BACTERIAL INFECTIONS A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R EFERENCES
J AMES N. P ARKER , M.D. AND P HILIP M. P ARKER , P H .D., E DITORS
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ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright ©2004 by ICON Group International, Inc. Copyright ©2004 by ICON Group International, Inc. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without written permission from the publisher. Printed in the United States of America. Last digit indicates print number: 10 9 8 7 6 4 5 3 2 1
Publisher, Health Care: Philip Parker, Ph.D. Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher's note: The ideas, procedures, and suggestions contained in this book are not intended for the diagnosis or treatment of a health problem. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960Bacterial Infections: 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: 0-597-84344-9 1. Bacterial Infections-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 bacterial infections. 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 BACTERIAL INFECTIONS ........................................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Bacterial Infections........................................................................ 4 E-Journals: PubMed Central ....................................................................................................... 43 The National Library of Medicine: PubMed ................................................................................ 44 CHAPTER 2. NUTRITION AND BACTERIAL INFECTIONS ................................................................. 89 Overview...................................................................................................................................... 89 Finding Nutrition Studies on Bacterial Infections ...................................................................... 89 Federal Resources on Nutrition ................................................................................................... 90 Additional Web Resources ........................................................................................................... 91 CHAPTER 3. ALTERNATIVE MEDICINE AND BACTERIAL INFECTIONS ........................................... 93 Overview...................................................................................................................................... 93 National Center for Complementary and Alternative Medicine.................................................. 93 Additional Web Resources ........................................................................................................... 95 General References ....................................................................................................................... 99 CHAPTER 4. DISSERTATIONS ON BACTERIAL INFECTIONS ........................................................... 101 Overview.................................................................................................................................... 101 Dissertations on Bacterial Infections ......................................................................................... 101 Keeping Current ........................................................................................................................ 101 CHAPTER 5. CLINICAL TRIALS AND BACTERIAL INFECTIONS ...................................................... 103 Overview.................................................................................................................................... 103 Recent Trials on Bacterial Infections ......................................................................................... 103 Keeping Current on Clinical Trials ........................................................................................... 108 CHAPTER 6. PATENTS ON BACTERIAL INFECTIONS ...................................................................... 111 Overview.................................................................................................................................... 111 Patents on Bacterial Infections................................................................................................... 111 Patent Applications on Bacterial Infections............................................................................... 136 Keeping Current ........................................................................................................................ 165 CHAPTER 7. BOOKS ON BACTERIAL INFECTIONS.......................................................................... 167 Overview.................................................................................................................................... 167 Book Summaries: Federal Agencies............................................................................................ 167 Book Summaries: Online Booksellers......................................................................................... 174 Chapters on Bacterial Infections ................................................................................................ 177 CHAPTER 8. MULTIMEDIA ON BACTERIAL INFECTIONS ............................................................... 179 Overview.................................................................................................................................... 179 Video Recordings ....................................................................................................................... 179 Audio Recordings....................................................................................................................... 180 CHAPTER 9. PERIODICALS AND NEWS ON BACTERIAL INFECTIONS ............................................ 181 Overview.................................................................................................................................... 181 News Services and Press Releases.............................................................................................. 181 Newsletters on Bacterial Infections............................................................................................ 183 Newsletter Articles .................................................................................................................... 184 Academic Periodicals covering Bacterial Infections................................................................... 186 CHAPTER 10. RESEARCHING MEDICATIONS................................................................................. 189 Overview.................................................................................................................................... 189 U.S. Pharmacopeia..................................................................................................................... 189 Commercial Databases ............................................................................................................... 192 Researching Orphan Drugs ....................................................................................................... 193 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 197
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Overview.................................................................................................................................... 197 NIH Guidelines.......................................................................................................................... 197 NIH Databases........................................................................................................................... 199 Other Commercial Databases..................................................................................................... 201 APPENDIX B. PATIENT RESOURCES ............................................................................................... 203 Overview.................................................................................................................................... 203 Patient Guideline Sources.......................................................................................................... 203 Finding Associations.................................................................................................................. 210 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 213 Overview.................................................................................................................................... 213 Preparation................................................................................................................................. 213 Finding a Local Medical Library................................................................................................ 213 Medical Libraries in the U.S. and Canada ................................................................................. 213 ONLINE GLOSSARIES................................................................................................................ 219 Online Dictionary Directories ................................................................................................... 219 BACTERIAL INFECTIONS DICTIONARY ............................................................................. 221 INDEX .............................................................................................................................................. 305
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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 bacterial infections 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 bacterial infections, 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 bacterial infections, 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 bacterial infections. 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 bacterial infections, 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 bacterial infections. 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 BACTERIAL INFECTIONS Overview In this chapter, we will show you how to locate peer-reviewed references and studies on bacterial infections.
The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and bacterial infections, 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 “bacterial infections” (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: •
Bacterial Infections of the Small Intestine and Colon Source: Current Opinion in Gastroenterology. 15(1): 43-52. January 1999. Contact: Available from Lippincott Williams and Wilkins Publishers. 12107 Insurance Way, Hagerstown, MD 21740. (800) 637-3030. Fax (301) 824-7390. Summary: This article reviews research on bacterial infections of the small and large intestine. The author notes that enterotoxigenic Escherichia coli, Vibrio cholerae O1, Campylobacter jejuni, Salmonella species, and Shigella species are major causes of morbidity and death in diarrheal disease. Children are most severely affected, and the prevalence is higher in subtropical and tropical countries than in temperate ones. Infections are spread almost exclusively via the fecal oral route (e.g., by water, food, and
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vegetables tainted by water containing manure and small children putting contaminated fingers or items in their mouths). Infections of the small intestine are mediated mainly by bacteria attaching to the epithelium and are aggravated by production of toxins. They generally induce a severe loss of fluid and rarely invade the intestinal wall. Bacteria causing infections of the colon often invade the epithelium. Bacterial species traversing the intestinal epithelium, such as Salmonella and Campylobacter species, commonly cause systemic disease and can be localized to either the small or large intestine. More recently recognized pathogens are V. cholerae O139 and enterohemorrhagic E. coli. In addition to this, several presumptive virulence factors have been identified in diarrheagenic E. coli and in other species. The author concludes that, to confirm these as virulence factors, physicians need good diagnostic tools and good epidemiologic studies, which are of vital importance in creating vaccines for diarrheal diseases. 2 tables. 72 references (43 annotated).
Federally Funded Research on Bacterial Infections The U.S. Government supports a variety of research studies relating to bacterial infections. 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 bacterial infections. 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 bacterial infections. The following is typical of the type of information found when searching the CRISP database for bacterial infections: •
Project Title: ACTIN BASED MOTILITY OF A BACTERIAL PATHOGEN Principal Investigator & Institution: Theriot, Julie A.; Assistant Professor; Biochemistry; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2002; Project Start 01-DEC-1994; Project End 28-FEB-2005 Summary: Listeria rnonocytogenes is a ubiquitous Gram-positive bacterium that can cause serious food-borne infections in pregnant women, newborns and immunocompromised adults. The bacterium grows directly in the cytoplasm of infected host cells and moves rapidly throughout and between infected cells using a form of actin-based motility. An L. rnonocytogenes protein, ActA, induces polymerization of host cell actin to form a "comet tail" structure that pushes the bacterium through the host cell cytoplasm. The overall goal of this proposal is to understand the mechanism of the actin-based motility of L. monocytogenes. Three complementary approaches will be used to study this problem: biochemical, biophysical, and cell biological. A major goal is the establishment of a simplified biochemical system that can support L. monocytogenes
2 Healthcare projects are funded by the National Institutes of Health (NIH), Substance Abuse and Mental Health Services (SAMHSA), Health Resources and Services Administration (HRSA), Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDCP), Agency for Healthcare Research and Quality (AHRQ), and Office of Assistant Secretary of Health (OASH).
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motility, and development of quantitative assays so that the precise role of each component in actin-based motility can be assessed. The amount of force generated by moving bacteria will be measured directly using a laser force trap (optical tweezers) and compliant microneedles. The mechanism of coupling between actin filament polymerization and production of a motile force will be examined. Finally, videomicroscopy techniques will be used to observe the process of bacterial spread from one host cell to another, and a combination of genetic and pharmacological perturbations will be used to define the contributions of the bacterium, the host cell, and the actin-rich comet tail associated with the moving bacterium, to the process of intercellular spread. Successful completion of our research goals would give significant insight into the mechanisms by which pathogenic bacteria such as L. monocytogenes communicate specifically with the cells of their human hosts. This understanding might pave the way for the development of new ways to prevent and cure bacterial infections. In addition, the results of our research would contribute to our understanding of a wide variety of basic biological process involving actin-based cell movement, including wound healing, immune system responses, and embryonic development. Furthermore, since most malignant tumors do not become lethal until the cancer cells move away from the tumor site and invade other tissues, a detailed understanding of the basic mechanisms that regulate actin-based motility may also be important in the development of therapeutic strategies for combating metastatic cancers. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ASM CONFERENCE ON POLYMICROBIAL DISEASES Principal Investigator & Institution: Brogden, Kim A.; American Society for Microbiology 1752 N St Nw Washington, Dc 20036 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2004 Summary: (provided by applicant): Animals and humans can become infected with more than one pathogen and the resulting clinical diseases and lesions are far greater than that capable from each pathogen alone. These are called polymicrobial diseases and originate from multiple viral infections, multiple bacterial infections, viral and bacterial infections, multiple mycotic infections, and opportunistic infections secondary to microbe-induced immunosuppression. Polymicrobial Diseases is the topic of an American Society for Microbiology sponsored conference October 2003, at the Hotel and Conference Center in Lake Tahoe, Nevada, USA. The purpose of the conference is a) to bring together a diverse group of investigators like physicians, dentists, veterinarians, molecular biologists, and researchers with backgrounds in virology, bacteriology, parasitology, and mycology, b) to discuss the complex etiology and pathogenesis of polymicrobial diseases, and c) to foster interdisciplinary research, possibly leading to productive collaborations. The format is typical of ASM sponsored conferences. Throughout the sessions and discussion periods, we have the following aims for the conference. Aim 1. To increase our understanding of the etiologic agents of polymicrobial disease. In this conference, we will identify and discuss the complex interactions among etiologic agents and the methods to study polymicrobial interactions in vitro and in vivo, which may lead to more effective diagnostic strategies. Aim 2. To increase our understanding of the determinants of polymicrobial pathogenicity and the underlying mechanisms of polymicrobial disease pathogenesis. In this conference we will identify and discuss the determinants that increase the virulence of two or more microorganisms or strains of microorganisms and delineate the common underlying mechanisms of polymicrobial disease pathogenesis. This includes identifying both host and microbial factors that increase the susceptibility of the host to multiple infections.
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Aim 3. To increase our understanding of immune or probiotic intervention of polymicrobial infections. In this conference, we will identify and discuss methods to prevent polymicrobial infections, which may lead to more effective prevention and treatment strategies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: AUTOIMMUNE DETERMINANTS OF HUMAN CARDIAC MYOSIN Principal Investigator & Institution: Cunningham, Madeline W.; George Lynn Cross Research Professor; Microbiology and Immunology; University of Oklahoma Hlth Sciences Ctr Health Sciences Center Oklahoma City, Ok 73126 Timing: Fiscal Year 2002; Project Start 01-AUG-1997; Project End 30-JUN-2007 Summary: (provided by applicant): Myocarditis and rheumatic carditis are sequelae of viral and bacterial infections, respectively, and occur in humans and animal models following coxsackievirus infection, group A streptococcal infection, or immunization with cardiac myosin. The pathogenesis of these diseases may be due to molecular mimicry between the infectious pathogen and the host autoantigen cardiac myosin. Although cardiac myosin can induce myocarditis in animals, the molecular pathogenesis of the disease in humans is unclear. In addition, there are few studies in humans, which define the immunological parameters of disease. The goal of the proposed work is to define the parameters of the autoimmune response to human cardiac myosin in humans and in a cardiac myosin-induced rat model of myocarditis and valvulitis. We will test the hypothesis that molecular mimicry and the influence of the cytokine environment leads to development of disease. We plan: 1)To produce and investigate human T cell clones from myocarditis patients which are crossreactive with human cardiac myosin, streptococcal M protein and coxsackievirus and their peptides; to determine cytokine responses of human T cell clones as well as HLA class I and II restriction of responses and cell surface antigens by FACS analysis 2)To evaluate expression of genes by crossreactive CD4+/- and CD8+ T cell clones and by normal and myocarditis patient peripheral blood CD4+ and CD8+ lymphocytes in response to stimulation with myosin, M protein and coxsackievirus or their peptides by DNA array analysis, cytokine production, and to study the cell surface markers on T lymphocytes by FACS analysis 3) To investigate a Lewis rat cardiac S2 peptide-induced model of severe myocarditis for parameters of inflammatory heart disease including the role of molecular mimicry and cytokines in susceptible, resistant, and tolerized rat strains (Lewis and BB/DR), to determine the epitope specificity of the heart specific infiltrating T cells from hearts in the Lewis rat model and to determine cytokine expression in hearts using the RNase protection assay for TH1/TH2 cytokines and expression of a large group of genes using DNA arrays. We will establish a tolerance model to investigate the downregulation of myosin specific I cells, antibodies and cytokines in disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: BACTERIAL INFECTION INDUCES CYTOKINE PRODUCTION Principal Investigator & Institution: Marriott, Ian; Biology; University of North Carolina Charlotte Office of Research Services Charlotte, Nc 282230001 Timing: Fiscal Year 2002; Project Start 12-APR-2001; Project End 31-JAN-2004 Summary: Staphylococcus aureus and Salmonella are common causes of bone and joint infections in humans. Unfortunately, the pathogenesis of bacterial bone and joint infections are poorly understood. Bacteria, including S. aureus, can infect osteoblasts
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and survive intracellularly within these bone-forming cells which begins to explain how bone infections might be chronic, and how the host's immune response might have difficulty in eliminating these pathogens. While osteoblasts can internalize and harbor bacteria, it is not at all clear if infected osteoblasts contribute to the immune responses to the invasion. Recently, we have described the surprising ability of osteoblasts to secrete significant amounts of bioactive IL-12. These cells are stimulated to produce this key pro- inflammatory cytokine when exposed to bacteria previously demonstrated to reside intracellularly. Such a finding is particularly significant given the central role IL-12 plays in the preferential initiation of Th1-type, cell- mediated, immune responses. Such immune responses are essential for the successful elimination of intracellular pathogens. The ability of these non-leukocytic cells to produce this IL-12 may point to a previously unrecognized role for osteoblasts in the generation of protective inflammatory responses and the resolution of infection. In the present application, we propose to investigate the mechanisms responsible for inducing the production of this important cytokine by osteoblasts. We will utilize RT-PCR and immunofluorescent techniques to determine whether IL-12 induction in human and mouse osteoblasts occurs as either a direct or indirect consequence of bacterial invasion. Furthermore, we will determine whether the production of IL-12 seen in vitro is reproducible in vivo using an animal model developed in our laboratory. Finally we will attempt to determine the biological significance of IL-12 production by osteoblasts in infected tissues in vivo by monitoring bacterial burden and T-cell infiltration utilization immunofluorescence techniques. In this manner, we will examine whether IL-12 attenuates or exacerbates bacterial infection of osteoblasts and local inflammation, thereby expanding the recognized role of these cells to include being integral components in the host responses to intracellular pathogens at these sites. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BACTERIAL ANTIMICROBIALS
RNASE
P
AS
A
TARGET
FOR
NOVEL
Principal Investigator & Institution: Eder, Paul S.; Message Pharmaceuticals, Inc. 30 Spring Mill Dr Malvern, Pa 19355 Timing: Fiscal Year 2002; Project Start 15-MAR-2002; Project End 31-DEC-2002 Summary: (provided by applicant): Antibiotic resistance is a growing health threat worldwide. Small-molecule screens that target specific complexes that are essential for bacterial metabolism will be useful in identifying new classes of microbial inhibitors. Bacterial RNase P represents an excellent target for developing novel anti-infectives: it is essential for viability of bacteria; it is well-characterized enzymatically and structurally; and it differs structurally and functionally from mammalian RNase P. Message Pharmaceuticals is dedicated to developing drugs that target RNA via posttranscriptional regulation. With its high-throughput capacity, Message has screened nearly 150,000 compounds for inhibitors of Neisseria gonorrhoeae RNase P. More than fifty compounds among six classes have exhibited dose-dependent inhibition of N. gonorrhoeae RNase P in vitro. Message proposes to develop these classes of leads further by: 1) determining their minimal inhibitory concentration endpoint against known bacterial isolates; 2) measuring the inhibition of RNase P enzymes from other evolutionarily diverse pathogenic bacteria; 3) comparing the inhibition to that of human RNase P; 4) assessing cytotoxicity in mammalian cells in culture. In addition to identifying novel anti-infectives, the results will advance our understanding of the function of an evolutionarily ancient RNA enzyme, and, more importantly, reveal new classes of small molecules that interact with structured RNAs. PROPOSED
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COMMERCIAL APPLICATION: With the worldwide emergence and expansion of antibiotic resistance in both the nosocomial and community settings, new classes of antibiotics are needed to combat the resistance. The results from this grant will contribute to the development of novel classes of antibiotics for a variety of resistant bacterial infections. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BIOCHEMICAL ROLE OF AIRWAY MUCINS IN CYSTIC FIBROSIS Principal Investigator & Institution: Sachdev, Goverdhan P.; Pharmaceutical Sciences; University of Oklahoma Hlth Sciences Ctr Health Sciences Center Oklahoma City, Ok 73126 Timing: Fiscal Year 2002; Project Start 01-AUG-2001; Project End 31-JUL-2004 Summary: (provided by applicant): Cystic Fibrosis (CF) is the most lethal genetic disease in Caucasians and is characterized by production of excessive amounts of viscous mucus secretions in the airways of the patient. This causes airway obstruction as well as chronic bacterial infections which eventually lead to respiratory failure. Mucins provide protection to epithelia through interaction of their saccharides with bacterial adhesins. Chronic colonization with Pseudomonas aeruginosa, is considered the principal cause of death in CF patients. Our laboratory and others have shown that P. aeruginosa had considerably stronger binding affinity for CF airway mucin than normal airway mucin. These observations implicate altered glycosylation of CF mucins. Indeed, aberrant glycosylation has been reported for CF mucin. However, to date, the molecular basis of increased interaction between P. aeruginosa and CF airway mucin has not been established. We hypothesize that altered glycosylation of CF mucin is responsible for its stronger binding with P. aeruginosa. We will determine structural features of the CF mucin carbohydrate ligand(s) that provide increased binding to P. aeruginosa by preparing glycopeptides and individual saccharides from CF and control mucins. The glycopeptide(s) which show high inhibition of asialo-GM; binding to P. aeruginosa will be used to isolate 0-linked glycans for further testing of inhibitory activity and structural determination using state-of-the-art highly sensitive mass spectrometry and enzymnatic methods. Affinity gels containing selected mucin glycopeptide or mucin saccharide will be used to purify the P. aeruginosa adhesins which interact with airway mucins and glycolipids, respectively. The primary structure of the major adhesins will be determined using molecular cloning techniques. Structural characterization of major adhesins will open additional approaches to prevent the binding of P. aeruginosa to airway epithelial cells and mucins of CF patients. Information on the adhesin binding sites will permit molecular modeling, design and synthesis of potent 0-glycan inhibitors of the P. aeruginosa infection. The overall long-term goal of this study is to prevent and/or treat lung infections in CF patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: BIOFILM ANTIBIOTIC RESISTANCE IN STAPHYLOCOCCUS Principal Investigator & Institution: O'toole, George A.; Assistant Professor; Microbiology and Immunology; Dartmouth College 11 Rope Ferry Rd. #6210 Hanover, Nh 03755 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2005 Summary: (provided by applicant): Biofilms are complex bacterial communities attached to a surface. The most widely recognized property of biofilm bacteria is their increased resistance to antimicrobial agents. The recalcitrance of biofilm-related
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infections to conventional antibiotic therapy has a profound impact on the medical industry and human health. Although this problem has been studied in numerous different model systems, little is known about the molecular mechanisms that confer antibiotic resistance to biofilm cells. Recent work suggests that a genetic program controls biofilm formation and we have genetic evidence that indicates that the development of antibiotic resistance in biofilms is similarly regulated. Furthermore, socalled "small colony variants" or SCV have been proposed to play a role in biofilmmediated resistance in P. aeruginosa. The role of SCV in S. aureus biofilm resistance has not yet been investigated. The central hypothesis of this application is that antimicrobial resistance of biofilm-grown cells requires specific genetic elements. We propose to identify genetic elements required for the development of biofilm antibiotic resistance by Staphylococcus aureus using techniques developed in our previous studies in Pseudomonas aeruginosa. The identification of genes required for biofilm antibiotic resistance may provide new targets for anti-biofilm therapies and increase our understanding of biofilm antibiotic resistance. The Specific Aims of this application are: Specific Aim 1. Identify genetic elements required for biofilm antibiotic resistance in S. aureus. Specific Aim 2. Characterize mutants defective in biofilm antibiotic resistance. Specific Aim 3. Determine the role of small colony variants (SCV) in biofilm antibiotic resistance. The studies proposed here explore a poorly characterized aspect of microbial resistance that is elaborated when microbes grow in a biofilm. No genetic elements contributing to biofilm resistance have been identified in S. aureus. We propose a genetic screen (already validated in P. aeruginosa) with the goal of identifying genes involved in this process. Future studies will uncover the mechanisms of resistance mediated by the genes identified as a result of this work. We will also perform studies to determine whether SCV, thought to be generated in chronic bacterial infections in vivo: i) play a role in biofilm resistance and ii) utilize the same genetic pathways as biofilmgrown cells to resist the action of antibiotics. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BIOFILM FORMATION AND DISPERSAL MECHANISMS Principal Investigator & Institution: Romeo, Tony; Professor; Microbiology and Immunology; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2003; Project Start 19-SEP-2003; Project End 31-AUG-2007 Summary: (provided by applicant): In the natural environment, bacteria grow predominantly within sessile, matrix-enclosed communities known as biofilms, rather than as unattached planktonic cells. Biofilms protect resident bacteria from attack by the immune system, compromise antimicrobial therapy, and disperse planktonic cells, which promote the spread of infection to distant body sites. Biofilms complicate about 65 percent of recalcitrant bacterial infections. Nevertheless, the regulatory mechanisms of biofilm development, especially biofilm dispersal, remain poorly defined in any species. Our studies revealed that the RNA-binding global regulatory protein CsrA is a potent repressor of biofilm formation in Escherichia coli K-12 and pathogenic relatives. This effect is mediated primarily through its regulation of intracelluar glycogen synthesis and turnover. Further evidence supports a role for glycogen in the synthesis of a polysaccharide adhesin. Mutations that inhibit biofilm formation were isolated in a 4gene operon, which was cloned and found to needed for the production of a GIcN-rich polysaccharide. Remarkably, csrA-induction within cells of a preformed biofilm caused extensive dispersal, releasing viable planktonic cells. This finding offers a key to unlock the biochemical and genetic bases of biofilm dispersal. The Aims of this proposal are to: 1) Characterize a novel polysaccharide adhesin needed for E. coli biofilm formation. The
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molecular genetics of its synthesis, its chemistry, and its function in biofilm formation will be assessed. 2) Investigate the genetic and metabolic determinants of polysaccharide production. The precursor-product relationship of glycogen to the polysaccharide adhesin will be examined by ELISA analysis of existing mutants and by 13C NMR labeling studies in conjunction with appropriate structural and regulatory mutations. The genetic regulation of its biosynthesis will be examined with reporter fusions and other approaches. 3) Biofilm dispersal will be assessed systematically by examining the effects of csrA induction on the polysaccharide adhesin, membrane and periplasmic proteins, LPS and the transcriptome. Results will pave the way for studies defining the mechanisms of the dispersal process.The long-range goal of these studies is to develop a full understanding of the regulatory factors, metabolic pathways and structural elements that interact in biofilm formation, and thereby obtain useful information for combating biofilm infections. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BIOFILM FORMATION AND P. AERUGINOSA INFECTION OF THE EYE Principal Investigator & Institution: Zegans, Michael E.; Surgery; Dartmouth College 11 Rope Ferry Rd. #6210 Hanover, Nh 03755 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2007 Summary: (Applicant's Abstract) Bacterial infections of the eye can have visionthreatening complications and often are associated with prosthetic devices such as contact lenses, scleral buckles, and intraocular lenses. Pseudomonas aeruginosa (PA) is one of the most common causes of bacterial keratitis. The central hypothesis of this proposal is that biofilm formation plays an important role in the pathogenesis of ocular infections of PA and that an understanding of the biology and genetics of Pseudomonas aeruginosa biofilm formation will have relevance to the development of novel antimicrobial therapies. Bacteria grow as planktonic (or free-living) cells or as surfaceattached communities known as biofilms. Biofilm formation contributes to the pathogenesis of many clinical infections associated with prosthetic devices by allowing bacteria to persist on abiotic surfaces which come in contact with the body, by facilitating colonization of biotic surfaces and by rendering bacteria more resistant to antimicrobial agents. However, the relevance of biofilm formation to ocular infections has not been extensively studied. Bacterial keratitis caused by PA will be the model system studied in this project. Existing biofilm mutants of PA, as well as additional mutants that will be developed in the course of the project, will be used to elucidate the biology and genetics related to PA biofilm formation on abiotic and biotic surfaces relevant to the eye. The functions mutated in these strains may define novel drug targets. In addition, inhibitor studies may identify new classes of compounds that prevent and/or eliminate eye infections. The ability of growth in a biofilm to render PA resistant to the innate immune system, specifically the human B-defensin (hBD) 1 and 2 will be investigated. hBD 1 and 2 are recently described antimicrobial peptides secreted by the corneal and conjunctival epithelium. hBD 1 and 2 are active against PA under planktonic conditions, but have not been tested against organisms growing in a biofilm. If biofilm-based resistance exists, it would presumably contribute to keratitis and identification of genes that play a role in this process may be novel targets for rendering biofilm bacteria sensitive to antibiotics and defensins. If biofilm and planktonic cells are as equally sensitive to hBD-l and hBD-2, this would suggest that B-defensins can bypass biofilm-specific biocide resistance, and furthermore, these compounds (or derivatives) might make excellent therapeutics to prevent and/or treat biofilm-based infections.
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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CAVEOLAE MEDIATED BACTERIAL UPTAKE BY MAST CELLS Principal Investigator & Institution: Abraham, Soman N.; Associate Professor; Pathology; Duke University Durham, Nc 27706 Timing: Fiscal Year 2002; Project Start 01-JUL-2001; Project End 31-MAY-2006 Summary: (provided by the applicant): Recently, we discovered that the bacterial receptor for FimH-expressing bacteria was localized in plasmalemmal caveolae of mast cells and that these caveolae were actively involved in the internalization of the bacteria. Caveolae are subcellular entities rich in glycolipid; and cholesterol and typically contain the scaffolding protein, caveolin. Caveolae mediated bacterial uptake is remarkable because intracellular bacteria remain viable and encased in membranes comprising of caveolar components. Although the significance and scope of caveolae-mediated bacterial uptake by mast cells is, as yet, unknown, this observation represents a novel activity for cellular caveolae in immune cells. To extend our observations, the following specific aims are proposed: (I), Define the scope and molecular basis for caveolaemediated uptake of bacteria (II), Elucidate the ultimate fate of bacteria internalized via caveolae and (III), Investigate the molecular basis for the caveolae-mediated uptake of FimH-expressing bacteria in human mast cells. Our observations highlighting the role of cellular caveolae in the uptake of bacteria represents an important and novel activity triggered by pathogens in immune cells. The proposed studies should provide new insights into the cellular response of mast cells and possibly other immune cells to infectious agents and provide new clues for devising effective strategies to combat bacterial infections. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CONJUGATE VACCINE FOR THE PREVENTION OF TULAREMIA Principal Investigator & Institution: Tzianabos, Arthur O.; Associate Professor of Medicine; Harvard University (Medical School) Medical School Campus Boston, Ma 02115 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2008 Summary: Francisella tularensis is a highly infectious bacterium that poses a serious threat as an agent of bioterrorism. A live whole cell vaccine is currently available for atrisk populations, but it is associated with incomplete immunity and side-effects. Studies of humans and mice vaccinated with this preparation indicate that humoral and cellmediated immune responses are required for complete protection in the infected host. Currently, little is known concerning the virulence factors associated with F. tularensis that contribute to its ability to cause lethal disease. However, previous studies have identified the capsule and LPS as principle determinants of its pathogenic potential. Our analysis of the recently released genome of F. tularensis Schu S4 has shown that it possesses a single polysaccharide biosynthetic locus responsible for expression of one surface polysaccharide. Based on these data, we hypothesize that the previously described capsule and O-antigen of this organism actually represents a single Oantigen/capsule that has the same repeating unit structure, but is expressed as a distinct large molecular-weight polymer and smaller molecular-weight Lipid A-linked polysaccharide. We predict that this structure has a central role in the pathogenesis of this organism and can be used as the basis for novel glycoconjugate vaccines that will elicit complete protection against experimental tularemia. To address the structural nature of this virulence factor and its role in the pathogenesis and immunity to F.
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tularensis, we propose to: 1) Characterize the structural and genetic nature of the Oantigen/capsule; 2) Determine the role of the O-antigen/capsule in virulence; 3) Determine the humoral and cell-mediated immune responses to the O-antigen/capsule and proteins of F. tularensis; and 4) Develop a conjugate vaccine for F. tularensis infections. These studies will employ a proteomics-based approach to identify new immunogenic proteins from F. tularensis that can be used as carriers in the development of novel acellular glycoconjugate vaccines. It is anticipated that these vaccines will activate both humoral and cell-mediated immune responses and elicit complete protection against tularemia. Glycoconjugate vaccines have been among the most effective biologics ever developed for the prevention of bacterial infections. It is expected that this approach can be applied successfully to the development of a vaccine that can ultimately be tested in clinical trials for the prevention of tularemia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CONTROL OF BACTERIAL TOXINS BY VIRUSES AND PLASMIDS 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 30-SEP-1976; Project End 31-MAR-2005 Summary: (Adapted from the Applicant's Abstract): The long term goals of this project are to determine molecular mechanisms for virulence regulation in pathogenic bacteria and to develop new methods to treat bacterial infections. The investigators will study Corynebacterium diphtheriae, a paradigm for toxin-mediated bacterial infections, and Mycobacterium tuberculosis, a prototype for intracellular bacterial infections. These very different bacterial pathogens produce closely related, iron-activated, global regulatory proteins that govern virulence: the diphtheria toxin repressor (DtxR) and the iron-dependent regulator (IdeR), respectively. The investigators will determine the molecular basis for function of DtxR, IdeR and the homologous regulator SirR from Staphylococcus epidermidis. The investigators will use structure-based design to develop new antimicrobial drugs called "super-activators" that will target DtxR, IdeR or their homologs; activate them by iron-independent mechanisms; and inhibit production of virulence factors that are negatively regulated by iron- and DtxR-related repressors. The development of IdeR as a novel target for antimicrobial therapy could address the urgent global need for improved treatment of tuberculosis. The investigators will characterize the genes and gene products that are iron-regulated and under control of DtxR and IdeR, both to provide new insights into the pathogenesis of diphtheria and tuberculosis and for development of additional classes of antimicrobial agents. Specific Aim I will analyze structure and function of DtxR, IdeR and SirR. The investigators will investigate the molecular basis for repressor-operator interactions, for iron-independent super-repressor activity, and for domain function in biological activity of these regulatory proteins. Specific Aim 2 will characterize the DtxR and IdeR regulons in C. diphtheriae and M. tuberculosis. The investigators will develop an allelic exchange system for C. diphtheriae, characterize the DtxR and IdeR regulons by proteomic and molecular genetic methods, assess physiological functions of DtxR and IdeR domain 3, and investigate atypical phenotypes among clinical isolates of C. diphtheriae. Specific Aim 3 will develop super-activators of DtxR and IdeR by structure-based design. The investigators will design combinatorial peptide libraries, test them for super-activator function, identify individual peptides with activity, determine the structural basis for that activity, and develop better super-activators by iterative application of these methods. The investigators will also use molecular genetic methods to identify novel
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mechanisms for super-repressor activity and new lead compounds for development as tools against these bacterial infections. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CONTROL OF BIOFILMS BY NATURAL PRODUCTS Principal Investigator & Institution: Costerton, John William.; Professor & Director; Sequoia Sciences 11199 Sorrento Valley Rd, Ste H San Diego, Ca 92121 Timing: Fiscal Year 2003; Project Start 01-APR-2001; Project End 31-JAN-2005 Summary: (provided by applicant): Chronic bacterial infections are serious medical problems in the United States. In chronic bacterial infections, biofilms protect bacteria from antibiotics and immune response mechanisms, thus increasing the rates of reoccurring symptoms and resistance to antibiotics. We discovered four novel compounds in Phase I under this STTR project that prevent the formation and disrupt biofilms, and we expect to identify additional novel compounds in Phase II. We propose to use the strategies developed in Phase I to prioritize the other active samples that have been identified. We will elucidate the structures of the active compounds and characterize their biological activity as biofilm inhibitors or antibacterials. We will also continue the discovery process for additional active samples. This work will enable us to commercialize these compounds that regulate biofilms and to further optimize or methods and strategies by which to discover more novel compounds that regulate formation of biofilms that are needed for a wide range of applications. In the United States, the market for microbial biofilm inhibitors is contained within the $8.5 billion market for antibiotics. Biofilms are involved in 65% of human bacterial infections; accordingly, biofilm inhibitors could capture a $4 to $6-billion segment of the antibiotic market. Biofilm inhibitors will have the greatest medical impact by treating many chronic infections, reducing catheter- and medical device-related infections, and in treating cystic fibrosis patients. Research has clearly established that biofilms play a significant role in these areas, representing a large market whose needs are unmet. The potential market penetration for potent biofilm inhibitors is exemplified by the sheer number of cases in which biofilms cause medical problems. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CRANBERRY JUICE AND URINARY TRACT INFECTIONS Principal Investigator & Institution: Barbosa-Cesnik, Cibele T.; Epidemiology; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2004; Project Start 15-JAN-2004; Project End 31-DEC-2007 Summary: (provided by applicant): Urinary tract infection (UTI) is one of the most commonly acquired bacterial infections in ambulatory and hospitalized populations and E.coli is the most common urinary pathogen, accounting for 90% of UTIs acquired in the community. Antimicrobial treatment and prophylaxis has resulted in increasing resistance to antimicrobials among uropathogenic bacteria both in the United States and worldwide. Several observational studies and a few randomized trials suggest that cranberry juice reduces the incidence of UTI. Reduced incidence of UTI could decrease antibiotic use and ultimately minimize prevalence of antibiotic resistance. Our overall goal is to determine the effect of cranberry on reducing the rate of recurrent UTI and duration of symptoms over antibiotics alone. We propose a randomized clinical trial of 600 college women presenting to the University Health Service with acute urinary tract infection. The study will have 3 arms and patients will be randomly assigned to taking 8
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ounces of juice twice a day containing either 27% cranberry juice, 13.5% cranberry juice, or placebo juice. In addition, we will determine whether regularly taking cranberry juice changes the 3 and 6 month prevalence of bladder, rectal, vaginal and periurethral colonization with E coli containing known uropathogenic virulence factors relative to placebo controls. The results of this study will increase our understanding of the cranberry juice effect on reducing the symptoms of acute UTI, and on preventing recurring UTIs. We will be able to understand the dose-response effects on the outcomes of interest, including on side effects and compliance. We will also be able to evaluate if the bacterial population in the vagina, periurethra and stool is different after regularly drinking cranberry juice compared to placebo. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DETERMINANTS OF INNATE IMMUNITY TO GROUP B STREPTOCOCCI Principal Investigator & Institution: Levy, Ofer; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2002; Project Start 01-MAR-2002; Project End 28-FEB-2006 Summary: (provided by applicant): The central goal of this project is to understand the role of innate immunity in infections caused by Group B streptococci (S. agalactiae or GBS). GBS are the major cause of neonatal sepsis and meningitis and thus a leading cause of neonatal morbidity and mortality. GBS-induced inflammatory mediators include tumor necrosis factor (TNF) that, when excessive, can contribute to host morbidity and mortality. Recent evidence suggests that a variety of Gram-positive bacterial surface molecules activate the innate immune system via phagocyte innate immune receptors including cellular differentiation antigen-14 (CD14), complement receptors-3 and -4 (CR3/4), and Toll-like receptor 2 (TLR2). The candidate will further characterize bacterial and host determinants of innate immunity to GBS and test the following hypotheses: Specific molecular interactions between GBS surface components and phagocyte innate immune receptors mediate the host inflammatory response to GBS infection, that such responses are down-regulated by neutrophil-derived antimicrobial peptides that bind and neutralize inflammatory GBS surface molecules, and that these pro- and anti-inflammatory innate immune responses differ between newborns and adults. In Aim 1, GBS surface components that activate host phagocytes (i.e., neutrophils and monocytes) will be identified and characterized. In Aim 2, newborn and adult phagocytes will be compared with respect to expression and function of CR3/4, CD14, and TLR2. In Aim 3, putative neutrophil-derived peptides with anti-inflammatory activity against GBS will be isolated and characterized. The candidate seeks an intensive, formal, mentored training as preparation for becoming an independent scientist. As a specialist in pediatric infectious diseases, his long-term goal is to identify molecular pathways of innate immunity that might someday be modulated to improve outcomes of GBS and other bacterial infections in neonates. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: DEVELOPMENT EXPRESSION OF CHEMOKINES AND THEIR RECEPTORS Principal Investigator & Institution: Calhoun, Darlene A.; Pediatrics; University of South Florida 4202 E Fowler Ave Tampa, Fl 33620 Timing: Fiscal Year 2002; Project Start 13-AUG-2001; Project End 31-JUL-2003
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Summary: (provided by applicant) Despite the development of newer and more effective antibiotic therapies, sepsis related mortality in neonates undergoing intensive care has remained constant for nearly two decades. The rate of infection among these neonates ranges from 25% to 50%, with bacterial infection remaining a major cause of death and long-term morbidity. The cost of caring for premature neonates, who are the most susceptible to infection, represents over 50% of the total dollars expended for neonatal intensive care unit (NICU) services. The unique susceptibility of the human neonate to serious and overwhelming bacterial infections relates in part to deficiencies of antibody, complement, and T lymphocytes. However, while deficiencies in these contribute to the neonate s susceptibility, neutrophil defects appear to be the major host defense abnormality. Functional defects in neonatal polymorphonuclear leukocyte adherence, aggregation, chemotaxis, phagocytosis, and intracellular killing have been described in both the term and preterm infant. Of these defects, neutrophil chemotaxis, as assessed by in vitro assays, is abnormal at birth. While term infants rapidly establish normal chemotactic function, the process of postnatal maturation begins two to three weeks after birth in the preterm infant and proceeds very slowly. Neutrophils follow a concentration gradient of chemotactic factors in their movement from the vascular compartment to the site of microbial invasion. Chemokines are chemotactic cytokines that largely control leukocyte migration. While considerable information has emerged in the past ten years related to the role of chemokines in the adult, very little information exists as to the physiologic significance of chemokines in the neonate. Candidate chemokine/chemokine receptors for influencing neutrophil chemotaxis include members of the CXC chemokines. We propose that understanding the gene regulation for the expression of specific chemokine receptors (CXCR) during development would enhance our understanding of chemotaxis in the neonate. We further propose that defining circulating concentrations of chemokines critical for neutrophil migration would be essential to understanding their role in both health and disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DNA GYRASE AND QUINOLONE RESISTANCE IN TUBERCULOSIS Principal Investigator & Institution: Drlica, Karl A.; Associate Professor; Public Health Research Institute 225 Warren St Newark, Nj 07103 Timing: Fiscal Year 2003; Project Start 30-SEP-1993; Project End 31-DEC-2007 Summary: (provided by applicant): The goals of this program are to understand how the quinolones act in mycobacteria and to discover ways to protect the compounds from the development of resistance. Previous work showed that structure modifications at the C8 position of fluoroquinolones increase antibacterial activity, particularly with fluoroquinolone-resistant mutants. This feature, plus other variations in fluoroquinolone structure, will be examined to explore the hypothesis that lethal activity arises in part from the dissociation of gyrase subunits attached to cleaved DNA. Since gyrase subunit dissociation is assayed as lethal activity in the absence of protein synthesis, this work may reveal ways to improve action against nongrowing bacteria. To define how low fluoroquinolone concentrations affect the development of resistance, non-gyrase resistance mutants of Mycobacterium tuberculosis, obtained through selective growth at low drug concentration, will be examined for their ability to increase the frequency at which subsequent gyrase mutants are selectively enriched. This portion of the study is expected to influence fluoroquinolone dosing strategies. In patients, M. tuberculosis develops resistance so readily that anti-tuberculosis agents are administered as combination therapies; consequently, the lethal activity of new fluoroquinolones will be examined in combination with traditional agents to identify combinations of
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compounds that are unlikely to have intrinsic interfering activities. Traditional agents will also be combined with C-8-methoxy fluoroquinolones in a dynamic in vitro model to examine the effect of pharmacodynamic mismatch on the development of resistance. These two aspects of the program will help optimize the use of new fluoroquinolones. To provide a clinical context for the work, isolates from New York City will be examined for susceptibility to fluoroquinolones. Comparison of isolates obtained in the early 1990s with those obtained recently will indicate whether susceptibility is being lost. Principles emerging from these in vitro studies may be generally applicable to bacterial infections for which fluoroquinolone treatment is indicated; ideas concerning resistance may also extend to other compounds in which de novo antimicrobial resistance develops in a gradual, stepwise manner. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: EFFECTS OF TOBACCO SMOKE ON AIRWAY BACTERICIDAL ACTIVITY Principal Investigator & Institution: Di, Yuan-Pu P.; Environ & Occupational Health; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2002; Project Start 18-SEP-2002; Project End 31-JUL-2005 Summary: (Taken from the Investigator's Abstract) Environmental stresses such as microorganisms and toxic chemicals have profound effects on lung injury and pulmonary disease. Airway bacterial infection has been associated with various lung diseases such as pneumonia, cystic fibrosis, and tuberculosis. Tobacco smoke (TS) is known to induce pulmonary diseases such as emphysema and lung cancer and has effects on the host defense mechanism against pathogens, but the molecular mechanisms by which this occurs is not completely understood. The long-term goal of this proposal is to investigate the functional characteristics of a novel airway specific gene, DD4, its regulation and its potential role in health and human lung diseases that relate to tobacco smoke. The human DD4 gene is specifically expressed in serous cells of submucosal glands where bactericidal proteins such as lysozyme and lactoferrin are secreted. This novel gene has exhibited significant response to promoting agents of mucous cell differentiation such as UTP and retinoids, as well as to several mediators of inflammation and proliferation such as tumor necrosis factor-alpha (TNF-alpha) and epidermal growth factor (EGF). Of potential significance, the candidate?s preliminary studies revealed that DD4 has antibacterial properties and that its secretion varied dramatically between different lung diseases. In addition, the candidate?s laboratory also observed that human DD4 MRNA expression is elevated upon TS stimulations in both time and dose dependent manner. The objective of this application is to elucidate effects of TS on the regulatory mechanism of DD4?s gene expression and to examine DD4?s function after TS exposure both in vitro and in vivo. The central hypothesis to be tested is that DD4 is a secreted bactericidal protein that plays a role in airway defense mechanisms against pathogens. The rationale behind this research is that modulation (such as TS exposure) of the secretary DD4 protein is one means of directly affecting host defense response against human airway infection. Therefore, regulation of DD4 gene expression and protein secretion in response to pathological stimuli must be understood before the mobilization of host defenses and the pathogenesis of airway diseases that are related to DD4 can be fully appreciated. To accomplish the objectives of this application, they will pursue three specific aims: (1) to characterize the bactericidal activity of DD4; (2) to elucidate the regulatory mechanism of TS exposure on DD4?s bactericidal function; (3) to evaluate DD4?s antibacterial effect in vivo. At the completion of this research, the candidate expects to have determined the bactericidal
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potency of DD4 and the regulation by TS of the antibacterial defense mechanism of DD4. The candidate expects that regulation of DD4 will prove to be related, at least in part, to the inflammatory response and tobacco smoke exposure. Finally, the candidate may obtain a better understanding of the pathogenesis of bacterial infections in certain lung diseases under effects of tobacco smoke, and the development of new therapeutic strategies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ELR-CXC CHEMOKINES IN LUNG ANTIBACTERIAL HOST DEFENSE Principal Investigator & Institution: Standiford, Theodore J.; Professor; Internal Medicine; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2002; Project Start 01-DEC-1996; Project End 30-NOV-2005 Summary: (provided by applicant): Bacterial pneumonia is the second most common cause of hospital-acquired infection, and is leading cause of death among all nosocomial infections. Innate, or natural immunity, is the principal pathway for effective elimination of bacterial organisms from the lung. While ELR-CXC chemokines have been shown to be expressed during the generation of Th1 cell-mediated immune responses against intracellular microbial pathogens, the contribution of this family of chemokines to innate immunity against common gram-positive and gram-negative bacterial pathogens is unknown. We have focused this competitive renewal on ELRCXC chemokines, as our preliminary observations indicate that the in-vivo depletion of selected ELR-CXC chemokines substantially impairs bacterial clearance and survival of mice with pneumonia due to Klebsiella pneumoniae. It is the hypothesis of this proposal that ELR-CXC chemokines are integral components of the innate neutrophil-dependent immune response against gram-negative bacterial infection of the lung. A murine model of Klebsiella pneumonia will be employed to achieve the following specific aims: 1) to determine the time course of expression and cellular sources of ELR-CXC chemokines and their common receptor (CXCR3) during the evolution of gram-negative bacterial pneumonia; 2) to determine the contribution of ELR-CXC chemokines and their receptor to leukocyte recruitment, proinflammatory cytokine expression, bacterial clearance, survival in Klebsiella pneumonia using specific neutralizing antibodies or knockout mice; 3) to determine the effect of IP-10 or MIG administration/transgenic expression on proinflammatory cytokine expression, bacterial clearance, and survival in murine Klebsiella pneumonia in-vivo and on alveolar macrophage effector cell function in-vitro; and 4) to identify endogenous signals that regulate the expression of ELR-CXC chemokines during the evolution of Klebsiella pneumonia in-vivo and in isolated lung cells in-vitro. Elucidation of specific cellular and molecular mechanisms of lung antibacterial host defense, in conjunction with the use of novel gene therapy approaches will provide important insights into the treatment of patients with serious multi-drug resistant bacterial infections of the lung. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: EMERGING DRUG-RESISTANT INFECTIONS Principal Investigator & Institution: Riley, Lee W.; Professor; None; University of California Berkeley Berkeley, Ca 94720 Timing: Fiscal Year 2003; Project Start 04-SEP-2003; Project End 31-MAR-2008
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Summary: (provided by applicant): Drug-resistant bacterial infections that occur in both hospital and community settings are an emerging infectious disease problem in large urban centers of middle-income developing countries, such as Brazil. This training program will build on the last 5 years of a training program supported under the Fogarty International Training and Research in Emerging Infectious Diseases (ITREID) to create a sustainable research training infrastructure in Brazil to address the problem of drug-resistant bacterial infections that occur in both hospital and community settings. This infrastructure will be established at the Federal University of Rio de Janeiro (FUR J), involving faculty members at FURJ and in the US who have already been collaborating over the last 5 years. Specifically, the new program will build a training program structured around three areas of research: 1) field epidemiology, 2) molecular epidemiology, and 3) molecular biology of bacterial drug resistance. The training sites in the US will include the Infectious Disease and Epidemiology programs of the School of Public Health at University of California at Berkeley (UCB), the Infectious Disease program at the University of California at San Francisco (UCSF), and Department of Medicine at Weill Medical College of Cornell University in New York City. On-site training at FURJ will be provided for MD, master's and PhD-level students, while a select set of master's, PhD, and postdoctoral students, as well as junior faculty members will be trained short- (3-6 months), intermediate-(6-12 months), or long- (>12 months) term at the US sites. The field epidemiology activities will include on-the-job training in research study design, outbreak investigations, data collection and analyses, disease surveillance, and biostatistics. The molecular epidemiology training will focus on the development, validation, and application of new molecular strain typing methods and computer-based analysis of strain subtyping database to address specific epidemiologic questions. Training in molecular biology of drug-resistance mechanisms will include the analysis of genetic elements (integrons, cassettes, plasmids) that mediate drug resistance. Through these training activities, the program hopes to create a cadre of researchers who will not only become future trainers themselves, but who can generate and provide quality information that will assure evidence-based decision-making by clinicians, nosocomial infection control services, metropolitan public health authorities, and state and national government policy makers in Brazil. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: EXPRESSION AND FUNCTION OF MSP HOMOLOGUES IN T PALLIDUM Principal Investigator & Institution: Centurion-Lara, Arturo; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2002 Summary: As primary syphilis resolves, most treponemes are cleared from the chancre. However, a few organisms escape the immune response to cause secondary syphilis and ultimately to establish chronic infection. May theories have been proposed to explain Treponema pallidum's capacity for immune evasion, yet none has convincing experimental support. Antigen variation is one of the most intriguing theories, but not candidate antigens have been identified until now. The recent identification of a polymorphic multicopy gene family in T. pallidum that encodes for proteins with predicated amino acid homology to the major sheath protein (msp) of Treponema denticola provides a family of likely candidates. We call these T. pallidum proteins the msp-homologues. The broad goal of this proposal is to determine the cellular location and the function of the msp-homologue proteins. The specific aims of the project are the following: 1. Determine whether msp-homologues are surface exposed antigens in T.
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pallidum Nichols strain. This aim will test the hypothesis that some of the msphomologues are surface exposed in living organisms. 2. Determine whether msphomologues are involved in cell attachment and function as porins. This aim will determine whether the msp-homologue family has a role in two well-recognized mechanisms of pathogenesis of bacterial infections. 3. Determine whether T. pallidum Nichols strain represents a colonal bacterial population or is comprised of subpopulations of treponemes. This aim will test the hypothesis that, like other spirochetes, T. pallidum strains contain subpopulations that express heterogeneous msp- homologues. 4. Determine whether the msp-homologues undergo antigen variation or phase variation. Antigenic variation is common other pathogenic treponemes and the msp-homologue gene family has characteristics highly suggestive of genetic recombination and reassortment. This aim will test the hypothesis that individual msp-homologues either change (antigenic variation) or are no longer expressed (phase variation) during the course of infection. The studies proposed in this application will define the role of the msp- homologues in immune evasion and in the pathogenesis of syphilis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GAMMA DELTA T CELLS IN ANTI-BACTERIAL HOST DEFENSE Principal Investigator & Institution: Moore, Thomas A.; Internal Medicine; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2002; Project Start 01-APR-2001; Project End 28-FEB-2006 Summary: (provided by applicant): Klebsiella pneumoniae is a leading cause of community-acquired and nosocomial infections. Moreover, K pneumoniae is the second leading cause of nosocomial gram negative bacteremia. The recent emergence of multiantibiotic resistant strains of K pneumoniae due to extended-spectrum B-lactamase (ESBL) production is cause for significant clinical concern. Interestingly, antibiotic resistance appears to be more prevalent in blood isolates than from other sources. While the innate host response towards gram-negative bacterial infections has been characterized, little is known about gamma delta-T cells and their role in these infections. Our preliminary studies indicate that gamma delta-T cell knockout (KO) mice have significantly impaired early expression of pulmonary and hepatic IFN-gamma and TNF-alpha mRNA following intratracheal K. pneumoniae infection, increased blood bacterial dissemination, and increased hepatic bacterial burden subsequent to the initial pulmonary infection. Additional studies indicate increased mortality following intravenous bacterial inoculation in gamma delta-T cell KO mice and uncontrolled blood bacterial growth. Combined, our preliminary data suggest gamma delta-T cell KO mice succumb from an impaired ability to clear disseminated bacteria rather than from an inability to clear the organism from the primary pulmonary infection. The hypothesis of this proposal is that gamma delta T cells play a critical role in the host acute inflammatory response during gram-negative bacteremia via recognition of heat shock protein 60 expression in the liver following infection. A murine model of blood-borne K pneumoniae infection will be used to perform the following Specific Aims: 1)To contrast the host response in gamma delta T cell knockout and wildtype mice during K pneumoniae bacteremia, 2) To assess the kinetics of gamma delta T cell A) recruitment and activation and B) cytokine production during K pneumonia bacteremia, 3) To reconstitute resistance to K pneumoniae in gamma delta T cell knockout mice by adoptive transfer of gamma delta T cells from wildtype and cytokine deficient (IFNgamma or TNF-alpha) mice, 4) To confer resistance to K. pneumoniae in gamma delta T cell knockout mice by TNF-alpha or IFN-gamma reconstitution using systemic
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adenovirus gene therapy, and 5) To assess the requirement of heat shock protein 60 for gamma delta T cell activation during K. pneumoniae bacteremia. These studies will provide insights for the development of therapeutic modalities aimed at augmenting host responses, resulting in enhanced resolution of bacterial infections. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENOME ANALYSIS OF STREPTOCOCCUS AGALACTIAE Principal Investigator & Institution: Tettelin, Herve S.; Associate Investigator; Institute for Genomic Research Rockville, Md 20850 Timing: Fiscal Year 2002; Project Start 30-SEP-2001; Project End 29-SEP-2004 Summary: (provided by applicant): Group B streptococci (GBS) or Streptococcus agalactiae are weakly beta-hemolytic, facultatively anaerobic Gram-positive cocci, which have emerged over the past 50 years as the most significant bacterial cause of neonatal sepsis, pneumonia, and meningitis. GBS account for 30-50 percent of neonatal bacterial infections and increases in adult GBS infections have also been noted. This demonstrates that GBS infections remain an important public health problem. We propose to sequence the 2.1 Mb genome of S. agalactiae serotype Ia strain A909 using a genome-wide random shotgun approach. We will then use the final assembled sequence and its complete annotation to perform detailed comparative genomics analyses between serotype Ia and other organisms causing pneumonia and meningitis. These analyses will allow to identify virulence determinants shared by all organisms or specific to individual ones. These determinants will be related to Drs. Jones and Rubens? experiments on signature tagged mutagenesis and TnphoZ translational fusion (identification of secreted proteins) mutant libraries constructed through transposon insertions in strain A909. Regions where transposons inserted will be aligned to the genome sequence to identify the genes affected. A subset of the mutants conserved across serotypes will be analyzed in the rat sepsis model to evaluate their virulence. This collaborative effort will provide extensive preliminary data for future proposals relevant to understanding the pathogenesis of S. agalactiae infections. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: HIV SURVEILLANCE AFFECTS MACROPHAGE FUNCTION Principal Investigator & Institution: Wewers, Mark D.; Professor; Internal Medicine; Ohio State University 1960 Kenny Road Columbus, Oh 43210 Timing: Fiscal Year 2002; Project Start 30-SEP-1998; Project End 31-AUG-2003 Summary: Bacterial pneumonia remains one of the most common complications of HIV infections. In spite of our growing understanding of the pathogenesis of the immune deficiency associated with HIV infection, the factors that predispose HIV+ individuals to pneumonia remain obscure. For example, the risk of pneumonia for HIV infected individuals is 6 fold higher than for HIV-individuals. This risk can only partially be explained by lower blood CD4 counts. Our preliminary experiments demonstrate that the lung CD4 counts remain normal in the face of falling peripheral counts when compared to HIV uninfected subjects. However, CD8+ lymphocytes are markedly increased in the lung, a hallmark of HIV infection. These cytotoxic CD8+ lymphocytes (CTLs) are believed to function to suppress viral replication. In this context, the primary defense against bacterial infections in the lung is provided by alveolar macrophages which are also the prime source of HIV in the lung. Since macrophage HIV infection is enhanced by inflammatory events, we have hypothesized that 1) initiation of antibacterial function by lung macrophages induces local HIV replication, and 2) as a
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consequence of this increase in viral burden, lung CTLs may be signaled to suppress this viral replication. This suppression of virus may in the process suppress macrophage antibacterial function. We therefore, propose to test these hypotheses by studying the macrophage's ability to phagocytose opsonized particles. We will evaluate lung macrophages from HIV infected individuals and normal controls to test whether opsonized phagocytosis induces viral replication in the macrophage. As a corollary we will determine whether CTLs can impair macrophage phagocytosis. These in vitro experiments will be corroborated by studies of lung macrophages taken at the time of bacterial pneumonia. Together these experiments will improve our understanding of how the innate immune defense against bacteria is affected by attempts to suppress HIV in macrophages. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HOST-PATHOGEN INTERACTIONS IN THE MAMMALIAN AIRWAY Principal Investigator & Institution: Diamond, Gill; Associate Professor; Biochem and Molecular Biology; Univ of Med/Dent Nj Newark Newark, Nj 07103 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2007 Summary: (provided by applicant): Epithelial cells lining the mammalian trachea form a crucial site in the host defense against airborne microbial pathogens, releasing numerous antimicrobial factors. Deficiencies in these defenses may result in recurrent airway infections. One of these defense mechanisms is the inducible production of betadefensins, a class of homologous antibiotic peptides highly abundant in mammalian epithelial cells. The genes encoding beta-defensins are expressed at high levels in the respiratory epithelium, and are induced by bacterial products and inflammatory mediators. Preliminary and published data support the hypothesis that some pathogenic strains of bacteria can evade the innate immune system in the airway by inhibiting beta-defensin gene expression, which can in turn diminish the antimicrobial defense of the airway. The mechanisms by which the specific bacterial virulence factors allow evasion of the first lines of host defense to colonize the airway are not yet defined. Elucidation of these mechanisms will aid in the development of therapeutic strategies for airway infections. The long-range goal of our research is to better understand the dynamic host defense systems in the airway. In this proposal we focus on the interactions of the airway pathogen, Bordetella bronchiseptica with its target cells in the respiratory epithelium. B. bronchiseptica is associated with respiratory infections in animals, and is closely related to B. pertussis, the causative agent of whooping cough in humans. We hypothesize that airway epithelial cells respond to bacteria by recognition of molecular patterns by specific receptors, resulting in the activation of NF-kappaB and induction of beta-defensin gene expression in order to prevent colonization. Pathogenic strains of B. bronchiseptica can prevent the increased production of antimicrobial peptides by interfering with the upregulation of the antimicrobial peptide genes through a type III secretion factor which interferes with the innate immune response. To test these hypotheses, the following aims are proposed: 1. Define the interaction of B. bronchiseptica with airway epithelial cells and the resultant induction of an innate immune response. 2. Define the mechanism of inhibition of innate immune induction by virulent B. bronchiseptica. The objective of these studies is to define how the airway epithelium responds to this model pathogen by the initiation of a host defense response. The second aim will determine how the bacterium circumvents this response utilizing proteomics to identify the bacterial factor responsible for this action, as well as a comprehensive characterization of the interaction of this factor and the defense
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response. The information will serve as a foundation for the development of novel therapies designed to work in the respiratory tract. This would include strategies to modulate the endogenous antimicrobial peptide expression to prevent serious bacterial infections. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: IMMUNOPATHOGENESIS OF GROUP A STREPTOCOCCAL INFECTION Principal Investigator & Institution: Kotb, Malak; Professor; Surgery; University of Tennessee Health Sci Ctr Memphis, Tn 38163 Timing: Fiscal Year 2003; Project Start 15-AUG-2003; Project End 29-FEB-2008 Summary: (provided by applicant): The overall goal of the present application is to explore the way specific host genetic factors and specific bacterial virulence determinants interact together to influence the outcome of an important infectious disease. This paradigm is critical to explain the wide variety of potential outcomes that occur when a human host encounters a potentially pathogenic organism like Group A streptococcus (GAS), from asymptomatic colonization to mild infection to severe morbidity or mortality. The model we have developed studies GAS-induced severe systemic disease (SSD; the bacterial superantigens (SAgs) that are key players in eliciting SSD; and the host factors involved are the HLA class II molecules that present the SAgs to T cells. The pathogenic link of the host genetic and bacterial virulence factors is clear, since the HLA molecules are receptors for SAgs, presenting them to the TCR and transmitting biochemical signals into APCs. We found that the host immunogenetic makeup influences the clinical outcome of invasive GAS disease. Specific HLA class II haplotypes conferred strong protection from the severe forms of the invasive disease, while others increased the risk for SSD. We also determined the underlying mechanism for these genetic associations by demonstrating that the presentation of Strep SAgs by the class II DRB1( 1501/DQB1*0602 haplotype, which was strongly associated with protection from SSD (P=0.0007), elicited significantly lower inflammatory responses as compared to their presentation by either risk or neutral haplotypes (P<0.0001). Patients with this protective haplotype mounted significantly reduced responses to the Strep SAgs (low responders) and were less likely to develop SSD. By contrast patients who lacked this protective haplotypes or had the DRB1*14/DQB1*0503 high risk haplotype were high responders to the Strep SAgs and were more likely to develop SSD. Our working hypothesis is that HLA class II association with risk/protection from SSD is the same for patients with invasive infections caused by particular GAS serotypes that are commonly isolated from invasive GAS infections and that share a similar SAg repertoire. The robust nature of our model is manifested in our initial identification human HLA haplotypes associated with high-risk and protection against GAS associated SSD. In this application, our combined bacterial and mammalian genetic approach will allow identification of how specific GAS SAg/human HLA combinations determine risk for a particular disease outcome. It is our hope that these results will inform the future design and application of specific therapeutic and vaccine strategies against GAS infection, and serve as a model for investigating the complex pathogenesis of other human bacterial infections. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: INHIBITION OF GBS CARRIAGE BY ENGINEERED LACTOBACILLI Principal Investigator & Institution: Pritchard, David G.; Biochem & Molecular Genetics; University of Alabama at Birmingham Uab Station Birmingham, Al 35294
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Timing: Fiscal Year 2003; Project Start 01-FEB-2003; Project End 31-JAN-2005 Summary: (provided by applicant): Group B Streptococci (GBS) are a major cause of serious neonatal bacterial infections in this country. The origin of the bacteria for babies born with early-onset GBS infections is the birth canal of their mothers. This application describes an entirely new approach for preventing or eliminating vaginal carriage of GBS, thereby reducing the incidence of neonatal GBS infections. The goal is to genetically engineer a normal commensal organism present in the vagina, a Lactobacillus, to secrete a substance that will specifically prevent the growth of GBS. The substance selected is a GBS phage lysin that degrades the cell walls of GBS. The first specific aim is to clone and express the GBS phage lysin in E. coli and assess the bacteriocidal activity of purified recombinant enzyme. The ability of the purified lysin to kill GBS and various other bacteria will be first studied in vitro. Then it will then be determined if vaginal instillation of the enzyme will eliminate GBS in vaginally colonized mice. The second specific aim is to determine basic biochemical properties of the GBS phage lysin, including identifying the enzyme class to which it belongs and the identity of the cell wall component(s) necessary for specific peptidoglycan cleavage. The third specific aim is to engineer a Lactobacillus to secrete the GBS phage lysin. This will be done initially using a plasmid construct containing all the elements necessary for efficient secretion of the lysin from the transformed Lactobacillus. Then, in order to overcome inherent plasmid instability and also to eliminate the antibiotic selection markers, the lysin gene secretion cassette will be integrated into the chromosome of the Lactobacillus. The final specific aim is to determine if vaginal colonization of mice with the engineered Lactobacillus will prevent GBS from establishing a persistent colonization. In addition, it will also be determined if vaginal inoculation with the lactobacillus engineered to secrete GBS phage lysin will result in the clearance of GBS from the vaginas of mice previously colonized with the organism. The proposed research may lead to the development of an effective new method for long-term inhibition of GBS vaginal colonization, even though women may be repeatedly reexposed to the bacteria. The method is unlikely to disturb the normal bacterial flora and should be very safe. If successful, this approach might also be used to protect against other genital, oral, and intestinal pathogens, especially those to which no effective mucosal immunity appears to develop. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: INTERSPECIFIC COMPETITION BETWEEN RICKETTSIAE IN TICKS Principal Investigator & Institution: Azad, Abdu F.; Professor; Microbiology and Immunology; University of Maryland Balt Prof School Baltimore, Md 21201 Timing: Fiscal Year 2002; Project Start 01-MAR-1998; Project End 31-AUG-2004 Summary: In nature, individual ticks can be concomittently infected with more than one species of intracellular bacteria. Some may be important human pathogens acquired either from an infectious bloodmeal or transovarially. Others may be nonpathogenic symbionts acquired transovarially. The consequences and epidemiological significance of multiple bacterial infections in ticks are largely unexplored. We propose that the interactive effects between certain intracellular bacterial species within individual ticks may be of sufficient prevalence and magnitude to alter the vector competence of ticks. Ovaries of Dermacentor andersoni ticks harboring a particular nonpathogenic species of spotted fever group rickettsia, namely Rickettsia peacockii, have been shown to be refractory to subsequent co- infection with otherwise invasive R. rickettsii. Thus, ovarial infection of D. andersoni with R. peacockii rickettsiae interferes or blocks normal transovarial transmission of R. rickettsii. Infections with two or more closely-related
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rickettsial species may result either in interference (i.e., one species inhibits the development and/or transmission of the other), mutualism (i.e., enhanced transmission of both species), or phenotypic mixing (i.e., increased or decreased virulence). This proposal specifically addresses transovarial interference of the human pathogen, Rickettsia rickettsii, in the tick vector transovarially infected with nonpathogenic rickettsiae. We will investigate the phenomenon of transovarial interference in the context of its epidemiological significance and the mechanism(s) by which it occurs. Two specific aims are proposed: 1) We will investigate the prevalence and relative efficiency of transovarial interference of R. rickettsii as medicated by other indigenous species of nonpathogenic spotted fever group rickettsiae within D. andersoni and D. variabilis. This will entail field collections of ticks and laboratory evaluation of the interference potential of these agents; and 2) We will initiate studies to examine the molecular mechanism (s) of transovarial interference of R. rickettsii by R. peacockii and other nonpathogenic spotted fever group rickettsiae. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: IRAK FAMILY FUNCTION IN BACTERIAL INFECTION Principal Investigator & Institution: Thomas, James A.; Pediatrics; University of Texas Sw Med Ctr/Dallas Dallas, Tx 753909105 Timing: Fiscal Year 2002; Project Start 01-MAY-2002; Project End 30-APR-2007 Summary: Infection represents one of the most fundamental threats to host integrity. When bacterial pathogens breach an epithelial barrier, the host innate immune system detects the attack and triggers a response to contain and eliminate the invader. Cellular sensors, such as macrophages and dendritic cells, detect pathogen through receptors that recognize bacterial macromolecules. These cells then mount a proinflammatory reaction that leads to cellular responses that contain and eliminate the infection. Thus, the innate immune response contains both afferent (pathogen-sensing) and efferent (proinflammatory) limbs. The Toll/IL-1 signal transduction pathway mediates both arms of this innate response to infection. This conserved signaling cascade consists of the proteins MyD88, the interleukin-1 receptor-associated kinase (IRAK) family of molecules (IRAK, IRAK2, and IRAK-M) and the tumor necrosis factor associated factor 6. It processes signals from at least 10 Toll-like receptors (TLRs) and three IL-1 receptor family members (IL-1, IL-18, and Ti/ST2), distributing them to multiple downstream targets, including NF-kB and several mitogen activated protein kinase cascades. We have genetically deleted IRAK, the primary proximal kinase in this pathway, in mice. IRAK-deficient animals and macrophages exhibit impaired responses to lipopolysachharide (LPS), peptidoglycan (PGN), lipotechoic acid (LTA), and CpG DNA, bacterial molecules that activate the afferent arm of innate immunity through TLR4 and TLR2. These mice also exhibit attenuated proinflammatory (efferent) responses due to disrupted IL-1 and IL-18 signaling. The overall objective of this proposal is to determine IRAK function in the host response to Gram-negative and Gram-positive infections. Aim 1 is to determine the role of IRAK in the acute inflammatory response to Gram-negative and Gram-positive infections. We will subject IRAK- deficient macrophages and mice to increasingly complex models of these infections, using toxin challenges, stimulation with nonreplicating bacteria, and Klesiella pneumoniae and Staphylococcus aureus pneumonia. Aim 2 is to isolate IRAK function genetically to either the TLR4 or IL1receptor pathway by generating IRAK/IL-121 and IRAK/TLR4 double knockout animals and comparing the responses of double and single KO macrophages and mice to LPS stimulation, nonreplicating K. pneumoniae, and K. pneumoniae pneumonia. Aim 3 is to determine the contributions of IRAK2 and IRAK-M to residual TLR signaling in
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IRAK-deficient cells, as deletion of IRAK impairs, but does not completely abrogate signaling. These studies should provide fundamental new information about the role of IRAK in the innate immune response to acute bacterial infection and may eventually lead to the development of strategies to modulate deleterious aspects of this response. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: IRON ACTINOMYCETEMCOMITANS
UPTAKE
IN
ACTINOBACILLUS
Principal Investigator & Institution: Actis, Luis A.; Associate Professor; Microbiology; Miami University Oxford 500 E High St Oxford, Oh 45056 Timing: Fiscal Year 2002; Project Start 01-AUG-2001; Project End 30-JUN-2005 Summary: (adapted from the Investigator's abstract): Localized juvenile periodontitis (LJP) is the disease that occurs when bacteria accumulate on the junctional epithelium in the oral cavity. It was found in the middle of the last decade that Actinobacillus actinomycetemcomitans is the major causative agent of LJP and, more recently, as one of the microorganisms responsible for adult periodontitis. Periodontitis is the most prevalent chronic inflammatory diseases in humans, and it is major cause of tooth loss. It is evident that this dental pathogen grows actively and persists during the infectious process, which depends upon the ability of this microorganism to obtain growthessential nutrients such as iron. Iron withholding by vertebrate hosts is an efficient mechanism against bacterial infections, and, thus bacteria must express efficient transport systems to acquire this essential nutrient to multiply during infection. There are indications that A. actinomycetemcomitans does not secrete siderophore compounds and it may acquire iron through periplasmic-binding protein-dependent transport systems. However, the genes and bacterial products involved in these processes and their role in virulence remain to be characterized. Therefore, the long-term objective of this application is the characterization of the mechanisms that A. actinomycetemcomitans uses to acquire iron and their participation in the pathogenesis of juvenile and adult periodontitis. In this proposal, the Principal Investigator addresses these goals through several approaches, combining methods used in classical and molecular bacterial genetics with molecular biology techniques designed to examine differential gene expression. The first specific aim involves a detailed genetic and molecular characterization of two potential iron periplasmic-transport systems, while the second specific aim focuses on the analysis of the expression of these systems in bacterial cells cultured in bacteriological media and in tissue culture flasks containing monolayers of human oral epithelial cells. The third specific aim proposes to determine the role of these potential iron transport systems in iron acquisition and the virulence of A. actinomycetemcomitans by creating and testing isogenic mutants. These proposed studies address an important and largely unexplored aspect of the pathogenesis caused by A. actinomycetemcomitans. Furthermore, these studies will lead to a better understanding of the nature of the interactions between the host and this pathogen during colonization and invasion of oral tissues. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MAMMAL CECROPINS AS ANTIBIOTICS FOR CORNEAL INFECTIONS Principal Investigator & Institution: Dai, Wei; Professor; Cytopro Company 16826 Twin Hill Dr Hacienda Heights, Ca 917455704 Timing: Fiscal Year 2004; Project Start 01-JAN-2004; Project End 31-DEC-2004
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Bacterial Infections
Summary: (provided by applicant): The emerging bacterial infections that are resistant to the current antibiotic arsenal have accelerated search for therapeutic agents with a novel mechanism of action. Recent studies suggest that the gene-encoded peptide antibiotics may hold great promise as a new generation of therapeutic agents. These agents have the potential to become medications used on a daily basis by ophthalmologists to treat or prevent ocular infections, especially those infections caused by bacteria resistant to other drugs. Cecropins, a family of structurally related small peptides originally isolated from invertebrates, are potent against a wide spectrum of gram-negative and gram-positive bacteria. Cecropins form an amphipathic helix, which anchors to and penetrate the surface of bacterial cell membrane, resulting in cell lysis. Whereas mammals have evolved an adaptive immune response they also retain many ancient genes encoding products with bactericidal activities, functioning as an innate immune response. Given that a porcine cecropin (cecropin P1) has been identified and characterized and that cecropins are highly specific for killing microorganisms including those commonly found in corneal infections we propose that humans have retained cecropin-homologous genes whose products can be explored as new antibiotics used in the ophthalmic clinics. The major goals of this project are to identify and characterize the human homologue of cecropin P1 and to explore cecropin P1 and its human counterpart for commercial applications as novel antibiotics in ophthalmology. It is anticipated that the studies proposed in this Phase I application will result in structural and functional characterization of human cecropin. Phase II will be aimed at testing the efficacy and potential side-effects of mammalian cecropins using animal model systems as well as at regulatory submission and clinical testing. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MECHANISM OF PATHOGENIC ACTIVITY OF PEPTIDOGLYCAN Principal Investigator & Institution: Dziarski, Roman; Professor of Microbiology and Immunology; Microbiology and Immunology; Indiana Univ-Purdue Univ at Indianapolis 620 Union Drive, Room 618 Indianapolis, in 462025167 Timing: Fiscal Year 2003; Project Start 01-JUL-1992; Project End 30-NOV-2007 Summary: (provided by applicant): Bacterial infections are still the major cause of morbidity and mortality, and innate immunity is the first line of host defense against infections. The overall objective of this project is to elucidate how innate immunity protects the host from infections with Gram-positive bacteria and how the host response to bacterial components causes clinical manifestations and pathologic changes associated with infections. This project investigates the main component of Grampositive bacterial cell walls, peptidoglycan, which can reproduce several major clinical manifestations of bacterial infections. This laboratory has identified a novel family of four pattern recognition proteins in humans that recognize peptidoglycan (PGRPs). These human PGRPs are differentially expressed in the bone marrow, neutrophils, liver, esophagus, tonsils, and thymus, and are highly homologous to the family of 12 insect PGRPs. This project will test the hypothesis that mammalian PGRPs interact with peptidoglycan and bacteria and are involved in innate immunity to bacteria. Specifically, the objective will be to identify the function of PGRPs in mammalian immunity using two approaches: First, it will be determined if PGRP-S knockout mice (generated in this laboratory) are immunodeficient, by testing the following aspects of their immunity: (i) development of lymphoid organs and cells; (ii) susceptibility to infections; (iii) inflammatory responses; (iv) induction of cytokines and chemokines;(v) chemotactic and phagocytic responses; and (vi) antibody responses. Second, the functions of the remaining PGRPs (PGRP-L, PGRP-I-alpha, and PGRP-I-beta) will be
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determined by identifying: (i) tissues and cell types that express these PGRPs; (ii) subcellular localization of each PGRP; (iii) their ligands; (iv) association of PGRPs with other proteins; (v) ability of these PGRPs to induce acute-phase response and uptake of bacteria; (vi) functional domains of these PGRPs; and (vii) inhibitory effects of soluble PGRP-S on the functions of transmembrane PGRPs. This study may discover a new mechanism of innate immunity and a new immunodeficiency, and may provide tools for developing new preventive and therapeutic measures against infections with Grampositive bacteria. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MEMBRANE PROTEINS INVOLVED IN CELL DIVISION IN E.COLI Principal Investigator & Institution: Beckwith, Jonathan R.; Professor of Microbiology and Molecular; Microbiol & Molecular Genetics; Harvard University (Medical School) Medical School Campus Boston, Ma 02115 Timing: Fiscal Year 2002; Project Start 01-SEP-1987; Project End 28-FEB-2006 Summary: (Provided by applicant): This proposal is designed to yield new information on the process of cell division in the bacterium Escherichia coli. Understanding the details of this process is important in designing new classes of antibiotics that can be used in the treatment of bacterial infections. We are currently focusing on two cytoplasmic membrane proteins required for cell division, FtsL and FtsQ. We wish to determine the features of these proteins that cause them to localize to the cell division site. We will obtain a collection of dominant negative mutations in the ftsQ and ftsL genes. Localization of these mutant proteins to mid-cell will be determined with green fluorescent protein (GFP) fusions, using fluorescence microscopy. The dominantnegative mutants will be used to select for mutations that fail to localize to the cell division site. These mutations will help define the region(s) of these proteins that direct them to that site. Mutations in other genes or multi-copy plasmids that suppress the localization defects in FtsQ and FtsL may reveal other proteins these proteins interact with. Multi-copy suppressors of the dominant mutants themselves could reveal the identity of interacting proteins. Protein-protein interactions will be further probed by examining the functioning in E. coli of pairs of proteins from closely-related species of bacteria. A newly discovered gene will provide a test case of this approach. We will use genetic analysis with bioinformatic approaches to help uncover the function of the FtsQ and FtsL proteins. The dominant-negative and other mutations of ftsQ should yield information on the functional regions of the protein. Defining residues important for the activity of this protein would point to particular regions of the protein to study further. We would then continue our computer searches of databases for proteins that share small regions of homology with such regions of FtsQ. In addition, suppressors of an ftsQ null mutant, if obtained, may give a clue as to the protein's function. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MOLECULAR BIOLOGY OF MYCOBACTERIA AND THEIR PHAGES Principal Investigator & Institution: Hatfull, Graham F.; Professor; Biological Sciences; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2002; Project Start 01-DEC-1989; Project End 30-JUN-2005 Summary: (provided by the applicant): Mycobacterium tuberculosis, the causative agent of human tuberculosis, kills more people than any other single infectious agent. The prevalence of TB is greatest in the developing world but its control in the United States has become severely complicated by the appearance of multidrug resistant strains of M.
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tuberculosis. There has recently been a sharp increase in the incidence of these MDRTB strains in developing countries. Effective control of tuberculosis requires improved and more rapid diagnostic methods, more efficacious vaccines, and better antimycobacterial drugs, particularly for treatment of multidrug resistant infections. With the recent advances in mycobacterial genetics and the determination of the complete genome sequence of M. tuberculosis, there is now renewed hope that a more sophisticated understanding of the physiology, genetics, and metabolism of M. tuberculosis will lead to novel strategies for controlling mycobacterial infections. Unfortunately, in spite of these genetic tools and genomic information, we know little about the molecular basis of the fundamental aspects of mycobacterial physiology-such as slow growth, their unique cell wall, and DNA replication-let alone the molecular basis of mycobacterial pathogenesis. Viruses are powerful tools for genetic analysis of a broad range of organisms, and the viruses of mycobacteria (mycobacteriophages) are no exception. The use of mycobacteriophages was instrumental in the establishment of mycobacterial genetics and the creation of cloning vectors for the introduction of DNA into mycobacteria. More recently, recombinant reporter mycobacteriophages have been proposed as clinical tools for rapid determination of drug susceptibilities of clinical isolates of M. tuberculosis. This project aims at understanding the intimate interface between mycobacteriophages and their hosts. This interaction begins with the association of free phage particles with bacterial cells followed by injection of phage DNA into the cell. Phage DNA may then either integrate into the host genome and be genetically silenced, or reprogram the cell to direct it towards phage gene expression and subsequent cell lysis. By exploring these events we will gain insights into the regulation of gene expression, the structure of the mycobacterial envelope, and the process of phage-mediated cell lysis. We will also use proteomic approaches to understand the influence of phage gene expression on that of its host. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MOLECULAR TARGETS IN PEPTIDOGLYCAN SYNTHESIS Principal Investigator & Institution: Davies, Christopher; Assistant Professor; Biochem and Molecular Biology; Medical University of South Carolina 171 Ashley Ave Charleston, Sc 29425 Timing: Fiscal Year 2003; Project Start 01-FEB-2003; Project End 31-JAN-2007 Summary: (provided by applicant): The murein sacculus is a mesh of cross-linked peptidoglycan strands that confers rigidity to the bacterial cell wall. Beta-lactam antibiotics, which target the essential transpeptidases (penicillin-binding proteins or PBPs) that cross-link the peptidoglycan strands, are important compounds in the treatment of bacterial diseases. Unfortunately, the emergence of multiple mechanisms of antibiotic resistance threatens to make these and other antibiotics obsolete in the treatment of bacterial infections. Along with other pathogenic bacteria, antibiotic resistance in Neisseria gonorrhoeae is a growing problem. Penicillin and tetracycline, once the antibiotics of choice for treatment of gonococcal infections, are no longer be used due to the emergence of resistant strains. Moreover, increasing numbers of strains are now resistant to the fluoroquinolones, one of the two antibiotics current recommended in the treatment of gonorrhea. Clearly there is an urgent need to develop new antimicrobials directed both against well-known molecular targets, such as PBPs, but also against novel targets. In this proposal we describe structural and biochemical studies of three enzymes involved in peptidoglycan metabolism: a D-Dcarboxypeptidase from E. coli (PBP 5) that serves as a model system for elucidating PBP function, an essential transpeptidase (PBP 2) from N. gonorrhoeae that is the lethal
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target of current beta-lactam antibiotics, and a lytic transglycosylase, MltA, also from N. gonorrhoeae, that serves as the lynchpin of the cell wall synthesizing complex. Each of these proteins has been selected to address one or more of the following aims: (a) to understand the biology of peptidoglycan synthesis, (b) to explore their interactions with antibiotics, (c) to elucidate the molecular basis for antibiotic resistance and (d) to examine their potential as targets for drug development. Studies on PBP 5 will elucidate the mechanism by which this enzyme hydrolyzes substrate and will provide a better understanding of PBP-antibiotic interactions in general. The molecular basis for antibiotic resistance in PBP 2 will be investigated by structural studies of the native enzyme and of a mutant isolated from a penicillin-resistant strain. The role of MltA as part of a multienzyme complex mediating peptidoglycan synthesis as well as its suitability as a novel target for antimicrobials will be examined by solving its crystal structure. These studies will provide a framework for future studies aimed at structurebased drug design and will provide substantial insight into the mechanisms of peptidoglycan synthesis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NEUTROPHIL FUNCTION & SIGNALING IN POLYNESIAN CHILDREN WITH INCREASED INFECTIONS Principal Investigator & Institution: Kyono, Wade T.; University of Hawaii at Manoa Honolulu, Hi 96822 Timing: Fiscal Year 2002 Summary: The overall objective of this research proposal is to examine neutrophil function and signaling in Polynesian children with severe or recurrent infections. Remarkably, fifty percent of all children admitted for bacterial infections at the primary pediatric hospital in Hawaii are of Polynesia ethnicity. We propose to examine neutrophil respiratory burst activity, phagocytosis, chemotaxis, and the expression of the high affinity receptor for IgG (FcgammaRI) in these children. A novel disorder of neutrophil actin polymerization in a Tongan child and his family in Los Angeles, characterized by impaired neutrophil chemotaxis and the increased expression of an actin binding protein identified as lymphocyte specific protein 1 (LSP1) suggests a mechanism for the increase in infections. We propose to examine both functional and biochemical characteristics of neutrophils in Polynesian children with infections to test the hypothesis that defects in neutrophil function and cellular signaling pathways result in their increased susceptibility to infection. The following specific aims will be performed. Aim 1: Investigate neutrophil chemotaxis, phagocytosis, superoxide production, and neutrophil FcgammaRI expression in Polynesian children who prevent with severe and/or recurrent bacterial infections. Aim 2: Determine the activation of the small GTPase proteins Rac and Cdc42, the activation of p38 mitogen activated protein kinase (p38 MAPK) and mitogen activated protein kinase activated protein kinase 2 (MAPKAP K2), and the protein level and phosphorylation status of the actinbinding protein LSP1 in neutrophils of Polynesia children with increased infections and impaired chemotaxis. Aim 3: Investigate the involvement of LSP1 in F c receptormediated respiratory burst and cytoskeletal rearrangement in neutrophils and neutrophil-like or monocyte-like cell lines by protein immunoprecipitation and the measurement of Rac, Cdc42, phosphatidylinositol 3-kinase, p38MAPK, MAPKAP K2 and protein kinase C activation. Aim 4: Over-express LSP1 in neutrophil-like myeloid cell lines to determine its functional and biochemical effect on cytoskeleton organization, cell motility and FcgammaRI signal transduction. The finding of neutrophil dysfunction in Polynesia children with increased bacterial infections, along with associated
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Bacterial Infections
biochemical abnormalities, will lead to improved diagnosis and potential treatment of these children. The use of immune modulators such as gamma-interferon, based on its up-regulation of FcgammaRI expression and enhancement of neutrophil function, may improve the clinical outcome of those with the severest infections. 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 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
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Project Title: NOVEL LEADS FOR THE THERAPY OF GRAM-POSITIVE SEPSIS Principal Investigator & Institution: David, Sunil A.; None; University of Kansas Lawrence Youngberg Hall Lawrence, Ks 660457563
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31
Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2005 Summary: (provided by applicant): Sepsis is the leading cause of mortality in the intensive care unit. A common and serious sequel of systemic bacterial infections, sepsis accounts for some 200,000 fatalities annually in the US alone, a figure higher than that attributable to AIDS and breast cancer combined. The pathogenesis of septic shock is a consequence of the host response to bacterial components. In the Gram-negative organism, lipopolysaccharide, found on the outer membrane, plays a major role in inducing the systemic inflammatory response that ultimately leads to the shock state. Although the clinical outcome of Gram-negative and Gram-positive infections are indistinguishable, until very recently, the causative factor in the Gram-positive organism was unknown. Compelling evidence now points to a major role for lipoteichoic acid, an integral component of the cell wall in Gram-positive organisms. In the course of our continuing efforts in identifying small-molecules that would specifically bind and neutralize Gram-negative lipopolysaccharide, we have found that certain classes of compounds also inhibit lethality in murine models of Gram-positive shock. In this proposal, we aim to initiate preliminary screening of select compounds based on the leads we have already obtained. We will first compare the biological activities of isolated, homogeneous, lipoteichoic acid and petidoglycan and verify that lipoteichoic acid is toxic on a molar basis comparable to that of reference lipopolysaccharide. Of the many classes of compounds screened in the past for antiendotoxin activity, useful leads have been found in three classes: (1) the lipopolyamines (2) dendrimers, and (3) bis-amidines. Focused libraries of these compounds will be subjected to two levels of screening. In the primary screen, the inhibition of key cytokines induced by lipoteichoic acid in human peripheral blood mononuclear cells will be quantified. Active compounds will be subjected to a secondary screen in which upstream cellular events (cytokine mRNA transcription) will be examined. This is to demonstrate that inhibition of cytokine release, if observed, is attributable to the blockade of the cellular recognition of lipoteichoic acid. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NRAMP1 IN MACROPHAGE DEFENCES AGAINST INFECTIONS Principal Investigator & Institution: Gros, Philippe; Mc Gill University James Admin. Bldg., Room 429 Montreal, Pq H3a 2T5 Timing: Fiscal Year 2002; Project Start 30-SEP-1993; Project End 31-JUL-2004 Summary: (Adapted from the Applicant's Abstract): Infectious diseases have reemerged as a major health problem in North America, in part due to the widespread emergence of antibiotics resistance. The mechanisms of defense against intracellular parasites, and the bacterial strategies underlying survival and replication in host phagocytes remain poorly understood. A better understanding of host defenses against such infections may suggest new strategies for intervention in these diseases. Using a genetic approach, the investigators have identified a new component (Nramp1) of antimicrobial defenses of phagocytes. Mutations at Nramp1 in mice cause susceptibility to several intracellular infections, and polymorphic variants at human NRAMP1 are also associated with susceptibility to Mycobacterial infections in endemic areas of disease. Nramp1 is part of a large family of membrane transporters that has been highly conserved from bacteria to man. Nramp1 is expressed in the lysosomal compartment of macrophages and is targeted to the membrane of bacterial phagosomes soon after phagocytosis. By homology with the known substrates of other Nramp family members, they propose that Nramp1 functions as a divalent cation efflux pump at the phagosomal membrane to suppress bacterial replication. The current proposal has four major goals.
