STAPHYLOCOCCUS AUREUS
A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R E FERENCES
J AMES N. P ARKER , M.D. AND P HILIP M. P ARKER , P H .D., E DITORS
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ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright 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., 1960Staphylococcus aureus: 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: 0-597-84636-7 1. Staphylococcus aureus-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 Staphylococcus aureus. 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 STAPHYLOCOCCUS AUREUS...................................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Staphylococcus aureus .................................................................. 4 E-Journals: PubMed Central ....................................................................................................... 57 The National Library of Medicine: PubMed .............................................................................. 100 CHAPTER 2. NUTRITION AND STAPHYLOCOCCUS AUREUS .......................................................... 149 Overview.................................................................................................................................... 149 Finding Nutrition Studies on Staphylococcus aureus ............................................................... 149 Federal Resources on Nutrition ................................................................................................. 153 Additional Web Resources ......................................................................................................... 154 CHAPTER 3. DISSERTATIONS ON STAPHYLOCOCCUS AUREUS ..................................................... 155 Overview.................................................................................................................................... 155 Dissertations on Staphylococcus aureus.................................................................................... 155 Keeping Current ........................................................................................................................ 156 CHAPTER 4. CLINICAL TRIALS AND STAPHYLOCOCCUS AUREUS ................................................ 157 Overview.................................................................................................................................... 157 Recent Trials on Staphylococcus aureus .................................................................................... 157 Keeping Current on Clinical Trials ........................................................................................... 158 CHAPTER 5. PATENTS ON STAPHYLOCOCCUS AUREUS ................................................................ 161 Overview.................................................................................................................................... 161 Patents on Staphylococcus aureus ............................................................................................. 161 Patent Applications on Staphylococcus aureus ......................................................................... 184 Keeping Current ........................................................................................................................ 214 CHAPTER 6. BOOKS ON STAPHYLOCOCCUS AUREUS .................................................................... 215 Overview.................................................................................................................................... 215 Chapters on Staphylococcus aureus ........................................................................................... 215 CHAPTER 7. PERIODICALS AND NEWS ON STAPHYLOCOCCUS AUREUS ...................................... 221 Overview.................................................................................................................................... 221 News Services and Press Releases.............................................................................................. 221 Newsletter Articles .................................................................................................................... 223 Academic Periodicals covering Staphylococcus aureus ............................................................. 223 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 227 Overview.................................................................................................................................... 227 NIH Guidelines.......................................................................................................................... 227 NIH Databases........................................................................................................................... 229 Other Commercial Databases..................................................................................................... 231 APPENDIX B. PATIENT RESOURCES ............................................................................................... 233 Overview.................................................................................................................................... 233 Patient Guideline Sources.......................................................................................................... 233 Finding Associations.................................................................................................................. 236 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 239 Overview.................................................................................................................................... 239 Preparation................................................................................................................................. 239 Finding a Local Medical Library................................................................................................ 239 Medical Libraries in the U.S. and Canada ................................................................................. 239 ONLINE GLOSSARIES................................................................................................................ 245 Online Dictionary Directories ................................................................................................... 245
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STAPHYLOCOCCUS AUREUS DICTIONARY...................................................................... 247 INDEX .............................................................................................................................................. 317
1
FORWARD In March 2001, the National Institutes of Health issued the following warning: "The number of Web sites offering health-related resources grows every day. Many sites provide valuable information, while others may have information that is unreliable or misleading."1 Furthermore, because of the rapid increase in Internet-based information, many hours can be wasted searching, selecting, and printing. Since only the smallest fraction of information dealing with Staphylococcus aureus 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 Staphylococcus aureus, 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 Staphylococcus aureus, 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 Staphylococcus aureus. 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 Staphylococcus aureus, 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 Staphylococcus aureus. The Editors
1
From the NIH, National Cancer Institute (NCI): http://www.cancer.gov/cancerinfo/ten-things-to-know.
3
CHAPTER 1. STUDIES ON STAPHYLOCOCCUS AUREUS Overview In this chapter, we will show you how to locate peer-reviewed references and studies on Staphylococcus aureus.
The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and Staphylococcus aureus, 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 “Staphylococcus aureus” (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: •
Review of Staphylococcus aureus Exit-Site and Tunnel Infections in Peritoneal Dialysis Patients: In-Depth Review Source: American Journal of Kidney Diseases. 16(2): 89-95. August 1990. Summary: This article focuses on risk factors and potential preventive measures for Staphylococcus aureus exit-site and tunnel infections, a source of considerable morbidity for peritoneal dialysis patients. Difficult to resolve, these infections can lead to peritonitis, and often require removal of the peritoneal catheter. Staphylococcal nasal carriage is the major risk factor for S aureus exit-site infections and peritonitis episodes. In the future, identification of patients who are S aureus nasal carriers and treatment of the carriage state with rifampin may prove to be a means of decreasing infection rates. The best treatment for S aureus exit-site and tunnel infections has not been established.
4
Staphylococcus aureus
Treatment regimens generally used include oral antibiotics or intraperitoneal vancomycin. The optimal length of therapy is also unclear. To further decrease peritonitis rates, attention must now be directed at catheter-related peritonitis episodes, with S aureus the most common cause of such episodes. It is suggested that controlled, prospective studies designed to investigate methods of preventing and treating S aureus exit-site infections in peritoneal dialysis patients are needed. 3 tables. 60 references. (AAM).
Federally Funded Research on Staphylococcus aureus The U.S. Government supports a variety of research studies relating to Staphylococcus aureus. 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 Staphylococcus aureus. 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 Staphylococcus aureus. The following is typical of the type of information found when searching the CRISP database for Staphylococcus aureus: •
Project Title: A NOVEL PEPTIDE-BASED ASSAY FOR FTSZ POLYMERIZATION Principal Investigator & Institution: Duncan, Leonard R.; Cumbre, Inc. 1502 Viceroy Dr Dallas, Tx 75235 Timing: Fiscal Year 2004; Project Start 01-JUL-2004; Project End 31-DEC-2004 Summary: (provided by applicant): The recent emergence of bacterial strains resistant to many or all currently-prescribed antibiotics represents a serious threat to global public health. Clearly, the development of novel anti-microbial agents with unique mechanisms of action that target previously unexploited proteins or processes is urgently needed. The long-term objective of the research presented in this proposal is the development of an antibiotic with activity directed against the critical bacterial celldivision protein FtsZ, which assembles into a polymeric ring-like structure at the site of cell division. The recently discovered ZapA protein binds to FtsZ and greatly facilitates its assembly into higher-order structures. These Phase I studies will study the feasibility of using fluorescently-labeled ZapA peptides as probes to monitor the in vitro polymerization state of the FtsZ protein from the Gram positive human pathogen S. aureus with the goal of creating a robust assay format suitable for high-throughput screening of large chemical libraries for compounds that either inhibit or stabilize the formation of FtsZ polymers. Phase II studies will involve implementation of such a
2
Healthcare projects are funded by the National Institutes of Health (NIH), Substance Abuse and Mental Health Services (SAMHSA), Health Resources and Services Administration (HRSA), Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDCP), Agency for Healthcare Research and Quality (AHRQ), and Office of Assistant Secretary of Health (OASH).
Studies
5
highthroughput screen and systematic studies of promising compounds in secondary biochemical and cell-based assays. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ANALYSIS INTERACTIONS
OF
STAPHYLOCOCCUS
AUREUS
HOST
Principal Investigator & Institution: Hook, a Magnus.; Director; None; Texas A&M University Health Science Ctr College Station, Tx 778433578 Timing: Fiscal Year 2002; Project Start 01-DEC-1989; Project End 31-MAR-2005 Summary: The ultimate goal of our studies is to understand in molecular terms how bacteria cause diseases. A bacterial infection can be regarded as a war between the microbe and the host where the bacteria's attempt to adhere to and colonize the host tissue represent the first battle in the campaign. For our model organism, Staphylococcus aureus tissue adherence is mediated by a sub-family of bacterial surface adhesins called MSCRAMMs. In previous work, we discovered the MSCRAMMs, cloned and sequenced several MSCRAMM genes and began characterizing the encoded proteins and their interactions with host components. These studies revealed amazingly sophistical mechanisms of host tissue adherence designed to avoid inactivation by host defense systems. We hypothesize that the MSCRAMMs are in the first line of bacterial attachment and their molecular design makes them uniquely suited for this role. Consequently, we now propose a detailed molecular analysis of Staphylococcal surface proteins and their interactions with host components. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: B CELL SUPERANTIGENS AND IMMUNE REGULATION Principal Investigator & Institution: Silverman, Gregg J.; Associate Professor; Medicine; University of California San Diego 9500 Gilman Dr, Dept. 0934 La Jolla, Ca 920930934 Timing: Fiscal Year 2004; Project Start 01-MAY-1998; Project End 31-JAN-2009 Summary: (provided by applicant): Superantigens (SAgs) for B lymphocytes interact via conserved V region framework sites in the B cell antigen receptor (BCR) to target large sets of lymphocytes. We have previously elucidated central structural and immunobiologic properties of protein A of Staphylococcus aureus (SpA), and established SpA as the prototypic experimental B-cell superantigen. Based on an understanding of the molecular basis by which naturally pentameric SpA binds B-cells, we have recently developed the murine T15i Ig "knockin" system for investigations of the in vivo outcome of SpA exposure. In these mice, most B cells express a VH transgene product that is targeted by SpA, and we have shown that SpA treatments rapidly induce activation-associated apoptotic death of targeted B cells. In the current research program, we will use different forms of SpA to elucidate key mechanisms responsible for BCR-mediated determinations of lymphocyte clonal fate. The Specific Aims will include: AIM 1: To define the nature of the SAg-induced BCR complex responsible for B lymphocyte activation and apoptosis. AIM 2: To determine how membrane co-receptors may affect clonal fate after interactions with SpA. AIM 3: To investigate how Bcl-2 family members may be involved in determining B-cell clonalfate after interactions with SpA. AIM 4: To evaluate how co-exposure to other immunologically active components of S. aureus can affect the outcome of in vivo SpA exposure. These investigations will provide important insights into the fundamental properties of B-cells. In addition, these studies will lead to a better understanding of the immunobiologic activities of a
6
Staphylococcus aureus
virulence factor from one of the most important causes of life-threatening infection in the US. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: B SUBTILIS ECF SIGMA FACTORS: ROLES AND REGULATION Principal Investigator & Institution: Helmann, John D.; Professor; Microbiology; Cornell University Ithaca Office of Sponsored Programs Ithaca, Ny 14853 Timing: Fiscal Year 2002; Project Start 01-MAY-1992; Project End 31-DEC-2004 Summary: (adapted from the investigator's summary): The widespread emergence of antibiotic resistant bacteria poses a grave threat to our ability to manage and control infectious disease. While tremendous progress has been made in understanding the role of transmissible plasmids and high-level resistance genes in antibiotic resistance, the role and regulation of chromosomally-encoded determinants is less well understood. This project focuses on the genetically well characterized model organism Bacillus subtilis, to investigate the functional genomics of antibiotic resistance and responses. The close evolutionary between B. subtilis and important human pathogens (especially Staphylococcus aureus, Mycobacterium tuberculosis, Enterococcus, and Streptococcus), allows knowledge gained in our system to be directly used in understanding the other. The goal of this project is to understand the role of alternative sigma factors in coordinating the genetic responses triggered by exposure of B. subtilis to antibiotics that target the cell envelope. Recently, the SigX and SigW regulators have been found to activate transcription of a large number of genes affecting the structure and function of cell surface polymers, antibiotic resistance mechanisms, and the production of antimicrobial peptides. Expression of these sigma factors is strongly induced by several clinically important antibiotics, including vancomycin and cephalospirins. To better define these genetic responses, and their roles in protecting the cell against antibiotics, two aims will be pursued. First, promoters controlled by each sigma factor will be identified and the rules that govern promoter selectivity will be explored. The identification of target promoters will reveal the complete set of genes (the regulon) activated by each sigma. The PI will define the overlap the overlap between the various regulons controlled by SigX, SigW and other sigma factors. This aim will include both proteomics and genomics based approaches. Second, the physiological roles of selected taarget genes will also be investigated. For this aim the PI will focus on those operons implicated on defense against antibiotics, modification of the cell envelope, or the production of antimicrobial compounds. In addition, the signaling pathways that control the expression of these regulons will be investigated. Although many different antibiotics can induce each regulon, it is likely that these antibiotics lead to the accumulation of common signaling molecules that are perceived by the anti-sigma factor which then releases the sigma factor. Genetic approaches have been devised to identify components of these signaling pathways. Together, these two aims will provide a unified picture of these two large regulons and their roles in B. subtilis physiology. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: BACTERIAL INFECTION INDUCES CYTOKINE PRODUCTION Principal Investigator & Institution: Marriott, Ian; Assistant Professor; 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
Studies
7
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 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: BACTERICIDAL AGENTS FOR SLOW-GROWING BACTERIA Principal Investigator & Institution: Markham, Penelope N.; Director of Research; Influx, Inc. 2201 W Campbell Park Dr Chicago, Il 60612 Timing: Fiscal Year 2003; Project Start 01-MAY-2003; Project End 31-DEC-2003 Summary: (provided by applicant): In many chronic infections, including all biofilm related infections, the slow growth of bacteria is believed to account not only for resistance to antibiotics, but also for the high incidence of persistence and relapse. Considering that all currently prescribed antibiotics are significantly more effective against rapidly growing pathogens, the development of antibiotics highly effective against bacteria in the slow mode of growth is of utmost importance. By screening a chemical library for compounds bactericidal for slow-growing S. aureus, we have succeeded in identifying a very promising class of compounds, pyridinium thiol ethers (PTEs). Preliminary data indicate that PTEs are not only effective against fluid-phase S. aureus, but also against biofilms as well as against other bacteria in a slow mode of growth. In the proposed Phase I project, we will synthesize and screen a library of PTEs in order to identify compounds that will be bactericidal against slow and logarithmically growing S. aureus. Feasibility of the medical use of the most active derivatives will be analyzed. Finally, the basic principles underlying the molecular mechanism of action of PTE compounds will be investigated. The Phase I project will provide the basis for the Phase II project, which will involve chemical improvement of the lead compounds,
8
Staphylococcus aureus
investigation of their activity in various biofilm models, and in vivo toxicology studies. PTE compounds could provide a unique opportunity for eradication of infections associated with slow bacterial growth. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BECTA LACTAMASES AND DD PEPTIDASES ACTIVE SITE CHEMISTRY Principal Investigator & Institution: Pratt, Rex F.; Professor; Chemistry; Wesleyan University Middletown, Ct 064590241 Timing: Fiscal Year 2002; Project Start 30-SEP-1982; Project End 31-JUL-2003 Summary: Bacterial resistance to beta-lactam antibiotics continues to become more prevalent and more clinically important. A large part of the resistance can be understood and investigated experimentally in terms of the chemistry of the interactions of beta-lactam antibiotics with the active sites of two groups of bacterial enzymes, the beta-lactamases on one hand, which catalyze the hydrolysis of the antibiotics, and the Dalanyl-D-alanine transpeptidase/carboxypeptidases on the other, which catalyze the synthesis an maintenance of the peptide cross-links of bacterial cell walls, and which are inhibited by beta-lactam antibiotics. There is now good reason to believe that all of these beta-lactam binding sites have much in common. An understanding o the structure and function of these sites and of the relationship between them is fundamental to future antibiotic design--both beta-lactam and otherwise. Th object of the proposed research is to explore further the chemical functionality and the substrate binding properties of a series of these active sites, using a number of modified substrates, novel inhibitors, and potential effecters. A mechanistic study of these sites, designed to determine the role of the functional groups present and the relationship between the proteinases, will be performed. Computational methods will be employed in order to interpre the results in terms of available crystal structures of these enzymes and to thus establish new guidelines to inhibitor design. In order to understand the structural and mechanistic basis of bacterial beta-lactam-resistance through mutation of transpeptidases, one important example of such beta-lactam-resistant enzymes, penicillin binding protein 2a of the methicillin-resistant Staphylococcus aureus (MRSA), will be studied in detail. These studies will lead to a clearer view of the chemistry of beta-lactamase and transpeptidase active sites, and thus to new directions in antibiotic design. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
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 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, so-
Studies
9
called "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: BIO-ORGANIC MECHANISMS OF PEPTIDE ANTIBIOTICS Principal Investigator & Institution: Mccafferty, Dewey G.; Assistant Professor; Biochemistry and Biophysics; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 01-JUN-2000; Project End 31-MAY-2005 Summary: Bacterial resistance to antibiotics has seriously limited our capacity to overcome infectious disease. Cases of resistance have emerged in virtually all hospitalacquired pathogen-antimicrobial combinations. Soon our most serious infectious threats will be untreatable given our dwindling arsenal of effective antibiotics. Our long-term research goals are to develop synthetic access to biologically interesting peptide antibiotics, to gain insight into their mechanism/mode of action, and to apply the knowledge gained to the development of alternative antibiotics with improved activity against resistant phenotypes. This proposal describes the total synthesis and mechanistic characterization of Ramoplanin, a novel beta-sheet lipodepsipeptide antibiotic with proven activity against methicillin-resistant Staphylococcus aureus, vancomycinresistant Enterococcus faecium, and cephalosporin-resistant Streptococcus pneumonia, three important Gram positive opportunistic human pathogens. By an unclear mechanism, Ramoplanin appears to arrest bacterial cell wall development at the level of MurG, a glycosyltransferase involved in an intermediate stage of peptidoglycan biosynthesis. Since MurG activity is essential for proper bacterial cell wall development, it is an attractive target for antibacterial design. Harnessing the clinical antibiotic potential of Ramoplanin critically hinges on gaining synthetic access to its structure and deconvoluting the most intimate details of its mechanism of action. To accomplish this we will synergistically merge total synthesis, mechanistic enzymology and protein biophysics to completely correlate structure to antibiotic function. We plan to synthesize Ramoplanin and related analogues using solid-phase methods, thus providing a general synthetic route to favorably modulate its physiochemical properties. We plan to identify
10
Staphylococcus aureus
the molecular target of Ramoplanin and determine the interaction energies, specificities, and structure of the inhibitory complex. We will assess the inhibitory effect of Ramoplanin on the MurG reaction and on the mechanistically related peptidoglycan transglycosylation cross-linking reaction that takes place on the outer surface of the bacterial cell membrane. Collectively these studies will provide a clear picture of the mechanism of Ramoplanin inhibition of peptidoglycan biosynthesis and promote the design, synthesis, and biological evaluation of a new generation of antibiotics capable of combating bacterial resistance to antibiotics. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: C. PATHOGENESIS
ELEGANS
AS
A
MODEL
SYSTEM
FOR
S.AUREUS
Principal Investigator & Institution: Sifri, Costi D.; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2003; Project Start 01-FEB-2003; Project End 31-JAN-2006 Summary: (provided by applicant): This Research Career Award Application describes a mentored research program for the candidate, Dr. Costi Sifri, in bacterial pathogenesis and immunology. The program will be facilitated by supplemental coursework in microbiology, genetics, immunology, and Caenorhabditis elegans biology at Harvard Medical School, the Harvard School of Public Health, and Cold Spring Harbor. The candidate is trained in Infectious Diseases and proposes a research program to study virulence mechanisms of and host response to Staphylococcus aureus infection. The candidate's sponsor, Dr. Stephen Calderwood, and cosponsor, Dr. Frederick Ausubel, have a longstanding collaborative interest in using simple organisms as model hosts for the study of human bacterial pathogens. The candidate has developed a novel system for studying genetic and molecular mechanisms of S. aureus pathogenesis and host defense mechanisms, using the nematode model organism C. elegans. He has found that C. elegans die by an active infectious process when exposed to live S. aureus. Mutants of several S. aureus pathogenicity-related genes, including the virulence regulator agr, the alternative sigma factor sigB, and the V8 protease gene sspA, are significantly attenuated in their ability to kill adult nematodes, suggesting that the molecular basis of S. aureus pathogenicity may be conserved in evolutionary distant hosts. The Specific Aims are as follows: 1) to use the C. elegans model system to screen a library of S. aureus transposon insertion mutants and identify clones attenuated in both nematodes and a mouse sepsis model, 2) to perform in-depth molecular genetic analysis for one or more selected S. aureus mutants, and 3) to identify and characterize C. elegans mutants with altered susceptibility to S. aureus infection. The studies are designed to contribute to our understanding of S. aureus pathogenesis and explore primitive mechanisms of host defense. In addition, these studies will concurrently provide the candidate with the training and experience necessary to develop an independent research career. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CELL SURFACE PROTEIN ANCHORING IN GRAM-POSITIVE BACTERIA Principal Investigator & Institution: Clubb, Robert T.; Assistant Professor; Molecular & Med Pharmacology; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2002; Project Start 01-JUN-2002; Project End 31-MAY-2006
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Summary: (provided by applicant):Research will study the molecular mechanism used to covalently anchor surface proteins to the cell wall of Gram-positive bacteria.Surface proteins play important roles during the pathogenesis of human infections and are covalently anchored by sortase enzymes.The mechanism of sortase-mediated attachment is universally conserved,responsible for attaching up to 30 percent of surface proteins and required for infectivity.Work in this proposal will focus on the SrtA protein from S.aureus.We will localize its substrate-binding site,determine the functional significance of amino acids within its active site,and investigate how it is activated by calcium.This work will be complemented by the design,synthesis and in vitro testing of peptide-based inhibitors of SrtA.This will enable the structure of a SrtA-inhibitor complex to be determined to gain insights in the molecular basis of substrate recognition.S.aureus encodes a second sortase-like enzyme,SrtB,which has no known function.We hypothesize that SrtB anchors proteins to the cell wall by recognizing a sorting signal that has yet to be identified.We will use a unique biopanning method to determine the full range of amino acid sequences that can be processed by SrtA and to search for a SrtB sorting signal.Finally,we will elucidate the three-dimensional structure of the SrtB protein to reveal conserved structural features within its active site and insights into its function.The results of this work will shed light onto the underlying chemistry of cell wall anchoring,identify new peptide signals that target proteins for cell wall attachment,and may facilitate the development of new therapeutically useful antiinfective agents. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CHEMISTRY AND BIOLOGY OF COLLAGEN Principal Investigator & Institution: Raines, Ronald T.; Professor; Biochemistry; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2004; Project Start 15-JUL-1996; Project End 31-MAR-2008 Summary: (provided by applicant): Collagen comprises one-third of the protein in humans. Collagen abnormalities are associated with a wide variety of human diseases, such as osteogenesis imperfecta, Ehlers-Danlos syndrome, and some types of osteoporosis and arthritis. The long-term objective of the proposed research is to reveal in atomic detail the chemical basis for the unique triple-helical structure of collagen, and the roles of collagen in human health and disease. Specific Aims: (1) Basis for Triple Helix Stability. The hypothesis to be evaluated is that individual strands of collagen are preorganized to form a triple helix. The experiments make use of collagen strands containing nonnatural amino acids (in particular, 4-fluoroproline diastereomers and Nmethylglycine) that impose distinct stereoelectronic and steric effects. Data on conformational stability will be reinforced by computational and structural analyses. (2) Cystine Knot Templates. A collagen triple helix cross-linked by two disulfide bonds (that is, a cystine knot) can contain three different strands, and provides a realistic mimic of natural collagen. An efficient solid-phase synthesis of triple helices crosslinked by a cystine knot will be developed, and those helices will be used to evaluate the contribution of the ladder of interstrand main-chain-main-chain hydrogen bonds to collagen stability, assess the ability of a single strand of collagen to invade a triple helix, and self-assemble long, well-defined triple helices. (3) Encoded Collagen Library. Phage display of a cystine knot will be used to generate encoded libraries of collagen triple helices. These libraries will be screened for triple helices with high affinity for collagenbinding proteins, in particular, the adhesin protein from the pathogenic bacterium Staphyloccocus aureus. Significance: The results of the proposed research will provide new insights into the structure and conformational stability of the collagen triple helix
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and on its interaction with other proteins, and could ultimatley lead to the creation of collagen mimics and collagen-based biomaterials with important therapeutic applications. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: COCAINE SMOKING EFFECTS ON LUNG IMMUNITY & HOST DEFENSE Principal Investigator & Institution: Tashkin, Donald P.; Professor of Medicine; Medicine; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2003; Project Start 01-JUN-1993; Project End 31-JAN-2007 Summary: (provided by applicant): Over the past 8 years we have identified several novel and potentially serious health consequences associated with crack cocaine. Our research has examined two general areas: 1) the effects of crack cocaine on lung inflammation, injury and physiology and 2) the impact of cocaine on immunity and host defense. This second line of investigation, the impact of cocaine on immunity and host defense, has become the primary focus for this competitive renewal. In this respect, we have demonstrated that alveolar macrophages recovered from the lungs of crack users exhibit a marked deficiency in their ability to upregulate inducible nitric oxide synthase, produce nitric oxide, and limit the growth of Staphylococcus aureus. When tested in a mouse model, cocaine adversely regulated T-helper cytokine (Thl/Th2) balance leading to over-expression of TGF-beta and IL-10, suppressed T cell function, and allowed the uncontrolled growth of implanted lung tumor cells. Novel experiments have identified sigma receptors as likely to be involved in these effects both in vitro and in vivo. We have also developed an important new model for studying the interaction between cocaine and HIV. Administration of cocaine to severe-combined immunodeficiency (SCID) mice reconstituted with human peripheral blood leukocytes (huPBL/SCID), and infected with HIV, results in dramatic increases in viral replication, down-regulation of CD4 counts and CD4/CD8 ratios, and changes in expression of HIV co-receptors. More recently, we have identified altered immune function in blood collected from crackabusing subjects. Building on these findings, we propose 3 specific aims' 1) To define the mechanisms by which cocaine enhances HIV replication and infection in vivo in the huPBL/SCID and SCID-hu models. 2) To determine the pathway(s) by which cocaine suppresses immune responses in a murine model of anti-tumor immunity (effects on T cells, dendritic cells, cytokines) and delineate the role of the sigma-receptor signaling in this process. 3) To demonstrate the type and magnitude of cocaine-related alterations in HIV co-factors and immune function as they occur in a well-described cohort of crack cocaine users. Correlations will also be sought between a history of crack use and the development and progression of HIV-related diseases in an established database from the Multicenter AIDS Cohort Study (MACS). By the completion of these studies we will have relevant animal data and human clinical correlates linking inhaled cocaine abuse to the regulation of immune function and host defense, and the modulation of risk factors important to the pathogenesis and progression of HIV. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: COMBATING MULT-DRUG RESISTANT BACTERIA Principal Investigator & Institution: Hergenrother, Paul J.; Chemistry; University of Illinois Urbana-Champaign Henry Administration Bldg Champaign, Il 61820 Timing: Fiscal Year 2003; Project Start 15-APR-2003; Project End 31-MAR-2008
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Summary: (provided by applicant): Bacterial resistance to antibiotics has emerged as a considerable threat to human health. Methicillin-resistant Staphloccous aureus (MRSA) and vancomycin-resistant enterococci (VRE) are multi-drug resistant bacteria that cause life threatening infections in the hospital setting and in some cases have leapt to the larger community. It is clear that new strategies and tactics are needed to combat these insidious bacteria. Often times, bacteria owe their antibiotic resistance to the proteins encoded by plasmids that they harbor. Plasmids are small, circular, extra-chromosomal pieces of DNA that can be transferred from one bacterium to another. These plasmids often contain genes that encode proteins that confer resistance to a wide array of antibiotics. Indeed, for several classes of antibiotics (including beta-lactams, macrolides, and aminoglycosides) plasmid-borne resistance is ubiquitous. In addition, many of the worst multi-drug resistant bacteria (including MRSA and VRE) are resistant by virtue of the plasmid they harbor. Proposed herein is a strategy to attack this plasmid-encoded resistance through the creation of "anti-plasmid" agents, small molecules that will vanquish the plasmid from the cell, thus rendering the bacteria sensitive to antibiotics. These compounds are designed to mimic a known, naturally occurring mechanism for plasmid elimination, known as plasmid incompatibility. The bio-molecules that determine plasmid incompatibility are typically small pieces of RNA and DNA iterons. It has been shown that genetic mutation of these RNA incompatibility determinants disrupts RNA loop-loop interactions and leads to plasmid elimination. In Specific Aims 1 and2 of this proposal, small molecules are described that will disrupt the RNA looploop interaction in a completely analogous manner, thus leading to plasmid elimination. Specific Aims 3 and 4 describe studies on the mechanism and inhibition of the plasmid replication initiation protein, RepA. The successful completion of the experiments described herein could lead to a dramatic change in the manner in which antibiotic resistant infections are treated. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CONTROL OF DNA TOPOLOGY Principal Investigator & Institution: Tse-Dinh, Yuk-Ching; Professor; Biochem and Molecular Biology; New York Medical College Valhalla, Ny 10595 Timing: Fiscal Year 2002; Project Start 01-APR-1996; Project End 31-MAR-2004 Summary: Due to the recent emergence of pathogenic bacteria resistant to all antibiotics currently used, there is an urgent lead to develop new antibiotics against novel targets. Bacterial topoisomerase I is a promising new target for antibacterial therapy with lead compounds having MIC's of 4.0 mug against Staphylococcus aureus. E. coli topoisomerase I is the best studied example of bacterial topoisomerase I and share extensive homology with topoisomerase I from both gram-positive and gram- negative bacteria. Topoisomerase I targeting drugs that inhibit DNA religation would lead to cell killing in a mechanism similar to those of many drugs targeting bacterial DNA gyrase and human topoisomerases. Loss of topoisomerase I function may also affect the ability of the bacteria to respond to environmental challenges encountered in pathogenesis. The long term goals of this project include the elucidation of the mechanism, regulation and physiological roles of E. coli topoisomerase I, which would greatly aid the development of novel bacterial agents targeting this class of enzyme. The aims for this proposal include: 1. Structure-function analysis by different mutagenesis approaches to identify residues required for the individual steps of catalysis by E. coli topoisomerase I 2. Limited proteolysis and chemical cleavage of topoisomerase I in the absence and presence of DNA to identify sites of cleavage altered due to either enzyme conformational change or protection by DNA substrate. 3. Test of peptide sequences
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identified by panning as potential inhibitor of topoisomerase I 4. Study of the molecular basis of topoisomerase I involvement in bacterial adaptation to environmental challenges for survival. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CORE--MONOCLONAL ANTIBODY Principal Investigator & Institution: Scharff, Matthew D.; Harry Eagle Professor of Cancer Research; Yeshiva University 500 W 185Th St New York, Ny 10033 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-AUG-2008 Summary: (provided by applicant): Passive antibody administration is the only strategy available for conferring immediate immunity to individuals exposed to biological weapons. Furthermore, toxin-specific antibodies are toxin neutralizing agents par excellence and currently constitute the only means of neutralizing toxins in the human host. The efficacy of antitoxin sera in human therapy is known since the 1890s when Behring and Kitasato developed antisera to tetanus and diphtheria toxins and demonstrated their prophylactic and therapeutic properties. However, despite a century of immunological study we know relatively little about what antibody properties are important for antitoxin efficacy and the mechanisms involved in toxin neutralization are largely conjecture. This application is focused on the generation of antibodies to four toxins: B. anthracis toxins (protective antigen, lethal factor, and edema factor protein subunits) and Staphylococcus aureus enterotoxins with the goal of generating therapeutic antibodies to protect against biological attack with these agents. In addition we will generate neutralizing antibodies to West Nile Virus (WNV). The United States is currently in the midst of an unfolding WNV epidemic and there has been some concern that this agent was deliberately introduced into this country in an act of bioterrorism. While this is unlikely, the morbidity and mortality associated with WNV remain a significant public health concern. Four Specific Aims are proposed: 1) To generate neutralizing (murine and human) monoclonal antibodies to anthrax toxin protein components, S. aureus enterotoxin, and WNV envelope (E) protein; 2) To identify the antibody attributes necessary for optimal toxin and viral neutralizing activity; 3) To generate very high affinity derivatives of neutralizing antitoxin and antiviral mAbs by increasing the rate of somatic hypermutation in selected hybridomas through expression of activation induced deaminase (AID); 4) To identify the mechanism(s) of antibodymediated toxin and virus neutralization. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: DEVICE USE IN NURSING HOMES: REDUCING RISK OF INFECTION Principal Investigator & Institution: Mody, Lona; Internal Medicine; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-AUG-2008 Summary: (provided by applicant): Dr. Mody's primary research interest is epidemiology of nosocomial infections in long-term care and developing effective infection control strategies targeted at reducing these infections with a goal to reduce antimicrobial usage, antimicrobial resistance, and adverse events related to antibiotics. Nosocomial infections and adverse drug events particularly related to antibiotics are common preventable medical problems in nursing homes. Dr. Mody's goal is to develop infection control strategies that are targeted and practical while recognizing staffing, budget and care concerns of older adults in nursing homes. Indwelling devices,
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especially urinary catheters and feeding tubes, are commonly used and appear to play a key role in the development of urinary tract infections and aspiration pneumonias. Dr. Mody's immediate research goals during the Career Development Program are: 1. To assess the epidemiology of colonization with antibiotic-resistant pathogens associated with commonly used devices (urinary catheters, feeding tubes & intravenous lines) in nursing homes in Southeast Michigan. 2. Quantify infection risk and antimicrobial usage attributed to devices. 3. To assess knowledge, attitudes, opinions, and practices of nursing personnel to existing infection control guidelines to prevent device-related infections 4. Assess the efficacy of a targeted infection control program in reducing infections related to devices incorporating educational needs of healthcare workers in nursing homes. This Career Development Award will serve 3 goals: First, this grant will allow Dr. Mody to build on her previous projects conducted during residency and fellowship focusing on the epidemiology and prevention of infection in older adults. Second, it will provide her with an opportunity to take formal coursework in epidemiology and health services research, which will be instrumental to advancing her research career. Third, it will give me a chance to collaborate with a group of community nursing homes in Southeast Michigan. The primary goal of this collaboration will be to design and conduct further outcomes based research projects focusing on nosocomial infections as adverse events and leading to meaningful strategies to improve quality of care of older adults in institutional setting. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DIAGNOSIS OF INFECTIONS IN HUMANS WITH MICROARRAYS Principal Investigator & Institution: Ramilo, Octavio; Associate Professor; Ut Southwestern Medical Center Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-AUG-2008 Summary: Project 3: The diagnostic methods currently used in clinical microbiology have limited capabilities to identify pathogens in a rapid turn-around time that allows prompt initiation of a therapeutic intervention and appropriate infection control measures. This is especially relevant when facing novel emerging and reemerging pathogens and potential biothreat agents. Rather than focusing on the identification of hundreds of potentially pathogenic agents in a traditional microbe-based approach, we propose a comprehensive analysis of the host response to different classes of pathogens as a novel diagnostic tool. Based on our preliminary studies in individuals with acute infections, we hypothesize that each class/group of microorganisms induces a host response pattern [in the immune system] which defines a characteristic biosignature that can be used for diagnostic purposes. Using microarray gene expression analysis we will determine: a) whether there are infection-induced specific biosignatures which are different than those induced by other non-infectious conditions and/or stressors such as autoimmune diseases, cancer, trauma, and transplantation; b) whether this biosignature can identify different classes of pathogenic microorganisms, and c) whether the biosignature can be used as a prognostic indicator of disease severity in different types of infections. Aim 1 will determine whether Gram positive and GRam negative bacteria yield different biosignatures in human blood in vivo. Aim 2 will determine whether gene expression in human blood will permit to distinguish between bacterial and viral infections. Aim 3 will determine whether established biosignatures permit diagnosis of "unknown infection". Aim 4 will determine which immune cells in blood carry the microbe biosignature. This study will establish the diagnostic and prognostic value of pathogen biosignatures in vivo. Our goal is to establish microarray analysis of blood
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leukocytes as a platform technology for the diagnosis of biothreat exposure and decision making with regard to therapeutics and, on a larger scale, Public Health. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DYNAMIC PLATELET - STAPHYLOCOCCAL INTERACTIONS Principal Investigator & Institution: Ross, Julia M.; Assistant Professor; Center for Criminal Justice; University of Maryland Balt Co Campus Baltimore, Md 21250 Timing: Fiscal Year 2002; Project Start 01-SEP-2001; Project End 31-AUG-2005 Summary: (Verbatim from Applicant's Abstract): The broad objective of the proposed research is to comprehensively characterize the molecular interactions between Staphylococcus aureus and platelets as a function of the dynamic shear environment in order to provide a rational basis for the development of novel treatments to combat staphylococcal cardiovascular infections. The hypothesis to be tested is that shear stress affects the adhesive interactions between platelets and S. aureus by modulating the (i) relative importance of the adhesive molecules involved and (ii) the reaction binding kinetics. The proposed approach uses controlled, dynamic, in vitro experimental systems to systematically and comprehensively examine the importance of platelet activation, blood components, blood flow, and bacteria in the development of bloodborn staphylococcal infections. A long-term goal of this work is to investigate the interrelationship between thrombogenesis and cardiovascular infection mechanisms. The specific aims of the project are to: 1) comprehensively elucidate the molecular mechanisms of S. aureus-platelet interactions under shear conditions of direct physiological relevance; 2) characterize S. aureus-platelet heteroaggregation in cell suspensions subjected to controlled levels of shear and; 3) develop a protocol to study S. aureus-platelet aggregation in whole blood and to evaluate the effect of this extension on S. aureus-platelet interactions under shear conditions. Completion of these specific aims will provide a rational basis for the design of new therapeutic molecules to block specific adhesion events, as well as identify the most important bacterial receptors to target in vaccine development. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ENZYMOLOGY OF ANTIBIOTIC RESISTANCE Principal Investigator & Institution: Armstrong, Richard N.; Professor; Biochemistry; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2003; Project Start 01-FEB-1998; Project End 31-DEC-2007 Summary: (provided by applicant): In the last two decades it has become increasingly clear that the efficacy of antibiotics for the treatment of infectious diseases is in jeopardy due to the common appearance of drug resistant strains of microorganisms. Understanding the mechanisms of antimicrobial resistance is crucial for effective patient care in the clinic and essential for developing strategies to enhance biodefense against intentionally disseminated of pathogens. Fosfomycin is a potent, broad-spectrum antibiotic effective against both Gram-positive and Gram-negative microorganisms. A decade after its introduction plasmid-mediated resistance to fosfomycin was observed in the clinic. Investigations supported by this project have established that the resistance is due to a metalloenzyme (FosA) that catalyzes the addition of glutathione to the antibiotic, rendering it inactive. Similar resistance elements have now been shown to exist in the genomes of several pathogenic microorganisms including, Pseudomonas aeruginosa, Staphylococcus aureus, Bacillus anthrasis, Brucella melitensis, Listeria monocytogenes and Clostridium botulinum. Genomic and biochemical analysis from
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this project suggest that there are three distinct subgroups of metalloenzymes, termed FosA, FosB and FosX, that confer resistance through somewhat different chemical mechanisms. The objectives of this research project are to identify plasmid and genomically encoded proteins involved in microbial resistance to fosfomycin and to elucidate the underlying structural and mechanistic enzymology of resistance. These objectives will be accomplished by integrating enzymological, biophysical and genomic analyses of the resistance problem. The three-dimensional structures of the FosA from Pseudomonas aeruginosa and its relatives FosB and FosX will be determined by X-ray crystallography. The chemical mechanisms of catalysis will be elucidated by: (i) examination of the inner coordination sphere of Mn 2+ in FosA and FosX by EPR and ENDOR spectroscopy; (ii) a steady state kinetic analysis of the thiol selectivity of FosA and FosB, and (iii) a mechanistic study of the unique hydration reaction catalyzed by FosX. Potential transition state inhibitors will investigated by structural, spectroscopic and kinetic techniques. The thermodynamics of the interaction of substrates and inhibitors with the enzymes will be examined by isothermal titration calorimetry Particular emphasis will be placed on the enzymes from the pathogens Pseudomonas aeruginosa, Staphylococcus aureus, Listeria monocytogenes and Clostridium botulinum. The intent of this investigation is to establish the mechanistic and structural bases for the design of drugs to counter both plasmid borne and genomically encoded resistance to fosfomycin. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ERADICATING BIOFILMS WITH ATMOSPHERIC GLOW PLASMA Principal Investigator & Institution: Kelly-Wintenberg, Kimberly K.; President & Ceo; Atmospheric Glow Technologies, Llc 924 Corridor Park Blvd Knoxville, Tn 37932 Timing: Fiscal Year 2003; Project Start 01-SEP-2000; Project End 31-MAY-2005 Summary: (provided by applicant): Atmospheric Glow Technologies proposes a novel method of cold sterilization and biofilm destruction of medical and dental materials. The effort will use the One Atmosphere Uniform Glow Discharge Plasma (OAUGDP) technology to attack and destroy biofilms, which cause serious problems on medical and dental instruments and devices. The use of atmospheric plasma to sterilize/decontaminate instrumentation contaminated with biofilms is a new application of a proven baseline technology. The efficacy of the OAUGDP using direct exposure was clearly demonstrated in Phase I studies. In this proposed effort, a remote atmospheric plasma reactor will be optimized to create a flow of concentrated reactive oxidative species (ROS) over 3-D workpieces and a novel direct plamsa delivery system for treating lumened devices. The performance of this reactor will be assessed against mixed species biofilms and in the presence of organic debris. Analytical studies will be undertaken to examine the composition of plasma ROS and any physical or chemical alterations that occur in materials and biological substances. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: FCR DEFICIENT MICE SUSCEPTIBILITY TO PATHOGENS Principal Investigator & Institution: Ravetch, Jeffrey V.; Theresa & Eugene M. Lang Professor; Lab/Molec Genetics & Immunol; Rockefeller University New York, Ny 100216399 Timing: Fiscal Year 2004; Project Start 01-MAY-1994; Project End 31-JAN-2009 Summary: (provided by applicant): The host response to blood borne pathogenic organisms involves the responses facilitated by the marginal zone where pathogens first
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come in contact with cells of the immune system. The antibody response elicited by the marginal zone upon exposure to encapsulated microorganisms is dominated by the mouse IgG3 subclass in a T independent and complement C3 dependent reaction. Our work has focused on the genetic pathways that contribute to the organization of the marginal zone and the cellular responses that are triggered by this anatomic structure upon exposure to encapsulated microbial pathogens. Two main areas of investigation will be pursued in this proposal for the next granting period - 1) characterization of a novel FcgammaR that engages IgG3, called FcgammaRIV, and its role in the host response to encapsulated microbial pathogens and 2) dissection of the mechanisms that govern the coordinated movement of marginal zone B cells and macrophages in response to microbial challenge through the analysis of specific genetic pathways, such as pyk2 and SHIP, that we have identified as being critical in the organization and function of the marginal zone. To accomplish these broad goals, four specific aims will be addressed: 1) Define the structure, function and expression of FcgammaRIV on myeloid and lymphoid cells. Experiments are proposed to define the expression and regulation on various cell types, the structural basis for its IgG3 binding specificity, the subunit composition and signaling properties of the receptor and its interactions with complement pathways and inhibitory signaling responses. 2) Analyze the in vivo role of FcgammaRIVin host response to encapsulated pathogens. Mice with conditional deficiency of FcgammaRIV in either lymphoid or myeloid cells will be constructed, combined with similar deficiencies in FcgammaRI, II or III and studied in both thymic dependent and thymic independent responses. Passive or active pathogen specific anticapsular polysaccharide responses will be generated in these strains and the resulting animals challenged with S. pneumoniae and C. neoformans to determine the role of specific FcRs in protection or enhancement. 3) Characterize the molecular interactions between marginal zone macrophages and marginal zone B cells. The endogenous ligand for the MARCO scavenger receptor on marginal zone B cells will be identified and characterized for its expression and function in vitro and in vivo. The role of this receptor/ligand pair in marginal zone organization and response to capsular polysaccharides will be pursued. 4) Determine the mechanism of cellular migration in the marginal zone in response to microbial challenge. Pyk2 and SHIP conditional mutants will be analyzed for their role in marginal zone B cell migration, retention and survival. The role of specific macrophages subsets will be investigated in the B cell and macrophage movement triggered by S. pneumoniae and S. aureus. These studies will clarify the host response to encapsulated microbial pathogens through the analysis of the marginal zone and specific antibody response elicited by these pathogens. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENETIC BASIS OF P. AERUGINOSA LUNG INFECTIONS IN MICE Principal Investigator & Institution: Yu, Hongwei; Micro/Immunol/Molec Genetics; Marshall University Huntington, Wv 25701 Timing: Fiscal Year 2004; Project Start 01-JUL-2000; Project End 31-MAR-2006 Summary: (provided by applicant): Cystic fibrosis (CF) is an autosomal recessive lethal disease that mainly affects the Caucasian populations. Chronic lung infections with Pseudomonas aeruginosa is the leading cause of the morbidity and mortality in CF. Although CFTR mutations predispose the host with increased susceptibility to this and other bacterial pathogens, it is still unclear what innate susceptibility mechanisms are required for the establishment of initial phase of bacterial lung colonizations. To better understand the etiology of bacterial lung infections in conjunction with genetic defects in CF, we identified a P. aeruginosa-susceptible mouse strain and will use this inbred
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mice to map and identify a mouse susceptibility gene. Using a bacterial aerosol infection mouse model, we screened seven inbred mice for the altered susceptibility to P. aeruginosa and S. aureus lung colonizations. DBA/2 mice were extremely susceptible to lung colonizations by both CF-relevant pathogens while C57BL/6, C3H/HeN, and NJ mice displayed a resistant phenotype. This susceptibility trait is autosomal recessive and seems to be controlled by a single allele. While DBA/2 neutrophils were bactericidal, the delay of neutrophil infiltrations to the lungs in response to bacterial aerosol challenges appeared to be associated with increased susceptibility. In this proposal, we will further examine the genetic basis of bacterial lung infections in mice by pursuing the following two specific aims: 1) to map a mouse susceptibility locus to P. aeruginosa and S. aureus lung infections; and 2) to identify the components of innate lung defenses associated with the P. aeruginosa and S. aureus clearance. We also plan to produce a congenic CFTR mutant mouse in DBA/2 background to test whether homozygous CFTR mice carrying P. aeruginosa-susceptible allele will naturally acquire lung infections as seen in humans with CF. The discovery of the mouse susceptibility gene may lead to the identification of the human homologue (lung-specific modifier gene) presumed to mediate susceptibility in the initial phase of infection. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENETIC POLYMORPHISMS IN WEGENER'S GRANULOMATOSIS Principal Investigator & Institution: Edberg, Jeffrey C.; Associate Professor; Medicine; University of Alabama at Birmingham Uab Station Birmingham, Al 35294 Timing: Fiscal Year 2002; Project Start 30-SEP-2000; Project End 31-AUG-2004 Summary: (investigator's abstract): Wegener's Granulomatosis is one of the antineutrophil cytoplasmic antibody (ANCA) positive systemic vasculitides which is characterized by inflammatory lesions with granuloma formation in the upper and lower airways, by pauci-immune glomerulonephritis and by anti-proteinase 3 autoantibodies (PR#-ANCA). Although WG is idiopathic, there has been substantial interest in environmental factors as either etiologic or accelerating risk factors. Because of epidemiological studies implicating nasal carriage and therapeutic studies implicating efficacy of anti-staphylococcal agents at least for upper airway disease, Staphylococcus aureus has attracted substantial attention as one such environmental factor. Although consensus about etiology remains elusive, the nature of the host response has emerged as an important determinant for disease phenotype and severity. There are may examples of human disease, provoked by environmental exposures, which have important genetic factors contributing to both susceptibility and severity. HIV presents one such example. Thus the identification of important genetic factors in a disease such as WG is not only feasible but also potentially very fruitful in providing insights into pathogenesis and potential therapeutic targets. Building on the clinical trial of Etanercept in WG (Wegener's Granulomatosis Etanercept Trial, WGET), we propose to develop a renewable genetic repository which will provide resources to all WGET investigators and to explore the relationship between the WG diathesis and genetic polymorphisms in candidate molecules, selected for their role in pathophysiology. We also propose to discover new polymorphisms in such molecules and apply these to this cohort. Accordingly, our specific aims are: 1) To establish a renewable biological resource of all WG patients screened and enrolled in the WGET clinical trial, including two ethnically and geographically matched controls for each patient; 2) To determine if known variations in genes involved in the innate inflammatory response, in lymphocyte activation and in target antigen biology influence the susceptibility to or severity of WG; 3) Recognizing that the knowledge base about biologically significant genetic variants
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will increase, we will determine, through direct discovery and through continual evaluation of SNP databases, if newly identified variation in gene categories outline in Specific Aim 2 influence the susceptibility to or severity of WG. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GLYCOMIMETICS OF S. AUREUS CP AMINOSUGARS Principal Investigator & Institution: Norris, Peter; Chemistry; Youngstown State University 410 Wick Ave Youngstown, Oh 44555 Timing: Fiscal Year 2003; Project Start 01-JUN-2003; Project End 31-MAY-2006 Summary: (provided by applicant): Antibiotic resistant bacteria are an immediate concern in the clinic and there is an obvious and growing need for new and more effective treatments. Staphylococcus aureus is one of the most worrying of these microorganisms since strains have developed that do not respond to even the most potent antibiotics currently available such as vancomycin. Since S. aureus produces a capsular polysaccharide (CP) to protect itself from phagocytosis, attacking the biochemical machinery that is used to create this polymeric coating should be a viable target for therapeutic intervention. The glycosyl transferase enzymes that build the polysaccharides have yet to be isolated therefore creating small molecule glycomimetics that might inhibit enzymatic activity will provide tools for enzyme isolation, as well as possible lead compounds for antibiotic treatment. The three amino sugars that make up the capsular polysaccharides of the most prevalent strains of S.aureus are N-acetyI-Dmannose uronic acid (D-ManAcA), N-acetyI-D-fucosamine and N-acetyI-L-fucosamine. Glycomimetics of each of these sugars will be produced. The specific goals of this proposal are:1. Chemical synthesis of N-acetyI-D-mannose uronic acid N-glycosides from an azidodeoxy synthon; 2. Development of our dithiane approach to C-glycosides and C-disaccharides, especially focusing on D-ManAcA analogs; 3. Preparation of 1deoxy iminosugar derivatives of D-ManAcA; 4. Formation of N-acetyI-D-fucosamineand N-acetyI-L-fucosamine-derived nitroglycals that will serve as precursors to both Nand C-glycoside analogs of these compounds; 5. Studies towards the synthesis of 3component potential inhibitors of the enzymes putatively used to form the 13-DManAcA- (1,4)-o_-L-FucNAc linkage in S.aureus type 5 CP and the corresponding J3DManAcA-(1,3)-alpha-L-FucNAc linkage in the type 8 CP. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: HEALTH IMPROVEMENT & COST REDUCTION IN ANIMAL FACILITIES Principal Investigator & Institution: Smith, Abigail L.; Professor of Pathology; Jackson Laboratory 600 Main St Bar Harbor, Me 04609 Timing: Fiscal Year 2002; Project Start 30-SEP-1998; Project End 31-MAR-2005 Summary: (Provided by applicant): The overall goal of the proposed studies is to establish environmental conditions that optimize the health of mice used in biomedical research, provide a safe and comfortable workplace, and minimize the costs associated with doing animal-based research. The methods by which the applicants will approach this goal include: (1) determining housing conditions that minimize pathogen transfer, (2) evaluating effects of culling on reproductive success, (3) identifying husbandry and hygiene practices that reduce caretaker exposure to mouse allergen, and (4) instituting workplace activities that may improve the health of animal caretakers. The investigators will first study the capacity of ventilated caging maintained at "neutral" airflow and negatively ventilated changing tables to reduce worker exposure to allergen and to
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reduce or eliminate transfer of Pasteurella pneumotropica, Helicobacter spp. and Pneumocystis carinii from infected mice to pathogen-free immunocompromised mice. The applicants will determine reproductive success of mice whose litters are culled or not and housed under different ventilation conditions. The efficacy of water, dilute tannic acid, and dilute sodium hypochlorite used to reduce breathing zone allergen levels during bedding changes will be tested. Skin and clothing of caretakers will be sampled for Staphylococcus aureus upon entry into mouse rooms through air or wet showers and for allergen upon exiting the facility through air or wet showers. In an effort to reduce employee workplace injuries, a functional capacity checklist will be developed and will be used to design an employee exercise program. Lastly, a preemployment Functional Capacity Assessment tool to help slot new hires in positions for which they are physically capable will be used. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HEMOSTATIC FACTORS AND THE INFLAMMATORY RESPONSE Principal Investigator & Institution: Degen, Jay L.; Professor; Children's Hospital Med Ctr (Cincinnati) 3333 Burnet Ave Cincinnati, Oh 452293039 Timing: Fiscal Year 2002; Project Start 01-JUN-1999; Project End 31-MAY-2003 Summary: The long-term goal of this research program is to understand of the roles of coagulation and fibrinolytic factors in hemostasis, wound repair, inflammatory response, and disease pathobiology. The recent generation of viable mouse lines with selected deficits in key hemostatic factors has provided a unique opportunity to rigorously define the roles of specific factors in both physiological and disease processes. The primary objective of this research proposal is to exploit this opportunity to directly establish the importance and mechanistic role of hemostatic factors in bacterial virulence and host inflammatory response. The focus of these studies will be the bacterial pathogens, Y. pestis and S. aureus, two microorganisms that express welldescribed bacterial plasminogen activators, procoagulants, and fibrin(ogen) binding proteins. The project aims center on the following specific hypotheses: i) host coagulation and fibrinolytic factors are critical in bacterial virulence and pathogenesis, ii) fibrin(ogen) and plasmin(ogen) have a fundamental role in mediating host inflammatory response at sites of infection, iii) fibrin(ogen) alters inflammatory cell activity at sites of infection through the engagement of the integrin, CD11b/CD18, and iv) hemostatic factors play an important role in the inflammatory response, regardless of the challenge or tissue. These hypotheses will be tested though detailed studies of Y. pestis and S. aureus infection and host inflammatory response in mice with specific deficits in plasminogen activator, plasminogen, and fibrinogen (Specific Aims 1 and 2). The mechanistic role of fibrin(ogen)-integrin interaction in the inflammatory response will be explored by comparative studies of infection and inflammation in mice expressing mutant forms of fibrinogen lacking the motifs recognized by the platelet integrin, alphaIIbbeta3, and the leukocyte integrin, CD11b/CD18 (Specific Aims 2 and 3). Finally, the role of fibrin(ogen) in inflammatory processes unrelated to bacterial infection will be explored by studying the impact of fibrinogen deficiency on leukocyte emigration, adhesion, and function, using peritonitis and dermatitis model systems (Specific Aim 4). The proposed studies will provide a more detailed understanding of the role of coagulation/fibrinolytic factors in bacterial pathogenesis and the inflammatory response, and could ultimately lead to the development of new therapeutic strategies for the treatment of both bacterial infection and inflammatory diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Staphylococcus aureus
Project Title: HOST RESPONSE IN S. AUREUS INFECTIONS: ROLE OF T CELLS Principal Investigator & Institution: Tzianabos, Arthur O.; Associate Professor of Medicine; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2002; Project Start 01-JUN-2002; Project End 31-MAY-2007 Summary: (provided by applicant): Staphylococcus aureus is an opportunistic bacterial pathogen responsible for a diverse spectrum of human and animal diseases, including wound infections, osteomyelitis, endocarditis, and bacteremia leading to secondary abscesses in any of the major organ systems. Staphylococcal infections occur most frequently when mucosal barriers are breached, following insertion of a foreign body, or in the presence of other factors that compromise the immune system of the host. Currently, the host response to this organism is poorly understood. The majority of studies to date have focused on the role of PMNs modulating the host response to staphylococcal infections. S. aureus is typically classified as an extracellular pathogen that does not directly interact with the host immune system via T cells. However, we have shown that the Staphylococcus produces a capsule with both free amino and negatively charged carboxyl groups that mediates its pathogenic potential in an experimental model of intraabdominal abscess formation in a T cell-dependent manner. This capsule can activate CD4+ T cells and induce the production of CXC chemokines, peptides that activate and recruit PMNs to sites of inflammation. The transfer of CD4+ T cells that have been activated by the S. aureus capsule promotes abscess formation in naive recipient animals. Based on these data, we hypothesize that CD4+ T cells activated by S. aureus capsules are critical in determining the outcome of staphylococcal infections through the release of CXC chemokines that control PMN trafficking to infected sites. This hypothesis will be tested in staphylococcal animal models of subcutaneous abscess formation and surgical wound infection. These models are clinically relevant, low-inoculum murine models of staphylococcal disease that mimic important aspects of human disease. We propose to: 1) Characterize the mechanism by which S. aureus synthesizes a capsule with a zwitterionic charge motif; 2) Evaluate the role of the capsular polysaccharide in the interaction between S. aureus and the host; 3) Determine the role of T cells in the pathogenesis of and host response to staphylococcal infections; and 4) Characterize the T cell-mediated CXC chemokine response to S. aureus infection and its role in regulation of PMN trafficking. Results from the proposed studies should provide insight regarding the under appreciated role of T cells in the pathogenesis and host response in S. aureus infections. This information may reveal new strategies for the prevention or treatment of S. aureus infections through immunomodulation of the host response to this organism. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: IL-1 AND IL-1RA STIMULATION OF S AUREUS REPLICATION Principal Investigator & Institution: Kanangat, Sivadasan; Medicine; University of Tennessee Health Sci Ctr Memphis, Tn 38163 Timing: Fiscal Year 2002; Project Start 28-SEP-2001; Project End 31-AUG-2004 Summary: (provided by applicant): Septic arthritis /bacterial arthritis is a serious complication of rheumatoid arthritis (RA) and other forms of arthritis. It can also occur in seemingly normal joints. If it is not rapidly diagnosed and treated, it can lead to acute joint destruction, osteomyelitis, sepsis and even death. Staphylococcus aureus is the predominant organism invading the RA joints. Synovium of active RA joints contains many cytokines amongst which is the members of the IL-1 family namely, IL-l alpha, IL1beta and IL-1 receptor antagonist(IL-Ira). We have observed and previously reported
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that S. aureus is able to use IL-1beta and IL-1ra as growth factors. Furthermore, these molecules specifically bind to the receptors on the surface of S. aureus (referred hereafter as IL-1R). A major and minor epitope on IL-1beta has been identified to reside in the amino acid residues 208-240 and 118-147 respectively. We hypothesize that specific epitopes in IL-1beta and IL-1 ra bind to IL-1 receptor as a first step in initiating receptor post-receptor mediated events which result in stimulation of replication of the bacterium. Four specific aims will address this hypothesis as follows: 1) Isolate and characterize the S. aureus IL-1R; 2) Clone the S. aureus IL-1 R; 3) Determine the structural requirements of IL-1beta for binding to S. aureus IL-1R and 4) Determine the structural requirements of IL-1ra necessary for binding to S. aureus IL-1R. This study identifies and characterizes a previously unknown mechanism by which S. aureus utilize members of the IL-1 family as growth factors to defeat the host defense response against infection and persistent inflammation. This particular study is very relevant to septic arthritis in RA and non-RA patients in whom the rapid diagnosis and appropriate treatment to protect the joint structures are very important. A better understanding of how bacteria such as S. aureus use IL-1 family of cytokines to replicate and defeat the host defense is highly relevant to the study of septic arthritis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: IN VIVO EFFECTS OF BACTERIAL SUPERANTIGENS Principal Investigator & Institution: Blackman, Marcia A.; Associate Member; Trudeau Institute, Inc. Saranac Lake, Ny 12983 Timing: Fiscal Year 2002; Project Start 01-MAR-1996; Project End 31-DEC-2004 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: JEOL JEM-1010 TRANSMISSION ELECTRON MICROSCOPE & CAMERA Principal Investigator & Institution: Compton, Duane A.; Associate Professor; Biochemistry; Dartmouth College 11 Rope Ferry Rd. #6210 Hanover, Nh 03755 Timing: Fiscal Year 2002; Project Start 01-JUN-2002; Project End 31-MAY-2003 Summary: (provided by applicant): This proposal is for the acquisition of a new transmission electron microscope and digital camera for use in NIH funded research and training, and other research, as well as undergraduate education. NIH-funded research on identification of proteins and characterization of molecular mechanisms involved in organizing microtubule minus ends at spindle poles in mammalian cells, interaction of Staphylococcus aureus with mammalian cells, and human colonization by the bacterium Vibrio cholera , all depend on high quality transmission electron microscopy for examination and evaluation of experiments. The transmission electron microscope (ThM) chosen is a JEOL USA, Inc. JEM-lOlO TEM, a 100KV microscope with 0.2 nm resolution, high tilt (+ or -60 degrees) pole piece, while the camera is a Gatan, Inc. Model 792 BioScan 1K by 1K wide angle CCD camera. The microscope and camera will be housed in the Rippel Electron Microscope Facility (REMF), an institutional resource, where it will be covered by service contract and a full time staff for training, research assistance and maintenance. The existing Faculty Advisory Committee will be extended to include the PIs for the purpose of ensuring access to the TEM. The TEM? to be replaced is 24 years old and has an anticipated life of no more than two years, despite having been continuously under service contract. The research of the principle
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Staphylococcus aureus
investigators cannot be completed without continued availability of a transmission electron microscope. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MECHANISM OF STAPHYLOCOAGULASE-ACTIVATED BLOOD CLOTTING Principal Investigator & Institution: Bock, Paul E.; Associate Professor; Pathology; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2003; Project Start 01-JAN-2003; Project End 31-DEC-2007 Summary: (provided by applicant): The broad goal of the proposed studies is to define the molecular mechanism of the activation of human blood coagulation by the S. aureus protein, staphylocoagulase (SC), and the role of the mechanism in the pathogenesis of endocarditis. SC binds tightly to human prothrombin (Pro) and induces formation of a functional catalytic site in the zymogen without the usual strictly required peptide bond cleavages. This unique conformational activation mechanism is hypothesized to involve initial encounter of SC and Pro, followed by activation of the catalytic site and occupation of regulatory proexosite I in two or more discrete conformational changes. The mechanism may involve conformational linkage between proexosite I occupation and catalytic site activation, stabilization by high affinity binding of SC to the active conformation, and is unlikely to require insertion of the SC amino-terminus into a binding pocket in the Pro catalytic domain. The mechanism underlying the unique specificity of SC-Pro to convert fibrinogen (Fbg) to fibrin (Fbn) is hypothesized to bypass and inhibit the normal reactions of Pro activation. This mechanism is central to the propagation of platelet- Fbn-bacteria vegetations on heart valves in endocarditis. Fbg clofting activity of the SC-Pro/T complexes is hypothesized to involve specific recognition of Fbg as a substrate through expression of a Fbg-binding exosite on the SCPro/T complexes, in addition to changes in catalytic site specificity. Biochemical, biophysical, and structural approaches employing novel active site-labeled fluorescent derivatives of Pro are proposed to test hypotheses for conformational activation of Pro by SC and the basis of its specificity for conversion of Fbg to Fbn. Specific Aims are: (1) To determine the thermodynamic mechanism of conformational activation of Pro by SC; (2) To define the kinetic pathway of individual molecular events in conformational activation; (3) To elucidate the mechanism of specific recognition of Fbg as a substrate of SC-Pro/T complexes; and (4) To determine the three dimensional structures of SCI-327 bound to Pro/T species. The proposed studies are of fundamental significance in understanding how SC can circumvent the otherwise strict requirement for peptide bond cleavage in serine proteinase zymogen activation. The studies will provide new insight into the role of activation of Pro by SC in the pathogenesis of endocarditis and may ultimately allow therapy adjunctive to antibiotics to be developed based on inhibition of SC-activated blood coagulation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MECHANISMS OF BLISTER FORMATION BY STAPHYLOCOCCAL TOXINS Principal Investigator & Institution: Stanley, John R.; Milton B. Hartzell Professor; Dermatology; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2007 Summary: Exfoliative toxin A (ETA), produced by Staphylococcus aureus, causes staphylococcal scalded skin syndrome (SSSS) and its more localized form, bullous
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impetigo. The crystal structure of ETA suggests that it is a serine protease with an inactive catalytic site which becomes activated when ETA binds a specific receptor. In pemphigus foliaceus autoantibodies that cause dysfunction of Dsg 1 cause blisters identical to those caused by ETA in the superficial epidermis of mouse and man. Therefore, we hypothesize that Dsg 1 specifically binds and activates ETA, which in turn cleaves the bound Dsg 1, resulting in blister formation. We propose that another staphylococcal toxin, exfoliative toxin B (ETB), that also causes bullous impetigo and SSSS, is also activated by, and cleaves, Dsg 1. Finally, we hypothesize that binding of ETA to Dsg 1 and/or cleavage of Dsg 1 by ETA might elicit an autoimmune response against Dsg 1, thus suggesting a mechanism for autoantibody production in PF patients. We have shown that ETA cleaves Dsg 1. Specific aim 1 will characterize this cleavage by determining if cleavage is dependent on Dsg 1 conformation, and by defining the site of cleavage and the domains of Dsg 1 needed for cleavage. Aim 2 will characterize binding of ETA to Dsg 1, and define the domains of each necessary. Aim 3 will determine, using Dsg 3 knockout and involucrin-Dsg 3 transgenic mice, if compensation by Dsg 3 can compensate for ETA-induced loss of function of Dsg 1, thereby explaining the sites of blister localization. Aim 4 contains studies designed to define the kinetics of Dsg 1 cleavage by ETA. Aim 5 will extend the results of the previous aims to include the mechanisms of action of ETB. The final aim will determine if patients with bullous impetigo and SSSS develop an antibody response against Dsg 1, if patients with pemphigus foliaceus have an enhanced immune response against ETA and ETB, and if mice injected with ETA develop an immune response against Dsg 1. These studies will provide insight regarding the molecular pathophysiology of a very common disease, bullous impetigo, and, for the first time, identify a potential trigger or exacerbating factor in a tissue-specific autoimmune disease, pemphigus. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MECHANISMS STAPHYLOCOCCI
OF
GLYCOPEPTIDE
RESISTANCE
IN
Principal Investigator & Institution: Daum, Robert S.; Professor; Pediatrics; University of Chicago 5801 S Ellis Ave Chicago, Il 60637 Timing: Fiscal Year 2003; Project Start 15-NOV-1998; Project End 31-MAR-2007 Summary: (provided by applicant): Staphylococcus aureus is a leading cause of community and nosocomially-acquired infectious and toxin-mediated syndromes, some life threatening, that affect patients of all ages. The glycopeptides (GP) have been the most reliable alternatives for the therapy of S. aureus isolates that are resistant to methicillin, cross resistant to all beta-lactams, and often resistant to a wide spectrum of unrelated antimicrobials. However, the effectiveness of GPs has been eroded by the increasing recognition of resistant isolates. Our ongoing studies are aimed at identifying GP resistance mechanisms. Despite the description of numerous phenotypic and biochemical characteristics among resistant isolates, the mechanism(s) of GP resistance in S. aureus has remained incompletely defined. Available data suggest that acquisition of the resistance phenotype involves cell wall reorganization; pleiotropic changes have been documented such as altered peptidoglycan structure, coagulase activity, binding of vancomycin, autolytic activity and lysostaphin susceptibility. However, it seems unlikely that a single mechanism or sequence of mechanisms will account for resistance in all clinical glycopeptide-resistant isolates studied to date since no phenotypic or biochemical change has been uniformly found. We believe that the resistant phenotype involves multiple genetic changes. We plan to investigate the mechanism(s) of resistance with a multi-pronged approach. First, with the complete genomic sequence of four S.
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Staphylococcus aureus
aureus isolates at hand, we will employ microarray analysis to compare expression patterns of relevant cell wall metabolic and 2-component signal transduction genes between GP-susceptible and resistant isolates. The availability of isogenic susceptible and resistant clinical isolate pairs will provide invaluable tools for this analysis. Appropriate up and down regulated genes will be targeted for further investigation including sequence comparison, Northern blot analysis, allelic inactivation and overexpression in relevant genetic backgrounds. These studies should lead to an understanding of the mechanisms by which S. aureus resist the bactericidal effect of GPs and hopefully can identify new ideas regarding therapy of infections caused by resistant isolates. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MECHANISMS OF GRAM-POSITIVE BACTERIAL TOLERANCE Principal Investigator & Institution: Peck, Octavia M.; Physiology and Neuroscience; Medical University of South Carolina 171 Ashley Ave Charleston, Sc 29425 Timing: Fiscal Year 2002; Project Start 12-MAR-2003; Project End 31-AUG-2005 Summary: (provided by applicant): Activation of macrophages (MO) by the Gramnegative bacterial product lipopolysaccharide (LPS) or Gram-positive bacteria initiate multiple signaling cascades and pro-inflammatory mediators important in the pathogenesis of septic shock. The latter play a major role in the pathogenesis of sepsis. LPS and the Gram-positive bacteria heat-killed Staphylococcus aureus (HK-SA) activate MO through Gi protein-coupled and Toll-like receptor (TLR) signaling pathways. Potential links between these signaling pathways are unknown. Gi protein-coupled and TLR signaling pathways are profoundly altered in the phenomenon of LPS tolerance (TOL). LPS TOL is induced by pre-exposure of ME) to low concentrations of LPS, which suppresses pro-inflammatory mediator production. HK-SA TOL induces a similar form of TOL. However, HK-SA TOL induces priming to LPS rather than cross TOL. These results prompted the hypothesis that Staphylococcus aureus induces homologous tolerance and priming to bacterial lipopolysaccharide through changes in heterotrimeric Gi proteins and Toll-like receptor-coupled signaling pathways. Two interrelated specific aims will test the hypothesis. Specific aim 1 will determine the effects of HK-SA and LPS induced homolgous TOL on signaling though Gi protein and TLR coupled pathways and to LPS mediator production. Specific aim 2 will determine the mechanisms whereby HK-SA TOL induced priming responses to LPS alters Gi protein-coupled and TLR signaling pathways and mediator. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MECHANISMS OF TOPOISOMERASE POISONS Principal Investigator & Institution: Hiasa, Hiroshi; Pharmacology; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2002; Project Start 01-JAN-1999; Project End 31-DEC-2003 Summary: Topoisomerase are ubiquitous enzymes that alter the linking number of DNA. As such, they play essential roles in every aspect of DNA metabolism. Their importance is underscored by the fact that in eukaryotes these enzymes are the cellular targets of potent anticancer drugs, whereas in prokaryotes both DNA Gyrase and topoisomerase IV (Topo IV) are targets of the most potent broad-spectrum antibacterial agents (e.q., ciprofloxacin). These drugs convert topoisomerases to poisons that inhibit DNA replication and lead to double-strand break (DSB) generation. Thus, it is crucial to understand the molecular basis of the cytotoxicity of these topoisomerase inhibitors. I
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have shown that the encounter of a replication fork with a Topo IV- quinolone-DNA ternary complex converts the ternary complex to a nonreversible form. (I) We will examine if a complete replication fork is required for the conversion of a ternary complex to a nonreversible form. It is possible that the DnaB helicase alone is the active agent. (II) We will study the effects of a topoisomerase trapped at a site of DNA damage on the replication fork. It has been demonstrated that DNA lesions, such as an apurinic site, stimulate eukaryotic topoisomerase- mediated DNA cleavages. We will examine if an apurinic site also acts as a topoisomerase poison for bacterial enzymes. We will compare effects of an apurinic site-induced Topo IV-DNA complex and a Topo IVquinolone-DNA ternary complex on the replication fork to determine if these two distinct mechanisms of poisoning topoisomerases have the same consequences. (III) Recent studies have demonstrated that quinolones do not stimulate S. aureus DNA gyrase (Gyrase)-mediated DNA cleavages. We will characterize S. aureus Gyrase and a ternary complex formed with this enzyme. Furthermore, we will examine if DNA strand cleavage is always required for replication fork arrest by a topoisomerase- quinoloneDNA ternary complex. (IV) We have proposed that quinolone- induced DSB generation is a two-step process. Using an assay where replication forks collide with a ternary complex, I detected an activity in an E. coli extract that could generate DSBs at dead-end topoisomerase complexes. We will identify the protein(s) required for the second step of DSB formation and complete the reconstitution of the DSB process in vitro with purified-proteins. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MECHANISTIC STUDIES AT THE HOST-PATHOGEN INTERFACE Principal Investigator & Institution: Mcmurray, David N.; Regents Professor; Medical Microbiol & Immunology; Texas A&M University Health Science Ctr College Station, Tx 778433578 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-JUL-2008 Summary: (provided by applicant): The never-ending struggle between humans and infectious diseases will be won at the interface between the host and the pathogen. This is precisely the research emphasis of the faculty members who are participating in this training grant. The faculty consists of an outstanding group of extramurally funded investigators with a cumulative wealth of experience in training predoctoral students. Faculty members are drawn from components of the Texas A&M University System Health Science Center and the College of Veterinary Medicine. Research training opportunities exist in several important human bacterial and viral pathogens, including Salmonella species, papillomavirus, Mycobacterium tuberculosis, Brucella abortus, Bartonella species, influenza virus, Borrelia burgdorferi, rotavirus, Coxiella burnetii, and hepatitis virus. Other research projects focus upon pathogen-host interactions mediated by microbial toxins, such as Shiga-like and C. perfringens toxins. Another large project will give trainees the opportunity to learn about microbial surface components which facilitate the binding of pathogens such as Staphylococcus aureus, Enterococcus faecalis, and B. burgdorferi to host cell adhesive matrix molecules. These discrete projects are organized into three distinct themes: (1) Microbe-host cell interactions: intracelluar pathogens, microbial adhesion, and agents of bioterrorism; (2) Enteric diseases; and (3) Vaccine development and evaluation. Extensive collaboration already exists between many of the participating faculty members, and the research training environment will be seamless from the trainee's perspective. The faculty have access to extensive animal care facilities (both conventional and BL-3) for small and large animal models, cutting edge technologies, and core facilities on the main campus. An excellent
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Staphylococcus aureus
interdisciplinary curriculum, enriched by an outstanding, seminar series and plentiful opportunities for trainees to attend and present their findings at regional and national meetings will guarantee the ultimate success of our trainees as independent scientists. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MECHANISTIC STUDIES OF TYPE II IPP ISOMERASE Principal Investigator & Institution: Rothman, Steven C.; Chemistry; University of Utah Salt Lake City, Ut 84102 Timing: Fiscal Year 2004; Project Start 01-APR-2004; Project End 31-MAR-2007 Summary: (provided by applicant): A recent report describes the cloning and preliminary characterization of an unusual flavin mononucleotide (FMN) dependent enzyme, the type II isopentenyl diphosphate (IPP) isomerase. IPP isomerases interconvert isopentenyl diphosphate and dimethylallyl diphosphate, the metabolic building blocks for a wide array of biological isoprenoid compounds. The newly identified type II enzyme represents an attractive antimicrobial drug target as sequence analyses suggest that it is essential in the pathogen Staphylococcus aureus and is not present in humans. The initial study with the type II IPP isomerase indicated that catalysis requires both FMN and NADPH. The role is these two cofactors is unclear, given that isomerization does not entail a net oxidation/reduction and that the type l isomerase catalyzes a proton addition-proton elimination reaction that does not include a transient oxidation/reduction. This proposed work intends to elucidate the functions of the two cofactors, the chemical mechanism, and the roles of active site residues in the reaction catalyzed by type II isopentenyl diphosphate isomerase from Synechocystis sp. PCC 6803. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MODULATION TRANSPLANTATION
OF
INNATE
IMMUNITY
IN
LUNG
Principal Investigator & Institution: Matalon, Sadis; Acting Associate Provost for Research; Anesthesiology; University of Alabama at Birmingham Uab Station Birmingham, Al 35294 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-JUL-2006 Summary: (provided by applicant): A multi-center clinical trial sponsored by Fujisawa Healthcare, Inc, was planned to compare the efficacy of treating lung transplant patients with tacrolimus and sirolimus versus tacrolimus and azathioprine in reducing the incidence of acute rejection during the first twelve months after lung transplantation. Infection is a secondary endpoint and is assessed throughout the trial (i.e. for 3 years after randomization). Presently the mechanisms by which these agents may modify lung innate immunity have not been identified. Herein, we are proposing to isolate SP-A and AMs from the bronchoalveolar lavage fluid (BALF) of patients participating in this clinical trial to identify differences in the ability of AMs to kill gram positive and gramnegative bacterial pathogens and to identify differences in quantity of SP-A and modifications thereof. These data will be correlated with incidences of infection and rejection in patients participating in the clinical trial. We are also proposing to identify basic mechanisms by which normal but not nitrated SP-A enhances phagocytosis. These goals will be accomplished by completing the set of measurements outlined in the following specific aims: (1) Measure levels of surfactant lipids and SP-A in bronchoalveolar lavage (BAL) samples from patients treated with tacrolimus and sirolimus vs. tacrolimus and azathioprine. Oxidative modification to SP-A (oxidation
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and nitration) will be assessed by Western blotting, ELISA and mass spectrometry analysis using techniques already established in our laboratory; (2) Quantitate levels of inflammatory cytokines (TNFa, INFgamma, IL-6 and IL-lb), as well as levels of nitrate and nitrite, the stable end products of NO metabolism, and nitrotyrosine in the BAL of these patients; (3) Assess the extent of pathogen killing (Klebsiella pneumoniae, a gram negative bacterium and Staphylococcus aureus, a gram positive bacterium) by AMs isolated from the lungs of these patients in the presence of SP-A and surfactant lipids, and (4) Identify putative mechanisms responsible for decreased ability of oxidized or nitrated SP-A to mediate pathogen killing by AMs. We propose that SP-A binding to AM receptors leads to activation of phospholipase C (PLC) which releases 1,4,5 inositol triphosphate (IP3) resulting in Ca+2 release from the endoplasmic reticulum. SP-A nitration may lead to decreased binding, diminishing or abrogating intracellular Ca+2 changes. Our data may provide mechanistic insight into why some patients may develop clinical infection and acute and chronic rejection and thereby form the rationale basis for choosing between these two immunosuppressive regiments for the management of patients with lung transplantation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MOLECULAR & CELLULAR BASIS OF HOST-PATHOGEN INTERACTIONS Principal Investigator & Institution: Bohach, Gregory A.; Professor; Microbiol/Molec Biol & Biotech; University of Idaho Moscow, Id 838443020 Timing: Fiscal Year 2002; Project Start 15-SEP-2000; Project End 31-AUG-2005 Summary: Although the number of faculty engaged in biomedical research at the University of Idaho (U of I) is not large, our institution is strongly committed to research related to microbial pathogenesis and food-borne illness. The overall objective of this project is to build upon our current core of strength in the "study of the molecular and cellular basis of host- pathogen interactions". We will establish the U of I as a premier institutional having a nationally recognized biomedical program with this thematic focus. COBRE funding will allow us to integrate the programs of several established biomedical scientists with those of tow new tenure- track faculty (a virologist and cell biologist) on the main campus in Moscow, ID. In doing so, we will emphasize career development, mentoring, and grantsmanship of all faculty in the Center. We will strengthen our graduate training and research collaboration with the Infectious Diseases Unit of Boise Veterans Affairs Medical Center. Finally, we will integrate the five-state (Wyoming, Washing, Alaska, Montana, and Idaho) WWAMI Medical Program into the COBRE Center to provide a unique opportunity for medical students to become immersed in biomedical research. COBRE center research projects will initially be led by four Co-Investigators , each of whom has proposed an area of multi-disciplinary research relevant to human health and to the overall theme of the Center. This team and their collaborators will work under the administrative and collaborative guidance of Dr. Gregory A. Bohach an investigator established in several areas of microbial pathogenesis. The four independent but complementary projects include: 1) An investigation of the anti-viral activity of Escherichia coli Shiga toxin; 2) Mx expression and uterine mucosal immunity; 3) The mechanism and significance of the internalization of Staphylococcus aureus by epithelial cells; and 4) Phospholipase-C induced plateletleukocyte interactions and defective diapedesis in gas gangrene. In addition to these four projects, our new virologist and cell biologist will submit research proposal to the COBRE Center and our Advisory Board for approval. A plan to develop funding independence following termination of COBRE support has been developed.
