materials within membrane-limited vacuoles or microvesicles. Endosomes play a central role in endocytosis. [NIH] 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] Endotoxic: Of, relating to, or acting as an endotoxin (= a heat-stable toxin, associated with the outer membranes of certain gram-negative bacteria. Endotoxins are not secreted and are released only when the cells are disrupted). [EU] Endotoxin: Toxin from cell walls of bacteria. [NIH] Energetic: Exhibiting energy : strenuous; operating with force, vigour, or effect. [EU] Energy balance: Energy is the capacity of a body or a physical system for doing work. Energy balance is the state in which the total energy intake equals total energy needs. [NIH] Enkephalin: A natural opiate painkiller, in the hypothalamus. [NIH] Enteric bacteria: Single-celled microorganisms that lack chlorophyll. Some bacteria are capable of causing human, animal, or plant diseases; others are essential in pollution control because they break down organic matter in the air and in the water. [NIH]
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Enteric Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Enteritis: Inflammation of the intestine, applied chiefly to inflammation of the small intestine; see also enterocolitis. [EU] Enterobactin: An iron-binding cyclic trimer of 2,3-dihydroxy-N-benzoyl-L-serine. It is produced by E. coli and other enteric bacteria. [NIH] Enterocolitis: Inflammation of the intestinal mucosa of the small and large bowel. [NIH] Enteropeptidase: A specialized proteolytic enzyme secreted by intestinal cells. It converts trypsinogen into its active form trypsin by removing the N-terminal peptide. EC 3.4.21.9. [NIH]
Enterotoxins: Substances that are toxic to the intestinal tract causing vomiting, diarrhea, etc.; most common enterotoxins are produced by bacteria. [NIH] Environmental Exposure: The exposure to potentially harmful chemical, physical, or biological agents in the environment or to environmental factors that may include ionizing radiation, pathogenic organisms, or toxic chemicals. [NIH] Environmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health. [NIH]
Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] 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] Epidermal: Pertaining to or resembling epidermis. Called also epidermic or epidermoid. [EU] Epidermal Growth Factor: A 6 kD polypeptide growth factor initially discovered in mouse submaxillary glands. Human epidermal growth factor was originally isolated from urine based on its ability to inhibit gastric secretion and called urogastrone. epidermal growth factor exerts a wide variety of biological effects including the promotion of proliferation and differentiation of mesenchymal and epithelial cells. [NIH] Epidermis: Nonvascular layer of the skin. It is made up, from within outward, of five layers: 1) basal layer (stratum basale epidermidis); 2) spinous layer (stratum spinosum epidermidis); 3) granular layer (stratum granulosum epidermidis); 4) clear layer (stratum lucidum epidermidis); and 5) horny layer (stratum corneum epidermidis). [NIH] Epidermoid carcinoma: A type of cancer in which the cells are flat and look like fish scales. Also called squamous cell carcinoma. [NIH] Epigastric: Having to do with the upper middle area of the abdomen. [NIH] Epinephrine: The active sympathomimetic hormone from the adrenal medulla in most species. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. It is used in asthma and cardiac failure and to delay absorption of local anesthetics. [NIH] Epithelial: Refers to the cells that line the internal and external surfaces of the body. [NIH] 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]
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Epitope: A molecule or portion of a molecule capable of binding to the combining site of an antibody. For every given antigenic determinant, the body can construct a variety of antibody-combining sites, some of which fit almost perfectly, and others which barely fit. [NIH]
Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] 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] Escherichia: A genus of gram-negative, facultatively anaerobic, rod-shaped bacteria whose organisms occur in the lower part of the intestine of warm-blooded animals. The species are either nonpathogenic or opportunistic pathogens. [NIH] Escherichia coli: A species of gram-negative, facultatively anaerobic, rod-shaped bacteria commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce diarrhea and pyogenic infections. [NIH]
Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]
Estradiol: The most potent mammalian estrogenic hormone. It is produced in the ovary, placenta, testis, and possibly the adrenal cortex. [NIH] Ethanol: A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in alcoholic beverages. [NIH] Ethmoid: An unpaired cranial bone which helps form the medial walls of the orbits and contains the themoidal air cells which drain into the nose. [NIH] Ethnic Groups: A group of people with a common cultural heritage that sets them apart from others in a variety of social relationships. [NIH] Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [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] Excitatory: When cortical neurons are excited, their output increases and each new input they receive while they are still excited raises their output markedly. [NIH] Exhaustion: The feeling of weariness of mind and body. [NIH] Exocrine: Secreting outwardly, via a duct. [EU] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Exotoxin: Toxic substance excreted by living bacterial cells. [NIH] Extracellular: Outside a cell or cells. [EU] Extracellular Matrix: A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. [NIH] Extraction: The process or act of pulling or drawing out. [EU]
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Faecal: Pertaining to or of the nature of feces. [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] Fatal Outcome: Death resulting from the presence of a disease in an individual, as shown by a single case report or a limited number of patients. This should be differentiated from death, the physiological cessation of life and from mortality, an epidemiological or statistical concept. [NIH] Fatigue: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. [NIH]
Fatty acids: A major component of fats that are used by the body for energy and tissue development. [NIH] Feces: The excrement discharged from the intestines, consisting of bacteria, cells exfoliated from the intestines, secretions, chiefly of the liver, and a small amount of food residue. [EU] Fermentation: An enzyme-induced chemical change in organic compounds that takes place in the absence of oxygen. The change usually results in the production of ethanol or lactic acid, and the production of energy. [NIH] Ferrets: Semidomesticated variety of European polecat much used for hunting rodents and/or rabbits and as a laboratory animal. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Filariasis: Infections with nematodes of the superfamily Filarioidea. The presence of living worms in the body is mainly asymptomatic but the death of adult worms leads to granulomatous inflammation and permanent fibrosis. Organisms of the genus Elaeophora infect wild elk and domestic sheep causing ischaemic necrosis of the brain, blindness, and dermatosis of the face. [NIH] Filtration: The passage of a liquid through a filter, accomplished by gravity, pressure, or vacuum (suction). [EU] Flagellin: A protein with a molecular weight of 40,000 isolated from bacterial flagella. At appropriate pH and salt concentration, three flagellin monomers can spontaneously reaggregate to form structures which appear identical to intact flagella. [NIH] Flatus: Gas passed through the rectum. [NIH] Fleas: Parasitic, blood-sucking, wingless insects comprising the order Siphonaptera. [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]
274 Cholera
Fluid Therapy: Therapy whose basic objective is to restore the volume and composition of the body fluids to normal with respect to water-electrolyte balance. Fluids may be administered intravenously, orally, by intermittent gavage, or by hypodermoclysis. [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] Flush: Transient, episodic redness of the face and neck caused by certain diseases, ingestion of certain drugs or other substances, heat, emotional factors, or physical exertion. [EU] Fold: A plication or doubling of various parts of the body. [NIH] Food Microbiology: The presence of bacteria, viruses, and fungi in food and food products. This term is not restricted to pathogenic organisms: the presence of various non-pathogenic bacteria and fungi in cheeses and wines, for example, is included in this concept. [NIH] Forearm: The part between the elbow and the wrist. [NIH] Fractionation: Dividing the total dose of radiation therapy into several smaller, equal doses delivered over a period of several days. [NIH] Frameshift: A type of mutation which causes out-of-phase transcription of the base sequence; such mutations arise from the addition or delection of nucleotide(s) in numbers other than 3 or multiples of 3. [NIH] Frameshift Mutation: A type of mutation in which a number of nucleotides not divisible by three is deleted from or inserted into a coding sequence, thereby causing an alteration in the reading frame of the entire sequence downstream of the mutation. These mutations may be induced by certain types of mutagens or may occur spontaneously. [NIH] Fucose: Deoxysugar. [NIH] Fucosyltransferases: Enzymes catalyzing the transfer of fucose from a nucleoside diphosphate fucose to an acceptor molecule which is frequently another carbohydrate, a glycoprotein, or a glycolipid molecule. Elevated activity of some fucosyltransferases in human serum may serve as an indicator of malignancy. The class includes EC 2.4.1.65; EC 2.4.1.68; EC 2.4.1.69; EC 2.4.1.89. [NIH] Fungi: A kingdom of eukaryotic, heterotrophic organisms that live as saprobes or parasites, including mushrooms, yeasts, smuts, molds, etc. They reproduce either sexually or asexually, and have life cycles that range from simple to complex. Filamentous fungi refer to those that grow as multicelluar colonies (mushrooms and molds). [NIH] Fungus: A general term used to denote a group of eukaryotic protists, including mushrooms, yeasts, rusts, moulds, smuts, etc., which are characterized by the absence of chlorophyll and by the presence of a rigid cell wall composed of chitin, mannans, and sometimes cellulose. They are usually of simple morphological form or show some reversible cellular specialization, such as the formation of pseudoparenchymatous tissue in the fruiting body of a mushroom. The dimorphic fungi grow, according to environmental conditions, as moulds or yeasts. [EU] GABA: The most common inhibitory neurotransmitter in the central nervous system. [NIH] Galanin: A neurotransmitter. [NIH]
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Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Gamma-Glutamyltransferase: An enzyme that catalyzes reversibly the transfer of a glutamyl group from a glutamyl-peptide and an amino acid to a peptide and a glutamylamino acid. EC 2.3.2.2. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] Ganglion: 1. A knot, or knotlike mass. 2. A general term for a group of nerve cell bodies located outside the central nervous system; occasionally applied to certain nuclear groups within the brain or spinal cord, e.g. basal ganglia. 3. A benign cystic tumour occurring on a aponeurosis or tendon, as in the wrist or dorsum of the foot; it consists of a thin fibrous capsule enclosing a clear mucinous fluid. [EU] Ganglioside: Protein kinase C's inhibitor which reduces ischemia-related brain damage. [NIH]
Gangrenous: A circumscribed, deep-seated, suppurative inflammation of the subcutaneous tissue of the eyelid discharging pus from several points. [NIH] Gap Junctions: Connections between cells which allow passage of small molecules and electric current. Gap junctions were first described anatomically as regions of close apposition between cells with a narrow (1-2 nm) gap between cell membranes. The variety in the properties of gap junctions is reflected in the number of connexins, the family of proteins which form the junctions. [NIH] Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] Gastric: Having to do with the stomach. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]
Gastritis: Inflammation of the stomach. [EU] Gastroenteritis: An acute inflammation of the lining of the stomach and intestines, characterized by anorexia, nausea, diarrhoea, abdominal pain, and weakness, which has various causes, including food poisoning due to infection with such organisms as Escherichia coli, Staphylococcus aureus, and Salmonella species; consumption of irritating food or drink; or psychological factors such as anger, stress, and fear. Called also enterogastritis. [EU] Gastroenterology: A subspecialty of internal medicine concerned with the study of the physiology and diseases of the digestive system and related structures (esophagus, liver, gallbladder, and pancreas). [NIH] Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] Gavage: Feeding by a tube passed into the stomach; called also tube feeding. [NIH] Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]
Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Gene Fusion: Fusion of structural genes to analyze protein behavior or fusion of regulatory sequences with structural genes to determine mechanisms of regulation. [NIH]
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Gene Targeting: The integration of exogenous DNA into the genome of an organism at sites where its expression can be suitably controlled. This integration occurs as a result of homologous recombination. [NIH] Genetic Code: The specifications for how information, stored in nucleic acid sequence (base sequence), is translated into protein sequence (amino acid sequence). The start, stop, and order of amino acids of a protein is specified by consecutive triplets of nucleotides called codons (codon). [NIH] Genetic Engineering: Directed modification of the gene complement of a living organism by such techniques as altering the DNA, substituting genetic material by means of a virus, transplanting whole nuclei, transplanting cell hybrids, etc. [NIH] Genetic testing: Analyzing DNA to look for a genetic alteration that may indicate an increased risk for developing a specific disease or disorder. [NIH] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Genital: Pertaining to the genitalia. [EU] Genitourinary: Pertaining to the genital and urinary organs; urogenital; urinosexual. [EU] Genitourinary system: The parts of the body that play a role in reproduction, getting rid of waste products in the form of urine, or both. [NIH] Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Germ Cells: The reproductive cells in multicellular organisms. [NIH] Germfree: Free from all living micro-organisms. [NIH] Giardia: A genus of flagellate intestinal protozoa parasitic in various vertebrates, including humans. Characteristics include the presence of four pairs of flagella arising from a complicated system of axonemes and cysts that are ellipsoidal to ovoidal in shape. [NIH] Giardia lamblia: A species of parasitic protozoa that attaches itself to the intestinal mucosa and feeds on mucous secretions. The organism is roughly pear-shaped and motility is somewhat erratic, with a slow oscillation about the long axis. Considered for many years to be non-pathogenic and often found in completely asymptomatic individuals, there is presently strong evidence for its pathogenic potential. [NIH] Giardiasis: An infection of the small intestine caused by the flagellated protozoan Giardia lamblia. It is spread via contaminated food and water and by direct person-to-person contact. [NIH] 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] Glioblastoma: A malignant form of astrocytoma histologically characterized by pleomorphism of cells, nuclear atypia, microhemorrhage, and necrosis. They may arise in any region of the central nervous system, with a predilection for the cerebral hemispheres, basal ganglia, and commissural pathways. Clinical presentation most frequently occurs in the fifth or sixth decade of life with focal neurologic signs or seizures. [NIH] Glioblastoma multiforme: A type of brain tumor that forms from glial (supportive) tissue of the brain. It grows very quickly and has cells that look very different from normal cells. Also called grade IV astrocytoma. [NIH] Glomerular: Pertaining to or of the nature of a glomerulus, especially a renal glomerulus. [EU]
Glomerular Filtration Rate: The volume of water filtered out of plasma through glomerular
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capillary walls into Bowman's capsules per unit of time. It is considered to be equivalent to inulin clearance. [NIH] Glomeruli: Plural of glomerulus. [NIH] Glottis: The vocal apparatus of the larynx, consisting of the true vocal cords (plica vocalis) and the opening between them (rima glottidis). [NIH] Glucocorticoid: A compound that belongs to the family of compounds called corticosteroids (steroids). Glucocorticoids affect metabolism and have anti-inflammatory and immunosuppressive effects. They may be naturally produced (hormones) or synthetic (drugs). [NIH] Glucose: D-Glucose. A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. [NIH] Glutamate: Excitatory neurotransmitter of the brain. [NIH] Glutamate Decarboxylase: A pyridoxal-phosphate protein that catalyzes the alphadecarboxylation of L-glutamic acid to form gamma-aminobutyric acid and carbon dioxide. The enzyme is found in bacteria and in invertebrate and vertebrate nervous systems. It is the rate-limiting enzyme in determining gaba levels in normal nervous tissues. The brain enzyme also acts on L-cysteate, L-cysteine sulfinate, and L-aspartate. EC 4.1.1.15. [NIH] Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid (glutamate) is the most common excitatory neurotransmitter in the central nervous system. [NIH]
Glycerol: A trihydroxy sugar alcohol that is an intermediate in carbohydrate and lipid metabolism. It is used as a solvent, emollient, pharmaceutical agent, and sweetening agent. [NIH]
Glycerophospholipids: Derivatives of phosphatidic acid in which the hydrophobic regions are composed of two fatty acids and a polar alcohol is joined to the C-3 position of glycerol through a phosphodiester bond. They are named according to their polar head groups, such as phosphatidylcholine and phosphatidylethanolamine. [NIH] Glycine: A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter. [NIH] Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Glycosidic: Formed by elimination of water between the anomeric hydroxyl of one sugar and a hydroxyl of another sugar molecule. [NIH] Goats: Any of numerous agile, hollow-horned ruminants of the genus Capra, closely related to the sheep. [NIH] Gonorrhea: Acute infectious disease characterized by primary invasion of the urogenital tract. The etiologic agent, Neisseria gonorrhoeae, was isolated by Neisser in 1879. [NIH] Gout: Hereditary metabolic disorder characterized by recurrent acute arthritis, hyperuricemia and deposition of sodium urate in and around the joints, sometimes with formation of uric acid calculi. [NIH] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Gp120: 120-kD HIV envelope glycoprotein which is involved in the binding of the virus to its membrane receptor, the CD4 molecule, found on the surface of certain cells in the body. [NIH]
Grade: The grade of a tumor depends on how abnormal the cancer cells look under a
278 Cholera
microscope and how quickly the tumor is likely to grow and spread. Grading systems are different for each type of cancer. [NIH] Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to replace diseased or injured tissue removed from another part of the body. [NIH] Graft Rejection: An immune response with both cellular and humoral components, directed against an allogeneic transplant, whose tissue antigens are not compatible with those of the recipient. [NIH] Gram-negative: Losing the stain or decolorized by alcohol in Gram's method of staining, a primary characteristic of bacteria having a cell wall composed of a thin layer of peptidoglycan covered by an outer membrane of lipoprotein and lipopolysaccharide. [EU] 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] Gram-Positive Bacteria: Bacteria which retain the crystal violet stain when treated by Gram's method. [NIH] Granule: A small pill made from sucrose. [EU] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups: neutrophils, eosinophils, and basophils. [NIH] 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] Granulosa Cells: Cells of the membrana granulosa lining the vesicular ovarian follicle which become luteal cells after ovulation. [NIH] Growth: The progressive development of a living being or part of an organism from its earliest stage to maturity. [NIH] Growth factors: Substances made by the body that function to regulate cell division and cell survival. Some growth factors are also produced in the laboratory and used in biological therapy. [NIH] Guinea Pigs: A common name used for the family Caviidae. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research. [NIH]
Gyrase: An enzyme that causes negative supercoiling of E. coli DNA during replication. [NIH]
Habitual: Of the nature of a habit; according to habit; established by or repeated by force of habit, customary. [EU] Hair follicles: Shafts or openings on the surface of the skin through which hair grows. [NIH] Haploid: An organism with one basic chromosome set, symbolized by n; the normal condition of gametes in diploids. [NIH] Haplotypes: The genetic constitution of individuals with respect to one member of a pair of allelic genes, or sets of genes that are closely linked and tend to be inherited together such as those of the major histocompatibility complex. [NIH] Haptens: Small antigenic determinants capable of eliciting an immune response only when coupled to a carrier. Haptens bind to antibodies but by themselves cannot elicit an antibody