32
Bacterial Infections
The first, is to understand how Nramp1 delivery affects the physiological properties of the phagosome including maturation, acidification, and bactericidal activity of macrophages and neutrophils. The second, is to identify the substrate and mechanism of transport of Nramp1 at the phagosomal membrane. The third is to identify protein determinants responsible for Nramp1 targeting to the lysosome and residues essential for substrate binding and transport. The fourth is to map new mouse loci that affect, in an Nramp1-independent fashion, host resistance to infection with clinically relevant Mycobacteria. Together, these studies should clarify the role and mechanism of action of Nramp1 in phagocytes anti-microbial defenses, which may in turn suggest new avenues for intervention in infectious diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: N-THIOLATED BETA-LACTAMS Principal Investigator & Institution: Turos, Edward; Chemistry; University of South Florida 4202 E Fowler Ave Tampa, Fl 33620 Timing: Fiscal Year 2002; Project Start 01-MAR-2002; Project End 28-FEB-2007 Summary: This project focuses on a very challenging problem in the medical community, the development of treatments for drug- resistant bacterial infections. The leading cause of clinical complications in the United States is nocosomial infections caused by the drug-resistant pathogen, Staphylococcus aureus. There is currently a dire need for new drugs to be developed for controlling these infections. Towards this goal, our proposal discusses efforts to identify the biochemical and chemical basis for antibacterial activity of N-thiolated beta-lactams, a new class of antibiotics discovered in our laboratory at University of South Florida. Preliminary data on more than 50 active analogues indicates that these substances possess antimicrobial behavior selective for Staphylococcus bacteria, with enhanced activity towards multi-drug resistant strains (MRSA). Unlike all previously known beta-lactam drugs, these compounds appear to affect early developmental events during cell replication, not cell wall crosslinking. These compounds have highly unusual structure-activity profiles which need to be explored further. Electron microscopy experiments indicate that our lactams produce no morphological defects in MRSA cells, or cytotoxic effects in human fibroblasts. The compounds are stable over a wide pH range (pH 1 to 10), and are totally transparent to penicillinases as well as to most chemical reagents we have studied. Our Proposed Studies consist of three Specific Aims. Aim 1 is to study the biochemical and chemical basis for antimicrobial activity, and will include (1) electron microscopy experiments to look for morphological defects in bacterial cells due to damage by the lactams, and to identify where the drug accumulates in the cell, (2) radiolabeling to determine which of the primary cellular processes (cell wall synthesis, protein synthesis, or nucleic acid synthesis) are affected by the beta-lactams, and the means by which the drugs function chemically, and (3) studies to define whether the lactams bind covalently or noncovalently to the biological target, and to identify the cellular target. Aim 2 is to assess further whether the lactams are cytotoxic to mammalian cells. Aim 3 is to develop new approaches to solid phase synthesis of affinity resins (for experiments on isolating the cellular target) and lactam libraries (for expanded drug screening). We also aim to develop novel prodrug delivery systems for the prevention and treatment of MRSA infections. We believe that these studies will provide extraordinary opportunities to develop new therapeutics and approaches for the control of hospital-borne drugresistant infections. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PEPTIDOMIMETICS ANTIBACTERIALS
OF
D-ALA-D-ALA
AS
33
NOVEL
Principal Investigator & Institution: Dunlap, Norma K.; Chemistry; Middle Tennessee State University Murfreesboro, Tn 37132 Timing: Fiscal Year 2003; Project Start 01-JUN-2003; Project End 31-MAY-2006 Summary: (provided by applicant): Although there are currently numerous antibacterial drugs on the market, many bacteria are becoming resistant to existing drugs, and the emergence of these drug-resistant microorganisms is a significant threat to public health. Virtually all classes of antibacterials in use have been circumvented to some extent by various resistance mechanisms and as a result there is a continual need for new structural classes of antibacterials. Penicillins are bacterial cell wall synthesis inhibitors and act by inhibition of Penicillin Binding Proteins (PBP's), also know as D-Dpeptidases. The substrate for the D-D-peptidases is the cell wall peptidoglycan strand ending in D-alanine-D-alanine. However, penicillins and other drugs of that class were not designed to inhibit the D-D-peptidases. The objective of this application is to design and synthesize inhibitors of the D-D-peptidases as potential antibacterial drugs. Hydroxyethylene peptidomimetics of peptidic enzyme substrates such as the HIV protease substrate have been previously developed as drugs. A similar design concept should also apply to the D-D-peptidase substrate. The long-term objective of this project is to synthesize a series of peptidomimetics of the dipeptide D-alanine-D-alanine. These compounds will be tested for enzyme binding and for antibacterial activity. Various peptidomimetics have been designed and the syntheses of several have been initiated. Linear analogs of D-ala-D-ala containing a carboxylic acid will be synthesized, as will cyclopropyl analogs. Tetrazoles have been used successfully as bioisosteric replacements for the carboxylic acids in a number of drugs. An example is the angiotensin receptor antagonist Losartan. Along those lines, both linear and cyclopropyl analogs of D-ala-Dala containing a tetrazole as a replacement for the carboxylic acid will be synthesized and tested for enzyme binding and antibacterial activity. The proposed compounds constitute an entirely new structural class of potential antibacterials and as such should possess activity against resistant organisms. This would have a significant impact in the ability to treat bacterial infections. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PREVENTION OF SERIOUS BACTERIAL IN HIV CHILDREN Principal Investigator & Institution: Ruff, Andrea J.; Associate Professor; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002; Project Start 01-DEC-2001; Project End 30-NOV-2002 Summary: In this Phase II/III study, the regimen of azithromycin plus atovaquone is being compared to trimethoprim-sulfamethoxazole in the prevention of serious bacterial infections among 2-18 year old HIV-infected children. Pneumocystis carinii breakthrough rates and the occurrence of other opportunistic infections is also being monitored. Two children have been enrolled in this study at JHU. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PREVENTION OF UTI IN PERSONS WITH SPINAL CORD INJURY Principal Investigator & Institution: Darouiche, Rabih O.; Phys Med and Rehabilitation; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2004; Project Start 01-FEB-2004; Project End 31-JAN-2008
34
Bacterial Infections
Summary: (provided by applicant): People who have spinal cord injury (SCI) experience an increase in bacterial infections. These infections always interfere with quality of life of the patient, frequently result in lost productivity due to hospitalization and, in the long term, cause significant morbidity. Bacteria that cause symptomatic urinary tract infections (UTI) can usually be found in the urine beforehand. However, not all bacteria present in the bladder of people with SCI lead to UTI. Bacteria usually colonize the bladder of most SCI patients who rely upon indwelling catheterization, and of many others who use other methods for bladder management. Some of these bacteria result in UTI while other bacteria colonize the bladder without causing overt symptoms of infection. In the SCI patient group, seemingly benign bacterial colonization of the bladder is often left untreated as it may offer some protection against more harmful bacteria. One such seemingly benign bacterium, called E. coli 83972, was identified previously. Several studies revealed that E. coli 83972 was able to persist in the human bladder for extended periods, up to four years (8 to 12 months on average), after it was experimentally implanted. SCI test subjects who maintained bladder colonization with E. coli 83972 remained essentially free from symptoms of bladder infection for as long as E. coli 83972 was present. They remained essentially free of symptoms even when other bacteria were present in the urine together with E. coli 83972. UTI is an almost universal occurrence among persons with SCI. It is associated with large personal and monetary cost to the patient and to society. As a consequence, study of the impact of deliberate bladder colonization with E. coil 83972 on the occurrence of symptomatic UTI has the potential for improving the quality of life of SCI patients and decreasing the cost of health care. The proposed study consists of a single aim that deals with the efficacy of this method in SCI patients. The PIs propose a prospective, randomized, double-blind placebo-controlled multicenter trial to evaluate the clinical efficacy of this innovative therapeutic protocol. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PROMOTION OF PNEUMOCOCCAL ADHERENCE BY VIRAL INFECTION Principal Investigator & Institution: Zhang, Jing-Ren; Alld Health Education Programs; Albany Medical College of Union Univ Albany, Ny 12208 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 29-SEP-2005 Summary: (provided by applicant): Respiratory diseases caused by Streptococcus pneumoniae (pneumococcus) and influenza virus infections are major public health problems worldwide. Many studies have suggested a synergistic interaction between S. pneumoniae and influenza virus in causing human diseases. It is well known that influenza virus infection of the upper respiratory tract predisposes to secondary infections caused by S. pneumoniae in humans and experimental animals. In fact, most mortality during influenza epidemics arises from secondary bacterial infections including pneumococcal infection. Therefore, unraveling this synergy by therapeutic interventions is an attractive strategy to control human diseases caused by S. pneumoniae and influenza virus infections. Although the mechanisms of this virusbacterial synergy remain to be defined, recent studies have implicated that viral infection may promote pneumococcal infection by promoting bacterial adhesion to respiratory epithelium. Our long-term goal is to understand how this viruspneumococcus synergy can be modulated therapeutically for effective control of pneumococcal infection. The objective of this application is to determine how viral infection promotes pneumococcal adhesion to epithelial cells. We hypothesize that viral infection promotes pneumococcal adhesion by modulating the expression of cellular
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receptors. We will test our hypothesis and achieve the objective of this application by pursuing the following two specific aims. Specific Aim 1: We will determine host epithelial receptors for S. pneumoniae that are induced by influenza virus. Primary human respiratory epithelial cells will be infected with influenza virus to identify virusinduced epithelial membrane proteins by proteomic approach. The virus-induced proteins will be further evaluated for potential interactions with S. pneumoniae. Specific Aim 2: We will identify bacterial surface proteins that are involved in virus-promoted adhesion by signature-tagged mutagenesis. It is our expectation that these approaches will identify novel ligand-receptor interactions required for bacterial adhesion. These results will be significant because they are expected to open up new areas for future investigation of virus-bacterial interaction in microbial pathogenesis. Furthermore, novel pneumococcal proteins and host receptors identified in this application may provide new targets for preventive interventions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: REDUCING ANTIMICROBIAL RESISTANCE: A RANDOMIZED TRIAL Principal Investigator & Institution: Finkelstein, Jonathan A.; Harvard Pilgrim Health Care, Inc. 93 Worcester St Wellesley, Ma 02481 Timing: Fiscal Year 2003; Project Start 30-SEP-1999; Project End 29-SEP-2004 Summary: Reducing antimicrobial use and its impact on the growing threat of antimicrobial resistance will require collaboration of physicians, health care delivery systems, public health officials, and the community. We propose to develop and test physician and patient level interventions in entire communities in a randomized trial to determine if they reduce prescribing and the prevalence of resistance. We will also assess the direct and indirect costs of such a program. The state's two leading managed care organizations, the Massachusetts Department of Public Health (MDPH), and Harvard Medical School will collaborate to achieve the following specific aims: 1. Perform a randomized controlled effectiveness trial in 16 entire communities of an intervention to decrease unnecessary antimicrobial prescribing for children. 2. Measure the effect of the intervention on nasopharyngeal carriage of resistant and susceptible pneumococus and other respiratory pathogens in children. 3. Using targeted active surveillance, measure the intervention's effect on the incidence of both susceptible and resistant serious bacterial infections. 4. Assess the intervention's cost-effectiveness, taking into account the overall costs of medical care, and non-medical care costs for target conditions. 5. Assess physician and patient attitudes about reduced antimicrobial use. Sixteen Massachusetts communities in which most children receive care from a few practices will be randomized to intervention or observation status. We will work through the practices, the MCOs and local institutions to distribute educational materials to all parents in these practices, as well as implement a physician behavior change intervention using credible experts, community opinion leaders, and practicebased peer leaders. We will use MCOs' automated pharmacy and claims data to assess changes in prescribing and utilization of health care, and to provide feedback to prescribers. The prevalence of resistant respiratory flora will be assessed by surveillance cultures from healthy children and the occurrence of resistant bacterial infections will be determined through active surveillance systems in the participating communities. Cost-effectiveness analysis will estimate the financial and other costs per resistant infection avoided. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Bacterial Infections
Project Title: REGULATION OF B CELL CLONAL DIVERSITY Principal Investigator & Institution: Kearney, John F.; Professor; Microbiology; University of Alabama at Birmingham Uab Station Birmingham, Al 35294 Timing: Fiscal Year 2002; Project Start 01-SEP-1978; Project End 31-JAN-2006 Summary: B cells develop in a series of programmed developmental stages. These inbuilt mechanisms are subject to selective forces through the B cell receptor (BCR) from both self and extrinsic antigens. It is proposed that interactions through the BCR influence the fate of individual cells with respect to their phenotype and function. Conventional and germfree mice will be compared with respect to the diversity of B cells that populate the different areas of the spleen and other sites including the peritoneal cavity and gut-associated tissues. The localization of follicular (FO), marginal zone (MZ) in the spleen and B-1 cells in the peritoneal cavity reflects the different functions of each with respect to the types of antigens recognized by each subset and their roles as antibody producers and antigen presenters. MZ B cells are strategically located in the spleen where they are able to interact with blood borne antigens. The hypothesis will be tested that this B cell subset expresses BCR's that bind common bacterial antigens.and can mount a rapid, protective T cell-independent antibody response to blood borne organisms. In addition, we propose that MZ B cells play an important role in the presentation of antigens in T- dependent responses involving Tfollicular B cell interactions. The MZ is a late developing site with the important consequence, that in man and mouse, neonates are particularly susceptible to bacterial infections including Gram positive organisms. A variety of transgenic and gene targeted mice will be used to determine the developmental origins of this area of the spleen. Monoclonal antibodies (blabs) specific for MZ B cells will be used to identify (1) these and related B cells in other tissues, and (ii) to define molecules expressed by these cells that are involved in localizing them to this area of the spleen and endow them with unique functions. MZ B and B- 1 cells, different from FO B cells, appear to be chronically activated by self-antigen and have special survival mechanisms that permit them to remain as useful members of the B cell repertoire despite their self-reactivity. Genes will be sought that are uniquely expressed in these subsets, that keep them in this activated state, and are responsible for their survival. A consequence of their activated states is a predisposition to give rise to lymphomas with characteristic phenotypes. The various Mabs and genetic probes developed to characterize normal B cells will be used to race the development of B cell neoplasia in mouse models. By this approach a role will be determined for chronic antigenic stimulation in the development of B cell tumors. The overall goals of this proposal are to determine the role that these B cell subsets play in the development of the normal immune system. As a result, new information will be forthcoming with respect to the immune response to bacterial infections, immunodeficiencies, autoimmune diseases, and B cell neoplasia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: REGULATORY ROLES OF LACTOFERRIN IN HEMOSTASIS Principal Investigator & Institution: Wu, Haifeng M.; Pathology; Ohio State University 1960 Kenny Road Columbus, Oh 43210 Timing: Fiscal Year 2002; Project Start 01-APR-1995; Project End 31-MAR-2004 Summary: Lactoferrin is a prominent component of neutrophil secondary granules and can be released when neutrophils are activated. The concentration of lactoferrin in blood has been demonstrated to be increased in certain inflammatory diseases. In contrast to a well described biochemical characterization of lactoferrin as an iron-binding protein, its
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37
physiological role in the regulation of inflammation and other host defense mechanisms is unclear. The current proposed study will test three hypotheses: (i) lactoferrin derived from neutrophils is an important physiological mediator in the down-regulation of blood anticoagulation; (ii) the significant elevation of lactoferrin in blood, or at sites of inflammation can contribute significantly to the development of prothrombotic sequelae as seen in the disseminated intravascular coagulation (DIC) associated with bacterial infections; and (iii) the structural determinant(s) of lactoferrin involved in heparin binding is located within a specific sequence (residues 25-31) of the N-terminus. Thus, specific aims of this proposal are: (1) to determine the relationship between the elevation of plasma lactoferrin and the development of prothrombotic complications in patients with bacterial infections. The plasma lactoferrin concentration in patients with DIC resulting from different underlying diseases or with different inflammatory diseases will be examined; (2) to define the structural determinant(s) of lactoferrin involved in heparin binding. Both site- specific and domain-replacement mutagenesis will be used to determine the contribution of N-terminal basic residues (25 to 31) in heparin binding; (3) to study the activity of lactoferrin in the regulation of protein C anticoagulant pathway. Both the effect of lactoferrin on the generation of activated protein C and the specific binding of lactoferrin to chondroitin sulfate moiety of thrombomodulin will be examined. The completion of these studies will enable us to understand the biological role of lactoferrin in the regulation of inflammation and blood coagulation, and will provide new scientific background for the clinical evaluation and management of infectious diseases with thrombotic complications. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: RNA-SPECIFIC LIGANDS: AN APPROACH TO NEW ANTIVIRALS Principal Investigator & Institution: Beal, Peter A.; Associate Professor; Chemistry; University of Utah Salt Lake City, Ut 84102 Timing: Fiscal Year 2002; Project Start 01-JAN-2001; Project End 31-DEC-2003 Summary: Ribonucleic acid (RNA) function is central to all life, including that of viruses and bacteria. Antibacterial agents such as neomycin and erythromycin are examples of existing drugs that target sites in bacterial ribosomal RNAs. Unfortunately, bacteria are becoming increasingly resistant to these compounds via adaptation that allows for the modification of the RNA target or modification of the antibiotic. Human immunodeficiency virus (HIV), adenovirus (AV) and Epstein-Barr virus (EBV) are examples of human pathogens that all have unique RNA structures that appear necessary for replication. Each of these RNAs are potential targets for drug intervention. Unfortunately, our lack of understanding of the recognition of RNA by small molecules limits our ability to design high affinity ligands. The goal of this project is to identify low molecular weight ligands (<-l000 Da) that bind selectively to predefined RNA structures and inhibit the formation of protein-RNA complexes. This will be accomplished via the generation of structurally diverse libraries of molecules and the selection of library members with the requisite affinity and selectivity properties. The libraries are designed to contain intercalating ligands with appended functional groups capable of making specific contacts in the grooves of an RNA double helix. These experiments will ultimately lead to the ability to design and synthesize molecules that bind selectively to specific sequences of duplex RNA. In addition, these new compounds would have the potential to be developed into therapeutics for viral and bacterial infections. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Bacterial Infections
Project Title: ROLE OF SURFACTANT PROTEIN B IN INNATE AIRWAY DEFENSE Principal Investigator & Institution: Baatz, John E.; Assistant Professor; Pediatrics; Medical University of South Carolina 171 Ashley Ave Charleston, Sc 29425 Timing: Fiscal Year 2002; Project Start 01-JUL-2001; Project End 30-JUN-2005 Summary: (Applicant's Abstract): Surfactant protein B (SP-B) is essential for postnatal survival and normal surfactant function. SP-B is capable of reorganizing lipid bilayers and is fusigenic protein. Based on these characteristics and the similarity of SP-B's amino acid sequence to those of several antimicrobial peptides, we hypothesized that SP-B itself has antimicrobial properties. Preliminary data obtained by our laboratory have demonstrated he SP-B has in vitro antibacterial activity. The significance of this observation is three-fold. First SP-B is expressed solely in mammalian lungs where it is secreted into the airway lining fluid by bronchial, bronchiolar and alveolar epithelial cells at relatively high concentrations. For that reason, it may act as a component of local mucosal immunity to prevent bacterial infections in these and other regions of the lung. Second, surfactant replacement preparations containing SP-B are presently used for safe treatment of neonatal respiratory distress syndrome, and such preparations do not elicit immunological responses. Third, SP-B is easily isolated or synthesized. Thus, there is potential for safe therapeutic use of SP-B for treatment of pulmonary bacterial infections. Use of SP-B to prevent or eradicate bacterial growth in the airway would be of particular importance in cystic fibrosis (CF), where progressive lung damage occurs as a result of persistent bacterial infection. Moreover, we have found aberrant forms of SP-B in bronchoalveolar lavage (BAL) of adult CF patients and that mature SP-B may be degraded or modified. We will test the hypothesis that SP-B is a component of the innate pulmonary immune system, protecting the human airway against bacterial infection, and this activity may be compromised in the airways of CF patients. The aims of this proposal are 1) to determine molecular forms and activity of SP-B in BAL from CF patients vs. those of normal humans, 2) to delineate the sites in the airway where SPB is found and in which it may play a defensive role, 3) to characterize the antibacterial activity of SP-B in vitro, and 4) to develop preparations containing native or synthetic SP-B for use as antibacterial agents in vivo. Results from the proposed experiments will lay the foundation for therapeutic use of SP-B for eradication of bacterial lung infections. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ROLE INFLAMMATION
OF
THE
CD14
LPS
RECEPTOR
IN
CORNEAL
Principal Investigator & Institution: Ansel, John C.; Professor and Chair; Dermatology; Northwestern University Office of Sponsored Research Chicago, Il 60611 Timing: Fiscal Year 2002; Project Start 01-MAY-2000; Project End 30-JUN-2004 Summary: Gram negative infections of the cornea with organisms such as Pseudomonas can have profound consequences for patients including bacterial keratitis which can lead to visual loss. A significant portion of the inflammatory response to Pseudomonas is mediated by LPS. We have recently reported that the cornea expresses one of the principal LPS receptors, CDI4. The long-term goal of this project is to determine the role of the cornea itself in mediating host innate immune responses to bacterial infections. This application will test the hypothesis that corneal cells express functional CD14 receptors that, when activated by LPS, are capable of triggering the expression of proinflammatory peptides which facilitate the host resolution of gram negative corneal infections. To experimentally test this hypothesis, we will undertake the following Specific Aims: SPECIFIC AIM #1: To examine the expression and regulation of the CD14
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receptor in the cornea; SPECIFIC AIM #2: To assess the functional competence of corneal CD14 receptors; SPECIFIC AIM #3: To assess the ability of CD14 activation to induce innate inflammatory responses in the cornea; and SPECIFIC AIM #4: To determine the in vivo role of the corneal CD14 receptor in mediating corneal inflammatory responses in a murine experimental model of Pseudomonas bacterial keratitis. To carry out these studies, human and murine corneal cells and corneal tissue will be used as well as genetically altered strains of mice in which CD14 expression is absent, diminished, or overexpressed. Cornea CD14 expression will be measured constitutively and after exposure to bacterial reagents (Pseudomonas, LPS, LPS/LBP) and cytokines (IL-1 and TNFa). CD14 functional activity to bacterial reagents will be measured by intracellular calcium responses, tyrosine kinase activity, and NF-kappaB activity. Corneal CD14 induced innate inflammatory responses to bacterial reagents will be determined by measuring the expression of corneal cytoidnes (IL-I, IL-6, and TNFa), chemokines (IL-8), and cell adhesion molecules (ICAM-1). A murine model using CD14 genetically altered animals will be utilized to assess the in vivo role of CDI4 in experimental Pseudomonas bacterial keratitis. The activation of corneal CD14 may have both beneficial and detrimental inflammatory responses. Understanding the role of CD14 in mediating corneal innate immunity may result in novel approaches to the management of corneal infectious diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ROLE PATHOGENESIS
OF
TYROSINE
KINASES
IN
EPEC
AND
EHEC
Principal Investigator & Institution: Kalman, Daniel; Pathology and Lab Medicine; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 29-FEB-2008 Summary: (provided by applicant): Enteropathogenic E.coli (EPEC) and enterohaemorrhagic E. coli (EHEC O157:H7) are deadly contaminants in food and water world wide causing diarrhea and death. Formation of actin-filled membrane "pedestals" (also called "A/E lesions") beneath EPEC and EHEC are essential for the development of disease. Tyrosine phosphorylation by an unidentified host cell kinase of a translocated bacterial virulence factor, called Tir, is essential for EPEC pedestal formation. Our preliminary evidence indicates (i) that the cellular kinase resembles Abl, but that other tyrosine kinases may also suffice, (ii) that Abl or a related kinase regulates both EPEC and EHEC pathogenesis, and (iii) that PD compounds, which inhibit Abl kinase and are being developed to treat cancer caused by dysregulated Abl, block pathogenic effects in vitro of EPEC and EHEC, and of C. rodentium, a related pathogen that forms A/E lesions in mice. The goal of Aim I is to identify redundant Abl-like kinases. The goal of Aim II is to determine how Abl kinase regulates formation of A/E lesions. Such information will prove essential to understanding the physiological mechanisms of A/E lesion formation, and will inform the design of even more specific inhibitors useful in treating not only bacterial infections but also cancers caused by dysregulated tyrosine kinases. The goal of Aim III is to establish the efficacy of PD inhibitors in mice infected with C. rodentium. Such experiments are an important prelude to clinical testing of drug efficacy in human patients infected with EPEC or EHEC. The need is apparent. EPEC and EHEC are classified by the NIAID as Category B pathogens. In developing countries, antibiotics and rehydration therapy are generally unavailable to treat EPEC infections, and a requirement for high patient compliance further reduces their efficacy when they are available. For EHEC, antibiotics exacerbate symptoms perhaps by lysing bacteria and releasing toxins and, in the United States, are contraindicated. Furthermore,
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Bacterial Infections
drug-resistant EHEC strains have been documented. In this regard, because PD compounds affect the host and not the bacterium, selecting resistant strains with PD is far less likely than with conventional antibiotics or antimicrobial compounds. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SERINE PROTEINASES & LUNG HOST DEFENSE AGAINST BACTERIA Principal Investigator & Institution: Belaaouaj, Abderazzaq; Assistant Professor in Medicine; Barnes-Jewish Hospital Ms 90-94-212 St. Louis, Mo 63110 Timing: Fiscal Year 2002; Project Start 15-FEB-2001; Project End 31-JAN-2005 Summary: (Applicant's abstract): Human and mouse neutrophils contain neutrophil elastase (NE), cathepsin G (CG) and proteinase 3 (PR 3). The capacity of these serine proteinases, especially NE, to kill bacteria in vitro and to cleave extracellular matrix (ECM) proteins leading to tissue damage is well established, but whether these enzymes kill bacteria in vivo and have specific bacterial target molecules remains unknown. Also, the potential role of the ECM degradation products generated by these proteinases in host defense against bacteria has not been explored. Using mice deficient in NE and CG, we have demonstrated that NE, but not CG, reduces mortality from Gram negative bacterial infections. To date, the antibacterial role of PR 3 has not been clarified in vivo. We propose to generate mice deficient in PR 3 by gene targeting and subject them to bacterial lung infections to determine the relative importance of PR 3 in host defense against bacteria in the lung. Our preliminary data show that the outer membrane protein (Omp) A represents a critical target for NE-mediated killing of E. coli. We hypothesize that Omps represent essential targets of NE to kill other Gram negative bacteria. Recently, we have found that NE kills Pseudomonas aeruginosa in vitro, and degrades its major Omp F, which is unrelated to Omp A. We propose to determine the importance of Omp F in NE-mediated killing of Pseudomonas aeruginosa in isolated neutrophils and in vivo models of acute and chronic pulmonary infections. Wild type Pseudomonas aeruginosa and isogenic strains deficient in Omp F will be used in these studies. We have observed that elastin peptides from NE-digested human lung elastin are bactericidal for Klebsiella pneumoniae in vitro. These data constitute the first evidence of antibacterial role of ECM derived peptides and reveal a novel role for ECM. We will isolate these elastin fragment(s) and investigate their bactericidal activity in vitro and in vivo. These studies will advance our knowledge of the functional properties of lung serine proteinases and ECM peptides. Also, characterization of NE-degraded elastin may provide novel antimicrobial peptides in humans. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: STRUCTURAL STUDIES OF BACTERIAL QUORUM SENSING REGULATOR Principal Investigator & Institution: Churchill, Mair E.; Associate Professor; Pharmacology; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, Co 800450508 Timing: Fiscal Year 2002; Project Start 01-JUL-2001; Project End 31-MAY-2006 Summary: (provided by applicant): Persistent bacterial infections are a major cause of death in cystic fibrosis patients and immune-compromised individuals. A number of gram-negative bacteria including Pseudomonas aeruginosa, a major pathogen in cystic fibrosis, cause infections that are difficult to treat because the bacteria form a "biofilm community" that renders them less sensitive to traditional antibiotics. Quorum sensing,
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mediated by acylhomoserine lactone (AHL) signaling molecules, regulates pathogenesis and biofilm formation in P. aeruginosa. Therefore, understanding the molecular basis of quorum sensing is a high priority in the development of novel anti-bacterial agents. The long term goal of this project is to extend the understanding of the quorum-sensing system to the atomic level to develop a detailed description of the mechanisms that control bacterial pathogenesis. The main focus of this proposal is the class of enzymes that produce the AHL signal, AHL-synthases, because bacteria lacking the AHL signal fail to become pathogenic or form stable biofilms. Although there are models of the mechanism of action of the AHL-synthases, there are currently no structures of any AHL synthase. High resolution structural information is absolutely essential for fully understanding the mechanism of AHL synthesis and will provide the basis for future structure-based inhibitor design for development of novel therapeutics. The specific aims for this project are: (I) determine the high resolution crystal structure of the Pantoea stewartii subsp. Stewartii AHL-synthase (EsaI) to understand its function, mechanism, and relationship to other enzymes that utilize similar substrates. Perform mutagenesis, binding and kinetics experiments with EsaI to better understand the catalytic mechanism and substrate specificity. (II) Study the P. aeruginosa AHLsynthase, LasI, using structural and biochemical techniques to understand how specificity of AHL production is determined. (III) Establish whether the AHL-synthase homologues in divergent organisms produce a homoserine lactone signal using mass spectrometry and activity assays. Study the structures and mechanisms to determine similarities to other AHL synthases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: STRUCTURE/FUNCTION OF BACTERIAL ADHESION PILI Principal Investigator & Institution: Bullitt, Esther S.; Assistant Professor; Physiology and Biophysics; Boston University Medical Campus 715 Albany St, 560 Boston, Ma 02118 Timing: Fiscal Year 2002; Project Start 01-MAY-1998; Project End 30-APR-2004 Summary: The aim of this research is to understand the structure and assembly of adhesion pili found on pathogenic bacteria, thereby providing insight into how the architecture of these pili supports their role as a virulence factor. Bacterial survival and colonization require attachment of the bacteria to hosts. In many stains, this process is initiated and maintained by pili; in Escherichia coli that cause pyelonephritis, adhesion and virulence depend on P-pili. Hib-pili expressed on the surface of Haemophilus influenzae mediate H. flu's colonization of the upper respiratory tract, and thus its ability to cause diseases such as childhood meningitis, otitis media, and pneumonia of the elderly. As bacteria become more resistant to traditional antibiotics, it is important to develop new therapies against bacterial infections. Structural information about adhesion pili will provide a basis for future rational design of new therapies to prevent bacterial binding or to remove pathogenic bacteria bound to the human host. The proposed research addresses this long-term goal through structural studies of bacterial adhesion pili. These studies focus on: 1) electron microscopy and three-dimensional (3D) helical reconstruction of P-pili preserved in vitreous ice and of Hib-pili negative stain, 2) controlled damage/recovery of pili to investigate the possibility of re-formation of intact helical filaments, 3) investigation of the 3-D structure of P-pili with mutant structural proteins (pilins), to examine regions of the PapA pilin essential for their assembly into tightly coiled helical filaments, 4) bacterial attachment assays, to assess the effect of mutations and the effect of damage on bacterial binding, and 5) in vitro
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reconstitution of hetero-pilin polymers from chaperone-pilin complexes, to improve our understanding of the bioassembly process of a prototypical macromolecule. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PROTEIN
STRUCTURE-FUNCTION
RELATIONSHIPS
OF
C-REACTIVE
Principal Investigator & Institution: Agrawal, Alok; Biochemistry; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-OCT-2002 Summary: (provided by applicant): C-reactive protein (CRP) is a major human acute phase protein and a component of the innate immune response. Its serum concentration is increased during inflammatory states, persists for the duration of the inflammatory process and returns to its normal low concentration following subsidence of inflammation. While CRP is felt to play a significant role in inflammation and host defense, the mechanisms by which CRP exerts its effects are unclear. In vitro, CRP binds to phosphocholine (PCh) moieties and can then bind to complement C1q and activate the classical complement pathway. In addition, binding of CRP to phagocytic cells via Fc receptors, with a variety of functional consequences, has been described. Recent publication of the crystal structures of CRP has provided insight into the amino acids that mediate binding of CRP to PCh, to Fc receptors, and to C1q, permitting generation of CRP mutants incapable of binding to PCh and to Fc receptors, as well as incapable of activating complement. Most known functional activities of CRP, in vitro, are associated with ligand-binding and subsequent complement activation or phagocytosis. Accordingly, we will employ such mutants to define the roles of binding to PCh and Fe receptors, and of complement activation in 2 model systems: a) the protective role of CRP in bacterial infections and b) the putative role of CRP in the pathogenesis of atherosclerosis resulting from its ability to bind to enzymatically-degraded LDL (ELDL). Our specific aims are: 1.To precisely define the ligand-binding sites on CRP required for binding to PCh, FcR and C1q and to generate mutants lacking these critical binding capabilities. 2. To define the role of these 3 binding capabilities in the protective effects of CRP in infection with Streptococcus pneumoniae, known to bind to CRP, and Salmonella typhimuriurn, which does not. We hypothesize that both complement activation and phagocytosis will be found to be involved in CRP-mediated protection of mice from bacterial infections. 3) To define the role of the 3 binding capabilities of interest on CRP-E-LDL interaction, and the role of such interaction in the pathogenesis of atherosclerosis. Our working hypothesis is that all 3 binding sites participate in the pathogenesis of atherosclerosis, by binding to E-LDL and initiating complement activation and uptake of E-LDL by macrophages. We will also determine the effects of injecting wild-type and mutant CRPs on the size of the atherosclerotic lesions formed in ApoE knock-out mice. These studies will provide substantial insight into the mechanisms by which this ancient protein may contribute to host defense, or alternatively, to pathogenesis of disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SURFACE PROTEIN ANCHORING IN GRAM-POSITIVE BACTERIA Principal Investigator & Institution: Schneewind, Olaf; Professor; Molecular Genetics & Cell Biol; University of Chicago 5801 S Ellis Ave Chicago, Il 60637 Timing: Fiscal Year 2002; Project Start 01-FEB-1996; Project End 31-JAN-2005
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Summary: (Adapted from the Applicant's Abstract): Human infections caused by Grampositive bacteria present a serious therapeutic challenge due to the appearance of antibiotic-resistant strains. Of particular concern is Staphylococcus aureus, Staphylococcus epidermidis, and Enterococcus faecalis, Gram-positive organisms that are the most common cause of bacterial infections in American hospitals. These nosocomial pathogens have developed resistance mechanisms to all known antibiotic regimens and the development of novel targets for antimicrobial therapy is urgently needed. Surface proteins of Gram-positive organisms fulfill many important functions during the pathogenesis of human infections. This proposal describes the mechanism for surface protein anchoring in Gram-positive bacteria, which may serve as a target for antibacterial therapy. Staphylococcal surface proteins harbor a C-terminal sorting signal that functions first to retain polypeptides within the secretory pathway. Retention is followed by cleavage of the sorting signal between the threonine (T) and the glycine (G) of the LPXTG motif. The carboxyl of threonine is subsequently amide linked to the free amino group of peptidoglycan crossbridges, thereby anchoring the C-terminal end of surface proteins to the staphylococcal cell wall. Sortase, a membrane anchored enzyme of S. aureus, catalyzes a transpeptidation reaction, capturing cleaved surface protein as a thioester intermediate at the active site sulfhydryl. Nucleophilic attack of the amino group of pentaglycine crossbridges resolves the thioester intermediate, resulting in cell wall anchored surface protein and in regeneration of enzyme sulfhydryl. The elements and enzymes of surface protein anchoring, i.e., the LPXTG motif, the amino groups of peptidoglycan as well as sortase, are conserved in Gram-positive bacteria. This, we propose that surface protein anchoring is a universal mechanism. To test this hypothesis, we will characterize sortase function in S. aureus, E. faecalis and L. monocytogenes. Further, we propose identification of the peptidoglycan substrate of the sortase reaction, using in vivo labeling techniques as well as biochemical characterization of sorting intermediates in S. aureus, E. faecalis and L. monocytogenes. A genetic screen for S. aureus mutants defective in the retention step of surface protein anchoring will identify missing components of the cell wall sorting machinery. 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 “bacterial infections” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for bacterial infections in the PubMed Central database: •
3 4
Efficacies of ABT-773, a New Ketolide, against Experimental Bacterial Infections. by Mitten MJ, Meulbroek J, Nukkala M, Paige L, Jarvis K, Oleksijew A, Tovcimak A, 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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Hernandez L, Alder JD, Ewing P, Or YS, Ma Z, Nilius AM, Mollison K, Flamm RK.; 2001 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=90696 •
Role of Interleukin-18 (IL-18) in Mycobacterial Infection in IL-18-Gene-Disrupted Mice. by Sugawara I, Yamada H, Kaneko H, Mizuno S, Takeda K, Akira S.; 1999 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=116007
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 bacterial infections, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “bacterial infections” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for bacterial infections (hyperlinks lead to article summaries): •
A multicenter comparative study of cefepime versus broad-spectrum antibacterial therapy in moderate and severe bacterial infections. Author(s): Badaro R, Molinar F, Seas C, Stamboulian D, Mendonca J, Massud J, Nascimento LO; Latin American Antibiotic Research Group (LAARG). Source: The Brazilian Journal of Infectious Diseases : an Official Publication of the Brazilian Society of Infectious Diseases. 2002 October; 6(5): 206-18. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12495602&dopt=Abstract
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A prospective study of hemodialysis access-related bacterial infections. Author(s): Saeed Abdulrahman I, Al-Mueilo SH, Bokhary HA, Ladipo GO, Al-Rubaish A. Source: Journal of Infection and Chemotherapy : Official Journal of the Japan Society of Chemotherapy. 2002 September; 8(3): 242-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12373488&dopt=Abstract
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A randomized controlled clinical trial on etimicin, a new aminoglycoside antibiotic, versus netilmicin in the treatment of bacterial infections. Author(s): Zhao C, Li J, Hou J, Guo M, Zhang Y, Chen Y. Source: Chinese Medical Journal. 2000 November; 113(11): 1026-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11776118&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 randomized controlled clinical trial on piperacillin/tazobactam versus ticarcillin/clavulanic acid for the treatment of bacterial infections. Author(s): Hou F, Li J, Gao L, Chen Y. Source: Chinese Medical Journal. 1998 November; 111(11): 1039-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11189212&dopt=Abstract
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A randomized, controlled clinical trial on meropenem versus imipenem/cilastatin for the treatment of bacterial infections. Author(s): Hou F, Li J, Wu G, Zheng B, Chen Y, Gu J, Wang H, Huo L, Xue X, Jia C, Yin Y, Tian X, Ren S. Source: Chinese Medical Journal. 2002 December; 115(12): 1849-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12622937&dopt=Abstract
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A study of orofacial bacterial infections in elderly Nigerians. Author(s): Ugboko VI, Owotade FJ, Ajike SO, Ndukwe KC, Onipede AO. Source: Sadj. 2002 October; 57(10): 391-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12518690&dopt=Abstract
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Abnormal directed migration of blood polymorphonuclear leukocytes in rheumatoid arthritis. Potential role in increased susceptibility to bacterial infections. Author(s): Aglas F, Hermann J, Egger G. Source: Mediators of Inflammation. 1998; 7(1): 19-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9839694&dopt=Abstract
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Acute bacterial infections and HIV disease. Author(s): Gilks CF. Source: British Medical Bulletin. 1998; 54(2): 383-93. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9830204&dopt=Abstract
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Acute viral and bacterial infections of the salivary glands. Author(s): McQuone SJ. Source: Otolaryngologic Clinics of North America. 1999 October; 32(5): 793-811. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10477787&dopt=Abstract
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Advances in the research and development of chemotherapeutic agents for respiratory tract bacterial infections. Author(s): Cazzola M, Blasi F, Centanni S, Donner CF, Allegra L. Source: Pulmonary Pharmacology & Therapeutics. 2001; 14(5): 367-81. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11603950&dopt=Abstract
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Amino-terminal truncation of procalcitonin, a marker for systemic bacterial infections, by dipeptidyl peptidase IV (DP IV). Author(s): Wrenger S, Kahne T, Bohuon C, Weglohner W, Ansorge S, Reinhold D. Source: Febs Letters. 2000 January 21; 466(1): 155-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10648832&dopt=Abstract
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Amoxicillin-clavulanic acid versus cefotaxime in the therapy of bacterial infections in cirrhotic patients. Author(s): Ricart E, Soriano G, Novella MT, Ortiz J, Sabat M, Kolle L, Sola-Vera J, Minana J, Dedeu JM, Gomez C, Barrio JL, Guarner C. Source: Journal of Hepatology. 2000 April; 32(4): 596-602. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10782908&dopt=Abstract
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Anatomical considerations in the diagnosis and management of acute maxillofacial bacterial infections. Author(s): Bridgeman A, Wiesenfeld D, Newland S. Source: Aust Dent J. 1996 August; 41(4): 238-45. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8870277&dopt=Abstract
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Antibiotic prophylaxis for the prevention of bacterial infections in cirrhotic patients with gastrointestinal bleeding: a meta-analysis. Author(s): Bernard B, Grange JD, Khac EN, Amiot X, Opolon P, Poynard T. Source: Hepatology (Baltimore, Md.). 1999 June; 29(6): 1655-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10347104&dopt=Abstract
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Antibiotic prophylaxis for the prevention of bacterial infections in cirrhotic patients with gastrointestinal hemorrhage. Author(s): Lin HC. Source: Zhonghua Yi Xue Za Zhi (Taipei). 2002 August; 65(8): 361-2. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12455804&dopt=Abstract
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Antibiotic prophylaxis of bacterial infections in cirrhotic inpatients: a meta-analysis of randomized controlled trials. Author(s): Soares-Weiser K, Brezis M, Tur-Kaspa R, Paul M, Yahav J, Leibovici L. Source: Scandinavian Journal of Gastroenterology. 2003 February; 38(2): 193-200. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12678337&dopt=Abstract
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Antibiotics for gram-positive bacterial infections. Vancomycin, teicoplanin, quinupristin/dalfopristin, and linezolid. Author(s): Lundstrom TS, Sobel JD. Source: Infectious Disease Clinics of North America. 2000 June; 14(2): 463-74. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10829266&dopt=Abstract
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Antimicrobial therapy for serious bacterial infections in children in a primary care setting--a poll of experts. Author(s): Zar HJ, Hussey G. Source: South African Medical Journal. Suid-Afrikaanse Tydskrif Vir Geneeskunde. 1999 July; 89(7): 739-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10470305&dopt=Abstract
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Association between antibodies to heat shock protein 65 and coronary atherosclerosis. Possible mechanism of action of Helicobacter pylori and other bacterial infections in increasing cardiovascular risk. Author(s): Birnie DH, Holme ER, McKay IC, Hood S, McColl KE, Hillis WS. Source: European Heart Journal. 1998 March; 19(3): 387-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9568442&dopt=Abstract
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Autoantibodies with a protective function: polyreactive antibodies against alkaline phosphatase in bacterial infections. Author(s): Ritter K, Fudickar A, Heine N, Thomssen R. Source: Medical Microbiology and Immunology. 1997 October; 186(2-3): 109-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9403838&dopt=Abstract
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Bacterial infections after renal transplantation. Author(s): Schmaldienst S, Horl WH. Source: Nephron. 1997; 75(2): 140-53. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9041533&dopt=Abstract
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Bacterial infections and atopic dermatitis. Author(s): Breuer K, Kapp A, Werfel T. Source: Allergy. 2001 November; 56(11): 1034-41. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11703215&dopt=Abstract
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Bacterial infections as a cause of cancer. Author(s): Correa P. Source: Journal of the National Cancer Institute. 2003 April 2; 95(7): E3. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12671026&dopt=Abstract
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Bacterial infections during immunosuppression - immunosuppressive agents interfere not only with immune response, but also with polymorphonuclear cell function. Author(s): Schmaldienst S, Horl WH. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 1996 July; 11(7): 1243-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8672015&dopt=Abstract
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Bacterial infections in adult patients hospitalized with AIDS: case-control study of prophylactic efficacy of trimethoprim-sulfamethoxazole versus aerosolized pentamidine. Author(s): Tabet SR, Krone MR, Hooton TM, Koutsky LA, Holmes KK. Source: International Journal of Std & Aids. 1997 September; 8(9): 563-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9292345&dopt=Abstract
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Bacterial infections in cirrhosis: epidemiological changes with invasive procedures and norfloxacin prophylaxis. Author(s): Fernandez J, Navasa M, Gomez J, Colmenero J, Vila J, Arroyo V, Rodes J. Source: Hepatology (Baltimore, Md.). 2002 January; 35(1): 140-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11786970&dopt=Abstract
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Bacterial infections in cirrhotics: do they cause upper gastrointestinal bleeding? Author(s): Dasarathy D. Source: Natl Med J India. 1998 May-June; 11(3): 129-30. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9707704&dopt=Abstract
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Bacterial infections in HIV: the extent and nature of the problem. Author(s): Brettle RP. Source: International Journal of Std & Aids. 1997 January; 8(1): 5-15. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9043975&dopt=Abstract
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Bacterial infections in liver disease. Author(s): Navasa M, Rimola A, Rodes J. Source: Seminars in Liver Disease. 1997; 17(4): 323-33. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9408968&dopt=Abstract
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Bacterial infections in patients requiring admission for an acute exacerbation of COPD; a 1-year prospective study. Author(s): Groenewegen KH, Wouters EF. Source: Respiratory Medicine. 2003 July; 97(7): 770-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12854626&dopt=Abstract
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Bacterial infections in patients with cephalocele epidemiological data and therapy. Author(s): Mantero E, Russo G, Dondero M, Levato GL, Piatelli GI, Gastaldi M, Cama A. Source: European Journal of Pediatric Surgery : Official Journal of Austrian Association of Pediatric Surgery. [et Al] = Zeitschrift Fur Kinderchirurgie. 1996 December; 6 Suppl 1: 40-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9008824&dopt=Abstract
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Bacterial infections of the bronchial tree. Author(s): Wilson R. Source: Current Opinion in Pulmonary Medicine. 1997 March; 3(2): 105-10. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9193854&dopt=Abstract
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Bacterial infections remain a danger. Author(s): Miller C. Source: Rdh. 1996 August; 16(8): 26, 32. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9442639&dopt=Abstract
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Bacterial infections, immune overload, and MMR vaccine. Measles, mumps, and rubella. Author(s): Miller E, Andrews N, Waight P, Taylor B. Source: Archives of Disease in Childhood. 2003 March; 88(3): 222-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12598383&dopt=Abstract
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Bacterial infections. Author(s): Kovacs A, Leaf HL, Simberkoff MS. Source: The Medical Clinics of North America. 1997 March; 81(2): 319-43. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9093231&dopt=Abstract
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Bacterial infections. Author(s): Gray F. Source: Brain Pathology (Zurich, Switzerland). 1997 January; 7(1): 629-47. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9034570&dopt=Abstract
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Bactericidal group IIA phospholipase A2 in serum of patients with bacterial infections. Author(s): Gronroos JO, Laine VJ, Nevalainen TJ. Source: The Journal of Infectious Diseases. 2002 June 15; 185(12): 1767-72. Epub 2002 May 31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12085323&dopt=Abstract
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Bacteriophages: potential treatment for bacterial infections. Author(s): Duckworth DH, Gulig PA. Source: Biodrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy. 2002; 16(1): 57-62. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11909002&dopt=Abstract
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Bacterial Infections
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Beta-lactam/beta-lactamase inhibitor combinations: pharmacodynamic considerations and possible role in the management of bacterial infections in the neutropenic host. Author(s): Okereke C, Dudley MN. Source: The Journal of Antimicrobial Chemotherapy. 1998 June; 41 Suppl D: 43-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9688450&dopt=Abstract
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BPI-ANCA in transporter associated with antigen presentation (TAP) deficiency: possible role in susceptibility to Gram-negative bacterial infections. Author(s): Schultz H, Schinke S, Weiss J, Cerundolo V, Gross WL, Gadola S. Source: Clinical and Experimental Immunology. 2003 August; 133(2): 252-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12869032&dopt=Abstract
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CD1 molecules and CD1-dependent T cells in bacterial infections: a link from innate to acquired immunity? Author(s): Schaible UE, Kaufmann SH. Source: Seminars in Immunology. 2000 December; 12(6): 527-35. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11145858&dopt=Abstract
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Cefepime versus ceftazidime for the treatment of serious bacterial infections. Author(s): Ponce-de-Leon A, Lopez-Meneses M, Sifuentes-Osornio J. Source: Diagnostic Microbiology and Infectious Disease. 1999 December; 35(4): 263-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10668583&dopt=Abstract
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Cefpodoxime proxetil: a review of its use in the management of bacterial infections in paediatric patients. Author(s): Fulton B, Perry CM. Source: Paediatric Drugs. 2001; 3(2): 137-58. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11269640&dopt=Abstract
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Cefuroxime axetil: an updated review of its use in the management of bacterial infections. Author(s): Scott LJ, Ormrod D, Goa KL. Source: Drugs. 2001; 61(10): 1455-500. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11558834&dopt=Abstract
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Cerebrospinal fluid levels of soluble CD14 in inflammatory and non-inflammatory diseases of the CNS: upregulation during bacterial infections and viral meningitis. Author(s): Nockher WA, Wick M, Pfister HW. Source: Journal of Neuroimmunology. 1999 November 15; 101(2): 161-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10580799&dopt=Abstract
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Characteristics of Streptococcus pneumoniae and atypical bacterial infections in children 2-5 years of age with community-acquired pneumonia. Author(s): Esposito S, Bosis S, Cavagna R, Faelli N, Begliatti E, Marchisio P, Blasi F, Bianchi C, Principi N. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2002 December 1; 35(11): 1345-52. Epub 2002 November 13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12439797&dopt=Abstract
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Childhood visceral leishmaniasis complicated by bacterial infections. Author(s): Kadivar MR, Kajbaf TZ, Karimi A, Alborzi A. Source: East Mediterr Health J. 2000 September-November; 6(5-6): 879-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12197344&dopt=Abstract
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Chronic bacterial infections: living with unwanted guests. Author(s): Young D, Hussell T, Dougan G. Source: Nature Immunology. 2002 November; 3(11): 1026-32. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12407411&dopt=Abstract
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Circulating cytokine concentrations in tuberculosis and other chronic bacterial infections. Author(s): Poveda F, Camacho J, Arnalich F, Codoceo R, del Arco A, MartinezHernandez P. Source: Infection. 1999; 27(4-5): 272-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10885842&dopt=Abstract
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Cirrhosis and bacterial infections. Author(s): Vilstrup H. Source: Rom J Gastroenterol. 2003 December; 12(4): 297-302. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14726975&dopt=Abstract
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Clinical applications of a new parenteral antibiotic in the treatment of severe bacterial infections. Author(s): Holloway WJ, Palmer D. Source: The American Journal of Medicine. 1996 June 24; 100(6A): 52S-59S. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8678098&dopt=Abstract
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Combination antimicrobial therapy for bacterial infections. Guidelines for the clinician. Author(s): Rybak MJ, McGrath BJ. Source: Drugs. 1996 September; 52(3): 390-405. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8875129&dopt=Abstract
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Community acquired bacterial infections and their antimicrobial susceptibility in Nairobi, Kenya. Author(s): Malonza IM, Omari MA, Bwayo JJ, Mwatha AK, Mutere AN, Murage EM, Ndinya-Achola JO. Source: East Afr Med J. 1997 March; 74(3): 166-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9185414&dopt=Abstract
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Comparison of procalcitonin with interleukin 8, C-reactive protein and differential white blood cell count for the early diagnosis of bacterial infections in newborn infants. Author(s): Franz AR, Kron M, Pohlandt F, Steinbach G. Source: The Pediatric Infectious Disease Journal. 1999 August; 18(8): 666-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10462333&dopt=Abstract
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Concurrent serious bacterial infections in 2396 infants and children hospitalized with respiratory syncytial virus lower respiratory tract infections. Author(s): Purcell K, Fergie J. Source: Archives of Pediatrics & Adolescent Medicine. 2002 April; 156(4): 322-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11929363&dopt=Abstract
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Continuation of antibiotic therapy for serious bacterial infections outside of the hospital. Author(s): Gutierrez K. Source: Pediatric Annals. 1996 November; 25(11): 639-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8938001&dopt=Abstract
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Control of bacterial infections in the hard tick Dermacentor variabilis (Acari: Ixodidae): evidence for the existence of antimicrobial proteins in tick hemolymph. Author(s): Johns R, Sonenshine DE, Hynes WL. Source: Journal of Medical Entomology. 1998 July; 35(4): 458-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9701927&dopt=Abstract
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Critical evaluation of guidelines for the treatment of lower respiratory tract bacterial infections. Author(s): Cazzola M, Blasi E, Allegra L. Source: Respiratory Medicine. 2001 February; 95(2): 95-108. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11217915&dopt=Abstract
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Current aspects of bacterial infections of the skin. Author(s): Sadick NS. Source: Dermatologic Clinics. 1997 April; 15(2): 341-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9098643&dopt=Abstract
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Current spectrum of bacterial infections in patients with cancer. Author(s): Yadegarynia D, Tarrand J, Raad I, Rolston K. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2003 October 15; 37(8): 1144-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14523785&dopt=Abstract
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Definition of a discontinuous immunodominant epitope of intestinal alkaline phosphatase, an autoantigen in acute bacterial infections. Author(s): Kolbus N, Beuche W, Felgenhauer K, Mader M. Source: Clinical Immunology and Immunopathology. 1996 September; 80(3 Pt 1): 298306. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8811051&dopt=Abstract
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Demographics of community-acquired bacterial infections in hospitalized children. Author(s): Grossman M, Applebaum MN. Source: The Pediatric Infectious Disease Journal. 1992 February; 11(2): 139-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1741191&dopt=Abstract
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Dermo-hypodermal bacterial infections. Current concepts. Author(s): Bernard P. Source: Eur J Med. 1992 May; 1(2): 97-104. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1342380&dopt=Abstract
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Detection of serum interferon-alpha by dissociation-enhanced lanthanide fluoroimmunoassay. Studies of patients with acute viral and bacterial infections. Author(s): Ronnblom LE, Perers A, Vallin HS, Eriksson I, Osterlind A, Cederblad B, Alm G. Source: Apmis : Acta Pathologica, Microbiologica, Et Immunologica Scandinavica. 1997 July; 105(7): 531-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9269299&dopt=Abstract
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Detection of T cells reactive to intestinal alkaline phosphatase, an autoantigen in acute bacterial infections, and discrimination between autoantigen-specific CD5+ and CD5- B cells. Author(s): Kolbus N, Fleischer U, Mader M, Felgenhauer K, Beuche W. Source: Clinical and Experimental Immunology. 1997 April; 108(1): 19-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9097906&dopt=Abstract
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Detection of viral and bacterial infections in women with normal and abnormal colposcopy. Author(s): Pisani S, Gallinelli C, Seganti L, Lukic A, Nobili F, Vetrano G, Imperi M, Degener AM, Chiarini F. Source: Eur J Gynaecol Oncol. 1999; 20(1): 69-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10422688&dopt=Abstract
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Determination of D-lactate concentration for rapid diagnosis of bacterial infections of body fluids. Author(s): Marcos MA, Vila J, Gratacos J, Brancos MA, Jimenez de Anta MT. Source: European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology. 1991 November; 10(11): 966-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1794370&dopt=Abstract
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Development of a novel, rapid processing protocol for polymerase chain reactionbased detection of bacterial infections in synovial fluids. Author(s): Mariani BD, Levine MJ, Booth RE Jr, Tuan RS. Source: Molecular Biotechnology. 1995 December; 4(3): 227-37. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8680929&dopt=Abstract
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Diagnosis and treatment of cutaneous bacterial infections. Author(s): Khorshid SM. Source: The Practitioner. 1998 October; 242(1591): 692-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10343446&dopt=Abstract
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Diagnosis of bacterial infections of the lung. Author(s): Bartlett JG. Source: Clinics in Chest Medicine. 1987 March; 8(1): 119-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3552385&dopt=Abstract
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Diagnostic testing for serious bacterial infections in infants aged 90 days or younger with bronchiolitis. Author(s): Liebelt EL, Qi K, Harvey K. Source: Archives of Pediatrics & Adolescent Medicine. 1999 May; 153(5): 525-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10323635&dopt=Abstract
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Diagnostic tests for bacterial infections. Author(s): Franz AR, Pohlandt F. Source: Archives of Disease in Childhood. Fetal and Neonatal Edition. 1999 January; 80(1): F78-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10325823&dopt=Abstract
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Diagnostic tests that are worthwhile for patients with sexually transmitted bacterial infections in industrialized countries. Author(s): Taylor-Robinson D, Renton A. Source: International Journal of Std & Aids. 1999 January; 10(1): 1-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10215121&dopt=Abstract
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Differential cytokine production in stimulated blood cultures from intensive care patients with bacterial infections. Author(s): Mitov IG, Kropec A, Benzing A, Just H, Garotta G, Galanos C, Freudenberg M. Source: Infection. 1997 July-August; 25(4): 206-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9266258&dopt=Abstract
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Direct amplification of rRNA genes in diagnosis of bacterial infections. Author(s): Rantakokko-Jalava K, Nikkari S, Jalava J, Eerola E, Skurnik M, Meurman O, Ruuskanen O, Alanen A, Kotilainen E, Toivanen P, Kotilainen P. Source: Journal of Clinical Microbiology. 2000 January; 38(1): 32-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10618059&dopt=Abstract
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Disseminated intravascular coagulation and bacterial infections in the elderly. Author(s): Anandadas JA, Banerjee AK. Source: Br J Clin Pract. 1990 July; 44(7): 266-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2206823&dopt=Abstract
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Distinct mutations in IRAK-4 confer hyporesponsiveness to lipopolysaccharide and interleukin-1 in a patient with recurrent bacterial infections. Author(s): Medvedev AE, Lentschat A, Kuhns DB, Blanco JC, Salkowski C, Zhang S, Arditi M, Gallin JI, Vogel SN. Source: The Journal of Experimental Medicine. 2003 August 18; 198(4): 521-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12925671&dopt=Abstract
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D-lactic acid measurements in the diagnosis of bacterial infections. Author(s): Smith SM, Eng RH, Campos JM, Chmel H. Source: Journal of Clinical Microbiology. 1989 March; 27(3): 385-8. Erratum In: J Clin Microbiol 1989 June; 27(6): 1430. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2715313&dopt=Abstract
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Does iron cause bacterial infections in patients with end stage renal disease? Author(s): Cieri E. Source: Anna J. 1999 December; 26(6): 591-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10876474&dopt=Abstract
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Dog-associated bacterial infections in humans: isolates submitted to an Australian reference laboratory, 1981-1992. Author(s): Peel MM. Source: Pathology. 1993 October; 25(4): 379-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8165003&dopt=Abstract
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Early onset neonatal bacterial infections. Author(s): Kaftan H, Kinney JS. Source: Semin Perinatol. 1998 February; 22(1): 15-24. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9523396&dopt=Abstract
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Effectiveness of short-course therapy (5 days) with cefuroxime axetil in treatment of secondary bacterial infections of acute bronchitis. Author(s): Henry D, Ruoff GE, Rhudy J, Puopolo A, Drehobl M, Schoenberger J, Giguere G, Collins JJ. Source: Antimicrobial Agents and Chemotherapy. 1995 November; 39(11): 2528-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8585739&dopt=Abstract
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Effects of age on neutrophil function and its relevance to bacterial infections in the elderly. Author(s): Angelis P, Scharf S, Christophidis N. Source: J Clin Lab Immunol. 1997; 49(1): 33-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9819671&dopt=Abstract
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Efficacy and cost of ampicillin-sulbactam and ticarcillin-clavulanate in the treatment of hospitalized patients with bacterial infections. Author(s): McKinnon PS, Neuhauser MM. Source: Pharmacotherapy. 1999 June; 19(6): 724-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10391418&dopt=Abstract
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Efficacy and safety of cefepime in the treatment of serious bacterial infections in hospitalized adult patients. Author(s): Sheng WH, Wang JT, Chang SC. Source: J Microbiol Immunol Infect. 2000 June; 33(2): 109-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10917881&dopt=Abstract
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Efficacy and safety of cefepime treatment in Chinese patients with severe bacterial infections: in comparison with ceftazidime treatment. Author(s): Chang SC, Fang CT, Hsueh PR, Liu CJ, Sheng WH, Hsieh SM, Hung CC, Chen YC. Source: International Journal of Antimicrobial Agents. 1998 August; 10(3): 245-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9832286&dopt=Abstract
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Efficacy of trimethoprim-sulfamethoxazole for the prevention of bacterial infections in a randomized prophylaxis trial of patients with advanced HIV infection. Author(s): DiRienzo AG, van Der Horst C, Finkelstein DM, Frame P, Bozzette SA, Tashima KT. Source: Aids Research and Human Retroviruses. 2002 January 20; 18(2): 89-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11839141&dopt=Abstract
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Emerging therapies for serious gram-positive bacterial infections: a focus on linezolid. Author(s): Plouffe JF. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2000 September; 31 Suppl 4: S144-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11017864&dopt=Abstract
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Empiric therapy of bacterial infections in patients with severe neutropenia. Author(s): Glauser M. Source: Diagnostic Microbiology and Infectious Disease. 1998 July; 31(3): 467-72. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9635238&dopt=Abstract
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Empirical monotherapy with meropenem in serious bacterial infections in children. Author(s): Hsu HL, Lu CY, Tseng HY, Lee PI, Lai HP, Lin WC, Hsieh YC, Lee CY, Huang LM. Source: J Microbiol Immunol Infect. 2001 December; 34(4): 275-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11825008&dopt=Abstract
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Endotoxin and IL-1 hyporesponsiveness in a patient with recurrent bacterial infections. Author(s): Kuhns DB, Long Priel DA, Gallin JI. Source: Journal of Immunology (Baltimore, Md. : 1950). 1997 April 15; 158(8): 3959-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9103466&dopt=Abstract
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Epstein-Barr virus-associated recurrent necrotic papulovesicles with repeated bacterial infections ending in sepsis and death: consideration of the relationship between Epstein-Barr virus infection and immune defect. Author(s): Yoon TY, Yang TH, Hahn YS, Huh JR, Soo Y. Source: The Journal of Dermatology. 2001 August; 28(8): 442-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11560162&dopt=Abstract
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Ertapenem: a review of its use in the management of bacterial infections. Author(s): Curran M, Simpson D, Perry C. Source: Drugs. 2003; 63(17): 1855-78. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12921489&dopt=Abstract
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Establishing a laboratory for surveillance of invasive bacterial infections in a tertiary care government hospital in a rural province in the Philippines. Author(s): Herva E, Sombrero L, Lupisan S, Arcay J, Ruutu P. Source: The American Journal of Tropical Medicine and Hygiene. 1999 June; 60(6): 103540. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10403339&dopt=Abstract
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Establishment of a multiplex PCR system to diagnose tuberculosis and other bacterial infections. Author(s): Fang F, Xiang Z, Chen R. Source: J Tongji Med Univ. 2000; 20(4): 324-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12840925&dopt=Abstract
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Evaluation of the patient with recurrent bacterial infections. Author(s): Holland SM, Gallin JI. Source: Annual Review of Medicine. 1998; 49: 185-99. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9509258&dopt=Abstract
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Evaluation of the substrate specificity of human mast cell tryptase beta I and demonstration of its importance in bacterial infections of the lung. Author(s): Huang C, De Sanctis GT, O'Brien PJ, Mizgerd JP, Friend DS, Drazen JM, Brass LF, Stevens RL. Source: The Journal of Biological Chemistry. 2001 July 13; 276(28): 26276-84. Epub 2001 May 02. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11335723&dopt=Abstract
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Evidence for an increased rate of bacterial infections in liver transplant patients with cytomegalovirus infection. Author(s): van den Berg AP, Klompmaker IJ, Haagsma EB, Peeters PM, Meerman L, Verwer R, The TH, Slooff MJ. Source: Clinical Transplantation. 1996 April; 10(2): 224-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8664524&dopt=Abstract
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Expression of MxA protein in blood lymphocytes discriminates between viral and bacterial infections in febrile children. Author(s): Halminen M, Ilonen J, Julkunen I, Ruuskanen O, Simell O, Makela MJ. Source: Pediatric Research. 1997 May; 41(5): 647-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9128286&dopt=Abstract
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Expression patterns of the lipopolysaccharide receptor CD14, and the FCgamma receptors CD16 and CD64 on polymorphonuclear neutrophils: data from patients with severe bacterial infections and lipopolysaccharide-exposed cells. Author(s): Wagner C, Deppisch R, Denefleh B, Hug F, Andrassy K, Hansch GM. Source: Shock (Augusta, Ga.). 2003 January; 19(1): 5-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12558136&dopt=Abstract
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Familial neutrophil chemotaxis defect, recurrent bacterial infections, mucocutaneous candidiasis, and hyperimmunoglobulinemia E. Author(s): Van Scoy RE, Hill HR, Ritts RE, Quie PG. Source: Annals of Internal Medicine. 1975 June; 82(6): 766-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1138587&dopt=Abstract
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Fc gamma IIA receptor phenotype and opsonophagocytosis in two patients with recurrent bacterial infections. Author(s): Sanders EA, Van de Winkel JG, Feldman RG, Voorhorst-Ogink MM, Rijkers GT, Capel PJ, Zegers BJ. Source: Immunodeficiency. 1993; 4(1-4): 163-5. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8167694&dopt=Abstract
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Fetal and maternal features of antenatal bacterial infections. Author(s): Naeye RL, Dellinger WS, Blanc WA. Source: The Journal of Pediatrics. 1971 November; 79(5): 733-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5000610&dopt=Abstract
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Fever response to acetaminophen in viral vs. bacterial infections. Author(s): Weisse ME, Miller G, Brien JH. Source: The Pediatric Infectious Disease Journal. 1987 December; 6(12): 1091-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3324040&dopt=Abstract
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Fever without apparent source on clinical examination, lower respiratory infections in children, bacterial infections, and acute gastroenteritis and diarrhea of infancy and early childhood. Author(s): McCarthy PL, Bachman DT, Shapiro ED, Baron MA. Source: Current Opinion in Pediatrics. 1995 February; 7(1): 107-25. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7728195&dopt=Abstract
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Fever without apparent source on clinical examination, lower respiratory infections in children, bacterial infections, and acute gastroenteritis and diarrhea of infancy and early childhood. Author(s): McCarthy PL, Bachman DT, Shapiro ED, Baron MA. Source: Current Opinion in Pediatrics. 1994 February; 6(1): 105-25. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8205167&dopt=Abstract
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Flow cytometric studies on phagocyte function in bacterial infections. Author(s): Bassoe CF. Source: Acta Pathol Microbiol Immunol Scand [c]. 1984 June; 92(3): 167-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6507103&dopt=Abstract
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Fluorescent-antibody technique in the rapid diagnosis of clinical bacterial infections. Author(s): Nahmias AJ, Brahen L, Luce C. Source: Antimicrobial Agents Chemother. 1965; 5: 84-90. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5327532&dopt=Abstract
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Management of bacterial infections in haematological patients. Author(s): Galea G. Source: Br J Hosp Med. 1982 July; 28(1): 74, 76, 79 Passim. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6289951&dopt=Abstract
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Marked disparity in incidence of bacterial infections in patients with the acquired immunodeficiency syndrome receiving interleukin-2 or interferon-gamma. Author(s): Murphy PM, Lane HC, Gallin JI, Fauci AS. Source: Annals of Internal Medicine. 1988 January; 108(1): 36-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3122616&dopt=Abstract
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Membrane receptors on human neutrophils in oral bacterial infections. Author(s): Nagumo M, Sakurada S, Enomoto S. Source: Journal of Dental Research. 1982 August; 61(8): 962-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7050198&dopt=Abstract
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Metronidazole in anaerobic bacterial infections. Author(s): Apgar DA, Lackner TE, Butler CD. Source: Pharmacotherapy. 1981 November-December; 1(3): 212-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6927606&dopt=Abstract
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Modern management of mixed bacterial infections. Author(s): Madhavan T. Source: Compr Ther. 1984 June; 10(6): 55-64. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6734133&dopt=Abstract
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Molecular epidemiology of bacterial infections. Author(s): Bjorvatn B, Kristiansen BE. Source: Clin Lab Med. 1985 September; 5(3): 437-45. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3930133&dopt=Abstract
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Monotherapy versus combination therapy for bacterial infections. Author(s): Bouza E, Munoz P. Source: The Medical Clinics of North America. 2000 November; 84(6): 1357-89, V. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11155848&dopt=Abstract
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Mortality and morbidity from invasive bacterial infections during a clinical trial of acellular pertussis vaccines in Sweden. Author(s): Storsaeter J, Olin P, Renemar B, Lagergard T, Norberg R, Romanus V, Tiru M. Source: The Pediatric Infectious Disease Journal. 1988 September; 7(9): 637-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3050858&dopt=Abstract
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Mucoraceae infections of antibiotic-loaded cement spacers in the treatment of bacterial infections caused by knee arthroplasty. Author(s): Ceffa R, Andreoni S, Borre S, Ghisellini F, Fornara P, Brugo G, Ritter MA. Source: The Journal of Arthroplasty. 2002 February; 17(2): 235-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11847627&dopt=Abstract
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Neglected pathogens: bacterial infections in persons with human immunodeficiency virus infection. A review of the literature (2). Author(s): Fish DN, Danziger LH. Source: Pharmacotherapy. 1993 November-December; 13(6): 543-63. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8302678&dopt=Abstract
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Neonatal fever: utility of the Rochester criteria in determining low risk for serious bacterial infections. Author(s): Ferrera PC, Bartfield JM, Snyder HS. Source: The American Journal of Emergency Medicine. 1997 May; 15(3): 299-302. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9148992&dopt=Abstract
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Neurosurgical bacterial infections. Author(s): Flint G. Source: British Journal of Neurosurgery. 1987; 1(4): 519-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3268150&dopt=Abstract
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Neutropenia, recurrent bacterial infections, and congenital deafness in patients with monocytopenia. Absence of peripheral blood colony-stimulating activity. Author(s): Chilcote RR, Rierden WJ, Baehner RL. Source: Am J Dis Child. 1983 October; 137(10): 964-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6604450&dopt=Abstract
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Neutrophil alkaline phosphatase activity increase in bacterial infections is not associated with a general increase in secretory vesicle membrane components. Author(s): Karlsson A, Khalfan L, Dahlgren C, Stigbrand T, Follin P. Source: Infection and Immunity. 1995 March; 63(3): 911-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7868263&dopt=Abstract
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Neutrophil response of transgenic mice expressing human group IIA phospholipase A2 in bacterial infections. Author(s): Laine VJ, Rajamaki A, Grass DS, Nevalainen TJ. Source: Scandinavian Journal of Immunology. 2000 October; 52(4): 362-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11013007&dopt=Abstract
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Neutrophil-Kupffer cell interaction: a critical component of host defenses to systemic bacterial infections. Author(s): Gregory SH, Wing EJ. Source: Journal of Leukocyte Biology. 2002 August; 72(2): 239-48. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12149414&dopt=Abstract
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Neutrophils from term and preterm newborn infants express the high affinity Fcgamma-receptor I (CD64) during bacterial infections. Author(s): Fjaertoft G, Hakansson L, Ewald U, Foucard T, Venge P. Source: Pediatric Research. 1999 June; 45(6): 871-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10367781&dopt=Abstract
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New antibiotics for bacterial infections. Author(s): Mah FS. Source: Ophthalmology Clinics of North America. 2003 March; 16(1): 11-27. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12683245&dopt=Abstract
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New approaches in the treatment of bacterial infections. Author(s): Bush K, Macielag M. Source: Current Opinion in Chemical Biology. 2000 August; 4(4): 433-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10959772&dopt=Abstract
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New ways to treat bacterial infections. Author(s): Taylor PW, Stapleton PD, Paul Luzio J. Source: Drug Discovery Today. 2002 November 1; 7(21): 1086-91. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12546840&dopt=Abstract
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Norfloxacin for prevention of bacterial infections during severe granulocytopenia after bone marrow transplantation. Author(s): Schmeiser T, Kurrle E, Arnold R, Wiesneth M, Bunjes D, Hertenstein B, Kern W, Heit W, Heimpel H. Source: Scandinavian Journal of Infectious Diseases. 1988; 20(6): 625-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3065930&dopt=Abstract
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Norfloxacin primary prophylaxis of bacterial infections in cirrhotic patients with ascites: a double-blind randomized trial. Author(s): Grange JD, Roulot D, Pelletier G, Pariente EA, Denis J, Ink O, Blanc P, Richardet JP, Vinel JP, Delisle F, Fischer D, Flahault A, Amiot X. Source: Journal of Hepatology. 1998 September; 29(3): 430-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9764990&dopt=Abstract
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Nosocomial bacterial infections among children with severe protein energy malnutrition. Author(s): Isaack H, Mbise RL, Hirji KF. Source: East Afr Med J. 1992 August; 69(8): 433-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1396209&dopt=Abstract
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Once-daily ceftriaxone therapy for serious bacterial infections in children. Author(s): Congeni BL, Chonmaitree T, Rakusan TA, Box QT. Source: Antimicrobial Agents and Chemotherapy. 1985 February; 27(2): 181-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3985602&dopt=Abstract
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Once-daily dosing regimen for aminoglycoside plus beta-lactam combination therapy of serious bacterial infections: comparative trial with netilmicin plus ceftriaxone. Author(s): ter Braak EW, de Vries PJ, Bouter KP, van der Vegt SG, Dorrestein GC, Nortier JW, van Dijk A, Verkooyen RP, Verbrugh HA. Source: The American Journal of Medicine. 1990 July; 89(1): 58-66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2195890&dopt=Abstract
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Open trial of imipenem/cilastatin therapy for serious bacterial infections. Author(s): Brooks RG, McCabe RE, Vosti KL, Remington JS. Source: Reviews of Infectious Diseases. 1985 July-August; 7 Suppl 3: S496-505. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3901213&dopt=Abstract
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Opportunistic nosocomial multiply resistant bacterial infections--their treatment and prevention. Author(s): Bergogne-Berezin E, Decre D, Joly-Guillou ML. Source: The Journal of Antimicrobial Chemotherapy. 1993 July; 32 Suppl A: 39-47. Review. Erratum In: J Antimicrob Chemother 1994 December; 34(6): 1083. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7755661&dopt=Abstract
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Optimized localization of bacterial infections with technetium-99m labelled human immunoglobulin after protein charge selection. Author(s): Welling M, Feitsma HI, Calame W, Ensing GJ, Goedemans W, Pauwels EK. Source: European Journal of Nuclear Medicine. 1994 October; 21(10): 1135-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7828624&dopt=Abstract
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Oral acyclovir as prophylaxis for bacterial infections during induction therapy for acute leukaemia in adults. The Leukemia Group of Middle Sweden. Author(s): Lonnqvist B, Palmblad J, Ljungman P, Grimfors G, Jarnmark M, Lerner R, Nystrom-Rosander C, Oberg G. Source: Supportive Care in Cancer : Official Journal of the Multinational Association of Supportive Care in Cancer. 1993 May; 1(3): 139-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8149141&dopt=Abstract
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Oral fungal and bacterial infections in HIV-infected individuals: an overview in Africa. Author(s): Hodgson TA, Rachanis CC. Source: Oral Diseases. 2002; 8 Suppl 2: 80-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12164666&dopt=Abstract
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Oral manifestations in HIV infection: fungal and bacterial infections, Kaposi's sarcoma. Author(s): Reichart PA. Source: Medical Microbiology and Immunology. 2003 August; 192(3): 165-9. Epub 2003 March 05. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12684760&dopt=Abstract
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Oral vaccination against enteric bacterial infections: an overview. Author(s): Germanier R. Source: Behring Inst Mitt. 1984 November; (76): 98-105. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6395852&dopt=Abstract
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Osteoarticular bacterial infections are rare in HIV-infected patients. 14 cases found among 4,023 HIV-infected patients. Author(s): Ventura G, Gasparini G, Lucia MB, Tumbarello M, Tacconelli E, Caldarola G, Cauda R. Source: Acta Orthopaedica Scandinavica. 1997 December; 68(6): 554-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9462355&dopt=Abstract
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Pattern of bacterial infections and antimicrobial susceptibility at the Kenyatta National Hospital, Nairobi, Kenya. Author(s): Omari MA, Malonza IM, Bwayo JJ, Mutere AN, Murage EM, Mwatha AK, Ndinya-Achola JO. Source: East Afr Med J. 1997 March; 74(3): 134-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9185406&dopt=Abstract
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Pharmacological inhibition of quorum sensing for the treatment of chronic bacterial infections. Author(s): Hentzer M, Givskov M. Source: The Journal of Clinical Investigation. 2003 November; 112(9): 1300-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14597754&dopt=Abstract
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Predictors and outcome of early- versus late-onset major bacterial infections in liver transplant recipients receiving tacrolimus (FK506) as primary immunosuppression. Author(s): Singh N, Gayowski T, Wagener MM, Marino IR. Source: European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology. 1997 November; 16(11): 821-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9447904&dopt=Abstract
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Prevalence of serious bacterial infections in febrile infants with respiratory syncytial virus infection. Author(s): Titus MO, Wright SW. Source: Pediatrics. 2003 August; 112(2): 282-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12897274&dopt=Abstract
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Procalcitonin in pediatric emergency departments for the early diagnosis of invasive bacterial infections in febrile infants: results of a multicenter study and utility of a rapid qualitative test for this marker. Author(s): Fernandez Lopez A, Luaces Cubells C, Garcia Garcia JJ, Fernandez Pou J; Spanish Society of Pediatric Emergencies. Source: The Pediatric Infectious Disease Journal. 2003 October; 22(10): 895-903. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14551491&dopt=Abstract
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Procalcitonin--a new indicator for bacterial infections. Author(s): Steinbach G, Grunert A. Source: Experimental and Clinical Endocrinology & Diabetes : Official Journal, German Society of Endocrinology [and] German Diabetes Association. 1998; 106(3): 164-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9710354&dopt=Abstract
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Prophylaxis and pre-emptive therapy of bacterial infections following allogeneic bone marrow transplantation in children. Author(s): Vossen JM, de Tollenaer S, van Weel-Sipman MH. Source: Bone Marrow Transplantation. 1996 November; 18 Suppl 2: 93-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8932807&dopt=Abstract
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Prophylaxis with fluoroquinolones for bacterial infections in neutropenic patients: a meta-analysis. Author(s): Cruciani M, Rampazzo R, Malena M, Lazzarini L, Todeschini G, Messori A, Concia E. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 1996 October; 23(4): 795-805. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8909847&dopt=Abstract
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Quinolinic acid in tumors, hemorrhage and bacterial infections of the central nervous system in children. Author(s): Heyes MP, Saito K, Milstien S, Schiff SJ. Source: Journal of the Neurological Sciences. 1995 November; 133(1-2): 112-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8583213&dopt=Abstract
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Reduced acute phase response to differentiate between viral and bacterial infections in children. Author(s): Urbach J, Rotstein R, Fusman R, Zeltser D, Shapira I, Branski D, Berliner S. Source: Pediatric Pathology & Molecular Medicine. 2002 November-December; 21(6): 557-67. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12537773&dopt=Abstract
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Reduction of unnecessary antibiotic therapy in newborn infants using interleukin-8 and C-reactive protein as markers of bacterial infections. Author(s): Franz AR, Steinbach G, Kron M, Pohlandt F. Source: Pediatrics. 1999 September; 104(3 Pt 1): 447-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10469768&dopt=Abstract
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Relationships between atopy and bacterial infections. Author(s): Mucha SM, Baroody FM. Source: Curr Allergy Asthma Rep. 2003 May; 3(3): 232-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12662473&dopt=Abstract
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Respiratory syncytial virus infection and the risk of serious bacterial infections. Author(s): Kuppermann N. Source: Archives of Pediatrics & Adolescent Medicine. 2002 October; 156(10): 1055-6; Author Reply 1056-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12361456&dopt=Abstract
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Return of a killer. Phages may once again fight tough bacterial infections. Author(s): Koerner BI. Source: U.S. News & World Report. 1998 November 2; 125(17): 51-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10187346&dopt=Abstract
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Risk factors for the development of bacterial infections in hospitalized patients with cirrhosis. Author(s): Deschenes M, Villeneuve JP. Source: The American Journal of Gastroenterology. 1999 August; 94(8): 2193-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10445549&dopt=Abstract
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Risk factors in HIV-1-infected patients developing repetitive bacterial infections: toxicological, clinical, specific antibody class responses, opsonophagocytosis and Fc(gamma) RIIa polymorphism characteristics. Author(s): Payeras A, Martinez P, Mila J, Riera M, Pareja A, Casal J, Matamoros N. Source: Clinical and Experimental Immunology. 2002 November; 130(2): 271-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12390315&dopt=Abstract
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Risk of serious bacterial infections in infants with bronchiolitis. Author(s): St Jacques DM, Barton LL, Rhee KH. Source: Archives of Pediatrics & Adolescent Medicine. 1998 August; 152(8): 819-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9701147&dopt=Abstract
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Role of bacterial antigen tests in the diagnosis of invasive bacterial infections. Author(s): Marshall GS. Source: The Pediatric Infectious Disease Journal. 1997 June; 16(6): 632-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9194121&dopt=Abstract
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Role of bacterial infections in children with asthma. Author(s): Just J, Fayon M, Charavel A, Grimfeld A. Source: Pediatr Pulmonol Suppl. 1997; 16: 76. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9443212&dopt=Abstract
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Secondary bacterial infections complicating skin lesions. Author(s): Brook I. Source: Journal of Medical Microbiology. 2002 October; 51(10): 808-12. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12435058&dopt=Abstract
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Serious bacterial infections in febrile infants younger than 90 days of age: the importance of ampicillin-resistant pathogens. Author(s): Byington CL, Rittichier KK, Bassett KE, Castillo H, Glasgow TS, Daly J, Pavia AT. Source: Pediatrics. 2003 May; 111(5 Pt 1): 964-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12728072&dopt=Abstract
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Serious bacterial infections in patients with rheumatoid arthritis under anti-TNFalpha therapy. Author(s): Kroesen S, Widmer AF, Tyndall A, Hasler P. Source: Rheumatology (Oxford, England). 2003 May; 42(5): 617-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12709536&dopt=Abstract
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Serum C-reactive protein and C3 complement protein levels in severely malnourished Nigerian children with and without bacterial infections. Author(s): Ekanem EE, Umotong AB, Raykundalia C, Catty D. Source: Acta Paediatrica (Oslo, Norway : 1992). 1997 December; 86(12): 1317-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9475308&dopt=Abstract
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Skin microflora and bacterial infections of the skin. Author(s): Chiller K, Selkin BA, Murakawa GJ. Source: The Journal of Investigative Dermatology. Symposium Proceedings / the Society for Investigative Dermatology, Inc. [and] European Society for Dermatological Research. 2001 December; 6(3): 170-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11924823&dopt=Abstract
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Stroke-induced immunodeficiency promotes spontaneous bacterial infections and is mediated by sympathetic activation reversal by poststroke T helper cell type 1-like immunostimulation. Author(s): Prass K, Meisel C, Hoflich C, Braun J, Halle E, Wolf T, Ruscher K, Victorov IV, Priller J, Dirnagl U, Volk HD, Meisel A. Source: The Journal of Experimental Medicine. 2003 September 1; 198(5): 725-36. Epub 2003 August 25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12939340&dopt=Abstract
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Study of fungal and bacterial infections of the diabetic foot. Author(s): Chincholikar DA, Pal RB. Source: Indian J Pathol Microbiol. 2002 January; 45(1): 15-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12593559&dopt=Abstract
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Sulbactam/cefoperazone versus cefotaxime for the treatment of moderate-to-severe bacterial infections: results of a randomized, controlled clinical trial. Author(s): Li JT, Lu Y, Hou J, Chen YF, Miao JZ, Jia YX, Hou J, Zhang XZ, Chen DK, Hu WZ, Li LJ, Liu DM, Wang Z, Wu J, Gu JM, Wang HL, Zhang YL, Sun L. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 1997 March; 24(3): 498-505. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9114206&dopt=Abstract
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Superiority of a functional leukocyte adhesiveness/aggregation test over the white blood cell count to discriminate between mild and significant inflammatory response in patients with acute bacterial infections. Author(s): Rogowski O, Rotstein R, Zeltzer D, Misgav S, Justo D, Avitzour D, Mardi T, Serov J, Arber N, Berliner S, Shapira I. Source: Journal of Clinical Laboratory Analysis. 2002; 16(4): 187-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12112391&dopt=Abstract
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Survey of aerobic bacterial infections in paediatric surgical intensive care unit patients. Author(s): Yap KP, Tan ML, Tan CE. Source: Ann Acad Med Singapore. 1998 March; 27(2): 223-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9663315&dopt=Abstract
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The application of biofilm science to the study and control of chronic bacterial infections. Author(s): Costerton W, Veeh R, Shirtliff M, Pasmore M, Post C, Ehrlich G. Source: The Journal of Clinical Investigation. 2003 November; 112(10): 1466-77. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14617746&dopt=Abstract
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The basis of persistent bacterial infections. Author(s): Rhen M, Eriksson S, Clements M, Bergstrom S, Normark SJ. Source: Trends in Microbiology. 2003 February; 11(2): 80-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12598130&dopt=Abstract
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The importance of bacterial infections as precipating factors of chronic hepatic encephalopathy in cirrhosis. Author(s): Strauss E, da Costa MF. Source: Hepatogastroenterology. 1998 May-June; 45(21): 900-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9684155&dopt=Abstract
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The interaction between NK cells and dendritic cells in bacterial infections results in rapid induction of NK cell activation and in the lysis of uninfected dendritic cells. Author(s): Ferlazzo G, Morandi B, D'Agostino A, Meazza R, Melioli G, Moretta A, Moretta L. Source: European Journal of Immunology. 2003 February; 33(2): 306-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12548561&dopt=Abstract
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The role of the stringent response in the pathogenesis of bacterial infections. Author(s): Godfrey HP, Bugrysheva JV, Cabello FC. Source: Trends in Microbiology. 2002 August; 10(8): 349-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12160623&dopt=Abstract
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Therapeutic indications for local anti-infectives. Bacterial infections of the eye. Author(s): Bialasiewicz AA. Source: Dev Ophthalmol. 2002; 33: 243-9. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12236116&dopt=Abstract
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Timing and aetiology of bacterial infections in a liver intensive care unit. Author(s): Wade J, Rolando N, Philpott-Howard J, Wendon J. Source: The Journal of Hospital Infection. 2003 February; 53(2): 144-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12586576&dopt=Abstract
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Treatment of bacterial infections. Author(s): Chesney PJ, Halsey NA, Marcy SM. Source: The New England Journal of Medicine. 1997 September 11; 337(11): 793-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9289652&dopt=Abstract
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Treatment of ocular bacterial infections: an update. Author(s): Hammond RW, Edmondson W. Source: J Am Optom Assoc. 1997 March; 68(3): 178-87. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9109296&dopt=Abstract
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Tropism in bacterial infections: urinary tract infections. Author(s): Roberts JA. Source: The Journal of Urology. 1996 November; 156(5): 1552-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8863537&dopt=Abstract
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Unsuspected bacterial infections in febrile convulsions. Author(s): McIntyre PB, Gray SV, Vance JC. Source: The Medical Journal of Australia. 1990 February 19; 152(4): 183-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2300024&dopt=Abstract
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Unusual bacterial infections of the urinary tract in diabetic patients--rare but frequently lethal. Author(s): Kumar A, Turney JH, Brownjohn AM, McMahon MJ. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 2001 May; 16(5): 1062-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11328918&dopt=Abstract
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Up-regulation of the dendritic cell marker CD83 on polymorphonuclear neutrophils (PMN): divergent expression in acute bacterial infections and chronic inflammatory disease. Author(s): Iking-Konert C, Wagner C, Denefleh B, Hug F, Schneider M, Andrassy K, Hansch GM. Source: Clinical and Experimental Immunology. 2002 December; 130(3): 501-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12452842&dopt=Abstract
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Uptake of positron emission tomography tracers in experimental bacterial infections: a comparative biodistribution study of radiolabeled FDG, thymidine, L-methionine, 67Ga-citrate, and 125I-HSA. Author(s): Sugawara Y, Gutowski TD, Fisher SJ, Brown RS, Wahl RL. Source: European Journal of Nuclear Medicine. 1999 April; 26(4): 333-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10199938&dopt=Abstract
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Urinary trypsin inhibitory activity: not a useful test for detecting bacterial infections in elderly people. Author(s): Merle M, Jeandel C. Source: Eur J Med. 1993 March; 2(3): 189. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7505160&dopt=Abstract
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Use of immune modulators in nonspecific therapy of bacterial infections. Author(s): Vogels MT, van der Meer JW. Source: Antimicrobial Agents and Chemotherapy. 1992 January; 36(1): 1-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1590674&dopt=Abstract
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Use of linezolid, an oxazolidinone, in the treatment of multidrug-resistant grampositive bacterial infections. Author(s): Chien JW, Kucia ML, Salata RA. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2000 January; 30(1): 146-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10619743&dopt=Abstract
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Use of low-frequency-cleavage restriction endonucleases for DNA analysis in epidemiological investigations of nosocomial bacterial infections. Author(s): Allardet-Servent A, Bouziges N, Carles-Nurit MJ, Bourg G, Gouby A, Ramuz M. Source: Journal of Clinical Microbiology. 1989 September; 27(9): 2057-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2550517&dopt=Abstract
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Use of the quinolones in treatment of severe bacterial infections in premature infants. Author(s): Wlazlowski J, Krzyzanska-Oberbek A, Sikora JP, Chlebna-Sokol D. Source: Acta Pol Pharm. 2000 November; 57 Suppl: 28-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11293256&dopt=Abstract
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Use of trimethoprim-sulfamethoxazole to prevent bacterial infections in children with acute lymphoblastic leukemia. Author(s): Goorin AM, Hershey BJ, Levin MJ, Siber GR, Gelber RD, Flynn K, Lew M, Beckett K, Blanding P, Sallan SE. Source: Pediatr Infect Dis. 1985 May-June; 4(3): 265-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3889875&dopt=Abstract
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Vaccinations against bacterial infections. Author(s): Ocklitz HW. Source: Paediatrician. 1979; 8 Suppl 1: 26-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=492737&dopt=Abstract
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Vaccinations against bacterial infections. Author(s): Ocklitz HW. Source: Padiatr Grenzgeb. 1979; 18(3): 137-46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=388293&dopt=Abstract
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Variations in adrenocortical responsiveness during severe bacterial infections. Unrecognized adrenocortical insufficiency in severe bacterial infections. Author(s): Sibbald WJ, Short A, Cohen MP, Wilson RF. Source: Annals of Surgery. 1977 July; 186(1): 29-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=195542&dopt=Abstract
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Veterinary use of antimicrobial agents and problems of resistance in human bacterial infections. Author(s): Johnson AP. Source: The Journal of Antimicrobial Chemotherapy. 1997 February; 39(2): 285-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9069555&dopt=Abstract
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Viral and bacterial infections in adults with chronic asthma. Author(s): Hudgel DW, Langston L Jr, Selner JC, McIntosh K. Source: Am Rev Respir Dis. 1979 August; 120(2): 393-7. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=475158&dopt=Abstract
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Viral and bacterial infections in patients with acute myocardial infarction. Author(s): Mattila KJ. Source: Journal of Internal Medicine. 1989 May; 225(5): 293-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2732669&dopt=Abstract
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Viral and bacterial infections in the development and progression of asthma. Author(s): Gern JE. Source: The Journal of Allergy and Clinical Immunology. 2000 February; 105(2 Pt 2): S497-502. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10669531&dopt=Abstract
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Viral infections predisposing to bacterial infections. Author(s): Mills EL. Source: Annual Review of Medicine. 1984; 35: 469-79. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6326662&dopt=Abstract
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Viral, mycoplasma and bacterial infections in nurses with symptoms of respiratory diseases. Author(s): Lowenberg A, Orie NG. Source: Scand J Respir Dis. 1976; 57(6): 290-300. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=189386&dopt=Abstract
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Virus-induced neutrophil dysfunction: role in the pathogenesis of bacterial infections. Author(s): Abramson JS, Wheeler JG. Source: The Pediatric Infectious Disease Journal. 1994 July; 13(7): 643-52. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7970955&dopt=Abstract
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White blood cell and differential counts in acute respiratory viral and bacterial infections in children. Author(s): Korppi M, Kroger L, Laitinen M. Source: Scandinavian Journal of Infectious Diseases. 1993; 25(4): 435-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8248742&dopt=Abstract
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Whole blood microassay of luminol dependent chemiluminescence stimulated by phorbol myristate acetate or human IgG coated zymosan for monitoring disease activity of bacterial infections. Author(s): Kohashi O, Kohashi Y, Kuroiwa A, Okada H, Shigematsu N. Source: Fukuoka Igaku Zasshi. 1987 October; 78(10): 491-502. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3440561&dopt=Abstract
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CHAPTER 2. NUTRITION AND BACTERIAL INFECTIONS Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and bacterial infections.