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Staphylococcus aureus
Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MOLECULAR ANALYSIS OF STAPHYLOCOCCAL EXFOLIATIVE TOXIN A Principal Investigator & Institution: Plano, Lisa R.; Pediatrics; University of MiamiMedical Box 248293 Coral Gables, Fl 33124 Timing: Fiscal Year 2003; Project Start 01-JUN-2003; Project End 31-MAY-2008 Summary: (provided by applicant): Staphylococcal scalded skin syndrome, SSSS, is a disease primarily of the young and immunocompromised that is rarely seen in healthy adults. SSSS is characterized by specific exfoliation of the upper epidermis in the stratum granulosum of the skin at a site distal to a focus of infection with exfoliative toxin (ET) producing Staphylococcus aureus. The exact mechanism of the relative protection of adults or susceptibility of newborns is not known. In an animal model these skin manifestations result from the injection of one of two species-specific exfoliative toxins, ETA or ETB. The mechanism by which these toxins result in exfoliation is now assumed to involve cleavage of desmoglein 1 (Dsgl), a desmosomal protein member of the cadherin family of cell adhesion molecules, by a unique serine protease activity of the exfoliative toxins. Cleavage of this protein fits the clinical picture of SSSS as it is primarily expressed at this layer of this skin. Our hypothesis is that characteristics of the interaction between the exfoliative toxins of S. aureus and their target desmoglein 1 explain the species, target and age specificity of these toxins as well as contribute to the pathogenicity of these bacteria. We propose in this study to use molecular techniques to characterize the interaction between the toxin, ETA and the target, Dsgl of humans and mice. The goal is to determine the domains or amino acids of Dsgl needed for recognition and cleavage by ETA and the domains or amino acids of ETA responsible for target binding and localization to the skin. Results from these analyses will provide insight into the mechanism for the age and species specificity of this unique serine protease. We further propose to develop an animal model of staphylococcal impetigo to address the role of the exfoliative toxins in pathogenesis of these bacteria. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MRSA AS A COMMUNITY ORGANISM. Principal Investigator & Institution: Eguia, Jose M.; Medicine; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 941222747 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2008 Summary: (provided by applicant): The proposed research seeks to examine the factors that allow the transmission and amplification of antibiotic-resistant bacterial clones in the community. By examining the population dynamics of different strains of methicillin-resistant Staphylococcus aureus (MRSA) in the community, we will identify genotypic and clinical predictors for their persistent carriage and determine whether "community strains" do in fact behave differently from previously recognized healthcare-associated MRSA strains in the community environment. Resistance to the beta-lactam antibiotics is mediated by SCCmec (staphylococcal cassette chromosome), which has been recently shown to have four types. Multiple reports have suggested an association between SCCmec type IV and strains isolated from patients in the community without recognized risk factors for MRSA carriage; on the other hand, SCCmec type II (and I and III, though these are not prevalent at our institution) has been classically associated with healthcare-related strains of MRSA. We plan to use SCCmec
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type as a marker for MRSA strains. Further molecular studies will allow the distinction between the SCCrnec element and the remainder of the host bacterial chromosome; we will thus be able to investigate other potential genes that may contribute to increased fitness of different MRSA strains. This three-part study will consist of (1) a crosssectional survey of all MRSA submitted as clinical specimens to the Clinical Microbiology Laboratory at our institution, to examine the relative proportions of SCCmec types in these isolates; (2) a case-control study of patients hospitalized with MRSA infection, to identify predisposing risk factors that may predict carriage of MRSA of the different SCCmec types; and (3) a cohort study of MRSA-colonized patients after hospital discharge, to determine whether SCCmec type predicts persistent colonization in the community. The applicant, Dr. Jose M. Eguia, is an infectious disease specialist with training in epidemiology. This proposal is intended to provide him with additional training in the essentials of molecular epidemiology and microbiology, advanced epidemiology and biostatistics, in the setting of a strong mentored research program. With these skills, he will be able to utilize classical and molecular epidemiology to investigate the microbiologic, clinical and ecologic factors responsible for the transmission of antibiotic resistant bacteria; this will lead to improved, rational methods of containing resistance, and thereby contribute to the public health. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NEUTROPHILS AND BACTERIAL PHOSPHOLIPID DEGRADATION Principal Investigator & Institution: Weiss, Jerrold P.; Professor; Internal Medicine; University of Iowa Iowa City, Ia 52242 Timing: Fiscal Year 2002; Project Start 01-SEP-1985; Project End 31-AUG-2004 Summary: (Adapted and modified from applicant's abstract): This proposal concerns the role and regulation of the action of mammalian Group IIA phospholipase A2 (PLA2) during inflammation and the determinants of the degradation of Gram-negative bacterial lipopolysaccharides (LPS) during host antibacterial action. The specific aims are to examine: (1) the molecular determinants of the antibacterial actions of mammalian Group IIA PLA2; (2) the regulation and role of PLA2 antibacterial action at inflammatory sites; (3) the cellular and molecular determinants of LPS degradation during intraphagocytic and extracellular antibacterial action; (4) the molecular determinants and possible physiologic role of Group IIA PLA2 action against host cellderived membrane phospholipids (PL). These aims have their origin in the applicant's earlier work and their pursuit will therefore rest heavily on well-tested methods used in his laboratory including: collection of phagocytes and inflammatory exudates from experimental animals; in vitro and ex vivo functional assays of phagocyte (or cell-free protein)-bacteria interactions such as phagocytosis, bacterial killing, and (bacterial) PL and LPS degradation; expression and purification of recombinant proteins including PLA2 variants; and construction and use of bacterial mutants. Planned studies will also include assessment of PLA2 function in vivo to further establish the contribution of this enzyme to innate host antibacterial defenses. The long-term objectives of this proposal concern two fundamental questions: (1) What determines the extent of bacterial digestion and disassembly during host antibacterial action? (2) What regulates the action of defined phospholipases on the PL of biological membranes? The proposed studies are likely to provide new insights related to the mechanisms of host defenses in infection and of the function of membranes in general. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Staphylococcus aureus
Project Title: NEUTROPHILS AND STAPHYLOCOCCUS AUREUS Principal Investigator & Institution: Gresham, Hattie D.; Associate Professor; Molecular Genetics & Microbiol; University of New Mexico Albuquerque Controller's Office Albuquerque, Nm 87131 Timing: Fiscal Year 2002; Project Start 01-SEP-2000; Project End 31-MAY-2005 Summary: Description (Adapted from applicant's abstract): Staphylococcus aureus is a major human pathogen causing significant morbidity and mortality in both communityand hospital-acquired infections. Concern over the emergence of multidrug resistant strains, particularly strains which lack sensitivity to all currently available antibiotics, has renewed interest in understanding the virulence mechanisms of this pathogen at the molecular level and in elucidating host defense elements which either provide protection from or which limit infection. Neutrophils (PMN) have long been thought to provide significant host defense against S. aureus infection. However, our studies of S. aureus-induced peritonitis and sepsis in mice have suggested that PMN have both a protective and a deleterious role. In order to demonstrate that PMN contribute to the pathogenesis of S. aureus infection, we have used multiple approaches which either limit or promote PMN migration into the infectious site. Our data indicate that excessive numbers of PMN and elevated levels of a C-X-C chemokine, MIP-2, at the site of a S. aureus infection create an environment which leads to enhanced extracellular replication of the pathogen and its intracellular survival in PMN to the detriment of the host; that PMN isolated from this environment are sufficient to establish infection in naive animals; that some of the bacteria inside these infected PMN are in endosomes with partially or fully degraded membranes; and that two regulatory loci mutants (agrand sar-) which lack the expression of several virulence factors are less able to survive and/or avoid clearance in the presence of excess PMN and MIP-2. We hypothesize that S. aureus manifests as a virulence determinant the ability to exploit the host's inflammatory response in order to enhance its survival. Moreover, we hypothesize that exogenous modulation of the inflammatory response is sufficient to alter the susceptibility of the host to infection. To test this hypothesis, we will pursue the following specific aims: #1) determine the number of PMN necessary for protection and for their deleterious role in two models of S. aureus infection; #2) define the contribution of C-X-C chemokines, the CXCR2 receptor, and specific virulence factors expressed by S. aureus to the creation of the environment which leads to both enhanced extracellular replication and intracellular survival of the pathogen; #3) elucidate known virulence factors whose genes are activated both in vivo and in vitro specifically in the presence of C-X-C chemokines and PMN; and #4) determine the mechanism of uptake and the intracellular locale of wild-type and isogenic mutants of S. aureus taken up both in vivo and in vitro by C-X-C chemokine-stimulated PMN. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: NOVEL ANTIBACTERIAL AGENTS FOR TREATMENT OF TULAREMIA Principal Investigator & Institution: Schmid, Molly B.; Senior Vice President; Affinium Pharmaceuticals, Inc. 100 University Ave, 12Th Fl, North Tower Toronto, Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-AUG-2005 Summary: (provided by applicant): A series of enoyI-ACP reductase (Fabl) inhibitors have been identified with potent, narrow spectrum in vitro antibacterial activity against the agent of Tularemia, Francisella tularensis, as well as excellent in vitro potency against Staphylococci. Lead compounds have shown good in vivo activity in treating
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Staphylococcus aureus infections in rats and have good oral bioavailability. We propose experiments to assess the in vivo safety of the lead compounds, the frequencies and mechanisms of resistance development, and the efficacy of the lead compounds in animal models of F. tularensis infection. The experiments in this application aim to complete the preclinical characterization of the lead compounds, identify additional compounds with improved characteristics that retain excellent potency against Staphylococci and Francisella, and produce sufficient cGMP material to initiate Phase I clinical studies. We will determine the high-resolution protein structures of the Staphylococcal and Francisella Fabl targets to guide the medicinal chemistry efforts. We aim to select a development candidate compound from this program that has excellent antimicrobial activity both in vitro and in vivo against Staphylococci and Francisella and that can be formulated for both IV and oral administration. Phase I and Phase II clinical trials are proposed in Years 4 and 5, as a narrow spectrum agent for the treatment of Staphylococcal infections. This funding will assure rapid progress of this new class of antibacterial agent through the last stages of discovery and preclinical studies and into the initiation of clinical trials. The funding will also assure that there are sufficient F. tularensis microbiological data and animal model data to warrant inclusion of the information on the product label as a narrow spectrum agent that could be used in the event of a F. tularensis release. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NOVEL MACROLIDE ANTIBIOTICS Principal Investigator & Institution: Katz, Leonard; Vice Present of Biological Sciences; Kosan Biosciences 3832 Bay Center Pl Hayward, Ca 94545 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2004 Summary: (provided by applicant): The long term goal of this project is to prepare novel macrolide antibiotics that are active against methicillin-resistant, macrolide-resistant, Staphylococcus aureus strains, in an attempt to augment chemotherapy of diseases caused by antibiotic-resistant human pathogens. These compounds will simultaneously block protein synthesis by inhibiting the peptidyl transferase (PT) activity of the ribosomes and at the same time overcome the loss of binding of normal macrolides to macrolide-resistant ribosomes by carrying chemical extensions that enable binding to other ribosomal sites. We will test the concept that this approach is feasible by producing a small series of novel molecules that can be chemically modified at different sites to inhibit PT and to bind tightly to ribosomes. The specific aims for the Phase I research are: (1) Construct recombinant microorganisms making a small series of 14membered macrolides containing the disaccharide mycaminose-mycarose at the C5 position as direct fermentation products. (2) If production of a 14-membered macrolides containing the disaccaride is not possible, construct organisms making a small series of 14-membered macrolides containing the monosaccharide mycaminose at the C5 position. (3) Chemically acylate the sugars of the compounds produced in aims 1 or 2 and determine if PT activity of bacterial ribosomes is inhibited in a variety of assays. (4) Add side chains to the macrolactone backbone of the molecules that inhibit PT activity to enable tight binding to methylated and non-methylated bacterial ribosomes. The lead compounds discovered would be optimized in Phase II research. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: NOVEL THERAPY FOR STAPHYLOCOCCAL INFECTION Principal Investigator & Institution: Wright, Susan C.; Senior Scientist; Panorama Research, Inc. 2462 Wyandotte St Mountain View, Ca 94043
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Staphylococcus aureus
Timing: Fiscal Year 2002; Project Start 01-APR-2000; Project End 31-AUG-2004 Summary: The emergence of antibiotic-resistant Staphylococcus aureus has created an urgent need for new therapeutic approaches to treat the variety of diseases caused by this common pathogen. S. aureus damages host tissues by the secretion of a variety of toxic exomolecules known as virulence factors. The expression of these factors is controlled by an autocrine regulatory system whereby bacteria secrete autoinducing pheromone peptides that act on the cell to upregulate expression of the set of genes encoding virulence factors. This proposal is based on the serendipitous discovery of a modified peptide contaminating a batch of synthetic pheromone peptide based on the sequence of a non- pathogenic strain of Staphylococcus. This peptide, called virulence inhibitory factor (VIF), inhibited synthesis of alpha toxin and toxic shock syndrome toxin in all Staphylococcal strains tested. Further studies revealed that small molecule analogs of VIF inhibited virulence factor production in vitro and protected mice from a lethal systemic S. aureus infection. The goal of this proposal is to evaluate a large panel of small VIF analogs in vitro and select the best drug candidate for further studies in vivo. Proposed studies include pharmacology, toxicology, and various animal models of S. aureus infection in preparation of an IND. This novel therapeutic approach has promise in the treatment of antibiotic-resistant Staphylococci. PROPOSED COMMERCIAL APPLICATIONS: Due to the emergence of drug-resistant strains of Staphylococci, many infections are not treatable with conventional antibiotics. The pathogenesis of Staph. infections depend on the production of virulence factors that promote bacterial colonization and are toxic to the host tissues. The present application proposes to develop a novel drug that inhibits production of virulence factors and should be therapeutic to antibiotic resistant Staph. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: OPTIMIZING DOSING TO PREVENT ANTIBIOTIC RESISTANCE Principal Investigator & Institution: Evans, Martin E.; Medicine; University of Kentucky 109 Kinkead Hall Lexington, Ky 40506 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2006 Summary: (provided by applicant): Antibiotic resistance among bacteria is a major problem in medicine. There have been repeated calls for the prudent use of antibiotics, but little is known about optimizing use to conserve efficacy. A better understanding of the relationship between dosing and the selection of resistance mechanisms may be useful. We have taken an approach that integrates pharmacokinetic, bacteriological, and molecular data into a pharmacodynamic model that examines the emergence of resistance when Staphylococcus aureus is exposed to ciprofloxacin in an in vitro system. This system allows accurate simulations of human pharmacokinetics and monitoring of the pharmacodynamic effect on bacteria. We found that antibiotic "sensitive" (S) cultures often harbor subpopulations with low-level resistance (RL); regimens providing low antibiotic concentrations may kill S, but allow RL to survive without evolving into bacteria with high-level resistance (Ru); regimens producing moderate concentrations may eradicate S, but cause RL to evolve into RH through a variety of mechanisms; and regimens producing high concentrations may eradicate S and RL strains before they evolve into RH Thus, the evolution of RL to RH, and ultimately treatment success or failure, appears to be dependent. in part, upon antibiotic dosing. A preliminary pharmacodynamic model described the experimental data well. Based on these findings, we hypothesize that novel regimens may prevent the emergence of resistance, and these regimens can be rationally designed by understanding the effect of antibiotic concentrations on the selection of antibiotic
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resistance mechanisms. To test this hypothesis, we will expose bacteria to constant and fluctuating ciprofloxacin concentrations in the in vitro system and monitor the incidence and prevalence of bacteria with up-regulated efflux and/or mutations in the quinolone resistance determining regions of topoisomerase genes with conventional assays and real-time PCR. Correlations between phannacokinetic parameters and resistance mechanisms will be used to develop alternative pharmacodynamic models that more accurately characterize the relationship between dosing and resistance. The ability of the pharmacodynamic models to predict the outcome of regimens designed to prevent (or allow) the emergence of resistance will be tested using artificially constructed cultures comprised of varying proportions of S, RL, and RH bacteria. We believe understanding the mechanisms underlying resistance will enhance our ability to design alternative dosing strategies to effect clinical cure. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: APPLICATION
ORGANIC
NANOTUBES
DESIGN
AND
BIOLOGICAL
Principal Investigator & Institution: Ghadiri, M. Reza.; Professor; Scripps Research Institute Tpc7 La Jolla, Ca 92037 Timing: Fiscal Year 2002; Project Start 01-JAN-1995; Project End 31-DEC-2005 Summary: (provided by applicant) The emergence of multidrug-resistant infections is on the rise worldwide at an alarming pace underscoring the need for novel therapeutic agents. Self-assembling peptide nanotubes are a versatile class of synthetic supramolecular structures with considerable potential for addressing this urgent need. Several designed cyclic D, L-alpha-peptides have been shown recently to possess potent and selective in vitro and in vivo (mice) activities against multidrug resistant bacterial infections including vancomycin-resistant Enterococcus faecalis (VRE) and methicillinresistant Staphylococcus aureus (MRSA). We propose here a multidisciplinary research program that not only is aimed at further advancing new concepts in the design and use of functional peptide nanotubes, but also directed toward large-scale mapping of the scope and utility of this class of supramolecular structures as novel antimicrobial and anticancer agents. The scope of the proposed studies range from basic research endeavors in the design of capped transmembrane channels for use in stochastic sensing, design of photo-regulated transmembrane channels and tubular materials, to rational and combinatorial library approaches in the design, selection, and structureactivity relationship analyses of antimicrobial agents. The specific aims of the proposed research program are: (1) Design, synthesis, characterization, and utility of capped transmembrane D, L-alpha-peptide nanotubes in stochastic sensing; (2) design and analysis of photo-regulated peptide nanotubes and transmembrane ion channels; (3) Design, synthesis, in vitro selection, and characterization of antimicrobial and cytotoxic self-assembling nanotubes from encoded single-bead combinatorial libraries of six- and eight-residue cyclic D, L-alpha-peptides; quantitative structure-activity analyses and biophysical characterizations for use in rational lead optimizations; in vivo (mice) efficacy, toxicology, pharmacokinetics, and bioavailability studies; and (4) design, synthesis, and characterization of amphiphilic beta3-cyclic peptide nanotubes and in vitro evaluation of biological activity, membrane selectivity, and biophysical characterizations. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Staphylococcus aureus
Project Title: PATHOGENIC MECHANISMS OF ANAEROBES IN SEPSIS Principal Investigator & Institution: Kasper, Dennis L.; Associate Director; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2003; Project Start 01-MAY-1997; Project End 31-DEC-2007 Summary: (provided by applicant): Abscess formation is a classic host response to bacteria during sepsis. Certain bacterial species, particularly Bacteroides fragilis and Staphylococcus aureus are predisposed to induce abscesses. The essential bacterial virulence factor required for abscess induction by these two pathogens is a capsular polysaccharide with a zwitterionic charge motif. Zwitterionic polysaccharides (ZPS) induce the host to form abscesses by their ability to activate T cells initiating a proinflammatory Th1 cytokine response. In contrast to the immunologic paradigm defining polysaccharides as T cell independent antigens, ZPS activate T cells in vitro as well as in vivo when incubated with antigen presenting cells (APC). There is currently no immunologic model that describes how purified polysaccharides can activate T cells. ZPS are internalized and can be detected in lysates of intracellular vesicles from the APC. Blocking of endosomal acidification results in the failure of ZPS to activate T cells. ZPS recovered from endosomal vesicles has a substantially reduced molecular size, indicating processing. We have demonstrated that MHC class II DR appears to be the molecule used by the APC to present ZPS to the T cell and that TCR alpha beta( is required for T cell activation. We hypothesize that ZPS are internalized and cycle through the APC, and that this process is required for presentation of the ZPS to the T cell. We intend to define a novel immunologic paradigm that describes how an important class of biologic molecules (carbohydrates) is recognized by the cell-mediated immune system. This will be done by investigating the cellular pathway by which ZPS cycle through the APC and activate CD4+ T cells. We have defined four specific aims: 1) Determine how ZPS are altered within the endocytic pathway and define the molecular requirements for ZPS-mediated T-cell activation; 2) Investigate the vesicular trafficking and intracellular interactions of ZPSs in the endocytic pathway; 3) Characterize the binding interactions of the MHC class II DR molecule with ZPS; 4) Determine whether T-cell activation results from "processed antigen" presentation or superantigen presentation and whether the processing of ZPS uses the same pathway as protein processing. The delineation of a mechanism for carbohydrate processing and presentation has broad relevance to the fields of microbiology and immunology and could lead to new concepts for enhancing T cell recognition of other polysaccharides. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PENICILLIN INTERACTIVE PROTEINS OF STAPHYLOCOCCUS AUREUS Principal Investigator & Institution: Chambers, Henry F.; Professor; Medicine; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 941222747 Timing: Fiscal Year 2002; Project Start 01-FEB-2000; Project End 31-JAN-2004 Summary: Methicillin-resistant strains of Staphylococcus aureus are a major clinical problem. They are multiple drug resistant, but ineffectiveness of penicillins and betalactam antibiotics is the real problem, as these are drug of choice to treat staphylococcal infections. The objective of this research is to further knowledge of mechanisms of methicillin resistance. Resistance is determined by several proteins that interact with penicillin. The interactions among these proteins are critical, but poorly understood. Knowledge of these interrelationships may lead to new drug discovery and new and more effective approaches to therapy./ Resistance is mainly due to production a novel
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low affinity penicillin bind protein, PBP 2a, a well wall synthetic enzyme. PBP 2a seems to substitute for all other PBPs. mecA, the gene encoding PBP 2a, is regulated by the same regulatory genes that control production of inducible beta-lactamase. Another type of penicillin interactive protein, a penicillin sensory signal transducer BlaR1, signals the cell to express PBP 2a and beta-lactamase, which together mediate all betalactam resistance in staphylococci. BlaR1 appears to be a PBP fused to an intracellular Zn++ metalloprotease, and as such may represent a completely new type of transmembrane signaling system. There are three aims. Aim1. To determine the intracellular pathway by which penicillin binding to BlaR1 signals induction of betalactamase and PBP 2a. The effect of specific mutations in BlaR1 on signaling will be determined to prove whether or not Blar1 is a metalloprotease. Putative consensus motifs of this superfamily of proteins will be targeted. The relationship between BlaR1 activation and proteolysis of BlaI, the repressor of the beta-lactamase regulon, will be defined. Aim 2. To identify PBPs, structural determinants, and other elements that interfere with PBP 2a mediated resistance. Effects of PBP deletion and mutations on PBP 2a mediated resistance will test whether PBP 2a can substitute for other PBPs and where essential functions reside within the molecule. The curious phenomenon of negative selection for expression of PBP 2a that we observed in mec naive cells also will be examined. Aim 3. To determine when during the cell cycle PBPs are expressed and where they are localized. An electron microscopic method for immunolocalization of specific myc-targeted PBPs in the cell will be developed. To augment information about where PBPs localize, when they are expressed during the cell cycle will be determined by Northern blotting. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PENICILLIN-BINDING PROTEINS, MECHANISM AND INHIBITION Principal Investigator & Institution: Mobashery, Shahriar; Professor; Chemistry; Wayne State University 656 W. Kirby Detroit, Mi 48202 Timing: Fiscal Year 2002; Project Start 01-APR-2001; Project End 31-MAR-2005 Summary: (Applicant's Description) Penicillin-binding proteins (PBPs) are a group of enzymes involved in a number of functions in the assembly and regulation of bacterial cell wall. These enzymes are the targets of beta-lactam antibiotics for inhibition of bacterial growth. A multidisciplinary approach has been outlined for the study of PBPs, which builds on the mechanistic findings from this laboratory presented as Preliminary Results. Pour Specific Aims are outlined. Specific Aim 1 details the plans for cloning, expression and large-scale production of two PBPs, one from Escherichia coli (a Gramnegative bacterium) and another from Staphylococcus aureus (a Gram-positive bacterium). These proteins will be used in the biochemical studies and also will be provided to Professor Judy Kelly of the University of Connecticut for crystallization. Specific Aim 2 describes our design and proposed syntheses for two cephalosporins that are incorporated with structural components of the cell wall (peptidogylcan). These cephalosporins, in conjunction with one that is already synthesized, are proposed as mechanistic probes for the transpeptidase reaction carried out by certain PBP in the last step of cell wall biosynthesis (cross-linking of cell wall). Biochemical and structural experiments are detailed for the use of these cephalosporins as probes of mechanisms for PBPs. An assay for the cell wall cross-linking reaction of the transpeptidases (a PBP) is described in Specific Aim 3. The enzymic reaction is biochemically dissected into the acylation and deacylation steps, for each of which a quantitative assay method is described. These methodologies will allow investigations of the mechanistic details of these PBPs. Furthermore, a series of four peptidoglycan derivatives have been proposed
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Staphylococcus aureus
to investigate the requirements for a minimal substrate for the transpeptidation reaction of the PBPs. Specific Aim 4 details the search for novel non-f3-lactam inhibitors for PBPs. These molecules will be synthesized and their potential PBP inhibitory and antibacterial activities will be investigated in both in vivo and in vitro experiments. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PHOTODYNAMIC THERAPY OF LOCALIZED INFECTIONS Principal Investigator & Institution: Hamblin, Michael R.; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 31-DEC-2006 Summary: (provided by applicant): The overall goal of this proposal is to explore a novel photochemical method for killing antibiotic resistant pathogenic bacteria in localized models of infection. Photodynamic therapy (PDT) employs a non-toxic dye termed a photosensitizer (PS) and low intensity visible light, which in the presence of oxygen produce cytotoxic species. PDT has the advantage of dual selectivity in that the PS can be targeted to its destination cell or tissue, and in addition the illumination can be spatially directed to the lesion. PDT has previously been used to kill pathogenic microorganisms in vitro, but until now this has not been accomplished in animal models of infection. We have developed a novel method of targeting PS conjugates to both Gram (+) and Gram (-) pathogenic bacteria that can produce up to 6 logs of killing in vitro, while in vivo it increases the selectivity of the treatment for bacteria while sparing host tissue. This is based on the covalent attachment of the PS chlorin e6 to polycationic delivery vehicles such as poly-L-lysine, that increases the selective binding to bacteria and enables the PS to penetrate the cell walls of Gram (-) bacteria to gain access to sensitive intracellular sites. Multi-antibiotic resistant strains are as easily killed as wildtype strains. We have generated preliminary data using luminescent bacteria and a lowlight imaging camera, that PDT will kill both Gram (-) species (Escherichia coli and Pseudomonas aeruginosa) and Gram (+) species Staphylococcus aureus) in vivo in animal models of both early and established infections. In the case of the invasive P. aeruginosa mice are cured of an otherwise fatal infection. Localized PDT may have an additional advantage in that it is also possible to inactivate secreted extracellular virulence factors that pathogenic bacteria use to establish infections and invade tissue. This project will seek to explore the determinants of PDT for localized infections. Four specific aims will focus on optimizing the treatment in different mouse models of early, acute and chronic infections, comprising excisional wounds, established soft tissue infection, chronic abscesses, burns and urinary tract infections. Since one of the advantages of PDT is its rapidity compared to traditional antibiotic therapy, we will also study the use of PDT to quickly reduce the bacterial burden in the infection, followed by antibiotics to eliminate the residual bacteria. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PLASMID PT181 DNA REPLICATION IN STAPHYLOCOCCUS AUREUS Principal Investigator & Institution: Khan, Saleem A.; Professor; Molecular Genetics & Biochem; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2002; Project Start 01-JUL-1982; Project End 31-JAN-2004 Summary: (adapted from the investigator's abstract): Staphylococcus aureus is an important human pathogen and a reservoir for a large number of plasmids that encode resistance to many commonly used antibiotics. A large group of multicopy plasmids in
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S. aureus encode resistance to a single antibiotic and replicate by a rolling-circle (RC) mechanism. While several RC plasmids found in S. aureus have a narrow host range, many are able to be stably maintained in a wide range of Gram-positive bacteria. The long term goals of this proposal are to understand the molecular basis for stable replication of RC plasmids in S. aureus and other Gram-positive bacteria, using pTl8l and related plasmids as model systems. We will carry out site-directed mutagenesis to understand the role of ssoA-type origins in lagging strand synthesis of RC plasmids, and the basis of their host-specific function. The molecular basis for broad host range function of the ssoU-type origins will also be investigated. The effect of RepC and the pTl8l origin on the helicase activity of PcrA will be determined. These studies are expected to provide information on the role of this interaction in the initiation and termination of plasmid pTl8l RC replication. The RepC protein acts as a dimer and has DNA binding and nicking-closing domains. Purified heterodimers of wild-type and mutant RepC proteins will be used to identify the role of each monomer during the initiation and termination of pTl8l replication. A new series of experiments utilizing fluorescence microscopy will be initiated to determine whether the pTl81 plasmid replicates at a discrete site in the cell termed the "replication factory." We have obtained co-crystals of RepC bound to its specific binding site and will continue efforts to obtain larger crystals of RepC and RepC-DNA complex and determine their structure by X-ray crystallography. These studies are expected to provide information on the replication and maintenance of drug resistance plasmids in S. aureus and other Gram-positive bacteria that replicate by an RC mechanism. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: POTENTIATING ANTIOBIOTICS
COMPOUNDS
FOR
AMINOGLYCOSIDE
Principal Investigator & Institution: Dedkova, Larisa; Pinnacle Pharmaceuticals Charlottesville, Va 22911 Timing: Fiscal Year 2004; Project Start 01-MAR-2004; Project End 31-AUG-2004 Summary: (provided by investigator): There is a continuing need for new antimicrobial agents. Pinnacle Pharmaceuticals proposes a genomically-based strategy for the identification of compounds that potentiate the action of known antibiotics. In preliminary experiments, Pinnacle scientists have identified a physiological function that is metabolically related to a known aminoglycoside antibiotic. These observations lead to the hypothesis that targeting this function will lead to compounds that potentiate known aminoglycoside antibiotics. The specific aims of the present application are to (1) carry out high-throughput screening to identify these potentiating compounds and to identify the active principles and (2) to characterize the action of these compounds against wild-type cells, clinically relevant R-determinants, and pathogenic bacteria. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PREVENTION OF BIOFILMS IN MEDICAL DEVICES Principal Investigator & Institution: Shenoy, Bhami C.; Altus Biologics, Inc. 625 Putnam Ave Cambridge, Ma 021394807 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JAN-2004 Summary: (provided by applicant): Design of new efficient drug delivery systems for proteins is one of the major themes of modern biotechnology and biopharmaceutical industry. We found that cross-linked enzyme crystals (CLECs) show remarkable stability at various pHs, on storage, against proteolysis and organic solvents. These
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properties make them ideal for treatment against biofilm formation on medical devices /implants such as urethral catheters, ureteric and prostatic stents, penile and testicular implants, artificial urinary sphincters, prostheses for hip and knee replacements, shunts for hydrocephalus, vascular grafts, heart valves, vascular access devices, voice prostheses, etc. In addition, the CLECS can be used for the prevention of blood clot formation, for example, in venous catheters. The CLEC agent will be used to coat the medical devices for the prevention of formation of bacterial biofilms on these devices as well as the prevention of blood clots. The biofilms form on the above medical devices by colonization of bacteria embedded in a matrix, which become resistant to commonly used antibiotics. In this Phase I study, we propose to develop two prototypes of CLECs of enzyme - Serratiopeptidase and Streptokinase for prevention of biofilms by Pseudomonas aeruginosa and Staphylococcus aureus microorganisms. The coating will prevent the adherence of these bacteria to medical devices. Currently, there are more than 850,000 case infections associated with aid devices annually in the United States. These may be associated with as many as 100,000 deaths per year. The CLECs of Serratiopeptidase and Streptokinase have enormous commercial potential over the currently available treatment for the prevention of contamination of medical devices by minimizing the need for replacement once they are implanted. The CLECs of Serratiopeptidase and Streptokinase will also be important in preventing biofilm-related infections which are resistant to commercially available antibiotics. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PROTEOLYTIC ENZYMES AND INHIBITORS IN LUNG DISEASE Principal Investigator & Institution: Travis, James; Professor; Biochem and Molecular Biology; University of Georgia 617 Boyd, Gsrc Athens, Ga 306027411 Timing: Fiscal Year 2002; Project Start 01-JAN-1982; Project End 31-MAR-2006 Summary: (provided by applicant): Host proteolytic enzymes are believed to play a central role in the pathogenesis of pulmonary emphysema, through degradation of alveolar connective tissue proteins. However, little is known about whether this lung disease can be either caused or exacerbated by proteinases secreted by bacterial or fungal respiratory pathogens. Significantly, none of these enzymes are known to be regulated by host proteinase inhibitors. While it is believed that their primary function is to degrade host proteins to provide nutrients for the growth and proliferation of the invading organism, we propose that they also provide a means for evasion of host defense. For these reasons, the specific aims of this project are as follows: 1) to isolate and characterize selected proteinases secreted by lung pathogens, including Aspergillus fuimigatus, Stachybotrys chartarum, Pseudomonas aeruginosa, and Staphylococcus aureus, 2) to investigate the effect of pathogen-derived proteinases on the degradation/inactivation of host bactericidal peptides and proteins utilized to maintain homeostasis within the lung, and 3) to study the effect of exposure to these proteinases on a) the responsiveness of human monocytes and neutrophils to major pro-and antiinflammatory stimulation and b) the ability of proteinase-exposed monocytes to clear apoptotic neutrophils. Our long-term goals are to determine whether the proteinases to be investigated play major roles in host defense evasion and tissue destruction within the lung. If this is the case, then they might be considered as targets for the development of inhibitors in order to control or eradicate lung microbial infections. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PROTEOMICS OF STAPHYLOCOCCUS AUREUS NASAL CARRIAGE Principal Investigator & Institution: Cole, Alexander M.; Assistant Professor; Medicine; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2004 Summary: (provided by applicant): The human nasal mucosa is an accessible and clinically important model for the study of microbial interactions with host defenses. Nasal carriage of Staphylococcus aureus (SA) is the most common clinical disorder of mucosal host defense but its molecular and cellular basis is not understood. The disorder is of increasing clinical importance because nosocomial infections are commonly spread by nasal carriers of methicillin-resistant SA and other SA strains increasingly resistant to antibiotics. Our evidence indicates that colonization may be due to impaired innate antimicrobial activity of nasal fluid. The current proposal aims to identify the underlying cause(s) of SA carriage by examining protein determinants of SA carrier airways colonization and comparing microbicidal components of SA carrier fluid to nasal fluids from donors that are not colonized with SA. We hypothesize that 1) noncarriers express antimicrobial (poly)peptide factors some of which are either lacking or defective in SA carrier fluid, 2) altered or deficient host defense factors in airways fluid contribute to the progressive colonization of SA in carriers, and 3) correcting the dysregulated components will restore the antimicrobial activity of SA carrier airway fluid against isolates of SA. To test these hypotheses, we will: 1) detect cationic (poly)peptides that are differentially expressed between nasal fluid from donors carrying SA and fluid from donors that are not colonized with SA utilizing a novel twodimensional gel electrophoresis (2-DE) approach, 2) identify (poly)peptides that are differentially expressed between donors carrying SA and donors that are not colonized with SA, and 3) reconstitute the antimicrobial activity of SA carrier nasal fluid by replacing abnormal or missing (poly)peptides with intact counterparts purified from noncarrier fluid. Our proposed studies represent a novel approach to identify and link human airway disease biomarkers (cationic polypeptide antimicrobials) with their effects (SA nasal carriage). Together, these studies will for the first time characterize the host resistance factors for a common and increasingly important source of nosocomial infection, and will develop a neglected but very useful natural model for the study of the interactions of bacteria with an accessible mucosal surface. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: QUINOLONE RESISTANCE MECHANISMS IN STAPHYLOCOCCUS AUREUS Principal Investigator & Institution: Hooper, David C.; Associate Professor of Medicine; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2002; Project Start 01-SEP-1986; Project End 31-MAR-2003 Summary: (Adapted from the applicant's abstract): The PI is interested in studying fluoroquinolone resistance in Staphylococcus spp. for three reasons. First, staphylococci are important pathogens and are growing more and more resistant to fluoroquinolones and other antibiotics. Understanding the mechanism of quinolone resistance, which appears to be different from that seen in the gram-negative bacteria, is thus an important goal. A second reason is that topoisomerase IV seems to be the main fluoroquinolone target in the gram positive bacteria rather than DNA gyrase, and this makes it possible to investigate the function and regulation of topoisomerases in ways not possible in the gram-negative bacteria. Finally, the PI is interested in the mechanism
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Staphylococcus aureus
and regulation of multidrug efflux transporters that provide yet another mechanism of fluoroquinolone resistance in addition to alterations in topoisomerase itself. More specifically, the PI proposes the following: 1. To determine how mutations in the two topoisomerase IV subunits, ParC and ParD, make the topoisomerase less susceptible to fluoroquinolone action. To this end, the PI will purify and characterize mutant topoisomerases to determine if their binding of the antibiotic is reduced or affect the catalytic activity of the enzyme. Results of this analysis should indicate not only how the resistance mechanism works but whether quinolones act by reducing enzyme activity or more indirectly by stabilizing enzyme-DNA complexes. 2. To determine the location of topoisomerase IV relative to the DNA replication complex. Topoisomerase IV is thought to act by decatenation of newly replicated daughter chromosomes to allow segregation. Fluoroquinolones can be used to trap enzyme-DNA complexes and thus determine the sites where topoisomerase acts. Sites preferentially used by topo IV will be identified. The PI will also determine how rapidly the antibiotic stops new DNA synthesis, an indication of whether the topo IV acts near or far from the replication complex. The PI has isolated a new type of resistance-producing mutation that he hopes may shed light on the involvement of topo IV in DNA replication. These mutants will be characterized in detail. 3. To characterize the regulation and function of NorA, a multidrug efflux pump that mediates fluoroquinolone resistance. Gene fusions will be used to follow expression and the effect of various known global regulators will be determined. The promoter of norA will be located. NorA function will be assessed by purifying NorA protein and incorporating it in liposomes. 4. To characterize factors affecting the evolution of fluoroquinolone resistance. It has been noted that methicillin-resistant S. aureus strains are far more likely to become resistant to fluoroquinolones than methicillin-sensitive strains. The PI has evidence suggesting that this might be due to linkage of the methicillin resistance gene, mecA, to gyrA genes that have already started on the mutation pathway to detectable resistance. The PI will also determine whether the induction of fibronectin-binding proteins by quinolones in MSSA strains is responsible for the tendency of the MSSA that become quinolone resistant to spread clonally, in contrast to MRSA. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: QUORUM SENSING, BACTERIAL INTERACTION AND DISEASE Principal Investigator & Institution: Balaban, Naomi; Assistant Professor; Veterinary Biomedical Sciences; Tufts University Boston Boston, Ma 02111 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2005 Summary: (provided by applicant): The polymicrobial nature of the skin is illustrated by the isolation of both Gram-negative and Gram-positive bacteria, which altogether seem to constitute a natural barrier for opportunistic or pathogenic microbes. Bacterial cells communicate with one another by quorum sensing mechanisms, through the secretion of signaling organic molecules such as derivatives of homoserine lactones in Gramnegative bacteria and proteins and peptides in Gram-positive bacteria to activate or suppress functions necessary for their survival. As a model system for the study of the effect of quorum sensing on bacterial interaction, we will examine the effect(s) of RIP, a quorum sensing heptapeptide produced by Staphylococcus xylosus, on the survival and virulence of S. aureus and S. epidermidis. S. aureus and S. epidermidis are part of the normal flora of the human skin but can cause fatal diseases when their density increases, probably due to the expression of toxic exomolecules or due to the formation of biofilms. The expression of toxic exomolecules as well as biofilm formation can be inhibited by RIP, which interferes with staphylococcal quorum sensing mechanisms. RIP
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does not kill the bacteria but keeps them in a non-pathogenic stage, suggesting that the natural composition of the normal flora would not be effected. To further develop RIP as a therapeutic peptide, it is important to understand its molecular targets and to test its effect(s) on the normal flora in a polymicrobial environment. To achieve these goals, we propose to determine the molecular targets of RIP in S. aureus and S. epidermidis by functional genomics and proteomics and, funding and time permitting, to test its effects in vivo on the survival of a polymicrobial inoculum of both S. aureus and S. epidermidis, using the murine air sac model. Using the same in vivo model, we will also test the effect of S. xylosus that naturally produces RIP as a probiotic to prevent staphylococcal pathogenesis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: REGULATION OF METHIONINE METABOLISM IN BACILLUS SUBTILIS Principal Investigator & Institution: Henkin, Tina M.; Professor; Microbiology; Ohio State University 1960 Kenny Road Columbus, Oh 43210 Timing: Fiscal Year 2002; Project Start 01-AUG-2001; Project End 31-JUL-2005 Summary: (provided by applicant): A novel global regulation system for control of genes involved in methionine metabolism has been uncovered in Bacillus subtilis. Genes utilizing this mechanism, designated the S box family, contain in their mRNA leader regions a complex set of conserved primary sequence and structural elements, including a transcriptional terminator, competing antiterminator, and anti-antiterminator. Genetic analyses indicate that during growth in methionine, sequences in the leader are required for stabilization of the anti-antiterminator, which prevents formation of the antiterminator, which in turn allows termination. The molecular mechanism for control of the leader RNA structure in response to methionine levels is unknown, although preliminary studies suggest that binding of a regulatory factor is required to prevent readthrough. This system is widely used for control of methionine-related genes in a variety of Gram-positive bacteria, including important pathogens such as Staphylococcus aureus, and is also found in the Gram-negative bacteria Chlorobium tepidum and Geobacter sulforreducens. Eleven transcriptional units are controlled by this mechanism in B. subtilis alone, so the total number of genes involved is high. The major goal of this study is to further investigate the molecular mechanism of transcription termination control, and to elucidate the physiological role of this system, using a combination of genetic and biochemical approaches. The required cis-acting sequence elements will be identified by site-directed mutagenesis. The trans-acting regulatory factors required for the methionine response will be identified, and the system will be examined both in vivo and in vitro. A requirement for ppGpp for efficient readthrough in vivo has been demonstrated, and the molecular basis for this requirement will be examined. Finally, the physiological role of genes of unknown function which appear to be regulated by this mechanism will be examined. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ROLE OF BRRA-BRRB IN ANTHRAX Principal Investigator & Institution: Schlievert, Patrick M.; Professor; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2003; Project Start 04-SEP-2003; Project End 31-AUG-2005 Summary: The long-term goals are to understand human pathogenesis of Bacillus anthracis, which has potential for use in bioterrorism. Our studies are also directed
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Staphylococcus aureus
towards identifying methods to prevent production of virulence factors by this organism to cause disease. We have shown bacterial surface-active agents, glycerol monolaurate and chitosan malate, preventing production of the superantigens when produced in B. subtilis. In addition, we have suggested (with success) that patients with inhalation anthrax be treated with clindamycin in addition to other therapy because of the antibiotic's known ability to inhibit gram positive exotoxin production at subbacterial inhibitory levels. We have shown that Staphylococcus aureus requires oxygen and carbon dioxide in its external environment for maximal production of TSST-1. This observation led to our identification of a two-component regulatory system that is involved in oxygen control of superantigen production by the organism. We have shown that over-expression of this system, designated srrA/B (for staphylococcal respiratory response), in S. aureus significantly represses superantigen production. By computer analysis we identified a Bacillus anthracis homolog of SrrA-SrrB, tentatively designated BrrA-BrrB, and hypothesize that this two-component regulatory system is important in controlling anthrax toxin and capsule production. Furthermore, we hypothesize that BrrA-BrrB is an important target for the action of glycerol monolaurate and chitosan malate. In this application we propose one specific aim: 1) to characterize BrrA-BrrB and its effect on production of B. anthracis toxin and capsule. We hypothesize that this system functions as a repressor of genes for both virulence factors. Overexpression of the system will interfere with production of exotoxin and capsule by the organism, even under highly aerobic conditions. Finally, we hypothesize that exotoxin and capsule production will be suppressed by both glycerol monolaurate and chitosan malate through activation of BrrA-BrrB. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ROLE OF CD14 AND OTHER LPS RECEPTORS IN ENDOTOXIC SHOCK Principal Investigator & Institution: Goyert, Sanna M.; Associate Professor; North Shore University Hospital 300 Community Dr Manhasset, Ny 11030 Timing: Fiscal Year 2002; Project Start 01-JAN-1989; Project End 31-DEC-2005 Summary: (Verbatim from the applicant's abstract) The studies proposed will focus on further elucidating mechanisms through which CD14 influences the inflammatory response. Specific Aim 1: To define the relative role of the CD14:LPS interaction in the shock response to bacterial pathogens posessing various virulence fqactors. We have previously shown that CD14-deficient mice are highly resistant to the lethal effects of LPS and E. Coli 0111. Our hypothesis is that some Gram-negative bacteria will induce shock predominently via the CD14:LPS pathway while other bacteria having different virulance factors will induce shock via CD14 independent mechanisms. To test this hypothesis, we will first study the shock response of CD14-deficient and normal mice to a well characterized panel of E. coli expressing defined virulence determinants. Next, we will test the role of the CD14:LPS interaction in a peritonitis model of shock induced by cecal ligation and puncture. Finally, we will use an oral model of shock to examine the role of CD14 in the response to intracellular organisms that use unique mechanisms to evade the host immune defense. These studies will expand our understanding of the relative roleof the CD14:LPS interaction in shock induced by bacteria and will begin to elucidate the mechanisms operating in CD14:LPS mediated shock versus CD14independent shock. Specific Aim 2: To define the relative role of the CD14:LPS interaction in local infection. We believe that the mechanisms operating systemic models will also operateon the local level. That is, those bacteria which cause inflammation in CD!14-deficient mice will cause a local inflammatory response in CD14-/- mice, similar
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to that of normal mice; those bacteria which do not cause shock in CD14-deficient mice will not cause tissue damage and will be quickly cleared. The results from these experiments should complement those in the shock model and lead to an enhanced understandingf of the mechanisms regulating virulence of these bacteria and their role im imflammation. Specific Aim 3: To determine the role of soluble CD14 (sCD14) in septic shock and local inflammation induced by LPS and various bacteria (Gramnegative, Gram-positive). Studies suggest that there are two pathways for activation with LPS; One that stimulates via membrane CD14 and one that stimulates via another pathway and requires a complex of performance sites. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ROLE OF LYSOZYME IN AIRWAYS HOST DEFENSE Principal Investigator & Institution: Akinbi, Henry T.; Children's Hospital Med Ctr (Cincinnati) 3333 Burnet Ave Cincinnati, Oh 452293039 Timing: Fiscal Year 2002; Project Start 15-FEB-2002; Project End 31-JAN-2007 Summary: Lysozyme is a cationic protein of 146 amino acid residues (Mr approximately 14k) that is bactericidal against multiple gram-positive bacteria in vitro. Although lysozyme is the most abundant antimicrobial protein in airway surface fluid (ASL), its role in protecting the airways against infection, chronic colonization, and inflammation in vivo remains unproven. The results of preliminary studies reported in this application demonstrate a dose-dependent relationship between the level of lysozyme activity in bronchoalveolar lavage fluid and the rate of bacterial killing, of both gram positive and negative organisms, in acutely infected transgenic mice that overexpress lysozyme. Studies proposed in this application will test the central hypothesis that lysozyme is a critical component of airway host defense in vivo. Pathogen killing will be assessed in lysozyme (-/-) mice and lysozyme overexpressing mice following acute and chronic lung infection. The antimicrobial spectrum and potency of exogenouslyadministered recombinant lysozyme protein will also be assessed. These studies will provide insight into the role of lysozyme in airway host defense and provide a preliminary assessment of the therapeutic potential of exogenously administered lysozyme. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: S AUREUS PATHOGENESIS IN HIV INFECTION AND IN DRUG USE Principal Investigator & Institution: Lowy, Franklin D.; Professor; Medicine; Columbia University Health Sciences New York, Ny 10032 Timing: Fiscal Year 2002; Project Start 01-JUN-1998; Project End 31-MAY-2004 Summary: Applicant's Abstract S. aureus is the most common cause of infections in drug users and is a major cause of life-threatening infections in AIDS patients. Surprisingly little is known about the factors that predispose these two overlapping groups to staphylococcal disease. Drug users and HIV-infected subjects have a high S. aureus colonization rate and are believed to become infected with the strains they carry. This proposal will integrate a molecular epidemiologic analysis of S. aureus colonization and infection in these high risk groups with a biologic investigation of the basis for this process. By targeting patients less than 60 admitted to the hospital, we will focus on HIV-infected drug users in a case series. Endpoints will include evidence of S. aureus colonization or infection. The goals include the following. 1) Identify the factors, such as patterns of drug use, HIV status and form of medical intervention, that maximally
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increase the risk of S. aureus infection. 2) Use DNA fingerprinting techniques to determine whether: strains that colonize also cause infection; carriage is clonal; hospitalization affects carriage or acquisition of new strains; there is clonal spread of strains among enrolled subjects including HIV-infected, drug users or controls as well as hospital personnel. 3) Determine the impact of hospitalization and antimicrobial therapy on the emergence of multidrug resistant staphylococci including whether antibiotic therapy alters colonization or infection or the susceptibility patterns of colonizing strains. Investigate if there is linkage of other virulence determinants with drug resistance or if there is evidence of clonal spread of resistant isolates among the cohort or hospital personnel. 4) Identify if specific determinants are critical to colonization, and if their presence is associated with sites of colonization and pattern of drug use. The emerging problems of multidrug-resistant staphylococci has added urgency to the need for new, nonantimicrobial approaches to the prevention of these life-threatening diseases. In order to develop alternatives, we must first - be able to identify when high risk individuals are at maximal risk of infection and, second - sufficiently understand the strain and host determinants that play a critical role in this process. The ability to integrate both epidemiologic and biologic studies using a well defined high risk cohort of drug users and HIV-infected subjects provides an ideal setting to examine these issues. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: S. AUREUS SARU AND ROT REGULATE VIRULENCE FACTOR GENES Principal Investigator & Institution: Mcnamara, Peter J.; Medical Microbiol & Immunology; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2004; Project Start 01-APR-2004; Project End 31-MAR-2005 Summary: (provided by applicant): Historically, antimicrobial therapy dramatically reduced the mortality of Staphylococcus aureus infections. Because of multidrug resistance, successful treatment of S. aureus can be difficult to achieve. Novel therapeutic interventions are desperately needed. One promising approach is to develop drugs that target the regulators of virulence factor (VF) expression. A detailed molecular mechanism of action will greatly benefit the search for an appropriate target for regulator-specific drugs. VF regulation in S. aureus is controlled by the cooperative and redundant action of the products of many loci including a family of at least six MarRfamily transcriptional regulators, the SarA-homologues. This proposal focuses elucidating the molecular mechanism of two SarA-homologues, Rot and SarU. Genetic evidence suggests that Rot and SarU have a reciprocal effect on the expression of VFs. Using alpha-toxin as an example we will define the molecular interactions that lead to Rot acting as a repressor of the gene encoding alpha-toxin (hlalpha) and SarU acting as an activator of hla transcription. Our hypothesis is that Rot is a constitutively expressed repressor that directly downregulates transcription of hlalpha. This repression is relieved by RNAIII, a riboregulator that is upregulated by both a direct interaction between SarU and the agr promoters and an indirect interaction of SarU on the sarA promoters. To test this hypothesis, we propose: Aim 1. To characterize mechanism(s) of Rot repression of a-toxin production that is antagonized by RNAIII. Aim 2. To characterize mechanism(s) of SarU activation of a-toxin production by demonstrating direct and temporally appropriate interactions between SarU and its target genes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: SCORE AT NEW MEXICO STATE UNIVERSITY, LAS CRUCES Principal Investigator & Institution: Kuehn, Glenn D.; Professor of Biochemistry; Chemistry and Biochemistry; New Mexico State University Las Cruces Las Cruces, Nm 880038001 Timing: Fiscal Year 2002; Project Start 09-SEP-1991; Project End 31-MAY-2004 Summary: (provided by applicant): This is an application for supplemental funding for a SCORE Program at New Mexico State University (NMSU) at Las Cruces. A goal of NMSU is to expand research at the institution for participation by ethnic minority students who desire to pursue careers in the biomedical science disciplines. The proposed SCORE Program has as its goals: (1) To significantly improve the capabilities of NMSU to conduct biomedically relevant research by increasing the numbers of faculty who conduct biomedical research, increasing the numbers of trained research personnel, increasing the inventory of specialized single-user research instrumentation, and improving the capacity to maintain research instrumentation; (ii) To significantly improve the quantity and quality of biomedical research conducted at NMSU by broadening grantsmanship efforts of faculty participants and increasing the numbers and quality of research publications; (iii) To integrate the activities of the SCORE Program with an anticipated RISE Program to maximize resources for training minority scientists in the biomedical sciences by engaging students in SCORE Program research projects; (iv) To increase the capacity of NMSU to self-evaluate, assess, and monitor its multi-component research programs by engaging trained personnel in the SCORE Program's evaluation plan and subjecting the Program to annual review by an external evaluation committee. This application contains research proposals for two research subprojects. One is a regular subproject and the other is a pilot subproject. Disciplines represented among these proposals include medical microbiology (Gustafson, pilot subproject) and organismal/cell biology (Shuster, regular subproject). The research topics of these subprojects include salicylate responses in the bacterial pathogen, Staphylococcus aureus (Gustafson), and regulation of mitosis and cytokinesis by the septation initiation network (SIN) signaling cascade in animal cells. NMSU has an existing SCORE Program which was initiated on June 1, 2000. This Program funds eleven regular and two pilot subprojects. The existing SCORE Program succeeded a 25year old associate MBRS Program which advanced 327 underrepresented minority students (81% of participants) into post-baccalaureate training in the biomedical sciences during the period 1974-2000. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: SEX PHEROMONE INDUCED PLASMID TRANSFER Principal Investigator & Institution: Clewell, Don B.; Professor; Biologic & Materials Sciences; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2002; Project Start 01-MAR-1985; Project End 31-MAR-2004 Summary: Enterococcus faecalis is an important opportunistic pathogen that is now the second leading cause of bacteremia and third leading cause of endocarditis in humans. Conjugative plasmids encoding a mating response to peptide sex pheromones are ubiquitous in E. faecalis and probably contribute significantly to the dissemination of antibiotic resistance and cytolysin (e.g. hemolysin/bacteriocin) production in this species. The cytolysin-encoding plasmid pAD1 is an example of such a plasmid and has been a subject of intense scrutiny in the laboratory of the PI for a number of years. Recent identification of key regulatory genes and determination of their nucleotide
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sequence, along with related physiological studies, has enabled the formulation of a working hypothesis to explain the circuitry which may be utilized during induction of the conjugation response. A key aspect of the model concerns the control of expression of traE1 by a negative regulator encoded by traA that influences transcriptional readthrough of the termination site TTS1/TTS2. The bulk of the proposed study is designed to test this model and further characterize related processes. More specifically the proposed studies will: 1) determine the nature of transcription events that occur between the iad promoter and TTS1 with an emphasis on examining the relationship between transcripts that have been designated m3, m4, and m5; 2) examine the role TraA plays in regulating transcription beyond TTS1/TTS2 and into the traE1 determinant including a determination of whether TraA directly binds to the cAD1 peptide; 3) examine additional factors (i.e. other than TraA) operating at TTS1/TTS2 and affecting transcriptional readthrough; 4) determine if TraE1 plays a role in its own regulation by controlling initiation of the transcript designated m3'; 5) examine the kinetics of shutdown of the pheromone response; 6) characterize the basis of the Dry+/Dryc phase variation mechanism that facilitates a bypass of the physiological response to cAD1; 7) determine if TraA, TraE1, RepA, RepB or other proteins interact with each other; and 8) continue our efforts to clone and characterize cad, the chromosomal determinant for cAD1. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SINGLE CELL DNA FRAGMENT SIZING Principal Investigator & Institution: Keller, Richard A.; Laboratory Fellow; None; University of Calif-Los Alamos Nat Lab Ms G758 Los Alamos, Nm 87545 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 31-MAY-2006 Summary: (provided by applicant): We propose to develop a microscope-based imaging system for analysis of bacterial DNA fragments from single bacterial cells. Our approach eliminates the need for cell culturing common to other DNA fingerprinting methods, thereby reducing the analysis time from several days to hours. The proposed technique will allow DNA fragments, from a few hundred base pairs to millions of base pairs, originating from a single cell RFLP, to be sized. We envision many applications of this new capability in biomedicine to: more rapid diagnosis of infectious disease; determination of the source of an infectious disease outbreak; and measurement of the genotoxicity of drugs or environmental agents. In addition, this technique will impact biological research by providing a new measurement tool for single cell DNA analysis, as well as having immediate application to anti-bioterrorism, forensics, food safety, and agriculture. This technology will give researchers a powerful method for studying individual cells and organisms in the absence of averaging effects of ensemble measurements. Likewise, by making measurements on a number of single cells, information about the presence or extent of DNA heterogeneity will be established. The technique relies on performing all sample preparation reactions and analyses in an ultra-thin gel mounted on a microscope slide. Cell lysis, protein digestion, DNA restriction, and DNA staining, along with other reactions, will be carded out by diffusion of reagents into the gel. Staining conditions will be such that the fluorescence intensity is proportional to the fragment size. An electric field will be applied to the gel to electrophoretically separate the DNA fragments. Fluorescence from individual stained and separated fragments will then be detected and quantitated with a microscope-based, high sensitivity imaging system. The resulting DNA fragment size distribution histogram can be used as a fingerprint to identify individual organisms to the level of species and strain, detect damage in the DNA resulting from exposure to
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ionizing radiation or chemicals, or to monitor genetic variability. To demonstrate this technology we must complete the following specific aims: 1) assemble and characterize the apparatus and measurement approach; 2) develop and optimize the sample preparation chemistry; 3) demonstrate applicability to species and strain identification of representative bacteria. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: STAPHYLOCOCCAL METHICILLIN RESISTANCE LOCUS Principal Investigator & Institution: Archer, Gordon L.; Professor of Medicine and Microbiology/i; Internal Medicine; Virginia Commonwealth University Richmond, Va 232980568 Timing: Fiscal Year 2004; Project Start 01-APR-1994; Project End 31-DEC-2008 Summary: (provided by applicant): Staphylococci are the leading cause of hospitalacquired infections, especially nosocomial bacteremia. The two most effective and widely used anti-staphylococcal therapeutic agents are glycopeptides and beta-lactams, both of which target cell wall biosynthesis. However, therapy with these agents is becoming less effective as resistance has developed, first to beta-lactams and, more recently, to glycopeptides. The most important mechanism of resistance to beta-lactams is the acquisition of a new target, a cell wall transpeptidase or penicillin binding protein (PBP2a) that is not inactivated by the antibiotic. This type is called methicillin or oxacillin resistance (OR) and the gene that mediates this resistance, mecA, is encoded within a pathogenicity island called SCCmec. The following proposal seeks to continue studies that explore the origin, dissemination and regulation of genes that mediate OR and genomic adaptations required for staphylococci to become resistant to agents that damage their cell walls. The First Specific Aim will be to investigate the transfer of SCCmec between strains of Staphylococcus aureus (SA) and from a different staphylococcal species, S. epidermidis (SE), to SA. There is evidence that a new SCCmec type, Type IV, has recently moved into SA isolates prevalent in the community and it is present in the majority of SE isolates. The excision, transfer (by plasmid and phage) and reinsertion of this element will be investigated. The Second Specific Aim will be to continue studies on the induction of mecA transcription through the sensor/transducer, MecR1, resulting in the release of the transcriptional repressor, Mecl, from its DNA binding site. The basis of signal transduction and role of proteolytic cleavage of inducer and repressor will be assessed by constructing chimeric molecules, determining the crystal structure of repressors and identifying additional chromosomal genes required for induction. The Third Specific Aim will be to confirm and expand observations made by microarray transcriptional profiling that purine biosynthesis is altered in strains that develop high level resistance to vancomycin and oxacillin, but in opposite directions (increased and decreased respectively). These two phenotypes appear to be mutually exclusive. The purine biosynthetic operons will be genetically manipulated and correlated with development of VR and OR. In addition, microarray and proteomic studies will be pursued on other agents that perturb the cell wall. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: SYNTHESIS
STRATEGIES
AND TACTICS FOR
NATURAL
PRODUCTS
Principal Investigator & Institution: Sulikowski, Gary A.; Professor; Chemistry; Texas A&M University System College Station, Tx 778433578 Timing: Fiscal Year 2004; Project Start 01-JAN-2004; Project End 31-DEC-2007
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Staphylococcus aureus
Summary: (provided by applicant): The long-term objective of this research program is to advance the practice of complex molecule synthesis. Special emphasis is placed on natural products that contain nitrogen since an unusually large number of pharmacologically active compounds incorporate this element within their structure. Despite the many advances in organic synthesis in the past 20th century the efficient and economical synthesis of complex natural products remains a challenging endeavor. Our plan is to introduce new inexpensive building blocks to the field of organic synthesis for use in asymmetric synthesis of nitrogen heterocycles. These building blocks would expedite the chemical synthesis of the rare marine alkaloid upenamide, the stemona alkaloids and 2-substituted piperidine alkaloids. We also present a plan for the synthesis of Iomaiviticins A and B, secondary metabolites isolated from fermentation of a marine derived actinomycetes. Lomaiviticins A and B are potent antibiotics against Gram-positive bacteria Staphylococcus aureus and Enterococcus faecium (MIC 6-25 ng/spot). An unusual structural feature of the Iomaiviticins is the incorporation of two diazo groups within their structure. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: STRUCTURE AND MECHANISM OF FOLATE BIOSYNTHETIC ENZYMES Principal Investigator & Institution: Yan, Honggao; Associate Professor; Biochem and Molecular Biology; Michigan State University 301 Administration Bldg East Lansing, Mi 48824 Timing: Fiscal Year 2004; Project Start 01-AUG-1999; Project End 31-MAR-2008 Summary: (provided by applicant): The long-term goal of the project is to determine the structures and molecular mechanisms of catalysis for enzymes in the folate biosynthetic pathway, a proven target pathway for developing antimicrobial agents. The proposed research is to continue our current study on 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase (HPPK), and to expand our research to include dihydroneopterin aldolase (DHNA). HPPK is an excellent model for studying mechanism of enzymatic pyrophosphoryl transfer. DHNA is a unique aldolase because it requires neither the formation of a Schiff base between the enzyme and its substrate nor metal ions for catalysis, and the enzyme also catalyzes the epimerization of its substrate. The central hypothesis behind the proposed research on HPPK, which is based on the results obtained in the previous funding period, is that HPPK undergoes dramatic conformational changes during its catalytic cycle and the conformational changes play critical roles in its catalysis. Thus, in Specific Aim 1, we will continue our quest for structure determination of HPPK along the catalytic cycle by X-ray crystallography. In Specific Aim 2, we will determine the conformational dynamics of the catalytic loops of HPPK by time-resolved fluorescence energy transfer (FRET) at equilibrium conditions and even as the reaction progresses and the dynamics of its core structure by heteronuclear NMR relaxation at the sub-nanosecond to nanosecond and microsecond to millisecond time scales. Most importantly, in Specific Aim 3, we will correlate the structure and conformational dynamics of HPPK with its catalysis by site-directed mutagenesis, biochemical analysis (particularly transient kinetic analysis), and biophysical methods. The main hypotheses behind the proposed research on DHNA are that (1) the two adlolases from Staphylococcus aureus and E. coil have different binding/catalytic properties and distinct responses to inhibitors and (2) general acid/base catalysis plays a most critical role in the catalytic mechanism of this unique aldolase. Thus, in Specific Aim 4, we will determine the structures of DHNA by X-ray crystallography, particularly the structures of the complexes with neopterin and
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monopterin, the closest mimics of the Michaelis complexes of DHNA. In Specific Aim 5, we will identify residues involved in general acid/base catalysis in DHNA by a combination of site-directed mutagenesis, transient kinetic pH-rate profile analysis, and NMR spectroscopic titration. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: STRUCTURE OF PROTEINS IN CELL WALLS BY REDOR NMR Principal Investigator & Institution: Schaefer, Jacob; Professor; Chemistry; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2002; Project Start 01-AUG-1994; Project End 31-JUL-2006 Summary: (provided by applicant): We propose new solid-state rotational-echo doubleresonance (REDOR) NMR experiments to determine in situ the mode of action of vancomycin and vancomycin analogues in actively dividing cells of Staphylococcus aureus. Both the vancomycins and the bacteria will be labeled with combinations of 13C, 15N, 2H, and 19F. Detection of the labels will use custom-built, high-efficiency 6frequency transmission-line NMR probes. Three new types of REDOR experiments will provide site-specific detection of labels in cell walls of whole cells (both in suspension and aggregated in biofilms) with no interferences from cytoplasmic labels or from the natural-abundance background. REDOR experiments will also be performed on whole cells whose thick, outer layer of mature peptidoglycan has been removed. These protoplasts will be examined in various stages of reversion to normal bacteria, and so with varying amounts of attached nascent peptidoglycan. The vancomycin bound close to the exoface of the cytoplasmic membrane is therapeutically active. In addition to vancomycin, other peptide antibiotics including synthetic and natural magainins, nisin, and mersacidin will be used in REDOR experiments. Binding will be examined in whole cells, protoplasts, reverting protoplasts, multi-lamellar vesicles, and mechanically aligned bilayers on glass plates. The overall goal of the project is to use REDOR to define antibacterial modes of action thereby aiding the drug-discovery process aimed against anticipated lethal strains of S. aureus that are resistant to every presently known antibiotic. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: STRUCTURE/FUNCTION OF ENGINEERED B LACTAMASES Principal Investigator & Institution: Herzberg, Osnat; Professor; None; University of Md Biotechnology Institute Baltimore, Md 212023101 Timing: Fiscal Year 2002; Project Start 01-JAN-1989; Project End 31-DEC-2003 Summary: The susceptibility of pathogenic bacteria to penicillins and related compounds has been greatly reduced because of the production of beta-lactamases, a group of enzymes that hydrolyze the beta-lactam amide bond characteristic of these antibiotics. The rapid increase in multi-resistant infectious bacteria, together with the prevalence of patients whose immune system has been compromised underscores the urgency of recovering the effectiveness of antibiotics in general, and of beta-lactam therapy in particular. Future design of novel drugs will benefit from the understanding o the mechanism of two enzyme families: the beta- lactamases - the penicillin-degrading enzymes; and the peptidases involved in bacterial cell-wall synthesis and repair - the penicillin-binding proteins. The plasmid mediated class A beta-lactamases have emerged in recent years as the group of enzymes that evolve most rapidly when betalactam antibiotics are introduced. The proposed studies will investigate the structural basis for the activity an evolution of these enzymes, using the class A beta-lactamase
52
Staphylococcus aureus
from Staphylococcus aureus PC1 as a model system. Questions about the catalytic mechanism, substrate specificity, and stability of the enzyme will be addresse by engineering variant molecules and analyzing them by biochemical and X-ray crystallographic methods. The structures of acyl-enzyme complexes with representative substrates will be determined so that insight into the basis fo substrate specificity at the atomic level will be gained. The evolutionary lin between the class A and the class C beta-lactamases, and between these beta-lactamases and the cell-wall peptidases will be investigated by designing specific changes that will convert the protein from a class A enzyme into one of the other related enzyme families. The design is structurally driven, based on analysis of crystal structures of representative members of each family. A mutant beta-lactamase that has lost its ability to hydrolyze beta-lactams and instead is inhibited by these compounds will be further altered to introduce a new deacylation mechanism that resembles that of the class C beta-lactamases. This mutant and the native proteins will serve as the parent molecules for engineering a carboxypeptidase activity toward D-Ala-D-ala peptide, the natura substrate of the bacterial cell wall peptidases. 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 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.
Studies
53
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 •
Project Title: SYNDECAN AND BACTERIAL TRANSLOCATION IN SHOCK AND TRAUMA Principal Investigator & Institution: Wells, Carol L.; Professor; Lab Medicine and Pathology; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2003; Project Start 01-FEB-2003; Project End 31-JAN-2007 Summary: (provided by applicant): Normal enteric bacteria, such as Escherichia coli and Enterococcus faecalis, frequently cause complicating infections in patients with shock and trauma. A common finding in these patients is increased intestinal epithelial permeability, and experiments with cultured enterocytes have shown that bacterial adherence to and internalization by enterocytes is increased following opening of enterocyte tight junctions, exposing the enterocyte lateral surface. Syndecan-1, expressed on the basolateral surface of human enterocytes, is a cell surface transmembrane proteoglycan that expresses heparan sulfate (HS) on its extracellular domain. Our working hypothesis is that HS chains of cell surface proteoglycans, and specifically syndecan-1, may act as an enterocyte receptor or co-receptor for a variety of enteric bacteria. Preliminary data indicated that,like human enterocytes, HS and syndecan-1 are prominently expressed on the basolateral surface of cultured HT-29 enterocytes but not Caco-2 enterocytes. Experiments with HT-29 enterocytes (designed to open enterocyte tight junctions and interfere with bacterial binding to the HS chains on syndecan-1) suggested that HS may be a receptor for gram-positive but not gram-negative bacteria. The HS analog heparin, and HS itself, inhibited adherence and internalization of grampositive Listeria monocytogenes by HT-29 enterocytes, and experiments with related glycosaminoglycans indicated that this inhibition was specific for HS. Additional preliminary experiments with HT-29 enterocytes indicated that heparin and HS similarly inhibited internalization of gram-positive E. faecalis and Staphylococcus aureus, but not gram-negative Salmonella typhimurium, Proteus mirabilis, and E. coli. Heparin did not have a noticeable effect on internalization of any bacterial species using Caco-2 enterocytes, which express low levels of HS and syndecan-1 Other preliminary experiments indicated that heparin-treated L. monocytogenes was less invasive in orally inoculated mice than was untreated L monocytogenes. In this proposal several experimental tools are used to clarify the interactions of cultured enterocytes with a variety of gram-negative bacteria, while focusing on gram-positive L. monocytogenes, E. faecalis, and S. aureus. These tools include monoclonal antibodies, glycosamino glycans, and heparin disaccharides, and two cell lines transfected to over express syndecan-1, namely ARH-77 myeloma cells and Caco-2 enterocytes. Data from in vitro studies are used to design experiments in mice (outbred and syndecan-1 knockout) to clarify the role of HS and syndecan-1 in intestinal colonization and extra intestinal dissemination of enteric bacteria. Data from these experiments may indicate that enterocytes have a receptor (related to cell surface HS and perhaps syndecan-1) involved in adherence and internalization of a variety of gram-positive bacteria including E. faecalis and S. aureus. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: THE ROLE OF BACTERIAL TOXINS IN HUMAN SKIN DISEASE Principal Investigator & Institution: Leung, Donald Y.; Head, Div of Pediatric Allergy & Immunol; National Jewish Medical & Res Ctr and Research Center Denver, Co 80206
54
Staphylococcus aureus
Timing: Fiscal Year 2002; Project Start 17-JUL-1992; Project End 31-MAY-2005 Summary: Atopic dermatitis (AD) and psoriasis are the two most common chronic inflammatory skin diseases in the general population. Colonization and infection with S. aureus has been reported to exacerbate AD and psoriasis. The mechanisms by which bacteria participate in the pathogenesis of these skin diseases are unknown. Recent studies demonstrating that approximately 60% of Staphylococcus aureus from AD and psoriasis patients produce superantigens (SAgs) provide a plausible mechanism by which S. aureus could exacerbate skin inflammation. In particular, it has been shown that staphylococcal SAgs can engage HLA-DR on macrophages and activated keratinocytes to induce the release of cytokines and cause the selective stimulation of T cells expressing specific T cell receptor(TCR) Vbeta regions. Indeed in AD, SAg production has been associated with more severe skin disease. S aureus, which do not secrete SAgs, produce alpha toxin, a potent keratinocyte activator in vitro whose effects on the immune response in vivo is unknown. The specific aims of this competing renewal grant application will be: First, to determine whether AD and psoriasis skin lesions and their respective peripheral blood skin homing receptor positive T cells are associated with a selective expansion of T cells expressing TCR Vbeta regions that react with SAgs on lesional skin. Second, to investigate whether SAgs contribute to the severity of AD by inducing glucocorticoid insensitivity in skin homing T cells, and to assess the mechanisms by which this occurs. Third, to determine the histologic and immunologic effects of staphylococcal alpha toxin vs SAgs on the skin of normal controls vs patients with AD or psoriasis. Genetically-engineered mutant SAgs incapable of binding to either HLA-DR or the TCR will be used to decipher the molecular mechanisms of SAg-mediated skin inflammation in vivo. Fourth, to investigate the mechanisms leading to enhanced colonization of S aureus on the skin of patients with AD and psoriasis. Mutant S. aureus selectively deficient in various adhesin genes will be used to define the precise molecules involved in the attachment of S. aureus to inflamed skin surfaces. The role of bacterial toxins in the pathogenesis of skin diseases are poorly understood. The skin is an important model to study the pathogenesis of immunologic reactions in tissues. Thus, the elucidation of immune mechanisms by which SAgs exacerbate AD and psoriasis should have important consequences for the development of effective therapeutic modalities in the treatment of a variety of inflammatory diseases. With the increased prevalence of antibiotic resistant S. aureus and drug allergy, it is essential to develop new non-antibiotic strategies in combating bacterial toxin-mediated skin diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: THE ROLE OF IGA IN S. AUREUS MEDIATED INFLAMMATION Principal Investigator & Institution: Arulanandam, Bernard P.; Biology; University of Texas San Antonio San Antonio, Tx 78249 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2005 Summary: (provided by applicant): Staphylococcus aureus infections often lead to hematogenous spread that result in inflammation and joint destruction. Although the virulence factors associated with this bacteria have been defined, the role of the host immune response in limiting the inflammatory process is still poorly understood. Using mice with a targeted disruption in IgA gene expression (IgA-/- mice), we have recently shown another yet unrecognized role for IgA. Specifically, IgA appears to serve an essential role in maintenance of overt inflammatory cytokine and nitric oxide (NO) production. We will now investigate in detail the basis for the immunoregulatory role of IgA in modulating systemic inflammatory responses upon bacterial insult. Using a
Studies
55
strain of S. aureus that induces sepsis and joint destruction, we will initially examine the precise role of IgA in limiting inflammatory processes using IgA-/- mice. Bacteremia will be assessed in the blood, spleen and kidneys after infection. Inflammatory cytokine production will be monitored in the blood and lymphoid tissues by ELISA and ribonuclease protection analysis respectively. Inflammation in the joints of these animals will be assessed by immunohistochemistry. Since NO production may have both detrimental and beneficial effects during S. aureus infection, we will examine if the absence of IgA potentiates NO expression in the joints of infected mice by histological analyses. Given that the NF-kB pathway is essential in the regulation of iNOS and NO production, we will examine how the absence of IgA affects various components of this pathway by cellular and molecular analyses. Finally we will determine if IgA regulates an inhibitory signaling pathway in macrophages upon bacterial stimulation. Together, these studies will determine if IgA modulates inflammatory responses to systemic bacterial infection by direct interaction with the innate immune system. The results will provide insight on the role of serum IgA to regulate inflammatory processes such as bacterial sepsis and may lead to the use of use of IgA as a therapeutic anti-inflammatory agent. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: UNDERSTANDING THE PATHOGENESIS OF STAPHYLOCOCCUS AUREUS Principal Investigator & Institution: Fowler, Vance G.; Medicine; Duke University Durham, Nc 27706 Timing: Fiscal Year 2002; Project Start 01-SEP-1999; Project End 31-MAY-2004 Summary: Staphylococcus aureus bacteremia, is a serious, common infection. The broad, long-term objectives of this proposal are to identify clinical and bacterial features that determine the clinical severity of S. aureus bacteremia, and to use these features to develop a clinically useful predictive model for assessing risk of individual patients with this infection. The Specific Aims of this proposal are 1.) To prospectively identify patients with S. aureus bacteremia at high risk for complications and death and 2.) To define the impact of selected bacterial characteristics (virulence factors) on the clinical outcome of patients with S. aureus bacteremia. This will be a prospective cohort study with outcomes data. The methods to be used include three related components. First, logistic regression will be employed on a large (n = 502) existing cohort of prospectively identified patients with S. aureus bacteremia to identify clinical features associated with complicated Staphylococcal infection. Second, assays for selected virulence factors will be performed on the stored S. aureus isolates from this large existing patient cohort. These assays will be performed through existing collaborations with established investigators. Results of these assays will then be correlated with patient outcomes. Third, prospective collection of clinical data and bacterial isolates from patients with S. aureus bacteremia will continue throughout the grant period in order to create a new cohort of patients with S. aureus bacteremia. This cohort will be used to validate the findings of this investigation. Accomplishing the aims of this proposal will contribute to improved clinical management of patients with S. aureus bacteremia, and will add to the understanding of S. aureus virulence factors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: USE OF MICROARRAYS TO UNDERSTAND SYSTEMIC ARTHRITIS Principal Investigator & Institution: Pascual, Maria Virginia.; Associate Professor; Baylor Research Institute 3434 Live Oak St, Ste 125 Dallas, Tx 75204
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Staphylococcus aureus
Timing: Fiscal Year 2003; Project Start 22-SEP-2003; Project End 31-AUG-2007 Summary: (provided by applicant): Systemic Onset Juvenile Chronic Arthritis (SOJCA) is a disease that carries severe long-term disability for 50% of the children who suffer from it. The pathogenesis of this disease remains a mystery and there are no animal models to reproduce it. As opposed to other forms of Juvenile Chronic Arthritis, no serologic markers like autoantibodies, HLA associations, or other specific diagnostic tests are available. We now have preliminary data showing significant alterations in the blood mononuclear cells from SOJCA patients, including 1) increased numbers of blood monocytes with an activated phenotype, 2) a gene signature shared with patients with bacterial infections, 3) a unique gene signature. The present proposal aims at further strengthening these data through the accrual of a larger number of patients and the analyses of a larger selection of genes. We expect that these studies will provide us with clues to understand the pathogenesis of the disease. We are particularly intrigued by the similarities observed between SOJCA and systemic infections especially with those caused by Staphylococcus aureus. We propose to correlate the SOJCA genetic signature with the outcome of the disease. In particular, the four-year proposed study will permit us to compare the gene profiles of patients who get disease resolution from those who develop a chronic, highly debilitating disease. In vitro studies are designed to eventually identify the cellular and molecular mechanisms leading to the SOJCA signature, thereby allowing us to better understand the disease. Our ultimate goal is to design novel therapies to antagonize the causative agent and/or the genetic pathways responsible for the establishment of this intriguing disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: VIRULENCE AND IMMUNITY TO STAPHYLCOCCI Principal Investigator & Institution: Pier, Gerald B.; Professor; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2002; Project Start 01-FEB-2001; Project End 31-JAN-2006 Summary: (Verbatim from Applicant's Abstract): The long-term goal of this study is to understand the role in pathogenesis and immunity of an environmentally regulated surface polysaccharide of Staphylococcus aureus chemically characterized as poly-Nsuccinyl-B-1-6 glucosamine (PNSG). PNSG has previously been determined to be the protective capsular polysaccharide/adhesin (PS/A) antigen of Staphylococcus epidermidis, raising the possibility that PNSG could be used as a "pan-staphylococcal" vaccine. To define the role of PNSG in pathogenesis of S. aureus infection 5 different PNSG-deficient S. aureus strains representative of major lineages will be constructed by genetic means via interruption of the genes in the intracellular adhesin (ica) locus that encodes proteins needed for synthesis of PNSG. Isogenic parental, mutant and ica complemented strains will be evaluated in vitro to determine the role of PNSG in promoting S. aureus adherence to catheters and in providing resistance of bacterial cells to phagocytic killing by leukocytes and complement. The same strains will also be tested for infectious capability in several animal systems of S. aureus infection, including animals actively and passively immunized with ica-deleted S. aureus and normal human serum to reflect the immunologic status of humans, who have high levels of natural antibody to S. aureus surface antigens. Because PNSG isolated from some strains of staphylococci have up to 30 percent of the succinate substituents on the polyglucosamine backbone replaced by acetate, purified PNSG, with differing ratios of succinate and acetate substituents on the polyglucosamine backbone, will be produced for immunologic studies. Rabbits will be immunized with the variants and sera assessed for antibody titer and opsonic killing ability. The PNSG variant structures will be used
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to immunize mice to evaluate their ability to generate protective immunity in the same systems used for the study of the role of PNSG in S. aureus virulence. In addition, passive protection by the rabbit sera raised to the variant PNSG constructs will be evaluated in the animal systems. All the above mentioned studies will provide new and useful information regarding pathogenesis and immunity of staphylococcal infections, stressing the use of animal systems that reflect naturally acquired immunity in humans to S. aureus. By the end of these studies we expect to have a clear understanding of the role of PNSG in virulence, as determined in a variety of staphylococcal infection systems, the immunochemical properties of PNSG that can engender protective immunity, and the types of S. aureus infections wherein PNSG-specific immunotherapies show the most potential for success. 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 “Staphylococcus aureus” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for Staphylococcus aureus in the PubMed Central database: •
[final sigma]B Activity Depends on RsbU in Staphylococcus aureus. by Giachino P, Engelmann S, Bischoff M.; 2001 Mar 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=95078
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[sigma]B Modulates Virulence Determinant Expression and Stress Resistance: Characterization of a Functional rsbU Strain Derived from Staphylococcus aureus 8325-4. by Horsburgh MJ, Aish JL, White IJ, Shaw L, Lithgow JK, Foster SJ.; 2002 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=135357
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A Convenient Assay for Estimating the Possible Involvement of Efflux of Fluoroquinolones by Streptococcus pneumoniae and Staphylococcus aureus: Evidence for Diminished Moxifloxacin, Sparfloxacin, and Trovafloxacin Efflux. by Beyer R, Pestova E, Millichap JJ, Stosor V, Noskin GA, Peterson LR.; 2000 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89772
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A New Two-Component Regulatory System Involved in Adhesion, Autolysis, and Extracellular Proteolytic Activity of Staphylococcus aureus. by Fournier B, Hooper DC.; 2000 Jul 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=94580
3 4
Adapted from the National Library of Medicine: http://www.pubmedcentral.nih.gov/about/intro.html.
With PubMed Central, NCBI is taking the lead in preservation and maintenance of open access to electronic literature, just as NLM has done for decades with printed biomedical literature. PubMed Central aims to become a world-class library of the digital age. 5 The value of PubMed Central, in addition to its role as an archive, lies in the availability of data from diverse sources stored in a common format in a single repository. Many journals already have online publishing operations, and there is a growing tendency to publish material online only, to the exclusion of print.