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response. [NIH] Headache: Pain in the cranial region that may occur as an isolated and benign symptom or as a manifestation of a wide variety of conditions including subarachnoid hemorrhage; craniocerebral trauma; central nervous system infections; intracranial hypertension; and other disorders. In general, recurrent headaches that are not associated with a primary disease process are referred to as headache disorders (e.g., migraine). [NIH] Headache Disorders: Common conditions characterized by persistent or recurrent headaches. Headache syndrome classification systems may be based on etiology (e.g., vascular headache, post-traumatic headaches, etc.), temporal pattern (e.g., cluster headache, paroxysmal hemicrania, etc.), and precipitating factors (e.g., cough headache). [NIH] Health Services: Services for the diagnosis and treatment of disease and the maintenance of health. [NIH] Health Status: The level of health of the individual, group, or population as subjectively assessed by the individual or by more objective measures. [NIH] Heart attack: A seizure of weak or abnormal functioning of the heart. [NIH] Heart failure: Loss of pumping ability by the heart, often accompanied by fatigue, breathlessness, and excess fluid accumulation in body tissues. [NIH] Helicobacter: A genus of gram-negative, spiral-shaped bacteria that is pathogenic and has been isolated from the intestinal tract of mammals, including humans. [NIH] Helicobacter pylori: A spiral bacterium active as a human gastric pathogen. It is a gramnegative, urease-positive, curved or slightly spiral organism initially isolated in 1982 from patients with lesions of gastritis or peptic ulcers in Western Australia. Helicobacter pylori was originally classified in the genus Campylobacter, but RNA sequencing, cellular fatty acid profiles, growth patterns, and other taxonomic characteristics indicate that the microorganism should be included in the genus Helicobacter. It has been officially transferred to Helicobacter gen. nov. (see Int J Syst Bacteriol 1989 Oct;39(4):297-405). [NIH] Hemagglutinins: Agents that cause agglutination of red blood cells. They include antibodies, blood group antigens, lectins, autoimmune factors, bacterial, viral, or parasitic blood agglutinins, etc. [NIH] Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. [NIH] Hemodynamics: The movements of the blood and the forces involved in systemic or regional blood circulation. [NIH] Hemoglobin: One of the fractions of glycosylated hemoglobin A1c. Glycosylated hemoglobin is formed when linkages of glucose and related monosaccharides bind to hemoglobin A and its concentration represents the average blood glucose level over the previous several weeks. HbA1c levels are used as a measure of long-term control of plasma glucose (normal, 4 to 6 percent). In controlled diabetes mellitus, the concentration of glycosylated hemoglobin A is within the normal range, but in uncontrolled cases the level may be 3 to 4 times the normal conentration. Generally, complications are substantially lower among patients with Hb levels of 7 percent or less than in patients with HbA1c levels of 9 percent or more. [NIH] Hemolytic: A disease that affects the blood and blood vessels. It destroys red blood cells, cells that cause the blood to clot, and the lining of blood vessels. HUS is often caused by the Escherichia coli bacterium in contaminated food. People with HUS may develop acute renal failure. [NIH] Hemolytic-Uremic Syndrome: Syndrome of hemolytic anemia, thrombocytopenia, and
280 Cholera
acute renal failure, with pathological finding of thrombotic microangiopathy in kidney and renal cortical necrosis. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hemostasis: The process which spontaneously arrests the flow of blood from vessels carrying blood under pressure. It is accomplished by contraction of the vessels, adhesion and aggregation of formed blood elements, and the process of blood or plasma coagulation. [NIH]
Hepatic: Refers to the liver. [NIH] Hepatitis: Inflammation of the liver and liver disease involving degenerative or necrotic alterations of hepatocytes. [NIH] Hepatocytes: The main structural component of the liver. They are specialized epithelial cells that are organized into interconnected plates called lobules. [NIH] Hereditary: Of, relating to, or denoting factors that can be transmitted genetically from one generation to another. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Herpes: Any inflammatory skin disease caused by a herpesvirus and characterized by the formation of clusters of small vesicles. When used alone, the term may refer to herpes simplex or to herpes zoster. [EU] Herpes Zoster: Acute vesicular inflammation. [NIH] Heterogeneity: The property of one or more samples or populations which implies that they are not identical in respect of some or all of their parameters, e. g. heterogeneity of variance. [NIH]
Heterotrophic: Pertaining to organisms that are consumers and dependent on other organisms for their source of energy (food). [NIH] Histamine: 1H-Imidazole-4-ethanamine. A depressor amine derived by enzymatic decarboxylation of histidine. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter. [NIH] Histidine: An essential amino acid important in a number of metabolic processes. It is required for the production of histamine. [NIH] Hog Cholera: An acute, highly contagious disease affecting swine of all ages and caused by the hog cholera virus. It has a sudden onset with high morbidity and mortality. [NIH] Hog Cholera Virus: A species of the Pestivirus genus causing exceedingly contagious and fatal hemorrhagic disease of swine. [NIH] Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] Hormonal: Pertaining to or of the nature of a hormone. [EU] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Host: Any animal that receives a transplanted graft. [NIH] Host-Parasite Relations: The interactions between two organisms, one of which lives at the expense of the other. [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]
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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] Hybridomas: Cells artificially created by fusion of activated lymphocytes with neoplastic cells. The resulting hybrid cells are cloned and produce pure or "monoclonal" antibodies or T-cell products, identical to those produced by the immunologically competent parent, and continually grow and divide as the neoplastic parent. [NIH] Hydrochloric Acid: A strong corrosive acid that is commonly used as a laboratory reagent. It is formed by dissolving hydrogen chloride in water. Gastric acid is the hydrochloric acid component of gastric juice. [NIH] Hydrocortisone: The main glucocorticoid secreted by the adrenal cortex. Its synthetic counterpart is used, either as an injection or topically, in the treatment of inflammation, allergy, collagen diseases, asthma, adrenocortical deficiency, shock, and some neoplastic conditions. [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] Hydrophilic: Readily absorbing moisture; hygroscopic; having strongly polar groups that readily interact with water. [EU] Hydrophobic: Not readily absorbing water, or being adversely affected by water, as a hydrophobic colloid. [EU] Hydroxylysine: A hydroxylated derivative of the amino acid lysine that is present in certain collagens. [NIH] Hydroxyproline: A hydroxylated form of the imino acid proline. A deficiency in ascorbic acid can result in impaired hydroxyproline formation. [NIH] Hydroxyquinolines: The 8-hydroxy derivatives inhibit various enzymes and their halogenated derivatives, though neurotoxic, are used as topical anti-infective agents, among other uses. [NIH] Hygienic: Pertaining to hygiene, or conducive to health. [EU] Hyperaemia: An excess of blood in a part; engorgement. [EU] Hyperglycemia: Abnormally high blood sugar. [NIH] Hyperplasia: An increase in the number of cells in a tissue or organ, not due to tumor formation. It differs from hypertrophy, which is an increase in bulk without an increase in the number of cells. [NIH] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels
282 Cholera
are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hypertrophy: General increase in bulk of a part or organ, not due to tumor formation, nor to an increase in the number of cells. [NIH] Hypothalamic: Of or involving the hypothalamus. [EU] Hypothalamus: Ventral part of the diencephalon extending from the region of the optic chiasm to the caudal border of the mammillary bodies and forming the inferior and lateral walls of the third ventricle. [NIH] Id: The part of the personality structure which harbors the unconscious instinctive desires and strivings of the individual. [NIH] Ileal: Related to the ileum, the lowest end of the small intestine. [NIH] Ileostomy: Surgical creation of an external opening into the ileum for fecal diversion or drainage. Loop or tube procedures are most often employed. [NIH] Ileum: The lower end of the small intestine. [NIH] Imaging procedures: Methods of producing pictures of areas inside the body. [NIH] Imidazole: C3H4N2. The ring is present in polybenzimidazoles. [NIH] Immune function: Production and action of cells that fight disease or infection. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]
Immune Sera: Serum that contains antibodies. It is obtained from an animal that has been immunized either by antigen injection or infection with microorganisms containing the antigen. [NIH] Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] Immunity: Nonsusceptibility to the invasive or pathogenic microorganisms or to the toxic effect of antigenic substances. [NIH]
effects
of
foreign
Immunization: Deliberate stimulation of the host's immune response. Active immunization involves administration of antigens or immunologic adjuvants. Passive immunization involves administration of immune sera or lymphocytes or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow). [NIH] Immunoassay: Immunochemical assay or detection of a substance by serologic or immunologic methods. Usually the substance being studied serves as antigen both in antibody production and in measurement of antibody by the test substance. [NIH] Immunoblotting: Immunologic methods for isolating and quantitatively measuring immunoreactive substances. When used with immune reagents such as monoclonal antibodies, the process is known generically as western blot analysis (blotting, western). [NIH]
Immunodeficiency: The decreased ability of the body to fight infection and disease. [NIH] Immunodeficiency syndrome: The inability of the body to produce an immune response. [NIH]
Immunodiffusion: Technique involving the diffusion of antigen or antibody through a 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
Dictionary 283
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] Immunogen: A substance that is capable of causing antibody formation. [NIH] Immunogenic: Producing immunity; evoking an immune response. [EU] Immunoglobulin: A protein that acts as an antibody. [NIH] Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents. [NIH] Immunologic: The ability of the antibody-forming system to recall a previous experience with an antigen and to respond to a second exposure with the prompt production of large amounts of antibody. [NIH] Immunology: The study of the body's immune system. [NIH] Immunosuppressive: Describes the ability to lower immune system responses. [NIH] Immunosuppressive therapy: Therapy used to decrease the body's immune response, such as drugs given to prevent transplant rejection. [NIH] Immunotherapy: Manipulation of the host's immune system in treatment of disease. It includes both active and passive immunization as well as immunosuppressive therapy to prevent graft rejection. [NIH] Immunotoxin: An antibody linked to a toxic substance. Some immmunotoxins can bind to cancer cells and kill them. [NIH] In situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU] In Situ Hybridization: A technique that localizes specific nucleic acid sequences within intact chromosomes, eukaryotic cells, or bacterial cells through the use of specific nucleic acid-labeled probes. [NIH] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incision: A cut made in the body during surgery. [NIH] Incisional: The removal of a sample of tissue for examination under a microscope. [NIH] Incubated: Grown in the laboratory under controlled conditions. (For instance, white blood cells can be grown in special conditions so that they attack specific cancer cells when returned to the body.) [NIH] Incubation: The development of an infectious disease from the entrance of the pathogen to the appearance of clinical symptoms. [EU] Incubation period: The period of time likely to elapse between exposure to the agent of the disease and the onset of clinical symptoms. [NIH] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU] Indomethacin: A non-steroidal anti-inflammatory agent (NSAID) that inhibits the enzyme cyclooxygenase necessary for the formation of prostaglandins and other autacoids. It also inhibits the motility of polymorphonuclear leukocytes. [NIH] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU]
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Infancy: The period of complete dependency prior to the acquisition of competence in walking, talking, and self-feeding. [NIH] Infant, Newborn: An infant during the first month after birth. [NIH] Infantile: Pertaining to an infant or to infancy. [EU] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]
Infection Control: Programs of disease surveillance, generally within health care facilities, designed to investigate, prevent, and control the spread of infections and their causative microorganisms. [NIH] Infectious Diarrhea: Diarrhea caused by infection from bacteria, viruses, or parasites. [NIH] Infertility: The diminished or absent ability to conceive or produce an offspring while sterility is the complete inability to conceive or produce an offspring. [NIH] Infestation: Parasitic attack or subsistence on the skin and/or its appendages, as by insects, mites, or ticks; sometimes used to denote parasitic invasion of the organs and tissues, as by helminths. [NIH] 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] Inflammatory bowel disease: A general term that refers to the inflammation of the colon and rectum. Inflammatory bowel disease includes ulcerative colitis and Crohn's disease. [NIH]
Influenza: An acute viral infection involving the respiratory tract. It is marked by inflammation of the nasal mucosa, the pharynx, and conjunctiva, and by headache and severe, often generalized, myalgia. [NIH] 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] Innervation: 1. The distribution or supply of nerves to a part. 2. The supply of nervous energy or of nerve stimulus sent to a part. [EU] Inorganic: Pertaining to substances not of organic origin. [EU] Insight: The capacity to understand one's own motives, to be aware of one's own psychodynamics, to appreciate the meaning of symbolic behavior. [NIH] Insulator: Material covering the metal conductor of the lead. It is usually polyurethane or silicone. [NIH] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of
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glucose. It is also an important regulator of protein and lipid metabolism. Insulin is used as a drug to control insulin-dependent diabetes mellitus. [NIH] Insulin-dependent diabetes mellitus: A disease characterized by high levels of blood glucose resulting from defects in insulin secretion, insulin action, or both. Autoimmune, genetic, and environmental factors are involved in the development of type I diabetes. [NIH] Interferons: Proteins secreted by vertebrate cells in response to a wide variety of inducers. They confer resistance against many different viruses, inhibit proliferation of normal and malignant cells, impede multiplication of intracellular parasites, enhance macrophage and granulocyte phagocytosis, augment natural killer cell activity, and show several other immunomodulatory functions. [NIH] Interleukin-2: Chemical mediator produced by activated T lymphocytes and which regulates the proliferation of T cells, as well as playing a role in the regulation of NK cell activity. [NIH] Interleukin-4: Soluble factor produced by activated T-lymphocytes that causes proliferation and differentiation of B-cells. Interleukin-4 induces the expression of class II major histocompatibility complex and Fc receptors on B-cells. It also acts on T-lymphocytes, mast cell lines, and several other hematopoietic lineage cells including granulocyte, megakaryocyte, and erythroid precursors, as well as macrophages. [NIH] Interleukin-8: A cytokine that activates neutrophils and attracts neutrophils and Tlymphocytes. It is released by several cell types including monocytes, macrophages, Tlymphocytes, fibroblasts, endothelial cells, and keratinocytes by an inflammatory stimulus. IL-8 is a member of the beta-thromboglobulin superfamily and structurally related to platelet factor 4. [NIH] Intermediate Filaments: Cytoplasmic filaments intermediate in diameter (about 10 nanometers) between the microfilaments and the microtubules. They may be composed of any of a number of different proteins and form a ring around the cell nucleus. [NIH] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Internal Medicine: A medical specialty concerned with the diagnosis and treatment of diseases of the internal organ systems of adults. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intestinal: Having to do with the intestines. [NIH] Intestinal Flora: The bacteria, yeasts, and fungi that grow normally in the intestines. [NIH] Intestine: A long, tube-shaped organ in the abdomen that completes the process of digestion. There is both a large intestine and a small intestine. Also called the bowel. [NIH] Intoxication: Poisoning, the state of being poisoned. [EU] Intracellular: Inside a cell. [NIH] Intracellular Membranes: Membranes of subcellular structures. [NIH] Intramuscular: IM. Within or into muscle. [NIH] 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]
Invertebrates: Animals that have no spinal column. [NIH] Ion Channels: Gated, ion-selective glycoproteins that traverse membranes. The stimulus for
286 Cholera
channel gating can be a membrane potential, drug, transmitter, cytoplasmic messenger, or a mechanical deformation. Ion channels which are integral parts of ionotropic neurotransmitter receptors are not included. [NIH] Ion Exchange: Reversible chemical reaction between a solid, often an ION exchange resin, and a fluid whereby ions may be exchanged from one substance to another. This technique is used in water purification, in research, and in industry. [NIH] Ion Transport: The movement of ions across energy-transducing cell membranes. Transport can be active or passive. Passive ion transport (facilitated diffusion) derives its energy from the concentration gradient of the ion itself and allows the transport of a single solute in one direction (uniport). Active ion transport is usually coupled to an energy-yielding chemical or photochemical reaction such as ATP hydrolysis. This form of primary active transport is called an ion pump. Secondary active transport utilizes the voltage and ion gradients produced by the primary transport to drive the cotransport of other ions or molecules. These may be transported in the same (symport) or opposite (antiport) direction. [NIH] Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as cations; those with a negative charge are anions. [NIH] Irritants: Drugs that act locally on cutaneous or mucosal surfaces to produce inflammation; those that cause redness due to hyperemia are rubefacients; those that raise blisters are vesicants and those that penetrate sebaceous glands and cause abscesses are pustulants; tear gases and mustard gases are also irritants. [NIH] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Isotonic: A biological term denoting a solution in which body cells can be bathed without a net flow of water across the semipermeable cell membrane. Also, denoting a solution having the same tonicity as some other solution with which it is compared, such as physiologic salt solution and the blood serum. [EU] Jejunum: That portion of the small intestine which extends from the duodenum to the ileum; called also intestinum jejunum. [EU] 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] Keratin: A class of fibrous proteins or scleroproteins important both as structural proteins and as keys to the study of protein conformation. The family represents the principal constituent of epidermis, hair, nails, horny tissues, and the organic matrix of tooth enamel. Two major conformational groups have been characterized, alpha-keratin, whose peptide backbone forms an alpha-helix, and beta-keratin, whose backbone forms a zigzag or pleated sheet structure. [NIH] Keratinocytes: Epidermal cells which synthesize keratin and undergo characteristic changes as they move upward from the basal layers of the epidermis to the cornified (horny) layer of the skin. Successive stages of differentiation of the keratinocytes forming the epidermal layers are basal cell, spinous or prickle cell, and the granular cell. [NIH] Keratolytic: An agent that promotes keratolysis. [EU] Kidney Disease: Any one of several chronic conditions that are caused by damage to the cells of the kidney. People who have had diabetes for a long time may have kidney damage. Also called nephropathy. [NIH] Kidney Failure: The inability of a kidney to excrete metabolites at normal plasma levels under conditions of normal loading, or the inability to retain electrolytes under conditions of
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normal intake. In the acute form (kidney failure, acute), it is marked by uremia and usually by oliguria or anuria, with hyperkalemia and pulmonary edema. The chronic form (kidney failure, chronic) is irreversible and requires hemodialysis. [NIH] Killer Cells: Lymphocyte-like effector cells which mediate antibody-dependent cell cytotoxicity. They kill antibody-coated target cells which they bind with their Fc receptors. [NIH]
Kinetic: Pertaining to or producing motion. [EU] Labile: 1. Gliding; moving from point to point over the surface; unstable; fluctuating. 2. Chemically unstable. [EU] Laceration: 1. The act of tearing. 2. A torn, ragged, mangled wound. [EU] Large Intestine: The part of the intestine that goes from the cecum to the rectum. The large intestine absorbs water from stool and changes it from a liquid to a solid form. The large intestine is 5 feet long and includes the appendix, cecum, colon, and rectum. Also called colon. [NIH] Larva: Wormlike or grublike stage, following the egg in the life cycle of insects, worms, and other metamorphosing animals. [NIH] Larva Migrans: Infections caused by nematode larvae which never develop into the adult stage and migrate through various body tissues. They commonly infect the skin, eyes, and viscera in man. Ancylostoma brasiliensis causes cutaneous larva migrans. Toxocara causes visceral larva migrans. [NIH] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH] Laxative: An agent that acts to promote evacuation of the bowel; a cathartic or purgative. [EU]
Lectin: A complex molecule that has both protein and sugars. Lectins are able to bind to the outside of a cell and cause biochemical changes in it. Lectins are made by both animals and plants. [NIH] Leishmaniasis: A disease caused by any of a number of species of protozoa in the genus Leishmania. There are four major clinical types of this infection: cutaneous (Old and New World), diffuse cutaneous, mucocutaneous, and visceral leishmaniasis. [NIH] Lens: The transparent, double convex (outward curve on both sides) structure suspended between the aqueous and vitreous; helps to focus light on the retina. [NIH] Leptin: A 16-kD peptide hormone secreted from white adipocytes and implicated in the regulation of food intake and energy balance. Leptin provides the key afferent signal from fat cells in the feedback system that controls body fat stores. [NIH] Lesion: An area of abnormal tissue change. [NIH] Lethal: Deadly, fatal. [EU] Leucine: An essential branched-chain amino acid important for hemoglobin formation. [NIH] Leukemia: Cancer of blood-forming tissue. [NIH] Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [NIH] Library Services: Services offered to the library user. They include reference and circulation. [NIH]