Finding Nutrition Studies on Bacterial Infections 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 “bacterial infections” (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 “bacterial infections” (or a synonym): •
Manduca sexta lipopolysaccharide-specific immulectin-2 protects larvae from bacterial infection. Author(s): Department of Cell Biology and Biophysics, School of Biological Sciences, University of Missouri-Kansas City, Kansas City, MO 64110, USA. Source: Yu, X Q Kanost, M R Dev-Comp-Immunol. 2003 March; 27(3): 189-96 0145-305X
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Protective effect of kappa-carrageenan against bacterial infections in carp Cyprinus carpio. Author(s): Kyushu Univ., Fukuoka (Japan). Faculty of Agriculture Source: Fujiki, K. Shin, D.H. Nakao, M. Yano, T. Journal-of-the-Faculty-of-AgricultureKyushu-University (Japan). (December 1997). volume 42(1-2) page 113-119. cyprinus carrageenans bacterioses immunization chondrus 0023-6152
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Roles of prostaglandins and leukotrienes in acute inflammation caused by bacterial infection. Author(s): Laboratory of Host Defense and Germfree Life, Research Institute for Disease Mechanism and Control, Nagoya University School of Medicine, Nagoya, Japan.
[email protected] Source: Yoshikai, Y Curr-Opin-Infect-Dis. 2001 June; 14(3): 257-63 0951-7375
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Treatment of post-burns bacterial infections by bacteriophages, specifically ubiquitous Pseudomonas spp. notoriously resistant to antibiotics. Author(s): Department of Life Sciences, Nottingham Trent University, Nottingham, England.
[email protected] Source: Ahmad, S I Med-Hypotheses. 2002 April; 58(4): 327-31 0306-9877
Federal Resources on Nutrition In addition to the IBIDS, the United States Department of Health and Human Services (HHS) and the United States Department of Agriculture (USDA) provide many sources of information on general nutrition and health. Recommended resources include: •
healthfinder®, HHS’s gateway to health information, including diet and nutrition: http://www.healthfinder.gov/scripts/SearchContext.asp?topic=238&page=0
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The United States Department of Agriculture’s Web site dedicated to nutrition information: www.nutrition.gov
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The Food and Drug Administration’s Web site for federal food safety information: www.foodsafety.gov
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The National Action Plan on Overweight and Obesity sponsored by the United States Surgeon General: http://www.surgeongeneral.gov/topics/obesity/
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The Center for Food Safety and Applied Nutrition has an Internet site sponsored by the Food and Drug Administration and the Department of Health and Human Services: http://vm.cfsan.fda.gov/
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Center for Nutrition Policy and Promotion sponsored by the United States Department of Agriculture: http://www.usda.gov/cnpp/
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Food and Nutrition Information Center, National Agricultural Library sponsored by the United States Department of Agriculture: http://www.nal.usda.gov/fnic/
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Food and Nutrition Service sponsored by the United States Department of Agriculture: http://www.fns.usda.gov/fns/
Additional Web Resources A number of additional Web sites offer encyclopedic information covering food and nutrition. The following is a representative sample: •
AOL: http://search.aol.com/cat.adp?id=174&layer=&from=subcats
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Family Village: http://www.familyvillage.wisc.edu/med_nutrition.html
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Google: http://directory.google.com/Top/Health/Nutrition/
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Healthnotes: http://www.healthnotes.com/
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Open Directory Project: http://dmoz.org/Health/Nutrition/
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Yahoo.com: http://dir.yahoo.com/Health/Nutrition/
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WebMD®Health: http://my.webmd.com/nutrition
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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html
The following is a specific Web list relating to bacterial infections; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: •
Vitamins Riboflavin Alternative names: Vitamin B2 (Riboflavin) Source: Integrative Medicine Communications; www.drkoop.com Vitamin B2 (Riboflavin) Source: Integrative Medicine Communications; www.drkoop.com
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CHAPTER 3. ALTERNATIVE MEDICINE AND BACTERIAL INFECTIONS Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to bacterial infections. 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 bacterial infections 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 “bacterial infections” (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 bacterial infections: •
“Essentially Christian, eminently philanthropic”: the Mission to Lepers in British India. Author(s): Joseph DG. Source: Hist Cienc Saude Manguinhos. 2003; 10(Suppl 1): 247-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14650416&dopt=Abstract
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(-)Epigallocatechin-3-gallate inhibits gelatinase activity of some bacterial isolates from ocular infection, and limits their invasion through gelatine. Author(s): Blanco AR, La Terra Mule S, Babini G, Garbisa S, Enea V, Rusciano D. Source: Biochimica Et Biophysica Acta. 2003 March 17; 1620(1-3): 273-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12595099&dopt=Abstract
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(n-3) Fatty acids and infectious disease resistance. Author(s): Anderson M, Fritsche KL. Source: The Journal of Nutrition. 2002 December; 132(12): 3566-76. Review. Erratum In: J Nutr. 2003 February; 133(2): 535-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12468590&dopt=Abstract
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Esberitox N as supportive therapy when providing standard antibiotic treatment in subjects with a severe bacterial infection (acute exacerbation of chronic bronchitis). A multicentric, prospective, double-blind, placebo-controlled study. Author(s): Hauke W, Kohler G, Henneicke-Von Zepelin HH, Freudenstein J. Source: Chemotherapy. 2002 December; 48(5): 259-66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12476043&dopt=Abstract
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Herbal medicines for treatment of bacterial infections: a review of controlled clinical trials. Author(s): Martin KW, Ernst E. Source: The Journal of Antimicrobial Chemotherapy. 2003 February; 51(2): 241-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12562687&dopt=Abstract
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Hot-tub-associated mycobacterial infections in immunosuppressed persons. Author(s): Graham DR. Source: Emerging Infectious Diseases. 2002 July; 8(7): 750. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12095454&dopt=Abstract
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Rapidly growing mycobacterial infections after pedicures. Author(s): Sniezek PJ, Graham BS, Busch HB, Lederman ER, Lim ML, Poggemyer K, Kao A, Mizrahi M, Washabaugh G, Yakrus M, Winthrop K. Source: Archives of Dermatology. 2003 May; 139(5): 629-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12756100&dopt=Abstract
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The effects of the periodical use of in-feed chlortetracycline on the reproductive performance of gilts and sows of a commercial pig farm with a history of clinical and subclinical viral and bacterial infections. Author(s): Alexopoulos C, Fthenakis GC, Burriel A, Bourtzi-Hatzopoulou E, Kritas SK, Sbiraki A, Kyriakis SC. Source: Reproduction in Domestic Animals = Zuchthygiene. 2003 June; 38(3): 187-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12753551&dopt=Abstract
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Treatment of post-burns bacterial infections by bacteriophages, specifically ubiquitous Pseudomonas spp. notoriously resistant to antibiotics. Author(s): Ahmad SI.
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Source: Medical Hypotheses. 2002 April; 58(4): 327-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12027527&dopt=Abstract
Additional Web Resources A number of additional Web sites offer encyclopedic information covering CAM and related topics. The following is a representative sample: •
Alternative Medicine Foundation, Inc.: http://www.herbmed.org/
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AOL: http://search.aol.com/cat.adp?id=169&layer=&from=subcats
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Chinese Medicine: http://www.newcenturynutrition.com/
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drkoop.com®: http://www.drkoop.com/InteractiveMedicine/IndexC.html
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Family Village: http://www.familyvillage.wisc.edu/med_altn.htm
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Google: http://directory.google.com/Top/Health/Alternative/
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Healthnotes: http://www.healthnotes.com/
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MedWebPlus: http://medwebplus.com/subject/Alternative_and_Complementary_Medicine
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Open Directory Project: http://dmoz.org/Health/Alternative/
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HealthGate: http://www.tnp.com/
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WebMD®Health: http://my.webmd.com/drugs_and_herbs
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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html
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Yahoo.com: http://dir.yahoo.com/Health/Alternative_Medicine/
The following is a specific Web list relating to bacterial infections; 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 Abdominal Wall Inflammation Source: Integrative Medicine Communications; www.drkoop.com Acne Source: Integrative Medicine Communications; www.drkoop.com Acne Vulgaris Source: Healthnotes, Inc.; www.healthnotes.com Ascariasis Source: Integrative Medicine Communications; www.drkoop.com
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Bronchitis Source: Healthnotes, Inc.; www.healthnotes.com Bronchitis Source: Integrative Medicine Communications; www.drkoop.com Bursitis Source: Integrative Medicine Communications; www.drkoop.com Candidiasis Source: Integrative Medicine Communications; www.drkoop.com Cellulitis Source: Integrative Medicine Communications; www.drkoop.com Colds and Flus Source: Prima Communications, Inc.www.personalhealthzone.com Conjunctivitis Source: Integrative Medicine Communications; www.drkoop.com Conjunctivitis and Blepharitis Source: Healthnotes, Inc.; www.healthnotes.com Endocarditis Source: Integrative Medicine Communications; www.drkoop.com Gastritis Source: Healthnotes, Inc.; www.healthnotes.com Guinea Worm Disease Source: Integrative Medicine Communications; www.drkoop.com Hair Disorders Source: Integrative Medicine Communications; www.drkoop.com HIV and AIDS Support Source: Healthnotes, Inc.; www.healthnotes.com Hookworm Source: Integrative Medicine Communications; www.drkoop.com Influenza Source: Healthnotes, Inc.; www.healthnotes.com Laryngitis Source: Integrative Medicine Communications; www.drkoop.com Loiasis Source: Integrative Medicine Communications; www.drkoop.com
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Lymphatic Filariasis Source: Integrative Medicine Communications; www.drkoop.com Measles Source: Integrative Medicine Communications; www.drkoop.com Meningitis Source: Integrative Medicine Communications; www.drkoop.com Peritonitis Source: Integrative Medicine Communications; www.drkoop.com Photodermatitis Source: Integrative Medicine Communications; www.drkoop.com Pink Eye Source: Integrative Medicine Communications; www.drkoop.com Pinworm Source: Integrative Medicine Communications; www.drkoop.com Proctitis Source: Integrative Medicine Communications; www.drkoop.com Rectal Inflammation Source: Integrative Medicine Communications; www.drkoop.com River Blindness Source: Integrative Medicine Communications; www.drkoop.com Roundworms Source: Integrative Medicine Communications; www.drkoop.com Shock Source: Integrative Medicine Communications; www.drkoop.com Sinus Headache Source: Integrative Medicine Communications; www.drkoop.com Skin Infection Source: Integrative Medicine Communications; www.drkoop.com Sunburn Source: Integrative Medicine Communications; www.drkoop.com Threadworm Source: Integrative Medicine Communications; www.drkoop.com Trichinosis Source: Integrative Medicine Communications; www.drkoop.com
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Urethral Inflammation Source: Integrative Medicine Communications; www.drkoop.com Urethritis Source: Integrative Medicine Communications; www.drkoop.com Visceral Larva Migrans Source: Integrative Medicine Communications; www.drkoop.com Whipworm Source: Integrative Medicine Communications; www.drkoop.com Yeast Infection Source: Integrative Medicine Communications; www.drkoop.com •
Alternative Therapy Aromatherapy Source: Integrative Medicine Communications; www.drkoop.com
•
Herbs and Supplements Amoxicillin Source: Healthnotes, Inc.; www.healthnotes.com Astragalus Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10006,00.html Chamomile Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,766,00.html Curcuma Longa Source: Integrative Medicine Communications; www.drkoop.com FOS Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10026,00.html Gamma-Linolenic Acid (GLA) Alternative names: GLA Source: Integrative Medicine Communications; www.drkoop.com GLA Alternative names: Gamma-Linolenic Acid (GLA) Source: Integrative Medicine Communications; www.drkoop.com
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Glycyrrhiza glabra Source: Integrative Medicine Communications; www.drkoop.com Levofloxacin Source: Healthnotes, Inc.; www.healthnotes.com Licorice Alternative names: Glycyrrhiza glabra, Spanish Licorice Source: Integrative Medicine Communications; www.drkoop.com Loracarbef Source: Healthnotes, Inc.; www.healthnotes.com Neem Source: Prima Communications, Inc.www.personalhealthzone.com Nitrofurantoin Source: Healthnotes, Inc.; www.healthnotes.com Ofloxacin Source: Healthnotes, Inc.; www.healthnotes.com Penicillin V Source: Healthnotes, Inc.; www.healthnotes.com Spanish Licorice Source: Integrative Medicine Communications; www.drkoop.com Sulfamethoxazole Source: Healthnotes, Inc.; www.healthnotes.com Turmeric Alternative names: Curcuma longa Source: Integrative Medicine Communications; www.drkoop.com
General References A good place to find general background information on CAM is the National Library of Medicine. It has prepared within the MEDLINEplus system an information topic page dedicated to complementary and alternative medicine. To access this page, go to the MEDLINEplus site at http://www.nlm.nih.gov/medlineplus/alternativemedicine.html. This Web site provides a general overview of various topics and can lead to a number of general sources.
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CHAPTER 4. DISSERTATIONS ON BACTERIAL INFECTIONS Overview In this chapter, we will give you a bibliography on recent dissertations relating to bacterial infections. 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 “bacterial infections” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on bacterial infections, we have not necessarily excluded non-medical dissertations in this bibliography.
Dissertations on Bacterial Infections 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 bacterial infections. 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: •
The Role of Toll-Like Receptors in the Battle against Bacterial Infections by Krutzik, Stephan Richard, PhD from University of California, Los Angeles, 2003, 139 pages http://wwwlib.umi.com/dissertations/fullcit/3100703
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. INFECTIONS
CLINICAL
TRIALS
AND
BACTERIAL
Overview In this chapter, we will show you how to keep informed of the latest clinical trials concerning bacterial infections.
Recent Trials on Bacterial Infections The following is a list of recent trials dedicated to bacterial infections.8 Further information on a trial is available at the Web site indicated. •
Antibiotic treatment for patients with infections of short term in-dwelling vascular catheters due to a specific bacteria (gram positive bacteria) Condition(s): Bacterial Infections; Gram-Positive Bacterial Infections; Bacteremia Study Status: This study is currently recruiting patients. Sponsor(s): (Sponsor Name Pending) Purpose - Excerpt: This study will treat patients who have a short term central catheter that is thought to be infected with a specific bacteria (gram positive bacteria) Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00037050
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ARBELIC(tm) (TD 6424) for Treatment of Uncomplicated Staphylococcus aureus Bacteremia Condition(s): Gram-Positive Bacterial Infections Study Status: This study is currently recruiting patients. Sponsor(s): Theravance
8
These are listed at www.ClinicalTrials.gov.
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Purpose - Excerpt: The purpose of this study is to determine whether ARBELIC (TD6424) can be safety administered to patients with bloodstream infections and whether ARBELIC (TD-6424) is effective in treating these infections. Phase(s): Phase II Study Type: Interventional Contact(s): Steven Barriere, PharmD 650 808 6132 Web Site: http://clinicaltrials.gov/ct/show/NCT00062647 •
New antibiotic to treat pediatric patients with infections due to a specific bacteria (Vancomycin-Resistant Enterococcus) Condition(s): Drug Resistance, Microbial; Bacterial Infections Study Status: This study is currently recruiting patients. Sponsor(s): (Sponsor Name Pending) Purpose - Excerpt: This study will treat pediatric patients who have infections that are due to a specific bacteria (Vancomycin-Resistant Enterococcus) Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00035854
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A Study to Compare Different Drugs Used to Prevent Serious Bacterial Infections in HIV-Positive Children Condition(s): Bacterial Infections; Pneumonia, Pneumocystis carinii; HIV Infections Study Status: This study is no longer recruiting patients. Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID); Pfizer; Glaxo Wellcome; National Institute of Child Health and Human Development (NICHD) Purpose - Excerpt: This study compares 2 different treatments administered to try to prevent serious bacterial infections (such as pneumonia) in HIV-positive children. A combination of drugs (azithromycin plus atovaquone) will be compared to sulfamethoxazole-trimethoprim (SMX/TMP) alone. This study also evaluates the longterm safety and tolerance of these different drugs. SMX/TMP is a commonly prescribed drug for the prevention of bacterial infections. However, the combination of azithromycin and atovaquone may be safer and more effective than SMX/TMP. This study compares the 2 treatments. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00000811
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Daptomycin for the Treatment of Infections Due to Gram-positive Bacteria Condition(s): Gram-Positive Bacterial Infections Study Status: This study is no longer recruiting patients. Sponsor(s): Cubist Pharmaceuticals
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Purpose - Excerpt: The purpose of this study is to provide daptomycin, an antibiotic, to patients who are failing conventional therapy, or who cannot take approved antibiotics for one reason or another. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00055198 •
Evaluation of Two Type III GBS Polysaccharide-Tetanus Toxoid Conjugate Vaccines Condition(s): Bacterial Infections; Group B Streptococcus Study Status: This study is no longer recruiting patients. Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID) Purpose - Excerpt: The purpose of this study is to test the safety and favorable immune response to an anti-streptococcal vaccine (a vaccine that treats a common bacterial infection) in healthy non-pregnant women. Group B Streptococcus (GBS) continues to be the single most frequent cause of life-threatening bacterial infection during the first 2 months of life. Further, GBS pregnancy-related morbidity afflicts more than 50,000 women annually in the US. Therefore, active immunization of women is an appealing strategy for the prevention of GBS disease in pregnant women and their infants during the first 3 months of infant life. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00008853
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A Study of Azithromycin in HIV-Infected Patients Condition(s): Bacterial Infections; HIV Infections Study Status: This study is completed. Sponsor(s): Pfizer Purpose - Excerpt: To assess the dose proportionality of azithromycin concentrations and toleration when delivered in tablet formulation to HIV-infected patients. The need exists to further assess the antibacterial agent azithromycin at differing doses in an HIVinfected population. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00002344
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Effect of Fluconazole, Clarithromycin, and Rifabutin on the Pharmacokinetics of Sulfamethoxazole-Trimethoprim and Dapsone and Their Hydroxylamine Metabolites Condition(s): Bacterial Infections; Mycoses; HIV Infections Study Status: This study is completed. Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID)
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Purpose - Excerpt: To determine the effects of fluconazole and either rifabutin or clarithromycin, alone and in combination, on the pharmacokinetics of first sulfamethoxazole-trimethoprim and then dapsone in HIV-infected patients. Although prophylaxis for more than one opportunistic infection is emerging as a common clinical practice in patients with advanced HIV disease, little is known about possible adverse drug interactions. The need exists to define pharmacokinetics and pharmacodynamic adverse interactions of the many combination prophylactic regimens that may be prescribed. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00000826 •
Interleukin-12 in the Treatment of Severe Nontuberculous Mycobacterial Infections Condition(s): Atypical Mycobacterium Infection Study Status: This study is completed. Sponsor(s): National Institute of Allergy and Infectious Diseases (NIAID) Purpose - Excerpt: This study will test the safety and effectiveness of a drug called interleukin-12 (IL-12) in fighting severe infectious (other than tuberculosis) caused by a group of bacteria called mycobacteria. IL-12 is similar to a substance the body produces naturally to strengthen immune function (infection-fighting ability). It works by stimulating white blood cells to increase production of a chemical called interferon gamma, which can improve or cure mycobacterial infections in some patients. In previous studies, IL-12 has improved immune function against mycobacteria in test tube experiments and in mice. A recent study of three patients with mycobacterial infections treated with the drug showed encouraging results. The drug has also been studied more extensively in patients with cancer, HIV infection and hepatitis C. Patients in this study will receive IL-12 injections under the skin twice a week for one year. They will be taught how to self-administer the drug, but a home care nurse or a physician may also give the injections. The drug dosage will be increased each week to determine the safest and most effective dose for fighting this infection. If intolerable side effects develop at a certain dose, the previous dose level will be used for the next injection. That dose will then be used for the rest of the study, unless unacceptable side effects develop at that level, in which case the dose will again be lowered. Patients will receive an antibiotic against mycobacteria. Physical examinations and blood and urine tests will be done once a month for at least the first year and then every 3 months the following year to evaluate kidney, liver, and immune function. The first evaluation-at the start of the study-is done on an inpatient basis. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001911
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•
New Antibiotic to treat patients with community-acquired pneumonia due to a specific bacteria (S. pneumoniae pneumonia) Condition(s): Pneumonia, Pneumococcal; Community Acquired Infections; GramPositive Bacterial Infections Study Status: This study is completed. Sponsor(s): (Sponsor Name Pending) Purpose - Excerpt: This study will treat patients who have a community-acquired pneumonia that is due to a specific bacteria (S. pneumoniae) Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00035269
•
Phase I Study of the Clinical Pharmacology of Azithromycin in Buffy Coat of HIVInfected Subjects. Condition(s): Bacterial Infections; HIV Infections Study Status: This study is completed. Sponsor(s): Pfizer Purpose - Excerpt: To compare the uptake of azithromycin in white cells relative to plasma concentrations in HIV-infected patients. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00002139
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Phase II Randomized, Double-Blind, Placebo-Controlled Study of Intravenous Mucoid Exopolysaccharide Pseudomonas Aeruginosa Immune Globulin for Cystic Fibrosis Condition(s): Cystic Fibrosis; Bacterial Infections Study Status: This study is completed. Sponsor(s): National Center for Research Resources (NCRR); Vanderbilt University Medical Center Purpose - Excerpt: Objectives: I. Assess the efficacy of monthly intravenous mucoid exopolysaccharide Pseudomonas aeruginosa immune globulin (MEP IGIV) given over 1 year in reducing the frequency of acute pulmonary exacerbation in patients with cystic fibrosis, mild to moderate pulmonary disease, and mucoid P. aeruginosa colonization. II. Assess the effect of MEP IGIV on FEV1, sputum density of mucoid P. aeruginosa, and the quality of life in these patients. III. Assess the safety of monthly MEP IGIV. IV. Assess population-based MEP IGIV pharmacokinetics during chronic therapy. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004747
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Bacterial Infections
Phase III Randomized Study of the Inhalation of Tobramycin in Patients with Cystic Fibrosis Condition(s): Cystic Fibrosis; Bacterial Infection Study Status: This study is completed. Sponsor(s): FDA Office of Orphan Products Development Purpose - Excerpt: Objectives: I. Determine the safety and efficacy of tobramycin in patients with cystic fibrosis who are chronically colonized with Pseudomonas aeruginosa. II. Determine whether this treatment produces tobramycin-resistant bacteria at a frequency different from the placebo group and whether the emergence of resistance is associated with a lack of clinical response. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004829
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Treatment of neutropenic patients with fever who are suspected to have a gram positive infection (a specific kind of bacteria) Condition(s): Neutropenia; Fever; Gram-Positive Bacterial Infections; Neoplasms Study Status: This study is completed. Sponsor(s): (Sponsor Name Pending) Purpose - Excerpt: This study will treat patients who have fever and neutropenia (after cancer chemotherapy) that is possibly due to a specific bacteria (gram positive bacteria) Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00035425
Keeping Current on Clinical Trials The U.S. National Institutes of Health, through the National Library of Medicine, has developed ClinicalTrials.gov to provide current information about clinical research across the broadest number of diseases and conditions. The site was launched in February 2000 and currently contains approximately 5,700 clinical studies in over 59,000 locations worldwide, with most studies being conducted in the United States. ClinicalTrials.gov receives about 2 million hits per month and hosts approximately 5,400 visitors daily. To access this database, simply go to the Web site at http://www.clinicaltrials.gov/ and search by “bacterial infections” (or synonyms). While ClinicalTrials.gov is the most comprehensive listing of NIH-supported clinical trials available, not all trials are in the database. The database is updated regularly, so clinical trials are continually being added. The following is a list of specialty databases affiliated with the National Institutes of Health that offer additional information on trials:
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•
For clinical studies at the Warren Grant Magnuson Clinical Center located in Bethesda, Maryland, visit their Web site: http://clinicalstudies.info.nih.gov/
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For clinical studies conducted at the Bayview Campus in Baltimore, Maryland, visit their Web site: http://www.jhbmc.jhu.edu/studies/index.html
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For cancer trials, visit the National Cancer Institute: http://cancertrials.nci.nih.gov/
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For eye-related trials, visit and search the Web page of the National Eye Institute: http://www.nei.nih.gov/neitrials/index.htm
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For heart, lung and blood trials, visit the Web page of the National Heart, Lung and Blood Institute: http://www.nhlbi.nih.gov/studies/index.htm
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For trials on aging, visit and search the Web site of the National Institute on Aging: http://www.grc.nia.nih.gov/studies/index.htm
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For rare diseases, visit and search the Web site sponsored by the Office of Rare Diseases: http://ord.aspensys.com/asp/resources/rsch_trials.asp
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For alcoholism, visit the National Institute on Alcohol Abuse and Alcoholism: http://www.niaaa.nih.gov/intramural/Web_dicbr_hp/particip.htm
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For trials on infectious, immune, and allergic diseases, visit the site of the National Institute of Allergy and Infectious Diseases: http://www.niaid.nih.gov/clintrials/
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For trials on arthritis, musculoskeletal and skin diseases, visit newly revised site of the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health: http://www.niams.nih.gov/hi/studies/index.htm
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For hearing-related trials, visit the National Institute on Deafness and Other Communication Disorders: http://www.nidcd.nih.gov/health/clinical/index.htm
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For trials on diseases of the digestive system and kidneys, and diabetes, visit the National Institute of Diabetes and Digestive and Kidney Diseases: http://www.niddk.nih.gov/patient/patient.htm
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For drug abuse trials, visit and search the Web site sponsored by the National Institute on Drug Abuse: http://www.nida.nih.gov/CTN/Index.htm
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For trials on mental disorders, visit and search the Web site of the National Institute of Mental Health: http://www.nimh.nih.gov/studies/index.cfm
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For trials on neurological disorders and stroke, visit and search the Web site sponsored by the National Institute of Neurological Disorders and Stroke of the NIH: http://www.ninds.nih.gov/funding/funding_opportunities.htm#Clinical_Trials
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CHAPTER 6. PATENTS ON BACTERIAL INFECTIONS Overview Patents can be physical innovations (e.g. chemicals, pharmaceuticals, medical equipment) or processes (e.g. treatments or diagnostic procedures). The United States Patent and Trademark Office defines a patent as a grant of a property right to the inventor, issued by the Patent and Trademark Office.9 Patents, therefore, are intellectual property. For the United States, the term of a new patent is 20 years from the date when the patent application was filed. If the inventor wishes to receive economic benefits, it is likely that the invention will become commercially available within 20 years of the initial filing. It is important to understand, therefore, that an inventor’s patent does not indicate that a product or service is or will be commercially available. The patent implies only that the inventor has “the right to exclude others from making, using, offering for sale, or selling” the invention in the United States. While this relates to U.S. patents, similar rules govern foreign patents. In this chapter, we show you how to locate information on patents and their inventors. If you find a patent that is particularly interesting to you, contact the inventor or the assignee for further information. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical patents that use the generic term “bacterial infections” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on bacterial infections, we have not necessarily excluded nonmedical patents in this bibliography.
Patents on Bacterial Infections By performing a patent search focusing on bacterial infections, you can obtain information such as the title of the invention, the names of the inventor(s), the assignee(s) or the company that owns or controls the patent, a short abstract that summarizes the patent, and a few excerpts from the description of the patent. The abstract of a patent tends to be more technical in nature, while the description is often written for the public. Full patent descriptions contain much more information than is presented here (e.g. claims, references, figures, diagrams, etc.). We will tell you how to obtain this information later in the chapter. 9Adapted
from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.
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The following is an example of the type of information that you can expect to obtain from a patent search on bacterial infections: •
11-O-substituted macrolides and their descladinose derivatives Inventor(s): Niu; Deqiang (Waltham, MA), Or; Yat Sun (Cambridge, MA), Phan; Ly Tam Phan (Malden, MA) Assignee(s): Enanta Pharmaceuticals, Inc. (watertown, Ma) Patent Number: 6,673,774 Date filed: December 3, 2001 Abstract: There are described 11-O-substituted macrolides and their descladinose derivatives and pharmaceutically acceptable compositions comprising a therapeutically effective amount of a compound of the invention in combination with a pharmaceutically acceptable carrier. Also described is a method for treating bacterial infections by administering to a mammal a pharmaceutical composition containing a therapeutically-effective amount of a compound of the invention, and processes for the preparation of such compounds. Excerpt(s): The present invention relates to novel macrolides having antibacterial activity and useful in the treatment and prevention of bacterial infections. More particularly, the invention relates to a novel class of 11-O-substituted Clarithromycin derivatives, compositions containing such compounds and methods for using the same, as well as processes for making such compounds. The search for macrolides active against MLS.sub.B -resistant strains (MLS.sub.B =Macrolides-Lincosamides-type B Streptogramines) has become a major goal, together with retaining the overall profile of the macrolides in terms of stability, tolerance and pharmacokinetics. g. --NR.sub.6 R.sub.7, where R.sub.6 and R.sub.7 are as previously defined. Web site: http://www.delphion.com/details?pn=US06673774__
•
4'-O-substituted tylosin analogs Inventor(s): Jian; Tianying (Boston, MA), Or; Yat Sun (Cambridge, MA), Phan; Ly Tam (Malden, MA), Qiu; Yao-Ling (Somerville, MA) Assignee(s): Enanta Pharmaceuticals, Inc. (watertown, Ma) Patent Number: 6,576,615 Date filed: November 8, 2001 Abstract: There are described novel 4' substituted tylosin analogs and pharmaceutically acceptable compositions comprising a therapeutically effective amount of a compound of the invention in combination with a pharmaceutically acceptable carrier. Also described is a method for treating bacterial infections by administering to a mammal a pharmaceutical composition containing a therapeutically-effective amount of a compound of the invention, and processes for the preparation of such compounds. Excerpt(s): The present invention relates to novel macrolides having antibacterial activity and useful in the treatment and prevention of bacterial infections. More particularly, the invention relates to a novel class of 4'-substituted 16-membered macrolides, compositions containing such compounds and methods for using the same, as well as processes for making such compounds. Macrolide antibiotics play a
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therapeutically important role, particularly with the emergence of new pathogens. Structural differences are related to the size of the lactone ring and to the number and nature (neutral or basic) of the sugars. Macrolides are classified according to the size of the lactone ring (12, 14, 15 or 16 atoms). The macrolide antibiotic family (14-, 15- and 16membered ring derivatives) exhibits a wide range of characteristics (antibacterial spectrum, side-effects and bioavailability). Among the commonly used macrolides are erythromycin and josamycin. Considerable research efforts have been carried out on tylosin and its derivatives but not much success has been observed with this subclass. The search for macrolides active against MLS-resistant strains (MLS.dbd.MacrolidesLincosamides-Streptogramines) has become a major goal, in addition to improving the overall profile of the macrolides in terms of acid stability, tolerance and pharmacokinetics. Web site: http://www.delphion.com/details?pn=US06576615__ •
7, 9-substituted tetracycline compounds Inventor(s): Bhatia; Beena (Arlington, MA), Bowser; Todd (Charlton, MA), Frechette; Roger (Reading, MA), Hawkins; Paul (Cambridge, MA), Ismail; Mohamed (Bedford, MA), McIntyre; Laura (Arlington, MA), Nelson; Mark L. (Wellesley, MA), Reddy; Laxma (Lexington, MA), Sheahan; Paul (Hopkinton, MA), Stapleton; Karen (Weymouth, MA), Viski; Peter (Brookline, MA), Warchol; Tad (Acton, MA) Assignee(s): Paratek Pharmaceuticals, Inc. (boston, Ma) Patent Number: 6,683,068 Date filed: June 29, 2001 Abstract: The present invention pertains to novel 7,9-substituted tetracycline compounds. These tetracycline compounds can be used to treat numerous tetracycline compound-responsive states, such as bacterial infections and neoplasms, as well as other known applications for minocycline and tetracycline compounds in general, such as blocking tetracycline efflux and modulation of gene expression. Excerpt(s): The development of the tetracycline antibiotics was the direct result of a systematic screening of soil specimens collected from many parts of the world for evidence of microorganisms capable of producing bacteriocidal and/or bacteriostatic compositions. The first of these novel compounds was introduced in 1948 under the name chlortetracycline. Two years later, oxytetracycline became available. The elucidation of the chemical structure of these compounds confirmed their similarity and furnished the analytical basis for the production of a third member of this group in 1952, tetracycline. A new family of tetracycline compounds, without the ring-attached methyl group present in earlier tetracyclines, was prepared in 1957 and became publicly available in 1967; and minocycline was in use by 1972. Recently, research efforts have focused on developing new tetracycline antibiotic compositions effective under varying therapeutic conditions and routes of administration. New tetracycline analogues have also been investigated which may prove to be equal to or more effective than the originally introduced tetracycline compounds. Examples include U.S. Pat. Nos. 2,980,584; 2,990,331; 3,062,717; 3,165,531; 3,454,697; 3,557,280; 3,674,859; 3,957,980; 4,018,889; 4,024,272; and 4,126,680. These patents are representative of the range of pharmaceutically active tetracycline and tetracycline analogue compositions. Historically, soon after their initial development and introduction, the tetracyclines were found to be highly effective pharmacologically against rickettsiae; a number of grampositive and gram-negative bacteria; and the agents responsible for lymphogranuloma
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venereum, inclusion conjunctivitis, and psittacosis. Hence, tetracyclines became known as "broad spectrum" antibiotics. With the subsequent establishment of their in vitro antimicrobial activity, effectiveness in experimental infections, and pharmacological properties, the tetracyclines as a class rapidly became widely used for therapeutic purposes. However, this widespread use of tetracyclines for both major and minor illnesses and diseases led directly to the emergence of resistance to these antibiotics even among highly susceptible bacterial species both commensal and pathogenic (e.g., pneumococci and Salmonella). The rise of tetracycline-resistant organisms has resulted in a general decline in use of tetracyclines and tetracycline analogue compositions as antibiotics of choice. Web site: http://www.delphion.com/details?pn=US06683068__ •
Antifungal and antibacterial peptides Inventor(s): Friden; Phillip M. (Bedford, MA), Oppenheim; Frank G. (Chestnut Hill, MA), Roberts; F. Donald (Dover, MA), Spacciapoli; Peter (Newbury, MA), Xu; Tao (Newton, MA) Assignee(s): Periodontix, Inc. (boston, Ma), Trustees of Boston University (watertown, Ma) Patent Number: 6,531,573 Date filed: December 18, 1997 Abstract: Substantially pure peptides containing between 13 and 20 amino acids, inclusive, having the amino acid sequence: R1-R2-R3-R4-R5-R6-R7-R8-R9-R10-R11-R12R13-R14-R15-R16-R17-R18-R19-R20-R21 -R22-R23, where R1 is Asp or is absent; R2 is Ser or is absent; R3 is His or is absent; R4 is Ala; R5 is Lys, Gln, Arg, or another basic amino acid; R6 is Arg, Gln, Lys, or another basic amino acid; R7 is His, Phe, Tyr, Leu, or another hydrophobic amino acid; R8 is His, Phe, Tyr, Leu, or another hydrophobic amino acid; R9 is Gly, Lys, Arg, or another basic amino acid; R10 is Tyr; R11 is Lys, His, Phe, or another hydrophobic amino acid; R12 is Arg, Gln, Lys, or another basic amino acid; R13 is Lys, Gln, Arg, another basic amino acid, or is absent; R14 is Phe or is absent; R15 is His, Phe, Tyr, Leu, another hydrophobic amino acid, or is absent; R16 is Glu or is absent; R17 is Lys or is absent; R18 is His or is absent; R19 is His or is absent; R20 is Ser or is absent; R21 is His or is absent; R22 is Arg or is absent; and R23 is Gly or is absent; and where Gln cannot simultaneously occupy positions R5, R6, R12, and R13 of the amino acid sequence, as well as pharmaceutical compositions containing these peptides and methods for treating fuingal and bacterial infections using these peptides, are disclosed. Excerpt(s): The invention relates to antifingal and antibacterial peptides. Bacterial and fungal infections are prevalent and, in some cases, life-threatening conditions that affect otherwise healthy patients. Bacterial and fungal infections are especially dangerous for immuno-compromised patients. For these patients, systemic fungal infections can lead to death, since there are few safe and effective antifungal pharmaceuticals for intravenous use. Similarly, infections with various bacterial species can cause sever disease states and even death. Although several antifungal agents (e.g., clotrimazole, miconazole, ketoconazole, and nystatin) and antibacterial agents (e.g., penicillin, streptomycin, tetracycline, and chlorhexidine) are currently available, these agents are not completely effective. These agents can also lead to drug resistant organisms and can produce adverse side effects. In addition, many are not appropriate for oral or systemic administration.
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Web site: http://www.delphion.com/details?pn=US06531573__ •
Antimicrobial polypeptides and methods of use Inventor(s): Hillman; Jeffrey D. (Gainsville, FL) Assignee(s): University of Florida Research Foundation (gainesville, Fl) Patent Number: 6,475,771 Date filed: March 13, 2002 Abstract: Antimicrobial compounds and compositions and uses thereof, including the treatment and prevention of bacterial infections are described. The compounds and compositions include lantibiotic polypeptides and the nucleic acid sequences encoding the polypeptides. The compounds and compositions are useful as antimicrobials in antibiotic pharmaceutical preparation and as an antimicrobial or antiseptic dentifrice. Excerpt(s): The subject invention concerns novel polypeptides and nucleic acid sequences encoding those polypeptides. The polypeptides are related to bacteriocins, e.g. mutacins, produced by microbes for providing a selective advantage for the microbe. The invention includes methods of use which exploit the advantageous activities or properties of the polypeptides or nucleic acid sequences. The phenotypically similar bacteria collectively known as the mutans streptococci are considered major etiologic agents responsible for dental caries. The species most commonly associated with human disease is Streptococcus mutans. Pathogenicity of S. mutans includes the ability to produce antimicrobial substances generally referred to as bacteriocin-like inhibitory substances (BLIS) or bacteriocins. Bacteriocins produced by Streptococcus mutans are known as mutacins. These substances are produced by microorganisms to provide a selective force necessary for sustained colonization in a milieu of densely packed competing organisms found in dental plaque. To date, most bacteriocins remain only partially characterized because they are made in small quantities and only under special cultivation conditions. In addition, mutacins are known to be difficult to isolate from liquid medium. The spectrum of activity and chemical and physical properties of mutacins can vary widely. Web site: http://www.delphion.com/details?pn=US06475771__
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Antimicrobial quinolone derivatives and use of the same to treat bacterial infections Inventor(s): Barbachyn; Michael R. (Kalamazoo, MI), Gage; James R. (Portage, MI), Gordeev; Mikhail F. (Castro Valley, CA), Patel; Dinesh V. (Fremont, CA) Assignee(s): Pharmacia & Upjohn Company (kalamazoo, Mi) Patent Number: 6,689,769 Date filed: November 29, 2001 Abstract: Substituted quinolone derivatives in which an oxazolidinone, isoxazolinone, or isoxazoline is covalently bonded to a quinolone, methods of using the quinolone derivatives, and pharmaceutical compositions containing the quinolone derivatives are disclosed. Methods of synthesizing these substituted quinolone derivatives are also disclosed, and in particular a method of manufacturing a 7-(2-oxo-1,3-oxazolidin-3yl)aryl-3-quinolinecarboxylic acid by condensing a 4-(2-oxo-1,3-oxazolidin-5-yl)aryl boronic acid with a 7-halo-quinolone derivative. The quinolone derivatives possess
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antibacterial activity, and are effective against a number of human and veterinary pathogens in the treatment of bacterial diseases. Excerpt(s): The present invention relates to substituted quinolone derivatives wherein an oxazolidinone, isoxazolinone, or isoxazoline compound is chemically combined with a quinolone. The present invention also relates to a method of preparing pharmacologically active quinolone derivatives and various intermediates used in the method. The present quinolone derivatives are useful as broad spectrum antimicrobial agents effective against a number of human and veterinary Gram positive and Gram negative pathogens, including the Staphylococci, for example S. aureus; Enterococci, for example E. faecalis; Streptococci, for example S. pneumoniae; Haemophilus, for example H. influenza; Moraxella, for example M. catarrhalis; and Escherichia for example E. coli; Mycobacteria, for example M. tuberculosis; intercellular microbes, for example Chlamydia and Rickettsiae; and Mycoplasma, for example M. pneumoniae, amongst others. The present invention also relates to pharmaceutical compositions containing the quinolone derivatives, to methods of treating a bacterial infection using the quinolone derivatives, and to a process for producing the quinolone derivatives. The increase in bacterial resistance to existing antibacterial agents is a major clinical problem. Accordingly, there is a need in the art for compounds, compositions, and methods of treating warm-blooded animals that suffer from a bacterial infection and are resistant to conventional antibacterial treatments. The development and increase in resistance to the quinolone carboxylic acid class of antibacterial compounds has not been as pervasive as with other antibacterial agents. Therefore, new quinolone carboxylic acid compounds may be useful in combating resistant bacteria. Oxazolidinones (III) having an arylbenzene substituent on the oxazolidinone ring are disclosed in U.S. Pat. Nos. 4,948,801 and 5,130,316. 3-[(Di- or fused-ring substituted)phenyl]-2-oxazolidinones are disclosed in U.S. Pat. Nos. 4,977,173; 4,921,869; 4,801,600; and 5,164,510. European Patent Applications 0 697 412; 0 694 544; 0 694 543; and 0 693 491, and International Patent Publication No. WO 93/09103, disclose 5- to 9-membered substituted aryl- and heteroaryl-phenyl oxazolidinones as antibacterial agents. U.S. Pat. No. 5,254,577 discloses aminomethyloxooxazolidinyl arylbenzene derivatives as antibacterial agents. Other references disclosing oxazolidinones include U.S. Pat. Nos. 4,801,600 and 4,921,869. Some of the pyridine-substituted phenyl oxazolidinone derivatives disclosed in the above patents are effective against Gram positive bacteria, such as Staphylococcus aureus and Streptococcus pneumoniae. However, the oxazolidinones are not active against Gram negative bacteria, such as Escherichia coli, Klebsiella, Proteus, and Seratia marcenses. Moreover, oxazolidinones cannot be administered as an injection solution because their free amino forms are sparingly soluble. Web site: http://www.delphion.com/details?pn=US06689769__ •
Combinatorial library synthesis and pharmaceutically active compounds produced thereby Inventor(s): Iyer; Radhakrishnan (Shrewsbury, MA), Jin; Yi (Montreal, CA), Roland; Arlene (Montreal, CA), Zhou; Wenqiang (Montreal, CA) Assignee(s): Micrologix Biotech Inc. (vancouver, Ca) Patent Number: 6,620,796 Date filed: November 8, 2000 Abstract: The invention provides new methods for synthesis of nucleotide-based compounds and new libraries of such compounds. Compounds of the invention are
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useful for a variety of therapeutic applications, including treatment of viral or bacterial infections and associated diseases and disorders. Excerpt(s): The invention provides new methods for synthesis of nucleotide-based compounds and libraries of such compounds. Compounds of the invention are useful for a variety of therapeutic applications, including treatment of viral or bacterial infections and associated diseases and disorders. The important initial step in the development of therapeutic agents is the discovery of compounds that bind to a protein, enzyme or receptor of interest. Through careful structure/activity work of resulting active compounds, one arrives at a lead compound for further development into a clinical candidate. This traditional process of drug discovery is a long and arduous endeavor. Often it takes 10 to 15 years before a new drug makes it into the marketplace. Recent advances in molecular biology and genomics have led to identification of new molecular targets for drug discovery. As a result of the limitation of traditional drug discovery, new approaches to the discovery of therapeutics have been developed. In the more modern approaches, large libraries of diverse compounds are synthesized by a number of methods and subjected to high throughput in vitro screening against a particular molecular target implicated in a disease. The active compounds so identified are then subjected to Structure-Activity Relationship (SAR) work to eventually identify the lead compound. Web site: http://www.delphion.com/details?pn=US06620796__ •
Composition for treatment of drug resistant bacterial infections and a method of treating drug resistant bacterial infections Inventor(s): Brindavanam; Narasimha Baba (Ghaziabad, IN), Katiyar; Chandra Kant (Ghaziabad, IN), Narayana; Dasalukunte Bhimrao Ananta (Ghaziabad, IN) Assignee(s): Dabur Research Foundation (utter Pradesh, In) Patent Number: 6,599,541 Date filed: September 15, 2000 Abstract: The invention provides a novel composition useful in the treatment of resistant bacterial infections, said composition comprising an extract obtained from Azadiracta indica or Melia azadirachta and an effective amount of an antibiotic or chemotherapuetic antibacterial drug. Further, the invention provides a method for the treatment of resistant bacterial infections. The invention also provides a process for the preparation of the composition of the invention. Excerpt(s): The invention provides a synergistic novel composition which can be used against bacteria that have developed resistance to conventional antibiotics and other chemotherapuetic anti-microbial agents. Preferably, the invention provides a composition comprising of an herbal agent to re-sensitize the resistant bacterial strains and an antibiotic or a chemotherapuetic anti-bacterial drug to which, the bacterial strain was resistant. The invention also provides a process for the preparation of the composition. Bacterial resistance to conventional antibiotics and other chemotherapuetic agents has been an area of serious concern in clinical practice. Sulfa-resistant gonococci were widespread 10 years after their introduction. Penicillin was introduced during 1940's. Although originally was highly susceptible, Staphylococcus aureus quickly developed.beta.-lactamase mediated resistance and caused epidemics during 1950's. Semi-synthetic penicillins were developed for a broad-spectrum of anti bacterial activity. For a long time, the first member of this group, Ampicillin has been most
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widely prescribed drug. But, now 20-70% of E. coli strains are Ampicillin resistant (Beam Jr. TR 1992 on Principles of anti-infectives Use--chapter-47 in Text Book of Pharmacology, ed. Smith C M and Raynard A M, published by W. B. Saunders Company, 1.sup.st ed., p-812-814). This phenomenon has been an important factor necessitating the development of newer anti-microbial molecules. The bacterial resistance to an antibiotic can be of two kinds (Beam Jr. T R, 1992 on Principles of Antiinfectives Use--chapter47 in Text Book of Pharmacology, ed. Smith C M and Raynard A M, published by W. B. Saunders Company, 1.sup.st ed., p-812-814.). The first one is called intrinsic resistance. This is a natural phenomenon and hence, all antibiotics do not exhibit activity against all sorts of bacteria but work in a selective manner. The second type is an acquired resistance. In this type, a particular bacterial species appear to be susceptible to an antibiotic initially but develops resistance over a period of time. Acquired resistance by bacteria to an antibiotic in use poses a specific problem in clinical practice, as the patients hosting such resistant organisms do not respond to the therapy. Web site: http://www.delphion.com/details?pn=US06599541__ •
Compositions and methods for treating bacterial infections Inventor(s): Batts; Donald H. (Kalamazoo, MI), Hiramatsu; Keiichi (Tokyo, JP) Assignee(s): Pharmacia & Upjohn Company (kalamazoo, Mi) Patent Number: 6,544,991 Date filed: June 21, 2001 Abstract: A composition having antibacterial activity is disclosed. More particularly, a mixture of an oxazolidinone compound, sulbactam, and ampicillin active agents, demonstrating activity against resistant strains of bacteria is disclosed. Methods for using an oxazolidinone compound, sulbactam, and ampicillin to treat a bacterial infection are also described. Excerpt(s): The invention relates to compositions having antibacterial activity, and methods of treating bacterial infections. More particularly, the invention relates to the use of an oxazolidinone compound, sulbactam, and ampicillin in treating a patient having a bacterial infection. Many classes of compounds, including aminoglycosides, oxazolidinones, and.beta.-lactams, have been described for the treatment of infectious diseases, particularly bacterial infections. As the use of the these antibacterial agents becomes more widespread, the emergence of new resistant strains of bacteria is imminent. The new resistant strains, for example, methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococci (VRE), vancomycin-resistant Staphylococcus aureus (VRSA), glycopeptide-intermediate Staphylococcus aureus (GISA), and vancomycin-intermediate Staphylococcus aureus (VISA), have reduced susceptibility to known antibacterial agents, creating an ongoing need for developing effective therapeutic measures. Oxazolidinones are known to have good activity against gram-positive microorganisms. In particular, the oxazolidinone compounds have demonstrated beneficial characteristics in treating urinary tract infections, caused by resistant bacterial agents including infections induced by vancomycin-resistant Enterococci. Web site: http://www.delphion.com/details?pn=US06544991__
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Disubstituted imidazoles useful in the treatment of bacterial infections Inventor(s): Heerding; Dirk (Malvern, PA), Newlander; Kenneth A. (West Chester, PA) Assignee(s): Smithkline Beecham Corporation (philadelphia, Pa) Patent Number: 6,559,172 Date filed: November 14, 2001 Abstract: Novel disubstituted imidazoles are disclosed which are useful in the treatment of bacterial infections, particularly through the inhibition of FAB I. Excerpt(s): This invention relates to pharmaceutically active compounds which are useful for the treatment of bacterial infections. There is a medical need for novel antibiotics and a market opportunity for new antibacterial agents. Thus, the object of this invention is to identify novel compounds having antibiotic activity. While the overall pathway of saturated fatty acid biosynthesis is similar in all organisms, the fatty acid synthase (FAS) systems vary considerably with respect to their structural organization. Vertebrates and yeast possess a FAS in which all the enzymatic activities are encoded on one or two polypeptide chains, respectively, and the acyl carrier protein (ACP) is an integral part of the complex. In contrast, in bacterial FAS, each of the reactions is catalyzed by a distinct, mono-functional enzyme and the ACP is a discrete protein. Therefore, there is considerable potential for the selective inhibition of the bacterial system by antibacterial agents. Web site: http://www.delphion.com/details?pn=US06559172__
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Enoyl reductases and methods of use thereof Inventor(s): Heath; Richard John (Memphis, TN), Rock; Charles O. (Bartlett, TN) Assignee(s): St. Jude Children's Research Hospital (memphis, Tn) Patent Number: 6,613,553 Date filed: February 4, 2000 Abstract: The present provides structurally related enzymes that act as enoyl reductases. These enoyl reductases share a common amino acid consensus sequence, and bind a flavin cofactor. One particular enoyl reductase provided, FabK, catalyzes the identical reaction as the NADH-dependent enoyl-ACP reductase, FabI. Nucleic acids encoding the enoyl reductases, the enoyl reductases, and anitbodies for the enoyl reductases are also included. Methods are also provides for identifying agents that can act to prevent and/or treat bacterial infections. Excerpt(s): The present invention relates to novel enzymes that act as enoyl reductases. Two distinct families of enoyl reductases have been identified in bacteria, each of which have a consensus amino acid sequence. The enoyl reductases can be used as targets for designing both new prophylactics and treatments for bacterial infections. Nucleic acid and amino acid sequences of the novel enoyl reductases are also provided. Essentially all living organisms synthesize saturated fatty acids by the same biochemical mechanism. However, whereas vertebrates and yeast synthesize saturated fatty acids using either one or two multifunctional enzymes (i.e., type I fatty acid synthases, FASs), with the acyl carrier protein (ACP) being an integral part of the complex, most bacteria and plants synthesize saturated fatty acids through the use of a set of distinct enzymes that are each encoded by an individual gene (i.e., type II FASs). In the type II FAS system, ACP is also a distinct protein. The initial step in the biosynthetic cycle of
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saturated fatty acids is performed by the enzyme FabH [Tsay et al., J. Biol. Chem. 267:6807-68014 (1992), and U.S. Pat. No: 5,759,832, Issued Jun. 2, 1998, both of which are hereby incorporated by reference in their entireties] which catalyzes the condensation of malonyl-ACP with acetyl-COA. Malonyl-ACP is condensed with the growing-chain acyl-ACP in subsequent rounds by FabB synthase I or by FabF, synthase II. The next step is a ketoester reduction that is catalyzed by an NADPH-dependent.beta.-ketoacylACP reductase (FabG). A.beta.-hydroxyacyl-ACP dehydrase (FabA, dehydrase I or FabZ, dehydrase II) catalyzes the subsequent dehydration forming trans-2-enoyl-ACP. FabI, an NADH-dependent enoyl-ACP reductase, then catalyzes the conversion of trans2-enoyl-ACP to acyl-ACP to complete the elongation cycle. The addition of two carbon atoms per elongation cycle continues until palmitoyl-ACP is synthesized. PalmitoylACP is one end-product of the pathway and acts as a feedback inhibitor for both FabH and FabI [Heath, et al, J.Biol. Chem. 271:1833-1836 (1996)]. Web site: http://www.delphion.com/details?pn=US06613553__ •
Formulation comprising thymol useful in the treatment of drug resistant bacterial infections Inventor(s): Agarwal; Krishna Kumar (Lucknow, IN), Ahmed; Ateeque (Lucknow, IN), Darokar; Mahendra Pandurang (Lucknow, IN), Dhawan; Sunita (Lucknow, IN), Khanuja; Suman Preet Singh (Lucknow, IN), Kumar; Sushil (Lucknow, IN), Kumar; Tiruppadiripuliyur Ranganathan Santha (Lucknow, IN), Patra; Nirmal Kumar (Lucknow, IN), Saikia; Dharmendra (Lucknow, IN), Shasney; Ajit Kumar (Lucknow, IN), Sinha; Prachi (Lucknow, IN), Srivastava; Suchi (Lucknow, IN) Assignee(s): Council of Scientific and Industrial Research (new Delhi, Id) Patent Number: 6,514,541 Date filed: March 28, 2000 Abstract: A formulation useful in the treatment of drug resistant bacterial infections comprising an effective amount of thymol obtained from the plant Trachyspermum ammi, mint oil containing an appropriate amount of monoterpenes obtained from a hybrid of Mentha spicata and Mentha arvensis, and conventional additives. A method for producing the formulation by mixing the above ingredients and a method for the treatment of drug resistance in a patient by administration of a therapeutically effective amount of the formulation. Excerpt(s): The present invention relates to a novel synergistic composition useful in the treatment of drug resistant bacterial infections. The composition comprises an effective amount of thymol, a mixture of the essential oils of Mentha arvensis and Mentha spicata or their monoterpene components in appropriate ratio and conventional additives. The composition is useful in the treatment of drug resistant enteric and systemic infections. The formulation with enhanced activity of thymol action comprises thymol in combination with the oil which is a combination containing the rare mixture of carvone, limonene and menthol. The invention also provides methods of producing the composition and a method of using thymol obtained from the seeds of the plant Trachyspermum ammi (Ajwain) as a fourth generation antibiotic formulation for control of drug resistant bacteria. More particularly, the invention relates to the use of a compound `Thymol` isolated from the oil distilled from the seeds of the plant Trachyspermum ammi (Ajwain) to kill the bacteria resistant to even prevalent third generation antibiotics and multi-drug resistant (mdr) microbial pathogens and thus useful as a plant based fourth generation herbal antibiotic formulation. Microbial
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infections are a major cause of human health hazards and misery leading to sizeable number of human deaths globally. In addition, the infections drastically affect human efficiency by incapacitating various metabolic functions and systems like digestive, respiratory, urinary, circulatory, nervous systems and skin. This then leads to continuous human suffering till the patient is completely cured of the causative microbes. Bacterial infections present a serious threat to the health and well being of people of all ages Antibiotics and antimicrobial drugs ever since the discovery of Penicillin by Alexander Fleming in the 1940s have been used by the medical practitioners to eliminate infective agents and curing the diseases. However, the infective microbes have always been able to fight back every new drug through development of resistance against the drug/antibiotic in use. Emergence of multiple drug resistant strains has appeared as a real problem in the field of medical science. The primary cause of the development of resistance is occurrence of random mutations. Mutations m ay occur in genes responsible for conferring sensitivity against a drug. With a relative dearth of new antibiotics with novel mode of action we may find ourselves on the verge of a medical disaster. It is high time to revive the hidden wonders of plant molecules with the modem tools of target based screening to develop newer advanced generation drugs and antibiotics with novel modes of actions. Newer antimicrobials have been arising through structural modifications of existing agents leading to the development of higher generation drugs with wider spectrum of activity and enhanced potency. Well-exemplified cases for evolution of higher generation families of antimicrobial agents are penicillins and cephalosporins. These are evolved by the chemical modification of th e basic.beta.-lactam ring. Cephalosporin represents great-grand daughter-drug of cephalothin. Similarly, since the development of nalidixic acid as the first generation antimicrobial quinolone drug in 1962 by Lesher and colleagues, members of quino lone family have also evolved upto third generation. In fact, nalidixic acid found limited utility in treating systemic infections and subsequently marginally improved quinolones like oxolinic acid, pipemidic acid and cinoxacin were released in 1970's. Then came a breakthrough in early 1980's with the beginning of evolution of fluorinated quinolones. First to come up was norfloxacin, a secondgeneration quinolone having 6-fluorine and 7-piperazine substituents developed by Wolfson and Hooper. It had enhanced activity against both gram-negative and grampositive bacteria like Pseudomonas aeruginosa and Staphylococcus aureus, respectively. This followed the development of sister drug molecules like ciprofloxacin, enoxacin, ofloxacin and pefloxacin etc. Almost concurrent has been the development of third generation agents such as lomefloxacin, fleroxacin, temafloxacin, tosufloxacin possessing one or more additional fluorine substituents as compared to second generation quinolones having a fluorine on position-6 on the basic quinolones. Web site: http://www.delphion.com/details?pn=US06514541__ •
High throughput screen for inhibitors of fatty acid biosynthesis in bacteria Inventor(s): Murphy; Christopher (Upton, MA), Youngman; Philip (Boston, MA) Assignee(s): Millennium Pharamaceuticals, Inc. (cambridge, Ma) Patent Number: 6,656,703 Date filed: December 29, 1999 Abstract: Methods for identifying compounds that are inhibitors of bacterial fatty acid biosynthesis are disclosed. Such compounds can be used as lead compounds in methods for preparing antibacterial agents for treating bacterial infections (e.g., in humans,
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animals, and plants). Inhibitors of bacterial fatty acid synthesis can also be tested for their ability to inhibit synthesis of acylated homoserine lactones. Compounds that inhibit synthesis of acylated homoserine lactones can be used as inhibitors of bacterial virulence. The disclosed methods allow for high throughput screening of libraries of test compounds. Excerpt(s): The invention relates to methods for identifying inhibitors of fatty acid biosynthesis in bacteria. Fatty acid biosynthesis (FAB) is necessary for the production of bacterial cell walls, and therefore is essential for the survival of bacteria (Magnuson et al., 1993, Microbiol. Rev. 57:522-542). The fatty acid synthase system in E. coli is the archetypal type II fatty acid synthase system. Multiple enzymes are involved in fatty acid biosynthesis, and genes encoding the enzymes fabH, fabD, fabG, acpP, and fabF are clustered together on the E. coli chromosome. Clusters of FAB genes have also been found in Bacillus subtilis, Haemophilus influenza Rd, Vibrio harveyi, and Rhodobacier capsulatus. Examples of FAB genes in B. subtilis include fabD, yjaX and yhjB (encoding synthase III), fabG, ywpB, yjbW, yjaY, ylpC, fabG, and acpA. The ylpC, fabG, and acpA genes are contained within a single operon that is controlled by the PylpC promoter. The invention is based upon the discovery that the activity of promoters of certain genes is increased in the presence of compounds that inhibit B. subtilis FAB. Thus, compounds that inhibit FAB can be identified by their ability to increase the activity of the B. subtilis PyhfB and PylpC promoters. Various promoters can be used in the invention, provided that the activity of the promoter is upregulated by a FAB inhibitor, such as cerulenin or triclosan. FAB inhibitors that slow the growth of, or kill, bacteria are candidate antibacterial agents that can be used in methods of treating bacterial infections. The invention thus provides a rapid and convenient method for identifying (i) compounds that inhibit FAB and which can subsequently be derivatized to produce antibacterial agents, as well as (ii) compounds that inhibit FAB and which are antibacterial agents. Because the FAB pathway is involved in the synthesis of HSLs, the invention also provides a method for identifying compounds that inhibit HSL synthesis. Such compounds can be used to inhibit bacterial virulence. If desired, such inhibitors of HSL synthesis can be further derivatized using standard medicinal chemistry techniques to produce inhibitors of virulence having increased potency. Web site: http://www.delphion.com/details?pn=US06656703__ •
Immunity against pasteurella haemolytica leukotoxin Inventor(s): Hodgson; Adrian Leslie Mark (East Malvern, AU), Prideaux; Christopher Thomas (Coburg North, AU) Assignee(s): Commonwealth Scientific and Industrial Research Organisation (campbell, Au), The State of New South Wales Through Its Department of Agriculture (new South Wales, Au), The State of Queensland Through Its Department of Primary Industries (queensland, Au), The University of New England of Armidale (new South Wales, Au) Patent Number: 6,610,307 Date filed: June 23, 1998 Abstract: Bovine respiratory disease (BRD) complex, shipping fever, or pneumomic pasteurellosis, is a multifactorial disease whereby a combination of viral infection, adverse environment and poor immune status may combine to predispose animals to bacterial infections. The exotoxin, or leukotoxin (Lkt), may contribute to pathogenesis by impairing the primary lung defenses and subsequent immune responses or by causing inflammations as a result of leukocyte lysis. The present invention provides a
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modified microorganism which produces an Lkt toxin, wherein said Lkt toxin is partially or fully inactivated. In a further embodiment of the present invention, there is provided a modified microorganism wherein an Lkt toxin operon including an Lkt structural gene and/or a post transational activator of the organism is partially or fully inactivated. The present applicants have found that a precursor of Lkt toxin has reduced toxic activity. Surprisingly, the Lkt toxin precursor is capable of inducing an immune response in an animal that offers cross protection against heterologous challenge with a microorganism which produces the Lkt toxin. A microorganism which naturally produces an Lkt toxin may be engineered to produce an inactive Lkt toxin precursor by eliminating the post-translational activator of the precursor product. Accordingly, in a preferred embodiment the microorganism is unable to produce a post-translational activator of the Lkt toxin precursor or produces an inactivated post-translational activator of the Lkt toxin precursor. The post-translational activator may be a product of the Lkt C gene. Excerpt(s): The present invention relates to modified microorganisms suitable for use as live vaccines. The present invention also relates to the use of modified microorganisms as biological vectors. The present invention further relates to vaccine compositions. Bovine respiratory disease (BRD) complex, shipping fever, or pneumonic pasteurellosis, is a multifactorial disease whereby a combination of viral infection, adverse environment and poor immune status may combine to predispose animals to bacterial infections. BRD is a major cause of economic loss in the cattle feed lot industry. The principal microorganism associated with the disease is the bacteria Pasteurella haemolytica serotype 1. (Schiefer, et al., 1978). Under normal conditions P. haemolytica is a component of the normal flora of the upper respiratory tract, it is only when pulmonary clearance mechanisms are impaired that colonisation of the lung occurs resulting in disease (Frank and Smith, 1983). A number of virulence factors have been associated with P. haemolytica, including surface structures such as the capsular polysaccharide (Adam et al. 1984), and a secreted exotoxin which is heat labile and specific for ruminant leukocytes (Shewen and Wilkie, 1982). The exotoxin, or leukotoxin (Lkt), may contribute to pathogenesis by impairing the primary lung defenses and subsequent immune responses or by causing inflammation as a result of leukocyte lysis. Characterisation of the Lkt has shown it to be a member of the RTX family of toxins (Strathdee and Lo, 1989) which are produced by a variety of bacteria including Actinobacillus spp, Proteus vulgaris, Morganella morganii, Bordetella pertussis, and the most characterised produced by E. coli. All RTX toxins function by producing pores in the target cells, thereby interrupting osmotic balance, leading to rupture of the target cell. Although the mode of action is identical for RTX toxins their target cells vary greatly in type and cross-species specificity. Structurally, this family of toxins are characterised by the presence of glycine rich repeat structures within the toxin that bind to calcium and may have a role in target cell recognition and binding, a region of hydrophobic domains that are involved in pore formation, the requirement for post translational activation, and dependence on a C-terminal signal sequence for secretion. Production and secretion of an active RTX toxin requires the activity of at least four genes, C, A, B, and D. The A gene encodes the structural toxin, the C gene encodes a post-translational activator and the B and D genes encode proteins that are required for secretion of the active toxin. The Lkt is encoded by an operon that consists of the four contiguous genes (CABD), transcribed by a single promoter. The Lkt differs from a number of other RTX toxins, which have a broad host cell specificity, by having a target cell specificity restricted to ruminant leukocytes (Reviewed: Coote, 1992). Web site: http://www.delphion.com/details?pn=US06610307__
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Indole compounds useful for treating bacterial infections Inventor(s): Chambers; Pamela A. (King of Prussia, PA), Daines; Robert A. (Lansdale, PA) Assignee(s): Smithkline Beecham Corporation (philadelphia, Pa) Patent Number: 6,486,192 Date filed: November 28, 2001 Abstract: This invention relates to the use of certain indole compounds, which are active as inhibitors of the fatty acid synthase FabH, for the treatment of bacterial infections. Excerpt(s): This invention relates to the use of compounds as inhibitors of the fatty acid synthase FabH. The first step in the biosynthetic cycle is the condensation of malonylACP with acetyl-CoA by FabH. In subsequent rounds malonyl-ACP is condensed with the growing-chain acyl-ACP (FabB and FabF, syntheses I and II respectively). The second step in the elongation cycle is ketoester reduction by NADPH-dependent.beta.ketoacyl-ACP reductase (FabG). Subsequent dehydration by.beta.-hydroxyacyl-ACP dehydrase (either FabA or FabZ) leads to trans-2-enoyl-ACP which is in turn converted to acyl-ACP by NADH-dependent enoyl-ACP reductase (FabI). Further rounds of this cycle, adding two carbon atoms per cycle, eventually lead to palmitoyl-ACP whereupon the cycle is stopped largely due to feedback inhibition of FabH and I by palmitoyl-ACP (Heath, et al, (1996), J.Biol.Chem. 271, 1833-1836). Fab H is therefore a major biosynthetic enzyme which is also a key regulatory point in the overall synthetic pathway (Heath, R. J. and Rock, C. O. 1996. J.Biol.Chem. 271, 1833-1836; Heath, R. J. and Rock, C. O. 1996. J.Biol.Chem. 271, 10996-11000). The antibiotic thiolactomycin has broad-spectrum antibacterial activity both in vivo and in vitro and has been shown to specifically inhibit all three condensing enzymes. It is non-toxic and does not inhibit mammalian FASs (Hayashi, T. et al., 1984. J. Antibiotics 37, 1456-1461; Miyakawa, S. et al., 1982. J. Antibiotics 35, 411-419; Nawata, Y et al., 1989. Acta Cryst. C45, 978-979; Noto, T. et al., 1982. J. Antibiotics 35,401-410; Oishi, H. et al., 1982. J. Antibiotics 35, 391-396. Similarly, cerulenin is a potent inhibitor of FabB & F and is bactericidal but is toxic to eukaryotes because it competes for the fatty-acyl binding site common to both FAS types (D'Agnolo, G. et al., 1973. Biochim. Biophys. Acta. 326, 155-166). Extensive work with these inhibitors has proved that these enzymes are essential for viability. Little work has been carried out in Gram-positive bacteria. Web site: http://www.delphion.com/details?pn=US06486192__
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Inhalable dry powder aztreonam for treatment and prevention of pulmonary bacterial infections Inventor(s): Montgomery; Alan Bruce (Seattle, WA) Assignee(s): Salus Pharma, Inc. (seattle, Wa) Patent Number: 6,660,249 Date filed: December 20, 2001 Abstract: A method and a composition for treatment of pulmonary bacterial infections caused by gram-negative bacteria suitable for treatment of infection caused by Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Pseudomonas aeruginosa, Haemophilus influenzae, Proteus mirabilis, Enterobacter species, Serratia marcescens as well as those caused by Burkholderia cepacia, Stenotrophomonas maltophilia,
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Alcaligenes xylosoxidans, and multidrug resistant Pseudomonas aeruginosa, using a concentrated formulation of aztreonam, or a pharmaceutically acceptable salt thereof, delivered as an aerosol or dry powder formulation. Excerpt(s): The current invention concerns a novel, safe, nonirritating and physiologically compatible inhalable aztreonam formulation suitable for treatment of pulmonary bacterial infections caused by gram negative bacteria, such as Escherichia coli, Enterobacteria species, Klebsiella pneumoniae, K. oxytoca, Proteus mirabilis, Pseudomonas aeruginosa, Serratia marcescens, Haemophilus influenzae, Burkholderia cepacia, Stenotrophomonas maltophilia, Alcaligenes xylosoxidans. In particular, the invention concerns the inhalable formulation comprising aztreonam or a pharmaceutically acceptable salt thereof suitable for treatment and prophylaxis of acute and chronic pulmonary bacterial infections, particularly those caused by gram-negative bacteria Burkholderia cepacia, Stenotrophomonas maltophlia, Alcaligenes xylosoxidans, and multidrug resistant Pseudomonas aeruginosa which are resistant to treatment with other antibiotics. The inhalable formulation is delivered as an aerosol or as an inhalable dry powder. For aerosolization, about 1 to about 250 mg of aztreonam is dissolved in about 1 to about 5 ml of saline or other aqueous solution having a pH between 4.5 and 7.5, delivered to the lung endobronchial space in an aerosol having mass medium average diameter particles predominantly between 1 to 5.mu. using a nebulizer able to atomize the aztreonam solution into particles of required sizes. The aerosol formulation has a small volume yet delivers a therapeutically efficacious dose of aztreonam to the site of the infection in amounts sufficient to treat bacterial pulmonary infections. A combination of the novel formulation with the atomizing nebulizer permits about 50% delivery of the administered dose of aztreonam into airways. For delivery of dry inhalable powder, aztreonam is milled or spray dried to particle sizes between about 1 and 5.mu. The dry powder formulation or a reconstituted aztreonam solid for aerosolization have a long shelf-life and storage stability. A wide variety of gramnegative bacteria cause severe pulmonary infections. Many of these bacteria are or become resistant to commonly used or specialty antibiotics and require treatment with new types of antibiotics. The pulmonary infections caused by gram-negative bacteria are particularly dangerous to patients who have decreased immunoprotective responses, such as for example cystic fibrosis and HIV patients, patients with bronchiectasis or those on mechanical ventilation. Therefore, the bacterial respiratory infections caused by organisms resistant to antibiotics continues to be a major problem, particularly in immunocompromised or hospitalized patients, as well as in patients assisted by mechanical ventilation, as described in Principles and Practice of Infectious Diseases, Eds. Mandel, G. L., Bennett, J. E., and Dolin, R., Churchill Livingstone Inc., New York, N.Y., (1995). Web site: http://www.delphion.com/details?pn=US06660249__ •
Method of treating aquatic animals with an antimicrobial agent and chelating agent Inventor(s): Burnley; Victoria V. (Bogart, GA), Ritchie; Branson W. (Athens, GA), Wooley; Richard E. (Athens, GA) Assignee(s): University of Georgia Research Foundation, Inc. (athens, Ga) Patent Number: 6,518,252 Date filed: September 18, 2001 Abstract: The present invention relates to novel method of reducing microbial infections, especially bacterial infections, of animals, especially of aquatic animals such as fish
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maintained in tanks or aquaria. The present invention provides bathing and dipping methods for reducing a microbial infection of an animal with an antibiotic solution of enhanced antimicrobial activity comprising at least one chelating agent and at least one antibiotic effective against the microbial infection. The present invention also provides a method for reducing a microbial infection of an animal comprising bathing or dipping an animal having a microbial infection in an antimicrobial solution comprising the chelating agent EDTA, and at least one antibiotic, and optionally a pH buffering agent. The immersion of the aquatic animal in the antimicrobial solution containing the EDTA, antibiotic and pH buffering agent may be repeated until the microbial burden of the animal is eliminated. The present invention further provides kits for use in administering an enhanced activity antibiotic solution. Excerpt(s): The present invention relates generally to methods of treatment of microbial infections of animals, including aquatic animals and fish. The present invention also relates to kits for the application of the method of administering an effective antimicrobial agent to the external surface of an animal. Aquatic animals are regularly exposed to a medium with a high microbial population. Although the animals have physical and immune system barriers that resist opportunistic infections, such defenses are occasionally breached and an infection results. In the natural environment, the infected animal will overcome the disease and survive, or it will succumb, weaken and die. Since naturally aquatic animals are in limited physical contact with one another, or the water in which they live circulates freely, cross-infection and epidemics are rare unless the water is heavily polluted and/or the animal population is at high density. In the confines of a small aquarium or pond, with ornamental fish or the much larger tanks of fish farming (aquaculture) operations, the possibility of a microbial infection of an entire population is greater. The fish farming, or aquaculture, industry is particularly susceptible to infections of a stock population and the economic consequences of a disease ravaging a tank of fish can be significant. The rapid and effective treatment of a microbial infection, therefore, is essential to save individual fish, and to prevent the spread of disease to healthy animals. Fish confined to tanks, especially under the highdensity conditions prevalent in aquaculture, are sensitive to stress-induced illness. Fish health maintenance for the keeping of ornamental or tropical fish or for the rearing of farmed fish for human consumption, therefore, demands paying close attention to a combination of factors to minimize stress to the fish. The proper environmental conditions of temperature and pH, balanced nutrient delivery and regular provision of food, lack of overcrowding and minimal physical handling contribute to the overall health of fish stock. An imbalance or perturbation of one or more of these factors can significantly increase susceptibility to microbial infection and disease. Web site: http://www.delphion.com/details?pn=US06518252__ •
Modified release pharmaceutical formulation comprising amoxycillin Inventor(s): Conley; Creighton P. (Bristol, TN), Roush; John A. (Kingsport, TN), Storm; Kevin H. (Bristol, TN) Assignee(s): Beecham Pharmaceuticals Limited (jurong, Sg) Patent Number: 6,660,299 Date filed: July 24, 2001 Abstract: Bacterial infections may be treated using a high dosage regimen of amoxycillin. Preferably, the dosage is provided by a bilayer tablet.