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A second gene in the Staphylococcus aureus cadA cadmium resistance determinant of plasmid pI258. by Yoon KP, Silver S.; 1991 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=212532
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A Shared Noncapsular Antigen Is Responsible for False-Positive Reactions by Staphylococcus epidermidis in Commercial Agglutination Tests for Staphylococcus aureus. by Blake JE, Metcalfe MA.; 2001 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=87773
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A single clone of Staphylococcus aureus causes the majority of cases of toxic shock syndrome. by Musser JM, Schlievert PM, Chow AW, Ewan P, Kreiswirth BN, Rosdahl VT, Naidu AS, Witte W, Selander RK.; 1990 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=53234
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A site-directed Staphylococcus aureus hemB mutant is a small-colony variant which persists intracellularly. by von Eiff C, Heilmann C, Proctor RA, Woltz C, Peters G, Gotz F.; 1997 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=179315
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A Spectrum of Changes Occurs in Peptidoglycan Composition of GlycopeptideIntermediate Clinical Staphylococcus aureus Isolates. by Boyle-Vavra S, Labischinski H, Ebert CC, Ehlert K, Daum RS.; 2001 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=90273
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A Staphylococcus aureus Autolysin that has an N-Acetylmuramoyl-L-Alanine Amidase Domain and an Endo-[beta]-N-Acetylglucosaminidase Domain: Cloning, Sequence Analysis, and Characterization. by Oshida T, Sugai M, Komatsuzawa H, Hong Y, Suginaka H, Tomasz A.; 1995 Jan 3; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=42863
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Ability of Staphylococcus aureus coagulase genotypes to resist neutrophil bactericidal activity and phagocytosis. by Aarestrup FM, Scott NL, Sordillo LM.; 1994 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=303320
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Accessory Gene Regulator (agr) Locus in Geographically Diverse Staphylococcus aureus Isolates with Reduced Susceptibility to Vancomycin. by Sakoulas G, Eliopoulos GM, Moellering RC Jr, Wennersten C, Venkataraman L, Novick RP, Gold HS.; 2002 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=127153
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Activities of the Combination of Quinupristin-Dalfopristin with Rifampin In Vitro and in Experimental Endocarditis Due to Staphylococcus aureus Strains with Various Phenotypes of Resistance to Macrolide-Lincosamide-Streptogramin Antibiotics. by Zarrouk V, Bozdogan B, Leclercq R, Garry L, Feger C, Carbon C, Fantin B.; 2001 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=90450
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Activities of Trovafloxacin and Ampicillin-Sulbactam Alone or in Combination versus Three Strains of Vancomycin- Intermediate Staphylococcus aureus in an In Vitro Pharmacodynamic Infection Model. by Aeschlimann JR, Hershberger E, Rybak MJ.; 2000 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89837
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Activities of Trovafloxacin Compared with Those of Other Fluoroquinolones against Purified Topoisomerases and gyrA and grlA Mutants of Staphylococcus aureus. by Gootz TD, Zaniewski RP, Haskell SL, Kaczmarek FS, Maurice AE.; 1999 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89379
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Activity of and Resistance to Moxifloxacin in Staphylococcus aureus. by Ince D, Zhang X, Hooper DC.; 2003 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=152517
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Adherence of Staphylococcus aureus to Endothelial Cells: Influence of Capsular Polysaccharide, Global Regulator agr, and Bacterial Growth Phase. by PohlmannDietze P, Ulrich M, Kiser KB, Doring G, Lee JC, Fournier JM, Botzenhart K, Wolz C.; 2000 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=101683
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Adherence Properties of Staphylococcus aureus under Static and Flow Conditions: Roles of agr and sar Loci, Platelets, and Plasma Ligands. by Shenkman B, Rubinstein E, Cheung AL, Brill GE, Dardik R, Tamarin I, Savion N, Varon D.; 2001 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98521
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agr Expression Precedes Escape of Internalized Staphylococcus aureus from the Host Endosome. by Qazi SN, Counil E, Morrissey J, Rees CE, Cockayne A, Winzer K, Chan WC, Williams P, Hill PJ.; 2001 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=100088
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Alterations in the DNA topoisomerase IV grlA gene responsible for quinolone resistance in Staphylococcus aureus. by Yamagishi J, Kojima T, Oyamada Y, Fujimoto K, Hattori H, Nakamura S, Inoue M.; 1996 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=163283
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Altered Gene Expression in Staphylococcus aureus upon Interaction with Human Endothelial Cells. by Vriesema AJ, Beekhuizen H, Hamdi M, Soufan A, Lammers A, Willekens B, Bakker O, Welten AG, Veltrop MH, van de Gevel JS, Dankert J, Zaat SA.; 2000 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=97346
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An autolysin ring associated with cell separation of Staphylococcus aureus. by Yamada S, Sugai M, Komatsuzawa H, Nakashima S, Oshida T, Matsumoto A, Suginaka H.; 1996 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=177839
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An Elevated Mutation Frequency Favors Development of Vancomycin Resistance in Staphylococcus aureus. by Schaaff F, Reipert A, Bierbaum G.; 2002 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=128741
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An IS257-Derived Hybrid Promoter Directs Transcription of a tetA(K) Tetracycline Resistance Gene in the Staphylococcus aureus Chromosomal mec Region. by Simpson AE, Skurray RA, Firth N.; 2000 Jun 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=101884
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Anaerobic Conditions Induce Expression of Polysaccharide Intercellular Adhesin in Staphylococcus aureus and Staphylococcus epidermidis. by Cramton SE, Ulrich M, Gotz F, Doring G.; 2001 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98472
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Analysis of an outbreak of non-phage-typeable methicillin-resistant Staphylococcus aureus by using a randomly amplified polymorphic DNA assay. by Tambic A, Power EG, Talsania H, Anthony RM, French GL.; 1997 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=230128
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Analysis of Ebh, a 1.1-Megadalton Cell Wall-Associated Fibronectin-Binding Protein of Staphylococcus aureus. by Clarke SR, Harris LG, Richards RG, Foster SJ.; 2002 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=133066
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Analysis of expression of the alpha-toxin gene (hla) of Staphylococcus aureus by using a chromosomally encoded hla::lacZ gene fusion. by Ohlsen K, Koller KP, Hacker J.; 1997 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=175513
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Analysis of gyrA and grlA mutations in stepwise-selected ciprofloxacin-resistant mutants of Staphylococcus aureus. by Ferrero L, Cameron B, Crouzet J.; 1995 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=162780
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Analysis of Transcription of the Staphylococcus aureus Aerobic Class Ib and Anaerobic Class III Ribonucleotide Reductase Genes in Response to Oxygen. by Masalha M, Borovok I, Schreiber R, Aharonowitz Y, Cohen G.; 2001 Dec 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=95576
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Antagonism between Aminoglycosides and [beta]-Lactams in a Methicillin-Resistant Staphylococcus aureus Isolate Involves Induction of an Aminoglycoside-Modifying Enzyme. by Ida T, Okamoto R, Nonoyama M, Irinoda K, Kurazono M, Inoue M.; 2002 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=127169
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Antibacterial Action of Extracellular Mammalian Group IIA Phospholipase A2 against Grossly Clumped Staphylococcus aureus. by Dominiecki ME, Weiss J.; 1999 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=115970
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Antibiotic-Induced Release of Lipoteichoic Acid and Peptidoglycan from Staphylococcus aureus: Quantitative Measurements and Biological Reactivities. by van Langevelde P, van Dissel JT, Ravensbergen E, Appelmelk BJ, Schrijver IA, Groeneveld PH.; 1998 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=106001
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Antibody response to Staphylococcus aureus surface proteins in rabbits with persistent osteomyelitis after treatment with demineralized bone implants. by Thomas VL, Sanford BA, Keogh BS, Triplett RG.; 1989 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=313111
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Application of Pulsed-Field Gel Electrophoresis and Binary Typing as Tools in Veterinary Clinical Microbiology and Molecular Epidemiologic Analysis of Bovine and Human Staphylococcus aureus Isolates. by Zadoks R, van Leeuwen W, Barkema H, Sampimon O, Verbrugh H, Schukken YH, van Belkum A.; 2000 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=86626
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Arsenic efflux governed by the arsenic resistance determinant of Staphylococcus aureus plasmid pI258. by Broer S, Ji G, Broer A, Silver S.; 1993 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=204747
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Association of mutations in grlA and gyrA topoisomerase genes with resistance to ciprofloxacin in epidemic and sporadic isolates of methicillin-resistant Staphylococcus aureus. by Deplano A, Zekhnini A, Allali N, Couturier M, Struelens MJ.; 1997 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=164058
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Autolysis of methicillin-resistant Staphylococcus aureus is involved in synergism between imipenem and cefotiam. by Matsuda K, Nakamura K, Adachi Y, Inoue M, Kawakami M.; 1995 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=163002
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Autolysis-defective mutant of Staphylococcus aureus: pathological considerations, genetic mapping, and electron microscopic studies. by Mani N, Baddour LM, Offutt DQ, Vijaranakul U, Nadakavukaren MJ, Jayaswal RK.; 1994 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=186294
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Availability of Complement Bound to Staphylococcus aureus To Interact with Membrane Complement Receptors Influences Efficiency of Phagocytosis. by Cunnion KM, Zhang HM, Frank MM.; 2003 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=145377
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Bactericidal Activities of BMS-284756, a Novel Des-F(6)-Quinolone, against Staphylococcus aureus Strains with Topoisomerase Mutations. by Lawrence LE, Frosco M, Ryan B, Chaniewski S, Yang H, Hooper DC, Barrett JF.; 2002 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=126973
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Bactericidal Activities of Two Daptomycin Regimens against Clinical Strains of Glycopeptide Intermediate-Resistant Staphylococcus aureus, Vancomycin-Resistant Enterococcus faecium, and Methicillin-Resistant Staphylococcus aureus Isolates in an In Vitro Pharmacodynamic Model with Simulated Endocardial Vegetations. by Akins RL, Rybak MJ.; 2001 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=90312
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Bactericidal/Permeability-Increasing Protein Inhibits Growth of a Strain of Acholeplasma laidlawii and L Forms of the Gram-Positive Bacteria Staphylococcus aureus and Streptococcus pyogenes. by Horwitz AH, Williams RE, Liu PS, Nadell R.; 1999 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89470
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Bap, a Staphylococcus aureus Surface Protein Involved in Biofilm Formation. by Cucarella C, Solano C, Valle J, Amorena B, Lasa I', Penades JR.; 2001 May 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=99507
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Biosynthesis of the Glycolipid Anchor in Lipoteichoic Acid of Staphylococcus aureus RN4220: Role of YpfP, the Diglucosyldiacylglycerol Synthase. by Kiriukhin MY, Debabov DV, Shinabarger DL, Neuhaus FC.; 2001 Jun 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=99649
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Borderline methicillin-susceptible Staphylococcus aureus strains have more in common than reduced susceptibility to penicillinase-resistant penicillins. by Massidda O, Montanari MP, Mingoia M, Varaldo PE.; 1996 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=163619
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Bovine and rabbit models for the study of a Staphylococcus aureus avirulent mutant strain, RC122. by Reinoso E, Magnano G, Giraudo J, Calzolari A, Bogni C.; 2002 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=227018
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Breast Milk Transmission of a Panton-Valentine Leukocidin-Producing Staphylococcus aureus Strain Causing Infantile Pneumonia. by Le Thomas I, MarianiKurkdjian P, Collignon A, Gravet A, Clermont O, Brahimi N, Gaudelus J, Aujard Y, Navarro J, Beaufils F, Bingen E.; 2001 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=87805
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Caenorhabditis elegans as a Model Host for Staphylococcus aureus Pathogenesis. by Sifri CD, Begun J, Ausubel FM, Calderwood SB.; 2003 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=152095
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Capsule Expression by Bovine Isolates of Staphylococcus aureus from Argentina: Genetic and Epidemiologic Analyses. by Sordelli DO, Buzzola FR, Gomez MI, SteeleMoore L, Berg D, Gentilini E, Catalano M, Reitz AJ, Tollersrud T, Denamiel G, Jeric P, Lee JC.; 2000 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=86219
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Capsule Production and Growth Phase Influence Binding of Complement to Staphylococcus aureus. by Cunnion KM, Lee JC, Frank MM.; 2001 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=100057
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Characterization of a Chromosomal Gene Encoding Type B [beta]-Lactamase in Phage Group II Isolates of Staphylococcus aureus. by Voladri RK, Kernodle DS.; 1998 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=106017
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Characterization of a Putative Pathogenicity Island from Bovine Staphylococcus aureus Encoding Multiple Superantigens. by Fitzgerald JR, Monday SR, Foster TJ, Bohach GA, Hartigan PJ, Meaney WJ, Smyth CJ.; 2001 Jan 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=94850
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Characterization of an NaCl-sensitive Staphylococcus aureus mutant and rescue of the NaCl-sensitive phenotype by glycine betaine but not by other compatible solutes. by Vijaranakul U, Nadakavukaren MJ, Bayles DO, Wilkinson BJ, Jayaswal RK.; 1997 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=168480
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Characterization of fmtA, a Gene That Modulates the Expression of Methicillin Resistance in Staphylococcus aureus. by Komatsuzawa H, Ohta K, Labischinski H, Sugai M, Suginaka H.; 1999 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89433
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Characterization of Gentamicin-Susceptible Strains of Methicillin-Resistant Staphylococcus aureus Involved in Nosocomial Spread. by Lemaitre N, Sougakoff W, Masmoudi A, Fievet MH, Bismuth R, Jarlier V.; 1998 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=124812
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Characterization of NorR Protein, a Multifunctional Regulator of norA Expression in Staphylococcus aureus. by Truong-Bolduc QC, Zhang X, Hooper DC.; 2003 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=154082
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Characterization of Passage-Selected Vancomycin-Resistant Staphylococcus aureus Strains of Diverse Parental Backgrounds. by Pfeltz RF, Singh VK, Schmidt JL, Batten MA, Baranyk CS, Nadakavukaren MJ, Jayaswal RK, Wilkinson BJ.; 2000 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89674
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Characterization of Staphylococcus aureus Coagulase Type VII Isolates from Staphylococcal Food Poisoning Outbreaks (1980 --1995) in Tokyo, Japan, by PulsedField Gel Electrophoresis. by Shimizu A, Fujita M, Igarashi H, Takagi M, Nagase N, Sasaki A, Kawano J.; 2000 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=87468
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Characterization of Staphylococcus aureus SarA Binding Sites. by Sterba KM, Mackintosh SG, Blevins JS, Hurlburt BK, Smeltzer MS.; 2003 Aug 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=165759
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Characterization of the [final sigma]B Regulon in Staphylococcus aureus. by Gertz S, Engelmann S, Schmid R, Ziebandt AK, Tischer K, Scharf C, Hacker J, Hecker M.; 2000 Dec 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=94824
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Characterization of the Major Superoxide Dismutase of Staphylococcus aureus and Its Role in Starvation Survival, Stress Resistance, and Pathogenicity. by Clements MO, Watson SP, Foster SJ.; 1999 Jul 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=93877
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Characterization of the Starvation-Survival Response of Staphylococcus aureus. by Watson SP, Clements MO, Foster SJ.; 1998 Apr 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=107086
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Ciprofloxacin resistance in coagulase-positive and -negative staphylococci: role of mutations at serine 84 in the DNA gyrase A protein of Staphylococcus aureus and Staphylococcus epidermidis. by Sreedharan S, Peterson LR, Fisher LM.; 1991 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=245345
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Clinical Impact of a PCR Assay for Identification of Staphylococcus aureus and Determination of Methicillin Resistance Directly from Blood Cultures. by Hallin M, Maes N, Byl B, Jacobs F, De Gheldre Y, Struelens MJ.; 2003 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=179783
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Clinical Isolate of Vancomycin-Heterointermediate Staphylococcus aureus Susceptible to Methicillin and In Vitro Selection of a Vancomycin-Resistant Derivative. by Bobin-Dubreux S, Reverdy ME, Nervi C, Rougier M, Bolmstrom A, Vandenesch F, Etienne J.; 2001 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=90291
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Clonal analysis of methicillin-resistant Staphylococcus aureus strains from intercontinental sources: association of the mec gene with divergent phylogenetic lineages implies dissemination by horizontal transfer and recombination. by Musser JM, Kapur V.; 1992 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=265442
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Clonal Associations among Staphylococcus aureus Isolates from Various Sites of Infection. by Booth MC, Pence LM, Mahasreshti P, Callegan MC, Gilmore MS.; 2001 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=97889
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Clonal Characterization of Staphylococcus aureus by Multilocus Restriction Fragment Typing, a Rapid Screening Approach for Molecular Epidemiology. by Diep BA, Perdreau-Remington F, Sensabaugh GF.; 2003 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=254328
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Clonal Distribution of Methicillin-Resistant Staphylococcus aureus in Poland. by Leski T, Oliveira D, Trzcinski K, Sanches IS, de Sousa MA, Hryniewicz W, de Lencastre H.; 1998 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105235
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Clonal Spread of Staphylococcus aureus Heterogeneously Resistant to Vancomycin in a University Hospital in Korea. by Kim MN, Hwang SH, Pyo YJ, Mun HM, Pai CH.; 2002 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=140376
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Cloning and expression of the norA gene for fluoroquinolone resistance in Staphylococcus aureus. by Ubukata K, Itoh-Yamashita N, Konno M.; 1989 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=172697
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Cloning and Functional Characterization of an NAD +-Dependent DNA Ligase from Staphylococcus aureus. by Kaczmarek FS, Zaniewski RP, Gootz TD, Danley DE, Mansour MN, Griffor M, Kamath AV, Cronan M, Mueller J, Sun D, Martin PK, Benton B, McDowell L, Biek D, Schmid MB.; 2001 May 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=95200
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Cloning and Nucleotide Sequence Determination of the Entire mec DNA of PreMethicillin-Resistant Staphylococcus aureus N315. by Ito T, Katayama Y, Hiramatsu K.; 1999 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89295
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Cloning, Characterization, and Inactivation of the Gene pbpC, Encoding PenicillinBinding Protein 3 of Staphylococcus aureus. by Pinho MG, de Lencastre H, Tomasz A.; 2000 Feb 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=94384
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Cloning, expression, and mutagenesis of phosphatidylinositol-specific phospholipase C from Staphylococcus aureus: a potential staphylococcal virulence factor. by Daugherty S, Low MG.; 1993 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=281286
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Coagulase expression in Staphylococcus aureus is positively and negatively modulated by an agr-dependent mechanism. by Lebeau C, Vandenesch F, Greenland T, Novick RP, Etienne J.; 1994 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=196743
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Combination Effect of Vancomycin and [beta]-Lactams against a Staphylococcus aureus Strain, Mu3, with Heterogeneous Resistance to Vancomycin. by Aritaka N, Hanaki H, Cui L, Hiramatsu K.; 2001 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=90459
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Combination of flucloxacillin and gentamicin inhibits toxic shock syndrome toxin 1 production by Staphylococcus aureus in both logarithmic and stationary phases of growth. by van Langevelde P, van Dissel JT, Meurs CJ, Renz J, Groeneveld PH.; 1997 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=163985
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Community Acquisition of Gentamicin-Sensitive Methicillin-Resistant Staphylococcus aureus in Southeast Queensland, Australia. by Nimmo GR, Schooneveldt J, O'Kane G, McCall B, Vickery A.; 2000 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=87519
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Community Strain of Methicillin-Resistant Staphylococcus aureus Involved in a Hospital Outbreak. by O'Brien FG, Pearman JW, Gracey M, Riley TV, Grubb WB.; 1999 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=85396
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Comparative Analysis of Multidrug-Resistant, Non-Multidrug-Resistant, and Archaic Methicillin-Resistant Staphylococcus aureus Isolates from Central Sydney, Australia. by Watson J, Givney R, Beard-Pegler M, Rose B, Merlino J, Vickery A, Gottlieb T, Bradbury R, Harbour C.; 2003 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=149719
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Comparative Molecular Analysis of Community- or Hospital-Acquired MethicillinResistant Staphylococcus aureus. by Fey PD, Said-Salim B, Rupp ME, Hinrichs SH, Boxrud DJ, Davis CC, Kreiswirth BN, Schlievert PM.; 2003 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=149027
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Comparison of Culture Screening Methods for Detection of Nasal Carriage of Methicillin-Resistant Staphylococcus aureus: a Prospective Study Comparing 32 Methods. by Safdar N, Narans L, Gordon B, Maki DG.; 2003 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=165368
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Comparison of DNA Sequencing of the Protein A Gene Polymorphic Region with Other Molecular Typing Techniques for Typing Two Epidemiologically Diverse Collections of Methicillin-Resistant Staphylococcus aureus. by Oliveira DC, Crisostomo I, Santos-Sanches I, Major P, Alves CR, Aires-de-Sousa M, Thege MK, de Lencastre H.; 2001 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=87778
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Comparison of five tests for identification of Staphylococcus aureus from clinical samples. by Luijendijk A, van Belkum A, Verbrugh H, Kluytmans J.; 1996 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229229
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Comparison of MIDI Sherlock system and pulsed-field gel electrophoresis in characterizing strains of methicillin-resistant Staphylococcus aureus from a recent hospital outbreak. by Leonard RB, Mayer J, Sasser M, Woods ML, Mooney BR, Brinton BG, Newcomb-Gayman PL, Carroll KC.; 1995 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=228563
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Comparison of Multilocus Sequence Typing and Pulsed-Field Gel Electrophoresis as Tools for Typing Staphylococcus aureus Isolates in a Microepidemiological Setting. by Peacock SJ, de Silva GD, Justice A, Cowland A, Moore CE, Winearls CG, Day NP.; 2002 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=130877
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Comparison of phage typing and DNA fingerprinting by polymerase chain reaction for discrimination of methicillin-resistant Staphylococcus aureus strains. by van Belkum A, Bax R, Peerbooms P, Goessens WH, van Leeuwen N, Quint WG.; 1993 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=263566
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Comparison of phenotypic methods and DNA hybridization for detection of methicillin-resistant Staphylococcus aureus. by Richard P, Meyran M, Carpentier E, Thabaut A, Drugeon HB.; 1994 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=263095
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Comparison of Protein A Gene Sequencing with Pulsed-Field Gel Electrophoresis and Epidemiologic Data for Molecular Typing of Methicillin-Resistant Staphylococcus aureus. by Tang YW, Waddington MG, Smith DH, Manahan JM, Kohner PC, Highsmith LM, Li H, Cockerill FR III, Thompson RL, Montgomery SO, Persing DH.; 2000 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=86443
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Comparison of Pulsed-Field Gel Electrophoresis and Coagulase Gene Restriction Profile Analysis Techniques in the Molecular Typing of Staphylococcus aureus. by Chiou CS, Wei HL, Yang LC.; 2000 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=86760
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Comparison of Pulsed-Field Gel Electrophoresis and PCR Analysis of Polymorphisms on the mec Hypervariable Region for Typing Methicillin-Resistant Staphylococcus aureus. by Senna JP, Pinto CA, Carvalho LP, Santos DS.; 2002 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=130718
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Comparison of Staphylococcus aureus Isolates from Bovine and Human Skin, Milking Equipment, and Bovine Milk by Phage Typing, Pulsed-Field Gel Electrophoresis, and Binary Typing. by Zadoks RN, van Leeuwen WB, Kreft D, Fox LK, Barkema HW, Schukken YH, van Belkum A.; 2002 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=139627
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Complementation of the Essential Peptidoglycan Transpeptidase Function of Penicillin-Binding Protein 2 (PBP2) by the Drug Resistance Protein PBP2A in Staphylococcus aureus. by Pinho MG, Filipe SR, de Lencastre H, Tomasz A.; 2001 Nov 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=95481
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Complete Nucleotide Sequence of a Staphylococcus aureus Exfoliative Toxin B Plasmid and Identification of a Novel ADP-Ribosyltransferase, EDIN-C. by Yamaguchi T, Hayashi T, Takami H, Ohnishi M, Murata T, Nakayama K, Asakawa K, Ohara M, Komatsuzawa H, Sugai M.; 2001 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98872
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Concordant clonal delineation of methicillin-resistant Staphylococcus aureus by macrorestriction analysis and polymerase chain reaction genome fingerprinting. by Struelens MJ, Bax R, Deplano A, Quint WG, Van Belkum A.; 1993 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=265680
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Contribution of a Thickened Cell Wall and Its Glutamine Nonamidated Component to the Vancomycin Resistance Expressed by Staphylococcus aureus Mu50. by Cui L, Murakami H, Kuwahara-Arai K, Hanaki H, Hiramatsu K.; 2000 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=90058
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Correlation between esterase electrophoretic types and capsular polysaccharide types 5 and 8 among methicillin-susceptible and methicillin-resistant strains of Staphylococcus aureus. by Branger C, Goullet P, Boutonnier A, Fournier JM.; 1990 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=269560
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Correlation between the Resistance Genotype Determined by Multiplex PCR Assays and the Antibiotic Susceptibility Patterns of Staphylococcus aureus and Staphylococcus epidermidis. by Martineau F, Picard FJ, Lansac N, Menard C, Roy PH, Ouellette M, Bergeron MG.; 2000 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89663
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Correlation of Acetate Catabolism and Growth Yield in Staphylococcus aureus: Implications for Host-Pathogen Interactions. by Somerville GA, Said-Salim B, Wickman JM, Raffel SJ, Kreiswirth BN, Musser JM.; 2003 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=166023
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Correlation of Daptomycin Bactericidal Activity and Membrane Depolarization in Staphylococcus aureus. by Silverman JA, Perlmutter NG, Shapiro HM.; 2003 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=166110
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Correlation of Staphylococcus aureus icaADBC Genotype and Biofilm Expression Phenotype. by Rohde H, Knobloch JK, Horstkotte MA, Mack D.; 2001 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=88600
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Crystal Structure of the SarS Protein from Staphylococcus aureus. by Li R, Manna AC, Dai S, Cheung AL, Zhang G.; 2003 Jul 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=164878
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CtaA of Staphylococcus aureus Is Required for Starvation Survival, Recovery, and Cytochrome Biosynthesis. by Clements MO, Watson SP, Poole RK, Foster SJ.; 1999 Jan 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=93404
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Cutaneous Microenvironment of Human Immunodeficiency Virus (HIV)Seropositive and HIV-Seronegative Individuals, with Special Reference to Staphylococcus aureus Colonization. by Shapiro M, Smith KJ, James WD, Giblin WJ, Margolis DJ, Foglia AN, McGinley K, Leyden JJ.; 2000 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=87347
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Daptomycin disrupts membrane potential in growing Staphylococcus aureus. by Alborn WE Jr, Allen NE, Preston DA.; 1991 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=245372
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Decreased Amounts of Cell Wall-Associated Protein A and Fibronectin-Binding Proteins in Staphylococcus aureus sarA Mutants due to Up-Regulation of Extracellular Proteases. by Karlsson A, Saravia-Otten P, Tegmark K, Morfeldt E, Arvidson S.; 2001 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98560
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Description of Staphylococcus Serine Protease (ssp) Operon in Staphylococcus aureus and Nonpolar Inactivation of sspA-Encoded Serine Protease. by Rice K, Peralta R, Bast D, de Azavedo J, McGavin MJ.; 2001 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=97868
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Detection of an Archaic Clone of Staphylococcus aureus with Low-Level Resistance to Methicillin in a Pediatric Hospital in Portugal and in International Samples: Relics of a Formerly Widely Disseminated Strain? by Sa-Leao R, Santos Sanches I, Dias D, Peres I, Barros RM, de Lencastre H.; 1999 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=84983
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Detection of Differential Gene Expression in Biofilm-Forming versus Planktonic Populations of Staphylococcus aureus Using Micro-Representational-Difference Analysis. by Becker P, Hufnagle W, Peters G, Herrmann M.; 2001 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=92967
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Detection of enterotoxigenic Staphylococcus aureus in dried skimmed milk: use of the polymerase chain reaction for amplification and detection of staphylococcal enterotoxin genes entB and entC1 and the thermonuclease gene nuc. by Wilson IG, Cooper JE, Gilmour A.; 1991 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=183470
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Detection of genes for enterotoxins, exfoliative toxins, and toxic shock syndrome toxin 1 in Staphylococcus aureus by the polymerase chain reaction. by Johnson WM, Tyler SD, Ewan EP, Ashton FE, Pollard DR, Rozee KR.; 1991 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=269793
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Detection of genes regulating beta-lactamase production in Enterococcus faecalis and Staphylococcus aureus. by Okamoto R, Okubo T, Inoue M.; 1996 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=163573
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Detection of Low-Level Methicillin-Resistant Staphylococcus aureus with Commercially Available Tests. by B. Poulsen A, Skov R, Pallesen L.; 2003 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=165329
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Detection of Methicillin-Resistant Staphylococcus aureus (MRSA) in Blood with the EVIGENE MRSA Detection Kit. by Levi K, Towner KJ.; 2003 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=179827
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Detection of Methicillin-Resistant Staphylococcus aureus and Simultaneous Confirmation by Automated Nucleic Acid Extraction and Real-Time PCR. by Grisold AJ, Leitner E, Muhlbauer G, Marth E, Kessler HH.; 2002 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=120553
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Detection of Staphylococcus aureus by polymerase chain reaction amplification of the nuc gene. by Brakstad OG, Aasbakk K, Maeland JA.; 1992 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=265359
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Detection of Staphylococcus aureus Clinical Isolates Harboring the ica Gene Cluster Needed for Biofilm Establishment. by VictoriaMartin-Lopez J, Perez-Roth E, ClaverieMartin F.; 2002 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=140324
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Detection of Staphylococcus aureus Enterotoxins A to D by Real-Time Fluorescence PCR Assay. by Klotz M, Opper S, Heeg K, Zimmermann S.; 2003 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=254329
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Determinants of Staphylococcus aureus Nasal Carriage. by Cole AM, Tahk S, Oren A, Yoshioka D, Kim YH, Park A, Ganz T.; 2001 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=96227
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Development of a Canadian Standardized Protocol for Subtyping MethicillinResistant Staphylococcus aureus Using Pulsed-Field Gel Electrophoresis. by Mulvey MR, Chui L, Ismail J, Louie L, Murphy C, Chang N, Alfa M.; 2001 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=88375
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Development of a Single-Reaction Multiplex PCR Toxin Typing Assay for Staphylococcus aureus Strains. by Sharma NK, Rees CE, Dodd CE.; 2000 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=91991
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Differences between Staphylococcus aureus Isolates from Medical and Nonmedical Hospital Personnel. by Cespedes C, Miller M, Quagliarello B, Vavagiakis P, Klein RS, Lowy FD.; 2002 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=120551
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Different Aminoglycoside-Resistant Phenotypes in a Rabbit Staphylococcus aureus Endocarditis Infection Model. by Asseray N, Caillon J, Roux N, Jacqueline C, Bismuth R, Kergueris MF, Potel G, Bugnon D.; 2002 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=127149
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Diminished Virulence of an Alpha-Toxin Mutant of Staphylococcus aureus in Experimental Brain Abscesses. by Kielian T, Cheung A, Hickey WF.; 2001 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=100070
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Discrimination of epidemic and nonepidemic methicillin-resistant Staphylococcus aureus strains on the basis of protein A gene polymorphism. by Frenay HM, Theelen JP, Schouls LM, Vandenbroucke-Grauls CM, Verhoef J, van Leeuwen WJ, Mooi FR.; 1994 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=263139
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Disk with High Oxacillin Content Discriminates between Methicillin-Resistant and Borderline Methicillin-Susceptible Staphylococcus aureus Strains in Disk Diffusion Assays Using a Low Salt Concentration. by Petersson AC, Kamme C, Miorner H.; 1999 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=85027
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Dissemination of New Methicillin-Resistant Staphylococcus aureus Clones in the Community. by Okuma K, Iwakawa K, Turnidge JD, Grubb WB, Bell JM, O'Brien FG, Coombs GW, Pearman JW, Tenover FC, Kapi M, Tiensasitorn C, Ito T, Hiramatsu K.; 2002 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=139674
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Dissemination of Two Methicillin-Resistant Staphylococcus aureus Clones Exhibiting Negative Staphylase Reactions in Intensive Care Units. by Hsueh PR, Teng LJ, Yang PC, Pan HJ, Chen YC, Wang LH, Ho SW, Luh KT.; 1999 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=84445
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Diversity and stability of restriction enzyme profiles of plasmid DNA from methicillin-resistant Staphylococcus aureus. by Zuccarelli AJ, Roy I, Harding GP, Couperus JJ.; 1990 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=269544
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DNA fingerprinting by pulsed-field gel electrophoresis is more effective than ribotyping in distinguishing among methicillin-resistant Staphylococcus aureus isolates. by Prevost G, Jaulhac B, Piemont Y.; 1992 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=265195
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DNA fingerprinting of isolates of Staphylococcus aureus from newborns and their contacts. by Tveten Y, Kristiansen BE, Ask E, Jenkins A, Hofstad T.; 1991 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=269952
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DNA polymorphisms in methicillin-susceptible and methicillin-resistant strains of Staphylococcus aureus. by Carles-Nurit MJ, Christophle B, Broche S, Gouby A, Bouziges N, Ramuz M.; 1992 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=265449
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Effect of Duplicate Isolates of Methicillin-Susceptible and Methicillin-Resistant Staphylococcus aureus on Antibiogram Data. by Horvat RT, Klutman NE, Lacy MK, Grauer D, Wilson M.; 2003 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=254318
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Effect of highly purified coagulase and culture filtrate on virulence and immunity of a coagulase-negative mutant of Staphylococcus aureus BB. by Hasegawa N, Kondo I, Hoshina S, Kurosaka K, Igarashi H.; 1983 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=348089
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Effects of Amoxicillin, Gentamicin, and Moxifloxacin on the Hemolytic Activity of Staphylococcus aureus In Vitro and In Vivo. by Worlitzsch D, Kaygin H, Steinhuber A, Dalhoff A, Botzenhart K, Doring G.; 2001 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=90260
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Effects of growth of methicillin-resistant and -susceptible Staphylococcus aureus in the presence of beta-lactams on peptidoglycan structure and susceptibility to lytic enzymes. by Qoronfleh MW, Wilkinson BJ.; 1986 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=176386
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Effects of in vitro and in vivo growth conditions on expression of type 8 capsular polysaccharide by Staphylococcus aureus. by Lee JC, Takeda S, Livolsi PJ, Paoletti LC.; 1993 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=280775
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Effects of temperature, NaCl, and methicillin on penicillin-binding proteins, growth, peptidoglycan synthesis, and autolysis in methicillin-resistant Staphylococcus aureus. by Madiraju MV, Brunner DP, Wilkinson BJ.; 1987 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=175029
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Efficacies of Moxifloxacin, Ciprofloxacin, and Vancomycin against Experimental Endocarditis Due to Methicillin-Resistant Staphylococcus aureus Expressing Various Degrees of Ciprofloxacin Resistance. by Entenza JM, Que YA, Vouillamoz J, Glauser MP, Moreillon P.; 2001 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=90785
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Efficacy of Linezolid in Treatment of Experimental Endocarditis Caused by Methicillin-Resistant Staphylococcus aureus. by Dailey CF, Dileto-Fang CL, Buchanan LV, Oramas-Shirey MP, Batts DH, Ford CW, Gibson JK.; 2001 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=90646
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Efflux Pump-Mediated Quinolone Resistance in Staphylococcus aureus Strains Wild Type for gyrA, gyrB, grlA, and norA. by Munoz-Bellido JL, Manzanares MA, Andres JA, Zufiaurre MN, Ortiz G, Hernandez MS, Garcia-Rodriguez JA.; 1999 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89076
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Emergence and Spread in French Hospitals of Methicillin-Resistant Staphylococcus aureus with Increasing Susceptibility to Gentamicin and Other Antibiotics. by Lelievre H, Lina G, Jones ME, Olive C, Forey F, Roussel-Delvallez M, Nicolas-Chanoine MH, Bebear CM, Jarlier V, Andremont A, Vandenesch F, Etienne J.; 1999 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=85665
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Emergence of homogeneously methicillin-resistant Staphylococcus aureus. by FungTomc J, Huczko E, Gradelski E, Denbleyker K, Bonner DP, Kessler RE.; 1991 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=270453
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Epidemiologic Genotyping of Methicillin-Resistant Staphylococcus aureus by Pulsed-Field Gel Electrophoresis at a University Hospital and Comparison with Antibiotyping and Protein A and Coagulase Gene Polymorphisms. by Montesinos I, Salido E, Delgado T, Cuervo M, Sierra A.; 2002 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=130756
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Epidemiologic typing and delineation of genetic relatedness of methicillin-resistant Staphylococcus aureus by macrorestriction analysis of genomic DNA by using
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Epidemiologic typing of Staphylococcus aureus by DNA restriction fragment length polymorphisms of rRNA genes: elucidation of the clonal nature of a group of bacteriophage-nontypeable, ciprofloxacin-resistant, methicillin-susceptible S. aureus isolates. by Blumberg HM, Rimland D, Kiehlbauch JA, Terry PM, Wachsmuth IK.; 1992 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=265061
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Epidemiological markers for epidemic strain and carrier isolates in an outbreak of nosocomial oxacillin-resistant Staphylococcus aureus. by Bouvet A, Fournier JM, Audurier A, Branger C, Orsoni A, Girard C.; 1990 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=267929
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Epidemiological Validation of Pulsed-Field Gel Electrophoresis Patterns for Methicillin-Resistant Staphylococcus aureus. by Blanc DS, Struelens MJ, Deplano A, De Ryck R, Hauser PM, Petignat C, Francioli P.; 2001 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=88369
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Epidemiology and Susceptibility of 3,051 Staphylococcus aureus Isolates from 25 University Hospitals Participating in the European SENTRY Study. by Fluit AC, Wielders CL, Verhoef J, Schmitz FJ.; 2001 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=88419
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epr, which encodes glycylglycine endopeptidase resistance, is homologous to femAB and affects serine content of peptidoglycan cross bridges in Staphylococcus capitis and Staphylococcus aureus. by Sugai M, Fujiwara T, Ohta K, Komatsuzawa H, Ohara M, Suginaka H.; 1997 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=179255
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Equivalence of Lauric Acid and Glycerol Monolaurate as Inhibitors of Signal Transduction in Staphylococcus aureus. by Ruzin A, Novick RP.; 2000 May 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=111339
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Essentiality, Expression, and Characterization of the Class II 3-Hydroxy-3Methylglutaryl Coenzyme A Reductase of Staphylococcus aureus. by Wilding EI, Kim DY, Bryant AP, Gwynn MN, Lunsford RD, McDevitt D, Myers JE Jr, Rosenberg M, Sylvester D, Stauffacher CV, Rodwell VW.; 2000 Sep 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=94663
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Evaluation of a New Medium, Oxacillin Resistance Screening Agar Base, for the Detection of Methicillin-Resistant Staphylococcus aureus from Clinical Specimens. by Simor AE, Goodfellow J, Louie L, Louie M.; 2001 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=88364
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Evaluation of a Novel Medium for Screening Specimens from Hospitalized Patients To Detect Methicillin-Resistant Staphylococcus aureus. by Blanc DS, Wenger A, Bille J.; 2003 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=179788
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Evaluation of a Tetracycline-Inducible Promoter in Staphylococcus aureus In Vitro and In Vivo and Its Application in Demonstrating the Role of sigB in Microcolony Formation. by Bateman BT, Donegan NP, Jarry TM, Palma M, Cheung AL.; 2001 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98881
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Evaluation of a Triplex PCR Assay To Discriminate Staphylococcus aureus from Coagulase-Negative Staphylococci and Determine Methicillin Resistance from Blood Cultures. by Maes N, Magdalena J, Rottiers S, De Gheldre Y, Struelens MJ.; 2002 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=140352
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Evaluation of an Isothermal Signal Amplification Method for Rapid Detection of Methicillin-Resistant Staphylococcus aureus from Patient-Screening Swabs. by Levi K, Bailey C, Bennett A, Marsh P, Cardy DL, Towner KJ.; 2003 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=165283
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Evaluation of CHROMagar Staph. aureus, a New Chromogenic Medium, for Isolation and Presumptive Identification of Staphylococcus aureus from Human Clinical Specimens. by Gaillot O, Wetsch M, Fortineau N, Berche P.; 2000 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=86496
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Evaluation of commercial and standard methodology for determination of oxacillin susceptibility in Staphylococcus aureus. by Skulnick M, Simor AE, Gregson D, Patel M, Small GW, Kreiswirth B, Hathoway D, Low DE.; 1992 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=265428
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Evaluation of Mannitol Salt Agar for Detection of Oxacillin Resistance in Staphylococcus aureus by Disk Diffusion and Agar Screening. by Kampf G, Lecke C, Cimbal AK, Weist K, Ruden H.; 1998 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105027
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Evaluation of new agglutination test for identification of oxacillin-susceptible and oxacillin-resistant Staphylococcus aureus. by Tveten Y.; 1995 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=228156
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Evaluation of Protein A Gene Polymorphic Region DNA Sequencing for Typing of Staphylococcus aureus Strains. by Shopsin B, Gomez M, Montgomery SO, Smith DH, Waddington M, Dodge DE, Bost DA, Riehman M, Naidich S, Kreiswirth BN.; 1999 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=85690
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Evaluation of Three Techniques for Detection of Low-Level Methicillin-Resistant Staphylococcus aureus (MRSA): a Disk Diffusion Method with Cefoxitin and Moxalactam, the Vitek 2 System, and the MRSA-Screen Latex Agglutination Test. by Felten A, Grandry B, Lagrange PH, Casin I.; 2002 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=120619
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Evidence for the geographic spread of a methicillin-resistant Staphylococcus aureus clone between Portugal and Spain. by Sanches IS, Ramirez M, Troni H, Abecassis M, Padua M, Tomasz A, de Lencastre H.; 1995 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=228138
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Evidence that the National Committee for Clinical Laboratory Standards disk test is less sensitive than the screen plate for detection of low-expression-class methicillinresistant Staphylococcus aureus. by Mackenzie AM, Richardson H, Lannigan R, Wood D.; 1995 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=228296
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Evolution of a Vancomycin-Intermediate Staphylococcus aureus Strain In Vivo: Multiple Changes in the Antibiotic Resistance Phenotypes of a Single Lineage of Methicillin-Resistant S. aureus under the Impact of Antibiotics Administered for Chemotherapy. by Sieradzki K, Leski T, Dick J, Borio L, Tomasz A.; 2003 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=153915
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Evolution of an Endemic Methicillin-Resistant Staphylococcus aureus Population in an Australian Hospital from 1967 to 1996. by Givney R, Vickery A, Holliday A, Pegler M, Benn R.; 1998 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=104576
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Evolution of Sporadic Isolates of Methicillin-Resistant Staphylococcus aureus (MRSA) in Hospitals and Their Similarities to Isolates of Community-Acquired MRSA. by Aires de Sousa M, de Lencastre H.; 2003 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=179813
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Evolutionary genomics of Staphylococcus aureus: Insights into the origin of methicillin-resistant strains and the toxic shock syndrome epidemic. by Fitzgerald JR, Sturdevant DE, Mackie SM, Gill SR, Musser JM.; 2001 Jul 17; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=37519
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Examination of Methicillin-Resistant and Methicillin-Susceptible Staphylococcus aureus Mutants with Low-Level Fluoroquinolone Resistance. by Sulavik MC, Barg NL.; 1998 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=106046
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Exfoliatin-Producing Strains Define a Fourth agr Specificity Group in Staphylococcus aureus. by Jarraud S, Lyon GJ, Figueiredo AM, Gerard L, Vandenesch F, Etienne J, Muir TW, Novick RP.; 2000 Nov 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=94802
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Expression of pls, a Gene Closely Associated with the mecA Gene of MethicillinResistant Staphylococcus aureus, Prevents Bacterial Adhesion In Vitro. by Savolainen K, Paulin L, Westerlund-Wikstrom B, Foster TJ, Korhonen TK, Kuusela P.; 2001 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98255
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Expression of Staphylococcus aureus Clumping Factor A in Lactococcus lactis subsp. cremoris Using a New Shuttle Vector. by Que YA, Haefliger JA, Francioli P, Moreillon P.; 2000 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=97637
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Expression of type 8 capsular polysaccharide and production of toxic shock syndrome toxin 1 are associated among vaginal isolates of Staphylococcus aureus. by Lee JC, Liu MJ, Parsonnet J, Arbeit RD.; 1990 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=268243
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Fibronectin Binding Protein and Host Cell Tyrosine Kinase Are Required for Internalization of Staphylococcus aureus by Epithelial Cells. by Dziewanowska K, Patti JM, Deobald CF, Bayles KW, Trumble WR, Bohach GA.; 1999 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=96793
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Fibronectin Bound to the Surface of Staphylococcus aureus Induces Association of Very Late Antigen 5 and Intracellular Signaling Factors with Macrophage Cytoskeleton. by Shinji H, Seki K, Tajima A, Uchida A, Masuda S.; 2003 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=143151
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Fibronectin-Binding Proteins of Staphylococcus aureus Are Involved in Adherence to Human Airway Epithelium. by Mongodin E, Bajolet O, Cutrona J, Bonnet N, Dupuit F, Puchelle E, Bentzmann SD.; 2002 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=127664
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First Report of Methicillin-Resistant Staphylococcus aureus with Reduced Susceptibility to Vancomycin in Thailand. by Trakulsomboon S, Danchaivijitr S, Rongrungruang Y, Dhiraputra C, Susaemgrat W, Ito T, Hiramatsu K.; 2001 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=87781
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Functional Blocking of Staphylococcus aureus Adhesins following Growth in Ex Vivo Media. by Massey RC, Dissanayeke SR, Cameron B, Ferguson D, Foster TJ, Peacock SJ.; 2002 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=128300
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Functional Selection of Vaccine Candidate Peptides from Staphylococcus aureus Whole-Genome Expression Libraries In Vitro. by Weichhart T, Horky M, Sollner J, Gangl S, Henics T, Nagy E, Meinke A, von Gabain A, Fraser CM, Gill SR, Hafner M, von Ahsen U.; 2003 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=166000
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Genetic and Serologic Evaluation of Capsule Production by Bovine Mammary Isolates of Staphylococcus aureus and Other Staphylococcus spp. from Europe and the United States. by Tollersrud T, Kenny K, Reitz AJ Jr, Lee JC.; 2000 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=87170
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Genetic Relationship between Methicillin-Sensitive and Methicillin-Resistant Staphylococcus aureus Strains from France and from International Sources: Delineation of Genomic Groups. by Branger C, Gardye C, Galdbart JO, Deschamps C, Lambert N.; 2003 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=165281
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Genetic Variation among Hospital Isolates of Methicillin-Sensitive Staphylococcus aureus: Evidence for Horizontal Transfer of Virulence Genes. by Moore PC, Lindsay JA.; 2001 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=88236
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Genotyping of Clinical Methicillin-Susceptible Staphylococcus aureus Isolates in a Dutch Teaching Hospital. by Van Dijk Y, Wielders CL, Fluit AC, Paauw A, Diepersloot RJ, Mascini EM.; 2002 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=153415
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Genotyping of Methicillin-Resistant Staphylococcus aureus by Assaying for the Presence of Variable Elements Associated with mecA. by Huygens F, Nimmo GR, Schooneveldt J, Munckhof WJ, Giffard PM.; 2002 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=120667
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Global Regulation of Staphylococcus aureus Genes by Rot. by Said-Salim B, Dunman PM, McAleese FM, Macapagal D, Murphy E, McNamara PJ, Arvidson S, Foster TJ, Projan SJ, Kreiswirth BN.; 2003 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=145333
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Gradual Alterations in Cell Wall Structure and Metabolism in Vancomycin-Resistant Mutants of Staphylococcus aureus. by Sieradzki K, Tomasz A.; 1999 Dec 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=94215
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Harmonization of Pulsed-Field Gel Electrophoresis Protocols for Epidemiological Typing of Strains of Methicillin-Resistant Staphylococcus aureus: a Single Approach Developed by Consensus in 10 European Laboratories and Its Application for Tracing the Spread of Related Strains. by Murchan S, Kaufmann ME, Deplano A, de Ryck R, Struelens M, Zinn CE, Fussing V, Salmenlinna S, Vuopio-Varkila J, El Solh N, Cuny C, Witte W, Tassios PT, Legakis N, van Leeuwen W, van Belkum A, Vindel A, Laconcha I, Garaizar J, Haeggman S, Olsson-Liljequist B, Ransjo U, Coombes G, Cookson B.; 2003 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=153895
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Heterogeneity of cell-associated CP5 expression on Staphylococcus aureus strains demonstrated by flow cytometry. by Poutrel B, Rainard P, Sarradin P.; 1997 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=170518
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Heterogeneous Vancomycin Resistance in Methicillin-Resistant Staphylococcus aureus Strains Isolated in a Large Italian Hospital. by Marchese A, Balistreri G, Tonoli E, Debbia EA, Schito GC.; 2000 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=86227
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High Percentage of Methicillin-Resistant Staphylococcus aureus Isolates with Reduced Susceptibility to Glycopeptides in The Netherlands. by Van Griethuysen A, Van 't Veen A, Buiting A, Walsh T, Kluytmans J.; 2003 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=156556
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High-level mupirocin resistance in Staphylococcus aureus: evidence for two distinct isoleucyl-tRNA synthetases. by Gilbart J, Perry CR, Slocombe B.; 1993 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=187600
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How Clonal Is Staphylococcus aureus? by Feil EJ, Cooper JE, Grundmann H, Robinson DA, Enright MC, Berendt T, Peacock SJ, Smith JM, Murphy M, Spratt BG, Moore CE, Day NP.; 2003 Jun 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=155367
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Identification and Analysis of Staphylococcus aureus Components Expressed by a Model System of Growth in Serum. by Wiltshire MD, Foster SJ.; 2001 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98621
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Identification and Characterization of a Novel 38.5-Kilodalton Cell Surface Protein of Staphylococcus aureus with Extended-Spectrum Binding Activity for Extracellular Matrix and Plasma Proteins. by Hussain M, Becker K, von Eiff C, Schrenzel J, Peters G, Herrmann M.; 2001 Dec 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=95517
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Identification and Characterization of a Second Superoxide Dismutase Gene (sodM) from Staphylococcus aureus. by Valderas MW, Hart ME.; 2001 Jun 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=99638
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Identification and Characterization of Phage Variants of a Strain of Epidemic Methicillin-Resistant Staphylococcus aureus (EMRSA-15). by O'Neill GL, Murchan S, Gil-Setas A, Aucken HM.; 2001 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=87967
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Identification and Characterization of SirA, an Iron-Regulated Protein from Staphylococcus aureus. by Heinrichs JH, Gatlin LE, Kunsch C, Choi GH, Hanson MS.; 1999 Mar 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=93531
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Identification and characterization of the pckA gene from Staphylococcus aureus. by Scovill WH, Schreier HJ, Bayles KW.; 1996 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=178095
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Identification in Methicillin-Susceptible Staphylococcus hominis of an Active Primordial Mobile Genetic Element for the Staphylococcal Cassette Chromosome mec of Methicillin-Resistant Staphylococcus aureus. by Katayama Y, Takeuchi F, Ito T, Ma XX, Ui-Mizutani Y, Kobayashi I, Hiramatsu K.; 2003 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=154413
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Identification of a Novel Methicillin-Resistant Staphylococcus aureus Epidemic Clone in Cordoba, Argentina, Involved in Nosocomial Infections. by Sola C, Gribaudo G, Vindel A, Patrito L, Bocco JL.; 2002 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=140375
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Identification of a Novel Two-Component Regulatory System That Acts in Global Regulation of Virulence Factors of Staphylococcus aureus. by Yarwood JM, McCormick JK, Schlievert PM.; 2001 Feb 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=94983
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Identification of Aminoglycoside-Modifying Enzymes by Susceptibility Testing: Epidemiology of Methicillin-Resistant Staphylococcus aureus in Japan. by Ida T, Okamoto R, Shimauchi C, Okubo T, Kuga A, Inoue M.; 2001 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=88306
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Identification of the Staphylococcus aureus etd Pathogenicity Island Which Encodes a Novel Exfoliative Toxin, ETD, and EDIN-B. by Yamaguchi T, Nishifuji K, Sasaki M, Fudaba Y, Aepfelbacher M, Takata T, Ohara M, Komatsuzawa H, Amagai M, Sugai M.; 2002 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=128317
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Identification, Cloning, and Initial Characterization of rot, a Locus Encoding a Regulator of Virulence Factor Expression in Staphylococcus aureus. by McNamara PJ, Milligan-Monroe KC, Khalili S, Proctor RA.; 2000 Jun 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=94507
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Immunization with Alpha-Toxin Toxoid Protects the Cornea against Tissue Damage during Experimental Staphylococcus aureus Keratitis. by Hume EB, Dajcs JJ, Moreau JM, O'Callaghan RJ.; 2000 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=101573
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Impact of the High-Affinity Proline Permease Gene (putP) on the Virulence of Staphylococcus aureus in Experimental Endocarditis. by Bayer AS, Coulter SN, Stover CK, Schwan WR.; 1999 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=96381
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Importance of penicillinase production for activity of penicillin alone or in combination with sulbactam in experimental endocarditis due to methicillin-resistant Staphylococcus aureus. by Fantin B, Pierre J, Castela-Papin N, Saint-Julien L, Drugeon H, Farinotti R, Carbon C.; 1996 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=163295
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Improved Detection of Methicillin-Resistant Staphylococcus aureus Using Phenyl Mannitol Broth Containing Aztreonam and Ceftizoxime. by Wertheim H, Verbrugh HA, van Pelt C, de Man P, van Belkum A, Vos MC.; 2001 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=88205
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In Staphylococcus aureus, Fur Is an Interactive Regulator with PerR, Contributes to Virulence, and Is Necessary for Oxidative Stress Resistance through Positive Regulation of Catalase and Iron Homeostasis. by Horsburgh MJ, Ingham E, Foster SJ.; 2001 Jan 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=94901
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In Vitro Activities of Novel Nonfluorinated Quinolones PGE 9262932 and PGE 9509924 against Clinical Isolates of Staphylococcus aureus and Streptococcus pneumoniae with Defined Mutations in DNA Gyrase and Topoisomerase IV. by Jones ME, Critchley IA, Karlowsky JA, Blosser-Middleton RS, Schmitz FJ, Thornsberry C, Sahm DF.; 2002 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=127266
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In Vitro Activities of Six Quinolones and Mechanisms of Resistance in Staphylococcus aureus and Coagulase-Negative Staphylococci. by Linde HJ, Schmidt M, Fuchs E, Reischl U, Niller HH, Lehn N.; 2001 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=90505
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In Vitro Bactericidal Activities of Daptomycin against Staphylococcus aureus and Enterococcus faecalis Are Not Mediated by Inhibition of Lipoteichoic Acid Biosynthesis. by Laganas V, Alder J, Silverman JA.; 2003 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=166111
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In Vitro Serial Passage of Staphylococcus aureus: Changes in Physiology, Virulence Factor Production, and agr Nucleotide Sequence. by Somerville GA, Beres SB, Fitzgerald JR, DeLeo FR, Cole RL, Hoff JS, Musser JM.; 2002 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=134861
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In vivo selection during pefloxacin therapy of a mutant of Staphylococcus aureus with two mechanisms of fluoroquinolone resistance. by Tankovic J, Desplaces N, Duval J, Courvalin P.; 1994 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=188166
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In vivo stability and discriminatory power of methicillin-resistant Staphylococcus aureus typing by restriction endonuclease analysis of plasmid DNA compared with those of other molecular methods. by Hartstein AI, Phelps CL, Kwok RY, Mulligan ME.; 1995 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=228328
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Increase of methicillin resistance in Staphylococcus aureus caused by deletion of a gene whose product is homologous to lytic enzymes. by Fujimura T, Murakami K.; 1997 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=179542
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Increased cell size and shortened peptidoglycan interpeptide bridge of NaCl-stressed Staphylococcus aureus and their reversal by glycine betaine. by Vijaranakul U, Nadakavukaren MJ, de Jonge BL, Wilkinson BJ, Jayaswal RK.; 1995 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=177291
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Increased Expression of Clumping Factor and Fibronectin-Binding Proteins by hemB Mutants of Staphylococcus aureus Expressing Small Colony Variant Phenotypes. by Vaudaux P, Francois P, Bisognano C, Kelley WL, Lew DP, Schrenzel J, Proctor RA, McNamara PJ, Peters G, Von Eiff C.; 2002 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=128368
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Increased expression of fibronectin-binding proteins by fluoroquinolone-resistant Staphylococcus aureus exposed to subinhibitory levels of ciprofloxacin. by Bisognano C, Vaudaux PE, Lew DP, Ng EY, Hooper DC.; 1997 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=163823
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Increased Glycan Chain Length Distribution and Decreased Susceptibility to Moenomycin in a Vancomycin-Resistant Staphylococcus aureus Mutant. by Komatsuzawa H, Ohta K, Yamada S, Ehlert K, Labischinski H, Kajimura J, Fujiwara T, Sugai M.; 2002 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=126989
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Increased production of penicillin-binding protein 2, increased detection of other penicillin-binding proteins, and decreased coagulase activity associated with glycopeptide resistance in Staphylococcus aureus. by Moreira B, Boyle-Vavra S, deJonge BL, Daum RS.; 1997 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=164006
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Increased Virulence of a Fibronectin-Binding Protein Mutant of Staphylococcus aureus in a Rat Model of Pneumonia. by McElroy MC, Cain DJ, Tyrrell C, Foster TJ, Haslett C.; 2002 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=128079
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Inducible NorA-mediated multidrug resistance in Staphylococcus aureus. by Kaatz GW, Seo SM.; 1995 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=163006
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Induction of macrophage-mediated production of tumor necrosis factor alpha by an L-form derived from Staphylococcus aureus. by Kuwano K, Akashi A, Matsu-ura I, Nishimoto M, Arai S.; 1993 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=280754
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Influence of agr on fibrinogen binding in Staphylococcus aureus Newman. by Wolz C, McDevitt D, Foster TJ, Cheung AL.; 1996 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=174199
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Influence of femB on methicillin resistance and peptidoglycan metabolism in Staphylococcus aureus. by Henze U, Sidow T, Wecke J, Labischinski H, Berger-Bachi B.; 1993 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=203954
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Influence of Reduced Susceptibility to Glycopeptides on Activities of Vancomycin and Teicoplanin against Staphylococcus aureus in Experimental Endocarditis. by Pavie J, Lefort A, Ploy MC, Massias L, Chau F, Garry L, Denis F, Fantin B.; 2003 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=155861
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Inhibition by quinolones of DNA gyrase from Staphylococcus aureus. by Tanaka M, Sato K, Kimura Y, Hayakawa I, Osada Y, Nishino T.; 1991 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=245197
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Inhibition of the multidrug transporter NorA prevents emergence of norfloxacin resistance in Staphylococcus aureus. by Markham PN, Neyfakh AA.; 1996 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=163601
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Inhibitory activities of quinolones against DNA gyrase and topoisomerase IV purified from Staphylococcus aureus. by Tanaka M, Onodera Y, Uchida Y, Sato K, Hayakawa I.; 1997 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=164129
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Inhibitory effects of ciprofloxacin and sparfloxacin on DNA gyrase purified from fluoroquinolone-resistant strains of methicillin-resistant Staphylococcus aureus. by Okuda J, Okamoto S, Takahata M, Nishino T.; 1991 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=245373
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Insertional Inactivation of eap in Staphylococcus aureus Strain Newman Confers Reduced Staphylococcal Binding to Fibroblasts. by Hussain M, Haggar A, Heilmann C, Peters G, Flock JI, Herrmann M.; 2002 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=128007
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Intercontinental Spread of a Multidrug-Resistant MethicillinResistant Staphylococcus aureus Clone. by de Sousa MA, Sanches IS, Ferro ML, Vaz MJ, Saraiva Z, Tendeiro T, Serra J, de Lencastre H.; 1998 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105168
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Internalization of Staphylococcus aureus by Endothelial Cells Induces Apoptosis. by Menzies BE, Kourteva I.; 1998 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=108759
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Internalization of Staphylococcus aureus by endothelial cells induces cytokine gene expression. by Yao L, Bengualid V, Lowy FD, Gibbons JJ, Hatcher VB, Berman JW.; 1995 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=173232
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International Multicenter Evaluation of Latex Agglutination Tests for Identification of Staphylococcus aureus. by van Griethuysen A, Bes M, Etienne J, Zbinden R, Kluytmans J.; 2001 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=87684
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Introduction of a norA Promoter Region Mutation into the Chromosome of a Fluoroquinolone-Susceptible Strain of Staphylococcus aureus Using Plasmid Integration. by Kaatz GW, Seo SM, Foster TJ.; 1999 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89450
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Introduction of the mec Element (Methicillin Resistance) into Staphylococcus aureus Alters In Vitro Functional Activities of Fibrinogen and Fibronectin Adhesins. by Vaudaux PE, Monzillo V, Francois P, Lew DP, Foster TJ, Berger-Bachi B.; 1998 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105499
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Involvement of Mitogen-Activated Protein Kinase Pathways in Staphylococcus aureus Invasion of Normal Osteoblasts. by Ellington JK, Elhofy A, Bost KL, Hudson MC.; 2001 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98631
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Involvement of multiple genetic determinants in high-level methicillin resistance in Staphylococcus aureus. by Murakami K, Tomasz A.; 1989 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=209677
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Isolation and characterization of autolysis-defective mutants of Staphylococcus aureus created by Tn917-lacZ mutagenesis. by Mani N, Tobin P, Jayaswal RK.; 1993 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=193237
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Jumping the Barrier to [beta]-Lactam Resistance in Staphylococcus aureus. by Katayama Y, Zhang HZ, Hong D, Chambers HF.; 2003 Sep 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=193760
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Katanosin B and Plusbacin A3, Inhibitors of Peptidoglycan Synthesis in MethicillinResistant Staphylococcus aureus. by Maki H, Miura K, Yamano Y.; 2001 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=90552
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Killing of Staphylococcus aureus by C-8-Methoxy Fluoroquinolones. by Zhao X, Wang JY, Xu C, Dong Y, Zhou J, Domagala J, Drlica K.; 1998 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105579
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Lack of Evidence for Involvement of Hypermutability in Emergence of VancomycinIntermediate Staphylococcus aureus. by O'Neill AJ, Chopra I.; 2003 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=152534
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Localized perforation of the cell wall by a major autolysin: atl gene products and the onset of penicillin-induced lysis of Staphylococcus aureus. by Sugai M, Yamada S, Nakashima S, Komatsuzawa H, Matsumoto A, Oshida T, Suginaka H.; 1997 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=179060
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Low Concentrations of Mupirocin in the Pharynx following Intranasal Application May Contribute to Mupirocin Resistance in Methicillin-Resistant Staphylococcus aureus. by Watanabe H, Masaki H, Asoh N, Watanabe K, Oishi K, Kobayashi S, Sato A, Sugita R, Nagatake T.; 2001 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=88432
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Macrolide antibiotics inhibit 50S ribosomal subunit assembly in Bacillus subtilis and Staphylococcus aureus. by Champney WS, Burdine R.; 1995 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=162898
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mecA-blaZ Corepressors in Clinical Staphylococcus aureus Isolates. by Rosato AE, Kreiswirth BN, Craig WA, Eisner W, Climo MW, Archer GL.; 2003 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=152515
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Mechanism and Suppression of Lysostaphin Resistance in Oxacillin-Resistant Staphylococcus aureus. by Climo MW, Ehlert K, Archer GL.; 2001 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=90484
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Mechanism of Action of Melaleuca alternifolia (Tea Tree) Oil on Staphylococcus aureus Determined by Time-Kill, Lysis, Leakage, and Salt Tolerance Assays and Electron Microscopy. by Carson CF, Mee BJ, Riley TV.; 2002 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=127210
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Mechanisms and Frequency of Resistance to Gatifloxacin in Comparison to AM-1121 and Ciprofloxacin in Staphylococcus aureus. by Ince D, Hooper DC.; 2001 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=90727
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Mechanisms of fluoroquinolone resistance in genetically related strains of Staphylococcus aureus. by Kaatz GW, Seo SM.; 1997 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=164198
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Methicillin-Resistant Staphylococcus aureus Clonal Types in the Czech Republic. by Melter O, Santos Sanches I, Schindler J, Aires de Sousa M, Mato R, Kovarova V, Zemlickova H, de Lencastre H.; 1999 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=85383
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Methicillin-resistant Staphylococcus aureus isolates recovered from a New York City hospital: analysis by molecular fingerprinting techniques. by de Lencastre H, de Lencastre A, Tomasz A.; 1996 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229201
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Methicillin-Resistant Staphylococcus aureus Outbreak in a Veterinary Teaching Hospital: Potential Human-to-Animal Transmission. by Seguin JC, Walker RD, Caron JP, Kloos WE, George CG, Hollis RJ, Jones RN, Pfaller MA.; 1999 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=84801
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Methicillin-Resistant Staphylococcus aureus: Comparison of Susceptibility Testing Methods and Analysis of mecA-Positive Susceptible Strains. by Sakoulas G, Gold HS, Venkataraman L, DeGirolami PC, Eliopoulos GM, Qian Q.; 2001 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=88469
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Methicillin-Resistant, Quinupristin-Dalfopristin-Resistant Staphylococcus aureus with Reduced Sensitivity to Glycopeptides. by Werner G, Cuny C, Schmitz FJ, Witte W.; 2001 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=88393
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mgr, a Novel Global Regulator in Staphylococcus aureus. by Luong TT, Newell SW, Lee CY.; 2003 Jul 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=161569
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Microarray Transcription Analysis of Clinical Staphylococcus aureus Isolates Resistant to Vancomycin. by Mongodin E, Finan J, Climo MW, Rosato A, Gill S, Archer GL.; 2003 Aug 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=165753
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Microbiologic Surveillance Using Nasal Cultures Alone Is Sufficient for Detection of Methicillin-Resistant Staphylococcus aureus Isolates in Neonates. by Singh K, Gavin PJ, Vescio T, Thomson, Jr. RB, Deddish RB, Fisher A, Noskin GA, Peterson LR.; 2003 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=156533
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Modulation of Neutrophil Chemokine Receptors by Staphylococcus aureus Supernate. by Veldkamp KE, Heezius HC, Verhoef J, van Strijp JA, van Kessel KP.; 2000 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=101553
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Molecular Analysis of Methicillin-Resistant Staphylococcus aureus as a Causative Agent of Bronchopulmonary Infection: Relation to Colonization in the Upper Respiratory Tract. by Watanabe H, Masaki H, Asoh N, Watanabe K, Oishi K, Kobayashi S, Sato A, Nagatake T.; 2000 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=87496
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Molecular Analysis of Staphylococcus aureus Blood Isolates Shows Lack of Polyclonal Bacteremia. by Khatib R, Sharma M, Naqvi SA, Riederer K, Almoujahed MO, Fakih MG.; 2003 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=153877
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Molecular Characterization of a Novel Staphylococcus aureus Serine Protease Operon. by Reed SB, Wesson CA, Liou LE, Trumble WR, Schlievert PM, Bohach GA, Bayles KW.; 2001 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98051
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Molecular characterization of epidemic ciprofloxacin- and methicillin-resistant Staphylococcus aureus strains colonizing patients in an intensive care unit. by Udo EE, al-Obaid IA, Jacob LE, Chugh TD.; 1996 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229496
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Molecular Cloning and Analysis of a Putative Siderophore ABC Transporter from Staphylococcus aureus. by Morrissey JA, Cockayne A, Hill PJ, Williams P.; 2000 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=97710
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Molecular Epidemiology of Methicillin-Resistant Staphylococcus aureus Strains Causing Neonatal Toxic Shock Syndrome-Like Exanthematous Disease in Neonatal and Perinatal Wards. by Kikuchi K, Takahashi N, Piao C, Totsuka K, Nishida H, Uchiyama T.; 2003 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=165377
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Molecular Epidemiology of Staphylococcus aureus and Enterococcus faecalis in Endophthalmitis. by Booth MC, Hatter KL, Miller D, Davis J, Kowalski R, Parke DW, Chodosh J, Jett BD, Callegan MC, Penland R, Gilmore MS.; 1998 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=107899
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Molecular genotyping of methicillin-resistant Staphylococcus aureus via fluorophoreenhanced repetitive-sequence PCR. by Del Vecchio VG, Petroziello JM, Gress MJ, McCleskey FK, Melcher GP, Crouch HK, Lupski JR.; 1995 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=228351
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Molecular Genotyping of Staphylococcus aureus Strains: Comparison of Repetitive Element Sequence-Based PCR with Various Typing Methods and Isolation of a Novel Epidemicity Marker. by van der Zee A, Verbakel H, van Zon JC, Frenay I, van Belkum A, Peeters M, Buiting A, Bergmans A.; 1999 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=84303
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Molecular population genetic analysis of Staphylococcus aureus recovered from cows. by Kapur V, Sischo WM, Greer RS, Whittam TS, Musser JM.; 1995 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=227951
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Molecular Typing of Methicillin-Resistant Staphylococcus aureus: Can PCR Replace Pulsed-Field Gel Electrophoresis? by Stranden A, Frei R, Widmer AF.; 2003 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=165370
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Morphological and Genetic Differences in Two Isogenic Staphylococcus aureus Strains with Decreased Susceptibilities to Vancomycin. by Reipert A, Ehlert K, Kast T, Bierbaum G.; 2003 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=151770
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Moxifloxacin Efficacy and Vitreous Penetration in a Rabbit Model of Staphylococcus aureus Endophthalmitis and Effect on Gene Expression of Leucotoxins and Virulence Regulator Factors. by Bronner S, Jehl F, Peter JD, Ploy MC, Renault C, Arvis P, Monteil H, Prevost G.; 2003 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=153310
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MprF-Mediated Lysinylation of Phospholipids in Staphylococcus aureus Leads to Protection against Oxygen-Independent Neutrophil Killing. by Kristian SA, Durr M, Van Strijp JA, Neumeister B, Peschel A.; 2003 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=143157
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Multicenter evaluation of arbitrarily primed PCR for typing of Staphylococcus aureus strains. by van Belkum A, Kluytmans J, van Leeuwen W, Bax R, Quint W, Peters E, Fluit A, Vandenbroucke-Grauls C, van den Brule A, Koeleman H.; 1995 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=228211
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Multicenter Evaluation of Epidemiological Typing of Methicillin-Resistant Staphylococcus aureus Strains by Repetitive-Element PCR Analysis. by Deplano A, Schuermans A, Van Eldere J, Witte W, Meugnier H, Etienne J, Grundmann H, Jonas D, Noordhoek GT, Dijkstra J, van Belkum A, van Leeuwen W, Tassios PT, Legakis NJ, van der Zee A, Bergmans A, Blanc DS, Tenover FC, Cookson BC, O'Neil G, Struelens MJ.; 2000 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=87431
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Multilocus Sequence Typing for Characterization of Methicillin-Resistant and Methicillin-Susceptible Clones of Staphylococcus aureus. by Enright MC, Day NP, Davies CE, Peacock SJ, Spratt BG.; 2000 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=86325
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Multilocus Sequence Typing of Staphylococcus aureus with DNA Array Technology. by van Leeuwen WB, Jay C, Snijders S, Durin N, Lacroix B, Verbrugh HA, Enright MC, Troesch A, van Belkum A.; 2003 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=165280
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Multiple mechanisms of methicillin resistance and improved methods for detection in clinical isolates of Staphylococcus aureus. by de Lencastre H, Sa Figueiredo AM, Urban C, Rahal J, Tomasz A.; 1991 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=245071
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Multiplex PCR for Detection of Genes for Staphylococcus aureus Enterotoxins, Exfoliative Toxins, Toxic Shock Syndrome Toxin 1, and Methicillin Resistance. by Mehrotra M, Wang G, Johnson WM.; 2000 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=86330
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Multiplex PCR for Simultaneous Identification of Staphylococcus aureus and Detection of Methicillin and Mupirocin Resistance. by Perez-Roth E, Claverie-Martin F, Villar J, Mendez-Alvarez S.; 2001 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=88484
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Multiplex PCR Strategy for Rapid Identification of Structural Types and Variants of the mec Element in Methicillin-Resistant Staphylococcus aureus. by Oliveira DC, Lencastre HD.; 2002 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=127318
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Mutations Affecting the Rossman Fold of Isoleucyl-tRNA Synthetase Are Correlated with Low-Level Mupirocin Resistance in Staphylococcus aureus. by Antonio M, McFerran N, Pallen MJ.; 2002 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=127053
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Mutations in Topoisomerase IV and DNA Gyrase of Staphylococcus aureus: Novel Pleiotropic Effects on Quinolone and Coumarin Activity. by Fournier B, Hooper DC.; 1998 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105466
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New latex reagent using monoclonal antibodies to capsular polysaccharide for reliable identification of both oxacillin-susceptible and oxacillin-resistant Staphylococcus aureus. by Fournier JM, Bouvet A, Mathieu D, Nato F, Boutonnier A, Gerbal R, Brunengo P, Saulnier C, Sagot N, Slizewicz B, et al.; 1993 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=262934
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New mechanism for methicillin resistance in Staphylococcus aureus: clinical isolates that lack the PBP 2a gene and contain normal penicillin-binding proteins with modified penicillin-binding capacity. by Tomasz A, Drugeon HB, de Lencastre HM, Jabes D, McDougall L, Bille J.; 1989 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=172779
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New Method for Typing Staphylococcus aureus Strains: Multiple-Locus VariableNumber Tandem Repeat Analysis of Polymorphism and Genetic Relationships of Clinical Isolates. by Sabat A, Krzyszton-Russjan J, Strzalka W, Filipek R, Kosowska K, Hryniewicz W, Travis J, Potempa J.; 2003 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=153872
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Nosocomial Spread of an Unusual Methicillin-Resistant Staphylococcus aureus Clone That Is Sensitive to All Non-[beta]-Lactam Antibiotics, Including Tobramycin. by Pournaras S, Slavakis A, Polyzou A, Sofianou D, Maniatis AN, Tsakris A.; 2001 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=87820
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Novel Type of Staphylococcal Cassette Chromosome mec Identified in CommunityAcquired Methicillin-Resistant Staphylococcus aureus Strains. by Ma XX, Ito T, Tiensasitorn C, Jamklang M, Chongtrakool P, Boyle-Vavra S, Daum RS, Hiramatsu K.; 2002 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=127097
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Nucleotide sequence and characterization of the Staphylococcus aureus norA gene, which confers resistance to quinolones. by Yoshida H, Bogaki M, Nakamura S, Ubukata K, Konno M.; 1990 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=210814
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Numerical analysis of electrophoretic protein patterns of methicillin-resistant strains of Staphylococcus aureus. by Costas M, Cookson BD, Talsania HG, Owen RJ.; 1989 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=267079
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On the nature and use of randomly amplified DNA from Staphylococcus aureus. by van Leeuwen W, Sijmons M, Sluijs J, Verbrugh H, van Belkum A.; 1996 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229402
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Optimal Inoculation Methods and Quality Control for the NCCLS Oxacillin Agar Screen Test for Detection of Oxacillin Resistance in Staphylococcus aureus. by Swenson JM, Spargo J, Tenover FC, Ferraro MJ.; 2001 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=88434
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Outbreak of Methicillin-Resistant Staphylococcus aureus with Reduced Susceptibility to Glycopeptides in a Parisian Hospital. by Guerin F, Buu-Hoi A, Mainardi JL, Kac G, Colardelle N, Vaupre S, Gutmann L, Podglajen I.; 2000 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=87166
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Outermost-cell-surface changes in an encapsulated strain of Staphylococcus aureus after preservation by freeze-drying. by Ohtomo T, Yamada T, Yoshida K.; 1988 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=204292
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Overproduction of a 37-kilodalton cytoplasmic protein homologous to NAD+-linked D-lactate dehydrogenase associated with vancomycin resistance in Staphylococcus aureus. by Milewski WM, Boyle-Vavra S, Moreira B, Ebert CC, Daum RS.; 1996 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=163077
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Overproduction of Type 8 Capsular Polysaccharide Augments Staphylococcus aureus Virulence. by Luong TT, Lee CY.; 2002 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=128096
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Oxygen and Carbon Dioxide Regulation of Toxic Shock Syndrome Toxin 1 Production by Staphylococcus aureus MN8. by Yarwood JM, Schlievert PM.; 2000 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=86591
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Penicillin-binding protein 4 overproduction increases beta-lactam resistance in Staphylococcus aureus. by Henze UU, Berger-Bachi B.; 1996 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=163484
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Peptide Deformylase in Staphylococcus aureus: Resistance to Inhibition Is Mediated by Mutations in the Formyltransferase Gene. by Margolis PS, Hackbarth CJ, Young DC, Wang W, Chen D, Yuan Z, White R, Trias J.; 2000 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89968
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Performance of the Chromogenic Medium CHROMagar Staph aureus and the Staphychrom Coagulase Test in the Detection and Identification of Staphylococcus aureus in Clinical Specimens. by Carricajo A, Treny A, Fonsale N, Bes M, Reverdy ME, Gille Y, Aubert G, Freydiere AM.; 2001 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=88188
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PerR Controls Oxidative Stress Resistance and Iron Storage Proteins and Is Required for Virulence in Staphylococcus aureus. by Horsburgh MJ, Clements MO, Crossley H, Ingham E, Foster SJ.; 2001 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98383
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Phage pattern-specific oxacillin-resistant and borderline oxacillin-resistant Staphylococcus aureus in U.S. hospitals: epidemiological significance. by Zierdt CH, Hosein IK, Shively R, MacLowry JD.; 1992 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=265036
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Phagocytosis of mastitis isolates of Staphylococcus aureus and expression of type 5 capsular polysaccharide are influenced by growth in the presence of milk. by Sutra L, Rainard P, Poutrel B.; 1990 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=268157
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Phase variation of slime production in Staphylococcus aureus: implications in colonization and virulence. by Baselga R, Albizu I, De La Cruz M, Del Cacho E, Barberan M, Amorena B.; 1993 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=281244
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Phenotypic and Genotypic Characterization of Nosocomial Staphylococcus aureus Isolates from Trauma Patients. by Na'was T, Hawwari A, Hendrix E, Hebden J, Edelman R, Martin M, Campbell W, Naso R, Schwalbe R, Fattom AI.; 1998 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=104552
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Phenotypic and Molecular Typing of Nosocomial Methicillin-Resistant Staphylococcus aureus Strains Susceptible to Gentamicin Isolated in France from 1995 to 1997. by Galdbart JO, Morvan A, El Solh N.; 2000 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=88693
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Phenotypic characterization of epidemic versus sporadic strains of methicillinresistant Staphylococcus aureus. by Van Wamel WJ, Fluit AC, Wadstrom T, van Dijk H, Verhoef J, Vandenbroucke-Grauls CM.; 1995 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=228266
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Phenotypical and genotypical characterization of epidemic clumping factor-negative, oxacillin-resistant Staphylococcus aureus. by Schwarzkopf A, Karch H, Schmidt H, Lenz W, Heesemann J.; 1993 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=265747
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Plasmid profiles as indicators of the source of contamination of Staphylococcus aureus endemic within poultry processing plants. by Dodd CE, Chaffey BJ, Waites WM.; 1988 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=202693
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Population Studies of Methicillin-Resistant and -Sensitive Staphylococcus aureus Strains Reveal a Lack of Variability in the agrD Gene, Encoding a Staphylococcal Autoinducer Peptide. by van Leeuwen W, van Nieuwenhuizen W, Gijzen C, Verbrugh H, van Belkum A.; 2000 Oct 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=94693
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Practical Disk Diffusion Method for Detection of Inducible Clindamycin Resistance in Staphylococcus aureus and Coagulase-Negative Staphylococci. by Fiebelkorn KR, Crawford SA, McElmeel ML, Jorgensen JH.; 2003 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=254362
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Practical Strategies for Detecting and Confirming Vancomycin-Intermediate Staphylococcus aureus: a Tertiary-Care Hospital Laboratory's Experience. by Marlowe EM, Cohen MD, Hindler JF, Ward KW, Bruckner DA.; 2001 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=88198
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Predominant Staphylococcus aureus Isolated from Antibiotic-Associated Diarrhea Is Clinically Relevant and Produces Enterotoxin A and the Bicomponent Toxin LukELukD. by Gravet A, Rondeau M, Harf-Monteil C, Grunenberger F, Monteil H, Scheftel JM, Prevost G.; 1999 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=85868
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Prevalence of agr Specificity Groups among Staphylococcus aureus Strains Colonizing Children and Their Guardians. by Shopsin B, Mathema B, Alcabes P, SaidSalim B, Lina G, Matsuka A, Martinez J, Kreiswirth BN.; 2003 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=149583
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Prevalence of capsular polysaccharide types 5 and 8 among Staphylococcus aureus isolates from cow, goat, and ewe milk. by Poutrel B, Boutonnier A, Sutra L, Fournier JM.; 1988 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=266176
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Prevalence of Genes Encoding Pyrogenic Toxin Superantigens and Exfoliative Toxins among Strains of Staphylococcus aureus Isolated from Blood and Nasal Specimens. by Becker K, Friedrich AW, Lubritz G, Weilert M, Peters G, von Eiff C.; 2003 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=153929
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Quantitation of mecA Transcription in Oxacillin-Resistant Staphylococcus aureus Clinical Isolates. by Rosato AE, Craig WA, Archer GL.; 2003 Jun 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=155368
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Quantitative antibiogram typing using inhibition zone diameters compared with ribotyping for epidemiological typing of methicillin-resistant Staphylococcus aureus. by Blanc DS, Lugeon C, Wenger A, Siegrist HH, Francioli P.; 1994 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=264092
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Quinolone resistance mutations in topoisomerase IV: relationship to the flqA locus and genetic evidence that topoisomerase IV is the primary target and DNA gyrase is the secondary target of fluoroquinolones in Staphylococcus aureus. by Ng EY, Trucksis M, Hooper DC.; 1996 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=163434
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Random amplified polymorphic DNA assay is less discriminant than pulsed-field gel electrophoresis for typing strains of methicillin-resistant Staphylococcus aureus. by Saulnier P, Bourneix C, Prevost G, Andremont A.; 1993 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=263599
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Rapid and Specific Detection of Toxigenic Staphylococcus aureus: Use of Two Multiplex PCR Enzyme Immunoassays for Amplification and Hybridization of Staphylococcal Enterotoxin Genes, Exfoliative Toxin Genes, and Toxic Shock Syndrome Toxin 1 Gene. by Becker K, Roth R, Peters G.; 1998 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105160
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Rapid and Specific Molecular Identification of Methicillin-Resistant Staphylococcus aureus in Endotracheal Aspirates from Mechanically Ventilated Patients. by Vannuffel P, Laterre PF, Bouyer M, Gigi J, Vandercam B, Reynaert M, Gala JL.; 1998 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105052
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Rapid Detection of Epidemic Strains of Methicillin-Resistant Staphylococcus aureus. by Wichelhaus TA, Kern S, Schafer V, Brade V.; 1999 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=84522
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Rapid Detection of Methicillin-Resistant Staphylococcus aureus Directly from Sterile or Nonsterile Clinical Samples by a New Molecular Assay. by Francois P, Pittet D, Bento M, Pepey B, Vaudaux P, Lew D, Schrenzel J.; 2003 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=149566
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Rapid detection of methicillin-resistant Staphylococcus aureus strains not identified by slide agglutination tests. by Kuusela P, Hilden P, Savolainen K, Vuento M, Lyytikainen O, Vuopio-Varkila J.; 1994 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=262985
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Rapid detection of oxacillin-resistant Staphylococcus aureus in blood cultures by an impedance method. by Wu JJ, Huang AH, Dai JH, Chang TC.; 1997 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229767
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Rapid Identification and Typing of Staphylococcus aureus by PCR-Restriction Fragment Length Polymorphism Analysis of the aroA Gene. by Marcos JY, Soriano AC, Salazar MS, Moral CH, Ramos SS, Smeltzer MS, Carrasco GN.; 1999 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=84472
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Rapid Identification of Methicillin-Resistant Staphylococcus aureus and Simultaneous Species Confirmation Using Real-Time Fluorescence PCR. by Reischl U, Linde HJ, Metz M, Leppmeier B, Lehn N.; 2000 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=86833
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Rapid Identification of Methicillin-Resistant Staphylococcus aureus from Positive Blood Cultures by Real-Time Fluorescence PCR. by Tan TY, Corden S, Barnes R, Cookson B.; 2001 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=88580
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Rapid Identification of Staphylococcus aureus and the mecA Gene from BacT/ALERT Blood Culture Bottles by Using the LightCycler System. by Shrestha NK, Tuohy MJ, Hall GS, Isada CM, Procop GW.; 2002 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=120611
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Rapid Identification of Staphylococcus aureus Directly from Blood Cultures by Fluorescence In Situ Hybridization with Peptide Nucleic Acid Probes. by Oliveira K, Procop GW, Wilson D, Coull J, Stender H.; 2002 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=120122