Lice: A general name for small, wingless, parasitic insects, previously of the order Phthiraptera. Though exact taxonomy is still controversial, they can be grouped in the orders Anoplura (sucking lice), Mallophaga (biting lice), and Rhynchophthirina (elephant
288 Cholera
lice). [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] Limbic: Pertaining to a limbus, or margin; forming a border around. [EU] Limbic System: A set of forebrain structures common to all mammals that is defined functionally and anatomically. It is implicated in the higher integration of visceral, olfactory, and somatic information as well as homeostatic responses including fundamental survival behaviors (feeding, mating, emotion). For most authors, it includes the amygdala, epithalamus, gyrus cinguli, hippocampal formation (see hippocampus), hypothalamus, parahippocampal gyrus, septal nuclei, anterior nuclear group of thalamus, and portions of the basal ganglia. (Parent, Carpenter's Human Neuroanatomy, 9th ed, p744; NeuroNames, http://rprcsgi.rprc.washington.edu/neuronames/index.html (September 2, 1998)). [NIH] Linkage: The tendency of two or more genes in the same chromosome to remain together from one generation to the next more frequently than expected according to the law of independent assortment. [NIH] Lipase: An enzyme of the hydrolase class that catalyzes the reaction of triacylglycerol and water to yield diacylglycerol and a fatty acid anion. It is produced by glands on the tongue and by the pancreas and initiates the digestion of dietary fats. (From Dorland, 27th ed) EC 3.1.1.3. [NIH] Lipid: Fat. [NIH] Lipid A: Lipid A is the biologically active component of lipopolysaccharides. It shows strong endotoxic activity and exhibits immunogenic properties. [NIH] Lipid Peroxidation: Peroxidase catalyzed oxidation of lipids using hydrogen peroxide as an electron acceptor. [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-lowdensity lipoproteins and chylomicrons. [EU] Liposomal: A drug preparation that contains the active drug in very tiny fat particles. This fat-encapsulated drug is absorbed better, and its distribution to the tumor site is improved. [NIH]
Liposome: A spherical particle in an aqueous medium, formed by a lipid bilayer enclosing an aqueous compartment. [EU] Liquor: 1. A liquid, especially an aqueous solution containing a medicinal substance. 2. A general term used in anatomical nomenclature for certain fluids of the body. [EU] 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] Locomotion: Movement or the ability to move from one place or another. It can refer to humans, vertebrate or invertebrate animals, and microorganisms. [NIH]
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Loop: A wire usually of platinum bent at one end into a small loop (usually 4 mm inside diameter) and used in transferring microorganisms. [NIH] Loperamide: 4-(p-Chlorophenyl)-4-hydroxy-N.N-dimethyl-alpha,alpha-diphenyl-1piperidine butyramide hydrochloride. Synthetic anti-diarrheal agent with a long duration of action; it is not significantly absorbed from the gut, has no effect on the adrenergic system or central nervous system, but may antagonize histamine and interfere with acetylcholine release locally. [NIH] Lumen: The cavity or channel within a tube or tubular organ. [EU] Lupus: A form of cutaneous tuberculosis. It is seen predominantly in women and typically involves the nasal, buccal, and conjunctival mucosa. [NIH] Luxation: The displacement of the particular surface of a bone from its normal joint, without fracture. [NIH] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Lymph node: A rounded mass of lymphatic tissue that is surrounded by a capsule of connective tissue. Also known as a lymph gland. Lymph nodes are spread out along lymphatic vessels and contain many lymphocytes, which filter the lymphatic fluid (lymph). [NIH]
Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] Lymphatic system: The tissues and organs that produce, store, and carry white blood cells that fight infection and other diseases. This system includes the bone marrow, spleen, thymus, lymph nodes and a network of thin tubes that carry lymph and white blood cells. These tubes branch, like blood vessels, into all the tissues of the body. [NIH] Lymphocyte: A white blood cell. Lymphocytes have a number of roles in the immune system, including the production of antibodies and other substances that fight infection and diseases. [NIH] 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] Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue. [NIH] Lysine: An essential amino acid. It is often added to animal feed. [NIH] 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] 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
290 Cholera
animal to respond immunologically to antigenic stimuli, and genes which determine the structure and/or level of the first four components of complement. [NIH] Malabsorption: Impaired intestinal absorption of nutrients. [EU] Malabsorption syndrome: A group of symptoms such as gas, bloating, abdominal pain, and diarrhea resulting from the body's inability to properly absorb nutrients. [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 islands. It is characterized by extreme exhaustion associated with paroxysms of high fever, sweating, shaking chills, and anemia. Malaria in animals is caused by other species of plasmodia. [NIH] Malaria, Falciparum: Malaria caused by Plasmodium falciparum. This is the severest form of malaria and is associated with the highest levels of parasites in the blood. This disease is characterized by irregularly recurring febrile paroxysms that in extreme cases occur with acute cerebral, renal, or gastrointestinal manifestations. [NIH] Malaria, Vivax: Malaria caused by Plasmodium vivax. This form of malaria is less severe than malaria, falciparum, but there is a higher probability for relapses to occur. Febrile paroxysms often occur every other day. [NIH] Malignancy: A cancerous tumor that can invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malignant tumor: A tumor capable of metastasizing. [NIH] Malnutrition: A condition caused by not eating enough food or not eating a balanced diet. [NIH]
Mammary: Pertaining to the mamma, or breast. [EU] Manifest: Being the part or aspect of a phenomenon that is directly observable : concretely expressed in behaviour. [EU] Mannans: Polysaccharides consisting of mannose units. [NIH] Mannitol: A diuretic and renal diagnostic aid related to sorbitol. It has little significant energy value as it is largely eliminated from the body before any metabolism can take place. It can be used to treat oliguria associated with kidney failure or other manifestations of inadequate renal function and has been used for determination of glomerular filtration rate. Mannitol is also commonly used as a research tool in cell biological studies, usually to control osmolarity. [NIH] Mastitis: Inflammatory disease of the breast, or mammary gland. [NIH] Meat: The edible portions of any animal used for food including domestic mammals (the major ones being cattle, swine, and sheep) along with poultry, fish, shellfish, and game. [NIH]
Medial: Lying near the midsaggital plane of the body; opposed to lateral. [NIH] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] Mediator: An object or substance by which something is mediated, such as (1) a structure of the nervous system that transmits impulses eliciting a specific response; (2) a chemical substance (transmitter substance) that induces activity in an excitable tissue, such as nerve
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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] Meiosis: A special method of cell division, occurring in maturation of the germ cells, by means of which each daughter nucleus receives half the number of chromosomes characteristic of the somatic cells of the species. [NIH] Melanin: The substance that gives the skin its color. [NIH] Melanocytes: Epidermal dendritic pigment cells which control long-term morphological color changes by alteration in their number or in the amount of pigment they produce and store in the pigment containing organelles called melanosomes. Melanophores are larger cells which do not exist in mammals. [NIH] Melanoma: A form of skin cancer that arises in melanocytes, the cells that produce pigment. Melanoma usually begins in a mole. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Membrane Microdomains: Detergent-insoluble cell membrane components. They are enriched in sphingolipids and cholesterol and clustered with glycosyl-phosphatidylinositol (GPI)-anchored proteins. [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] Mental Processes: Conceptual functions or thinking in all its forms. [NIH] Meperidine: 1-Methyl-4-phenyl-4-piperidinecarboxylic acid ethyl ester. A narcotic analgesic that can be used for the relief of most types of moderate to severe pain, including postoperative pain and the pain of labor. Prolonged use may lead to dependence of the morphine type; withdrawal symptoms appear more rapidly than with morphine and are of shorter duration. [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] Mesenchymal: Refers to cells that develop into connective tissue, blood vessels, and lymphatic tissue. [NIH] Mesenteric: Pertaining to the mesentery : a membranous fold attaching various organs to the body wall. [EU]
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Mesentery: A layer of the peritoneum which attaches the abdominal viscera to the abdominal wall and conveys their blood vessels and nerves. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] Metaphase: The second phase of cell division, in which the chromosomes line up across the equatorial plane of the spindle prior to separation. [NIH] Metastasis: The spread of cancer from one part of the body to another. Tumors formed from cells that have spread are called "secondary tumors" and contain cells that are like those in the original (primary) tumor. The plural is metastases. [NIH] Methionine: A sulfur containing essential amino acid that is important in many body functions. It is a chelating agent for heavy metals. [NIH] Metronidazole: Antiprotozoal used in amebiasis, trichomoniasis, giardiasis, and as treponemacide in livestock. It has also been proposed as a radiation sensitizer for hypoxic cells. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985, p133), this substance may reasonably be anticipated to be a carcinogen (Merck, 11th ed). [NIH] MI: Myocardial infarction. Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Micelles: Electrically charged colloidal particles or ions consisting of oriented molecules; aggregates of a number of molecules held loosely together by secondary bonds. [NIH] Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [NIH] Microfilaments: The smallest of the cytoskeletal filaments. They are composed chiefly of actin. [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] Microscopy, Confocal: A light microscopic technique in which only a small spot is illuminated and observed at a time. An image is constructed through point-by-point scanning of the field in this manner. Light sources may be conventional or laser, and fluorescence or transmitted observations are possible. [NIH] Microspheres: Small uniformly-sized spherical particles frequently radioisotopes or various reagents acting as tags or markers. [NIH]
labeled
with
Mitochondria: Parts of a cell where aerobic production (also known as cell respiration) takes place. [NIH] Mitochondrial Swelling: Increase in volume of mitochondria due to an influx of fluid; it occurs in hypotonic solutions due to osmotic pressure and in isotonic solutions as a result of altered permeability of the membranes of respiring mitochondria. [NIH] 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]
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Mobilization: The process of making a fixed part or stored substance mobile, as by separating a part from surrounding structures to make it accessible for an operative procedure or by causing release into the circulation for body use of a substance stored in the body. [EU] Modeling: A treatment procedure whereby the therapist presents the target behavior which the learner is to imitate and make part of his repertoire. [NIH] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecular Probes: A group of atoms or molecules attached to other molecules or cellular structures and used in studying the properties of these molecules and structures. Radioactive DNA or RNA sequences are used in molecular genetics to detect the presence of a complementary sequence by molecular hybridization. [NIH] Molecular Structure: The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds. [NIH] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] Monitor: An apparatus which automatically records such physiological signs as respiration, pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH] Monoamine: Enzyme that breaks down dopamine in the astrocytes and microglia. [NIH] Monoclonal: An antibody produced by culturing a single type of cell. It therefore consists of a single species of immunoglobulin molecules. [NIH] Monoclonal antibodies: Laboratory-produced substances that can locate and bind to cancer cells wherever they are in the body. Many monoclonal antibodies are used in cancer detection or therapy; each one recognizes a different protein on certain cancer cells. Monoclonal antibodies can be used alone, or they can be used to deliver drugs, toxins, or radioactive material directly to a tumor. [NIH] Monocytes: Large, phagocytic mononuclear leukocytes produced in the vertebrate bone marrow and released into the blood; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles. [NIH] Mononuclear: A cell with one nucleus. [NIH] Monophosphate: So called second messenger for neurotransmitters and hormones. [NIH] Morphine: The principal alkaloid in opium and the prototype opiate analgesic and narcotic. Morphine has widespread effects in the central nervous system and on smooth muscle. [NIH] Morphological: Relating to the configuration or the structure of live organs. [NIH] 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] Mucinous: Containing or resembling mucin, the main compound in mucus. [NIH] Mucins: A secretion containing mucopolysaccharides and protein that is the chief constituent of mucus. [NIH] Mucociliary: Pertaining to or affecting the mucus membrane and hairs (including eyelashes,
294 Cholera
nose hair, .): mucociliary clearing: the clearance of mucus by ciliary movement ( particularly in the respiratory system). [EU] Mucocutaneous: Pertaining to or affecting the mucous membrane and the skin. [EU] Mucolytic: Destroying or dissolving mucin; an agent that so acts : a mucopolysaccharide or glycoprotein, the chief constituent of mucus. [EU] Mucosa: A mucous membrane, or tunica mucosa. [EU] Mucus: The viscous secretion of mucous membranes. It contains mucin, white blood cells, water, inorganic salts, and exfoliated cells. [NIH] Multiple sclerosis: A disorder of the central nervous system marked by weakness, numbness, a loss of muscle coordination, and problems with vision, speech, and bladder control. Multiple sclerosis is thought to be an autoimmune disease in which the body's immune system destroys myelin. Myelin is a substance that contains both protein and fat (lipid) and serves as a nerve insulator and helps in the transmission of nerve signals. [NIH] Multivalent: Pertaining to a group of 5 or more homologous or partly homologous chromosomes during the zygotene stage of prophase to first metaphasis in meiosis. [NIH] Muscle Contraction: A process leading to shortening and/or development of tension in muscle tissue. Muscle contraction occurs by a sliding filament mechanism whereby actin filaments slide inward among the myosin filaments. [NIH] Muscle Fibers: Large single cells, either cylindrical or prismatic in shape, that form the basic unit of muscle tissue. They consist of a soft contractile substance enclosed in a tubular sheath. [NIH] Mutagenesis: Process of generating genetic mutations. It may occur spontaneously or be induced by mutagens. [NIH] Mutagens: Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes. [NIH] Myalgia: Pain in a muscle or muscles. [EU] Myelin: The fatty substance that covers and protects nerves. [NIH] Myiasis: The invasion of living tissues of man and other mammals by dipterous larvae. [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] Myosin: Chief protein in muscle and the main constituent of the thick filaments of muscle fibers. In conjunction with actin, it is responsible for the contraction and relaxation of muscles. [NIH] Naive: Used to describe an individual who has never taken a certain drug or class of drugs (e. g., AZT-naive, antiretroviral-naive), or to refer to an undifferentiated immune system cell. [NIH] Naloxone: A specific opiate antagonist that has no agonist activity. It is a competitive antagonist at mu, delta, and kappa opioid receptors. [NIH] Narcolepsy: A condition of unknown cause characterized by a periodic uncontrollable tendency to fall asleep. [NIH] Narcotic: 1. Pertaining to or producing narcosis. 2. An agent that produces insensibility or stupor, applied especially to the opioids, i.e. to any natural or synthetic drug that has
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morphine-like actions. [EU] Nasal Cavity: The proximal portion of the respiratory passages on either side of the nasal septum, lined with ciliated mucosa, extending from the nares to the pharynx. [NIH] Nasal Mucosa: The mucous membrane lining the nasal cavity. [NIH] Nasopharynx: The nasal part of the pharynx, lying above the level of the soft palate. [NIH] Natural killer cells: NK cells. A type of white blood cell that contains granules with enzymes that can kill tumor cells or microbial cells. Also called large granular lymphocytes (LGL). [NIH] Nausea: An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. [NIH] 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] Necrotizing Enterocolitis: A condition in which part of the tissue in the intestines is destroyed. Occurs mainly in under-weight newborn babies. A temporary ileostomy may be necessary. [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] Neomycin: Antibiotic complex produced by Streptomyces fradiae. It is composed of neomycins A, B, and C. It acts by inhibiting translation during protein synthesis. [NIH] Neonatal: Pertaining to the first four weeks after birth. [EU] Neoplasm: A new growth of benign or malignant tissue. [NIH] Neoplastic: Pertaining to or like a neoplasm (= any new and abnormal growth); pertaining to neoplasia (= the formation of a neoplasm). [EU] Nephron: A tiny part of the kidneys. Each kidney is made up of about 1 million nephrons, which are the working units of the kidneys, removing wastes and extra fluids from the blood. [NIH] Nephropathy: Disease of the kidneys. [EU] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Networks: Pertaining to a nerve or to the nerves, a meshlike structure of interlocking fibers or strands. [NIH] Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU] Neural Pathways: Neural tracts connecting one part of the nervous system with another. [NIH]
Neuraminidase: An enzyme that catalyzes the hydrolysis of alpha-2,3, alpha-2,6-, and alpha-2,8-glycosidic linkages (at a decreasing rate, respectively) of terminal sialic residues in oligosaccharides, glycoproteins, glycolipids, colominic acid, and synthetic substrate. (From Enzyme Nomenclature, 1992) EC 3.2.1.18. [NIH] Neuroblastoma: Cancer that arises in immature nerve cells and affects mostly infants and children. [NIH]
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Neuroendocrine: Having to do with the interactions between the nervous system and the endocrine system. Describes certain cells that release hormones into the blood in response to stimulation of the nervous system. [NIH] Neurologic: Having to do with nerves or the nervous system. [NIH] Neuromuscular: Pertaining to muscles and nerves. [EU] Neuromuscular Junction: The synapse between a neuron and a muscle. [NIH] Neuronal: Pertaining to a neuron or neurons (= conducting cells of the nervous system). [EU] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] Neuropeptide: A member of a class of protein-like molecules made in the brain. Neuropeptides consist of short chains of amino acids, with some functioning as neurotransmitters and some functioning as hormones. [NIH] Neurosecretory Systems: A system of neurons that has the specialized function to produce and secrete hormones, and that constitutes, in whole or in part, an endocrine organ or system. [NIH] Neurotoxic: Poisonous or destructive to nerve tissue. [EU] Neurotoxin: A substance that is poisonous to nerve tissue. [NIH] Neurotransmitters: Endogenous signaling molecules that alter the behavior of neurons or effector cells. Neurotransmitter is used here in its most general sense, including not only messengers that act directly to regulate ion channels, but also those that act through second messenger systems, and those that act at a distance from their site of release. Included are neuromodulators, neuroregulators, neuromediators, and neurohumors, whether or not acting at synapses. [NIH] Neutralization: An act or process of neutralizing. [EU] 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] Nitrogen: An element with the atomic symbol N, atomic number 7, and atomic weight 14. Nitrogen exists as a diatomic gas and makes up about 78% of the earth's atmosphere by volume. It is a constituent of proteins and nucleic acids and found in all living cells. [NIH] Norepinephrine: Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic. [NIH] Norfloxacin: Quinoline-derived synthetic antibacterial agent with a very broad spectrum of action. Oral administration yields highly bactericidal plasma, tissue, and urine levels. Norfloxacin inhibits bacterial DNA-gyrase and is used in gastrointestinal, eye, and urinary infections. [NIH] Nosocomial: Pertaining to or originating in the hospital, said of an infection not present or incubating prior to admittance to the hospital, but generally occurring 72 hours after admittance; the term is usually used to refer to patient disease, but hospital personnel may also acquire nosocomial infection. [EU] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through