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Excerpt(s): This invention relates to a novel method of treatment using amoxycillin and for novel formulations, in particular tablet formulations, for use in such methods. Amoxycillin is a well known.beta.-lactam antibiotic which has been available for many years. Despite the suspectibility of amoxycillin to inhibition by.beta.-lactamases produced by resistant organisms, amoxycillin still enjoys widespread usage as a broad spectrum antibiotic for the treatment of commonly occurring bacterial infections. In particular, amoxycillin is particularly effective in treating sore throats--acute bacterial tonsillitis and/or pharyngitis where the causative organism is almost exclusively Streptococcus pyogenes. Amoxycillin is available commercially in a variety of formulations, for instance as capsules containing either 250 or 500 mg amoxycillin, as tablets comprising 500 or 875 mg amoxycillin, as chewable tablets comprising either 125 or 250 mg amoxycillin and as dry powder formulation, for reconstitution into an oral suspension. Other formulation types include dispersible tablets providing 500 mg amoxycillin, chewable effervescent tablets, comprising 125, 250 or 500 mg amoxycillin and single dose sachets comprising 750 or 3000 mg amoxycillin. The standard adult dosage is 250 mg. three times daily (tid), increasing to 500 mg tid for more severe infections. In addition, the 875 mg tablet is intended for dosing twice daily (bid), as an alternative to the dosage regimen of 500 mg tid. Recently, a 1000 mg chewing tablet has been advertised as being under development (AC Pharma, see SCRIP No 2472 Sep. 15, 1999, page 11). A high dosage of 3 g, bid, is recommended in appropriate cases for the treatment of severe or recurrent purulent infection of the respiratory tract. For short course therapy, in simple urinary tract infections, two 3 g doses, at an interval of 10-12 hours, are given while for a dental abscess, the dosage is two 3 g doses at an interval of 8 h and for gonorrhoea, a single dose of 3 g. Furthermore, the use of 1 g of amoxycillin, bid, is used as one arm of a combination therapy, for eradication of Helicobacter pylori in peptic ulcer disease. Web site: http://www.delphion.com/details?pn=US06660299__ •
Moxifloxacin formulation containing common salt Inventor(s): Eisele; Michael (Bergisch Gladbach, DE), Kuhn; Bernd (Koln, DE), Mahler; Hans-Friedrich (Koln, DE) Assignee(s): Bayer Aktiengesellschaft (leverkusen, De) Patent Number: 6,548,079 Date filed: February 5, 2002 Abstract: The present invention relates to an aqueous formulation comprising moxifloxacin hydrochloride and sodium chloride, to the formulation for use as a medicament and to the use of the formulation for preparing a medicament for preventing or treating bacterial infections in humans or animals. Excerpt(s): This application is a 371 continuation of PCT/EP00/07098 filed Jul. 25, 2000. It is a highly effective anti-infective agent and was described for the first time in EP-A-0 350 733. However, EP-A-0 350 733 does not describe any pharmaceutical preparations which are suitable for parenteral administration. Such solutions for infusion, which can be administered parenterally, are, however, needed for treating patients in intensive care units which cannot be treated orally. Web site: http://www.delphion.com/details?pn=US06548079__
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Novispirins: antimicrobial peptides Inventor(s): Lehrer; Robert I. (Santa Monica, CA), Tack; Brian F. (Iowa City, IA), Waring; Alan J. (Irvine, CA) Assignee(s): The Regents of the University of California (oakland, Ca), The University of Iowa Research Foundation (iowa City, Ia) Patent Number: 6,492,328 Date filed: April 19, 2001 Abstract: Novispirin peptides are antimicrobial agents with potent activity against Gram-negative bacteria. The peptides are nonhemolytic, exhibit reduced in vitro cytotoxicity relative to other antimicrobial peptides, and were well-tolerated in vivo after intravenous injection. Novispirins also bind lipopolysaccharide (LPS), a property that may mitigate symptoms associated with Gram-negative bacterial infection. A pharmaceutical composition comprising novispirin as an active agent is administered to a patient suffering from or predisposed to a microbial infection, particularly Gramnegative bacterial infections. Excerpt(s): The development of effective antimicrobial agents was once seen as a definitive cure for bacterial diseases. But even before the development of the first antibiotics, bacteria had demonstrated an ability to adapt to stress in the environment, resulting in the development of resistance. In recent years, the variety of antimicrobial agents has increased substantially, along with a parallel increase in resistant pathogenic microorganisms. Resistance is now recognized against all clinically available antimicrobial agents. The response to antimicrobial resistance in the medical community has been to use new or alternative antibiotics not previously used against the resistant bacteria. This approach has required the continuous development of new antibiotics, either as modifications of currently existing compounds or as combinations of compounds that may inhibit or bypass the bacterial resistance mechanisms. Natural polycationic antibiotic peptides have been found in many different species of animals and insects and shown to have broad antimicrobial activity. In mammals, these antimicrobial peptides are mainly represented by two families, the defensins and the cathelicidins. Nearly all of these peptides have membrane affinity, and can permeate and permeabilize bacterial membranes, resulting in injury, lysis, and/or death to the microbes. For example, the human peptides termed alpha-defensins are produced by neutrophils and intestinal Paneth cells. In three-dimensions, defensins manifest an amphiphilic, largely beta-sheet structure, with a polar face formed largely by its arginines and with N- and C-terminal residues playing an important role in defining antimicrobial potency and spectrum. (See Gudmundsson et al. (1999) J Immunol Methods 232(1-2):45-54.) Antimicrobial peptides are reviewed by Hancock and Lehrer (1998) Trends in Biotechnology 16:82. Cystic fibrosis (CF) is an inherited disorder that occurs in one of every 3,300 U.S. newborns. It affects some 30,000 Americans today. The median survival age of patients with CF is only 31.3 years, making CF the most common life-shortening inherited disease in the U.S. Most CF patients die from pulmonary failure that results from chronic, progressive infection by Pseudomonas aeruginosa--a Gram-negative bacterium that is widely distributed throughout the environment. P. aeruginosa has limited ability to infect normal individuals, but can be a devastating secondary invader in immunocompromised, severely burned, or antibiotic-treated persons. Because Pseudomonas aeruginosa strains frequently are or become resistant to conventional antibiotics, infections caused by them are often difficult to eradicate. Web site: http://www.delphion.com/details?pn=US06492328__
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Perchloramido phosphonyl reagents and analogs thereof Inventor(s): Bottaro; Jeffrey C. (Mountain View, CA), Penwell; Paul E. (Palo Alto, CA), Petrie; Mark A. (Cupertino, CA), Schmitt; Robert J. (Palo Alto, CA) Assignee(s): Sri International (menlo Park, Ca) Patent Number: 6,613,926 Date filed: November 1, 2000 Abstract: Novel compounds are provided in the form of nucleoside pyrophosphate and triphosphate analogs. In these analogs, the pyrophosphate or triphosphate group is replaced with a moiety that is isosterically and electronically identical thereto, but is hydrolytically and enzymatically more stable. The compounds are useful as therapeutic agents, e.g., as antiviral agents, anticancer agents, metabolic moderators and the like. The invention also provides pharmaceutical compositions containing a compound of the invention as an active agent, and in addition provides methods of treating disease, including viral infections, cancer, bacterial infections, inflammatory and/or autoimmune diseases, and the like, by administering a compound of the invention to a patient in need of such treatment. Excerpt(s): The present invention provides novel compounds that are useful as therapeutic agents, e.g., as antiviral agents, anticancer agents and metabolic moderators. The invention additionally relates to pharmaceutical compositions containing a compound of the invention as the active agent and to methods of using the novel compounds as therapeutic agents. The invention has application in the fields of biochemistry and medicinal chemistry and particularly provides nucleoside pyrophosphate and triphosphate analogs and related compounds for use in the treatment of disease. The four principal ribonucleotide triphosphates may be polymerized to provide "RNA," or "ribonucleic acid." In addition to its role in all normal cells, RNA represents the genetic material of one major class of pathogenic viruses known as the RNA viruses, examples of which are HIV and herpes viruses. When the sugar moiety is deoxyribose, the four principal deoxyribonucleotide triphosphates are polymerized into deoxyribonucleic acid strands, or "DNA," the genetic material of all plants and animals. There is also another class of pathogenic viruses known as DNA viruses, examples of which include measles and mumps. The body triphosphorylates and dephosphorylates drug and metabolic intermediates at extremely high rates, resulting in a constant low level of triphosphorylated materials that are then used in cellular processes. Phosphates, pyrophosphates and triphosphates of antiviral drugs, nucleosides, inositol, isoprenoids, and other biochemical building blocks are critical intermediates in the biosynthesis of nucleosides, proteins and hormones. Web site: http://www.delphion.com/details?pn=US06613926__
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Pharmaceutical moxifloxacin preparation Inventor(s): Bosche; Patrick (Odenthal, DE), Mahler; Hans Friedrich (Koln, DE), Weisemann; Claus (Apex, NC) Assignee(s): Bayer Aktiengesellschaft (leverkusen, De) Patent Number: 6,610,327 Date filed: April 30, 2001
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Abstract: The present invention relates to a pharmaceutical preparation for oral administration which comprises moxifloxacin, its salt and/or hydrate and lactose, to a process for its preparation, and to the use of this preparation for controlling bacterial infections in humans and animals. Excerpt(s): This application is a 371 of PCT/EP99/08230 filed Oct. 29, 1999. It is a highly effective antiinfective agent and was described for the first time in EP-A-0 350 733. EPA-0 350 733 describes a pharmaceutical preparation which comprises the active compound, microcrystalline cellulose, maize starch, poly-(1-vinyl)-2-pyrrolidone (insoluble), finely divided silica and magnesium stearate. Web site: http://www.delphion.com/details?pn=US06610327__ •
Protein complex from ion-exchange chromatography of casein for treatment of bacterial infections Inventor(s): Sabharwal; H. (Bjorn Jansidas Grand, S-224 77 Lund, SE), Svanborg; Catharina (Arkivgatan 4, S-223 59 Lund, SE) Assignee(s): None Reported Patent Number: 6,599,874 Date filed: August 17, 2000 Abstract: Antibacterial protein complexes designated as Anti-adhesive Lactalbumin Like Protein (ALLP) are obtained by ion-exchange chromatography of casein and alphalactalbumin. Casein isolated from human milk by acid precipitation is subjected to ionexchange chromatography using an NaCl gradient to obtain six fractions. Fraction six contains the antibacterial protein complex and is recovered. Ion-exchange chromatography of human or bovine alpha-lactalbumin using an NaCl gradient resulted in a fraction that was retained and eluted that contained an antibacterial multimeric protein complex. The protein complexes inhibit attachment of S. pneumoniae and H. influenzae to human respiratory tract epithelial cells when tested in vitro, and the protein complexes can be used to treat a bacterial infection in the respiratory tract. The protein complexes are administered in a pharmaceutical composition or in a food or feed-stuff. Excerpt(s): The present invention relates to a novel antibacterial protein and compositions, in the form of pharmaceutical compositions, human food compositions, and animal feedstuffs comprising said protein to be used in the therapeutic and/or prophylactic treatment of infections caused by bacteria, in particular Streptococcus pneumoniae and/or Haemophilus influenzae, as well as a method for diagnosing infections caused by said bacteria. The object of the present invention is to obtain a protein and compositions containing said protein for prophylactic and/or therapeutic treatment of infections caused by bacteria, in particular Streptococcus pneumoniae and Haemophilus influenzae in the upper airways, ear-nose-and-throat infections, but also in the lower airways, e.g., the lungs by preventing adhesion of and/or causing a bactericidal effect on these bacteria. A further object is to be able to diagnose infections caused by these bacteria. Natural antimicrobial compounds exist in secreted form as well as in cells of immune and non-immune origin. Web site: http://www.delphion.com/details?pn=US06599874__
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Quinoline derivatives and their use as antibacterial agents Inventor(s): Davies; David Thomas (Harlow, GB), Markwell; Roger Edward (Harlow, GB), Pearson; Neil David (Harlow, GB), Takle; Andrew Kenneth (Harlow, GB) Assignee(s): Smithkline Beecham P.l.c. (brentford, Gb) Patent Number: 6,602,882 Date filed: May 24, 2001 Abstract: Piperidine derivatives and pharmaceutical derivatives thereof useful in methods of treatment of bacterial infections in mammals, particularly in man. Excerpt(s): This application is a 371 of PCT/EP99/07766, filed on Oct. 11, 1999. This invention relates to novel medicaments, being novel antibacterial compounds and compositions. A is NHC(O)NH or NHC(O)O. Web site: http://www.delphion.com/details?pn=US06602882__
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Reaction product of arginine and p-aminobenzoic acid, cosmetic, and human and animal health compositions thereof Inventor(s): Schutt; Steven R. (Prescott, AZ) Assignee(s): Epicare Ltd. (prescott, Az) Patent Number: 6,585,988 Date filed: April 1, 2002 Abstract: A method of controlling the regulatory mechanism in humans that governs cell division in a damaged cell structure which comprises reactivating the proliferative phase regulated by DNA, to enable the damaged cell to redifferentiate itself according to its basic genetic code, by administering to the human the reaction product of arginine and p-aminobenzoic acid. A method in which said reactivation process suppresses sexual inflammations, enhances positive neural responses, precludes aggressive bacterial infections, promotes internal wound healing, and/or provides an infusible treatment for non-specific prostatitis. Excerpt(s): This invention relates to cosmetic and human and animal health compositions, and, more particularly, to the reaction product of arginine and paminobenzoic acid (PABA), and compositions thereof, useful for treating wounds, lesions, burns, sunburn, the hair and scalp, hemorrhoids and teeth, in animals and humans, including bovine mastitis. The prior art does not disclose the reaction product of arginine and p-aminobenzoic acid (PABA), and cosmetic and health compositions and formulations thereof. For example, U.S. Pat. No. 4,499,067 discloses only acyl arginine derivatives without PABA; U.S. Pat. No. 4,921,939 discloses only forming guanidine sweetening agents by reaction of substituted arcyl amines with guanidino moieties; U.S. Pat. No. 5,110,797 discloses peptide substituted/reacted arginine, however, without PABA; and U.S. Pat. No. 5,298,647 discloses PABA/amino acid reaction products which may be used as ultraviolet protecting agents, but arginine is not disclosed. Web site: http://www.delphion.com/details?pn=US06585988__
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Recombinant phages Inventor(s): M.ang.rdh; Sven (S-582 25, Linkoping, SE) Assignee(s): None Reported Patent Number: 6,497,874 Date filed: June 23, 2000 Abstract: The present invention relates to bacteriophages for use in the treatment or prophylaxis of bacterial infections, especially mucosal bacterial infections such as Heliobacter pylori infections, in particular, it relates to modified filamentous bacteriophages, e.g. M13 phages, for such use, which bacteriophages present at the surface a recombinant protein comprising (i) a first component derived from a bacteriophage surface protein; and (ii) a second component comprising variable region sequences of an antibody to provide a bacterial antigen binding site, said second component rendering said bacteriophage capable of binding to and thereby inhibiting growth of bacterial cells involved in the etiology of said infection. Excerpt(s): This invention relates to bacteriophages useful for the treatment of bacterial infections, especially mucosal bacterial infections such as Helicobacter pylori infections. Resistance to antibiotics is a global problem of increasing medical and economical importance. There is thus a great need for alternative methods to eradicate bacteria which will circumvent the problem of such resistance. A bacteriophage, or phage, is a virus which specifically infects bacteria. Phages bind to their host bacterium and transfer genes encoding various phage proteins. They utilize the proteinsynthesizing machinery, amino acids etc., and the energy provided by the host bacterium for their replication (Maloy et al. (eds.): Microbial genetics. Jones and Bartlett Publishers, 1994). Web site: http://www.delphion.com/details?pn=US06497874__
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Screening for antibiotics Inventor(s): Rothstein; David M. (Lexington, MA) Assignee(s): Millennium Pharmaceuticals, Inc. (cambridge, Ma) Patent Number: 6,534,278 Date filed: March 3, 2000 Abstract: Assays for the detection of.beta.-lactamase induction can be used to identify compounds that kill bacteria (i.e., bacteriocidal activity) or inhibit bacterial growth (i.e., bacteriostatic activity). The.beta.-lactamase can be encoded, for example, by a.beta.lactamase gene carried by a bacterial host. The identified compounds can be use to treat bacterial infections in organisms such as mammals. The new methods can be used, for example, for high throughput screening of libraries of potential inhibitors. Excerpt(s): The invention relates to methods for identifying compounds that kill bacteria or inhibit bacterial growth. The invention also relates to methods for identifying compounds that can be used to treat infections (e.g., bacterial infections in organisms such as mammals). One mode of defense that gram positive bacteria use to resist a certain class of antibacterial agents (i.e., the.beta.-lactams, which inhibit peptidoglycan formation) is to produce an enzyme called.beta.-lactamase. Production of.beta.lactamase is induced in some bacterial strains by the presence of.beta.-lactams in the cell.beta.-Lactamase reacts with.beta.-lactam drugs (e.g., penicillin or cephalosporin),
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rendering the drugs inactive. Certain species of gram negative bacteria such as Enterobacter (e.g., E. cloacae, E. kobei, E. agglomerans, or E. flavus) and Citrobacter freundii also produce.beta.-lactamase, in response to the build-up of cell wall degradation products, not just in the presence of.beta.-lactams per se. Because bacterial cell walls are continuously degraded and reassembled throughout the life cycle of a bacterium, the build-up of degradation products can be due to inhibition of at least one step in the peptidoglycan biosynthetic pathway. The invention features new assays based on the discovery that induction of the.beta.-lactamase gene can be used to identify compounds that kill bacteria (i.e., bacteriocidal activity) or inhibit bacterial growth (i.e., bacteriostatic activity), and thus to treat bacterial infections (i.e., to reduce symptoms of existing infections and to prevent infections) in organisms such as mammals. The.beta.lactamase can be encoded, for example, by a.beta.-lactamase gene normally carried by a bacterial host, or inserted into a host, e.g., a heterologous host. The new methods are highly efficient and sensitive, and can be used, for example, for high throughput screening of libraries of potential inhibitors. Web site: http://www.delphion.com/details?pn=US06534278__ •
Staphylococcus aureus histidine protein kinase essential genes Inventor(s): Benton; Bret (San Bruno, CA), Malouin; Francois (Los Gatos, CA), Martin; Patrick K. (Sunnyvale, CA), Schmid; Molly B. (Los Altos, CA), Sun; Dongxu (Cupertino, CA) Assignee(s): Essential Therapeutics, Inc. (mountain View, Ca) Patent Number: 6,514,746 Date filed: May 20, 1998 Abstract: This disclosure describes isolated or purified deoxyribonucleotide (DNA) sequences, useful for the development of antibacterial agents, which contain the coding sequences of bacterial genes which encode the components of a two-component regulatory pair. It further describes isolated or purified DNA sequences which are portions of such bacterial genes, which are useful as probes to identify the presence of the corresponding gene or the presence of a bacteria containing that gene. Also described are hypersensitive mutant cells containing a mutant gene corresponding to any of the identified sequences and methods of screening for antibacterial agents using such hypersensitive cells. In addition it describes methods of treating bacterial infections by administering an antibacterial agent active against one of the identified targets, as well as pharmaceutical compositions effective in such treatments. Excerpt(s): This invention relates to the field of antibacterial treatments and to targets for antibacterial agents. In particular, it relates to genes essential for survival of a bacterial strain in vitro or in vivo. The following background information is not admitted to be prior art to the pending claims, but is provided only to aid the understanding of the reader. Despite the development of numerous antibacterial agents, bacterial infections continue as a major, and currently increasing, medical problem. Prior to the 1980s, bacterial infections in developed countries could be readily treated with available antibiotics. However, during the 1980s and 1990s, antibiotic resistant bacterial strains emerged and have become a major therapeutic problem. There are, in fact, strains resistant to essentially all of the commonly used antibacterial agents, which have been observed in the clinical setting, notably including strains of Staphylococcus aureus (S. aureus) The consequences of the increase in resistant strains include higher morbidity and mortality, longer patient hospitalization, and an increase in treatment costs (B.
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Murray, 1994, New Engl. J. Med. 330:1229-1230). Therefore, there is a pressing need for the development of new antibacterial agents which are not significantly affected by the existing bacterial resistance mechanisms. Web site: http://www.delphion.com/details?pn=US06514746__ •
Use of granulysin as an antimicrobial agent Inventor(s): Hanson; Dennis Alan (Mountain View, CA), Krensky; Alan M. (Stanford, CA), Modlin; Robert L. (Sherman Oaks, CA), Stenger; Steffen (Erlangen, DE) Assignee(s): The Board of Trustees of the Leland Stanford Junior University (palo Alto, Ca), The Regents of the University of California (palo Alto, Ca) Patent Number: 6,485,928 Date filed: November 3, 1998 Abstract: The T cell activation marker, granulysin, is demonstrated to be an effective antimicrobial agent. It is used in vitro and in vivo to reduce the population of viable cells in a microbial population. Of particular interest is the use of the active fragment of human granulysin, or modified forms thereof, to treat bacterial infections. Excerpt(s): It was not long ago that the war against microbial disease was thought to be won, through the use of antibiotics and vaccines. It is now seen that there remains much to be done in this field. Although antibiotics are a huge industry, totaling $22.9 billion in worldwide sales, there are still significant unmet clinical needs caused by growing bacterial resistance problems that require new antibacterial therapies. A bacterial pathogen of major concern is Mycobacterium tuberculae (M. tb.). It is highly infectious, and treatment requires a long course of antibiotics. Frequently, patients fail to complete treatment, thereby selecting for antibiotic resistant bacteria. Significant reservoirs of virtually untreatable M.tb. are already present in some lesser developed parts of the world. It is expected that these will cause a pandemic in the future, unless improved therapies can be produced. The mammalian immune system plays a key role in controlling the course of microbial infection in vivo. T cells play a pivotal role as regulators and effectors in the immune response. Cytolytic T cells (CTL) are directly involved in the lysis of foreign and virally infected cells. Two major types of T cellmediated cytolysis have been well characterized. The regulated, directional release of cytoplasmic granule contents is a primary mechanism by which CTL and NK cells initiate the target cell death process. In addition, Fas-Fas ligand interaction mediates Tcell directed cytolysis. Web site: http://www.delphion.com/details?pn=US06485928__
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Use of yacM and yqeJ, essential bacterial genes and polypeptides and their use Inventor(s): Fritz; Christian (Natick, MA), Guzman; Luz-Maria (Boston, MA), Youngman; Philip (Boston, MA) Assignee(s): Millennium Pharmaceuticals, Inc. (cambridge, Ma) Patent Number: 6,664,074 Date filed: February 23, 2001 Abstract: Disclosed are genes, termed "yacM" and "yqeJ," which are essential for survival for a wide range of bacteria, such as Streptococcus pneumoniae, Bacillus
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subtilis, and E. coli. These genes and the essential polypeptides they encode can be used to identify antibacterial agents for treating a broad spectrum of bacterial infections. Excerpt(s): The invention relates to the use of yacM and yqeJ, which are essential bacterial genes, in identifying antibacterial agents. Bacterial infections may be cutaneous, subcutaneous, or systemic. Opportunistic bacterial infections can be life threatening, especially in patients afflicted with AIDS or other diseases that compromise the immune system. Most bacteria that are pathogenic to humans are gram-positive bacteria. The bacterium Streptococcus pneumoniae, for example, typically infects the respiratory tract and can cause lobar pneumonia, as well as meningitis, sinusitis, and other infections. The invention is based on the discovery that the yacM and yqeJ genes of the gram positive bacterium Streptococcus pneumoniae, termed "S-yacM" and "SyqeJ," are essential for survival. Thus, the essential polypeptides that these genes encode are useful targets for identifying compounds that are inhibitors of the bacteria in which the polypeptides are expressed. Such inhibitors can inhibit bacterial growth by inhibiting the activity of an essential protein, or by inhibiting transcription of an essential gene or translation of the mRNA transcribed from the essential gene. The amino acid and nucleic acid sequences of the Streptococcus yacM and yqeJ polypeptides and genes are set forth in FIGS. 1 and 2, as summarized in Table 1. Web site: http://www.delphion.com/details?pn=US06664074__ •
Use of YLQF, YQEG, YYBQ, and YSXC, essential bacterial genes and polypeptides Inventor(s): Fritz; Christian (Natick, MA), Guzman; Luz-Maria (Boston, MA), Youngman; Philip (Boston, MA) Assignee(s): Millennium Pharmaceuticals, Inc. (cambridge, Ma) Patent Number: 6,638,729 Date filed: December 17, 2001 Abstract: Disclosed are genes found in Streptococcus pneumoniae that are essential for survival for a wide range of bacteria. These genes are termed "S-ylqF," "S-yqeG," "SyybQ," "S-yerL," and "S-ysxC." These genes and the polypeptides that they encode, as well as homologs and orthologs thereof can be used to identify antibacterial agents for treating a broad spectrum of bacterial infections. Excerpt(s): The invention relates to the use of ylqF, yqeG, yybQ, yerL, and ysxC, essential bacterial genes and polypeptides in identifying antibacterial agents. Bacterial infections may be cutaneous, subcutaneous, or systemic. Opportunistic bacterial infections proliferate, especially in patients afflicted with AIDS or other diseases that compromise the immune system. Most bacteria that are pathogenic to humans are gram positive bacteria. The bacterium Streptococcus pneumoniae, for example, typically infects the respiratory tract and can cause lobar pneumonia, as well as meningitis, sinusitis, and other infections. The invention is based on the identification of ten genes of the gram positive bacterium Streptococcus pneumoniae and of Bacillus subtilis as being essential for survival. The Streptococcus pneumoniae genes are termed "S-ylqF," "S-yqeG," "S-yybQ," "S-yerL," and "S-ysxC." The orthologs of these genes in Bacillus subtilis are termed "B-ylqF," "B-yqeG," "B-yybQ," "B-yerL," and "B-ysxC," respectively. The terms "ylqF," "yqeG," "yybQ," "yerL," and "ysxC" genes and polypeptides are used to refer to the Streptococcus pneumoniae and Bacillus subtilis genes and polypeptides, as well as their homologs and orthologs, collectively. While "homologs" are structurally similar genes contained within a species, "orthologs" are functionally equivalent genes
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from other species (within or outside of a given genus, e.g., from E. coli). These genes are considered "essential" genes, and their polypeptides are considered "essential" polypeptides. Each gene and polypeptide can be used in methods for identifying similar genes and polypeptides in pathogenic and non-pathogenic microorganisms. Each polypeptide can be used to identify compounds that are inhibitors of the pathogens in which the polypeptide (ylqF, yqeG, yybQ, yerL, or ysxC) is expressed. Such inhibitors attenuate bacterial growth by inhibiting the activity of ylqF, yqeG, yybQ, yerL, or ysxC polypeptide, or by inhibiting gene transcription or translation. Web site: http://www.delphion.com/details?pn=US06638729__
Patent Applications on Bacterial Infections As of December 2000, U.S. patent applications are open to public viewing.10 Applications are patent requests which have yet to be granted. (The process to achieve a patent can take several years.) The following patent applications have been filed since December 2000 relating to bacterial infections: •
11-C-substituted ketolides Inventor(s): Farmer, Jay Judson; (New Haven, CT), Or, Yat Sun; (Watertown, MA), Phan, Ly Tam; (Malden, MA) Correspondence: Enanta Pharmaceuticals, INC.; Attn: Patent DEPT.; 500 Arsenal Street; Watertown; MA; 02472; US Patent Application Number: 20040002464 Date filed: June 25, 2002 Abstract: There are described 11-C-substituted derivatives of erythromycin and pharmaceutically acceptable compositions comprising a therapeutically effective amount of a compound of the invention in combination with a pharmaceutically acceptable carrier. Also described is a method for treating bacterial infections by administering to an animal a pharmaceutical composition containing a therapeuticallyeffective amount of a compound of the invention, and processes for the preparation of such compounds. Excerpt(s): This application is related to commonly assigned United States patent application, serial no. (Attorney Docket No. ENP041), filed on even date herewith. The present invention relates to novel macrolides having antibacterial activity and useful in the treatment and prevention of bacterial infections. More particularly, the invention relates to a novel class of 11-C-substituted erythromycin derivatives, compositions containing such compounds and methods for using the same, as well as processes for making such compounds. The search for macrolides active against MLS.sub.B-resistant strains (MLS.sub.B=Macrolides-Lincosamides-type B Streptogramines) has become a major goal, together with retaining the overall profile of the macrolides in terms of stability, tolerance and pharmacokinetics. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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This has been a common practice outside the United States prior to December 2000.
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1-Methylcarbapenem derivatives Inventor(s): Kanno, Osamu; (Kawasaki-shi, JP), Kobayashi, Yoshiyuki; (Sagamihara-shi, JP), Shinozuka, Tsuyoshi; (Yokohama-shi, JP) Correspondence: Frishauf, Holtz, Goodman & Chick, PC; 767 Third Avenue; 25th Floor; New York; NY; 10017-2023; US Patent Application Number: 20040014962 Date filed: May 15, 2003 Abstract: 1-Methylcarbapenem compounds having antibacterial activity, pharmacologically acceptable esters or salts thereof and pharmaceutical compositions (particularly antibacterial agents) containing them as an active ingredient are described. In addition, the invention includes the use of these compounds, ester derivatives or salts for the manufacture of pharmaceutical compositions, or a method for the prevention or treatment of diseases (particularly bacterial infections) by administering a pharmacologically effective amount of the compounds, ester derivatives or salts to warm-blooded animals (particularly human beings). Excerpt(s): This is a Continuation-in-Part application of International Application No. PCT/JP01/09960 filed Nov. 14, 2001, which is incorporated herein by reference in its entirety. The present invention relates to 1-methylcarbapenem compounds having excellent antibacterial activity, pharmacologically acceptable esters or salts thereof, pharmaceutical compositions (particularly antibacterial agents) containing them as an active ingredient, use of said compounds, ester derivatives or salts for the manufacture of said pharmaceutical compositions, or a method for the prevention or treatment of diseases (particularly bacterial infections) which comprises administering a pharmacologically effective amount of said compounds, ester derivatives or salts to warm-blooded animals (particularly human beings). There is a need for development of carbapenem derivatives having strong and balanced antibacterial activity against a wide range of pathogenic bacteria. 1-methylcarbapenem compounds having a structure analogous to that of the present invention are disclosed in Japanese Patent Application (Kokai) No. Hei 8-53453. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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6,11-4-carbon bridged ketolides Inventor(s): Niu, Deqiang; (Lexington, MA), Or, Yat Sun; (Watertown, MA), Phan, Ly Tam; (Malden, MA), Wang, Guoqiang; (Belmont, MA) Correspondence: Enanta Pharmaceuticals, INC.; Attn: Patent DEPT.; 500 Arsenal Street; Watertown; MA; 02472; US Patent Application Number: 20040023895 Date filed: July 25, 2002 Abstract: Novel 6,11-4-carbon bridged ketolides, pharmaceutically-acceptable compositions comprising a therapeutically effective amount of a compound of the invention in combination with a pharmaceutically-acceptable carrier are described. Also described are a method for treating bacterial infections by administering to an animal a pharmaceutical composition containing a therapeutically effective amount of a compound of the invention and processes for the preparation of such compounds.
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Excerpt(s): Reference is made to commonly assigned United States patent application (Attorney docket No. ENP039), filed on even date herewith. The present invention relates to novel semisynthetic macrolides having antibacterial activity that are useful in the treatment and prevention of bacterial infections. More particularly, the invention relates to 6,11-4-carbon bridged ketolide compounds, compositions containing such compounds and methods for using the same, as well as processes for making such compounds. The spectrum of activity of macrolides, including erythromycin, covers most relevant bacterial species responsible for upper and lower respiratory tract infections. 14-membered ring macrolides are well known for their overall efficacy, safety and lack of serious side effects. Erythromycin however is quickly degraded into inactive products in the acidic medium of the stomach resulting in low bioavailability and gastrointestinal side effects. Improvement of erythromycin pharmacokinetics has been achieved through the synthesis of more acid-stable derivatives, for example, roxithromycin, clarithromycin, and the 15-membered ring macrolide azithromycin. However, all these drugs, including 16-membered ring macrolides, present several drawbacks. They are inactive against MLSB-resistant streptococci (MLS.sub.B=Macrolides-Li- ncosamides-type B Streptogramines) and with the exception of azithromycin, weakly active against Haemophilus influenzae. Futhermore, the resistance of Streptococcus pneumoniae to erythromycin has increased significantly in recent years (5% to above 40%). There is a high percentage of cross-resistance to penicillin among these isolates, with a worldwide epidemic spread of 10-40% in some areas. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Aminopiperidine quinolines and their azaisosteric analogues with antibacterical activity Inventor(s): Davies, David Thomas; (Harlow Essex, GB), Jones, Graham Elgin; (Harlow Essex, GB), Markwell, Roger Edward; (Harlow Essex, GB), Pearson, Neil David; (Harlow Essex, GB), Peightfoot, Andrew; (Harlow Essex, GB) Correspondence: Smithkline Beecham Corporation; Corporate Intellectual Property-us, Uw2220; P. O. Box 1539; King OF Prussia; PA; 19406-0939; US Patent Application Number: 20040038998 Date filed: August 28, 2003 Abstract: Aminopiperidine derivatives of formula (I) and pharmaceutically acceptable derivatives thereof useful in methods of treatment of bacterial infections in mammals, particularly in man. 1 Excerpt(s): This invention relates to novel compounds, compositions containing them and their use as antibacterials. WO99/37635, WO00/21948, WO00/21952, WO00/25227, WO00/43383, WO00/78748, WO01/07432 and WO01/07433 disclose piperidine and piperazine derivatives having antibacterial activity. WO9717957 discloses piperidyl compounds which are haemoregulatory and stimulate haematopoesis. JP07179407 discloses piperidyl compounds which are useful for preventing thrombotic diseases, inhibiting tumour metastasis and accelerating wound healing. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Antibacterial compounds Inventor(s): Miller, William H.; (Collegeville, PA), Newlander, Kenneth A.; (West Chester, PA), Seefeld, Mark; (Collegeville, PA) Correspondence: Foley Hoag, Llp; Patent Group, World Trade Center West; 155 Seaport Blvd; Boston; MA; 02110; US Patent Application Number: 20030232850 Date filed: May 5, 2003 Abstract: Compounds of formula (I) are disclosed which are Fab I inhibitors and are useful in the treatment bacterial infections, wherein: R.sup.1 is Ar or Het; R.sup.2 is H, C.sub.1-6alkyl or Ar--C.sub.0-6alkyl; X is H, C.sub.1-4alkyl, OR', SR', C.sub.14alkylsulfonyl, C.sub.1-4alkylsulfonyl, CN, N(R').sub.2, CH.sub.2N(R').sub.2, NO.sub.2, CF.sub.3, CO.sub.2R', CON(R').sub.2, COR', NR'C(O)R', F, Cl, Br, I, or CF.sub.3S(O).sub.r; R' is H, C.sub.1-6alkyl or Ar--C.sub.0-6alkyl; and r is 0, 1 or 2; or a pharmaceutically acceptable salt thereof. 1 Excerpt(s): This invention relates to pharmaceutically active compounds which inhibit Fab I and are useful for the treatment of bacterial infections. While the overall pathway of saturated fatty acid biosynthesis is similar in all organisms, the fatty acid synthase (FAS) systems vary considerably with respect to their structural organization. Vertebrates and yeast possess a FAS in which all the enzymatic activities are encoded on one or two polypeptide chains, respectively, and the acyl carrier protein (ACP) is an integral part of the complex. In contrast, in bacterial FAS, each of the reactions is catalyzed by a distinct, mono-functional enzyme and the ACP is a discrete protein. Therefore, there is considerable potential for the selective inhibition of the bacterial system by antibacterial agents. Fab I (previously designated EnvM) functions as an enoyl-ACP reductase (Bergler, et al, (1994), J.Biol.Chem. 269.5 493-5496) in the final step of the four reactions involved in each cycle of bacterial fatty acid biosynthesis. In this pathway, the first step is catalyzed by.beta.-ketoacyl-ACP synthase, which condenses malonyl-ACP with acetyl-CoA (FabH, synthase III). In subsequent rounds, malonylACP is condensed with the growing-chain acyl-ACP (FabB and FabF, synthases I and II, respectively). The second step in the elongation cycle is ketoester reduction by NADPHdependent.beta.-ketoacyl-ACP reductase (FabG). Subsequent dehydration by.beta.hydroxyacyl-ACP dehydrase (either FabA or FabZ) leads to trans-2-enoyl-ACP, which in turn is converted to acyl-ACP by NADH-dependent enoyl-ACP reductase (Fab I). Further rounds of this cycle, adding two carbon atoms per cycle, eventually lead to palmitoyl-ACP (16C), where upon the cycle is stopped largely due to feedback inhibition of Fab I by palmitoyl-ACP (Heath, et al, (1996), J.Biol.Chem. 271, 1833-1836). Thus, Fab I is a major biosynthetic enzyme and is a key regulatory point in the overall synthetic pathway of bacterial fatty acid biosynthesis. Therefore, Fab I is an ideal target for antibacterial intervention. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Antibacterial compounds with improved pharmacokinetic profiles Inventor(s): Clark, Richard F.; (Gurnee, IL), Djuric, Stevan; (Libertyville, IL), Ma, Zhenkun; (Dallas, TX), Phan, Ly; (Malden, MA), Rupp, Michael; (Indianapolis, IN) Correspondence: Steven F. Weinstock; Abbott Laboratories; 100 Abbott Park Road; DEPT. 377/ap6a; Abbott Park; IL; 60064-6008; US Patent Application Number: 20030207820 Date filed: April 30, 2002 Abstract: Antibacterial compounds with improved pharmacokinetic profiles having formula (I) 1and salts, prodrugs, and salts of prodrugs thereof, processes for making the compounds and intermediates used in the processes, compositions containing the compounds, and methods for prophylaxis and treatment of bacterial infections using the compounds are disclosed. Excerpt(s): This invention is directed to compounds which are useful as antibacterials with improved pharmacokinetic profiles, processes for making the compounds and intermediates employed in the processes, compositions containing the compounds, and methods for prophylaxis and treatment of bacterial infections using the compounds. Because the effectiveness of many drugs currently available for prophylaxis and treatment of bacterial infections is being compromised by the emergence of drugresistant bacteria, the introduction of novel antibacterial compounds with improved pharmacokinetic profiles would be beneficial for their therapeutic value and their contribution to the antibacterial arts. in which the R.sup.3 tetrazolyl and the R.sup.4 tetrazolyl substituent are connected through a carbon atom and are independently unsubstituted or substituted on a 1H or 2H nitrogen atom with a substituent selected from the group consisting of alkyl, --(CH.sub.2)alkenyl, --(CH.sub.2)alkynyl, and alkyl substituted with a substituent selected from the group consisting of halo, --CN, --OH, -NH.sub.2, --NH(alkyl), --N(alkyl).sub.2, --CF.sub.3, --CH.sub.2CF.sub.3, -CF.sub.2CF.sub.3, --C(O)H,.dbd.O, --C(O)OH, --C(O)O(alkyl), --C(O)NH.sub.2, -C(O)NH(alkyl), --C(O)N(alkyl).sub.2, --OC(O)(alkyl), --OC(O)O(alkyl), -OC(O)NH.sub.2, --OC(O)NH(alkyl), --OC(O)N(alkyl).sub.2, --NHC(O)H, -NHC(O)(alkyl), --NHC(O)O(alkyl), --NHC(O)NH.sub.2, --NHC(O)NH(alkyl), and -NHC(O)N(alkyl).sub.2. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Antimicrobial thiadiazinone derivatives and their application for treatment of bacterial infections Inventor(s): Gordeev, Mikhail F.; (Castro Valley, CA), Leuhr, Gary W.; (Hayward, CA), Patel, Dinesh V.; (Fremont, CA) Correspondence: Burns, Doane, Swecker & Mathis, L.L.P.; P.O. Box 1404; Alexandria; VA; 22313-1404; US Patent Application Number: 20040014746 Date filed: February 4, 2003 Abstract: The present invention provides certain thiadiazinone derivatives of oxazolidinones of the following formula I: 1or pharmaceutically acceptable salts thereof that are antibacterial agents, pharmaceutical compositions containing them, methods for their use, and methods for preparing these compounds.
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Excerpt(s): This application claims the benefit of U.S. Provisional Patent Application Serial No: 60/354,598, which application was filed on Feb. 5, 2002. The present invention relates to novel thiadiazinone derivatives of oxazolidinones, pharmaceutical compositions thereof, methods for their use, and methods for preparing the thiadiazinone derivatives. These compounds have potent activities against grampositive and gram-negative bacteria. Due to ever-increasing antibiotic resistance, structurally novel antibacterials with a new mode of action have become increasingly important in the treatment of bacterial infections. Effective antibacterials should exhibit potent activity against a number of human and veterinary pathogens, including grampositive aerobic bacteria such as multiply-resistant staphylococci and streptococci, anaerobic microorganisms such as bacteroides and clostridia species, and acid-fast microorganisms such as Mycobacterium tuberculosis and Mycobacterium avium. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Bacteriophage having multiple host range Inventor(s): Adhya, Sankar; (Gaithersburg, MD), Merril, Carl R.; (Rockville, MD), Scholl, Dean; (Kensington, MD) Correspondence: Knobbe Martens Olson & Bear Llp; 2040 Main Street; Fourteenth Floor; Irvine; CA; 92614; US Patent Application Number: 20030216338 Date filed: January 21, 2003 Excerpt(s): This application is a continuation of international application number PCT/US01/23390, and claims the benefit of priority of international application number PCT/US01/23390, having international filing date of Jul. 25, 2001, designating the United States of America and published in English, which claims the benefit of priority of U.S. provisional patent application No. 60/220,987, filed Jul. 25, 2000, both of which are hereby expressly incorporated by reference in their entireties. The present invention discloses compositions and methods for the prophylaxis and treatment of bacterial infections by the use of polyvalent bacteriophage having multiple host range. Escherichia coli capsular polysaccharides (K antigens) have often been associated with increased virulence (17). The K1 antigen in particular increases the invasiveness of E. coli, and these strains are often involved in cases of meningitis and septicemia (32). These polysaccharide coats also act as recognition sites for bacteriophages, which often carry tail spikes that contain polysaccharide depolymerization activities. Several K1 specific phages have been described (10), one of which,.PHI.K1E, was found to possess N-acetylneuraminidase (endosialidase) as a part of the tail fiber protein (37). This enzyme catalyzes the cleavage of.alpha.-2,8-linked poly-N-acetylneuraminic acid carbohydrate polymer of the K1 capsule. It has been suggested that the tail fiber protein is involved in both adsorption to the cell surface and penetration into the cell by enzymatically degrading the polysaccharide capsule. The.PHI.K1E endosialidase gene has been cloned and sequenced (20). A similar gene has been cloned and sequenced from.PHI.K1F (29). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Bioactive hexane fraction from Vetiveria zizanioides Inventor(s): Gupta, Madan Mohan; (Lucknow, IN), Kishori Lal, Raj; (Lucknow, IN), Kumar Shasany, Ajit; (Lucknow, IN), Kumar Tripathy, Arvind; (Lucknow, IN), Kumar, Sushil; (Lucknow, IN), Pandurang Darokar, Mahendra; (Lucknow, IN), Preet Singh Khanuja, Suman; (Lucknow, IN), Raj Bahl, Janak; (Lucknow, IN), Santha Kumar, Tiruppadiripuliyur Ranganathan; (Lucknow, IN), Singh, Monika; (Lucknow, IN), Srivastava, Suchi; (Lucknow, IN) Correspondence: Nixon Peabody, Llp; 8180 Greensboro Drive; Suite 800; Mclean; VA; 22102; US Patent Application Number: 20030198698 Date filed: March 26, 2002 Abstract: The present invention relates a hexane bioactive fraction and obtained from the roots of an aromatic plant named Vetiveria zizanioides commonly found in India for inhibiting the growth of drug resistant bacterial infections in humans and animals; also relates to a pharmaceutical composition comprising the bioactive extract with other additives for inhibiting the growth of drug resistant bacterial infections in humans and animals and a process for the isolation of said bioactive extract Excerpt(s): The present invention relates a hexane bioactive fraction and obtained from the roots of an aromatic plant named Vetiveria zizanioides commonly found in India for inhibiting the growth of drug resistant bacterial infections in humans and animals. The invention also relates to a pharmaceutical composition comprising the bioactive extract with other additives for inhibiting the growth of drug resistant bacterial infections in humans and animals. The present invention also provides a process for the isolation of said bioactive extract. Antibiotics have been used for long to cure bacterial, fungal and other infectious diseases of humans. Penicillin was the first antibiotic used against infections during the Second World War. Since then a number of antibiotics and their derivatives have been identified and used by man almost all of which were isolated from microbial sources. All the antibiotics in clinical use today can be grouped or classified according to their structure or functional groups. Streptomycin, kanamycin, tetracycline some of the well-known examples are aminoglycosides whereas penicillin and its derivatives are beta-lactam antibiotics. One of the commonly used antibacterials are quinolones or fluoroquinolones such as nalidixic acid, ciprofloxacin, norfloxacin etc. Fluoroquinolones are now widely used to treat urinary tract infections, upper respiratory tract infections, and tuberculosis, which are resistant to first-line drugs. However, many of the pathogenic bacteria such as Haemophilus influenzae, Neisseria Sp., Staphylococcus aureus, Escherichia coli are developing resistance to fluoroquinolone class of antibiotics limiting their clinical usefulness. Since, the mechanism of action of all the quinolones against bacteria is similar, development of resistance to one of the quinolone antibiotic would confer simultaneous cross-resistance to almost all the other quinolones also. Fluoroquinolones act by inhibiting the function of a bacterial enzyme DNA gyrase essential for the maintenance of supercoil nature of the bacterial chromosome. Resistance development is observed when a mutation in the DNA gyrase enzyme A subunit (GyrA+) specifically in the region called "Quinolone Determining Region (QDR)" occurs. The modified mutant form of A subunit (GyrA-) is incapable of binding to quinolone antibiotics and therefore is resistant. Such quinolone resistant infections are particularly difficult to cure. Kumar et al (Phytotherapy Research 14: 14-15, 2000; U.S. Pat. No.6,127,405) have identified a semi-synthetic plant compound.alpha.-arteether which is capable of specifically killing quinolone drug resistant bacterial infections. The.alpha.-arteether was obtained by etherification of
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artemissinin a sesquiterpene lactone compound from a Chinese medicinal plant Artemisia annua. In our effort to isolate and identify more potent plant compounds which are active against quinolone resistant bacteria we carried out a systematic bioactivity guided fractionation of the ethanolic extract prepared from the roots of Indian medicinal plant Vetiveria zizanioides. The subject mentioned below specifically describes the manner in which the compound inhibiting quinolone resistant bacteria was isolated and identified. The main object of the invention is to develop a novel anti bacterial agent inhibiting the growth of multi drug resistant bacterial pathogens. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1) structure and uses thereof in drug identification and screening Inventor(s): Holmes, Kathryn V.; (Golden, CO), Meijers, Rob; (Somerville, MA), Tan, Kemin; (Waltham, MA), Wang, Jia-Huai; (Belmont, MA), Zelus, Bruce D.; (Lakewood, CO) Correspondence: Sheridan Ross P. C.; 1560 Broadway; Suite 1200; Denver; CO; 802025141; US Patent Application Number: 20030190600 Date filed: April 5, 2002 Abstract: Disclosed are novel crystal structures of a carcinoembryonic cell adhesion antigen functional domain that is characterized as having a unique N-terminal domain structure, called a CC' loop. This tertiary structure is used in a number of screening methods for identifying candidate molecules that have a binding affinity for the tertiary structure of the CC' loop. Pharmaceutical preparations that include one or more of such identified candidate may then be provided and used in treatments for bacterial infections, dysentery, angiogenesis, immune cell mediated disease, and related conditions thereto. Excerpt(s): CEACAM1 is a member of the carcinoembryonic antigen (CEA) family. Isoforms of murine CEACAM1 serve as receptors for mouse hepatitis virus (MHV), a murine coronavirus. Carcinoembryonic antigen (CEA; CD66e) was initially discovered as a tumor antigen (Gold and Freedman, 1965). A large group of related glycoproteins is now called the CEA family within Ig superfamily (IgSF). These anchored or secreted glycoproteins are expressed by epithelial cells, leukocytes, endothelial cells and placenta (Hammarstrom, 1999). In humans, the CEA family contains 29 genes or pseudogenes. The revised nomenclature of this family of glycoproteins was recently summarized (Beauchemin et al., 1999). The CEA family consists of the CEACAM (CEA-related cell adhesion molecule) and PSG (pregnancy-specific glycoprotein) subfamilies whose proteins share many common structural features (Hammarstrom, 1999). CEACAM1 (CD66a) is the most highly conserved member of the CEA family. Most species have only one CEACAM1 gene, but mice have two closely related genes called CEACAM1 and CEACAM2 (Beauchemin et al., 1999). CEACAM1 has many important biological functions. It is a potent vascular endothelial growth factor (Ergun et al., 2000) and a growth inhibitor in tumor cells (Izzi et al., 1999); plays a key role in differentiation of mammary glands (Huang et al., 1999); is an early marker of T cell activation; and modulates the functions of murine T lymphocytes (Morales et al., 1999; Nakajima et al., 2002). Human CEACAM1 is one of several human CEACAM proteins that serve as receptors for virulent strains of Neisseria gonorrhoeae, Neisseria meningitidis, and Hemophilus influenzae (Bos et al., 1999; Virji et al., 2000; Virji et al., 1999).
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Combination therapy for the treatment of bacterial infections Inventor(s): Hafkin, Barry; (Danbury, CT), Needleman, Philip; (Creve Coeur, MO) Correspondence: Pharmacia & Upjohn; 301 Henrietta ST; 0228-32-law; Kalamazoo; MI; 49007; US Patent Application Number: 20030191051 Date filed: January 21, 2003 Abstract: The present invention provides compositions and methods for treating or preventing bacterial infections. The compositions and methods include the use of antibiotics and cyclooxygenase inhibitors. Excerpt(s): This application claims the benefit of the following provisional application(s): U.S. Serial No. 60/351,058, filed January 23, 2002, under 35 USC 119(e)(i). Antibiotics were introduced into medical practice nearly 50 years ago. Antibiotics have been used to control many life-threatening diseases, to reduce death and illness, and to increase the life expectancy of the population. However, the benefits of antibiotics have not been gained without the introduction of some associated problems. Antibiotics are commonly administered to treat bacterial infections by, for example, injection, oral administration, or application to the skin in ointment form. Many antibiotics are potent anti-infective agents, but also cause toxic side effects. For example, penicillin is highly allergenic and can cause skin rashes, shock, and other allergic responses. Tetracyclines are capable of causing major changes in the intestinal bacterial population and can result in superinfection by fungi and other microorganisms. Chloramphenicol is known to produce severe blood diseases, which has led to restrictions in its use. Streptomycin can result in ear and kidney damage. Moreover, many antibiotics have lost their effectiveness against some bacterial diseases and, as a result, some illnesses that were once easily treatable now pose treatment problems for physicians and their patients. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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COMPOSITIONS AND METHODS FOR CONTROLLING PLANT PESTS Inventor(s): Heins, Sherry Darlene; (Davis, CA), Jimenez, Desmond Rito; (Woodland, CA), Manker, Denise Carol; (Davis, CA), Marrone, Pamela Gail; (Davis, CA), McCoy, Randy Jay; (Davis, CA), Orjala, Jimmy Ensio; (Davis, CA) Correspondence: Michael Ward, ESQ.; Morrison & Foerster L.L.P.; 425 Market Street; San Francisco; CA; 94105; US Patent Application Number: 20030186852 Date filed: November 27, 2001 Abstract: The present invention relates to a novel antibiotic-producing and metaboliteproducing Bacillus subtilis strain that exhibits insecticidal, antifungal and antibacterial activity. The supernatant of this novel strain contains effective insecticidal, antifungal and antibacterial agents. Also included in the invention is a solvent extractable, small molecular weight (<10,000 daltons) corn rootworm-active metabolite produced in the supernatant. Also included in the invention are methods of protecting or treating plants from fungal and bacterial infections and corn rootworm infestations comprising the
Patents 145
step of applying to the plant an effective amount of the antibiotic/metabolite-producing novel Bacillus subtilis strain, the antibiotic/metabolite produced by the novel Bacillus subtilis strain or a combination thereof, optionally further comprising another antibioticproducing bacterial strain and/or a chemical pesticide. The invention also includes methods of preventing or treating fungal and bacterial infections using whole broth cultures or supernatants obtained from cultures of the novel Bacillus subtilis strain alone or in combination with chemical pesticides and/or other biocontrol agents. The invention also includes novel antifungal and antibacterial compounds designated agrastatins and a novel combination comprising an A-type iturin, a plipastatin, a surfactin and an agrastatin. Methods of treating or protecting plants from fungal and bacterial infections and corn rootworm infestations comprising administering the novel agrastatins and the novel combination comprising an A-type iturin, a plipastatin, a surfactin and an agrastatin are provided. Further provided is a lipopeptide extract isolated from strain AQ713 with insecticidal activity and a surfactin lipopeptide isolated from strain AQ713 with insecticidal activity. Excerpt(s): This application is a continuation-in-part of application U.S. Ser. No. 09/074,870, filed May 8, 1998, which in turn is a continuation-in-part of application U.S. Ser. No. 08/853,753, filed May 9, 1997, the contents of which are hereby incorporated by reference. The present invention is in the field of biopesticides. More particularly, this invention relates to the finding that a novel strain of Bacillus subtilis, AQ713, can inhibit a broad range of fungal and bacterial plant diseases and also have activity against insects. The invention also relates to fungicidal, bactericidal, and insecticidal compositions comprising this novel Bacillus strain and the antibiotics and metabolites produced by this strain either alone, or in combination with other chemical and biological pesticides. For a number of years, it has been known that various microorganisms exhibit biological activity so as to be useful to control plant diseases. Although progress has been made in the field of identifying and developing biological pesticides for controlling various plant diseases of agronomic and horticultural importance, most of the pesticides in use are still synthetic compounds. Many of these chemical fungicides are classified as carcinogens by the EPA, are toxic to wildlife and other non-target species. In addition, pathogens may develop resistance to chemical pesticides (see, e.g., Schwinn et al., p. 244, ADVANCES IN PLANT PATHOLOGY: PHYTOPHTHORA INFESTANS, THE CAUSE OF LATE BLIGHT OF POTATO (Academic Press, San Diego 1991). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Compositions and methods for treating infections using cationic peptides alone or in combination with antibiotics Inventor(s): Erfle, Douglas; (Vancouver, CA), Fraser, Janet R.; (Vancouver, CA), Krieger, Timothy J.; (Monrovia, CA), MicNicol, Patricia J.; (Vancouver, CA), Taylor, Robert; (White Rock, CA), West, Michael H.P.; (Caledon East, CA) Correspondence: Seed Intellectual Property Law Group Pllc; 701 Fifth Ave; Suite 6300; Seattle; WA; 98104-7092; US Patent Application Number: 20030232750 Date filed: October 18, 2002 Abstract: Compositions and methods for treating infections, especially bacterial infections, are provided. Indolicidin peptide analogues containing at least two basic
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amino acids are prepared. The analogues are administered as modified peptides, preferably containing photo-oxidized solubilizer. Excerpt(s): The present application is a continuation of allowed U.S. patent application Ser. No. 09/030,619, filed Feb. 25, 1998, which application claims priority from U.S. Provisional Application No. 60/040,649, filed Mar. 10, 1997, and U.S. Provisional Application No. 60/060,099, filed Sep. 26, 1997, and is a continuation-in-part of U.S. application Ser. No. 08/915,314, filed Aug. 20, 1997, issued as U.S. Pat. No. 6,180,604 on Jan. 30, 2001 which claims priority from U.S. Provisional Application No. 60/024,754, filed Aug. 21, 1996, and U.S. Provisional Application No. 60/034,949, filed Jan. 13, 1997. The present invention relates generally to methods of treating microorganism-caused infections using cationic peptides or a combination of cationic peptides and antibiotic agents, and more particularly to using these peptides and antibiotic agents to overcome acquired resistance, tolerance, and inherent resistance of an infective organism to the antibiotic agent. For most healthy individuals, infections are irritating, but not generally life-threatening. Many infections are successfully combated by the immune system of the individual. Treatment is an adjunct and is generally readily available in developed countries. However, infectious diseases are a serious concern in developing countries and in immunocompromised individuals. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Cross-linked glycopeptide-cephalosporin antibiotics Inventor(s): Fatheree, Paul R.; (San Francisco, CA), Linsell, Martin S.; (San Francisco, CA), Long, Daniel D.; (San Francisco, CA), Marquess, Daniel; (Half Moon Bay, CA), Trapp, Sean G.; (San Francisco, CA), Turner, S. Derek; (San Francisco, CA) Correspondence: Theravance, INC.; 901 Gateway Boulevard; South San Francisco; CA; 94080; US Patent Application Number: 20040033939 Date filed: May 23, 2003 Abstract: This invention provides cross-linked glycopeptide-cephalosporin compounds and pharmaceutically acceptable salts thereof which are useful as antibiotics. This invention also provides pharmaceutical compositions containing such compounds; methods for treating bacterial infections in a mammal using such compounds; and processes and intermediates useful for preparing such compounds. Excerpt(s): This application claims the benefit of U.S. Provisional Application No. 60/383,274, filed on May 24, 2002; the entire disclosure of which is incorporated herein by reference in its entirety. This invention is directed to novel cross-linked glycopeptidecephalosporin compounds which are useful as antibiotics. This invention is also directed to pharmaceutical compositions comprising such compounds; methods of using such compounds as antibacterial agents; and processes and intermediates for preparing such compounds. Despite such compounds, a need exists for new antibiotics having improved properties including, by way of example, increased potency against grampositive bacteria. In particular, a need exists for new antibiotics which are highly effective against antibiotic-resistant strains of bacteria, such as methicillin-resistant Staphylococci aureus (MRSA). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Disruption of PQS synthesis using precursor analogs Inventor(s): Coleman, James P.; (Farmville, NC), Pesci, Everett C.; (Greenville, NC) Correspondence: Myers Bigel Sibley & Sajovec; PO Box 37428; Raleigh; NC; 27627; US Patent Application Number: 20040002130 Date filed: June 27, 2002 Abstract: The present invention concerns methods of detecting bacterial infections as well as methods of treating such infections with compounds such as methyl anthranilate. The detection and treatment of Pseudomonas is particularly preferred. Excerpt(s): The present invention concerns methods of detecting PQS and bacterial cells producing the same, as well as methods of treating bacterial infections in a subject in need thereof. Cell-to-cell signaling by Pseudomonas aeruginosa occurs through a complex circuitry of interconnected, regulatory systems that controls over 70 different genes (Pesci and Iglewski (1997) Trends in Micro. 5:132-135; Whiteley, et al. (1999) Proc. Nail. Acad. Sci. USA 96:13904-13909). The signaling systems of P. aeruginosa are necessary for virulence in multiple infectious disease model systems (de Kievet and Iglewski (2000) Infect. Immun. 68:4839-4848). P. aeruginosa produces two cell-to-cell signals from the acyl homoserine lactone family [N-3-oxododecanoyl)-L-homoserine lactone and N-butyryl-L-homoserine lactone], and a third, unique cell-to-cell Pseudomonas quinolone signal, referred to as PQS (Pesci, et al. (1999) Proc. Natl. Acad. Sci. USA 96:11229-11234; Pearson, et al. (1994) Proc. Nat. Acad. Sci. USA 91:197-201; Pearson, et al. (1995) Proc. Nat. Acad. Sci. USA 92:1490-1494). PQS, which induces the expression of virulence factors elastase and rhlI (encodes the N-butyryl-L-homoserine lactone synthase), is the only quinolone compound known to act as a cell-to-cell signal (Pesci, et al. (1999) Proc. Natl. Acad. Sci. USA 96:11229-11234; McKnight, et al. (2000) J. Bacteriol. 182:2702-2708). Although the role of this signal in the pathogenesis of human infections is not known, it is clearly important for P. aeruginosa virulence in a nematode killing assay (Gallagher and Manoil (2001) J. Bacteriol. 183:6207-6214). Also important to note, is that PQS signaling is regulated differently from acyl homoserine lactone signaling. Acyl homoserine lactone signals are produced at a time of rapid population growth, but PQS is produced maximally in the late stationary phase of growth (McKnight, et al. (2000) J. Bacteriol. 182:2702-2708). This suggests that PQS signaling is important when P. aeruginosa cells are under stressful conditions, such as those which would occur during a chronic infection in the lungs of cystic fibrosis (CF) patients. As an opportunistic pathogen, P. aeruginosa has found a specialized niche in the lungs of CF patients (Gilligan (1991) Clin. Microbiol. Rev. 4:35-51). Due to poor pulmonary clearance, P. aeruginosa chronically infects the lungs of a vast majority of CF patients at a young age (Welsh, et al. In: The Metabolic and Molecular Basis of Inherited Disease Vol. III (eds. Scriver, et al.) 3799-3876 (McGraw-Hill, New York, 1995)). These infections are difficult to treat and persist for the life of the patient, causing progressive lung damage that eventually leads to respiratory failure (Koch and Hoiby (1993) Lancet 341:1065-1069). Hence, as P. aeruginosa can have devastating effects on individuals suffering from CF or other infections and can rapidly develop antibiotic resistance there is a need in the art for novel therapeutic agents to combat P. aeruginosa infections. Intercellular signals and their synthetic pathways have been suggested as starting points for novel therapeutic targets (Govan and Deretic (1996) Microbiol. Rev. 60:539-547; Calfee, et al. (2001) Proc. Natl. Acad. Sci. USA 98:11633-11637). In fact, earlier work has shown that PQS is required for virulence in an insect model of infection (Gallagher & Manoil (2001) J. Bacteriol. 183:6207-6214). In addition, the use of a PQS precursor analog was found to interfere with PQS synthesis and inhibit the production of elastase, a PQS-
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controlled virulence factor (Calfee, et al. (2001) Proc. Natl. Acad. Sci. USA 98:1163311637). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Gyrase inhibitors and uses thereof Inventor(s): Badia, Michael; (Bedford, MA), Charifson, Paul; (Framingham, MA), Grillot, Anne Laure; (Cambridge, MA), Ronkin, Steven; (Watertown, MA), Stamos, Dean; (Framingham, MA), Trudeau, Martin; (Tewksbury, MA) Correspondence: Nandakumar Govindswamy; Vertex Pharmaceuticals Incorporated; 130 Waverly Street; Cambridge; MA; 02139-4242; US Patent Application Number: 20040024030 Date filed: March 24, 2003 Abstract: The present invention relates to compounds of the formula I: 1where Ring A is a thiazole, oxazole, imidazole or pyrazole and the substituents are as described in the specification, and pharmaceutically acceptable salts thereof. The compounds inhibit bacterial gyrase activity and therefore are useful for treating bacterial infections in mammals. Excerpt(s): This application claims the benefit of International PCT application No. US/01/01374, filed, Jan. 16, 2001, which claims the benefit of U.S. Provisional Application serial No. 60/176,671, filed Jan. 18, 2000 and U.S. Provisional Application serial No. 60/254,331 filed Dec. 8, 2000, all three applications being incorporated herein by reference. This invention is in the field of medicinal chemistry and relates to novel compounds, and pharmaceutical compositions thereof, that inhibit DNA gyrases. The invention also relates to methods of using the compounds and pharmaceutical compositions of this invention to treat bacterial infections, including nosocomial infections, that are susceptible to gyrase inhibition. Bacterial resistance to antibiotics has long been recognized, and it is today considered to be a serious worldwide health problem. As a result of resistance, some bacterial infections are either difficult to treat with antibiotics or even untreatable. This problem has become especially serious with the recent development of multiple drug resistance in certain strains of bacteria, such as Streptococcus pneumoniae (SP), Mycobacterium tuberculosis, and Enterococcus. The appearance of vancomycin resistant enterococcus was particularly alarming because vancomycin was formerly the only effective antibiotic for treating this infection, and had been considered for many infections to be the drug of "last resort". While many other drug-resistant bacteria do not cause life-threatening disease, such as enterococci, there is the fear that the genes which induce resistance might spread to more deadly organisms such as Staphylococcus aureus, where methicillin resistance is already prevalent (De Clerq, et al., Current Opinion in Anti-infective Investigational Drugs, 1999, 1, 1; Levy, "The Challenge of Antibiotic Resistance", Scientific American, March, 1998). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Inhibitors of serine and metallo-beta-lactamases Inventor(s): Buynak, John D.; (Dallas, TX), Chen, Hansong; (Dallas, TX) Correspondence: Schwegman, Lundberg, Woessner & Kluth, P.A.; P.O. Box 2938; Minneapolis; MN; 55402; US Patent Application Number: 20030216372 Date filed: April 4, 2003 Abstract: Compounds of formula (I): 1wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4 and n have any of the values defined in the specification, and their pharmaceutically acceptable salts, are useful for inhibiting simultaneously serine and metallo-.beta.lactamase enzymes, for enhancing the activity of.beta.-lactam antibiotics, and for treating.beta.-lactam resistant bacterial infections in a mammal. The invention also provides pharmaceutical compositions, processes for preparing compounds of formula I, and novel intermediates useful for the synthesis of compounds of formula I. Excerpt(s): This application claims benefit under 35 U.S.C.sctn. 119(e) of U.S. provisional application Ser. No. 60/370,499, filed Apr. 4, 2002, which application is incorporated herein by reference. The most important mechanism of microbial resistance to.beta.lactam antibiotics is the bacterial production of.beta.-lactamases, enzymes that hydrolytically destroy.beta.-lactam antibiotics, such as penicillins and cephalosporins. This type of resistance can be transferred horizontally by plasmids that are capable of rapidly spreading the resistance, not only to other members of the same strain, but even to other species. Due to such rapid gene transfer, a patient can become infected with different organisms, each possessing the same.beta.-lactamase.beta.-lactamase enzymes have been organized into four molecular classes: A, B, C and D based on amino acid sequence. Class A, includes RTEM and the.beta.-lactamase of Staphylococcus aureus, class C, includes the lactamase derived from P99 Enterobacter cloacae, and class D are serine hydrolases. Class A enzymes have a molecular weight of about 29 kDa and preferentially hydrolyze penicillins. The class B lactamases are metalloenzymes and have a broader substrate profile than the proteins in the other classes. Class C enzymes include the chromosomal cephalosporinases of gram-negative bacteria and have molecular weights of approximately 39 kDa. The recently recognized class D enzymes exhibit a unique substrate profile that differs significantly from the profile of both class A and class C enzymes. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Macrolide antibacterial compounds Inventor(s): Djuric, Stevan; (Libertyville, IL), Ma, Zhenkun; (Dallas, TX) Correspondence: Steven F. Weinstock; Abbott Laboratories; 100 Abbott Park Road; DEPT. 377/ap6a; Abbott Park; IL; 60064-6008; US Patent Application Number: 20040014687 Date filed: April 22, 2003 Abstract: Macrolide antibacterial compounds having formula (I) 1and formula (II) 2and salts, prodrugs, and salts of prodrugs thereof, processes for making the compounds and intermediates employed in the processes, compositions containing the compounds, and methods for prophylaxis or treatment of bacterial infections in a fish or a mammal using the compounds are disclosed.
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Excerpt(s): This application claims benefit of co-pending U.S. Application Serial No. 60/375,513, filed Apr. 25, 2002, the specification of which is hereby incorporated by reference into this application. This invention is directed to compounds which are useful as antibacterials, processes for making the compounds and intermediates used in the processes, compositions containing the compounds, and methods for prophylaxis or treatment of bacterial infections using the compounds. Because the effectiveness of many drugs currently available for prophylaxis or treatment of bacterial infections is being compromised by the emergence of drug-resistant bacteria, novel antibacterials would be beneficial for their therapeutic value and their contribution to the antibacterial arts. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Method for treatment of bacterial infections with once or twice-weekly administered rifalazil Inventor(s): Montgomery, Alan B.; (Bellevue, WA), Porubek, David J.; (Seattle, WA), Rose, Lynn M.; (Seattle, WA) Correspondence: Hana Verny; Peters, Verny, Jones & Schmitt Llp; Suite 6; 385 Sherman Avenue; Palo Alto; CA; 94306; US Patent Application Number: 20030203903 Date filed: September 14, 2002 Abstract: A method for treatment of bacterial infections with rifalazil administered once-weekly, or twice-weekly. A method for treatment of tuberculosis caused by Mycobacterium tuberculosis, infections caused by Mycobacterium avium complex, infections caused by Chlamydia pneumoniae and infections caused by Helicobacter pylori by administering to a patient suffering from the bacterial infection 1-100 mg of rifalazil once or twice a week. In this dose regimen, the treatment is fast, efficacious and eliminates undesirable secondary symptoms observed with daily doses of 1-50 mg of rifalazil. Excerpt(s): This application is based on and claims priority of Provisional Application Serial No. 60/112,921 filed on Dec. 18, 1998. The current invention concerns a method for treatment of bacterial infections with rifalazil administered once-weekly or twiceweekly. In particular, the invention concerns a method for treatment of tuberculosis caused by Mycobacterium tuberculosis, infections caused by Mycobacterium avium complex, infections caused by Chlamydia pneumoniae and infections caused by Helicobacter pylori by administering to a patient suffering from the bacterial infection rifalazil once or twice a week. In this dose regimen, the treatment is fast, efficacious and eliminates undesirable secondary symptoms observed with daily doses of 1-50 mg of rifalazil. Bacterial infection caused by mycobacterium species and similar infections caused by Chlamydia pneumoniae or H. pylori cause serious health problems in the United States and worldwide. For example, tuberculosis, caused by Mycobacterium tuberculosis is one of the most serious infectious diseases outside of developed countries, with over one billion people infected worldwide. The worldwide infection rate results in eight million active tuberculosis cases annually and over two million deaths per year. In the United States, 26,000 new cases of active tuberculosis were reported in 1994. The number of active cases in the United States is high because of the increase in patients with AIDS and the increase in immigration from developing countries. Moreover, there is reported an increase in multidrug resistance tuberculosis and disseminated Mycobacterium avium complex infections.