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Rapid PCR-Based Identification of Methicillin-Resistant Staphylococcus aureus from Screening Swabs. by Jonas D, Speck M, Daschner FD, Grundmann H.; 2002 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=130653
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Rapid Screening and Identification of Methicillin-Resistant Staphylococcus aureus from Clinical Samples by Selective-Broth and Real-Time PCR Assay. by Fang H, Hedin G.; 2003 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=165274
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Rapid Solid-Phase Immunoassay for Detection of Methicillin-Resistant Staphylococcus aureus Using Cycling Probe Technology. by Fong WK, Modrusan Z, Mcnevin JP, Marostenmaki J, Zin B, Bekkaoui F.; 2000 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=86959
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Rational design of a global inhibitor of the virulence response in Staphylococcus aureus, based in part on localization of the site of inhibition to the receptor-histidine kinase, AgrC. by Lyon GJ, Mayville P, Muir TW, Novick RP.; 2000 Nov 21; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=27224
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Reaction Difference Rule for Phage Typing of Staphylococcus aureus at 100 Times the Routine Test Dilution. by Aucken HM, Westwell K.; 2002 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=120138
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Reactivity of coagulase-negative staphylococci isolated from cow and goat milk with monoclonal antibodies to Staphylococcus aureus capsular polysaccharide types 5 and 8. by Poutrel B, Mendolia C, Sutra L, Fournier JM.; 1990 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=269607
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Real-Time PCR Assay for Detection of Fluoroquinolone Resistance Associated with grlA Mutations in Staphylococcus aureus. by Lapierre P, Huletsky A, Fortin V, Picard FJ, Roy PH, Ouellette M, Bergeron MG.; 2003 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=165299
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Rebinding of Extracellular Adherence Protein Eap to Staphylococcus aureus Can Occur through a Surface-Bound Neutral Phosphatase. by Flock M, Flock JI.; 2001 Jul 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=95283
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Recognition of Two Groups of Methicillin-Resistant Staphylococcus aureus Strains Based on Epidemiology, Antimicrobial Susceptibility, Hypervariable-Region Type, and Ribotype in Finland. by Salmenlinna S, Vuopio-Varkila J.; 2001 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=88118
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Reconsideration of the role of fibronectin binding in endocarditis caused by Staphylococcus aureus. by Flock JI, Hienz SA, Heimdahl A, Schennings T.; 1996 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=174010
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Recruitment of the mecA Gene Homologue of Staphylococcus sciuri into a Resistance Determinant and Expression of the Resistant Phenotype in Staphylococcus aureus. by Wu SW, de Lencastre H, Tomasz A.; 2001 Apr 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=95156
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Recurrent Staphylococcus aureus bacteremia. by Hartstein AI, Mulligan ME, Morthland VH, Kwok RY.; 1992 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=265130
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Reduced adherence to traumatized rat heart valves by a low-fibronectin-binding mutant of Staphylococcus aureus. by Kuypers JM, Proctor RA.; 1989 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=313447
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Reemergence of Gentamicin-Susceptible Strains of Methicillin-Resistant Staphylococcus aureus in France: a Phylogenetic Approach. by Blanc DS, Francioli P, Le Coustumier A, Gazagne L, Lecaillon E, Gueudet P, Vandenesch F, Etienne J.; 2001 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=88126
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Regulated Antisense RNA Eliminates Alpha-Toxin Virulence in Staphylococcus aureus Infection. by Ji Y, Marra A, Rosenberg M, Woodnutt G.; 1999 Nov 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=94120
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Regulation of the cadA cadmium resistance determinant of Staphylococcus aureus plasmid pI258. by Yoon KP, Misra TK, Silver S.; 1991 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=212533
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Repression of the Staphylococcus aureus Accessory Gene Regulator in Serum and In Vivo. by Yarwood JM, McCormick JK, Paustian ML, Kapur V, Schlievert PM.; 2002 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=134826
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Resistance to Autolysis in Vancomycin-Selected Staphylococcus aureus Isolates Precedes Vancomycin-Intermediate Resistance. by Boyle-Vavra S, Challapalli M, Daum RS.; 2003 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=155830
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Respiratory activity is essential for post-exponential-phase production of type 5 capsular polysaccharide by Staphylococcus aureus. by Dassy B, Fournier JM.; 1996 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=174090
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Reversion of the Glycopeptide Resistance Phenotype in Staphylococcus aureus Clinical Isolates. by Boyle-Vavra S, Berke SK, Lee JC, Daum RS.; 2000 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89670
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RNA III Inhibiting Peptide Inhibits In Vivo Biofilm Formation by Drug-Resistant Staphylococcus aureus. by Giacometti A, Cirioni O, Gov Y, Ghiselli R, Del Prete MS, Mocchegiani F, Saba V, Orlando F, Scalise G, Balaban N, Dell'Acqua G.; 2003 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=155823
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Role of coagulase in a murine model of hematogenous pulmonary infection induced by intravenous injection of Staphylococcus aureus enmeshed in agar beads. by Sawai T, Tomono K, Yanagihara K, Yamamoto Y, Kaku M, Hirakata Y, Koga H, Tashiro T, Kohno S.; 1997 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=174618
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Role of SarA in Virulence Determinant Production and Environmental Signal Transduction in Staphylococcus aureus. by Chan PF, Foster SJ.; 1998 Dec 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=107708
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rRNA Stability in Heat-Killed and UV-Irradiated Enterotoxigenic Staphylococcus aureus and Escherichia coli O157:H7. by McKillip JL, Jaykus LA, Drake M.; 1998 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=106637
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SarA Represses agr Operon Expression in a Purified In Vitro Staphylococcus aureus Transcription System. by Chakrabarti SK, Misra TK.; 2000 Oct 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=94714
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SarS, a SarA Homolog Repressible by agr, Is an Activator of Protein A Synthesis in Staphylococcus aureus. by Cheung AL, Schmidt K, Bateman B, Manna AC.; 2001 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98178
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SarT Influences sarS Expression in Staphylococcus aureus. by Schmidt KA, Manna AC, Cheung AL.; 2003 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=187355
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SarT, a Repressor of [alpha]-Hemolysin in Staphylococcus aureus. by Schmidt KA, Manna AC, Gill S, Cheung AL.; 2001 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98561
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Screening method for recovery of methicillin-resistant Staphylococcus aureus from primary plates. by La Zonby JG, Starzyk MJ.; 1986 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=268872
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Selective Targeting of Topoisomerase IV and DNA Gyrase in Staphylococcus aureus: Different Patterns of Quinolone- Induced Inhibition of DNA Synthesis. by Fournier B, Zhao X, Lu T, Drlica K, Hooper DC.; 2000 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=90029
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Sensitization of Staphylococcus aureus and Escherichia coli to Antibiotics by the Sesquiterpenoids Nerolidol, Farnesol, Bisabolol, and Apritone. by Brehm-Stecher BF, Johnson EA.; 2003 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=201169
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Sequential acquisition of norfloxacin and ofloxacin resistance by methicillin-resistant and -susceptible Staphylococcus aureus. by Hori S, Ohshita Y, Utsui Y, Hiramatsu K.; 1993 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=192379
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Severity of Nonbullous Staphylococcus aureus Impetigo in Children Is Associated with Strains Harboring Genetic Markers for Exfoliative Toxin B, Panton-Valentine Leukocidin, and the Multidrug Resistance Plasmid pSK41. by Koning S, van Belkum A, Snijders S, van Leeuwen W, Verbrugh H, Nouwen J, Op [prime prime or minute]t Veld M, van Suijlekom-Smit LW, van der Wouden JC, Verduin C.; 2003 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=165350
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Sporadic Cases of Staphylococcus aureus Organisms Negative for a Species-Specific 442-Base Pair Chromosomal Fragment. by Sutterlin K, Englert R, Schmidt-Wieland T, Schmitt J.; 2003 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=165375
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Spread and maintenance of a dominant methicillin-resistant Staphylococcus aureus (MRSA) clone during an outbreak of MRSA disease in a Spanish hospital. by Dominguez MA, de Lencastre H, Linares J, Tomasz A.; 1994 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=263946
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Staff carriage of epidemic methicillin-resistant Staphylococcus aureus. by Cookson B, Peters B, Webster M, Phillips I, Rahman M, Noble W.; 1989 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=267597
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Staphylococcal Exanthematous Disease in a Newborn Due to a Virulent MethicillinResistant Staphylococcus aureus Strain Containing the TSST-1 Gene in Europe: an Alert for Neonatologists. by van der Mee-Marquet N, Lina G, Quentin R, YaouancLapalle H, Fievre C, Takahashi N, Etienne J.; 2003 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=254355
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Staphylococcus aureus - induced tumor necrosis factor - related apoptosis - inducing ligand expression mediates apoptosis and caspase-8 activation in infected osteoblasts. by Alexander EH, Rivera FA, Marriott I, Anguita J, Bost KL, Hudson MC.; 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=154098
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Staphylococcus aureus Aconitase Inactivation Unexpectedly Inhibits PostExponential-Phase Growth and Enhances Stationary-Phase Survival. by Somerville GA, Chaussee MS, Morgan CI, Fitzgerald JR, Dorward DW, Reitzer LJ, Musser JM.; 2002 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=130419
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Staphylococcus aureus Agr and Sar Global Regulators Influence Internalization and Induction of Apoptosis. by Wesson CA, Liou LE, Todd KM, Bohach GA, Trumble WR, Bayles KW.; 1998 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=108654
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Staphylococcus aureus agr Genotypes with Enterotoxin Production Capabilities Can Resist Neutrophil Bactericidal Activity. by Mullarky IK, Su C, Frieze N, Park YH, Sordillo LM.; 2001 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=97853
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Staphylococcus aureus Cap5O Has UDP-ManNAc Dehydrogenase Activity and Is Essential for Capsule Expression. by Portoles M, Kiser KB, Bhasin N, Chan KH, Lee JC.; 2001 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=97970
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Staphylococcus aureus Isolated in Cases of Impetigo Produces Both Epidermolysin A or B and LukE-LukD in 78% of 131 Retrospective and Prospective Cases. by Gravet A, Couppie P, Meunier O, Clyti E, Moreau B, Pradinaud R, Monteil H, Prevost G.; 2001 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=88548
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Staphylococcus aureus Isolates from Patients with Kawasaki Disease Express High Levels of Protein A. by Wann ER, Fehringer AP, Ezepchuk YV, Schlievert PM, Bina P, Reiser RF, Hook MM, Leung DY.; 1999 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=96803
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Staphylococcus aureus penicillin-binding protein 4 and intrinsic beta-lactam resistance. by Henze UU, Berger-Bachi B.; 1995 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=162958
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Staphylococcus aureus Protein A Recognizes Platelet gC1qR/p33: a Novel Mechanism for Staphylococcal Interactions with Platelets. by Nguyen T, Ghebrehiwet B, Peerschke EI.; 2000 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=97386
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Staphylococcus aureus proteins that bind to human endothelial cells. by Tompkins DC, Blackwell LJ, Hatcher VB, Elliott DA, O'Hagan-Sotsky C, Lowy FD.; 1992 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=257581
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Staphylococcus aureus Serotype 5 Capsular Polysaccharide Is Antiphagocytic and Enhances Bacterial Virulence in a Murine Bacteremia Model. by Thakker M, Park JS, Carey V, Lee JC.; 1998 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=108646
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Staphylococcus aureus sortase mutants defective in the display of surface proteins and in the pathogenesis of animal infections. by Mazmanian SK, Liu G, Jensen ER, Lenoy E, Schneewind O.; 2000 May 9; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=25859
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Staphylococcus aureus strains which are not identified by rapid agglutination methods are of capsular serotype 5. by Fournier JM, Boutonnier A, Bouvet A.; 1989 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=267559
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Staphylococcus aureus with Heterogeneous Resistance to Vancomycin: Epidemiology, Clinical Significance, and Critical Assessment of Diagnostic Methods. by Liu C, Chambers HF.; 2003 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=201119
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Strain-Dependent Differences in the Regulatory Roles of sarA and agr in Staphylococcus aureus. by Blevins JS, Beenken KE, Elasri MO, Hurlburt BK, Smeltzer MS.; 2002 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=127691
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Structural and Topological Differences between a Glycopeptide-Intermediate Clinical Strain and Glycopeptide-Susceptible Strains of Staphylococcus aureus Revealed by Atomic Force Microscopy. by Boyle-Vavra S, Hahm J, Sibener SJ, Daum RS.; 2000 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=90224
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Structure-activity analysis of synthetic autoinducing thiolactone peptides from Staphylococcus aureus responsible for virulence. by Mayville P, Ji G, Beavis R, Yang H, Goger M, Novick RP, Muir TW.; 1999 Feb 16; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=15443
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Study of Staphylococcus aureus Pathogenic Genes by Transfer and Expression in the Less Virulent Organism Streptococcus gordonii. by Stutzmann Meier P, Entenza JM, Vaudaux P, Francioli P, Glauser MP, Moreillon P.; 2001 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=97936
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Subinhibitory Clindamycin Differentially Inhibits Transcription of Exoprotein Genes in Staphylococcus aureus. by Herbert S, Barry P, Novick RP.; 2001 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98253
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Suppression of autolysis and cell wall turnover in heterogeneous Tn551 mutants of a methicillin-resistant Staphylococcus aureus strain. by de Jonge BL, de Lencastre H, Tomasz A.; 1991 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=207230
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Synthesis of Microcapsule by Staphylococcus aureus Is Not Responsive to Environmental Phosphate Concentrations. by Fox KF, Stewart GC, Fox A.; 1998 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=108475
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Synthetic exfoliative toxin A and B DNA probes for detection of toxigenic Staphylococcus aureus strains. by Rifai S, Barbancon V, Prevost G, Piemont Y.; 1989 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=267347
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Target Preference of 15 Quinolones against Staphylococcus aureus, Based on Antibacterial Activities and Target Inhibition. by Takei M, Fukuda H, Kishii R, Hosaka M.; 2001 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=90866
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Teicoplanin Stress-Selected Mutations Increasing [final sigma]B Activity in Staphylococcus aureus. by Bischoff M, Berger-Bachi B.; 2001 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=90536
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The AbcA Transporter of Staphylococcus aureus Affects Cell Autolysis. by SchraderFischer G, Berger-Bachi B.; 2001 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=90305
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The Carboxyl Terminus of Peptidoglycan Stem Peptides Is a Determinant for Methicillin Resistance in Staphylococcus aureus. by de Jonge BL, Gage, D, Xu N.; 2002 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=128806
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The d-Alanine Residues of Staphylococcus aureus Teichoic Acids Alter the Susceptibility to Vancomycin and the Activity of Autolytic Enzymes. by Peschel A, Vuong C, Otto M, Gotz F.; 2000 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=90160
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The essential Staphylococcus aureus gene fmhB is involved in the first step of peptidoglycan pentaglycine interpeptide formation. by Rohrer S, Ehlert K, Tschierske M, Labischinski H, Berger-Bachi B.; 1999 Aug 3; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=17786
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The evolution of methicillin resistance in Staphylococcus aureus: Similarity of genetic backgrounds in historically early methicillin-susceptible and -resistant isolates and contemporary epidemic clones. by Crisostomo MI, Westh H, Tomasz A, Chung M, Oliveira DC, de Lencastre H.; 2001 Aug 14; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=55544
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The evolutionary history of methicillin-resistant Staphylococcus aureus (MRSA). by Enright MC, Robinson DA, Randle G, Feil EJ, Grundmann H, Spratt BG.; 2002 May 28; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=124322
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The femC locus of Staphylococcus aureus required for methicillin resistance includes the glutamine synthetase operon. by Gustafson J, Strassle A, Hachler H, Kayser FH, Berger-Bachi B.; 1994 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=205213
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The Fibronectin-Binding Proteins of Staphylococcus aureus May Promote Mammary Gland Colonization in a Lactating Mouse Model of Mastitis. by Brouillette E, Talbot BG, Malouin F.; 2003 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=152093
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The Major Cold Shock Gene, cspA, Is Involved in the Susceptibility of Staphylococcus aureus to an Antimicrobial Peptide of Human Cathepsin G. by Katzif S, Danavall D, Bowers S, Balthazar JT, Shafer WM.; 2003 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=166043
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The molecular architecture of the sar locus in Staphylococcus aureus. by Bayer MG, Heinrichs JH, Cheung AL.; 1996 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=178224
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The rel Gene Is Essential for In Vitro Growth of Staphylococcus aureus. by Gentry D, Li T, Rosenberg M, McDevitt D.; 2000 Sep 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=111382
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The Staphylococcus aureus Alternative Sigma Factor [final sigma]B Controls the Environmental Stress Response but Not Starvation Survival or Pathogenicity in a Mouse Abscess Model. by Chan PF, Foster SJ, Ingham E, Clements MO.; 1998 Dec 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=107691
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The Staphylococcus aureus cidAB Operon: Evaluation of Its Role in Regulation of Murein Hydrolase Activity and Penicillin Tolerance. by Rice KC, Firek BA, Nelson JB, Yang SJ, Patton TG, Bayles KW.; 2003 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=152627
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The Staphylococcus aureus lrgAB Operon Modulates Murein Hydrolase Activity and Penicillin Tolerance. by Groicher KH, Firek BA, Fujimoto DF, Bayles KW.; 2000 Apr 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=101860
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The Staphylococcus aureus Map protein is an immunomodulator that interferes with T cell --mediated responses. by Lee LY, Miyamoto YJ, McIntyre BW, Hook M, McCrea KW, McDevitt D, Brown EL.; 2002 Nov 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=151818
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The Superoxide Dismutase Gene sodM Is Unique to Staphylococcus aureus: Absence of sodM in Coagulase-Negative Staphylococci. by Valderas MW, Gatson JW, Wreyford N, Hart ME.; 2002 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=134988
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The TetA(K) Tetracycline/H + Antiporter from Staphylococcus aureus: Mutagenesis and Functional Analysis of Motif C. by Ginn SL, Brown MH, Skurray RA.; 2000 Mar 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=94444
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Three-Year Assessment of Methicillin-Resistant Staphylococcus aureus Clones in Latin America from 1996 to 1998. by Aires de Sousa M, Miragaia M, Santos Sanches I, Avila S, Adamson I, Casagrande ST, Brandileone MC, Palacio R, Dell'Acqua L, Hortal M, Camou T, Rossi A, Velazquez-Meza ME, Echaniz-Aviles G, Solorzano-Santos F, Heitmann I, de Lencastre H.; 2001 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=88111
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Topoisomerase Targeting with and Resistance to Gemifloxacin in Staphylococcus aureus. by Ince D, Zhang X, Silver LC, Hooper DC.; 2003 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=149033
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Toxin Genes and Other Characteristics of Staphylococcus aureus Isolates from Milk of Cows with Mastitis. by Akineden O, Annemuller C, Hassan AA, Lammler C, Wolter W, Zschock M.; 2001 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=96179
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Transcription of Clumping Factor A in Attached and Unattached Staphylococcus aureus In Vitro and during Device-Related Infection. by Wolz C, Goerke C, Landmann R, Zimmerli W, Fluckiger U.; 2002 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=127962
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Transcription Profiling-Based Identification of Staphylococcus aureus Genes Regulated by the agr and/or sarA Loci. by Dunman PM, Murphy E, Haney S, Palacios D, Tucker-Kellogg G, Wu S, Brown EL, Zagursky RJ, Shlaes D, Projan SJ.; 2001 Dec 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=95583
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Transcriptional Induction of the Penicillin-Binding Protein 2 Gene in Staphylococcus aureus by Cell Wall-Active Antibiotics Oxacillin and Vancomycin. by Boyle-Vavra S, Yin S, Challapalli M, Daum RS.; 2003 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=149319
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Transfer of Erythromycin Resistance from Poultry to Human Clinical Strains of Staphylococcus aureus. by Khan SA, Nawaz MS, Khan AA, Cerniglia CE.; 2000 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=86602
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Transport of pefloxacin across the bacterial cytoplasmic membrane in quinolonesusceptible Staphylococcus aureus. by Furet YX, Deshusses J, Pechere JC.; 1992 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=284362
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Two Diarylurea Electron Transport Inhibitors Reduce Staphylococcus aureus Hemolytic Activity and Protect Cultured Endothelial Cells from Lysis. by Proctor RA, Dalal SC, Kahl B, Brar D, Peters G, Nichols WW.; 2002 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=127355
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Two International Methicillin-Resistant Staphylococcus aureus Clones Endemic in a University Hospital in Patras, Greece. by Aires de Sousa M, Bartzavali C, Spiliopoulou I, Santos Sanches I, Crisostomo MI, de Lencastre H.; 2003 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=154747
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Type 5 and 8 capsular polysaccharides are expressed by Staphylococcus aureus isolates from rabbits, poultry, pigs, and horses. by Poutrel B, Sutra L.; 1993 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=262793
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Typing multidrug-resistant Staphylococcus aureus: conflicting epidemiological data produced by genotypic and phenotypic methods clarified by phylogenetic analysis. by Jorgensen M, Givney R, Pegler M, Vickery A, Funnell G.; 1996 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=228805
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Typing of Staphylococcus aureus and Staphylococcus epidermidis strains by PCR analysis of inter-IS256 spacer length polymorphisms. by Deplano A, Vaneechoutte M, Verschraegen G, Struelens MJ.; 1997 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=230014
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Typing of Staphylococcus aureus by PCR for DNA sequences flanked by transposon Tn916 target region and ribosomal binding site. by Cuny C, Witte W.; 1996 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229050
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Typing of Staphylococcus aureus by pulsed-field gel electrophoresis, zymotyping, capsular typing, and phage typing: resolution of clonal relationships. by Schlichting C, Branger C, Fournier JM, Witte W, Boutonnier A, Wolz C, Goullet P, Doring G.; 1993 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=262740
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Unusually large number of methicillin-resistant Staphylococcus aureus clones in a Portuguese hospital. by Couto I, Melo-Cristino J, Fernandes ML, Garcia T, Serrano N, Salgado MJ, Torres-Pereira A, Sanches IS, de Lencastre H.; 1995 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=228330
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Use of Coagulase Gene (coa) Repeat Region Nucleotide Sequences for Typing of Methicillin-Resistant Staphylococcus aureus Strains. by Shopsin B, Gomez M, Waddington M, Riehman M, Kreiswirth BN.; 2000 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=87405
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Use of plasmid analysis and determination of aminoglycoside-modifying enzymes to characterize isolates from an outbreak of methicillin-resistant Staphylococcus aureus. by Licitra CM, Brooks RG, Terry PM, Shaw KJ, Hare RS.; 1989 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=267072
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Validation of Binary Typing for Staphylococcus aureus Strains. by van Leeuwen W, Verbrugh H, van der Velden J, van Leeuwen N, Heck M, van Belkum A.; 1999 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=84511
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Variable Expressions of Staphylococcus aureus Bicomponent Leucotoxins Semiquantified by Competitive Reverse Transcription-PCR. by Bronner S, Stoessel P, Gravet A, Monteil H, Prevost G.; 2000 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=92241
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Variance in Fibronectin Binding and fnb Locus Polymorphisms in Staphylococcus aureus: Identification of Antigenic Variation in a Fibronectin Binding Protein Adhesin of the Epidemic CMRSA-1 Strain of Methicillin-Resistant S. aureus. by Rice K, Huesca M, Vaz D, McGavin MJ.; 2001 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98394
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Variation in Extracellular Protease Production among Clinical Isolates of Staphylococcus aureus Due to Different Levels of Expression of the Protease Repressor sarA. by Karlsson A, Arvidson S.; 2002 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=128181
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Virulence of Staphylococcus aureus mutants altered in type 5 capsule production. by Albus A, Arbeit RD, Lee JC.; 1991 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=258360
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Virulent Combinations of Adhesin and Toxin Genes in Natural Populations of Staphylococcus aureus. by Peacock SJ, Moore CE, Justice A, Kantzanou M, Story L, Mackie K, O'Neill G, Day NP.; 2002 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=128268
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 Staphylococcus aureus, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “Staphylococcus aureus” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for Staphylococcus aureus (hyperlinks lead to article summaries): •
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A hospital-acquired outbreak of methicillin-resistant Staphylococcus aureus infection initiated by a surgeon carrier. Author(s): Wang JT, Chang SC, Ko WJ, Chang YY, Chen ML, Pan HJ, Luh KT. Source: The Journal of Hospital Infection. 2001 February; 47(2): 104-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11170773
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 major methicillin-resistant Staphylococcus aureus clone predominates in Malaysian hospitals. Author(s): Norazah A, Lim VK, Rohani MY, Alfizah H, Koh YT, Kamel AG. Source: Epidemiology and Infection. 2003 June; 130(3): 407-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12825724
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A prospective multicenter study of Staphylococcus aureus bacteremia: incidence of endocarditis, risk factors for mortality, and clinical impact of methicillin resistance. Author(s): Chang FY, MacDonald BB, Peacock JE Jr, Musher DM, Triplett P, Mylotte JM, O'Donnell A, Wagener MM, Yu VL. Source: Medicine; Analytical Reviews of General Medicine, Neurology, Psychiatry, Dermatology, and Pediatrics. 2003 September; 82(5): 322-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14530781
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Activity of moxifloxacin in combination with vancomycin or teicoplanin against Staphylococcus aureus isolated from device-associated infections unresponsive to glycopeptide therapy. Author(s): Tarasi A, Cassone M, Monaco M, Tarasi D, Pompeo ME, Venditti M. Source: J Chemother. 2003 June; 15(3): 239-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12868549
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Additional costs for preventing the spread of methicillin-resistant Staphylococcus aureus and a strategy for reducing these costs on a surgical ward. Author(s): Herr CE, Heckrodt TH, Hofmann FA, Schnettler R, Eikmann TF. Source: Infection Control and Hospital Epidemiology : the Official Journal of the Society of Hospital Epidemiologists of America. 2003 September; 24(9): 673-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14510250
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Adult Staphylococcus scalded skin syndrome in a peritoneal dialysis patient. Author(s): Suzuki R, Iwasaki S, Ito Y, Hasegawa T, Yamamoto T, Ideura T, Yoshimura A. Source: Clinical and Experimental Nephrology. 2003 March; 7(1): 77-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14586749
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agr-dependent bacterial interference has no impact on long-term colonization of Staphylococcus aureus during persistent airway infection of cystic fibrosis patients. Author(s): Kahl BC, Becker K, Friedrich AW, Clasen J, Sinha B, Von Eiff C, Peters G. Source: Journal of Clinical Microbiology. 2003 November; 41(11): 5199-201. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14605162
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Airborne dispersal of Staphylococcus aureus associated with symptomatic rhinitis allergica. Author(s): Bassetti S, Sherertz RJ, Pfaller MA. Source: Annals of Internal Medicine. 2003 August 5; 139(3): W-W60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12899606
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An in vitro resistance study of levofloxacin, ciprofloxacin, and ofloxacin using keratitis isolates of Staphylococcus aureus and Pseudomonas aeruginosa. Author(s): Kowalski RP, Pandya AN, Karenchak LM, Romanowski EG, Husted RC, Ritterband DC, Shah MK, Gordon YJ. Source: Ophthalmology. 2001 October; 108(10): 1826-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11581056
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An outbreak of community-onset methicillin-resistant Staphylococcus aureus skin infections in southwestern Alaska. Author(s): Baggett HC, Hennessy TW, Leman R, Hamlin C, Bruden D, Reasonover A, Martinez P, Butler JC. Source: Infection Control and Hospital Epidemiology : the Official Journal of the Society of Hospital Epidemiologists of America. 2003 June; 24(6): 397-402. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12828314
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Analysis of genomic diversity and evolution of the low-level antiseptic resistance gene smr in Staphylococcus aureus. Author(s): Alam MM, Ishino M, Kobayashi N. Source: Microbial Drug Resistance (Larchmont, N.Y.). 2003; 9 Suppl 1: S1-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14633361
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Antibacterial activity of 2,4-diacetylphloroglucinol produced by Pseudomonas sp. AMSN isolated from a marine alga, against vancomycin-resistant Staphylococcus aureus. Author(s): Isnansetyo A, Cui L, Hiramatsu K, Kamei Y. Source: International Journal of Antimicrobial Agents. 2003 November; 22(5): 545-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14602377
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Antibacterial susceptibility of a vancomycin-resistant Staphylococcus aureus strain isolated at the Hershey Medical Center. Author(s): Bozdogan B, Esel D, Whitener C, Browne FA, Appelbaum PC. Source: The Journal of Antimicrobial Chemotherapy. 2003 November; 52(5): 864-8. Epub 2003 October 16. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14563898
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Antibiotic susceptibility and genotypic characterization of methicillin-resistant Staphylococcus aureus strains in eastern France. Author(s): Bertrand X, Thouverez M, Talon D. Source: The Journal of Hospital Infection. 2000 December; 46(4): 280-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11170759
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Antibiotic susceptibility patterns of respiratory isolates of Staphylococcus aureus in a Turkish university hospital. Author(s): Gonlugur U, Akkurt I, Ozdemir L, Bakici MZ, Icagasioglu S, Gultekin F. Source: Acta Microbiol Pol. 2003; 52(2): 143-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14594401
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Antimicrobial resistance in Staphylococcus aureus at the University of Chicago Hospitals: a 15-year longitudinal assessment in a large university-based hospital. Author(s): Seal JB, Moreira B, Bethel CD, Daum RS. Source: Infection Control and Hospital Epidemiology : the Official Journal of the Society of Hospital Epidemiologists of America. 2003 June; 24(6): 403-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12828315
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Antimicrobial resistance in Staphylococcus aureus in Australian teaching hospitals, 1989-1999. Author(s): Nimmo GR, Bell JM, Mitchell D, Gosbell IB, Pearman JW, Turnidge JD; AGAR. Source: Microbial Drug Resistance (Larchmont, N.Y.). 2003 Summer; 9(2): 155-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12820800
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Antimicrobial susceptibility of Staphylococcus aureus isolates from hospitalized patients and dairy food (fresh cheese): a survey over a decade in southern Switzerland. Author(s): Valsangiacomo C, Dolina M, Peduzzi R, Jaggli M. Source: Clinical Microbiology and Infection : the Official Publication of the European Society of Clinical Microbiology and Infectious Diseases. 2000 July; 6(7): 395-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11168158
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Antimicrobials as potential adjunctive agents in the treatment of biofilm infection with Staphylococcus epidermidis. Author(s): Peck KR, Kim SW, Jung SI, Kim YS, Oh WS, Lee JY, Jin JH, Kim S, Song JH, Kobayashi H. Source: Chemotherapy. 2003 July; 49(4): 189-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12886054
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Aspirin sensitivity and IgE antibodies to Staphylococcus aureus enterotoxins in nasal polyposis: studies on the relationship. Author(s): Perez-Novo CA, Kowalski ML, Kuna P, Ptasinska A, Holtappels G, van Cauwenberge P, Gevaert P, Johannson S, Bachert C. Source: International Archives of Allergy and Immunology. 2004 March; 133(3): 255-60. Epub 2004 February 17. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14976394
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Backbone 1H, 15N and 13C resonance assignments of the Staphylococcus aureus acyl carrier protein synthase (AcpS). Author(s): Liu D, Black T, Macinga DR, Palermo R, Wyss DF. Source: Journal of Biomolecular Nmr. 2002 November; 24(3): 273-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12522316
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Bacteremic pneumococcal cellulitis compared with bacteremic cellulitis caused by Staphylococcus aureus and Streptococcus pyogenes. Author(s): Capdevila O, Grau I, Vadillo M, Cisnal M, Pallares R. Source: European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology. 2003 June; 22(6): 337-41. Epub 2003 June 03. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12783279
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Bactericidal activity of moxifloxacin against Staphylococcus aureus. Author(s): Berrington AW, Perry JD, Gould FK. Source: Clinical Microbiology and Infection : the Official Publication of the European Society of Clinical Microbiology and Infectious Diseases. 2001 March; 7(3): 161-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11318816
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Bactericidal effect of pulsed 1,064 nm Nd:YAG laser light on Staphylococcus epidermidis is of photothermal origin: an in vitro study. Author(s): Gronqvist A, Wistrom J, Axner O, Monsen TJ. Source: Lasers in Surgery and Medicine. 2000; 27(4): 336-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11074510
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Bacteriocin of Enterococcus from lactoserum able to cause oxidative stress in Staphylococcus aureus. Author(s): Eraso AJ, Ines A. Source: Biochemical and Biophysical Research Communications. 2004 February 13; 314(3): 897-901. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14741721
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Bacteriocin production by clinical Staphylococcus isolates. Author(s): Robredo B, Olarte I, Torres C. Source: Revista Espanola De Quimioterapia : Publicacion Oficial De La Sociedad Espanola De Quimioterapia. 2002 September; 15(3): 272-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12582432
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Bacteriostatic activity of human lactoferrin against Staphylococcus aureus is a function of its iron-binding properties and is not influenced by antibiotic resistance. Author(s): Aguila A, Herrera AG, Morrison D, Cosgrove B, Perojo A, Montesinos I, Perez J, Sierra G, Gemmell CG, Brock JH. Source: Fems Immunology and Medical Microbiology. 2001 August; 31(2): 145-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11549422
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Bap, a Staphylococcus aureus surface protein involved in biofilm formation. Author(s): Day NP, Moore CE, Enright MC, Berendt AP, Smith JM, Murphy MF, Peacock SJ, Spratt BG, Feil EJ. Science. 2002 Feb 8;295(5557):971 Source: Journal of Bacteriology. 2001 May; 183(9): 2888-96. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11887789
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Bed utilization of patients with methicillin-resistant Staphylococcus aureus in a Canadian tertiary-care center. Author(s): Cooper CL, Dyck B, Ormiston D, Olekson K, McLeod J, Nicolle LE, Embil JM. Source: Infection Control and Hospital Epidemiology : the Official Journal of the Society of Hospital Epidemiologists of America. 2002 September; 23(9): 483-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12269441
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Bilateral methicillin-resistant Staphylococcus aureus keratitis in a medical resident following an uneventful bilateral photorefractive keratectomy. Author(s): Solomon R, Donnenfeld ED, Perry HD, Biser S. Source: Eye & Contact Lens. 2003 July; 29(3): 187-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12861116
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Binary typing of Staphylococcus aureus strains through reversed hybridization using digoxigenin-universal linkage system-labeled bacterial genomic DNA. Author(s): van Leeuwen W, Libregts C, Schalk M, Veuskens J, Verbrugh H, van Belkum A. Source: Journal of Clinical Microbiology. 2001 January; 39(1): 328-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11136792
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Binding of human clusterin by Staphylococcus epidermidis. Author(s): Li DQ, Ljungh A. Source: Fems Immunology and Medical Microbiology. 2001 October; 31(3): 197-202. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11720815
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Biofilm formation by Staphylococcus epidermidis depends on functional RsbU, an activator of the sigB operon: differential activation mechanisms due to ethanol and salt stress. Author(s): Knobloch JK, Bartscht K, Sabottke A, Rohde H, Feucht HH, Mack D. Source: Journal of Bacteriology. 2001 April; 183(8): 2624-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11274123
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Biofilm testing of Staphylococcus epidermidis clinical isolates: low performance of vancomycin in relation to other antibiotics. Author(s): Monzon M, Oteiza C, Leiva J, Lamata M, Amorena B. Source: Diagnostic Microbiology and Infectious Disease. 2002 December; 44(4): 319-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12543535
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Biological cost and compensatory evolution in fusidic acid-resistant Staphylococcus aureus. Author(s): Nagaev I, Bjorkman J, Andersson DI, Hughes D. Source: Molecular Microbiology. 2001 April; 40(2): 433-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11309125
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Brachyspira (Serpulina) pilosicoli of human origin interfere with the haemolytic activity and the growth of Staphylococcus aureus beta-toxin producer. Author(s): Calderaro A, Dettori G, Ragni P, Guegan R, Arcangeletti MC, Medici MC, Chezzi C. Source: New Microbiol. 2002 April; 25(2): 149-55. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12019720
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Brain abscess caused by methicillin-resistant Staphylococcus aureus. Author(s): Ahlm C, Olsen B, Koskinen LO, Monsen T. Source: Scandinavian Journal of Infectious Diseases. 2000; 32(5): 562-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11055667
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Breast milk transmission of a Panton-Valentine leukocidin-producing Staphylococcus aureus strain causing infantile pneumonia. Author(s): Le Thomas I, Mariani-Kurkdjian P, Collignon A, Gravet A, Clermont O, Brahimi N, Gaudelus J, Aujard Y, Navarro J, Beaufils F, Bingen E. Source: Journal of Clinical Microbiology. 2001 February; 39(2): 728-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11158136
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Breastfeeding and Staphylococcus aureus: three case reports. Author(s): Amir L. Source: Breastfeed Rev. 2002 March; 10(1): 15-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12035967
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Catalase-negative Staphylococcus aureus: a rare cause of catheter-related bacteremia. Author(s): Friedberg B, Hauer E, Belkhirat M, Watine J, Le Coustumier A. Source: Clinical Microbiology and Infection : the Official Publication of the European Society of Clinical Microbiology and Infectious Diseases. 2003 December; 9(12): 1253-5. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14686997
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Changes in drug susceptibility and toxin genes in Staphylococcus aureus isolated from blood cultures at a university hospital. Author(s): Endo H, Higurashi Y, Okuzumi K, Hitomi S, Kimura S. Source: Journal of Infection and Chemotherapy : Official Journal of the Japan Society of Chemotherapy. 2004 February; 10(1): 8-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14991511
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Characterization of a protective monoclonal antibody recognizing Staphylococcus aureus MSCRAMM protein clumping factor A. Author(s): Hall AE, Domanski PJ, Patel PR, Vernachio JH, Syribeys PJ, Gorovits EL, Johnson MA, Ross JM, Hutchins JT, Patti JM. Source: Infection and Immunity. 2003 December; 71(12): 6864-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14638774
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Characterization of isolates of methicillin-resistant Staphylococcus aureus from Hong Kong by phage typing, pulsed-field gel electrophoresis, and fluorescent amplifiedfragment length polymorphism analysis. Author(s): Ip M, Lyon DJ, Chio F, Enright MC, Cheng AF. Source: Journal of Clinical Microbiology. 2003 November; 41(11): 4980-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14605127
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Ciprofloxacin and levofloxacin resistance among methicillin-sensitive Staphylococcus aureus isolates from keratitis and conjunctivitis. Author(s): Marangon FB, Miller D, Muallem MS, Romano AC, Alfonso EC. Source: American Journal of Ophthalmology. 2004 March; 137(3): 453-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15013867
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Clinical experience with Staphylococcus lugdunensis bacteremia: a retrospective analysis. Author(s): Ebright JR, Penugonda N, Brown W. Source: Diagnostic Microbiology and Infectious Disease. 2004 January; 48(1): 17-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14761717
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Clinical features associated with bacteremia due to heterogeneous vancomycinintermediate Staphylococcus aureus. Author(s): Charles PG, Ward PB, Johnson PD, Howden BP, Grayson ML. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2004 February 1; 38(3): 448-51. Epub 2004 January 12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14727222
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Clinical Staphylococcus aureus isolate negative for the Sa442 fragment. Author(s): Klaassen CH, de Valk HA, Horrevorts AM. Source: Journal of Clinical Microbiology. 2003 September; 41(9): 4493. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12958306
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Clonal characterization of Staphylococcus aureus by multilocus restriction fragment typing, a rapid screening approach for molecular epidemiology. Author(s): Diep BA, Perdreau-Remington F, Sensabaugh GF. Source: Journal of Clinical Microbiology. 2003 October; 41(10): 4559-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14532182
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Comment on "First report of a catalase-negative methicillin-resistant Staphylococcus aureus". Author(s): Watine J, Friedberg B, Le Coustumier A. Source: Diagnostic Microbiology and Infectious Disease. 2003 October; 47(2): 451-2; Author Reply 452. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14522521
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Community-acquired methicillin-resistant Staphylococcus aureus carrying PantonValentine leukocidin genes: worldwide emergence. Author(s): Vandenesch F, Naimi T, Enright MC, Lina G, Nimmo GR, Heffernan H, Liassine N, Bes M, Greenland T, Reverdy ME, Etienne J. Source: Emerging Infectious Diseases. 2003 August; 9(8): 978-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12967497
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Community-acquired methicillin-resistant Staphylococcus aureus in children and adolescents: changing trends. Author(s): Johnigan RH, Pereira KD, Poole MD. Source: Archives of Otolaryngology--Head & Neck Surgery. 2003 October; 129(10): 104952. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14568785
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Community-acquired methicillin-resistant Staphylococcus aureus isolated in Switzerland contains the Panton-Valentine leukocidin or exfoliative toxin genes. Author(s): Liassine N, Auckenthaler R, Descombes MC, Bes M, Vandenesch F, Etienne J. Source: Journal of Clinical Microbiology. 2004 February; 42(2): 825-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14766862
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Community-acquired methicillin-resistant Staphylococcus aureus skin infection: an emerging clinical problem. Author(s): Cohen PR, Kurzrock R. Source: Journal of the American Academy of Dermatology. 2004 February; 50(2): 277-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14726887
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Comparative activity of garenoxacin and other agents by susceptibility and time-kill testing against Staphylococcus aureus, Streptococcus pyogenes and respiratory pathogens. Author(s): Noviello S, Ianniello F, Leone S, Esposito S. Source: The Journal of Antimicrobial Chemotherapy. 2003 November; 52(5): 869-72. Epub 2003 September 30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14519672
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Comparative analysis of agr locus diversification and overall genetic variability among bovine and human Staphylococcus aureus isolates. Author(s): Gilot P, van Leeuwen W. Source: Journal of Clinical Microbiology. 2004 March; 42(3): 1265-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15004090
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Comparison of community- and health care-associated methicillin-resistant Staphylococcus aureus infection. Author(s): Naimi TS, LeDell KH, Como-Sabetti K, Borchardt SM, Boxrud DJ, Etienne J, Johnson SK, Vandenesch F, Fridkin S, O'Boyle C, Danila RN, Lynfield R. Source: Jama : the Journal of the American Medical Association. 2003 December 10; 290(22): 2976-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14665659
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Comparison of mortality associated with methicillin-susceptible and methicillinresistant Staphylococcus aureus bacteremia: an ecological analysis. Author(s): Hurley JC. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2003 September 15; 37(6): 866-8; Author Reply 868-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12955662
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Controlling methicillin resistant Staphylococcus aureus. Author(s): Duckworth G. Source: Bmj (Clinical Research Ed.). 2003 November 22; 327(7425): 1177-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14630728
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Cost analysis of switching from i.v. vancomycin to p.o. linezolid for the management of methicillin-resistant Staphylococcus species. Author(s): McCollum M, Rhew DC, Parodi S. Source: Clinical Therapeutics. 2003 December; 25(12): 3173-89. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14749155
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Daptomycin against multiple drug-resistant Staphylococcus and enterococcus isolates in an in vitro pharmacodynamic model with simulated endocardial vegetations. Author(s): Cha R, Rybak MJ. Source: Diagnostic Microbiology and Infectious Disease. 2003 November; 47(3): 539-46. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14596973
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Decreased vancomycin susceptibility of coagulase-negative staphylococci in a neonatal intensive care unit: evidence of spread of Staphylococcus warneri. Author(s): Center KJ, Reboli AC, Hubler R, Rodgers GL, Long SS. Source: Journal of Clinical Microbiology. 2003 October; 41(10): 4660-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14532199
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Degradation of antimicrobial histatin-variant peptides in Staphylococcus aureus and Streptococcus mutans. Author(s): Groenink J, Ruissen AL, Lowies D, van 't Hof W, Veerman EC, Nieuw Amerongen AV. Source: Journal of Dental Research. 2003 September; 82(9): 753-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12939363
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Detection of antibodies to Staphylococcus aureus Toxic Shock Syndrome Toxin-1 using a competitive agglutination inhibition assay. Author(s): Javid Khojasteh V, Rogan MT, Edwards-Jones V, Foster HA. Source: Letters in Applied Microbiology. 2003; 36(6): 372-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12753244
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Detection of intrinsic oxacillin resistance in non-multiresistant, oxacillin-resistant Staphylococcus aureus (NORSA). Author(s): Gosbell IB, Neville SA, Mercer JL, Fernandes LA, Fernandes CJ. Source: The Journal of Antimicrobial Chemotherapy. 2003 February; 51(2): 468-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12562728
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Detection of low-level methicillin-resistant Staphylococcus aureus with commercially available tests. Author(s): Poulsen AB, Skov R, Pallesen L. Source: Journal of Clinical Microbiology. 2003 July; 41(7): 3458. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12843124
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Detection of methicillin-resistant Staphylococcus aureus (MRSA) in blood with the EVIGENE MRSA detection kit. Author(s): Levi K, Towner KJ. Source: Journal of Clinical Microbiology. 2003 August; 41(8): 3890-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12904411
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Detection of mutations in quinolone resistance-determining regions in levofloxacinand methicillin-resistant Staphylococcus aureus: effects of the mutations on fluoroquinolone MICs. Author(s): Horii T, Suzuki Y, Monji A, Morita M, Muramatsu H, Kondo Y, Doi M, Takeshita A, Kanno T, Maekawa M. Source: Diagnostic Microbiology and Infectious Disease. 2003 June; 46(2): 139-45. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12812718
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Detection of Staphylococcus aureus biofilm on tampons and menses components. Author(s): Veeh RH, Shirtliff ME, Petik JR, Flood JA, Davis CC, Seymour JL, Hansmann MA, Kerr KM, Pasmore ME, Costerton JW. Source: The Journal of Infectious Diseases. 2003 August 15; 188(4): 519-30. Epub 2003 July 25. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12898438
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Detection of Staphylococcus aureus by 16S rRNA directed in situ hybridisation in a patient with a brain abscess caused by small colony variants. Author(s): Kipp F, Ziebuhr W, Becker K, Krimmer V, Hobeta N, Peters G, Von Eiff C. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 2003 July; 74(7): 1000-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12810807
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Detection of Staphylococcus aureus enterotoxins A to D by real-time fluorescence PCR assay. Author(s): Klotz M, Opper S, Heeg K, Zimmermann S. Source: Journal of Clinical Microbiology. 2003 October; 41(10): 4683-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14532203
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Detection of Staphylococcus aureus in peripheral blood stem cell cultures after sterilization of standard blood cultures. Author(s): Schwaber MJ, Krasner CN, Gold HS, Venkataraman L, Avigan DE, Karchmer AW, Uhl L. Source: Journal of Clinical Apheresis. 2003; 18(1): 37-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12717792
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Determinants of acquisition and carriage of Staphylococcus aureus in infancy. Author(s): Peacock SJ, Justice A, Griffiths D, de Silva GD, Kantzanou MN, Crook D, Sleeman K, Day NP. Source: Journal of Clinical Microbiology. 2003 December; 41(12): 5718-25. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14662966
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Development of a Canadian standardized protocol for subtyping methicillin-resistant Staphylococcus aureus using pulsed-field gel electrophoresis. Author(s): Mulvey MR, Chui L, Ismail J, Louie L, Murphy C, Chang N, Alfa M; Canadian Committee for the Standardization of Molecular Methods. Source: Journal of Clinical Microbiology. 2001 October; 39(10): 3481-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11574559
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Development of a universal probe for electronic microarray and its application in characterization of the Staphylococcus aureus polC gene. Author(s): Cooper KL, Goering RV. Source: The Journal of Molecular Diagnostics : Jmd. 2003 February; 5(1): 28-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12552077
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Development of antimicrobial resistance in Staphylococcus lugdunensis during treatment-report of a case of bacterial arthritis, vertebral osteomyelitis and infective endocarditis. Author(s): Kragsbjerg P, Bomfim-Loogna J, Tornqvist E, Soderquist B. Source: Clinical Microbiology and Infection : the Official Publication of the European Society of Clinical Microbiology and Infectious Diseases. 2000 September; 6(9): 496-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11168184
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Different susceptibilities of Staphylococcus and Gram-negative rods to epigallocatechin gallate. Author(s): Yoda Y, Hu ZQ, Zhao WH, Shimamura T. Source: Journal of Infection and Chemotherapy : Official Journal of the Japan Society of Chemotherapy. 2004 February; 10(1): 55-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14991521
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Dinosaurs, methicillin-resistant Staphylococcus aureus, and infection control personnel: survival through translating science into prevention. Author(s): Jarvis WR, Ostrowsky B. Source: Infection Control and Hospital Epidemiology : the Official Journal of the Society of Hospital Epidemiologists of America. 2003 June; 24(6): 392-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12828313
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Dispersal of methicillin resistant Staphylococcus aureus (MRSA) in a burn intensive care unit. Author(s): Torregrossa MV, Cannova L, Sucameli M, Cucchiara P, Masellis M, Mammina C. Source: Ann Ig. 2003 March-April; 15(2): 107-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12838825
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Drug-resistant Streptococcus pneumoniae and methicillin-resistant Staphylococcus aureus surveillance. Author(s): Hawley LA, Fridkin SK, Whitney CG. Source: Emerging Infectious Diseases. 2003 October; 9(10): 1358-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14626229
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Early activation events differentiate the reactivity of two T-cell families to Staphylococcus enterotoxin A. Author(s): D'Souza S, McGrath H, Sekaly RP. Source: Cellular Immunology. 2003 June; 223(2): 113-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14527509
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Effect of duplicate isolates of methicillin-susceptible and methicillin-resistant Staphylococcus aureus on antibiogram data. Author(s): Horvat RT, Klutman NE, Lacy MK, Grauer D, Wilson M. Source: Journal of Clinical Microbiology. 2003 October; 41(10): 4611-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14532191
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Emergence of a teicoplanin-resistant small colony variant of Staphylococcus epidermidis during vancomycin therapy. Author(s): Adler H, Widmer A, Frei R. Source: European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology. 2003 December; 22(12): 746-8. Epub 2003 November 06. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14605939
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Emergence of community-acquired methicillin-resistant Staphylococcus aureus (MRSA) infection in Queensland, Australia. Author(s): Munckhof WJ, Schooneveldt J, Coombs GW, Hoare J, Nimmo GR. Source: International Journal of Infectious Diseases : Ijid : Official Publication of the International Society for Infectious Diseases. 2003 December; 7(4): 259-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14656416
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Emergence of methicilllin resistant Staphylococcus aureus (MRSA) associated with wound infections. Author(s): Jahan Y, Jahan F, Mamun KZ, Hossain MA, Shirin T, Sahman S, Gomes DJ. Source: Mymensingh Med J. 2004 January; 13(1): 76-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14747792
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Endobronchial tuberculosis complicated with Staphylococcus aureus pneumonia and empyema in a child. Author(s): Uzuner N, Anal O, Karaman O, Sevinc C, Turkmen M, Canda T, Kazan E. Source: Turk J Pediatr. 2003 July-September; 45(3): 254-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14696807
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Endocarditis due to Staphylococcus aureus after minor dog bite. Author(s): Bradshaw SE. Source: Southern Medical Journal. 2003 April; 96(4): 407-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12916563
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Enhancement of antimicrobial effects of various antibiotics against methicillinresistant Staphylococcus aureus (MRSA) by combination with fosfomycin. Author(s): Nakazawa H, Kikuchi Y, Honda T, Isago T, Nozaki M. Source: Journal of Infection and Chemotherapy : Official Journal of the Japan Society of Chemotherapy. 2003 December; 9(4): 304-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14691650
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Enterotoxins and phage typing of Staphylococcus aureus isolated from clinical material and food in Libya. Author(s): el-Ghodban A, Ghenghesh KS, Marialigeti K, Tawil A. Source: Arch Inst Pasteur Tunis. 1999 January-April; 76(1-4): 23-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14666754
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Establishment and clonal dissemination of the methicillin-resistant Staphylococcus aureus UK-16 epidemic strain in a Spanish hospital. Author(s): Perez-Roth E, Lorenzo-Diaz F, Mendez-Alvarez S. Source: Journal of Clinical Microbiology. 2003 November; 41(11): 5353. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14605206
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Establishment of an arbitrary PCR for rapid identification of Tn917 insertion sites in Staphylococcus epidermidis: characterization of biofilm-negative and nonmucoid mutants. Author(s): Knobloch JK, Nedelmann M, Kiel K, Bartscht K, Horstkotte MA, Dobinsky S, Rohde H, Mack D. Source: Applied and Environmental Microbiology. 2003 October; 69(10): 5812-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14532029
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Evaluation of a novel method based on PCR Restriction Fragment Length Polymorphism Analysis of the tuf gene for the identification of Staphylococcus species. Author(s): Kontos F, Petinaki E, Spiliopoulou I, Maniati M, Maniatis AN. Source: Journal of Microbiological Methods. 2003 November; 55(2): 465-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14529969
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Evaluation of different disk diffusion/media combinations for detection of methicillin resistance in Staphylococcus aureus and coagulase-negative staphylococci. Author(s): Skov R, Larsen AR, Frimodt-Moller N, Espersen F. Source: Apmis : Acta Pathologica, Microbiologica, Et Immunologica Scandinavica. 2003 September; 111(9): 905-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14510648
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Evaluation of different methods to detect methicillin resistance in small-colony variants of Staphylococcus aureus. Author(s): Kipp F, Becker K, Peters G, von Eiff C. Source: Journal of Clinical Microbiology. 2004 March; 42(3): 1277-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15004093
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Evaluation of penicillin binding protein 2a latex agglutination assay for identification of methicillin-resistant Staphylococcus aureus directly from blood cultures. Author(s): Chapin KC, Musgnug MC. Source: Journal of Clinical Microbiology. 2004 March; 42(3): 1283-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15004095
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Evaluation of S. aureus ID, a new chromogenic agar medium for detection of Staphylococcus aureus. Author(s): Perry JD, Rennison C, Butterworth LA, Hopley AL, Gould FK. Source: Journal of Clinical Microbiology. 2003 December; 41(12): 5695-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14662963
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Evaluation of three rapid methods for the direct identification of Staphylococcus aureus from positive blood cultures. Author(s): Chapin K, Musgnug M. Source: Journal of Clinical Microbiology. 2003 September; 41(9): 4324-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12958264
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Evidence for the absence of Staphylococcus aureus in land applied biosolids. Author(s): Rusin PA, Maxwell SL, Brooks JP, Gerba CP, Pepper IL. Source: Environmental Science & Technology. 2003 September 15; 37(18): 4027-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14524431
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Experience in prevention of sternal wound infections in nasal carriers of Staphylococcus aureus. Author(s): Banbury MK. Source: Surgery. 2003 November; 134(5 Suppl): S18-22; Quiz S23-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14647029
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Expression of biofilm-associated genes in Staphylococcus epidermidis during in vitro and in vivo foreign body infections. Author(s): Vandecasteele SJ, Peetermans WE, Merckx R, Van Eldere J. Source: The Journal of Infectious Diseases. 2003 September 1; 188(5): 730-7. Epub 2003 August 04. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12934189
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Factors influencing physicians' decision to discharge hospitalized patients infected with methicillin-resistant Staphylococcus aureus. Author(s): Yaldo AZ, Sullivan JL, Li Z. Source: American Journal of Health-System Pharmacy : Ajhp : Official Journal of the American Society of Health-System Pharmacists. 2001 September 15; 58(18): 1756-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11571820
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Failure of clindamycin treatment of methicillin-resistant Staphylococcus aureus expressing inducible clindamycin resistance in vitro. Author(s): Siberry GK, Tekle T, Carroll K, Dick J. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2003 November 1; 37(9): 1257-60. Epub 2003 October 03. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14557972
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Fas (CD95)-Fas ligand interactions are responsible for monocyte apoptosis occurring as a result of phagocytosis and killing of Staphylococcus aureus. Author(s): Baran J, Weglarczyk K, Mysiak M, Guzik K, Ernst M, Flad HD, Pryjma J. Source: Infection and Immunity. 2001 March; 69(3): 1287-97. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11179290
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Fatal outcome of bacteraemic patients caused by infection with staphylokinasedeficient Staphylococcus aureus strains. Author(s): Jin T, Bokarewa M, McIntyre L, Tarkowski A, Corey GR, Reller LB, Fowler VG Jr. Source: Journal of Medical Microbiology. 2003 October; 52(Pt 10): 919-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12972589
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Favorable outcome of long-lasting thoracic spondylodiscitis with spinal epidural abscess induced by Staphylococcus aureus. Author(s): Finsterer J, Mahr K, Paral V. Source: Southern Medical Journal. 2003 January; 96(1): 70-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12602721
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Fibronectin bound to the surface of Staphylococcus aureus induces association of very late antigen 5 and intracellular signaling factors with macrophage cytoskeleton. Author(s): Shinji H, Seki K, Tajima A, Uchida A, Masuda S. Source: Infection and Immunity. 2003 January; 71(1): 140-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12496159
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Fibronectin-binding proteins of Staphylococcus aureus are involved in adherence to human airway epithelium. Author(s): Mongodin E, Bajolet O, Cutrona J, Bonnet N, Dupuit F, Puchelle E, de Bentzmann S. Source: Infection and Immunity. 2002 February; 70(2): 620-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11796591
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First report of clinical and microbiological failure in the eradication of glycopeptideintermediate methicillin-resistant Staphylococcus aureus carriage by mupirocin. Author(s): Decousser JW, Pina P, Ghnassia JC, Bedos JP, Allouch PY. Source: European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology. 2003 May; 22(5): 318-9. Epub 2003 May 08. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12736798
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Fistulating periprosthetic Staphylococcus lugdunensis hip infection cured by intraarticular teicoplanin injections--a case report. Author(s): Sanzeni L, Ringberg H. Source: Acta Orthopaedica Scandinavica. 2003 October; 74(5): 624-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14620988
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Fitness of antibiotic resistant Staphylococcus epidermidis assessed by competition on the skin of human volunteers. Author(s): Gustafsson I, Cars O, Andersson DI. Source: The Journal of Antimicrobial Chemotherapy. 2003 August; 52(2): 258-63. Epub 2003 July 15. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12865395
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Flavone markedly affects phenotypic expression of beta-lactam resistance in methicillin-resistant Staphylococcus aureus strains isolated clinically. Author(s): Shibata H, Shirakata C, Kawasaki H, Sato Y, Kuwahara T, Ohnishi Y, Arakaki N, Higuti T. Source: Biological & Pharmaceutical Bulletin. 2003 October; 26(10): 1478-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14519958
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Fluoroquinolones and the risk for methicillin-resistant Staphylococcus aureus in hospitalized patients. Author(s): Weber SG, Gold HS, Hooper DC, Karchmer AW, Carmeli Y. Source: Emerging Infectious Diseases. 2003 November; 9(11): 1415-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14718085
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Frequency and clinical role of Staphylococcus aureus overinfection in atopic dermatitis in children. Author(s): Ricci G, Patrizi A, Neri I, Bendandi B, Masi M. Source: Pediatric Dermatology. 2003 September-October; 20(5): 389-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14521553
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Frequency of isolation of Staphylococcus lugdunensis in consecutive urine cultures and relationship to urinary tract infection. Author(s): Haile DT, Hughes J, Vetter E, Kohner P, Snyder R, Patel R, Cockerill FR 3rd. Source: Journal of Clinical Microbiology. 2002 February; 40(2): 654-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11825988
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Frequent recovery of a single clonal type of multidrug-resistant Staphylococcus aureus from patients in two hospitals in Taiwan and China. Author(s): Aires de Sousa M, Crisostomo MI, Sanches IS, Wu JS, Fuzhong J, Tomasz A, de Lencastre H. Source: Journal of Clinical Microbiology. 2003 January; 41(1): 159-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12517842
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Functional blocking of Staphylococcus aureus adhesins following growth in ex vivo media. Author(s): Massey RC, Dissanayeke SR, Cameron B, Ferguson D, Foster TJ, Peacock SJ. Source: Infection and Immunity. 2002 October; 70(10): 5339-45. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12228257
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Functional selection of vaccine candidate peptides from Staphylococcus aureus whole-genome expression libraries in vitro. Author(s): Weichhart T, Horky M, Sollner J, Gangl S, Henics T, Nagy E, Meinke A, von Gabain A, Fraser CM, Gill SR, Hafner M, von Ahsen U. Source: Infection and Immunity. 2003 August; 71(8): 4633-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12874343
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Fusidic acid resistance in community isolates of methicillin-susceptible Staphylococcus aureus and fusidic acid prescribing. Author(s): Mason BW, Howard AJ, Magee JT. Source: The Journal of Antimicrobial Chemotherapy. 2003 April; 51(4): 1033-6. Epub 2003 March 13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12654748
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Fusidic acid resistance in Staphylococcus aureus isolates. Author(s): Brown EM, Thomas P. Source: Lancet. 2002 March 2; 359(9308): 803. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11888633
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Fusidic acid resistance in Staphylococcus aureus. Author(s): Dobie D, Gray J. Source: Archives of Disease in Childhood. 2004 January; 89(1): 74-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14709515
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Genetic analysis of a high-level vancomycin-resistant isolate of Staphylococcus aureus. Author(s): Weigel LM, Clewell DB, Gill SR, Clark NC, McDougal LK, Flannagan SE, Kolonay JF, Shetty J, Killgore GE, Tenover FC. Source: Science. 2003 November 28; 302(5650): 1569-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14645850
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Genetic analysis of methicillin-resistant Staphylococcus aureus expressing high- and low-level mupirocin resistance. Author(s): Udo EE, Jacob LE, Mathew B. Source: Journal of Medical Microbiology. 2001 October; 50(10): 909-15. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11599741
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Genetic analysis of Staphylococcus aureus from intravenous drug user lesions. Author(s): Monk AB, Curtis S, Paul J, Enright MC. Source: Journal of Medical Microbiology. 2004 March; 53(Pt 3): 223-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14970247
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Genetic and biochemical analysis of Staphylococcus epidermidis biofilm accumulation. Author(s): Mack D, Bartscht K, Fischer C, Rohde H, de Grahl C, Dobinsky S, Horstkotte MA, Kiel K, Knobloch JK. Source: Methods Enzymol. 2001; 336: 215-39. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11398401
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Genetic basis of neonatal methicillin-resistant Staphylococcus aureus in Japan. Author(s): Kikuchi K. Source: Pediatrics International : Official Journal of the Japan Pediatric Society. 2003 April; 45(2): 223-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12709160
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Genetic organization of mecA and mecA-regulatory genes in epidemic methicillinresistant Staphylococcus aureus from Australia and England. Author(s): Lim TT, Coombs GW, Grubb WB. Source: The Journal of Antimicrobial Chemotherapy. 2002 December; 50(6): 819-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12460999
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Genetic relationship between methicillin-sensitive and methicillin-resistant Staphylococcus aureus strains from France and from international sources: delineation of genomic groups. Author(s): Branger C, Gardye C, Galdbart JO, Deschamps C, Lambert N. Source: Journal of Clinical Microbiology. 2003 July; 41(7): 2946-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12843025
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Genome sequence survey identifies unique sequences and key virulence genes with unusual rates of amino Acid substitution in bovine Staphylococcus aureus. Author(s): Herron LL, Chakravarty R, Dwan C, Fitzgerald JR, Musser JM, Retzel E, Kapur V. Source: Infection and Immunity. 2002 July; 70(7): 3978-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12065548
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Genotype analysis of methicillin-resistant Staphylococcus aureus with and without reduced susceptibility to vancomycin using pulsed-field gel electrophoresis. Author(s): Furuya D, Yagihashi A, Uehara N, Yajima T, Kobayashi D, Watanabe N. Source: Infection Control and Hospital Epidemiology : the Official Journal of the Society of Hospital Epidemiologists of America. 2001 September; 22(9): 536-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11732780
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Genotyping of clinical methicillin-susceptible Staphylococcus aureus isolates in a Dutch teaching hospital. Author(s): Van Dijk Y, Wielders CL, Fluit AC, Paauw A, Diepersloot RJ, Mascini EM. Source: Journal of Clinical Microbiology. 2002 February; 40(2): 663-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11825991
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Genotyping of methicillin-resistant Staphylococcus aureus by assaying for the presence of variable elements associated with mecA. Author(s): Huygens F, Nimmo GR, Schooneveldt J, Munckhof WJ, Giffard PM. Source: Journal of Clinical Microbiology. 2002 August; 40(8): 3093-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12149390
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Genotyping of Staphylococcus aureus isolated from various sites on farms with dairy sheep using pulsed-field gel electrophoresis. Author(s): Vautor E, Abadie G, Guibert JM, Huard C, Pepin M. Source: Veterinary Microbiology. 2003 October 8; 96(1): 69-79. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14516709
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Global regulation of Staphylococcus aureus genes by Rot. Author(s): Said-Salim B, Dunman PM, McAleese FM, Macapagal D, Murphy E, McNamara PJ, Arvidson S, Foster TJ, Projan SJ, Kreiswirth BN. Source: Journal of Bacteriology. 2003 January; 185(2): 610-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12511508
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Glomerulonephritis after methicillin-resistant Staphylococcus aureus infection resulting in end-stage renal failure. Author(s): Yamashita Y, Tanase T, Terada Y, Tamura H, Akiba T, Inoue H, Ida T, Sasaki S, Marumo F, Nakamoto Y. Source: Intern Med. 2001 May; 40(5): 424-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11393416
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Glomerulonephritis induced by methicillin-sensitive Staphylococcus aureus infection. Author(s): Handa T, Ono T, Watanabe H, Takeda T, Muso E, Kita T. Source: Clinical and Experimental Nephrology. 2003 September; 7(3): 247-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14586723
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Staphylococcus aureus
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Glycopeptide resistance in an epidemic strain of methicillin-resistant Staphylococcus aureus. Author(s): Paton R, Snell T, Emmanuel FX, Miles RS. Source: The Journal of Antimicrobial Chemotherapy. 2001 December; 48(6): 941-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11733489
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Glycopeptide resistance in Staphylococcus aureus. Author(s): Dancer SJ. Source: The Journal of Antimicrobial Chemotherapy. 2003 May; 51(5): 1309-11. Epub 2003 March 28. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12668575
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Glycopeptide susceptibility profiles of nosocomial multiresistant Staphylococcus haemolyticus isolates. Author(s): Tabe Y, Nakamura A, Igari J. Source: Journal of Infection and Chemotherapy : Official Journal of the Japan Society of Chemotherapy. 2001 September; 7(3): 142-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11810575
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Glycopeptide-intermediate Staphylococcus aureus: rediscovery of an old problem? Author(s): Cercenado E. Source: Clinical Microbiology and Infection : the Official Publication of the European Society of Clinical Microbiology and Infectious Diseases. 2000 October; 6(10): 517-8. Erratum In: Clin Microbiol Infect 2001 March; 7(3): 170. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11168044
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Glycopeptide-resistant Staphylococcus aureus. Author(s): Johnson AP, Woodford N. Source: The Journal of Antimicrobial Chemotherapy. 2002 November; 50(5): 621-3. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12407116
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H(2)O(2) produced by viridans group streptococci may contribute to inhibition of methicillin-resistant Staphylococcus aureus colonization of oral cavities in newborns. Author(s): Uehara Y, Kikuchi K, Nakamura T, Nakama H, Agematsu K, Kawakami Y, Maruchi N, Totsuka K. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2001 May 15; 32(10): 1408-13. Epub 2001 April 17. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11317240
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Harmonization of pulsed-field gel electrophoresis protocols for epidemiological typing of strains of methicillin-resistant Staphylococcus aureus: a single approach developed by consensus in 10 European laboratories and its application for tracing the spread of related strains. Author(s): Murchan S, Kaufmann ME, Deplano A, de Ryck R, Struelens M, Zinn CE, Fussing V, Salmenlinna S, Vuopio-Varkila J, El Solh N, Cuny C, Witte W, Tassios PT, Legakis N, van Leeuwen W, van Belkum A, Vindel A, Laconcha I, Garaizar J, Haeggman S, Olsson-Liljequist B, Ransjo U, Coombes G, Cookson B. Source: Journal of Clinical Microbiology. 2003 April; 41(4): 1574-85. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12682148
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Hemoperfusion with polymyxin B-immobilized fiber in septic patients with methicillin-resistant Staphylococcus aureus-associated glomerulonephritis. Author(s): Nakamura T, Ushiyama C, Suzuki Y, Osada S, Inoue T, Shoji H, Hara M, Shimada N, Koide H. Source: Nephron. Clinical Practice [electronic Resource]. 2003; 94(2): C33-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12845235
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High frequency of colonization and absence of identifiable risk factors for methicillin-resistant Staphylococcus aureus (MRSA)in intensive care units in Brazil. Author(s): Korn GP, Martino MD, Mimica IM, Mimica LJ, Chiavone PA, Musolino LR. Source: The Brazilian Journal of Infectious Diseases : an Official Publication of the Brazilian Society of Infectious Diseases. 2001 February; 5(1): 1-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11290308
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High levels of fusidic acid-resistant Staphylococcus aureus in dermatology patients. Author(s): Shah M, Mohanraj M. Source: The British Journal of Dermatology. 2003 May; 148(5): 1018-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12786835
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High methicillin resistance of Staphylococcus aureus and coagulase-negative staphylococci in Imam Khomeini Hospital of Urmia, Iran. Author(s): Rahbar M, Babazadeh H, Zarghami N. Source: Infection Control and Hospital Epidemiology : the Official Journal of the Society of Hospital Epidemiologists of America. 2001 April; 22(4): 196-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11379707
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High mortality related with Staphylococcus aureus bacteremia after liver transplantation. Author(s): Torre-Cisneros J, Herrero C, Canas E, Reguera JM, De La Mata M, GomezBravo MA. Source: European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology. 2002 May; 21(5): 385-8. Epub 2002 May 08. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12072924
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Staphylococcus aureus
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High percentage of methicillin-resistant Staphylococcus aureus isolates with reduced susceptibility to glycopeptides in The Netherlands. Author(s): Van Griethuysen A, Van 't Veen A, Buiting A, Walsh T, Kluytmans J. Source: Journal of Clinical Microbiology. 2003 June; 41(6): 2487-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12791870
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High prevalence of oxacillin-resistant Staphylococcus aureus isolates from hospitalized patients in Asia-Pacific and South Africa: results from SENTRY antimicrobial surveillance program, 1998-1999. Author(s): Bell JM, Turnidge JD; SENTRY APAC. Source: Antimicrobial Agents and Chemotherapy. 2002 March; 46(3): 879-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11850278
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High prevalence of superantigens associated with the egc locus in Staphylococcus aureus isolates from patients with atopic eczema. Author(s): Mempel M, Lina G, Hojka M, Schnopp C, Seidl HP, Schafer T, Ring J, Vandenesch F, Abeck D. Source: European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology. 2003 May; 22(5): 306-9. Epub 2003 May 13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12743832
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High rate of macrolide resistance in Staphylococcus aureus strains from patients with cystic fibrosis reveals high proportions of hypermutable strains. Author(s): Prunier AL, Malbruny B, Laurans M, Brouard J, Duhamel JF, Leclercq R. Source: The Journal of Infectious Diseases. 2003 June 1; 187(11): 1709-16. Epub 2003 May 15. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12751028
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High rate of transfer of Staphylococcus aureus from parental skin to infant gut flora. Author(s): Lindberg E, Adlerberth I, Hesselmar B, Saalman R, Strannegard IL, Aberg N, Wold AE. Source: Journal of Clinical Microbiology. 2004 February; 42(2): 530-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14766812
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Hospital- and community-based surveillance of methicillin-resistant Staphylococcus aureus: previous hospitalization is the major risk factor. Author(s): Warshawsky B, Hussain Z, Gregson DB, Alder R, Austin M, Bruckschwaiger D, Chagla AH, Daley J, Duhaime C, McGhie K, Pollett G, Potters H, Schiedel L. Source: Infection Control and Hospital Epidemiology : the Official Journal of the Society of Hospital Epidemiologists of America. 2000 November; 21(11): 724-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11089657
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Hospital mortality for patients with bacteremia due to Staphylococcus aureus or Pseudomonas aeruginosa. Author(s): Osmon S, Ward S, Fraser VJ, Kollef MH. Source: Chest. 2004 February; 125(2): 607-16. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14769745
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Hospital transmission of community-acquired methicillin-resistant Staphylococcus aureus among postpartum women. Author(s): Saiman L, O'Keefe M, Graham PL 3rd, Wu F, Said-Salim B, Kreiswirth B, LaSala A, Schlievert PM, Della-Latta P. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2003 November 15; 37(10): 1313-9. Epub 2003 October 17. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14583864
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Host defense role of platelets: engulfment of HIV and Staphylococcus aureus occurs in a specific subcellular compartment and is enhanced by platelet activation. Author(s): Youssefian T, Drouin A, Masse JM, Guichard J, Cramer EM. Source: Blood. 2002 June 1; 99(11): 4021-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12010803
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Host-parasite interactions in Staphylococcus aureus keratitis. Author(s): Jett BD, Gilmore MS. Source: Dna and Cell Biology. 2002 May-June; 21(5-6): 397-404. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12167242
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How clonal is Staphylococcus aureus? Author(s): Feil EJ, Cooper JE, Grundmann H, Robinson DA, Enright MC, Berendt T, Peacock SJ, Smith JM, Murphy M, Spratt BG, Moore CE, Day NP. Source: Journal of Bacteriology. 2003 June; 185(11): 3307-16. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12754228
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Human leukocytes adhere to, penetrate, and respond to Staphylococcus aureus biofilms. Author(s): Leid JG, Shirtliff ME, Costerton JW, Stoodley AP. Source: Infection and Immunity. 2002 November; 70(11): 6339-45. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12379713
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Human transcobalamin II receptor binds to Staphylococcus aureus protein A: implications as to its structure and function. Author(s): Vanamala SK, Seetharam S, Yammani RR, Seetharam B. Source: Archives of Biochemistry and Biophysics. 2003 March 15; 411(2): 204-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12623069
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Staphylococcus aureus
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Identification of new phages to type Staphylococcus aureus strains and comparison with a genotypic method. Author(s): de Gialluly C, Loulergue J, Bruant G, Mereghetti L, Massuard S, van der Mee N, Audurier A, Quentin R. Source: The Journal of Hospital Infection. 2003 September; 55(1): 61-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14505611
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Immediate control of a methicillin-resistant Staphylococcus aureus outbreak in a neonatal intensive care unit. Author(s): Shiojima T, Ohki Y, Nako Y, Morikawa A, Okubo T, Iyobe S. Source: Journal of Infection and Chemotherapy : Official Journal of the Japan Society of Chemotherapy. 2003 September; 9(3): 243-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14513393
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In vitro studies of the pharmacodynamics of teicoplanin against Staphylococcus aureus, Staphylococcus epidermidis and Enterococcus faecium. Author(s): Odenholt I, Lowdin E, Cars O. Source: Clinical Microbiology and Infection : the Official Publication of the European Society of Clinical Microbiology and Infectious Diseases. 2003 September; 9(9): 930-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14616681
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Increased frequency of genomic alterations in Staphylococcus aureus during chronic infection is in part due to phage mobilization. Author(s): Goerke C, Matias y Papenberg S, Dasbach S, Dietz K, Ziebach R, Kahl BC, Wolz C. Source: The Journal of Infectious Diseases. 2004 February 15; 189(4): 724-34. Epub 2004 January 29. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14767828
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Increasing prevalence of methicillin-resistant Staphylococcus aureus infection in California jails. Author(s): Pan ES, Diep BA, Carleton HA, Charlebois ED, Sensabaugh GF, Haller BL, Perdreau-Remington F. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2003 November 15; 37(10): 1384-8. Epub 2003 October 17. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14583874
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Infection and colonization by Staphylococcus aureus in a high risk nursery of a Brazilian teaching hospital. Author(s): de Almeida Silva H, Steffen Abdallah VO, Carneiro CL, Gontijo PP PP. Source: The Brazilian Journal of Infectious Diseases : an Official Publication of the Brazilian Society of Infectious Diseases. 2003 December; 7(6): 381-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14636477
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Infective discitis due to Staphylococcus lugdunensis--a case of missed opportunity. Author(s): Cooke RP, James SE, Sallomi DF. Source: British Journal of Biomedical Science. 2003; 60(3): 162-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14560794
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Infective endocarditis due to Staphylococcus aureus involving three cardiac valves. A case study. Author(s): Maglioni E, Garosi M, Marchetti L, Galluzzi P, Marri D, Biagioli B. Source: Minerva Anestesiol. 2003 June; 69(6): 583-8, 588-90. English, Italian. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14564255
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Influenza B pneumonia with Staphylococcus aureus superinfection associated with parvovirus B19 and concomitant agranulocytosis. Author(s): Krell S, Adams I, Arnold U, Kalinski T, Aumann V, Konig W, Konig B. Source: Infection. 2003 October; 31(5): 353-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14556063
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Inhibition of Staphylococcus aureus by the commensal bacteria of human milk. Author(s): Heikkila MP, Saris PE. Source: Journal of Applied Microbiology. 2003; 95(3): 471-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12911694
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International clones of methicillin-resistant Staphylococcus aureus in two hospitals in Miami, Florida. Author(s): Chung M, Dickinson G, De Lencastre H, Tomasz A. Source: Journal of Clinical Microbiology. 2004 February; 42(2): 542-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14766814
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Intracellular Staphylococcus aureus. A mechanism for the indolence of osteomyelitis. Author(s): Ellington JK, Harris M, Webb L, Smith B, Smith T, Tan K, Hudson M. Source: The Journal of Bone and Joint Surgery. British Volume. 2003 August; 85(6): 91821. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12931819
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Intracellular survival of Staphylococcus aureus within cultured enterocytes. Author(s): Hess DJ, Henry-Stanley MJ, Erickson EA, Wells CL. Source: The Journal of Surgical Research. 2003 September; 114(1): 42-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=13678697
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Investigation of methicillin-resistant Staphylococcus aureus showing reduced vancomycin susceptibility isolated from a patient with infective endocarditis. Author(s): Takayama Y, Hanaki H, Irinoda K, Kokubun H, Yoshida K, Sunakawa K. Source: International Journal of Antimicrobial Agents. 2003 December; 22(6): 567-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14659653
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Investigation of Staphylococcus aureus isolates identified as erythromycin intermediate by the Vitek-1 System: comparison with results obtained with the Vitek2 and Phoenix systems. Author(s): Tang P, Low DE, Atkinson S, Pike K, Ashi-Sulaiman A, Simor A, Richardson S, Willey BM. Source: Journal of Clinical Microbiology. 2003 October; 41(10): 4823-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14532232
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Involvement of leucine residues at positions 107, 112, and 115 in a leucine-rich repeat motif of human Toll-like receptor 2 in the recognition of diacylated lipoproteins and lipopeptides and Staphylococcus aureus peptidoglycans. Author(s): Fujita M, Into T, Yasuda M, Okusawa T, Hamahira S, Kuroki Y, Eto A, Nisizawa T, Morita M, Shibata K. Source: Journal of Immunology (Baltimore, Md. : 1950). 2003 October 1; 171(7): 3675-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14500665
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Is methicillin-resistant Staphylococcus aureus more virulent than methicillinsusceptible S. aureus? A comparative cohort study of British patients with nosocomial infection and bacteremia. Author(s): Melzer M, Eykyn SJ, Gransden WR, Chinn S. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2003 December 1; 37(11): 1453-60. Epub 2003 November 06. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14614667
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Isolation and molecular characterization of multiresistant Staphylococcus sciuri and Staphylococcus haemolyticus associated with skin and soft-tissue infections. Author(s): Shittu A, Lin J, Morrison D, Kolawole D. Source: Journal of Medical Microbiology. 2004 January; 53(Pt 1): 51-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14663105
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Isolation of exfoliative toxin-producing Staphylococcus aureus. Author(s): Singal A, Thami GP. Source: The Pediatric Infectious Disease Journal. 2003 October; 22(10): 933; Author Reply 933-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14551496
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Isolation of members of the Staphylococcus sciuri group from urine and their relationship to urinary tract infections. Author(s): Stepanovic S, Jezek P, Vukovic D, Dakic I, Petras P. Source: Journal of Clinical Microbiology. 2003 November; 41(11): 5262-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14605178
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Laboratory characterization of methicillin-resistant Staphylococcus aureus in Canadian hospitals: results of 5 years of National Surveillance, 1995-1999. Author(s): Simor AE, Ofner-Agostini M, Bryce E, McGeer A, Paton S, Mulvey MR; Canadian Hospital Epidemiology Committee and Canadian Nosocomial Infection Surveillance Program, Health Canada. Source: The Journal of Infectious Diseases. 2002 September 1; 186(5): 652-60. Epub 2002 August 09. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12195352
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Laboratory detection and investigation of reduced susceptibility to vancomycin in oxacillin-resistant Staphylococcus aureus. Author(s): Midolo PD, Korman TM, Kotsanas D, Russo P, Kerr TG. Source: European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology. 2003 March; 22(3): 199-201. Epub 2003 March 05. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12649722
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Lack of efficacy of mupirocin in the prevention of infections with Staphylococcus aureus in liver transplant recipients and candidates. Author(s): Paterson DL, Rihs JD, Squier C, Gayowski T, Sagnimeni A, Singh N. Source: Transplantation. 2003 January 27; 75(2): 194-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12548122
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Late onset Ommaya reservoir infection due to Staphylococcus aureus: case report and review of Ommaya Infections. Author(s): Mechleb B, Khater F, Eid A, David G, Moorman JP. Source: The Journal of Infection. 2003 April; 46(3): 196-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12643873
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Lemierre syndrome due to non-multiresistant methicillin-resistant Staphylococcus aureus. Author(s): Fong SM, Watson M. Source: Journal of Paediatrics and Child Health. 2002 June; 38(3): 305-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12047702
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Length of hospital stay and cost of Staphylococcus and Streptococcus infections among hospitalized patients. Author(s): Zhao SZ, Dodge WE, Spalding W, Barr CE, Li JZ. Source: Clinical Therapeutics. 2002 May; 24(5): 818-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12075949
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Letter in response to article in Journal of Infection: linezolid treatment of prosthetic hip infections due to methicillin resistant Staphylococcus aureus (M. Bassetti et al.) Journal of Infection 2001; 43: 148-157. Author(s): Pareja-Cebrian L, Grigoris P. Source: The Journal of Infection. 2002 April; 44(3): 207. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12099758
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Limited success with open debridement and retention of components in the treatment of acute Staphylococcus aureus infections after total knee arthroplasty. Author(s): Deirmengian C, Greenbaum J, Lotke PA, Booth RE Jr, Lonner JH. Source: The Journal of Arthroplasty. 2003 October; 18(7 Suppl 1): 22-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14560406
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Linezolid for the treatment of methicillin-resistant Staphylococcus aureus infections in children. Author(s): Kaplan SL, Afghani B, Lopez P, Wu E, Fleishaker D, Edge-Padbury B, Naberhuis-Stehouwer S, Bruss JB. Source: The Pediatric Infectious Disease Journal. 2003 September; 22(9 Suppl): S178-85. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14520144
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Linezolid resistance in clinical isolates of Staphylococcus aureus. Author(s): Wilson P, Andrews JA, Charlesworth R, Walesby R, Singer M, Farrell DJ, Robbins M. Source: The Journal of Antimicrobial Chemotherapy. 2003 January; 51(1): 186-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12493812
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Linezolid resistance in Staphylococcus aureus: characterization and stability of resistant phenotype. Author(s): Pillai SK, Sakoulas G, Wennersten C, Eliopoulos GM, Moellering RC Jr, Ferraro MJ, Gold HS. Source: The Journal of Infectious Diseases. 2002 December 1; 186(11): 1603-7. Epub 2002 November 04. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12447736
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Linezolid to decrease length of stay in the hospital for patients with methicillinresistant Staphylococcus aureus infection. Author(s): Siegel RE. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2003 January 1; 36(1): 124; Author Reply 124-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12491215
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Linezolid treatment of total prosthetic knee infection due to methicillin-resistant Staphylococcus epidermidis. Author(s): Jover-Saenz A, Gaite FB, Ribelles AG, Porcel-Perez JM, Garrido-Calvo S. Source: The Journal of Infection. 2003 July; 47(1): 87-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12850170