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the kidneys. [NIH] Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the information (genetic code) for the transfer of genetic information from one generation to the next. [NIH] Nucleic Acid Hybridization: The process whereby two single-stranded polynucleotides form a double-stranded molecule, with hydrogen bonding between the complementary bases in the two strains. [NIH] Nucleic Acid Probes: Nucleic acid which complements a specific mRNA or DNA molecule, or fragment thereof; used for hybridization studies in order to identify microorganisms and for genetic studies. [NIH] Nucleocapsid: A protein-nucleic acid complex which forms part or all of a virion. It consists of a capsid plus enclosed nucleic acid. Depending on the virus, the nucleocapsid may correspond to a naked core or be surrounded by a membranous envelope. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Odour: A volatile emanation that is perceived by the sense of smell. [EU] Olfactory Bulb: Ovoid body resting on the cribriform plate of the ethmoid bone where the olfactory nerve terminates. The olfactory bulb contains several types of nerve cells including the mitral cells, on whose dendrites the olfactory nerve synapses, forming the olfactory glomeruli. The accessory olfactory bulb, which receives the projection from the vomeronasal organ via the vomeronasal nerve, is also included here. [NIH] Oligo: Chemical and mineral elements that exist in minimal (oligo) quantities in the body, in foods, in the air, in soil; name applied to any element observed as a microconstituent of plant or animal tissue and of beneficial, harmful, or even doubtful significance. [NIH] Oligonucleotide Probes: Synthetic or natural oligonucleotides used in hybridization studies in order to identify and study specific nucleic acid fragments, e.g., DNA segments near or within a specific gene locus or gene. The probe hybridizes with a specific mRNA, if present. Conventional techniques used for testing for the hybridization product include dot blot assays, Southern blot assays, and DNA:RNA hybrid-specific antibody tests. Conventional labels for the probe include the radioisotope labels 32P and 125I and the chemical label biotin. [NIH] Oligopeptides: Peptides composed of between two and twelve amino acids. [NIH] Oligosaccharides: Carbohydrates consisting of between two and ten monosaccharides connected by either an alpha- or beta-glycosidic link. They are found throughout nature in both the free and bound form. [NIH] Oliguria: Clinical manifestation of the urinary system consisting of a decrease in the amount of urine secreted. [NIH] Oncogene: A gene that normally directs cell growth. If altered, an oncogene can promote or allow the uncontrolled growth of cancer. Alterations can be inherited or caused by an environmental exposure to carcinogens. [NIH] Opacity: Degree of density (area most dense taken for reading). [NIH] Open Reading Frames: Reading frames where successive nucleotide triplets can be read as codons specifying amino acids and where the sequence of these triplets is not interrupted by
298 Cholera
stop codons. [NIH] Operon: The genetic unit consisting of a feedback system under the control of an operator gene, in which a structural gene transcribes its message in the form of mRNA upon blockade of a repressor produced by a regulator gene. Included here is the attenuator site of bacterial operons where transcription termination is regulated. [NIH] Opium: The air-dried exudate from the unripe seed capsule of the opium poppy, Papaver somniferum, or its variant, P. album. It contains a number of alkaloids, but only a few morphine, codeine, and papaverine - have clinical significance. Opium has been used as an analgesic, antitussive, antidiarrheal, and antispasmodic. [NIH] Optic Chiasm: The X-shaped structure formed by the meeting of the two optic nerves. At the optic chiasm the fibers from the medial part of each retina cross to project to the other side of the brain while the lateral retinal fibers continue on the same side. As a result each half of the brain receives information about the contralateral visual field from both eyes. [NIH]
Oral Health: The optimal state of the mouth and normal functioning of the organs of the mouth without evidence of disease. [NIH] Orderly: A male hospital attendant. [NIH] Orf: A specific disease of sheep and goats caused by a pox-virus that is transmissible to man and characterized by vesiculation and ulceration of the lips. [NIH] Organ Culture: The growth in aseptic culture of plant organs such as roots or shoots, beginning with organ primordia or segments and maintaining the characteristics of the organ. [NIH] Organelles: Specific particles of membrane-bound organized living substances present in eukaryotic cells, such as the mitochondria; the golgi apparatus; endoplasmic reticulum; lysomomes; plastids; and vacuoles. [NIH] Osmolality: The concentration of osmotically active particles in solution expressed in terms of osmoles of solute per kilogram of solvent. The osmolality is directly proportional to the colligative properties of solutions; osmotic pressure, boiling point elevation, freezing point depression, and vapour pressure lowering. [EU] Osmolarity: The concentration of osmotically active particles expressed in terms of osmoles of solute per litre of solution. [EU] Osmoles: The standard unit of osmotic pressure. [NIH] Osmosis: Tendency of fluids (e.g., water) to move from the less concentrated to the more concentrated side of a semipermeable membrane. [NIH] Osmotic: Pertaining to or of the nature of osmosis (= the passage of pure solvent from a solution of lesser to one of greater solute concentration when the two solutions are separated by a membrane which selectively prevents the passage of solute molecules, but is permeable to the solvent). [EU] Otitis: Inflammation of the ear, which may be marked by pain, fever, abnormalities of hearing, hearing loss, tinnitus, and vertigo. [EU] Otitis Media: Inflammation of the middle ear. [NIH] Outpatient: A patient who is not an inmate of a hospital but receives diagnosis or treatment in a clinic or dispensary connected with the hospital. [NIH] Ovalbumin: An albumin obtained from the white of eggs. It is a member of the serpin superfamily. [NIH] Ovarian Follicle: Spheroidal cell aggregation in the ovary containing an ovum. It consists of
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an external fibro-vascular coat, an internal coat of nucleated cells, and a transparent, albuminous fluid in which the ovum is suspended. [NIH] Ovary: Either of the paired glands in the female that produce the female germ cells and secrete some of the female sex hormones. [NIH] Overexpress: An excess of a particular protein on the surface of a cell. [NIH] Overweight: An excess of body weight but not necessarily body fat; a body mass index of 25 to 29.9 kg/m2. [NIH] Ovulation: The discharge of a secondary oocyte from a ruptured graafian follicle. [NIH] Ovum: A female germ cell extruded from the ovary at ovulation. [NIH] Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]
Oxidative Stress: A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi). [NIH] Pachymeningitis: Inflammation of the dura mater of the brain, the spinal cord or the optic nerve. [NIH] Paediatric: Of or relating to the care and medical treatment of children; belonging to or concerned with paediatrics. [EU] Palate: The structure that forms the roof of the mouth. It consists of the anterior hard palate and the posterior soft palate. [NIH] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Pancreatic: Having to do with the pancreas. [NIH] Pancreatic cancer: Cancer of the pancreas, a salivary gland of the abdomen. [NIH] Pancreatic enzymes: A group of proteins secreted by the pancreas which aid in the digestion of food. [NIH] Panic: A state of extreme acute, intense anxiety and unreasoning fear accompanied by disorganization of personality function. [NIH] Papilloma: A benign epithelial neoplasm which may arise from the skin, mucous membranes or glandular ducts. [NIH] Paranasal Sinuses: Air-filled extensions of the respiratory part of the nasal cavity into the frontal, ethmoid, sphenoid, and maxillary cranial bones. They vary in size and form in different individuals and are lined by the ciliated mucous membranes of the nasal cavity. [NIH]
Parasite: An animal or a plant that lives on or in an organism of another species and gets at least some of its nutrition from that other organism. [NIH] Parasitic: Having to do with or being a parasite. A parasite is an animal or a plant that lives on or in an organism of another species and gets at least some of its nutrients from it. [NIH]
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Parasitic Diseases: Infections or infestations with parasitic organisms. They are often contracted through contact with an intermediate vector, but may occur as the result of direct exposure. [NIH] Parenteral: Not through the alimentary canal but rather by injection through some other route, as subcutaneous, intramuscular, intraorbital, intracapsular, intraspinal, intrasternal, intravenous, etc. [EU] Parenteral Nutrition: The administering of nutrients for assimilation and utilization by a patient who cannot maintain adequate nutrition by enteral feeding alone. Nutrients are administered by a route other than the alimentary canal (e.g., intravenously, subcutaneously). [NIH] 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] Parietal Cells: Cells in the stomach wall that make hydrochloric acid. [NIH] Parietal Lobe: Upper central part of the cerebral hemisphere. [NIH] Paroxysmal: Recurring in paroxysms (= spasms or seizures). [EU] Particle: A tiny mass of material. [EU] Patch: A piece of material used to cover or protect a wound, an injured part, etc.: a patch over the eye. [NIH] Pathogen: Any disease-producing microorganism. [EU] Pathogenesis: The cellular events and reactions that occur in the development of disease. [NIH]
Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Pathologic Processes: The abnormal mechanisms and forms involved in the dysfunctions of tissues and organs. [NIH] Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Patient Education: The teaching or training of patients concerning their own health needs. [NIH]
Penicillin: An antibiotic drug used to treat infection. [NIH] Peptic: Pertaining to pepsin or to digestion; related to the action of gastric juices. [EU] Peptic Ulcer: Ulcer that occurs in those portions of the alimentary tract which come into contact with gastric juice containing pepsin and acid. It occurs when the amount of acid and pepsin is sufficient to overcome the gastric mucosal barrier. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Peptide Elongation Factors: Protein factors uniquely required during the elongation phase of protein synthesis. [NIH] Peptide Fragments: Partial proteins formed by partial hydrolysis of complete proteins. [NIH] Peptide T: N-(N-(N(2)-(N-(N-(N-(N-D-Alanyl L-seryl)-L-threonyl)-L-threonyl) L-threonyl)L-asparaginyl)-L-tyrosyl) L-threonine. Octapeptide sharing sequence homology with HIV envelope protein gp120. It is potentially useful as antiviral agent in AIDS therapy. The core pentapeptide sequence, TTNYT, consisting of amino acids 4-8 in peptide T, is the HIV envelope sequence required for attachment to the CD4 receptor. [NIH] Perforation: 1. The act of boring or piercing through a part. 2. A hole made through a part or
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substance. [EU] Periodontal disease: Disease involving the supporting structures of the teeth (as the gums and periodontal membranes). [NIH] Peripheral Nervous System: The nervous system outside of the brain and spinal cord. The peripheral nervous system has autonomic and somatic divisions. The autonomic nervous system includes the enteric, parasympathetic, and sympathetic subdivisions. The somatic nervous system includes the cranial and spinal nerves and their ganglia and the peripheral sensory receptors. [NIH] Peripheral Vascular Disease: Disease in the large blood vessels of the arms, legs, and feet. People who have had diabetes for a long time may get this because major blood vessels in their arms, legs, and feet are blocked and these limbs do not receive enough blood. The signs of PVD are aching pains in the arms, legs, and feet (especially when walking) and foot sores that heal slowly. Although people with diabetes cannot always avoid PVD, doctors say they have a better chance of avoiding it if they take good care of their feet, do not smoke, and keep both their blood pressure and diabetes under good control. [NIH] Periplasm: The space between the inner and outer membranes of a cell that is shared with the cell wall. [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] Peritoneum: Endothelial lining of the abdominal cavity, the parietal peritoneum covering the inside of the abdominal wall and the visceral peritoneum covering the bowel, the mesentery, and certain of the organs. The portion that covers the bowel becomes the serosal layer of the bowel wall. [NIH] Peritonitis: Inflammation of the peritoneum; a condition marked by exudations in the peritoneum of serum, fibrin, cells, and pus. It is attended by abdominal pain and tenderness, constipation, vomiting, and moderate fever. [EU] 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] Pertussis Toxins: Any of various biologically active proteins or toxins elaborated by Bordetella pertussis that cause the symptoms of whooping cough. Some activate pancreatic islets, others inhibit the adenylate cyclase cascade and some cause lymphocytosis. [NIH] Pestivirus: A genus of Flaviviridae, also known as mucosal disease virus group, which is not arthropod-borne. Transmission is by direct and indirect contact, and by transplacental and congenital transmission. Species include border disease virus, bovine viral diarrhea virus, and hog cholera virus. [NIH] PH: The symbol relating the hydrogen ion (H+) concentration or activity of a solution to that of a given standard solution. Numerically the pH is approximately equal to the negative logarithm of H+ concentration expressed in molarity. pH 7 is neutral; above it alkalinity increases and below it acidity increases. [EU]
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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] Pharmaceutical Preparations: Drugs intended for human or veterinary use, presented in their finished dosage form. Included here are materials used in the preparation and/or formulation of the finished dosage form. [NIH] Pharmacokinetic: The mathematical analysis of the time courses of absorption, distribution, and elimination of drugs. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Pharynx: The hollow tube about 5 inches long that starts behind the nose and ends at the top of the trachea (windpipe) and esophagus (the tube that goes to the stomach). [NIH] Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of yeasts. [NIH] Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor of melanin, dopamine, noradrenalin, and thyroxine. [NIH] Phospholipases: A class of enzymes that catalyze the hydrolysis of phosphoglycerides or glycerophosphatidates. EC 3.1.-. [NIH] Phospholipids: Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides; glycerophospholipids) or sphingosine (sphingolipids). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system. [NIH] Phosphorus: A non-metallic element that is found in the blood, muscles, nevers, bones, and teeth, and is a component of adenosine triphosphate (ATP; the primary energy source for the body's cells.) [NIH] Phosphorylated: Attached to a phosphate group. [NIH] Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. [NIH] Phylogeny: The relationships of groups of organisms as reflected by their evolutionary history. [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] Pigment: A substance that gives color to tissue. Pigments are responsible for the color of skin, eyes, and hair. [NIH] Placenta: A highly vascular fetal organ through which the fetus absorbs oxygen and other nutrients and excretes carbon dioxide and other wastes. It begins to form about the eighth day of gestation when the blastocyst adheres to the decidua. [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
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sylvatic rodent-flea ecosystems throughout the world. Bubonic plague is the most common form. [NIH] Plant Diseases: Diseases of plants. [NIH] Plant Proteins: Proteins found in plants (flowers, herbs, shrubs, trees, etc.). The concept does not include proteins found in vegetables for which vegetable proteins is available. [NIH] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] Plasma protein: One of the hundreds of different proteins present in blood plasma, including carrier proteins ( such albumin, transferrin, and haptoglobin), fibrinogen and other coagulation factors, complement components, immunoglobulins, enzyme inhibitors, precursors of substances such as angiotension and bradykinin, and many other types of proteins. [EU] Plasmid: An autonomously replicating, extra-chromosomal DNA molecule found in many bacteria. Plasmids are widely used as carriers of cloned genes. [NIH] Plastids: Self-replicating cytoplasmic organelles of plant and algal cells that contain pigments and may synthesize and accumulate various substances. Plastids are used in phylogenetic studies. [NIH] Platelet Activation: A series of progressive, overlapping events triggered by exposure of the platelets to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug. [NIH] Platelet Factor 4: A high-molecular-weight proteoglycan-platelet factor complex which is released from blood platelets by thrombin. It acts as a mediator in the heparin-neutralizing capacity of the blood and plays a role in platelet aggregation. At high ionic strength (I=0.75), the complex dissociates into the active component (molecular weight 29,000) and the proteoglycan carrier (chondroitin 4-sulfate, molecular weight 350,000). The molecule exists in the form of a dimer consisting of 8 moles of platelet factor 4 and 2 moles of proteoglycan. [NIH]
Platinum: Platinum. A heavy, soft, whitish metal, resembling tin, atomic number 78, atomic weight 195.09, symbol Pt. (From Dorland, 28th ed) It is used in manufacturing equipment for laboratory and industrial use. It occurs as a black powder (platinum black) and as a spongy substance (spongy platinum) and may have been known in Pliny's time as "alutiae". [NIH]
Pleated: Particular three-dimensional pattern of amyloidoses. [NIH] Pneumococcal Infections: Infections with bacteria of the species Streptococcus pneumoniae. [NIH]
Pneumonitis: A disease caused by inhaling a wide variety of substances such as dusts and molds. Also called "farmer's disease". [NIH] 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
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as a template. The polymerase copies the template in the 5'-3'direction provided that sufficient quantities of free nucleotides, dATP and dTTP are present. [NIH] Polymerase Chain Reaction: In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships. [NIH] Polymers: Compounds formed by the joining of smaller, usually repeating, units linked by covalent bonds. These compounds often form large macromolecules (e.g., polypeptides, proteins, plastics). [NIH] Polymorphic: Occurring in several or many forms; appearing in different forms at different stages of development. [EU] Polymorphism: The occurrence together of two or more distinct forms in the same population. [NIH] Polypeptide: A peptide which on hydrolysis yields more than two amino acids; called tripeptides, tetrapeptides, etc. according to the number of amino acids contained. [EU] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] Polyvalent: Having more than one valence. [EU] Population Dynamics: The pattern of any process, or the interrelationship of phenomena, which affects growth or change within a population. [NIH] Posterior: Situated in back of, or in the back part of, or affecting the back or dorsal surface of the body. In lower animals, it refers to the caudal end of the body. [EU] Postnatal: Occurring after birth, with reference to the newborn. [EU] Postoperative: After surgery. [NIH] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Post-translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Potassium: An element that is in the alkali group of metals. It has an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte and it plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. [NIH] Potentiates: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Potentiating: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Potentiation: An overall effect of two drugs taken together which is greater than the sum of the effects of each drug taken alone. [NIH] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of
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health care and delivery. [NIH] Preclinical: Before a disease becomes clinically recognizable. [EU] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Prenatal: Existing or occurring before birth, with reference to the fetus. [EU] Preoptic Area: Region of hypothalamus between the anterior commissure and optic chiasm. [NIH]
Presynaptic: Situated proximal to a synapse, or occurring before the synapse is crossed. [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] Prickle: Several layers of the epidermis where the individual cells are connected by cell bridges. [NIH] Probe: An instrument used in exploring cavities, or in the detection and dilatation of strictures, or in demonstrating the potency of channels; an elongated instrument for exploring or sounding body cavities. [NIH] Progeny: The offspring produced in any generation. [NIH] Prognostic factor: A situation or condition, or a characteristic of a patient, that can be used to estimate the chance of recovery from a disease, or the chance of the disease recurring (coming back). [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] Proinsulin: The substance made first in the pancreas that is then made into insulin. When insulin is purified from the pancreas of pork or beef, all the proinsulin is not fully removed. When some people use these insulins, the proinsulin can cause the body to react with a rash, to resist the insulin, or even to make dents or lumps in the skin at the place where the insulin is injected. The purified insulins have less proinsulin and other impurities than the other types of insulins. [NIH] Projection: A defense mechanism, operating unconsciously, whereby that which is emotionally unacceptable in the self is rejected and attributed (projected) to others. [NIH] Proline: A non-essential amino acid that is synthesized from glutamic acid. It is an essential component of collagen and is important for proper functioning of joints and tendons. [NIH] Promoter: A chemical substance that increases the activity of a carcinogenic process. [NIH] Prophase: The first phase of cell division, in which the chromosomes become visible, the nucleus starts to lose its identity, the spindle appears, and the centrioles migrate toward opposite poles. [NIH] Prophylaxis: An attempt to prevent disease. [NIH] Proportional: Being in proportion : corresponding in size, degree, or intensity, having the same or a constant ratio; of, relating to, or used in determining proportions. [EU] Prostaglandins: A group of compounds derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway. They are extremely potent mediators of a diverse group of physiological processes. [NIH] Prostaglandins