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Methods and devices for treating severe peripheral bacterial infections Inventor(s): Cantor, Tom L.; (El Cajon, CA) Correspondence: Morrison & Foerster Llp; 3811 Valley Centre Drive; Suite 500; San Diego; CA; 92130-2332; US Patent Application Number: 20040024343 Date filed: April 1, 2003 Abstract: The present invention relates to novel methods and devices for treating severe bacterial infections, such as septicemia, using an extracorporeal adsorption container. The device has a solid support disposed and confined within the container and a binding means associated with the solid support that is specific for affixing an infecting bacterium that is causing the severe peripheral bacterial infection and/or bacterial toxins from the bacterium. By passing the infected blood through the container. at least a portion of the infecting bacterium and/or bacterial toxins are removed. The treated blood is returned to the patient. Excerpt(s): This application claims priority to Provisional Patent Application S No. 60/369,692 filed Apr. 2, 2002 under 35 U.S.C.sctn. 119(e). The disclosure of the abovereferenced application is incorporated in its entirety by reference. The present invention relates to novel methods and devices for treating severe bacterial infections, such as septicemia or bacteremeia, using an extracorporeal adsorption container. The device has a solid support disposed and confined within the container and a binding means associated with the solid support that is specific for affixing an infecting bacterium that is causing the severe peripheral bacterial infection and/or bacterial toxins from the bacterium. By passing the infected blood through the container, at least a portion of the infecting bacterium and/or bacterial toxins are removed. The treated blood is returned to the patient. Bacterial infections are becoming a greater danger. Certain bacteria have become resistant to antibiotic treatment, in some cases to a number of antibiotics, either naturally or through genetic manipulation. Septicemia is now among the most common causes of death in the United States of America (13.sup.th as of the year 2000), accounting for over ten billion dollars annually in health care costs. Fatality rates for septicemia are around 20%, totaling over 50,000 deaths annually. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Methods of treating bacterial infections and diseases associated therewith Inventor(s): Sayada, Chalom B.; (Luxembourg City, LU) Correspondence: Clark & Elbing Llp; 101 Federal Street; Boston; MA; 02110; US Patent Application Number: 20030236265 Date filed: May 22, 2003 Abstract: The invention features methods and compositions for treating non-multiplying forms of bacterial infections. Excerpt(s): This application claims benefit of U.S. Provisional Application No. 60/382,805, filed May 23, 2002, which is hereby incorporated by reference. This invention relates to the field of treatment of bacterial infections. Bacteria have two
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general growth states, a multiplying phase and a non- multiplying phase. To date, most antibiotics have been developed against bacteria in the multiplying phase (i.e., multiplying bacteria). The non-multiplying form is highly resistant to most known antibiotics. This resistance is reversible; when non-multiplying bacteria start to multiply, they become sensitive to antibiotics. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Methods of treatment and formulations of cephalosporin Inventor(s): Blanchflower, Simon E.; (Sandwich, GB), Bronk, Brian S.; (Gales Ferry, CT), Kimball, Roger N.; (New York, NY), Reddy, Renuka D.; (Waterford, CT), Shalaev, Evgenyi Y.; (Old Lyme, CT) Correspondence: Pfizer INC.; Patent Department, Ms8260-1611; Eastern Point Road; Groton; CT; 06340; US Patent Application Number: 20030186957 Date filed: November 12, 2002 Abstract: Formulations containing an antibacterial alkali metal salt of a cephalosporin compound and methods of treating bacterial infections in dogs and cats. Excerpt(s): The invention is also directed to methods for treating bacterial infections in dogs and cats by administering a compound of Formula I. Cephalosporins are widely used and therapeutically important antibiotics. The compounds of Formula I are broad spectrum cephalosporin antibacterials and are, therefore, useful in the treatment of bacterial infections in animals. (U.S. Pat. No. 6,020,329, Col. 1, lines 13-14). In particular, Compound I is targeted for dogs and cats with indications for treatment of bacterial infections of the skin, soft tissue, periodontal and urinary tract. Compound I, wherein M is Na.sup.+, and the preparation thereof, are disclosed in U.S. Pat. Nos. 6,001,997, 6,020,329 and 6,077,952. The text of the aforementioned patents and all other references cited in this specification are hereby incorporated by reference in their entirety. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Mixed steroidal 1, 2, 4, 5- tetraoxane compounds and methods of making and using thereof Inventor(s): Kyle, Dennis E.; (Fig Tree Pocket, MD), Milhous, Wilbur K.; (Germantown, MD), Opsenica, Dejan M.; (Veljka, YU), Pocsfalvi, Gabriella; (Napoli, IT), Solaja, Bogdan; (Belgrade, YU) Correspondence: Office OF The Staff Judge Advocate; U.S. Army Medical Research And Materiel Command; Attn: Mcmr-ja (MS. Elizabeth Arwime); 504 Scott Street; Fort Detrick; MD; 21702-5012; US Patent Application Number: 20040019200 Date filed: February 7, 2003 Abstract: Disclosed herein are mixed steroidal tetraoxanes having the following structural formula 1 1wherein n is 0, 1, 2, or 3; R is H; ethanoyl, propanoyl, or benzoyl; R1 is H, methyl, ethyl, or isopropyl; R2 is H, methyl, or ethyl; R3 is H, methyl, or ethyl; R4 is H, methyl, ethyl, tert-butyl, phenyl, p-hydroxyphenyl, p-methoxyphenyl, or pnitrophenyl, or 2wherein Y is a C.sub.1-C.sub.4 straight or branched-chain alkoxy, or
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3wherein W is N, R5 is hydrogen, methyl, ethyl, n-propyl, isopropyl, or methyl ethanoate 2-yl, and R6 is hydrogen, methyl, ethyl, or n-propyl, or R5 and R6 are part of a pyrrolidine or piperidine ring; X is a C.sub.1-C.sub.4 straight or branched-chain alkoxy, a primary amino, a N-alkylamino wherein the alkyl is a straight-chain alkyl groups containing from 1 to 4 carbon atoms, methyl ethanoate-2-yl, N-phenylamino, pnitrophenyl, N,N-dimethylamino, N,N-diethylamino, N,N-di(n-propyl)amino, Npyrrolidino, or N-piperidino as single compounds, and any mixture of all possible stereoisomers at C(4"). n may be 0, 1, 2, or 3, and methods of making and using thereof. As disclosed herein, the mixed steroidal tetraoxanes of the present invention exhibit antimalarial, antibacterial, and antiproliferative activity. Thus, as disclosed herein, the mixed steroidal tetraoxanes of the present invention may be used to treat, prevent, or inhibit malaria, bacterial infections, and diseases and disorders associated with cell proliferation in a subject. Excerpt(s): This application claims the benefit of U.S. Provisional Patent Application No. 60/356,633 filed Feb. 9, 2002, which names Bogdan A. Solaja, Gabriella Pocsfalvi, Dennis E. Kyle, Dej an Opsenica, and Wilbur K. Milhous as joint inventors and is herein incorporated by reference in its entirety. The present invention relates to steroidal mixed tetraoxanes and to processes for the production thereof. In a preferred embodiment, the present invention relates to cycloalkyl-spiro-1,2,4,5-tetraoxacyclohexane- -spiro-cholic acids and derivatives thereof, which are active against chloroquine-resistant malaria. The present invention also relates to gem-dihydroperoxides of cholic acids and derivatives thereof, and 1,1-dihydroperoxy(susbstituted)cycloalkanes. The current global situation with respect to malaria indicates that about two billion people are exposed to the disease and of these 400 million people are already infected. See Trigg, P. I., and A. V. Kondrachine (1998) The Current Global Malaria Situation, Chapter 2, p. 1122, in MALARIA PARASITE BIOLOGY, PATHOGENESIS AND PROTECTION. Ed. I. W. Sherman, ASM Press, Washington, D.C. Each year between 100 to 200 million new cases of infection are reported and approximately 1 to 2 million people die due to malaria. The situation is rapidly worsening mainly due to non-availability of effective drugs and development of drug resistance of a large number of non-immune people in areas where malaria is frequently transmitted. See White, N. J. (1998) Br. Med. Bull. 54:703-715. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Monoclonal antibodies that are cross-reactive against bacterial collagen binding proteins Inventor(s): Pietrocola, Giampiero; (Pavia, IT), Speziale, Pietro; (Pavia, IT), Visai, Livia; (Rosate, IT) Correspondence: Larson & Taylor, Plc; 1199 North Fairfax Street; Suite 900; Alexandria; VA; 22314; US Patent Application Number: 20030190320 Date filed: February 21, 2003 Abstract: Cross-reactive monoclonal antibodies are provided which are generated from peptides from Enterococcus faecalis, including the ACE40 and the ACE19 protein, and the CNA19 peptide from Staphylococcus aureus, and which can bind to the collagenbinding proteins from bacteria from a variety of species including enterococcal bacteria, staphylococcal bacteria and streptococcal bacteria. These monoclonal antibodies may then be formed into suitable pharmaceutical compositions, and they are thus
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particularly effective in providing methods of treating or preventing bacterial infections from a wide range of bacterial species. Excerpt(s): The present application claims the benefit of U.S. provisional applications Ser. No. 60/361,347, filed Mar. 5, 2002, and Ser. No. 60/357,832, filed Feb. 21, 2002. The present invention relates in general to monoclonal antibodies that have been generated against collagen binding proteins and peptides from bacteria such as Staphylococcus aureus, Enterococcus faecalis, and Enterococcus faecium, as well as streptococcal bacteria, and in particular to monoclonal antibodies against certain peptide fragments from the collagen binding domains from these proteins such as ACE19 and ACE40 which evidence cross-reactivity across species, as well as their use in treating or preventing bacterial infections. The magnitude of gram-positive nosocomial infections has been documented extensively in both the scientific literature as well as in the lay press over the past two decades. Since staphylococci account for the single largest cause of nosocomial infections they have been the focus of most reports. Traditionally, the generic antibiotic vancomycin has been the drug of choice to treat gram-positive infections. However, the continued rise in the prevalence of methicillin resistant S. aureus (MRSA) and the emergence of vancomycin resistant isolates of S. aureus from intensive care units from around the world has served as a rallying point for the clinical community, biopharmaceutical companies, and governmental agencies to develop novel therapeutics. The continued overuse of vancomycin has not only led to the development of resistant S. aureus strains, but it has also resulted in the emergence of resistant strains of enterococci. In 1986, the first clinical isolates of Enterococcus faecium were reported in France. A decade later, vancomycin-resistant enterococci (VRE) have reported in 18 countries and 6 continents. The problem in the United States is extremely troublesome, were >20% of enterococcal isolates reported in the 1998 report of the National Nosocomial Infectious Surveillance System (NNIS) hospitals were vancomycin resistant. The resistant rate was >50% higher than that reported for the same hospitals from the period 1993-1997. Enterococci now account for 10% of all nosocomial bloodstream and 20% of cardiovascular infections in the U.S. Moreover, VRE tend to be concomitantly resistant to moderate to high levels of penicillins and aminoglycosides and therefore must be treated with unproven combinations of antibiotics. Even with the recent introductions of linezolid and quinupristin/dalfopristin for the treatment of certain types of VRE infections, a significant gap in the therapeutic armamentarium of the clinician exists. These data indicate that the development of novel therapies that can prevent infection in a prophylactic manner or enhance current treatment modalities or are warranted. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Multivalent macrolide antibiotics Inventor(s): Griffin, John H.; (Atherton, CA), Pace, John L.; (San Anselmo, CA) Correspondence: Theravance, INC.; 901 Gateway Boulevard; South San Francisco; CA; 94080; US Patent Application Number: 20030176670 Date filed: December 27, 2002 Abstract: Disclosed are multibinding compounds which include macrolide antibiotics, aminoglycosides, lincosamides, oxazolidinones, streptoramins, tetracycline and/or other compounds which bind to bacterial ribosomal RNA and/or to one or more proteins involved in ribosomal protein synthesis in the bacterium, which are useful in
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treating bacterial infections. The compounds adversely affect protein expression and have an antibacterial effect. The multibinding compounds of this invention containing from 2 to 10 ligands covalently attached to one or more linkers. Each ligand is macrolide antibiotic, aminoglycoside, lincosamide, oxazolidinone, streptogramin, tetracycline or other compound which binds to bacterial ribosomal RNA and/or one or more proteins involved in ribosomal protein synthesis in the bacterium. Excerpt(s): This application claims the benefit of U.S. Provisional Patent Application Serial Nos. 60/088,448 filed Jun. 8, 1998 and 60/093,072 filed Jul. 16, 1998 both of which are incorporated herein by reference in their entirety. This invention relates to novel multibinding compounds (agents) that are macrolide antibiotics, aminoglycosides, lincosamides, oxazolidinones, streptogramins, tetracyclines or other compounds which bind to bacterial ribosomal RNA or one or more proteins involved in ribosomal protein synthesis in the bacterium, and to pharmaceutical compositions comprising such compounds. The compounds are useful as antibacterial agents for treating a variety of bacterial infections. Organisms generate polypeptides (proteins) in order to survive. Organisms that cannot generate proteins cannot maintain viability. Because the majority of genes encode proteins, "gene expression" is nearly synonymous with protein synthesis. Gene expression involves two steps--transcription and translation. Genes code for proteins using various codons (units of three nucleotides), such as start codons (which initiate translation), stop codons (which stop translation) and codons in between the start and stop codons which selectively code for the various amino acids. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Mutant proteins, high potency inhibitory antibodies and fimch crystal structure Inventor(s): Bouckaert, Julie; (St. Louis, MO), Hultgren, Scott J.; (Town and Country, MO), Hung, Chia-Suei; (St. Louis, MO), Langermann, Solomon; (Baltimore, MD) Correspondence: Pennie And Edmonds; 1155 Avenue OF The Americas; New York; NY; 100362711 Patent Application Number: 20030199071 Date filed: December 10, 2001 Abstract: The present invention provides bacterial immunogenic agents for administration to humans and non-human animals to stimulate an immune response. It particularly relates to the vaccination of mammalian species, especially human patients, with variants of the E. coli FimCH protein that elicit antibodies that have better functional inhibitory activity than antibodies raised against wild type protein. In particular, such variants include mutations that promote a more open confirmation of the FimH protein, particularly in regions involved in mannose binding, to expose regions previously poorly exposed and mutations that abolish a significantly reduce mannose binding. In another aspect, the invention provides antibodies against such proteins and protein complexes that may be used in passive immunization to protect or treat pathogenic bacterial infections. The present invention also provides machine readable media embedded with the three-dimensional atomic structure coordinates of FimCH bound to mannose, and subsets thereof, and methods of using the crystal structure to provide candidate amino acid residues for mutation. Excerpt(s): This application claims priority to U.S. Provisional Patent Application No. 60/254,353, filed Dec. 8, 2000, and U.S. Provisional Patent Application No. 60/301,878, filed Jun. 29, 2001, the content of each of which is incorporated herein by reference in its
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entirety. The invention relates to methods of producing antibodies, preferably antibodies that inhibit binding of a protein to its binding partner. Further, the methods include producing antibodies having enhanced functional inhibitory activity against a protein, for example, that inhibit binding of the protein to a binding partner, by immunizing with a mutant form of the protein that elicits antibodies with greater inhibitory activity than those antibodies elicited by the wild type protein. In one example, mutant proteins are designed using the crystal structure of purified FimCH bound to mannose. Mutant proteins are expressed and used as antigens to elicit antibodies. Thus, this crystal structure, including its coordinates, and methods of designing vaccines and antibodies using information from the crystal structure are included herein. In particular embodiments, this invention relates to mutant bacterial adhesin proteins and active fragments thereof for use in the prevention, diagnosis and treatment of bacterial induced diseases such as those of the urinary tract. The invention encompasses use of mutant proteins as immunogenic agents in vaccine compositions to stimulate an immune response in humans and animals. The invention also encompasses the administration of antibodies to said mutant proteins to humans and animals in an effective amount, to treat, prevent or manage disease or infection. More specifically, the invention relates to the administration of purified mutant adhesin proteins or antibodies directed against said mutant adhesin proteins to a mammalian species as a mechanism to protect the vaccine or antibody recipient against infection by pathogenic bacterial species, including all types of Enterobacteriaceae. Urinary tract infections (herein, "UTI") present a disease process that is mediated (or assisted or otherwise induced) by the attachment of bacteria to cells. Escherichia coli is the most common pathogen of the urinary tract, accounting for more than 85% of cases of asymptomatic bacteriuria, acute cystitis and acute pyelonephritis, as well as greater than 60% of recurrent cystitis, and at least 35% of recurrent pyelonephritis infections. Furthermore, approximately 25%-30% of women experience a recurrent E. coli urinary tract infection within the first 12 months following an initial infection but after a second or third infection the rate of recurrence increases to 60%-75%. Given the high incidence, continued persistence, and significant expense associated with E. coli UTI, there is a need for a prophylactic treatment to reduce susceptibility to this disease. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Naphthrydine compounds and their azaisosteric analogues as antibacterials Inventor(s): Hatton, Ian Keith; (Reigate, Surrey, GB), Pearson, Neil David; (Harlow, Essex, GB) Correspondence: Glaxosmithkline; Corporate Intellectual Property - Uw2220; P.O. Box 1539; King OF Prussia; PA; 19406-0939; US Patent Application Number: 20030212084 Date filed: December 20, 2001 Abstract: Piperidine derivatives of formula (I) or a pharmaceutically acceptable derivative thereof and pharmaceutically acceptable derivatives thereof useful in methods of treatment of bacterial infections in mammals, particularly in man. 1 Excerpt(s): This invention relates to novel medicaments, being novel antibacterial compounds and compositions. WO9217475, WO9802438, WO9703069 and WO9639145 disclose certain bicyclic heteroaromatic compounds having cholinesterase inhibitor, protein tyrosine kinase inhibitor, cell proliferation inhibitor and human epidermal growth factor receptor type 2 inhibitor activity. provided that A and B cannot both be
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selected from NR.sup.11, O and S(O).sub.x and when one of A and B is CO the other is not CO, O or S(O).sub.x. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Nitrosated proton pump inhibitors, compositions and methods of use Inventor(s): Fang, Xinqin; (Lexington, MA), Garvey, David S.; (Dover, MA), Letts, L. Gordon; (Dover, MA) Correspondence: Edward D Grieff; Hale & Dorr Llp; 1455 Pennsylvania Ave, NW; Washington; DC; 20004; US Patent Application Number: 20040024014 Date filed: August 1, 2003 Abstract: The invention describes novel nitrosated proton pump inhibitor compounds and pharmaceutically acceptable salts thereof, and novel compositions comprising at least one nitrosated proton pump inhibitor compound, and, optionally, at least one compound that donates, transfers or releases nitric oxide, stimulates endogenous synthesis of nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor or is a substrate for nitric oxide synthase, and/or at least one therapeutic agent. The invention also provides novel compositions comprising at least one nitrosated proton pump inhibitor compound, and at least one compound that donates, transfers or releases nitric oxide, elevates endogenous levels of endothelium-derived relaxing factor, stimulates endogenous synthesis of nitric oxide or is a substrate for nitric oxide synthase and/or at least one therapeutic agent. The invention also provides novel kits comprising at least one nitrosated proton pump inhibitor compound, and, optionally, at least one nitric oxide donor and/or at least one therapeutic agent. The invention also provides methods for treating gastrointestinal disorders; facilitating ulcer healing; decreasing the recurrence of ulcers; improving gastroprotective properties, anti-Helicobacter pylori properties or antacid properties of proton pump inhibitors; decreasing or reducing the gastrointestinal toxicity associated with the use of nonsteroidal antiinflammatory compounds; treating bacterial infections and/or viral infections. Excerpt(s): This application claims priority to U.S. application Ser. No. 60/399,715 filed Aug. 1, 2002. The proton pump, located in the apical membrane of the parietal cell, is responsible for the secretion of acid in the stomach when it is stimulated by the enzyme adenosine triphosphate (H.sup.+, K.sup.+)-ATPase. Proton pump inhibitors are a class of anti-secretory compounds used in the management of gastrointestinal disorders. They suppress gastric acid secretion by the specific inhibition of the (H.sup.+, K.sup.+)ATPase enzyme system at the secretory surface of the gastric parietal cell. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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NOVEL 11,12-SUBSTITUTED LACTONE KETOLIDE DERIVATIVES HAVING ANTIBACTERIAL ACTIVITY Inventor(s): Hou, Ying; (Everett, MA), Liu, Tongzhu; (Auburndale, MA), Or, Yat Sun; (Watertown, MA), Phan, Ly Tam; (Malden, MA), Vo, Nha Huu; (Malden, MA) Correspondence: Enanta Pharmaceuticals, INC.; Attn: Patent DEPT.; 500 Arsenal Street; Watertown; MA; 02472; US Patent Application Number: 20040038915 Date filed: August 19, 2002 Abstract: Novel 11-12 substituted lactone ketolide derivatives and pharmaceuticallyacceptable compositions comprising a therapeutically effective amount of a compound of the invention in combination with a pharmaceutically-acceptable carrier are described. Also described are a method for treating bacterial infections by administering to an animal a pharmaceutical composition containing a therapeutically effective amount of a compound of the invention and processes for the preparation of such compounds. Excerpt(s): The present invention relates to novel macrolides having antibacterial activity and useful in the treatment and prevention of bacterial infections. More particularly, the invention relates to novel 11,12-lactone ketolides, 14-membered macrolides, compositions containing such compounds and methods for using the same, as well as processes for making such compounds. Macrolide antibiotics play a therapeutically important role, particularly with the emergence of new pathogens. Structural differences are related to the size of the lactone ring and to the number and nature (neutral or basic) of the sugars. Macrolides are classified according to the size of the lactone ring (12, 14, 15 or 16 atoms). The macrolide antibiotic families (14-, 15- and 16-membered ring derivatives) exhibit a wide range of characteristics (antibacterial spectrum, side-effects and bioavailability). Among the commonly used macrolides are erythromycin, clarithromycin and azithromycin. are well-known and potent antibacterial agents and are used widely to treat and prevent bacterial infection. As with other antibacterials, however, bacterial strains having resistance or insufficient susceptibility to erythromycin have been identified. Also, erythromycin A has only weak activity against Gram-negative bacteria. Therefore, there is a continuing need to identify new erythromycin derivative compounds which possess improved antibacterial activity, which have less potential for developing resistance, which possess the desired Gram-negative activity, or which possess unexpected selectivity against target microorganisms. Consequently, numerous investigators have prepared chemical derivatives of erythromycin in an attempt to obtain analogs having modified or improved profiles of antibiotic activity. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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NOVEL FORMULATION Inventor(s): Conley, Creighton P.; (Bristol, TN), Roush, John A.; (Kingsport, TN), Storm, Kevin H.; (Bristol, TN) Correspondence: Glaxosmithkline; Corporate Intellectual Property - Uw2220; P.O. Box 1539; King OF Prussia; PA; 19406-0939; US Patent Application Number: 20030224049 Date filed: June 13, 2003
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Abstract: Bacterial infections may be treated using a high dosage regimen of amoxycillin and potassium clavulanate. Preferably, the dosage is provided by a bilayer tablet Excerpt(s): This application claims the benefit of priority from Provisional Application No. 60/239,779 filed Oct. 12, 2000. This invention relates to a novel formulation comprising using amoxicillin and potassium clavulanate and the use thereof in treating bacterial infections. Amoxicillin and potassium clavulanate are respectively a known.beta.-lactam antibiotic and a known.beta.-lactamase inhibitor. Products comprising amoxicillin and potassium clavulanate are marketed under the trade name "Augmentin" by SmithKline Beecham. Such products are particularly effective for treatment of community acquired infections, in particular upper respiratory tract infections in adults and otitis media in children. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Novel substituted succinic acid metallo-beta-lactamase inhibitors and their use in treating bacterial infections Inventor(s): Balkovec, James M.; (Martinsville, NJ), Greenlee, Mark L.; (Rahway, NJ), Olson, Steven H.; (Metuchen, NJ), Rouen, Gregory P.; (New Brunswick, NJ) Correspondence: Merck And CO Inc; P O Box 2000; Rahway; NJ; 070650907 Patent Application Number: 20030207859 Date filed: January 9, 2003 Abstract: This invention relates to novel substituted succinic acid metallo-.beta.lactamase inhibitors which are useful potentiators of.beta.-lactam antibiotics. Accordingly, the present invention provides a method of treating bacterial infections in animals or humans which comprises administering, together with a b-lactam antibiotic, a therapeutically effective amount of a compound of formula I: 1including pharmaceutically acceptable salts, prodrugs, anhydrides, and solvates thereof. Excerpt(s): The present invention relates to compounds which have metallo-.beta.lactamase inhibitory characteristics. The invention also relates to methods of preparing, pharmaceutical compositions and uses of the compounds. Metallo-.beta.-lactamases are bacterial enzymes which confer resistance to virtually all clinically relevant.beta.-lactam antibiotics, including carbapenems and jeopardize the future use of all such agents. The increased treatment of infections with carbapenems and other.beta.-lactam antibiotics may lead to the proliferation of clinical bacterial strains which are able to produce metallo-.beta.-lactamases and thus resist the effects of.beta.-lactam antibiotics. In fact, metallo-.beta.-lactamases have now been identified in a number of pathogenic bacterial species including Bacillus cereus, Bacteroides fragilis, Aeromonas hydrophila, Klebsiella pneumoniae, Pseudomonas aeruginosa, Serratia marcescens, Stenotrophomonas maltophilia, Shigella flexneri, Legionella gormanii, Chryseobacterium meningosepticum, Chryseobacterium indologenes, Acinetobacter baumannii, Citrobacter freundii, and Aeromonas veronii. Accordingly, there is an increasing need for agents which when combined with a.beta.-lactam antibiotic, e.g. imipenem, will restore the effectiveness of the.beta.-lactam antibiotics and which are at the same time relatively free from undesirable side effects. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Phenalenone derivatives, processes for preparation and use thereof Inventor(s): Kurz, Michael; (Hofheim, DE), Li, Ziyu; (Offenbach, DE), Toti, Luigi; (Hochheim, DE), Vertesy, Laszlo; (Eppstein-Vockenhausen, DE) Correspondence: Ross J. Oehler; Aventis Pharmaceuticals INC.; Route 202-206; Mail Code: D303a; Bridgewater; NJ; 08807; US Patent Application Number: 20040014807 Date filed: February 14, 2003 Abstract: The present invention provides novel phenalenone derivatives of formula (I) which are formed by the microorganism Penicillium herquei Bainer & Sartory, DSM 14142, during fermentation. A process for their preparation, their use as pharmaceutical compositions, and their use for the treatment or prophylaxis of bacterial infections, mycoses, oncoses and rheumatic diseases are also disclosed and claimed. 1 Excerpt(s): This application claims the benefit of German priority document number 10206849.6, filed Feb. 18, 2002, and U.S. Provisional Application No. 60/366,744, filed Mar. 22, 2002. The present invention relates to phenalenone derivatives which are formed by the microorganism Penicillium herquei Bainer & Sartory, DSM 14142 during fermentation, processes for their preparation, their use as pharmaceutical compositions, and their use for the treatment or prophylaxis of bacterial infections, mycoses, oncoses and rheumatic diseases. Cancer is a disease of humans and animals which usually takes a fatal course and which is caused by the uncontrolled growth of endogenous cells. Cancer is the term for the formation of malignant growths (malignomas), of neoplasms (tumors and carcinomas) or for the malignant degeneration and maturation disorder of white blood cells (leukemia, blood cancer). Cancer or tumor cells are formed by conversion of endogenous cells. The malignancy of the cancer cell is expressed in the autonomy of growth, that is, its ability to grow is uninhibited in an infiltrating manner and without classification in the constructional plan of the organs and with tissue destruction. A certain sign of malignancy is the formation of tumor-remote deposits (metastases) after hematogenic or lymphogenic spread of tumor cells. Cancer is among the most frequent causes of death of man and therefore there is a great need for methods and means for the cure or treatment of malignant degenerations. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Specific and universal probes and amplification primers to rapidly detect and identify common bacterial pathogens and antibiotic resistance genes from clinical specimens for routine diagnosis in microbiology laboratories Inventor(s): Bergeron, Michel G.; (Sillery, CA), Ouellette, Marc; (Quebec, CA), Roy, Paul H.; (Loretteville, CA) Correspondence: Quarles & Brady Llp; 411 E. Wisconsin Avenue; Suite 2040; Milwaukee; WI; 53202-4497; US Patent Application Number: 20030180733 Date filed: April 11, 2002 Abstract: The present invention relates to DNA-based methods for universal bacterial detection, for specific detection of the common bacterial pathogens Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Proteus mirabilis, Streptococcus pneumoniae, Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis,
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Staphylococcus saprophyticus, Streptococcus pyogenes, Haemophilus influenzae and Moraxella catarrhalis as well as for specific detection of commonly encountered and clinically relevant bacterial antibiotic resistance genes directly from clinical specimens or, alternatively, from a bacterial colony. The above bacterial species can account for as much as 80% of bacterial pathogens isolated in routine microbiology laboratories.The core of this invention consists primarily of the DNA sequences from all species-specific genomic DNA fragments selected by hybridization from genomic libraries or, alternatively, selected from data banks as well as any oligonucleotide sequences derived from these sequences which can be used as probes or amplification primers for PCR or any other nucleic acid amplification methods. This invention also includes DNA sequences from the selected clinically relevant antibiotic resistance genes.With these methods, bacteria can be detected (universal primers and/or probes) and identified (species-specific primers and/or probes) directly from the clinical specimens or from an isolated bacterial colony. Bacteria are further evaluated for their putative susceptibility to antibiotics by resistance gene detection (antibiotic resistance gene specific primers and/or probes). Diagnostic kits for the detection of the presence, for the bacterial identification of the above-mentioned bacterial species and for the detection of antibiotic resistance genes are also claimed. These kits for the rapid (one hour or less) and accurate diagnosis of bacterial infections and antibiotic resistance will gradually replace conventional methods currently used in clinical microbiology laboratories for routine diagnosis. They should provide tools to clinicians to help prescribe promptly optimal treatments when necessary. Consequently, these tests should contribute to saving human lives, rationalizing treatment, reducing the development of antibiotic resistance and avoid unnecessary hospitalizations. Excerpt(s): Bacteria are classically identified by their ability to utilize different substrates as a source of carbon and nitrogen through the use of biochemical tests such as the API20E.TM. system. Susceptibility testing of Gram negative bacilli has progressed to microdilution tests. Although the API and the microdilution systems are cost-effective, at least two days are required to obtain preliminary results due to the necessity of two successive overnight incubations to isolate and identify the bacteria from the specimen. Some faster detection methods with sophisticated and expensive apparatus have been developed. For example, the fastest identification system, the autoSCAN-Walk-Away system.TM. identifies both Gram negative and Gram positive from isolated bacterial colonies in 2 hours and susceptibility patterns to antibiotics in only 7 hours. However, this system has an unacceptable margin of error, especially with bacterial species other than Enterobacteriaceae (York et al., 1992. J. Clin. Microbiol. 30:2903-2910). Nevertheless, even this fastest method requires primary isolation of the bacteria as a pure culture, a process which takes at least 18 hours if there is a pure culture or 2 to 3 days if there is a mixed culture. A large proportion (40-50%) of specimens received in routine diagnostic microbiology laboratories for bacterial identification are urine specimens (Pezzlo, 1988, Clin. Microbiol. Rev. 1:268-280). Urinary tract infections (UTI) are extremely common and affect up to 20% of women and account for extensive morbidity and increased mortality among hospitalized patients (Johnson and Stamm, 1989; Ann. Intern. Med. 111:906-917). UTI are usually of bacterial etiology and require antimicrobial therapy. The Gram negative bacillus Escherichia coli is by far the most prevalent urinary pathogen and accounts for 50 to 60% of UTI (Pezzlo, 1988, op. cit.). The prevalence for bacterial pathogens isolated from urine specimens observed recently at the "Centre Hospitalier de 1'Universit Laval (CHUL)" is given in Tables 1 and 2. Conventional pathogen identification in urine specimens. The search for pathogens in urine specimens is so preponderant in the routine microbiology laboratory that a myriad of tests have been developed. The gold standard is still the classical semi-quantitative plate culture method
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in which a calibrated loop of urine is streaked on plates and incubated for 18-24 hours. Colonies are then counted to determine the total number of colony forming units (CFU) per liter of urine. A bacterial UTI is normally associated with a bacterial count of.gtoreq.10.sup.7 CFU/L in urine. However, infections with less than 10.sup.7 CFU/L in urine are possible, particularly in patients with a high incidence of diseases or those catheterized (Stark and Maki, 1984, N. Engl. J. Med. 311:560-564). Importantly, close to 80% of urine specimens tested are considered negative (<10.sup.7 CFU/L; Table 3). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Sphingolipid derivatives and their methods of use Inventor(s): Bhalla, Kapil N.; (Atlanta, GA), Keane, Thomas E.; (Dunwoody, GA), Liotta, Dennis C.; (McDonough, GA), Merrill, Alfred H. JR.; (Dunwoody, GA), Schmelz, Eva M.; (Atlanta, GA) Correspondence: King & Spalding; 191 Peachtree Street, N.E.; Atlanta; GA; 30303-1763; US Patent Application Number: 20040039212 Date filed: August 25, 2003 Abstract: Derivatives of sphingolipids of the formula: 1are provided wherein the substituents are as defined in the specification and wherein there is at least one R.sup.2 substituent in the sphingolipid derivative. The compounds are useful in the treatment of of abnormal cell proliferation, including benign and malignant tumors, the promotion of cell differentiation, the induction of apoptosis, the inhibition of protein kinase C, and the treatment of inflammatory conditions, psoriasis, inflammatory bowel disease as well as proliferation of smooth muscle cells in the course of development of plaques in vascular tissue. The invention also includes a method for triggering the release of cytochrome c from mitochondria that includes administering an effective amount of a sphingolipid or its derivative or prodrug to a host in need thereof. Further, the invention provides a method for treating bacterial infections, including those that influence colon cancer and other disorders of the intestine, that includes administering an effective amount of one of the active compounds identified herein. Excerpt(s): This application is in the area of pharmaceutical chemistry, and in particular includes sphingolipid derivatives, prodrugs and pharmaceutical compositions and salts thereof for the treatment of abnormal cell proliferation, including benign and malignant tumors, the promotion of cell differentiation, the induction of apoptosis, the inhibition of protein kinase C, and the treatment of inflammatory conditions, psoriasis, inflammatory bowel disease as well as proliferation of smooth muscle cells in the course of development of plaques in vascular tissue. The invention also includes a method for triggering the release of cytochrome c from mitochondria that includes administering an effective amount of a sphingolipid or its derivative or prodrug to a host in need thereof. Further, the invention provides a method for treating bacterial infections, including those that influence colon cancer and other disorders of the intestine, that includes administering an effective amount of one of the active compounds identified herein. Mammalian sphingolipid compounds typically vary in the presence or absence of: (I) the 4,5-trans-double bond (for example, sphingosine has a double bond whereas sphinganine (also referred to as dihydrosphingosine) does not); (ii) double bond(s) at other positions, such as position 8; (iii) a hydroxyl group at position 4 (D-1hydroxysphinganine, also called "phytosphingosine") or elsewhere (Robson et al., J. Lipid Res. 35:2060-2068, 1994); (iv) methyl group(s) on the alkyl side chain or on the
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amino group, such as N,N,-dimethylsphingosine; and (v) acylation of the amino group (for example ceramide (also referred to as N-acylsphingosine), and dihydroceramide (also referred to as N-acyl-sphinganine)). The 4-hydroxysphinganines are the major long-chain bases of yeast (Wells, G. B. and Lester, R. L., J. Biol. Chem., 258:10200-10203, 1983), plants (Lynch, D. V., Lipid Metabolism in Plants (T. S. Moore, Jr., ed.), pp. 285308, CRC Press, Boca Raton, Fla. 1993), and fungi (Merrill et al., Fungal Lipids (R. Prasad and M. Ghanoum, eds.), CRC Press, Boca Raton, Fla., 1995a), but are also made by mammals (Crossman and Hirschberg, J. Biol. Chem, 252:5815-5819, 1977). Other modifications of the long-chain base backbone include phosphorylation at the hydroxyloxygen of carbon I (Buehrer and Bell, Adv. Lipid Res. 6:59-67, 1993), and acylation (Merrill and Wang, Methods Enzymol,. 209:427-437, 1992) (Igarashi and Hakomori, Biochim. Biophys. Res. Commun. 164:1411-1416, 1989; Felding-Habermann et al., Biochemistry 29:6314-6322, 1990) of the amino group. Each of these compounds can be found in various alkyl chain lengths, with 18 carbons predominating in most sphingolipids, but other homologs can constitute a major portion of specific sphingolipid (as exemplified by the large amounts of C.sub.20 sphingosine in brain gangliosides) (Valsecchi et al., J. Neurochem., 60:193-196, 1993) and in different sources (e.g., C.sub.16 sphingosine is a substantial component of milk sphingomyelin) (Morrison, Biochim. Biophys. Acta., 176:537-546, 1969). One difficulty in studying these compounds is that relatively few are commercially available in chemically-pure form. For example, most of the sphinganine that can be purchased from various vendors is a mixture of the D and L enantiomers (therefore, commercially available dihydroceramides are also mixtures) and the metabolism, and some of the functions, of these compounds are sensitive to stereochemistry (Stroffel and Bister, Hoppe-Seyler's Z. Physiol. Chem. 354:169-181, 1973; Buehrer and Bell, J. Biol. Chem. 267:3154-3159, 1992; Adv. Lipid Res. 26:59-67, 1993; Hauser et al., J. Biol. Chem. 269:6803-6809, 1994; Olivera et al., J. Biol. Chem. 269:17924-17930, 1994). For example, sphingosine kinase (which forms the signaling compound sphingosine 1-phosphate) will act only on the erythro stereoisomers--the threo stereoisomers are inhibitors of the enzyme (Buehrer and Bell, J. Biol. Chem. 267:3154-3159, 1992; Adv. Lipid Res. 26:59-67, 1993). Release of intracellular calcium is limited to D-(+)-erythro-sphingosine 1-phosphate. Sphingosines and other long-chain bases are cationic amphiphiles, which distinguishes them from most other naturally occurring lipids, which are neutral (including zwitterionic) or anionic. In the protonated form, they affect the phase behavior of both zwitterionic (Koiv et al., Chem. Phys. Lipids. 66:123-134, 1993; Lpez-Garcia et al., Biochim. Biophys. Acta., 1194:281-288, 1994) and acidic (Koiv et al., Chem. Phys. Lipids, 66:123-134, 1993; Lpez-Garcia et al., Biochim. Biophys. Acta. 1194:281-288, 1994) phospholipids. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Use of ylqF, yqeG, yybQ, yerL, and ysxC, essential bacterial genes and polypeptides Inventor(s): Fritz, Christian; (Natick, MA), Guzman, Luz-Maria; (Boston, MA), Youngman, Philip; (Boston, MA) Correspondence: Fish & Richardson PC; 225 Franklin ST; Boston; MA; 02110; US Patent Application Number: 20030228643 Date filed: April 25, 2003 Abstract: Disclosed are genes found in Streptococcus pneumoniae that are essential for survival for a wide range of bacteria. These genes are termed "S-ylqF," "S-yqeG," "SyybQ," "S-yerL," and "S-ysxC." These genes and the polypeptides that they encode, as
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well as homologs and orthologs thereof can be used to identify antibacterial agents for treating a broad spectrum of bacterial infections. Excerpt(s): The invention relates to the use of ylqF, yqeG, yybQ, yerL, and ysxC, essential bacterial genes and polypeptides in identifying antibacterial agents. Bacterial infections may be cutaneous, subcutaneous, or systemic. Opportunistic bacterial infections proliferate, especially in patients afflicted with AIDS or other diseases that compromise the immune system. Most bacteria that are pathogenic to humans are gram positive bacteria. The bacterium Streptococcus pneumoniae, for example, typically infects the respiratory tract and can cause lobar pneumonia, as well as meningitis, sinusitis, and other infections. The invention is based on the identification of ten genes of the gram positive bacterium Streptococcus pneumoniae and of Bacillus subtilis as being essential for survival. The Streptococcus pneumoniae genes are termed "S-ylqF," "S-yqeG," "S-yybQ," "S-yerL," and "S-ysxC." The orthologs of these genes in Bacillus subtilis are termed "B-ylqF," "B-yqeG," "B-ybQ," "B-yerL," and "B-ysxC," respectively. The terms "ylqF," "yqeG," "yybQ," "yerL," and "ysxC" genes and polypeptides are used to refer to the Streptococcus pneumoniae and Bacillus subtilis genes and polypeptides, as well as their homologs and orthologs, collectively. While "homologs" are structurally similar genes contained within a species, "orthologs" arefunctionally equivalent genes from other species (within or outside of a given genus, e.g., from E. coli). These genes are considered "essential" genes, and their polypeptides are considered "essential" polypeptides. Each gene and polypeptide can be used in methods for identifying similar genes and polypeptides in pathogenic and non-pathogenic microorganisms. Each polypeptide can be used to identify compounds that are inhibitors of the pathogens in which the polypeptide (ylqF, yqeG, yybQ, yerL, or ysxC) is expressed. Such inhibitors attenuate bacterial growth by inhibiting the activity of ylqF, yqeG, yybQ, yerL, or ysxC polypeptide, or by inhibiting gene transcription or translation. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Warming and nonirritating lubricant compositions and method of comparing irritation Inventor(s): Ahmad, Nawaz; (Monmouth Junction, NJ), Lamb, C. Scott; (Doylestown, PA), Lonardo, Emilia Casilio; (Plainsboro, NJ) Correspondence: Philip S. Johnson; Johnson & Johnson; One Johnson & Johnson Plaza; New Brunswick; NJ; 08933-7003; US Patent Application Number: 20030232090 Date filed: March 17, 2003 Abstract: This invention relates to substantially anhydrous warming, non-toxic and nonirritating lubricating compositions containing polyhydric alcohols, a gelling agent and alternatively a pH adjusting agent for treating fungal and bacterial infections. The invention also relates to methods of using such compositions for warming, lubrication, administration of active ingredients and for preventing or treating dysmenorrhea. Excerpt(s): This application is a continuation-in-part of patent application U.S. Ser. No. 10/137,509 and co-pending patent application Ser. No. ______ (Attorney Docket No. PPC 834 CIP) which are hereby incorporated herein by reference. This invention relates to clear, substantially anhydrous, gel compositions that are capable of dissolving certain azole antifungal compounds and delivering them in a soluble form. Currently, in all commercially available azole-containing antifungal and antibacterial formulations,
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antifungal agents such as miconazole, terconazole, itraconazole, clotrimazole and other azoles exist in insoluble form, dispersed in cream, suppository or ointment bases as micronized crystals. In general, drug agents are much more effective when delivered in a solution form. The azole compounds have almost no solubility, if any, in classical solvents used in the semisolid or solid dosage forms currently used to deliver these compounds. Most women, at least once in their lifetime, suffer from vaginal fungal infection. There are a variety of reasons for these infections to occur. The widespread use of antibiotics encourages the overgrowth of Candida albicans. This condition, known as vulvovaginitis (vulvovaginal Candidiasis or VVC) is usually treated by azole antifungal agents applied either intravaginally or orally. However, sufferers often mistakenly believe that their vaginal infection is a fungal infection that can be treated with over-the-counter (OTC) antifungal products. Such sufferers may actually have a bacterial infection, rather than a fungal infection. OTC antifungal products are not effective against bacterial infections (also known as "bacterial vaginosis"), a chronic condition which is much more common than VVC. Clinically, bacterial vaginosis is a polymicrobial vaginal infection caused by an increase in the number of anaerobic organisms with a concomitant decrease in Lactobacilli in the vagina. Indiscriminate use of OTC antifungal products may lead to an added risk of masking bacterial infections. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
Keeping Current In order to stay informed about patents and patent applications dealing with bacterial infections, 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 “bacterial infections” (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 bacterial infections. You can also use this procedure to view pending patent applications concerning bacterial infections. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.
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CHAPTER 7. BOOKS ON BACTERIAL INFECTIONS Overview This chapter provides bibliographic book references relating to bacterial infections. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on bacterial infections 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 “bacterial infections” (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 bacterial infections: •
Oral Complications of Cancer Therapies: Diagnosis, Prevention, and Treatment Source: Torrance, CA: Homestead Schools, Inc. 1999. 96 p. Contact: Available from Homestead Schools, Inc. 23844 Hawthorne Boulevard, Suite 200, Torrance, CA 90505. (310) 791-9975. Fax (310) 791-0135. E-mail:
[email protected]. Website: www.homesteadschools.com. PRICE: $48.00 plus shipping and handling. Course No. 6485. Summary: Cancer treatments may result in oral complications that are painful, diminish the quality of life, and may lead to significant compliance problems, often discouraging the patient from continuing treatment. This continuing education program for dentists focuses on the oral complications of cancer therapies. Topics include the role of pretherapy interventions that can reduce the incidence of oral complications in the cancer patient; the most effective strategies for management of acute oral complications;
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treatment options for managing chronic oral complications following cancer therapy; areas for future research in the diagnosis, prevention, and treatment of oral complications in the cancer patient; the different oral complications resulting from chemotherapy and radiation therapy; the objectives of pretreatment dental evaluation; the diagnosis and treatment of mucosal inflammation and ulceration, viral infection, oral candidiasis, bacterial infections, and mucosal bleeding; the oral complications arising from the treatment of cancer in children; the classification of patients according to their risk for oral complications; the use of supplemental fluoride; strategies for coping with dry mouth (xerostomia); follow up oral care for patients having undergone chemotherapy and radiation therapy; and special considerations for bone marrow and cell transplant patients. The document includes a posttest with which readers can qualify for continuing education credit. The document is illustrated with numerous black and white photographs. 2 tables. 25 references. •
Oral Manifestations of AIDS Source: Torrance, CA: Homestead Schools, Inc. 2000. [37 p.]. Contact: Available from Homestead Schools, Inc. 23844 Hawthorne Boulevard, Suite 200, Torrance, CA 90505. (310) 791-9975. Fax (310) 791-0135. E-mail:
[email protected]. Website: www.homesteadschools.com. PRICE: $36.00 plus shipping and handling. Course No. 6215. Summary: Knowledge of HIV infection has become a critically important requirement for professionals responsible for oral health care delivery. This continuing education program for dentists focuses on the oral manifestations of AIDS. Topics covered include the nature of HIV infection, including demographics, pathogenesis, transmission, progression, survival and treatment strategies; the oral manifestations of HIV infection, including the role of clinicians and dental professionals, transmission risks, saliva, other transmissible diseases, differential diagnosis, and patient approach; fungal infections, including candidiasis, histoplasmosis, and other oral fungal infections; viral infections, including herpes family viruses, Epstein-Barr virus (EBV) and oral hairy leukoplakia, varicella virus reactivation, cytomegalovirus (CMV), human papillomavirus (HPV) and condyloma acuminatum, molluscum contagiosum (MC), and hepatitis viruses; bacterial infections, including necrotizing ulcerative gingivitis and periodontitis, non-oral-flora opportunists, and tuberculosis (TB); HIV associated malignancies, including Kaposi's sarcoma (KS), non-Hodgkin's lymphoma, and squamous carcinoma; and other HIVassociated lesions, including recurrent aphthous-like stomatitis, hypersensitivity and lichenoid reaction, sialadenitis (inflamed salivary glands) and xerostomia (dry mouth), thrombocytopenia, and ulcerative stomatitis and unclassified lesions. The program includes a posttest with which readers can qualify for continuing education credit.
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Renal Disease: Classification and Atlas of Glomerular Diseases. 2nd ed Source: New York, NY: Igaku-Shoin Medical Publishers, Inc. 1995. 541 p. Contact: Available from Igaku-Shoin. One Madison Avenue, New York, NY 10010. (800) 765-0800 or (212) 779-0123. Fax (212) 779-0322. PRICE: $159.95 (as of 1996). ISBN: 0896402576. Summary: This atlas of renal diseases has two sections. The first provides a listing of glomerular lesions and gives their definitions. It also presents the main clinical and morphological features of glomerular processes in a tabular format. The second section describes and illustrates the various glomerular processes. Topics include: primary glomerular disease, including glomerulonephritis; lupus nephritis; IgA nephropathy;
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glomerular lesions in systemic bacterial infections; parasitic glomerulopathies; systemic vasculitis; thrombotic microangiopathy, including the hemolytic-uremic syndrome and thrombotic thrombocytopenic purpura; benign nephrosclerosis; diabetic glomerulopathy; dense deposit disease; the nephropathy of liver disease; Alport syndrome; Fabry disease; nephropathy of toxemia of pregnancy; and end-stage kidney glomerular lesions following transplantation. The appendix contains information about some of the more useful histologic techniques and about examination of renal specimens. The atlas presents numerous microscopy reproductions, in both black and white and color. A subject index concludes the volume. 306 references. •
Drugs of Abuse, Immunity, and Infection Contact: CRC Press, Incorporated, 2000 Corporate Blvd NW, Boca Raton, FL, 33431, (561) 994-0555. Summary: This book focuses on possible relationships among drugs of abuse, such as marijuana, morphine, cocaine, and alcohol, on immune response function and altered resistance to microorganisms, especially opportunistic ones. The book presents a number of literature reviews concerning various categories of drugs, immunity, and infectious diseases. The first series of chapters addresses the effects of marijuana on the immune response. The effects of opiates, including morphine, on infectious diseases, are described in the second set of reviews. Several reviews then describe the effects of ethanol on immunity, both in general and on bacterial infections. The final chapter explores the connection between psychiatric drugs and immunity.
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Pregnancy After a Loss: A Guide to Pregnancy After a Miscarriage, Stillbirth, or Infant Death Source: New York, NY: Berkley Books/Penguin Putnam, Inc. 1999. 391 p. Contact: Available from Berkley Books/Penguin Putnam, Inc., 375 Hudson Street, New York, NY 10014. (800) 788-6262 (orders), (800) 631-8571 (customer service hotline), (800) 227-9604 (Fax),
[email protected] (E-mail), http://www.penguinputnam.com (Web Site). $14.95. ISBN 0-425-17047-0. Summary: This book, written by a woman who lost her son, Patrick, to an umbilical cord problem on her due date, is designed to give hope and practical information to other women who have suffered a pregnancy loss. The author interviewed nearly 100 women while writing this book, all of whom made it through pregnancy after a loss and now have one or more healthy babies. The book focuses on the feelings that are unique to women who have suffered a pregnancy loss, and provides advice on reducing anxiety. Medical aspects of pregnancy loss are described in simple, straightforward language. Chapter 1 takes readers down the road that a bereaved mother would travel to find out why her baby died. This chapter covers the followup visit with the obstetrician, which is when the parents discuss the autopsy and any genetic testing that was done on the baby. If these do not provide an answer, the doctor may suggest that the mother be tested for autoimmune disorders, uterine abnormalities, genetic disorders, viral and bacterial infections, and hormone imbalances. Other common reasons for pregnancy loss are described (i.e., neural tube defects, placental problems, umbilical cord problems, incompetent cervix, and maternal illness) as are common reasons for early infant death: congenital problems, streptococcus infection, and sudden infant death syndrome. Chapter 2 discusses the subject of getting ready to get pregnant again, both physically and emotionally. This chapter covers the advantages and disadvantages of getting pregnant right away, factors that will affect one's decision to get pregnant, when
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partners disagree on the timing of another pregnancy, and where to find support and guidance during the decision-making process. Even if a woman has waited 6 months or a year to get pregnant again, there are certain things she should do to prepare for the pregnancy. Mothers to be should get a thorough physical exam; get into shape; take folic acid; keep track of her periods; and avoid drugs, alcohol, and cigarettes. This chapter also covers the pros and cons of choosing a new doctor or staying with the old one, questions one should ask each doctor under consideration, the stress of not getting pregnant right away, infertility problems and treatment, and when the pregnancy is a surprise. Chapter 4 focuses on the first trimester of a new pregnancy, including concerns over telling others about the pregnancy, suggestions for alleviating the anxiety, what to expect during the prenatal visits, tests one can have done at this time, and the signs of an impending miscarriage. Chapter 5 focuses on the second trimester, including concerns about answering awkward questions, the gender of the baby, delivering too early, exercising, and sexual intercourse. Feelings that may be common during this trimester are panic over the baby's movements, reluctance to bond with the baby, anxiety about surpassing the anniversary of the previous baby's death, superstitions about the pregnancy, and fear. Prenatal tests that can be offered at this time and symptoms that are not normal during the second trimester also are covered. Chapter 6 examines the concerns mothers are likely to have during the third trimester regarding early delivery, setting up the nursery, baby shower offers, choosing a name, and excessive weight gain. Feelings that may be common during this time include obsession over the baby's movements, constant worry, and being annoyed by unsolicited advice. Tips for alleviating the anxiety include taking a prepared childbirth class, writing a birth plan, getting a doula, calling the doctor frequently, insisting on frequent prenatal visits, eliminating unnecessary stress, and practicing relaxation techniques. The nature of prenatal visits during the third trimester, tests that are usually done at this time, monitoring the baby's kicks, and danger signals in late pregnancy also are discussed. Chapter 7 deals with the truly high-risk pregnancy. Common reasons for high-risk status are a history of preterm labor or delivery, incompetent cervix, impending multiple birth, history of placental problems, history of two or more miscarriages, genetic problems, chronic medical conditions, and pregnancy after age 35. Bed rest is a commonly prescribed treatment in high-risk pregnancies. This chapter provides suggestions for surviving extended bed rest as well as a chart of activities to help mothers and their OB/GYNs mutually define what she can and can't do. Other topics that are discussed include hospitalization, the impact of that and bed rest on family and career, selective reduction in cases of multiples, feelings that are common among mothers during bed rest, and tips for relieving the anxiety. The signs and treatment of preterm labor also are discussed. Chapter 8 deals with labor and delivery, including fetal monitoring during labor, bonding with the baby, feelings commonly reported after birth, what to expect if your baby goes to the NICU, and tips for relieving anxiety. Chapter 9 talks about the consequences of pregnancy loss on parenting the subsequent child. It is common for parents to feel anxious and overprotective, but their loss also may make them exceptional parents. There is often continued sadness and introspection and a totally changed outlook on life. This chapter also reviews some of the private and public ways in which parents have chosen to remember their infants who died. Chapter 10 looks at pregnancy after a loss from a father's perspective, including feelings that are common to fathers who are expecting again and ways in which the mother can ease her spouse's anxiety. A list of resources includes support organizations for pregnancy and infant loss, high-risk pregnancy, subsequent pregnancy, infertility, and pregnancy/childbirth; publishers of relevant books; and internet resources.
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Periodontal Complications of Diabetes Source: Torrance, CA: Homestead Schools, Inc. 2000. 87 p. Contact: Available from Homestead Schools, Inc. 23844 Hawthorne Boulevard, Suite 200, Torrance, CA 90505. (310) 791-9975. Fax (310) 791-0135. E-mail:
[email protected]. Website: www.homesteadschools.com. PRICE: $48.00 plus shipping and handling. Course No. 6575. Summary: This continuing education program for dentists focuses on the periodontal complications of diabetes. Topics include the epidemiology of diabetes mellitus in the United States, particularly in minority populations; the morbidity and mortality of diabetes; the importance of glycemic control in a patient with diabetes; the etiology and pathogenesis of type 1 and type 2 diabetes; the long term complications of diabetes; the genetics of diabetes; the interrelationship between glycemic control and periodontitis; the genetic connection between the increased risk for periodontitis and diabetes; the pathophysiological mechanism involved in the destruction of collagen, accelerated alveolar bone loss and diabetes; diabetes as a risk factor for periodontal health; the effect of mechanical periodontal treatment and systemic antibiotics therapy in improving periodontal status as well as glycemic control; the connection between diabetes and oral health in older adults; patient education; the connection between bacterial infections and diabetes; risk factors for periodontitis; the natural history of oral infections in diabetes; the etiology and pathogenesis of pulpal and periapical infections in diabetes patients; the effect of diabetes treatments on the oral microflora; the immune response to oral pathogens; how immune responses are related to glycemic control; the nature of the microflora and host mediators in healthy individuals and people with diabetes who do or do not have periodontitis; the genetic relationships between diabetes and periodontitis; behavior modification strategies; the effects of periodontal therapy on diabetes; the role of strict control of blood glucose; the effect of early intervention on the development and rate of progression of oral complications of diabetes; appropriate treatment therapies for periodontal diseases in the patient with diabetes; the periodontal manifestations of diabetes and the signs and symptoms that may help a dentist detect and monitor the presence of this disease; and patient education principles and strategies. The document includes a reproduction of a 50-item slide presentation that is a guide for health care providers on the detection and prevention of periodontal complications of diabetes mellitus (compiled by the National Institute of Dental and Craniofacial Research). The document concludes with a posttest with which readers can qualify for continuing education credit. The document is illustrated with numerous black and white photographs. 51 figures.
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AIDS and the Mouth: Diagnosis and Management of Oral Lesions Source: Copenhagen, Denmark: Munksgaard. 1992. 204 p. Contact: Available from Munksgaard. 35 Norre Sogade, P.O. Box 2148, DK-1016, Copenhagen K, Denmark. Telephone +45 33 12 70 30; Fax +45 33 12 93 87; E-mail:
[email protected]; http://www.munksgaard.dk/publishers/. PRICE: DKK 516 plus postage; contact directly for current price in US dollars. ISBN: 8716103211. Summary: This medical textbook provides a detailed treatise on the diagnosis and management of oral lesions related to AIDS as well as other oral manifestations of HIV. Eighteen chapters cover the history of HIV, definitions and classification issues, epidemiology, characteristics of the human immune deficiency viruses, animal models for AIDS, transmission of HIV, tests for HIV infection, the natural history of HIV infection, classification of the oral manifestations of HIV, fungal infections, bacterial
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infections, viral infections, neoplasms, neurologic manifestatations, oral manifestations of unknown etiology, orofacial manifestations of pediatric AIDS, the treatment of oral manifestations, and infection control issues. Each chapter includes tables, figures, and references. Numerous full-color photographic plates are included in some chapters. The book includes a glossary of terms and abbreviations. A subject index concludes the volume. •
Infection Control for the Dental Team Contact: Mosby - Year Book, 11830 Westline Industrial Dr, St. Louis, MO, 63146. American Federation of State County and Municipal Employees, District Council 47 (Philadelphia), 1606 Walnut St, Philadelphia, PA, 19103-5482, (215) 546-9880, http://www.dc47afscme.org. Summary: This monograph outlines infection-control guidelines for dental-care workers. It says that dental workers are obligated to treat anyone who seeks care, but that they also have an obligation to control cross-infection in the dental practice. The monograph explains infection-control procedures and disease prevention in general, looking at the spread of microorganisms, patient evaluation, universal precautions, and principles of sterilization and disinfection. Chapters deal specifically with instrument sterilization, surface and equipment disinfection, the laboratory, and office design. Groups which are perceived to be at high risk for Human immunodeficiency virus (HIV) infection are listed. One chapter focuses on several infectious diseases that it says are of special concern to dental workers; these include viral hepatitis, herpes virus, rubella, bacterial infections, and HIV.
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AIDS Prevention. Translated title Contact: Joint Publishing Company, Limited, 9 Queen Victoria St, Hong Kong. Summary: This monograph presents information for both the general public and health professionals about Acquired immunodeficiency syndrome (AIDS) and its prevention. First, it discusses the epidemiology of AIDS, involving the infection rate, the fatality rate, and the risk factors for various groups. Then, it describes the etiological cause of AIDS, immunology, a test to evaluate immune function, laboratory diagnosis of opportunistic infections of AIDS, and viral and bacterial infections. Also discussed are transfusion-associated AIDS, AIDS-related complex (ARC), and the opportunistic infections and malignancies associated with AIDS and Human immunodeficiency virus (HIV) infection. It also focuses on providing clear, scientific information on AIDS treatment and prevention to the general public. Reference materials, an appendix of medical terms, and questions and answers of common knowledge are included.
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AIDS and the Mouth; Diagnosis and Management of Oral Lesions Contact: Mosby - Year Book, 11830 Westline Industrial Dr, St. Louis, MO, 63146. Summary: This monograph, published due to rapid progress in knowledge about all aspects of Human immunodeficiency virus (HIV) infection, updates an earlier edition that dealt in less detail with the non-oral aspects of the HIV Porlbem. The section on infection control has been expanded. It includes 18 chapters, starting with one on the history of the Acquired immunodeficiency syndrome (AIDS) epidemic. Chapter 2 defines the different stages of HIV disease, while the third chapter looks at epidemiology. Chapter 4 analyzes the two different types of HIV, and Chapter 5 looks at animal models for AIDS in cats and simians. Chapter 6 studies HIV transmission, Chapter 7 explains the HIV-antibody test, and Chapter 8 looks at the natural history of
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HIV infection. Chapter 9 classifies different oral infections, while Chapter 10 turns to fungal infections; Chapter 11, bacterial infections; Chapter 12, viral infections; Chapter 13, neoplasms; and Chapter 14, neurologic manifestations. Chapter 15 explores oral manifestations of unknown etiology. The last three chapters look at orofacial manifestations of pediatric AIDS, treatment of oral manifestations, and infection control. •
Drug Information Handbook for Dentistry. 4th ed Source: Hudson, OH: Lexi-Comp, Inc. 1998. 1378 p. Contact: Available from Lexi-Comp, Inc. 1100 Terex Road, Hudson, OH 44236. (800) 8375394 or (330) 650-6506; Fax (330) 656-4307; http://www.lexi.com. PRICE: $34.75 each. ISBN: 0916589625. Summary: This reference book covers a combination of commonly used drugs in dentistry and medicine and presents important aspects of drug data in a concise format. The book features complete cross-referencing of generic and brand name drugs, medical and oral conditions, along with the therapeutic indication and example prescribing guidelines. The book includes the following six sections: an introduction; an alphabetical listing of over 1400 generic drugs, with over 3600 U.S. and foreign trade names; oral medicine, including dental management and therapeutic considerations in medically compromised patients and dental management and therapeutic considerations in patients with specific oral conditions; extensive appendices, including abbreviations and measurements, comparative drug charts, dental drug interactions, infectious disease information, and cancer chemotherapy regimens; a therapeutic category index; and an alphabetical index for generic drug names, brand names, and major headings from the chapters. In the oral medicine sections, the systemic conditions or the oral disease state is described briefly, followed by the pharmacologic considerations with which the dentist must be familiar. The sections also present specific sample prescriptions and how to use them. Topics in these two sections include cardiovascular diseases, respiratory diseases, endocrine disorders and pregnancy, HIV and AIDS, rheumatoid arthritis and osteoarthritis, nonviral infectious diseases, antibiotic prophylaxis, systemic viral diseases, oral pain, oral bacterial infections, oral fungal infections, oral viral infections, oral nonviral soft tissue ulcerations or erosions, dentin hypersensitivity, xerostomia, temporomandibular dysfunction (TMD), chemical dependency and smoking cessation, patients requiring sedations, animal and human bites, natural products, and dental office emergencies.
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Smith's General Urology. Fifteenth Edition Source: Columbus, OH: McGraw-Hill, Inc. 2000. 868 p. Contact: Available from McGraw-Hill. Medical Publishing. 1221 P.O. Box 182615, Columbus, OH 43272-5046. (800) 262-4729. PRICE: $54.95;plus shipping and handling. ISBN: 0838586074. Summary: This textbook offers a practical and concise guide to the understanding, diagnosis, and treatment of urologic diseases. The text includes 47 chapters covering the anatomy of the genitourinary tract, embryology of the genitourinary system, symptoms of disorders of the genitourinary tract, physical examination of the genitourinary tract, urologic laboratory examination, radiology of the urinary tract, vascular interventional radiology, percutaneous endourology and ureterorenoscopy, laparoscopic surgery, radionuclide imaging, retrograde instrumentation of the urinary tract, urinary obstruction and stasis, vesicoureteral reflux (return of urine through the ureters to the kidney), bacterial infections, specific infections, sexually transmitted diseases, urinary
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stone (urolithiasis) disease, extracorporeal shock wave lithotripsy (ESWL, used to break up stones), injuries to the genitourinary tract, immunology and immunotherapy of urologic cancers, urothelial carcinoma (cancers of the bladder, ureter, and renal pelvis), renal parenchymal neoplasms (growths in the body of the kidney), neoplasms of the prostate gland, genital tumors, urinary diversion and bladder substitution, urologic laser surgery, chemotherapy of urologic tumors, radiotherapy of urologic tumors, neuropathic (arising from the nervous system) bladder disorders, urodynamic studies, urinary incontinence (involuntary loss of urine), disorders of the adrenal glands, disorders of the kidneys, diagnosis of medical renal diseases, oliguria (acute renal failure, lack of urination), chronic renal failure (CRF) and dialysis, renal transplantation, disorders of the ureter and ureteropelvic junction, disorders of the bladder and prostate (and seminal vesicles), disorders of the penis and male urethra, disorders of the female urethra, disorders of the testis and scrotum (and spermatic cord), skin diseases of the external genitalia, abnormalities of sexual determination and differentiation, renovascular hypertension, male infertility, and male sexual dysfunction. Each chapter concludes with references categorized by subject; the text concludes with an appendix of normal laboratory values and a subject index. The text features over 400 illustrations, including CT scans, radionuclide imaging scans, and x rays. •
Mouth: Diagnosis and Treatment Source: St. Louis, MO: Mosby, Inc. 1998. 320 p. Contact: Available from Harcourt Health Sciences. Book Order Fulfillment Department, 11830 Westline Industrial Drive, St. Louis, MO 63146-9988. Website: www.mosby.com. PRICE: $79.95 plus shipping and handling. ISBN: 0815131054. Summary: This textbook offers information to primary care physicians and to many specialists in medicine and dentistry. The text discusses all aspects of mucosal disease including neoplasia; oral manifestations of systemic, genetic, and dermatologic disease; and the oral manifestations of infections, including HIV. The fifteen chapters cover normal oral anatomy, the diagnosis of oral diseases, reactive processes and injuries, developmental disorders, lesions (benign, premalignant, and malignant), oral bacterial infections, viral infections, fungal infections, vesiculoerosive diseases, disorders of pigmentation, genodermatoses, oral manifestations of systemic diseases, oral manifestations of HIV infection, salivary gland diseases, and the therapy of oral diseases. The book includes hundreds of color photographs of oral diseases to aid the clinician in accurate diagnosis and thus lead to appropriate therapy. Each chapter offers a lengthy list of suggested readings and the volume concludes with a detailed subject index.
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 “bacterial infections” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “bacterial infections” (or a synonym) in their titles. The following is indicative of the results you might find when searching for
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“bacterial infections” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •
Antigen Detection to Diagnose Bacterial Infections: Applications by Richard B., M.D. Kohler (Editor); ISBN: 0849366992; http://www.amazon.com/exec/obidos/ASIN/0849366992/icongroupinterna
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Antigen Detection to Diagnose Bacterial Infections: Applications, Set; ISBN: 0849366976; http://www.amazon.com/exec/obidos/ASIN/0849366976/icongroupinterna
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Antigen Detection to Diagnose Bacterial Infections: Methodology by Richard B. Kohler (Editor); ISBN: 0849366984; http://www.amazon.com/exec/obidos/ASIN/0849366984/icongroupinterna
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Bacterial Infection: Close Encounters at the Host Pathogen Interface (Current Topic in Microbiology and Immunology) by R.W. Compans (Editor), et al; ISBN: 3540632603; http://www.amazon.com/exec/obidos/ASIN/3540632603/icongroupinterna
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Bacterial Infections by Axel Dalhoff (Editor); ISBN: 380556841X; http://www.amazon.com/exec/obidos/ASIN/380556841X/icongroupinterna
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Bacterial Infections in the Fetus and Newborn Infant by Pamela A. Davies, Leif A. Gothefors (Editor); ISBN: 0721611850; http://www.amazon.com/exec/obidos/ASIN/0721611850/icongroupinterna
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Bacterial Infections of Humans: Epidemiology and Control by Alfred S. Evans (Editor), Philip S. Brachman (Editor); ISBN: 0306453231; http://www.amazon.com/exec/obidos/ASIN/0306453231/icongroupinterna
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Bacterial Infections: An Epidemiological Overview [DOWNLOAD: PDF] by Datamonitor (Author); ISBN: B0000AUH5V; http://www.amazon.com/exec/obidos/ASIN/B0000AUH5V/icongroupinterna
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Bacterial Infections: Medical Subject Analysis With Bibliography by Elizabeth H. Shipley; ISBN: 0881645257; http://www.amazon.com/exec/obidos/ASIN/0881645257/icongroupinterna
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Bacterial infections; changes in their causative agents, trends and possible basis; ISBN: 0387055576; http://www.amazon.com/exec/obidos/ASIN/0387055576/icongroupinterna
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Chemotherapeutic Agents for Bacterial Infections by Melvyn Lynn, Morris Solotorovsky; ISBN: 087933374X; http://www.amazon.com/exec/obidos/ASIN/087933374X/icongroupinterna
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Common Bacterial Infections in Infancy and Childhood by M.I. Marks (Editor); ISBN: 0852005091; http://www.amazon.com/exec/obidos/ASIN/0852005091/icongroupinterna
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Common bacterial infections in infancy and childhood : diagnosis and treatment; ISBN: 0839113455; http://www.amazon.com/exec/obidos/ASIN/0839113455/icongroupinterna
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Current concepts in the management of gram-negative bacterial infections: proceedings of an Excerpta Medica symposium held in Montreal, Canada, April 10, 1973; ISBN: 0444151036; http://www.amazon.com/exec/obidos/ASIN/0444151036/icongroupinterna
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Current Topics in Microbiology and Immunology: Genetic Control of the Susceptibility to Bacterial Infection by D. Briles (Editor); ISBN: 3540162380; http://www.amazon.com/exec/obidos/ASIN/3540162380/icongroupinterna
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Current Topics in Microbiology and Immunology: T-Cell Paradigms in Parasitic and Bacterial Infections; ISBN: 3540515151; http://www.amazon.com/exec/obidos/ASIN/3540515151/icongroupinterna
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Dermatology of Bacterial Infections by George Hudson Findlay; ISBN: 0632016981; http://www.amazon.com/exec/obidos/ASIN/0632016981/icongroupinterna
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Diagnostic Procedures for Bacterial Infections by Berttina B. Wentworth (Editor); ISBN: 0875531490; http://www.amazon.com/exec/obidos/ASIN/0875531490/icongroupinterna
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Genetic Control of the Susceptibility to Bacterial Infection (Current Topics in Microbiology and Immunology, 124) by David E. Briles (Editor); ISBN: 0387162380; http://www.amazon.com/exec/obidos/ASIN/0387162380/icongroupinterna
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Gram-Negative Bacterial Infections and Mode of Endotoxin Actions: Pathophysiological, Immunological and Clinical Aspects by B. Urbaschek (Editor), et al; ISBN: 038781292X; http://www.amazon.com/exec/obidos/ASIN/038781292X/icongroupinterna
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Laboratory Diagnosis of Bacterial Infections (Infectious Disease and Therapy, Vol 26) by Nevio Cimolai (Editor); ISBN: 0824705890; http://www.amazon.com/exec/obidos/ASIN/0824705890/icongroupinterna
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Manual of Acute Bacterial Infections; ISBN: 0316303275; http://www.amazon.com/exec/obidos/ASIN/0316303275/icongroupinterna
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Manual of Acute Bacterial Infections: Early Diagnosis and Treatment (Little, Brown Spiral Manual Series) by Pierce Gardner, Harriet T. Provine; ISBN: 0316303895; http://www.amazon.com/exec/obidos/ASIN/0316303895/icongroupinterna
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Molecular Biology of Bacterial Infection : Current Status and Future Perspectives by Carlos Hormaeche (Editor), et al; ISBN: 0521432987; http://www.amazon.com/exec/obidos/ASIN/0521432987/icongroupinterna
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Pathogenesis of Bacterial Infections in Animals by Carlton L. Gyles; ISBN: 0813829399; http://www.amazon.com/exec/obidos/ASIN/0813829399/icongroupinterna
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Pathogenesis of Bacterial Infections in Animals; ISBN: 0813813433; http://www.amazon.com/exec/obidos/ASIN/0813813433/icongroupinterna
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Persistent Bacterial Infections by James P. Nataro (Editor), et al; ISBN: 1555811590; http://www.amazon.com/exec/obidos/ASIN/1555811590/icongroupinterna
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T-Cell Paradigms in Parasitic and Bacterial Infections (Current Topics in Microbiology and Immunology, 155) by S.H.E. Kaufmann (Editor); ISBN: 0387515151; http://www.amazon.com/exec/obidos/ASIN/0387515151/icongroupinterna
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The Pathogenesis of Bacterial Infections (Bayer-Symposium, 8) by H. Thomas (Editor), George Gee Jackson; ISBN: 0387153047; http://www.amazon.com/exec/obidos/ASIN/0387153047/icongroupinterna
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Topley & Wilson's Microbiology and Microbial Infections, Volume 3: Bacterial Infections by Leslie Collier (Editor), et al; ISBN: 0340663189; http://www.amazon.com/exec/obidos/ASIN/0340663189/icongroupinterna
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Topley and Wilson's Microbiology and Microbial Infections: Systematic Bacteriology / Bacterial Infections by Albert Balows (Editor), et al; ISBN: 0340740442; http://www.amazon.com/exec/obidos/ASIN/0340740442/icongroupinterna
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Understanding Bacterial Infections Chart by Anatomical Chart; ISBN: 1587794829; http://www.amazon.com/exec/obidos/ASIN/1587794829/icongroupinterna
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WHO Model Prescribing Information: Drugs Used in Bacterial Infections; ISBN: 9241401079; http://www.amazon.com/exec/obidos/ASIN/9241401079/icongroupinterna
Chapters on Bacterial Infections In order to find chapters that specifically relate to bacterial infections, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and bacterial infections 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 “bacterial infections” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on bacterial infections: •
Oral Bacterial Infections Source: in Eisen, D. and Lynch, D.P. Mouth: Diagnosis and Treatment. St. Louis, MO: Mosby, Inc. 1998. p. 92-107. Contact: Available from Harcourt Health Sciences. Book Order Fulfillment Department, 11830 Westline Industrial Drive, St. Louis, MO 63146-9988. Website: www.mosby.com. PRICE: $79.95 plus shipping and handling. ISBN: 0815131054. Summary: More than 300 different bacteria, including Staphylococcus aureus, coliform bacteria, Kelsiella, and Pseudomonas, reside in the oral cavity and comprise what is regarded as normal oral flora. When a species of bacteria increases in number or when the host defense threshold is exceeded, disease arises. Two of the most common bacterial diseases that afflict humans are dental caries and periodontal disease. This chapter on oral bacterial infections is from a textbook on the mouth that offers information to primary care physicians and to many specialists in medicine and dentistry. Topics include gingivitis and periodontitis, necrotizing gingivostomatitis, tuberculosis, oral cutaneous fistulas, gonorrhea, syphilis, actinomycosis, parulis, and miscellaneous infections, including scarlet fever, diphtheria, tularemia, granuloma inguinale, leprosy, suppurative infection of the salivary glands, and noma. For each condition, the authors describe symptoms, identification, complications, and treatment. The chapter is illustrated with numerous full color photographs of the conditions under discussion. 19 figures. 46 references.
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Bacterial Infections of the Colon Source: in Textbook of Gastroenterology. 4th ed. [2-volume set]. Hagerstown, MD: Lippincott Williams and Wilkins. 2003. p. 1864-1882. Contact: Available from Lippincott Williams and Wilkins. P.O. Box 1600, Hagerstown, MD 21741. (800) 638-6423. Fax: (301) 223-2400. Website: www.lww.com. PRICE: $289.00. ISBN: 781728614.
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Summary: This chapter on bacterial infections of the colon is from a comprehensive gastroenterology textbook that provides an encyclopedic discussion of virtually all the disease states encountered in a gastroenterology practice. The author of this chapter covers Shigella, Campylobacter, Clostridium difficile, pathogenic Escherichia coli that causes colitis, and sexually transmitted infections of the anus and rectum. Individuals with bacterial colitis who seek medical attention tend to have more severe symptoms, such as bloody diarrhea, fever, and abdominal pain. The nonspecific nature of symptoms associated with infectious colitis requires that stool cultures and examination for parasites be performed to identify a specific pathogen. Colonic biopsies may be necessary to exclude the diagnosis of ulcerative or ischemic colitis. For each of the five major bacterial pathogens that affect the colon, the author discusses classification, epidemiological aspects, pathogenesis, clinical features, complications, and treatment. 2 figures. 4 tables. 218 references. •
Bacterial Infections of the Genitourinary Tract Source: in Tanagho, E.A. and McAninch, J.W., eds. Smith's General Urology. Fifteenth Edition. Columbus, OH: McGraw-Hill, Inc. 2000. p. 237-264. Contact: Available from McGraw-Hill. Medical Publishing. 1221 P.O. Box 182615, Columbus, OH 43272-5046. (800) 262-4729. PRICE: $54.95;plus shipping and handling. ISBN: 0838586074. Summary: Urinary tract infections (UTIs) caused by pathogenic bacteria are a significant source of morbidity (illness or disease) and mortality (death) in modern medicine, despite the widespread use of antibiotics. This chapter on bacterial infections of the genitourinary tract is from a textbook that offers a practical and concise guide to the understanding, diagnosis, and treatment of urologic diseases. The authors note that although most cases are susceptible to a variety of antibiotic agents and respond quickly to short term therapy, fulminant infections with resistant organisms are difficult to treat and require a multimodal therapeutic approach. Progress in the management of bacterial UTIs has come about with the development of new antibiotic agents that have excellent activity against the usual uropathogens while simultaneously having fewer adverse effects on the patients. The authors stress that, fortunately, the organisms responsible for UTIs are still quite predictable. They discuss classification of UTIs; pathogenesis of UTIs, including host susceptibility and bacterial virulence; diagnosis; antibiotic agents; antibiotic prophylaxis (preventive therapy) for endourologic procedures; kidney infections, including acute pyelonephritis, emphysematous pyelonephritis, chronic pyelonephritis, renal abscess, perinephric abscess, pyonephrosis and infected hydronephrosis, and xanthogranulomatous pyelonephritis; genitourinary malacoplakia; bladder infections; bacteriuria (bacteria in the urine) in pregnancy; prostatitis; and epididymitis. 6 figures. 7 tables. 156 references.
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CHAPTER 8. MULTIMEDIA ON BACTERIAL INFECTIONS Overview In this chapter, we show you how to keep current on multimedia sources of information on bacterial infections. 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 bacterial infections is the Combined Health Information Database. You will need to limit your search to “Videorecording” and “bacterial infections” 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 “bacterial infections” (or synonyms) into the “For these words:” box. The following is a typical result when searching for video recordings on bacterial infections: •
Cystitis: Don't Ignore Painful Urination Source: Madison, WI: University of Wisconsin Hospitals and Clinics, Department of Outreach Education. 2000. (videocassette). Contact: Available from University of Wisconsin Hospital and Clinics. Picture of Health, 702 North Blackhawk Avenue, Suite 215, Madison, WI 53705-3357. (800) 757-4354 or (608) 263-6510. Fax (608) 262-7172. PRICE: $19.95 plus shipping and handling; bulk copies available. Order number 032700R. Summary: Cystitis, or bladder infection or inflammation, is a common problem, characterized by frequency of urination, urgency to urinate, and burning upon urination. This videotape program, moderated by Carol Koby, discusses bacterial cystitis (bladder infection) and the more chronic interstitial cystitis (IC, an inflammation of the lining of the bladder). The program features nurse practitioners Sue Marten and Stacy Cesario, who identify symptoms, describe the different types of cystitis, and
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review medical and self care treatment options. The nurse practitioners first review the anatomy of the female urogenital tract and the types of symptoms that may be experienced. Although both types of cystitis are characterized by dysuria (painful urination) and urinary frequency and urgency, IC also tends to include intense abdominal pain, painful intercourse, and lack of response to antibiotic therapy. Other topics covered include the symptoms of an infection that has spread to the kidneys, risk factors for certain populations (pregnant women or women with diabetes), the causes of bacterial infections, diagnostic considerations, self help and prevention strategies, disorders associated with IC, the etiology of IC (which is largely unknown, but seems to require a previous inflammatory process), and treatment options for IC (bladder distention, chlorpactin, bladder instillation of DMSO, oral medications, and TENS, electrical stimulation). The program features interviews with some patients, who describe the difficulties of obtaining an accurate diagnosis of IC and their success with self care, diet therapy, bladder retraining, and stress reduction. The program concludes by referring viewers to the Interstitial Cystitis Association (ICA 301-610-5300).
Audio Recordings The Combined Health Information Database contains abstracts on audio productions. To search CHID, go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find audio productions, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Sound Recordings.” Type “bacterial infections” (or synonyms) into the “For these words:” box. The following is a typical result when searching for sound recordings on bacterial infections: •
Human Immunodeficiency Virus Infection Contact: American Dental Hygienists Association, 444 N Michigan Ave, Ste 3400, Chicago, IL, 60611, (312) 440-8900. Summary: This sound recording is the audio portion of a self-study course for dental hygienists about the Human immunodeficiency virus (HIV). A 32-page study guide with colored photographs and a bibliography of 31 items accompanies the sound recording. Eleven learning objectives are set out, including an understanding of the difference between HIV and Acquired immunodeficiency syndrome (AIDS), the structure of the virus, modes of infection, and opportunistic infections. The narrator explains that viruses need a host cell to replicate, and the action of HIV in the human body is explained in detail. Testing for HIV is discussed, and the difference between the ELISA and Western blot tests is explained. Opportunistic infections are then discussed, together with symptoms and drugs used in treatment. The viral, fungal, and bacterial infections of the mouth are discussed, as well as neoplasms and other oral manifestations of a compromised immune system. The epidemiology of HIV, and the modes of HIV transmission in the United States, are contrasted with those in Africa. Accidental transmission of HIV to health-care workers is detailed, together with a description of universal precaution procedures. The necessity of protecting the dental patient with a compromised immune system is emphasized.
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CHAPTER 9. PERIODICALS AND NEWS ON BACTERIAL INFECTIONS Overview In this chapter, we suggest a number of news sources and present various periodicals that cover bacterial infections.
News Services and Press Releases One of the simplest ways of tracking press releases on bacterial infections 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 “bacterial infections” (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 bacterial infections. 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 “bacterial infections” (or synonyms). The following was recently listed in this archive for bacterial infections: •
Genetic mutation ups bacterial infection risk Source: Reuters Health eLine Date: April 28, 2003
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Fecal lactoferrin predicts invasive bacterial infection in children with diarrhea Source: Reuters Medical News Date: March 13, 2003
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Antibiotic therapy improves lung function in asthmatics with bacterial infection Source: Reuters Industry Breifing Date: June 11, 2002
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Bacterial infection found in 25 surgery cases--paper Source: Reuters Health eLine Date: March 15, 2002
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TMP-SMZ prophylaxis prevents bacterial infections in advanced HIV disease Source: Reuters Industry Breifing Date: February 15, 2002 The NIH
Within MEDLINEplus, the NIH has made an agreement with the New York Times Syndicate, the AP News Service, and Reuters to deliver news that can be browsed by the public. Search news releases at http://www.nlm.nih.gov/medlineplus/alphanews_a.html. MEDLINEplus allows you to browse across an alphabetical index. Or you can search by date at the following Web page: http://www.nlm.nih.gov/medlineplus/newsbydate.html. Often, news items are indexed by MEDLINEplus within its search engine. 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 “bacterial infections” (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 “bacterial infections” (or synonyms). If you know the name of a company that is relevant to bacterial infections, you can go to any stock trading Web site (such as
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http://www.etrade.com/) and search for the company name there. News items across various news sources are reported on indicated hyperlinks. Google offers a similar service at http://news.google.com/. BBC Covering news from a more European perspective, the British Broadcasting Corporation (BBC) allows the public free access to their news archive located at http://www.bbc.co.uk/. Search by “bacterial infections” (or synonyms).
Newsletters on Bacterial Infections Find newsletters on bacterial infections using the Combined Health Information Database (CHID). You will need to use the “Detailed Search” option. To access CHID, go to the following hyperlink: http://chid.nih.gov/detail/detail.html. Limit your search to “Newsletter” and “bacterial infections.” Go to the bottom of the search page where “You may refine your search by.” Select the dates and language that you prefer. For the format option, select “Newsletter.” Type “bacterial infections” (or synonyms) into the “For these words:” box. The following list was generated using the options described above: •
Septic Arthritis Update Source: Bulletin on the Rheumatic Diseases. 51(1): 1-4. 2002. Contact: Available from Arthritis Foundation. 1330 West Peachtree Street, Atlanta, GA 30309. (800) 268-6942 or (404) 872-7100. Fax (404) 872-9559. Website: www.arthritis.org. Summary: This newsletter provides health professionals with information on septic arthritis, focusing on its risk factors, pathogenesis, clinical features, diagnosis, treatment, prevention, and outcome. Bacterial infections are the most serious infections affecting normal, diseased, and prosthetic joints. An impaired immune system is a predisposition to septic arthritis. Bacteremic seeding of the affected joint from an extraarticular infection site is the most common pathogenesis of septic arthritis. The Gram positive cocci are the major pathogens among nongonococcal causes of acute bacterial arthritis. Septic arthritis is usually monoarticular rather than polyarticular. Diagnosis is based on the results of arthrocentesis and synovial fluid analysis. A cell count, a Gram stained smear, and a wet preparation examined under a polarizing microscope are immediate tests to perform on the synovial fluid in addition to culturing for microorganisms. Antibiotics are used to treat septic arthritis. The type of antibiotic used is based on the identity and sensitivities of the microorganism. Factors that indicate poor outcome include young and old age, a virulent microorganism, a delay in diagnosis or treatment initiation, underlying joint disease, and occurrence in certain joints. Although opportunities to prevent septic arthritis are limited, they should be kept in mind in patients with underlying arthritis or patients who have had a total joint replacement. Accurate data are lacking on the cost effectiveness of antibiotic prophylaxis to prevent late infections in prosthetic joints. 18 references.
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Newsletter Articles Use the Combined Health Information Database, and limit your search criteria to “newsletter articles.” Again, you will need to use the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. Go to the bottom of the search page where “You may refine your search by.” Select the dates and language that you prefer. For the format option, select “Newsletter Article.” Type “bacterial infections” (or synonyms) into the “For these words:” box. You should check back periodically with this database as it is updated every three months. The following is a typical result when searching for newsletter articles on bacterial infections: •
Inflammatory Bowel Disease: Making Sense of a Mystery Ailment Source: Harvard Health Letter. 22(2): 4-6. December 1996. Contact: Available from Harvard Health Letter. P.O. Box 380, Boston, MA 02117. (617) 432-1485. Summary: This article introduces general readers to the symptoms and causes of inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis (UC). The authors discuss the differential diagnosis of IBD, including ruling out irritable bowel syndrome (IBS) and bacterial infections, and the diagnostic tests that are commonly used to confirm IBD. The authors note that IBD appears to run in families, and they report on current genetic research in this area as well as on research into a possible environmental stimulus that can trigger the disease in genetically susceptible people. The choice of therapy is largely determined by which part of the bowel is affected by IBD and whether the problem is Crohn's or UC. People can use topical therapy such as steroid suppositories or enemas to treat the inflammation directly if only the rectum or lower portion of the colon is affected. However, oral medication often becomes necessary. The first choice for drug therapy is sulfasalazine (Azulfidine). The authors conclude with a brief discussion of the surgical options available for people with IBD who don't respond to drug therapy. 1 table. (AA-M).
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Battle Against HBV: The Evolution of a Cure Source: B INFORMED. No. 28: 1,3-4. Spring 2000. Contact: Available from Hepatitis B Foundation. 700 East Butler Avenue, Doylestown, PA 18901-2697. (215) 489-4900. E-mail:
[email protected]. Summary: This article updates readers on research into hepatitis B virus (HBV) and its treatments. Present treatments for HBV infections include interferon alpha 2b (marketed under the name Intron A), an injected drug that was approved in 1991. This immunomodulator drug can be very effective but is only successful in 20 to 40 percent of a subpopulation of chronic HBV carriers. The drug also is administered only through injection and causes flulike side effects. Another drug, lamivudine (3TC), was discovered in 1989 and is a nucleoside analogue (it attacks the cell's nucleus, where the virus usually replicates). Viral reproduction can be halted by introducing these nucleoside analogue drugs aimed at inhibiting the DNA polymerase. Research has revealed that when the hepatitis virus is reproducing, mistakes may be made in copying the viral DNA. This may result in different mutant strains of HBV that are resistant to lamivudine; indeed, the resistance rate seen in lamivudine is significant (reminiscient of some bacterial infections that are resistant to antibiotics). The author stresses the importance of using combination therapy to treat patients with HBV. The last section of
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the article summarizes research into promising drugs now under development. Two of these HBV specific drugs are LFMAU, a nucleoside analogue, and adefovir dipivoxil (GS890), which appears to be effective against lamivudine resistant virus strains. Advancing research also continues on noninterferon immune enhancers. Vaccines such as theradigm, now in Phase II trials, also boost the helper T cell against infection. The author concludes by reminding readers of the importance of participating in clinical trials as these drugs are brought to market. •
Questions and Answers: Infection Risks Post-Transplant Source: CLASS Notes. p. 5-6. Spring 1998. Contact: Available from Children's Liver Association for Support Services (C.L.A.S.S.). 26444 Emerald Dove Drive, Valencia, CA 91355. (877) 689-8256. (661) 255-0353. E-mail:
[email protected]. Website: www.classkids.org. Summary: This newsletter article answers the concerns of one parent who writes to ask how to handle infection control in her daughter after the child receives a liver transplant. The parent is worried that drugs given to the child to prevent rejection of her new liver will leave her vulnerable to infectious diseases. The physician who addresses these concerns notes that precautions against infection must be individualized for each patient. Different patients are on different amounts of immunosuppression, and the more immunosuppression a patient has received the more precautions are necessary. Since the chance of rejection is highest during the first 3 months after a transplant, higher doses of immunosuppression are used, and therefore the risk of infection is highest during this time period. The most common infections after a transplant are viral infection; bacterial infections are also fairly common after a transplant (but most can be easily treated with antibiotics). The article concludes with a discussion of chicken pox, a viral infection that requires special consideration. If the patient is immune to chicken pox, the likelihood of having a problem later on is much less since this virus generally causes chicken pox only once. A vaccine is available for chicken pox and many transplant centers are starting to vaccinate children who will some day need a transplant in order to general immunity and prevent future infections. The vaccine is a live virus though, so it cannot be given once the child is on immunosuppression. Other topics covered in the article are childcare, having pets, and the types of immunosuppressant drugs that are usually prescribed.
•
What Causes a Urinary Tract Infection? Source: Columbia-Presbyterian Urology. p. 1-2. Spring 1997. Contact: Available from Columbia-Presbyterian Urology. Dana W. Atchley Pavilion, 11 Floor, 161 Fort Washington Avenue, New York, NY 10032-3784. (212) 305-0111. Summary: This newsletter article describes the causes of urinary tract infections (UTIs), the most common infections in women. The author first lists the symptoms that a person with a UTI may have: burning and pain on urination, urinating frequently, urge to urinate, blood in the urine, fever and chills, cloudy urine, and foul smelling urine. The author then discusses the causes of a UTI, including escherichia coli (bacteria) colonization, lack of vaginal estrogen, urinary blockages, and other bacterial infections. The article concludes with a list of strategies for treatment and prevention, including antibiotics for 3 to 7 days, increased fluid intake, aspirin or acetominophen for pain and discomfort, drinking acid-containing juice, refraining from sex during treatment for the infection, appropriate wiping after bowel movements (for women), drinking 4 to 6
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glasses of fluid each day, urinating 3 to 5 times each day, and having a urine culture test several days after the antibiotic is finished. •
Research '95: Spondyloarthropathy Investigations Source: Spondylitis Plus. 3-4; Spring 1996. Contact: Spondylitis Association of America. Summary: This newsletter article for individuals with ankylosing spondylitis (AS) and related diseases highlights some of the facts and findings presented by researchers in the spondyloarthropathy field at three international symposiums. Findings concerned the role of the genetic marker HLA - B27 in the development of rheumatic conditions, the various subtypes of HLA - B27 the role of bacterial infections in the development of AS, and the effectiveness of sulfasalazine and corticosteroid injections in treating AS patients.
•
Body Piercing and Branding Are the Latest Fads Source: Skin and Allergy News. 30(12): 27. December 1999. Contact: Available from Skin and Allergy News, Circulation. 12230 Wilkins Avenue, Rockville, MD 20852. (301) 816-8796. Summary: This newsletter article provides health professionals with information on the safety of body piercing and branding. One dermatologist who has studied various forms of body decorations for over 35 years believes that most people who have body art do not experience any problems. Nickel allergy does occur but is not all that common. Bacterial infections from Staphylococcus aureus and Streptococcus seem to cause most problems. Another type of infection common in patients who have body piercings is Pseudomonas. Colonization of this bacteria can liquify ear cartilage and may require treatment with intravenous antibiotics. Candidal infections commonly affect piercings of the navel. Infections are more likely to occur in moist areas such as the genitalia and the nose, mouth piercings rarely become infected. Umbilicus piercings are more prone to infection if exposed to friction. Infections can also occur from trauma-induced tears. Problems are more likely to arise if the piercing is done by an unqualified person. The newest symbols of teenage rebellion are branding and scarification. The latter involves cutting a design into the skin and placing sand or another agent in the wound to promote the formation of a keloid. Branding is performed using a branding iron with initials or some other design on a tip that is heated using an acetylene torch. 6 figures.
Academic Periodicals covering Bacterial Infections Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to bacterial infections. In addition to these sources, you can search for articles covering bacterial infections 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.
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At http://locatorplus.gov/, you can retrieve more indexing information on medical periodicals (e.g. the name of the publisher). Select the button “Search LOCATORplus.” Then type in the name of the journal and select the advanced search option “Journal Title Search.”
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CHAPTER 10. RESEARCHING MEDICATIONS Overview While a number of hard copy or CD-ROM resources are available for researching medications, a more flexible method is to use Internet-based databases. Broadly speaking, there are two sources of information on approved medications: public sources and private sources. We will emphasize free-to-use public sources.
U.S. Pharmacopeia Because of historical investments by various organizations and the emergence of the Internet, it has become rather simple to learn about the medications recommended for bacterial infections. One such source is the United States Pharmacopeia. In 1820, eleven physicians met in Washington, D.C. to establish the first compendium of standard drugs for the United States. They called this compendium the U.S. Pharmacopeia (USP). Today, the USP is a non-profit organization consisting of 800 volunteer scientists, eleven elected officials, and 400 representatives of state associations and colleges of medicine and pharmacy. The USP is located in Rockville, Maryland, and its home page is located at http://www.usp.org/. The USP currently provides standards for over 3,700 medications. The resulting USP DI® Advice for the Patient® can be accessed through the National Library of Medicine of the National Institutes of Health. The database is partially derived from lists of federally approved medications in the Food and Drug Administration’s (FDA) Drug Approvals database, located at http://www.fda.gov/cder/da/da.htm. While the FDA database is rather large and difficult to navigate, the Phamacopeia is both user-friendly and free to use. It covers more than 9,000 prescription and over-the-counter medications. To access this database, simply type the following hyperlink into your Web browser: http://www.nlm.nih.gov/medlineplus/druginformation.html. To view examples of a given medication (brand names, category, description, preparation, proper use, precautions, side effects, etc.), simply follow the hyperlinks indicated within the United States Pharmacopeia (USP). Below, we have compiled a list of medications associated with bacterial infections. If you would like more information on a particular medication, the provided hyperlinks will direct you to ample documentation (e.g. typical dosage, side effects, drug-interaction risks, etc.).
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The following drugs have been mentioned in the Pharmacopeia and other sources as being potentially applicable to bacterial infections: Aminoglycosides •
Systemic - U.S. Brands: Amikin; Garamycin; G-Mycin; Jenamicin; Kantrex; Nebcin; Netromycin http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202027.html
Azithromycin •
Systemic - U.S. Brands: Zithromax http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202642.html
Aztreonam •
Systemic - U.S. Brands: Azactam http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202078.html
Cephalosporins •
Systemic - U.S. Brands: Ancef; Ceclor; Ceclor CD; Cedax; Cefadyl; Cefizox; Cefobid; Cefotan; Ceftin; Cefzil; Ceptaz; Claforan; Duricef; Fortaz; Keflex 20; Keftab 20; Kefurox; Kefzol; Mandol; Maxipime; Mefoxin; Monocid; Omnicef; Rocephin; Suprax; Tazicef; Tazidime; Vantin http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202119.html
Ciprofloxacin •
Ophthalmic - U.S. Brands: Ciloxan http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202655.html
Clarithromycin •
Systemic - U.S. Brands: Biaxin http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202667.html
Clindamycin •
Systemic - U.S. Brands: Cleocin http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202145.html
Cycloserine •
Systemic - U.S. Brands: Seromycin http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202175.html
Dirithromycin •
Systemic - U.S. Brands: Dynabac http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202785.html
Ethambutol •
Systemic - U.S. Brands: Myambutol http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202229.html
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Fluoroquinolones •
Systemic - U.S. Brands: Avelox; Cipro; Cipro I.V.; Floxin; Floxin I.V.; Levaquin; Maxaquin; Noroxin; Penetrex; Tequin; Zagam http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202656.html
Furazolidone •
Oral - U.S. Brands: Furoxone http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202252.html
Gentamicin •
Topical - U.S. Brands: Garamycin; Gentamar; G-Myticin http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202258.html
Isotretinoin •
Systemic - U.S. Brands: Accutane http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202309.html
Levofloxacin •
Ophthalmic - U.S. Brands: Quixin http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/500189.html
Loracarbef •
Systemic - U.S. Brands: Lorabid http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202680.html
Metronidazole •
Systemic - U.S. Brands: Flagyl; Protostat http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202365.html
Mupirocin •
Topical - U.S. Brands: Bactroban http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202383.html
Neomycin, Polymyxin B, and Bacitracin •
Topical - U.S. Brands: Foille; Mycitracin; Topisporin http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202400.html
Ofloxacin •
Ophthalmic - U.S. Brands: Ocuflox http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202687.html
Penicillins •
Systemic - U.S. Brands: Amoxil; Bactocill; Beepen-VK; Betapen-VK; Bicillin L-A; Cloxapen; Crysticillin 300 A.S.; Dycill; Dynapen; Geocillin; Geopen; Ledercillin VK; Mezlin; Nafcil; Nallpen; Omnipen; Omnipen-N; Pathocil; Pen Vee K; Pentids; Permapen; Pfizerpen; Pfizerpen-AS http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202446.html
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Penicillins and Beta-Lactamase Inhibitors •
Systemic - U.S. Brands: Augmentin; Timentin; Unasyn; Zosyn http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202705.html
Rifampin •
Systemic - U.S. Brands: Rifadin; Rimactane http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202511.html
Sparfloxacin •
Systemic - U.S. Brands: Zagam http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203530.html
Sulfonamides •
Systemic - U.S. Brands: Gantanol; Gantrisin; Thiosulfil Forte; Urobak http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202540.html
•
Vaginal - U.S. Brands: AVC; Sultrin; Trysul http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202541.html
Sulfonamides and Trimethoprim •
Systemic - U.S. Brands: Bactrim; Bactrim DS; Bactrim I.V.; Bactrim Pediatric; Cofatrim Forte; Cotrim; Cotrim DS; Cotrim Pediatric; Septra; Septra DS; Septra Grape Suspension; Septra I.V.; Septra Suspension; Sulfatrim; Sulfatrim Pediatric; Sulfatrim S/S; Sulfatrim Suspension http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202781.html
Tetracyclines •
Systemic - U.S. Brands: Achromycin V; Declomycin; Doryx; Dynacin; Minocin; Monodox; Terramycin; Vibramycin; Vibra-Tabs http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202552.html
Tobramycin •
Ophthalmic - U.S. Brands: AKTob; Tobrex http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202570.html
Vancomycin •
Systemic - U.S. Brands: Vancocin http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202590.html
Commercial Databases In addition to the medications listed in the USP above, a number of commercial sites are available by subscription to physicians and their institutions. Or, you may be able to access these sources from your local medical library.
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Mosby’s Drug Consult™ Mosby’s Drug Consult™ database (also available on CD-ROM and book format) covers 45,000 drug products including generics and international brands. It provides prescribing information, drug interactions, and patient information. Subscription information is available at the following hyperlink: http://www.mosbysdrugconsult.com/. PDRhealth The PDRhealth database is a free-to-use, drug information search engine that has been written for the public in layman’s terms. It contains FDA-approved drug information adapted from the Physicians’ Desk Reference (PDR) database. PDRhealth can be searched by brand name, generic name, or indication. It features multiple drug interactions reports. Search PDRhealth at http://www.pdrhealth.com/drug_info/index.html. Other Web Sites Drugs.com (www.drugs.com) reproduces the information in the Pharmacopeia as well as commercial information. You may also want to consider the Web site of the Medical Letter, Inc. (http://www.medletter.com/) which allows users to download articles on various drugs and therapeutics for a nominal fee.