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Linezolid versus vancomycin for methicillin-resistant Staphylococcus aureus infections. Author(s): Johnson JR. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2003 January 15; 36(2): 236-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12522761
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Linezolid vs vancomycin: analysis of two double-blind studies of patients with methicillin-resistant Staphylococcus aureus nosocomial pneumonia. Author(s): Wunderink RG, Rello J, Cammarata SK, Croos-Dabrera RV, Kollef MH. Source: Chest. 2003 November; 124(5): 1789-97. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14605050
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Lipoteichoic acid (LTA) of Streptococcus pneumoniae and Staphylococcus aureus activates immune cells via Toll-like receptor (TLR)-2, lipopolysaccharide-binding protein (LBP), and CD14, whereas TLR-4 and MD-2 are not involved. Author(s): Schroder NW, Morath S, Alexander C, Hamann L, Hartung T, Zahringer U, Gobel UB, Weber JR, Schumann RR. Source: The Journal of Biological Chemistry. 2003 May 2; 278(18): 15587-94. Epub 2003 February 19. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12594207
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Local anesthetics impair human granulocyte phagocytosis activity, oxidative burst, and CD11b expression in response to Staphylococcus aureus. Author(s): Kiefer RT, Ploppa A, Krueger WA, Plank M, Nohe B, Haeberle HA, Unertl K, Dieterich HJ. Source: Anesthesiology. 2003 April; 98(4): 842-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12657844
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Local care of Staphylococcus aureus exit-site infection precludes antibiotic use. Author(s): Hirsch DJ, Jindal KK. Source: Perit Dial Int. 2003 May-June; 23(3): 301-2. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12938835
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Local variants of Staphylococcal cassette chromosome mec in sporadic methicillinresistant Staphylococcus aureus and methicillin-resistant coagulase-negative Staphylococci: evidence of horizontal gene transfer? Author(s): Hanssen AM, Kjeldsen G, Sollid JU. Source: Antimicrobial Agents and Chemotherapy. 2004 January; 48(1): 285-96. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14693553
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Low concentrations of mupirocin in the pharynx following intranasal application may contribute to mupirocin resistance in methicillin-resistant Staphylococcus aureus. Author(s): Watanabe H, Masaki H, Asoh N, Watanabe K, Oishi K, Kobayashi S, Sato A, Sugita R, Nagatake T. Source: Journal of Clinical Microbiology. 2001 October; 39(10): 3775-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11574616
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Management and outcome of children with skin and soft tissue abscesses caused by community-acquired methicillin-resistant Staphylococcus aureus. Author(s): Lee MC, Rios AM, Aten MF, Mejias A, Cavuoti D, McCracken GH Jr, Hardy RD. Source: The Pediatric Infectious Disease Journal. 2004 February; 23(2): 123-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14872177
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Methicillin-resistant Staphylococcus aureus (MRSA) in the practice of otolaryngology--an emerging community acquired organism? Author(s): Collins M, Tami TA. Source: Current Opinion in Otolaryngology & Head and Neck Surgery. 2003 June; 11(3): 179-83. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12923359
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Methicillin-resistant Staphylococcus aureus in children with cystic fibrosis: An eradication protocol. Author(s): Solis A, Brown D, Hughes J, Van Saene HK, Heaf DP. Source: Pediatric Pulmonology. 2003 September; 36(3): 189-95. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12910579
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Methicillin-resistant Staphylococcus aureus infections among competitive sports participants--Colorado, Indiana, Pennsylvania, and Los Angeles County, 2000-2003. Author(s): Centers for Disease Control and Prevention (CDC). Source: Mmwr. Morbidity and Mortality Weekly Report. 2003 August 22; 52(33): 793-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12931079
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Methicillin-resistant Staphylococcus aureus whole-body decolonization among hospitalized patients with variable site colonization by using mupirocin in combination with octenidine dihydrochloride. Author(s): Rohr U, Mueller C, Wilhelm M, Muhr G, Gatermann S. Source: The Journal of Hospital Infection. 2003 August; 54(4): 305-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12919762
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Methicillin-resistant Staphylococcus aureus: need for constant surveillance,stringent control and vigorous treatment measures. Author(s): Kakru DK, Assadullah S, Thoker MA, Wani T. Source: Indian J Pathol Microbiol. 2003 January; 46(1): 121-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15027752
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Molecular characterization of resistance to mupirocin in methicillin-susceptible and resistant isolates of Staphylococcus aureus from nasal samples. Author(s): Chaves F, Garcia-Martinez J, de Miguel S, Otero JR. Source: Journal of Clinical Microbiology. 2004 February; 42(2): 822-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14766861
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Molecular confirmation of transmission route of Staphylococcus intermedius in mastoid cavity infection from dog saliva. Author(s): Kikuchi K, Karasawa T, Piao C, Itoda I, Hidai H, Yamaura H, Totsuka K, Morikawa T, Takayama M. Source: Journal of Infection and Chemotherapy : Official Journal of the Japan Society of Chemotherapy. 2004 February; 10(1): 46-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14991518
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Molecular epidemiology of clinical isolates of methicillin-resistant Staphylococcus aureus in Taiwan. Author(s): Huang YC, Su LH, Wu TL, Liu CE, Young TG, Chen PY, Hseuh PR, Lin TY. Source: Journal of Clinical Microbiology. 2004 January; 42(1): 307-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14715770
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Molecular epidemiology of methicillin-resistant Staphylococcus aureus in a Kumamoto Hospital in 2002. Author(s): Kawano F, Miyazaki H, Takami J, Fujino T, Sekiguchi J, Saruta K, Kuratsuji T, Kirikae T. Source: Japanese Journal of Infectious Diseases. 2003 June; 56(3): 129-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12944684
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Morphostructural damage and the inhibition of bacterial adhesiveness of Staphylococcus aureus and Moraxella catarrhalis induced by moxifloxacin. Author(s): Braga PC, Culici M, Ricci D, Dal Sasso M. Source: J Chemother. 2003 December; 15(6): 543-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14998077
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Multilocus sequence typing and the evolution of methicillin-resistant Staphylococcus aureus. Author(s): Robinson DA, Enright MC. Source: Clinical Microbiology and Infection : the Official Publication of the European Society of Clinical Microbiology and Infectious Diseases. 2004 February; 10(2): 92-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14759234
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Multiplex PCR assay for simultaneous detection of nine clinically relevant antibiotic resistance genes in Staphylococcus aureus. Author(s): Strommenger B, Kettlitz C, Werner G, Witte W. Source: Journal of Clinical Microbiology. 2003 September; 41(9): 4089-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12958230
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Mupirocin prophylaxis against nosocomial Staphylococcus aureus infections in nonsurgical patients: a randomized study. Author(s): Wertheim HF, Vos MC, Ott A, Voss A, Kluytmans JA, VandenbrouckeGrauls CM, Meester MH, van Keulen PH, Verbrugh HA. Source: Annals of Internal Medicine. 2004 March 16; 140(6): 419-25. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15023707
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Mutations are involved in emergence of aminoglycoside-induced small colony variants of Staphylococcus aureus. Author(s): Schaaff F, Bierbaum G, Baumert N, Bartmann P, Sahl HG. Source: International Journal of Medical Microbiology : Ijmm. 2003 December; 293(6): 427-35. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14760974
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NADPH oxidase is not required for spontaneous and Staphylococcus aureus-induced apoptosis of monocytes. Author(s): v Bernuth H, Kulka C, Roesler J, Gahr M, Rosen-Wolff A. Source: Annals of Hematology. 2004 April; 83(4): 206-11. Epub 2004 January 17. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14730390
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Nasal and hand carriage of Staphylococcus aureus in staff at a Department for Thoracic and Cardiovascular Surgery: endogenous or exogenous source? Author(s): Tammelin A, Klotz F, Hambraeus A, Stahle E, Ransjo U. Source: Infection Control and Hospital Epidemiology : the Official Journal of the Society of Hospital Epidemiologists of America. 2003 September; 24(9): 686-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14510252
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Nasal carriage of methicillin-resistant Staphylococcus aureus in the children of hospital staff. Author(s): Palanduz A, Guler N, Yalcin I. Source: The Pediatric Infectious Disease Journal. 2003 July; 22(7): 672-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12867847
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National surveillance of methicillin-sensitive and methicillin-resistant Staphylococcus aureus in Austrian hospitals: 1994-1998. Author(s): Assadian O, Daxboeck F, Aspoeck C, Blacky A, Dunkl R, Koller W. Source: The Journal of Hospital Infection. 2003 November; 55(3): 175-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14572483
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Nationwide surveillance for Staphylococcus aureus with reduced susceptibility to vancomycin in Korea. Author(s): Kim HB, Park WB, Lee KD, Choi YJ, Park SW, Oh MD, Kim EC, Choe KW. Source: Journal of Clinical Microbiology. 2003 June; 41(6): 2279-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12791836
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Neutralization of Staphylococcus aureus Panton Valentine leukocidin by intravenous immunoglobulin in vitro. Author(s): Gauduchon V, Cozon G, Vandenesch F, Genestier AL, Eyssade N, Peyrol S, Etienne J, Lina G. Source: The Journal of Infectious Diseases. 2004 January 15; 189(2): 346-53. Epub 2004 Jan 09. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14722901
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New antimicrobial cystatin C-based peptide active against gram-positive bacterial pathogens, including methicillin-resistant Staphylococcus aureus and multiresistant coagulase-negative staphylococci. Author(s): Jasir A, Kasprzykowski F, Kasprzykowska R, Lindstrom V, Schalen C, Grubb A. Source: Apmis : Acta Pathologica, Microbiologica, Et Immunologica Scandinavica. 2003 November; 111(11): 1004-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14629266
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Non-specificity of Staphylococcus generic primers. Author(s): Ah Tow L, Cowan DA. Source: Microbiology (Reading, England). 2003 July; 149(Pt 7): 1605-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12855713
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Nosocomial infections: methicillin resistant Staphylococcus auerus in wound infection in Ibadan, Nigeria. Author(s): Okesola AO, Oni AA, Bakare RA. Source: Afr J Med Med Sci. 1999 March-June; 28(1-2): 55-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12953988
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Nosocomial transmission of methicillin-resistant Staphylococcus aureus: a blinded study to establish baseline acquisition rates. Author(s): Fishbain JT, Lee JC, Nguyen HD, Mikita JA, Mikita CP, Uyehara CF, Hospenthal DR. Source: Infection Control and Hospital Epidemiology : the Official Journal of the Society of Hospital Epidemiologists of America. 2003 June; 24(6): 415-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12828317
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Obvious lack of association between dynamics of epidemic methicillin-resistant Staphylococcus aureus in central Europe and agr specificity groups. Author(s): Strommenger B, Cuny C, Werner G, Witte W. Source: European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology. 2004 January; 23(1): 15-9. Epub 2003 December 02. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14652782
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Occurrence of ica genes for slime synthesis in a collection of Staphylococcus epidermidis strains from orthopedic prosthesis infections. Author(s): Arciola CR, Campoccia D, Gamberini S, Donati ME, Baldassarri L, Montanaro L. Source: Acta Orthopaedica Scandinavica. 2003 October; 74(5): 617-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14620986
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Optimal inoculation methods and quality control for the NCCLS oxacillin agar screen test for detection of oxacillin resistance in Staphylococcus aureus. Author(s): Swenson JM, Spargo J, Tenover FC, Ferraro MJ. Source: Journal of Clinical Microbiology. 2001 October; 39(10): 3781-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11574618
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Organism-specific neutrophil-endothelial cell interactions in response to Escherichia coli, Streptococcus pneumoniae, and Staphylococcus aureus. Author(s): Moreland JG, Bailey G, Nauseef WM, Weiss JP. Source: Journal of Immunology (Baltimore, Md. : 1950). 2004 January 1; 172(1): 426-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14688351
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Outbreak of invasive disease caused by methicillin-resistant Staphylococcus aureus in neonates and prevalence in the neonatal intensive care unit. Author(s): Nambiar S, Herwaldt LA, Singh N. Source: Pediatric Critical Care Medicine : a Journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies. 2003 April; 4(2): 220-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12749656
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Outbreaks of community-associated methicillin-resistant Staphylococcus aureus skin infections. Author(s): Favero MS. Source: Infection Control and Hospital Epidemiology : the Official Journal of the Society of Hospital Epidemiologists of America. 2003 October; 24(10): 787. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14587949
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Outcome of Staphylococcus aureus bacteremia in patients with eradicable foci versus noneradicable foci. Author(s): Kim SH, Park WB, Lee KD, Kang CI, Kim HB, Oh MD, Kim EC, Choe KW. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2003 September 15; 37(6): 794-9. Epub 2003 August 23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12955640
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Outcomes analysis of delayed antibiotic treatment for hospital-acquired Staphylococcus aureus bacteremia. Author(s): Lodise TP, McKinnon PS, Swiderski L, Rybak MJ. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2003 June 1; 36(11): 1418-23. Epub 2003 May 20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12766837
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Outcomes of Hickman catheter salvage in febrile neutropenic cancer patients with Staphylococcus aureus bacteremia. Author(s): Kim SH, Kang CI, Kim HB, Youn SS, Oh MD, Kim EC, Park SY, Kim BK, Choe KW. Source: Infection Control and Hospital Epidemiology : the Official Journal of the Society of Hospital Epidemiologists of America. 2003 December; 24(12): 897-904. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14700404
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Overwhelming septic infection with a multi-resistant Staphylococcus aureus (MRSA) after total knee replacement. Author(s): Roth A, Fuhrmann R, Lange M, Mollenhauer J, Straube E, Venbrocks R. Source: Archives of Orthopaedic and Trauma Surgery. 2003 October; 123(8): 429-32. Epub 2003 August 05. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14574603
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Plasmid content of a vancomycin-resistant Enterococcus faecalis isolate from a patient also colonized by Staphylococcus aureus with a VanA phenotype. Author(s): Flannagan SE, Chow JW, Donabedian SM, Brown WJ, Perri MB, Zervos MJ, Ozawa Y, Clewell DB. Source: Antimicrobial Agents and Chemotherapy. 2003 December; 47(12): 3954-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14638508
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Population dynamics of persistent Staphylococcus aureus isolated from the airways of cystic fibrosis patients during a 6-year prospective study. Author(s): Kahl BC, Duebbers A, Lubritz G, Haeberle J, Koch HG, Ritzerfeld B, Reilly M, Harms E, Proctor RA, Herrmann M, Peters G. Source: Journal of Clinical Microbiology. 2003 September; 41(9): 4424-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12958283
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Postoperative infection with meticillin-resistant Staphylococcus aureus and socioeconomic background. Author(s): Bagger JP, Zindrou D, Taylor KM. Source: Lancet. 2004 February 28; 363(9410): 706-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15001331
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Poststernotomy mediastinitis due to methicillin-resistant Staphylococcus aureus endemic in a hospital. Author(s): Lin CH, Hsu RB, Chang SC, Lin FY, Chu SH. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2003 September 1; 37(5): 679-84. Epub 2003 August 12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12942400
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Prevalence of methicillin resistant Staphylococcus aureus in Karnataka. Author(s): Hanumanthappa AR, Chandrappa NR, Rajasekharappa MG. Source: Indian J Pathol Microbiol. 2003 January; 46(1): 129-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15027755
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Prevalence of serum IgE antibodies to the Staphylococcus aureus enterotoxins (SAE, SEB, SEC, SED, TSST-1) in patients with persistent allergic rhinitis. Author(s): Rossi RE, Monasterolo G. Source: International Archives of Allergy and Immunology. 2004 March; 133(3): 261-6. Epub 2004 February 17. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14976395
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Prevalence of Staphylococcus aureus carriage by young Malaysian footballers during indoor training. Author(s): William JL, Radu S, Aziz SA, Rahim RA, Cheah YK, Liwan A, Lihan S. Source: British Journal of Sports Medicine. 2004 February; 38(1): 12-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14751938
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Prevalence of Streptococcus pneumoniae and Staphylococcus aureus nasopharyngeal colonization in healthy children in the United States. Author(s): Cheng Immergluck L, Kanungo S, Schwartz A, McIntyre A, Schreckenberger PC, Diaz PS. Source: Epidemiology and Infection. 2004 April; 132(2): 159-66. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15061489
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Prevalence, molecular epidemiology, and clinical significance of heterogeneous glycopeptide-intermediate Staphylococcus aureus in liver transplant recipients. Author(s): Bert F, Clarissou J, Durand F, Delefosse D, Chauvet C, Lefebvre P, Lambert N, Branger C. Source: Journal of Clinical Microbiology. 2003 November; 41(11): 5147-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14605151
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Prevention of Staphylococcus aureus infections among surgical patients: beyond traditional perioperative prophylaxis. Author(s): Perl TM. Source: Surgery. 2003 November; 134(5 Suppl): S10-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14647028
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Qualitative and (semi)quantitative characterization of nasal and skin methicillinresistant Staphylococcus aureus carriage of hospitalized patients. Author(s): Rohr U, Wilhelm M, Muhr G, Gatermann S. Source: International Journal of Hygiene and Environmental Health. 2004 January; 207(1): 51-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14762974
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Quantitation of mecA transcription in oxacillin-resistant Staphylococcus aureus clinical isolates. Author(s): Rosato AE, Craig WA, Archer GL. Source: Journal of Bacteriology. 2003 June; 185(11): 3446-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12754244
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Quantitative microbial risk assessment exemplified by Staphylococcus aureus in unripened cheese made from raw milk. Author(s): Lindqvist R, Sylven S, Vagsholm I. Source: International Journal of Food Microbiology. 2002 September 15; 78(1-2): 155-70. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12222631
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Rapid control of an outbreak of Staphylococcus aureus on a neonatal intensive care department using standard infection control practices and nasal mupirocin. Author(s): Lally RT, Lanz E, Schrock CG. Source: American Journal of Infection Control. 2004 February; 32(1): 44-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14755235
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Rapid identification of Staphylococcus aureus from BacT/ALERT blood culture bottles by direct Gram stain characteristics. Author(s): Murdoch DR, Greenlees RL. Source: Journal of Clinical Pathology. 2004 February; 57(2): 199-201. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14747451
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Re:"Staphylococcus aureus carrier state among elderly residents of a long-term care facility". Author(s): Iraqi A, Baickle E. Source: Journal of the American Medical Directors Association. 2003 NovemberDecember; 4(6): 353. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14625415
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Regulation of virulence determinants in vitro and in vivo in Staphylococcus aureus. Author(s): Cheung AL, Bayer AS, Zhang G, Gresham H, Xiong YQ. Source: Fems Immunology and Medical Microbiology. 2004 January 15; 40(1): 1-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14734180
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Relationship between molecular epidemiology and antibiotic susceptibility of methicillin-resistant Staphylococcus aureus (MRSA) in a French teaching hospital. Author(s): Thouverez M, Muller A, Hocquet D, Talon D, Bertrand X. Source: Journal of Medical Microbiology. 2003 September; 52(Pt 9): 801-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12909658
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Relationship of relapsing hip prosthesis infection by Staphylococcus aureus with gamma interferon deficiency. Author(s): Honstettre A, Mege JL, Lina G, Aubaniac JM, Drancourt M. Source: Journal of Clinical Microbiology. 2003 November; 41(11): 5344-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14605201
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Revision of linezolid disk diffusion quality control guidelines for testing Staphylococcus aureus ATCC 25923: an independent seven-laboratory trial. Author(s): Biedenbach DJ, Jones RN. Source: Clinical Microbiology and Infection : the Official Publication of the European Society of Clinical Microbiology and Infectious Diseases. 2003 October; 9(10): 1035-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14616748
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Role of a cysteine synthase in Staphylococcus aureus. Author(s): Lithgow JK, Hayhurst EJ, Cohen G, Aharonowitz Y, Foster SJ. Source: Journal of Bacteriology. 2004 March; 186(6): 1579-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14996787
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Role of comorbidity in mortality related to Staphylococcus aureus bacteremia: a prospective study using the Charlson weighted index of comorbidity. Author(s): Lesens O, Methlin C, Hansmann Y, Remy V, Martinot M, Bergin C, Meyer P, Christmann D. Source: Infection Control and Hospital Epidemiology : the Official Journal of the Society of Hospital Epidemiologists of America. 2003 December; 24(12): 890-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14700403
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Role of siderophore biosynthesis in virulence of Staphylococcus aureus: identification and characterization of genes involved in production of a siderophore. Author(s): Dale SE, Doherty-Kirby A, Lajoie G, Heinrichs DE. Source: Infection and Immunity. 2004 January; 72(1): 29-37. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14688077
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Sensitivity of methicillin-resistant Staphylococcus aureus (MRSA) to antimicrobial agents other than beta-lactams: profile and trend, 1998-2003. Author(s): Manfredi R, Nanetti A, Morelli S, Valentini R, Calza L, Chiodo F. Source: Isr Med Assoc J. 2004 March; 6(3): 191-2. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15055283
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Sources of Staphylococcus aureus for patients on continuous ambulatory peritoneal dialysis. Author(s): Herwaldt LA, Boyken LD, Coffman S, Hochstetler L, Flanigan MJ. Source: Perit Dial Int. 2003 May-June; 23(3): 237-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12938823
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spa typing method for discriminating among Staphylococcus aureus isolates: implications for use of a single marker to detect genetic micro- and macrovariation. Author(s): Koreen L, Ramaswamy SV, Graviss EA, Naidich S, Musser JM, Kreiswirth BN. Source: Journal of Clinical Microbiology. 2004 February; 42(2): 792-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14766855
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Spread of erythromycin-, tetracycline-, and aminoglycoside-resistant genes in methicillin-resistant Staphylococcus aureus clinical isolates in a Kumamoto Hospital. Author(s): Sekiguchi J, Fujino T, Saruta K, Kawano F, Takami J, Miyazaki H, Kuratsuji T, Yoshikura H, Kirikae T. Source: Japanese Journal of Infectious Diseases. 2003 June; 56(3): 133-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12944686
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Staphylococcus aureus alpha-toxin induces apoptosis in peripheral blood mononuclear cells: role of endogenous tumour necrosis factor-alpha and the mitochondrial death pathway. Author(s): Haslinger B, Strangfeld K, Peters G, Schulze-Osthoff K, Sinha B. Source: Cellular Microbiology. 2003 October; 5(10): 729-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12969378
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Staphylococcus aureus and food poisoning. Author(s): Le Loir Y, Baron F, Gautier M. Source: Genet Mol Res. 2003 March 31; 2(1): 63-76. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12917803
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Staphylococcus aureus bacteremia in patients with hematologic malignancies: a retrospective case-control study. Author(s): Venditti M, Falcone M, Micozzi A, Carfagna P, Taglietti F, Serra PF, Martino P. Source: Haematologica. 2003 August; 88(8): 923-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12935981
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Staphylococcus aureus with reduced susceptibility to vancomycin. Author(s): Weerakoon W, Atukorala SD, Gamage DS, Wijeratne M. Source: Ceylon Med J. 2003 June; 48(2): 58-9. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12971212
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Staphylococcus aureus, but not Staphylococcus epidermidis, modulates the oxidative response and induces apoptosis in human neutrophils. Author(s): Nilsdotter-Augustinsson A, Wilsson A, Larsson J, Stendahl O, Ohman L, Lundqvist-Gustafsson H. Source: Apmis : Acta Pathologica, Microbiologica, Et Immunologica Scandinavica. 2004 February; 112(2): 109-18. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15056227
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Survival of Staphylococcus aureus and Salmonella enteritidis on salted sardines (Sardina pilchardus) during ripening. Author(s): Arkoudelos JS, Samaras FJ, Tassou CC. Source: J Food Prot. 2003 August; 66(8): 1479-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12929841
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Ten years phage-typing of Belgian clinical methicillin-resistant Staphylococcus aureus isolates (1992-2001). Author(s): Wildemauwe C, Godard C, Verschraegen G, Claeys G, Duyck MC, De Beenhouwer H, Vanhoof R. Source: The Journal of Hospital Infection. 2004 January; 56(1): 16-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14706266
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The 1.15A crystal structure of the Staphylococcus aureus methionyl-aminopeptidase and complexes with triazole based inhibitors. Author(s): Oefner C, Douangamath A, D'Arcy A, Hafeli S, Mareque D, Mac Sweeney A, Padilla J, Pierau S, Schulz H, Thormann M, Wadman S, Dale GE. Source: Journal of Molecular Biology. 2003 September 5; 332(1): 13-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12946343
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The bacterial insertion sequence element IS256 occurs preferentially in nosocomial Staphylococcus epidermidis isolates: association with biofilm formation and resistance to aminoglycosides. Author(s): Kozitskaya S, Cho SH, Dietrich K, Marre R, Naber K, Ziebuhr W. Source: Infection and Immunity. 2004 February; 72(2): 1210-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14742578
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The impact of methicillin resistance on the outcome of poststernotomy mediastinitis due to Staphylococcus aureus. Author(s): Combes A, Trouillet JL, Joly-Guillou ML, Chastre J, Gibert C. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2004 March 15; 38(6): 822-9. Epub 2004 February 27. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14999626
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Theasinensin A, a tea polyphenol formed from (-)-epigallocatechin gallate, suppresses antibiotic resistance of methicillin-resistant Staphylococcus aureus. Author(s): Hatano T, Kusuda M, Hori M, Shiota S, Tsuchiya T, Yoshida T. Source: Planta Medica. 2003 November; 69(11): 984-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14735433
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Tips and tricks from Staphylococcus aureus. Author(s): van Kessel K, Veldkamp KE, Pesschel A, de Haas C, Verhoef J, van Strijp J. Source: Advances in Experimental Medicine and Biology. 2003; 531: 341-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12916804
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Toxic shock syndrome due to Staphylococcus aureus sepsis following diagnostic laparotomy for Hodgkin's disease. Author(s): Goksugur N, Ozaras R, Tahan V, Mert A, Soysal T, Aydemir E, Tabak F. Source: Journal of the European Academy of Dermatology and Venereology : Jeadv. 2003 November; 17(6): 732-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14761154
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Transcriptional regulation of the Staphylococcus aureus thioredoxin and thioredoxin reductase genes in response to oxygen and disulfide stress. Author(s): Uziel O, Borovok I, Schreiber R, Cohen G, Aharonowitz Y. Source: Journal of Bacteriology. 2004 January; 186(2): 326-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14702300
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Treatment of meningitis due to methicillin-resistant Staphylococcus epidermidis with linezolid. Author(s): Krueger WA, Kottler B, Will BE, Heininger A, Guggenberger H, Unertl KE. Source: Journal of Clinical Microbiology. 2004 February; 42(2): 929-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14766894
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Treatment outcomes for serious infections caused by methicillin-resistant Staphylococcus aureus with reduced vancomycin susceptibility. Author(s): Howden BP, Ward PB, Charles PG, Korman TM, Fuller A, du Cros P, Grabsch EA, Roberts SA, Robson J, Read K, Bak N, Hurley J, Johnson PD, Morris AJ, Mayall BC, Grayson ML. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2004 February 15; 38(4): 521-8. Epub 2004 January 29. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14765345
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Ubi pus ibi evacua: Staphylococcus aureus pericardial abscess--one more dreadful complication of this pathogen. Author(s): Caeiro JP. Source: Southern Medical Journal. 2003 September; 96(9): 839. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14513975
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Ultra-sonic nebulizers as a potential source of methicillin-resistant Staphylococcus aureus causing an outbreak in a university tertiary care hospital. Author(s): Schultsz C, Meester HH, Kranenburg AM, Savelkoul PH, Boeijen-Donkers LE, Kaiser AM, de Bree R, Snow GB, Vandenbroucke-Grauls CJ. Source: The Journal of Hospital Infection. 2003 December; 55(4): 269-75. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14629970
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Understanding and controlling methicillin-resistant Staphylococcus aureus infections. Author(s): Boyce JM. Source: Infection Control and Hospital Epidemiology : the Official Journal of the Society of Hospital Epidemiologists of America. 2002 September; 23(9): 485-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12269442
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Understanding the mechanism of action of the exfoliative toxins of Staphylococcus aureus. Author(s): Ladhani S. Source: Fems Immunology and Medical Microbiology. 2003 November 28; 39(2): 181-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14625102
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Update on the major clonal types of methicillin-resistant Staphylococcus aureus in the Czech Republic. Author(s): Melter O, Aires de Sousa M, Urbaskova P, Jakubu V, Zemlickova H, de Lencastre H. Source: Journal of Clinical Microbiology. 2003 November; 41(11): 4998-5005. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14605130
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Use of a Staphylococcus aureus conjugate vaccine in patients receiving hemodialysis. Author(s): Shinefield H, Black S, Fattom A, Horwith G, Rasgon S, Ordonez J, Yeoh H, Law D, Robbins JB, Schneerson R, Muenz L, Fuller S, Johnson J, Fireman B, Alcorn H, Naso R. Source: The New England Journal of Medicine. 2002 February 14; 346(7): 491-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11844850
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Use of multiplex PCR to identify Staphylococcus aureus adhesins involved in human hematogenous infections. Author(s): Tristan A, Ying L, Bes M, Etienne J, Vandenesch F, Lina G. Source: Journal of Clinical Microbiology. 2003 September; 41(9): 4465-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12958296
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Use of perioperative mupirocin to prevent methicillin-resistant Staphylococcus aureus (MRSA) orthopaedic surgical site infections. Author(s): Wilcox MH, Hall J, Pike H, Templeton PA, Fawley WN, Parnell P, Verity P. Source: The Journal of Hospital Infection. 2003 July; 54(3): 196-201. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12855234
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Use of quantitative antibiogram analysis to determine the clonality of coagulasenegative Staphylococcus species from blood culture. Author(s): Bearson BL, Labarca JA, Brankovic LE, Cohen M, Bruckner DA, Pegues DA. Source: Clinical Microbiology and Infection : the Official Publication of the European Society of Clinical Microbiology and Infectious Diseases. 2004 February; 10(2): 148-55. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14759240
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Use of the quorum-sensing inhibitor RNAIII-inhibiting peptide to prevent biofilm formation in vivo by drug-resistant Staphylococcus epidermidis. Author(s): Balaban N, Giacometti A, Cirioni O, Gov Y, Ghiselli R, Mocchegiani F, Viticchi C, Del Prete MS, Saba V, Scalise G, Dell'Acqua G. Source: The Journal of Infectious Diseases. 2003 February 15; 187(4): 625-30. Epub 2003 Feb 07. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12599079
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Vaginal infection with methicillin-resistant Staphylococcus aureus after laparoscopic supracervical hysterectomy. Author(s): Olesen A, Rudnicki M. Source: Acta Obstetricia Et Gynecologica Scandinavica. 2002 July; 81(7): 676-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12190844
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Value of broth cultures in detecting methicillin-resistant Staphylococcus aureus. Author(s): Roberts S, Young H, Faulkner S, Bilkey M, Eyres S, Renshaw S, Morris AJ. Source: N Z Med J. 2002 September 27; 115(1162): U191. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12386667
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Vancomycin for Staphylococcus aureus therapy of respiratory tract infections: the end of an era? Author(s): Nathwani D, Tillotson GS. Source: International Journal of Antimicrobial Agents. 2003 June; 21(6): 521-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12791464
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Vancomycin treatment failure associated with heterogeneous vancomycinintermediate Staphylococcus aureus in a patient with endocarditis and in the rabbit model of endocarditis. Author(s): Moore MR, Perdreau-Remington F, Chambers HF. Source: Antimicrobial Agents and Chemotherapy. 2003 April; 47(4): 1262-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12654656
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Vancomycin-intermediate Staphylococcus aureus with phenotypic susceptibility to methicillin in a patient with recurrent bacteremia. Author(s): Naimi TS, Anderson D, O'Boyle C, Boxrud DJ, Johnson SK, Tenover FC, Lynfield R. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2003 June 15; 36(12): 1609-12. Epub 2003 Jun 06. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12802763
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Vancomycin-resistant Staphylococcus aureus: no apocalypse now. Author(s): Goldstein FW, Kitzis MD. Source: Clinical Microbiology and Infection : the Official Publication of the European Society of Clinical Microbiology and Infectious Diseases. 2003 August; 9(8): 761-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14616695
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Vancomycin-resistant Staphylococcus aureus--New York, 2004. Author(s): Centers for Disease Control and Prevention (CDC). Source: Mmwr. Morbidity and Mortality Weekly Report. 2004 April 23; 53(15): 322-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15103297
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Varicella associated with Staphylococcus aureus purulent pericarditis. Author(s): Ulloa-Gutierrez R, Avila-Aguero ML. Source: The Pediatric Infectious Disease Journal. 2003 October; 22(10): 935-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14551498
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Vascular access infections in patients undergoing dialysis with special emphasis on the role and treatment of Staphylococcus aureus. Author(s): Sexton DJ. Source: Infectious Disease Clinics of North America. 2001 September; 15(3): 731-42, Vii. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11570139
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Virulent combinations of adhesin and toxin genes in natural populations of Staphylococcus aureus. Author(s): Peacock SJ, Moore CE, Justice A, Kantzanou M, Story L, Mackie K, O'Neill G, Day NP. Source: Infection and Immunity. 2002 September; 70(9): 4987-96. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12183545
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What determines nasal carriage of Staphylococcus aureus? Author(s): Peacock SJ, de Silva I, Lowy FD. Source: Trends in Microbiology. 2001 December; 9(12): 605-10. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11728874
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Whole genome sequencing of meticillin-resistant Staphylococcus aureus. Author(s): Kuroda M, Ohta T, Uchiyama I, Baba T, Yuzawa H, Kobayashi I, Cui L, Oguchi A, Aoki K, Nagai Y, Lian J, Ito T, Kanamori M, Matsumaru H, Maruyama A, Murakami H, Hosoyama A, Mizutani-Ui Y, Takahashi NK, Sawano T, Inoue R, Kaito C, Sekimizu K, Hirakawa H, Kuhara S, Goto S, Yabuzaki J, Kanehisa M, Yamashita A, Oshima K, Furuya K, Yoshino C, Shiba T, Hattori M, Ogasawara N, Hayashi H, Hiramatsu K. Source: Lancet. 2001 April 21; 357(9264): 1225-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11418146
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Would active surveillance cultures help control healthcare-related methicillinresistant Staphylococcus aureus infections? Author(s): Farr BM, Jarvis WR. Source: Infection Control and Hospital Epidemiology : the Official Journal of the Society of Hospital Epidemiologists of America. 2002 February; 23(2): 65-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11893150
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CHAPTER 2. NUTRITION AND STAPHYLOCOCCUS AUREUS Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and Staphylococcus aureus.
Finding Nutrition Studies on Staphylococcus aureus 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 “Staphylococcus aureus” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.
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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 “Staphylococcus aureus” (or a synonym): •
Copper complexes with bioactive ligands, 1: Antimicrobial activity. Author(s): Slovenska Technicka Univ., Bratislava (Slovak Republic). Fakulta Chemickej a Potravinarskej Technologie Source: Dudova, B. Hudecova, D. Pokorny, R. Mikulasova, M. Palicova, M. Segla, P. Melnik, M. Folia-Microbiologica (Czech Republic). (October 2001). volume 46(5) page 379-384.
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Isolation and partial characterization of an antibacterial substance produced by Enterococcus faecium. Author(s): University of Sofia (Bulgaria). Dept. of Microbiology Source: Pantev, A. Kabadjova, P. Ivanova, I. Dalgalarrondo, M. Haertle, T. Dousset, X. Prevost, H. Chobert, J. M. Folia-Microbiologica (Czech Republic). (August 2002). volume 47(4) page 391-400.
Additional physician-oriented references include: •
2-Oxoglutarate transport system in Staphylococcus aureus. Author(s): Department of Pharmaceutical Microbiology, Medical Academy, Lubartowska 85, 20-123 Lublin, Poland.
[email protected] Source: Tynecka, Z Korona Glowniak, I Los, R Arch-Microbiol. 2001 July; 176(1-2): 14350 0302-8933
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A genome-wide strategy for the identification of essential genes in Staphylococcus aureus. Author(s): Elitra Pharmaceuticals, San Diego, CA 92121, USA. Source: Forsyth, R Allyn Haselbeck, Robert J Ohlsen, Kari L Yamamoto, Robert T Xu, Howard Trawick, John D Wall, Daniel Wang, Liangsu Brown Driver, Vickie Froelich, Jamie M C, Kedar G King, Paula McCarthy, Melissa Malone, Cheryl Misiner, Brian Robbins, David Tan, Zehui Zhu Zy, Zhan yang Carr, Grant Mosca, Deborah A Zamudio, Carlos Foulkes, J Gordon Zyskind, Judith W Mol-Microbiol. 2002 March; 43(6): 1387-400 0950-382X
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A novel selective medium for the detection of methicillin-resistant Staphylococcus aureus enabling result reporting in under 24 h. Author(s): Department of Microbiology, Freeman Hospital, High Heaton, Newcastle upon Tyne, NE7 7DN, UK.
[email protected] Source: Gurran, C Holliday, M G Perry, J D Ford, M Morgan, S Orr, K E J-Hosp-Infect. 2002 October; 52(2): 148-51 0195-6701
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Actions of gluco-oligosaccharide against Staphylococcus aureus. Author(s): Department of Dermatology, Okayama University Graduate School of Medicine and Dentistry, Japan. Source: Akiyama, H Oono, T Huh, W K Yamasaki, O Akagi, Y Uemura, H Yamada, T Iwatsuki, K J-Dermatol. 2002 September; 29(9): 580-6 0385-2407
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An epidemic methicillin-resistant strain of Staphylococcus aureus in Spain. Author(s): Laboratorio de Referencia de Estafilococos, Centro Nacional de Microbiologia, Majadahonda, Madrid, Spain. Source: Aparicio, P Richardson, J Martin, S Vindel, A Marples, R R Cookson, B D Epidemiol-Infect. 1992 April; 108(2): 287-98 0950-2688
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An inhibitor of Staphylococcus aureus exfoliative toxin. Author(s): Department of Biology, College of Education, University of Basra, Basra, Iraq. Source: Al Sulami, A A Al Rubiay, K K Affat, A M East-Mediterr-Health-J. 2001 JanMarch; 7(1-2): 121-7 1020-3397
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An integrated critique of the efficacy of topical mupirocin in preventing catheterrelated Staphylococcus aureus infections in peritoneal dialysis clients. Author(s): University Health Network, Toronto General Hospital Site, Toronto, Ontario.
[email protected] Source: Pratt, Oneka CANNT-J. 2002 Jan-March; 12(1): 20-8
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Antibacterial action of several tannins against Staphylococcus aureus. Author(s): Department of Dermatology, Okayama University Graduate School of Medicine and Dentistry, Shikata-cho 2-5-1, Okayama 700-8558, Japan.
[email protected] Source: Akiyama, H Fujii, K Yamasaki, O Oono, T Iwatsuki, K J-Antimicrob-Chemother. 2001 October; 48(4): 487-91 0305-7453
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Antibacterial activity of Australian plant extracts against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE). Author(s): Environment and Biotechnology Centre, School of Engineering and Science, Swinburne University of Technology, Hawthorne, Victoria, Australia.
[email protected] Source: Palombo, E A Semple, S J J-Basic-Microbiol. 2002; 42(6): 444-8 0233-111X
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Antimicrobial activity of licorice flavonoids against methicillin-resistant Staphylococcus aureus. Author(s): School of Pharmaceutical Sciences, Toho University, 2-2-1 Miyama, Funabashi, Chiba 274-8510, Japan.
[email protected] Source: Fukai, T Marumo, A Kaitou, K Kanda, T Terada, S Nomura, T Fitoterapia. 2002 October; 73(6): 536-9 0367-326X
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Association between nasal methicillin-resistant Staphylococcus aureus carriage and infection in liver transplant recipients. Author(s): Mayo Clinic, Rochester, MN 55905, USA. Source: Patel, R Liver-Transpl. 2001 August; 7(8): 752-3 1527-6465
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Comparison of the effects in vitro of tea tree oil and plaunotol on methicillinsusceptible and methicillin-resistant strains of Staphylococcus aureus. Author(s): Department of Microbiology, Showa Pharmaceutical University, Machida, Tokyo, Japan. Source: Hada, T Furuse, S Matsumoto, Y Hamashima, H Masuda, K Shiojima, K Arai, T Sasatsu, M Microbios. 2001; 106 Suppl 2: 133-41 0026-2633
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Decolonization of methicillin-resistant Staphylococcus aureus using oral vancomycin and topical mupirocin. Author(s): Department of Medical Microbiology, St Elisabeth Hospital, PO Box 747, 5000 AS Tilburg, The Netherlands.
[email protected] Source: Maraha, B van Halteren, J Verzijl, J M Wintermans, R G Buiting, A G ClinMicrobiol-Infect. 2002 October; 8(10): 671-5 1198-743X
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Effect of preventing Staphylococcus aureus carriage on rates of peritoneal catheterrelated staphylococcal infections. Literature synthesis. Author(s): New Mexico VA Health Care System, and Department of Medicine, University of New Mexico School of Medicine, Albuquerque 87108, USA.
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Source: Ritzau, J Hoffman, R M Tzamaloukas, A H Perit-Dial-Int. 2001 Sep-October; 21(5): 471-9 0896-8608 •
Effectiveness of mupirocin and polymyxin B in experimental Staphylococcus aureus, Pseudomonas aeruginosa, and Serratia marcescens keratitis. Author(s): Department of Microbiology, Immunology, and Parasitology, LSU Health Sciences Center, New Orleans, LA 70112, USA. Source: Moreau, J M Conerly, L L Hume, E B Dajcs, J J Girgis, D O Cannon, B M Thibodeaux, B A Stroman, D W O'Callaghan, R J Cornea. 2002 November; 21(8): 807-11 0277-3740
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Evaluation of different detection methods of biofilm formation in Staphylococcus aureus. Author(s): Institut fur Medizinische Mikrobiologie und Immunologie, Universitatsklinikum Hamburg-Eppendorf, Martinistr. 52, Germany.
[email protected] Source: Knobloch, J K Horstkotte, M A Rohde, H Mack, D Med-Microbiol-Immunol(Berl). 2002 October; 191(2): 101-6 0300-8584
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Flavonoids with activity against methicillin-resistant Staphylococcus aureus from Dalea scandens var. paucifolia. Author(s): National Center for Natural Products Research, Research Institute of Pharmaceutical Sciences, School of Pharmacy, The University of Mississippi, University, MS 38677, USA.
[email protected] Source: Nanayakkara, N P Burandt, C L Jr Jacob, M R Planta-Med. 2002 June; 68(6): 51922 0032-0943
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Intranasal mupirocin to prevent postoperative Staphylococcus aureus infections. Author(s): University of Iowa Colleges of Medicine and Public Health, Iowa City, USA. Source: Perl, Trish M Cullen, Joseph J Wenzel, Richard P Zimmerman, M Bridget Pfaller, Michael A Sheppard, Deborah Twombley, Jennifer French, Pamela P Herwaldt, Loreen A N-Engl-J-Med. 2002 June 13; 346(24): 1871-7 1533-4406
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MntR modulates expression of the PerR regulon and superoxide resistance in Staphylococcus aureus through control of manganese uptake. Author(s): Department of Molecular Biology and Biotechnology, University of Sheffield, Western Bank, Sheffield S10 2TN, UK. Source: Horsburgh, M J Wharton, S J Cox, A G Ingham, E Peacock, S Foster, S J MolMicrobiol. 2002 June; 44(5): 1269-86 0950-382X
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Nosocomial transmission of methicillin-resistant Staphylococcus aureus from a mother to her preterm quadruplet infants. Author(s): Department of Pediatrics, Division of Infectious Diseases and New YorkPresbyterian Hospital, Columbia University, New York, NY 10032, USA. Source: Morel, Anne Sophie Wu, Fann Della Latta, Phyllis Cronquist, Alicia Rubenstein, David Saiman, Lisa Am-J-Infect-Control. 2002 May; 30(3): 170-3 0196-6553
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Post-antibiotic effect of the antimicrobial peptide lactoferricin on Escherichia coli and Staphylococcus aureus. Author(s): Department of Medical Microbiology, University Hospital of Tromso, N-9038 Tromso, Norway.
[email protected] Source: Haukland, H H Vorland, L H J-Antimicrob-Chemother. 2001 October; 48(4): 56971 0305-7453
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Preventing Staphylococcus aureus infection in the renal unit. Author(s): Nuffield Department of Clinical Laboratory Sciences, University of Oxford, John Radcliffe Hospital, Oxford, UK.
[email protected] Source: Peacock, S J Mandal, S Bowler, I C QJM. 2002 June; 95(6): 405-10 1460-2725
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Proteolytic activity of Staphylococcus aureus strains isolated from the colonized skin of patients with acute-phase atopic dermatitis. Author(s): Institute of Molecular Biology and Biotechnology, Jagiellonian University, ul. Gronostajowa 7, 30-387 Krakow, Poland.
[email protected] Source: Miedzobrodzki, J Kaszycki, P Bialecka, A Kasprowicz, A Eur-J-Clin-MicrobiolInfect-Dis. 2002 April; 21(4): 269-76 0934-9723
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Rapid reduction of Staphylococcus aureus populations on stainless steel surfaces by zeolite ceramic coatings containing silver and zinc ions. Author(s): University of Arizona, Tucson, AZ, USA. Source: Bright, K R Gerba, C P Rusin, P A J-Hosp-Infect. 2002 December; 52(4): 307-9 0195-6701
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Transfer of cationic antibacterial agents berberine, palmatine, and benzalkonium through bimolecular planar phospholipid film and Staphylococcus aureus membrane. Author(s): Department of Bioenergetics, A. N. Belozersky Institute of Physico-Chemical Biology, Moscow State University, Russia. Source: Severina, I I Muntyan, M S Lewis, K Skulachev, V P IUBMB-Life. 2001 December; 52(6): 321-4 1521-6543
Federal Resources on Nutrition In addition to the IBIDS, the United States Department of Health and Human Services (HHS) and the United States Department of Agriculture (USDA) provide many sources of information on general nutrition and health. Recommended resources include: •
healthfinder®, HHS’s gateway to health information, including diet and nutrition: http://www.healthfinder.gov/scripts/SearchContext.asp?topic=238&page=0
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The United States Department of Agriculture’s Web site dedicated to nutrition information: www.nutrition.gov
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The Food and Drug Administration’s Web site for federal food safety information: www.foodsafety.gov
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The National Action Plan on Overweight and Obesity sponsored by the United States Surgeon General: http://www.surgeongeneral.gov/topics/obesity/
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The Center for Food Safety and Applied Nutrition has an Internet site sponsored by the Food and Drug Administration and the Department of Health and Human Services: http://vm.cfsan.fda.gov/
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Center for Nutrition Policy and Promotion sponsored by the United States Department of Agriculture: http://www.usda.gov/cnpp/
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Food and Nutrition Information Center, National Agricultural Library sponsored by the United States Department of Agriculture: http://www.nal.usda.gov/fnic/
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Food and Nutrition Service sponsored by the United States Department of Agriculture: http://www.fns.usda.gov/fns/
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Additional Web Resources A number of additional Web sites offer encyclopedic information covering food and nutrition. The following is a representative sample: •
AOL: http://search.aol.com/cat.adp?id=174&layer=&from=subcats
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Family Village: http://www.familyvillage.wisc.edu/med_nutrition.html
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Google: http://directory.google.com/Top/Health/Nutrition/
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Healthnotes: http://www.healthnotes.com/
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Open Directory Project: http://dmoz.org/Health/Nutrition/
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Yahoo.com: http://dir.yahoo.com/Health/Nutrition/
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WebMDHealth: 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 Staphylococcus aureus; 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: •
Food and Diet Guava Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,139,00.html
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CHAPTER 3.
DISSERTATIONS ON STAPHYLOCOCCUS
AUREUS Overview In this chapter, we will give you a bibliography on recent dissertations relating to Staphylococcus aureus. 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 “Staphylococcus aureus” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on Staphylococcus aureus, we have not necessarily excluded non-medical dissertations in this bibliography.
Dissertations on Staphylococcus aureus 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 Staphylococcus aureus. 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: •
An Examination of Some Aspects of the Structure and Function of the Glycocalyces of Staphylococcus aureus Strains Wiley and Smith by Caputy, Gregory Gary James; PhD from University of Calgary (Canada), 1984 http://wwwlib.umi.com/dissertations/fullcit/NK66235
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Analysis of Promoter Activity in Staphylococcus aureus by Ross, Christian Allen; PhD from The University of Texas at Dallas, 2003, 170 pages http://wwwlib.umi.com/dissertations/fullcit/3098547
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Characterization of Sara, a Global Virulence Gene Regulator in Staphylococcus aureus by Sterba, Kristen Michelle; PhD from University of Arkansas for Medical Sciences, 2003, 112 pages http://wwwlib.umi.com/dissertations/fullcit/3093265
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Chemotherapy and Pathogenic Mechanisms of Staphylococcus aureus Keratitis by Dajcs, Joseph John; PhD from Louisiana State University Health Sciences Center, 2003, 147 pages http://wwwlib.umi.com/dissertations/fullcit/3102975
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Contact Activation on Bacterial Surfaces: a Virulence Mechanism (salmonella Typhimurium, Escherichia coli, Staphylococcus aureus) by Persson, Kristin Ulrika; PhD from Lunds Universitet (Sweden), 2003, 98 pages http://wwwlib.umi.com/dissertations/fullcit/f39793
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Further Studies on the Immunology of the Alpha Toxin of Staphylococcus aureus by Surujballi, Om P; PhD from University of Windsor (Canada), 1987 http://wwwlib.umi.com/dissertations/fullcit/NL39637
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Pharmacodynamic Modeling of Ciprofloxacin Resistance in Staphylococcus aureus by Campion, Jeffrey James; PhD from University of Kentucky, 2003, 248 pages http://wwwlib.umi.com/dissertations/fullcit/3086892
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Structural Insights into the Mechanism and Specificity of Pore-forming Toxins from Staphylococcus aureus and Vibrio Cholerae by Olson, Richard, III; PhD from Columbia University, 2003, 178 pages http://wwwlib.umi.com/dissertations/fullcit/3095598
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Studies on the Genetic Determinant Responsible for Penicillin Resistance in Staphylococcus aureus by Weling, Shashikant V; PhD from University of Toronto (Canada), 1971 http://wwwlib.umi.com/dissertations/fullcit/NK10834
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Studies on the Possible Roles of Beta-hemolysin of Staphylococcus aureus and Blood Serum in the Pathogenesis of Bovine Mastitis by Naidu, Talapala Govindaswamy; PhD from University of Guelph (Canada), 1974 http://wwwlib.umi.com/dissertations/fullcit/NK18023
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Studies with Gamma Hemolysin of Staphylococcus aureus by Fackrell, Hugh B; PhD from The University of Manitoba (Canada), 1974 http://wwwlib.umi.com/dissertations/fullcit/NK19210
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Targeting Receptor-histidine Kinase Signaling in Staphylococcus aureus by Lyon, Gholson J.; PhD from The Rockefeller University, 2003, 213 pages http://wwwlib.umi.com/dissertations/fullcit/3078506
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The Influence of Growth Parameters upon Production of Staphylococcal Enterotoxin A (SEA) by Staphylococcus aureus As Monitored by Immunodiffusion Tests by Dybdahl, Kimberly Ann; MS from Angelo State University, 2003, 43 pages http://wwwlib.umi.com/dissertations/fullcit/1413305
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 4. CLINICAL TRIALS AND STAPHYLOCOCCUS AUREUS Overview In this chapter, we will show you how to keep informed of the latest clinical trials concerning Staphylococcus aureus.
Recent Trials on Staphylococcus aureus The following is a list of recent trials dedicated to Staphylococcus aureus.8 Further information on a trial is available at the Web site indicated. •
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 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
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Safety Study of an Intravenous Staphylococcus aureus Immune Globulin (Human), [Altastaph] in Low-Birth-Weight-Neonates Condition(s): Staphylococcal Infections Study Status: This study is currently recruiting patients.
8
These are listed at www.ClinicalTrials.gov.
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Sponsor(s): Nabi Biopharmaceuticals Purpose - Excerpt: The main objective will be to test the safety of two intravenous infusions of Altastaph, a human immunoglobulin product. The study will also test the ability of Altastaph to protect against S. aureus infection. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00066989 •
Tigecycline in the Treatment of Selected Serious Infections Caused by VancomycinResistant Enterococcus (VRE) or Methicillin-Resistant Staphylococcus aureus (MRSA) Condition(s): Bacteremia; Pneumonia, Bacterial; Skin Diseases, Bacterial Study Status: This study is currently recruiting patients. Sponsor(s): Wyeth-Ayerst Research Purpose - Excerpt: A Phase 3, Multicenter, Double-Blind, Randomized (3:1) Study Evaluating Tigecycline And Linezolid For The Treatment Of Selected Serious Infections In Subjects With Vancomycin-Resistant Enterococcus And Evaluating Tigecycline And Vancomycin For The Treatment Of Selected Serious Infections In Subjects With Methicillin-Resistant Staphylococcus aureus. The primary objective of this study is to evaluate the safety and efficacy of tigecycline in the treatment of selected serious infections caused by VRE or MRSA. The primary efficacy endpoint will be the clinical response for all subjects. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00079976
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 “Staphylococcus aureus” (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 5. PATENTS ON STAPHYLOCOCCUS AUREUS 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 “Staphylococcus aureus” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on Staphylococcus aureus, we have not necessarily excluded non-medical patents in this bibliography.
Patents on Staphylococcus aureus By performing a patent search focusing on Staphylococcus aureus, 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 Staphylococcus aureus: •
Antibodies specific for Staphylococcus aureus, and use thereof Inventor(s): Battail; Nicole (Lyons, FR), Carret; Gerard (Feyzin, FR), Flandrois; JeanPierre (Lyons, FR), Merlin; Sylviane (Caluire, FR) Assignee(s): Bio Merieux (marcy L'etoile, Fr) Patent Number: 6,340,571 Date filed: November 13, 1997 Abstract: A monoclonal or polyclonal antibody specific for an epitope common to Staphylococcus aureus strains of various capsular serotypes, particularly methicillinresistant strains, the antibody being selected from immunoglobulins G, M, and A, and the use thereof in a reagent for detecting Staphylococcus aureus. Excerpt(s): The present invention relates to the field of the detection of Staphylococcus aureus bacteria, and in particular strains of Staphylococcus aureus which are resistant to methicillin. an antibody specifically recognizing the type 5 capsular serotype of Staphylococcus aureus or an antibody specifically recognizing the type 8 serotype of Staphylococcus aureus, and preferably a mixture of these two antibodies. According to the present invention, a monoclonal or polyclonal antibody is provided which specifically recognizes an epitope common to Staphylococcus aureus strains of various capsular serotypes, particularly the methicillin-resistant strains. This antibody is selected from the type G immunoglobulins, the type M immunoglobulins and the type A immunoglobulins. Web site: http://www.delphion.com/details?pn=US06340571__
•
Aqueous disinfectant Inventor(s): Arata; Andrew B. (Lake City, FL) Assignee(s): Innovative Medical Services () Patent Number: 6,583,176 Date filed: March 2, 2001 Abstract: A non-toxic environmentally friendly aqueous disinfectant is disclosed for specific use as prevention against contamination by potentially pathogenic bacteria and virus. The aqueous disinfectant is formulated by electrolytically generating silver ions in water in combination with a citric acid. The aqueous disinfectant may include a suitable alcohol and/or a detergent. The aqueous disinfectant has been shown to be very effective at eliminating standard indicator organisms such as Staphylococcus aureus, salmonella cholerasuis and pseudomonas aeruginosa. Excerpt(s): This invention relates to disinfectants and more particularly to an environmentally friendly, non-toxic aqueous disinfectant for specific use against pathogenic bacteria and viruses. The prior art has demonstrated that the presence of copper and silver ions in an aqueous solution is useful as a disinfectant. Many in the prior art have used copper and silver ions in an aqueous solution as a disinfectant in water systems such as cooling towers, swimming pools, hot water systems in hospitals, potable water systems, spa pools and the like. Typically, copper and silver electrodes
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were connected to a direct current power supply. When the direct current was applied to the copper and silver electrodes, copper and silver ions were generated by an electrolysis process from the copper and silver ions within the water. In one example of the prior art, water was passed continuously through an ion chamber having copper and silver electrodes. The water emanating from the ion chamber contained the copper and silver ions generated by copper and silver electrodes within the ion chamber. The water emanating from the ion chamber containing the copper and silver ions was used as a disinfectant in water systems such as cooling towers, swimming pools, hot water systems in hospitals, potable water systems, spa pools and the like. The copper and silver ions within the water systems acted as a disinfectant for controlling algae, viruses, bacteria and the like. Web site: http://www.delphion.com/details?pn=US06583176__ •
Asparaginyl tRNA synthetase from Staphylococcus aureus Inventor(s): Hodgson; John Edward (Malvern, PA), Lawlor; Elizabeth Jane (Malvern, PA) Assignee(s): Smithkline Beecham P.l.c. (gb) Patent Number: 6,410,286 Date filed: February 4, 1998 Abstract: The invention provides tRNA synthetase polypeptides and DNA (RNA) encoding tRNA synthetase polypetides and methods for producing such polypeptides by recombinant techniques. Also provided are methods for utilizing tRNA synthetase polypeptide for the protection against infection, particularly bacterial infections. Excerpt(s): This invention relates to newly identified polynucleotides and polypeptides, and their production and uses, as well as their variants, agonists and antagonists, and their uses. In particular, in these and in other regards, the invention relates to novel polynucleotides and polypeptides of the tRNA synthetase family, hereinafter referred to as "tRNA synthetase". It is particularly preferred to employ Staphylococcal genes and gene products as targets for the development of antibiotics. The Staphylococci make up a medically important genera of microbes. They are known to produce two types of disease, invasive and toxigenic. Invasive infections are characterized generally by abscess formation effecting both skin surfaces and deep tissues. S. aureus is the second leading cause of bacteremia in cancer patients. Osteomyelitis, septic arthritis, septic thrombophlebitis and acute bacterial endocarditis are also relatively common. There are at least three clinical conditions resulting from the toxigenic properties of Staphylococci. The manifestation of these diseases result from the actions of exotoxins as opposed to tissue invasion and bacteremia. These conditions include: Staphylococcal food poisoning, scalded skin syndrome and toxic shock syndrome. in which AA is an amino acid. Web site: http://www.delphion.com/details?pn=US06410286__
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Auxiliary gene and protein of methicillin resistant bacteria and antagonists thereof Inventor(s): De Lencastre; Herminia (New York, NY), Tomasz; Alexander (New York, NY) Assignee(s): The Rockefeller University (new York, Ny) Patent Number: 6,391,614 Date filed: October 15, 1999 Abstract: The present invention is directed to the identification of mutant strains of methicillin resistant bacteria, in particular methicillin resistant Staphylococcus aureus, to identify the characteristics of such bacteria and develop drugs that can reverse, inhibit, or reduce bacterial resistance to beta lactam antibiotics, e.g., methicillin. The invention particularly relates to identification of a novel mutant strain of methicillin resistant S. aureus that manifests a unique phenotype, having a block in cell wall synthesis at or close to the branch point in hexose metabolism involved in the synthesis of cell wall components. Accordingly, the invention provides for methods of treatment and corresponding pharmaceutical compositions for treating bacterial, particularly staphylococcal, infections. Excerpt(s): The present invention relates to the identification of auxiliary genes that encode proteins involved in antibiotic resistance in bacteria, and to compounds that can antagonize the activity of such proteins, thereby resensitizing resistant bacteria to antibiotics. Methicillin resistant strains of Staphylococcus aureus (MRSA) have become first ranking nosocomial pathogens worldwide. These bacteria are responsible for over 40% of all hospital-born staphylococcal infections in large teaching hospitals in the US. Most recently they have become prevalent in smaller hospitals (20% incidence in hospitals with 200 to 500 beds), as well as in nursing homes (Wenzel et al., 1992, Am. J. Med. 91(Supp 3B):221-7). An unusual and most unfortunate property of MRSA strains is their ability to pick up additional resistance factors which suppress the susceptibility of these strains to other, chemotherapeutically useful antibiotics. Such multiresistant strains of bacteria are now prevalent all over the world and the most "advanced" forms of these pathogens carry resistance mechanisms to all but one (vancomycin) of the usable antibacterial agents (Blumberg et al., 1991, J. Inf. Disease (63:1279-85). A most ominous and recent development is the appearance of a vancomycin resistance mechanism in another nosocomial pathogen--Enterococcus faecium--which is known for its ability to transfer from one cell to another plasmid-born resistance factors, such as vancomycin resistance. The arrival of vancomycin resistance to MRSA is only a matter of time. Once this happens, an invasive bacterial pathogen without any antibacterial agent to control it will result. This event would constitute nothing short of a potential public health disaster of immense proportion (Leclercg et at., 1988, New Eng. J. Med. 319:157-61). Web site: http://www.delphion.com/details?pn=US06391614__
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Bactericidal or bacteriostatic method Inventor(s): Hayashi; Michio (1-32-1012, Takasu-cho 2-chome, Nishinomiya-shi, Hyogo 663-8141, JP) Assignee(s): Hayashi; Michio (hyogo, Jp), Kato; Tsutae (nara, Jp), Yokoyama Co., Ltd. (osaka, Jp) Patent Number: 6,669,903 Date filed: June 1, 2001 Abstract: Sterilization or bacteriostasis is carried out using cellulose acetate. The cellulose acetate exhibits an excellent antibacterial property with respect to fungi such as Trichophyton, etc. and bacteria such as, for example, enteropathogenic Escherichia coli O-157 or Methicillin tolerance Staphylococcus aureus. The cellulose acetate may be mixed with resin such as, for example, polyethylene or polypropylene, and this mixture may be used to produce fibers. Then, a textile product may be manufactured using the fibers thus produced. The cellulose acetate may be dissolved in a mixed solvent of ethyl acetate, ethanol, and methyl alcohol, so that a coating material is prepared. This coating material is applied to an object to be sterilized and then is dried to form a coating film made of cellulose acetate. This coating film exhibits the antibacterial property. Excerpt(s): The present invention relates generally to a bactericidal or bacteriostatic method using cellulose acetate. Conventionally, inorganic antibacterial agents such as a silver compound or organic antibacterial agents containing an organic compound have been utilized as antibacterial agents used for sterilization or bacteriostasis. In addition, photocatalysts such as titanium oxide, etc. produce active oxygen by photoirradiation. This active oxygen provides an antibacterial action. Hence, titanium oxide or the like also may be used as antibacterial agents. However, there has been a problem that conventional antibacterial agents have short lives. Accordingly, even when, for instance, resin products using such conventional antibacterial agents exhibit an antibacterial action at the beginning of use, various bacteria propagate or molds (fungi) grow after a certain period of time. Furthermore, conventional antibacterial agents include those that cannot provide effective sterilization or bacteriostatic actions against pathogenic bacteria including, for example, serious alimentary intoxication bacteria such as enteropathogenic Escherichia coli O-157 and methicillin resistant Staphylococcus aureus (MRSA). Even if the conventional antibacterial agents are effective for such bacteria, some of them may have harmful effects on human bodies. In order to provide a resin product or the like with an antibacterial property by using a conventional antibacterial agent, it has been necessary to add and knead the conventional antibacterial agent as an additive. When a sufficient antibacterial property is intended to be provided, it has been necessary to add and knead a large amount of antibacterial agent. This causes a disadvantage in cost and also affects the characteristics of the resin product. On the other hand, the photocatalysts do not allow an antibacterial action to be expressed without the help of light. Therefore, the use of such photocatalysts may be limited in some cases. Moreover, many of the conventional antibacterial agents are expensive and thus their use may be limited in view of their cost. Web site: http://www.delphion.com/details?pn=US06669903__
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Chromogenic medium for detecting Staphylococcus aureus Inventor(s): Rambach; Alain (73, Bd Montparnasse, 75006 Paris, FR) Assignee(s): None Reported Patent Number: 6,548,268 Date filed: January 28, 2002 Abstract: The invention concerns a novel chromogenic medium for isolating Staphylococcus aureus, charcterised in that it comprises in a culture medium of Staphyloccus aureus at least one of the following two chromogenic agents: 5-bromo 6chloro 3-indoxyl phosphate and 5-brono 4-chloro 3-indoxyl glucoside and it further contains deferoxamine. Excerpt(s): The present invention relates to a novel chromogenic medium intended to reveal Staphylococcus aureus. Staphylococcus aureus is a bacterium, the detection of which is proving to be increasingly advantageous as it relates to bacteria which are often carried by patients who have to be subjected to traumatic care, syringes, catheter or various operations. In this case, there is a very great danger sooner or later of infection immediately these patients enter into care. It is therefore a pathogenic bacterium which is increasingly implicated in nocosomial infections in hospital environments, for example. Web site: http://www.delphion.com/details?pn=US06548268__
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Compositions and methods involving an essential Staphylococcus aureus gene and its encoded protein Inventor(s): DuBow; Mike (Montreal, CA), Gros; Philippe (St. Lambert, CA), Pelletier; Jerry (Baie-D'Urfe, CA) Assignee(s): Phagetech, Inc. (quebec, Ca) Patent Number: 6,376,652 Date filed: December 22, 1999 Abstract: This invention relates to newly identified polynucleotides and polypeptides, and their production and uses, as well as their variants, agonists and antagonists, and their uses. In particular, the invention relates to polynucleotides and polypeptides of a Staphylococcus aureus (S. aureus) DnaI related protein, as well as its variants, hereinafter referred to as "S. aureus DnaI", "S. aureus DnaI polypeptide(s)", and "S. aureus dnaI polynucleotides" as the case may be. Also, the invention relates to a specific interaction between the S. aureus DnaI related protein and a growth-inhibitory protein encoded by the S. aureus bacteriophage 77 genome. The phage ORF product interacts with the S. aureus DnaI polypeptide, and the invention contemplates use of this interaction target site for the basis of a drug screening assay. In addition, the invention relates to polynucleotides and polypeptides of a protein complex containing S. aureus DnaI and DnaC related proteins, as well as their variants. Excerpt(s): The invention relates to bacterial and bacteriophage genes. The Staphylococci make up a medically important genera of microbes known to cause several types of diseases in humans. S. aureus is a Gram positive organism which can be found on the skin of healthy human hosts. It is responsible for a large number of bacteremias, where its portal of entry can be the skin, lungs, urinary tract or infected intravascular devices (Steinberg et al., (1996)) Clin. Infect. Dis. 23: 255-259; R.o slashed.der et al., (1999) Arch.
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Intern. Med. 159: 462-469). It can cause fatal endocarditis or damage to the heart and, due to its exotoxin, can cause death via "Toxic Shock" (Frimodt-M.o slashed.ller et al., (1997) Clin. Microbiol. Infect. 3: 297-305; Sanabria et al., (1990) Arch. Intern. Med. 150: 1305-1309). Only S. aureus and Staphylococcus epidermidis, of the nineteen species of Staphylococcus described in Bergey's Manual (1992), have significant interactions with humans. They are among the normal flora of humans, and are found on nasal passages, skin and mucous membranes. S. aureus, when pathogenic in humans, can cause a number of suppurative (pus-forming) infections, as well as food poisoning, endocarditis, and toxic shock syndrome. Web site: http://www.delphion.com/details?pn=US06376652__ •
Crystallization and structure determination of Staphylococcus aureus thymidylate kinase Inventor(s): Benson; Timothy E. (Kalamazoo, MI) Assignee(s): Pharmacia & Upjohn Company (kalamazoo, Mi) Patent Number: 6,689,595 Date filed: August 4, 2000 Abstract: An unliganded form of Staphylococcus aureus thymidylate kinase (S. aureus TMK) has been crystallized, and the three dimensional x-ray crystal structure has been solved to 2.3.ANG. resolution. The x-ray crystal structure is useful for solving the structure of other molecules or molecular complexes, and designing inhibitors of S. aureus TMK activity. Excerpt(s): This invention relates to the crystallization and structure determination of thymidylate kinase (TMK) from Staphylococcus aureus. In another aspect, the present invention provides crystalline forms of an S. aureus thymidylate kinase molecule. In one embodiment, a crystal of S. aureus thymidylate kinase is provided having the trigonal space group symmetry P2.sub.1. In another aspect, the present invention provides a molecule or molecular complex that includes at least a portion of an S. aureus thymidylate kinase TMP and/or TMP/ATP substrate binding pocket. In one embodiment, the S. aureus thymidylate kinase TMP substrate binding pocket includes the amino acids listed in Table 1, preferably the amino acids listed in Table 2, and more preferably the amino acids listed in Table 3, the substrate binding pocket being defined by a set of points having a root mean square deviation of less than about 2.1.ANG., preferably less than about 1.5.ANG., more preferably less than about 1.0.ANG., and most preferably less than about 0.5.ANG. from points representing the backbone atoms of the amino acids. In another embodiment, the S. aureus thymidylate kinase TMP/ATP substrate binding pocket includes the amino acids listed in Table 4, preferably the amino acids listed in Table 5, and more preferably the amino acids listed in Table 6, the substrate binding pocket being defined by a set of points having a root mean square deviation of less than about 2.1.ANG., preferably less than about 1.5.ANG., more preferably less than about 1.0.ANG., and most preferably less than about 0.5.ANG. from points representing the backbone atoms of the amino acids. Web site: http://www.delphion.com/details?pn=US06689595__
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Extracellular matrix-binding proteins from Staphylococcus aureus Inventor(s): Eidhin; Deidre Ni (Dublin, IE), Foster; Timothy J. (Dublin, IE), Hook; Magnus A. O. (Houston, TX), Josefsson; Elisabet (Gothenburg, SE), Patti; Joseph M. (Cumming, GA), Perkins; Samuel E. (Houston, TX) Assignee(s): Bioresearch Ireland (dublin, Ie), Inhibitex, Inc. (norcross, Ga), The Texas A&m University System (college Station, Tx) Patent Number: 6,680,195 Date filed: November 25, 1998 Abstract: Isolated extracellular matrix-binding proteins, designated ClfB, SdrC, SdrD and SdrE, and their corresponding amino acid and nucleic acid sequences and motifs are described. The proteins, peptides, fragments thereof or antigenic portions thereof are useful for the prevention, inhibition, treatment and diagnosis of S. aureus infection and as scientific research tools. Further, antibodies or antibody fragments to the proteins, peptides, fragments thereof or antigenic portions thereof are also useful for the prevention, inhibition, treatment and diagnosis of S. aureus infection. In particular, the proteins or antibodies thereof may be administered to wounds or used to coat biomaterials to act as blocking agents to prevent or inhibit the binding of S. aureus to wounds or biomaterials. ClfB is a cell-wall associated protein having a predicted molecular weight of approximately 88 kDa and an apparent molecular weight of approximately 124 kDa, which binds both soluble and immobilized fibrinogen. ClfB binds both the alpha and beta chains of fibrinogen and acts as a clumping factor. SdrC, SdrD and SdrE are cell-wall associated proteins that exhibit cation-dependent ligand binding to the extracellular matrix. It has been discovered that in the A region of SdrC, SdrD, SdrE, ClfA and ClfB, there is a highly conserved amino acid sequence that can be used to derive a consensus motif of TYTFTDYVD (SEQ ID NO: 16). Excerpt(s): The present invention is in the fields of microbiology and molecular biology. The invention includes the isolation and use of extracellular matrix-binding proteins and genes that express the proteins from Staphylococcus aureus to inhibit, prevent and diagnose S. aureus infection. In hospitalized patients Staphylococcus aureus is a major cause of infections associated with indwelling medical devices, such as catheters and prostheses, and related infections of surgical wounds. A significant increase in Staphylococcus aureus isolates that exhibit resistance to most known antibiotics has been observed in hospitals throughout the world. The recent emergence of resistance to vancomycin, the last remaining antibiotic for treating methicillin-resistant Staphylococcus aureus (MRSA) infections, has emphasized the need for alternative prophylactic or vaccine strategies to reduce the risk of nosocomial S. aureus infections. Initial localized infections of wounds or indwelling medical devices can lead to serious invasive infections such as septicemia, osteomyelitis, and endocarditis. In infections associated with medical devices, plastic and metal surfaces become coated with host plasma and extracellular matrix proteins such as fibrinogen and fibronectin shortly after implantation. The ability of S. aureus to adhere to these proteins is of crucial importance for initiating infection. Vascular grafts, intravenous catheters, artificial heart valves, and cardiac assist devices are thrombogenic and prone to bacterial colonization. S. aureus is the most damaging pathogen to cause such infections. Web site: http://www.delphion.com/details?pn=US06680195__
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FabZ from Staphylococcus aureus Inventor(s): Kallender; Howard (Wayne, PA), Lonsdale; John T. (Exton, PA), Van Horn; Stephanie (Pottstown, PA), Warren; Patrick V. (Coatsville, PA) Assignee(s): Smithkline Beecham Corporation (philadelphia, Pa) Patent Number: 6,489,139 Date filed: June 24, 1999 Abstract: The invention provides fabZ polypeptides and polynucleotides encoding fabZ polypeptides and methods for producing such polypeptides by recombinant techniques. Also provided are methods for utilizing fabZ polypeptides to screen for antibacterial compounds. Excerpt(s): This invention relates to newly identified polynucleotides and polypeptides, and their production and uses, as well as their variants, agonists and antagonists, and their uses. In particular, the invention relates to polynucleotides and polypeptides of the fabZ family, as well as their variants, herein referred to as "fabZ," "fabZ polynucleotide(s)," and "fabZ polypeptide(s)" as the case may be. The first step in the biosynthetic cycle is the condensation of malonvl-ACP with acetyl-CoA by FabH. Prior to this, malonyl-ACP is synthesized from ACP and malonyl-CoA by FabD, malonyl CoA:ACP transacylase. In subsequent rounds malonyl-ACP 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 NADPH-dependent.beta.-ketoacylACP 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 acylACP by 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). Cerulenin and thiolactomycin are potent and selective inhibitors of bacterial fatty acid biosynthesis. Extensive work with these inhibitors has proved that this biosynthetic pathway is essential for bacterial viability. No marketed antibiotics are targeted against fatty acid biosynthesis, therefore it is unlikely that novel antibiotics would be rendered inactive by known antibiotic resistance mechanisms. There is an unmet need for developing new classes of antibiotic compounds, such as those that target FabZ. Web site: http://www.delphion.com/details?pn=US06489139__
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FtsH from Staphylococcus aureus Inventor(s): Hodgson; John Edward (Malvern, PA), Jenkins; Owen (Roydon Essex, GB), Sarginson; Gillian (Tadworth, GB) Assignee(s): Smithkline Beecham Corporation (philadelphia, Pa), Smithkline Beecham Plc (brentford, Gb) Patent Number: 6,573,066 Date filed: March 12, 1997 Abstract: The invention provides ftsH polypeptides, polynucleotides encoding ftsH polypeptides and related polynucleotides and methods for producing such polypeptides by recombinant techniques. Also provided are diagnostic methods for detecting Staphylococcus aureus.
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Excerpt(s): This invention relates to newly identified polynucleotides and polypeptides, and their production and uses, as well as their variants, agonists and antagonists, and their uses. In particular, in these and in other regards, the invention relates to novel polynucleotides and polypeptides of the ATPase family, hereinafter referred to as "FtsH". It is particularly preferred to employ Staphylococcal genes and gene products as targets for the development of antibiotics. The Staphylococci make up a medically important genera of microbes. They are known to produce two types of disease, invasive and toxigenic. Invasive infections are characterized generally by abscess formation effecting both skin surfaces and deep tissues. S. aureus is the second leading cause of bacteremia in cancer patients. Osteomyelitis, septic arthritis, septic thrombophlebitis and acute bacterial endocarditis are also relatively common. There are at least three clinical conditions resulting from the toxigenic properties of Staphylococci. The manifestation of these diseases result from the actions of exotoxins as opposed to tissue invasion and bacteremia. These conditions include: Staphylococcal food poisoning, scalded skin syndrome and toxic shock syndrome. The frequency of Staphylococcus aureus infections has risen dramatically in the past 20 years. This has been attributed to the emergence of multiply antibiotic resistant strains and an increasing population of people with weakened immune systems. It is no longer uncommon to isolate Staphylococcus aureus strains which are resistant to some or all of the standard antibiotics. This has created a demand for both new anti-microbial agents and diagnostic tests for this organism. Web site: http://www.delphion.com/details?pn=US06573066__ •
IgG-binding protein from Staphylococcus and nucleotide sequence encoding this protein Inventor(s): Frykberg; Lars (Uppsala, SE), Jacobsson; Karin (Uppsala, SE) Assignee(s): Biostapro AB (stockholm, Se) Patent Number: 6,548,639 Date filed: May 12, 2000 Abstract: A recombinant DNA molecule coding for a protein expressed by a Staphylococcus aureus bacterium, comprising the nucleotide sequence SEQ ID NO:1 or a homologous sequence, or a partial or homologous sequence of SEQ ID NO:1 coding for a polypeptide fragment comprising at least 15 amino acid residues, is described. Further, a protein expressed by such a bacterium or a polypeptide fragment comprising at least 15 amino acid residues, comprising the amino acid sequence SEQ ID NO:2 binds IgG and apolipoprotein H. Examples of the polypeptide fragments comprise the SEQ ID NO:3 through 6. These proteins and polypeptide fragments may be coupled to an inert carrier or matrix. Vectors comprising such a DNA molecule or the corresponding RNA molecule, and antibodies specifically binding to a polypeptide having an amino acid sequence of SEQ ID NO:4 or SEQ ID NO:6, are also disclosed. The DNA or RNA molecules, the vectors and the antibodies mentioned may all be used in different types of vaccines against Staphylococcal infections. Moreover, a method of isolating and/or purifying apolipoprotein H from a liquid medium, especially from serum, is described. Excerpt(s): The present invention relates to a new protein and a nucleotide sequence encoding said protein. More precisely, the invention relates to a DNA molecule coding for a protein expressed by a bacterium of the genus Staphylococcus aureus, said protein and polypeptide fragments of said protein. Vectors comprising the nucleotide sequence coding for the protein, the protein and fragments thereof, and antibodies specifically
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binding to the protein may all be used for different vaccines against Staphylococcal infections in mammals. The invention also relates to a method of isolating and/or purifying apolipoprotein H from e.g serum with an immobilised protein or polypeptide of the invention. Staphylococcus aureus is a pathogen responsible for a wide variety of diseases in humans and animals, including endocarditis, osteomyelitis, wound sepsis and mastitis. The bacterium produces several potential virulence factors such as alpha-, beta-, gamma- and delta-toxins, toxic shock syndrome toxin (TSST), enterotoxins, leucocidin, proteases, coagulase and clumping factor. It is generally accepted that adhesion to tissues is required for bacterial colonisation to occur. For this purpose staphylococci express surface adhesins, which interact with host matrix proteins such as fibronectin, vitronectin, collagen, laminin and bone sialoprotein. In addition, staphylococci are able to bind several serum proteins, such as IgG, fibronectin, fibrinogen, and thrombospondin, possibly masking the bacteria from the immune system of the host. However, the contribution and importance of each of these binding functions in different infections is still unclear. Web site: http://www.delphion.com/details?pn=US06548639__ •
Isolated strains of Staphylococcus aureus and vaccines manufactured therefrom Inventor(s): Leitner; Gabriel (Mazkeret Batya, IL), Liubashewsky; Eugenia (Bnei Aish, IL), Trainin; Ze'ev (Tel-Aviv, IL) Assignee(s): Maabarot Products Ltd. (kibbutz Maabarot, Il) Patent Number: 6,544,529 Date filed: September 1, 2000 Abstract: The invention provides antigenic compositions for the vaccination of an animal against bovine mastitis caused by infection with Staphylococcus aureus. The invention also provides methods for stimulating an animal's immune system to respond to antigens derived from selected strains of Staphylococcus aureus by administering the antigenic compositions of the invention to the animal. Excerpt(s): The present invention relates generally to bovine mastitis infections caused by Staphylococcus aureus and, more particularly, to vaccines derived from selected strains of Staphylococcus aureus. Bovine mastitis is the most important infectious disease affecting both the quality and quantity of milk production. Staphylococcus aureus (i.e., "S. aureus") is the prime agent causing bovine mastitis, and it is difficult to eliminate. In different countries, the prevalence of S. aureus mastitis ranges from 10% to 40% of all cows. The infected animals may serve as reservoirs of infection endangering other dairy cattle in the herd (Fox, L. K. and Hancock, D. 1989, "Effects of segregation on prevention of intramammary infection by Staphylococcus aureus", J. Dairy Sci. 72:540544). Recent estimates suggest that the annual production losses due to S. aureus are over 15 million dollars in Israel and over 2 billion dollars in the USA. The prevalence of S. aureus mastitis in dairy cattle raises several concerns. This bacterium can cause severe damage to milk-synthesizing tissues, drastically reducing milk production and altering milk composition. For more information on bovine mastitis and its effects, see, for example: (1) Oliver, S. P., Sordillo, L. M, 1988, "Udder health in the periparturient period", J Dairy Sd. 71:2584-2606; (2) Postle, D. S., Roguinsky, M., Poutrel, B., 1978, "Induced Staphylococcal infections in the bovine mammary gland", Am J Vet Res. 39:2935; (3) Sordillo, L. M., Nickerson, S. C and Akers, R. M., 1989, "Pathology of mastitis during lactogenesis: Relationships with bovine mammary structure and function", J. Dairy Sci. 72: 228-240; (4) Watson, D. L., McColl, M. L., Davies, H. I., 1996, "Field trial of
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a Staphylococcal mastitis vaccine in dairy herds: clinical, subclinical and microbiological assessments", Aust. Vet. J. 74:447-450. Web site: http://www.delphion.com/details?pn=US06544529__ •
Lymphocyte-derived antimicrobial protein (LDAP) and methods of isolating and producing and using the protein Inventor(s): Shafer-Weaver; Kimberly A. (Pleasant Gap, PA), Sordillo-Gandy; Lorraine M. (Port Matida, PA) Assignee(s): The Penn State Research Foundation (university Park, Pa) Patent Number: 6,593,457 Date filed: February 26, 1999 Abstract: A purified, soluble lymphocyte-derived antimicrobial protein that has a molecular weight of 16 kD on SDS-PAGE, is inactivated by heating at 56.degree. C. for 30 minutes or by treatment with trypsin, is expressed by CD3-, CD2+ cytokinestimulated cells', and is active against Gram positive or Gram-negative bacteria including Staphylococcus aureus. Excerpt(s): The present invention is drawn to a lymphocyte-derived antimicrobial protein (LDAP) which is useful in the prevention and treatment of bacterial, viral and fungal pathogen caused infection in food and companion animals. The present invention is further drawn to nucleic acids and nucleic acid analogues encoding the protein and methods of isolating the protein and expressing the protein as well as antibodies which recognize the protein. Bacterial, viral and fungal infections which effect food and companion animals are of clear and obvious concern throughout the world. Bacterial infections of concern include but are not limited to mastitis, including bovine mastitis, respiratory diseases, enteritis and septicemia. Viral diseases include, but are not limited to, leukosis virus, respiratory disease, rabies, rhinotracheitis, FeLV, distemper and warts. Fungal diseases include, but are not limited to, ringworm, histoplasmosis, systemic mycoses and dermatitis. As one example of a bacterial infectious condition, bovine mastitis is the most important infectious disease affecting both the quality and quantity of milk produced in the world. Bovine mastitis affects every dairy farm and approximately 38% of all cows. Mastitis can cause destruction of milk-synthesizing tissues, resulting in decreased milk production and altered milk composition. Depending on the duration and severity of disease, the productive performance of infected dairy cattle may be diminished permanently. Consequently, mastitis continues to be the greatest deterrent to profitable dairy production. On average, losses associated with mastitis will cost American dairy producers about 2 billion dollars annually; worldwide losses are estimated at 25 billion dollars annually. Web site: http://www.delphion.com/details?pn=US06593457__
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Mammalian-derived peptides for the treatment of microbial infections Inventor(s): Dubnick; Bernard (Old Tappan, NJ), Hoffman; Brian F. (Key Biscayne, FL) Assignee(s): Theragem, Inc. (oldtappan, Nj) Patent Number: 6,337,314 Date filed: July 14, 1999
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Abstract: The present invention provides compositions useful as antimicrobial agents which include mammalian hemoglobin, the.alpha. and.beta. chains of hemoglobin free of heme, fragments of the.alpha. and.beta. chains that result from cyanogen bromide cleavage of the.alpha. and.beta. chains, and synthetic peptides derived therefrom. The compositions exert antimicrobial activity against both bacteria and fungi that is comparable to known antimicrobial peptides from human neutrophils, cathepsin G and azurocidin. Sensitive organisms include Gram-negative bacteria such as Escherichia coli and Pseudomonas aeruginosa, Gram-positive bacteria such as Staphylococcus aureus and Streptococcus faecalis, and the fungus Candida albicans. Methods for preparing the compositions also are provided. Excerpt(s): The present invention relates to a method for treating microbial infections of mammals, including humans and other primates; a method for killing bacteria and fungi; and a method for treating material subject to microbial contamination by administration of an effective antimicrobial amount of hemoglobin, or of the.alpha. or.beta. chains of this molecule, free of heme, or polypeptide fragments of the.alpha. and.beta. chains resulting from cleavage by cyanogen bromide or synthetic fragments thereof. The invention also relates to compositions comprising such proteins, polypeptides or fragments. Many bacteria produce antimicrobial peptides (bacteriocins) and proteins; those released from Gram-negative bacteria are the more potent and have the wider spectrum of activity (2). The defensins are small antimicrobial peptides found in neutrophils, non-human macrophages and Paneth cells (3). Amphibian skin is a rich source of antimicrobial peptides, one of these, magainin, isolated from Xenopus laevis, currently is undergoing clinical trial (4,5). Plants form a variety of gene-encoded antimicrobial peptides including the phytoalexins, the PR proteins and the AMPs (6,7). Insects have been shown to synthesize bacteriocidal peptides and proteins such as cecropin obtained from the moth Cecropia (8,9,10) and the sarcotoxins obtained from the larvae of the flesh fly Sarcocphaga perigrina (11). The hemocytes of the horse-shoe crab Limulus are the source of the tachyplesins and squalamine, an aminosteroid with antimicrobial activity, has been isolated from the shark, Squalus acanthias (12). Thus, many antimicrobial substances lie within the families of "natural" antibiotics such as the cecropins, magainins, defensins, serprocidins and others. These substances are widely distributed in nature and provide an innate defense mechanism against infection in species ranging from insects to amphibians to mammals. Generally these substances are stored in cells, to be induced and secreted within the animal when challenged. Many act by disrupting the bacterial cell membrane selectively; many would be toxic to host cells as well, were they not sequestered (13). A number of these compounds have been proposed as being useful as antimicrobial agents (14,15). Web site: http://www.delphion.com/details?pn=US06337314__ •
Microorganism Inventor(s): Ono; Kotaro (Fukui, JP), Watanabe; Katsuyo (Tokyo, JP), Yamanaka; Noriaki (Osaka, JP) Assignee(s): Washi Kosan Co., Ltd. (tokyo, Jp) Patent Number: 6,399,056 Date filed: February 18, 2000 Abstract: A novel microorganism such as a Bacillus sp. OYK-01-600 (FERM BP-6394) which has no induction period, immediately undergoes exponential growth, and is nonhemolytic. The bacteria have antimicrobial activities against toxic bacteria such as
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Staphylococcus aureus, including methicillin-resistant Staphylococcus aureus, pathogenic Eschericia coli including O-157, Legionella pneumophila, and Klebsiella pneumoniac. The increased growth rate can inhibit bacteria which emit an ofensive odor and many noxious infection bacteria. Excerpt(s): The present invention relates to a novel nonhemolytic microorganism and to its utilization, and more particularly to a novel microorganism which expresses not only high antimicrobial activity against those noxious bacteria which give off offensive odors in the course of proliferation (for example, Staphylococcus aureus, Klebsiella neumoniae, etc.) and, as such, is capable of getting rid of the malodor originating from effluent treatment and facilities, but also high antimicrobial activity against other toxic bacteria (for example, meticillin-resistant Staphylococcus aureus, pathogenic Escherichia coli O-157, Legionella pneumophila, etc.), thus finding application in a broad spectrum of uses and to the utilization thereof. It should be understood that the antimicrobial activity of the novel microorganism according to the present invention is derived not only from the extracellular and intracellular secretions of this novel microorganism but also from the following mechanism. The novel microorganism of the present invention proliferates at an unusually high growth rate. Thus, at an incubation temperature of 20.about.40.degree. C., it multiplies from an initial population of 10.sup.3 cells/g (ml) to a population 10.sup.6 cells/g (ml) in about 2 hours and further to 10.sup.8 cells/g (ml) within 6 hours. Whereas growth of ordinary or adventitious bacteria occurs only after the so-called induction period, that is to say an acclimatization period (the time which a microorganism placed in a new environment requires for its being acclimatized to the new environment) of about 6 hours, the novel microorganism of the present invention has substantially no "induction period" as mentioned above but undergoes cell division and multiplies rapidly in an explosive manner after initiation of culture. As the microorganism of the present invention avariciously digests and assimilates available nutrients and grows explosively while said other adventitious bacteria are still in the induction period of growth, proliferation of the adventitious bacteria is inhibited and the above-mentioned antimicrobial activity against such adventitious bacteria is expressed. Thus, this novel microorganism having substantially no induction period and starting to grow immediately after commencement of culture inhibits growth of noxious bacteria. Web site: http://www.delphion.com/details?pn=US06399056__ •
MurD protein and gene of Staphylococcus aureus Inventor(s): El-Sherbeini; Mohammed (Rahway, NJ), Geissler; Wayne M. (Rahway, NJ), Wong; Kenny Kin (Rahway, NJ) Assignee(s): Merck & Co., Inc. (rahway, Nj) Patent Number: 6,534,284 Date filed: May 3, 2000 Abstract: This invention provides the murD gene of Staphylococcus aureas. Purified and isolated MurD recombinant proteins are also provided. Nucleic acid sequences which encode functionally active MurD proteins are described. Assays for the identification of modulators of the expression of murD and inhibitors of the activity of MurD, are also provided. Excerpt(s): Not applicable. This invention relates to the genes and enzymes involved in cell wall synthesis in bacteria, and particularly to the inhibition of such enzymes.