A:
(13E,15S)-15-Hydroxy-9-oxoprosta-10,13-dien-1-oic
acid
(PGA(1));
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(5Z,13E,15S)-15-hydroxy-9-oxoprosta-5,10,13-trien-1-oic acid (PGA(2)); (5Z,13E,15S,17Z)-15hydroxy-9-oxoprosta-5,10,13,17-tetraen-1-oic acid (PGA(3)). A group of naturally occurring secondary prostaglandins derived from PGE. PGA(1) and PGA(2) as well as their 19hydroxy derivatives are found in many organs and tissues. [NIH] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific proteinbinding measures are often used as assays in diagnostic assessments. [NIH] Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation. [NIH] Protein Conformation: The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. Quaternary protein structure describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain). [NIH] Protein S: The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH] Protein Subunits: Single chains of amino acids that are the units of a multimeric protein. They can be identical or non-identical subunits. [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] Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] Pruritic: Pertaining to or characterized by pruritus. [EU] Pseudomembranous Colitis: Severe irritation of the colon. Caused by Clostridium difficile bacteria. Occurs after taking oral antibiotics, which kill bacteria that normally live in the colon. [NIH] Psychology: The science dealing with the study of mental processes and behavior in man and animals. [NIH] Psychosexual: Pertaining to the mental aspects of sex. [NIH] Psychotomimetic: Psychosis miming. [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
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editors. Production may be by conventional printing methods or by electronic publishing. [NIH]
Pulmonary: Relating to the lungs. [NIH] Pulmonary Artery: The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs. [NIH] Pulmonary Edema: An accumulation of an excessive amount of watery fluid in the lungs, may be caused by acute exposure to dangerous concentrations of irritant gasses. [NIH] Pulse: The rhythmical expansion and contraction of an artery produced by waves of pressure caused by the ejection of blood from the left ventricle of the heart as it contracts. [NIH]
Purified Insulins: Insulins with much less of the impure proinsulin. It is thought that the use of purified insulins may help avoid or reduce some of the problems of people with diabetes such as allergic reactions. [NIH] Purifying: Respiratory equipment whose function is to remove contaminants from otherwise wholesome air. [NIH] Purines: A series of heterocyclic compounds that are variously substituted in nature and are known also as purine bases. They include adenine and guanine, constituents of nucleic acids, as well as many alkaloids such as caffeine and theophylline. Uric acid is the metabolic end product of purine metabolism. [NIH] Purulent: Consisting of or containing pus; associated with the formation of or caused by pus. [EU] Pyogenic: Producing pus; pyopoietic (= liquid inflammation product made up of cells and a thin fluid called liquor puris). [EU] Pyridoxal: 3-Hydroxy-5-(hydroxymethyl)-2-methyl-4- pyridinecarboxaldehyde. [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] Radiation therapy: The use of high-energy radiation from x-rays, gamma rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body in the area near cancer cells (internal radiation therapy, implant radiation, or brachytherapy). Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Also called radiotherapy. [NIH] Radioactive: Giving off radiation. [NIH] Radioisotope: An unstable element that releases radiation as it breaks down. Radioisotopes can be used in imaging tests or as a treatment for cancer. [NIH] Radius: The lateral bone of the forearm. [NIH] Randomized: Describes an experiment or clinical trial in which animal or human subjects are assigned by chance to separate groups that compare different treatments. [NIH] Reactive Oxygen Species: Reactive intermediate oxygen species including both radicals and non-radicals. These substances are constantly formed in the human body and have been shown to kill bacteria and inactivate proteins, and have been implicated in a number of
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diseases. Scientific data exist that link the reactive oxygen species produced by inflammatory phagocytes to cancer development. [NIH] Reading Frames: The sequence of codons by which translation may occur. A segment of mRNA 5'AUCCGA3' could be translated in three reading frames, 5'AUC. or 5'UCC. or 5'CCG., depending on the location of the start codon. [NIH] Reagent: A substance employed to produce a chemical reaction so as to detect, measure, produce, etc., other substances. [EU] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Receptors, Serotonin: Cell-surface proteins that bind serotonin and trigger intracellular changes which influence the behavior of cells. Several types of serotonin receptors have been recognized which differ in their pharmacology, molecular biology, and mode of action. [NIH] Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Recombinant Proteins: Proteins prepared by recombinant DNA technology. [NIH] Recombination: The formation of new combinations of genes as a result of segregation in crosses between genetically different parents; also the rearrangement of linked genes due to crossing-over. [NIH] Reconstitution: 1. A type of regeneration in which a new organ forms by the rearrangement of tissues rather than from new formation at an injured surface. 2. The restoration to original form of a substance previously altered for preservation and storage, as the restoration to a liquid state of blood serum or plasma that has been dried and stored. [EU] Rectal: By or having to do with the rectum. The rectum is the last 8 to 10 inches of the large intestine and ends at the anus. [NIH] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Recurrence: The return of a sign, symptom, or disease after a remission. [NIH] Red blood cells: RBCs. Cells that carry oxygen to all parts of the body. Also called erythrocytes. [NIH] Reductase: Enzyme converting testosterone to dihydrotestosterone. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH] Regeneration: The natural renewal of a structure, as of a lost tissue or part. [EU] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Regulon: In eukaryotes, a genetic unit consisting of a noncontiguous group of genes under the control of a single regulator gene. In bacteria, regulons are global regulatory systems involved in the interplay of pleiotropic regulatory domains. These regulatory systems consist of several operons. [NIH] Rehydration: The restoration of water or of fluid content to a body or to substance which has become dehydrated. [EU] Rehydration Solutions: Fluids restored to the body in order to maintain normal waterelectrolyte balance. [NIH] Relapse: The return of signs and symptoms of cancer after a period of improvement. [NIH] Renal failure: Progressive renal insufficiency and uremia, due to irreversible and
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progressive renal glomerular tubular or interstitial disease. [NIH] Repressor: Any of the specific allosteric protein molecules, products of regulator genes, which bind to the operator of operons and prevent RNA polymerase from proceeding into the operon to transcribe messenger RNA. [NIH] Resection: Removal of tissue or part or all of an organ by surgery. [NIH] Respiratory Mucosa: The mucous membrane lining the respiratory tract. [NIH] Response rate: The percentage of patients whose cancer shrinks or disappears after treatment. [NIH] Restoration: Broad term applied to any inlay, crown, bridge or complete denture which restores or replaces loss of teeth or oral tissues. [NIH] Retina: The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outer-most layer is pigmented, whereas the inner nine layers are transparent. [NIH] Retrograde: 1. Moving backward or against the usual direction of flow. 2. Degenerating, deteriorating, or catabolic. [EU] Reversion: A return to the original condition, e. g. the reappearance of the normal or wild type in previously mutated cells, tissues, or organisms. [NIH] Rhinitis: Inflammation of the mucous membrane of the nose. [NIH] Ribose: A pentose active in biological systems usually in its D-form. [NIH] Ribosome: A granule of protein and RNA, synthesized in the nucleolus and found in the cytoplasm of cells. Ribosomes are the main sites of protein synthesis. Messenger RNA attaches to them and there receives molecules of transfer RNA bearing amino acids. [NIH] 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] Rigidity: Stiffness or inflexibility, chiefly that which is abnormal or morbid; rigor. [EU] Riots: A form of violent crowd behavior which expresses the emotional release of resentments and prejudices, usually relevant to grievances toward the social system. [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] Rotavirus: A genus of Reoviridae, causing acute gastroenteritis in birds and mammals, including humans. Transmission is horizontal and by environmental contamination. [NIH] Rural Population: The inhabitants of rural areas or of small towns classified as rural. [NIH] Saline: A solution of salt and water. [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] Salmonella: A genus of gram-negative, facultatively anaerobic, rod-shaped bacteria that utilizes citrate as a sole carbon source. It is pathogenic for humans, causing enteric fevers, gastroenteritis, and bacteremia. Food poisoning is the most common clinical manifestation. Organisms within this genus are separated on the basis of antigenic characteristics, sugar
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fermentation patterns, and bacteriophage susceptibility. [NIH] Salmonella typhi: A serotype of Salmonella enterica which is the etiologic agent of typhoid fever. [NIH] Salmonellosis: Infection by salmonellae. [NIH] Sanitation: The development and establishment of environmental conditions favorable to the health of the public. [NIH] Sarcoplasmic Reticulum: A network of tubules and sacs in the cytoplasm of skeletal muscles that assist with muscle contraction and relaxation by releasing and storing calcium ions. [NIH] Satellite: Applied to a vein which closely accompanies an artery for some distance; in cytogenetics, a chromosomal agent separated by a secondary constriction from the main body of the chromosome. [NIH] Scabies: A contagious cutaneous inflammation caused by the bite of the mite Sarcoptes scabiei. It is characterized by pruritic papular eruptions and burrows and affects primarily the axillae, elbows, wrists, and genitalia, although it can spread to cover the entire body. [NIH]
Scleroproteins: Simple proteins characterized by their insolubility and fibrous structure. Within the body, they perform a supportive or protective function. [NIH] Sclerosis: A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Sebaceous: Gland that secretes sebum. [NIH] Second Messenger Systems: Systems in which an intracellular signal is generated in response to an intercellular primary messenger such as a hormone or neurotransmitter. They are intermediate signals in cellular processes such as metabolism, secretion, contraction, phototransduction, and cell growth. Examples of second messenger systems are the adenyl cyclase-cyclic AMP system, the phosphatidylinositol diphosphate-inositol triphosphate system, and the cyclic GMP system. [NIH] Secretion: 1. The process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. Any substance produced by secretion. [EU] Secretory: Secreting; relating to or influencing secretion or the secretions. [NIH] Sedentary: 1. Sitting habitually; of inactive habits. 2. Pertaining to a sitting posture. [EU] Segregation: The separation in meiotic cell division of homologous chromosome pairs and their contained allelomorphic gene pairs. [NIH] Seizures: Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as epilepsy or "seizure disorder." [NIH] Sensor: A device designed to respond to physical stimuli such as temperature, light, magnetism or movement and transmit resulting impulses for interpretation, recording, movement, or operating control. [NIH] Sepsis: The presence of bacteria in the bloodstream. [NIH] Septicaemia: A term originally used to denote a putrefactive process in the body, but now usually referring to infection with pyogenic micro-organisms; a genus of Diptera; the severe type of infection in which the blood stream is invaded by large numbers of the causal. [NIH]
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Septicemia: Systemic disease associated with the presence and persistence of pathogenic microorganisms or their toxins in the blood. Called also blood poisoning. [EU] Sequence Analysis: A multistage process that includes the determination of a sequence (protein, carbohydrate, etc.), its fragmentation and analysis, and the interpretation of the resulting sequence information. [NIH] Sequence Homology: The degree of similarity between sequences. Studies of amino acid and nucleotide sequences provide useful information about the genetic relatedness of certain species. [NIH] Sequencing: The determination of the order of nucleotides in a DNA or RNA chain. [NIH] Serine: A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from glycine or threonine. It is involved in the biosynthesis of purines, pyrimidines, and other amino acids. [NIH] Seroconversion: The change of a serologic test from negative to positive, indicating the development of antibodies in response to infection or immunization. [EU] Serologic: Analysis of a person's serum, especially specific immune or lytic serums. [NIH] Serotonin: A biochemical messenger and regulator, synthesized from the essential amino acid L-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (receptors, serotonin) explain the broad physiological actions and distribution of this biochemical mediator. [NIH] Serotypes: A cause of haemorrhagic septicaemia (in cattle, sheep and pigs), fowl cholera of birds, pasteurellosis of rabbits, and gangrenous mastitis of ewes. It is also commonly found in atrophic rhinitis of pigs. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Serum Albumin: A major plasma protein that serves in maintaining the plasma colloidal osmotic pressure and transporting large organic anions. [NIH] Sexually Transmitted Diseases: Diseases due to or propagated by sexual contact. [NIH] Shedding: Release of infectious particles (e. g., bacteria, viruses) into the environment, for example by sneezing, by fecal excretion, or from an open lesion. [NIH] Shiga Toxin: A toxin produced by Shigella dysenteriae. It is the protype of class of toxins that inhibit protein synthesis by blocking the interaction of ribosomal RNA with peptide elongation factors. [NIH] Shigella: A genus of gram-negative, facultatively anaerobic, rod-shaped bacteria that ferments sugar without gas production. Its organisms are intestinal pathogens of man and other primates and cause bacillary dysentery. [NIH] Shigellosis: Infection with the bacterium Shigella. Usually causes a high fever, acute diarrhea, and dehydration. [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]
Short Bowel Syndrome: A malabsorption syndrome resulting from extensive operative resection of small bowel. [NIH] Side effect: A consequence other than the one(s) for which an agent or measure is used, as
312 Cholera
the adverse effects produced by a drug, especially on a tissue or organ system other than the one sought to be benefited by its administration. [EU] Signal Transduction: The intercellular or intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GABA-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptormediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. [NIH] Signs and Symptoms: Clinical manifestations that can be either objective when observed by a physician, or subjective when perceived by the patient. [NIH] Single Parent: A natural, adoptive, or substitute parent of a dependent child, who lives with only one parent. The single parent may live with or visit the child. The concept includes the never-married, as well as the divorced and widowed. [NIH] Sinusitis: An inflammatory process of the mucous membranes of the paranasal sinuses that occurs in three stages: acute, subacute, and chronic. Sinusitis results from any condition causing ostial obstruction or from pathophysiologic changes in the mucociliary transport mechanism. [NIH] Skeletal: Having to do with the skeleton (boney part of the body). [NIH] Skeleton: The framework that supports the soft tissues of vertebrate animals and protects many of their internal organs. The skeletons of vertebrates are made of bone and/or cartilage. [NIH] Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Smallpox: A generalized virus infection with a vesicular rash. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]
Sneezing: Sudden, forceful, involuntary expulsion of air from the nose and mouth caused by irritation to the mucous membranes of the upper respiratory tract. [NIH] 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] Sodium-Calcium Exchanger: An electrogenic ion exchange protein that maintains a steady level of calcium by removing an amount of calcium equal to that which enters the cells. It is widely distributed in most excitable membranes, including the brain and heart. [NIH] Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of
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the body. [NIH] Solid tumor: Cancer of body tissues other than blood, bone marrow, or the lymphatic system. [NIH] Solvent: 1. Dissolving; effecting a solution. 2. A liquid that dissolves or that is capable of dissolving; the component of a solution that is present in greater amount. [EU] Soma: The body as distinct from the mind; all the body tissue except the germ cells; all the axial body. [NIH] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] Somatostatin: A polypeptide hormone produced in the hypothalamus, and other tissues and organs. It inhibits the release of human growth hormone, and also modulates important physiological functions of the kidney, pancreas, and gastrointestinal tract. Somatostatin receptors are widely expressed throughout the body. Somatostatin also acts as a neurotransmitter in the central and peripheral nervous systems. [NIH] Sorbitol: A polyhydric alcohol with about half the sweetness of sucrose. Sorbitol occurs naturally and is also produced synthetically from glucose. It was formerly used as a diuretic and may still be used as a laxative and in irrigating solutions for some surgical procedures. It is also used in many manufacturing processes, as a pharmaceutical aid, and in several research applications. [NIH] Spasm: An involuntary contraction of a muscle or group of muscles. Spasms may involve skeletal muscle or smooth muscle. [NIH] 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 Latinized adjective or noun. [EU] Specificity: Degree of selectivity shown by an antibody with respect to the number and types of antigens with which the antibody combines, as well as with respect to the rates and the extents of these reactions. [NIH] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU] Sperm: The fecundating fluid of the male. [NIH] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] Spinous: Like a spine or thorn in shape; having spines. [NIH] Spirochete: Lyme disease. [NIH] Spleen: An organ that is part of the lymphatic system. The spleen produces lymphocytes, filters the blood, stores blood cells, and destroys old blood cells. It is located on the left side of the abdomen near the stomach. [NIH] Spores: The reproductive elements of lower organisms, such as protozoa, fungi, and cryptogamic plants. [NIH] Sporotrichosis: The commonest and least serious of the deep mycoses, characterized by
314 Cholera
nodular lesions of the cutaneous and subcutaneous tissues. It is caused by inhalation of contaminated dust or by infection of a wound. [NIH] Squamous: Scaly, or platelike. [EU] Squamous cell carcinoma: Cancer that begins in squamous cells, which are thin, flat cells resembling fish scales. Squamous cells are found in the tissue that forms the surface of the skin, the lining of the hollow organs of the body, and the passages of the respiratory and digestive tracts. Also called epidermoid carcinoma. [NIH] Squamous cell carcinoma: Cancer that begins in squamous cells, which are thin, flat cells resembling fish scales. Squamous cells are found in the tissue that forms the surface of the skin, the lining of the hollow organs of the body, and the passages of the respiratory and digestive tracts. Also called epidermoid carcinoma. [NIH] Steady state: Dynamic equilibrium. [EU] Stem Cells: Relatively undifferentiated cells of the same lineage (family type) that retain the ability to divide and cycle throughout postnatal life to provide cells that can become specialized and take the place of those that die or are lost. [NIH] Sterility: 1. The inability to produce offspring, i.e., the inability to conceive (female s.) or to induce conception (male s.). 2. The state of being aseptic, or free from microorganisms. [EU] Steroids: Drugs used to relieve swelling and inflammation. [NIH] Stimulant: 1. Producing stimulation; especially producing stimulation by causing tension on muscle fibre through the nervous tissue. 2. An agent or remedy that produces stimulation. [EU]
Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Stool: The waste matter discharged in a bowel movement; feces. [NIH] Strand: DNA normally exists in the bacterial nucleus in a helix, in which two strands are coiled together. [NIH] 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] Streptomycin: O-2-Deoxy-2-(methylamino)-alpha-L-glucopyranosyl-(1-2)-O-5- deoxy-3-Cformyl-alpha-L-lyxofuranosyl-(1-4)-N,N'-bis(aminoiminomethyl)-D-streptamine. Antibiotic substance produced by the soil actinomycete Streptomyces griseus. It acts by inhibiting the initiation and elongation processes during protein synthesis. [NIH] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] Stress Fibers: Bundles of actin filaments (microfilaments) and myosin-II that span across the cell attaching to the cell membrane at focal adhesions and to the network of intermediate filaments that surrounds the nucleus. [NIH] Striatum: A higher brain's domain thus called because of its stripes. [NIH] Stroke: Sudden loss of function of part of the brain because of loss of blood flow. Stroke may