Researching Orphan Drugs Although the list of orphan drugs is revised on a daily basis, you can quickly research orphan drugs that might be applicable to bacterial infections by using the database managed by the National Organization for Rare Disorders, Inc. (NORD), at http://www.rarediseases.org/. Scroll down the page, and on the left toolbar, click on “Orphan Drug Designation Database.” On this page (http://www.rarediseases.org/search/noddsearch.html), type “bacterial infections” (or synonyms) into the search box, and click “Submit Query.” When you receive your results, note that not all of the drugs may be relevant, as some may have been withdrawn from orphan status. Write down or print out the name of each drug and the relevant contact information. From there, visit the Pharmacopeia Web site and type the name of each orphan drug into the search box at http://www.nlm.nih.gov/medlineplus/druginformation.html. You may need to contact the sponsor or NORD for further information. NORD conducts “early access programs for investigational new drugs (IND) under the Food and Drug Administration’s (FDA’s) approval ‘Treatment INDs’ programs which allow for a limited number of individuals to receive investigational drugs before FDA marketing approval.” If the orphan product about which you are seeking information is approved for marketing, information on side effects can be found on the product’s label. If the product is not approved, you may need to contact the sponsor. The following is a list of orphan drugs currently listed in the NORD Orphan Drug Designation Database for bacterial infections: •
Thalidomide http://www.rarediseases.org/nord/search/nodd_full?code=23
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Mafenide acetate solution (trade name: Sulfamylon solution) http://www.rarediseases.org/nord/search/nodd_full?code=134
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/
•
National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html
•
National Cancer Institute (NCI); guidelines available at http://www.cancer.gov/cancerinfo/list.aspx?viewid=5f35036e-5497-4d86-8c2c714a9f7c8d25
•
National Eye Institute (NEI); guidelines available at http://www.nei.nih.gov/order/index.htm
•
National Heart, Lung, and Blood Institute (NHLBI); guidelines available at http://www.nhlbi.nih.gov/guidelines/index.htm
•
National Human Genome Research Institute (NHGRI); research available at http://www.genome.gov/page.cfm?pageID=10000375
•
National Institute on Aging (NIA); guidelines available at http://www.nia.nih.gov/health/
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
•
National Institute of Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/
•
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm
•
National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm
•
National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/
•
National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/
•
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm
•
National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html
•
National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm
•
National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/practitioners/index.cfm
•
National Institute of Neurological Disorders and Stroke (NINDS); neurological disorder information pages available at http://www.ninds.nih.gov/health_and_medical/disorder_index.htm
•
National Institute of Nursing Research (NINR); publications on selected illnesses at http://www.nih.gov/ninr/news-info/publications.html
•
National Institute of Biomedical Imaging and Bioengineering; general information at http://grants.nih.gov/grants/becon/becon_info.htm
•
Center for Information Technology (CIT); referrals to other agencies based on keyword searches available at http://kb.nih.gov/www_query_main.asp
•
National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/
•
National Center for Research Resources (NCRR); various information directories available at http://www.ncrr.nih.gov/publications.asp
•
Office of Rare Diseases; various fact sheets available at http://rarediseases.info.nih.gov/html/resources/rep_pubs.html
•
Centers for Disease Control and Prevention; various fact sheets on infectious diseases available at http://www.cdc.gov/publications.htm
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NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.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/
•
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
•
Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html
•
MEDLINE: Bibliographic database covering the fields of medicine, nursing, dentistry, veterinary medicine, the healthcare system, and the pre-clinical sciences: http://www.nlm.nih.gov/databases/databases_medline.html
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 NLM Gateway14 The NLM (National Library of Medicine) Gateway is a Web-based system that lets users search simultaneously in multiple retrieval systems at the U.S. National Library of Medicine (NLM). It allows users of NLM services to initiate searches from one Web interface, providing one-stop searching for many of NLM’s information resources or databases.15 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “bacterial infections” (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 418033 867 1098 352 83 420433
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 “bacterial infections” (or synonyms) at the following Web site: http://text.nlm.nih.gov.
14
Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.
15
The NLM Gateway is currently being developed by the Lister Hill National Center for Biomedical Communications (LHNCBC) at the National Library of Medicine (NLM) of the National Institutes of Health (NIH). 16 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 17 18
The HSTAT URL is http://hstat.nlm.nih.gov/.
Other important documents in HSTAT include: the National Institutes of Health (NIH) Consensus Conference Reports and Technology Assessment Reports; the HIV/AIDS Treatment Information Service (ATIS) resource documents; the Substance Abuse and Mental Health Services Administration's Center for Substance Abuse Treatment (SAMHSA/CSAT) Treatment Improvement Protocols (TIP) and Center for Substance Abuse Prevention (SAMHSA/CSAP) Prevention Enhancement Protocols System (PEPS); the Public Health Service (PHS) Preventive Services Task Force's Guide to Clinical Preventive Services; the independent, nonfederal Task Force on Community Services’ Guide to Community Preventive Services; and the Health Technology Advisory Committee (HTAC) of the Minnesota Health Care Commission (MHCC) health technology evaluations.
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Coffee Break: Tutorials for Biologists19 Coffee Break is a general healthcare site that takes a scientific view of the news and covers recent breakthroughs in biology that may one day assist physicians in developing treatments. Here you will find a collection of short reports on recent biological discoveries. Each report incorporates interactive tutorials that demonstrate how bioinformatics tools are used as a part of the research process. Currently, all Coffee Breaks are written by NCBI staff.20 Each report is about 400 words and is usually based on a discovery reported in one or more articles from recently published, peer-reviewed literature.21 This site has new articles every few weeks, so it can be considered an online magazine of sorts. It is intended for general background information. You can access the Coffee Break Web site at the following hyperlink: http://www.ncbi.nlm.nih.gov/Coffeebreak/.
Other Commercial Databases In addition to resources maintained by official agencies, other databases exist that are commercial ventures addressing medical professionals. Here are some examples that may interest you: •
CliniWeb International: Index and table of contents to selected clinical information on the Internet; see http://www.ohsu.edu/cliniweb/.
•
Medical World Search: Searches full text from thousands of selected medical sites on the Internet; see http://www.mwsearch.com/.
19 Adapted 20
from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html.
The figure that accompanies each article is frequently supplied by an expert external to NCBI, in which case the source of the figure is cited. The result is an interactive tutorial that tells a biological story. 21 After a brief introduction that sets the work described into a broader context, the report focuses on how a molecular understanding can provide explanations of observed biology and lead to therapies for diseases. Each vignette is accompanied by a figure and hypertext links that lead to a series of pages that interactively show how NCBI tools and resources are used in the research process.
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APPENDIX B. PATIENT RESOURCES Overview Official agencies, as well as federally funded institutions supported by national grants, frequently publish a variety of guidelines written with the patient in mind. These are typically called “Fact Sheets” or “Guidelines.” They can take the form of a brochure, information kit, pamphlet, or flyer. Often they are only a few pages in length. Since new guidelines on bacterial infections can appear at any moment and be published by a number of sources, the best approach to finding guidelines is to systematically scan the Internetbased 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 bacterial infections. 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 bacterial infections. 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 “bacterial infections”:
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Guides on bacterial infections Bacterial Infections http://www.nlm.nih.gov/medlineplus/bacterialinfections.html
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Other guides Candidiasis http://www.nlm.nih.gov/medlineplus/candidiasis.html Meningitis http://www.nlm.nih.gov/medlineplus/meningitis.html Staphylococcal Infections http://www.nlm.nih.gov/medlineplus/staphylococcalinfections.html Vaginal Diseases http://www.nlm.nih.gov/medlineplus/vaginaldiseases.html Viral Infections http://www.nlm.nih.gov/medlineplus/viralinfections.html
Within the health topic page dedicated to bacterial infections, the following was listed: •
General/Overviews Bacteria Source: American Society for Microbiology http://www.microbe.org/microbes/bacterium1.asp Virus or Bacterium? Source: American Society for Microbiology http://www.microbe.org/microbes/virus_or_bacterium.asp
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Diagnosis/Symptoms Blood Cultures Source: American Association for Clinical Chemistry http://labtestsonline.org/understanding/analytes/blood_culture/test.html
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Treatment Antibiotics: When They Can and Can't Help Source: American Academy of Family Physicians http://familydoctor.org/680.xml Linezolid Source: American College of Physicians http://www.annals.org/cgi/content/full/138/2/I-44
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Specific Conditions/Aspects Brucellosis Source: National Center for Infectious Diseases, Division of Bacterial and Mycotic Diseases http://www.cdc.gov/ncidod/dbmd/diseaseinfo/brucellosis_g.htm Campylobacter Source: Centers for Disease Control and Prevention http://www.cdc.gov/ncidod/dbmd/diseaseinfo/campylobacter_g.htm Cholera Source: National Center for Infectious Diseases http://www.cdc.gov/ncidod/dbmd/diseaseinfo/cholera_g.htm Glanders Source: National Center for Infectious Diseases, Division of Bacterial and Mycotic Diseases http://www.cdc.gov/ncidod/dbmd/diseaseinfo/glanders_g.htm Hansen's Disease: Leprosy Source: National Center for Infectious Diseases, Division of Bacterial and Mycotic Diseases http://www.cdc.gov/ncidod/dbmd/diseaseinfo/hansens_t.htm Helicobacter pylori Infections (H. pylori) Source: Centers for Disease Control and Prevention http://www.cdc.gov/ncidod/dbmd/diseaseinfo/hpylori_g.htm Hot Tub Lung Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=AN00660 Leptospirosis Source: National Center for Infectious Diseases http://www.cdc.gov/ncidod/dbmd/diseaseinfo/leptospirosis_g.htm Melioidosis Source: National Center for Infectious Diseases, Division of Bacterial and Mycotic Diseases http://www.cdc.gov/ncidod/dbmd/diseaseinfo/melioidosis_g.htm Nontuberculous Mycobacteria (NTM) Source: National Jewish Medical and Research Center http://www.nationaljewish.org/medfacts/nontuberculosis.html Q Fever Source: Centers for Disease Control and Prevention http://www.cdc.gov/ncidod/dvrd/qfever/index.htm Shigellosis Source: Centers for Disease Control and Prevention http://www.cdc.gov/ncidod/dbmd/diseaseinfo/shigellosis_g.htm Tularemia Source: National Institute of Allergy and Infectious Diseases http://www.niaid.nih.gov/factsheets/tularemia.htm
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Typhoid Fever Source: National Center for Infectious Diseases, Division of Bacterial and Mycotic Diseases http://www.cdc.gov/ncidod/dbmd/diseaseinfo/typhoidfever_g.htm Vibrio Parahaemolyticus Source: National Center for Infectious Diseases, Division of Bacterial and Mycotic Diseases http://www.cdc.gov/ncidod/dbmd/diseaseinfo/vibrioparahaemolyticus_g.htm Vibrio Vulnificus Source: National Center for Infectious Diseases, Division of Bacterial and Mycotic Diseases http://www.cdc.gov/ncidod/dbmd/diseaseinfo/vibriovulnificus_g.htm Yersinia Enterocolitica Source: Centers for Disease Control and Prevention http://www.cdc.gov/ncidod/dbmd/diseaseinfo/yersinia_g.htm •
Children Campylobacter Infections Source: Nemours Foundation http://kidshealth.org/parent/infections/stomach/campylobacter.html Cat Scratch Disease Source: Nemours Foundation http://kidshealth.org/parent/infections/bacterial_viral/cat_scratch.html Clostridial Infections Source: Nemours Foundation http://kidshealth.org/parent/infections/bacterial_viral/clostridium.html Helicobacter pylori Source: Nemours Foundation http://kidshealth.org/parent/infections/stomach/h_pylori.html Pattern of Newborn Infections Changes Source: National Institute of Child Health and Human Development http://www.nih.gov/news/pr/jul2002/nichd-25.htm Shigellosis Source: Nemours Foundation http://kidshealth.org/parent/infections/bacterial_viral/shigellosis.html Yersinia Enterocolitica Source: Nemours Foundation http://kidshealth.org/parent/infections/bacterial_viral/yersinia.html
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From the National Institutes of Health Microbes in Sickness and in Health Source: National Institute of Allergy and Infectious Diseases http://www.niaid.nih.gov/publications/microbes.htm
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Latest News Bacterial Link Found To Cerebral Palsy Source: 02/17/2004, United Press International http://www.nlm.nih.gov//www.nlm.nih.gov/medlineplus/news/fullstory_16094 .html More News on Bacterial Infections http://www.nlm.nih.gov//www.nlm.nih.gov/medlineplus/alphanews_b.html#B acterialInfections UK Medics to Prescribe Maggots As Wound Cleansers Source: 02/20/2004, Reuters Health http://www.nlm.nih.gov//www.nlm.nih.gov/medlineplus/news/fullstory_16182 .html Wiping Out Stomach Bug Improves Cholesterol Level Source: 02/18/2004, Reuters Health http://www.nlm.nih.gov//www.nlm.nih.gov/medlineplus/news/fullstory_16136 .html
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Organizations National Center for Infectious Diseases http://www.cdc.gov/ncidod/index.htm National Center for Infectious Diseases, Division of Bacterial and Mycotic Diseases http://www.cdc.gov/ncidod/dbmd/ National Foundation for Infectious Diseases http://www.nfid.org/ National Institute of Allergy and Infectious Diseases http://www.niaid.nih.gov/
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Prevention/Screening Answers to Your Questions about the Hazards of Antibacterial Cleaners Source: College of American Pathologists http://www.cap.org/apps/docs/fact_sheets/germs.htm Handwashing Source: University of Utah, Health Sciences Center http://www.med.utah.edu/healthinfo/adult/infectious/handwash.htm
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Research Diagnosing Catheter-Related Bloodstream Infections Source: American College of Physicians http://www.annals.org/cgi/content/full/140/1/I-39 Research Brief: Bacteria Study Sheds Light on Cell Communication Source: National Institute of General Medical Sciences http://www.nigms.nih.gov/news/releases/brief_kiessling.html
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Research Brief: Stop Cell Death, Help Treat Sepsis? Source: National Institute of General Medical Sciences http://www.nigms.nih.gov/news/releases/brief_coopersmith.html Single Protein Is Key in Response to Bacterial, Viral Infections Source: National Institute of Allergy and Infectious Diseases http://www.nih.gov/news/pr/jul2003/niaid-20.htm •
Teenagers Why Should I Care about Germs? Source: Nemours Foundation http://kidshealth.org/teen/your_body/health_basics/care_about_germs.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 bacterial infections. 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: •
Bacterial Infections Contact: National AIDS Treatment Information Project, Beth Israel Deaconess Medical Center, Beth Israel Hospital, 330 Brookline Ave Libby Bldg 317, Boston, MA, 02215, (617) 667-5520, http://www.natip.org. Summary: This fact sheet, for individuals with the human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS), presents information about bacterial infections. Bacterial infections in HIV-positive individuals may occur repeatedly and can even result in significant disability or death if left untreated. Some bacterial infections are staphylococcus aureus (staph), streptococcus pneumoniae (pneumococcus), hemophilus influenzae (H flu), and enteric organisms such as Salmonella. Factors that may predispose individuals to bacterial infections include dermatitis, skin lacerations or lesions, injection drug use, intravenous catheter use, cigarette smoking, alcohol use, poor oral hygiene, and improper hygiene. People with HIV are at increased risk for bacterial infection because their immune system is weakened. Symptoms of bacterial infections may include fever, chills, a localized area of skin redness, warmth, and tenderness, pain or bleeding with toothbrushing or eating, headache, and chest pain made worse by breathing. Other symptoms include diarrhea, mental confusion, and a cough that produces a thick, cloudy phlegm. Bacterial infections
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are diagnosed primarily through medical history and physical examination; tests may be used depending upon the type of infection that is suspected. Bacterial infections are treated with antibiotics. Some general tips for the prevention of bacterial infections are provided, as is a table that lists infections, body areas they affect, and treatment modality. 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: •
Awareness of a Group B Strep Infection During Pregnancy Summary: This brochure answers questions about this Group B Strep, a bacterial infection that causes illness in newborn babies, pregnant women, the elderly, and adults with other illnesses. Source: Group B Strep Association http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=3039
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Gonorrhea Summary: This booklet discusses the symptoms, diagnosis, treatment, complications, and prevention of gonorrhea -- a highly contagious bacterial infection usually spread through sexual contact. Source: National Institute of Allergy and Infectious Diseases, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=105
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Tuberculosis Summary: Tuberculosis (TB), a chronic bacterial infection, causes more deaths worldwide than any other infectious disease. With appropriate antibiotic therapy, TB usually can be cured. Source: National Institute of Allergy and Infectious Diseases, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=222 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 bacterial infections. 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
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rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html. Additional Web Sources A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •
AOL: http://search.aol.com/cat.adp?id=168&layer=&from=subcats
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Family Village: http://www.familyvillage.wisc.edu/specific.htm
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Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/
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Med Help International: http://www.medhelp.org/HealthTopics/A.html
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Open Directory Project: http://dmoz.org/Health/Conditions_and_Diseases/
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Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/
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WebMD®Health: http://my.webmd.com/health_topics
Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to bacterial infections. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with bacterial infections. 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 bacterial infections. 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 “bacterial infections” (or a synonym), and you will receive information on all relevant organizations listed in the database.
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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 “bacterial infections”. Type the following hyperlink into your Web browser: http://chid.nih.gov/detail/detail.html. To find associations, use the drop boxes at the bottom of the search page where “You may refine your search by.” For publication date, select “All Years.” Then, select your preferred language and the format option “Organization Resource Sheet.” Type “bacterial infections” (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 “bacterial infections” (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/
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Alabama: Richard M. Scrushy Library (American Sports Medicine Institute)
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Arizona: Samaritan Regional Medical Center: The Learning Center (Samaritan Health System, Phoenix, Arizona), http://www.samaritan.edu/library/bannerlibs.htm
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California: Kris Kelly Health Information Center (St. Joseph Health System, Humboldt), http://www.humboldt1.com/~kkhic/index.html
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California: Community Health Library of Los Gatos, http://www.healthlib.org/orgresources.html
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California: Consumer Health Program and Services (CHIPS) (County of Los Angeles Public Library, Los Angeles County Harbor-UCLA Medical Center Library) - Carson, CA, http://www.colapublib.org/services/chips.html
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California: Gateway Health Library (Sutter Gould Medical Foundation)
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California: Health Library (Stanford University Medical Center), http://wwwmed.stanford.edu/healthlibrary/
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California: Patient Education Resource Center - Health Information and Resources (University of California, San Francisco), http://sfghdean.ucsf.edu/barnett/PERC/default.asp
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California: Redwood Health Library (Petaluma Health Care District), http://www.phcd.org/rdwdlib.html
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California: Los Gatos PlaneTree Health Library, http://planetreesanjose.org/
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California: Sutter Resource Library (Sutter Hospitals Foundation, Sacramento), http://suttermedicalcenter.org/library/
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California: Health Sciences Libraries (University of California, Davis), http://www.lib.ucdavis.edu/healthsci/
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California: ValleyCare Health Library & Ryan Comer Cancer Resource Center (ValleyCare Health System, Pleasanton), http://gaelnet.stmarysca.edu/other.libs/gbal/east/vchl.html
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California: Washington Community Health Resource Library (Fremont), http://www.healthlibrary.org/
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Colorado: William V. Gervasini Memorial Library (Exempla Healthcare), http://www.saintjosephdenver.org/yourhealth/libraries/
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Connecticut: Hartford Hospital Health Science Libraries (Hartford Hospital), http://www.harthosp.org/library/
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Connecticut: Healthnet: Connecticut Consumer Health Information Center (University of Connecticut Health Center, Lyman Maynard Stowe Library), http://library.uchc.edu/departm/hnet/
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Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.
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Connecticut: Waterbury Hospital Health Center Library (Waterbury Hospital, Waterbury), http://www.waterburyhospital.com/library/consumer.shtml
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Delaware: Consumer Health Library (Christiana Care Health System, Eugene du Pont Preventive Medicine & Rehabilitation Institute, Wilmington), http://www.christianacare.org/health_guide/health_guide_pmri_health_info.cfm
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Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine, Wilmington), http://www.delamed.org/chls.html
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Georgia: Family Resource Library (Medical College of Georgia, Augusta), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm
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Georgia: Health Resource Center (Medical Center of Central Georgia, Macon), http://www.mccg.org/hrc/hrchome.asp
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Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library, Honolulu), http://hml.org/CHIS/
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Idaho: DeArmond Consumer Health Library (Kootenai Medical Center, Coeur d’Alene), http://www.nicon.org/DeArmond/index.htm
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Illinois: Health Learning Center of Northwestern Memorial Hospital (Chicago), http://www.nmh.org/health_info/hlc.html
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Illinois: Medical Library (OSF Saint Francis Medical Center, Peoria), http://www.osfsaintfrancis.org/general/library/
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Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital, Lexington), http://www.centralbap.com/education/community/library.cfm
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Kentucky: University of Kentucky - Health Information Library (Chandler Medical Center, Lexington), http://www.mc.uky.edu/PatientEd/
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Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation, New Orleans), http://www.ochsner.org/library/
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Louisiana: Louisiana State University Health Sciences Center Medical LibraryShreveport, http://lib-sh.lsuhsc.edu/
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Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital, Farmington), http://www.fchn.org/fmh/lib.htm
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Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center, Lewiston), http://www.cmmc.org/library/library.html
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Maine: Hadley Parrot Health Science Library (Eastern Maine Healthcare, Bangor), http://www.emh.org/hll/hpl/guide.htm
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Maine: Maine Medical Center Library (Maine Medical Center, Portland), http://www.mmc.org/library/
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Maine: Parkview Hospital (Brunswick), http://www.parkviewhospital.org/
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Maine: Southern Maine Medical Center Health Sciences Library (Southern Maine Medical Center, Biddeford), http://www.smmc.org/services/service.php3?choice=10
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Maine: Stephens Memorial Hospital’s Health Information Library (Western Maine Health, Norway), http://www.wmhcc.org/Library/
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Manitoba, Canada: Consumer & Patient Health Information Service (University of Manitoba Libraries), http://www.umanitoba.ca/libraries/units/health/reference/chis.html
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Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre, Winnipeg), http://www.deerlodge.mb.ca/crane_library/about.asp
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Maryland: Health Information Center at the Wheaton Regional Library (Montgomery County, Dept. of Public Libraries, Wheaton Regional Library), http://www.mont.lib.md.us/healthinfo/hic.asp
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Massachusetts: Baystate Medical Center Library (Baystate Health System), http://www.baystatehealth.com/1024/
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Massachusetts: Boston University Medical Center Alumni Medical Library (Boston University Medical Center), http://med-libwww.bu.edu/library/lib.html
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Massachusetts: Lowell General Hospital Health Sciences Library (Lowell General Hospital, Lowell), http://www.lowellgeneral.org/library/HomePageLinks/WWW.htm
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Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital, Boston), http://www.nebh.org/health_lib.asp
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Massachusetts: St. Luke’s Hospital Health Sciences Library (St. Luke’s Hospital, Southcoast Health System, New Bedford), http://www.southcoast.org/library/
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Massachusetts: Treadwell Library Consumer Health Reference Center (Massachusetts General Hospital), http://www.mgh.harvard.edu/library/chrcindex.html
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Massachusetts: UMass HealthNet (University of Massachusetts Medical School, Worchester), http://healthnet.umassmed.edu/
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Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm
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Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/
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Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html
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Michigan: Patient Education Resouce Center - University of Michigan Cancer Center (University of Michigan Comprehensive Cancer Center, Ann Arbor), http://www.cancer.med.umich.edu/learn/leares.htm
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Michigan: Sladen Library & Center for Health Information Resources - Consumer Health Information (Detroit), http://www.henryford.com/body.cfm?id=39330
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Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center, Missoula)
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National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html
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National: National Network of Libraries of Medicine (National Library of Medicine) provides library services for health professionals in the United States who do not have access to a medical library, http://nnlm.gov/
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National: NN/LM List of Libraries Serving the Public (National Network of Libraries of Medicine), http://nnlm.gov/members/
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Nevada: Health Science Library, West Charleston Library (Las Vegas-Clark County Library District, Las Vegas), http://www.lvccld.org/special_collections/medical/index.htm
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New Hampshire: Dartmouth Biomedical Libraries (Dartmouth College Library, Hanover), http://www.dartmouth.edu/~biomed/resources.htmld/conshealth.htmld/
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New Jersey: Consumer Health Library (Rahway Hospital, Rahway), http://www.rahwayhospital.com/library.htm
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New Jersey: Dr. Walter Phillips Health Sciences Library (Englewood Hospital and Medical Center, Englewood), http://www.englewoodhospital.com/links/index.htm
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New Jersey: Meland Foundation (Englewood Hospital and Medical Center, Englewood), http://www.geocities.com/ResearchTriangle/9360/
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New York: Choices in Health Information (New York Public Library) - NLM Consumer Pilot Project participant, http://www.nypl.org/branch/health/links.html
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New York: Health Information Center (Upstate Medical University, State University of New York, Syracuse), http://www.upstate.edu/library/hic/
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New York: Health Sciences Library (Long Island Jewish Medical Center, New Hyde Park), http://www.lij.edu/library/library.html
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New York: ViaHealth Medical Library (Rochester General Hospital), http://www.nyam.org/library/
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Ohio: Consumer Health Library (Akron General Medical Center, Medical & Consumer Health Library), http://www.akrongeneral.org/hwlibrary.htm
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Oklahoma: The Health Information Center at Saint Francis Hospital (Saint Francis Health System, Tulsa), http://www.sfh-tulsa.com/services/healthinfo.asp
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Oregon: Planetree Health Resource Center (Mid-Columbia Medical Center, The Dalles), http://www.mcmc.net/phrc/
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Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center, Hershey), http://www.hmc.psu.edu/commhealth/
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Pennsylvania: Community Health Resource Library (Geisinger Medical Center, Danville), http://www.geisinger.edu/education/commlib.shtml
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Pennsylvania: HealthInfo Library (Moses Taylor Hospital, Scranton), http://www.mth.org/healthwellness.html
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Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System, Pittsburgh), http://www.hsls.pitt.edu/guides/chi/hopwood/index_html
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Pennsylvania: Koop Community Health Information Center (College of Physicians of Philadelphia), http://www.collphyphil.org/kooppg1.shtml
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Pennsylvania: Learning Resources Center - Medical Library (Susquehanna Health System, Williamsport), http://www.shscares.org/services/lrc/index.asp
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Pennsylvania: Medical Library (UPMC Health System, Pittsburgh), http://www.upmc.edu/passavant/library.htm
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Quebec, Canada: Medical Library (Montreal General Hospital), http://www.mghlib.mcgill.ca/
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South Dakota: Rapid City Regional Hospital Medical Library (Rapid City Regional Hospital), http://www.rcrh.org/Services/Library/Default.asp
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Texas: Houston HealthWays (Houston Academy of Medicine-Texas Medical Center Library), http://hhw.library.tmc.edu/
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Washington: Community Health Library (Kittitas Valley Community Hospital), http://www.kvch.com/
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Washington: Southwest Washington Medical Center Library (Southwest Washington Medical Center, Vancouver), http://www.swmedicalcenter.com/body.cfm?id=72
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ONLINE GLOSSARIES The Internet provides access to a number of free-to-use medical dictionaries. The National Library of Medicine has compiled the following list of online dictionaries: •
ADAM Medical Encyclopedia (A.D.A.M., Inc.), comprehensive medical reference: http://www.nlm.nih.gov/medlineplus/encyclopedia.html
•
MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp
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Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/
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Multilingual Glossary of Technical and Popular Medical Terms in Eight European Languages (European Commission) - Danish, Dutch, English, French, German, Italian, Portuguese, and Spanish: http://allserv.rug.ac.be/~rvdstich/eugloss/welcome.html
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On-line Medical Dictionary (CancerWEB): http://cancerweb.ncl.ac.uk/omd/
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Rare Diseases Terms (Office of Rare Diseases): http://ord.aspensys.com/asp/diseases/diseases.asp
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Technology Glossary (National Library of Medicine) - Health Care Technology: http://www.nlm.nih.gov/nichsr/ta101/ta10108.htm
Beyond these, MEDLINEplus contains a very patient-friendly encyclopedia covering every aspect of medicine (licensed from A.D.A.M., Inc.). The ADAM Medical Encyclopedia can be accessed at http://www.nlm.nih.gov/medlineplus/encyclopedia.html. ADAM is also available on commercial Web sites such as drkoop.com (http://www.drkoop.com/) and Web MD (http://my.webmd.com/adam/asset/adam_disease_articles/a_to_z/a).
Online Dictionary Directories The following are additional online directories compiled by the National Library of Medicine, including a number of specialized medical dictionaries: •
Medical Dictionaries: Medical & Biological (World Health Organization): http://www.who.int/hlt/virtuallibrary/English/diction.htm#Medical
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MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html
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Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/
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Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine
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BACTERIAL INFECTIONS DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. 1-phosphate: A drug that halts cell suicide in human white blood cells. [NIH] Abdomen: That portion of the body that lies between the thorax and the pelvis. [NIH] Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Abdominal Pain: Sensation of discomfort, distress, or agony in the abdominal region. [NIH] Aberrant: Wandering or deviating from the usual or normal course. [EU] Abscess: A localized, circumscribed collection of pus. [NIH] Acetaminophen: Analgesic antipyretic derivative of acetanilide. It has weak antiinflammatory properties and is used as a common analgesic, but may cause liver, blood cell, and kidney damage. [NIH] Acetylcholine: A neurotransmitter. Acetylcholine in vertebrates is the major transmitter at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. It is generally not used as an administered drug because it is broken down very rapidly by cholinesterases, but it is useful in some ophthalmological applications. [NIH] Acne: A disorder of the skin marked by inflammation of oil glands and hair glands. [NIH] Acquired Immunodeficiency Syndrome: An acquired defect of cellular immunity associated with infection by the human immunodeficiency virus (HIV), a CD4-positive Tlymphocyte count under 200 cells/microliter or less than 14% of total lymphocytes, and increased susceptibility to opportunistic infections and malignant neoplasms. Clinical manifestations also include emaciation (wasting) and dementia. These elements reflect criteria for AIDS as defined by the CDC in 1993. [NIH] Acremonium: A mitosporic fungal genus with many reported ascomycetous teleomorphs. Cephalosporin antibiotics are derived from this genus. [NIH] Actin: Essential component of the cell skeleton. [NIH] Actinomycosis: Infections with bacteria of the genus Actinomyces. [NIH] Acute lymphoblastic leukemia: ALL. A quickly progressing disease in which too many immature white blood cells called lymphoblasts are found in the blood and bone marrow. Also called acute lymphocytic leukemia. [NIH] Acute lymphocytic leukemia: ALL. A quickly progressing disease in which too many immature white blood cells called lymphoblasts are found in the blood and bone marrow. Also called acute lymphoblastic leukemia. [NIH] Acute renal: A condition in which the kidneys suddenly stop working. In most cases, kidneys can recover from almost complete loss of function. [NIH] Acyclovir: Functional analog of the nucleoside guanosine. It acts as an antimetabolite, especially in viruses. It is used as an antiviral agent, especially in herpes infections. [NIH] Acyl: Chemical signal used by bacteria to communicate. [NIH] Acyl Carrier Protein: Consists of a polypeptide chain and 4'-phosphopantetheine linked to a
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serine residue by a phosphodiester bond. Acyl groups are bound as thiol esters to the pantothenyl group. Acyl carrier protein is involved in every step of fatty acid synthesis by the cytoplasmic system. [NIH] Acylation: The addition of an organic acid radical into a molecule. [NIH] Adaptability: Ability to develop some form of tolerance to conditions extremely different from those under which a living organism evolved. [NIH] Adaptation: 1. The adjustment of an organism to its environment, or the process by which it enhances such fitness. 2. The normal ability of the eye to adjust itself to variations in the 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 Triphosphate: Adenosine 5'-(tetrahydrogen triphosphate). An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter. [NIH] Adenovirus: A group of viruses that cause respiratory tract and eye infections. Adenoviruses used in gene therapy are altered to carry a specific tumor-fighting gene. [NIH] Adenylate Cyclase: An enzyme of the lyase class that catalyzes the formation of cyclic AMP and pyrophosphate from ATP. EC 4.6.1.1. [NIH] Adjustment: The dynamic process wherein the thoughts, feelings, behavior, and biophysiological mechanisms of the individual continually change to adjust to the environment. [NIH] Adoptive Transfer: Form of passive immunization where previously sensitized immunologic agents (cells or serum) are transferred to non-immune recipients. When transfer of cells is used as a therapy for the treatment of neoplasms, it is called adoptive immunotherapy (immunotherapy, adoptive). [NIH] Adrenal Cortex: The outer layer of the adrenal gland. It secretes mineralocorticoids, androgens, and glucocorticoids. [NIH] Adrenal Glands: Paired glands situated in the retroperitoneal tissues at the superior pole of each kidney. [NIH] Adsorption: The condensation of gases, liquids, or dissolved substances on the surfaces of solids. It includes adsorptive phenomena of bacteria and viruses as well as of tissues treated with exogenous drugs and chemicals. [NIH] Adsorptive: It captures volatile compounds by binding them to agents such as activated carbon or adsorptive resins. [NIH] Adverse Effect: An unwanted side effect of treatment. [NIH] Aerobic: In biochemistry, reactions that need oxygen to happen or happen when oxygen is present. [NIH] 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]
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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] 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 of Onset: The age or period of life at which a disease or the initial symptoms or manifestations of a disease appear in an individual. [NIH] Airway: A device for securing unobstructed passage of air into and out of the lungs during general anesthesia. [NIH] Airway Obstruction: Any hindrance to the passage of air into and out of the lungs. [NIH] Alanine: A non-essential amino acid that occurs in high levels in its free state in plasma. It is produced from pyruvate by transamination. It is involved in sugar and acid metabolism, increases immunity, and provides energy for muscle tissue, brain, and the central nervous system. [NIH] Albumin: 1. Any protein that is soluble in water and moderately concentrated salt solutions and is coagulable by heat. 2. Serum albumin; the major plasma protein (approximately 60 per cent of the total), which is responsible for much of the plasma colloidal osmotic pressure and serves as a transport protein carrying large organic anions, such as fatty acids, bilirubin, and many drugs, and also carrying certain hormones, such as cortisol and thyroxine, when their specific binding globulins are saturated. Albumin is synthesized in the liver. Low serum levels occur in protein malnutrition, active inflammation and serious hepatic and renal disease. [EU] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alimentary: Pertaining to food or nutritive material, or to the organs of digestion. [EU] Alkaline: Having the reactions of an alkali. [EU] Alkaline Phosphatase: An enzyme that catalyzes the conversion of an orthophosphoric monoester and water to an alcohol and orthophosphate. EC 3.1.3.1. [NIH] 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] Allogeneic: Taken from different individuals of the same species. [NIH] Allogeneic bone marrow transplantation: A procedure in which a person receives stem cells, the cells from which all blood cells develop, from a compatible, though not genetically identical, donor. [NIH]
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Alpha Particles: Positively charged particles composed of two protons and two neutrons, i.e., helium nuclei, emitted during disintegration of very heavy isotopes; a beam of alpha particles or an alpha ray has very strong ionizing power, but weak penetrability. [NIH] Alpha-Defensins: Defensins found in azurophilic granules of neutrophils and in the secretory granules of intestinal paneth cells. [NIH] Alpha-lactalbumin: A human milk protein which could be used as a nutritional supplement. [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] Alveolar Bone Loss: The resorption of bone in the supporting structures of the maxilla or mandible as a result of periodontal disease. [NIH] Alveoli: Tiny air sacs at the end of the bronchioles in the lungs. [NIH] Amino Acid Motifs: Commonly observed structural components of proteins formed by simple combinations of adjacent secondary structures. A commonly observed structure may be composed of a conserved sequence which can be represented by a consensus sequence. [NIH]
Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amoxicillin: A broad-spectrum semisynthetic antibiotic similar to ampicillin except that its resistance to gastric acid permits higher serum levels with oral administration. [NIH] Amphetamines: Analogs or derivatives of amphetamine. Many are sympathomimetics and central nervous system stimulators causing excitation, vasopression, bronchodilation, and to varying degrees, anorexia, analepsis, nasal decongestion, and some smooth muscle relaxation. [NIH] Ampicillin: Semi-synthetic derivative of penicillin that functions as an orally active broadspectrum antibiotic. [NIH] Amplification: The production of additional copies of a chromosomal DNA sequence, found as either intrachromosomal or extrachromosomal DNA. [NIH] Anaerobic: 1. Lacking molecular oxygen. 2. Growing, living, or occurring in the absence of molecular oxygen; pertaining to an anaerobe. [EU] Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Anal: Having to do with the anus, which is the posterior opening of the large bowel. [NIH] Analgesic: An agent that alleviates pain without causing loss of consciousness. [EU] Analog: In chemistry, a substance that is similar, but not identical, to another. [NIH]
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Analogous: Resembling or similar in some respects, as in function or appearance, but not in origin or development;. [EU] Analytes: A component of a test sample the presence of which has to be demonstrated. The term "analyte" includes where appropriate formed from the analyte during the analyses. [NIH]
Anaphylatoxins: The family of peptides C3a, C4a, C5a, and C5a des-arginine produced in the serum during complement activation. They produce smooth muscle contraction, mast cell histamine release, affect platelet aggregation, and act as mediators of the local inflammatory process. The order of anaphylatoxin activity from strongest to weakest is C5a, C3a, C4a, and C5a des-arginine. The latter is the so-called "classical" anaphylatoxin but shows no spasmogenic activity though it contains some chemotactic ability. [NIH] Anaplasia: Loss of structural differentiation and useful function of neoplastic cells. [NIH] Androgens: A class of sex hormones associated with the development and maintenance of the secondary male sex characteristics, sperm induction, and sexual differentiation. In addition to increasing virility and libido, they also increase nitrogen and water retention and stimulate skeletal growth. [NIH] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Anergy: Absence of immune response to particular substances. [NIH] Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH] Angiogenesis: Blood vessel formation. Tumor angiogenesis is the growth of blood vessels from surrounding tissue to a solid tumor. This is caused by the release of chemicals by the tumor. [NIH] Anhydrides: Chemical compounds derived from acids by the elimination of a molecule of water. [NIH] Animal model: An animal with a disease either the same as or like a disease in humans. Animal models are used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Anionic: Pertaining to or containing an anion. [EU] Annealing: The spontaneous alignment of two single DNA strands to form a double helix. [NIH]
Anorexia: Lack or loss of appetite for food. Appetite is psychologic, dependent on memory and associations. Anorexia can be brought about by unattractive food, surroundings, or company. [NIH] Antiallergic: Counteracting allergy or allergic conditions. [EU] Antibacterial: A substance that destroys bacteria or suppresses their growth or reproduction. [EU] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]
Antibiotic Prophylaxis: Use of antibiotics before, during, or after a diagnostic, therapeutic, or surgical procedure to prevent infectious complications. [NIH] Antibiotics, Aminoglycoside: Antibiotics whose structure contains amino sugars attached to an aminocyclitol ring (hexose nucleus) by glycosidic bonds. Aminoglycoside antibiotics
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are derived from various species of Streptomyces and Micromonospora or are produced synthetically. They act by inhibiting protein synthesis. [NIH] Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] Antifungal: Destructive to fungi, or suppressing their reproduction or growth; effective against fungal infections. [EU] Antifungal Agents: Substances that destroy fungi by suppressing their ability to grow or reproduce. They differ from fungicides, industrial because they defend against fungi present in human or animal tissues. [NIH] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Antigen-Antibody Complex: The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes immune complex diseases. [NIH] Antigen-presenting cell: APC. A cell that shows antigen on its surface to other cells of the immune system. This is an important part of an immune response. [NIH] Anti-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] Anti-Inflammatory Agents: Substances that reduce or suppress inflammation. [NIH] Antimetabolite: A chemical that is very similar to one required in a normal biochemical reaction in cells. Antimetabolites can stop or slow down the reaction. [NIH] Antimicrobial: Killing microorganisms, or suppressing their multiplication or growth. [EU] Antimycotic: Suppressing the growth of fungi. [EU] Antineoplastic: Inhibiting or preventing the development of neoplasms, checking the maturation and proliferation of malignant cells. [EU] Antiproliferative: Counteracting a process of proliferation. [EU] Antipyretic: An agent that relieves or reduces fever. Called also antifebrile, antithermic and febrifuge. [EU] Antiseptic: A substance that inhibits the growth and development of microorganisms without necessarily killing them. [EU]
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Antiviral: Destroying viruses or suppressing their replication. [EU] Antiviral Agents: Agents used in the prophylaxis or therapy of virus diseases. Some of the ways they may act include preventing viral replication by inhibiting viral DNA polymerase; binding to specific cell-surface receptors and inhibiting viral penetration or uncoating; inhibiting viral protein synthesis; or blocking late stages of virus assembly. [NIH] Anus: The opening of the rectum to the outside of the body. [NIH] Anxiety: Persistent feeling of dread, apprehension, and impending disaster. [NIH] Apoptosis: One of the two mechanisms by which cell death occurs (the other being the pathological process of necrosis). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA (DNA fragmentation) at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. [NIH] Aqueous: Having to do with water. [NIH] Arachidonic Acid: An unsaturated, essential fatty acid. It is found in animal and human fat as well as in the liver, brain, and glandular organs, and is a constituent of animal phosphatides. It is formed by the synthesis from dietary linoleic acid and is a precursor in the biosynthesis of prostaglandins, thromboxanes, and leukotrienes. [NIH] 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] Arthroplasty: Surgical reconstruction of a joint to relieve pain or restore motion. [NIH] Articular: Of or pertaining to a joint. [EU] Ascites: Accumulation or retention of free fluid within the peritoneal cavity. [NIH] Aspergillosis: Infections with fungi of the genus Aspergillus. [NIH] Aspirin: A drug that reduces pain, fever, inflammation, and blood clotting. Aspirin belongs to the family of drugs called nonsteroidal anti-inflammatory agents. It is also being studied in cancer prevention. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Asymptomatic: Having no signs or symptoms of disease. [NIH] Atopic: Pertaining to an atopen or to atopy; allergic. [EU] Attenuated: Strain with weakened or reduced virulence. [NIH] Attenuation: Reduction of transmitted sound energy or its electrical equivalent. [NIH] Atypical: Irregular; not conformable to the type; in microbiology, applied specifically to strains of unusual type. [EU] Autodigestion: Autolysis; a condition found in disease of the stomach: the stomach wall is digested by the gastric juice. [NIH] Autoimmune disease: A condition in which the body recognizes its own tissues as foreign and directs an immune response against them. [NIH] Autopsy: Postmortem examination of the body. [NIH]
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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] Aztreonam: A monocyclic beta-lactam antibiotic originally isolated from Chromobacterium violaceum. It is resistant to beta-lactamases and is used in gram-negative infections, especially of the meninges, bladder, and kidneys. It may cause a superinfection with grampositive organisms. [NIH] Bacillus: A genus of Bacillaceae that are spore-forming, rod-shaped cells. Most species are saprophytic soil forms with only a few species being pathogenic. [NIH] Bacteremia: The presence of viable bacteria circulating in the blood. Fever, chills, tachycardia, and tachypnea are common acute manifestations of bacteremia. The majority of cases are seen in already hospitalized patients, most of whom have underlying diseases or procedures which render their bloodstreams susceptible to invasion. [NIH] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Bacterial Adhesion: Physicochemical property of fimbriated and non-fimbriated bacteria of attaching to cells, tissue, and nonbiological surfaces. It is a factor in bacterial colonization and pathogenicity. [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] Bacteriocins: Substances elaborated by specific strains of bacteria that are lethal against other strains of the same or related species. They are protein or lipopolysaccharide-protein complexes used in taxonomy studies of bacteria. [NIH] Bacteriophage: A virus whose host is a bacterial cell; A virus that exclusively infects bacteria. It generally has a protein coat surrounding the genome (DNA or RNA). One of the coliphages most extensively studied is the lambda phage, which is also one of the most important. [NIH] 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] Bacteriuria: The presence of bacteria in the urine with or without consequent urinary tract infection. Since bacteriuria is a clinical entity, the term does not preclude the use of urine/microbiology for technical discussions on the isolation and segregation of bacteria in the urine. [NIH] Bacteroides: A genus of gram-negative, anaerobic, rod-shaped bacteria. Its organisms are normal inhabitants of the oral, respiratory, intestinal, and urogenital cavities of humans, animals, and insects. Some species may be pathogenic. [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]
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Base Sequence: The sequence of purines and pyrimidines in nucleic acids and polynucleotides. It is also called nucleotide or nucleoside sequence. [NIH] Basement Membrane: Ubiquitous supportive tissue adjacent to epithelium and around smooth and striated muscle cells. This tissue contains intrinsic macromolecular components such as collagen, laminin, and sulfated proteoglycans. As seen by light microscopy one of its subdivisions is the basal (basement) lamina. [NIH] Basophils: Granular leukocytes characterized by a relatively pale-staining, lobate nucleus and cytoplasm containing coarse dark-staining granules of variable size and stainable by basic dyes. [NIH] Bed Rest: Confinement of an individual to bed for therapeutic or experimental reasons. [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-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-sheet: Two or more parallel or anti-parallel strands are arranged in rows. [NIH] Beta-Thalassemia: A disorder characterized by reduced synthesis of the beta chains of hemoglobin. There is retardation of hemoglobin A synthesis in the heterozygous form (thalassemia minor), which is asymptomatic, while in the homozygous form (thalassemia major, Cooley's anemia, Mediterranean anemia, erythroblastic anemia), which can result in severe complications and even death, hemoglobin A synthesis is absent. [NIH] Beta-Thromboglobulin: A platelet-specific protein which is released when platelets aggregate. Elevated plasma levels have been reported after deep venous thrombosis, preeclampsia, myocardial infarction with mural thrombosis, and myeloproliferative disorders. Measurement of beta-thromboglobulin in biological fluids by radioimmunoassay is used for the diagnosis and assessment of progress of thromboembolic disorders. [NIH] Bewilderment: Impairment or loss of will power. [NIH] Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Biliary: Having to do with the liver, bile ducts, and/or gallbladder. [NIH] Biliary Tract: The gallbladder and its ducts. [NIH] Binding Sites: The reactive parts of a macromolecule that directly participate in its specific combination with another molecule. [NIH] Bioavailability: The degree to which a drug or other substance becomes available to the target tissue after administration. [EU] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biofilms: Films of bacteria or other microbial organisms, usually embedded in extracellular polymers such as implanted medical devices, which adhere to surfaces submerged in, or subjected to, aquatic environments (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed). Biofilms consist of multilayers of microbial cells glued together to form microbial communities which are highly resistant to both phagocytes and antibiotics. [NIH] Biological response modifier: BRM. A substance that stimulates the body's response to
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infection and disease. [NIH] Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body. [NIH] Biosynthesis: The building up of a chemical compound in the physiologic processes of a living organism. [EU] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Bioterrorism: The use of biological agents in terrorism. This includes the malevolent use of bacteria, viruses, or toxins against people, animals, or plants. [NIH] Biotic: Pertaining to living organisms in their ecological rather than their physiological relations. [NIH] Biotypes: Causes septicemic and pneumonic pasteurellosis in cattle and sheep, usually in conjunction with a virus infection such as parainfluenza 3. Also recorded as a cause of acute mastitis in cattle. [NIH] Bladder: The organ that stores urine. [NIH] Blastocyst: The mammalian embryo in the post-morula stage in which a fluid-filled cavity, enclosed primarily by trophoblast, contains an inner cell mass which becomes the embryonic disc. [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] Blennorrhoea: A general term including any inflammatory process of the external eye which gives a mucoid discharge, more exactly, a discharge of mucus. [NIH] Bloating: Fullness or swelling in the abdomen that often occurs after meals. [NIH] Blood Cell Count: A count of the number of leukocytes and erythrocytes per unit volume in a sample of venous blood. A complete blood count (CBC) also includes measurement of the hemoglobin, hematocrit, and erythrocyte indices. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood Coagulation Factors: Endogenous substances, usually proteins, that are involved in the blood coagulation process. [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 vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH]
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Blot: To transfer DNA, RNA, or proteins to an immobilizing matrix such as nitrocellulose. [NIH]
Body Fluids: Liquid components of living organisms. [NIH] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bone Marrow Transplantation: The transference of bone marrow from one human or animal to another. [NIH] Bone scan: A technique to create images of bones on a computer screen or on film. A small amount of radioactive material is injected into a blood vessel and travels through the bloodstream; it collects in the bones and is detected by a scanner. [NIH] Bowel: The long tube-shaped organ in the abdomen that completes the process of digestion. There is both a small and a large bowel. Also called the intestine. [NIH] Bowel Movement: Body wastes passed through the rectum and anus. [NIH] Brachytherapy: A collective term for interstitial, intracavity, and surface radiotherapy. It uses small sealed or partly-sealed sources that may be placed on or near the body surface or within a natural body cavity or implanted directly into the tissues. [NIH] Bradykinin: A nonapeptide messenger that is enzymatically produced from kallidin in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from mast cells during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter. [NIH] Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]
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] Bronchioles: The tiny branches of air tubes in the lungs. [NIH] Bronchiolitis: Inflammation of the bronchioles. [NIH] Bronchiseptica: A small, gram-negative, motile bacillus. A normal inhabitant of the respiratory tract in man, dogs, and pigs, but is also associated with canine infectious tracheobronchitis and atrophic rhinitis in pigs. [NIH] Bronchitis: Inflammation (swelling and reddening) of the bronchi. [NIH] Bronchoalveolar Lavage: Washing out of the lungs with saline or mucolytic agents for diagnostic or therapeutic purposes. It is very useful in the diagnosis of diffuse pulmonary infiltrates in immunosuppressed patients. [NIH] Brucellosis: Infection caused by bacteria of the genus Brucella mainly involving the reticuloendothelial system. This condition is characterized by fever, weakness, malaise, and weight loss. [NIH] Buccal: Pertaining to or directed toward the cheek. In dental anatomy, used to refer to the buccal surface of a tooth. [EU]
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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] Bypass: A surgical procedure in which the doctor creates a new pathway for the flow of body fluids. [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] Campylobacter: A genus of bacteria found in the reproductive organs, intestinal tract, and oral cavity of animals and man. Some species are pathogenic. [NIH] Candidiasis: Infection with a fungus of the genus Candida. It is usually a superficial infection of the moist cutaneous areas of the body, and is generally caused by C. albicans; it most commonly involves the skin (dermatocandidiasis), oral mucous membranes (thrush, def. 1), respiratory tract (bronchocandidiasis), and vagina (vaginitis). Rarely there is a systemic infection or endocarditis. Called also moniliasis, candidosis, oidiomycosis, and formerly blastodendriosis. [EU] 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]
Capsular: Cataract which is initiated by an opacification at the surface of the lens. [NIH] Capsules: Hard or soft soluble containers used for the oral administration of medicine. [NIH] Carbapenems: A group of beta-lactam antibiotics in which the sulfur atom in the thiazolidine ring of the penicillin molecule is replaced by a carbon atom. Thienamycins are a subgroup of carbapenems which have a sulfur atom as the first constituent of the side chain. [NIH]
Carbenicillin: Broad-spectrum semisynthetic penicillin derivative used parenterally. It is susceptible to gastric juice and penicillinase and may damage platelet function. [NIH] Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen are usually in the proportion to form water, (CH2O)n. The most important carbohydrates are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, polyand heterosaccharides. [EU] Carbon Dioxide: A colorless, odorless gas that can be formed by the body and is necessary for the respiration cycle of plants and animals. [NIH] Carboxy: Cannabinoid. [NIH] Carboxylic Acids: Organic compounds containing the carboxy group (-COOH). This group of compounds includes amino acids and fatty acids. Carboxylic acids can be saturated, unsaturated, or aromatic. [NIH] Carcinoembryonic Antigen: A glycoprotein that is secreted into the luminal surface of the epithelia in the gastrointestinal tract. It is found in the feces and pancreaticobiliary secretions and is used to monitor the respone to colon cancer treatment. [NIH] Carcinogenic: Producing carcinoma. [EU] Carcinogens: Substances that increase the risk of neoplasms in humans or animals. Both
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genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism, are included. [NIH] Carcinoma: Cancer that begins in the skin or in tissues that line or cover internal organs. [NIH]
Cardiac: Having to do with the heart. [NIH] Cardiovascular: Having to do with the heart and blood vessels. [NIH] 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] Catheterization: Use or insertion of a tubular device into a duct, blood vessel, hollow organ, or body cavity for injecting or withdrawing fluids for diagnostic or therapeutic purposes. It differs from intubation in that the tube here is used to restore or maintain patency in obstructions. [NIH] Catheters: A small, flexible tube that may be inserted into various parts of the body to inject or remove liquids. [NIH] Causal: Pertaining to a cause; directed against a cause. [EU] Cause of Death: Factors which produce cessation of all vital bodily functions. They can be analyzed from an epidemiologic viewpoint. [NIH] 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] Cecum: The beginning of the large intestine. The cecum is connected to the lower part of the small intestine, called the ileum. [NIH] Cefoperazone: Semisynthetic broad-spectrum cephalosporin with a tetrazolyl moiety that is resistant to beta-lactamase. It has been proposed especially against Pseudomonas infections. [NIH]
Cefotaxime: Semisynthetic broad-spectrum cephalosporin. [NIH] Ceftazidime: Semisynthetic, broad-spectrum antibacterial derived from cephaloridine and used especially for Pseudomonas and other gram-negative infections in debilitated patients. [NIH]
Ceftriaxone: Broad-spectrum cephalosporin antibiotic with a very long half-life and high penetrability to usually inaccessible infections, including those involving the meninges, eyes, inner ears, and urinary tract. [NIH] Cefuroxime: Broad-spectrum cephalosporin antibiotic resistant to beta-lactamase. It has been proposed for infections with gram-negative and gram-positive organisms, gonorrhea, and haemophilus. [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 Adhesion: Adherence of cells to surfaces or to other cells. [NIH] Cell Adhesion Molecules: Surface ligands, usually glycoproteins, that mediate cell-to-cell adhesion. Their functions include the assembly and interconnection of various vertebrate systems, as well as maintenance of tissue integration, wound healing, morphogenic
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movements, cellular migrations, and metastasis. [NIH] Cell Count: A count of the number of cells of a specific kind, usually measured per unit volume of sample. [NIH] Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function which takes place during the development of the embryo and leads to the formation of specialized cells, tissues, and organs. [NIH] Cell Division: The fission of a cell. [NIH] Cell 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 motility: The ability of a cell to move. [NIH] Cell Movement: The movement of cells from one location to another. [NIH] Cell proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH] Cell Respiration: The metabolic process of all living cells (animal and plant) in which oxygen is used to provide a source of energy for the cell. [NIH] Cellobiose: A disaccharide consisting of two glucose units in beta (1-4) glycosidic linkage. Obtained from the partial hydrolysis of cellulose. [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] Cephaloridine: A cephalosporin antibiotic. [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] Cephalothin: A cephalosporin antibiotic. [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] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU] Cerulenin: Antifungal antibiotic isolated from several species, including Acremonium
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(Cephalosporium), Acrocylindrum, and Helicoceras. It inhibits the biosynthesis of several lipids by interfering with enzyme function and is used as a biochemical tool. [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] Chancre: The primary sore of syphilis, a painless indurated, eroded papule, occurring at the site of entry of the infection. [NIH] Chemical Warfare: Tactical warfare using incendiary mixtures, smokes, or irritant, burning, or asphyxiating gases. [NIH] Chemical Warfare Agents: Chemicals that are used to cause the disturbance, disease, or death of humans during war. [NIH] Chemokines: Class of pro-inflammatory cytokines that have the ability to attract and activate leukocytes. They can be divided into at least three structural branches: C (chemokines, C), CC (chemokines, CC), and CXC (chemokines, CXC), according to variations in a shared cysteine motif. [NIH] Chemotactic Factors: Chemical substances that attract or repel cells or organisms. The concept denotes especially those factors released as a result of tissue injury, invasion, or immunologic activity, that attract leukocytes, macrophages, or other cells to the site of infection or insult. [NIH] 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] Chest Pain: Pressure, burning, or numbness in the chest. [NIH] Chlorhexidine: Disinfectant and topical anti-infective agent used also as mouthwash to prevent oral plaque. [NIH] Chlorophyll: Porphyrin derivatives containing magnesium that act to convert light energy in photosynthetic organisms. [NIH] Chlortetracycline: An antibiotic substance isolated from the substrate of Streptomyces aureofaciens and used as an antibacterial and antiprotozoal agent. [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] Cholic Acid: A major primary bile acid produced in the liver and usually conjugated with glycine or taurine. It facilitates fat absorption and cholesterol excretion. [NIH] Chondroitin sulfate: The major glycosaminoglycan (a type of sugar molecule) in cartilage. [NIH]
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Chromatin: The material of chromosomes. It is a complex of DNA, histones, and nonhistone proteins (chromosomal proteins, non-histone) found within the nucleus of a cell. [NIH] Chromosomal: Pertaining to chromosomes. [EU] Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chronic Disease: Disease or ailment of long duration. [NIH] Chronic renal: Slow and progressive loss of kidney function over several years, often resulting in end-stage renal disease. People with end-stage renal disease need dialysis or transplantation to replace the work of the kidneys. [NIH] Cicatrix: The formation of new tissue in the process of wound healing. [NIH] Cilastatin: A renal dehydropeptidase-I and leukotriene D4 dipeptidase inhibitor. Since the antibiotic, imipenem, is hydrolyzed by dehydropeptidase-I, which resides in the brush border of the renal tubule, cilastatin is administered with imipenem to increase its effectiveness. The drug also inhibits the metabolism of leukotriene D4 to leukeotriene E4. [NIH]
Cinoxacin: Synthetic antimicrobial related to oxolinic and nalidixic acids and used in urinary tract infections. [NIH] Ciprofloxacin: A carboxyfluoroquinoline antimicrobial agent that is effective against a wide range of microorganisms. It has been successfully and safely used in the treatment of resistant respiratory, skin, bone, joint, gastrointestinal, urinary, and genital infections. [NIH] Clarithromycin: A semisynthetic macrolide antibiotic derived from erythromycin that is active against a variety of microorganisms. It can inhibit protein synthesis in bacteria by reversibly binding to the 50S ribosomal subunits. This inhibits the translocation of aminoacyl transfer-RNA and prevents peptide chain elongation. [NIH] Clavulanic Acid: Clavulanic acid (C8H9O5N) and its salts and esters. The acid is a suicide inhibitor of bacterial beta-lactamase enzymes from Streptomyces clavuligerus. Administered alone, it has only weak antibacterial activity against most organisms, but given in combination with beta-lactam antibiotics prevents antibiotic inactivation by microbial lactamase. [NIH] Cleave: A double-stranded cut in DNA with a restriction endonuclease. [NIH] Clinical Medicine: The study and practice of medicine by direct examination of the patient. [NIH]
Clinical 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]
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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] Clotrimazole: An imidazole derivative with a broad spectrum of antimycotic activity. It inhibits biosynthesis of the sterol ergostol, an important component of fungal cell membranes. Its action leads to increased membrane permeability and apparent disruption of enzyme systems bound to the membrane. [NIH] Coagulation: 1. The process of clot formation. 2. In colloid chemistry, the solidification of a sol into a gelatinous mass; an alteration of a disperse phase or of a dissolved solid which causes the separation of the system into a liquid phase and an insoluble mass called the clot or curd. Coagulation is usually irreversible. 3. In surgery, the disruption of tissue by physical means to form an amorphous residuum, as in electrocoagulation and photocoagulation. [EU] 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] Codon: A set of three nucleotides in a protein coding sequence that specifies individual amino acids or a termination signal (codon, terminator). Most codons are universal, but some organisms do not produce the transfer RNAs (RNA, transfer) complementary to all codons. These codons are referred to as unassigned codons (codons, nonsense). [NIH] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] Cohort Studies: Studies in which subsets of a defined population are identified. These groups may or may not be exposed to factors hypothesized to influence the probability of the occurrence of a particular disease or other outcome. Cohorts are defined populations which, as a whole, are followed in an attempt to determine distinguishing subgroup characteristics. [NIH] 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] Colposcopy: The examination, therapy or surgery of the cervix and vagina by means of a specially designed endoscope introduced vaginally. [NIH] Combination Therapy: Association of 3 drugs to treat AIDS (AZT + DDC or DDI + protease inhibitor). [NIH] Combinatorial: A cut-and-paste process that churns out thousands of potentially valuable compounds at once. [NIH]
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Commensal: 1. Living on or within another organism, and deriving benefit without injuring or benefiting the other individual. 2. An organism living on or within another, but not causing injury to the host. [EU] Communicable disease: A disease that can be transmitted by contact between persons. [NIH] Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complement Activation: The sequential activation of serum components C1 through C9, initiated by an erythrocyte-antibody complex or by microbial polysaccharides and properdin, and producing an inflammatory response. [NIH] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Computed tomography: CT scan. A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized tomography and computerized axial tomography (CAT) scan. [NIH] Computerized axial tomography: A series of detailed pictures of areas inside the body,
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taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called CAT scan, computed tomography (CT scan), or computerized tomography. [NIH] Concomitant: Accompanying; accessory; joined with another. [EU] Condyloma: C. acuminatum; a papilloma with a central core of connective tissue in a treelike structure covered with epithelium, usually occurring on the mucous membrane or skin of the external genitals or in the perianal region. [EU] Cone: One of the special retinal receptor elements which are presumed to be primarily concerned with perception of light and color stimuli when the eye is adapted to light. [NIH] Confusion: A mental state characterized by bewilderment, emotional disturbance, lack of clear thinking, and perceptual disorientation. [NIH] Conjugated: Acting or operating as if joined; simultaneous. [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] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Consciousness: Sense of awareness of self and of the environment. [NIH] 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] Constipation: Infrequent or difficult evacuation of feces. [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] Controlled clinical trial: A clinical study that includes a comparison (control) group. The comparison group receives a placebo, another treatment, or no treatment at all. [NIH] Controlled study: An experiment or clinical trial that includes a comparison (control) group. [NIH]
Conventional therapy: A currently accepted and widely used treatment for a certain type of disease, based on the results of past research. Also called conventional treatment. [NIH] Conventional treatment: A currently accepted and widely used treatment for a certain type of disease, based on the results of past research. Also called conventional therapy. [NIH]
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Convulsions: A general term referring to sudden and often violent motor activity of cerebral or brainstem origin. Convulsions may also occur in the absence of an electrical cerebral discharge (e.g., in response to hypotension). [NIH] Cornea: The transparent part of the eye that covers the iris and the pupil and allows light to enter the inside. [NIH] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary heart disease: A type of heart disease caused by narrowing of the coronary arteries that feed the heart, which needs a constant supply of oxygen and nutrients carried by the blood in the coronary arteries. When the coronary arteries become narrowed or clogged by fat and cholesterol deposits and cannot supply enough blood to the heart, CHD results. [NIH] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Coronavirus: A genus of the family Coronaviridae which causes respiratory or gastrointestinal disease in a variety of vertebrates. [NIH] Corpus: The body of the uterus. [NIH] Cortical: Pertaining to or of the nature of a cortex or bark. [EU] Corticosteroid: Any of the steroids elaborated by the adrenal cortex (excluding the sex hormones of adrenal origin) in response to the release of corticotrophin (adrenocorticotropic hormone) by the pituitary gland, to any of the synthetic equivalents of these steroids, or to angiotensin II. They are divided, according to their predominant biological activity, into three major groups: glucocorticoids, chiefly influencing carbohydrate, fat, and protein metabolism; mineralocorticoids, affecting the regulation of electrolyte and water balance; and C19 androgens. Some corticosteroids exhibit both types of activity in varying degrees, and others exert only one type of effect. The corticosteroids are used clinically for hormonal replacement therapy, for suppression of ACTH secretion by the anterior pituitary, as antineoplastic, antiallergic, and anti-inflammatory agents, and to suppress the immune response. Called also adrenocortical hormone and corticoid. [EU] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU] Craniocerebral Trauma: Traumatic injuries involving the cranium and intracranial structures (i.e., brain; cranial nerves; meninges; and other structures). Injuries may be classified by whether or not the skull is penetrated (i.e., penetrating vs. nonpenetrating) or whether there is an associated hemorrhage. [NIH] Crossing-over: The exchange of corresponding segments between chromatids of homologous chromosomes during meiosia, forming a chiasma. [NIH] Cross-Sectional Studies: Studies in which the presence or absence of disease or other healthrelated variables are determined in each member of the study population or in a representative sample at one particular time. This contrasts with longitudinal studies which are followed over a period of time. [NIH] Cryptosporidiosis: Parasitic intestinal infection with severe diarrhea caused by a protozoan, Cryptosporidium. It occurs in both animals and humans. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Cutaneous: Having to do with the skin. [NIH]
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Cutaneous Fistula: An abnormal passage or communication leading from an internal organ to the surface of the body. [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] Cyclooxygenase Inhibitors: Compounds or agents that combine with cyclooxygenase (prostaglandin-endoperoxide synthase) and thereby prevent its substrate-enzyme combination with arachidonic acid and the formation of eicosanoids, prostaglandins, and thromboxanes. [NIH] Cysteine: A thiol-containing non-essential amino acid that is oxidized to form cystine. [NIH] Cystitis: Inflammation of the urinary bladder. [EU] Cytochrome: Any electron transfer hemoprotein having a mode of action in which the transfer of a single electron is effected by a reversible valence change of the central iron atom of the heme prosthetic group between the +2 and +3 oxidation states; classified as cytochromes a in which the heme contains a formyl side chain, cytochromes b, which contain protoheme or a closely similar heme that is not covalently bound to the protein, cytochromes c in which protoheme or other heme is covalently bound to the protein, and cytochromes d in which the iron-tetrapyrrole has fewer conjugated double bonds than the hemes have. Well-known cytochromes have been numbered consecutively within groups and are designated by subscripts (beginning with no subscript), e.g. cytochromes c, c1, C2, . New cytochromes are named according to the wavelength in nanometres of the absorption maximum of the a-band of the iron (II) form in pyridine, e.g., c-555. [EU] Cytochrome b: Cytochromes (electron-transporting proteins) with protoheme or a related heme as the prosthetic group. The prosthetic group is not covalently bound to the protein moiety. [NIH] Cytokine: Small but highly potent protein that modulates the activity of many cell types, including T and B cells. [NIH] Cytomegalovirus: A genus of the family Herpesviridae, subfamily Betaherpesvirinae, infecting the salivary glands, liver, spleen, lungs, eyes, and other organs, in which they produce characteristically enlarged cells with intranuclear inclusions. Infection with Cytomegalovirus is also seen as an opportunistic infection in AIDS. [NIH] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a continuous aqueous solution (cytosol) and the organelles and inclusions suspended in it (phaneroplasm), and is the site of most of the chemical activities of the cell. [EU] Cytoplasmic Vesicles: Membrane-limited structures derived from the plasma membrane or various intracellular membranes which function in storage, transport or metabolism. [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] Dairy Products: Raw and processed or manufactured milk and milk-derived products. These are usually from cows (bovine) but are also from goats, sheep, reindeer, and water buffalo. [NIH] Daptomycin: A lipopeptide antibiotic that inhibits gram-positive bacteria. [NIH] Data Collection: Systematic gathering of data for a particular purpose from various sources, including questionnaires, interviews, observation, existing records, and electronic devices.