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Web site: http://www.delphion.com/details?pn=US06534284__ •
Nanosilver-containing antibacterial and antifungal granules and methods for preparing and using the same Inventor(s): Cheng; Jiachong (Beijing, CN), Yan; Jixiong (Wuhan, CN) Assignee(s): Globoasia, L.l.c. (hanover, Md) Patent Number: 6,379,712 Date filed: April 25, 2001 Abstract: The present invention relates to nanosilver-containing antibacterial and antifungal granules ("NAGs"). The NAGs have longlasting inhibitory effect on a broadspectrum of bacteria and fungi, which include, but are not limited to, Escherichia coli, Methicillin resistant Staphylococcus aureus, Chlamydia trachomatis, Providencia stuartii, Vibrio vulnificus, Pneumobacillus, Nitrate-negative bacillus, Staphylococcus aureus, Candida albicans, Bacillus cloacae, Bacillus allantoides, Morgan's bacillus (Salmonella morgani), Pseudomonas maltophila, Pseudomonas aeruginosa, Neisseria gonorrhoeae, Bacillus subtilis, Bacillus foecalis alkaligenes, Streptococcus hemolyticus B, Citrobacter, and Salmonella paratyphi C. The NAGs contain ground stalk marrow of the plant Juncus effusus L. which has been dispersed with nanosilver particles. The nanosilver particles are about 1-100 nm in diameter. Each of the nanosilver particles contain a metallic silver core which is surrounded by silver oxide. The present invention also provides a process for making the NAGs. The NAGs can be used in a variety of healthcare and industrial products. Examples of the healthcare products include, but are not limited to, ointments or lotions to treat skin trauma, soaking solutions or cleansing solutions for dental or women hygiene, medications for treating gastrointestinal bacteria infections, sexual related diseases, and eye diseases. Examples of industrial products include, but are not limited to, food preservatives, water disinfectants, paper disinfectants, construction filling materials (to prevent mold formation). Excerpt(s): The present invention relates to nanosilver particles-containing antibacterial and antifungal granules (NAGs). The nanosilver particles are attached to the surfaces and pores of stalk marrow of Juncus effusus L, which acts as an inert carrier for nanosilver. Each of the nanosilver particles contains a metallic silver core which is surrounded by silver oxide. The size of the nanosilver particle is between 1-100 nm in diameter. The present invention also relates to methods for preparing the NAGs and for using the NAGs. The NAGs can be used in a variety of healthcare, medicinal and industrial products. Metals including silver, copper, mercury, and zinc are known for anti-bacterial properties. Bacteria treated by these metals do not acquire resistance to the metals. Therefore, the bactericidal metals have advantages over the conventional antibiotics which often cause the selection of antibiotic-resistant microorganism. Silver is generally a safe and effective antimicrobial metal. Silver ions function in adversely affecting cellular metabolism to inhibit bacterial cell growth. When silver ions are absorbed into bacterial cells, silver ions suppress respiration, basal metabolism of the electron transfer system, and transport of substrate in the microbial cell membrane. Silver ions also inhibit bacterial growth by producing active oxygen on the surface of silver powder and silver-plated articles. Silver has been studied for antibacterial purposes in the form of powder, metal-substituted zeolite, metal-plated non-woven fabric, and crosslinked compound. Web site: http://www.delphion.com/details?pn=US06379712__
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NrdF from Staphylococcus aureus Inventor(s): Black; Michael Terence (Chester Springs, PA), Traini; Christopher Michael (Media, PA) Assignee(s): Smithkline Beecham Corporation (philadelphia, Pa) Patent Number: 6,555,338 Date filed: March 17, 1998 Abstract: The invention provides nrdF polynucleotides encoding nrdF polypeptides from Staphylococcus aureus and methods for producing such polypeptides by recombinant techniques. The invention also provides polynucleotides having high identity to the nrdF polynucleotides. Also provided are preferred methods for utilizing these polynucleotides and polypeptides as diagnostic reagents and in diagnostic assays to screen for microbial infections in organisms and materials. Excerpt(s): It is particularly preferred to employ Staphylococcal genes and gene products as targets for the development of antibiotics. The Staphylococci make up a medically important genera of microbes. They are known to produce two types of disease, invasive and toxigenic. Invasive infections are characterized generally by abscess formation effecting both skin surfaces and deep tissues. S. aureus is the second leading cause of bacteremia in cancer patients. Osteomyelitis, septic arthritis, septic thrombophlebitis and acute bacterial endocarditis are also relatively common. There are at least three clinical conditions resulting from the toxigenic properties of Staphylococci. The manifestation of these diseases result from the actions of exotoxins as opposed to tissue invasion and bacteremia. These conditions include: Staphylococcal food poisoning, scalded skin syndrome and toxic shock syndrome. The frequency of Staphylococcus aureus infections has risen dramatically in the past few decades. This has been attributed to the emergence of multiply antibiotic resistant strains and an increasing population of people with weakened immune systems. It is no longer uncommon to isolate Staphylococcus aureus strains which are resistant to some or all of the standard antibiotics. This phenomenon has created an unmet medical need and demand for new anti-microbial agents, vaccines, drug screening methods, and diagnostic tests for this organism. Moreover, the drug discovery process is currently undergoing a fundamental revolution as it embraces "functional genomics," that is, high throughput genome- or gene-based biology. This approach is rapidly superseding earlier approaches based on "positional cloning" and other methods. Functional genomics relies heavily on the various tools of bioinformatics to identify gene sequences of potential interest from the many molecular biology databases now available as well as from other sources. There is a continuing and significant need to identify and characterize further genes and other polynucleotides sequences and their related polypeptides, as targets for drug discovery. Web site: http://www.delphion.com/details?pn=US06555338__
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PNA probes, probe sets, methods and kits pertaining to the detection of microorganisms Inventor(s): Coull; James M. (Westford, MA), Hyldig-Nielsen; Jens J. (Holliston, MA) Assignee(s): Boston Probes, Inc. (bedford, Ma) Patent Number: 6,664,045 Date filed: June 18, 1999
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Abstract: This invention is related to novel PNA probes, probe sets, methods and kits pertaining to the detection of microorganisms. The probes, probe sets, methods and kits of this invention can be used to detect, identify or quantitate one or more organisms in a sample wherein the organisms are selected from the group consisting of E. coli, Staphylococcus aureus, Pseudomonas aeruginosa, Pseudomonas cepatia, Pseudomonas fluorescens or organisms of a bacterial genus including the Salmonella genus, Bacillus genus or Pseudomonas genus. The preferred probing nucleobase sequence of the PNA probes used to detect the bacteria listed above are TCA-ATG-AGC-AAA-GGT (E. coli); GCT-TCT-CGT-CCG-TTC (Staphylococcus aureus); CTG-AAT-CCA-GGA-GCA and AAC-TTG-CTG-AAC-CAC (Pseudomonas aeruginosa); CCA-TCG-CAT-CTA-ACA (Pseudomonas cepatia); TCT-AGT-CAG-TCA-GTT (Pseudomonas fluorescens); CCGACT-TGA-CAG-ACC and CCT-GCC-AGT-TTC-GAA (Salmonella genus); CTT-TGTTCT-GTC-CAT (Bacillus genus); GCT-GGC-CTA-GCC-TTC, GTC-CTC-CTT-GCG-GTT and TTC-TCA-TCC-GCT-CGA (Pseudomonas genus). The PNA probes, probe sets, methods and kits of this invention are particularly well suited for use in multiplex PNAFISH assays. Excerpt(s): This invention is related to the field of probe-based detection, analysis and quantitation of microorganisms. More specifically, this invention relates to novel PNA probes, probe sets, methods and kits pertaining for the detection of microorganisms. The PNA probes, probe sets, methods and kits of this invention can be used to detect, identify or quantitate one or more organisms in a sample wherein the organisms of interest may include E. coli, Staphylococcus aureus, Pseudomonas aeruginosa, Pseudomonas cepatia, Pseudomonas fluorescens or organisms of a bacterial genus including the Salmonella genus, Bacillus genus or Pseudomonas genus. Nucleic acid hybridization is a fundamental process in molecular biology. Probe-based assays are useful in the detection, quantitation and analysis of nucleic acids. Nucleic acid probes have long been used to analyze samples for the presence of nucleic acid from bacteria, fungi, virus or other organisms and are also useful in examining genetically-based disease states or clinical conditions of interest. Nonetheless, probe-based assays have been slow to achieve commercial success. This lack of commercial success is, at least partially, the result of difficulties associated with specificity, sensitivity and reliability. Hybridization assays hold promise as a means to screen large numbers of samples for conditions of interest. In practice, however, it is often difficult to multiplex a hybridization assay given the requirement that each of the many very different probes in the assay must exhibit a very high degree of specificity for a specific target nucleic acid under the same or similar conditions of stringency. Given the difficulties in specificity, sensitivity and reliability of nucleic acid probes in assays designed to detect a single target nucleic acid, sensitive and reliable methods for the multiplex analysis of samples has been particularly elusive. Web site: http://www.delphion.com/details?pn=US06664045__ •
Precipitation recovery process for food waste sludge Inventor(s): Lee; John H. (Olathe, KS) Assignee(s): Rigel Technology Corporation (olathe, Ks) Patent Number: 6,368,657 Date filed: August 1, 2001 Abstract: A practical precipitation recovery process for food waste sludge from dissolved air floatation (DAF) units and sugar by products is provided. Typical meat
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DAF (dissolved air floatation) skimming sludge has about 12% solid with about 40% fat and 42% protein in solid basis. The skimming sludge is often for land application to cause a pollution problem. Much of the potential nutritive value of the skimming is lost through microbiological degradation. The process converts the skimming sludge and animal blood into a precipitate, which binds most nutrients. Then the precipitate product can be separated easily by a centrifuge, screen or press process. The dry process cost can be reduced because the extra water is removed and the product surface area is increased. The process can convert the waste skimming sludge into a value added product as a good and safe ingredient for feed and nutritional applications. A typical dry product has about protein 54%, pepsin digestible protein 96%, fat 23%, ash 8.5%, moisture 6%, very low levels of aerobic plate count, total coliforms, Staphylococcus aureus, yeast and mold, undetected E. coli and negative salmonella. This process can also be used to improve the properties of animal feed block products. If the precipitation process can be scaled up into commercialization production, the process could save and create millions of dollars for food and feed industries every year. Excerpt(s): The present invention relates to process methods of treating food waste sludge, and more particularly to a process method of converting the DAF (dissolved air floatation) skimming sludge of a food processing plant into a value added product with good nutritional value for feed and fertilizer nutritional applications and precipitating molasses sludge from a sugar processing plant into a product with much more hardness and less moisture absorption. The waste water from a food processing plant has high BOD (biochemical oxygen demand), FOG (fats, oils and grease), SS (suspended solids) and TKN (total Kjeldahl nitrogen). Dissolved air floatation (DAF) units are used in meat, milk product, snack food processing and waste water treatment plants. The primary purpose is to reduce BOD, SS, FOG and TKN in the waste water passing to sewage. But it creates another problem to dispose of the pasty and oily skimming sludge, which is separated into the top portion because of the low density. The waste skimming sludge has very attractive nutrients--protein, fat, carbohydrate and minerals. Animal meat industry is a major industry to use dissolved air floatation (DAF) units to reduce BOD, SS, FOG and TKN in the waste water passing to sewage. Animals are grown and slaughtered to meet people's needs every year, which includes beefs, pigs, chickens, turkeys and others. In the animal processing industry, an average of 4.5 kg of protein is lost to the sewer for every 454 kg of live weight kill (Ockerman and Hansen, 2000). The percentage is about 1%. If half of the protein now lost to the sewer were recovered, there would be at least an additional 181 million kg of protein each year, worth perhaps $ 400 million from animal processing in the United States (Hansen, 1983). It is very important to use animal wastes and by products for economic and public health achievements. Web site: http://www.delphion.com/details?pn=US06368657__ •
Rnase P polypeptides, polynucleotides, and methods using their mechanisms of action Inventor(s): Gress; Michael J. (Wayne, PA), Hegg; Lisa A (Devon, PA), Li; Hu (Eagleville, PA), Park; Joseph J. (King of Prussia, PA) Assignee(s): Smithkline Beecham Corporation (philadelphia, Pa), Smithkline Beecham P.l.c. (brentford Middlesex, Gb) Patent Number: 6,649,744 Date filed: November 5, 2001
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Abstract: This invention relates to a novel bacterial ribonucleoprotein complex and the component parts thereof. More specifically, this invention relates to RNase P RNA isolated from Staphylococcus aureus and the use of RNase P RNA in screens for the identification of antimicrobial compounds and to the use of such compounds in therapy. Excerpt(s): This invention relates to newly identified polynucleotides, polypeptides encoded by certain of these polynucleotides, molecular complexes of RNAs and polypeptides, the uses of such polynucleotides and polypeptides, as well as the production of such polynucleotides and polypeptides and recombinant host cells transformed with the polynucleotides. The invention relates particularly to such polynucleotides and polypeptides from Staphylococci, especially S. aureus. This invention also relates to inhibiting the biosynthesis, assembly or action of such polynucleotides and/or polypeptides and to the use of such inhibitors in therapy. This invention relates to a novel bacterial ribonucleoprotein complex and the component parts thereof. More specifically, this invention relates to RNase P, particularly RNase P from Staphylococcus aureus, and the use of RNase P or components thereof in screens for the identification of antimicrobial compounds and to the use of such compounds in therapy. The Staphylococci make up a medically important genera of microbes. They are known to produce two types of disease, invasive and toxigenic. Invasive infections are characterized generally by abscess formation effecting both skin surfaces and deep tissues. S. aureus is the second leading cause of bacteremia in cancer patients. Osteomyelitis, septic arthritis, septic thrombophlebitis and acute bacterial endocarditis are also relatively common. There are at least three clinical conditions resulting from the toxigenic properties of Staphylococci. The manifestation of these diseases result from the actions of exotoxins as opposed to tissue invasion and bacteremia. These conditions include: Staphylococcal food poisoning, scalded skin syndrome and toxic shock syndrome. Web site: http://www.delphion.com/details?pn=US06649744__ •
Skin-protective composition Inventor(s): Clair; James (1 Woodlands, Cloghroe, Blarney, County Cork, IE), Eggers; Sabine (11 Manor Downs, Thornbury View, Rochestown, County Cork, IE), Van Der Meer; Michael John (Marian House, Ballydulae, County Cork, IE) Assignee(s): None Reported Patent Number: 6,461,624 Date filed: December 17, 1999 Abstract: The present invention relates to a protective composition for skin, which protects against bacterial, viral and fungal infections. The compositions comprise a C.sub.8 -C.sub.20 fatty acid, one or more parabens or a combination of these. The compositions of the invention are particularly effective in controlling infections by Methicillin Resistant Staphylococcus aureus (MRSA) as well as other organisms. The invention includes protective hand creams such as barrier hand creams, as well as body lotions, liquid soaps, shampoos, soap bars and creams generally, which are all protective. Excerpt(s): The present invention relates to a protective composition for skin which protects against bacterial, viral and fungal infection In particular, the invention relates to anti-infective (infection preventing) products, to be used to control infections caused by gram positive organisms such as Methicillin Resistant Staphylococcus aureus (MRSA),
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Pneumococci and Vancomycin Resistant Enterococci (VRE) as well as gram negative bacteria such as Escherichia coli and Pseudomonas aeruginosa. The invention provides a durable handcream which is retained on the hands despite use of the hands. More particularly the invention relates to a protective handcream of the type known as a "barrier" handcream. The invention also provides body lotions, liquid soaps, shampoos, soap bars and creams generally, which are protective. Although medical science is continually advancing with new techniques and drugs being developed almost daily, cross-infection in hospitals is still a common occurrence with major implications. Microorganisms may be acquired and transmitted by one of the following routes: direct contact, airborne or via fomites. Although these routes are well understood and procedures to control them are standard practice, pathogenic organisms still exist in the hospital environment. The spread of infection by direct contact is considered to be the most important method of transmission both for gram positive and gram negative organisms, and it is agreed that the hands of hospital personnel play an important role in the transmission of infection. Web site: http://www.delphion.com/details?pn=US06461624__ •
Staphylococcal ABC transporter protein Inventor(s): Burnie; James Peter (Alderley Edge, GB) Assignee(s): Neutec Pharma Plc (manchester, Gb) Patent Number: 6,627,730 Date filed: September 29, 2000 Abstract: The present invention concerns the treatment and diagnosis of Staphylococcal infections, particularly those of Staphylococcus aureus, and provides a protein, epitopes of same, and antibodies and other binding and neutralizing agents specific against same. Excerpt(s): The present invention concerns the treatment and diagnosis of Staphylococcal infections, particularly those of Staphylococcus aureus, and provides a protein, epitopes of same, and antibodies and other binding and neutralising agents specific against same. Multiple drug resistance (MDR) is an increasing problem amongst gram-positive bacteria (Banergee, S. N. et al. 1991, Am. J. Med. 91: 865-895; Shaberg, D. R. et al., 1991, Am. J. Med. suppl., 88: 72-75; Gaynes, R. P. et al., 1994, Infect. Dis. Clin. Pract., 6: 452-455), particularly in hospitals. In particular, methicillin-resistant Staphylococcus aureus (MRSA) and coagulase-negative staphylococci (CNS), particularly methicillin-resistant CNS, prove problematic, being resistant to all penicillins and cephalosporins. Resistance to other agents such as quinolones is widespread (Malabarta, A. et al., 1997, Eur. J. Med. Chem., 32: 459-478; Lewis, K., 1994, TIBS, 19: 119-123; Traub, W. H. et al., 1996, Chemotherapy, 42: 118-132). Treatment is typically effected using vancomycin or teicoplanin. However, resistance to these agents is spreading and so new therapies are needed. A Staphylococcal ABC transporter protein having an apparent molecular weight of 67 KDA has now been successfully isolated and purified by the present inventor from an epidemic MRSA strain, and has the coding sequence of SEQ ID NO: 1 and the amino acid sequence of SEQ ID NO: 2. These sequences are partially identified by the S. aureus NCTC 8325 genome sequencing project as contig 1184, contig 1177 and contig 1158 containing amino-terminal sequence data. This protein has not previously been suggested to be an ABC transporter protein, and no diagnostic or therapeutic uses have previously been suggested for it. The protein has a calculated true molecular weight of 60.1 kDa, although post-translational
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modifications result in its being identified in experiments as having an apparent molecular weight of 67 kDa. Web site: http://www.delphion.com/details?pn=US06627730__ •
Staphylococcus aureus antigen-containing whole cell vaccine Inventor(s): Fattom; Ali Ibrahim (Rockville, MD) Assignee(s): Nabi (rockville, Md) Patent Number: 6,537,559 Date filed: September 24, 2001 Abstract: A negatively-charged S. aureus antigen contains.beta.-hexosamine as a major carbohydrate component. S. aureus strains that carry the antigen account for nearly all of the clinically significant strains of S. aureus that are not Type 5 or Type 8 strains. The antigen can be used in combination with S. aureus Type 5 polysaccharide antigen and S. aureus Type 8 polysaccharide antigen to provide nearly 100% coverage of S. aureus infection. The antigen and antibodies to the antigen are useful in kits and assays for diagnosing S. aureus infection. A whole cell vaccine of cells that contain the antigen is particularly useful in the treatment of mastitis. Excerpt(s): The present invention relates to a novel Staphylococcus aureus antigen, and to a method for obtaining and using the antigen. S. aureus causes several diseases in animals and in humans by various pathogenic mechanisms. The most frequent and serious of these diseases are bacteremia and its complications in hospitalized patients. In particular, S. aureus can cause wound infections and infections associated with catheters and prosthetic devices. Serious infections associated with S. aureus bacteremia include osteomyelitis, invasive endocarditis and septicemia. The problem is compounded by multiple antibiotic resistance in hospital strains, which severely limits the choice of therapy. In addition, S. aureus is a major cause of mastitis in dairy and beef cattle, where the infection causes a major loss of income. A S. aureus vaccine would provide a solution for the problem of antibiotic resistance. At least eight different serotypes of S. aureus have been identified using polyclonal and monoclonal antibodies to capsular polysaccharide (CPS). Karakawa et al., J. Clin. Microbiol. 22:445 (1985). The contents of this document and all others listed herein are incorporated herein by reference. Web site: http://www.delphion.com/details?pn=US06537559__
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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
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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. 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__ •
Staphylococcus aureus polynucleotides and sequences Inventor(s): Barash; Steven (Rockville, MD), Choi; Gil H. (Rockville, MD), Dillon; Patrick J. (Carlsbad, CA), Fannon; Michael R. (Silver Spring, MD), Kunsch; Charles A. (Norcross, GA), Rosen; Craig A. (Laytonsville, MD) Assignee(s): Human Genome Sciences, Inc. (rockville, Md) Patent Number: 6,593,114 Date filed: October 20, 1997 Abstract: The present invention provides polynucleotide sequences of the genome of Staphylococcus aureus, polypeptide sequences encoded by the polynucleotide sequences, corresponding polynucleotides and polypeptides, vectors and hosts comprising the polynucleotides, and assays and other uses thereof. The present invention further provides polynucleotide and polypeptide sequence information stored on computer readable media, and computer-based systems and methods which facilitate its use. Excerpt(s): The present invention relates to the field of molecular biology. In particular, it relates to, among other things, nucleotide sequences of Staphylococcus aureus, contigs, ORFs, fragments, probes, primers and related polynucleotides thereof, peptides and polypeptides encoded by the sequences, and uses of the polynucleotides and sequences thereof, such as in fermentation, polypeptide production, assays and pharmaceutical development, among others. The genus Staphylococcus includes at least 20 distinct species. (For a review see Novick, R. P., The Staphylococcus as a Molecular Genetic System, Chapter 1, pgs. 1-37 in MOLECULAR BIOLOGY OF THE
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STAPHYLOCOCCI, R. Novick, Ed., VCH Publishers, New York (1990)). Species differ from one another by 80% or more, by hybridization kinetics, whereas strains within a species are at least 90% identical by the same measure. The species Staphylococcus aureus, a gram-positive, facultatively aerobic, clump-forming cocci, is among the most important etiological agents of bacterial infection in humans, as discussed briefly below. Web site: http://www.delphion.com/details?pn=US06593114__ •
Use of the crystal structure of Staphylococcus aureus isoleucyl-tRNA synthetase in antibiotic design Inventor(s): Wang; Jimin (Hamden, CT), Silvian; Laura F. (Newton, MA), Steitz; Thomas A. (Branford, CT) Assignee(s): Yale University (new Haven, Ct) Patent Number: 6,631,329 Date filed: July 31, 2000 Abstract: The present invention provides the atomic coordinates derived from high resolution x-ray diffraction of the cocrystal complex comprising mupirocin with its target enzyme, isoleucyl-tRNA synthetase from Staphylococcus aureus, and the cognate tRNA.sup.ile from Escherichia coli. The present invention further provides methods of using the atomic coordinates to identify and design new agents which modulate protein synthesis as well as the agents themselves. Excerpt(s): The present invention relates to the crystalline structure of isoleucyl-tRNA synthetase and the cognate tRNA.sup.ile and to methods of producing such crystals. The invention also relates to the atomic coordinates of isoleucyl-tRNA synthetase and the cognate tRNA.sup.ile, obtained by x-ray diffraction at high resolution. The present invention also relates to methods for identifying and designing new classes of ligands which target the isoleucyl-tRNA synthetases of specific organisms. The methods and compositions of the present invention find wide applicability in the design and production of antibiotics, insecticides, miticides and herbicides. The most important invention in medicine in this century is perhaps the discovery of penicillin by Alexander Fleming in 1928, a naturally occurring antibiotic that inhibits cell-wall synthesis in many pathogenic bacteria. In 1940, E. B. Chain and H. W. Florey were able to produce stable commercial formulations of this antibiotic. For this invention, Fleming, Chain, and Florey shared the Nobel Prize in medicine or physiology in 1945. In the past half century, from penicillin to methicilin to vancomycin, over 130 related antibiotics have been discovered that inhibit cell-wall synthesis (Neu, 1991). The art of the discovery is relatively simple; it requires simply a combination of microbiology and organic chemistry. Any organic chemical that inhibits bacterial cell growth by acting on cell-wall synthesis are good antibiotics, since only bacteria, not human cells, have cell wall. In comparison, the same approach that has worked for the discovery of antibiotics that inhibit cell-wall synthesis has not worked well for the discovery of antibiotics that inhibit protein synthesis. Web site: http://www.delphion.com/details?pn=US06631329__
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Patent Applications on Staphylococcus aureus 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 Staphylococcus aureus: •
Administration of negamycin or deoxynegamycin for the treatment of bacterial infections Inventor(s): Patel, Dinesh V.; (Fremont, CA), Raju, Bore G.; (Fremont, CA), Trias, Joaquim; (Millbrae, CA) Correspondence: Gerald F. Swiss; Burns, Doane, Swecker & Mathis, L.L.P.; P.O. Box 1404; Alexandria; VA; 22313-1404; US Patent Application Number: 20030109583 Date filed: July 25, 2002 Abstract: The invention provides a method for treating bacterial infections. In one aspect, the invention comprises orally administering a pharmaceutical composition to an animal, wherein the composition comprises a pharmaceutically acceptable excipient and an antibacterial effective amount of negamycin, or a pharmaceutically acceptable salt, prodrug or isomer thereof. An aspect of the invention also relates to a method of treating a bacterial infection, wherein the method comprises intravenously administering a pharmaceutical composition to an animal, and wherein the composition comprises a pharmaceutically acceptable excipient and an antibacterial effective amount of deoxynegamycin, or a pharmaceutically acceptable salt, prodrug or isomer thereof. An aspect of the invention also relates to a method of treating a bacterial infection, wherein the method comprises administering to an animal an antibacterial effective amount of negamycin or deoxynegamycin, or a pharmaceutically acceptable salt, prodrug or isomer thereof, and wherein the infecting bacteria are selected from a group of bacteria consisting of the following: Acinetobacter baumanii, Citrobacter freundii, Enterobacter aerogenes, haemophilus influenzae, Moraxella catarrhalis, Staphylococcus aureus MRSA, Staphylococcus aureus GISA, Staphylococcus epidermis, Streptococcus pneumoniae PenR, Streptococcus pneumoniae PenS and Streptococcus pyogenes. Excerpt(s): This application claims the benefit of U.S. Provisional Application No. 60/308,001, filed Jul. 25, 2001, which is herein incorporated by reference in its entirety. The present invention is generally related to the treatment of bacterial infections in animals, preferably mammals.sup.1 M. Hamada et al., "A New Antibiotic, Negamycin," J. Antibiotics, 23(3):170-71 (1970). 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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Anti-bacterial methods and materials Inventor(s): Holden, David; (London, GB), Mei, Ji Min; (Middlesex, GB) Correspondence: Nabeela R. Mcmillian; Marshall, Gerstein & Borun; Sears Tower, Suite 6300; 233 S. Wacker Drive; Chicago; IL; 60606-6357; US Patent Application Number: 20030148346 Date filed: November 22, 2002 Abstract: Staphylococcus aureus virulence genes are identified, thereby allowing the identification of novel anti-bacterial agents that target these virulence genes and their products, and the provision of novel S. aureus mutants useful in vaccines. Excerpt(s): The invention relates generally to the identification of genes responsible for the virulence of Staphylococcus bacteria, thereby allowing the identification of new antibacterial agents that target these virulence genes and their products and the provision of novel S. aureus mutants useful in vaccines. The staphylococci, of which Staphylococcus aureus is the most important human pathogen, are hardy, gram-positive bacteria that colonize the skin of most humans. Staphylococcal strains that produce coagulase are designated S. aureus; other clinically important coagulase-negative staphylococci are S. epidermidis and S. saprophyticus. When the skin or mucous membrane barriers are disrupted, staphylococci can cause localized and superficial infections that are commonly harmless and self-limiting. However, when staphylococci invade the lymphatics and the blood, potentially serious complications may result, such as bacteremia, septic shock, and serious metastatic infections, including endocarditis, arthritis, osteomyelitis, pneumonia and abscesses in virtually any organ. Certain strains of S. aureus produce toxins that cause skin rashes, food poisoning, or multisystem dysfunction (as in toxic shock syndrome). S. aureus and S. epidermidis together have become the most common cause of nosocomial non-urinary tract infection in U.S. hospitals. They are the most frequently isolated pathogens in both primary and secondary bacteremias and in cutaneous and surgical wound infections. See generally Harrison's Principles of Internal Medicine, 13th ed., Isselbacher et al., eds., McGraw-Hill, New York (1994), particularly pages 611-617. Transient colonization of the nose by S. aureus is seen in 70 to 90 percent of people, of which 20 to 30 percent carry the bacteria for relatively prolonged periods of time. Independent colonization of the perineal area occurs in 5 to 20 percent of people. Higher carriage rates of S. aureus have been documented in persons with atopic dermatitis, hospital employees, hospitalized patients, patients whose care requires frequent puncture of the skin, and intravenous drug abusers. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Antimicrobial amino acid sequences derived from alpha-melanocyte-stimulati- ng hormone Inventor(s): Catania, Anna Pia; (Milano, IT), Lipton, James M.; (Woodland Hills, CA) Correspondence: Lyon & Lyon Llp; Suite 4700; 633 West Fifth Street; Los Angeles; CA; 90071; US Patent Application Number: 20020137685 Date filed: September 21, 2001
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Abstract: The presence of the ancient anti-inflammatory peptide.alpha.-melanocyte stimulating hormone (.alpha.-MSH [1-13], SYSMEHFRWGKPV) in barrier organs such as gut and skin suggests a role in the nonspecific (innate) host defense system.alpha.MSH and other amino acid sequences derived from.alpha.-MSH were determined to have antimicrobial influences, including against two major and representative cutaneous and mucosal pathogens: Staphylococcus aureus and Candida albicans.alpha.-MSH peptides had antimicrobial effects against S. aureus and significantly reversed the enhancing effect of urokinase on S. aureus colony formation.alpha.-MSH and other amino acid sequences reduced C. albicans viability and germination.alpha.-MSH peptides also enhanced C. albicans killing by human neutrophils. The antimicrobial agent is selected from the group consisting of one or more peptides including the amino acid sequence KPV, one or more peptides including the amino acid sequence MEHFRWG, or a biologically functional equivalent of any of the foregoing. The most effective of the peptides were those bearing the C-terminal amino acid sequence of.alpha.-MSH, i.e.,.alpha.-MSH (1-13), (6-13), and (11-13). The.alpha.-MSH "core" sequence (4-10), important for melanotropic effects, was also effective but significantly less potent. Antimicrobial influences of.alpha.-MSH peptides could be mediated by their well-known capacity to increase cellular cAMP; this messenger was significantly augmented in peptide-treated yeast.alpha.-MSH has potent anti-inflammatory effects and is expected to be useful for treatment of inflammation in human and veterinary disorders. Reduced killing of pathogens is a detrimental consequence of therapy with corticosteroids and nonsteroidal anti-inflammatory drugs during infection. Therefore, anti-inflammatory agents based on.alpha.-MSH peptides that do not reduce microbial killing, but rather enhance it, would be very useful. The antimicrobial effects of these.alpha.-MSH peptides occurred over a broad range of concentrations including the physiological (picomolar) range. Excerpt(s): The present invention relates to new pharmaceutical compositions useful as antimicrobial agents, including, for example, for use in reducing the viability of microbes, reducing the germination of yeasts, killing microbes without reducing the killing of microbes by human neutrophils, for treating inflammation in which there is microbial infection without reducing microbial killing, and for increasing the accumulation of cAMP in microbes. More particularly, this invention relates to antimicrobial agents including amino acid sequences derived from alpha-melanocytestimulating hormone (.alpha.-MSH) and biologically functional equivalents thereof. Mucosal secretions, phagocytes, and other components of the nonspecific (innate) host defense system initiate the response to microbial penetration before time-consuming adaptive immunity starts. Survival of plants and invertebrates, which lack adaptive immunity, illustrates effectiveness of host defense based on such innate mechanisms. Endogenous antimicrobial peptides are significant in epithelia, the barrier to environmental challenge that provides the first line of defense against pathogens. Production of natural antimicrobial peptides by phagocytes has been recognized for a long time. These natural antimicrobial peptides generally have a broad spectrum of activity against bacteria, fungi, and viruses. Martin, E., Ganz, T., Lehrer, R. I., Defensins and Other Endogenous Peptide Antibiotics of Vertebrates, J. Leukoc. Biol. 58, 128-136 (1995); Ganz, T., Weiss, J., Antimicrobial Peptides of Phagocytes and Epithelia, Sem. Hematol. 34, 343-354 (1997). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Catamenial device Inventor(s): Butensky, Irwin; (Teaneck, NJ), Mauro, Anthony J.; (Allenhurst, NJ), Rosengarten, Mark E.; (Suffern, NJ) Correspondence: Charles N.J. Ruggiero, ESQ.; Ohlandt, Greeley, Ruggiero & Perle, L.L.P.; 10th Floor; One Landmark Square; Stamford; CT; 06901-2682; US Patent Application Number: 20030100871 Date filed: November 2, 2001 Abstract: There is provided a fibrous absorbent article for absorbing body fluids made up of a fibrous material defining a structure suitable for absorbing the body fluids, and disposed within the structure an effective amount, so as to reduce Staphylococcus aureus bacterial growth and neutralize TSS toxin-1 within the vagina, of one or more antimicrobial agents and one or more finishing agents. Excerpt(s): The present invention relates to absorbent products and, in particular, to absorbent products such as tampons and similar catamenial devices. More particularly, the present invention relates to tampons and other catamenial devices that reduce or inhibit the amount of bacteria within the vagina coming into contact with the catamenial device. Menstrually occurring toxic shock syndrome (TSS), a multi-system disease associated with colonization by Staphylococcus aureus (S. aureus) bacteria, has been associated with the use of tampons during menstruation. It is believed that the disease is caused by toxic shock syndrome toxin-1 (TSST-1). This toxin has been found to have been produced by Staphylococcal strains isolated from menstrual TSS patients. Staphylococci may be present in the vagina or in the nose or the throat or on the skin. The blood, desquamated tissue and other materials present in the vagina during menstruation are a culture medium for S. aureus and organisms symbiotic to Staphylococci. As the Staphylococci increase in number, toxins may be produced that are absorbed through the vaginal wall, potentially resulting in toxic shock syndrome. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Compositions and methods for affecting virulence determinants in bacteria Inventor(s): Cheung, Ambrose L.; (Hanover, NH), Manna, Adhar; (Lebanon, NH), Zhang, Gongyi; (Denver, CO) Correspondence: Licatla & Tyrrell P.C.; 66 E. Main Street; Marlton; NJ; 08053; US Patent Application Number: 20030114650 Date filed: January 11, 2002 Abstract: A novel sarR gene and sarR gene product which down regulates the expression of sarA and the resulting virulence determinants in Staphylococcus aureus is provided. Methods for modulating the expression of sarA and virulence determinants are also provided. A preferred embodiment of the present invention provides structural information relating to the gene product and enables the identification and formulation of lead compounds and reducements for treating and preventing infections by S. aureus and related bacteria. Excerpt(s): This application claims priority to U.S. Provisional Application Serial No. 60/261,233, filed Jan. 12, 2001, U.S. Provisional Application Serial No. 60/261,607, filed Jan. 12, 2001, and U.S. Provisional Application Serial No. 60/289,601, filed May 8, 2001. These applications are hereby incorporated by references herein in their entirety. The
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present invention relates generally to the field of molecular biology. More particularly, certain embodiments concern methods and compositions comprising DNA segments and protein derived from Staphyloccocus aureus and other bacterial species. The present invention also relates to the three-dimensional structure of proteins derived from S. aureus and other bacterial species and methods of identifying and developing pharmaceuticals using, among other things, drug screening assays. Throughout this application, various publications are referenced by Arabic numerals within parentheses. Full citations for these publications is found at the end of the specification immediately preceding the claims. The disclosures of these publications in their entireties are hereby incorporated by reference into this application. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Compositions and methods involving an essential Staphylococcus aureus gene and its encoded protein STAAU_R9 Inventor(s): DuBow, Michael; (Montreal, CA), Gros, Philippe; (St. Lambert, CA), Pelletier, Jerry; (Baie-D'Urfe, CA) Correspondence: Wesley B. Ames; Foley & Lardner; P.O. Box 80278; San Diego; CA; 92138-0278; US Patent Application Number: 20030003444 Date filed: December 19, 2001 Excerpt(s): This application claims the benefit of U.S. Provisional application No. 60/256,349, filed Dec. 19, 2000, which is incorporated herein by reference in its entirety, including drawings. The invention relates to bacterial genes and proteins that are implicated in the process of DNA replication and also to bacteriophage genes and their protein products that interact with bacterial proteins involved in DNA replication. More particularly, the invention relates to compositions and methods involving an essential Staphylococcus aureus gene and its encoded protein STAAU_R9. In addition, the invention relates to screening assays to identify compounds which modulate the level and/or activity of STAAU_R9 and to such compounds. The Staphylococci make up a medically important genera of microbes known to cause several types of diseases in humans. S. aureus is a Gram positive organism which can be found on the skin of healthy human hosts and it is responsible for a large number of bacteremias. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Cross-reactive monoclonal and polyclonal antibodies which recognize surface proteins from coagulase-negative staphylococci and Staphylococcus aureus Inventor(s): Foster, Timothy; (Dublin, IE), Hutchins, Jeff T.; (Cumming, GA), Pallen, Mark; (Worcs, GB), Patti, Joseph M.; (Cumming, GA), Roche, Fiona; (Dublin, IE), Speziale, Pietro; (Pavia, IT) Correspondence: Larson & Taylor, Plc; 1199 North Fairfax Street; Suite 900; Alexandria; VA; 22314; US Patent Application Number: 20030185833 Date filed: June 17, 2002
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Abstract: Polyclonal and monoclonal antibodies which are cross-reactive to both coagulase-positive Staphylococcus bacteria, such as S. aureus and to coagulase-negative bacteria, such as S. epidermidis and S. hemolyticus, are provided which can recognize surface proteins from both coagulase-positive and coagulase negative staph bacteria. The antibodies may be generated from surface proteins that have been isolated on the basis of characteristics that may be common between S. aureus and coagulase-negative staphylococci, and these recombinant surface proteins are used to generate the antibodies of the invention. There is also provided vaccines and methods which utilize these proteins and antibodies for the treatment or protection against a wide variety of staphylococcal infections. Excerpt(s): The present application claims the benefit of U.S. provisional application Ser. No. 60/298,098 filed Jun. 15, 2001. The present invention relates in general to surface proteins from Staphylococcus aureus and their active regions such as their A domains which have homologue proteins on coagulase-negative Staphylococci such as S. epidermidis and S. hemolyticus as well as antibodies which recognize said proteins, and in particular to isolated monoclonal and polyclonal antibodies which recognize specific proteins from Staphylococcus aureus and coagulase-negative Staphylococci and which are cross-reactive against S. aureus and coagulase-negative Staphylococci and can thus be utilized in vaccines and methods useful for preventing or treating a wide variety of infections caused by staphylococcal bacteria. The successful colonization of the host is a process required for most microorganisms to cause infections in animals and humans. Microbial adhesion is the first crucial step in a series of events that can eventually lead to disease. Pathogenic microorganisms colonize the host by attaching to host tissues or serum conditioned implanted biomaterials, such as catheters, artificial joints, and vascular grafts, through specific adhesins present on the surface of the bacteria. MSCRAMM.RTM.s (Microbial Surface Components Recognizing Adhesive Matrix Molecules) are a family of cell surface adhesins that recognize and specifically bind to distinct components in the host's extracellular matrix. Once the bacteria have successfully adhered and colonized host tissues, their physiology is dramatically altered and damaging components such as toxins and proteolytic enzymes are secreted. Moreover, adherent bacteria often produce a biofilm and quickly become more resistant to the killing effect of most antibiotics. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Crystallization and structure determination of Staphylococcus aureus NAD synthetase Inventor(s): Benson, Timothy E.; (Kalamazoo, MI), Prince, Donald Bryan; (Parchment, MI) Correspondence: Mueting, Raasch & Gebhardt, P.A.; P.O. Box 581415; Minneapolis; MN; 55458; US Patent Application Number: 20030166233 Date filed: January 30, 2001 Abstract: An unliganded form of Staphylococcus aureus NAD synthetase (S. aureus NadE) has been crystallized, and the three-dimensional x-ray crystal structure has been solved to 2.3.ANG. resolution. The x-ray crystal structure is useful for solving the structure of other molecules or molecular complexes, and designing inhibitors of S. aureus NadE activity.
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Excerpt(s): This application claims the benefit of U.S. Provisional Application Serial No. 60/179,261, filed Jan. 31, 2000, which is incorporated herein by reference in its entirety. This invention relates to the crystallization and structure determination of NAD synthetase (NadE) from Staphylococcus aureus. NAD synthetase belongs to a family of enzymes known as N-type ATP pyrophosphatases which share a common mechanism for adenylation of their substrates prior to amidation reactions. NAD synthetase also belongs to a class of enzymes known as amidotransferases which transfer ammonia to their substrates. Amidotransferases are typically characterized by the presence of two domains (present in a single polypeptide or as independent polypeptide subunits) one of which generates ammonia utilizing glutamine as a nitrogen source (glutamine amide transfer (GAT) domain), and the other which is responsible for the actual transfer of ammonia to the substrate. However the S. aureus NAD synthetase, like the Bacillus subtilis enzyme, does not contain a GAT domain and instead takes advantage of free ammonia as its nitrogen source. A separate GAT protein has yet to be identified in these organisms. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Crystallization and structure determination of Staphylococcus aureus UDP-Nacetylenolpyruvylglucosamine reductase (S. aureus MurB) Inventor(s): Benson, Timothy E.; (Kalamazoo, MI) Correspondence: Mueting, Raasch & Gebhardt, P.A.; P.O. Box 581415; Minneapolis; MN; 55458; US Patent Application Number: 20020156585 Date filed: November 21, 2001 Abstract: The substrate free form of Staphylococcus aureus UDP-Nacetylenolpyruvylgl- ucosamine reductase (S. aureus MurB) has been crystallized, and the three dimensional x-ray crystal structure has been solved to 2.3.ANG. resolution. The x-ray crystal structure is useful for solving the structure of other molecules or molecular complexes, and designing inhibitors of S. aureus MurB. Excerpt(s): This application claims the benefit of U.S. Provisional Application Serial No. 60/147,164 filed Aug. 4, 1999, which is incorporated herein by reference in its entirety. This invention relates to the crystallization and structure determination of Staphylococcus aureus UDP-N-acetylenolpyruvylglucosamine reductase (S. aureus MurB). Reports of an increase in antibiotic resistant bacteria have stimulated efforts to find new classes of therapeutic agents that will prevent society from entering a "postantibiotic age." Historically, three important cellular functions have been the major targets of antibiotics--cell wall biosynthesis, DNA replication, and protein translation. The biosynthesis of the bacterial cell wall, in particular the peptidoglycan polymer, is a particularly attractive target since this flexible structure provides protection for the cell against osmotic lysis. To date, most of the therapeutic agents discovered that target cell wall biosynthesis inhibit the later stages of peptidoglycan biosynthesis at the point where interstrand cross linking occurs between the peptide chains. Recent efforts have been directed toward purifying and characterizing all the enzymes in the peptidoglycan biosynthetic pathway with an eye toward designing novel enzyme inhibitors of these essential targets. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Crystallization and structure of Staphylococcus aureus peptide deformylase Inventor(s): Baldwin, Eric T.; (Portage, MI), Harris, Melissa S.; (Marshall, MI) Correspondence: Mueting, Raasch & Gebhardt, P.A.; P.O. Box 581415; Minneapolis; MN; 55458; US Patent Application Number: 20030170868 Date filed: June 29, 2001 Abstract: Staphylococcus aureus peptide deformylase has been crystallized, and the three-dimensional x-ray crystal structure has been solved to 1.9.ANG. resolution. The xray crystal structure is useful for solving the structure of other molecules or molecular complexes, and designing modifiers of peptide deformylase activity. Excerpt(s): This application claims the benefit of the U.S. Provisional Application Serial No. 60/215,550, filed Jun. 30, 2000, which is incorporated herein by reference in its entirety. The present invention is related to the crystallization and structure determination of Staphylococcus aureus peptide deformylase (S. aureus pdf). In one aspect, the present invention provides crystalline S. aureus peptide deformylase. Optionally, one or more methionine may be replaced with selenomethionine. The crystal may optionally include a coordinated metal ion selected from the group of metals consisting of Fe, Zn, Ni and combinations thereof. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Culture medium and method for detecting thermonuclease-positive staphylococci Inventor(s): Mach, Patrick A.; (Shorewood, MN), Sandberg, Gregory P.; (St. Louis Park, MN) Correspondence: 3M Innovative Properties Company; PO Box 33427; ST. Paul; MN; 55133-3427; US Patent Application Number: 20030235879 Date filed: June 20, 2002 Abstract: The present invention provides a method of detecting thermonuclease-positive staphylococci that does not require inactivation of DNase-positive/TNase-negative bacteria with heat. The method includes (a) providing a culture medium selective for growing staphylococci; (b) inoculating the culture medium with a sample; (c) incubating the inoculated culture medium under conditions effective to promote the growth of staphylococci; (d) providing an indicator system that produces a differentiable, detectable signal in the presence of thermonuclease-positive staphylococci; (e) contacting the indicator system with the inoculated, incubated culture medium, thereby forming a detection assembly; (f) incubating the detection assembly under conditions effective for generating the differentiable, detectable signal; and (g) detecting the detectable signal.The present invention also provides a culture medium for the selective identification of Staphylococcus aureus. The culture medium includes at least one first selective agent that selects for growth of staphylococci; at least one second selective agent for differentiating Staphylococcus aureus from other staphylococci; at least one first indicator for indicating the presence of staphylococci; and at least one second indicator for differentially indicating the presence of non-staphylococci bacteria. The present invention also provides a method of selectively identifying Staphylococcus aureus in a sample by using the culture medium of the present invention.
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Excerpt(s): Detection of potentially enterotoxigenic staphylococci is an important aspect of food processing, and may be used as a means of screening for indications of contamination during processing and for post-processing contamination. Food sample evaluations for potentially enterotoxigenic staphylococci can serve as a direct indication of the presence of potential pathogenic species in food. The detection of Staphylococcus aureus (S. aureus), a known enterotoxigenic species, is especially important in food processing. Other potentially enterotoxigenic species of Staphylococcus are known and the testing of samples for contamination with these species also may be important. In addition, the testing of patient samples to indicate possible pathogenic staphylococcal infection is of importance in the clinical setting. One method for testing a sample for the presence of staphylococci includes a thin film culture device that includes a dry, reconstitutable culture medium. The culture medium includes a two-indicator system that provides differential colony staining after about 24-40 hours of incubation. Staphylococci in the sample produce metabolites that react with one indicator, a phosphatase substrate, to produce red or red-violet colonies. Non-staphylococci bacteria produce metabolites that react with the second indicator, a glucopyranoside substrate, to produce blue colonies. This method cannot distinguish between S. aureus and other staphylococci. One current method for detecting S. aureus uses Baird-Parker egg yolktellurite-pyruvate agar medium (abbreviated as BPA) for determining the presumptive presence of S. aureus in a fractional part of a sample. In this method, BPA plates are examined for the presence of "typical" and "a typical" colonies after 48 hours incubation. Samples of the colonies are then transferred to brain heart infusion for an additional incubation of up to 24 hours. The broth cultures are mixed with rabbit plasma for an additional 6-24 hours incubation. The culture-plasma mixtures are then evaluated for the presence of coagulation of the plasma (i.e., clotting). Cultures giving rise to a clot are considered to be coagulase positive. A presumptive positive from BPA followed by a coagulase-positive result is considered to be confirmation of the presence of S. aureus in the sample. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Detection of antibacterial activity in excretory secretory product of adult trichuris suis Inventor(s): Abner, Sheila R; (Atlanta, GA), Mansfield, Linda S; (Bath, MI) Correspondence: Mcleod & Moyne, P.C.; 2190 Commons Parkway; Okemos; MI; 48864; US Patent Application Number: 20040029802 Date filed: April 25, 2003 Abstract: The present invention provides a heat-stable and protease-resistant antibacterial activity in excretory-secretory products (ESP) of Trichuris suis. The antibacterial activity is not more than 10,000 MW; is resistant to boiling, trypsin, and pronase E; has a bactericidal mode of action; and is effective against Gram positive and Gram negative bacteria, including Escherichia coli, Campylobacter jejuni, Campylobactercoli, and Staphylococcus aureus. The antibacterial activity is useful in applications for killing or inhibiting the growth of microorganisms, in particular bacteria. Excerpt(s): This application claims priority to Provisional Application No. 60/246,203, which was filed Nov. 6, 2000. Not Applicable. The present invention relates to heatstable and protease-resistant antibacterial activity in excretory-secretory products (ESP) of Trichuris suis. The antibacterial activity is not more than 10,000 MW; is resistant to
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boiling, trypsin, and pronase E; has a bactericidal mode of action; and is effective against Gram positive and Gram negative bacteria, including Escherichia coli, Campylobacter jejuni, Campylobacter coli, and Staphylococcus aureus. The antibacterial activity is useful in applications for killing or inhibiting the growth of microorganisms, in particular bacteria. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Disinfectant and method of making Inventor(s): Arata, Andrew B.; (Lake City, FL) Correspondence: Frijouf, Rust & Pyle, P.A.; 201 East Davis Boulevard; Tampa; FL; 33606; US Patent Application Number: 20020123523 Date filed: March 2, 2001 Abstract: A non-toxic environmentally friendly aqueous disinfectant is disclosed for specific use as prevention against contamination by potentially pathogenic bacteria and virus. The aqueous disinfectant is formulated by electrolytically generating silver ions in water in combination with a citric acid. The aqueous disinfectant may include a suitable alcohol and/or a detergent. The aqueous disinfectant has been shown to be very effective at eliminating standard indicator organisms such as Staphylococcus aureus, salmonella cholerasuis and pseudomonas aeruginosa. Excerpt(s): This application claims benefit of United States Patent Provisional application serial No. 60/061,673 filed Oct. 10, 1997. All subject matter set forth in provisional application serial No. 60/061,673 is hereby incorporated by reference into the present application as if fully set forth herein. This invention relates to disinfectants and more particularly to an environmentally friendly, non-toxic aqueous disinfectant for specific use against pathogenic bacteria and viruses. The prior art has demonstrated that the presence of copper and silver ions in an aqueous solution is useful as a disinfectant. Many in the prior art have used copper and silver ions in an aqueous solution as a disinfectant in water systems such as cooling towers, swimming pools, hot water systems in hospitals, potable water systems, spa pools and the like. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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DNA vaccine against Staphylococcus aureus Inventor(s): Brouillette, Eric; (Sherbrooke, CA), Lacasse, Pierre; (Lennoxville, CA), Talbot, Brian; (Lennoxville, CA) Correspondence: Merchant & Gould PC; P.O. Box 2903; Minneapolis; MN; 55402-0903; US Patent Application Number: 20030087864 Date filed: July 9, 2002 Abstract: The present invention relates to the use of a plasmid encoding Staphylococcus aureus polypeptides and its use in the preparation of compositions and vaccines. More specifically, the present invention is concerned with compositions, DNA vaccines and methods for providing an immune response and/or a protective immunity into mammals against a Staphylococcus aureus associated disease, such as mastitis. The
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plasmid used in the composition or DNA vaccine comprises at least one nucleotide coding sequence of a Staphylococcus aureus polypeptide, such as the Clumping factor A (ClfA), the fibronectin-binding protein A, the sortase-A or the pre-pheromone (ArgD). Excerpt(s): The present invention relates to compositions, DNA vaccines and methods for providing an immune response and/or a protective immunity into mammals, particularly humans and bovines, against a Staphylococcus aureus associated disease. Staphylococcus aureus is a potentially pathogenic bacteria found in nasal, skin, hair follicles, and perineum of warm-blooded mammals, such as human and bovines. This bacteria may cause a wide range of infections and intoxications. Recently, Staphylococcus aureus has been identified as the most important causative organism of bovine mastitis. Mastitis is one of the most important and costly diseases of dairy cow herds. It is found in 19 to 45% of cattle during lactation worldwide. Despite treatment and different levels of infection, mastitis has long-lasting effects on the milk yield of infected animals. Bovine mastitis has also become an important environmental issue because of increasing public resistance to the use of antibiotics and the development of resistance strains of the pathogens. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Identification of essential genes in microorganisms Inventor(s): Carr, Grant J.; (Escondido, CA), Forsyth, R. Allyn; (San Diego, CA), Haselbeck, Robert; (San Diego, CA), Malone, Cheryl; (Santee, CA), Ohlsen, kari L.; (San Diego, CA), Trawick, John D.; (La Mesa, CA), Wall, Daniel; (San Diego, CA), Wang, Liangsu; (San Diego, CA), Xu, H. Howard; (San Diego, CA), Yamamoto, Robert; (San Diego, CA), Zamudio, Carlos; (La Jolla, CA), Zyskind, Judith W.; (La Jolla, CA) Correspondence: Knobbe Martens Olson & Bear Llp; 2040 Main Street; Fourteenth Floor; Irvine; CA; 92614; US Patent Application Number: 20040029129 Date filed: October 25, 2002 Abstract: The sequences of antisense nucleic acids which inhibit the proliferation of prokaryotes are disclosed. Cell-based assays which employ the antisense nucleic acids to identify and develop antibiotics are also disclosed. The antisense nucleic acids can also be used to identify proteins required for proliferation, express these proteins or portions thereof, obtain antibodies capable of specifically binding to the expressed proteins, and to use those expressed proteins as a screen to isolate candidate molecules for rational drug discovery programs. The nucleic acids can also be used to screen for homologous nucleic acids that are required for proliferation in cells other than Staphylococcus aureus, Salmonella typhimurium, Klebsiella pneumoniae, and Pseudomonas aeruginosa. The nucleic acids of the present invention can also be used in various assay systems to screen for proliferation required genes in other organisms. Excerpt(s): This application claims priority from International Application Number PCT/US02/09107, entitled IDENTIFICATION OF ESSENTIAL GENES IN MICROORGANISMS, filed Mar. 21, 2002, U.S. Provisional Patent Application No. 60/362,699, entitled IDENTIFICATION OF ESSENTIAL GENES IN MICROORGANISMS, filed Mar. 6, 2002, U.S. patent application Ser. No. 10/072,851, entitled METHODS FOR IDENTIFYING THE TARGET OF A COMPOUND WHICH INHIBITS CELLULAR PROLIFERATION, filed Feb. 8, 2002, U.S. Provisional Patent Application No. 60/342,923, entitled STAPHYLOCOCCUS AUREUS ESSENTIAL
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GENES AND METHODS OF USE, filed Oct. 25, 2001, U.S. patent application Ser. No. 09/948,993, entitled RAPID METHOD FOR REGULATING GENE EXPRESSION, filed Sep. 6, 2001, U.S. patent application Ser. No., 09/815,242, IDENTIFICATION OF ESSENTIAL GENES IN PROKARYOTES, filed Mar. 21, 2001, U.S. Provisional Patent Application No. 60/269,308, entitled IDENTIFICATION OF ESSENTIAL GENES IN STAPHYLOCOCCUS AUREUS, PSEUDOMONAS AERUGINOSA, KLEBSIELLA PNEUMONIAE, SALMONELLA TYPHIMURIUM, AND ENTEROCOCCUS FAECALIS, filed Feb. 16, 2001, U.S. Provisional Patent Application No. 60/267,636, entitled METHODS FOR IDENTIFYING THE TARGET OF A COMPOUND WHICH INHIBITS CELLULAR PROLIFERATION, filed Feb. 9, 2001, U.S. Provisional Patent Application No. 60/257,931, entitled IDENTIFICATION OF ESSENTIAL GENES IN STAPHYLOCOCCUS AUREUS, PSEUDOMONAS AERUGINOSA, KLEBSIELLA PNEUMONIAE AND SALMONELLA TYPHIMURIUM, filed Dec. 22, 2000, U.S. Provisional Patent Application No. 60/253,625, entitled IDENTIFICATION OF ESSENTIAL GENES IN STAPHYLOCOCCUS AUREUS, PSEUDOMONAS AERUGINOSA, KLEBSIELLA PNEUMONIAE AND SALMONELLA TYPHIMURIUM, filed Nov. 27, 2000, U.S. Provisional Patent Application No. 60/242,578, entitled GENES IDENTIFIED AS ESSENTIAL IN STAPHLOCOCCUS AUREUS, filed Oct. 23, 2000, U.S. Provisional Patent Application No. 60/230,347, entitled RAPID PCR METHOD FOR DETERMINATION OF WHETHER A GENE IS ESSENTIAL, filed Sep. 6, 2000, U.S. Provisional Patent Application No. 60/230,335, entitled RAPID REPLACEMENT OF GENOMIC PROMOTERS TO GENERATE STRAINS FOR USE IN A CELL-BASED ASSAY FOR ANTIBIOTICS, filed Sep. 6, 2000, U.S. Provisional Patent Application No. 60/207,727, entitled GENES IDENTIFIED AS ESSENTIAL IN STAPHYLOCOCCUS AUREUS, filed May 26, 2000, U.S. Provisional Patent Application No. 60/206,848, enititled GENES IDENTIFIED AS ESSENTIAL IN STAPHYLOCOCCUS AUREUS, filed May 23, 2000, and U.S. Provisional Patent Application No. 60/191,078, entitled, GENES IDENTIFIED AS REQUIRED FOR PROLIFERATION IN STAPHYLOCOCCUS AUREUS, filed March 21, 2000, the disclosures of which are incorporated herein by reference in their entireties. The present application is being filed along with duplicate copies of a CD-ROM marked "Copy 1" and "Copy 2" containing a Sequence Listing in electronic format. The duplicate copies of the CD-ROM each contain a file entitled 034A_FINAL.ST25.txt created on Oct. 25, 2002 which is 181,323,992 bytes in size. The information on these duplicate CD-ROMs is incorporated herein by reference in its entirety. Table IA is provided in electronic format on duplicate copies of a CD-ROM filed herewith and marked "Tables-Copy 1" and "Tables-Copy 2." The duplicate copies of the CD-ROM each contain a file entitled FINAL_CLONE_LIST created on Feb. 26, 2002 which is 248,535 bytes in size and which contains Table IA. The information on these duplicate CD-ROMs is incorporated herein by reference in its entirety. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Identification of sortase gene Inventor(s): Liu, Gwen; (Los Angeles, CA), Mazmanian, Sarkis; (Sherman Oaks, CA), Schneewind, Olaf; (Los Angeles, CA), Ton-That, Hung; (Los Angeles, CA) Correspondence: Knobbe Martens Olson & Bear Llp; 620 Newport Center Drive; Sixteenth Floor; Newport Beach; CA; 92660; US Patent Application Number: 20030022178 Date filed: August 21, 2001
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Abstract: The present invention is a substantially purified sortase-transamidase enzyme from Gram-positive bacteria, such as Staphylococcus aureus. The enzyme having a molecular weight of about 23,539 or about 29,076 daltons and catalyzing a reaction that covalently cross-links the carboxyl terminus of a protein having a sorting signal to the peptidoglycan of a Gram-positive bacterium, the sorting signal having: (1) a motif of LPX.sub.3X.sub.4G therein; (2) a substantially hydrophobic domain of at least 31 amino acids carboxyl to the motif; and (3) a charged tail region with at least two positively charged residues carboxyl to the substantially hydrophobic domain, at least one of the two positively charged residues being arginine, the two positively charged residues being located at residues 31-33 from the motif, wherein X.sub.3 is any of the twenty naturally-occurring L-amino acids and X.sub.4 is selected from the group consisting of alanine, serine, and threonine, and wherein sorting occurs by cleavage between the fourth and fifth residues of the LPX.sub.3X.sub.4G motif. Variants of the enzyme, methods for cloning the gene encoding the enzyme and expressing the cloned gene, and methods of use of the enzyme, including for screening for antibiotics and for display of proteins or peptides on the surfaces of Gram-positive bacteria, are also disclosed. Excerpt(s): This application is a continuation-in-part of pending U.S. patent application Ser. No. 09/292,437, filed Apr. 15, 1999 which is hereby incorporated by reference in its entirety. General Background and State of the Art: This invention is directed to an enzyme from Gram-positive bacteria, designated sortase-transamidase, nucleic acid segments encoding the enzyme, and methods of use of the enzyme. Human infections caused by Gram-positive bacteria present a medical challenge due to the dramatic increase in multiple antibiotic resistance strains in recent years. Gram-positive bacteria that can cause serious or fatal infections in humans include Staphylococcus, Streptococcus, Enterococcus, Pneumococcus, Bacillus, Actinomyces, Mycobacterium, and Listeria, as well as others. Infections caused by these pathogens are particularly severe and difficult to treat in immunologically compromised patients. These include patients suffering from infection with the Human Immunodeficiency Virus (HIV), the virus that causes AIDS, as well as patients given immune-suppressive agents for treatment of cancer or autoimmune diseases. In particular, infections caused by various Mycobacterium species, including M. tuberculosis, M. bovis, M. avium, and M. intracellulare, are frequently the cause of disease in patients with AIDS. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Macrolides with activity against methicillin-resistant Staphylococcus aureus Inventor(s): Djuric, Stevan; (Libertyville, IL), Keyes, Robert; (Pleasant Prairie, WI), Ma, Zhenkun; (Gurnee, IL), Yong, Hong; (Grayslake, IL) Correspondence: Steven F. Weinstock; Abbott Laboratories; 100 Abbott Park Road; DEPT. 377/ap6a; Abbott Park; IL; 60064-6008; US Patent Application Number: 20030162729 Date filed: February 13, 2002 Abstract: Compounds having activity against methicillin-resistant Staphylococcus aureus (MRSA), the compounds 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 MRSA infections using the compounds are disclosed.
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Excerpt(s): This invention is directed to compounds having activity against methicillinresistant Staphylococcus aureus (MRSA), processes for making the compounds and intermediates used in the processes, compositions containing the compounds, and methods for prophylaxis and treatment of MRSA infections using the compounds. Because the effectiveness of drugs currently available for the prophylaxis and treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections is being compromised by increasing bacterial resistance, the development of compounds which demonstrate modified or improved profiles of activity against MRSA would provide significant therapeutic value and an important contribution to the antibacterial arts. Reference is made to commonly-owned U.S. Pat. No. 6,054,435 which discloses a series of antibacterial compounds but does not teach that the compounds would be useful against MRSA. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Method and compositions for the eradication and control of methicillin-resistant Staphylococcus aureus bacteria and the prevention of the development of antibiotic drug resistance in said bacteria Inventor(s): Costin, James C.; (Lower Gwynedd, PA) Correspondence: Kenneth Watov; Watov & Kipnes, P.C.; P.O. Box 247; Princeton Junction; NJ; 08550; US Patent Application Number: 20020161003 Date filed: July 25, 2001 Abstract: The use of 4,4-methylenebis (tetrahydro-1,2,4-thiadiazine-1,2-dioxide) in the prevention and control of the development of antibiotic drug resistance in Staphylococcus aureus bacteria and in the prevention of bacteria-to-bacteria transfer of genes capable of resisting antibiotics is disclosed. Excerpt(s): This application is a continuation-in-part of U.S. Application Ser. No. 09/151,885 filed Sep. 11, 1998. This invention relates to a method and compositions for the treatment of bacterial infection which reduces or eliminates the ability of bacteria to acquire resistance to antibiotic drug treatment. Moreover, this invention relates to a method and compositions for the reduction or elimination of bacteria-to-bacteria transfer of antibiotic drug resistance through genetic or other means. Specifically, the present invention relates to the use of 4,4'-methylenebis(tetrahydro-1,2,4-thiadiazine-1,2dioxide) known generically as taurolidine to treat antibiotic drug (e.g. gentamicin, methicillin and vancomycin) resistant bacterial infections, nosocomial infections and/or eradication of these organisms from an individual acting as a "carrier" for these organisms. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Method for detecting Staphylococcus aureus Inventor(s): Ho, Jo-Yun; (Hsinchu, TW), Liu, Lu-Yieng; (Hsinchu, TW), Terng, HarnJing; (Hsinchu, TW) Correspondence: Fish & Richardson PC; 225 Franklin ST; Boston; MA; 02110; US Patent Application Number: 20030175716 Date filed: March 13, 2002 Abstract: Specific nucleic acid sequences, e.g., SEQ ID NOs:2-8, for detecting Staphylococcus aureus. Also disclosed is a method of detecting Staphylococcus aureus. The method includes providing a sample having a nucleic acid from an unknown microorganism; amplifying the nucleic acid with a pair of primers, each containing an oligo-nucleotide selected from the Staphylococcus aureus gap regulator gene region (SEQ ID NO:1) and each having 14-40 nucleotides in length; and detecting an amplification product. Detection of the amplification product, e.g., using SEQ ID NO:2, 7, or 8 as a probe, indicates the presence of Staphylococcus aureus. Excerpt(s): Traditional methods of detecting microorganisms rely on time-consuming growth in culture media, followed by isolation and biochemical or serological identification. The entire process usually takes 24-48 hours. Many methods for rapid detection of microorganisms have recently been developed, including miniaturized biochemical analyses, antibody- and DNA-based tests, and modified conventional assays. Staphylococcus aureus has been identified as the causative agent in many food poisoning outbreaks (Bennet and Lancette (2001) Bacteriological Analytical Manual Online, Chapter 12 Staphylococcus aureus; U.S. Food & Drug Administration, Center for Food Safety and Applied Nutrition; www.cfsan.fda.gov/.about.bam/bam-12.html). It is also one of the major pathogens responsible for many opportunistic infections in humans and animals (Kloos and Bannerman (1995) Staphylococcus and Micrococcus, p. 282-298. In Murray et al. (ed.), Manual of Clinical Microbiology, 6h ed. American Society for Microbiology, Wasgington, D.C.). Rapid and accurate detection of Staphylococcus aureus is important for preventing food poisoning outbreaks, and for diagnosis and treatment of Staphylococcus aureus infections. The present invention relates to specific nucleic acid sequences selected from the Staphylococcus aureus gap regulator gene region for detecting Staphylococcus aureus. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Method for identifying validated target and assay combinations for drug development Inventor(s): Connelly, Gene; (Waltham, MA), Gallant, Paul L.; (Dedham, MA), Tally, Francis P.; (Lincoln, MA), Tao, Jianshi; (North Andover, MA), Wendler, Philip A.; (Sudbury, MA) Correspondence: Cubist Pharmaceuticals, INC.; 65 Hayden Avenue; Lexington; MA; 02421; US Patent Application Number: 20040033481 Date filed: October 22, 2002 Abstract: The invention comprises methods useful within a larger process for identifying compounds and/or designing further compounds with activity to produce a desired phenotype (for example, growth inhibition) in cells whose target cell component
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is the subject of certain studies to identify such compounds. The invention employs constructed cells comprising a regulable gene encoding a biomolecule which modulates (inhibits or activates) in vivo the function of a target component of the cell which can be an enzyme, for example, methionyl-tRNA synthetase of Staphylococcus aureus. The process incorporates methods for identifying biomolecules that bind to a chosen target cell component in vitro, methods for identifying biomolecules that also bind to the chosen target and modulate its function intracellularly, causing a phenotypic effect. The intracellular effect of a biomolecule can be tested in cell culture, or tested after introduction of the constructed cells into a host mammal in vivo, and methods for identifying compounds that compete with the biomolecules for sites on the target in competitive binding assays. Compounds identified by the series of steps in this process are candidates for drugs with the desired activity on the cell. Targets for which such compounds can be identified are validated as being essential to a phenotype of the cell. Excerpt(s): This application is a continuation of 09/344,783 filed on Jun. 25, 1999, which is a continuation-in-part of U.S. patent application Ser. No. 09/291,874 filed on Apr. 14, 1999, which is a continuation-in-part of U.S. patent application Ser. No. 09/227,687 filed on Jan. 8, 1999, and which also claims the benefit of U.S. Provisional Application No. 60/122,949 filed on Mar. 5, 1999. This application is also a continuation-in-part of U.S. patent application Ser. No. 09/227,687 filed on Jan. 8, 1999, which claims the benefit of U.S. Provisional Application No. 60/107,751 filed on Nov. 10, 1998; U.S. Provisional Application No. 60/101,718 filed on Sep. 24, 1998; U.S. Provisional Application No. 60/100,211 filed on Sep. 14, 1998; U.S. Provisional Application No. 60/094,698 filed on Jul. 30, 1998; U.S. Provisional Application No. 60/089,828 filed on Jun. 19, 1998; U.S. Provisional Application No. 60/085,844 filed on May 18, 1998; U.S. Provisional Application No. 60/081,753 filed on Apr. 14, 1998; U.S. Provisional Application No. 60/076,638 filed on Mar. 3, 1998; and U.S. Provisional Application No. 60/070,965 filed on Jan. 9, 1998. This application also claims the benefit of U.S. Provisional Application No. 60/122,949 filed on Mar. 5, 1999. The teachings of each of these referenced applications are incorporated herein by reference in their entirety. In the discovery and development of new drugs, it is a common strategy to first try to identify molecules or complexes of molecules, naturally occurring within cells, that are involved in producing symptoms of a disease. These naturally occurring molecules can be thought of as "targets." A second major part of the strategy is then to find molecules that bind to the targets. These molecules are candidates for drug development, on the theory that a molecule that binds to a target can modulate (inhibit or enhance) the function of the target, thereby causing a change in the biological status of the cell containing the target. The change caused in the cell (e.g., a change in phenotype towards wild type, or a change in growth rate) may be therapeutically beneficial to the animal or human host of the cell. Although methods currently available to validate targets do provide some guidelines in selection of drug targets, they are usually not conducted under the conditions in which a drug actually interacts with its target, and therefore provide a limited set of information. In addition, they do not directly address, among other things: 1) if a wild type (normal) target is essential for cell growth and viability during the disease state; 2) if the wild type gene products themselves are suitable targets for drug discovery; 3) if specific sites on a target are suitable for drug interaction (for example, in a pathogenic organism, there can be one gene coding for a single protein target with two activities--one activity essential for growth and infectivity, the second activity nonessential); 4) if a compensatory mechanism in the cell, either in vitro or in vivo, can overcome or compensate for target modulation or, 5) if a disease state can be cured by modulation of function of the candidate target. These methods also do not provide a direct route for testing wild type target proteins in high throughput screening assays.
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Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Method of preventing T cell-mediated responses by the use of the major histocompatibility complex class II analog protein (map protein) from Staphylococcus aureus Inventor(s): Brown, Eric; (Houston, TX), Hook, Magnus; (Houston, TX), Lee, Lawrence; (Houston, TX) Correspondence: Larson & Taylor, Plc; 1199 North Fairfax Street; Suite 900; Alexandria; VA; 22314; US Patent Application Number: 20030108564 Date filed: January 10, 2002 Abstract: A method of immunomodulating the T cell response in Staphylococcal bacteria is provided wherein an effective amount of the Map protein from Staphylococcus aureus is administered to a host to prevent or suppress the T cell response. The present method may be utilized with either the Map protein or an effective subdomain or fragment thereof such as the Map 10 or Map 19 protein. The present invention is advantageous in that suppression or prevention of the T cell response in a host can prevent or ameliorate a wide variety of the pathogenic conditions such as T cell lymphoproliferative disease and toxic shock syndrome wherein the overstimulation of T cells needs to be suppressed or modulated. Excerpt(s): This application claims the benefit of U.S. Provisional application Serial No. 60/260,523, filed Jan. 10, 2001. The present invention relates in general to the utilization of major histocompatibility complex class II analog protein, or "Map" protein, and its biologically effective fragments and domains thereof, in therapeutic methods to combat conditions associated with T cell proliferation, and in particular to the use of the Map protein and effective or active fragments thereof, including the Map10 or Map19 protein, in methods of suppressing or modulating T cell-mediated responses where necessary to alleviate a pathogenic condition. Staphylococcus aureus (SA) is an opportunistic pathogen that can cause a wide spectrum of infections from superficial local skin infections to life-threatening systemic infections that can affect internal organs and tissues. In addition, bacterial arthritis, as well as acute and chronic osteomyelitis caused by haematogenous spread or by direct inoculation in open trauma or surgical intervention such as internal fixation or joint replacement, affect hundreds of thousands of patients each year (1-6). SA is also a major cause of infections associated with indwelling medical devices, such as catheters and prosthesis (6). The cost to society in patient care, which often involves extended hospital stays and repeated surgery, can be estimated at several billion dollars per year. With the documented emergence of multidrug resistance SA strains, the threat of this widely distributed pathogen is now appreciated and novel therapies for treatment and prevention are needed. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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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 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
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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 •
Monoclonal antibodies to the map protein and method of use in treating or preventing infections Inventor(s): Domanski, Paul; (Atlanta, GA), Patel, Pratiksha; (Suwanee, GA), Patti, Joseph M.; (Cumming, GA) Correspondence: Larson & Taylor, Plc; 1199 North Fairfax Street; Suite 900; Alexandria; VA; 22314; US Patent Application Number: 20020164337 Date filed: October 22, 2001 Abstract: Monoclonal and polyclonal antibodies to the binding subdomains of the MAP protein, including the Map10 protein, or other immunogenic subregions of the MAP protein, are provided which can be useful in the treatment of and protection against infection from staphylococcal bacteria such as Staphylococcus aureus. In addition, medical instruments can be treated using the antibodies of the invention in order to reduce or eliminate the possibility of their becoming infected or further spreading the infection. In particular, the antibodies of the present invention are advantageous because they serve the double purpose of preventing adherence of the bacteria to host cells and enhancing the killing of the bacteria in an infected host. Excerpt(s): The present invention relates in general to antibodies that have been generated against the MAP protein, a surface localized protein expressed by virtually every strain of Staphylococcus aureus, and in particular to monoclonal antibodies against Map10 protein and their use in the treatment of and protection against S. aureus infections. Staphylococcus aureus is a bacterial pathogen that is capable of colonizing a wide range of host tissues and causing a spectrum of infections that range from cutaneous lesions such as wound infections, impetigo, and furuncles to life-threatening conditions that include pneumonia, septic arthritis, sepsis, endocarditis, and biomaterial related infections. The successful colonization of the host is a process required for most microorganisms, including S. aureus, to cause infections in animals and humans. Microbial adhesion is the first crucial step in a series of events that can eventually lead to disease. Pathogenic microorganisms colonize the host by attaching to host tissues or serum conditioned implanted biomaterials, such as catheters, artificial joints, and vascular grafts, through specific adhesins present on the surface of the bacteria. MSCRAMM.TM.s (Microbial Surface Components Recognizing Adhesive Matrix Molecules) are a family of cell surface adhesins that recognize and specifically bind to distinct components in the host's extracellular matrix. Once the bacteria have successfully adhered and colonized host tissues, their physiology is dramatically altered and damaging components such as toxins and proteolytic enzymes are secreted. Moreover, adherent bacteria often produce a biofilm and quickly become more resistant to the killing effect of most antibiotics. S. aureus is thus known to express a repertoire of different MSCRAMM.TM.s that can act individually or in concert to facilitate microbial adhesion to specific host tissue components. One such protein in known as the MAP protein, a surface localized protein expressed by virtually every S. aureus strain, as described for example in McGavin et al, Infect. Immun. p 2479-2485 (1993). However, it has still remained a problem to identify and utilize the information concerning MSCRAMM.TM.s from S. aureus such as the MAP protein because of the variability in
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the binding properties of the different MSCRAMM.TM.s and their role in infectivity and spread of bacterial infections. It has thus remained a highly desirable goal in the field of infectious diseases to develop compositions which are successful not only in preventing a wide variety of staph infections, but in facilitating a rapid or increased clearance of staph organisms from an infected host. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Multivalent silver pharmaceuticals Inventor(s): Antelman, Marvin S.; (Rehovot, IL) Correspondence: Akin, Gump, Strauss, Hauer & Feld, L.L.P.; One Commerce Square; 2005 Market Street, Suite 2200; Philadelphia; PA; 19103; US Patent Application Number: 20020127282 Date filed: February 5, 2002 Abstract: Novel pharmaceuticals are described based on multivalent silver compounds containing Ag(II) or Ag(III) capable of killing pathogenic gram positive and negative bacteria, fungi and algae such as E. coli, Staphylococcus aureus and epidermidis, and Candida albicans. The efficacy of these compounds is enhanced by oxidizing agents such as persulfates. They can also be utilized to preserve pharmaceutical, cosmetic and chemical specialty products against these pathogens. Excerpt(s): This patent application is a continuation of copending U.S. patent application Ser. No. 07/802,478, filed on Dec. 5, 1991, entitled "Multivalent Silver Pharmaceuticals." The entire disclosure of U.S. patent Ser. No. 07/805,478 as filed is incorporated herein by reference. The present invention relates to the employment of multivalent silver compounds and their utilization as pharmaceuticals. This invention, however, relates more particularly to the utilization of bactericidal, viricidal, algicidal and fungicidal activity exhibited by this class of compounds in pharmaceuticals. The compounds involved range from divalent to trivalent silver compositions including mixed crystals in which silver is present in a multivalent state along with monovalent silver, such as tetrasilver tetroxide which contains two monovalent silver ions and two trivalent ions per molecule. The utilization of water-soluble divalent silver (Ag II) complex bactericides is the subject of U.S. Pat. No. 5,017,295 of the present inventor. I have also been granted U.S. Pat. Nos. 5,073,382, 5,078,902, 5,089,275, and 5,098,582 which all deal with Ag(II) bactericides but more particularly with (respectively), alkaline pH, halides, stabilized complexes, and the divalent oxide. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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N-thiolated beta-lactams: Staphylococcus aureus
novel
antibacterial
agents
for
methicillin-resistant
Inventor(s): Turos, Edward; (Wesley Chapel, FL) Correspondence: Saliwanchik Lloyd & Saliwanchik; A Professional Association; 2421 N.W. 41st Street; Suite A-1; Gainesville; FL; 326066669 Patent Application Number: 20030191108 Date filed: November 5, 2002
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Abstract: The invention relates generally to novel N-thiolated.beta.-lactams. More specially, the invention relates to the use of these novel antibacterial agents in the treatment or inhibition of methicillin-resistant Staphylococcus aureaus. Excerpt(s): The clinical use of antibiotics in the 20.sup.th century has substantially decreased morbidity from bacterial infections. The early success of penicillin was extended by various sulfonamide drugs developed in the 1930s, and subsequently by a "golden" period of discovery, between 1945 and 1970, during which a wide array of highly effective agents are discovered and developed (Chopra, I., et al., "The Search for Antimicrobial Agents Effective against Bacteria Resistant to Multiple Antibiotics" Antimicrobial Agents and Chemotherapy, 1997, 41:497-503). However, since the 1980s the introduction of new antibiotics has slowed, and, concurrently, there has been an alarming increase in bacterial resistance to existing agents that now constitutes a serious threat to public health (Brown, A. G. "Discovery and Development of New.beta.-Lactam Antibiotics" Pure & Appl. Chem., 1987, 59:475-484). Hospitals, nursing homes and infant day care centers have become breeding grounds for the most tenacious drug-resistant pathogens ("Frontiers in Biotechnology" Science, 1994, 264:359-393). There has been an alarming rise in drug resistant staphylococci, enterococci, streptococci, and pneumococci infections, and a rise in tuberculosis, influenza and sepsis. Monocyclic antibiotics successfully developed by derivatization of this core structure include the monobactams (Slusarchyk, W. A. et al. "Monobactams: Ring Activating N-1-Substituents in Monocyclic.beta.-Lactam Antibiotics" Heterocycles, 1984, 21:191-209), which have 2oxoazetidine sulfonic acid as their characteristic structure. A key feature of the monobactams is the activation of the.beta.-lactam ring towards nucleophilic attack by bacterial transpeptidases that is caused by the electron-withdrawing potential of the sulfonated nitrogen atom. Alternative activating groups for monobactam derivatives have been discovered, including phosphate, phosphonate, and analogues in which a spacer atom is interposed between the ring nitrogen and activating group (Breuer, H. et al. "[(2-oxo-1-azetidinyl)oxy]acetic acids: a new class of synthetic monobactams" J. Antibiotics, 1985, 38:813-818; Slusarchyk, W. A. et al. "Monobactams: Ring Activating N1-Substituents in Monocyclic.beta.-Lactam Antibiotics" Heterocycles, 1984, 21:191-209). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Oligonucleotides for detecting bacteria and detection process Inventor(s): Fukushima, Shigeru; (Otsu-shi, JP), Nakayama, Tomoko; (Osaka, JP), Ohashi, Tetsuo; (Kyoto-shi, JP), Tada, Jun; (Muko-shi, JP) Correspondence: Birch Stewart Kolasch & Birch; PO Box 747; Falls Church; VA; 220400747; US Patent Application Number: 20030064388 Date filed: May 6, 2002 Abstract: A synthetic oligonucleotide which is complementary to a nucleotide sequence of a gene selected from the group consisting of the Shiga toxin gene of Shigella species, the ipaH gene of Shigella species and EIEC, the invE gene of Shigella species and EIEC, the araC gene of Salmonella species, the Verocytotoxin-1 gene of EHEC or VTEC, the Verocytotoxin-2 gene of EHEC or VTEC, the toxic shock syndrome toxin-1 gene of Staphylococcus aureus, the ctx gene of Vibrio cholerae, and the enterotoxin gene of Clostridium perfringens; a method for detecting a bacterial strain by amplifying a region of the above gene by PCR using the above oligonucleotides as primers and detecting the amplified region; and a kit for the detection of the bacterial strain.
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Excerpt(s): The present invention relates to detection of pathogenic bacteria in samples (e.g., clinical isolates and food specimens) for the purposes of diagnoses, screenings, quarantine inspections, and clinical tests. Specifically, it relates to detection of pathogens associated with bacterial food poisoning and bacterial diarrhea. More specifically, it relates to detection of enteropathogenic bacteria including Shigella species, Salmonella species, enterohemorrhagic Escherichia coli or Verocytotoxin-producing Escherichia coli, Staphylococcus aureus, Vibrio cholerae, and Clostridlum perfringens. Detection of pathogenic bacteria such as Shigella species, Salmonella species, enterohemorrhagic Escherichia coli (hereinafter simply referred to as EHEC) or Verocytotoxin-producing Escherichia coli (hereinafter simply referred to as VTEC), Staphylococcus aureus, Vibrio cholerae, and Clostridium perfringens is an important task in the field of medicine and public hygiene, and various methods have been used. Conventionally, detection of a pathogenic bacterial strain involves isolation of several pathogenic bacterial colonies and identification of the species of the bacteria by serological or biochemical method. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Polysaccharide vaccine for staphylococcal infections Inventor(s): McKenney, David; (Quincy, MA), Pier, Gerald; (Brookline, MA), Wang, Ying; (Brookline, MA) Correspondence: Helen C. Lockhart; Wolf, Greenfield & Sacks, P.C.; 600 Atlantic Avenue; Boston; MA; 02210; US Patent Application Number: 20020119166 Date filed: January 26, 2001 Abstract: The invention relates to compositions of the capsular polysaccharide/adhesin (PS/A) of staphylococci. The PS/A may be isolated or synthesized and includes various modifications to the structure of native PS/A based on the chemical characterization of PS/A. The invention also relates to the use of the PS/A as a vaccine for inducing active immunity to infections caused by Staphylococcus aureus, S. epidermidis, other related coagulase-negative staphylococci and organisms carrying the ica (intracellular adhesin) locus, and to the use of antibodies directed to PS/A for inducing passive immunity to the same class of infections. Excerpt(s): This application is a continuation in part of U.S. Ser. No. 09/399,904 filed on Sep. 21, 1999 and entitled Polysaccharide Vaccine for Staphylococcal Infections, now pending, which is a continuation in part of U.S. Ser. No. 09/354,408 filed on Jul. 15, 1999 and entitled Polysaccharide Vaccine for Staphylococcal Infections, now pending, which claims priority to U.S. Provisional Patent Application No. 60/093,117, filed Jul. 15, 1998, the entire contents of which are hereby incorporated by reference. The present invention relates to polysaccharide compositions useful for inducing immunity for the prevention and treatment of staphylococcal infections. The invention also relates to methods of making and using polysaccharide based antigens, related antibodies and diagnostic kits and for inducing active and passive immunity using the polysaccharide material and antibodies thereto. Staphylococci are gram-positive bacteria which normally inhabit and colonize the skin and mucus membranes of humans. If the skin or mucus membrane becomes damaged during surgery or other trauma, the staphylococci may gain access to internal tissues causing infection to develop. If the staphylococci proliferate locally or enter the lymphatic or blood system, serious infectious complications such as those associated with staphylococcal bacteremia may result. Complications associated with
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staphylococcal bacteremia include septic shock, endocarditis, arthritis, osteomyelitis, pneumonia, and abscesses in various organs. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Reagent for the detection of Staphylococcus aureus by agglutination Inventor(s): Boutonnier, Alain; (Paris, FR), Fournier, Jean-Michel; (Paris, FR) Correspondence: Finnegan, Henderson, Farabow,; Garrett And Dunner, L.L.P.; 1300 I Street, N.W.; Washington; DC; 20005-3315; US Patent Application Number: 20030068662 Date filed: August 7, 2002 Abstract: Reagents and methods for the detection of Staphylococcus aureus are provided. The reagents contain an antibody that binds to a capsular polysaccharide of type 5 of Staphylococcus aureus, and can be used in methods for detection of oxacillin resistant Staphylococcus aureus that escapes detection by agglutination in the presence of fibrinogen and antibodies directed against protein A of Staphylococcus. Excerpt(s): The present invention relates to a reagent for the detection of Staphylococcus aureus by agglutination. Various reagents are already known for the detection of Staphylococcus aureus. These reagents are based on the search for either protein A of Staphylococcus or the affinity factor for fibrinogen, or both simultaneously. Protein A is an antigen of protein nature, an external component of the wall of the majority of the strains of Staphylococcus aureus of human origin (85 to 95%). By a non-immunological process, protein A binds the Fc fragment of the immunoglobulins, leaving the Fab part free. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Regulable gene expression in Gram-positive bacteria Inventor(s): Shen, Xiaoyu; (Boston, MA), Tally, Francis P.; (Lincoln, MA), Tao, Jianshi; (North Andover, MA), Zhang, Jiansu; (Roslindale, MA) Correspondence: Hamilton, Brook, Smith & Reynolds, P.C.; 530 Virginia Road; P.O. Box 9133; Concord; MA; 01742-9133; US Patent Application Number: 20030054537 Date filed: May 17, 2002 Abstract: A system has been constructed which is suitable for tetracycline-inducible gene expression in Gram-positive bacteria such as Staphylococcus aureus and Bacillus subtilis. The replicon/host gene expression system is tightly regulated, can be used in complex as well as minimal media, and can produce a high level of gene expression upon induction, with a variety of gene products. The gene expression system is suitable for production of products toxic to the host cells, and can be used, for example, for the analysis of gene expression and gene products in Gram-positive bacteria, and in a test of the effect of a peptide or polypeptide inhibitor of an S. aureus enzyme on the growth of S. aureus cells in culture or during infection of an animal. Excerpt(s): This application is a divisional of U.S. patent application Ser. No. 09/291,874 filed on Apr. 14, 1999, which is a continuation-in-part of U.S. patent application Ser. No.