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be caused by a clot (thrombosis) or rupture (hemorrhage) of a blood vessel to the brain. [NIH] Stromal: Large, veil-like cell in the bone marrow. [NIH] Subacute: Somewhat acute; between acute and chronic. [EU] Subarachnoid: Situated or occurring between the arachnoid and the pia mater. [EU] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] Subcutaneous: Beneath the skin. [NIH] Submaxillary: Four to six lymph glands, located between the lower jaw and the submandibular salivary gland. [NIH] Submucous: Occurring beneath the mucosa or a mucous membrane. [NIH] Subspecies: A category intermediate in rank between species and variety, based on a smaller number of correlated characters than are used to differentiate species and generally conditioned by geographical and/or ecological occurrence. [NIH] Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of pain, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses. [NIH]
Substrate: A substance upon which an enzyme acts. [EU] Suction: The removal of secretions, gas or fluid from hollow or tubular organs or cavities by means of a tube and a device that acts on negative pressure. [NIH] Supplementation: Adding nutrients to the diet. [NIH] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Suprachiasmatic Nucleus: An ovoid densely packed collection of small cells of the anterior hypothalamus lying close to the midline in a shallow impression of the optic chiasm. [NIH] Surface Plasmon Resonance: A biosensing technique in which biomolecules capable of binding to specific analytes or ligands are first immobilized on one side of a metallic film. Light is then focused on the opposite side of the film to excite the surface plasmons, that is, the oscillations of free electrons propagating along the film's surface. The refractive index of light reflecting off this surface is measured. When the immobilized biomolecules are bound by their ligands, an alteration in surface plasmons on the opposite side of the film is created which is directly proportional to the change in bound, or adsorbed, mass. Binding is measured by changes in the refractive index. The technique is used to study biomolecular interactions, such as antigen-antibody binding. [NIH] Surfactant: A fat-containing protein in the respiratory passages which reduces the surface tension of pulmonary fluids and contributes to the elastic properties of pulmonary tissue. [NIH]
Suspensions: Colloids with liquid continuous phase and solid dispersed phase; the term is used loosely also for solid-in-gas (aerosol) and other colloidal systems; water-insoluble drugs may be given as suspensions. [NIH] Sympathomimetic: 1. Mimicking the effects of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. 2. An agent that produces effects similar to those of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. Called also adrenergic. [EU]
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Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] Synapses: Specialized junctions at which a neuron communicates with a target cell. At classical synapses, a neuron's presynaptic terminal releases a chemical transmitter stored in synaptic vesicles which diffuses across a narrow synaptic cleft and activates receptors on the postsynaptic membrane of the target cell. The target may be a dendrite, cell body, or axon of another neuron, or a specialized region of a muscle or secretory cell. Neurons may also communicate through direct electrical connections which are sometimes called electrical synapses; these are not included here but rather in gap junctions. [NIH] Synapsis: The pairing between homologous chromosomes of maternal and paternal origin during the prophase of meiosis, leading to the formation of gametes. [NIH] Synaptic: Pertaining to or affecting a synapse (= site of functional apposition between neurons, at which an impulse is transmitted from one neuron to another by electrical or chemical means); pertaining to synapsis (= pairing off in point-for-point association of homologous chromosomes from the male and female pronuclei during the early prophase of meiosis). [EU] Synaptophysin: A 38-kDa integral membrane glycoprotein of the presynaptic vesicles in neuron and neuroendocrine cells. It is expressed by a variety of normal and neoplastic neuroendocrine cells and is therefore used as an immunocytochemical marker for neuroendocrine differentiation in various tumors. In Alzheimer disease and other dementing disorders there is an important synapse loss due in part to a decrease of synaptophysin in the presynaptic vesicles. [NIH] Synergistic: Acting together; enhancing the effect of another force or agent. [EU] Syphilis: A contagious venereal disease caused by the spirochete Treponema pallidum. [NIH]
Systemic: Affecting the entire body. [NIH] Systemic disease: Disease that affects the whole body. [NIH] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] Tachycardia: Excessive rapidity in the action of the heart, usually with a heart rate above 100 beats per minute. [NIH] Tachypnea: Rapid breathing. [NIH] Telecommunications: Transmission of information over distances via electronic means. [NIH]
Telemedicine: Delivery of health services via remote telecommunications. This includes interactive consultative and diagnostic services. [NIH] Temporal: One of the two irregular bones forming part of the lateral surfaces and base of the skull, and containing the organs of hearing. [NIH] Temporal Lobe: Lower lateral part of the cerebral hemisphere. [NIH] Tenesmus: Straining, especially ineffectual and painful straining at stool or in urination. [EU] Terminator: A DNA sequence sited at the end of a transcriptional unit that signals the end of transcription. [NIH] Testis: Either of the paired male reproductive glands that produce the male germ cells and the male hormones. [NIH] Testosterone: A hormone that promotes the development and maintenance of male sex characteristics. [NIH] Tetani: Causal agent of tetanus. [NIH]
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Tetanic: Having the characteristics of, or relating to tetanus. [NIH] Tetanus: A disease caused by tetanospasmin, a powerful protein toxin produced by Clostridium tetani. Tetanus usually occurs after an acute injury, such as a puncture wound or laceration. Generalized tetanus, the most common form, is characterized by tetanic muscular contractions and hyperreflexia. Localized tetanus presents itself as a mild condition with manifestations restricted to muscles near the wound. It may progress to the generalized form. [NIH] Tetanus Toxin: The toxin elaborated by Clostridium tetani. It is a protein with a molecular weight of about 150,000, probably consisting of two fragments, tetanolysin being the hemolytic and tetanospasmin the neurotoxic principle. The toxin causes disruption of the inhibitory mechanisms of the CNS, thus permitting uncontrolled nervous activity, leading to fatal convulsions. [NIH] Tetracycline: An antibiotic originally produced by Streptomyces viridifaciens, but used mostly in synthetic form. It is an inhibitor of aminoacyl-tRNA binding during protein synthesis. [NIH] Thalassemia: A group of hereditary hemolytic anemias in which there is decreased synthesis of one or more hemoglobin polypeptide chains. There are several genetic types with clinical pictures ranging from barely detectable hematologic abnormality to severe and fatal anemia. [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] Third Ventricle: A narrow cleft inferior to the corpus callosum, within the diencephalon, between the paired thalami. Its floor is formed by the hypothalamus, its anterior wall by the lamina terminalis, and its roof by ependyma. It communicates with the fourth ventricle by the cerebral aqueduct, and with the lateral ventricles by the interventricular foramina. [NIH] Threonine: An essential amino acid occurring naturally in the L-form, which is the active form. It is found in eggs, milk, gelatin, and other proteins. [NIH] Threshold: For a specified sensory modality (e. g. light, sound, vibration), the lowest level (absolute threshold) or smallest difference (difference threshold, difference limen) or intensity of the stimulus discernible in prescribed conditions of stimulation. [NIH] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] Thrombocytopenia: A decrease in the number of blood platelets. [NIH] 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] Thylakoids: Membranous cisternae of the chloroplast containing photosynthetic pigments, reaction centers, and the electron-transport chain. Each thylakoid consists of a flattened sac of membrane enclosing a narrow intra-thylakoid space (Lackie and Dow, Dictionary of Cell Biology, 2nd ed). Individual thylakoids are interconnected and tend to stack to form aggregates called grana. They are found in cyanobacteria and all plants. [NIH] Thymus: An organ that is part of the lymphatic system, in which T lymphocytes grow and multiply. The thymus is in the chest behind the breastbone. [NIH] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH]
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Thyroid Gland: A highly vascular endocrine gland consisting of two lobes, one on either side of the trachea, joined by a narrow isthmus; it produces the thyroid hormones which are concerned in regulating the metabolic rate of the body. [NIH] Thyroid Hormones: Hormones secreted by the thyroid gland. [NIH] Thyrotropin: A peptide hormone secreted by the anterior pituitary. It promotes the growth of the thyroid gland and stimulates the synthesis of thyroid hormones and the release of thyroxine by the thyroid gland. [NIH] Thyroxine: An amino acid of the thyroid gland which exerts a stimulating effect on thyroid metabolism. [NIH] Tinnitus: Sounds that are perceived in the absence of any external noise source which may take the form of buzzing, ringing, clicking, pulsations, and other noises. Objective tinnitus refers to noises generated from within the ear or adjacent structures that can be heard by other individuals. The term subjective tinnitus is used when the sound is audible only to the affected individual. Tinnitus may occur as a manifestation of cochlear diseases; vestibulocochlear nerve diseases; intracranial hypertension; craniocerebral trauma; and other conditions. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tissue Culture: Maintaining or growing of tissue, organ primordia, or the whole or part of an organ in vitro so as to preserve its architecture and/or function (Dorland, 28th ed). Tissue culture includes both organ culture and cell culture. [NIH] Titre: The quantity of a substance required to produce a reaction with a given volume of another substance, or the amount of one substance required to correspond with a given amount of another substance. [EU] Togaviridae: A family of RNA viruses, mainly arboviruses, consisting of two genera: Alphavirus (group A arboviruses), and Rubivirus. Virions are spherical, 60-70 nm in diameter, with a lipoprotein envelope tightly applied to the icosahedral nucleocapsid. [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] Tonicity: The normal state of muscular tension. [NIH] Tooth Preparation: Procedures carried out with regard to the teeth or tooth structures preparatory to specified dental therapeutic and surgical measures. [NIH] Topical: On the surface of the body. [NIH] Torovirus: A genus of the family Coronaviridae characterized by enveloped, peplomerbearing particles containing an elongated tubular nucleocapsid with helical symmetry. Toroviruses have been found in association with enteric infections in horses (Berne virus), cattle (Breda virus), and humans. Transmission takes place probably via the fecal-oral route. [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]
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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] Toxoplasmosis: The acquired form of infection by Toxoplasma gondii in animals and man. [NIH]
Tracer: A substance (such as a radioisotope) used in imaging procedures. [NIH] Trachea: The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi. [NIH] Transcutaneous: Transdermal. [EU] Transduction: The transfer of genes from one cell to another by means of a viral (in the case of bacteria, a bacteriophage) vector or a vector which is similar to a virus particle (pseudovirion). [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Transfer Factor: Factor derived from leukocyte lysates of immune donors which can transfer both local and systemic cellular immunity to nonimmune recipients. [NIH] Transfusion: The infusion of components of blood or whole blood into the bloodstream. The blood may be donated from another person, or it may have been taken from the person earlier and stored until needed. [NIH] Translation: The process whereby the genetic information present in the linear sequence of ribonucleotides in mRNA is converted into a corresponding sequence of amino acids in a protein. It occurs on the ribosome and is unidirectional. [NIH] Translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Translocation: The movement of material in solution inside the body of the plant. [NIH] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell to the other at the synapse. [NIH] Transplantation: Transference of a tissue or organ, alive or dead, within an individual, between individuals of the same species, or between individuals of different species. [NIH] Transposase: An enzyme that binds to single-stranded DNA. It is thought to recognize the repetitive ends of a transposon and to participate in the cleavage of the recipient site into which the new transposon copy inserts. EC 2.7.7.-. [NIH] Transposons: Discrete genetic elements capable of inserting, in a non-permuted fashion, into the chromosomes of many bacteria. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Trees: Woody, usually tall, perennial higher plants (Angiosperms, Gymnosperms, and some Pterophyta) having usually a main stem and numerous branches. [NIH] Trichinosis: A disease due to infection with Trichinella spiralis. It is caused by eating undercooked meat, usually pork. [NIH] Trichomoniasis: An infection with the protozoan parasite Trichomonas vaginalis. [NIH] Trichuriasis: Infection with nematodes of the genus Trichuris, formerly called Trichocephalus. [NIH]
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Trypsin: A serine endopeptidase that is formed from trypsinogen in the pancreas. It is converted into its active form by enteropeptidase in the small intestine. It catalyzes hydrolysis of the carboxyl group of either arginine or lysine. EC 3.4.21.4. [NIH] Tryptophan: An essential amino acid that is necessary for normal growth in infants and for nitrogen balance in adults. It is a precursor serotonin and niacin. [NIH] Tuberculosis: Any of the infectious diseases of man and other animals caused by species of Mycobacterium. [NIH] Tubulin: A microtubule subunit protein found in large quantities in mammalian brain. It has also been isolated from sperm flagella, cilia, and other sources. Structurally, the protein is a dimer with a molecular weight of approximately 120,000 and a sedimentation coefficient of 5.8S. It binds to colchicine, vincristine, and vinblastine. [NIH] Tumor model: A type of animal model which can be 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] 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] Tumorigenic: Chemical, viral, radioactive or other agent that causes cancer; carcinogenic. [NIH]
Tumour: 1. Swelling, one of the cardinal signs of inflammations; morbid enlargement. 2. A new growth of tissue in which the multiplication of cells is uncontrolled and progressive; called also neoplasm. [EU] TYPHI: The bacterium that gives rise to typhoid fever. [NIH] Typhimurium: Microbial assay which measures his-his+ reversion by chemicals which cause base substitutions or frameshift mutations in the genome of this organism. [NIH] Typhoid fever: The most important member of the enteric group of fevers which also includes the paratyphoids. [NIH] Typhoid fever: The most important member of the enteric group of fevers which also includes the paratyphoids. [NIH] Tyrosine: A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine, thyroid hormones, and melanin. [NIH] Ulcer: A localized necrotic lesion of the skin or a mucous surface. [NIH] Ulceration: 1. The formation or development of an ulcer. 2. An ulcer. [EU] Ulcerative colitis: Chronic inflammation of the colon that produces ulcers in its lining. This condition is marked by abdominal pain, cramps, and loose discharges of pus, blood, and mucus from the bowel. [NIH] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Uremia: The illness associated with the buildup of urea in the blood because the kidneys are not working effectively. Symptoms include nausea, vomiting, loss of appetite, weakness, and mental confusion. [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]
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Urine: Fluid containing water and waste products. Urine is made by the kidneys, stored in the bladder, and leaves the body through the urethra. [NIH] Urogenital: Pertaining to the urinary and genital apparatus; genitourinary. [EU] Uterus: The small, hollow, pear-shaped organ in a woman's pelvis. This is the organ in which a fetus develops. Also called the womb. [NIH] Vaccination: Administration of vaccines to stimulate the host's immune response. This includes any preparation intended for active immunological prophylaxis. [NIH] Vaccine: A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. [NIH] Vaccinia: The cutaneous and occasional systemic reactions associated with vaccination using smallpox (variola) vaccine. [NIH] Vaccinia Virus: The type species of Orthopoxvirus, related to cowpox virus, but whose true origin is unknown. It has been used as a live vaccine against smallpox. It is also used as a vector for inserting foreign DNA into animals. Rabbitpox virus is a subspecies of vaccinia virus. [NIH] Vacuoles: Any spaces or cavities within a cell. They may function in digestion, storage, secretion, or excretion. [NIH] Vagina: The muscular canal extending from the uterus to the exterior of the body. Also called the birth canal. [NIH] Vaginal: Of or having to do with the vagina, the birth canal. [NIH] Variola: A generalized virus infection with a vesicular rash. [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vasoactive: Exerting an effect upon the calibre of blood vessels. [EU] Vasodilator: An agent that widens blood vessels. [NIH] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH] Vegetable Proteins: Proteins which are present in or isolated from vegetables or vegetable products used as food. The concept is distinguished from plant proteins which refers to nondietary proteins from plants. [NIH] Vegetative: 1. Concerned with growth and with nutrition. 2. Functioning involuntarily or unconsciously, as the vegetative nervous system. 3. Resting; denoting the portion of a cell cycle during which the cell is not involved in replication. 4. Of, pertaining to, or characteristic of plants. [EU] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venereal: Pertaining or related to or transmitted by sexual contact. [EU] Venoms: Poisonous animal secretions forming fluid mixtures of many different enzymes, toxins, and other substances. These substances are produced in specialized glands and secreted through specialized delivery systems (nematocysts, spines, fangs, etc.) for disabling prey or predator. [NIH] Venous: Of or pertaining to the veins. [EU] Ventral: 1. Pertaining to the belly or to any venter. 2. Denoting a position more toward the belly surface than some other object of reference; same as anterior in human anatomy. [EU] Ventricle: One of the two pumping chambers of the heart. The right ventricle receives oxygen-poor blood from the right atrium and pumps it to the lungs through the pulmonary artery. The left ventricle receives oxygen-rich blood from the left atrium and pumps it to the
322 Cholera
body through the aorta. [NIH] Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Vertigo: An illusion of movement; a sensation as if the external world were revolving around the patient (objective vertigo) or as if he himself were revolving in space (subjective vertigo). The term is sometimes erroneously used to mean any form of dizziness. [EU] Vesicular: 1. Composed of or relating to small, saclike bodies. 2. Pertaining to or made up of vesicles on the skin. [EU] Vesicular Exanthema of Swine: A calicivirus infection of swine characterized by hydropic degeneration of the oral and cutaneous epithelia. [NIH] Vesicular Exanthema of Swine Virus: The type species of the genus Calicivirus, an RNA virus infecting pigs. The resulting infection is an acute febrile disease which is clinically indistinguishable from foot and mouth disease. Transmission is by contaminated food. [NIH] Vestibular: Pertaining to or toward a vestibule. In dental anatomy, used to refer to the tooth surface directed toward the vestibule of the mouth. [EU] Vestibule: A small, oval, bony chamber of the labyrinth. The vestibule contains the utricle and saccule, organs which are part of the balancing apparatus of the ear. [NIH] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Vibrio: A genus of Vibrionaceae, made up of short, slightly curved, motile, gram-negative rods. Various species produce cholera and other gastrointestinal disorders as well as abortion in sheep and cattle. [NIH] Vibrio cholerae: The etiologic agent of cholera. [NIH] Vibrio Infections: Infections with bacteria of the genus Vibrio. [NIH] Vinblastine: An anticancer drug that belongs to the family of plant drugs called vinca alkaloids. It is a mitotic inhibitor. [NIH] Vincristine: An anticancer drug that belongs to the family of plant drugs called vinca alkaloids. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Virion: The infective system of a virus, composed of the viral genome, a protein core, and a protein coat called a capsid, which may be naked or enclosed in a lipoprotein envelope called the peplos. [NIH] 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] Viscera: Any of the large interior organs in any one of the three great cavities of the body, especially in the abdomen. [NIH] Visceral: , from viscus a viscus) pertaining to a viscus. [EU] Visceral Larva Migrans: Infestation of the dermis by various larvae, characterized by bizarre red irregular lines which are broad at one end and fade at the other, produced by
Dictionary 323