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The process is usually preliminary to statistical analysis of the data. [NIH] Databases, Bibliographic: Extensive collections, reputedly complete, of references and citations to books, articles, publications, etc., generally on a single subject or specialized subject area. Databases can operate through automated files, libraries, or computer disks. The concept should be differentiated from factual databases which is used for collections of data and facts apart from bibliographic references to them. [NIH] De novo: In cancer, the first occurrence of cancer in the body. [NIH] Decidua: The epithelial lining of the endometrium that is formed before the fertilized ovum reaches the uterus. The fertilized ovum embeds in the decidua. If the ovum is not fertilized, the decidua is shed during menstruation. [NIH] Decontamination: The removal of contaminating material, such as radioactive materials, biological materials, or chemical warfare agents, from a person or object. [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] Delivery of Health Care: The concept concerned with all aspects of providing and distributing health services to a patient population. [NIH] Dementia: An acquired organic mental disorder with loss of intellectual abilities of sufficient severity to interfere with social or occupational functioning. The dysfunction is multifaceted and involves memory, behavior, personality, judgment, attention, spatial relations, language, abstract thought, and other executive functions. The intellectual decline is usually progressive, and initially spares the level of consciousness. [NIH] Denaturation: Rupture of the hydrogen bonds by heating a DNA solution and then cooling it rapidly causes the two complementary strands to separate. [NIH] Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other neurons. [NIH] Dendritic: 1. Branched like a tree. 2. Pertaining to or possessing dendrites. [EU] Dendritic cell: A special type of antigen-presenting cell (APC) that activates T lymphocytes. [NIH]
Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] Dental 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]
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Dental Hygienists: Persons trained in an accredited school or dental college and licensed by the state in which they reside to provide dental prophylaxis under the direction of a licensed dentist. [NIH] Dental Plaque: A film that attaches to teeth, often causing dental caries and gingivitis. It is composed of mucins, secreted from salivary glands, and microorganisms. [NIH] Dentists: Individuals licensed to practice dentistry. [NIH] Deoxyribonucleic: A polymer of subunits called deoxyribonucleotides which is the primary genetic material of a cell, the material equivalent to genetic information. [NIH] Deoxyribonucleic acid: A polymer of subunits called deoxyribonucleotides which is the primary genetic material of a cell, the material equivalent to genetic information. [NIH] Deoxyribonucleotides: A purine or pyrimidine base bonded to a deoxyribose containing a bond to a phosphate group. [NIH] 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] Dermatitis: Any inflammation of the skin. [NIH] Dermatologist: A doctor who specializes in the diagnosis and treatment of skin problems. [NIH]
Deuterium: Deuterium. The stable isotope of hydrogen. It has one neutron and one proton in the nucleus. [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] Diabetes Mellitus: A heterogeneous group of disorders that share glucose intolerance in common. [NIH] Diabetic Foot: Ulcers of the foot as a complication of diabetes. Diabetic foot, often with infection, is a common serious complication of diabetes and may require hospitalization and disfiguring surgery. The foot ulcers are probably secondary to neuropathies and vascular problems. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Dialyzer: A part of the hemodialysis machine. (See hemodialysis under dialysis.) The dialyzer has two sections separated by a membrane. One section holds dialysate. The other holds the patient's blood. [NIH] Diarrhea: Passage of excessively liquid or excessively frequent stools. [NIH] Diarrhoea: Abnormal frequency and liquidity of faecal discharges. [EU] Diastolic: Of or pertaining to the diastole. [EU] Diffusion: The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself throughout the available space; a major mechanism of biological transport. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Digestive system: The organs that take in food and turn it into products that the body can
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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] Dilatation: The act of dilating. [NIH] Diphtheria: A localized infection of mucous membranes or skin caused by toxigenic strains of Corynebacterium diphtheriae. It is characterized by the presence of a pseudomembrane at the site of infection. Diphtheria toxin, produced by C. diphtheriae, can cause myocarditis, polyneuritis, and other systemic toxic effects. [NIH] 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] Disease Progression: The worsening of a disease over time. This concept is most often used for chronic and incurable diseases where the stage of the disease is an important determinant of therapy and prognosis. [NIH] Disinfectant: An agent that disinfects; applied particularly to agents used on inanimate objects. [EU] Disinfection: Rendering pathogens harmless through the use of heat, antiseptics, antibacterial agents, etc. [NIH] Disorientation: The loss of proper bearings, or a state of mental confusion as to time, place, or identity. [EU] Disparity: Failure of the two retinal images of an object to fall on corresponding retinal points. [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] Distention: The state of being distended or enlarged; the act of distending. [EU] Dopamine: An endogenous catecholamine and prominent neurotransmitter in several
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systems of the brain. In the synthesis of catecholamines from tyrosine, it is the immediate precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of dopaminergic receptor subtypes mediate its action. Dopamine is used pharmacologically for its direct (beta adrenergic agonist) and indirect (adrenergic releasing) sympathomimetic effects including its actions as an inotropic agent and as a renal vasodilator. [NIH] Dosage Forms: Completed forms of the pharmaceutical preparation in which prescribed doses of medication are included. They are designed to resist action by gastric fluids, prevent vomiting and nausea, reduce or alleviate the undesirable taste and smells associated with oral administration, achieve a high concentration of drug at target site, or produce a delayed or long-acting drug effect. They include capsules, liniments, ointments, pharmaceutical solutions, powders, tablets, etc. [NIH] Dose-dependent: Refers to the effects of treatment with a drug. If the effects change when the dose of the drug is changed, the effects are said to be dose dependent. [NIH] Drug Design: The molecular designing of drugs for specific purposes (such as DNAbinding, enzyme inhibition, anti-cancer efficacy, etc.) based on knowledge of molecular properties such as activity of functional groups, molecular geometry, and electronic structure, and also on information cataloged on analogous molecules. Drug design is generally computer-assisted molecular modeling and does not include pharmacokinetics, dosage analysis, or drug administration analysis. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Drug Resistance: Diminished or failed response of an organism, disease or tissue to the intended effectiveness of a chemical or drug. It should be differentiated from drug tolerance which is the progressive diminution of the susceptibility of a human or animal to the effects of a drug, as a result of continued administration. [NIH] Drug Tolerance: Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from drug resistance wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from maximum tolerated dose and no-observed-adverse-effect level. [NIH] 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]
Dysmenorrhea: Painful menstruation. [NIH] Dysuria: Painful or difficult urination. [EU] 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
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based on the results of a randomized control trial. [NIH] Ego: The conscious portion of the personality structure which serves to mediate between the demands of the primitive instinctual drives, (the id), of internalized parental and social prohibitions or the conscience, (the superego), and of reality. [NIH] Eicosanoids: A class of oxygenated, endogenous, unsaturated fatty acids derived from arachidonic acid. They include prostaglandins, leukotrienes, thromboxanes, and hydroxyeicosatetraenoic acid compounds (HETE). They are hormone-like substances that act near the site of synthesis without altering functions throughout the body. [NIH] Elastin: The protein that gives flexibility to tissues. [NIH] Electrocoagulation: Electrosurgical procedures used to treat hemorrhage (e.g., bleeding ulcers) and to ablate tumors, mucosal lesions, and refractory arrhythmias. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electrons: Stable elementary particles having the smallest known negative charge, present in all elements; also called negatrons. Positively charged electrons are called positrons. The numbers, energies and arrangement of electrons around atomic nuclei determine the chemical identities of elements. Beams of electrons are called cathode rays or beta rays, the latter being a high-energy biproduct of nuclear decay. [NIH] Emaciation: Clinical manifestation of excessive leanness usually caused by disease or a lack of nutrition. [NIH] Embolus: Bit of foreign matter which enters the blood stream at one point and is carried until it is lodged or impacted in an artery and obstructs it. It may be a blood clot, an air bubble, fat or other tissue, or clumps of bacteria. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Embryology: The study of the development of an organism during the embryonic and fetal stages of life. [NIH] Emollients: Oleagenous substances used topically to soothe, soften or protect skin or mucous membranes. They are used also as vehicles for other dermatologic agents. [NIH] Emphysema: A pathological accumulation of air in tissues or organs. [NIH] Empirical: A treatment based on an assumed diagnosis, prior to receiving confirmatory laboratory test results. [NIH] Enamel: A very hard whitish substance which covers the dentine of the anatomical crown of a tooth. [NIH] Encephalocele: Cerebral tissue herniation through a congenital or acquired defect in the skull. The majority of congenital encephaloceles occur in the occipital or frontal regions. Clinical features include a protuberant mass that may be pulsatile. The quantity and location of protruding neural tissue determines the type and degree of neurologic deficit. Visual defects, psychomotor developmental delay, and persistent motor deficits frequently occur. [NIH]
Encephalopathy: A disorder of the brain that can be caused by disease, injury, drugs, or chemicals. [NIH] Endemic: Present or usually prevalent in a population or geographical area at all times; said of a disease or agent. Called also endemial. [EU] Endocarditis: Exudative and proliferative inflammatory alterations of the endocardium, characterized by the presence of vegetations on the surface of the endocardium or in the
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endocardium itself, and most commonly involving a heart valve, but sometimes affecting the inner lining of the cardiac chambers or the endocardium elsewhere. It may occur as a primary disorder or as a complication of or in association with another disease. [EU] Endocardium: The innermost layer of the heart, comprised of endothelial cells. [NIH] Endocytosis: Cellular uptake of extracellular materials within membrane-limited vacuoles or microvesicles. Endosomes play a central role in endocytosis. [NIH] Endonucleases: Enzymes that catalyze the hydrolysis of the internal bonds and thereby the formation of polynucleotides or oligonucleotides from ribo- or deoxyribonucleotide chains. EC 3.1.-. [NIH] Endoscope: A thin, lighted tube used to look at tissues inside the body. [NIH] Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart. [NIH] Endothelium: A layer of epithelium that lines the heart, blood vessels (endothelium, vascular), lymph vessels (endothelium, lymphatic), and the serous cavities of the body. [NIH] Endothelium, Lymphatic: Unbroken cellular lining (intima) of the lymph vessels (e.g., the high endothelial lymphatic venules). It is more permeable than vascular endothelium, lacking selective absorption and functioning mainly to remove plasma proteins that have filtered through the capillaries into the tissue spaces. [NIH] Endothelium, Vascular: Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components from interstitium to lumen; this function has been most intensively studied in the blood capillaries. [NIH] Endothelium-derived: Small molecule that diffuses to the adjacent muscle layer and relaxes it. [NIH] Endotoxin: Toxin from cell walls of bacteria. [NIH] End-stage renal: Total chronic kidney failure. When the kidneys fail, the body retains fluid and harmful wastes build up. A person with ESRD needs treatment to replace the work of the failed kidneys. [NIH] Enhancers: Transcriptional element in the virus genome. [NIH] Enoxacin: An orally administered broad-spectrum fluoroquinolone antibacterial agent active against most gram-negative and gram-positive bacteria. Its clinical efficacy has been confirmed in a variety of systemic infections and particularly in urinary tract infections. The drug is well tolerated by adults, but should not be used in children and pregnant women. [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] Enterococcus: A genus of gram-positive, coccoid bacteria consisting of organisms causing variable hemolysis that are normal flora of the intestinal tract. Previously thought to be a member of the genus Streptococcus, it is now recognized as a separate genus. [NIH] Enteropeptidase: A specialized proteolytic enzyme secreted by intestinal cells. It converts trypsinogen into its active form trypsin by removing the N-terminal peptide. EC 3.4.21.9. [NIH]
Environmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health. [NIH]
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Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Eosinophils: Granular leukocytes with a nucleus that usually has two lobes connected by a slender thread of chromatin, and cytoplasm containing coarse, round granules that are uniform in size and stainable by eosin. [NIH] Epidemic: Occurring suddenly in numbers clearly in excess of normal expectancy; said especially of infectious diseases but applied also to any disease, injury, or other healthrelated event occurring in such outbreaks. [EU] Epidemiologic Studies: Studies designed to examine associations, commonly, hypothesized causal relations. They are usually concerned with identifying or measuring the effects of risk factors or exposures. The common types of analytic study are case-control studies, cohort studies, and cross-sectional studies. [NIH] Epidemiological: Relating to, or involving epidemiology. [EU] Epidermal: Pertaining to or resembling epidermis. Called also epidermic or epidermoid. [EU] 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] 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] Epistaxis: Bleeding from the nose. [NIH] Epithelial: Refers to the cells that line the internal and external surfaces of the body. [NIH] Epithelial Cells: Cells that line the inner and outer surfaces of the body. [NIH] Epithelium: One or more layers of epithelial cells, supported by the basal lamina, which covers the inner or outer surfaces of the body. [NIH] Epitope: A molecule or portion of a molecule capable of binding to the combining site of an antibody. For every given antigenic determinant, the body can construct a variety of antibody-combining sites, some of which fit almost perfectly, and others which barely fit. [NIH]
Erectile: The inability to get or maintain an erection for satisfactory sexual intercourse. Also called impotence. [NIH] Erythema: Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of causes. [NIH] Erythrocyte Indices: Quantification of size and cell hemoglobin content or concentration of the erythrocyte, usually derived from erythrocyte count, blood hemoglobin concentration, and hematocrit. Includes the mean cell volume (MCV), mean cell hemoglobin (MCH), and mean cell hemoglobin concentration (MCHC). Use also for cell diameter and thickness. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks
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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]
Estrogen: One of the two female sex hormones. [NIH] Ethanol: A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in alcoholic beverages. [NIH] Ether: One of a class of organic compounds in which any two organic radicals are attached directly to a single oxygen atom. [NIH] Evoke: The electric response recorded from the cerebral cortex after stimulation of a peripheral sense organ. [NIH] Exhaustion: The feeling of weariness of mind and body. [NIH] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Exotoxin: Toxic substance excreted by living bacterial cells. [NIH] Extensor: A muscle whose contraction tends to straighten a limb; the antagonist of a flexor. [NIH]
External-beam radiation: Radiation therapy that uses a machine to aim high-energy rays at the cancer. Also called external radiation. [NIH] Extracellular: Outside a cell or cells. [EU] Extracellular Matrix: A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. [NIH] Extracellular Space: Interstitial space between cells, occupied by fluid as well as amorphous and fibrous substances. [NIH] Extracorporeal: Situated or occurring outside the body. [EU] Eye Infections: Infection, moderate to severe, caused by bacteria, fungi, or viruses, which occurs either on the external surface of the eye or intraocularly with probable inflammation, visual impairment, or blindness. [NIH] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Fat: Total lipids including phospholipids. [NIH]
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Fathers: Male parents, human or animal. [NIH] Fatty acids: A major component of fats that are used by the body for energy and tissue development. [NIH] Febrile: Pertaining to or characterized by fever. [EU] 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] Fetal Development: Morphologic and physiologic growth and development of the mammalian embryo or fetus. [NIH] Fetal Monitoring: Physiologic or biochemical monitoring of the fetus. It is usually done during labor and may be performed in conjunction with the monitoring of uterine activity. It may also be performed prenatally as when the mother is undergoing surgery. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fibrin: A protein derived from fibrinogen in the presence of thrombin, which forms part of the blood clot. [NIH] Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [NIH] Fibronectin: An adhesive glycoprotein. One form circulates in plasma, acting as an opsonin; another is a cell-surface protein which mediates cellular adhesive interactions. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Fistulas: An abnormal passage from one hollow structure of the body to another, or from a hollow structure to the surface, formed by an abscess, disease process, incomplete closure of a wound, or by a congenital anomaly. [NIH] Fleroxacin: A third-generation fluoroquinolone derivative with a broad antimicrobial spectrum. The drug strongly inhibits the DNA-supercoiling activity of DNA gyrase which may account for its antibacterial activity. [NIH] Fluconazole: Triazole antifungal agent that is used to treat oropharyngeal candidiasis and cryptococcal meningitis in AIDS. [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 Antibody Technique: Test for tissue antigen using either a direct method by conjugation of antibody with fluorescent dye or an indirect method by formation of antigenantibody complex which is then labeled with fluorescein-conjugated anti-immunoglobulin antibody. The tissue is then examined by fluorescence microscopy. [NIH] Fluorine: A nonmetallic, diatomic gas that is a trace element and member of the halogen family. It is used in dentistry as flouride to prevent dental caries. [NIH] Fluoroimmunoassay: The use of fluorescence spectrometry to obtain quantitative results for the fluorescent antibody technique. One advantage over the other methods (e.g., radioimmunoassay) is its extreme sensitivity, with a detection limit on the order of tenths of microgram/liter. [NIH] Folate: A B-complex vitamin that is being studied as a cancer prevention agent. Also called
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folic acid. [NIH] Fold: A plication or doubling of various parts of the body. [NIH] Folic Acid: N-(4-(((2-Amino-1,4-dihydro-4-oxo-6-pteridinyl)methyl)amino)benzoyl)-Lglutamic acid. A member of the vitamin B family that stimulates the hematopoietic system. It is present in the liver and kidney and is found in mushrooms, spinach, yeast, green leaves, and grasses. Folic acid is used in the treatment and prevention of folate deficiencies and megaloblastic anemia. [NIH] Foot Ulcer: Lesion on the surface of the skin of the foot, usually accompanied by inflammation. The lesion may become infected or necrotic and is frequently associated with diabetes or leprosy. [NIH] Foramen: A natural hole of perforation, especially one in a bone. [NIH] Fractionation: Dividing the total dose of radiation therapy into several smaller, equal doses delivered over a period of several days. [NIH] Friction: Surface resistance to the relative motion of one body against the rubbing, sliding, rolling, or flowing of another with which it is in contact. [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] Fungicides, Industrial: Chemicals that kill or inhibit the growth of fungi in agricultural applications, on wood, plastics, or other materials, in swimming pools, etc. [NIH] Fungistatic: Inhibiting the growth of fungi. [EU] 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] Gallate: Antioxidant present in tea. [NIH] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Gamma Rays: Very powerful and penetrating, high-energy electromagnetic radiation of shorter wavelength than that of x-rays. They are emitted by a decaying nucleus, usually between 0.01 and 10 MeV. They are also called nuclear x-rays. [NIH] Gamma-interferon: Interferon produced by T-lymphocytes in response to various mitogens and antigens. Gamma interferon appears to have potent antineoplastic, immunoregulatory and antiviral activity. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] Gangliosides: 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] 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]
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Gas exchange: Primary function of the lungs; transfer of oxygen from inhaled air into the blood and of carbon dioxide from the blood into the lungs. [NIH] Gastric: Having to do with the stomach. [NIH] Gastric Acid: Hydrochloric acid present in gastric juice. [NIH] Gastric Juices: Liquids produced in the stomach to help break down food and kill bacteria. [NIH]
Gastric Mucosa: Surface epithelium in the stomach that invaginates into the lamina propria, forming gastric pits. Tubular glands, characteristic of each region of the stomach (cardiac, gastric, and pyloric), empty into the gastric pits. The gastric mucosa is made up of several different kinds of cells. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]
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 Hemorrhage: Bleeding in the gastrointestinal tract. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] Gelatin: A product formed from skin, white connective tissue, or bone collagen. It is used as a protein food adjuvant, plasma substitute, hemostatic, suspending agent in pharmaceutical preparations, and in the manufacturing of capsules and suppositories. [NIH] Gelatinase A: A secreted endopeptidase homologous with interstitial collagenase, but which possesses an additional fibronectin-like domain. EC 3.4.24.24. [NIH] Gels: Colloids with a solid continuous phase and liquid as the dispersed phase; gels may be unstable when, due to temperature or other cause, the solid phase liquifies; the resulting colloid is called a sol. [NIH] Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]
Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Gene Targeting: The integration of exogenous DNA into the genome of an organism at sites where its expression can be suitably controlled. This integration occurs as a result of homologous recombination. [NIH] 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,
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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] Genomics: The systematic study of the complete DNA sequences (genome) of organisms. [NIH]
Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Germ Cells: The reproductive cells in multicellular organisms. [NIH] Germfree: Free from all living micro-organisms. [NIH] Gestation: The period of development of the young in viviparous animals, from the time of fertilization of the ovum until birth. [EU] Gland: An organ that produces and releases one or more substances for use in the body. Some glands produce fluids that affect tissues or organs. Others produce hormones or participate in blood production. [NIH] Glanders: A contagious disease of horses that can be transmitted to humans. It is caused by Pseudomonas mallei and characterized by ulceration of the respiratory mucosa and an eruption of nodules on the skin. [NIH] Glomerular: Pertaining to or of the nature of a glomerulus, especially a renal glomerulus. [EU]
Glomeruli: Plural of glomerulus. [NIH] Glomerulonephritis: Glomerular disease characterized by an inflammatory reaction, with leukocyte infiltration and cellular proliferation of the glomeruli, or that appears to be the result of immune glomerular injury. [NIH] Glomerulus: A tiny set of looping blood vessels in the nephron where blood is filtered in the kidney. [NIH] Glottis: The vocal apparatus of the larynx, consisting of the true vocal cords (plica vocalis) and the opening between them (rima glottidis). [NIH] Glucocorticoids: A group of corticosteroids that affect carbohydrate metabolism (gluconeogenesis, liver glycogen deposition, elevation of blood sugar), inhibit corticotropin secretion, and possess pronounced anti-inflammatory activity. They also play a role in fat and protein metabolism, maintenance of arterial blood pressure, alteration of the connective tissue response to injury, reduction in the number of circulating lymphocytes, and functioning of the central nervous system. [NIH] Glucose: D-Glucose. A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. [NIH] Glucose Intolerance: A pathological state in which the fasting plasma glucose level is less than 140 mg per deciliter and the 30-, 60-, or 90-minute plasma glucose concentration following a glucose tolerance test exceeds 200 mg per deciliter. This condition is seen frequently in diabetes mellitus but also occurs with other diseases. [NIH]
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Glucuronic Acid: Derivatives of uronic acid found throughout the plant and animal kingdoms. They detoxify drugs and toxins by conjugating with them to form glucuronides in the liver which are more water-soluble metabolites that can be easily eliminated from the body. [NIH] 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] Glycogen: A sugar stored in the liver and muscles. It releases glucose into the blood when cells need it for energy. Glycogen is the chief source of stored fuel in the body. [NIH] Glycopeptides: Proteins which contain carbohydrate groups attached covalently to the polypeptide chain. The protein moiety is the predominant group with the carbohydrate making up only a small percentage of the total weight. [NIH] Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Glycosaminoglycan: A type of long, unbranched polysaccharide molecule. Glycosaminoglycans are major structural components of cartilage and are also found in the cornea of the eye. [NIH] Glycoside: Any compound that contains a carbohydrate molecule (sugar), particularly any such natural product in plants, convertible, by hydrolytic cleavage, into sugar and a nonsugar component (aglycone), and named specifically for the sugar contained, as glucoside (glucose), pentoside (pentose), fructoside (fructose) etc. [EU] Glycosidic: Formed by elimination of water between the anomeric hydroxyl of one sugar and a hydroxyl of another sugar molecule. [NIH] Glycosylation: The chemical or biochemical addition of carbohydrate or glycosyl groups to other chemicals, especially peptides or proteins. Glycosyl transferases are used in this biochemical reaction. [NIH] Gonadal: Pertaining to a gonad. [EU] Gonorrhea: Acute infectious disease characterized by primary invasion of the urogenital tract. The etiologic agent, Neisseria gonorrhoeae, was isolated by Neisser in 1879. [NIH] Gonorrhoea: Infection due to Neisseria gonorrhoeae transmitted sexually in most cases, but also by contact with infected exudates in neonatal children at birth, or by infants in households with infected inhabitants. It is marked in males by urethritis with pain and purulent discharge, but is commonly asymptomatic in females, although it may extend to produce suppurative salpingitis, oophoritis, tubo-ovarian abscess, and peritonitis. Bacteraemia occurs in both sexes, resulting in cutaneous lesions, arthritis, and rarely meningitis or endocarditis. Formerly called blennorrhagia and blennorrhoea. [EU] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to
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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-Negative Bacteria: Bacteria which lose crystal violet stain but are stained pink when treated by Gram's method. [NIH] Gram-Negative Bacterial Infections: Infections caused by bacteria that show up as pink (negative) when treated by the gram-staining method. [NIH] Gram-positive: Retaining the stain or resisting decolorization by alcohol in Gram's method of staining, a primary characteristic of bacteria whose cell wall is composed of a thick layer of peptidologlycan with attached teichoic acids. [EU] Gram-Positive Bacteria: Bacteria which retain the crystal violet stain when treated by Gram's method. [NIH] Gram-Positive Bacterial Infections: Infections caused by bacteria that retain the crystal violet stain (positive) when treated by the gram-staining 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] Granulocytopenia: A deficiency in the number of granulocytes, a type of white blood cell. [NIH]
Granuloma: A relatively small nodular inflammatory lesion containing grouped mononuclear phagocytes, caused by infectious and noninfectious agents. [NIH] Granuloma Inguinale: Anogenital ulcers caused by Calymmatobacterium granulomatis as distinguished from lymphogranuloma inguinale (see lymphogranuloma venereum) caused by Chlamydia trachomatis. Diagnosis is made by demonstration of typical intracellular Donovan bodies in crushed-tissue smears. [NIH] Granulomatous Disease, Chronic: A recessive X-linked defect of leukocyte function in which phagocytic cells ingest but fail to digest bacteria, resulting in recurring bacterial infections with granuloma formation. [NIH] Grasses: A large family, Gramineae, of narrow-leaved herbaceous monocots. Many grasses produce highly allergenic pollens and are hosts to cattle parasites and toxic fungi. [NIH] Growth: The progressive development of a living being or part of an organism from its earliest stage to maturity. [NIH] Guanidine: A strong organic base existing primarily as guanidium ions at physiological pH. It is found in the urine as a normal product of protein metabolism. It is also used in laboratory research as a protein denaturant. (From Martindale, the Extra Pharmacopoeia, 30th ed and Merck Index, 12th ed) It is also used in the treatment of myasthenia and as a fluorescent probe in HPLC. [NIH] Guanylate Cyclase: An enzyme that catalyzes the conversion of GTP to 3',5'-cyclic GMP and pyrophosphate. It also acts on ITP and dGTP. (From Enzyme Nomenclature, 1992) EC 4.6.1.2. [NIH] Gyrase: An enzyme that causes negative supercoiling of E. coli DNA during replication. [NIH]
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Habitat: An area considered in terms of its environment, particularly as this determines the type and quality of the vegetation the area can carry. [NIH] Haematological: Relating to haematology, that is that branch of medical science which treats of the morphology of the blood and blood-forming tissues. [EU] Haematology: The science of the blood, its nature, functions, and diseases. [NIH] Haemophilus: A genus of Pasteurellaceae that consists of several species occurring in animals and humans. Its organisms are described as gram-negative, facultatively anaerobic, coccobacillus or rod-shaped, and nonmotile. [NIH] Hair follicles: Shafts or openings on the surface of the skin through which hair grows. [NIH] Half-Life: The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity. [NIH] 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 response. [NIH] Headache: Pain in the cranial region that may occur as an isolated and benign symptom or as a manifestation of a wide variety of conditions including subarachnoid hemorrhage; craniocerebral trauma; central nervous system infections; intracranial hypertension; and other disorders. In general, recurrent headaches that are not associated with a primary disease process are referred to as headache disorders (e.g., migraine). [NIH] Headache Disorders: Common conditions characterized by persistent or recurrent headaches. Headache syndrome classification systems may be based on etiology (e.g., vascular headache, post-traumatic headaches, etc.), temporal pattern (e.g., cluster headache, paroxysmal hemicrania, etc.), and precipitating factors (e.g., cough headache). [NIH] Health Care Costs: The actual costs of providing services related to the delivery of health care, including the costs of procedures, therapies, and medications. It is differentiated from health expenditures, which refers to the amount of money paid for the services, and from fees, which refers to the amount charged, regardless of cost. [NIH] Health Expenditures: The amounts spent by individuals, groups, nations, or private or public organizations for total health care and/or its various components. These amounts may or may not be equivalent to the actual costs (health care costs) and may or may not be shared among the patient, insurers, and/or employers. [NIH] Heart attack: A seizure of weak or abnormal functioning of the heart. [NIH] Hematocrit: Measurement of the volume of packed red cells in a blood specimen by centrifugation. The procedure is performed using a tube with graduated markings or with automated blood cell counters. It is used as an indicator of erythrocyte status in disease. For example, anemia shows a low hematocrit, polycythemia, high values. [NIH] Hematologic malignancies: Cancers of the blood or bone marrow, including leukemia and lymphoma. Also called hematologic cancers. [NIH] Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. [NIH] Hemodialysis: The use of a machine to clean wastes from the blood after the kidneys have
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failed. The blood travels through tubes to a dialyzer, which removes wastes and extra fluid. The cleaned blood then flows through another set of tubes back into the body. [NIH] Hemoglobin: One of the fractions of glycosylated hemoglobin A1c. Glycosylated hemoglobin is formed when linkages of glucose and related monosaccharides bind to hemoglobin A and its concentration represents the average blood glucose level over the previous several weeks. HbA1c levels are used as a measure of long-term control of plasma glucose (normal, 4 to 6 percent). In controlled diabetes mellitus, the concentration of glycosylated hemoglobin A is within the normal range, but in uncontrolled cases the level may be 3 to 4 times the normal conentration. Generally, complications are substantially lower among patients with Hb levels of 7 percent or less than in patients with HbA1c levels of 9 percent or more. [NIH] Hemolymph: The blood/lymphlike nutrient fluid of some invertebrates. [NIH] Hemolysis: The destruction of erythrocytes by many different causal agents such as antibodies, bacteria, chemicals, temperature, and changes in tonicity. [NIH] Hemolytic: A disease that affects the blood and blood vessels. It destroys red blood cells, cells that cause the blood to clot, and the lining of blood vessels. HUS is often caused by the Escherichia coli bacterium in contaminated food. People with HUS may develop acute renal failure. [NIH] Hemolytic-Uremic Syndrome: Syndrome of hemolytic anemia, thrombocytopenia, and 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] Hemorrhoids: Varicosities of the hemorrhoidal venous plexuses. [NIH] Heparin: Heparinic acid. A highly acidic mucopolysaccharide formed of equal parts of sulfated D-glucosamine and D-glucuronic acid with sulfaminic bridges. The molecular weight ranges from six to twenty thousand. Heparin occurs in and is obtained from liver, lung, mast cells, etc., of vertebrates. Its function is unknown, but it is used to prevent blood clotting in vivo and vitro, in the form of many different salts. [NIH] Hepatic: Refers to the liver. [NIH] Hepatic Encephalopathy: A condition that may cause loss of consciousness and coma. It is usually the result of advanced liver disease. Also called hepatic coma. [NIH] Hepatitis: Inflammation of the liver and liver disease involving degenerative or necrotic alterations of hepatocytes. [NIH] Hepatitis Viruses: Any of the viruses that cause inflammation of the liver. They include both DNA and RNA viruses as well viruses from humans and animals. [NIH] 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 virus: A member of the herpes family of viruses. [NIH] Herpes Zoster: Acute vesicular inflammation. [NIH]
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Heterogeneity: The property of one or more samples or populations which implies that they are not identical in respect of some or all of their parameters, e. g. heterogeneity of variance. [NIH]
Heterotrophic: Pertaining to organisms that are consumers and dependent on other organisms for their source of energy (food). [NIH] Histamine: 1H-Imidazole-4-ethanamine. A depressor amine derived by enzymatic decarboxylation of histidine. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter. [NIH] Histidine: An essential amino acid important in a number of metabolic processes. It is required for the production of histamine. [NIH] Homogeneous: Consisting of or composed of similar elements or ingredients; of a uniform quality throughout. [EU] Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] 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] Human papillomavirus: HPV. A virus that causes abnormal tissue growth (warts) and is often associated with some types of cancer. [NIH] Humoral: Of, relating to, proceeding from, or involving a bodily humour - now often used of endocrine factors as opposed to neural or somatic. [EU] Humour: 1. A normal functioning fluid or semifluid of the body (as the blood, lymph or bile) especially of vertebrates. 2. A secretion that is itself an excitant of activity (as certain hormones). [EU] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [NIH] Hybridization: The genetic process of crossbreeding to produce a hybrid. Hybrid nucleic acids can be formed by nucleic acid hybridization of DNA and RNA molecules. Protein hybridization allows for hybrid proteins to be formed from polypeptide chains. [NIH] 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] Hydrolases: Any member of the class of enzymes that catalyze the cleavage of the substrate and the addition of water to the resulting molecules, e.g., esterases, glycosidases (glycoside hydrolases), lipases, nucleotidases, peptidases (peptide hydrolases), and phosphatases (phosphoric monoester hydrolases). EC 3. [NIH] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hydronephrosis: Abnormal enlargement of a kidney, which may be caused by blockage of the ureter (such as by a kidney stone) or chronic kidney disease that prevents urine from draining into the bladder. [NIH] Hydrophobic: Not readily absorbing water, or being adversely affected by water, as a
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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] Hyperaemia: An excess of blood in a part; engorgement. [EU] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hypotension: Abnormally low blood pressure. [NIH] Id: The part of the personality structure which harbors the unconscious instinctive desires and strivings of the individual. [NIH] Imidazole: C3H4N2. The ring is present in polybenzimidazoles. [NIH] Imipenem: Semisynthetic thienamycin that has a wide spectrum of antibacterial activity against gram-negative and gram-positive aerobic and anaerobic bacteria, including many multiresistant strains. It is stable to beta-lactamases. Clinical studies have demonstrated high efficacy in the treatment of infections of various body systems. Its effectiveness is enhanced when it is administered in combination with cilastatin, a renal dipeptidase inhibitor. [NIH] Immersion: The placing of a body or a part thereof into a liquid. [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] Immunocompromised: Having a weakened immune system caused by certain diseases or treatments. [NIH] Immunocompromised Host: A human or animal whose immunologic mechanism is deficient because of an immunodeficiency disorder or other disease or as the result of the administration of immunosuppressive drugs or radiation. [NIH] Immunodeficiency: The decreased ability of the body to fight infection and disease. [NIH] Immunodeficiency syndrome: The inability of the body to produce an immune response. [NIH]
Immunofluorescence: A technique for identifying molecules present on the surfaces of cells or in tissues using a highly fluorescent substance coupled to a specific antibody. [NIH]
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Immunogenic: Producing immunity; evoking an immune response. [EU] Immunoglobulin: A protein that acts as an antibody. [NIH] Immunologic: The ability of the antibody-forming system to recall a previous experience with an antigen and to respond to a second exposure with the prompt production of large amounts of antibody. [NIH] Immunology: The study of the body's immune system. [NIH] Immunomodulator: New type of drugs mainly using biotechnological methods. Treatment of cancer. [NIH] Immunosuppressant: An agent capable of suppressing immune responses. [EU] Immunosuppressive: Describes the ability to lower immune system responses. [NIH] Immunosuppressive Agents: Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of suppressor T-cell populations or by inhibiting the activation of helper cells. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of interleukins and other cytokines are emerging. [NIH] Immunosuppressive therapy: Therapy used to decrease the body's immune response, such as drugs given to prevent transplant rejection. [NIH] Immunotherapy: Manipulation of the host's immune system in treatment of disease. It includes both active and passive immunization as well as immunosuppressive therapy to prevent graft rejection. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] Implant radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called [NIH] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incision: A cut made in the body during surgery. [NIH] Incontinence: Inability to control the flow of urine from the bladder (urinary incontinence) or the escape of stool from the rectum (fecal incontinence). [NIH] Incubated: Grown in the laboratory under controlled conditions. (For instance, white blood cells can be grown in special conditions so that they attack specific cancer cells when returned to the body.) [NIH] Incubation: The development of an infectious disease from the entrance of the pathogen to the appearance of clinical symptoms. [EU] Incubation period: The period of time likely to elapse between exposure to the agent of the disease and the onset of clinical symptoms. [NIH] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU] 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] Induction therapy: Treatment designed to be used as a first step toward shrinking the cancer and in evaluating response to drugs and other agents. Induction therapy is followed by additional therapy to eliminate whatever cancer remains. [NIH]
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Infancy: The period of complete dependency prior to the acquisition of competence in walking, talking, and self-feeding. [NIH] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]
Infection Control: Programs of disease surveillance, generally within health care facilities, designed to investigate, prevent, and control the spread of infections and their causative microorganisms. [NIH] 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] Infiltration: The diffusion or accumulation in a tissue or cells of substances not normal to it or in amounts of the normal. Also, the material so accumulated. [EU] Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH] 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] Infusion: A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion. [NIH] Inguinal: Pertaining to the inguen, or groin. [EU] Inhalation: The drawing of air or other substances into the lungs. [EU] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Initiator: A chemically reactive substance which may cause cell changes if ingested, inhaled or absorbed into the body; the substance may thus initiate a carcinogenic process. [NIH] Inlay: In dentistry, a filling first made to correspond with the form of a dental cavity and then cemented into the cavity. [NIH] Inner ear: The labyrinth, comprising the vestibule, cochlea, and semicircular canals. [NIH] Inorganic: Pertaining to substances not of organic origin. [EU] Inositol: An isomer of glucose that has traditionally been considered to be a B vitamin although it has an uncertain status as a vitamin and a deficiency syndrome has not been identified in man. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1379) Inositol phospholipids are important in signal transduction. [NIH] Inpatients: Persons admitted to health facilities which provide board and room, for the
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purpose of observation, care, diagnosis or treatment. [NIH] Insecticides: Pesticides designed to control insects that are harmful to man. The insects may be directly harmful, as those acting as disease vectors, or indirectly harmful, as destroyers of crops, food products, or textile fabrics. [NIH] Insight: The capacity to understand one's own motives, to be aware of one's own psychodynamics, to appreciate the meaning of symbolic behavior. [NIH] Instillation: . [EU] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose. It is also an important regulator of protein and lipid metabolism. Insulin is used as a drug to control insulin-dependent diabetes mellitus. [NIH] Intensive Care: Advanced and highly specialized care provided to medical or surgical patients whose conditions are life-threatening and require comprehensive care and constant monitoring. It is usually administered in specially equipped units of a health care facility. [NIH]
Intensive Care Units: Hospital units providing continuous surveillance and care to acutely ill patients. [NIH] Interferon: A biological response modifier (a substance that can improve the body's natural response to disease). Interferons interfere with the division of cancer cells and can slow tumor growth. There are several types of interferons, including interferon-alpha, -beta, and gamma. These substances are normally produced by the body. They are also made in the laboratory for use in treating cancer and other diseases. [NIH] Interferon-alpha: One of the type I interferons produced by peripheral blood leukocytes or lymphoblastoid cells when exposed to live or inactivated virus, double-stranded RNA, or bacterial products. It is the major interferon produced by virus-induced leukocyte cultures and, in addition to its pronounced antiviral activity, it causes activation of NK cells. [NIH] Interleukin-1: A soluble factor produced by monocytes, macrophages, and other cells which activates T-lymphocytes and potentiates their response to mitogens or antigens. IL-1 consists of two distinct forms, IL-1 alpha and IL-1 beta which perform the same functions but are distinct proteins. The biological effects of IL-1 include the ability to replace macrophage requirements for T-cell activation. The factor is distinct from interleukin-2. [NIH] Interleukin-12: A heterodimeric cytokine that stimulates the production of interferon gamma from T-cells and natural killer cells, and also induces differentiation of Th1 helper cells. It is an initiator of cell-mediated immunity. [NIH] Interleukin-2: Chemical mediator produced by activated T lymphocytes and which regulates the proliferation of T cells, as well as playing a role in the regulation of NK cell activity. [NIH] Interleukin-8: A cytokine that activates neutrophils and attracts neutrophils and Tlymphocytes. It is released by several cell types including monocytes, macrophages, Tlymphocytes, fibroblasts, endothelial cells, and keratinocytes by an inflammatory stimulus. IL-8 is a member of the beta-thromboglobulin superfamily and structurally related to platelet factor 4. [NIH] Interleukins: Soluble factors which stimulate growth-related activities of leukocytes as well as other cell types. They enhance cell proliferation and differentiation, DNA synthesis, secretion of other biologically active molecules and responses to immune and inflammatory stimuli. [NIH] Internal Medicine: A medical specialty concerned with the diagnosis and treatment of
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diseases of the internal organ systems of adults. [NIH] Internal radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called brachytherapy, implant radiation, or interstitial radiation therapy. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Interstitial Collagenase: A member of the metalloproteinase family of enzymes that is principally responsible for cleaving fibrillar collagen. It can degrade interstitial collagens, types I, II and III. EC 3.4.24.7. [NIH] Intestinal: Having to do with the intestines. [NIH] Intestine: A long, tube-shaped organ in the abdomen that completes the process of digestion. There is both a large intestine and a small intestine. Also called the bowel. [NIH] Intoxication: Poisoning, the state of being poisoned. [EU] Intracellular: Inside a cell. [NIH] Intracellular Membranes: Membranes of subcellular structures. [NIH] Intramuscular: IM. Within or into muscle. [NIH] Intraocular: Within the eye. [EU] Intravascular: Within a vessel or vessels. [EU] Intravenous: IV. Into a vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Introns: Non-coding, intervening sequences of DNA that are transcribed, but are removed from within the primary gene transcript and rapidly degraded during maturation of messenger RNA. Most genes in the nuclei of eukaryotes contain introns, as do mitochondrial and chloroplast genes. [NIH] Introspection: Examination by a person of his own feelings, thoughts, and mental state. [NIH]
Intubation: Introduction of a tube into a hollow organ to restore or maintain patency if obstructed. It is differentiated from catheterization in that the insertion of a catheter is usually performed for the introducing or withdrawing of fluids from the body. [NIH] Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]
Invertebrates: Animals that have no spinal column. [NIH] Involuntary: Reaction occurring without intention or volition. [NIH] Ionizing: Radiation comprising charged particles, e. g. electrons, protons, alpha-particles, etc., having sufficient kinetic energy to produce ionization by collision. [NIH] Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as cations; those with a negative charge are anions. [NIH] Iris: The most anterior portion of the uveal layer, separating the anterior chamber from the posterior. It consists of two layers - the stroma and the pigmented epithelium. Color of the iris depends on the amount of melanin in the stroma on reflection from the pigmented epithelium. [NIH] Irritable Bowel Syndrome: A disorder that comes and goes. Nerves that control the muscles in the GI tract are too active. The GI tract becomes sensitive to food, stool, gas, and stress. Causes abdominal pain, bloating, and constipation or diarrhea. Also called spastic colon or
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mucous colitis. [NIH] 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] Ischemic Colitis: Decreased blood flow to the colon. Causes fever, pain, and bloody diarrhea. [NIH] Isoprenoids: Molecule that might anchor G protein to the cell membrane as it is hydrophobic. [NIH] Isopropyl: A gene mutation inducer. [NIH] Itraconazole: An antifungal agent that has been used in the treatment of histoplasmosis, blastomycosis, cryptococcal meningitis, and aspergillosis. [NIH] Joint: The point of contact between elements of an animal skeleton with the parts that surround and support it. [NIH] Kanamycin: Antibiotic complex produced by Streptomyces kanamyceticus from Japanese soil. Comprises 3 components: kanamycin A, the major component, and kanamycins B and C, the minor components. [NIH] Kb: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [NIH] Keloid: A sharply elevated, irregularly shaped, progressively enlarging scar resulting from formation of excessive amounts of collagen in the dermis during connective tissue repair. It is differentiated from a hypertrophic scar (cicatrix, hypertrophic) in that the former does not spread to surrounding tissues. [NIH] Keratinocytes: Epidermal cells which synthesize keratin and undergo characteristic changes as they move upward from the basal layers of the epidermis to the cornified (horny) layer of the skin. Successive stages of differentiation of the keratinocytes forming the epidermal layers are basal cell, spinous or prickle cell, and the granular cell. [NIH] Keratitis: Inflammation of the cornea. [NIH] Keratolytic: An agent that promotes keratolysis. [EU] Ketoconazole: Broad spectrum antifungal agent used for long periods at high doses, especially in immunosuppressed patients. [NIH] 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 Pelvis: The flattened, funnel-shaped expansion connecting the ureter to the kidney calices. [NIH] Kidney stone: A stone that develops from crystals that form in urine and build up on the inner surfaces of the kidney, in the renal pelvis, or in the ureters. [NIH] Kinetics: The study of rate dynamics in chemical or physical systems. [NIH] Labile: 1. Gliding; moving from point to point over the surface; unstable; fluctuating. 2. Chemically unstable. [EU] Lacerations: Torn, ragged, mangled wounds. [NIH] Lactobacillus: A genus of gram-positive, microaerophilic, rod-shaped bacteria occurring
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widely in nature. Its species are also part of the many normal flora of the mouth, intestinal tract, and vagina of many mammals, including humans. Pathogenicity from this genus is rare. [NIH] Lamivudine: A reverse transcriptase inhibitor and zalcitabine analog in which a sulfur atom replaces the 3' carbon of the pentose ring. It is used to treat HIV disease. [NIH] Large Intestine: The part of the intestine that goes from the cecum to the rectum. The large intestine absorbs water from stool and changes it from a liquid to a solid form. The large intestine is 5 feet long and includes the appendix, cecum, colon, and rectum. Also called colon. [NIH] Larynx: An irregularly shaped, musculocartilaginous tubular structure, lined with mucous membrane, located at the top of the trachea and below the root of the tongue and the hyoid bone. It is the essential sphincter guarding the entrance into the trachea and functioning secondarily as the organ of voice. [NIH] Laser Surgery: The use of a laser either to vaporize surface lesions or to make bloodless cuts in tissue. It does not include the coagulation of tissue by laser. [NIH] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH] Lavage: A cleaning of the stomach and colon. Uses a special drink and enemas. [NIH] Lectin: A complex molecule that has both protein and sugars. Lectins are able to bind to the outside of a cell and cause biochemical changes in it. Lectins are made by both animals and plants. [NIH] 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] Leprosy: A chronic granulomatous infection caused by Mycobacterium leprae. The granulomatous lesions are manifested in the skin, the mucous membranes, and the peripheral nerves. Two polar or principal types are lepromatous and tuberculoid. [NIH] Leptospirosis: Infections with bacteria of the genus Leptospira. [NIH] Lesion: An area of abnormal tissue change. [NIH] Lethal: Deadly, fatal. [EU] Leucocyte: All the white cells of the blood and their precursors (myeloid cell series, lymphoid cell series) but commonly used to indicate granulocytes exclusive of lymphocytes. [NIH]
Leukaemia: An acute or chronic disease of unknown cause in man and other warm-blooded animals that involves the blood-forming organs, is characterized by an abnormal increase in the number of leucocytes in the tissues of the body with or without a corresponding increase of those in the circulating blood, and is classified according of the type leucocyte most prominently involved. [EU] Leukemia: Cancer of blood-forming tissue. [NIH] Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [NIH] Leukoplakia: A white patch that may develop on mucous membranes such as the cheek, gums, or tongue and may become cancerous. [NIH] Leukotrienes: A family of biologically active compounds derived from arachidonic acid by
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oxidative metabolism through the 5-lipoxygenase pathway. They participate in host defense reactions and pathophysiological conditions such as immediate hypersensitivity and inflammation. They have potent actions on many essential organs and systems, including the cardiovascular, pulmonary, and central nervous system as well as the gastrointestinal tract and the immune system. [NIH] Library Services: Services offered to the library user. They include reference and circulation. [NIH]
Life cycle: The successive stages through which an organism passes from fertilized ovum or spore to the fertilized ovum or spore of the next generation. [NIH] Life Expectancy: A figure representing the number of years, based on known statistics, to which any person of a given age may reasonably expect to live. [NIH] Ligament: A band of fibrous tissue that connects bones or cartilages, serving to support and strengthen joints. [EU] Ligands: A RNA simulation method developed by the MIT. [NIH] Lipid: Fat. [NIH] Lipid Bilayers: Layers of lipid molecules which are two molecules thick. Bilayer systems are frequently studied as models of biological membranes. [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] Lipoxygenase: An enzyme of the oxidoreductase class that catalyzes reactions between linoleate and other fatty acids and oxygen to form hydroperoxy-fatty acid derivatives. Related enzymes in this class include the arachidonate lipoxygenases, arachidonate 5lipoxygenase, arachidonate 12-lipoxygenase, and arachidonate 15-lipoxygenase. EC 1.13.11.12. [NIH] Lithotripsy: The destruction of a calculus of the kidney, ureter, bladder, or gallbladder by physical forces, including crushing with a lithotriptor through a catheter. Focused percutaneous ultrasound and focused hydraulic shock waves may be used without surgery. Lithotripsy does not include the dissolving of stones by acids or litholysis. Lithotripsy by laser is laser lithotripsy. [NIH] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Liver scan: An image of the liver created on a computer screen or on film. A radioactive substance is injected into a blood vessel and travels through the bloodstream. It collects in the liver, especially in abnormal areas, and can be detected by the scanner. [NIH] Liver Transplantation: The transference of a part of or an entire liver from one human or animal to another. [NIH] Localization: The process of determining or marking the location or site of a lesion or disease. May also refer to the process of keeping a lesion or disease in a specific location or site. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Locomotion: Movement or the ability to move from one place or another. It can refer to humans, vertebrate or invertebrate animals, and microorganisms. [NIH]
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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] Lubricants: Oily or slippery substances. [NIH] Lubrication: The application of a substance to diminish friction between two surfaces. It may refer to oils, greases, and similar substances for the lubrication of medical equipment but it can be used for the application of substances to tissue to reduce friction, such as lotions for skin and vaginal lubricants. [NIH] Luminol: 5-Amino-2,3-dihydro-1,4-phthalazinedione. Substance that emits light on oxidation. It is used in chemical determinations. [NIH] Lupus: A form of cutaneous tuberculosis. It is seen predominantly in women and typically involves the nasal, buccal, and conjunctival mucosa. [NIH] Lupus Nephritis: Glomerulonephritis associated with systemic lupus erythematosus. It is classified into four histologic types: mesangial, focal, diffuse, and membranous. [NIH] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Lymph node: A rounded mass of lymphatic tissue that is surrounded by a capsule of connective tissue. Also known as a lymph gland. Lymph nodes are spread out along lymphatic vessels and contain many lymphocytes, which filter the lymphatic fluid (lymph). [NIH]
Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] Lymphatic system: The tissues and organs that produce, store, and carry white blood cells that fight infection and other diseases. This system includes the bone marrow, spleen, thymus, lymph nodes and a network of thin tubes that carry lymph and white blood cells. These tubes branch, like blood vessels, into all the tissues of the body. [NIH] Lymphoblastic: One of the most aggressive types of non-Hodgkin lymphoma. [NIH] Lymphoblasts: Interferon produced predominantly by leucocyte cells. [NIH] Lymphocyte: A white blood cell. Lymphocytes have a number of roles in the immune system, including the production of antibodies and other substances that fight infection and diseases. [NIH] Lymphocyte Count: A count of the number of lymphocytes in the blood. [NIH] Lymphocytic: Referring to lymphocytes, a type of white blood cell. [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] Macrolides: A group of organic compounds that contain a macrocyclic lactone ring linked
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glycosidically to one or more sugar moieties. [NIH] Macrophage: A type of white blood cell that surrounds and kills microorganisms, removes dead cells, and stimulates the action of other immune system cells. [NIH] Magnetic Resonance Imaging: Non-invasive method of demonstrating internal anatomy based on the principle that atomic nuclei in a strong magnetic field absorb pulses of radiofrequency energy and emit them as radiowaves which can be reconstructed into computerized images. The concept includes proton spin tomographic techniques. [NIH] Major Histocompatibility Complex: The genetic region which contains the loci of genes which determine the structure of the serologically defined (SD) and lymphocyte-defined (LD) transplantation antigens, genes which control the structure of the immune responseassociated (Ia) antigens, the immune response (Ir) genes which control the ability of an animal to respond immunologically to antigenic stimuli, and genes which determine the structure and/or level of the first four components of complement. [NIH] Malacoplakia: The formation of soft patches on the mucous membrane of a hollow organ, such as the urogenital tract or digestive tract. [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] Mandible: The largest and strongest bone of the face constituting the lower jaw. It supports the lower teeth. [NIH] Manifest: Being the part or aspect of a phenomenon that is directly observable : concretely expressed in behaviour. [EU] 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] Mechanical ventilation: Use of a machine called a ventilator or respirator to improve the
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exchange of air between the lungs and the atmosphere. [NIH] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] Mediator: An object or substance by which something is mediated, such as (1) a structure of the nervous system that transmits impulses eliciting a specific response; (2) a chemical substance (transmitter substance) that induces activity in an excitable tissue, such as nerve or muscle; or (3) a substance released from cells as the result of the interaction of antigen with antibody or by the action of antigen with a sensitized lymphocyte. [EU] Medicament: A medicinal substance or agent. [EU] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Megaloblastic: A large abnormal red blood cell appearing in the blood in pernicious anaemia. [EU] Melanin: The substance that gives the skin its color. [NIH] Melioidosis: A disease of humans and animals that resembles glanders. It is caused by Burkholderia pseudomallei and may range from a dormant infection to a condition that causes multiple abscesses, pneumonia, and bacteremia. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors. [NIH] 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] Menstruation: The normal physiologic discharge through the vagina of blood and mucosal tissues from the nonpregnant uterus. [NIH] Mental Disorders: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. [NIH] Mental Health: The state wherein the person is well adjusted. [NIH] Mental Processes: Conceptual functions or thinking in all its forms. [NIH] Menthol: An alcohol produced from mint oils or prepared synthetically. [NIH] Mesenchymal: Refers to cells that develop into connective tissue, blood vessels, and lymphatic tissue. [NIH] Meta-Analysis: A quantitative method of combining the results of independent studies (usually drawn from the published literature) and synthesizing summaries and conclusions which may be used to evaluate therapeutic effectiveness, plan new studies, etc., with application chiefly in the areas of research and medicine. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] Metastasis: The spread of cancer from one part of the body to another. Tumors formed from cells that have spread are called "secondary tumors" and contain cells that are like those in the original (primary) tumor. The plural is metastases. [NIH] Metastatic: Having to do with metastasis, which is the spread of cancer from one part of the body to another. [NIH]
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Metastatic cancer: Cancer that has spread from the place in which it started to other parts of the body. [NIH] Methicillin Resistance: Non-susceptibility of a microbe to the action of methicillin, a semisynthetic penicillin derivative. [NIH] Methionine: A sulfur containing essential amino acid that is important in many body functions. It is a chelating agent for heavy metals. [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] Miconazole: An imidazole antifungal agent that is used topically and by intravenous infusion. [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] Microgram: A unit of mass (weight) of the metric system, being one-millionth of a gram (106 gm.) or one one-thousandth of a milligram (10-3 mg.). [EU] Microorganism: An organism that can be seen only through a microscope. Microorganisms include bacteria, protozoa, algae, and fungi. Although viruses are not considered living organisms, they are sometimes classified as microorganisms. [NIH] Micro-organism: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microscopy: The application of microscope magnification to the study of materials that cannot be properly seen by the unaided eye. [NIH] Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [NIH] Mineralocorticoids: A group of corticosteroids primarily associated with the regulation of water and electrolyte balance. This is accomplished through the effect on ion transport in renal tubules, resulting in retention of sodium and loss of potassium. Mineralocorticoid secretion is itself regulated by plasma volume, serum potassium, and angiotensin II. [NIH] Minocycline: A semisynthetic staphylococcus infections. [NIH]
antibiotic
effective
against
tetracycline-resistant
Miscarriage: Spontaneous expulsion of the products of pregnancy before the middle of the second trimester. [NIH] Mitochondria: Parts of a cell where aerobic production (also known as cell respiration) takes place. [NIH] Mitochondrial Swelling: Increase in volume of mitochondria due to an influx of fluid; it occurs in hypotonic solutions due to osmotic pressure and in isotonic solutions as a result of altered permeability of the membranes of respiring mitochondria. [NIH] 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] 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]
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Modeling: A treatment procedure whereby the therapist presents the target behavior which the learner is to imitate and make part of his repertoire. [NIH] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] Monitor: An apparatus which automatically records such physiological signs as respiration, pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH] Monoclonal: An antibody produced by culturing a single type of cell. It therefore consists of a single species of immunoglobulin molecules. [NIH] Monoclonal antibodies: Laboratory-produced substances that can locate and bind to cancer cells wherever they are in the body. Many monoclonal antibodies are used in cancer detection or therapy; each one recognizes a different protein on certain cancer cells. Monoclonal antibodies can be used alone, or they can be used to deliver drugs, toxins, or radioactive material directly to a tumor. [NIH] Monocyte: A type of white blood cell. [NIH] Mononuclear: A cell with one nucleus. [NIH] Monotherapy: A therapy which uses only one drug. [EU] 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] Motor Activity: The physical activity of an organism as a behavioral phenomenon. [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, 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] Mucositis: A complication of some cancer therapies in which the lining of the digestive system becomes inflamed. Often seen as sores in the mouth. [NIH] Mucus: The viscous secretion of mucous membranes. It contains mucin, white blood cells, water, inorganic salts, and exfoliated cells. [NIH] Multicenter study: A clinical trial that is carried out at more than one medical institution. [NIH]
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Multidrug resistance: Adaptation of tumor cells to anticancer drugs in ways that make the drugs less effective. [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] Myasthenia: Muscular debility; any constitutional anomaly of muscle. [EU] Mycobacteriophages: Viruses whose host is one or more Mycobacterium species. They include both temperate and virulent types. [NIH] Mycobacterium: A genus of gram-positive, aerobic bacteria. Most species are free-living in soil and water, but the major habitat for some is the diseased tissue of warm-blooded hosts. [NIH]
Mycoplasma: A genus of gram-negative, facultatively anaerobic bacteria bounded by a plasma membrane only. Its organisms are parasites and pathogens, found on the mucous membranes of humans, animals, and birds. [NIH] Mycosis: Any disease caused by a fungus. [EU] Mycotic: Pertaining to a mycosis; caused by fungi. [EU] Myocardial infarction: Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Myocarditis: Inflammation of the myocardium; inflammation of the muscular walls of the heart. [EU] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] 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] Myristate: Pharmacological activator of protein kinase C. [NIH] Nalidixic Acid: Synthetic antimicrobial agent used in urinary tract infections. It is active against gram-negative bacteria but has little activity against gram-positive organisms or Pseudomonas. [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 morphine-like actions. [EU] Nasal Mucosa: The mucous membrane lining the nasal cavity. [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
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pain, food poisoning, and various enteroviruses. [NIH] NCI: National Cancer Institute. NCI, part of the National Institutes of Health of the United States Department of Health and Human Services, is the federal government's principal agency for cancer research. NCI conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the NCI Web site at http://cancer.gov. [NIH] Nebramycin: A complex of antibiotic substances produced by Streptomyces tenebrarius. [NIH]
Nebulizer: A device used to turn liquid into a fine spray. [NIH] Necrosis: A pathological process caused by the progressive degradative action of enzymes that is generally associated with severe cellular trauma. It is characterized by mitochondrial swelling, nuclear flocculation, uncontrolled cell lysis, and ultimately cell death. [NIH] Need: A state of tension or dissatisfaction felt by an individual that impels him to action toward a goal he believes will satisfy the impulse. [NIH] 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] Neoplasia: Abnormal and uncontrolled cell growth. [NIH] 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] Nephritis: Inflammation of the kidney; a focal or diffuse proliferative or destructive process which may involve the glomerulus, tubule, or interstitial renal tissue. [EU] Nephropathy: Disease of the kidneys. [EU] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Netilmicin: Semisynthetic 1-N-ethyl derivative of sisomycin, an aminoglycoside antibiotic with action similar to gentamicin, but less ear and kidney toxicity. [NIH] Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU] Neural tube defects: These defects include problems stemming from fetal development of the spinal cord, spine, brain, and skull, and include birth defects such as spina bifida, anencephaly, and encephalocele. Neural tube defects occur early in pregnancy at about 4 to 6 weeks, usually before a woman knows she is pregnant. Many babies with neural tube defects have difficulty walking and with bladder and bowel control. [NIH] Neurologic: Having to do with nerves or the nervous system. [NIH] Neurologic Manifestations: Clinical signs and symptoms caused by nervous system injury or dysfunction. [NIH] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] Neutrons: Electrically neutral elementary particles found in all atomic nuclei except light hydrogen; the mass is equal to that of the proton and electron combined and they are
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unstable when isolated from the nucleus, undergoing beta decay. Slow, thermal, epithermal, and fast neutrons refer to the energy levels with which the neutrons are ejected from heavier nuclei during their decay. [NIH] Neutropenia: An abnormal decrease in the number of neutrophils, a type of white blood cell. [NIH] Neutrophil: A type of white blood cell. [NIH] Niche: The ultimate unit of the habitat, i. e. the specific spot occupied by an individual organism; by extension, the more or less specialized relationships existing between an organism, individual or synusia(e), and its environment. [NIH] Nitric Oxide: A free radical gas produced endogenously by a variety of mammalian cells. It is synthesized from arginine by a complex reaction, catalyzed by nitric oxide synthase. Nitric oxide is endothelium-derived relaxing factor. It is released by the vascular endothelium and mediates the relaxation induced by some vasodilators such as acetylcholine and bradykinin. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic guanylate cyclase and thus elevates intracellular levels of cyclic GMP. [NIH] Nitrogen: An element with the atomic symbol N, atomic number 7, and atomic weight 14. Nitrogen exists as a diatomic gas and makes up about 78% of the earth's atmosphere by volume. It is a constituent of proteins and nucleic acids and found in all living cells. [NIH] 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 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] Nucleotidases: A class of enzymes that catalyze the conversion of a nucleotide and water to a nucleoside and orthophosphate. EC 3.1.3.-. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nurse Practitioners: Nurses who are specially trained to assume an expanded role in providing medical care under the supervision of a physician. [NIH] Nystatin: Macrolide antifungal antibiotic complex produced by Streptomyces noursei, S. aureus, and other Streptomyces species. The biologically active components of the complex
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are nystatin A1, A2, and A3. [NIH] Obsession: A recurrent, persistent thought, image, or impulse that is unwanted and distressing (ego-dystonic) and comes involuntarily to mind despite attempts to ignore or suppress it. Common obsessions involve thoughts of violence, contamination, and selfdoubt. [EU] Occult: Obscure; concealed from observation, difficult to understand. [EU] Ocular: 1. Of, pertaining to, or affecting the eye. 2. Eyepiece. [EU] Odour: A volatile emanation that is perceived by the sense of smell. [EU] Ofloxacin: An orally administered broad-spectrum quinolone antibacterial drug active against most gram-negative and gram-positive bacteria. [NIH] Ointment Bases: Various mixtures of fats, waxes, animal and plant oils and solid and liquid hydrocarbons; vehicles for medicinal substances intended for external application; there are four classes: hydrocarbon base, absorption base, water-removable base and water-soluble base; several are also emollients. [NIH] Ointments: Semisolid preparations used topically for protective emollient effects or as a vehicle for local administration of medications. Ointment bases are various mixtures of fats, waxes, animal and plant oils and solid and liquid hydrocarbons. [NIH] Oliguria: Clinical manifestation of the urinary system consisting of a decrease in the amount of urine secreted. [NIH] Oophoritis: Inflammation of an ovary. [NIH] Opacity: Degree of density (area most dense taken for reading). [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] Ophthalmic: Pertaining to the eye. [EU] Ophthalmology: A surgical specialty concerned with the structure and function of the eye and the medical and surgical treatment of its defects and diseases. [NIH] Opium: The air-dried exudate from the unripe seed capsule of the opium poppy, Papaver somniferum, or its variant, P. album. It contains a number of alkaloids, but only a few morphine, codeine, and papaverine - have clinical significance. Opium has been used as an analgesic, antitussive, antidiarrheal, and antispasmodic. [NIH] Opportunistic Infections: An infection caused by an organism which becomes pathogenic under certain conditions, e.g., during immunosuppression. [NIH] Oral Health: The optimal state of the mouth and normal functioning of the organs of the mouth without evidence of disease. [NIH] Oral Hygiene: The practice of personal hygiene of the mouth. It includes the maintenance of oral cleanliness, tissue tone, and general preservation of oral health. [NIH] Oral Manifestations: Disorders of the mouth attendant upon non-oral disease or injury. [NIH]
Organ Culture: The growth in aseptic culture of plant organs such as roots or shoots, beginning with organ primordia or segments and maintaining the characteristics of the organ. [NIH] Organelles: Specific particles of membrane-bound organized living substances present in eukaryotic cells, such as the mitochondria; the golgi apparatus; endoplasmic reticulum;
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lysomomes; plastids; and vacuoles. [NIH] Orofacial: Of or relating to the mouth and face. [EU] 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] Osteoarthritis: A progressive, degenerative joint disease, the most common form of arthritis, especially in older persons. The disease is thought to result not from the aging process but from biochemical changes and biomechanical stresses affecting articular cartilage. In the foreign literature it is often called osteoarthrosis deformans. [NIH] Osteoblasts: Bone-forming cells which secrete an extracellular matrix. Hydroxyapatite crystals are then deposited into the matrix to form bone. [NIH] Otitis: Inflammation of the ear, which may be marked by pain, fever, abnormalities of hearing, hearing loss, tinnitus, and vertigo. [EU] Otitis Media: Inflammation of the middle ear. [NIH] Ovum: A female germ cell extruded from the ovary at ovulation. [NIH] Oxazolidinones: Derivatives of oxazolidin-2-one. They represent an important class of synthetic antibiotic agents. [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 metabolism: A chemical process in which oxygen is used to make energy from carbohydrates (sugars). Also known as aerobic respiration, cell respiration, or aerobic metabolism. [NIH] Oxolinic Acid: Synthetic antimicrobial related to nalidixic acid and used in urinary tract infections. [NIH] Oxytetracycline: An antibiotic substance isolated from the actinomycete Streptomyces rimosus and used in a wide variety of clinical conditions. [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]
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Pancreatitis: Acute or chronic inflammation of the pancreas, which may be asymptomatic or symptomatic, and which is due to autodigestion of a pancreatic tissue by its own enzymes. It is caused most often by alcoholism or biliary tract disease; less commonly it may be associated with hyperlipaemia, hyperparathyroidism, abdominal trauma (accidental or operative injury), vasculitis, or uraemia. [EU] Paneth Cells: Epithelial cells found in the basal part of the intestinal glands (crypts of Lieberkuhn). Paneth cells synthesize and secrete lysozyme and cryptdins. [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] Papillomavirus: A genus of Papovaviridae causing proliferation of the epithelium, which may lead to malignancy. A wide range of animals are infected including humans, chimpanzees, cattle, rabbits, dogs, and horses. [NIH] Papule: A small circumscribed, superficial, solid elevation of the skin. [EU] 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] Parenteral: Not through the alimentary canal but rather by injection through some other route, as subcutaneous, intramuscular, intraorbital, intracapsular, intraspinal, intrasternal, intravenous, etc. [EU] Parietal: 1. Of or pertaining to the walls of a cavity. 2. Pertaining to or located near the parietal bone, as the parietal lobe. [EU] 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] Pasteurella: The oldest recognized genus of the family Pasteurellaceae. It consists of several species. Its organisms occur most frequently as coccobacillus or rod-shaped and are gramnegative, nonmotile, facultative anaerobes. Species of this genus are found in both animals and humans. [NIH] Pasteurella haemolytica: A species of gram-negative, facultatively anaerobic, rod-shaped bacteria normally found in the flora of cattle and sheep. It causes mastitis in sheep and shipping fever (see pasteurellosis, pneumonic) in cattle. [NIH] Pasteurellosis, Pneumonic: Bovine respiratory disease found in animals that have been shipped or exposed to cattle recently transported. It is thought to be caused by infection with the bovine parainfluenza virus 3 (see paramyxovirus) or one of several other respiratory viruses, followed by infection with either Pasteurella multocida or Pasteurella haemolytica. [NIH] 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]
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Pathogenesis: The cellular events and reactions that occur in the development of disease. [NIH]
Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Pathologic Processes: The abnormal mechanisms and forms involved in the dysfunctions of tissues and organs. [NIH] Patient Compliance: Voluntary cooperation of the patient in following a prescribed regimen. [NIH] Patient Education: The teaching or training of patients concerning their own health needs. [NIH]
Pefloxacin: An orally administered broad spectrum quinolone antibacterial agent active against most gram-negative and gram-positive bacteria. It is effective against urinary tract infections as well as against many other systemic infections. The drug is well tolerated in adults, but should not be given to children and pregnant women. [NIH] Pelvic: Pertaining to the pelvis. [EU] Penicillin: An antibiotic drug used to treat infection. [NIH] Penis: The external reproductive organ of males. It is composed of a mass of erectile tissue enclosed in three cylindrical fibrous compartments. Two of the three compartments, the corpus cavernosa, are placed side-by-side along the upper part of the organ. The third compartment below, the corpus spongiosum, houses the urethra. [NIH] Pentamidine: Antiprotozoal agent effective in trypanosomiasis, leishmaniasis, and some fungal infections; used in treatment of Pneumocystis carinii pneumonia in HIV-infected patients. It may cause diabetes mellitus, central nervous system damage, and other toxic effects. [NIH] Pepsin: An enzyme made in the stomach that breaks down proteins. [NIH] Pepsin A: Formed from pig pepsinogen by cleavage of one peptide bond. The enzyme is a single polypeptide chain and is inhibited by methyl 2-diaazoacetamidohexanoate. It cleaves peptides preferentially at the carbonyl linkages of phenylalanine or leucine and acts as the principal digestive enzyme of gastric juice. [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 Chain Elongation: The process whereby an amino acid is joined through a substituted amide linkage to a chain of peptides. [NIH] Peptide Fragments: Partial proteins formed by partial hydrolysis of complete proteins. [NIH] Peptide Hydrolases: A subclass of enzymes from the hydrolase class that catalyze the hydrolysis of peptide bonds. Exopeptidases and endopeptidases make up the sub-subclasses for this group. EC 3.4. [NIH] Percutaneous: Performed through the skin, as injection of radiopacque material in radiological examination, or the removal of tissue for biopsy accomplished by a needle. [EU] Perianal: Located around the anus. [EU] Perineum: The area between the anus and the sex organs. [NIH]
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Periodontal disease: Disease involving the supporting structures of the teeth (as the gums and periodontal membranes). [NIH] Periodontitis: Inflammation of the periodontal membrane; also called periodontitis simplex. [NIH]
Peripheral blood: Blood circulating throughout the body. [NIH] Peripheral Nerves: The nerves outside of the brain and spinal cord, including the autonomic, cranial, and spinal nerves. Peripheral nerves contain non-neuronal cells and connective tissue as well as axons. The connective tissue layers include, from the outside to the inside, the epineurium, the perineurium, and the endoneurium. [NIH] Peritoneal: Having to do with the peritoneum (the tissue that lines the abdominal wall and covers most of the organs in the abdomen). [NIH] Peritoneal Cavity: The space enclosed by the peritoneum. It is divided into two portions, the greater sac and the lesser sac or omental bursa, which lies behind the stomach. The two sacs are connected by the foramen of Winslow, or epiploic foramen. [NIH] 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] Pesticides: Chemicals used to destroy pests of any sort. The concept includes fungicides (industrial fungicides), insecticides, rodenticides, etc. [NIH] Phagocyte: An immune system cell that can surround and kill microorganisms and remove dead cells. Phagocytes include macrophages. [NIH] 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] Pharmaceutical Solutions: Homogeneous liquid preparations that contain one or more chemical substances dissolved, i.e., molecularly dispersed, in a suitable solvent or mixture of mutually miscible solvents. For reasons of their ingredients, method of preparation, or use,
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they do not fall into another group of products. [NIH] Pharmacodynamic: Is concerned with the response of living tissues to chemical stimuli, that is, the action of drugs on the living organism in the absence of disease. [NIH] Pharmacokinetic: The mathematical analysis of the time courses of absorption, distribution, and elimination of drugs. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Pharyngitis: Inflammation of the throat. [NIH] 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] Phenyl: Ingredient used in cold and flu remedies. [NIH] Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor of melanin, dopamine, noradrenalin, and thyroxine. [NIH] Phorbol: Class of chemicals that promotes the development of tumors. [NIH] Phorbol Esters: Tumor-promoting compounds obtained from croton oil (Croton tiglium). Some of these are used in cell biological experiments as activators of protein kinase C. [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] Phosphoric Monoester Hydrolases: A group of hydrolases which catalyze the hydrolysis of monophosphoric esters with the production of one mole of orthophosphate. EC 3.1.3. [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] Phosphorylates: 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] Photocoagulation: Using a special strong beam of light (laser) to seal off bleeding blood vessels such as in the eye. The laser can also burn away blood vessels that should not have grown in the eye. This is the main treatment for diabetic retinopathy. [NIH] Physical Examination: Systematic and thorough inspection of the patient for physical signs of disease or abnormality. [NIH] Physiologic: Having to do with the functions of the body. When used in the phrase "physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH]
Physiology: The science that deals with the life processes and functions of organismus, their cells, tissues, and organs. [NIH] Pigment: A substance that gives color to tissue. Pigments are responsible for the color of skin, eyes, and hair. [NIH]
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Pigmentation: Coloration or discoloration of a part by a pigment. [NIH] Pipemidic Acid: Antimicrobial against gram-negative and some gram-positive bacteria. It is protein bound and concentrated in bile and urine and used for gastrointestinal, biliary, and urinary infections. [NIH] Piperacillin: Semisynthetic, broad-spectrum, ampicillin-derived ureidopenicillin antibiotic proposed for pseudomonas infections. It is also used in combination with other antibiotics. [NIH]
Pituitary Gland: A small, unpaired gland situated in the sella turcica tissue. It is connected to the hypothalamus by a short stalk. [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 sylvatic rodent-flea ecosystems throughout the world. Bubonic plague is the most common form. [NIH] Plant Diseases: Diseases of plants. [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] Plaque: A clear zone in a bacterial culture grown on an agar plate caused by localized destruction of bacterial cells by a bacteriophage. The concentration of infective virus in a fluid can be estimated by applying the fluid to a culture and counting the number of. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] Plasmid: An autonomously replicating, extra-chromosomal DNA molecule found in many bacteria. Plasmids are widely used as carriers of cloned genes. [NIH] Platelet Activation: A series of progressive, overlapping events triggered by exposure of the platelets to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug. [NIH] Platelet Aggregation: The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin, collagen) and is part of the mechanism leading to the formation of a thrombus. [NIH] Platelet Factor 4: A high-molecular-weight proteoglycan-platelet factor complex which is released from blood platelets by thrombin. It acts as a mediator in the heparin-neutralizing capacity of the blood and plays a role in platelet aggregation. At high ionic strength (I=0.75), the complex dissociates into the active component (molecular weight 29,000) and the proteoglycan carrier (chondroitin 4-sulfate, molecular weight 350,000). The molecule exists in the form of a dimer consisting of 8 moles of platelet factor 4 and 2 moles of proteoglycan. [NIH]
Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Platinum: Platinum. A heavy, soft, whitish metal, resembling tin, atomic number 78, atomic
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weight 195.09, symbol Pt. (From Dorland, 28th ed) It is used in manufacturing equipment for laboratory and industrial use. It occurs as a black powder (platinum black) and as a spongy substance (spongy platinum) and may have been known in Pliny's time as "alutiae". [NIH] Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [NIH] Polymerase: An enzyme which catalyses the synthesis of DNA using a single DNA strand as a template. The polymerase copies the template in the 5'-3'direction provided that sufficient quantities of free nucleotides, dATP and dTTP are present. [NIH] Polymerase Chain Reaction: In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships. [NIH] Polymers: Compounds formed by the joining of smaller, usually repeating, units linked by covalent bonds. These compounds often form large macromolecules (e.g., polypeptides, proteins, plastics). [NIH] 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 Growth: Increase, over a specific period of time, in the number of individuals living in a country or region. [NIH] Porins: Protein molecules situated in the outer membrane of gram-negative bacteria that, in dimeric or trimeric form, constitute a water-filled transmembrane channel allowing passage of ions and other small molecules. Porins are also found in bacterial cell walls, and in plant, fungal, mammalian and other vertebrate cell and mitochondrial membranes. [NIH] Postnatal: Occurring after birth, with reference to the newborn. [EU] 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] Potentiation: An overall effect of two drugs taken together which is greater than the sum of the effects of each drug taken alone. [NIH]
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Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH] Precancerous: A term used to describe a condition that may (or is likely to) become cancer. Also called premalignant. [NIH] Precipitation: The act or process of precipitating. [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] Predisposition: A latent susceptibility to disease which may be activated under certain conditions, as by stress. [EU] Premalignant: A term used to describe a condition that may (or is likely to) become cancer. Also called precancerous. [NIH] Prenatal: Existing or occurring before birth, with reference to the fetus. [EU] Presumptive: A treatment based on an assumed diagnosis, prior to receiving confirmatory laboratory test results. [NIH] 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] Probe: An instrument used in exploring cavities, or in the detection and dilatation of strictures, or in demonstrating the potency of channels; an elongated instrument for exploring or sounding body cavities. [NIH] Prodrug: A substance that gives rise to a pharmacologically active metabolite, although not itself active (i. e. an inactive precursor). [NIH] Progesterone: Pregn-4-ene-3,20-dione. The principal progestational hormone of the body, secreted by the corpus luteum, adrenal cortex, and placenta. Its chief function is to prepare the uterus for the reception and development of the fertilized ovum. It acts as an antiovulatory agent when administered on days 5-25 of the menstrual cycle. [NIH] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] 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] Prone: Having the front portion of the body downwards. [NIH] Prophylaxis: An attempt to prevent disease. [NIH] Prospective study: An epidemiologic study in which a group of individuals (a cohort), all free of a particular disease and varying in their exposure to a possible risk factor, is followed over a specific amount of time to determine the incidence rates of the disease in the exposed and unexposed groups. [NIH]
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Prostaglandin: Any of a group of components derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway that are extremely potent mediators of a diverse group of physiologic processes. The abbreviation for prostaglandin is PG; specific compounds are designated by adding one of the letters A through I to indicate the type of substituents found on the hydrocarbon skeleton and a subscript (1, 2 or 3) to indicate the number of double bonds in the hydrocarbon skeleton e.g., PGE2. The predominant naturally occurring prostaglandins all have two double bonds and are synthesized from arachidonic acid (5,8,11,14-eicosatetraenoic acid) by the pathway shown in the illustration. The 1 series and 3 series are produced by the same pathway with fatty acids having one fewer double bond (8,11,14-eicosatrienoic acid or one more double bond (5,8,11,14,17-eicosapentaenoic acid) than arachidonic acid. The subscript a or ß indicates the configuration at C-9 (a denotes a substituent below the plane of the ring, ß, above the plane). The naturally occurring PGF's have the a configuration, e.g., PGF2a. All of the prostaglandins act by binding to specific cell-surface receptors causing an increase in the level of the intracellular second messenger cyclic AMP (and in some cases cyclic GMP also). The effect produced by the cyclic AMP increase depends on the specific cell type. In some cases there is also a positive feedback effect. Increased cyclic AMP increases prostaglandin synthesis leading to further increases in cyclic AMP. [EU] Prostaglandin-Endoperoxide Synthase: An enzyme complex that catalyzes the formation of prostaglandins from the appropriate unsaturated fatty acid, molecular oxygen, and a reduced acceptor. EC 1.14.99.1. [NIH] Prostaglandins A: (13E,15S)-15-Hydroxy-9-oxoprosta-10,13-dien-1-oic acid (PGA(1)); (5Z,13E,15S)-15-hydroxy-9-oxoprosta-5,10,13-trien-1-oic acid (PGA(2)); (5Z,13E,15S,17Z)-15hydroxy-9-oxoprosta-5,10,13,17-tetraen-1-oic acid (PGA(3)). A group of naturally occurring secondary prostaglandins derived from PGE. PGA(1) and PGA(2) as well as their 19hydroxy derivatives are found in many organs and tissues. [NIH] Prostaglandins D: Physiologically active prostaglandins found in many tissues and organs. They show pressor activity, are mediators of inflammation, and have potential antithrombotic effects. [NIH] Prostate: A gland in males that surrounds the neck of the bladder and the urethra. It secretes a substance that liquifies coagulated semen. It is situated in the pelvic cavity behind the lower part of the pubic symphysis, above the deep layer of the triangular ligament, and rests upon the rectum. [NIH] Prostate gland: A gland in the male reproductive system just below the bladder. It surrounds part of the urethra, the canal that empties the bladder, and produces a fluid that forms part of semen. [NIH] Prostatitis: Inflammation of the prostate. [EU] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation. [NIH] Protein Conformation: The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. Quaternary protein structure describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain). [NIH] Protein Kinase C: An enzyme that phosphorylates proteins on serine or threonine residues in the presence of physiological concentrations of calcium and membrane phospholipids.
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The additional presence of diacylglycerols markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by phorbol esters and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters. EC 2.7.1.-. [NIH] Protein S: The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] Proteolytic: 1. Pertaining to, characterized by, or promoting proteolysis. 2. An enzyme that promotes proteolysis (= the splitting of proteins by hydrolysis of the peptide bonds with formation of smaller polypeptides). [EU] Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or vaccine dosages, length of study, routes of administration, who may participate, and other aspects of trial design. [NIH] Proton Pump: Integral membrane proteins that transport protons across a membrane against a concentration gradient. This transport is driven by hydrolysis of ATP by H(+)transporting ATP synthase. [NIH] Proton Pump Inhibitors: Medicines that stop the stomach's acid pump. Examples are omeprazole (oh-MEH-prah-zol) (Prilosec) and lansoprazole (lan-SOH-prah-zol) (Prevacid). [NIH]
Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] Protozoa: A subkingdom consisting of unicellular organisms that are the simplest in the animal kingdom. Most are free living. They range in size from submicroscopic to macroscopic. Protozoa are divided into seven phyla: Sarcomastigophora, Labyrinthomorpha, Apicomplexa, Microspora, Ascetospora, Myxozoa, and Ciliophora. [NIH] Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] Pseudogenes: Genes bearing close resemblance to known genes at different loci, but rendered non-functional by additions or deletions in structure that prevent normal transcription or translation. When lacking introns and containing a poly-A segment near the downstream end (as a result of reverse copying from processed nuclear RNA into doublestranded DNA), they are called processed genes. [NIH] Pseudomonas: A genus of gram-negative, aerobic, rod-shaped bacteria widely distributed in nature. Some species are pathogenic for humans, animals, and plants. [NIH] Pseudomonas Infections: Infections with bacteria of the genus Pseudomonas. [NIH] Psittacosis: A lung disease caused by a Chlamydia bacterium; occurs in domestic fowls, ducks, pigeons, turkeys and many wild birds and is contracted by man by contact with these birds; the human symptoms are headache, nausea, epistaxis and fever and usually with added symptoms. [NIH] Psoriasis: A common genetically determined, chronic, inflammatory skin disease characterized by rounded erythematous, dry, scaling patches. The lesions have a predilection for nails, scalp, genitalia, extensor surfaces, and the lumbosacral region. Accelerated epidermopoiesis is considered to be the fundamental pathologic feature in psoriasis. [NIH] Psychiatric: Pertaining to or within the purview of psychiatry. [EU]
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Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders. [NIH] Psychology: The science dealing with the study of mental processes and behavior in man and animals. [NIH] Public Health: Branch of medicine concerned with the prevention and control of disease and disability, and the promotion of physical and mental health of the population on the international, national, state, or municipal level. [NIH] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] Publishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing. [NIH]
Pulmonary: Relating to the lungs. [NIH] Pulse: The rhythmical expansion and contraction of an artery produced by waves of pressure caused by the ejection of blood from the left ventricle of the heart as it contracts. [NIH]
Pupil: The aperture in the iris through which light passes. [NIH] Purines: A series of heterocyclic compounds that are variously substituted in nature and are known also as purine bases. They include adenine and guanine, constituents of nucleic acids, as well as many alkaloids such as caffeine and theophylline. Uric acid is the metabolic end product of purine metabolism. [NIH] Purpura: Purplish or brownish red discoloration, easily visible through the epidermis, caused by hemorrhage into the tissues. [NIH] Purulent: Consisting of or containing pus; associated with the formation of or caused by pus. [EU] Pyelonephritis: Inflammation of the kidney and its pelvis, beginning in the interstitium and rapidly extending to involve the tubules, glomeruli, and blood vessels; due to bacterial infection. [EU] Pyogenic: Producing pus; pyopoietic (= liquid inflammation product made up of cells and a thin fluid called liquor puris). [EU] Quality of Life: A generic concept reflecting concern with the modification and enhancement of life attributes, e.g., physical, political, moral and social environment. [NIH] Quinolones: Quinolines which are substituted in any position by one or more oxo groups. These compounds can have any degree of hydrogenation, any substituents, and fused ring systems. [NIH] Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radiation therapy: The use of high-energy radiation from x-rays, gamma rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body in the area near cancer cells (internal radiation therapy, implant radiation, or brachytherapy). Systemic radiation therapy uses a radioactive
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substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Also called radiotherapy. [NIH] Radioactive: Giving off radiation. [NIH] Radioimmunoassay: Classic quantitative assay for detection of antigen-antibody reactions using a radioactively labeled substance (radioligand) either directly or indirectly to measure the binding of the unlabeled substance to a specific antibody or other receptor system. Nonimmunogenic substances (e.g., haptens) can be measured if coupled to larger carrier proteins (e.g., bovine gamma-globulin or human serum albumin) capable of inducing antibody formation. [NIH] Radioimmunotherapy: Radiotherapy where cytotoxic radionuclides are linked to antibodies in order to deliver toxins directly to tumor targets. Therapy with targeted radiation rather than antibody-targeted toxins (immunotoxins) has the advantage that adjacent tumor cells, which lack the appropriate antigenic determinants, can be destroyed by radiation cross-fire. Radioimmunotherapy is sometimes called targeted radiotherapy, but this latter term can also refer to radionuclides linked to non-immune molecules (radiotherapy). [NIH] Radiolabeled: Any compound that has been joined with a radioactive substance. [NIH] Radiological: Pertaining to radiodiagnostic and radiotherapeutic procedures, and interventional radiology or other planning and guiding medical radiology. [NIH] Radiology: A specialty concerned with the use of x-ray and other forms of radiant energy in the diagnosis and treatment of disease. [NIH] Radionuclide Imaging: Process whereby a radionuclide is injected or measured (through tissue) from an external source, and a display is obtained from any one of several rectilinear scanner or gamma camera systems. The image obtained from a moving detector is called a scan, while the image obtained from a stationary camera device is called a scintiphotograph. [NIH]
Radiotherapy: The use of ionizing radiation to treat malignant neoplasms and other benign conditions. The most common forms of ionizing radiation used as therapy are x-rays, gamma rays, and electrons. A special form of radiotherapy, targeted radiotherapy, links a cytotoxic radionuclide to a molecule that targets the tumor. When this molecule is an antibody or other immunologic molecule, the technique is called radioimmunotherapy. [NIH] Randomized: Describes an experiment or clinical trial in which animal or human subjects are assigned by chance to separate groups that compare different treatments. [NIH] Randomized clinical trial: A study in which the participants are assigned by chance to separate groups that compare different treatments; neither the researchers nor the participants can choose which group. Using chance to assign people to groups means that the groups will be similar and that the treatments they receive can be compared objectively. At the time of the trial, it is not known which treatment is best. It is the patient's choice to be in a randomized trial. [NIH] Randomized Controlled Trials: Clinical trials that involve at least one test treatment and one control treatment, concurrent enrollment and follow-up of the test- and control-treated groups, and in which the treatments to be administered are selected by a random process, such as the use of a random-numbers table. Treatment allocations using coin flips, odd-even numbers, patient social security numbers, days of the week, medical record numbers, or other such pseudo- or quasi-random processes, are not truly randomized and trials employing any of these techniques for patient assignment are designated simply controlled clinical trials. [NIH] Reactivation: The restoration of activity to something that has been inactivated. [EU] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and
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causes a specific physiologic effect in the cell. [NIH] Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Recombination: The formation of new combinations of genes as a result of segregation in crosses between genetically different parents; also the rearrangement of linked genes due to crossing-over. [NIH] 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] Reflux: The term used when liquid backs up into the esophagus from the stomach. [NIH] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH] Refractory: Not readily yielding to treatment. [EU] 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] Rehydration: The restoration of water or of fluid content to a body or to substance which has become dehydrated. [EU] Relaxation Techniques: The use of muscular relaxation techniques in treatment. [NIH] Remission: A decrease in or disappearance of signs and symptoms of cancer. In partial remission, some, but not all, signs and symptoms of cancer have disappeared. In complete remission, all signs and symptoms of cancer have disappeared, although there still may be cancer in the body. [NIH] Renal failure: Progressive renal insufficiency and uremia, due to irreversible and progressive renal glomerular tubular or interstitial disease. [NIH] Renal pelvis: The area at the center of the kidney. Urine collects here and is funneled into the ureter, the tube that connects the kidney to the bladder. [NIH] Renovascular: Of or pertaining to the blood vessels of the kidneys. [EU] 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] Reproductive system: In women, this system includes the ovaries, the fallopian tubes, the uterus (womb), the cervix, and the vagina (birth canal). The reproductive system in men includes the prostate, the testes, and the penis. [NIH] Resorption: The loss of substance through physiologic or pathologic means, such as loss of
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dentin and cementum of a tooth, or of the alveolar process of the mandible or maxilla. [EU] Respiration: The act of breathing with the lungs, consisting of inspiration, or the taking into the lungs of the ambient air, and of expiration, or the expelling of the modified air which contains more carbon dioxide than the air taken in (Blakiston's Gould Medical Dictionary, 4th ed.). This does not include tissue respiration (= oxygen consumption) or cell respiration (= cell respiration). [NIH] Respirator: A mechanical device that helps a patient breathe; a mechanical ventilator. [NIH] Respiratory Burst: A large increase in oxygen uptake by neutrophils and most types of tissue macrophages through activation of an NADPH-cytochrome b-dependent oxidase that reduces oxygen to a superoxide. Individuals with an inherited defect in which the oxidase that reduces oxygen to superoxide is decreased or absent (granulomatous disease, chronic) often die as a result of recurrent bacterial infections. [NIH] Respiratory distress syndrome: A lung disease that occurs primarily in premature infants; the newborn must struggle for each breath and blueing of its skin reflects the baby's inability to get enough oxygen. [NIH] Respiratory failure: Inability of the lungs to conduct gas exchange. [NIH] Respiratory Mucosa: The mucous membrane lining the respiratory tract. [NIH] Respiratory Physiology: Functions and activities of the respiratory tract as a whole or of any of its parts. [NIH] Respiratory syncytial virus: RSV. A virus that causes respiratory infections with cold-like symptoms. [NIH] Restoration: Broad term applied to any inlay, crown, bridge or complete denture which restores or replaces loss of teeth or oral tissues. [NIH] Retinal: 1. Pertaining to the retina. 2. The aldehyde of retinol, derived by the oxidative enzymatic splitting of absorbed dietary carotene, and having vitamin A activity. In the retina, retinal combines with opsins to form visual pigments. One isomer, 11-cis retinal combines with opsin in the rods (scotopsin) to form rhodopsin, or visual purple. Another, all-trans retinal (trans-r.); visual yellow; xanthopsin) results from the bleaching of rhodopsin by light, in which the 11-cis form is converted to the all-trans form. Retinal also combines with opsins in the cones (photopsins) to form the three pigments responsible for colour vision. Called also retinal, and retinene1. [EU] Retinoids: Derivatives of vitamin A. Used clinically in the treatment of severe cystic acne, psoriasis, and other disorders of keratinization. Their possible use in the prophylaxis and treatment of cancer is being actively explored. [NIH] Retrograde: 1. Moving backward or against the usual direction of flow. 2. Degenerating, deteriorating, or catabolic. [EU] Retroperitoneal: Having to do with the area outside or behind the peritoneum (the tissue that lines the abdominal wall and covers most of the organs in the abdomen). [NIH] Rheumatic Diseases: Disorders of connective tissue, especially the joints and related structures, characterized by inflammation, degeneration, or metabolic derangement. [NIH] Rheumatism: A group of disorders marked by inflammation or pain in the connective tissue structures of the body. These structures include bone, cartilage, and fat. [NIH] Rheumatoid: Resembling rheumatism. [EU] Rheumatoid arthritis: A form of arthritis, the cause of which is unknown, although infection, hypersensitivity, hormone imbalance and psychologic stress have been suggested as possible causes. [NIH]
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Rhinitis: Inflammation of the mucous membrane of the nose. [NIH] Ribonucleic acid: RNA. One of the two nucleic acids found in all cells. The other is deoxyribonucleic acid (DNA). Ribonucleic acid transfers genetic information from DNA to proteins produced by the cell. [NIH] 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] Rickettsia: A genus of gram-negative, aerobic, rod-shaped bacteria often surrounded by a protein microcapsular layer and slime layer. The natural cycle of its organisms generally involves a vertebrate and an invertebrate host. Species of the genus are the etiological agents of human diseases, such as typhus. [NIH] Rickettsiae: One of a group of obligate intracellular parasitic microorganisms, once regarded as intermediate in their properties between bacteria and viruses but now classified as bacteria in the order Rickettsiales, which includes 17 genera and 3 families: Rickettsiace. [NIH]
Rifabutin: A broad-spectrum antibiotic that is being used as prophylaxis against disseminated Mycobacterium avium complex infection in HIV-positive patients. [NIH] Rigidity: Stiffness or inflexibility, chiefly that which is abnormal or morbid; rigor. [EU] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Ristocetin: An antibiotic mixture of two components, A and B, obtained from Nocardia lurida (or the same substance produced by any other means). It is no longer used clinically because of its toxicity. It causes platelet agglutination and blood coagulation and is used to assay those functions in vitro. [NIH] Rod: A reception for vision, located in the retina. [NIH] Rodenticides: Substances used to destroy or inhibit the action of rats, mice, or other rodents. [NIH]
Roxithromycin: Semisynthetic derivative of erythromycin. It is concentrated by human phagocytes and is bioactive intracellularly. While the drug is active against a wide spectrum of pathogens, it is particularly effective in the treatment of respiratory and genital tract infections. [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] Salpingitis: 1. Inflammation of the uterine tube. 2. Inflammation of the auditory tube. [EU] Saponins: Sapogenin glycosides. A type of glycoside widely distributed in plants. Each consists of a sapogenin as the aglycon moiety, and a sugar. The sapogenin may be a steroid or a triterpene and the sugar may be glucose, galactose, a pentose, or a methylpentose. Sapogenins are poisonous towards the lower forms of life and are powerful hemolytics when injected into the blood stream able to dissolve red blood cells at even extreme dilutions. [NIH] Sarcoma: A connective tissue neoplasm formed by proliferation of mesodermal cells; it is usually highly malignant. [NIH]
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Saturated fat: A type of fat found in greatest amounts in foods from animals, such as fatty cuts of meat, poultry with the skin, whole-milk dairy products, lard, and in some vegetable oils, including coconut, palm kernel, and palm oils. Saturated fat raises blood cholesterol more than anything else eaten. On a Step I Diet, no more than 8 to 10 percent of total calories should come from saturated fat, and in the Step II Diet, less than 7 percent of the day's total calories should come from saturated fat. [NIH] Scans: Pictures of structures inside the body. Scans often used in diagnosing, staging, and monitoring disease include liver scans, bone scans, and computed tomography (CT) or computerized axial tomography (CAT) scans and magnetic resonance imaging (MRI) scans. In liver scanning and bone scanning, radioactive substances that are injected into the bloodstream collect in these organs. A scanner that detects the radiation is used to create pictures. In CT scanning, an x-ray machine linked to a computer is used to produce detailed pictures of organs inside the body. MRI scans use a large magnet connected to a computer to create pictures of areas inside the body. [NIH] Scarlet Fever: Infection with group A streptococci that is characterized by tonsillitis and pharyngitis. An erythematous rash is commonly present. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Scrotum: In males, the external sac that contains the testicles. [NIH] Sebaceous: Gland that secretes sebum. [NIH] Secondary tumor: Cancer that has spread from the organ in which it first appeared to another organ. For example, breast cancer cells may spread (metastasize) to the lungs and cause the growth of a new tumor. When this happens, the disease is called metastatic breast cancer, and the tumor in the lungs is called a secondary tumor. Also called secondary cancer. [NIH] Secretion: 1. The process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. Any substance produced by secretion. [EU] Secretory: Secreting; relating to or influencing secretion or the secretions. [NIH] Segregation: The separation in meiotic cell division of homologous chromosome pairs and their contained allelomorphic gene pairs. [NIH] Self Care: Performance of activities or tasks traditionally performed by professional health care providers. The concept includes care of oneself or one's family and friends. [NIH] Semen: The thick, yellowish-white, viscid fluid secretion of male reproductive organs discharged upon ejaculation. In addition to reproductive organ secretions, it contains spermatozoa and their nutrient plasma. [NIH] Seminal vesicles: Glands that help produce semen. [NIH] Semisynthetic: Produced by chemical manipulation of naturally occurring substances. [EU] Sepsis: The presence of bacteria in the bloodstream. [NIH] Septic: Produced by or due to decomposition by microorganisms; putrefactive. [EU] Septicaemia: A term originally used to denote a putrefactive process in the body, but now usually referring to infection with pyogenic micro-organisms; a genus of Diptera; the severe type of infection in which the blood stream is invaded by large numbers of the causal. [NIH] Septicemia: Systemic disease associated with the presence and persistence of pathogenic microorganisms or their toxins in the blood. Called also blood poisoning. [EU] 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
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synthesized from glycine or threonine. It is involved in the biosynthesis of purines, pyrimidines, and other amino acids. [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] Serous: Having to do with serum, the clear liquid part of blood. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Sessile: Attached directly by the base, denoting a tumor without penduncle or stalk; in zoology, attached so that it is not possible to move about. [NIH] Sexually Transmitted Diseases: Diseases due to or propagated by sexual contact. [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]
Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the one sought to be benefited by its administration. [EU] Signal Transduction: The intercellular or intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GABA-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptormediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. [NIH] Signs and Symptoms: Clinical manifestations that can be either objective when observed by a physician, or subjective when perceived by the patient. [NIH] Sinusitis: An inflammatory process of the mucous membranes of the paranasal sinuses that occurs in three stages: acute, subacute, and chronic. Sinusitis results from any condition causing ostial obstruction or from pathophysiologic changes in the mucociliary transport mechanism. [NIH] 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] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels.