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09/227,687 filed on Jan. 8, 1999, which claims the benefit of U.S. provisional application Ser. No. 60/070,965 filed on Jan. 9, 1998; U.S. provisional application Ser. No. 60/076,638 filed on Mar. 3, 1998; U.S. provisional application Ser. No. 60/081,753 filed on Apr. 14, 1998; U.S. provisional application Ser. No. 60/085,844 filed on May 18, 1998; U.S. provisional application Ser. No. 60/089,828 filed on Jun. 19, 1998; U.S. provisional application Ser. No. 60/094,698 filed on Jul. 30, 1998; U.S. provisional application Ser. No. 60/100,211 filed on Sep. 14, 1998; U.S. provisional application Ser. No. 60/101,718 filed on Sep. 24, 1998; and U.S. provisional application Ser. No. 60/107,751 filed on Nov. 10, 1998. This application also claims the benefit of U.S. provisional application Ser. No. 60/122,949 filed on Mar. 5, 1999. The teachings of each of these referenced applications are incorporated herein by reference in their entirety. A number of different high and low copy number vector systems using a diversity of regulable promoter systems have been successfully developed to manipulate gene expression in Gram negative organisms such as Escherichia coli. As a result, E. coli can be genetically manipulated in a number of ways that have lead to a thorough understanding of the molecular basis for gene expression and to the elucidation of the function of many important proteins. As a further result, E. coli has been used as a production organism for the high level expression of a number of protein products, some of which are toxic. The majority of these vector systems developed in E. coli, however, do not function properly in Grampositive microorganisms, likely due to physiological differences between Gram-positive and Gram-negative species (de Vos, W. M., et al., Curr. Opin. Biotechnol. 8:547-553, 1997; de Vos, W. M., and G. F. M. Simons, "Gene cloning and expression systems in lactococci," pp. 52-105. In M. J. Gasson and W. M. de Vos (ed.) Genetics and Biotechnology of Lactic Acid Bacteria. Routledge, Chapman and Hall Inc., New York, N.Y., 1994). The lack of vectors providing for the efficiently regulated expression of genes in Gram-positive bacteria has been responsible, in part, for the lack of suitable Gram-positive systems for production of valuable gene products on an industrial scale. The characterization of the biology of Gram-positive bacteria has been hampered by the lack of cloning and expression vector systems that are stably maintained, tightly regulated and inducible, analogous to those developed in E. coli. As a result, the study of important Gram-positive pathogens, that can cause a variety of different illnesses including life threatening ones, has been severely limited, impeding the discovery of novel, life saving therapies to treat infectious diseases. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Retinoid compounds suited for antibacterial applications Inventor(s): Cavey, Marie-Therese; (Peymeinade, FR), Voegel, Johannes; (Chateauneuf/Grasse, FR) Correspondence: Norman H. Stepno, Esquire; Burns, Doane, Swecker & Mathis, L.L.P.; P.O. Box 1404; Alexandria; VA; 22313-1404; US Patent Application Number: 20030055110 Date filed: July 31, 2002 Abstract: A variety of retinoid compounds well suited for preventively or curatively treating a bacterial colonization infesting/infecting an individual subject exhibit pronounced antibacterial activity, notably pronounced antibacterial activity in respect of the bacterium Staphylococcus aureus, and are also well suited for the cleansing/deodorizing of human skin.
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Excerpt(s): This application claims priority under 35 U.S.C.sctn.119 of FR-00/01206, filed Jan. 31, 2000, and is a continuation of PCT/FR01/00280, filed Jan. 30, 2001 and designating the United States (published in the French language on Aug. 9, 2001 as WO 01/56554 A2; the title and abstract were also published in English), both hereby expressly incorporated by reference. The present invention relates to the administration of compositions containing at least one compound selected from among molecules of retinoid type for preventively or curatively treating bacterial colonizations, aggravations of pathologies or disease states caused by these colonizations and also cutaneous overinfections induced by these bacteria and, more particularly, by the bacterium Staphylococcus aureus. The present invention also relates to the formulation of at least one compound selected from among molecules of retinoid type into skin cleansing compositions and also to a cosmetic regime, regimen or treatment for cleansing the skin or correcting its odor, comprising topically applying such compositions onto the skin. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Salicylaldehyde-containing composition having antimicrobial and fragrancing properties and process for using same Inventor(s): De Meijere, Remco Johannes Hendrik; (Huizen, NL), Deans, Stanley G.; (South Ayrshire, GB), Lis-Balchin, Maria Therese; (London, GB), Simpson, Elisabeth J. M.; (South Ayrshire, GB), White, Michael John Robert; (Amsterdam, NL) Correspondence: Joseph F. Leightner, ESQ.; International Flavors & Fragrances INC.; 521 West 57th Street; New York; NY; 10019; US Patent Application Number: 20030156975 Date filed: November 8, 2002 Abstract: Described are synergistic antimicrobial-fragrance compositions including broad spectrum antimicrobial compositions containing salicylaldehyde and at least one organoleptically-compatible antimicrobial synergism cofactor substance. The weight ratio range of salicylaldehyde:synergism cofactors substance is from 1:10 up to 10:1. The cofactor substance is such that the degree of synergism of the resultant mixture is defined according to the IFF Antimicrobial Synergism Test wherein the difference between the actual and expected antimicrobial values of the mixture is greater than or equal to a multiple of (i) 0.05 and (ii) the expected antimicrobial value of the mixture. Cofactor substances include phenolics such as cresol, caravacrol and thymol; ethyl vanillin; benzyl alcohol; indol;.beta.-orcinol; and terpinenol-4. Microorganisms against which the synergistic compositions are effective include:Escherichia coli;Enterococcus hirae;Pseudomonas aeruginosa;Staphylococcus aureus; andSaccharomyces cerevisae.The compositions have application in all-purpose cleaning compositions, geltype toilet rim articles, liquid-type toilet rim articles, personal shower cleaning compositions, and body and hair care products including shower gel compositions, shampoo compositions and foam bath compositions. Excerpt(s): The present invention relates to fragrance compositions exhibiting antimicrobial activity with a hedonically acceptable odor. The present invention also relates to antimicrobial-flavor compositions which are capable of eliminating one or more microorganisms from a solid or semisolid surface (e.g., skin) or a three-space inhabited by said microorganisms, which compositions include salicylaldehyde and at least one organoleptically compatible antimicrobial synergism cofactor substance. The prior art, including U.S. Pat. No. 5,965,518 issued on Oct. 12, 1999, the specification for which is incorporated by reference herein, indicates that fragrances having antimicrobial
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activity may comprise between 3 up to 20% by weight of non-aromatic terpenoids. U.S. Pat. No. 5,965,518 further indicates that the fragrance composition may also, either alternatively or additionally, include essential oils containing phenoic compounds as a major constituent and/or essential oils containing non-aromatic terpenoids as the main constituent. U.S. Pat. No. 5,965,518 further indicates that the fragrance composition further has an odor intensity index of less than 100 and an odor evaluation acceptability index of greater than 50. Fragrances are commonly incorporated in a wide variety of household and industrial items, for example, counterwipes and cleansers, in order to impart a pleasing odor to a solid or semisolid surface or a three-space. A number of fragrances have been reported to have weak bacteria static activity. However, this activity has been ascertained to be too low to be of practical use. To overcome this weak activity and achieve antimicrobial fragrances of practical use either as bacteria static agents and preservatives or as bacteriacidal agents and sanitizers and disinfectants, combinations of fragrance materials with other materials are employed. For example, fragrances have been combined with a cationic phospholipid as taught in U.S. Pat. No. 5,420,104; and fragrances have been combined with a preservative and surface active agent as taught in U.S. Pat. No. 5,306,707. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Selective medium for gram-positive bacteria Inventor(s): McKillip, John L.; (Ruston, LA) Correspondence: R. Keith Harrison; 2139 E. Bert Kouns; Shreveport; LA; 71105; US Patent Application Number: 20020192741 Date filed: May 13, 2002 Abstract: A selective and differential medium for Gram-positive bacteria. In a preferred embodiment, the medium is characterized by a Gram-positive agar including appropriate quantities of sodium chloride, sodium glycerophosphate, lithium chloride, phenylethanol, mannitol, tryptone, yeast extract, bromcresol purple and agar. When streaked with mixed bacterial cultures containing both Gram-positive and Gramnegative bacteria, the agar promotes growth and colonization of the Gram-positive bacteria and inhibits growth of the Gram-negative bacteria in the culture. The pH indicator bromcresol purple facilitates differentiation of Gram-positive species which ferment the sugar mannitol in the agar, such as Staphylococcus aureus, from those which do not, such as Staphylococcus epidermis. In another embodiment, the medium is characterized by a Gram-positive broth including sodium chloride, sodium glycerophosphate, lithium chloride, phenylethanol, mannitol, tryptone, yeast extract and bromcresol purple. Excerpt(s): This is a continuation-in-part of application Ser. No. 09/676,606, filed Sep. 28, 2000. This invention relates to selective growth media for microorganisms and more particularly, to a selective and differential medium for Gram-positive bacteria, which medium in a preferred embodiment is characterized by a Gram-positive agar including appropriate quantities of sodium chloride, sodium glycerophosphate, lithium chloride, phenylethanol, mannitol, tryptone, yeast extract, bromcresol purple and agar. When streaked with mixed bacterial cultures containing both Gram-positive and Gramnegative bacteria, the agar promotes growth and colonization of Gram-positive bacteria and inhibits growth of Gram-negative bacteria in the culture. The pH indicator bromcresol purple enables differentiation of those species of Gram-positive bacteria which ferment the sugar mannitol, such as Staphylococcus aureus, from those which do
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not, such as Staphylococcus epidermis. In a second embodiment, the medium is characterized by a Gram-positive broth including sodium chloride, sodium glycerophosphate, lithium chloride, phenylethanol, mannitol, tryptone, yeast extract and bromcresol purple. In a typical undergraduate Introductory Microbiology laboratory course, students undertake a project in which they are given a broth tube containing a mixture of three bacteria of unknown genus and species and are required to implement an array of biochemical and morphological tests to separate and identify the types of bacteria from the tube. The project gives the students a chance to apply the procedures presented in the laboratory up to the time of the project, as well as an opportunity to practice their techniques and reasoning when presented with a typical microbiology problem. The students enjoy the benefits of working on their own problems and learning from any mistakes they make. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Signal recognition particle polypeptides and polynucleotides Inventor(s): Black, Michael T.; (Chester Springs, PA) Correspondence: Dechert; Attn: Allen Bloom, Esq; 4000 Bell Atlantic Tower; 1717 Arch Street; Philadelphia; PA; 19103; US Patent Application Number: 20030077585 Date filed: August 30, 2001 Abstract: This invention relates to a novel bacterial ribonucleoprotein complex and the component parts thereof. More specifically, this invention relates to SRP isolated from Staphylococcus aureus and the use of SRP or components thereof in screens for the identification of antimicrobial compounds and to the use of such compounds in therapy. Excerpt(s): This invention relates to newly identified polynucleotides, polypeptides encoded by certain of these polynucleotides, molecular complexes of RNAs and polypeptides, the uses of such polynucleotides and polypeptides, as well as the production of such polynucleotides and polypeptides and recombinant host cells transformed with the polynucleotides. The invention relates particularly to such polynucleotides and polypeptides from Staphylococci, especially S. aureus. This invention also relates to inhibiting the biosynthesis, assembly or action of such polynucleotides and/or polypeptides and to the use of such inhibitors in therapy. This invention relates to a novel bacterial ribonucleoprotein complex and the component parts thereof. More specifically, this invention relates to SRP, particularly SRP from Staphylococcus aureus. and the use of SRP or components thereof in screens for the identification of antimicrobial compounds and to the use of such compounds in therapy. While certain Staphylococcal proteins associated with pathogenicity have been identified, e.g., coagulase, hemolysins, leucocidins and exo- and enterotoxins, additional targets are always useful because it is appreciated that the target of a antimicrobial screen can often bias the outcome. Thus, new targets allow for the discovery of new classes of antimicrobials. 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, 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,
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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 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 •
Staphylococcus aureus genes and polypeptides Inventor(s): Choi, Gil H.; (Rockville, MD), Simpson, Andrew J.G.; (Sao Paulo, BR) Correspondence: Human Genome Sciences Inc; 9410 Key West Avenue; Rockville; MD; 20850 Patent Application Number: 20030153733 Date filed: October 24, 2002 Abstract: The present invention relates to 11 novel genes from S. aureus and the polypeptides they encode. Also provided as are vectors, host cells, antibodies and recombinant methods for producing the same. The invention further relates to screening methods for identifying agonists and antagonists of S. aureus polypeptide activity. The invention additionally relates to diagnostic methods for detecting Staphylococcus nucleic acids, polypeptides and antibodies in a biological sample. The present invention further relates to novel vaccines for the prevention or attenuation of infection by Staphylococcus. Excerpt(s): This application is a divisional of and claims priority under 35 U.S.C.sctn.120 to U.S. application Ser. No. 09/830,217, filed Apr. 24, 2001, which is the National Stage of International Application No. PCT/US99/06199, filed Mar. 18, 1999, which claims priority to U.S. Provisional Application Nos. 60/084,674, filed May 7, 1998, 60/080,296, filed Apr. 1, 1998, and 60/078,682, filed Mar. 20, 1998. All of the foregoing applications are hereby incorporated by reference herein. The present invention relates to novel Staphylococcus aureus genes (S. aureus) nucleic acids and polypeptides. Also provided are vectors, host cells and recombinant methods for producing the same. Further provided are diagnostic methods for detecting Staphylococcus aureus using probes, primers, and antibodies to the S. aureus nucleic acids and polypeptides of the present
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invention. The invention further relates to screening methods for identifying agonists and antagonists of S. aureus polypeptide activity and to vaccines using S. aureus nucleic acids and polypeptides. The genus Staphylococcus includes at least 20 distinct species. (For a review see Novick, R. P., The Staphylococcus as a Molecular Genetic System in MOLECULAR BIOLOGY OF THE STAPHYLOCOCCI, 1-37 (R. Novick, Ed., VCH Publishers, New York (1990)). Species differ from one another by 80% or more, by hybridization kinetics, whereas strains within a species are at least 90% identical by the same measure. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Vaccine against Staphylococcus intoxication Inventor(s): Lee, John S.; (Hagerstown, MD), Pushko, Peter; (Frederick, MD), Smith, Jonathan F.; (Sabillasville, MD), Ulrich, Robert G.; (Frederick, MD) Correspondence: Attn:mcmr-ja; U.S. Army Medical Research And Materiel Command; 504 Scott Street; FT. Detrick; MD; 21702-5012; US Patent Application Number: 20040009183 Date filed: April 2, 2003 Abstract: Using nucleic acids encoding mutant SEA and SEB exotoxins from Staphylococcus aureus, compositions and methods for use in inducing an immune response which is protective against staphylococcal aureus intoxication in subjects is described. Excerpt(s): This invention relates to vaccines for bacterial toxins from Staphylococcus aureus. The most common cases of food poisoning are caused by the bacteria Staphylococcus aureus. Exotoxins produced by the organism cause gastrointestinal distress, to include diarrhea and vomiting, and can also cause toxic shock syndrome which may lead to death. These exotoxins, also called enterotoxins since they typically exert their effects on the gastrointestinal tract, cause disease by binding to the major histocompatibility complex (MHC) on T-cells which results in the release of large amounts of various cytokines. This cytokine release has been postulated to mediate the many toxic effects of the S. aureus exotoxins. There are at least eight antigenically distinct exotoxins (labeled SEA, SEB, SEC1, SEC2, SEC3, SED, SEE, and SEG) produced by S. aureus. Presently, there is no approved/licensed SEA or SEB vaccine. Treatment for Staphylococcus aureus infections is becoming more difficult since the organism has become resistant to most antibiotics. Therefore, there is a need for an efficacious vaccine protective against Staphylococcus aureus intoxication. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Vaccine for the prevention of bacterial infection of the bovine mammary gland Inventor(s): Guidry, Albert; (Nellysford, VA), O'Brien, Celia; (Ellicott City, MD) Correspondence: Usda, Ars, Ott; 5601 Sunnyside Ave; RM 4-1159; Beltsville; MD; 207055131; US Patent Application Number: 20040028688 Date filed: July 5, 2002
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Abstract: A novel vaccine for immunizing animals against Staphylococcus aureus induced mastitis is disclosed. The vaccine is comprised of whole killed cells of S. aureus in a dosage effective to immunize an animal against the organism, in combination with a pharmaceutically acceptable carrier. Excerpt(s): This invention relates to a novel vaccine specific for Staphylococcus aureus, the major bacterium responsible for bovine mastitis. The strains of the invention are used in vaccine development, to protect individuals from S. aureus infection and to treat and control S. aureus-induced mastitis. S. aureus mastitis affects 90% of US. Dairy herds. Annual loss due to mastitis in the United States is two billion dollars (Nickerson et al. 1984. J. Dairy Res. 51: 209-217). Antibiotic treatment of S. aureus infections has met with limited success due to the development of antibiotic resistant strains and their ability to survive within polymorphonuclear neutrophils (PMN) and macrophages where very few antibiotics achieve effective intracellular concentrations (Craven and Anderson. 1984. J. Dairy Res. 51:513-523). S. aureus mastitis is rarely acute, but causes subclinical, chronic infections (Bramley and Dodd. 1984. J. Dairy Res. 51:481-512). Cows are most susceptible to S. aureus infections during the transition from lactation to involution and from involution to colostrogenesis (Oliver and Sordillo. 1988. J. Dairy Sci. 71: 2584-2606). The bovine udder has numerous defense mechanisms to protect against invading pathogens. The first line of defense against bacterial invasion of the udder is the smooth muscle sphincter surrounding the teat end (Frost, A. J. 1990. In: Proc. Int. Symp. Bovine Mastitis, Page 1) and keratin, a waxy material found in the teat canal (Murphy, J. M. 1959. Cornell Vet. 49: 411-421). However, bacteria can breach the teat canal and enter the gland cistern by multiplication or reverse flow during milking machine pulsation (Nickerson, S. C. 1986. In: Dairy Research Report, Louisiana Agric. Experiment Station, Page 211; Schalm et al. 1971. In: Bovine Mastitis, Lea and Febiger, Philadelphia, Pa., Page 209). 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 Staphylococcus aureus, 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 “Staphylococcus aureus” (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 Staphylococcus aureus. You can also use this procedure to view pending patent applications concerning Staphylococcus aureus. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.
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CHAPTER 6. BOOKS ON STAPHYLOCOCCUS AUREUS Overview This chapter provides bibliographic book references relating to Staphylococcus aureus. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on Staphylococcus aureus include the Combined Health Information Database and the National Library of Medicine. Your local medical library also may have these titles available for loan.
Chapters on Staphylococcus aureus In order to find chapters that specifically relate to Staphylococcus aureus, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and Staphylococcus aureus 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 “Staphylococcus aureus” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on Staphylococcus aureus: •
Medical Issues in the Dental Care of Older Adults Source: in Holm-Pedersen, P.; Loe, H., eds. Textbook of Geriatric Dentistry. 2nd ed. Copenhagen, Denmark: Munksgaard. 1996. p. 194-211. 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 520,000; contact directly for current price in US dollars. ISBN: 8716105338. Summary: As patients live longer with significant chronic disease, and as more older patients seek dental care, practitioners are more likely to encounter medically and functionally compromised individuals. This chapter on medical issues in the dental care of older adults is from a comprehensive text on the processes of aging and their relevance to the delivery of dental health care. Topics include indications for medical consultation, assessing patient stability, selected geriatric problems relevant to dentistry,
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and ethical issues in medical and dental management. The authors discuss infections, including influence, tuberculosis, methicillin-resistant Staphylococcus aureus, and infective endocarditis; cardiovascular conditions; rheumatic conditions, including giant cell arteritis and arthritis; endocrine disorders, notably diabetes mellitus; thyroid disorders; osteoporosis; nervous system and mental disorders, including cerebrovascular disease (stroke), dementia, depressive disorders, Parkinsonism, and tardive dyskinesia. 1 figure. 2 tables. 58 references. (AA-M). •
Food-Borne Illness Source: in Hagan, P.T., ed. Mayo Clinic Guide to Self-Care: Answers for Everyday Health Problems. New York, NY: Kensington Publishers. 1999. p. 26-27. Contact: Available from Mayo Clinic. 200 First Street, S.W., Rochester, MN 55905. (800) 291-1128 or (507) 284-2511. Fax (507) 284-0161. Website: www.mayo.edu. PRICE: $16.95 plus shipping and handling. ISBN: 0962786578. Summary: Foodborne illness is a growing problem in the U.S. This chapter on foodborne illness is from a self care handbook on everyday health problems published by the Mayo Clinic. The handbook offers readers a guide to symptoms, diagnosis, and treatment for common problems (particularly self care strategies and tips for handling these problems in children). All foods naturally contain small amounts of bacteria. When food is poorly handled, improperly cooked, or inadequately stored, bacteria can multiply in great enough numbers to cause illness. Parasites, viruses, and chemicals can also contaminate food, but foodborne illness from these sources is less common. Eating contaminated food can result in illness, depending on the organism, the amount of exposure, one's age, and health status. As people age, their immune cells may not respond as quickly and effectively to infectious organisms. Young children are at increased risk of illness because their immune systems haven't developed fully. Conditions such as diabetes, AIDS, and cancer treatment also reduce the immune response, making one more susceptible to foodborne illness. The chapter briefly lists self care strategies, particularly for handling short lived (less than 12 hours) food poisoning. One section cautions readers about botulism, a potentially fatal food poisoning. A side bar reviews how to handle food safely. The chapter concludes with a chart of common troublesome bacteria, how each is spread, the symptoms caused by infection, and prevention strategies. Bacteria included are Campylobacter jejuni, Clostridium perfringens, Escherichia coli 0157:H7, Salmonella, Staphylococcus aureus, and Vibrio vulnificus. The book is focused on how to prevent illness, how to detect illness before it becomes a serious and costly problem, and how to avoid unnecessary trips to the clinic or emergency room. 1 table.
•
Infection Control and Universal Precautions Source: in Gutch, C.F.; Stoner, M.H.; Corea, A.L. Review of Hemodialysis for Nurses and Dialysis Personnel. 6th ed. St. Louis, MO: Mosby. 1999. p. 264-278. Contact: Available from Harcourt Publishers. Foots Cray High Street, Sidcup, Kent DA14 5HP UK. 02083085700. Fax 02083085702. E-mail:
[email protected]. Website: www.harcourt-international.com. PRICE: $37.95 plus shipping and handling. ISBN: 0815120990. Summary: Infection control is used in the dialysis setting to prevent patients and staff from acquiring infections specific to the dialysis unit. Infection control incorporates policies and procedures that include surveillance and monitoring activities for water treatment, dialyzer reuse, bacterial contamination, and transmission of blood borne and other infectious diseases. This chapter on infection control and universal precautions is
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from a nursing text that poses questions and then answers those questions with the aim of giving a good understanding of the basic principles, basic diseases, and basic problems in the treatment of kidney patients by dialysis. The authors of the chapter first review guidelines from the CDC on infection control strategies and precautions, and regulations from the Occupational Safety and Health Administration (OSHA) that enforce the use of universal precautions and other infection control strategies for all health care agencies. The authors review information that dialysis personnel should know to help prevent the spread of infectious diseases in dialysis facilities. The chapter also includes a review of blood borne diseases, universal precautions (as published by the CDC), as well as strategies to prevent the spread of methicillin resistant Staphylococcus aureus (MRSA), vancomycin resistant enterococcus (VRE), and tuberculosis (TB). Universal precautions in a dialysis unit can be summarized into four main categories: barrier precautions and personal protective equipment (PPE) such as gloves, face shield masks, protective eyewear, gowns, aprons; protection against penetration caused by sharps; good personal hygiene; and good environment control or avoidance of environmental contamination. The two most significant blood borne pathogens are hepatitis B virus (HBV) and HIV. 3 tables. •
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.
•
Approach to Patients with Gastrointestinal Tract Infections and Food Poisoning Source: in Feigin, R.D. and Cherry, J.D., eds. Textbook of Pediatric Infectious Diseases. 4th ed. Volume 1. Philadelphia, PA: W.B. Saunders Company. 1998. p. 567-601. Contact: Available from W.B. Saunders Company. Order Fulfillment, 6277 Sea Harbor Drive, Orlando, FL 32887. (800) 545-2522. Fax (800) 874-6418 or (407) 352-3445. PRICE: $315.00. ISBN: 0721664482. Summary: This chapter on managing young patients with gastrointestinal (GI) tract infections and food poisoning is from a textbook on pediatric infectious diseases. The authors stress that the approach to patients must begin with a thorough medical history, including information about epidemiologic factors, a physical examination, and
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knowledge of the pathophysiology of various enteropathogens. GI tract infections can include a wide range of symptoms and can be caused by a variety of agents and organisms. However, most infectious diarrhea illness can be classified into a category based on its cause, its pathophysiology, and the clinical response. This information can then be used to determine the appropriate diagnostic and monitoring tests and to decide which therapy to use. All patients with diarrhea require some degree of fluid and electrolyte therapy, a few need other nonspecific support, and for some, specific antimicrobial therapy is indicated to shorten the illness. The authors consider epidemiology and etiology, including outbreaks in child care centers and hospitals, foodborne or waterborne diarrhea, antimicrobial-associated diarrhea, travelers' diarrhea, and diarrhea in immunocompromised patients, including those with AIDS; bacterial organisms that cause gastroenteritis, including Aeromanas hydrophila, Bacillus cereus, Campylobacter, Clostridium difficile, Clostridium perfringens, Escherichia coli, Plesiomonas shigelloides, Salmonella, Shigella, Staphylococcus aureus, Vibrio cholerae, Vibrio parahaemolyticus, and Yersinia enterocolitica; viral agents, including rotaviruses, astroviruses, calciviruses, and enteric adenoviruses; and parasites, including Cryptosporidium, Entamoeba histolytica, Giardia lamblia, Strongyloides stercoralis, Isospora belli, microsporidia, and Cyclospora. Diagnostic considerations, including laboratory testing, are reviewed. The authors also discuss treatment options, including fluid and electrolyte therapy, dietary manipulation, nonspecific therapy with antidiarrheal compounds, and specific therapy with antimicrobial agents. 5 figures. 18 tables. 392 references. (AA-M). •
Chapter 197: Soft Tissue Infections: Erysipelas, Cellulitis, and Gangrenous Cellulitis Source: in Freedberg, I.M., et al., eds. Fitzpatrick's Dermatology in General Medicine. 5th ed., Vol. 2. New York, NY: McGraw-Hill. 1999. p. 2213-2231. Contact: Available from McGraw-Hill Customer Services. P.O. Box 548, Blacklick, OH 43004-0548. (800) 262-4729 or (877) 833-5524. Fax (614) 759-3749 or (614) 759-3641. E-mail:
[email protected]. PRICE: $395.00 plus shipping and handling. ISBN: 0070219435. Summary: This chapter provides health professionals with information on the etiology, pathogenesis, clinical features, differential diagnosis, laboratory findings, course, prognosis, treatment, and prevention of soft tissue infections (STIs). Normal skin has a critical role in the defense against many pathogens. The details of the host-pathogen interaction are not well understood, but they appear to involve barrier function, bacterial factors, and host factors. STIs are characterized by an acute, diffuse, spreading, edematous, suppurative inflammation of the dermis and subcutaneous tissues. Erysipelas is a distinct type of painful, bright-red, superficial cutaneous cellulitis with marked dermal lymphatic vessel involvement resulting from group A beta-hemolytic streptococcus. Cellulitis involves more of the soft tissues. The tissue feels hard upon palpation and is extremely painful. Staphylococcus aureus and group A streptococci are the most common etiologic agents. Surgical wound infections are classified as incisional or deep. The complications of wound infection arise locally or are systemic. Gangrenous cellulitis is characterized by necrosis of the dermis, hypodermis, fascia, or muscle. Types of necrotizing fasciitis include streptococcal gangrene, necrotizing fasciitis other than streptococcal gangrene, Fournier's gangrene, and synergistic necrotizing cellulitis. Clostridial soft tissue infections are classified as anaerobic cellulitis, anaerobic myonecrosis, and spontaneous, nontraumatic anaerobic myonecrosis. Other forms of gangrenous cellulitis include progressive bacterial synergistic gangrene and gangrenous cellulitis in the immunosuppressed individual. Other infections include infections of
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intravascular catheters, cellulitis complicating a pressure ulcer, and cellulitis arising at sites of animal bites. Helpful laboratory investigations include smears of pus, exudate, and aspirates; hematology; cultures; skin biopsy; and imaging. The differential diagnosis of STIs includes noninfectious inflammatory disorders and other infections. Bacterial species associated with cellulitis include Staphylococcus aureus, beta-hemolytic streptococcus, streptococcus pneumoniae, neisseria meningitidis, haemophilus influenzae, escherichia coli, and other gram-negative bacilli. Specific pathogens are also associated with aqueous environments, soil exposure, and animal exposure. Treatment of STIs involve use of antibiotics, immobilization and elevation of the area affected by a local lesion, and surgery. 12 figures, 7 tables, and 104 references.
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CHAPTER 7. PERIODICALS STAPHYLOCOCCUS AUREUS
AND
NEWS
ON
Overview In this chapter, we suggest a number of news sources and present various periodicals that cover Staphylococcus aureus.
News Services and Press Releases One of the simplest ways of tracking press releases on Staphylococcus aureus 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 “Staphylococcus aureus” (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 Staphylococcus aureus. 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 “Staphylococcus aureus” (or synonyms). The following was recently listed in this archive for Staphylococcus aureus: •
Salicylic acid attenuates Staphylococcus aureus virulence Source: Reuters Industry Breifing Date: July 22, 2003
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•
Staphylococcus aureus mechanism may explain frequency of infection Source: Reuters Medical News Date: May 01, 2003
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First case of Staphylococcus aureus to linezolid to identified Source: Reuters Medical News Date: July 19, 2001
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Nasal carriage implicated in Staphylococcus aureus bacteremia Source: Reuters Medical News Date: January 04, 2001 The NIH
Within MEDLINEplus, the NIH has made an agreement with the New York Times Syndicate, the AP News Service, and Reuters to deliver news that can be browsed by the public. Search news releases at http://www.nlm.nih.gov/medlineplus/alphanews_a.html. MEDLINEplus allows you to browse across an alphabetical index. Or you can search by date at the following Web page: http://www.nlm.nih.gov/medlineplus/newsbydate.html. Often, news items are indexed by MEDLINEplus within its search engine. Business Wire Business Wire is similar to PR Newswire. To access this archive, simply go to http://www.businesswire.com/. You can scan the news by industry category or company name. Market Wire Market Wire is more focused on technology than the other wires. To browse the latest press releases by topic, such as alternative medicine, biotechnology, fitness, healthcare, legal, nutrition, and pharmaceuticals, access Market Wire’s Medical/Health channel at http://www.marketwire.com/mw/release_index?channel=MedicalHealth. Or simply go to Market Wire’s home page at http://www.marketwire.com/mw/home, type “Staphylococcus aureus” (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 “Staphylococcus aureus” (or synonyms). If you know the name of a company that is relevant to Staphylococcus aureus, you can go to any stock trading Web site (such as http://www.etrade.com/) and search for the company name there. News items across various news sources are reported on indicated hyperlinks. Google offers a similar service at http://news.google.com/.
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BBC Covering news from a more European perspective, the British Broadcasting Corporation (BBC) allows the public free access to their news archive located at http://www.bbc.co.uk/. Search by “Staphylococcus aureus” (or synonyms).
Newsletter Articles Use the Combined Health Information Database, and limit your search criteria to “newsletter articles.” Again, you will need to use the “Detailed Search” option. Go directly 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 “Staphylococcus aureus” (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 Staphylococcus aureus: •
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 Staphylococcus aureus Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to Staphylococcus aureus. In addition to these sources, you can search for articles covering Staphylococcus aureus 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.”
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If you want complete details about the historical contents of a journal, you can also visit the following Web site: http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi. Here, type in the name of the journal or its abbreviation, and you will receive an index of published articles. At http://locatorplus.gov/, you can retrieve more indexing information on medical periodicals (e.g. the name of the publisher). Select the button “Search LOCATORplus.” Then type in the name of the journal and select the advanced search option “Journal Title Search.”
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APPENDICES
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APPENDIX A. PHYSICIAN RESOURCES Overview In this chapter, we focus on databases and Internet-based guidelines and information resources created or written for a professional audience.
NIH Guidelines Commonly referred to as “clinical” or “professional” guidelines, the National Institutes of Health publish physician guidelines for the most common diseases. Publications are available at the following by relevant Institute11: •
Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm
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National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/news/facts/
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National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html
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National Cancer Institute (NCI); guidelines available at http://www.cancer.gov/cancerinfo/list.aspx?viewid=5f35036e-5497-4d86-8c2c714a9f7c8d25
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National Eye Institute (NEI); guidelines available at http://www.nei.nih.gov/order/index.htm
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National Heart, Lung, and Blood Institute (NHLBI); guidelines available at http://www.nhlbi.nih.gov/guidelines/index.htm
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National Human Genome Research Institute (NHGRI); research available at http://www.genome.gov/page.cfm?pageID=10000375
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National Institute on Aging (NIA); guidelines available at http://www.nia.nih.gov/health/
11
These publications are typically written by one or more of the various NIH Institutes.
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National Institute on Alcohol Abuse and Alcoholism (NIAAA); guidelines available at http://www.niaaa.nih.gov/publications/publications.htm
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National Institute of Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/
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National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm
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National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm
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National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/
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National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/
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National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm
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National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html
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National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm
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National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/practitioners/index.cfm
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National Institute of Neurological Disorders and Stroke (NINDS); neurological disorder information pages available at http://www.ninds.nih.gov/health_and_medical/disorder_index.htm
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National Institute of Nursing Research (NINR); publications on selected illnesses at http://www.nih.gov/ninr/news-info/publications.html
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National Institute of Biomedical Imaging and Bioengineering; general information at http://grants.nih.gov/grants/becon/becon_info.htm
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Center for Information Technology (CIT); referrals to other agencies based on keyword searches available at http://kb.nih.gov/www_query_main.asp
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National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/
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National Center for Research Resources (NCRR); various information directories available at http://www.ncrr.nih.gov/publications.asp
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Office of Rare Diseases; various fact sheets available at http://rarediseases.info.nih.gov/html/resources/rep_pubs.html
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Centers for Disease Control and Prevention; various fact sheets on infectious diseases available at http://www.cdc.gov/publications.htm
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NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.12 Physician-oriented resources provide a wide variety of information related to the biomedical and health sciences, both past and present. The format of these resources varies. Searchable databases, bibliographic citations, full-text articles (when available), archival collections, and images are all available. The following are referenced by the National Library of Medicine:13 •
Bioethics: Access to published literature on the ethical, legal, and public policy issues surrounding healthcare and biomedical research. This information is provided in conjunction with the Kennedy Institute of Ethics located at Georgetown University, Washington, D.C.: http://www.nlm.nih.gov/databases/databases_bioethics.html
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HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html
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NLM Online Exhibitions: Describes “Exhibitions in the History of Medicine”: http://www.nlm.nih.gov/exhibition/exhibition.html. Additional resources for historical scholarship in medicine: http://www.nlm.nih.gov/hmd/hmd.html
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Biotechnology Information: Access to public databases. The National Center for Biotechnology Information conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information for the better understanding of molecular processes affecting human health and disease: http://www.ncbi.nlm.nih.gov/
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Population Information: The National Library of Medicine provides access to worldwide coverage of population, family planning, and related health issues, including family planning technology and programs, fertility, and population law and policy: http://www.nlm.nih.gov/databases/databases_population.html
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Cancer Information: Access to cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html
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Profiles in Science: Offering the archival collections of prominent twentieth-century biomedical scientists to the public through modern digital technology: http://www.profiles.nlm.nih.gov/
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Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html
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Clinical Alerts: Reports the release of findings from the NIH-funded clinical trials where such release could significantly affect morbidity and mortality: http://www.nlm.nih.gov/databases/alerts/clinical_alerts.html
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Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html
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MEDLINE: Bibliographic database covering the fields of medicine, nursing, dentistry, veterinary medicine, the healthcare system, and the pre-clinical sciences: http://www.nlm.nih.gov/databases/databases_medline.html
12
Remember, for the general public, the National Library of Medicine recommends the databases referenced in MEDLINEplus (http://medlineplus.gov/ or http://www.nlm.nih.gov/medlineplus/databases.html). 13 See http://www.nlm.nih.gov/databases/databases.html.
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Toxicology and Environmental Health Information (TOXNET): Databases covering toxicology and environmental health: http://sis.nlm.nih.gov/Tox/ToxMain.html
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Visible Human Interface: Anatomically detailed, three-dimensional representations of normal male and female human bodies: http://www.nlm.nih.gov/research/visible/visible_human.html
The NLM Gateway14 The NLM (National Library of Medicine) Gateway is a Web-based system that lets users search simultaneously in multiple retrieval systems at the U.S. National Library of Medicine (NLM). It allows users of NLM services to initiate searches from one Web interface, providing one-stop searching for many of NLM’s information resources or databases.15 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “Staphylococcus aureus” (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 46681 104 444 477 83 47789
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 “Staphylococcus aureus” (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 Staphylococcus aureus can appear at any moment and be published by a number of sources, the best approach to finding guidelines is to systematically scan the Internet-based services that post them.
Patient Guideline Sources The remainder of this chapter directs you to sources which either publish or can help you find additional guidelines on topics related to Staphylococcus aureus. 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 Staphylococcus aureus. 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 “Staphylococcus aureus”:
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Food Contamination and Poisoning http://www.nlm.nih.gov/medlineplus/foodcontaminationandpoisoning.html Impetigo http://www.nlm.nih.gov/medlineplus/impetigo.html Occupational Health for Healthcare Providers http://www.nlm.nih.gov/medlineplus/occupationalhealthforhealthcareproviders.t ml Staphylococcal Infections http://www.nlm.nih.gov/medlineplus/staphylococcalinfections.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 Staphylococcus aureus. 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 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
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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: •
Antimicrobial Resistance Summary: This consumer health information fact sheet discusses drug-resistant infectious agents, including methicillin-resistant Staphylococcus aureus (MRSA), and vancomycin-resistant Staphylococcus aureus Source: National Institute of Allergy and Infectious Diseases, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=3767 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 Staphylococcus aureus. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html. Additional Web Sources A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •
AOL: http://search.aol.com/cat.adp?id=168&layer=&from=subcats
•
Family Village: http://www.familyvillage.wisc.edu/specific.htm
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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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WebMDHealth: http://my.webmd.com/health_topics
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Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to Staphylococcus aureus. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with Staphylococcus aureus. 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 Staphylococcus aureus. 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 “Staphylococcus aureus” (or a synonym), and you will receive information on all relevant organizations listed in the database. Health Hotlines directs you to toll-free numbers to over 300 organizations. You can access this database directly at http://www.sis.nlm.nih.gov/hotlines/. On this page, you are given the option to search by keyword or by browsing the subject list. When you have received your search results, click on the name of the organization for its description and contact information. The Combined Health Information Database Another comprehensive source of information on healthcare associations is the Combined Health Information Database. Using the “Detailed Search” option, you will need to limit your search to “Organizations” and “Staphylococcus aureus”. 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 “Staphylococcus aureus” (or synonyms) into the “For these words:” box. You should check back periodically with this database since it is updated every three months.
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The National Organization for Rare Disorders, Inc. The National Organization for Rare Disorders, Inc. has prepared a Web site that provides, at no charge, lists of associations organized by health topic. You can access this database at the following Web site: http://www.rarediseases.org/search/orgsearch.html. Type “Staphylococcus aureus” (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)
•
California: Health Library (Stanford University Medical Center), http://wwwmed.stanford.edu/healthlibrary/
•
California: Patient Education Resource Center - Health Information and Resources (University of California, San Francisco), http://sfghdean.ucsf.edu/barnett/PERC/default.asp
•
California: Redwood Health Library (Petaluma Health Care District), http://www.phcd.org/rdwdlib.html
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California: Los Gatos PlaneTree Health Library, http://planetreesanjose.org/
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California: Sutter Resource Library (Sutter Hospitals Foundation, Sacramento), http://suttermedicalcenter.org/library/
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California: Health Sciences Libraries (University of California, Davis), http://www.lib.ucdavis.edu/healthsci/
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California: ValleyCare Health Library & Ryan Comer Cancer Resource Center (ValleyCare Health System, Pleasanton), http://gaelnet.stmarysca.edu/other.libs/gbal/east/vchl.html
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California: Washington Community Health Resource Library (Fremont), http://www.healthlibrary.org/
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Colorado: William V. Gervasini Memorial Library (Exempla Healthcare), http://www.saintjosephdenver.org/yourhealth/libraries/
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Connecticut: Hartford Hospital Health Science Libraries (Hartford Hospital), http://www.harthosp.org/library/
•
Connecticut: Healthnet: Connecticut Consumer Health Information Center (University of Connecticut Health Center, Lyman Maynard Stowe Library), http://library.uchc.edu/departm/hnet/
23
Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.
Finding Medical Libraries 241
•
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)
•
National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html
•
National: National Network of Libraries of Medicine (National Library of Medicine) provides library services for health professionals in the United States who do not have access to a medical library, http://nnlm.gov/
•
National: NN/LM List of Libraries Serving the Public (National Network of Libraries of Medicine), http://nnlm.gov/members/
Finding Medical Libraries 243
•
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/
•
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
•
New Jersey: Meland Foundation (Englewood Hospital and Medical Center, Englewood), http://www.geocities.com/ResearchTriangle/9360/
•
New York: Choices in Health Information (New York Public Library) - NLM Consumer Pilot Project participant, http://www.nypl.org/branch/health/links.html
•
New York: Health Information Center (Upstate Medical University, State University of New York, Syracuse), http://www.upstate.edu/library/hic/
•
New York: Health Sciences Library (Long Island Jewish Medical Center, New Hyde Park), http://www.lij.edu/library/library.html
•
New York: ViaHealth Medical Library (Rochester General Hospital), http://www.nyam.org/library/
•
Ohio: Consumer Health Library (Akron General Medical Center, Medical & Consumer Health Library), http://www.akrongeneral.org/hwlibrary.htm
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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
•
Oregon: Planetree Health Resource Center (Mid-Columbia Medical Center, The Dalles), http://www.mcmc.net/phrc/
•
Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center, Hershey), http://www.hmc.psu.edu/commhealth/
•
Pennsylvania: Community Health Resource Library (Geisinger Medical Center, Danville), http://www.geisinger.edu/education/commlib.shtml
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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
•
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
•
Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/
•
Multilingual Glossary of Technical and Popular Medical Terms in Eight European Languages (European Commission) - Danish, Dutch, English, French, German, Italian, Portuguese, and Spanish: http://allserv.rug.ac.be/~rvdstich/eugloss/welcome.html
•
On-line Medical Dictionary (CancerWEB): http://cancerweb.ncl.ac.uk/omd/
•
Rare Diseases Terms (Office of Rare Diseases): http://ord.aspensys.com/asp/diseases/diseases.asp
•
Technology Glossary (National Library of Medicine) - Health Care Technology: http://www.nlm.nih.gov/nichsr/ta101/ta10108.htm
Beyond these, MEDLINEplus contains a very patient-friendly encyclopedia covering every aspect of medicine (licensed from A.D.A.M., Inc.). The ADAM Medical Encyclopedia can be accessed at http://www.nlm.nih.gov/medlineplus/encyclopedia.html. ADAM is also available on commercial Web sites such as drkoop.com (http://www.drkoop.com/) and Web MD (http://my.webmd.com/adam/asset/adam_disease_articles/a_to_z/a).
Online Dictionary Directories The following are additional online directories compiled by the National Library of Medicine, including a number of specialized medical dictionaries: •
Medical Dictionaries: Medical & Biological (World Health Organization): http://www.who.int/hlt/virtuallibrary/English/diction.htm#Medical
•
MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html
•
Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/
•
Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine
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STAPHYLOCOCCUS AUREUS DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Abdominal Pain: Sensation of discomfort, distress, or agony in the abdominal region. [NIH] Abortion: 1. The premature expulsion from the uterus of the products of conception - of the embryo, or of a nonviable fetus. The four classic symptoms, usually present in each type of abortion, are uterine contractions, uterine haemorrhage, softening and dilatation of the cervix, and presentation or expulsion of all or part of the products of conception. 2. Premature stoppage of a natural or a pathological process. [EU] Abscess: A localized, circumscribed collection of pus. [NIH] Acantholysis: Separation of the prickle cells of the stratum spinosum of the epidermis, resulting in atrophy of the prickle cell layer. It is seen in diseases such as pemphigus vulgaris (see pemphigus) and keratosis follicularis. [NIH] Acatalasia: A rare autosomal recessive disorder resulting from the absence of catalase activity. Though usually asymptomatic, a syndrome of oral ulcerations and gangrene may be present. [NIH] Acceptor: A substance which, while normally not oxidized by oxygen or reduced by hydrogen, can be oxidized or reduced in presence of a substance which is itself undergoing oxidation or reduction. [NIH] Acclimatization: Adaptation to a new environment or to a change in the old. [NIH] Acetic Acids: Acetic acid and its derivatives which may be formed by substitution reactions. Mono- and di-substituted, as well as halogenated compounds have been synthesized. [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] Acetylgalactosamine: The N-acetyl derivative of galactosamine. [NIH] Acetylglucosamine: The N-acetyl derivative of glucosamine. [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 renal: A condition in which the kidneys suddenly stop working. In most cases, kidneys can recover from almost complete loss of function. [NIH] Acyl: Chemical signal used by bacteria to communicate. [NIH] Acyl Carrier Protein: Consists of a polypeptide chain and 4'-phosphopantetheine linked to a 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
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the cytoplasmic system. [NIH] Acylation: The addition of an organic acid radical into a molecule. [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] Adjustment: The dynamic process wherein the thoughts, feelings, behavior, and biophysiological mechanisms of the individual continually change to adjust to the environment. [NIH] Aerobic: In biochemistry, reactions that need oxygen to happen or happen when oxygen is present. [NIH] Aerosol: A solution of a drug which can be atomized into a fine mist for inhalation therapy. [EU]
Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among simple, uniform antigenic determinants such as haptens. Expressed as the association constant (K litres mole -1), which, owing to the heterogeneity of affinities in a population of antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU] Agar: A complex sulfated polymer of galactose units, extracted from Gelidium cartilagineum, Gracilaria confervoides, and related red algae. It is used as a gel in the preparation of solid culture media for microorganisms, as a bulk laxative, in making emulsions, and as a supporting medium for immunodiffusion and immunoelectrophoresis. [NIH]
Agarose: A polysaccharide complex, free of nitrogen and prepared from agar-agar which is produced by certain seaweeds (red algae). It dissolves in warm water to form a viscid solution. [NIH] Agonists: Drugs that trigger an action from a cell or another drug. [NIH] Agranulocytosis: A decrease in the number of granulocytes (basophils, eosinophils, and neutrophils). [NIH] Airway: A device for securing unobstructed passage of air into and out of the lungs during general anesthesia. [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] 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]
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Alkaline: Having the reactions of an alkali. [EU] Alkaloid: A member of a large group of chemicals that are made by plants and have nitrogen in them. Some alkaloids have been shown to work against cancer. [NIH] Allergen: An antigenic substance capable of producing immediate-type hypersensitivity (allergy). [EU] Allergic Rhinitis: Inflammation of the nasal mucous membrane associated with hay fever; fits may be provoked by substances in the working environment. [NIH] Allograft: An organ or tissue transplant between two humans. [NIH] Alpha Particles: Positively charged particles composed of two protons and two neutrons, i.e., helium nuclei, emitted during disintegration of very heavy isotopes; a beam of alpha particles or an alpha ray has very strong ionizing power, but weak penetrability. [NIH] Alpha-Defensins: Defensins found in azurophilic granules of neutrophils and in the secretory granules of intestinal paneth cells. [NIH] Alpha-helix: One of the secondary element of protein. [NIH] Alternative medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used instead of standard treatments. Alternative medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Alveoli: Tiny air sacs at the end of the bronchioles in the lungs. [NIH] Amber: A yellowish fossil resin, the gum of several species of coniferous trees, found in the alluvial deposits of northeastern Germany. It is used in molecular biology in the analysis of organic matter fossilized in amber. [NIH] Amino acid: Any organic compound containing an amino (-NH2 and a carboxyl (- COOH) group. The 20 a-amino acids listed in the accompanying table are the amino acids from which proteins are synthesized by formation of peptide bonds during ribosomal translation of messenger RNA; all except glycine, which is not optically active, have the L configuration. Other amino acids occurring in proteins, such as hydroxyproline in collagen, are formed by posttranslational enzymatic modification of amino acids residues in polypeptide chains. There are also several important amino acids, such as the neurotransmitter y-aminobutyric acid, that have no relation to proteins. Abbreviated AA. [EU] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Amino-terminal: The end of a protein or polypeptide chain that contains a free amino group (-NH2). [NIH] Ammonia: A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. [NIH] 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] 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]
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Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Anal: Having to do with the anus, which is the posterior opening of the large bowel. [NIH] Analog: In chemistry, a substance that is similar, but not identical, to another. [NIH] Analogous: Resembling or similar in some respects, as in function or appearance, but not in origin or development;. [EU] Anaphylatoxins: The family of peptides C3a, C4a, C5a, and C5a des-arginine produced in the serum during complement activation. They produce smooth muscle contraction, mast cell histamine release, affect platelet aggregation, and act as mediators of the local inflammatory process. The order of anaphylatoxin activity from strongest to weakest is C5a, C3a, C4a, and C5a des-arginine. The latter is the so-called "classical" anaphylatoxin but shows no spasmogenic activity though it contains some chemotactic ability. [NIH] 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] Anesthetics: Agents that are capable of inducing a total or partial loss of sensation, especially tactile sensation and pain. They may act to induce general anesthesia, in which an unconscious state is achieved, or may act locally to induce numbness or lack of sensation at a targeted site. [NIH] Animal model: An animal with a disease either the same as or like a disease in humans. Animal models are used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis. [NIH] Annealing: The spontaneous alignment of two single DNA strands to form a double helix. [NIH]
Anorexia: Lack or loss of appetite for food. Appetite is psychologic, dependent on memory and associations. Anorexia can be brought about by unattractive food, surroundings, or company. [NIH] Anthrax: An acute bacterial infection caused by ingestion of bacillus organisms. Carnivores may become infected from ingestion of infected carcasses. It is transmitted to humans by contact with infected animals or contaminated animal products. The most common form in humans is cutaneous anthrax. [NIH] Antibacterial: A substance that destroys bacteria or suppresses their growth or reproduction. [EU] Antibiogram: An examination that measures the biological resistance of substances causing disease; performed prior to chemotherapy so as to make it more efficient. [EU] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]
Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this
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binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] Antifungal: Destructive to fungi, or suppressing their reproduction or growth; effective against fungal infections. [EU] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Antigen-Antibody Complex: The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes immune complex diseases. [NIH] Antigen-presenting cell: APC. A cell that shows antigen on its surface to other cells of the immune system. This is an important part of an immune response. [NIH] Anti-infective: An agent that so acts. [EU] Anti-Infective Agents: Substances that prevent infectious agents or organisms from spreading or kill infectious agents in order to prevent the spread of infection. [NIH] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Anti-Inflammatory Agents: Substances that reduce or suppress inflammation. [NIH] Antimicrobial: Killing microorganisms, or suppressing their multiplication or growth. [EU] Antineoplastic: Inhibiting or preventing the development of neoplasms, checking the maturation and proliferation of malignant cells. [EU] Antioxidant: A substance that prevents damage caused by free radicals. Free radicals are highly reactive chemicals that often contain oxygen. They are produced when molecules are split to give products that have unpaired electrons. This process is called oxidation. [NIH] Antiseptic: A substance that inhibits the growth and development of microorganisms without necessarily killing them. [EU] Antiserum: The blood serum obtained from an animal after it has been immunized with a particular antigen. It will contain antibodies which are specific for that antigen as well as antibodies specific for any other antigen with which the animal has previously been immunized. [NIH] Antitoxin: A purified antiserum from animals (usually horses) immunized by injections of a toxin or toxoid, administered as a passive immunizing agent to neutralize a specific bacterial toxin, e.g., botulinus, tetanus or diphtheria. [EU] Antiviral: Destroying viruses or suppressing their replication. [EU] Anus: The opening of the rectum to the outside of the body. [NIH] 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
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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] Applicability: A list of the commodities to which the candidate method can be applied as presented or with minor modifications. [NIH] Aqueous: Having to do with water. [NIH] Archaea: One of the three domains of life (the others being bacteria and Eucarya), formerly called Archaebacteria under the taxon Bacteria, but now considered separate and distinct. They are characterized by: 1) the presence of characteristic tRNAs and ribosomal RNAs; 2) the absence of peptidoglycan cell walls; 3) the presence of ether-linked lipids built from branched-chain subunits; and 4) their occurrence in unusual habitats. While archaea resemble bacteria in morphology and genomic organization, they resemble eukarya in their method of genomic replication. The domain contains at least three kingdoms: crenarchaeota, euryarchaeota, and korarchaeota. [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] Arteritis: Inflammation of an artery. [NIH] Artery: Vessel-carrying blood from the heart to various parts of the body. [NIH] Arthroplasty: Surgical reconstruction of a joint to relieve pain or restore motion. [NIH] Articular: Of or pertaining to a joint. [EU] Aseptic: Free from infection or septic material; sterile. [EU] Aspiration: The act of inhaling. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Astringents: Agents, usually topical, that cause the contraction of tissues for the control of bleeding or secretions. [NIH] Atopic: Pertaining to an atopen or to atopy; allergic. [EU] Atopic Eczema: Generic term for acute or chronic inflammatory conditions of the skin, typically erythematous, edematous, papular, vesicular, and crusting; often accompanied by sensations of itching and burning. [NIH] Attenuation: Reduction of transmitted sound energy or its electrical equivalent. [NIH] Autoantibodies: Antibodies that react with self-antigens (autoantigens) of the organism that produced them. [NIH] Autoantigens: Endogenous tissue constituents that have the ability to interact with autoantibodies and cause an immune response. [NIH] Autoimmune disease: A condition in which the body recognizes its own tissues as foreign and directs an immune response against them. [NIH] Autolysis: The spontaneous disintegration of tissues or cells by the action of their own autogenous enzymes. [NIH] Autonomic: Self-controlling; functionally independent. [EU] Autonomic Nervous System: The enteric, parasympathetic, and sympathetic nervous systems taken together. Generally speaking, the autonomic nervous system regulates the
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internal environment during both peaceful activity and physical or emotional stress. Autonomic activity is controlled and integrated by the central nervous system, especially the hypothalamus and the solitary nucleus, which receive information relayed from visceral afferents; these and related central and sensory structures are sometimes (but not here) considered to be part of the autonomic nervous system itself. [NIH] Bacillus: A genus of Bacillaceae that are spore-forming, rod-shaped cells. Most species are saprophytic soil forms with only a few species being pathogenic. [NIH] Bacteremia: The presence of viable bacteria circulating in the blood. Fever, chills, tachycardia, and tachypnea are common acute manifestations of bacteremia. The majority of cases are seen in already hospitalized patients, most of whom have underlying diseases or procedures which render their bloodstreams susceptible to invasion. [NIH] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Bacterial Infections: Infections by bacteria, general or unspecified. [NIH] Bacterial Physiology: Physiological processes and activities of bacteria. [NIH] Bacterial Proteins: Proteins found in any species of bacterium. [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] 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] 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] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]
Benzyl Alcohol: A colorless liquid with a sharp burning taste and slight odor. It is used as a local anesthetic and to reduce pain associated with lidocaine injection. Also, it is used in the
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manufacture of other benzyl compounds, as a pharmaceutic aid, and in perfumery and flavoring. [NIH] Berberine: An alkaloid from Hydrastis canadensis L., Berberidaceae. It is also found in many other plants. It is relatively toxic parenterally, but has been used orally for various parasitic and fungal infections and as antidiarrheal. [NIH] Beta-Defensins: Defensins found mainly in epithelial cells. [NIH] Beta-Lactam Resistance: Nonsusceptibility of an organism to the action of the beta-lactam antibiotics. [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] Bilateral: Affecting both the right and left side of body. [NIH] Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] 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] Biochemical reactions: In living cells, chemical reactions that help sustain life and allow cells to grow. [NIH] Biofilms: Films of bacteria or other microbial organisms, usually embedded in extracellular polymers such as implanted medical devices, which adhere to surfaces submerged in, or subjected to, aquatic environments (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed). Biofilms consist of multilayers of microbial cells glued together to form microbial communities which are highly resistant to both phagocytes and antibiotics. [NIH] Biological response modifier: BRM. A substance that stimulates the body's response to infection and disease. [NIH] Biological therapy: Treatment to stimulate or restore the ability of the immune system to fight infection and disease. Also used to lessen side effects that may be caused by some cancer treatments. Also known as immunotherapy, biotherapy, or biological response modifier (BRM) therapy. [NIH] Biomarkers: Substances sometimes found in an increased amount in the blood, other body fluids, or tissues and that may suggest the presence of some types of cancer. Biomarkers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and GI tract cancers), and PSA (prostate cancer). Also called tumor markers. [NIH] Biophysics: The science of physical phenomena and processes in living organisms. [NIH] Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body. [NIH]
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Biopterin: A natural product that has been considered as a growth factor for some insects. [NIH]
Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and 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] 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] Blister: Visible accumulations of fluid within or beneath the epidermis. [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 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] Blot: To transfer DNA, RNA, or proteins to an immobilizing matrix such as nitrocellulose. [NIH]
Body Fluids: Liquid components of living organisms. [NIH] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bowel: The long tube-shaped organ in the abdomen that completes the process of digestion. There is both a small and a large bowel. Also called the intestine. [NIH] Bowel Movement: Body wastes passed through the rectum and anus. [NIH] Bradykinin: A nonapeptide messenger that is enzymatically produced from kallidin in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from mast cells during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter. [NIH] Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]
Breakdown: A physical, metal, or nervous collapse. [NIH]
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Breeding: The science or art of changing the constitution of a population of plants or animals through sexual reproduction. [NIH] Broad-spectrum: Effective against a wide range of microorganisms; said of an antibiotic. [EU] Bromcresol Purple: An indicator and reatgent. It has been used for several purposes including the determination of serum albumin concentrations [NIH] Bronchioles: The tiny branches of air tubes in the lungs. [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] Bronchoalveolar Lavage Fluid: Fluid obtained by washout of the alveolar compartment of the lung. It is used to assess biochemical and inflammatory changes in and effects of therapy on the interstitial lung tissue. [NIH] Bullous: Pertaining to or characterized by bullae. [EU] 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] Cadmium: An element with atomic symbol Cd, atomic number 48, and atomic weight 114. It is a metal and ingestion will lead to cadmium poisoning. [NIH] Cadmium Poisoning: Poisoning occurring after exposure to cadmium compounds or fumes. It may cause gastrointestinal syndromes, anemia, or pneumonitis. [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] 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] 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] Carboxypeptidases: Enzymes that act at a free C-terminus of a polypeptide to liberate a single amino acid residue. They are further divided based on their catalytic mechanism into serine-type carboxypeptidases EC 3.4.16; metallocarboxypeptidases, EC 3.4.17; and cysteinetype carboxypeptidases, EC 3.4.18. EC 3.4.-. [NIH] Carcinogenic: Producing carcinoma. [EU] Cardiac: Having to do with the heart. [NIH] Cardiovascular: Having to do with the heart and blood vessels. [NIH]
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Cardiovascular System: The heart and the blood vessels by which blood is pumped and circulated through the body. [NIH] Carrier State: The condition of harboring an infective organism without manifesting symptoms of infection. The organism must be readily transmissable to another susceptible host. [NIH] Case report: A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin). [NIH] Case series: A group or series of case reports involving patients who were given similar treatment. Reports of case series usually contain detailed information about the individual patients. This includes demographic information (for example, age, gender, ethnic origin) and information on diagnosis, treatment, response to treatment, and follow-up after treatment. [NIH] Caspase: Enzyme released by the cell at a crucial stage in apoptosis in order to shred all cellular proteins. [NIH] Catalase: An oxidoreductase that catalyzes the conversion of hydrogen peroxide to water and oxygen. It is present in many animal cells. A deficiency of this enzyme results in acatalasia. EC 1.11.1.6. [NIH] Catalytic Domain: The region of an enzyme that interacts with its substrate to cause the enzymatic reaction. [NIH] Catheter: A flexible tube used to deliver fluids into or withdraw fluids from the body. [NIH] Cations: Postively charged atoms, radicals or groups of atoms which travel to the cathode or negative pole during electrolysis. [NIH] Caustic: An escharotic or corrosive agent. Called also cauterant. [EU] Cefotiam: A cephalosporin antibiotic that has a broad spectrum of activity against both gram-positive and gram-negative microorganisms. It is the drug of choice for biliary tract infections and is a safe drug for perinatal infections. [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 movements, cellular migrations, and metastasis. [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 proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH]
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Cell Respiration: The metabolic process of all living cells (animal and plant) in which oxygen is used to provide a source of energy for the cell. [NIH] Cell Size: The physical dimensions of a cell. It refers mainly to changes in dimensions correlated with physiological or pathological changes in cells. [NIH] Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. [NIH] Cellobiose: A disaccharide consisting of two glucose units in beta (1-4) glycosidic linkage. Obtained from the partial hydrolysis of cellulose. [NIH] Cellular metabolism: The sum of all chemical changes that take place in a cell through which energy and basic components are provided for essential processes, including the synthesis of new molecules and the breakdown and removal of others. [NIH] Cellulitis: An acute, diffuse, and suppurative inflammation of loose connective tissue, particularly the deep subcutaneous tissues, and sometimes muscle, which is most commonly seen as a result of infection of a wound, ulcer, or other skin lesions. [NIH] Cellulose: A polysaccharide with glucose units linked as in cellobiose. It is the chief constituent of plant fibers, cotton being the purest natural form of the substance. As a raw material, it forms the basis for many derivatives used in chromatography, ion exchange materials, explosives manufacturing, and pharmaceutical preparations. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Central Nervous System Infections: Pathogenic infections of the brain, spinal cord, and meninges. DNA virus infections; RNA virus infections; bacterial infections; mycoplasma infections; Spirochaetales infections; fungal infections; protozoan infections; helminthiasis; and prion diseases may involve the central nervous system as a primary or secondary process. [NIH] Cephalosporins: A group of broad-spectrum antibiotics first isolated from the Mediterranean fungus Acremonium (Cephalosporium acremonium). They contain the betalactam moiety thia-azabicyclo-octenecarboxylic acid also called 7-aminocephalosporanic acid. [NIH] Cerebrospinal: Pertaining to the brain and spinal cord. [EU] Cerebrospinal fluid: CSF. The fluid flowing around the brain and spinal cord. Cerebrospinal fluid is produced in the ventricles in the brain. [NIH] Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU] Cerebrum: The largest part of the brain. It is divided into two hemispheres, or halves, called the cerebral hemispheres. The cerebrum controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. [NIH] 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] Chemotherapy: Treatment with anticancer drugs. [NIH]
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Chest Pain: Pressure, burning, or numbness in the chest. [NIH] Child Care: Care of children in the home or institution. [NIH] Chin: The anatomical frontal portion of the mandible, also known as the mentum, that contains the line of fusion of the two separate halves of the mandible (symphysis menti). This line of fusion divides inferiorly to enclose a triangular area called the mental protuberance. On each side, inferior to the second premolar tooth, is the mental foramen for the passage of blood vessels and a nerve. [NIH] Chlorophyll: Porphyrin derivatives containing magnesium that act to convert light energy in photosynthetic organisms. [NIH] Cholera: An acute diarrheal disease endemic in India and Southeast Asia whose causative agent is vibrio cholerae. This condition can lead to severe dehydration in a matter of hours unless quickly treated. [NIH] 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] Chymopapain: A cysteine endopeptidase isolated from papaya latex. Preferential cleavage at glutamic and aspartic acid residues. EC 3.4.22.6. [NIH] Cicatrix: The formation of new tissue in the process of wound healing. [NIH] Cicatrix, Hypertrophic: An elevated scar, resembling a keloid, but which does not spread into surrounding tissues. It is formed by enlargement and overgrowth of cicatricial tissue and regresses spontaneously. [NIH] Cilastatin: A renal dehydropeptidase-I and leukotriene D4 dipeptidase inhibitor. Since the antibiotic, imipenem, is hydrolyzed by dehydropeptidase-I, which resides in the brush border of the renal tubule, cilastatin is administered with imipenem to increase its effectiveness. The drug also inhibits the metabolism of leukotriene D4 to leukeotriene E4. [NIH]
Ciprofloxacin: A carboxyfluoroquinoline antimicrobial agent that is effective against a wide range of microorganisms. It has been successfully and safely used in the treatment of resistant respiratory, skin, bone, joint, gastrointestinal, urinary, and genital infections. [NIH] CIS: Cancer Information Service. The CIS is the National Cancer Institute's link to the public, interpreting and explaining research findings in a clear and understandable manner, and providing personalized responses to specific questions about cancer. Access the CIS by calling 1-800-4-CANCER, or by using the Web site at http://cis.nci.nih.gov. [NIH] Citric Acid: A key intermediate in metabolism. It is an acid compound found in citrus fruits. The salts of citric acid (citrates) can be used as anticoagulants due to their calcium chelating ability. [NIH] Citrus: Any tree or shrub of the Rue family or the fruit of these plants. [NIH] Clathrin: The main structural coat protein of coated vesicles which play a key role in the intracellular transport between membranous organelles. Clathrin also interacts with cytoskeletal proteins. [NIH] Clindamycin: An antibacterial agent that is a semisynthetic analog of lincomycin. [NIH]
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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] Clot Retraction: Retraction of a clot resulting from contraction of platelet pseudopods attached to fibrin strands that is dependent on the contractile protein thrombosthenin. Used as a measure of platelet function. [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] Coated Vesicles: Vesicles formed when cell-membrane coated pits invaginate and pinch off. The outer surface of these vesicles are covered with a lattice-like network of coat proteins, such as clathrin, coat protein complex proteins, or caveolins. [NIH] Coca: Any of several South American shrubs of the Erythroxylon genus (and family) that yield cocaine; the leaves are chewed with alum for CNS stimulation. [NIH] Cocaine: An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake. [NIH] Coenzyme: An organic nonprotein molecule, frequently a phosphorylated derivative of a water-soluble vitamin, that binds with the protein molecule (apoenzyme) to form the active enzyme (holoenzyme). [EU] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] Coliphages: Viruses whose host is Escherichia coli. [NIH] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline, hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [NIH] Colloidal: Of the nature of a colloid. [EU] Colon: The long, coiled, tubelike organ that removes water from digested food. The remaining material, solid waste called stool, moves through the colon to the rectum and leaves the body through the anus. [NIH]
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Combinatorial: A cut-and-paste process that churns out thousands of potentially valuable compounds at once. [NIH] 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] Comorbidity: The presence of co-existing or additional diseases with reference to an initial diagnosis or with reference to the index condition that is the subject of study. Comorbidity may affect the ability of affected individuals to function and also their survival; it may be used as a prognostic indicator for length of hospital stay, cost factors, and outcome or survival. [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] Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Concomitant: Accompanying; accessory; joined with another. [EU] Conjugated: Acting or operating as if joined; simultaneous. [EU] Conjugation: 1. The act of joining together or the state of being conjugated. 2. A sexual process seen in bacteria, ciliate protozoa, and certain fungi in which nuclear material is exchanged during the temporary fusion of two cells (conjugants). In bacterial genetics a form of sexual reproduction in which a donor bacterium (male) contributes some, or all, of its DNA (in the form of a replicated set) to a recipient (female) which then incorporates differing genetic information into its own chromosome by recombination and passes the recombined set on to its progeny by replication. In ciliate protozoa, two conjugants of separate mating types exchange micronuclear material and then separate, each now being a fertilized cell. In certain fungi, the process involves fusion of two gametes, resulting in union
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of their nuclei and formation of a zygote. 3. In chemistry, the joining together of two compounds to produce another compound, such as the combination of a toxic product with some substance in the body to form a detoxified product, which is then eliminated. [EU] Conjunctiva: The mucous membrane that lines the inner surface of the eyelids and the anterior part of the sclera. [NIH] Conjunctivitis: Inflammation of the conjunctiva, generally consisting of conjunctival hyperaemia associated with a discharge. [EU] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] 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 Cells: A group of cells that includes fibroblasts, cartilage cells, adipocytes, smooth muscle cells, and bone cells. [NIH] Consciousness: Sense of awareness of self and of the environment. [NIH] Constipation: Infrequent or difficult evacuation of feces. [NIH] Consultation: A deliberation between two or more physicians concerning the diagnosis and the proper method of treatment in a case. [NIH] Consumption: Pulmonary tuberculosis. [NIH] Contamination: The soiling or pollution by inferior material, as by the introduction of organisms into a wound, or sewage into a stream. [EU] Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] Coordination: Muscular or motor regulation or the harmonious cooperation of muscles or groups of muscles, in a complex action or series of actions. [NIH] Cornea: The transparent part of the eye that covers the iris and the pupil and allows light to enter the inside. [NIH] Corneum: The superficial layer of the epidermis containing keratinized cells. [NIH] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [EU] Corticosteroids: Hormones that have antitumor activity in lymphomas and lymphoid leukemias; in addition, corticosteroids (steroids) may be used for hormone replacement and for the management of some of the complications of cancer and its treatment. [NIH] Crack Cocaine: The purified, alkaloidal, extra-potent form of cocaine. It is smoked (freebased), injected intravenously, and orally ingested. Use of crack results in alterations in function of the cardiovascular system, the autonomic nervous system, the central nervous system, and the gastrointestinal system. The slang term "crack" was derived from the crackling sound made upon igniting of this form of cocaine for smoking. [NIH] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU] Craniocerebral Trauma: Traumatic injuries involving the cranium and intracranial
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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] Crystallization: The formation of crystals; conversion to a crystalline form. [EU] Culture Media: Any liquid or solid preparation made specifically for the growth, storage, or transport of microorganisms or other types of cells. The variety of media that exist allow for the culturing of specific microorganisms and cell types, such as differential media, selective media, test media, and defined media. Solid media consist of liquid media that have been solidified with an agent such as agar or gelatin. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Cutaneous: Having to do with the skin. [NIH] Cutaneous Fistula: An abnormal passage or communication leading from an internal organ to the surface of the body. [NIH] Cyanogen Bromide: Cyanogen bromide (CNBr). A compound used in molecular biology to digest some proteins and as a coupling reagent for phosphoroamidate or pyrophosphate internucleotide bonds in DNA duplexes. [NIH] Cyclic: Pertaining to or occurring in a cycle or cycles; the term is applied to chemical compounds that contain a ring of atoms in the nucleus. [EU] Cysteine Synthase: An enzyme that catalyzes the biosynthesis of cysteine in microorganisms and plants from O-acetyl-L-serine and hydrogen sulfide. EC 4.2.99.8. [NIH] Cystine: A covalently linked dimeric nonessential amino acid formed by the oxidation of cysteine. Two molecules of cysteine are joined together by a disulfide bridge to form cystine. [NIH]
Cytokine: Small but highly potent protein that modulates the activity of many cell types, including T and B cells. [NIH] Cytokinesis: Division of the rest of cell. [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] 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] Day Care: Institutional health care of patients during the day. The patients return home at night. [NIH] Decision Making: The process of making a selective intellectual judgment when presented with several complex alternatives consisting of several variables, and usually defining a course of action or an idea. [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,
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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] Deferoxamine: Natural product isolated from Streptomyces pilosus. It forms iron complexes and is used as a chelating agent, particularly in the form of its mesylate. [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] 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 Care: The total of dental diagnostic, preventive, and restorative services provided to meet the needs of a patient (from Illustrated Dictionary of Dentistry, 1982). [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]
Dental Instruments: Hand-held tools or implements especially used by dental professionals for the performance of clinical tasks. [NIH] Dental Materials: Materials used in the production of dental bases, restorations, impressions, prostheses, etc. [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] Depressive Disorder: An affective disorder manifested by either a dysphoric mood or loss of interest or pleasure in usual activities. The mood disturbance is prominent and relatively persistent. [NIH] Dermal: Pertaining to or coming from the skin. [NIH] Dermatitis: Any inflammation of the skin. [NIH] Dermatologist: A doctor who specializes in the diagnosis and treatment of skin problems. [NIH]
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Dermatology: A medical specialty concerned with the skin, its structure, functions, diseases, and treatment. [NIH] Dermis: A layer of vascular connective tissue underneath the epidermis. The surface of the dermis contains sensitive papillae. Embedded in or beneath the dermis are sweat glands, hair follicles, and sebaceous glands. [NIH] Detergents: Purifying or cleansing agents, usually salts of long-chain aliphatic bases or acids, that exert cleansing (oil-dissolving) and antimicrobial effects through a surface action that depends on possessing both hydrophilic and hydrophobic properties. [NIH] 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] Diabetes Mellitus: A heterogeneous group of disorders that share glucose intolerance in common. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Dialysate: A cleansing liquid used in the two major forms of dialysis--hemodialysis and peritoneal dialysis. [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] Diapedesis: The emigration of leucocytes across the endothelium. [NIH] Diarrhea: Passage of excessively liquid or excessively frequent stools. [NIH] Diarrhoea: Abnormal frequency and liquidity of faecal discharges. [EU] Diathesis: A constitution or condition of the body which makes the tissues react in special ways to certain extrinsic stimuli and thus tends to make the person more than usually susceptible to certain diseases. [EU] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Digestive system: The organs that take in food and turn it into products that the body can use to stay healthy. Waste products the body cannot use leave the body through bowel movements. The digestive system includes the salivary glands, mouth, esophagus, stomach, liver, pancreas, gallbladder, small and large intestines, and rectum. [NIH] Digoxigenin: 3 beta,12 beta,14-Trihydroxy-5 beta-card-20(22)-enolide. A cardenolide which is the aglycon of digoxin. Can be obtained by hydrolysis of digoxin or from Digitalis orientalis L. and Digitalis lanata Ehrh. [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]
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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] Disaccharides: Sugars composed of two monosaccharides linked by glycoside bonds. [NIH] Discitis: Inflammation of an intervertebral disk or disk space which may lead to disk erosion. Until recently, discitis has been defined as a nonbacterial inflammation and has been attributed to aseptic processes (e.g., chemical reaction to an injected substance). However, recent studies provide evidence that infection may be the initial cause, but perhaps not the promoter, of most cases of discitis. Discitis has been diagnosed in patients following discography, myelography, lumbar puncture, paravertebral injection, and obstetrical epidural anesthesia. Discitis following chemonucleolysis (especially with chymopapain) is attributed to chemical reaction by some and to introduction of microorganisms by others. [NIH] Discrete: Made up of separate parts or characterized by lesions which do not become blended; not running together; separate. [NIH] Discrimination: The act of qualitative and/or quantitative differentiation between two or more stimuli. [NIH] Disease Vectors: Invertebrates or non-human vertebrates which transmit infective organisms from one host to another. [NIH] Disinfectant: An agent that disinfects; applied particularly to agents used on inanimate objects. [EU] Dissection: Cutting up of an organism for study. [NIH] Dissociation: 1. The act of separating or state of being separated. 2. The separation of a molecule into two or more fragments (atoms, molecules, ions, or free radicals) produced by the absorption of light or thermal energy or by solvation. 3. In psychology, a defense mechanism in which a group of mental processes are segregated from the rest of a person's mental activity in order to avoid emotional distress, as in the dissociative disorders (q.v.), or in which an idea or object is segregated from its emotional significance; in the first sense it is roughly equivalent to splitting, in the second, to isolation. 4. A defect of mental integration in which one or more groups of mental processes become separated off from normal consciousness and, thus separated, function as a unitary whole. [EU] 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] Distemper: A name for several highly contagious viral diseases of animals, especially canine distemper. In dogs, it is caused by the canine distemper virus (distemper virus, canine). It is characterized by a diphasic fever, leukopenia, gastrointestinal and respiratory inflammation and sometimes, neurologic complications. In cats it is known as feline panleukopenia. [NIH] Distemper Virus, Canine: A species of morbillivirus causing distemper in dogs, wolves, foxes, raccoons, and ferrets. [NIH] Dopamine: An endogenous catecholamine and prominent neurotransmitter in several systems of the brain. In the synthesis of catecholamines from tyrosine, it is the immediate precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of dopaminergic receptor subtypes mediate its action. Dopamine is used pharmacologically for its direct (beta adrenergic agonist) and indirect (adrenergic releasing) sympathomimetic effects including its actions as an inotropic agent and as a renal vasodilator. [NIH] Dose-dependent: Refers to the effects of treatment with a drug. If the effects change when
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the dose of the drug is changed, the effects are said to be dose dependent. [NIH] Double-blind: Pertaining to a clinical trial or other experiment in which neither the subject nor the person administering treatment knows which treatment any particular subject is receiving. [EU] Drug Delivery Systems: Systems of administering drugs through controlled delivery so that an optimum amount reaches the target site. Drug delivery systems encompass the carrier, route, and target. [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] Dura mater: The outermost, toughest, and most fibrous of the three membranes (meninges) covering the brain and spinal cord; called also pachymeninx. [EU] Dyskinesia: Impairment of the power of voluntary movement, resulting in fragmentary or incomplete movements. [EU] Dysphoric: A feeling of unpleasantness and discomfort. [NIH] Edema: Excessive amount of watery fluid accumulated in the intercellular spaces, most commonly present in subcutaneous tissue. [NIH] Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [NIH] Efficacy: The extent to which a specific intervention, procedure, regimen, or service produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is based on the results of a randomized control trial. [NIH] Egg Yolk: Cytoplasm stored in an egg that contains nutritional reserves for the developing embryo. It is rich in polysaccharides, lipids, and proteins. [NIH] Elastic: Susceptible of resisting and recovering from stretching, compression or distortion applied by a force. [EU] Elastin: The protein that gives flexibility to tissues. [NIH] Elective: Subject to the choice or decision of the patient or physician; applied to procedures that are advantageous to the patient but not urgent. [EU] Electrocoagulation: Electrosurgical procedures used to treat hemorrhage (e.g., bleeding ulcers) and to ablate tumors, mucosal lesions, and refractory arrhythmias. [NIH] Electrolysis: Destruction by passage of a galvanic electric current, as in disintegration of a chemical compound in solution. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electron microscope: A microscope (device used to magnify small objects) that uses electrons (instead of light) to produce an enlarged image. An electron microscopes shows tiny details better than any other type of microscope. [NIH]
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Electrophoresis: An electrochemical process in which macromolecules or colloidal particles with a net electric charge migrate in a solution under the influence of an electric current. [NIH]
Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Emollient: Softening or soothing; called also malactic. [EU] Emphysema: A pathological accumulation of air in tissues or organs. [NIH] Empyema: Presence of pus in a hollow organ or body cavity. [NIH] Emulsion: A preparation of one liquid distributed in small globules throughout the body of a second liquid. The dispersed liquid is the discontinuous phase, and the dispersion medium is the continuous phase. When oil is the dispersed liquid and an aqueous solution is the continuous phase, it is known as an oil-in-water emulsion, whereas when water or aqueous solution is the dispersed phase and oil or oleaginous substance is the continuous phase, it is known as a water-in-oil emulsion. Pharmaceutical emulsions for which official standards have been promulgated include cod liver oil emulsion, cod liver oil emulsion with malt, liquid petrolatum emulsion, and phenolphthalein in liquid petrolatum emulsion. [EU] Enamel: A very hard whitish substance which covers the dentine of the anatomical crown of a tooth. [NIH] Encapsulated: Confined to a specific, localized area and surrounded by a thin layer of tissue. [NIH]
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 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] Endogenous: Produced inside an organism or cell. The opposite is external (exogenous) production. [NIH] Endosomes: Cytoplasmic vesicles formed when coated vesicles shed their clathrin coat. Endosomes internalize macromolecules bound by receptors on the cell surface. [NIH] Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart. [NIH] Endothelium: A layer of epithelium that lines the heart, blood vessels (endothelium, vascular), lymph vessels (endothelium, lymphatic), and the serous cavities of the body. [NIH] Endothelium-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] 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] Enteritis: Inflammation of the intestine, applied chiefly to inflammation of the small
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intestine; see also enterocolitis. [EU] 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] Enterocolitis: Inflammation of the intestinal mucosa of the small and large bowel. [NIH] Enterocytes: Terminally differentiated cells comprising the majority of the external surface of the intestinal epithelium (see intestinal mucosa). Unlike goblet cells, they do not produce or secrete mucins, nor do they secrete cryptdins as do the paneth cells. [NIH] Enteropeptidase: A specialized proteolytic enzyme secreted by intestinal cells. It converts trypsinogen into its active form trypsin by removing the N-terminal peptide. EC 3.4.21.9. [NIH]
Enterotoxins: Substances that are toxic to the intestinal tract causing vomiting, diarrhea, etc.; most common enterotoxins are produced by bacteria. [NIH] Environmental Exposure: The exposure to potentially harmful chemical, physical, or biological agents in the environment or to environmental factors that may include ionizing radiation, pathogenic organisms, or toxic chemicals. [NIH] Environmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health. [NIH]
Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. [NIH] Eosinophilia: Abnormal increase in eosinophils in the blood, tissues or organs. [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 Factors: Events, characteristics, or other definable entities that have the potential to bring about a change in a health condition or other defined outcome. [NIH] Epidemiological: Relating to, or involving epidemiology. [EU] Epidermal: Pertaining to or resembling epidermis. Called also epidermic or epidermoid. [EU] 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] Epidural: The space between the wall of the spinal canal and the covering of the spinal cord. An epidural injection is given into this space. [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
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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]
ERV: The expiratory reserve volume is the largest volume of gas that can be expired from the end-expiratory level. [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]