burrowing larvae. [NIH] Viscosity: A physical property of fluids that determines the internal resistance to shear forces. [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] Volvulus: A twisting of the stomach or large intestine. May be caused by the stomach being in the wrong position, a foreign substance, or abnormal joining of one part of the stomach or intestine to another. Volvulus can lead to blockage, perforation, peritonitis, and poor blood flow. [NIH] Vomeronasal Organ: A specialized part of the olfactory system located anteriorly in the nasal cavity within the nasal septum. Chemosensitive cells of the vomeronasal organ project via the vomeronasal nerve to the accessory olfactory bulb. The primary function of this organ appears to be in sensing pheromones which regulate reproductive and other social behaviors. While the structure has been thought absent in higher primate adults, data now suggests it may be present in adult humans. [NIH] Vulgaris: An affection of the skin, especially of the face, the back and the chest, due to chronic inflammation of the sebaceous glands and the hair follicles. [NIH] 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] Windpipe: A rigid tube, 10 cm long, extending from the cricoid cartilage to the upper border of the fifth thoracic vertebra. [NIH] Wound Healing: Restoration of integrity to traumatized tissue. [NIH] Xenograft: The cells of one species transplanted to another species. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH] 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] Yellow Fever: An acute infectious disease primarily of the tropics, caused by a virus and transmitted to man by mosquitoes of the genera Aedes and Haemagogus. [NIH] Yellow Fever Vaccine: Vaccine used to prevent yellow fever. It consists of a live attenuated 17D strain of the yellow fever virus. [NIH] Yellow Fever Virus: The type species of the Flavivirus genus. Principal vector transmission to humans is by Aedes spp. mosquitoes. [NIH] Yersinia: A genus of gram-negative, facultatively anaerobic rod- to coccobacillus-shaped
324 Cholera
bacteria that occurs in a broad spectrum of habitats. [NIH] Yersinia Infections: Infections with bacteria of the genus Yersinia. [NIH] Zoonoses: Diseases of non-human animals that may be transmitted to man or may be transmitted from man to non-human animals. [NIH] Zygote: The fertilized ovum. [NIH] Zymogen: Inactive form of an enzyme which can then be converted to the active form, usually by excision of a polypeptide, e. g. trypsinogen is the zymogen of trypsin. [NIH]
325
INDEX A Abdominal, 16, 241, 245, 246, 275, 290, 292, 299, 301, 320 Abdominal Cramps, 16, 245 Abdominal Pain, 245, 275, 290, 301, 320 Ablate, 21, 245 Ablation, 22, 245 Abscess, 128, 245 Acceptor, 245, 274, 288, 299 Acetylcholine, 21, 245, 259, 289 Acetylcysteine, 76, 111, 245 Acetylglucosamine, 183, 245 Acidosis, 183, 245 Actin, 23, 32, 108, 245, 292, 294, 314 Acute renal, 245, 279, 280 Adaptation, 167, 245 Adenine, 70, 245, 307 Adenosine, 7, 113, 147, 245, 246, 302 Adenosine Diphosphate, 7, 245, 246 Adenosine Diphosphate Ribose, 7, 246 Adenylate Cyclase, 10, 41, 53, 141, 143, 148, 166, 178, 186, 188, 246, 259, 301 Adhesions, 246, 314 Adipocytes, 246, 287 Adjustment, 245, 246 Adrenal Cortex, 246, 263, 272, 281 Adrenergic, 53, 246, 268, 271, 289, 315 Adverse Effect, 246, 312 Aerosol, 11, 31, 246, 315 Aetiology, 94, 246 Afferent, 34, 246, 287 Affinity, 11, 12, 41, 56, 169, 181, 246, 247, 312 Affinity Chromatography, 11, 246 Agar, 174, 191, 246, 264, 282 Age Groups, 109, 246 Aged, 80 and Over, 246 Agglutinins, 247, 279 Agonist, 5, 247, 256, 268, 294 Airway, 21, 29, 247 Albumin, 51, 247, 252, 298, 303 Algorithms, 247, 254 Alimentary, 206, 247, 300 Alkaline, 245, 247, 248, 255 Alkaloid, 247, 251, 256, 260, 261, 293 Alleles, 21, 46, 247 Allergen, 28, 138, 247 Allylamine, 247, 248
Alpha-Defensins, 247, 265 Alpha-helix, 247, 286 Alternative medicine, 215, 247 Aluminum, 182, 247 Aluminum Hydroxide, 182, 247 Amebiasis, 226, 247, 292 Ameliorating, 187, 248 Amine, 136, 248, 280 Amino Acid Motifs, 248, 263 Amino Acid Sequence, 33, 166, 177, 188, 248, 249, 253, 263, 276 Amino Acid Substitution, 186, 187, 248 Ammonia, 248 Amphetamine, 13, 248, 266 Amplification, 10, 83, 84, 99, 173, 174, 190, 192, 248 Amygdala, 17, 248, 288 Anaerobic, 248, 272, 309, 311, 323 Anaesthesia, 248, 283 Analgesic, 248, 267, 291, 293, 298 Analog, 18, 61, 170, 248 Analogous, 178, 248, 268, 319 Analytes, 249, 315 Anaphylatoxins, 249, 262 Anaplasia, 249 Anatomical, 13, 34, 249, 270, 288, 310 Anemia, 249, 279, 290, 317 Anesthesia, 247, 249 Animal model, 17, 26, 37, 121, 184, 186, 214, 249, 320 Anions, 204, 247, 249, 286, 311 Annealing, 175, 249, 304 Anode, 249 Anorexia, 163, 249, 275 Anterograde, 136, 249 Anthracycline, 249, 265 Anthrax, 10, 11, 18, 249 Antibacterial, 184, 249, 268, 296, 313 Anticoagulant, 250, 306 Antiemetic, 198, 250 Antigen-Antibody Complex, 250, 261 Antigen-presenting cell, 250, 265 Anti-infective, 250, 281 Anti-Infective Agents, 250, 281 Anti-inflammatory, 250, 277, 283 Antimicrobial, 31, 89, 92, 100, 108, 122, 126, 129, 133, 205, 226, 250, 265, 266 Antioxidant, 250, 299
326 Cholera
Antiporters, 126, 250 Antiserum, 250 Antispasmodics, 4, 250 Antitoxin, 75, 110, 250 Antiviral, 245, 250, 300 Anus, 250, 251, 255, 308 Anxiety, 250, 299 Aorta, 137, 250, 322 Aponeurosis, 251, 275 Apoptosis, 44, 57, 251 Aquaporins, 122, 251 Aqueous, 167, 251, 252, 264, 270, 287, 288 Arginine, 31, 249, 251, 320 Aromatic, 12, 251, 302 Arterial, 247, 251, 281, 306, 316 Arteries, 250, 251, 254, 263, 292 Arterioles, 251, 254, 256 Ascariasis, 91, 251 Aspartate, 251, 277 Assay, 31, 53, 69, 77, 84, 96, 127, 185, 190, 251, 282, 320 Astringents, 251, 291 Astrocytoma, 251, 276 Astrovirus, 205, 251 Asymptomatic, 244, 247, 251, 273, 276 Atresia, 167, 251 Atropine, 250, 251, 267 Attenuation, 44, 251 Autacoids, 251, 283 Autoantibodies, 251, 252 Autoantigens, 57, 187, 251, 252 Autoimmune disease, 43, 57, 187, 252, 294 Autologous, 26, 173, 182, 252 Autonomic, 149, 245, 252, 296, 301 Avidin, 13, 252 Axonal, 44, 252 Azithromycin, 92, 95, 212, 252 B Bacillus, 10, 12, 31, 187, 205, 249, 252, 255 Bacteraemia, 118, 252 Bacteremia, 61, 90, 118, 133, 168, 189, 252, 309 Bacteria, 9, 10, 11, 20, 25, 31, 36, 43, 52, 58, 59, 87, 90, 160, 167, 168, 172, 177, 178, 179, 180, 181, 183, 187, 189, 191, 206, 249, 250, 252, 253, 256, 258, 262, 266, 269, 270, 271, 272, 273, 274, 277, 278, 279, 284, 285, 292, 303, 306, 307, 308, 309, 310, 311, 313, 314, 319, 321, 322, 324 Bacterial Infections, 8, 43, 181, 230, 252, 258 Bacterial Physiology, 245, 252
Bacterial toxin, 5, 7, 15, 23, 26, 42, 48, 250, 252 Bactericidal, 58, 84, 127, 252, 272, 296 Bacteriolysis, 85, 129, 252 Bacteriophage, 9, 11, 38, 40, 62, 64, 86, 92, 252, 310, 319, 322 Bacteriostatic, 252, 272 Bacterium, 34, 35, 36, 40, 59, 107, 172, 180, 230, 252, 262, 279, 311, 320 Basal Ganglia, 252, 275, 276, 288 Base, 175, 183, 191, 206, 245, 252, 265, 266, 274, 276, 286, 316, 320 Base Sequence, 175, 191, 252, 274, 276 Benign, 253, 275, 279, 295, 299 Beta-Defensins, 253, 265 Beta-Endorphin, 138, 253 Beta-glucans, 253, 258 Beta-Lactamases, 122, 253 Beta-Thromboglobulin, 253, 285 Bile, 63, 86, 88, 174, 253, 275, 281, 288 Bile Acids, 253 Bile Acids and Salts, 253 Bile Ducts, 253 Biliary, 205, 253, 267 Bilirubin, 247, 253 Binding Sites, 41, 253 Biological therapy, 253, 278 Biological Transport, 253, 267 Biomass, 192, 253 Biomolecular, 254, 315 Biosynthesis, 12, 17, 47, 58, 66, 254, 311 Biotechnology, 60, 89, 161, 175, 202, 215, 225, 254 Biotin, 13, 252, 254, 297 Biotype, 68, 69, 70, 78, 79, 86, 98, 100, 104, 106, 108, 117, 118, 125, 161, 178, 254 Bivalent, 71, 72, 84, 93, 254 Bladder, 254, 294, 320, 321 Blastomycosis, 205, 254 Blood Coagulation, 254, 255, 317 Blood Glucose, 254, 279, 285 Blood Platelets, 254, 303, 311, 317 Blood pressure, 53, 254, 256, 281, 293, 301, 312 Blood transfusion, 254 Blood vessel, 254, 256, 258, 260, 270, 279, 286, 289, 291, 292, 301, 312, 315, 317, 321 Blot, 40, 44, 192, 254, 282, 297 Blotting, Western, 254, 282 Body Fluids, 254, 269, 274, 312 Body Mass Index, 254, 299
Index 327
Bone Marrow, 72, 254, 282, 289, 293, 313, 315 Border Disease, 163, 185, 255, 301 Border Disease Virus, 163, 185, 255, 301 Bowel, 16, 147, 167, 183, 241, 245, 255, 267, 271, 284, 285, 287, 301, 311, 314, 320 Bowel Movement, 255, 267, 314 Branch, 239, 255, 264, 289, 300, 306, 313, 317 Breakdown, 255, 267, 275 Broad-spectrum, 11, 85, 255, 258 Bronchi, 255, 271, 319 Bronchial, 255, 280 Bronchiectasis, 55, 255 Bronchiseptica, 255, 301 Bronchitis, 55, 255 Buccal, 255, 289 Buffers, 66, 255 Burns, 165, 255 Burns, Electric, 255 C Calcium, 5, 21, 44, 53, 138, 143, 255, 261, 310, 312 Calcium Signaling, 44, 255 Calicivirus, 205, 255, 322 Calmodulin, 21, 255 Campylobacter, 12, 77, 167, 205, 209, 226, 256, 279 Campylobacter Infections, 226, 256 Candidosis, 205, 256 Capillary, 52, 256, 277, 322 Capsaicin, 137, 256 Capsid, 11, 185, 193, 256, 297, 322 Capsular, 46, 58, 73, 85, 88, 95, 189, 256 Carbachol, 5, 256 Carbohydrate, 68, 119, 131, 174, 179, 256, 274, 277, 304, 311 Carbon Dioxide, 256, 265, 277, 302 Carcinogen, 256, 292 Carcinogenesis, 143, 256 Carcinogenic, 256, 284, 305, 320 Carcinoma, 133, 164, 256 Cardiac, 53, 247, 256, 271, 294 Cardiovascular, 53, 248, 256, 267, 311 Cardiovascular disease, 53, 256 Carrier State, 247, 256 Case report, 95, 118, 256, 260, 273 Case series, 256, 260 Castor Oil, 257, 309 Catalytic Domain, 23, 38, 49, 257 Cathode, 249, 257, 270 Cations, 169, 257, 286
Caudal, 257, 267, 282, 304 Causal, 194, 257, 262, 310, 316 Caveolae, 25, 51, 102, 103, 257 Caveolins, 257, 260 Cell Death, 251, 257, 295 Cell Differentiation, 257, 312 Cell Division, 252, 257, 264, 278, 291, 292, 303, 305, 310 Cell membrane, 48, 178, 180, 253, 257, 266, 275, 286, 291, 302, 314 Cell Membrane Structures, 257 Cell Physiology, 5, 257 Cell Polarity, 25, 257 Cell proliferation, 41, 47, 182, 257, 312 Cell Size, 257, 273 Cell Survival, 257, 278 Cellobiose, 258 Cellular Structures, 258, 293 Cellulase, 194, 258 Cellulose, 194, 258, 274, 303 Central Nervous System, 245, 248, 258, 259, 260, 266, 274, 275, 276, 277, 279, 289, 293, 294, 311 Central Nervous System Infections, 258, 279 Cephalosporins, 253, 258 Ceramide, 32, 258 Cerebellar, 44, 258 Cerebellum, 258 Cerebral, 76, 252, 258, 263, 271, 276, 290, 300, 316, 317 Cerebral hemispheres, 252, 258, 276 Cerebrovascular, 256, 258 Cerebrum, 258 Cervical, 7, 17, 27, 258 Cervix, 27, 258 Character, 189, 258, 265 Chemokines, 4, 36, 258 Chemotactic Factors, 258, 262 Chemotaxis, 10, 46, 52, 259 Chemotherapy, 13, 100, 108, 122, 126, 129, 133, 259 Chimeras, 10, 79, 259 Chimeric Proteins, 172, 259 Chlorine, 50, 58, 259 Chlorophyll, 259, 270, 274 Chloroplasts, 192, 259 Cholecystokinin, 34, 259 Cholesterol, 13, 32, 130, 253, 257, 259, 263, 288, 291 Cholinergic, 256, 259 Chromaffin System, 259, 270
328 Cholera
Chromatin, 18, 251, 259, 296 Chromosomal, 38, 178, 248, 259, 303, 310 Chromosome, 18, 38, 40, 43, 175, 183, 259, 262, 278, 288, 310 Chronic, 31, 53, 55, 163, 167, 189, 204, 247, 254, 259, 261, 284, 286, 287, 312, 315, 320, 323 Chronic Disease, 189, 259, 261 Circadian, 21, 33, 259, 260 Circadian Rhythm, 33, 260 Circulatory system, 260, 270 Clathrin, 13, 260, 270 Clear cell carcinoma, 260, 266 Clinical Medicine, 260, 305 Clinical study, 35, 54, 55, 260 Clinical trial, 4, 6, 8, 31, 32, 192, 225, 260, 263, 307 Clone, 7, 70, 77, 80, 121, 125, 175, 260 Cloning, 12, 66, 94, 185, 254, 260 Clostridium, 67, 68, 170, 181, 205, 260, 306, 317 Clostridium difficile, 67, 170, 181, 260, 306 Coated Vesicles, 260, 270 Coca, 143, 260 Cocaine, 13, 260 Coccidioidomycosis, 205, 260 Codon, 192, 261, 276, 308 Cofactor, 261, 306, 317 Colchicine, 33, 261, 320 Colicins, 11, 261 Coliphages, 252, 261 Colitis, 74, 170, 261 Collagen, 53, 261, 273, 281, 305 Collagen disease, 261, 281 Colloidal, 247, 261, 270, 292, 311, 315 Combinatorial, 41, 42, 261 Communis, 257, 261, 309 Complement, 18, 85, 129, 189, 249, 261, 262, 276, 290, 303 Complementary and alternative medicine, 141, 154, 262 Complementary medicine, 141, 262 Complementation, 58, 262 Computational Biology, 225, 262 Confounder, 24, 262 Confusion, 262, 320 Congestive heart failure, 53, 262 Conjugated, 87, 189, 253, 262 Conjugation, 33, 128, 189, 262 Conjunctiva, 262, 284 Conjunctivitis, 137, 262
Connective Tissue, 255, 261, 262, 263, 273, 275, 289, 291 Connexins, 163, 263, 275 Consciousness, 248, 263, 268 Consensus Sequence, 71, 248, 263 Conserved Sequence, 248, 263 Constriction, 263, 286, 310 Consumption, 61, 90, 194, 263, 266, 275 Contamination, 23, 122, 230, 263, 309 Contraindications, ii, 263 Control group, 35, 263 Convalescence, 101, 263 Convulsions, 263, 317 Coordination, 258, 263, 294 Coronary, 256, 263, 292 Coronary heart disease, 256, 263 Coronary Thrombosis, 263, 292 Cortex, 263 Cortical, 20, 32, 263, 272, 280, 310 Cortisol, 247, 263 Cowpox, 264, 321 Cowpox Virus, 264, 321 Cranial, 258, 264, 272, 279, 299, 301 Craniocerebral Trauma, 264, 279, 318 Cribriform, 264, 297 Crossing-over, 264, 308 Crowding, 52, 264 Cryptococcosis, 205, 264 Cryptosporidiosis, 252, 264 Crystallization, 12, 51, 264 Culture Media, 246, 264 Cultured cells, 51, 264 Curative, 13, 264, 317 Cutaneous, 165, 249, 254, 264, 286, 287, 289, 310, 314, 321, 322 Cyclic, 20, 65, 68, 72, 147, 246, 256, 264, 271, 310 Cysteine, 11, 31, 245, 258, 264, 265, 277 Cystine, 264 Cytogenetics, 264, 310 Cytokine, 4, 28, 38, 56, 65, 69, 97, 98, 186, 264, 285 Cytoplasm, 19, 22, 23, 176, 251, 255, 257, 259, 264, 265, 269, 278, 293, 296, 309, 310 Cytoplasmic Vesicles, 264, 302 Cytoskeletal Proteins, 260, 265 Cytoskeleton, 25, 32, 265 Cytotoxic, 6, 26, 32, 75, 81, 256, 265, 312 Cytotoxicity, 23, 247, 265, 287 Cytotoxins, 31, 193, 265 D Databases, Bibliographic, 225, 265
Index 329
Daunorubicin, 13, 265, 268 Day Care, 226, 265 De novo, 42, 265 Decarboxylation, 265, 277, 280 Defense Mechanisms, 189, 265 Defensins, 4, 247, 253, 265 Degenerative, 265, 280 Dehydration, 55, 166, 171, 180, 183, 188, 259, 265, 311 Deletion, 161, 171, 251, 265 Denaturation, 265, 304 Dendrites, 265, 296, 297 Dendritic, 6, 21, 26, 29, 37, 65, 75, 99, 113, 187, 265, 291 Dendritic cell, 6, 26, 29, 37, 99, 113, 187, 265 Density, 14, 17, 173, 254, 265, 273, 288, 297 Dental Caries, 7, 35, 49, 266 Dentifrices, 247, 266 Deoxyribonucleic, 175, 266 Deoxyribonucleic acid, 175, 266 Deoxyribonucleotides, 266 Depolarization, 266, 312 Deprivation, 205, 266 Dermatosis, 266, 273 DES, 249, 266 Detergents, 193, 266 Developed Countries, 3, 16, 55, 192, 266 Developing Countries, 3, 22, 55, 61, 165, 266, 289 Dextroamphetamine, 248, 266 Diabetes Mellitus, 266, 279 Diagnostic procedure, 159, 215, 266 Diagnostic Services, 266, 316 Diarrhoea, 91, 114, 118, 133, 165, 166, 178, 188, 197, 198, 201, 267, 275 Diastolic, 267, 282 Dicyclomine, 250, 267 Diencephalon, 267, 282, 317 Dietary Fats, 267, 288 Diffusion, 184, 199, 253, 267, 282, 286 Digestion, 247, 253, 255, 267, 285, 288, 299, 300, 314, 321 Digestive system, 198, 226, 267, 275 Digestive tract, 206, 267, 312, 314 Dihydrotestosterone, 267, 308 Dihydroxy, 267, 271 Dilatation, 255, 267, 305 Dilution, 147, 267 Dimethyl, 267, 289 Diphenoxylate, 198, 205, 267 Diphtheria, 21, 33, 45, 88, 176, 250, 267
Diphtheria Toxin, 21, 88, 176, 267 Diploid, 262, 267, 303 Direct, iii, 27, 32, 39, 58, 67, 68, 69, 87, 171, 178, 180, 190, 191, 217, 257, 260, 267, 268, 276, 300, 301, 308, 316 Discrimination, 45, 267 Disinfectant, 267, 272 Disinfection, 103, 128, 213, 268 Dislocation, 32, 268 Disposition, 40, 268 Dissection, 19, 268 Dissociation, 28, 246, 268 Dissociative Disorders, 268 Distal, 252, 268, 306 Diuretic, 268, 290, 313 Domesticated, 268, 278 Dopamine, 248, 260, 266, 268, 293, 302 Dorsal, 17, 268, 304 Dorsum, 268, 275 Doxorubicin, 40, 268 Drive, ii, vi, 135, 164, 204, 205, 268, 286 Drug Design, 15, 268 Drug Interactions, 218, 268 Drug Resistance, 18, 269 Drug Tolerance, 269, 318 Dry Eye Syndrome, 55, 269 Duct, 269, 272, 309 Duodenum, 253, 269, 286, 314 Dura mater, 269, 291, 299 Dysentery, 3, 10, 94, 122, 197, 201, 209, 247, 269, 311 E Echinococcosis, 205, 269 Edema, 18, 269 Effector, 36, 39, 41, 51, 128, 162, 245, 261, 269, 287, 296 Effector cell, 269, 287, 296 Egg Yolk, 119, 269 Elastin, 261, 269 Elective, 84, 269 Electrolysis, 249, 257, 269 Electrolyte, 144, 178, 206, 269, 274, 304, 308, 312 Electron microscope, 34, 269 Electrons, 250, 252, 257, 269, 286, 299, 307, 315 Electrophoresis, 46, 69, 78, 82, 97, 101, 104, 116, 123, 270, 282 Embryo, 257, 269, 270, 283 Emulsions, 246, 270 Enamel, 266, 270, 286 Encapsulated, 14, 270, 288
330 Cholera
Encephalitis, 270 Encephalomyelitis, 87, 116, 270 Endemic, 16, 30, 45, 50, 52, 66, 70, 73, 92, 100, 105, 108, 116, 125, 129, 166, 168, 188, 207, 244, 259, 270, 290 Endocrine Glands, 270 Endocrine System, 48, 270, 296 Endocytosis, 13, 18, 22, 32, 51, 130, 257, 270 Endosomes, 8, 15, 270 Endothelial cell, 51, 270, 285, 317 Endotoxic, 270, 288 Endotoxin, 72, 270, 320 Energetic, 42, 270 Energy balance, 270, 287 Enkephalin, 253, 270 Enteric bacteria, 181, 270, 271 Enteric Nervous System, 206, 271 Enteritis, 130, 271 Enterobactin, 57, 74, 271 Enterocolitis, 31, 260, 271 Enteropeptidase, 271, 320 Enterotoxins, 22, 56, 67, 169, 178, 186, 191, 206, 271 Environmental Exposure, 271, 297 Environmental Health, 224, 226, 271 Enzymatic, 32, 45, 170, 255, 257, 262, 266, 271, 280, 304 Epidemiological, 58, 99, 101, 115, 131, 271, 273 Epidermal, 143, 173, 182, 193, 271, 286, 291 Epidermal Growth Factor, 173, 182, 193, 271 Epidermis, 271, 286, 305 Epidermoid carcinoma, 182, 271, 314 Epigastric, 271, 299 Epinephrine, 246, 268, 271, 296, 320 Epithelial Cells, 4, 5, 12, 17, 21, 25, 57, 63, 88, 102, 133, 162, 164, 253, 259, 271, 280 Epithelium, 178, 189, 271 Epitope, 14, 27, 52, 63, 75, 164, 177, 272 Erythrocytes, 31, 96, 249, 255, 272, 308 Erythromycin, 95, 252, 272 Esophagus, 251, 267, 272, 275, 302, 314 Estradiol, 17, 272 Ethanol, 136, 272, 273 Ethmoid, 272, 297, 299 Ethnic Groups, 205, 272 Eukaryotic Cells, 169, 265, 272, 283, 298 Excitation, 272, 273 Excitatory, 20, 272, 277 Exhaustion, 272, 290
Exocrine, 259, 272, 299 Exogenous, 20, 57, 72, 272, 276, 306 Exotoxin, 13, 75, 170, 272 Extracellular, 33, 36, 58, 71, 75, 79, 138, 142, 156, 191, 262, 263, 270, 272, 273, 312 Extracellular Matrix, 262, 263, 272, 273 Extraction, 174, 272 F Faecal, 91, 96, 101, 267, 273 Family Planning, 225, 273 Fat, 193, 246, 253, 254, 258, 263, 273, 287, 288, 294, 299, 312, 315 Fatal Outcome, 273, 307 Fatigue, 273, 279 Fatty acids, 247, 273, 277, 305 Feces, 3, 206, 251, 273, 314 Fermentation, 193, 273, 310 Ferrets, 17, 273 Fetus, 273, 302, 305, 321 Fibroblasts, 164, 173, 273, 285 Fibrosis, 6, 21, 55, 205, 206, 247, 273, 310 Filariasis, 190, 205, 273 Filtration, 61, 126, 212, 273 Flagellin, 176, 273 Flatus, 273, 275 Fleas, 205, 273 Flow Cytometry, 48, 56, 273 Fluid Therapy, 119, 205, 274 Fluorescence, 25, 48, 55, 273, 274, 292 Fluorescent Dyes, 273, 274 Flush, 115, 274 Fold, 9, 41, 192, 193, 274, 291 Food Microbiology, 137, 274 Forearm, 254, 274, 307 Fractionation, 32, 149, 274 Frameshift, 274, 320 Frameshift Mutation, 274, 320 Fucose, 12, 274 Fucosyltransferases, 12, 274 Fungi, 12, 160, 179, 258, 262, 274, 285, 292, 313, 323 Fungus, 167, 258, 260, 264, 274 G GABA, 33, 274, 277, 312 Galanin, 17, 274 Gallbladder, 245, 253, 259, 267, 275 Gamma-Glutamyltransferase, 138, 275 Ganglia, 245, 271, 275, 295, 301 Ganglion, 137, 275 Ganglioside, 13, 32, 44, 48, 61, 62, 68, 79, 89, 103, 130, 137, 147, 169, 180, 192, 275 Gangrenous, 275, 311
Index 331
Gap Junctions, 263, 275, 316 Gas, 174, 248, 256, 259, 267, 273, 275, 281, 290, 296, 311, 315 Gastric, 35, 41, 56, 247, 253, 271, 275, 279, 280, 281, 300 Gastrin, 19, 34, 275, 280 Gastritis, 70, 275, 279 Gastroenteritis, 11, 104, 167, 191, 194, 206, 209, 230, 251, 275, 309 Gastroenterology, 106, 109, 117, 145, 204, 275 Gastrointestinal tract, 40, 65, 162, 189, 205, 272, 275, 311, 313 Gavage, 274, 275 Gene Expression, 14, 18, 20, 34, 43, 50, 58, 69, 70, 82, 88, 124, 126, 156, 177, 213, 275 Gene Fusion, 58, 178, 275 Gene Targeting, 20, 276 Genetic Code, 276, 297 Genetic Engineering, 191, 254, 260, 276 Genetic testing, 276, 304 Genetics, 11, 22, 30, 45, 56, 71, 178, 262, 264, 276, 293 Genital, 27, 63, 84, 260, 276, 321 Genitourinary, 162, 189, 276, 321 Genitourinary system, 162, 276 Genotype, 254, 276, 302 Germ Cells, 276, 291, 299, 313, 316 Germfree, 68, 80, 276 Giardia, 110, 226, 276 Giardia lamblia, 226, 276 Giardiasis, 197, 276, 292 Gland, 5, 57, 246, 259, 276, 289, 290, 299, 310, 314, 315, 317, 318 Glioblastoma, 182, 276 Glioblastoma multiforme, 182, 276 Glomerular, 276, 290, 309 Glomerular Filtration Rate, 276, 290 Glomeruli, 277, 297 Glottis, 277, 301 Glucocorticoid, 277, 281 Glucose, 97, 106, 145, 169, 254, 258, 266, 277, 279, 284, 313 Glutamate, 44, 57, 277 Glutamate Decarboxylase, 57, 277 Glutamic Acid, 277, 305 Glycerol, 251, 277, 302 Glycerophospholipids, 277, 302 Glycine, 253, 277, 311 Glycoprotein, 13, 33, 40, 177, 274, 277, 294, 316, 317, 320 Glycosidic, 12, 14, 258, 277, 295, 297
Goats, 277, 298 Gonorrhea, 9, 25, 277 Gout, 261, 277 Governing Board, 277, 304 Gp120, 277, 300 Grade, 276, 277 Graft, 278, 280, 283 Graft Rejection, 278, 283 Gram-negative, 9, 23, 38, 40, 59, 166, 188, 255, 270, 272, 278, 279, 309, 311, 322, 323 Gram-positive, 260, 278, 314 Gram-Positive Bacteria, 260, 278 Granule, 44, 278, 309 Granulocytes, 278, 312, 323 Granuloma, 205, 278, 289 Granuloma Inguinale, 205, 278, 289 Granulosa Cells, 151, 278 Growth, 6, 13, 23, 36, 47, 56, 58, 66, 138, 163, 167, 175, 182, 192, 193, 249, 250, 251, 252, 254, 255, 257, 264, 266, 271, 278, 279, 290, 295, 297, 298, 303, 304, 310, 313, 317, 318, 320, 321, 322 Growth factors, 47, 182, 193, 278 Guinea Pigs, 120, 278 Gyrase, 174, 278, 296 H Habitual, 258, 278 Hair follicles, 278, 323 Haploid, 278, 303 Haplotypes, 26, 278 Haptens, 246, 278 Headache, 16, 279, 284 Headache Disorders, 279 Health Services, 198, 279, 316 Health Status, 198, 279 Heart attack, 256, 279 Heart failure, 53, 279 Helicobacter, 70, 77, 78, 107, 120, 226, 279 Helicobacter pylori, 70, 77, 107, 120, 226, 279 Hemagglutinins, 181, 279 Heme, 57, 253, 279 Hemodynamics, 53, 279 Hemoglobin, 190, 249, 272, 279, 287, 317 Hemolytic, 181, 191, 226, 279, 317 Hemolytic-Uremic Syndrome, 226, 279 Hemorrhage, 264, 279, 280, 309, 315 Hemostasis, 280, 311 Hepatic, 247, 280 Hepatitis, 6, 107, 177, 193, 198, 206, 226, 280 Hepatocytes, 280
332 Cholera
Hereditary, 277, 280, 317 Heredity, 275, 276, 280 Herpes, 8, 280 Herpes Zoster, 280 Heterogeneity, 12, 25, 32, 107, 246, 280 Heterotrophic, 274, 280 Histamine, 20, 41, 249, 280, 289 Histidine, 280 Hog Cholera, 156, 163, 185, 200, 280, 301 Hog Cholera Virus, 163, 185, 280, 301 Homologous, 51, 58, 247, 254, 263, 264, 276, 280, 294, 310, 316 Hormonal, 53, 280 Host-Parasite Relations, 187, 280 Humoral, 60, 146, 278, 280 Humour, 280, 281 Hybrid, 15, 56, 73, 85, 108, 119, 164, 165, 176, 178, 179, 186, 187, 260, 281, 297 Hybridization, 14, 191, 281, 293, 297 Hybridomas, 27, 281 Hydrochloric Acid, 281, 300 Hydrocortisone, 173, 281 Hydrogen, 245, 248, 252, 255, 256, 265, 281, 288, 293, 297, 299, 301 Hydrolysis, 253, 258, 281, 286, 295, 300, 302, 304, 306, 320 Hydrophilic, 165, 266, 281 Hydrophobic, 266, 277, 281, 288 Hydroxylysine, 261, 281 Hydroxyproline, 261, 281 Hydroxyquinolines, 198, 281 Hygienic, 170, 281 Hyperaemia, 262, 281 Hyperglycemia, 57, 281 Hyperplasia, 48, 143, 243, 281 Hypersensitivity, 247, 281 Hypertension, 28, 53, 256, 279, 281, 318 Hypertrophy, 53, 281, 282 Hypothalamic, 13, 17, 20, 33, 282 Hypothalamus, 17, 20, 267, 270, 282, 288, 305, 313, 315, 317 I Id, 139, 152, 231, 238, 240, 282 Ileal, 5, 31, 75, 109, 282 Ileostomy, 74, 282, 295 Ileum, 5, 282, 286 Imaging procedures, 282, 319 Imidazole, 254, 280, 282 Immune function, 188, 282 Immune Sera, 282 Immunoassay, 185, 282 Immunoblotting, 41, 282