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[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] Soaps: Sodium or potassium salts of long chain fatty acids. These detergent substances are obtained by boiling natural oils or fats with caustic alkali. Sodium soaps are harder and are used as topical anti-infectives and vehicles in pills and liniments; potassium soaps are soft, used as vehicles for ointments and also as topical antimicrobials. [NIH] Social Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [NIH] Sodium: An element that is a member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23. With a valence of 1, it has a strong affinity for oxygen and other nonmetallic elements. Sodium provides the chief cation of the extracellular body fluids. Its salts are the most widely used in medicine. (From Dorland, 27th ed) Physiologically the sodium ion plays a major role in blood pressure regulation, maintenance of fluid volume, and electrolyte balance. [NIH] Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] Solid tumor: Cancer of body tissues other than blood, bone marrow, or the lymphatic system. [NIH] Solvent: 1. Dissolving; effecting a solution. 2. A liquid that dissolves or that is capable of dissolving; the component of a solution that is present in greater amount. [EU] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] Spasmodic: Of the nature of a spasm. [EU] Spastic: 1. Of the nature of or characterized by spasms. 2. Hypertonic, so that the muscles are stiff and the movements awkward. 3. A person exhibiting spasticity, such as occurs in spastic paralysis or in cerebral palsy. [EU] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Species Specificity: Restriction of a characteristic or response to the members of one species; it usually refers to that property of the immune response which differentiates one species from another on the basis of antigen recognition, but the concept is not limited to immunology and is used loosely at levels higher than the species. [NIH] Specificity: Degree of selectivity shown by an antibody with respect to the number and types of antigens with which the antibody combines, as well as with respect to the rates and the extents of these reactions. [NIH] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU] Sperm: The fecundating fluid of the male. [NIH] Spermatic: A cord-like structure formed by the vas deferens and the blood vessels, nerves
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and lymphatics of the testis. [NIH] Spina bifida: A defect in development of the vertebral column in which there is a central deficiency of the vertebral lamina. [NIH] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] Spirochete: Lyme disease. [NIH] Spleen: An organ that is part of the lymphatic system. The spleen produces lymphocytes, filters the blood, stores blood cells, and destroys old blood cells. It is located on the left side of the abdomen near the stomach. [NIH] Spondylitis: Inflammation of the vertebrae. [EU] Sputum: The material expelled from the respiratory passages by coughing or clearing the throat. [NIH] Squamous: Scaly, or platelike. [EU] Staging: Performing exams and tests to learn the extent of the cancer within the body, especially whether the disease has spread from the original site to other parts of the body. [NIH]
Staphylococcus: A genus of gram-positive, facultatively anaerobic, coccoid bacteria. Its organisms occur singly, in pairs, and in tetrads and characteristically divide in more than one plane to form irregular clusters. Natural populations of Staphylococcus are membranes of warm-blooded animals. Some species are opportunistic pathogens of humans and animals. [NIH] Staphylococcus aureus: Potentially pathogenic bacteria found in nasal membranes, skin, hair follicles, and perineum of warm-blooded animals. They may cause a wide range of infections and intoxications. [NIH] Stasis: A word termination indicating the maintenance of (or maintaining) a constant level; preventing increase or multiplication. [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] Sterilization: The destroying of all forms of life, especially microorganisms, by heat, chemical, or other means. [NIH] Steroid: A group name for lipids that contain a hydrogenated cyclopentanoperhydrophenanthrene ring system. Some of the substances included in this group are progesterone, adrenocortical hormones, the gonadal hormones, cardiac aglycones, bile acids, sterols (such as cholesterol), toad poisons, saponins, and some of the carcinogenic hydrocarbons. [EU] Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Stomatitis: Inflammation of the oral mucosa, due to local or systemic factors which may involve the buccal and labial mucosa, palate, tongue, floor of the mouth, and the gingivae. [EU]
Stool: The waste matter discharged in a bowel movement; feces. [NIH]
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Strand: DNA normally exists in the bacterial nucleus in a helix, in which two strands are coiled together. [NIH] Streptococcal: Caused by infection due to any species of streptococcus. [NIH] Streptococci: A genus of spherical Gram-positive bacteria occurring in chains or pairs. They are widely distributed in nature, being important pathogens but often found as normal commensals in the mouth, skin, and intestine of humans and other animals. [NIH] Streptococcus: A genus of gram-positive, coccoid bacteria whose organisms occur in pairs or chains. No endospores are produced. Many species exist as commensals or parasites on man or animals with some being highly pathogenic. A few species are saprophytes and occur in the natural environment. [NIH] Streptococcus pneumoniae: A gram-positive organism found in the upper respiratory tract, inflammatory exudates, and various body fluids of normal and/or diseased humans and, rarely, domestic animals. [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] Stroke: Sudden loss of function of part of the brain because of loss of blood flow. Stroke may be caused by a clot (thrombosis) or rupture (hemorrhage) of a blood vessel to the brain. [NIH] 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] 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] Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts. [NIH] Sulbactam: A beta-lactamase inhibitor with very weak antibacterial action. The compound prevents antibiotic destruction of beta-lactam antibiotics by inhibiting beta-lactamases, thus extending their spectrum activity. Combinations of sulbactam with beta-lactam antibiotics have been used successfully for the therapy of infections caused by organisms resistant to the antibiotic alone. [NIH] Sulfur: An element that is a member of the chalcogen family. It has an atomic symbol S,
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atomic number 16, and atomic weight 32.066. It is found in the amino acids cysteine and methionine. [NIH] Sunburn: An injury to the skin causing erythema, tenderness, and sometimes blistering and resulting from excessive exposure to the sun. The reaction is produced by the ultraviolet radiation in sunlight. [NIH] Superantigens: Microbial antigens that have in common an extremely potent activating effect on T-cells that bear a specific variable region. Superantigens cross-link the variable region with class II MHC proteins regardless of the peptide binding in the T-cell receptor's pocket. The result is a transient expansion and subsequent death and anergy of the T-cells with the appropriate variable regions. [NIH] Superinfection: A frequent complication of drug therapy for microbial infection. It may result from opportunistic colonization following immunosuppression by the primary pathogen and can be influenced by the time interval between infections, microbial physiology, or host resistance. Experimental challenge and in vitro models are sometimes used in virulence and infectivity studies. [NIH] Superoxide: Derivative of molecular oxygen that can damage cells. [NIH] Superstitions: A belief or practice which lacks adequate basis for proof; an embodiment of fear of the unknown, magic, and ignorance. [NIH] Suppositories: A small cone-shaped medicament having cocoa butter or gelatin at its basis and usually intended for the treatment of local conditions in the rectum. [NIH] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Suppurative: Consisting of, containing, associated with, or identified by the formation of pus. [NIH] Surfactant: A fat-containing protein in the respiratory passages which reduces the surface tension of pulmonary fluids and contributes to the elastic properties of pulmonary tissue. [NIH]
Symphysis: A secondary cartilaginous joint. [NIH] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] Synaptic: Pertaining to or affecting a synapse (= site of functional apposition between neurons, at which an impulse is transmitted from one neuron to another by electrical or chemical means); pertaining to synapsis (= pairing off in point-for-point association of homologous chromosomes from the male and female pronuclei during the early prophase of meiosis). [EU] Synergistic: Acting together; enhancing the effect of another force or agent. [EU] Synovial: Of pertaining to, or secreting synovia. [EU] Synovial Fluid: The clear, viscous fluid secreted by the synovial membrane. It contains mucin, albumin, fat, and mineral salts and serves to lubricate joints. [NIH] Synovial Membrane: The inner membrane of a joint capsule surrounding a freely movable joint. It is loosely attached to the external fibrous capsule and secretes synovial fluid. [NIH] 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] Systemic lupus erythematosus: SLE. A chronic inflammatory connective tissue disease marked by skin rashes, joint pain and swelling, inflammation of the kidneys, inflammation
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of the fibrous tissue surrounding the heart (i.e., the pericardium), as well as other problems. Not all affected individuals display all of these problems. May be referred to as lupus. [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] Tacrolimus: A macrolide isolated from the culture broth of a strain of Streptomyces tsukubaensis that has strong immunosuppressive activity in vivo and prevents the activation of T-lymphocytes in response to antigenic or mitogenic stimulation in vitro. [NIH] Taurine: 2-Aminoethanesulfonic acid. A conditionally essential nutrient, important during mammalian development. It is present in milk but is isolated mostly from ox bile and strongly conjugates bile acids. [NIH] Technetium: The first artificially produced element and a radioactive fission product of uranium. The stablest isotope has a mass number 99 and is used diagnostically as a radioactive imaging agent. Technetium has the atomic symbol Tc, atomic number 43, and atomic weight 98.91. [NIH] Teichoic Acids: Bacterial polysaccharides that are rich in phosphodiester linkages. They are the major components of the cell walls and membranes of many bacteria. [NIH] Teicoplanin: Glycopeptide antibiotic complex from Actinoplanes teichomyceticus active against gram-positive bacteria. It consists of five major components each with a different fatty acid moiety. [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] Tenesmus: Straining, especially ineffectual and painful straining at stool or in urination. [EU] Testicles: The two egg-shaped glands found inside the scrotum. They produce sperm and male hormones. Also called testes. [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] 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] 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]
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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] Thromboxanes: Physiologically active compounds found in many organs of the body. They are formed in vivo from the prostaglandin endoperoxides and cause platelet aggregation, contraction of arteries, and other biological effects. Thromboxanes are important mediators of the actions of polyunsaturated fatty acids transformed by cyclooxygenase. [NIH] Thrombus: An aggregation of blood factors, primarily platelets and fibrin with entrapment of cellular elements, frequently causing vascular obstruction at the point of its formation. Some authorities thus differentiate thrombus formation from simple coagulation or clot formation. [EU] Thymidine: A chemical compound found in DNA. Also used as treatment for mucositis. [NIH]
Thymus: An organ that is part of the lymphatic system, in which T lymphocytes grow and multiply. The thymus is in the chest behind the breastbone. [NIH] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH] Ticarcillin: An antibiotic derived from penicillin similar to carbenicillin in action. [NIH] Ticks: Blood-sucking arachnids of the order Acarina. [NIH] Tinnitus: Sounds that are perceived in the absence of any external noise source which may take the form of buzzing, ringing, clicking, pulsations, and other noises. Objective tinnitus refers to noises generated from within the ear or adjacent structures that can be heard by other individuals. The term subjective tinnitus is used when the sound is audible only to the affected individual. Tinnitus may occur as a manifestation of cochlear diseases; vestibulocochlear nerve diseases; intracranial hypertension; craniocerebral trauma; and other conditions. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tissue Culture: Maintaining or growing of tissue, organ primordia, or the whole or part of an organ in vitro so as to preserve its architecture and/or function (Dorland, 28th ed). Tissue culture includes both organ culture and cell culture. [NIH] Tobramycin: An aminoglycoside, broad-spectrum antibiotic produced by Streptomyces tenebrarius. It is effective against gram-negative bacteria, especially the Pseudomonas species. It is a 10% component of the antibiotic complex, nebramycin, produced by the same species. [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] Tomography: Imaging methods that result in sharp images of objects located on a chosen plane and blurred images located above or below the plane. [NIH] Tonsillitis: Inflammation of the tonsils, especially the palatine tonsils. It is often caused by a bacterium. Tonsillitis may be acute, chronic, or recurrent. [NIH]
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Tonsils: Small masses of lymphoid tissue on either side of the throat. [NIH] Tooth Loss: The failure to retain teeth as a result of disease or injury. [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] Torsion: A twisting or rotation of a bodily part or member on its axis. [NIH] Toxemia: A generalized intoxication produced by toxins and other substances elaborated by an infectious agent. [NIH] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxins: Specific, characterizable, poisonous chemicals, often proteins, with specific biological properties, including immunogenicity, produced by microbes, higher plants, or animals. [NIH] Toxoplasmosis: The acquired form of infection by Toxoplasma gondii in animals and man. [NIH]
Trace element: Substance or element essential to plant or animal life, but present in extremely small amounts. [NIH] Trachea: The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi. [NIH] Transcriptase: An enzyme which catalyses the synthesis of a complementary mRNA molecule from a DNA template in the presence of a mixture of the four ribonucleotides (ATP, UTP, GTP and CTP). [NIH] Transduction: The transfer of genes from one cell to another by means of a viral (in the case of bacteria, a bacteriophage) vector or a vector which is similar to a virus particle (pseudovirion). [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Transfer Factor: Factor derived from leukocyte lysates of immune donors which can transfer both local and systemic cellular immunity to nonimmune recipients. [NIH] Transferases: Transferases are enzymes transferring a group, for example, the methyl group or a glycosyl group, from one compound (generally regarded as donor) to another compound (generally regarded as acceptor). The classification is based on the scheme "donor:acceptor group transferase". (Enzyme Nomenclature, 1992) EC 2. [NIH] Transfusion: The infusion of components of blood or whole blood into the bloodstream. The blood may be donated from another person, or it may have been taken from the person earlier and stored until needed. [NIH] 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
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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] 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] Triclosan: A diphenyl ether derivative used in cosmetics and toilet soaps as an antiseptic. It has some bacteriostatic and fungistatic action. [NIH] Trimethoprim-sulfamethoxazole: An antibiotic drug used to treat infection and prevent pneumocystis carinii pneumonia. [NIH] Trypanosomiasis: Infection with protozoa of the genus Trypanosoma. [NIH] Trypsin: A serine endopeptidase that is formed from trypsinogen in the pancreas. It is converted into its active form by enteropeptidase in the small intestine. It catalyzes hydrolysis of the carboxyl group of either arginine or lysine. EC 3.4.21.4. [NIH] 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] Tuberculosis, Oral: Tuberculosis of the mouth, tongue, and salivary glands. [NIH] Tularemia: A plague-like disease of rodents, transmissible to man. It is caused by Francisella tularensis and is characterized by fever, chills, headache, backache, and weakness. [NIH] Tumor 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] 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] Tylosin: Macrolide antibiotic obtained from cultures of Streptomyces fradiae. The drug is effective against many microorganisms in animals but not in humans. [NIH] Type 2 diabetes: Usually characterized by a gradual onset with minimal or no symptoms of metabolic disturbance and no requirement for exogenous insulin. The peak age of onset is 50 to 60 years. Obesity and possibly a genetic factor are usually present. [NIH] Tyrosine: A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine, thyroid hormones, and melanin. [NIH] 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] Umbilical Arteries: Either of a pair of arteries originating from the internal iliac artery and
Dictionary 301
passing through the umbilical cord to carry blood from the fetus to the placenta. [NIH] Umbilical Cord: The flexible structure, giving passage to the umbilical arteries and vein, which connects the embryo or fetus to the placenta. [NIH] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Universal Precautions: Prudent standard preventive measures to be taken by professional and other health personnel in contact with persons afflicted with a communicable disease, to avoid contracting the disease by contagion or infection. Precautions are especially applicable in the diagnosis and care of AIDS patients. [NIH] Uraemia: 1. An excess in the blood of urea, creatinine, and other nitrogenous end products of protein and amino acids metabolism; more correctly referred to as azotemia. 2. In current usage the entire constellation of signs and symptoms of chronic renal failure, including nausea, vomiting anorexia, a metallic taste in the mouth, a uraemic odour of the breath, pruritus, uraemic frost on the skin, neuromuscular disorders, pain and twitching in the muscles, hypertension, edema, mental confusion, and acid-base and electrolyte imbalances. [EU]
Uranium: A radioactive element of the actinide series of metals. It has an atomic symbol U, atomic number 92, and atomic weight 238.03. U-235 is used as the fissionable fuel in nuclear weapons and as fuel in nuclear power reactors. [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] Ureter: One of a pair of thick-walled tubes that transports urine from the kidney pelvis to the bladder. [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]
Urethritis: Inflammation of the urethra. [EU] Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] Urinary tract: The organs of the body that produce and discharge urine. These include the kidneys, ureters, bladder, and urethra. [NIH] Urinary tract infection: An illness caused by harmful bacteria growing in the urinary tract. [NIH]
Urinate: To release urine from the bladder to the outside. [NIH] Urine: Fluid containing water and waste products. Urine is made by the kidneys, stored in the bladder, and leaves the body through the urethra. [NIH] Urodynamic: Measures of the bladder's ability to hold and release urine. [NIH] Urogenital: Pertaining to the urinary and genital apparatus; genitourinary. [EU] Urogenital Diseases: Diseases of the urogenital tract. [NIH] Urolithiasis: Stones in the urinary system. [NIH] Urologic Diseases: Diseases of the urinary tract in both male and female. It does not include the male genitalia for which urogenital diseases is used for general discussions of diseases of both the urinary tract and the genitalia. [NIH] Uterus: The small, hollow, pear-shaped organ in a woman's pelvis. This is the organ in which a fetus develops. Also called the womb. [NIH]
302
Bacterial Infections
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] 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] Vaginitis: Inflammation of the vagina characterized by pain and a purulent discharge. [NIH] Vaginosis: A condition caused by the overgrowth of anaerobic bacteria (e. g., Gardnerella vaginalis), resulting in vaginal irritation and discharge. [NIH] Vancomycin: Antibacterial obtained from Streptomyces orientalis. It is a glycopeptide related to ristocetin that inhibits bacterial cell wall assembly and is toxic to kidneys and the inner ear. [NIH] Varicella: Chicken pox. [EU] Vas Deferens: The excretory duct of the testes that carries spermatozoa. It rises from the scrotum and joins the seminal vesicles to form the ejaculatory duct. [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vascular endothelial growth factor: VEGF. A substance made by cells that stimulates new blood vessel formation. [NIH] Vasculitis: Inflammation of a blood vessel. [NIH] Vasodilators: Any nerve or agent which induces dilatation of the blood vessels. [NIH] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venereal: Pertaining or related to or transmitted by sexual contact. [EU] Venous: Of or pertaining to the veins. [EU] Venous blood: Blood that has given up its oxygen to the tissues and carries carbon dioxide back for gas exchange. [NIH] Ventilation: 1. In respiratory physiology, the process of exchange of air between the lungs and the ambient air. Pulmonary ventilation (usually measured in litres per minute) refers to the total exchange, whereas alveolar ventilation refers to the effective ventilation of the alveoli, in which gas exchange with the blood takes place. 2. In psychiatry, verbalization of one's emotional problems. [EU] Ventilator: A breathing machine that is used to treat respiratory failure by promoting ventilation; also called a respirator. [NIH] Vertebrae: A bony unit of the segmented spinal column. [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] Vesicoureteral: An abnormal condition in which urine backs up into the ureters, and occasionally into the kidneys, raising the risk of infection. [NIH] Veterinarians: Individuals with a degree in veterinary medicine that provides them with training and qualifications to treat diseases and injuries of animals. [NIH] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and
Dictionary 303
treatment of diseases in animals. [NIH] Vibrio: A genus of Vibrionaceae, made up of short, slightly curved, motile, gram-negative rods. Various species produce cholera and other gastrointestinal disorders as well as abortion in sheep and cattle. [NIH] Vibrio cholerae: The etiologic agent of cholera. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Viral Hepatitis: Hepatitis caused by a virus. Five different viruses (A, B, C, D, and E) most commonly cause this form of hepatitis. Other rare viruses may also cause hepatitis. [NIH] Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [NIH] Virulent: A virus or bacteriophage capable only of lytic growth, as opposed to temperate phages establishing the lysogenic response. [NIH] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH] Virus Diseases: A general term for diseases produced by viruses. [NIH] Visceral: , from viscus a viscus) pertaining to a viscus. [EU] Visual Acuity: Acuteness or clearness of vision, especially of form vision, which is dependent mainly on the sharpness of the retinal focus. [NIH] Vitamin A: A substance used in cancer prevention; it belongs to the family of drugs called retinoids. [NIH] Vitro: Descriptive of an event or enzyme reaction under experimental investigation occurring outside a living organism. Parts of an organism or microorganism are used together with artificial substrates and/or conditions. [NIH] Vivo: Outside of or removed from the body of a living organism. [NIH] Volition: Voluntary activity without external compulsion. [NIH] Vulgaris: An affection of the skin, especially of the face, the back and the chest, due to chronic inflammation of the sebaceous glands and the hair follicles. [NIH] Vulva: The external female genital organs, including the clitoris, vaginal lips, and the opening to the vagina. [NIH] Vulvovaginitis: Inflammation of the vulva and vagina, or of the vulvovaginal glands. [EU] War: Hostile conflict between organized groups of people. [NIH] Warts: Benign epidermal proliferations or tumors; some are viral in origin. [NIH] Weight Gain: Increase in body weight over existing weight. [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]
304
Bacterial Infections
Wound Healing: Restoration of integrity to traumatized tissue. [NIH] Xenograft: The cells of one species transplanted to another species. [NIH] Xerostomia: Decreased salivary flow. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH] Yeasts: A general term for single-celled rounded fungi that reproduce by budding. Brewers' and bakers' yeasts are Saccharomyces cerevisiae; therapeutic dried yeast is dried yeast. [NIH] Yersinia: A genus of gram-negative, facultatively anaerobic rod- to coccobacillus-shaped bacteria that occurs in a broad spectrum of habitats. [NIH] Zalcitabine: A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by a hydrogen. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. The compound is a potent inhibitor of HIV replication at low concentrations, acting as a chainterminator of viral DNA by binding to reverse transcriptase. Its principal toxic side effect is axonal degeneration resulting in peripheral neuropathy. [NIH] 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]
305
INDEX 1 1-phosphate, 163, 221 A Abdomen, 221, 230, 231, 245, 263, 266, 279, 289, 294 Abdominal, 95, 178, 180, 221, 252, 263, 276, 277, 279, 289, 300 Abdominal Pain, 178, 180, 221, 252, 263, 279, 300 Aberrant, 8, 38, 221 Abscess, 127, 178, 221, 250, 254 Acetaminophen, 59, 221 Acetylcholine, 221, 274 Acne, 95, 221, 289 Acquired Immunodeficiency Syndrome, 72, 221 Acremonium, 221, 234 Actin, 4, 29, 39, 221, 272 Actinomycosis, 177, 221 Acute lymphoblastic leukemia, 86, 221 Acute lymphocytic leukemia, 221 Acute renal, 174, 221, 257 Acyclovir, 77, 221 Acyl, 119, 124, 131, 139, 147, 163, 221 Acyl Carrier Protein, 119, 139, 221 Acylation, 163, 222 Adaptability, 222, 234 Adaptation, 37, 222, 272 Adenine, 222, 286 Adenosine, 157, 222, 280 Adenosine Triphosphate, 157, 222, 280 Adenovirus, 20, 37, 222 Adenylate Cyclase, 222, 235 Adjustment, 222 Adoptive Transfer, 19, 222 Adrenal Cortex, 222, 240, 283 Adrenal Glands, 174, 222 Adsorption, 141, 151, 222 Adsorptive, 222 Adverse Effect, 178, 222, 292 Aerobic, 83, 141, 222, 259, 270, 272, 276, 285, 290 Aerosol, 125, 222 Aetiology, 84, 222 Afferent, 24, 223 Affinity, 8, 29, 32, 37, 75, 128, 143, 223, 293 Agar, 223, 281 Age of Onset, 223, 300
Airway, 8, 16, 21, 38, 223 Airway Obstruction, 8, 223 Alanine, 33, 223 Albumin, 223, 287, 296 Algorithms, 223, 230 Alimentary, 223, 277, 278 Alkaline, 47, 53, 65, 69, 70, 74, 223, 232 Alkaline Phosphatase, 47, 53, 65, 69, 70, 74, 223 Alkaloid, 223, 237, 271 Allogeneic, 64, 80, 223, 255 Allogeneic bone marrow transplantation, 80, 223 Alpha Particles, 224, 286 Alpha-Defensins, 128, 224, 242 Alpha-lactalbumin, 130, 224 Alternative medicine, 93, 99, 182, 224, 238 Alveolar Bone Loss, 171, 224 Alveoli, 224, 302 Amino Acid Motifs, 224, 239 Amino Acid Sequence, 38, 114, 119, 149, 224, 226, 239, 252 Amoxicillin, 46, 98, 159, 224 Amphetamines, 224, 237 Ampicillin, 56, 82, 117, 118, 224, 281 Amplification, 55, 160, 161, 224 Anaerobic, 20, 72, 141, 165, 224, 228, 249, 256, 259, 272, 277, 294, 302, 304 Anaesthesia, 224, 260 Anal, 224, 248, 277 Analgesic, 221, 224, 271, 275 Analog, 147, 221, 224, 265 Analogous, 137, 225, 245, 299 Analytes, 204, 225 Anaphylatoxins, 225, 238 Anaplasia, 225 Androgens, 222, 225, 240 Anemia, 225, 229, 251, 256, 257, 268, 297 Anergy, 225, 296 Anesthesia, 223, 225 Angiogenesis, 143, 225 Anhydrides, 159, 225 Animal model, 6, 7, 26, 171, 172, 225 Anionic, 163, 225 Annealing, 225, 282 Anorexia, 224, 225, 252, 301 Antiallergic, 225, 240 Antibiotic Prophylaxis, 173, 178, 183, 225
306
Bacterial Infections
Antibiotics, Aminoglycoside, 154, 155, 225 Antibodies, 6, 17, 36, 47, 153, 154, 155, 156, 226, 256, 257, 259, 267, 271, 281, 287 Anticoagulant, 37, 226, 284 Antifungal, 114, 144, 164, 226, 234, 250, 264, 270, 274 Antifungal Agents, 114, 165, 226 Antigen-Antibody Complex, 226, 238, 250 Antigen-presenting cell, 226, 242 Anti-infective, 7, 84, 118, 127, 144, 148, 226, 235, 293 Anti-Infective Agents, 144, 226 Anti-inflammatory, 14, 221, 226, 227, 240, 253 Anti-Inflammatory Agents, 226, 227, 240 Antimetabolite, 221, 226 Antimycotic, 226, 237 Antineoplastic, 226, 240, 251 Antiproliferative, 153, 226 Antipyretic, 221, 226 Antiseptic, 115, 226, 300 Antiviral, 129, 221, 227, 251, 262 Antiviral Agents, 129, 227 Anus, 178, 224, 227, 231, 278, 288 Anxiety, 169, 227, 277 Apoptosis, 162, 227 Aqueous, 125, 127, 227, 228, 241, 265 Arachidonic Acid, 227, 241, 246, 265, 284 Arginine, 131, 225, 227, 274, 300 Aromatic, 142, 227, 232, 280 Arterial, 227, 253, 259, 285, 297 Arteries, 227, 230, 240, 270, 272, 298, 300, 301 Arthroplasty, 73, 227 Articular, 227, 276 Ascites, 76, 227 Aspergillosis, 227, 264 Aspirin, 185, 227 Assay, 6, 147, 227, 287, 290 Asymptomatic, 22, 156, 227, 229, 254, 277 Atopic, 47, 227 Attenuated, 24, 227 Attenuation, 30, 227 Atypical, 12, 51, 106, 227 Autodigestion, 227, 277 Autoimmune disease, 36, 67, 129, 227 Autopsy, 169, 227 Azithromycin, 33, 104, 105, 107, 138, 158, 190, 228 Aztreonam, 124, 125, 190, 228
B Bacillus, 122, 134, 135, 144, 145, 159, 161, 164, 228, 231 Bacteremia, 19, 78, 103, 228, 269 Bacterial Adhesion, 34, 41, 228 Bacterial Physiology, 228 Bacterial toxin, 151, 228 Bactericidal, 16, 26, 32, 40, 49, 124, 130, 145, 228, 249, 274 Bacteriocins, 115, 228 Bacteriophage, 132, 141, 228, 281, 299, 303 Bacteriostatic, 113, 132, 133, 228, 249, 300 Bacteriuria, 156, 178, 228 Bacteroides, 141, 159, 228 Base, 4, 54, 163, 222, 228, 229, 242, 243, 252, 255, 264, 275, 292, 297, 301 Base Sequence, 229, 252 Basement Membrane, 229, 249 Basophils, 229, 255, 265 Bed Rest, 170, 229 Benign, 34, 162, 169, 174, 229, 256, 273, 277, 287, 303 Beta-Defensins, 21, 229, 242 Beta-Lactamases, 149, 228, 229, 259, 295 Beta-sheet, 128, 229 Beta-Thalassemia, 66, 229 Beta-Thromboglobulin, 229, 262 Bewilderment, 229, 239 Bile, 229, 235, 251, 258, 266, 281, 294, 297 Biliary, 229, 277, 281 Biliary Tract, 229, 277 Binding Sites, 8, 42, 229 Bioavailability, 113, 138, 158, 229 Biofilms, 8, 9, 10, 13, 41, 229 Biological response modifier, 229, 262 Biopsy, 230, 278 Biosynthesis, 10, 119, 121, 122, 129, 139, 227, 230, 235, 237, 292 Biotechnology, 43, 44, 54, 128, 182, 199, 230 Bioterrorism, 11, 230 Biotic, 10, 230 Biotypes, 30, 230 Bladder, 14, 34, 174, 178, 179, 228, 230, 241, 258, 260, 266, 273, 284, 288, 301 Blastocyst, 230, 281 Blastomycosis, 230, 264 Blennorrhoea, 230, 254 Bloating, 230, 263 Blood Cell Count, 52, 83, 230, 256 Blood Coagulation, 37, 230, 232, 290, 298 Blood Coagulation Factors, 230
Index 307
Blood Glucose, 171, 230, 257 Blood Platelets, 230, 281, 298 Blood pressure, 230, 233, 253, 259, 271, 293 Blot, 180, 231 Body Fluids, 54, 231, 232, 245, 293, 295 Bone Marrow, 26, 64, 76, 80, 168, 221, 223, 231, 256, 259, 267, 293 Bone Marrow Transplantation, 64, 76, 80, 223, 231 Bone scan, 231, 291 Bowel, 162, 184, 185, 224, 231, 244, 261, 263, 273, 279, 294, 300 Bowel Movement, 185, 231, 244, 294 Brachytherapy, 231, 263, 286 Bradykinin, 231, 274 Branch, 217, 231, 256, 267, 278, 286, 293, 297 Broad-spectrum, 44, 117, 124, 224, 231, 232, 233, 234, 247, 275, 281, 290, 298 Bronchi, 231, 248, 299 Bronchial, 38, 49, 231, 258 Bronchiectasis, 125, 231 Bronchioles, 224, 231 Bronchiolitis, 54, 81, 231 Bronchiseptica, 21, 231, 279 Bronchitis, 56, 94, 96, 231 Bronchoalveolar Lavage, 38, 231 Brucellosis, 205, 231 Buccal, 231, 267, 294 Burns, 90, 94, 131, 232 Burns, Electric, 232 Bypass, 10, 128, 232 C Calcium, 39, 123, 163, 232, 238, 284, 292 Campylobacter, 3, 178, 205, 206, 232 Candidiasis, 59, 96, 165, 168, 204, 232, 250 Candidosis, 232 Capsular, 123, 141, 232 Capsules, 127, 232, 245, 252 Carbapenems, 159, 232 Carbenicillin, 232, 298 Carbohydrate, 8, 141, 232, 240, 253, 254, 282 Carbon Dioxide, 232, 252, 281, 289, 302 Carboxy, 232 Carboxylic Acids, 33, 232 Carcinoembryonic Antigen, 143, 232 Carcinogenic, 232, 261, 283, 294 Carcinogens, 145, 232 Carcinoma, 168, 174, 232, 233 Cardiac, 6, 233, 247, 248, 252, 272, 294 Cardiovascular, 47, 154, 173, 233, 266
Cardiovascular disease, 173, 233 Catheterization, 34, 233, 263 Catheters, 103, 233, 260, 263 Causal, 233, 248, 257, 291 Cause of Death, 8, 15, 17, 40, 233 Caveolae, 11, 233 Caveolins, 233 Cecum, 233, 265 Cefoperazone, 83, 233 Cefotaxime, 46, 83, 233 Ceftazidime, 50, 56, 233 Ceftriaxone, 76, 77, 233 Cefuroxime, 50, 56, 233 Cell, 4, 6, 7, 11, 16, 17, 19, 23, 26, 27, 28, 29, 31, 32, 33, 36, 39, 42, 43, 47, 52, 58, 66, 75, 82, 83, 84, 85, 87, 90, 122, 123, 131, 132, 134, 141, 143, 147, 153, 156, 157, 160, 162, 168, 176, 180, 183, 184, 207, 208, 221, 225, 226, 227, 228, 230, 233, 234, 236, 237, 238, 241, 242, 243, 245, 247, 248, 249, 250, 251, 253, 255, 256, 259, 260, 261, 262, 263, 264, 265, 267, 268, 269, 270, 271, 272, 273, 274, 276, 279, 280, 281, 282, 284, 287, 288, 289, 290, 291, 292, 296, 297, 298, 299, 300, 302, 303 Cell Adhesion, 39, 143, 233 Cell Adhesion Molecules, 39, 233 Cell Count, 52, 83, 183, 230, 234, 256 Cell Death, 134, 208, 227, 234, 273 Cell Differentiation, 16, 162, 234, 292 Cell Division, 27, 131, 228, 234, 270, 281, 291 Cell membrane, 26, 233, 234, 237, 243, 264, 280 Cell Membrane Structures, 233, 234 Cell motility, 29, 234 Cell Movement, 5, 234 Cell proliferation, 153, 156, 162, 234, 262, 292 Cell Respiration, 234, 270, 276, 289 Cellobiose, 234 Cellulose, 130, 234, 251, 281 Central Nervous System, 80, 221, 223, 224, 234, 237, 251, 253, 254, 256, 266, 271, 278 Central Nervous System Infections, 234, 256 Cephaloridine, 233, 234 Cephalosporins, 68, 121, 149, 152, 190, 229, 234 Cephalothin, 121, 234 Ceramide, 163, 234
308
Bacterial Infections
Cerebral, 207, 234, 240, 246, 248, 249, 268, 277, 293 Cerebrovascular, 233, 234 Cerulenin, 122, 124, 234 Cervical, 235 Cervix, 169, 235, 237, 288 Chancre, 18, 235 Chemical Warfare, 235, 242 Chemical Warfare Agents, 235, 242 Chemokines, 15, 17, 26, 39, 235 Chemotactic Factors, 15, 235, 238 Chemotaxis, 15, 29, 59, 235 Chemotherapy, 44, 50, 56, 61, 63, 68, 70, 71, 76, 77, 78, 85, 86, 94, 108, 168, 173, 174, 235 Chest Pain, 208, 235 Chlorhexidine, 114, 235 Chlorophyll, 235, 247, 251 Chlortetracycline, 94, 113, 235 Cholera, 30, 205, 235, 292, 303 Cholera Toxin, 30, 235 Cholesterol, 11, 207, 229, 233, 235, 240, 266, 291, 294 Cholic Acid, 153, 235 Chondroitin sulfate, 37, 235 Chromatin, 227, 236, 248 Chromosomal, 149, 224, 236, 281 Chromosome, 23, 30, 122, 142, 236, 256, 291 Chronic, 7, 8, 9, 13, 18, 25, 36, 40, 51, 61, 64, 79, 83, 85, 87, 94, 107, 125, 128, 147, 165, 168, 170, 174, 178, 179, 184, 209, 230, 236, 244, 247, 255, 258, 261, 264, 265, 277, 285, 289, 292, 295, 296, 298, 300, 301, 303 Chronic Disease, 236, 265 Chronic renal, 174, 236, 301 Cicatrix, 236, 264 Cilastatin, 45, 66, 68, 72, 77, 236, 259 Cinoxacin, 121, 236 Ciprofloxacin, 121, 142, 190, 236 Clarithromycin, 105, 106, 112, 138, 158, 190, 236 Clavulanic Acid, 45, 46, 236 Cleave, 40, 236 Clinical Medicine, 236, 283 Clinical study, 236, 239 Clinical trial, 4, 12, 13, 44, 45, 61, 63, 67, 73, 83, 94, 103, 108, 185, 199, 236, 239, 271, 285, 287 Clone, 23, 236 Cloning, 8, 28, 230, 236
Clostridium, 178, 206, 237 Clotrimazole, 114, 165, 237 Coagulation, 37, 55, 230, 232, 237, 265, 290, 298 Coca, 237 Cocaine, 169, 237 Codon, 237, 252 Cofactor, 119, 237, 285, 298 Cohort Studies, 237, 248 Coliphages, 228, 237 Colitis, 178, 184, 237, 261, 264, 300 Collagen, 153, 154, 171, 229, 237, 250, 252, 263, 264, 281, 283 Colposcopy, 54, 237 Combination Therapy, 73, 77, 127, 184, 237 Combinatorial, 12, 116, 237 Commensal, 23, 114, 238 Communicable disease, 238, 301 Complement, 14, 15, 42, 82, 225, 238, 252, 268 Complement Activation, 42, 225, 238 Complementary and alternative medicine, 93, 99, 238 Complementary medicine, 93, 238 Computational Biology, 199, 238 Computed tomography, 238, 239, 291 Computerized axial tomography, 238, 291 Concomitant, 165, 239 Condyloma, 168, 239 Cone, 239, 296 Confusion, 208, 239, 244, 301 Conjugated, 235, 239, 241, 250 Conjunctiva, 239, 261 Conjunctivitis, 96, 114, 239 Connective Tissue, 231, 237, 239, 250, 251, 252, 253, 264, 267, 269, 279, 289, 290, 296 Consciousness, 224, 239, 242, 244, 257 Consensus Sequence, 119, 224, 239 Conserved Sequence, 224, 239 Constipation, 239, 263, 279 Consumption, 126, 239, 243, 252, 289 Contamination, 239, 275 Contraindications, ii, 239 Controlled clinical trial, 44, 45, 63, 83, 94, 239, 287 Controlled study, 94, 239 Conventional therapy, 105, 239 Conventional treatment, 239 Convulsions, 84, 240 Cornea, 38, 240, 254, 264 Coronary, 47, 233, 240, 270, 272
Index 309
Coronary heart disease, 233, 240 Coronary Thrombosis, 240, 270, 272 Coronavirus, 143, 240 Corpus, 240, 278, 283 Cortical, 240, 257 Corticosteroid, 186, 240 Cranial, 240, 256, 277, 279 Craniocerebral Trauma, 240, 256, 298 Crossing-over, 240, 288 Cross-Sectional Studies, 240, 248 Cryptosporidiosis, 228, 240 Curative, 240, 297 Cutaneous, 54, 135, 164, 177, 230, 232, 240, 241, 254, 264, 265, 267 Cutaneous Fistula, 177, 241 Cyclic, 222, 241, 255, 274, 284 Cyclooxygenase Inhibitors, 144, 241 Cysteine, 235, 241, 242, 296 Cystitis, 156, 179, 241 Cytochrome, 162, 241, 289 Cytochrome b, 241, 289 Cytokine, 6, 7, 17, 19, 31, 51, 55, 66, 67, 241, 262 Cytomegalovirus, 58, 168, 241 Cytoplasm, 4, 227, 229, 234, 235, 241, 248, 255, 290 Cytoplasmic Vesicles, 241, 279 Cytoskeleton, 29, 241 Cytotoxic, 20, 32, 241, 260, 287, 292 Cytotoxicity, 7, 128, 241 D Dairy Products, 241, 291 Daptomycin, 104, 105, 241 Data Collection, 18, 241 Databases, Bibliographic, 199, 242 De novo, 16, 242 Decidua, 242, 281 Decontamination, 64, 242 Defense Mechanisms, 16, 21, 37, 242 Defensins, 10, 21, 128, 224, 229, 242 Degenerative, 242, 257, 276 Dehydration, 120, 124, 139, 235, 242, 292 Deletion, 25, 227, 242 Delivery of Health Care, 242, 256 Dementia, 221, 242 Denaturation, 242, 282 Dendrites, 242, 273 Dendritic, 24, 84, 85, 242 Dendritic cell, 24, 84, 85, 242 Density, 107, 126, 242, 266, 275 Dental Caries, 115, 177, 242, 243, 250 Dental Hygienists, 180, 243
Dental Plaque, 115, 243 Dentists, 5, 167, 168, 171, 243 Deoxyribonucleic, 129, 243, 290 Deoxyribonucleic acid, 129, 243, 290 Deoxyribonucleotides, 243 Depolarization, 243, 292 Dermatitis, 47, 208, 243 Dermatologist, 186, 243 Deuterium, 243, 258 Developed Countries, 133, 146, 150, 243 Developing Countries, 18, 28, 39, 146, 150, 243, 267 Diabetes Mellitus, 171, 243, 253, 257, 262, 278 Diabetic Foot, 82, 243 Diagnostic procedure, 111, 182, 243 Dialyzer, 243, 257 Diarrhea, 4, 39, 59, 178, 182, 208, 240, 243, 249, 263, 264, 292 Diarrhoea, 243, 252 Diastolic, 243, 259 Diffusion, 243, 261 Digestion, 223, 229, 231, 243, 263, 266, 278, 294 Digestive system, 109, 243, 252, 271 Digestive tract, 244, 268, 292 Dihydrotestosterone, 244, 288 Dilatation, 231, 244, 283, 302 Diphtheria, 12, 177, 244 Diphtheria Toxin, 12, 244 Diploid, 244, 281 Direct, iii, 7, 27, 28, 35, 55, 113, 189, 236, 244, 245, 250, 288 Discrimination, 53, 244 Disease Progression, 71, 244 Disinfectant, 235, 244, 249 Disinfection, 172, 244 Disorientation, 239, 244 Disparity, 72, 244 Dissociation, 15, 53, 223, 244 Dissociative Disorders, 244 Distal, 244, 285 Distention, 180, 244 Dopamine, 237, 244, 280 Dosage Forms, 165, 245 Dose-dependent, 7, 245 Drug Design, 29, 193, 245 Drug Interactions, 106, 173, 193, 245 Drug Resistance, 18, 104, 120, 148, 153, 245 Drug Tolerance, 245, 298 Duct, 233, 245, 290, 302 Duodenum, 229, 245, 294
310
Bacterial Infections
Dura mater, 245, 269, 276 Dysentery, 143, 245 Dysmenorrhea, 164, 245 Dysuria, 180, 245 E Effector, 17, 66, 221, 238, 245 Effector cell, 17, 245 Efficacy, 26, 34, 39, 48, 56, 57, 107, 108, 138, 245, 247, 259 Ego, 246, 275 Eicosanoids, 241, 246 Elastin, 40, 237, 246 Electrocoagulation, 237, 246 Electrolyte, 240, 246, 270, 282, 293, 301 Electrons, 228, 246, 263, 276, 286, 287 Emaciation, 221, 246 Embolus, 246, 261 Embryo, 230, 234, 246, 250, 260, 301 Embryology, 173, 246 Emollients, 246, 275 Emphysema, 16, 246 Empirical, 57, 72, 246 Enamel, 242, 246 Encephalocele, 246, 273 Encephalopathy, 83, 246, 257 Endemic, 31, 235, 246, 268 Endocarditis, 62, 96, 232, 246, 254 Endocardium, 246, 247 Endocytosis, 233, 247 Endonucleases, 86, 247 Endoscope, 237, 247 Endothelial cell, 143, 247, 262, 298 Endothelium, 157, 247, 274 Endothelium, Lymphatic, 247 Endothelium, Vascular, 247 Endothelium-derived, 157, 247, 274 Endotoxin, 31, 57, 176, 247, 300 End-stage renal, 236, 247 Enhancers, 185, 247 Enoxacin, 121, 247 Enteric bacteria, 70, 78, 247 Enterococcus, 43, 104, 148, 153, 154, 160, 247 Enteropeptidase, 247, 300 Environmental Health, 198, 200, 247 Enzymatic, 119, 139, 232, 238, 242, 248, 258, 282, 289 Eosinophils, 248, 255, 265 Epidemic, 30, 138, 172, 248 Epidemiologic Studies, 4, 248 Epidemiological, 23, 48, 64, 86, 175, 178, 248
Epidermal, 16, 156, 248, 264, 303 Epidermal Growth Factor, 16, 156, 248 Epidermis, 248, 264, 286 Epinephrine, 245, 248, 300 Epistaxis, 248, 285 Epithelial, 8, 21, 24, 25, 34, 38, 130, 143, 229, 235, 242, 248, 257, 277 Epithelial Cells, 8, 21, 25, 34, 38, 130, 143, 229, 235, 248, 257 Epithelium, 4, 10, 21, 25, 34, 229, 239, 247, 248, 252, 263, 277 Epitope, 6, 53, 248 Erectile, 248, 278 Erythema, 248, 296 Erythrocyte Indices, 230, 248 Erythrocytes, 225, 230, 231, 248, 257, 288 Erythromycin, 37, 113, 136, 138, 158, 228, 236, 249, 290 Escherichia, 3, 9, 27, 41, 116, 124, 125, 141, 142, 156, 160, 161, 178, 185, 237, 249, 252, 257 Esophagus, 26, 244, 249, 252, 280, 288, 294 Estrogen, 185, 249 Ethanol, 169, 249, 250 Ether, 249, 300 Evoke, 249, 294 Exhaustion, 249, 268 Exogenous, 222, 249, 252, 300 Exotoxin, 122, 123, 249 Extensor, 249, 285 External-beam radiation, 249, 286 Extracellular, 40, 229, 239, 247, 249, 250, 276, 293 Extracellular Matrix, 40, 239, 249, 250, 276 Extracellular Space, 249 Extracorporeal, 151, 174, 249 Eye Infections, 10, 222, 249 F Family Planning, 199, 249 Fat, 227, 231, 234, 235, 240, 246, 249, 253, 266, 289, 291, 293, 296 Fathers, 170, 250 Fatty acids, 94, 119, 223, 232, 246, 250, 254, 266, 284, 293, 298 Febrile, 58, 65, 79, 82, 84, 250, 268 Feces, 232, 239, 250, 294 Fermentation, 160, 250 Fetal Development, 250, 273 Fetal Monitoring, 170, 250 Fetus, 175, 250, 281, 283, 301 Fibrin, 230, 250, 279, 298 Fibroblasts, 32, 250, 262
Index 311
Fibronectin, 250, 252 Fibrosis, 8, 13, 16, 38, 40, 107, 108, 125, 128, 147, 250 Fistulas, 177, 250 Fleroxacin, 121, 250 Fluconazole, 105, 106, 250 Fluorescence, 27, 250 Fluorescent Antibody Technique, 250 Fluorine, 121, 250 Fluoroimmunoassay, 53, 250 Folate, 250, 251 Fold, 20, 38, 251 Folic Acid, 170, 251 Foot Ulcer, 243, 251 Foramen, 251, 279 Fractionation, 143, 251 Friction, 186, 251, 267 Fungi, 144, 163, 226, 227, 249, 251, 255, 270, 272, 304 Fungicides, Industrial, 226, 251 Fungistatic, 251, 300 Fungus, 232, 234, 251, 272 G Gallate, 93, 251 Gallbladder, 221, 229, 244, 251, 252, 266 Gamma Rays, 251, 286, 287 Gamma-interferon, 30, 251 Ganglia, 221, 251, 273 Gangliosides, 163, 251 Gangrenous, 251, 292 Gas, 61, 232, 243, 250, 251, 252, 258, 263, 274, 289, 302 Gas exchange, 252, 289, 302 Gastric, 157, 224, 227, 232, 245, 248, 252, 258, 278 Gastric Acid, 157, 224, 252 Gastric Juices, 252, 278 Gastric Mucosa, 252, 278 Gastrin, 252, 258 Gastroenteritis, 59, 252 Gastroenterology, 3, 46, 67, 81, 177, 178, 252 Gastrointestinal Hemorrhage, 46, 252 Gastrointestinal tract, 232, 249, 252, 266 Gelatin, 252, 254, 296, 297 Gelatinase A, 93, 252 Gels, 8, 252 Gene Expression, 16, 21, 25, 28, 30, 113, 155, 252 Gene Targeting, 40, 252 Genetic Code, 131, 252, 274 Genetic Engineering, 230, 236, 252
Genetic testing, 169, 253, 282 Genetics, 10, 22, 25, 27, 28, 42, 132, 171, 253 Genital, 23, 174, 236, 253, 290, 301, 303 Genitourinary, 173, 178, 253, 301 Genitourinary system, 173, 253 Genomics, 20, 117, 253 Genotype, 253, 280 Germ Cells, 253, 297 Germfree, 36, 90, 253 Gestation, 253, 281 Gland, 174, 222, 240, 253, 267, 268, 276, 281, 284, 291, 294, 295, 298 Glanders, 205, 253, 269 Glomerular, 168, 253, 288 Glomeruli, 253, 286 Glomerulonephritis, 62, 168, 253, 267 Glomerulus, 253, 273 Glottis, 253, 279 Glucocorticoids, 222, 240, 253 Glucose, 62, 171, 230, 234, 243, 253, 254, 257, 261, 262, 290 Glucose Intolerance, 243, 253 Glucuronic Acid, 254, 257 Glutamic Acid, 251, 254, 283 Glycerol, 254, 280 Glycerophospholipids, 254, 280 Glycine, 43, 123, 235, 254, 292 Glycogen, 9, 253, 254 Glycopeptides, 8, 254 Glycoprotein, 143, 232, 250, 254, 271, 298, 300 Glycosaminoglycan, 235, 254 Glycoside, 254, 258, 290 Glycosidic, 225, 234, 254 Glycosylation, 8, 254 Gonadal, 254, 294 Gonorrhea, 28, 177, 209, 233, 254 Gonorrhoea, 127, 254 Governing Board, 254, 283 Graft, 254, 255, 258, 260 Graft Rejection, 255, 260 Gram-Negative Bacteria, 17, 19, 40, 67, 113, 124, 125, 141, 149, 175, 176, 255, 272, 282, 298 Gram-Negative Bacterial Infections, 19, 67, 175, 176, 255 Gram-Positive Bacterial Infections, 46, 57, 64, 85, 103, 104, 107, 108, 255 Granule, 134, 255, 290 Granulocytes, 61, 255, 265, 292, 303 Granulocytopenia, 76, 255
312
Bacterial Infections
Granuloma, 177, 255, 267 Granuloma Inguinale, 177, 255, 267 Granulomatous Disease, Chronic, 255, 289 Grasses, 251, 255 Guanidine, 131, 255 Guanylate Cyclase, 255, 274 Gyrase, 15, 142, 148, 250, 255, 274 H Habitat, 256, 272, 274 Haematological, 71, 256 Haematology, 61, 256 Haemophilus, 41, 68, 116, 122, 124, 125, 130, 138, 142, 161, 233, 256 Hair follicles, 256, 294, 303 Half-Life, 233, 256 Haploid, 256, 281 Haplotypes, 22, 256 Haptens, 223, 256, 287 Headache, 97, 208, 256, 261, 285, 300 Headache Disorders, 256 Health Care Costs, 151, 256 Health Expenditures, 256 Heart attack, 233, 256 Hematocrit, 230, 248, 256 Hematologic malignancies, 60, 256 Heme, 241, 256 Hemodialysis, 44, 243, 256 Hemoglobin, 225, 229, 230, 248, 249, 256, 257, 297 Hemolymph, 52, 257 Hemolysis, 247, 257 Hemolytic, 20, 169, 257, 297 Hemolytic-Uremic Syndrome, 169, 257 Hemorrhage, 46, 80, 240, 246, 252, 256, 257, 286, 295 Hemorrhoids, 131, 257 Heparin, 37, 257, 281 Hepatic, 19, 63, 83, 223, 257 Hepatic Encephalopathy, 83, 257 Hepatitis, 106, 143, 168, 172, 184, 257, 303 Hepatitis Viruses, 168, 257 Hepatocytes, 257 Hereditary, 257, 297 Heredity, 252, 253, 257 Herpes, 129, 168, 172, 221, 257 Herpes virus, 129, 172, 257 Herpes Zoster, 257 Heterogeneity, 223, 258 Heterotrophic, 251, 258 Histamine, 225, 258 Histidine, 133, 258 Homogeneous, 31, 258, 279
Homologous, 12, 21, 26, 240, 252, 258, 291, 296 Hormonal, 240, 258 Hormone, 169, 240, 246, 248, 252, 258, 262, 269, 283, 289, 292, 297, 298 Human papillomavirus, 168, 258 Humoral, 11, 69, 255, 258 Humour, 258 Hybrid, 120, 236, 258 Hybridization, 161, 258, 274 Hydrogen, 153, 228, 232, 242, 243, 258, 271, 273, 274, 276, 285, 304 Hydrolases, 149, 258, 278, 280 Hydrolysis, 229, 234, 247, 258, 278, 280, 282, 285, 300 Hydronephrosis, 178, 258 Hydrophobic, 114, 123, 254, 258, 264, 266 Hydroxylysine, 237, 259 Hydroxyproline, 237, 259 Hyperaemia, 239, 259 Hypersensitivity, 168, 173, 259, 266, 289 Hypertension, 174, 233, 256, 259, 298, 301 Hypotension, 240, 259 I Id, 91, 95, 120, 205, 210, 216, 218, 246, 259 Imidazole, 148, 237, 258, 259, 270 Imipenem, 45, 66, 68, 72, 77, 159, 236, 259 Immersion, 126, 259 Immune function, 106, 172, 259, 260 Immune Sera, 259 Immunization, 6, 90, 105, 155, 222, 259, 260 Immunocompromised, 4, 61, 125, 128, 146, 259 Immunocompromised Host, 61, 259 Immunodeficiency, 27, 37, 59, 60, 66, 72, 74, 82, 172, 180, 208, 221, 259 Immunodeficiency syndrome, 72, 172, 180, 259 Immunofluorescence, 7, 259 Immunogenic, 12, 155, 156, 260, 287 Immunoglobulin, 77, 226, 250, 260, 271 Immunologic, 222, 235, 259, 260, 287 Immunomodulator, 184, 260 Immunosuppressant, 185, 260 Immunosuppressive, 47, 259, 260, 297 Immunosuppressive Agents, 47, 260 Immunosuppressive therapy, 260 Immunotherapy, 174, 222, 260 Impairment, 66, 229, 249, 260, 269 Implant radiation, 260, 263, 286
Index 313
In vivo, 5, 7, 9, 16, 30, 38, 39, 40, 43, 124, 128, 133, 134, 257, 260, 297, 298 Incision, 260, 263 Incontinence, 174, 260 Incubated, 162, 260 Incubation, 260, 279 Incubation period, 260, 279 Indicative, 174, 260, 278, 302 Induction, 7, 9, 21, 26, 77, 84, 132, 133, 162, 225, 260 Induction therapy, 77, 260 Infancy, 59, 175, 261 Infarction, 87, 229, 240, 261, 270, 272 Infection Control, 18, 64, 172, 185, 261 Infertility, 170, 174, 261 Infiltration, 7, 253, 261 Inflammatory bowel disease, 162, 184, 261 Influenza, 34, 96, 116, 122, 261 Infusion, 127, 261, 270, 299 Inguinal, 261, 267 Inhalation, 108, 222, 261, 282 Initiation, 7, 20, 21, 183, 261, 295 Initiator, 261, 262 Inlay, 261, 289 Inner ear, 233, 261, 302 Inorganic, 261, 271 Inositol, 129, 261 Inpatients, 46, 261 Insecticides, 262, 279 Insight, 5, 29, 41, 42, 262 Instillation, 23, 180, 262 Insulin, 262, 300 Intensive Care, 15, 31, 55, 67, 72, 83, 84, 127, 154, 262 Intensive Care Units, 127, 154, 262 Interferon, 30, 53, 67, 72, 106, 184, 251, 262, 267 Interferon-alpha, 53, 262 Interleukin-1, 24, 44, 55, 106, 262 Interleukin-12, 106, 262 Interleukin-2, 72, 262 Interleukin-8, 80, 262 Interleukins, 260, 262 Internal Medicine, 17, 19, 20, 59, 72, 87, 252, 262 Internal radiation, 263, 286 Interstitial, 179, 231, 249, 252, 263, 273, 288 Interstitial Collagenase, 252, 263 Intestinal, 4, 23, 53, 64, 65, 66, 128, 144, 224, 228, 232, 235, 237, 240, 247, 263, 265, 277
Intestine, 3, 4, 162, 231, 233, 245, 249, 258, 263, 265, 288, 292, 295, 300 Intoxication, 263, 299 Intracellular, 7, 11, 12, 15, 17, 23, 31, 39, 70, 163, 241, 255, 261, 263, 269, 274, 282, 284, 290, 292 Intracellular Membranes, 241, 263, 269 Intramuscular, 263, 277 Intraocular, 10, 263 Intravascular, 37, 55, 263 Intravenous, 19, 67, 68, 107, 114, 128, 186, 208, 261, 263, 270, 277 Intrinsic, 16, 118, 223, 229, 263 Introns, 263, 285 Introspection, 170, 263 Intubation, 233, 263 Invasive, 22, 23, 48, 58, 68, 73, 79, 81, 182, 259, 263, 268 Invertebrates, 26, 257, 263 Involuntary, 174, 263, 272, 293 Ionizing, 224, 263, 287 Ions, 228, 244, 246, 255, 258, 263, 282 Iris, 240, 263, 286 Irritable Bowel Syndrome, 184, 263 Irritants, 245, 264 Ischemia, 251, 264 Ischemic Colitis, 178, 264 Isoprenoids, 129, 264 Isopropyl, 152, 264 Itraconazole, 165, 264 J Joint, 6, 68, 153, 172, 183, 227, 236, 264, 276, 296 K Kanamycin, 142, 264 Kb, 198, 264 Keloid, 186, 264 Keratinocytes, 262, 264 Keratitis, 10, 38, 264 Keratolytic, 242, 264 Ketoconazole, 114, 264 Kidney Disease, 109, 198, 258, 264 Kidney Pelvis, 264, 301 Kidney stone, 258, 264 Kinetics, 19, 41, 62, 264 L Labile, 123, 238, 264 Lacerations, 208, 264 Lactobacillus, 23, 264 Lamivudine, 184, 265 Large Intestine, 3, 233, 244, 263, 265, 288, 292
314
Bacterial Infections
Larynx, 253, 265, 299 Laser Surgery, 174, 265 Latent, 265, 283 Lavage, 38, 231, 265 Lectin, 265, 269 Leishmaniasis, 51, 265, 278 Lens, 232, 265 Leprosy, 177, 205, 251, 265 Leptospirosis, 205, 265 Lesion, 39, 230, 251, 255, 265, 266, 300 Lethal, 5, 8, 11, 15, 28, 85, 228, 244, 265 Leucocyte, 69, 265, 267 Leukaemia, 61, 77, 265 Leukemia, 77, 86, 160, 221, 256, 265 Leukocytes, 45, 123, 143, 229, 230, 231, 235, 248, 255, 262, 265, 300 Leukoplakia, 168, 265 Leukotrienes, 90, 227, 246, 265 Library Services, 216, 266 Life cycle, 133, 251, 266 Life Expectancy, 144, 266 Ligament, 266, 284 Ligands, 27, 37, 155, 233, 266 Lipid, 11, 38, 162, 233, 254, 262, 266 Lipid Bilayers, 38, 266 Lipopolysaccharide, 31, 55, 59, 90, 128, 228, 255, 266 Lipoprotein, 255, 266 Lipoxygenase, 266 Lithotripsy, 174, 266 Liver scan, 266, 291 Liver Transplantation, 71, 266 Localization, 27, 36, 77, 266 Localized, 4, 11, 25, 208, 221, 242, 244, 261, 266, 281, 300 Locomotion, 266, 281 Loop, 143, 162, 267 Lubricants, 267 Lubrication, 164, 267 Luminol, 88, 267 Lupus, 168, 267, 297 Lupus Nephritis, 168, 267 Lymph, 235, 247, 258, 267, 295 Lymph node, 235, 267 Lymphatic, 97, 247, 261, 267, 269, 293, 294, 298 Lymphatic system, 267, 293, 294, 298 Lymphoblastic, 86, 221, 267 Lymphoblasts, 221, 267 Lymphocyte, 29, 221, 226, 267, 268, 269 Lymphocyte Count, 221, 267 Lymphocytic, 61, 221, 267
Lymphogranuloma Venereum, 114, 255, 267 Lymphoid, 26, 226, 265, 267, 299 Lymphoma, 168, 256, 267 Lysine, 259, 267, 300 Lysosome, 32, 267, 279 Lytic, 29, 267, 303 M Macrolides, 112, 136, 138, 158, 267 Macrophage, 17, 20, 71, 262, 268 Magnetic Resonance Imaging, 268, 291 Major Histocompatibility Complex, 256, 268 Malacoplakia, 178, 268 Malaise, 231, 268 Malaria, 153, 268 Malaria, Falciparum, 268 Malaria, Vivax, 268 Malignancy, 160, 268, 277 Malignant, 5, 74, 160, 162, 174, 221, 226, 268, 273, 287, 290 Malignant tumor, 5, 162, 268 Malnutrition, 76, 223, 268 Mammary, 143, 268 Mandible, 224, 268, 289 Manifest, 128, 268 Mastitis, 131, 230, 268, 277, 292 Meat, 268, 291 Mechanical ventilation, 125, 268 Mediate, 14, 17, 18, 41, 42, 134, 233, 245, 246, 262, 269 Mediator, 37, 262, 269, 281 Medicament, 127, 269, 296 MEDLINE, 199, 269 Megaloblastic, 251, 269 Melanin, 263, 269, 280, 300 Melioidosis, 205, 269 Membrane Proteins, 27, 35, 233, 269, 285 Meninges, 228, 233, 234, 240, 245, 269 Meningitis, 14, 20, 41, 50, 69, 70, 97, 135, 141, 164, 204, 250, 254, 264, 269 Menstruation, 242, 245, 269 Mental Disorders, 109, 269, 286 Mental Health, iv, 4, 109, 198, 200, 269, 286 Mental Processes, 244, 269, 286 Menthol, 120, 269 Mesenchymal, 248, 269 Meta-Analysis, 46, 78, 80, 269 Metabolite, 144, 269, 283 Metastasis, 138, 234, 269 Metastatic, 5, 269, 270, 291
Index 315
Metastatic cancer, 5, 270 Methicillin Resistance, 148, 270 Methionine, 85, 270, 296 MI, 115, 118, 170, 219, 270 Miconazole, 114, 165, 270 Microbe, 5, 115, 204, 270, 299 Microgram, 250, 270 Microorganism, 25, 123, 146, 160, 183, 237, 270, 277, 303 Micro-organism, 242, 253, 270, 291 Microscopy, 27, 32, 41, 169, 229, 250, 270 Migration, 15, 45, 71, 270 Mineralocorticoids, 222, 240, 270 Minocycline, 113, 270 Miscarriage, 169, 170, 270 Mitochondria, 162, 270, 275 Mitochondrial Swelling, 270, 273 Mitosis, 227, 270 Mobilization, 16, 270 Modeling, 8, 245, 271 Modification, 37, 121, 171, 252, 271, 286, 304 Monitor, 171, 232, 271, 274 Monoclonal, 36, 153, 154, 271, 287 Monoclonal antibodies, 36, 153, 154, 271 Monocyte, 29, 271 Mononuclear, 31, 255, 271, 300 Monotherapy, 57, 72, 73, 271 Morphine, 169, 271, 272, 275 Morphological, 32, 168, 246, 251, 271 Morphology, 256, 271 Motility, 4, 29, 234, 271 Motor Activity, 240, 271 Mucins, 8, 243, 271, 290 Mucociliary, 271, 292 Mucocutaneous, 59, 265, 271 Mucolytic, 231, 271 Mucosa, 252, 253, 261, 267, 271, 272, 289, 294 Mucositis, 271, 298 Mucus, 8, 230, 245, 271, 300 Multicenter study, 79, 271 Multidrug resistance, 150, 272 Muscle Fibers, 272 Mutagenesis, 20, 35, 37, 41, 272 Mutagens, 272 Myalgia, 261, 272 Myasthenia, 255, 272 Mycobacteriophages, 28, 272 Mycobacterium, 12, 15, 27, 66, 106, 134, 141, 148, 150, 228, 265, 272, 290, 300 Mycoplasma, 87, 116, 234, 272
Mycosis, 272 Mycotic, 5, 205, 206, 207, 272 Myocardial infarction, 87, 229, 240, 270, 272 Myocarditis, 6, 244, 272 Myocardium, 270, 272 Myosin, 6, 272 Myristate, 88, 272 N Nalidixic Acid, 121, 142, 236, 272, 276 Narcotic, 271, 272 Nasal Mucosa, 261, 272 Natural killer cells, 262, 272 Nausea, 245, 252, 272, 285, 301 NCI, 1, 109, 197, 273 Nebramycin, 273, 298 Nebulizer, 125, 273 Necrosis, 14, 16, 24, 227, 257, 261, 270, 272, 273, 300 Neomycin, 37, 191, 273 Neonatal, 14, 15, 20, 23, 38, 54, 56, 67, 69, 70, 72, 74, 79, 254, 273 Neoplasia, 36, 174, 273 Neoplasm, 273, 277, 290, 300 Neoplastic, 225, 267, 273 Nephritis, 168, 267, 273 Nephropathy, 168, 264, 273 Nerve, 225, 242, 269, 273, 276, 282, 294, 298, 300, 302 Nervous System, 80, 121, 174, 221, 223, 224, 234, 237, 251, 253, 254, 256, 266, 269, 271, 273, 278, 295 Netilmicin, 44, 77, 273 Neural, 131, 169, 223, 246, 258, 273 Neural tube defects, 169, 273 Neurologic, 172, 173, 246, 273 Neurologic Manifestations, 173, 273 Neurons, 237, 242, 251, 273, 296 Neutrons, 224, 273, 286 Neutropenia, 57, 74, 108, 274 Neutrophil, 14, 15, 17, 29, 36, 40, 56, 59, 65, 74, 75, 87, 274 Niche, 147, 274 Nitric Oxide, 157, 274 Nitrogen, 140, 161, 223, 225, 274, 300 Norfloxacin, 48, 76, 121, 142, 274 Nosocomial, 8, 17, 18, 19, 43, 76, 77, 86, 148, 154, 274 Nuclear, 65, 77, 85, 246, 251, 273, 274, 285, 301 Nuclei, 224, 246, 253, 263, 268, 270, 273, 274, 285
316
Bacterial Infections
Nucleic acid, 32, 115, 119, 135, 161, 229, 252, 258, 272, 274, 286, 290, 304 Nucleic Acid Hybridization, 258, 274 Nucleotidases, 258, 274 Nucleus, 184, 225, 227, 229, 236, 241, 243, 248, 251, 271, 274, 285, 295 Nurse Practitioners, 179, 274 Nystatin, 114, 274 O Obsession, 170, 275 Occult, 78, 275 Ocular, 10, 26, 84, 93, 275 Odour, 227, 275, 301 Ofloxacin, 77, 99, 121, 191, 275 Ointment Bases, 165, 275 Ointments, 245, 275, 293 Oliguria, 174, 275 Oophoritis, 254, 275 Opacity, 242, 275 Operon, 9, 122, 123, 275, 288 Ophthalmic, 26, 190, 191, 192, 275 Ophthalmology, 26, 75, 275 Opium, 271, 275 Opportunistic Infections, 5, 33, 126, 172, 180, 221, 275 Oral Health, 168, 171, 275 Oral Hygiene, 208, 275 Oral Manifestations, 168, 171, 173, 174, 180, 275 Organ Culture, 275, 298 Organelles, 241, 275 Orofacial, 45, 172, 173, 276 Osmosis, 276 Osmotic, 123, 223, 270, 276 Osteoarthritis, 173, 276 Osteoblasts, 6, 276 Otitis, 41, 159, 276 Otitis Media, 41, 159, 276 Ovum, 242, 253, 266, 276, 283 Oxazolidinones, 116, 118, 140, 141, 154, 155, 276 Oxidation, 241, 267, 276 Oxidative metabolism, 266, 276 Oxolinic Acid, 121, 276 Oxytetracycline, 113, 276 P Pachymeningitis, 269, 276 Paediatric, 50, 83, 276 Palate, 276, 294 Palliative, 276, 297 Pancreas, 221, 244, 252, 262, 276, 277, 300 Pancreatic, 276, 277
Pancreatitis, 67, 277 Paneth Cells, 224, 277 Panic, 170, 277 Papilloma, 239, 277 Papillomavirus, 168, 258, 277 Papule, 235, 277 Paranasal Sinuses, 277, 292 Parasite, 277 Parasitic, 169, 176, 240, 245, 277, 290 Parenteral, 51, 78, 127, 277 Parietal, 157, 277, 279 Parietal Lobe, 277 Paroxysmal, 256, 277, 279, 303 Particle, 125, 277, 299 Pasteurella, 122, 123, 277 Pasteurella haemolytica, 122, 123, 277 Pasteurellosis, Pneumonic, 277 Patch, 265, 277 Pathogen, 5, 6, 13, 21, 24, 25, 32, 39, 40, 134, 147, 156, 161, 175, 178, 260, 277, 296 Pathologic, 26, 227, 230, 232, 240, 259, 278, 285, 288 Pathologic Processes, 227, 278 Patient Compliance, 39, 278 Patient Education, 171, 208, 214, 216, 219, 278 Pefloxacin, 121, 278 Pelvic, 278, 284 Penicillin, 28, 33, 99, 114, 117, 121, 132, 138, 142, 144, 224, 232, 270, 278, 298 Penis, 174, 278, 288 Pentamidine, 48, 278 Pepsin, 278 Pepsin A, 278 Peptic, 127, 278 Peptic Ulcer, 127, 278 Peptide, 6, 12, 21, 26, 65, 131, 145, 153, 154, 235, 236, 247, 258, 278, 282, 284, 285, 296 Peptide Chain Elongation, 236, 278 Peptide Fragments, 154, 278 Peptide Hydrolases, 258, 278 Percutaneous, 173, 266, 278 Perianal, 239, 278 Perineum, 278, 294 Periodontal disease, 171, 177, 224, 279 Periodontitis, 25, 168, 171, 177, 279 Peripheral blood, 6, 31, 74, 262, 279 Peripheral Nerves, 265, 279 Peritoneal, 36, 227, 279 Peritoneal Cavity, 36, 227, 279 Peritoneum, 279, 289 Peritonitis, 97, 254, 279
Index 317
Pertussis, 21, 73, 123, 279, 303 Pesticides, 145, 262, 279 Phagocyte, 14, 60, 66, 279 Phagocytosis, 15, 21, 29, 31, 42, 279 Phagosomes, 31, 279 Pharmaceutical Preparations, 127, 234, 249, 252, 279 Pharmaceutical Solutions, 245, 279 Pharmacodynamic, 16, 50, 106, 280 Pharmacokinetic, 140, 280 Pharmacologic, 173, 225, 256, 280, 299 Pharyngitis, 127, 280, 291 Pharynx, 261, 280 Phenotype, 36, 59, 280 Phenyl, 116, 152, 280 Phenylalanine, 278, 280, 300 Phorbol, 88, 280, 285 Phorbol Esters, 280, 285 Phospholipases, 280, 292 Phospholipids, 163, 249, 261, 266, 280, 284 Phosphoric Monoester Hydrolases, 258, 280 Phosphorus, 232, 280 Phosphorylates, 280, 284 Phosphorylation, 29, 39, 163, 280 Photocoagulation, 237, 280 Physical Examination, 173, 209, 280 Physiologic, 15, 230, 250, 256, 269, 280, 284, 288 Physiology, 28, 30, 41, 222, 228, 252, 280, 289, 296, 302 Pigment, 280, 281 Pigmentation, 174, 281 Pipemidic Acid, 121, 281 Piperacillin, 45, 281 Pituitary Gland, 240, 281 Placenta, 143, 281, 283, 301 Plague, 281, 300 Plant Diseases, 145, 247, 281 Plants, 119, 122, 129, 144, 163, 223, 230, 232, 237, 242, 253, 254, 265, 271, 281, 285, 290, 299 Plaque, 115, 235, 243, 281 Plasma cells, 226, 281 Plasmid, 23, 62, 281, 302 Platelet Activation, 281, 292 Platelet Aggregation, 225, 274, 281, 298 Platelet Factor 4, 262, 281 Platelets, 229, 230, 274, 281, 298 Platinum, 267, 281 Poisoning, 252, 263, 273, 282, 291 Polymerase, 54, 184, 227, 282, 288
Polymerase Chain Reaction, 54, 282 Polymers, 42, 229, 282, 285 Polymorphic, 18, 31, 282 Polymorphism, 81, 282 Polypeptide, 119, 136, 139, 164, 221, 224, 237, 239, 248, 254, 258, 278, 282, 284, 297, 304 Polysaccharide, 9, 11, 105, 123, 141, 226, 234, 254, 282 Polyvalent, 141, 282 Population Growth, 147, 282 Porins, 19, 282 Postnatal, 15, 38, 282, 294 Postsynaptic, 282, 292 Post-translational, 123, 282 Potassium, 159, 270, 282, 293 Potentiates, 262, 282 Potentiation, 282, 292 Practice Guidelines, 200, 283 Precancerous, 283 Precipitation, 130, 283 Precursor, 10, 123, 147, 227, 245, 248, 280, 283, 300 Predisposition, 36, 183, 283 Premalignant, 174, 283 Prenatal, 170, 246, 283 Presumptive, 4, 283 Prevalence, 3, 13, 23, 27, 35, 79, 154, 161, 283 Probe, 255, 283 Prodrug, 32, 162, 283 Progesterone, 283, 294 Progression, 71, 87, 168, 171, 225, 244, 283 Progressive, 38, 128, 147, 234, 236, 242, 245, 255, 273, 276, 281, 283, 288, 300 Projection, 242, 283 Proline, 237, 259, 283 Promoter, 30, 122, 123, 283 Prone, 186, 283 Prospective study, 44, 48, 71, 283 Prostaglandin, 241, 284, 298 Prostaglandin-Endoperoxide Synthase, 241, 284 Prostaglandins A, 90, 284 Prostaglandins D, 284 Prostate, 174, 284, 288 Prostate gland, 174, 284 Prostatitis, 131, 178, 284 Protease, 33, 237, 284 Protein C, 77, 130, 132, 155, 223, 224, 228, 237, 266, 284 Protein Conformation, 224, 284
318
Bacterial Infections
Protein Kinase C, 24, 284 Protein S, 15, 16, 32, 154, 155, 226, 227, 230, 236, 239, 244, 249, 252, 273, 284, 285, 290, 295, 297 Proteolytic, 238, 247, 285 Protocol, 34, 54, 285 Proton Pump, 157, 285 Proton Pump Inhibitors, 157, 285 Protons, 224, 258, 263, 285, 286 Protozoa, 245, 265, 270, 285, 300 Proximal, 24, 244, 285 Pseudogenes, 143, 285 Pseudomonas Infections, 281, 285 Psittacosis, 114, 285 Psoriasis, 162, 285, 289 Psychiatric, 169, 269, 285 Psychiatry, 285, 286, 302 Psychology, 244, 286 Public Health, 15, 18, 20, 33, 34, 35, 200, 286 Public Policy, 199, 286 Publishing, 43, 172, 173, 178, 286 Pulse, 271, 286 Pupil, 240, 286 Purines, 229, 286, 292 Purpura, 169, 286 Purulent, 127, 254, 286, 302 Pyelonephritis, 41, 156, 178, 286 Pyogenic, 249, 286, 291 Q Quality of Life, 34, 107, 167, 286 Quinolones, 15, 86, 121, 142, 286 R Race, 36, 270, 286 Radiation, 168, 249, 250, 251, 259, 260, 263, 286, 287, 291, 296, 304 Radiation therapy, 168, 249, 251, 263, 286 Radioactive, 231, 242, 256, 258, 260, 263, 266, 271, 274, 286, 287, 291, 297, 301 Radioimmunoassay, 229, 250, 287 Radioimmunotherapy, 287 Radiolabeled, 85, 287 Radiological, 278, 287 Radiology, 173, 287 Radionuclide Imaging, 173, 287 Radiotherapy, 174, 231, 287 Randomized, 13, 34, 35, 44, 45, 46, 57, 67, 76, 83, 107, 108, 246, 287 Randomized clinical trial, 13, 67, 287 Randomized Controlled Trials, 46, 287 Reactivation, 131, 168, 287
Receptor, 11, 14, 17, 24, 29, 33, 35, 36, 39, 59, 65, 75, 117, 156, 222, 226, 239, 245, 285, 287, 292, 296 Recombinant, 23, 28, 132, 288, 302 Recombination, 19, 252, 288 Reconstitution, 19, 42, 127, 288 Rectal, 14, 97, 288 Rectum, 178, 184, 227, 231, 244, 251, 260, 261, 265, 284, 288, 296 Recurrence, 156, 157, 288 Red blood cells, 248, 257, 288, 290 Reductase, 119, 120, 124, 139, 288 Refer, 1, 135, 164, 231, 238, 251, 257, 266, 267, 274, 287, 288 Reflux, 173, 288 Refraction, 288, 293 Refractory, 23, 246, 288 Regeneration, 43, 288 Regimen, 33, 77, 126, 127, 150, 159, 245, 278, 288 Rehydration, 39, 288 Relaxation Techniques, 170, 288 Remission, 288 Renal failure, 174, 257, 288, 301 Renal pelvis, 174, 264, 288 Renovascular, 174, 288 Repressor, 9, 12, 275, 288 Reproductive system, 284, 288 Resorption, 224, 288 Respiration, 232, 234, 270, 271, 276, 289 Respirator, 268, 289, 302 Respiratory Burst, 29, 289 Respiratory distress syndrome, 38, 289 Respiratory failure, 8, 147, 289, 302 Respiratory Mucosa, 253, 289 Respiratory Physiology, 289, 302 Respiratory syncytial virus, 52, 79, 80, 289 Restoration, 64, 287, 288, 289, 304 Retinal, 239, 244, 289, 303 Retinoids, 16, 289, 303 Retrograde, 173, 289 Retroperitoneal, 222, 289 Rheumatic Diseases, 160, 183, 289 Rheumatism, 289 Rheumatoid, 45, 82, 173, 289 Rheumatoid arthritis, 45, 82, 173, 289 Rhinitis, 231, 290, 292 Ribonucleic acid, 37, 129, 290 Ribose, 222, 290 Ribosome, 290, 299 Rickettsia, 23, 290 Rickettsiae, 23, 113, 116, 290
Index 319
Rifabutin, 105, 106, 290 Rigidity, 28, 281, 290 Risk factor, 81, 171, 172, 180, 183, 248, 283, 290 Ristocetin, 290, 302 Rod, 228, 249, 256, 264, 277, 285, 290, 304 Rodenticides, 279, 290 Roxithromycin, 138, 290 Rubella, 49, 172 S Saline, 125, 231, 290 Saliva, 168, 290 Salivary, 45, 168, 174, 177, 241, 243, 244, 290, 295, 300, 304 Salivary glands, 45, 168, 177, 241, 243, 244, 290, 300 Salpingitis, 254, 290 Saponins, 290, 294 Sarcoma, 78, 168, 290 Saturated fat, 119, 139, 291 Scans, 174, 291 Scarlet Fever, 177, 291 Screening, 31, 32, 113, 117, 121, 122, 132, 133, 143, 207, 236, 291 Scrotum, 174, 291, 297, 302 Sebaceous, 264, 291, 303 Secondary tumor, 269, 291 Secretion, 16, 21, 23, 123, 157, 240, 248, 253, 258, 262, 270, 271, 291 Secretory, 43, 74, 157, 224, 291 Segregation, 228, 288, 291 Self Care, 180, 291 Semen, 284, 291 Seminal vesicles, 174, 291, 302 Semisynthetic, 138, 224, 232, 233, 236, 259, 270, 273, 281, 290, 291 Sepsis, 14, 15, 20, 31, 57, 208, 291 Septic, 31, 183, 291 Septicaemia, 291, 292 Septicemia, 69, 141, 151, 291 Sequencing, 282, 291 Serine, 40, 149, 222, 284, 291, 300 Serotypes, 20, 22, 292 Serous, 16, 247, 292 Serum, 42, 49, 53, 69, 82, 222, 223, 224, 225, 238, 259, 270, 279, 287, 288, 292, 300 Sessile, 9, 292 Sexually Transmitted Diseases, 173, 292 Shigellosis, 205, 206, 292 Shock, 19, 31, 47, 59, 63, 97, 144, 174, 266, 292, 300
Side effect, 14, 106, 114, 138, 144, 159, 184, 189, 193, 222, 292, 299, 304 Signal Transduction, 24, 29, 233, 261, 292 Signs and Symptoms, 171, 273, 288, 292, 301 Sinusitis, 135, 164, 292 Skeleton, 221, 264, 284, 292 Skull, 240, 246, 273, 292, 297 Small intestine, 4, 233, 245, 258, 263, 292, 300 Smooth muscle, 162, 224, 225, 258, 271, 292, 295 Sneezing, 279, 293 Soaps, 293, 300 Social Environment, 286, 293 Sodium, 127, 270, 293 Soft tissue, 152, 173, 231, 292, 293 Solid tumor, 225, 293 Solvent, 144, 249, 254, 276, 279, 293 Somatic, 258, 270, 293 Spasmodic, 279, 293 Spastic, 263, 293 Specialist, 14, 210, 293 Species, 3, 9, 23, 27, 114, 115, 118, 123, 124, 125, 128, 133, 135, 138, 141, 143, 145, 149, 150, 153, 154, 155, 156, 159, 161, 164, 177, 223, 226, 228, 232, 234, 237, 239, 248, 249, 252, 256, 258, 265, 268, 270, 271, 272, 274, 277, 285, 286, 290, 293, 294, 295, 298, 300, 303, 304 Species Specificity, 123, 293 Specificity, 6, 41, 58, 123, 223, 293, 295 Sperm, 225, 236, 293, 297 Spermatic, 174, 293 Spina bifida, 273, 294 Spinal cord, 34, 234, 235, 245, 269, 273, 276, 279, 294 Spirochete, 294, 296 Spleen, 36, 241, 267, 294 Spondylitis, 186, 294 Sputum, 107, 294 Squamous, 168, 294 Staging, 291, 294 Stasis, 173, 294 Stem Cells, 223, 294 Sterility, 261, 294 Sterilization, 172, 294 Steroid, 184, 290, 294 Stimulus, 184, 245, 262, 294, 297 Stomatitis, 168, 294 Stool, 14, 178, 260, 263, 265, 294, 297 Strand, 33, 282, 295
320
Bacterial Infections
Streptococcal, 6, 105, 153, 154, 295 Streptococci, 14, 20, 23, 115, 116, 138, 141, 291, 295 Streptococcus pneumoniae, 34, 42, 51, 78, 116, 130, 134, 135, 138, 148, 160, 163, 164, 208, 295 Streptomycin, 114, 142, 144, 295 Stress, 126, 128, 170, 178, 180, 252, 263, 272, 283, 289, 295 Stroke, 82, 109, 198, 233, 295 Subacute, 261, 267, 292, 295 Subarachnoid, 256, 295 Subclinical, 94, 261, 295 Subcutaneous, 135, 164, 251, 277, 295 Submaxillary, 248, 295 Subspecies, 293, 295 Substance P, 249, 269, 288, 290, 291, 295 Substrate, 29, 32, 33, 41, 43, 58, 149, 157, 235, 241, 258, 295 Substrate Specificity, 41, 58, 295 Sulbactam, 56, 83, 118, 295 Sulfur, 232, 265, 270, 295 Sunburn, 97, 131, 296 Superantigens, 22, 296 Superinfection, 144, 228, 296 Superoxide, 29, 289, 296 Superstitions, 170, 296 Suppositories, 184, 252, 296 Suppression, 21, 240, 296 Suppurative, 177, 251, 254, 296 Surfactant, 38, 296 Symphysis, 284, 296 Symptomatic, 34, 277, 296 Synaptic, 292, 296 Synergistic, 34, 117, 120, 296 Synovial, 54, 183, 296 Synovial Fluid, 54, 183, 296 Synovial Membrane, 296 Syphilis, 18, 177, 235, 296 Systemic disease, 4, 22, 174, 291, 296 Systemic lupus erythematosus, 267, 296 Systolic, 259, 297 T Tachycardia, 228, 297 Tachypnea, 228, 297 Tacrolimus, 79, 297 Taurine, 235, 297 Technetium, 77, 297 Teichoic Acids, 255, 297 Teicoplanin, 46, 64, 297 Temporal, 68, 256, 297 Tenesmus, 245, 297
Testicles, 291, 297 Testis, 174, 294, 297 Testosterone, 288, 297 Tetracycline, 28, 113, 114, 142, 154, 270, 297 Thalassemia, 66, 229, 297 Therapeutics, 10, 32, 37, 41, 45, 64, 117, 133, 154, 193, 297 Thermal, 244, 274, 282, 297 Threonine, 43, 284, 292, 297 Threshold, 177, 259, 297 Thrombin, 250, 281, 284, 298 Thrombocytopenia, 168, 257, 298 Thrombomodulin, 37, 284, 298 Thrombosis, 229, 240, 270, 272, 285, 295, 298 Thromboxanes, 227, 241, 246, 298 Thrombus, 240, 261, 281, 298 Thymidine, 85, 298 Thymus, 26, 259, 267, 298 Thyroid, 298, 300 Ticarcillin, 45, 56, 298 Ticks, 23, 298 Tinnitus, 276, 298 Tissue Culture, 25, 298 Tobramycin, 108, 192, 298 Tolerance, 6, 104, 112, 113, 136, 146, 222, 245, 253, 298 Tomography, 85, 238, 239, 291, 298 Tonsillitis, 127, 291, 298 Tonsils, 26, 298, 299 Tooth Loss, 25, 299 Tooth Preparation, 222, 299 Topical, 184, 191, 235, 249, 293, 299 Torsion, 261, 299 Toxemia, 169, 299 Toxic, iv, 16, 31, 123, 124, 144, 145, 164, 228, 241, 244, 249, 255, 259, 278, 299, 302, 304 Toxicity, 157, 245, 273, 290, 299 Toxicology, 200, 299 Toxins, 4, 39, 123, 151, 226, 230, 254, 261, 271, 287, 291, 299 Toxoplasmosis, 228, 299 Trace element, 250, 299 Trachea, 21, 231, 265, 280, 298, 299 Transcriptase, 265, 299, 304 Transduction, 24, 29, 233, 261, 292, 299 Transfection, 230, 299 Transfer Factor, 259, 299 Transferases, 254, 299 Transfusion, 63, 64, 172, 299
Index 321
Translation, 135, 136, 155, 164, 249, 273, 285, 299 Translational, 20, 123, 282, 299 Translocation, 236, 249, 300 Transmitter, 221, 245, 269, 300 Transplantation, 47, 58, 64, 67, 71, 76, 80, 85, 169, 174, 231, 236, 259, 266, 268, 300 Transposons, 20, 300 Trauma, 186, 240, 256, 273, 277, 298, 300 Triclosan, 122, 300 Trimethoprim-sulfamethoxazole, 33, 48, 57, 86, 300 Trypanosomiasis, 278, 300 Trypsin, 85, 247, 300, 304 Tryptophan, 237, 300 Tuberculosis, 12, 15, 16, 27, 51, 58, 106, 116, 141, 142, 148, 150, 168, 177, 209, 239, 267, 300 Tuberculosis, Oral, 177, 300 Tularemia, 11, 177, 205, 300 Tumor Necrosis Factor, 14, 16, 24, 300 Tumour, 138, 300 Tylosin, 112, 113, 300 Type 2 diabetes, 171, 300 Tyrosine, 39, 156, 245, 300 U Ulcer, 127, 157, 251, 278, 300 Ulceration, 168, 253, 300 Ulcerative colitis, 184, 261, 300 Umbilical Arteries, 300, 301 Umbilical Cord, 169, 301 Unconscious, 242, 259, 301 Universal Precautions, 172, 301 Uraemia, 277, 301 Uranium, 297, 301 Uremia, 288, 301 Ureter, 174, 258, 264, 266, 288, 301 Urethra, 174, 278, 284, 301 Urethritis, 98, 254, 301 Urinary, 13, 34, 84, 85, 118, 121, 127, 142, 152, 156, 161, 173, 178, 180, 185, 228, 233, 236, 241, 247, 253, 260, 272, 274, 275, 276, 278, 281, 301 Urinate, 179, 185, 301 Urodynamic, 174, 301 Urogenital, 180, 228, 253, 254, 268, 301 Urogenital Diseases, 301 Urolithiasis, 174, 301 Urologic Diseases, 173, 178, 301 Uterus, 235, 240, 242, 269, 283, 288, 301, 302
V Vaccination, 78, 155, 302 Vaccine, 12, 22, 49, 105, 123, 156, 185, 285, 302, 303 Vagina, 14, 23, 165, 232, 235, 237, 265, 269, 288, 302, 303 Vaginal, 14, 23, 165, 185, 192, 204, 267, 302, 303 Vaginitis, 232, 302 Vaginosis, 165, 302 Vancomycin, 46, 104, 118, 148, 154, 192, 302 Varicella, 168, 302 Vas Deferens, 293, 302 Vascular, 15, 103, 143, 162, 173, 243, 247, 256, 261, 274, 281, 298, 302 Vascular endothelial growth factor, 143, 302 Vasculitis, 169, 277, 302 Vasodilators, 274, 302 Vector, 23, 299, 302 Vein, 263, 274, 301, 302 Venereal, 296, 302 Venous, 229, 230, 257, 285, 302 Venous blood, 230, 302 Ventilation, 125, 268, 302 Ventilator, 268, 289, 302 Vertebrae, 294, 302 Vertigo, 276, 302 Vesicoureteral, 173, 302 Veterinarians, 5, 302 Veterinary Medicine, 199, 302 Vibrio, 3, 30, 122, 206, 235, 303 Vibrio cholerae, 3, 30, 235, 303 Viral Hepatitis, 172, 303 Virulent, 21, 143, 183, 272, 303 Virus Diseases, 227, 303 Visceral, 51, 98, 265, 279, 303 Visual Acuity, 303 Vitamin A, 261, 303 Vitro, 5, 7, 15, 16, 17, 21, 23, 38, 39, 40, 41, 42, 114, 117, 124, 128, 130, 133, 134, 257, 260, 282, 290, 296, 297, 298, 303 Vivo, 5, 7, 9, 16, 17, 30, 38, 39, 40, 43, 124, 128, 133, 134, 257, 260, 297, 298, 303 Volition, 263, 303 Vulgaris, 95, 123, 303 Vulva, 303 Vulvovaginitis, 165, 303 W War, 134, 142, 235, 303 Warts, 258, 303
322
Bacterial Infections
Weight Gain, 170, 303 Whole cell vaccine, 11, 303 Whooping Cough, 21, 279, 303 Wound Healing, 5, 131, 138, 233, 236, 304 X Xenograft, 225, 304 Xerostomia, 168, 173, 304
X-ray, 238, 239, 250, 251, 274, 286, 287, 291, 304 Y Yeasts, 232, 251, 280, 304 Yersinia, 206, 281, 304 Z Zalcitabine, 265, 304 Zymogen, 284, 304
Index 323
324
Bacterial Infections