Immunodeficiency, 76, 107, 208, 282 Immunodeficiency syndrome, 208, 282 Immunodiffusion, 246, 282 Immunoelectrophoresis, 246, 282 Immunofluorescence, 14, 283 Immunogen, 8, 172, 283 Immunogenic, 4, 6, 164, 165, 166, 171, 172, 175, 177, 179, 188, 189, 191, 194, 283, 288 Immunoglobulin, 29, 80, 92, 172, 249, 283, 293 Immunohistochemistry, 29, 283 Immunologic, 29, 37, 49, 74, 167, 171, 259, 282, 283 Immunosuppressive, 31, 137, 277, 283 Immunosuppressive therapy, 283 Immunotherapy, 13, 28, 182, 253, 283 Immunotoxin, 33, 283 In situ, 14, 20, 283 In Situ Hybridization, 14, 20, 85, 283 In vitro, 7, 8, 10, 12, 13, 19, 23, 27, 31, 32, 38, 108, 129, 160, 179, 283, 304, 318 In vivo, 12, 13, 21, 23, 27, 31, 40, 44, 47, 57, 108, 131, 160, 179, 283 Incision, 283, 285 Incisional, 165, 283 Incubated, 52, 283 Incubation, 164, 283, 301 Incubation period, 283, 301 Indicative, 199, 283, 300, 321 Indomethacin, 169, 170, 283 Induction, 4, 6, 21, 26, 27, 29, 38, 40, 49, 56, 65, 75, 109, 110, 129, 162, 164, 173, 183, 283 Infancy, 284 Infant, Newborn, 246, 284 Infantile, 194, 284 Infarction, 253, 263, 284, 292 Infection Control, 118, 226, 230, 284 Infectious Diarrhea, 15, 31, 205, 284 Infertility, 163, 284 Infestation, 269, 284, 322 Inflammatory bowel disease, 167, 284 Influenza, 39, 90, 183, 200, 208, 284 Ingestion, 59, 166, 188, 249, 251, 274, 284, 303 Inhalation, 246, 260, 284, 303, 314 Initiation, 11, 18, 35, 36, 284, 314 Innervation, 14, 284 Inorganic, 284, 294 Insight, 20, 42, 53, 284 Insulator, 284, 294
Index 333
Insulin, 21, 57, 60, 95, 119, 173, 192, 284, 285, 305 Insulin-dependent diabetes mellitus, 285 Interferons, 192, 285 Interleukin-2, 73, 108, 285 Interleukin-4, 80, 285 Interleukin-8, 69, 97, 285 Intermediate Filaments, 285, 314 Intermittent, 269, 274, 285 Internal Medicine, 6, 41, 275, 285 Interstitial, 36, 285, 309 Intestinal Flora, 16, 285 Intestine, 5, 16, 23, 59, 97, 106, 122, 137, 138, 145, 149, 150, 151, 167, 174, 183, 206, 230, 253, 255, 269, 271, 272, 276, 280, 282, 285, 286, 287, 312, 314, 320, 323 Intoxication, 10, 33, 42, 94, 178, 285 Intracellular Membranes, 265, 285, 291 Intramuscular, 285, 300 Intravenous, 244, 285, 300 Intrinsic, 33, 45, 246, 251, 285 Invasive, 109, 177, 183, 188, 205, 282, 285 Invertebrates, 168, 285 Ion Channels, 6, 285, 296 Ion Exchange, 258, 286, 312 Ion Transport, 206, 286 Ions, 5, 184, 252, 255, 268, 269, 281, 286, 292, 293, 310 Irritants, 269, 286 Ischemia, 275, 286 Isotonic, 173, 286, 292 J Jejunum, 144, 286 K Kb, 185, 224, 286 Keratin, 163, 164, 286 Keratinocytes, 173, 285, 286 Keratolytic, 266, 286 Kidney Disease, 55, 224, 286 Kidney Failure, 286, 290 Killer Cells, 287 Kinetic, 45, 48, 287 L Laceration, 287, 317 Large Intestine, 267, 285, 287, 308, 312, 323 Larva, 205, 287 Larva Migrans, 205, 287 Latent, 15, 287 Laxative, 246, 287, 313 Lectin, 287, 291 Leishmaniasis, 205, 287 Lens, 251, 256, 287
Leptin, 13, 166, 167, 287 Lesion, 137, 254, 278, 287, 288, 311, 320 Lethal, 5, 21, 23, 52, 68, 252, 261, 267, 287, 309 Leucine, 253, 287 Leukemia, 127, 268, 287 Leukocytes, 255, 258, 259, 278, 283, 287, 293, 296, 320 Library Services, 238, 287 Lice, 205, 287 Life cycle, 50, 274, 287, 288 Ligands, 13, 41, 42, 169, 181, 288, 315 Limbic, 248, 288 Limbic System, 248, 288 Linkage, 169, 258, 288 Lipase, 64, 194, 288 Lipid, 13, 25, 32, 35, 38, 49, 257, 270, 277, 285, 288, 294, 299 Lipid A, 25, 288 Lipid Peroxidation, 288, 299 Lipopolysaccharide, 64, 66, 72, 76, 82, 96, 112, 123, 261, 278, 288 Lipoprotein, 278, 288, 318, 322 Liposomal, 35, 288 Liposome, 21, 35, 288 Liquor, 288, 307 Liver, 113, 205, 245, 247, 253, 254, 267, 269, 273, 275, 280, 288 Localization, 34, 80, 147, 283, 288 Localized, 19, 51, 266, 267, 270, 284, 288, 303, 317, 320 Locomotion, 288, 303 Loop, 14, 31, 62, 282, 289 Loperamide, 198, 205, 289 Lumen, 19, 186, 289 Lupus, 187, 261, 289 Luxation, 268, 289 Lymph, 7, 56, 57, 258, 260, 270, 281, 289, 315 Lymph node, 7, 56, 57, 258, 289 Lymphatic, 284, 289, 291, 313, 317 Lymphatic system, 289, 313, 317 Lymphocyte, 4, 30, 57, 75, 250, 287, 289, 291 Lymphocytosis, 289, 301 Lymphogranuloma Venereum, 278, 289 Lymphoid, 7, 56, 57, 75, 80, 156, 249, 289 Lymphoma, 136, 289 Lysine, 38, 281, 289, 320 Lysosome, 289, 302 Lytic, 31, 252, 289, 311, 322
334 Cholera
M Macrophage, 285, 289 Major Histocompatibility Complex, 278, 285, 289 Malabsorption, 290, 311 Malabsorption syndrome, 290, 311 Malaise, 16, 242, 290 Malaria, 99, 107, 137, 177, 198, 200, 205, 226, 290 Malaria, Falciparum, 290 Malaria, Vivax, 290 Malignancy, 274, 290 Malignant, 182, 276, 285, 290, 295 Malignant tumor, 182, 290 Malnutrition, 30, 247, 290 Mammary, 162, 290 Manifest, 252, 290 Mannans, 274, 290 Mannitol, 144, 290 Mastitis, 290, 311 Meat, 267, 290, 319 Medial, 17, 272, 290, 298 Mediate, 27, 33, 46, 58, 169, 250, 268, 287, 290 Mediator, 13, 259, 285, 290, 303, 311 MEDLINE, 225, 291 Meiosis, 254, 291, 294, 316 Melanin, 291, 302, 320 Melanocytes, 291 Melanoma, 147, 291 Membrane Microdomains, 25, 32, 102, 291 Membrane Proteins, 32, 33, 51, 73, 86, 108, 182, 257, 291 Memory, 7, 37, 49, 57, 173, 249, 291 Meninges, 258, 264, 269, 291 Meningitis, 172, 189, 291 Mental Health, iv, 4, 224, 227, 291, 306 Mental Processes, 268, 291, 306 Meperidine, 267, 291 Mercury, 183, 273, 291 Mesenchymal, 271, 291 Mesenteric, 57, 291 Mesentery, 291, 292, 301 Metabolite, 267, 292 Metaphase, 254, 292 Metastasis, 292 Methionine, 253, 267, 292 Metronidazole, 170, 292 MI, 145, 163, 244, 292 Micelles, 190, 292 Microbe, 292, 318 Microfilaments, 285, 292, 314
Microorganism, 166, 167, 170, 171, 180, 188, 261, 292, 300, 323 Micro-organism, 266, 276, 279, 292, 310 Microscopy, 9, 14, 32, 34, 40, 51, 52, 56, 73, 107, 292 Microscopy, Confocal, 51, 292 Microspheres, 53, 182, 292 Mitochondria, 292, 298 Mitochondrial Swelling, 292, 295 Mitosis, 251, 292 Mobilization, 255, 293 Modeling, 14, 268, 293 Modification, 7, 45, 113, 192, 276, 293 Molecular Probes, 172, 293 Molecular Structure, 41, 293 Molecule, 10, 12, 19, 31, 43, 65, 78, 163, 164, 175, 176, 177, 180, 181, 192, 246, 250, 252, 253, 261, 268, 269, 272, 274, 277, 281, 287, 293, 297, 299, 303, 308, 312, 321 Monitor, 293, 296 Monoamine, 248, 266, 293 Monoclonal, 27, 32, 62, 63, 68, 71, 87, 128, 185, 193, 281, 282, 293, 307 Monoclonal antibodies, 32, 128, 193, 282, 293 Monocytes, 10, 136, 285, 287, 293 Mononuclear, 278, 293, 320 Monophosphate, 147, 293 Morphine, 138, 267, 291, 293, 295, 298 Morphological, 20, 58, 270, 274, 291, 293 Morphology, 47, 50, 293 Motility, 9, 52, 62, 63, 79, 121, 276, 283, 293, 311 Mucinous, 275, 293 Mucins, 293, 309 Mucociliary, 293, 312 Mucocutaneous, 287, 294 Mucolytic, 245, 294 Mucosa, 27, 132, 142, 259, 271, 276, 289, 294, 295, 315 Mucus, 172, 242, 269, 293, 294, 320 Multiple sclerosis, 187, 294 Multivalent, 35, 48, 294 Muscle Contraction, 294, 310 Muscle Fibers, 149, 294 Mutagenesis, 41, 58, 63, 166, 178, 188, 294 Mutagens, 274, 294 Myalgia, 284, 294 Myelin, 87, 294 Myiasis, 205, 294 Myocarditis, 267, 294
Index 335
Myocardium, 292, 294 Myosin, 294, 314 N Naive, 37, 97, 294 Naloxone, 253, 294 Narcolepsy, 21, 266, 294 Narcotic, 291, 293, 294 Nasal Cavity, 295, 299, 323 Nasal Mucosa, 75, 171, 284, 295 Nasopharynx, 172, 295 Natural killer cells, 31, 295 Nausea, 242, 250, 275, 295, 320 Necrosis, 163, 251, 273, 276, 280, 284, 292, 295 Necrotizing Enterocolitis, 167, 295 Neomycin, 198, 295 Neonatal, 55, 116, 295 Neoplasm, 295, 299, 320 Neoplastic, 249, 281, 289, 295, 316 Nephron, 97, 138, 295 Nephropathy, 286, 295 Nervous System, 17, 149, 246, 248, 258, 277, 290, 295, 296, 301, 307, 315, 321 Networks, 54, 295 Neural, 22, 246, 280, 295 Neural Pathways, 22, 295 Neuraminidase, 93, 295 Neuroblastoma, 13, 44, 295 Neuroendocrine, 296, 316 Neurologic, 276, 296 Neuromuscular, 245, 296 Neuromuscular Junction, 245, 296 Neuronal, 44, 296 Neurons, 13, 17, 20, 33, 44, 137, 260, 265, 272, 275, 296, 316 Neuropeptide, 13, 21, 296 Neurosecretory Systems, 270, 296 Neurotoxic, 281, 296, 317 Neurotoxin, 35, 176, 296 Neurotransmitters, 27, 293, 296 Neutralization, 181, 296 Neutrophils, 247, 278, 285, 287, 296 Nitrogen, 247, 248, 296, 320 Norepinephrine, 246, 268, 296 Norfloxacin, 118, 120, 296 Nosocomial, 9, 118, 296 Nuclear, 44, 192, 193, 252, 262, 270, 272, 275, 276, 288, 295, 296 Nuclei, 20, 248, 262, 270, 276, 288, 292, 297 Nucleic acid, 7, 46, 163, 252, 256, 276, 281, 283, 294, 296, 297, 307 Nucleic Acid Hybridization, 281, 297
Nucleic Acid Probes, 46, 297 Nucleocapsid, 297, 318 Nucleus, 13, 33, 44, 251, 259, 264, 272, 285, 291, 293, 296, 297, 305, 314 O Odour, 251, 297 Olfactory Bulb, 17, 297, 323 Oligo, 42, 297 Oligonucleotide Probes, 180, 297 Oligopeptides, 41, 297 Oligosaccharides, 12, 14, 32, 295, 297 Oliguria, 242, 287, 290, 297 Oncogene, 47, 297 Opacity, 265, 297 Open Reading Frames, 59, 297 Operon, 36, 64, 69, 83, 298, 309 Opium, 293, 298 Optic Chiasm, 282, 298, 305, 315 Oral Health, 205, 298 Orderly, 204, 298 Orf, 59, 298 Organ Culture, 298, 318 Organelles, 9, 260, 264, 265, 291, 293, 298, 303 Osmolality, 204, 298 Osmolarity, 204, 290, 298 Osmoles, 298 Osmosis, 298 Osmotic, 204, 247, 292, 298, 311 Otitis, 168, 189, 298 Otitis Media, 168, 189, 298 Outpatient, 66, 298 Ovalbumin, 4, 13, 28, 298 Ovarian Follicle, 278, 298 Ovary, 82, 84, 272, 298, 299 Overexpress, 25, 299 Overweight, 53, 139, 299 Ovulation, 278, 299 Ovum, 288, 298, 299, 324 Oxidation, 245, 250, 264, 288, 299 Oxidative Stress, 50, 299 P Pachymeningitis, 291, 299 Paediatric, 198, 299 Palate, 295, 299 Palliative, 299, 317 Pancreas, 57, 205, 245, 254, 267, 275, 284, 288, 299, 305, 313, 320 Pancreatic, 128, 145, 259, 299, 301 Pancreatic cancer, 128, 299 Pancreatic enzymes, 145, 299 Panic, 149, 299
336 Cholera
Papilloma, 8, 299 Paranasal Sinuses, 299, 312 Parasite, 187, 299, 319 Parasitic, 190, 205, 226, 264, 269, 273, 276, 279, 284, 287, 299, 300 Parasitic Diseases, 190, 226, 300 Parenteral, 167, 170, 179, 187, 300 Parenteral Nutrition, 167, 300 Parietal, 19, 41, 300, 301 Parietal Cells, 20, 41, 300 Parietal Lobe, 300 Paroxysmal, 279, 300, 301, 323 Particle, 11, 288, 300, 319 Patch, 27, 54, 300 Pathogen, 10, 14, 15, 17, 19, 23, 30, 31, 35, 38, 50, 56, 57, 98, 107, 171, 185, 189, 279, 283, 300 Pathologic, 245, 251, 256, 263, 281, 300 Pathologic Processes, 251, 300 Pathophysiology, 12, 28, 138, 204, 205, 206, 300 Patient Education, 230, 236, 238, 244, 300 Penicillin, 208, 300 Peptic, 279, 300 Peptic Ulcer, 279, 300 Peptide Elongation Factors, 300, 311 Peptide Fragments, 171, 300 Peptide T, 20, 178, 300 Perforation, 300, 323 Periodontal disease, 38, 301 Peripheral Nervous System, 301, 313, 315 Peripheral Vascular Disease, 165, 301 Periplasm, 178, 301 Peritoneal, 205, 301 Peritoneum, 292, 301 Peritonitis, 301, 323 Pertussis, 27, 45, 59, 61, 78, 113, 138, 176, 183, 301, 323 Pertussis Toxins, 45, 301 Pestivirus, 163, 185, 255, 280, 301 PH, 55, 94, 102, 121, 301 Phagocytosis, 10, 189, 285, 302 Phagosomes, 15, 302 Pharmaceutical Preparations, 258, 272, 302 Pharmacokinetic, 40, 302 Pharmacologic, 28, 249, 251, 302, 318 Pharynx, 284, 295, 302 Phenotype, 52, 262, 302 Phenylalanine, 302, 320 Phospholipases, 302, 312 Phospholipids, 25, 273, 288, 302
Phosphorus, 255, 302 Phosphorylated, 7, 302 Phosphorylation, 47, 51, 121, 136, 142, 302 Phylogeny, 46, 81, 302 Physiologic, 7, 20, 52, 58, 247, 254, 286, 302, 308 Physiology, 5, 6, 19, 39, 43, 46, 53, 113, 117, 137, 138, 162, 206, 275, 302 Phytotoxin, 302, 309 Pigment, 253, 259, 291, 302 Placenta, 272, 302 Plague, 11, 18, 43, 138, 144, 200, 201, 207, 302 Plant Diseases, 270, 303 Plant Proteins, 32, 303, 321 Plasma cells, 162, 249, 303 Plasma protein, 247, 303, 311 Plasmid, 18, 21, 29, 36, 40, 63, 65, 68, 81, 122, 142, 164, 172, 175, 177, 303, 321 Plastids, 192, 298, 303 Platelet Activation, 303, 312 Platelet Factor 4, 285, 303 Platinum, 289, 303 Pleated, 286, 303 Pneumococcal Infections, 171, 303 Pneumonitis, 251, 303 Poisoning, 121, 152, 174, 191, 205, 230, 275, 285, 291, 295, 303, 309, 311 Polymerase, 126, 148, 174, 177, 185, 303, 304, 309 Polymerase Chain Reaction, 148, 174, 185, 304 Polymers, 167, 183, 304, 306 Polymorphic, 82, 174, 304 Polymorphism, 72, 80, 82, 104, 105, 111, 115, 121, 304 Polysaccharide, 14, 46, 58, 73, 79, 81, 82, 85, 88, 95, 123, 182, 189, 250, 258, 304 Polyvalent, 204, 304 Population Dynamics, 45, 88, 304 Posterior, 258, 268, 299, 304 Postnatal, 304, 314 Postoperative, 174, 291, 304 Postsynaptic, 304, 312, 316 Post-translational, 9, 23, 304 Potassium, 204, 250, 304 Potentiates, 5, 304 Potentiating, 44, 304 Potentiation, 304, 312 Practice Guidelines, 227, 304 Preclinical, 8, 123, 305
Index 337
Precursor, 77, 114, 164, 268, 269, 271, 296, 302, 305, 320 Prenatal, 17, 270, 305 Preoptic Area, 17, 305 Presynaptic, 34, 305, 316 Prevalence, 28, 46, 123, 203, 305 Prickle, 286, 305 Probe, 10, 48, 297, 305 Progeny, 262, 305 Prognostic factor, 109, 305 Progression, 48, 181, 249, 305, 320 Progressive, 257, 269, 278, 295, 303, 305, 308, 320 Proinsulin, 57, 305, 307 Projection, 17, 34, 265, 296, 297, 305 Proline, 261, 281, 305 Promoter, 44, 51, 61, 69, 72, 77, 79, 82, 177, 178, 305 Prophase, 254, 294, 305, 316 Prophylaxis, 99, 137, 179, 226, 305, 321 Proportional, 298, 305, 315 Prostaglandins, 283, 305 Prostaglandins A, 283, 305 Protease, 37, 38, 63, 64, 69, 71, 81, 88, 96, 106, 133, 151, 165, 193, 306 Protein Binding, 9, 306 Protein Conformation, 248, 286, 306 Protein Subunits, 28, 306 Proteins, 6, 8, 11, 13, 19, 20, 22, 25, 27, 28, 33, 34, 41, 43, 45, 49, 50, 51, 52, 56, 57, 59, 60, 69, 73, 75, 107, 144, 151, 163, 165, 166, 171, 176, 178, 183, 185, 187, 188, 189, 192, 193, 248, 250, 251, 254, 255, 257, 259, 260, 261, 263, 269, 272, 275, 281, 282, 285, 286, 291, 293, 296, 299, 300, 301, 303, 304, 306, 307, 308, 310, 311, 317, 319, 321 Proteolytic, 32, 261, 271, 306, 309 Protozoa, 10, 167, 262, 269, 276, 287, 292, 306, 313 Proximal, 138, 268, 295, 305, 306 Pruritic, 306, 310 Pseudomembranous Colitis, 170, 306 Psychology, 268, 306 Psychosexual, 17, 306 Psychotomimetic, 248, 266, 306 Public Health, 3, 4, 9, 14, 28, 54, 92, 96, 107, 117, 120, 122, 125, 151, 155, 194, 198, 199, 202, 209, 227, 306 Public Policy, 225, 306 Publishing, 60, 231, 306
Pulmonary, 36, 51, 254, 259, 263, 287, 307, 315, 321 Pulmonary Artery, 254, 307, 321 Pulmonary Edema, 259, 287, 307 Pulse, 21, 242, 293, 307 Purified Insulins, 305, 307 Purifying, 51, 169, 266, 307 Purines, 252, 307, 311 Purulent, 245, 307 Pyogenic, 165, 272, 307, 310 Pyridoxal, 277, 307 R Rabies, 192, 205, 307 Radiation, 271, 274, 292, 307, 323 Radiation therapy, 274, 307 Radioactive, 281, 293, 296, 307, 320 Radioisotope, 297, 307, 319 Radius, 45, 307 Randomized, 24, 82, 83, 124, 269, 307 Reactive Oxygen Species, 10, 307 Reading Frames, 24, 308 Reagent, 259, 281, 308 Receptors, Serotonin, 308, 311 Recombinant Proteins, 192, 193, 308 Recombination, 38, 125, 262, 276, 308 Reconstitution, 33, 308 Rectal, 27, 77, 112, 131, 308 Rectum, 27, 250, 255, 267, 273, 275, 284, 287, 308 Recurrence, 260, 308 Red blood cells, 190, 272, 279, 308 Reductase, 142, 308 Refer, 1, 255, 261, 274, 280, 288, 294, 296, 308, 322 Refraction, 308, 313 Regeneration, 308 Regimen, 49, 60, 269, 308 Regulon, 59, 69, 77, 130, 308 Rehydration, 3, 91, 94, 99, 102, 142, 145, 151, 308 Rehydration Solutions, 145, 308 Relapse, 170, 308 Renal failure, 55, 308 Repressor, 61, 86, 298, 309 Resection, 167, 309, 311 Respiratory Mucosa, 189, 309 Response rate, 93, 309 Restoration, 156, 308, 309, 323 Retina, 287, 298, 309 Retrograde, 17, 18, 19, 32, 130, 136, 143, 309 Reversion, 179, 211, 309, 320
338 Cholera
Rhinitis, 255, 309, 311 Ribose, 7, 45, 245, 246, 309 Ribosome, 309, 319 Ricin, 18, 32, 48, 75, 130, 176, 309 Rigidity, 303, 309 Riots, 102, 309 Risk factor, 108, 148, 198, 309 Rod, 71, 100, 146, 252, 272, 309, 311, 323 Rotavirus, 3, 39, 84, 123, 127, 177, 194, 205, 309 Rural Population, 24, 309 S Saline, 126, 309 Saliva, 4, 7, 49, 80, 172, 185, 309 Salivary, 4, 7, 35, 49, 57, 81, 84, 162, 172, 267, 299, 309, 315 Salivary glands, 4, 7, 267, 309 Salmonella, 3, 10, 31, 65, 78, 80, 83, 84, 112, 128, 167, 172, 181, 275, 309, 310 Salmonella typhi, 10, 31, 65, 78, 83, 84, 112, 167, 172, 310 Salmonellosis, 205, 226, 310 Sanitation, 10, 168, 251, 310 Sarcoplasmic Reticulum, 53, 310 Satellite, 61, 310 Scabies, 205, 310 Scleroproteins, 286, 310 Sclerosis, 261, 294, 310 Screening, 12, 42, 83, 86, 130, 260, 310 Sebaceous, 286, 310, 323 Second Messenger Systems, 296, 310 Sedentary, 53, 310 Segregation, 308, 310 Seizures, 242, 276, 300, 310 Sensor, 48, 310 Sepsis, 118, 168, 172, 310 Septicaemia, 310, 311 Septicemia, 117, 311 Sequence Analysis, 46, 62, 71, 91, 311 Sequence Homology, 300, 311 Sequencing, 46, 66, 185, 279, 304, 311 Serine, 78, 80, 271, 311, 320 Seroconversion, 128, 149, 311 Serologic, 63, 74, 282, 311 Serotonin, 21, 34, 308, 311, 320 Serotypes, 36, 127, 161, 181, 251, 311 Serum Albumin, 192, 193, 311 Sexually Transmitted Diseases, 208, 311 Shedding, 52, 311 Shiga Toxin, 18, 19, 311 Shigella, 10, 79, 167, 197, 205, 311 Shigellosis, 33, 109, 132, 206, 226, 311
Shock, 33, 168, 183, 281, 311, 319 Short Bowel Syndrome, 167, 311 Side effect, 179, 188, 217, 246, 253, 311, 318 Signal Transduction, 5, 6, 13, 22, 25, 28, 30, 103, 130, 257, 312 Signs and Symptoms, 308, 312 Single Parent, 175, 312 Sinusitis, 172, 189, 312 Skeletal, 310, 312, 313 Skeleton, 245, 312 Skull, 264, 312, 316 Smallpox, 10, 144, 156, 201, 312, 321 Smooth muscle, 247, 249, 251, 280, 293, 312, 313, 315 Sneezing, 301, 311, 312 Sodium, 44, 70, 106, 126, 144, 149, 204, 250, 277, 312 Sodium-Calcium Exchanger, 44, 312 Soft tissue, 168, 254, 312 Solid tumor, 268, 313 Solvent, 272, 277, 298, 313 Soma, 313 Somatic, 111, 138, 149, 150, 280, 288, 291, 292, 301, 313 Somatostatin, 20, 313 Sorbitol, 290, 313 Spasm, 313 Spasmodic, 201, 245, 301, 313 Specialist, 232, 313 Specificity, 41, 48, 63, 68, 69, 88, 246, 313 Spectrum, 31, 81, 122, 165, 296, 313, 324 Sperm, 259, 313, 320 Spinal cord, 251, 258, 259, 269, 270, 271, 275, 291, 295, 299, 301, 313 Spinous, 271, 286, 313 Spirochete, 313, 316 Spleen, 57, 289, 313 Spores, 260, 313 Sporotrichosis, 205, 313 Squamous, 271, 314 Squamous cell carcinoma, 271, 314 Steady state, 52, 314 Stem Cells, 20, 314 Sterility, 284, 314 Steroids, 188, 277, 314 Stimulant, 248, 266, 280, 314 Stimulus, 268, 269, 272, 284, 285, 314, 317 Stomach, 19, 201, 245, 267, 272, 275, 280, 295, 300, 302, 312, 313, 314, 323 Stool, 52, 61, 71, 83, 87, 175, 243, 287, 314, 316 Strand, 110, 147, 163, 185, 303, 314
Index 339
Streptococci, 49, 314 Streptococcus, 7, 35, 49, 56, 73, 74, 80, 85, 123, 171, 172, 177, 189, 303, 314 Streptomycin, 61, 198, 314 Stress, 23, 264, 275, 295, 299, 314 Stress Fibers, 23, 314 Striatum, 20, 314 Stroke, 44, 224, 256, 314 Stromal, 164, 315 Subacute, 284, 289, 312, 315 Subarachnoid, 279, 315 Subclinical, 284, 310, 315 Subcutaneous, 246, 269, 275, 300, 314, 315 Submaxillary, 271, 315 Submucous, 205, 315 Subspecies, 313, 315, 321, 323 Substance P, 67, 272, 292, 308, 310, 314, 315 Substrate, 15, 22, 31, 38, 45, 48, 250, 257, 295, 315 Suction, 273, 315 Supplementation, 110, 128, 147, 149, 315 Suppression, 10, 31, 57, 73, 108, 315 Suprachiasmatic Nucleus, 33, 315 Surface Plasmon Resonance, 48, 315 Surfactant, 193, 315 Suspensions, 164, 315 Sympathomimetic, 248, 266, 268, 271, 296, 315 Symptomatic, 172, 316 Synapses, 296, 297, 316 Synapsis, 18, 316 Synaptic, 19, 312, 316 Synaptophysin, 34, 316 Synergistic, 184, 316 Syphilis, 54, 208, 316 Systemic disease, 39, 311, 316 Systolic, 53, 282, 316 T Tachycardia, 53, 242, 252, 316 Tachypnea, 252, 316 Telecommunications, 316 Telemedicine, 132, 316 Temporal, 18, 248, 279, 316 Temporal Lobe, 248, 316 Tenesmus, 269, 316 Terminator, 261, 316 Testis, 148, 272, 316 Testosterone, 308, 316 Tetani, 68, 316, 317 Tetanic, 317
Tetanus, 48, 54, 61, 82, 176, 182, 250, 316, 317 Tetanus Toxin, 61, 176, 317 Tetracycline, 99, 129, 153, 317 Thalassemia, 117, 317 Therapeutics, 18, 22, 26, 29, 53, 150, 192, 218, 317 Thermal, 268, 304, 317 Third Ventricle, 282, 317 Threonine, 300, 311, 317 Threshold, 281, 317 Thrombin, 303, 306, 317 Thrombocytopenia, 279, 317 Thrombomodulin, 306, 317 Thrombosis, 253, 306, 315, 317 Thylakoids, 259, 317 Thymus, 189, 282, 289, 317 Thyroid, 13, 47, 317, 318, 320 Thyroid Gland, 318 Thyroid Hormones, 318, 320 Thyrotropin, 47, 318 Thyroxine, 247, 302, 318 Tinnitus, 298, 318 Tissue Culture, 55, 170, 318 Titre, 119, 318 Togaviridae, 163, 318 Tolerance, 12, 29, 57, 65, 86, 129, 187, 318 Tonicity, 286, 318 Tooth Preparation, 245, 318 Topical, 31, 35, 251, 272, 281, 318 Torovirus, 205, 318 Toxicity, 6, 8, 22, 26, 89, 179, 268, 291, 318 Toxicology, 226, 318 Toxoid, 60, 82, 110, 138, 147, 171, 182, 250, 319 Toxoplasmosis, 205, 252, 319 Tracer, 17, 143, 151, 319 Trachea, 255, 302, 317, 318, 319 Transcutaneous, 54, 319 Transduction, 5, 6, 25, 47, 48, 62, 255, 312, 319 Transfection, 21, 29, 40, 164, 254, 319 Transfer Factor, 282, 319 Transfusion, 319 Translation, 177, 272, 295, 308, 319 Translational, 319 Translocation, 19, 33, 42, 176, 178, 272, 319 Transmitter, 245, 268, 286, 290, 296, 316, 319 Transplantation, 282, 289, 319 Transposase, 18, 319 Transposons, 18, 319
340 Cholera
Trauma, 295, 319 Trees, 303, 319 Trichinosis, 205, 319 Trichomoniasis, 292, 319 Trichuriasis, 205, 319 Trypsin, 164, 271, 320 Tryptophan, 261, 311, 320 Tuberculosis, 11, 15, 31, 36, 39, 107, 200, 205, 263, 289, 320 Tubulin, 29, 320 Tumor model, 40, 320 Tumor Necrosis Factor, 136, 320 Tumorigenic, 47, 320 Tumour, 275, 320 TYPHI, 10, 95, 320 Typhimurium, 320 Typhoid fever, 10, 84, 205, 206, 310, 320 Tyrosine, 51, 268, 320 U Ulcer, 168, 300, 320 Ulceration, 298, 320 Ulcerative colitis, 31, 167, 284, 320 Unconscious, 265, 282, 320 Uremia, 287, 308, 320 Urethra, 320, 321 Urinary, 267, 276, 296, 297, 320, 321 Urine, 109, 185, 242, 254, 268, 271, 276, 296, 297, 320, 321 Urogenital, 56, 63, 276, 277, 321 Uterus, 258, 321 V Vaccination, 6, 26, 29, 30, 35, 39, 42, 49, 63, 65, 70, 73, 74, 76, 83, 108, 120, 124, 179, 187, 321 Vaccinia, 57, 321 Vaccinia Virus, 57, 321 Vacuoles, 270, 298, 321 Vagina, 27, 76, 258, 266, 321 Vaginal, 17, 63, 321 Variola, 321 Vascular, 51, 132, 247, 279, 284, 299, 302, 318, 321 Vasoactive, 34, 151, 321 Vasodilator, 268, 280, 321 Vector, 6, 21, 35, 57, 68, 73, 74, 80, 163, 177, 300, 319, 321, 323 Vegetable Proteins, 303, 321 Vegetative, 253, 321 Vein, 285, 296, 310, 321 Venereal, 316, 321, 323 Venoms, 265, 321
Venous, 253, 306, 321 Ventral, 21, 282, 321 Ventricle, 248, 307, 316, 317, 321 Venules, 254, 256, 322 Vertigo, 298, 322 Vesicular, 8, 22, 25, 255, 278, 280, 312, 321, 322 Vesicular Exanthema of Swine, 255, 322 Vesicular Exanthema of Swine Virus, 255, 322 Vestibular, 147, 322 Vestibule, 322 Veterinary Medicine, 225, 322 Vibrio Infections, 226, 322 Vinblastine, 320, 322 Vincristine, 320, 322 Virion, 185, 297, 322 Virulent, 8, 16, 23, 59, 172, 185, 322 Viscera, 287, 292, 313, 322 Visceral, 287, 288, 301, 322 Visceral Larva Migrans, 287, 322 Viscosity, 245, 323 Vitro, 8, 23, 27, 31, 74, 82, 83, 138, 323 Vivo, 21, 47, 74, 80, 83, 97, 119, 323 Volvulus, 167, 323 Vomeronasal Organ, 297, 323 Vulgaris, 153, 323 W White blood cell, 249, 283, 287, 289, 294, 295, 303, 323 Whole cell vaccine, 59, 162, 323 Whooping Cough, 301, 323 Windpipe, 302, 317, 323 Wound Healing, 165, 173, 323 X Xenograft, 249, 320, 323 X-ray, 9, 12, 15, 42, 243, 257, 274, 296, 307, 323 Y Yaws, 205, 323 Yeasts, 256, 274, 285, 302, 323 Yellow Fever, 156, 203, 208, 218, 323 Yellow Fever Vaccine, 203, 218, 323 Yellow Fever Virus, 323 Yersinia, 10, 12, 43, 70, 167, 205, 226, 302, 323, 324 Yersinia Infections, 226, 324 Z Zoonoses, 307, 324 Zygote, 262, 324 Zymogen, 306, 324
Index 341
342 Cholera
Index 343
344 Cholera