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] Excipient: Any more or less inert substance added to a prescription in order to confer a suitable consistency or form to the drug; a vehicle. [EU] Excisional: The surgical procedure of removing a tumor by cutting it out. The biopsy is then examined under a microscope. [NIH] Excitation: An act of irritation or stimulation or of responding to a stimulus; the addition of energy, as the excitation of a molecule by absorption of photons. [EU] Exfoliation: A falling off in scales or layers. [EU] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Exotoxin: Toxic substance excreted by living bacterial cells. [NIH] Expiration: The act of breathing out, or expelling air from the lungs. [EU] Expiratory: The volume of air which leaves the breathing organs in each expiration. [NIH] Expiratory Reserve Volume: The extra volume of air that can be expired with maximum effort beyond the level reached at the end of a normal, quiet expiration. Common abbreviation is ERV. [NIH] Extensor: A muscle whose contraction tends to straighten a limb; the antagonist of a flexor. [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 Matrix Proteins: Macromolecular organic compounds that contain carbon, hydrogen, oxygen, nitrogen, and usually, sulfur. These macromolecules (proteins) form an
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intricate meshwork in which cells are embedded to construct tissues. Variations in the relative types of macromolecules and their organization determine the type of extracellular matrix, each adapted to the functional requirements of the tissue. The two main classes of macromolecules that form the extracellular matrix are: glycosaminoglycans, usually linked to proteins (proteoglycans), and fibrous proteins (e.g., collagen, elastin, fibronectins and laminin). [NIH] Extracellular Space: Interstitial space between cells, occupied by fluid as well as amorphous and fibrous substances. [NIH] Exudate: Material, such as fluid, cells, or cellular debris, which has escaped from blood vessels and has been deposited in tissues or on tissue surfaces, usually as a result of inflammation. An exudate, in contrast to a transudate, is characterized by a high content of protein, cells, or solid materials derived from cells. [EU] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Fasciitis: Inflammation of the fascia. There are three major types: 1) Eosinophilic fasciitis, an inflammatory reaction with eosinophilia, producing hard thickened skin with an orangepeel configuration suggestive of scleroderma and considered by some a variant of scleroderma; 2) Necrotizing fasciitis, a serious fulminating infection (usually by a beta hemolytic Streptococcus) causing extensive necrosis of superficial fascia; 3) Nodular/Pseudosarcomatous/Proliferative fasciitis, characterized by a rapid growth of fibroblasts with mononuclear inflammatory cells and proliferating capillaries in soft tissue, often the forearm; it is not malignant but is sometimes mistaken for fibrosarcoma. [NIH] Fat: Total lipids including phospholipids. [NIH] Fatal Outcome: Death resulting from the presence of a disease in an individual, as shown by a single case report or a limited number of patients. This should be differentiated from death, the physiological cessation of life and from mortality, an epidemiological or statistical concept. [NIH] 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] Feline Panleukopenia: A highly contagious DNA virus infection of the cat family and of mink, characterized by fever, enteritis and bone marrow changes. It is also called feline ataxia, feline agranulocytosis, feline infectious enteritis, cat fever, cat plague, show fever. [NIH]
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] Fibrin: A protein derived from fibrinogen in the presence of thrombin, which forms part of the blood clot. [NIH] Fibrinogen: Plasma glycoprotein clotted by thrombin, composed of a dimer of three nonidentical pairs of polypeptide chains (alpha, beta, gamma) held together by disulfide bonds. Fibrinogen clotting is a sol-gel change involving complex molecular arrangements: whereas fibrinogen is cleaved by thrombin to form polypeptides A and B, the proteolytic action of other enzymes yields different fibrinogen degradation products. [NIH] Fibrinolytic: Pertaining to, characterized by, or causing the dissolution of fibrin by enzymatic action [EU] Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen
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and other macromolecules. [NIH] Fibronectins: Glycoproteins found on the surfaces of cells, particularly in fibrillar structures. The proteins are lost or reduced when these cells undergo viral or chemical transformation. They are highly susceptible to proteolysis and are substrates for activated blood coagulation factor VIII. The forms present in plasma are called cold-insoluble globulins. [NIH] Fibrosarcoma: A type of soft tissue sarcoma that begins in fibrous tissue, which holds bones, muscles, and other organs in place. [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] Fixation: 1. The act or operation of holding, suturing, or fastening in a fixed position. 2. The condition of being held in a fixed position. 3. In psychiatry, a term with two related but distinct meanings : (1) arrest of development at a particular stage, which like regression (return to an earlier stage), if temporary is a normal reaction to setbacks and difficulties but if protracted or frequent is a cause of developmental failures and emotional problems, and (2) a close and suffocating attachment to another person, especially a childhood figure, such as one's mother or father. Both meanings are derived from psychoanalytic theory and refer to 'fixation' of libidinal energy either in a specific erogenous zone, hence fixation at the oral, anal, or phallic stage, or in a specific object, hence mother or father fixation. 4. The use of a fixative (q.v.) to preserve histological or cytological specimens. 5. In chemistry, the process whereby a substance is removed from the gaseous or solution phase and localized, as in carbon dioxide fixation or nitrogen fixation. 6. In ophthalmology, direction of the gaze so that the visual image of the object falls on the fovea centralis. 7. In film processing, the chemical removal of all undeveloped salts of the film emulsion, leaving only the developed silver to form a permanent image. [EU] Flatus: Gas passed through the rectum. [NIH] Flow Cytometry: Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake. [NIH] Fluorescence: The property of emitting radiation while being irradiated. The radiation emitted is usually of longer wavelength than that incident or absorbed, e.g., a substance can be irradiated with invisible radiation and emit visible light. X-ray fluorescence is used in diagnosis. [NIH] Fluorescent Dyes: Dyes that emit light when exposed to light. The wave length of the emitted light is usually longer than that of the incident light. Fluorochromes are substances that cause fluorescence in other substances, i.e., dyes used to mark or label other compounds with fluorescent tags. They are used as markers in biochemistry and immunology. [NIH] Folate: A B-complex vitamin that is being studied as a cancer prevention agent. Also called folic acid. [NIH] Folic
Acid:
N-(4-(((2-Amino-1,4-dihydro-4-oxo-6-pteridinyl)methyl)amino)benzoyl)-L-
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glutamic 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] Follicles: Shafts through which hair grows. [NIH] Food Preservatives: Substances capable of inhibiting, retarding or arresting the process of fermentation, acidification or other deterioration of foods. [NIH] Foodborne Illness: An acute gastrointestinal infection caused by food that contains harmful bacteria. Symptoms include diarrhea, abdominal pain, fever, and chills. Also called food poisoning. [NIH] Forearm: The part between the elbow and the wrist. [NIH] Fosfomycin: An antibiotic produced by Streptomyces fradiae. [NIH] Fovea: The central part of the macula that provides the sharpest vision. [NIH] Frameshift: A type of mutation which causes out-of-phase transcription of the base sequence; such mutations arise from the addition or delection of nucleotide(s) in numbers other than 3 or multiples of 3. [NIH] Frameshift Mutation: A type of mutation in which a number of nucleotides not divisible by three is deleted from or inserted into a coding sequence, thereby causing an alteration in the reading frame of the entire sequence downstream of the mutation. These mutations may be induced by certain types of mutagens or may occur spontaneously. [NIH] 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] Fructose: A type of sugar found in many fruits and vegetables and in honey. Fructose is used to sweeten some diet foods. It is considered a nutritive sweetener because it has calories. [NIH] Fungi: A kingdom of eukaryotic, heterotrophic organisms that live as saprobes or parasites, including mushrooms, yeasts, smuts, molds, etc. They reproduce either sexually or asexually, and have life cycles that range from simple to complex. Filamentous fungi refer to those that grow as multicelluar colonies (mushrooms and molds). [NIH] Fungus: A general term used to denote a group of eukaryotic protists, including mushrooms, yeasts, rusts, moulds, smuts, etc., which are characterized by the absence of chlorophyll and by the presence of a rigid cell wall composed of chitin, mannans, and sometimes cellulose. They are usually of simple morphological form or show some reversible cellular specialization, such as the formation of pseudoparenchymatous tissue in the fruiting body of a mushroom. The dimorphic fungi grow, according to environmental conditions, as moulds or yeasts. [EU] 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] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] Gangrene: Death and putrefaction of tissue usually due to a loss of blood supply. [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] Gas Gangrene: A severe condition resulting from bacteria invading healthy muscle from adjacent traumatized muscle or soft tissue. The infection originates in a wound contaminated with bacteria of the genus Clostridium. C. perfringens accounts for the majority of cases (over eighty percent), while C. noyvi, C. septicum, and C. histolyticum cause most of the other cases. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]
Gastroenteritis: An acute inflammation of the lining of the stomach and intestines, characterized by anorexia, nausea, diarrhoea, abdominal pain, and weakness, which has various causes, including food poisoning due to infection with such organisms as Escherichia coli, Staphylococcus aureus, and Salmonella species; consumption of irritating food or drink; or psychological factors such as anger, stress, and fear. Called also enterogastritis. [EU] Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] Gelatin: A product formed from skin, white connective tissue, or bone collagen. It is used as a protein food adjuvant, plasma substitute, hemostatic, suspending agent in pharmaceutical preparations, and in the manufacturing of capsules and suppositories. [NIH] Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]
Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Gene Fusion: Fusion of structural genes to analyze protein behavior or fusion of regulatory sequences with structural genes to determine mechanisms of regulation. [NIH] Genetic Code: The specifications for how information, stored in nucleic acid sequence (base sequence), is translated into protein sequence (amino acid sequence). The start, stop, and order of amino acids of a protein is specified by consecutive triplets of nucleotides called codons (codon). [NIH] Genetic Engineering: Directed modification of the gene complement of a living organism by such techniques as altering the DNA, substituting genetic material by means of a virus, transplanting whole nuclei, transplanting cell hybrids, etc. [NIH] Genetic testing: Analyzing DNA to look for a genetic alteration that may indicate an increased risk for developing a specific disease or disorder. [NIH] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Genital: Pertaining to the genitalia. [EU] Genitourinary: Pertaining to the genital and urinary organs; urogenital; urinosexual. [EU] 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] Gestation: The period of development of the young in viviparous animals, from the time of fertilization of the ovum until birth. [EU] Gingivitis: Inflammation of the gingivae. Gingivitis associated with bony changes is
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referred to as periodontitis. Called also oulitis and ulitis. [EU] Gland: An organ that produces and releases one or more substances for use in the body. Some glands produce fluids that affect tissues or organs. Others produce hormones or participate in blood production. [NIH] Glomerular: Pertaining to or of the nature of a glomerulus, especially a renal glomerulus. [EU]
Glomeruli: Plural of glomerulus. [NIH] Glomerulonephritis: Glomerular disease characterized by an inflammatory reaction, with leukocyte infiltration and cellular proliferation of the glomeruli, or that appears to be the result of immune glomerular injury. [NIH] Glucocorticoid: A compound that belongs to the family of compounds called corticosteroids (steroids). Glucocorticoids affect metabolism and have anti-inflammatory and immunosuppressive effects. They may be naturally produced (hormones) or synthetic (drugs). [NIH] Glucose: D-Glucose. A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. [NIH] 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] 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]
Glutamine: A non-essential amino acid present abundantly throught the body and is involved in many metabolic processes. It is synthesized from glutamic acid and ammonia. It is the principal carrier of nitrogen in the body and is an important energy source for many cells. [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] 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] Glycosaminoglycans: Heteropolysaccharides which contain an N-acetylated hexosamine in a characteristic repeating disaccharide unit. The repeating structure of each disaccharide
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involves alternate 1,4- and 1,3-linkages consisting of either N-acetylglucosamine or Nacetylgalactosamine. [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] Glycylglycine: N-Glycylglycine. The simplest of all peptides. It functions as a gammaglutamyl acceptor. [NIH] Goblet Cells: Cells of the epithelial lining that produce and secrete mucins. [NIH] Gonorrhea: Acute infectious disease characterized by primary invasion of the urogenital tract. The etiologic agent, Neisseria gonorrhoeae, was isolated by Neisser in 1879. [NIH] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Gp120: 120-kD HIV envelope glycoprotein which is involved in the binding of the virus to its membrane receptor, the CD4 molecule, found on the surface of certain cells in the body. [NIH]
Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to replace diseased or injured tissue removed from another part of the body. [NIH] Grafting: The operation of transfer of tissue from one site to another. [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-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 Cocci: Coccus-shaped bacteria that retain the crystal violet stain when treated by Gram's method. [NIH] Granulocyte: A type of white blood cell that fights bacterial infection. Neutrophils, eosinophils, and basophils are granulocytes. [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] 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] Growth factors: Substances made by the body that function to regulate cell division and cell survival. Some growth factors are also produced in the laboratory and used in biological therapy. [NIH]
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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]
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] Haemophilus influenzae: A species of Haemophilus found on the mucous membranes of humans and a variety of animals. The species is further divided into biotypes I through VIII. [NIH]
Hair follicles: Shafts or openings on the surface of the skin through which hair grows. [NIH] Haploid: An organism with one basic chromosome set, symbolized by n; the normal condition of gametes in diploids. [NIH] Haptens: Small antigenic determinants capable of eliciting an immune response only when coupled to a carrier. Haptens bind to antibodies but by themselves cannot elicit an antibody response. [NIH] Hay Fever: A seasonal variety of allergic rhinitis, marked by acute conjunctivitis with lacrimation and itching, regarded as an allergic condition triggered by specific allergens. [NIH]
Headache: Pain in the cranial region that may occur as an isolated and benign symptom or as a manifestation of a wide variety of conditions including subarachnoid hemorrhage; craniocerebral trauma; central nervous system infections; intracranial hypertension; and other disorders. In general, recurrent headaches that are not associated with a primary disease process are referred to as headache disorders (e.g., migraine). [NIH] Headache Disorders: Common conditions characterized by persistent or recurrent headaches. Headache syndrome classification systems may be based on etiology (e.g., vascular headache, post-traumatic headaches, etc.), temporal pattern (e.g., cluster headache, paroxysmal hemicrania, etc.), and precipitating factors (e.g., cough headache). [NIH] Health Services: Services for the diagnosis and treatment of disease and the maintenance of health. [NIH] Health Status: The level of health of the individual, group, or population as subjectively assessed by the individual or by more objective measures. [NIH] Hematogenous: Originating in the blood or spread through the bloodstream. [NIH] Hematologic malignancies: Cancers of the blood or bone marrow, including leukemia and lymphoma. Also called hematologic cancers. [NIH] Hematology: A subspecialty of internal medicine concerned with morphology, physiology, and pathology of the blood and blood-forming tissues. [NIH] Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. [NIH] Hemocytes: Any blood or formed element especially in invertebrates. [NIH] Hemodialysis: The use of a machine to clean wastes from the blood after the kidneys have failed. The blood travels through tubes to a dialyzer, which removes wastes and extra fluid. The cleaned blood then flows through another set of tubes back into the body. [NIH] Hemoglobin: One of the fractions of glycosylated hemoglobin A1c. Glycosylated hemoglobin is formed when linkages of glucose and related monosaccharides bind to
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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] Hemolysins: Substances, usually of biological origin, that destroy blood cells; they may be antibodies or other immunologic factors, toxins, enzymes, etc.; hemotoxins are toxic to blood in general, including the clotting mechanism; hematotoxins may refer to the hematopoietic system. [NIH] Hemolysis: The destruction of erythrocytes by many different causal agents such as antibodies, bacteria, chemicals, temperature, and changes in tonicity. [NIH] Hemolytic: A disease that affects the blood and blood vessels. It destroys red blood cells, cells that cause the blood to clot, and the lining of blood vessels. HUS is often caused by the Escherichia coli bacterium in contaminated food. People with HUS may develop acute renal failure. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hemostasis: The process which spontaneously arrests the flow of blood from vessels carrying blood under pressure. It is accomplished by contraction of the vessels, adhesion and aggregation of formed blood elements, and the process of blood or plasma coagulation. [NIH]
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] Hepatitis: Inflammation of the liver and liver disease involving degenerative or necrotic alterations of hepatocytes. [NIH] Hepatocytes: The main structural component of the liver. They are specialized epithelial cells that are organized into interconnected plates called lobules. [NIH] Herbicides: Pesticides used to destroy unwanted vegetation, especially various types of weeds, grasses, and woody plants. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Heterodimers: Zippered pair of nonidentical proteins. [NIH] Heterogeneity: The property of one or more samples or populations which implies that they are not identical in respect of some or all of their parameters, e. g. heterogeneity of variance. [NIH]
Heterotrophic: Pertaining to organisms that are consumers and dependent on other organisms for their source of energy (food). [NIH] Hip Prosthesis: Replacement for a hip joint. [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]
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Histocompatibility: The degree of antigenic similarity between the tissues of different individuals, which determines the acceptance or rejection of allografts. [NIH] HLA: A glycoprotein found on the surface of all human leucocytes. The HLA region of chromosome 6 produces four such glycoproteins-A, B, C and D. [NIH] Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable. [NIH] Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] 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] Horny layer: The superficial layer of the epidermis containing keratinized cells. [NIH] Host: Any animal that receives a transplanted graft. [NIH] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [NIH] Hybridization: The genetic process of crossbreeding to produce a hybrid. Hybrid nucleic acids can be formed by nucleic acid hybridization of DNA and RNA molecules. Protein hybridization allows for hybrid proteins to be formed from polypeptide chains. [NIH] Hybridomas: Cells artificially created by fusion of activated lymphocytes with neoplastic cells. The resulting hybrid cells are cloned and produce pure or "monoclonal" antibodies or T-cell products, identical to those produced by the immunologically competent parent, and continually grow and divide as the neoplastic parent. [NIH] Hydration: Combining with water. [NIH] Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H, atomic number 1, and atomic weight 1. It exists, under normal conditions, as a colorless, odorless, tasteless, diatomic gas. Hydrogen ions are protons. Besides the common H1 isotope, hydrogen exists as the stable isotope deuterium and the unstable, radioactive isotope tritium. [NIH] Hydrogen Peroxide: A strong oxidizing agent used in aqueous solution as a ripening agent, bleach, and topical anti-infective. It is relatively unstable and solutions deteriorate over time unless stabilized by the addition of acetanilide or similar organic materials. [NIH] Hydrogenation: Specific method of reduction in which hydrogen is added to a substance by the direct use of gaseous hydrogen. [NIH] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hydrophilic: Readily absorbing moisture; hygroscopic; having strongly polar groups that readily interact with water. [EU] Hydrophobic: Not readily absorbing water, or being adversely affected by water, as a hydrophobic colloid. [EU] Hydroxylysine: A hydroxylated derivative of the amino acid lysine that is present in certain collagens. [NIH] Hydroxyproline: A hydroxylated form of the imino acid proline. A deficiency in ascorbic acid can result in impaired hydroxyproline formation. [NIH] Hyperreflexia: Exaggeration of reflexes. [EU] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions
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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] Hysterectomy: Excision of the uterus. [NIH] Id: The part of the personality structure which harbors the unconscious instinctive desires and strivings of the individual. [NIH] Idiopathic: Describes a disease of unknown cause. [NIH] Imipenem: Semisynthetic thienamycin that has a wide spectrum of antibacterial activity against gram-negative and gram-positive aerobic and anaerobic bacteria, including many multiresistant strains. It is stable to beta-lactamases. Clinical studies have demonstrated high efficacy in the treatment of infections of various body systems. Its effectiveness is enhanced when it is administered in combination with cilastatin, a renal dipeptidase inhibitor. [NIH] Immune function: Production and action of cells that fight disease or infection. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]
Immune 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
Immunocompromised: Having a weakened immune system caused by certain diseases or treatments. [NIH] Immunodeficiency: The decreased ability of the body to fight infection and disease. [NIH] Immunodiffusion: Technique involving the diffusion of antigen or antibody through a semisolid medium, usually agar or agarose gel, with the result being a precipitin reaction. [NIH]
Immunoelectrophoresis: A technique that combines protein electrophoresis and double immunodiffusion. In this procedure proteins are first separated by gel electrophoresis (usually agarose), then made visible by immunodiffusion of specific antibodies. A distinct elliptical precipitin arc results for each protein detectable by the antisera. [NIH] Immunofluorescence: A technique for identifying molecules present on the surfaces of cells or in tissues using a highly fluorescent substance coupled to a specific antibody. [NIH] Immunogenic: Producing immunity; evoking an immune response. [EU] Immunoglobulin: A protein that acts as an antibody. [NIH] Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents. [NIH] Immunologic: The ability of the antibody-forming system to recall a previous experience with an antigen and to respond to a second exposure with the prompt production of large amounts of antibody. [NIH] Immunologic Factors: Biologically active substances whose activities affect or play a role in the functioning of the immune system. [NIH] Immunology: The study of the body's immune system. [NIH] Immunomodulator: New type of drugs mainly using biotechnological methods. Treatment of cancer. [NIH] Immunophilins: Members of a family of highly conserved proteins which are all cis-trans peptidyl-prolyl isomerases (peptidylprolyl isomerase). They bind the immunosuppressant
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drugs cyclosporine; tacrolimus and sirolimus. They possess rotomase activity, which is inhibited by the immunosuppressant drugs that bind to them. EC 5.2.1.- [NIH] Immunosuppressant: An agent capable of suppressing immune responses. [EU] Immunosuppressive: Describes the ability to lower immune system responses. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] Impetigo: A common superficial bacterial infection caused by Staphylococcus aureus or group A beta-hemolytic streptococci. Characteristics include pustular lesions that rupture and discharge a thin, amber-colored fluid that dries and forms a crust. This condition is commonly located on the face, especially about the mouth and nose. [NIH] Implantation: The insertion or grafting into the body of biological, living, inert, or radioactive material. [EU] In situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incision: A cut made in the body during surgery. [NIH] Incisional: The removal of a sample of tissue for examination under a microscope. [NIH] Incubated: Grown in the laboratory under controlled conditions. (For instance, white blood cells can be grown in special conditions so that they attack specific cancer cells when returned to the body.) [NIH] Incubation: The development of an infectious disease from the entrance of the pathogen to the appearance of clinical symptoms. [EU] 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] 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] Infectious Diarrhea: Diarrhea caused by infection from bacteria, viruses, or parasites. [NIH]
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Infiltration: The diffusion or accumulation in a tissue or cells of substances not normal to it or in amounts of the normal. Also, the material so accumulated. [EU] Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH] Influenza: An acute viral infection involving the respiratory tract. It is marked by inflammation of the nasal mucosa, the pharynx, and conjunctiva, and by headache and severe, often generalized, myalgia. [NIH] Infusion: A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion. [NIH] Ingestion: Taking into the body by mouth [NIH] Inhalation: The drawing of air or other substances into the lungs. [EU] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Inner ear: The labyrinth, comprising the vestibule, cochlea, and semicircular canals. [NIH] Inoculum: The spores or tissues of a pathogen that serve to initiate disease in a plant. [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] 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] 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] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Internal Medicine: A medical specialty concerned with the diagnosis and treatment of diseases of the internal organ systems of adults. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU]
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Intervertebral: Situated between two contiguous vertebrae. [EU] 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] Intraperitoneal: IP. Within the peritoneal cavity (the area that contains the abdominal organs). [NIH] Intravascular: Within a vessel or vessels. [EU] Intravenous: IV. Into a vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]
Invertebrates: Animals that have no spinal column. [NIH] Involution: 1. A rolling or turning inward. 2. One of the movements involved in the gastrulation of many animals. 3. A retrograde change of the entire body or in a particular organ, as the retrograde changes in the female genital organs that result in normal size after delivery. 4. The progressive degeneration occurring naturally with advancing age, resulting in shrivelling of organs or tissues. [EU] Ion Channels: Gated, ion-selective glycoproteins that traverse membranes. The stimulus for channel gating can be a membrane potential, drug, transmitter, cytoplasmic messenger, or a mechanical deformation. Ion channels which are integral parts of ionotropic neurotransmitter receptors are not included. [NIH] Ionization: 1. Any process by which a neutral atom gains or loses electrons, thus acquiring a net charge, as the dissociation of a substance in solution into ions or ion production by the passage of radioactive particles. 2. Iontophoresis. [EU] Ionizing: Radiation comprising charged particles, e. g. electrons, protons, alpha-particles, etc., having sufficient kinetic energy to produce ionization by collision. [NIH] 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] Isomerases: A class of enzymes that catalyze geometric or structural changes within a molecule to form a single product. The reactions do not involve a net change in the concentrations of compounds other than the substrate and the product.(from Dorland, 28th ed) EC 5. [NIH] Isoprenoid: Molecule that might anchor G protein to the cell membrane as it is hydrophobic. [NIH]
Joint: The point of contact between elements of an animal skeleton with the parts that surround and support it. [NIH] Kb: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [NIH]
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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] Keratectomy: The surgical removal of corneal tissue. [NIH] Keratin: A class of fibrous proteins or scleroproteins important both as structural proteins and as keys to the study of protein conformation. The family represents the principal constituent of epidermis, hair, nails, horny tissues, and the organic matrix of tooth enamel. Two major conformational groups have been characterized, alpha-keratin, whose peptide backbone forms an alpha-helix, and beta-keratin, whose backbone forms a zigzag or pleated sheet structure. [NIH] Keratinocytes: Epidermal cells which synthesize keratin and undergo characteristic changes as they move upward from the basal layers of the epidermis to the cornified (horny) layer of the skin. Successive stages of differentiation of the keratinocytes forming the epidermal layers are basal cell, spinous or prickle cell, and the granular cell. [NIH] Keratitis: Inflammation of the cornea. [NIH] Keratolytic: An agent that promotes keratolysis. [EU] Kidney Failure: The inability of a kidney to excrete metabolites at normal plasma levels under conditions of normal loading, or the inability to retain electrolytes under conditions of normal intake. In the acute form (kidney failure, acute), it is marked by uremia and usually by oliguria or anuria, with hyperkalemia and pulmonary edema. The chronic form (kidney failure, chronic) is irreversible and requires hemodialysis. [NIH] Kinetic: Pertaining to or producing motion. [EU] Labile: 1. Gliding; moving from point to point over the surface; unstable; fluctuating. 2. Chemically unstable. [EU] Laceration: 1. The act of tearing. 2. A torn, ragged, mangled wound. [EU] Lactate Dehydrogenase: A tetrameric enzyme that, along with the coenzyme NAD+, catalyzes the interconversion of lactate and pyruvate. In vertebrates, genes for three different subunits (LDH-A, LDH-B and LDH-C) exist. [NIH] Lactation: The period of the secretion of milk. [EU] Laminin: Large, noncollagenous glycoprotein with antigenic properties. It is localized in the basement membrane lamina lucida and functions to bind epithelial cells to the basement membrane. Evidence suggests that the protein plays a role in tumor invasion. [NIH] Laparotomy: A surgical incision made in the wall of the abdomen. [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] Lavage: A cleaning of the stomach and colon. Uses a special drink and enemas. [NIH] Laxative: An agent that acts to promote evacuation of the bowel; a cathartic or purgative. [EU]
Length of Stay: The period of confinement of a patient to a hospital or other health facility. [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
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granulomatous lesions are manifested in the skin, the mucous membranes, and the peripheral nerves. Two polar or principal types are lepromatous and tuberculoid. [NIH] Lethal: Deadly, fatal. [EU] Leucine: An essential branched-chain amino acid important for hemoglobin formation. [NIH] Leukemia: Cancer of blood-forming tissue. [NIH] Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [NIH] Leukopenia: A condition in which the number of leukocytes (white blood cells) in the blood is reduced. [NIH] Levofloxacin: A substance used to treat bacterial infections. It belongs to the family of drugs called quinolone antibiotics. [NIH] Library Services: Services offered to the library user. They include reference and circulation. [NIH]
Lidocaine: A local anesthetic and cardiac depressant used as an antiarrhythmia agent. Its actions are more intense and its effects more prolonged than those of procaine but its duration of action is shorter than that of bupivacaine or prilocaine. [NIH] Life cycle: The successive stages through which an organism passes from fertilized ovum or spore to the fertilized ovum or spore of the next generation. [NIH] Ligands: A RNA simulation method developed by the MIT. [NIH] Ligation: Application of a ligature to tie a vessel or strangulate a part. [NIH] Lincomycin: (2S-trans)-Methyl 6,8-dideoxy-6-(((1-methyl-4-propyl-2pyrrolidinyl)carbonyl)amino)-1-thio-D-erythro-alpha-D-galacto-octopyranoside. An antibiotic produced by Streptomyces lincolnensis var. lincolnensis. It has been used in the treatment of staphylococcal, streptococcal, and Bacteroides fragilis infections. [NIH] Linkage: The tendency of two or more genes in the same chromosome to remain together from one generation to the next more frequently than expected according to the law of independent assortment. [NIH] Lipid: Fat. [NIH] Lipid Peroxidation: Peroxidase catalyzed oxidation of lipids using hydrogen peroxide as an electron acceptor. [NIH] Lipophilic: Having an affinity for fat; pertaining to or characterized by lipophilia. [EU] 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] Liposomes: Artificial, single or multilaminar vesicles (made from lecithins or other lipids) that are used for the delivery of a variety of biological molecules or molecular complexes to cells, for example, drug delivery and gene transfer. They are also used to study membranes and membrane proteins. [NIH] Lithium: An element in the alkali metals family. It has the atomic symbol Li, atomic number 3, and atomic weight 6.94. Salts of lithium are used in treating manic-depressive disorders. [NIH]
Lithium Chloride: A salt of lithium that has been used experimentally as an
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immunomodulator. [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 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] Long-Term Care: Care over an extended period, usually for a chronic condition or disability, requiring periodic, intermittent, or continuous care. [NIH] Loop: A wire usually of platinum bent at one end into a small loop (usually 4 mm inside diameter) and used in transferring microorganisms. [NIH] Lucida: An instrument, invented by Wollaton, consisting essentially of a prism or a mirror through which an object can be viewed so as to appear on a plane surface seen in direct view and on which the outline of the object may be traced. [NIH] Lumbar: Pertaining to the loins, the part of the back between the thorax and the pelvis. [EU] Lumbar puncture: A procedure in which a needle is put into the lower part of the spinal column to collect cerebrospinal fluid or to give anticancer drugs intrathecally. Also called a spinal tap. [NIH] Lung Transplantation: The transference of either one or both of the lungs from one human or animal to another. [NIH] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Lymph node: A rounded mass of lymphatic tissue that is surrounded by a capsule of connective tissue. Also known as a lymph gland. Lymph nodes are spread out along lymphatic vessels and contain many lymphocytes, which filter the lymphatic fluid (lymph). [NIH]
Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] Lymphatic system: The tissues and organs that produce, store, and carry white blood cells that fight infection and other diseases. This system includes the bone marrow, spleen, thymus, lymph nodes and a network of thin tubes that carry lymph and white blood cells. These tubes branch, like blood vessels, into all the tissues of the body. [NIH] Lymphocyte: A white blood cell. Lymphocytes have a number of roles in the immune system, including the production of antibodies and other substances that fight infection and diseases. [NIH] 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]
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Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue. [NIH] Lymphoproliferative: Disorders characterized by proliferation of lymphoid tissue, general or unspecified. [NIH] Lysine: An essential amino acid. It is often added to animal feed. [NIH] Lysostaphin: A 25 kD peptidase produced by Staphylococcus simulans which cleaves a glycine-glcyine bond unique to an inter-peptide cross-bridge of the Staphylococcus aureus cell wall. EC 3.4.24.75. [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 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] 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] 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] Mammary: Pertaining to the mamma, or breast. [EU] Manic: Affected with mania. [EU] Mannans: Polysaccharides consisting of mannose units. [NIH] Mastitis: Inflammatory disease of the breast, or mammary gland. [NIH] Meat: The edible portions of any animal used for food including domestic mammals (the major ones being cattle, swine, and sheep) along with poultry, fish, shellfish, and game. [NIH]
Mediastinitis: Inflammation of the mediastinum, the area between the pleural sacs. [NIH] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] Mediator: An object or substance by which something is mediated, such as (1) a structure of the nervous system that transmits impulses eliciting a specific response; (2) a chemical substance (transmitter substance) that induces activity in an excitable tissue, such as nerve or muscle; or (3) a substance released from cells as the result of the interaction of antigen with antibody or by the action of antigen with a sensitized lymphocyte. [EU] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Meiosis: A special method of cell division, occurring in maturation of the germ cells, by means of which each daughter nucleus receives half the number of chromosomes characteristic of the somatic cells of the species. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Membrane Lipids: Lipids, predominantly phospholipids, cholesterol and small amounts of glycolipids found in membranes including cellular and intracellular membranes. These lipids may be arranged in bilayers in the membranes with integral proteins between the
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layers and peripheral proteins attached to the outside. Membrane lipids are required for active transport, several enzymatic activities and membrane formation. [NIH] Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors. [NIH] Memory: Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. [NIH] Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] Meningitis: Inflammation of the meninges. When it affects the dura mater, the disease is termed pachymeningitis; when the arachnoid and pia mater are involved, it is called leptomeningitis, or meningitis proper. [EU] Menstruation: The normal physiologic discharge through the vagina of blood and mucosal tissues from the nonpregnant uterus. [NIH] Mental: Pertaining to the mind; psychic. 2. (L. mentum chin) pertaining to the chin. [EU] Mental Disorders: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. [NIH] Mental Health: The state wherein the person is well adjusted. [NIH] Mercury: A silver metallic element that exists as a liquid at room temperature. It has the atomic symbol Hg (from hydrargyrum, liquid silver), atomic number 80, and atomic weight 200.59. Mercury is used in many industrial applications and its salts have been employed therapeutically as purgatives, antisyphilitics, disinfectants, and astringents. It can be absorbed through the skin and mucous membranes which leads to mercury poisoning. Because of its toxicity, the clinical use of mercury and mercurials is diminishing. [NIH] 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] 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] Mice Minute Virus: The type species of parvovirus prevalent in mouse colonies and found as a contaminant of many transplanted tumors or leukemias. [NIH] Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microbiological: Pertaining to microbiology : the science that deals with microorganisms, including algae, bacteria, fungi, protozoa and viruses. [EU] Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and
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viruses. [NIH] Microcirculation: The vascular network lying between the arterioles and venules; includes capillaries, metarterioles and arteriovenous anastomoses. Also, the flow of blood through this network. [NIH] Microorganism: An organism that can be seen only through a microscope. Microorganisms include bacteria, protozoa, algae, and fungi. Although viruses are not considered living organisms, they are sometimes classified as microorganisms. [NIH] Micro-organism: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microscopy: The application of microscope magnification to the study of materials that cannot be properly seen by the unaided eye. [NIH] Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [NIH] Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH] 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] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Molasses: The syrup remaining after sugar is crystallized out of sugar cane or sugar beet juice. It is also used in animal feed, and in a fermented form, is used to make industrial ethyl alcohol and alcoholic beverages. [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] Monobactams: Monocyclic, bacterially produced or semisynthetic beta-lactam antibiotics. They lack the double ring construction of the traditional beta-lactam antibiotics and can be easily synthesized. [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] Morphological: Relating to the configuration or the structure of live organs. [NIH]
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Morphology: The science of the form and structure of organisms (plants, animals, and other forms of life). [NIH] Mucins: A secretion containing mucopolysaccharides and protein that is the chief constituent of mucus. [NIH] Mucolytic: Destroying or dissolving mucin; an agent that so acts : a mucopolysaccharide or glycoprotein, the chief constituent of mucus. [EU] Mucosa: A mucous membrane, or tunica mucosa. [EU] Mucus: The viscous secretion of mucous membranes. It contains mucin, white blood cells, water, inorganic salts, and exfoliated cells. [NIH] Multicenter study: A clinical trial that is carried out at more than one medical institution. [NIH]
Multidrug resistance: Adaptation of tumor cells to anticancer drugs in ways that make the drugs less effective. [NIH] Multivalent: Pertaining to a group of 5 or more homologous or partly homologous chromosomes during the zygotene stage of prophase to first metaphasis in meiosis. [NIH] Mupirocin: A topically used antibiotic from a strain of Pseudomonas fluorescens. It has shown excellent activity against gram-positive staphylococci and streptococci. The antibiotic is used primarily for the treatment of primary and secondary skin disorders, nasal infections, and wound healing. [NIH] Musculoskeletal System: Themuscles, bones, and cartilage of the body. [NIH] Myalgia: Pain in a muscle or muscles. [EU] Myelography: X-ray visualization of the spinal cord following injection of contrast medium into the spinal arachnoid space. [NIH] Myeloid Cells: Cells which include the monocytes and the granulocytes. [NIH] Myeloma: Cancer that arises in plasma cells, a type of white blood cell. [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] Naive: Used to describe an individual who has never taken a certain drug or class of drugs (e. g., AZT-naive, antiretroviral-naive), or to refer to an undifferentiated immune system cell. [NIH] Nasal Cavity: The proximal portion of the respiratory passages on either side of the nasal septum, lined with ciliated mucosa, extending from the nares to the pharynx. [NIH] Nasal Mucosa: The mucous membrane lining the nasal cavity. [NIH] Nasopharynx: The nasal part of the pharynx, lying above the level of the soft palate. [NIH] Nausea: An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. [NIH] NCI: National Cancer Institute. NCI, part of the National Institutes of Health of the United States Department of Health and Human Services, is the federal government's principal agency for cancer research. NCI conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the NCI Web site at http://cancer.gov. [NIH] Need: A state of tension or dissatisfaction felt by an individual that impels him to action
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toward a goal he believes will satisfy the impulse. [NIH] Neisseria: A genus of gram-negative, aerobic, coccoid bacteria whose organisms are part of the normal flora of the oropharynx, nasopharynx, and genitourinary tract. Some species are primary pathogens for humans. [NIH] Neisseria meningitidis: A species of gram-negative, aerobic bacteria found in cerebrospinal fluid as the causative agent of cerebrospinal meningitis (meningitis, meningococcal) as well as in venereal discharges and blood. [NIH] Neonatal: Pertaining to the first four weeks after birth. [EU] Neoplasm: A new growth of benign or malignant tissue. [NIH] Neoplastic: Pertaining to or like a neoplasm (= any new and abnormal growth); pertaining to neoplasia (= the formation of a neoplasm). [EU] Neopterin: A pteridine derivative present in body fluids; elevated levels result from immune system activation, malignant disease, allograft rejection, and viral infections. (From Stedman, 26th ed) Neopterin also serves as a precursor in the biosynthesis of biopterin. [NIH] 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] Neurologic: Having to do with nerves or the nervous system. [NIH] Neuromuscular: Pertaining to muscles and nerves. [EU] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] Neurophysiology: The scientific discipline concerned with the physiology of the nervous system. [NIH] Neurotransmitter: Any of a group of substances that are released on excitation from the axon terminal of a presynaptic neuron of the central or peripheral nervous system and travel across the synaptic cleft to either excite or inhibit the target cell. Among the many substances that have the properties of a neurotransmitter are acetylcholine, norepinephrine, epinephrine, dopamine, glycine, y-aminobutyrate, glutamic acid, substance P, enkephalins, endorphins, and serotonin. [EU] Neutralization: An act or process of neutralizing. [EU] Neutrons: Electrically neutral elementary particles found in all atomic nuclei except light hydrogen; the mass is equal to that of the proton and electron combined and they are unstable when isolated from the nucleus, undergoing beta decay. Slow, thermal, epithermal, and fast neutrons refer to the energy levels with which the neutrons are ejected from heavier nuclei during their decay. [NIH] Neutrophil: A type of white blood cell. [NIH] Neutrophil Infiltration: The diffusion or accumulation of neutrophils in tissues or cells in response to a wide variety of substances released at the sites of inflammatory reactions. [NIH] Nisin: A 34-amino acid polypeptide antibiotic produced by Streptococcus lactis. It has been used as a food preservative in canned fruits and vegetables, and cheese. [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
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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] Nucleic Acid Probes: Nucleic acid which complements a specific mRNA or DNA molecule, or fragment thereof; used for hybridization studies in order to identify microorganisms and for genetic studies. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nutritive Value: An indication of the contribution of a food to the nutrient content of the diet. This value depends on the quantity of a food which is digested and absorbed and the amounts of the essential nutrients (protein, fat, carbohydrate, minerals, vitamins) which it contains. This value can be affected by soil and growing conditions, handling and storage, and processing. [NIH] 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] 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] Oligo: Chemical and mineral elements that exist in minimal (oligo) quantities in the body, in foods, in the air, in soil; name applied to any element observed as a microconstituent of plant or animal tissue and of beneficial, harmful, or even doubtful significance. [NIH] Opacity: Degree of density (area most dense taken for reading). [NIH]
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Operon: The genetic unit consisting of a feedback system under the control of an operator gene, in which a structural gene transcribes its message in the form of mRNA upon blockade of a repressor produced by a regulator gene. Included here is the attenuator site of bacterial operons where transcription termination is regulated. [NIH] Ophthalmology: A surgical specialty concerned with the structure and function of the eye and the medical and surgical treatment of its defects and diseases. [NIH] Opportunistic Infections: An infection caused by an organism which becomes pathogenic under certain conditions, e.g., during immunosuppression. [NIH] 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] Oropharynx: Oral part of the pharynx. [NIH] Orthopaedic: Pertaining to the correction of deformities of the musculoskeletal system; pertaining to orthopaedics. [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] Ossification: The formation of bone or of a bony substance; the conversion of fibrous tissue or of cartilage into bone or a bony substance. [EU] Osteoblasts: Bone-forming cells which secrete an extracellular matrix. Hydroxyapatite crystals are then deposited into the matrix to form bone. [NIH] Osteogenesis: The histogenesis of bone including ossification. It occurs continuously but particularly in the embryo and child and during fracture repair. [NIH] Osteomyelitis: Inflammation of bone caused by a pyogenic organism. It may remain localized or may spread through the bone to involve the marrow, cortex, cancellous tissue, and periosteum. [EU] Osteoporosis: Reduction of bone mass without alteration in the composition of bone, leading to fractures. Primary osteoporosis can be of two major types: postmenopausal osteoporosis and age-related (or senile) osteoporosis. [NIH] Otolaryngology: A surgical specialty concerned with the study and treatment of disorders of the ear, nose, and throat. [NIH] Overexpress: An excess of a particular protein on the surface of a cell. [NIH] Oxacillin: An antibiotic similar to flucloxacillin used in resistant staphylococci infections. [NIH]
Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]
Oxidative Stress: A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA
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bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi). [NIH] Oxygen Consumption: The oxygen consumption is determined by calculating the difference between the amount of oxygen inhaled and exhaled. [NIH] Pachymeningitis: Inflammation of the dura mater of the brain, the spinal cord or the optic nerve. [NIH] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Palpation: Application of fingers with light pressure to the surface of the body to determine consistence of parts beneath in physical diagnosis; includes palpation for determining the outlines of organs. [NIH] 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] 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] 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] Par excellence: The petrous portion of the temporal bone, containing the inner ear and wedged in at the base of the skull between the sphenoid and occipital bones. [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] Parvovirus: A genus of the family Parvoviridae, subfamily Parvovirinae, infecting a variety of vertebrates including humans. Parvoviruses are responsible for a number of important diseases but also can be non-pathogenic in certain hosts. The type species is mice minute virus. [NIH] Pathogen: Any disease-producing microorganism. [EU] Pathogenesis: The cellular events and reactions that occur in the development of disease. [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] Pathologies: The study of abnormality, especially the study of diseases. [NIH] Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Patient Education: The teaching or training of patients concerning their own health needs. [NIH]
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] Pemphigus: Group of chronic blistering diseases characterized histologically by
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acantholysis and blister formation within the epidermis. [NIH] Penicillin: An antibiotic drug used to treat infection. [NIH] Penicillinase: A beta-lactamase preferentially cleaving penicillins. (Dorland, 28th ed) EC 3.5.2.-. [NIH] Pepsin: An enzyme made in the stomach that breaks down proteins. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Peptide Fragments: Partial proteins formed by partial hydrolysis of complete proteins. [NIH] Peptide T: N-(N-(N(2)-(N-(N-(N-(N-D-Alanyl L-seryl)-L-threonyl)-L-threonyl) L-threonyl)L-asparaginyl)-L-tyrosyl) L-threonine. Octapeptide sharing sequence homology with HIV envelope protein gp120. It is potentially useful as antiviral agent in AIDS therapy. The core pentapeptide sequence, TTNYT, consisting of amino acids 4-8 in peptide T, is the HIV envelope sequence required for attachment to the CD4 receptor. [NIH] Perforation: 1. The act of boring or piercing through a part. 2. A hole made through a part or substance. [EU] Pericarditis: Inflammation of the pericardium. [EU] Pericardium: The fibroserous sac surrounding the heart and the roots of the great vessels. [NIH]
Perinatal: Pertaining to or occurring in the period shortly before and after birth; variously defined as beginning with completion of the twentieth to twenty-eighth week of gestation and ending 7 to 28 days after birth. [EU] Perineal: Pertaining to the perineum. [EU] Perineum: The area between the anus and the sex organs. [NIH] Periodontal disease: Disease involving the supporting structures of the teeth (as the gums and periodontal membranes). [NIH] Periodontal disease: Disease involving the supporting structures of the teeth (as the gums and periodontal membranes). [NIH] Periodontitis: Inflammation of the periodontal membrane; also called periodontitis simplex. [NIH]
Perioperative: Around the time of surgery; usually lasts from the time of going into the hospital or doctor's office for surgery until the time the patient goes home. [NIH] Peripheral blood: Blood circulating throughout the body. [NIH] Peripheral Nervous System: The nervous system outside of the brain and spinal cord. The peripheral nervous system has autonomic and somatic divisions. The autonomic nervous system includes the enteric, parasympathetic, and sympathetic subdivisions. The somatic nervous system includes the cranial and spinal nerves and their ganglia and the peripheral sensory receptors. [NIH] 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] Peritoneal Dialysis: Dialysis fluid being introduced into and removed from the peritoneal cavity as either a continuous or an intermittent procedure. [NIH] Peritoneum: Endothelial lining of the abdominal cavity, the parietal peritoneum covering
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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] 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] Phallic: Pertaining to the phallus, or penis. [EU] 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] Pharmacodynamics: The study of the biochemical and physiological effects of drugs and the mechanisms of their actions, including the correlation of actions and effects of drugs with their chemical structure; also, such effects on the actions of a particular drug or drugs. [EU] 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] Pheromone: A substance secreted externally by certain animal species, especially insects, to affect the behavior or development of other members of the species. [NIH] Phospholipases: A class of enzymes that catalyze the hydrolysis of phosphoglycerides or glycerophosphatidates. EC 3.1.-. [NIH] Phospholipids: Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides; glycerophospholipids) or sphingosine (sphingolipids). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system. [NIH] Phosphorus: A non-metallic element that is found in the blood, muscles, nevers, bones, and teeth, and is a component of adenosine triphosphate (ATP; the primary energy source for the body's cells.) [NIH] Phosphorylated: Attached to a phosphate group. [NIH] 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] Photodynamic therapy: Treatment with drugs that become active when exposed to light. These drugs kill cancer cells. [NIH] Photosensitizer: A drug used in photodynamic therapy. When absorbed by cancer cells and exposed to light, the drug becomes active and kills the cancer cells. [NIH]
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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] 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] Plant Oils: Oils derived from plants or plant products. [NIH] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] Plasma protein: One of the hundreds of different proteins present in blood plasma, including carrier proteins ( such albumin, transferrin, and haptoglobin), fibrinogen and other coagulation factors, complement components, immunoglobulins, enzyme inhibitors, precursors of substances such as angiotension and bradykinin, and many other types of proteins. [EU] Plasmid: An autonomously replicating, extra-chromosomal DNA molecule found in many bacteria. Plasmids are widely used as carriers of cloned genes. [NIH] Plasmin: A product of the lysis of plasminogen (profibrinolysin) by plasminogen activators. It is composed of two polypeptide chains, light (B) and heavy (A), with a molecular weight of 75,000. It is the major proteolytic enzyme involved in blood clot retraction or the lysis of fibrin and quickly inactivated by antiplasmins. EC 3.4.21.7. [NIH] Plasminogen: Precursor of fibrinolysin (plasmin). It is a single-chain beta-globulin of molecular weight 80-90,000 found mostly in association with fibrinogen in plasma; plasminogen activators change it to fibrinolysin. It is used in wound debriding and has been investigated as a thrombolytic agent. [NIH] Plasminogen Activators: A heterogeneous group of proteolytic enzymes that convert plasminogen to plasmin. They are concentrated in the lysosomes of most cells and in the vascular endothelium, particularly in the vessels of the microcirculation. EC 3.4.21.-. [NIH] 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] Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form.
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Also called thrombocytes. [NIH] Platinum: Platinum. A heavy, soft, whitish metal, resembling tin, atomic number 78, atomic weight 195.09, symbol Pt. (From Dorland, 28th ed) It is used in manufacturing equipment for laboratory and industrial use. It occurs as a black powder (platinum black) and as a spongy substance (spongy platinum) and may have been known in Pliny's time as "alutiae". [NIH]
Pleated: Particular three-dimensional pattern of amyloidoses. [NIH] Pleural: A circumscribed area of hyaline whorled fibrous tissue which appears on the surface of the parietal pleura, on the fibrous part of the diaphragm or on the pleura in the interlobar fissures. [NIH] Pneumonia: Inflammation of the lungs. [NIH] Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [NIH] Polyethylene: A vinyl polymer made from ethylene. It can be branched or linear. Branched or low-density polyethylene is tough and pliable but not to the same degree as linear polyethylene. Linear or high-density polyethylene has a greater hardness and tensile strength. Polyethylene is used in a variety of products, including implants and prostheses. [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] Polymyxin: Basic polypeptide antibiotic group obtained from Bacillus polymyxa. They affect the cell membrane by detergent action and may cause neuromuscular and kidney damage. At least eleven different members of the polymyxin group have been identified, each designated by a letter. [NIH] Polyneuritis: Inflammation of several peripheral nerves at the same time. [NIH] Polyposis: The development of numerous polyps (growths that protrude from a mucous membrane). [NIH] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] Population Dynamics: The pattern of any process, or the interrelationship of phenomena, which affects growth or change within a population. [NIH]
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Postmenopausal: Refers to the time after menopause. Menopause is the time in a woman's life when menstrual periods stop permanently; also called "change of life." [NIH] Postoperative: After surgery. [NIH] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Post-translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Potassium: An element that is in the alkali group of metals. It has an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte and it plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. [NIH] Potentiate: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Potentiating: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Potentiation: An overall effect of two drugs taken together which is greater than the sum of the effects of each drug taken alone. [NIH] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH] Precipitation: The act or process of precipitating. [EU] Preclinical: Before a disease becomes clinically recognizable. [EU] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] 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] Prickle: Several layers of the epidermis where the individual cells are connected by cell bridges. [NIH] Probe: An instrument used in exploring cavities, or in the detection and dilatation of strictures, or in demonstrating the potency of channels; an elongated instrument for exploring or sounding body cavities. [NIH] Prodrug: A substance that gives rise to a pharmacologically active metabolite, although not itself active (i. e. an inactive precursor). [NIH] Progeny: The offspring produced in any generation. [NIH] 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]
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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] Pronase: A proteolytic enzyme obtained from Streptomyces griseus. [NIH] Prone: Having the front portion of the body downwards. [NIH] Prophase: The first phase of cell division, in which the chromosomes become visible, the nucleus starts to lose its identity, the spindle appears, and the centrioles migrate toward opposite poles. [NIH] Prophylaxis: An attempt to prevent disease. [NIH] Proportional: Being in proportion : corresponding in size, degree, or intensity, having the same or a constant ratio; of, relating to, or used in determining proportions. [EU] Prospective Studies: Observation of a population for a sufficient number of persons over a sufficient number of years to generate incidence or mortality rates subsequent to the selection of the study group. [NIH] Prospective study: An epidemiologic study in which a group of individuals (a cohort), all free of a particular disease and varying in their exposure to a possible risk factor, is followed over a specific amount of time to determine the incidence rates of the disease in the exposed and unexposed groups. [NIH] Prostate: A gland in males that surrounds the neck of the bladder and the urethra. It secretes a substance that liquifies coagulated semen. It is situated in the pelvic cavity behind the lower part of the pubic symphysis, above the deep layer of the triangular ligament, and rests upon the rectum. [NIH] Prosthesis: An artificial replacement of a part of the body. [NIH] 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 S: The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH] Protein Subunits: Single chains of amino acids that are the units of a multimeric protein. They can be identical or non-identical subunits. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] Proteoglycan: A molecule that contains both protein and glycosaminoglycans, which are a type of polysaccharide. Proteoglycans are found in cartilage and other connective tissues. [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] Prothrombin: A plasma protein that is the inactive precursor of thrombin. It is converted to
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thrombin by a prothrombin activator complex consisting of factor Xa, factor V, phospholipid, and calcium ions. Deficiency of prothrombin leads to hypoprothrombinemia. [NIH]
Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or vaccine dosages, length of study, routes of administration, who may participate, and other aspects of trial design. [NIH] Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] Protozoa: A subkingdom consisting of unicellular organisms that are the simplest in the animal kingdom. Most are free living. They range in size from submicroscopic to macroscopic. Protozoa are divided into seven phyla: Sarcomastigophora, Labyrinthomorpha, Apicomplexa, Microspora, Ascetospora, Myxozoa, and Ciliophora. [NIH] Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] 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 aeruginosa: A species of gram-negative, aerobic, rod-shaped bacteria commonly isolated from clinical specimens (wound, burn, and urinary tract infections). It is also found widely distributed in soil and water. P. aeruginosa is a major agent of nosocomial infection. [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] Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders. [NIH] Psychic: Pertaining to the psyche or to the mind; mental. [EU] 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] Pulmonary: Relating to the lungs. [NIH] Pulmonary Emphysema: Condition of the lungs characterized by increase beyond normal in the size of air spaces distal to the terminal bronchioles, either from dilatation of the alveoli or from destruction of their walls. [NIH] Pulsation: A throb or rhythmical beat, as of the heart. [EU] 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] Purifying: Respiratory equipment whose function is to remove contaminants from otherwise wholesome air. [NIH] Purines: A series of heterocyclic compounds that are variously substituted in nature and are known also as purine bases. They include adenine and guanine, constituents of nucleic
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acids, as well as many alkaloids such as caffeine and theophylline. Uric acid is the metabolic end product of purine metabolism. [NIH] Purulent: Consisting of or containing pus; associated with the formation of or caused by pus. [EU] Pustular: Pertaining to or of the nature of a pustule; consisting of pustules (= a visible collection of pus within or beneath the epidermis). [EU] Putrefaction: The process of decomposition of animal and vegetable matter by living organisms. [NIH] Pyogenic: Producing pus; pyopoietic (= liquid inflammation product made up of cells and a thin fluid called liquor puris). [EU] Pyrimidines: A family of 6-membered heterocyclic compounds occurring in nature in a wide variety of forms. They include several nucleic acid constituents (cytosine, thymine, and uracil) and form the basic structure of the barbiturates. [NIH] Pyrophosphatases: A group of enzymes within the class EC 3.6.1.- that catalyze the hydrolysis of diphosphate bonds, chiefly in nucleoside di- and triphosphates. They may liberate either a mono- or diphosphate. EC 3.6.1.-. [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] Rabies: A highly fatal viral infection of the nervous system which affects all warm-blooded animal species. It is one of the most important of the zoonoses because of the inevitably fatal outcome for the infected human. [NIH] Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radioactive: Giving off radiation. [NIH] Random Allocation: A process involving chance used in therapeutic trials or other research endeavor for allocating experimental subjects, human or animal, between treatment and control groups, or among treatment groups. It may also apply to experiments on inanimate objects. [NIH] Randomization: Also called random allocation. Is allocation of individuals to groups, e.g., for experimental and control regimens, by chance. Within the limits of chance variation, random allocation should make the control and experimental groups similar at the start of an investigation and ensure that personal judgment and prejudices of the investigator do not influence allocation. [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] Reagent: A substance employed to produce a chemical reaction so as to detect, measure, produce, etc., other substances. [EU] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU]
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Recombinant Proteins: Proteins prepared by recombinant DNA technology. [NIH] Recombination: The formation of new combinations of genes as a result of segregation in crosses between genetically different parents; also the rearrangement of linked genes due to crossing-over. [NIH] Reconstitution: 1. A type of regeneration in which a new organ forms by the rearrangement of tissues rather than from new formation at an injured surface. 2. The restoration to original form of a substance previously altered for preservation and storage, as the restoration to a liquid state of blood serum or plasma that has been dried and stored. [EU] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Red blood cells: RBCs. Cells that carry oxygen to all parts of the body. Also called erythrocytes. [NIH] Reductase: Enzyme converting testosterone to dihydrotestosterone. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH] Regeneration: The natural renewal of a structure, as of a lost tissue or part. [EU] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Regulon: In eukaryotes, a genetic unit consisting of a noncontiguous group of genes under the control of a single regulator gene. In bacteria, regulons are global regulatory systems involved in the interplay of pleiotropic regulatory domains. These regulatory systems consist of several operons. [NIH] Relapse: The return of signs and symptoms of cancer after a period of improvement. [NIH] Reliability: Used technically, in a statistical sense, of consistency of a test with itself, i. e. the extent to which we can assume that it will yield the same result if repeated a second time. [NIH]
Replicon: In order to be replicated, DNA molecules must contain an origin of duplication and in bacteria and viruses there is usually only one per genome. Such molecules are called replicons. [NIH] 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] Research Personnel: Those individuals engaged in research. [NIH] Respiration: The act of breathing with the lungs, consisting of inspiration, or the taking into the lungs of the ambient air, and of expiration, or the expelling of the modified air which contains more carbon dioxide than the air taken in (Blakiston's Gould Medical Dictionary, 4th ed.). This does not include tissue respiration (= oxygen consumption) or cell respiration (= cell respiration). [NIH] Respiratory Physiology: Functions and activities of the respiratory tract as a whole or of any of its parts. [NIH] Restoration: Broad term applied to any inlay, crown, bridge or complete denture which restores or replaces loss of teeth or oral tissues. [NIH] Retinoid: Vitamin A or a vitamin A-like compound. [NIH] Retrograde: 1. Moving backward or against the usual direction of flow. 2. Degenerating, deteriorating, or catabolic. [EU]
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Retrospective: Looking back at events that have already taken place. [NIH] Reversion: A return to the original condition, e. g. the reappearance of the normal or wild type in previously mutated cells, tissues, or organisms. [NIH] Rheumatism: A group of disorders marked by inflammation or pain in the connective tissue structures of the body. These structures include bone, cartilage, and fat. [NIH] Rheumatoid: Resembling rheumatism. [EU] Rheumatoid arthritis: A form of arthritis, the cause of which is unknown, although infection, hypersensitivity, hormone imbalance and psychologic stress have been suggested as possible causes. [NIH] Rhinitis: Inflammation of the mucous membrane of the nose. [NIH] Ribonuclease: RNA-digesting enzyme. [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] Ribotyping: Restriction fragment length polymorphism analysis of rRNA genes that is used for differentiating between species or strains. [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] Rotavirus: A genus of Reoviridae, causing acute gastroenteritis in birds and mammals, including humans. Transmission is horizontal and by environmental contamination. [NIH] Salicylate: Non-steroidal anti-inflammatory drugs. [NIH] Saliva: The clear, viscous fluid secreted by the salivary glands and mucous glands of the mouth. It contains mucins, water, organic salts, and ptylin. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [NIH] Salmonella: A genus of gram-negative, facultatively anaerobic, rod-shaped bacteria that utilizes citrate as a sole carbon source. It is pathogenic for humans, causing enteric fevers, gastroenteritis, and bacteremia. Food poisoning is the most common clinical manifestation. Organisms within this genus are separated on the basis of antigenic characteristics, sugar fermentation patterns, and bacteriophage susceptibility. [NIH] Scarlet Fever: Infection with group A streptococci that is characterized by tonsillitis and pharyngitis. An erythematous rash is commonly present. [NIH] Scleroderma: A chronic disorder marked by hardening and thickening of the skin. Scleroderma can be localized or it can affect the entire body (systemic). [NIH] Scleroproteins: Simple proteins characterized by their insolubility and fibrous structure. Within the body, they perform a supportive or protective function. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Sebaceous: Gland that secretes sebum. [NIH]
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Sebaceous gland: Gland that secretes sebum. [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] Selenomethionine: Diagnostic aid in pancreas function determination. [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] Semisynthetic: Produced by chemical manipulation of naturally occurring substances. [EU] Senile: Relating or belonging to old age; characteristic of old age; resulting from infirmity of old age. [NIH] Sensor: A device designed to respond to physical stimuli such as temperature, light, magnetism or movement and transmit resulting impulses for interpretation, recording, movement, or operating control. [NIH] Sepsis: The presence of bacteria in the bloodstream. [NIH] 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] Sequence Homology: The degree of similarity between sequences. Studies of amino acid and nucleotide sequences provide useful information about the genetic relatedness of certain species. [NIH] Sequencing: The determination of the order of nucleotides in a DNA or RNA chain. [NIH] Serine: A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from glycine or threonine. It is involved in the biosynthesis of purines, pyrimidines, and other amino acids. [NIH] Serologic: Analysis of a person's serum, especially specific immune or lytic serums. [NIH] Serotypes: A cause of haemorrhagic septicaemia (in cattle, sheep and pigs), fowl cholera of birds, pasteurellosis of rabbits, and gangrenous mastitis of ewes. It is also commonly found in atrophic rhinitis of pigs. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Serum Albumin: A major plasma protein that serves in maintaining the plasma colloidal osmotic pressure and transporting large organic anions. [NIH] 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]
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Sigma Factor: A protein which is a subunit of RNA polymerase. It effects initiation of specific RNA chains from DNA. [NIH] 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] Silver Compounds: Inorganic compounds that contain silver as an integral part of the molecule. [NIH] Sirolimus: A macrolide compound obtained from Streptomyces hygroscopicus that acts by selectively blocking the transcriptional activation of cytokines thereby inhibiting cytokine production. It is bioactive only when bound to immunophilins. Sirolimus is a potent immunosuppressant and possesses both antifungal and antineoplastic properties. [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] Skin graft: Skin that is moved from one part of the body to another. [NIH] Skin Manifestations: Dermatologic disorders attendant upon non-dermatologic disease or injury. [NIH] Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] Sludge: A clump of agglutinated red blood cells. [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. [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] 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
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the body. [NIH] Solvent: 1. Dissolving; effecting a solution. 2. A liquid that dissolves or that is capable of dissolving; the component of a solution that is present in greater amount. [EU] Soma: The body as distinct from the mind; all the body tissue except the germ cells; all the axial body. [NIH] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] Somatic cells: All the body cells except the reproductive (germ) cells. [NIH] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] 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] Spectroscopic: The recognition of elements through their emission spectra. [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] Sphenoid: An unpaired cranial bone with a body containing the sphenoid sinus and forming the posterior part of the medial walls of the orbits. [NIH] Sphincter: A ringlike band of muscle fibres that constricts a passage or closes a natural orifice; called also musculus sphincter. [EU] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] Spinous: Like a spine or thorn in shape; having spines. [NIH] Spirochete: Lyme disease. [NIH] Spleen: An organ that is part of the lymphatic system. The spleen produces lymphocytes, filters the blood, stores blood cells, and destroys old blood cells. It is located on the left side of the abdomen near the stomach. [NIH] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [EU] Spores: The reproductive elements of lower organisms, such as protozoa, fungi, and cryptogamic plants. [NIH] Stabilization: The creation of a stable state. [EU] Staphylocoagulase: A substance produced by pathogenic strains of staphylococci, which has the property of coagulating human or rabbit plasma. [NIH]
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Staphylococcal Infections: Infections with bacteria of the genus Staphylococcus. [NIH] Staphylococcal Scalded Skin Syndrome: A disease of infants due to group 2 phage type 17 staphylococci that produce an epidermolytic exotoxin. Superficial fine vesicles and bullae form and rupture easily, resulting in loss of large sheets of epidermis. [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] Steady state: Dynamic equilibrium. [EU] Steel: A tough, malleable, iron-based alloy containing up to, but no more than, two percent carbon and often other metals. It is used in medicine and dentistry in implants and instrumentation. [NIH] Stents: Devices that provide support for tubular structures that are being anastomosed or for body cavities during skin grafting. [NIH] Sterilization: The destroying of all forms of life, especially microorganisms, by heat, chemical, or other means. [NIH] Steroids: Drugs used to relieve swelling and inflammation. [NIH] Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Strand: DNA normally exists in the bacterial nucleus in a helix, in which two strands are coiled together. [NIH] Streptococcal: Caused by infection due to any species of streptococcus. [NIH] Streptococci: A genus of spherical Gram-positive bacteria occurring in chains or pairs. They are widely distributed in nature, being important pathogens but often found as normal commensals in the mouth, skin, and intestine of humans and other animals. [NIH] Streptococcus: A genus of gram-positive, coccoid bacteria whose organisms occur in pairs or chains. No endospores are produced. Many species exist as commensals or parasites on man or animals with some being highly pathogenic. A few species are saprophytes and occur in the natural environment. [NIH] 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] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] Stringency: Experimental conditions (e. g. temperature, salt concentration) used during the hybridization of nucleic acids. [NIH] Stroke: Sudden loss of function of part of the brain because of loss of blood flow. Stroke may be caused by a clot (thrombosis) or rupture (hemorrhage) of a blood vessel to the brain. [NIH] Structure-Activity Relationship: The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed
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together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Other factors contributing to structure-activity relationship include chemical reactivity, electronic effects, resonance, and inductive effects. [NIH] Subacute: Somewhat acute; between acute and chronic. [EU] 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] 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, atomic number 16, and atomic weight 32.066. It is found in the amino acids cysteine and methionine. [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] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Suppressive: Tending to suppress : effecting suppression; specifically : serving to suppress activity, function, symptoms. [EU] Surface-Active Agents: Agents that modify interfacial tension of water; usually substances that have one lipophilic and one hydrophilic group in the molecule; includes soaps, detergents, emulsifiers, dispersing and wetting agents, and several groups of antiseptics.
310
Staphylococcus aureus
[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]
Surgical Wound Infection: Infection occurring at the site of a surgical incision. [NIH] Suspensions: Colloids with liquid continuous phase and solid dispersed phase; the term is used loosely also for solid-in-gas (aerosol) and other colloidal systems; water-insoluble drugs may be given as suspensions. [NIH] Sweat: The fluid excreted by the sweat glands. It consists of water containing sodium chloride, phosphate, urea, ammonia, and other waste products. [NIH] Sweat Glands: Sweat-producing structures that are embedded in the dermis. Each gland consists of a single tube, a coiled body, and a superficial duct. [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] Syphilis: A contagious venereal disease caused by the spirochete Treponema pallidum. [NIH]
Systemic: Affecting the entire body. [NIH] Tachycardia: Excessive rapidity in the action of the heart, usually with a heart rate above 100 beats per minute. [NIH] Tachypnea: Rapid breathing. [NIH] 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] Tardive: Marked by lateness, late; said of a disease in which the characteristic lesion is late in appearing. [EU] Tea Tree Oil: Essential oil extracted from Melaleuca alternifolia (tea tree). It is used as a topical antimicrobial due to the presence of terpineol. [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] Terminator: A DNA sequence sited at the end of a transcriptional unit that signals the end of transcription. [NIH] Testicular: Pertaining to a testis. [EU] 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
Dictionary 311
characteristics. [NIH] Tetani: Causal agent of tetanus. [NIH] Tetanic: Having the characteristics of, or relating to tetanus. [NIH] Tetanus: A disease caused by tetanospasmin, a powerful protein toxin produced by Clostridium tetani. Tetanus usually occurs after an acute injury, such as a puncture wound or laceration. Generalized tetanus, the most common form, is characterized by tetanic muscular contractions and hyperreflexia. Localized tetanus presents itself as a mild condition with manifestations restricted to muscles near the wound. It may progress to the generalized form. [NIH] 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] 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] Thioredoxin: A hydrogen-carrying protein that participates in a variety of biochemical reactions including ribonucleotide reduction. Thioredoxin is oxidized from a dithiol to a disulfide during ribonucleotide reduction. The disulfide form is then reduced by NADPH in a reaction catalyzed by thioredoxin reductase. [NIH] Thoracic: Having to do with the chest. [NIH] Threonine: An essential amino acid occurring naturally in the L-form, which is the active form. It is found in eggs, milk, gelatin, and other proteins. [NIH] Threshold: For a specified sensory modality (e. g. light, sound, vibration), the lowest level (absolute threshold) or smallest difference (difference threshold, difference limen) or intensity of the stimulus discernible in prescribed conditions of stimulation. [NIH] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] Thrombocytes: Blood cells that help prevent bleeding by causing blood clots to form. Also called platelets. [NIH] Thrombolytic: 1. Dissolving or splitting up a thrombus. 2. A thrombolytic agent. [EU] Thrombomodulin: A cell surface glycoprotein of endothelial cells that binds thrombin and serves as a cofactor in the activation of protein C and its regulation of blood coagulation. [NIH]
Thrombophlebitis: Inflammation of a vein associated with thrombus formation. [NIH] Thrombosis: The formation or presence of a blood clot inside a blood vessel. [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] 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] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH]
312
Staphylococcus aureus
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] Tone: 1. The normal degree of vigour and tension; in muscle, the resistance to passive elongation or stretch; tonus. 2. A particular quality of sound or of voice. 3. To make permanent, or to change, the colour of silver stain by chemical treatment, usually with a heavy metal. [EU] Tonsillitis: Inflammation of the tonsils, especially the palatine tonsils. It is often caused by a bacterium. Tonsillitis may be acute, chronic, or recurrent. [NIH] 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] Topoisomerase inhibitors: A family of anticancer drugs. The topoisomerase enzymes are responsible for the arrangement and rearrangement of DNA in the cell and for cell growth and replication. Inhibiting these enzymes may kill cancer cells or stop their growth. [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] Toxin: A poison; frequently used to refer specifically to a protein produced by some higher plants, certain animals, and pathogenic bacteria, which is highly toxic for other living organisms. Such substances are differentiated from the simple chemical poisons and the vegetable alkaloids by their high molecular weight and antigenicity. [EU] Toxoid: The material resulting from the treatment of toxin in such a way that the toxic properties are inactivated whilst the antigenic potency remains intact. [NIH] Trachea: The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi. [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] Translating: Conversion from one language to another language. [NIH] Translation: The process whereby the genetic information present in the linear sequence of ribonucleotides in mRNA is converted into a corresponding sequence of amino acids in a protein. It occurs on the ribosome and is unidirectional. [NIH] Translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Translocation: The movement of material in solution inside the body of the plant. [NIH] 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]
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Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Treatment Failure: A measure of the quality of health care by assessment of unsuccessful results of management and procedures used in combating disease, in individual cases or series. [NIH] Trichuris: A genus of nematode worms comprising the whipworms. [NIH] Trivalent: Having a valence of three. [EU] 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, 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 marker: A substance sometimes found in an increased amount in the blood, other body fluids, or tissues and which may mean that a certain type of cancer is in the body. Examples of tumor markers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and gastrointestinal tract cancers), and PSA (prostate cancer). Also called biomarker. [NIH] Tumor Necrosis Factor: Serum glycoprotein produced by activated macrophages and other mammalian mononuclear leukocytes which has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. It mimics the action of endotoxin but differs from it. It has a molecular weight of less than 70,000 kDa. [NIH] 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] Tunica: A rather vague term to denote the lining coat of hollow organs, tubes, or cavities. [NIH]
Typhimurium: Microbial assay which measures his-his+ reversion by chemicals which cause base substitutions or frameshift mutations in the genome of this organism. [NIH] Ulcer: A localized necrotic lesion of the skin or a mucous surface. [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] Ureters: Tubes that carry urine from the kidneys to the bladder. [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]
Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] Urinary tract: The organs of the body that produce and discharge urine. These include the kidneys, ureters, bladder, and urethra. [NIH] Urinary tract infection: An illness caused by harmful bacteria growing in the urinary tract.
314
Staphylococcus aureus
[NIH]
Urine: Fluid containing water and waste products. Urine is made by the kidneys, stored in the bladder, and leaves the body through the urethra. [NIH] Urogenital: Pertaining to the urinary and genital apparatus; genitourinary. [EU] Urokinase: A drug that dissolves blood clots or prevents them from forming. [NIH] Uterus: The small, hollow, pear-shaped organ in a woman's pelvis. This is the organ in which a fetus develops. Also called the womb. [NIH] Vaccination: Administration of vaccines to stimulate the host's immune response. This includes any preparation intended for active immunological prophylaxis. [NIH] Vaccine: 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] Valves: Flap-like structures that control the direction of blood flow through the heart. [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] Vancomycin Resistance: Nonsusceptibility of bacteria, especially gram-positive cocci, to the action of vancomycin, an inhibitor of cell wall synthesis. [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vasodilators: Any nerve or agent which induces dilatation of the blood vessels. [NIH] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH] 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] 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] Vertebral: Of or pertaining to a vertebra. [EU] Vesicular: 1. Composed of or relating to small, saclike bodies. 2. Pertaining to or made up of vesicles on the skin. [EU] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] 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] Virologist: A specialist of the study of viruses and viral disease. [NIH]
Dictionary 315
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] 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] War: Hostile conflict between organized groups of people. [NIH] Warts: Benign epidermal proliferations or tumors; some are viral in origin. [NIH] Wetting Agents: A surfactant that renders a surface wettable by water or enhances the spreading of water over the surface; used in foods and cosmetics; important in contrast media; also with contact lenses, dentures, and some prostheses. Synonyms: humectants; hydrating agents. [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] Windpipe: A rigid tube, 10 cm long, extending from the cricoid cartilage to the upper border of the fifth thoracic vertebra. [NIH] Wound Healing: Restoration of integrity to traumatized tissue. [NIH] Wound Infection: Invasion of the site of trauma by pathogenic microorganisms. [NIH] Xenograft: The cells of one species transplanted to another species. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH] Yeasts: A general term for single-celled rounded fungi that reproduce by budding. Brewers' and bakers' yeasts are Saccharomyces cerevisiae; therapeutic dried yeast is dried yeast. [NIH] Zoonoses: Diseases of non-human animals that may be transmitted to man or may be transmitted from man to non-human animals. [NIH] Zygote: The fertilized ovum. [NIH] Zymogen: Inactive form of an enzyme which can then be converted to the active form, usually by excision of a polypeptide, e. g. trypsinogen is the zymogen of trypsin. [NIH]
317
INDEX A Abdominal, 247, 273, 274, 283, 294, 295, 296 Abdominal Pain, 247, 273, 274, 296 Abortion, 247, 314 Abscess, 22, 36, 97, 106, 111, 117, 145, 163, 170, 176, 179, 247, 272 Acantholysis, 247, 295 Acatalasia, 247, 257 Acceptor, 247, 276, 285, 293 Acclimatization, 174, 247 Acetic Acids, 204, 247 Acetylgalactosamine, 247, 276 Acetylglucosamine, 247, 276 Acremonium, 247, 258 Actin, 43, 247 Actinomycosis, 217, 247 Acute renal, 247, 278 Acyl, 52, 104, 169, 247 Acyl Carrier Protein, 104, 247 Acylation, 37, 248 Adaptation, 14, 247, 248, 290 Adjustment, 248 Aerobic, 44, 60, 178, 183, 248, 280, 291, 301 Aerosol, 19, 248, 310 Affinity, 11, 14, 24, 37, 78, 206, 248, 285, 306 Agar, 72, 73, 86, 92, 115, 137, 192, 209, 248, 263, 280 Agarose, 248, 280 Agonists, 163, 166, 169, 170, 212, 213, 248 Agranulocytosis, 127, 248, 271 Airway, 19, 41, 45, 75, 101, 117, 248 Alanine, 8, 58, 96, 196, 248 Algorithms, 248, 255 Alimentary, 165, 248 Alkaline, 203, 249, 256 Alkaloid, 50, 249, 254, 260 Allergen, 20, 249 Allergic Rhinitis, 139, 249, 277 Allograft, 249, 291 Alpha Particles, 249, 302 Alpha-Defensins, 249, 264 Alpha-helix, 249, 284 Alternative medicine, 222, 249 Alveoli, 249, 301, 314 Amber, 249, 281
Amino acid, 11, 23, 30, 45, 163, 167, 168, 170, 180, 185, 186, 196 Amino Acid Sequence, 11, 168, 170, 180, 185, 186, 249, 250, 274 Amino-terminal, 180, 249 Ammonia, 190, 249, 275, 310 Amphetamines, 249, 260 Amplification, 30, 68, 69, 73, 89, 198, 211, 249 Anaerobic, 59, 60, 218, 249, 270, 277, 280, 304, 308 Anaesthesia, 250, 281 Anal, 114, 250, 272 Analog, 53, 200, 250, 259 Analogous, 13, 207, 250, 312 Anaphylatoxins, 250, 261 Anergy, 250, 309 Anesthesia, 248, 250, 266 Anesthetics, 131, 250 Animal model, 7, 22, 27, 30, 33, 34, 38, 56, 250 Anions, 250, 283, 305 Annealing, 250, 298 Anorexia, 249, 250, 274 Anthrax, 14, 44, 250 Antibacterial, 9, 13, 26, 31, 32, 38, 51, 52, 60, 96, 102, 150, 151, 153, 164, 165, 169, 175, 181, 182, 184, 192, 197, 203, 204, 207, 250, 259, 280, 292, 294, 307, 309, 314 Antibiogram, 70, 89, 113, 146, 250 Anticoagulant, 251, 300 Antifungal, 175, 251, 306 Antigen-Antibody Complex, 251, 261 Antigen-presenting cell, 251, 264 Anti-infective, 11, 179, 251, 279, 306 Anti-Infective Agents, 11, 251 Anti-inflammatory, 40, 55, 186, 251, 275, 304 Anti-Inflammatory Agents, 186, 251 Antineoplastic, 251, 306 Antioxidant, 251, 273, 293 Antiseptic, 102, 251 Antiserum, 251 Antitoxin, 14, 251 Antiviral, 14, 251, 282, 295 Anus, 250, 251, 255, 260, 295 Apoptosis, 5, 81, 94, 116, 135, 142, 143, 251, 257
318
Staphylococcus aureus
Applicability, 49, 183, 252 Aqueous, 162, 193, 219, 252, 253, 263, 268, 279, 284 Archaea, 252, 288 Arginine, 196, 250, 252, 291, 313 Aromatic, 209, 252 Arterial, 252, 280, 300 Arteries, 252, 255, 262, 288 Arteritis, 216, 252 Artery, 252, 255, 262, 301 Arthroplasty, 130, 252 Articular, 117, 252 Aseptic, 252, 266 Aspiration, 15, 252 Assay, 4, 27, 37, 57, 60, 63, 69, 73, 89, 90, 91, 110, 111, 115, 134, 166, 177, 194, 198, 252, 304, 313 Astringents, 252, 288 Atopic, 54, 118, 124, 153, 185, 252 Atopic Eczema, 124, 252 Attenuation, 85, 212, 252 Autoantibodies, 19, 25, 56, 252 Autoantigens, 252 Autoimmune disease, 15, 25, 196, 252 Autolysis, 57, 61, 71, 81, 92, 96, 252 Autonomic, 247, 252, 262, 295 Autonomic Nervous System, 252, 262, 295 B Bacillus, 6, 16, 43, 82, 173, 175, 177, 190, 196, 206, 212, 218, 250, 253, 298 Bacterial Infections, 9, 35, 52, 56, 163, 182, 184, 197, 201, 203, 204, 211, 217, 234 Bacterial Physiology, 248, 253 Bacterial Proteins, 188, 253 Bacterial toxin, 54, 213, 251, 253 Bactericidal, 7, 19, 26, 40, 45, 58, 61, 67, 79, 94, 104, 165, 175, 192, 193, 203, 253, 270, 292 Bacteriocins, 173, 253 Bacteriophage, 72, 166, 188, 253, 304, 312, 315 Bacteriostatic, 105, 165, 253, 270 Bacterium, 11, 13, 23, 29, 37, 166, 170, 171, 196, 207, 208, 214, 253, 261, 278, 312 Base, 15, 19, 48, 50, 72, 94, 177, 253, 264, 273, 274, 283, 294, 310, 313 Basement Membrane, 253, 270, 284 Basophils, 248, 253, 276, 285 Benign, 253, 277, 291, 315 Benzyl Alcohol, 208, 253 Berberine, 153, 254 Beta-Defensins, 254, 264
Beta-Lactam Resistance, 37, 87, 95, 118, 254 Beta-Lactamases, 8, 51, 254, 280, 309 Beta-sheet, 9, 254 Bilateral, 105, 254 Bile, 254, 273, 286 Biliary, 254, 257 Biliary Tract, 254, 257 Binding Sites, 8, 63, 254 Bioavailability, 33, 35, 254 Biochemical, 5, 16, 20, 24, 25, 37, 43, 50, 52, 178, 198, 205, 210, 211 Biochemical reactions, 254, 311 Biofilms, 7, 8, 17, 40, 42, 51, 125, 254 Biological response modifier, 254, 282 Biological therapy, 254, 276 Biomarkers, 41, 254 Biophysics, 9, 125, 254 Biopsy, 219, 254, 270 Biopterin, 255, 291 Biotechnology, 39, 51, 57, 100, 151, 152, 153, 204, 207, 222, 229, 255 Bioterrorism, 14, 27, 43, 48, 255 Biotypes, 255, 277 Bladder, 255, 300, 313, 314 Blister, 25, 255, 295 Blood Coagulation, 24, 255, 256, 272, 304, 311 Blood Coagulation Factors, 255 Blood Glucose, 255, 278 Blood pressure, 255, 280, 289, 306 Blood vessel, 255, 256, 257, 258, 259, 268, 271, 278, 286, 296, 306, 308, 311, 314 Blot, 26, 255 Body Fluids, 187, 254, 255, 256, 267, 291, 306, 308, 313 Bone Marrow, 255, 271, 277, 286 Bowel, 250, 255, 265, 269, 283, 284, 296 Bowel Movement, 255, 265 Bradykinin, 255, 292, 297 Branch, 164, 243, 255, 286, 294, 301, 307, 311 Breakdown, 255, 258, 265, 273 Breeding, 204, 256 Broad-spectrum, 16, 26, 175, 256, 258, 292 Bromcresol Purple, 209, 256 Bronchioles, 249, 256, 301 Bronchoalveolar Lavage, 28, 45, 256 Bronchoalveolar Lavage Fluid, 28, 45, 256 Bullous, 24, 256 Burns, 38, 184, 207, 256 Burns, Electric, 256
Index 319
Bypass, 24, 48, 256 C Cadmium, 58, 92, 256 Cadmium Poisoning, 256 Calcium, 11, 256, 259, 261, 301, 306 Capsular, 18, 20, 22, 36, 56, 59, 67, 71, 74, 86, 87, 89, 91, 92, 95, 99, 162, 181, 205, 206 Capsules, 22, 256, 274 Carbohydrate, 36, 178, 181, 256, 275, 276, 292, 298 Carbon Dioxide, 44, 87, 256, 272, 274, 303 Carboxypeptidases, 8, 256 Carcinogenic, 256, 282, 300 Cardiac, 127, 168, 256, 268, 285, 290 Cardiovascular, 16, 135, 201, 216, 256, 257, 262 Cardiovascular System, 257, 262 Carrier State, 140, 257 Case report, 106, 117, 129, 257, 271 Case series, 45, 257 Caspase, 94, 257 Catalase, 78, 107, 108, 247, 257 Catalytic Domain, 24, 257 Catheter, 3, 107, 138, 151, 166, 234, 257 Cations, 257, 283 Caustic, 257, 306 Cefotiam, 61, 257 Cell Adhesion, 30, 257 Cell Adhesion Molecules, 30, 257 Cell Death, 251, 257 Cell Differentiation, 257, 306 Cell Division, 4, 174, 253, 257, 276, 287, 289, 297, 300, 305 Cell membrane, 10, 173, 175, 257, 264, 283, 296, 298 Cell proliferation, 200, 257, 306 Cell Respiration, 258, 303 Cell Size, 79, 258, 272 Cell Survival, 258, 276 Cellobiose, 258 Cellular metabolism, 175, 258 Cellulitis, 104, 218, 258 Cellulose, 165, 258, 273, 297 Central Nervous System, 247, 248, 249, 253, 258, 260, 262, 273, 275, 277 Central Nervous System Infections, 258, 277 Cephalosporins, 37, 180, 254, 258 Cerebrospinal, 258, 286, 291 Cerebrospinal fluid, 258, 286, 291 Cerebrovascular, 216, 258
Cerebrum, 258 Chemokines, 22, 32, 258 Chemotactic Factors, 258, 261 Chemotherapy, 33, 74, 156, 180, 204 Chest Pain, 234, 259 Child Care, 218, 259 Chin, 259, 288 Chlorophyll, 259, 268, 273 Cholera, 23, 259, 305, 314 Chromatin, 251, 259, 269 Chromosomal, 13, 48, 49, 59, 62, 94, 249, 259, 297 Chromosome, 30, 77, 81, 86, 132, 259, 261, 277, 279, 285, 305 Chronic Disease, 215, 259 Chymopapain, 259, 266 Cicatrix, 259, 284 Cicatrix, Hypertrophic, 259, 284 Cilastatin, 259, 280 Ciprofloxacin, 26, 34, 60, 61, 63, 71, 72, 79, 81, 82, 84, 102, 107, 156, 259 CIS, 43, 259, 280 Citric Acid, 162, 193, 259 Citrus, 259 Clathrin, 259, 260, 268 Clindamycin, 44, 88, 96, 116, 259 Clinical trial, 4, 19, 28, 33, 157, 158, 173, 229, 260, 267, 290, 301, 302 Clone, 23, 48, 58, 68, 73, 77, 81, 86, 94, 101, 260 Cloning, 28, 37, 58, 64, 65, 78, 84, 176, 196, 207, 255, 260 Clot Retraction, 260, 297 Coagulation, 21, 24, 192, 255, 260, 278, 297, 311 Coated Vesicles, 259, 260, 268 Coca, 260 Cocaine, 12, 260, 262 Coenzyme, 72, 260, 284 Cofactor, 208, 260, 300, 311 Coliphages, 253, 260 Collagen, 11, 171, 201, 249, 253, 260, 271, 274, 284, 297, 300 Colloidal, 260, 268, 305, 310 Colon, 260, 284 Combinatorial, 35, 261 Commensal, 127, 261 Communicable disease, 261, 313 Comorbidity, 141, 261 Complement, 18, 45, 56, 61, 62, 250, 261, 274, 287, 297 Computational Biology, 229, 261
320
Staphylococcus aureus
Concomitant, 127, 261 Conjugated, 261 Conjugation, 48, 261 Conjunctiva, 262, 282 Conjunctivitis, 107, 262, 277 Connective Tissue, 40, 255, 258, 260, 262, 265, 272, 273, 274, 284, 286, 300, 304 Connective Tissue Cells, 262 Consciousness, 262, 264, 266 Constipation, 262, 296 Consultation, 215, 262 Consumption, 262, 265, 274, 294 Contamination, 40, 88, 162, 173, 192, 193, 216, 234, 262, 304 Contraindications, ii, 262 Coordination, 17, 262 Cornea, 78, 152, 262, 284 Corneum, 262, 269 Coronary, 262, 288 Coronary Thrombosis, 262, 288 Cortex, 262, 293 Corticosteroids, 186, 262, 275 Crack Cocaine, 12, 262 Cranial, 262, 263, 277, 295, 307 Craniocerebral Trauma, 262, 277 Crossing-over, 263, 303 Crystallization, 37, 167, 189, 190, 191, 263 Culture Media, 198, 248, 263 Curative, 263, 311 Cutaneous, 68, 185, 186, 202, 208, 217, 218, 250, 263 Cutaneous Fistula, 217, 263 Cyanogen Bromide, 173, 263 Cyclic, 35, 263, 277, 292 Cysteine Synthase, 141, 263 Cystine, 11, 263 Cytokine, 7, 12, 36, 54, 81, 172, 213, 263, 306 Cytokinesis, 47, 263 Cytoplasm, 251, 253, 257, 263, 267, 269, 304 Cytoskeleton, 75, 117, 263 Cytotoxic, 35, 38, 263, 306 Cytotoxicity, 26, 263 D Day Care, 204, 263 Decision Making, 16, 263 Defense Mechanisms, 10, 214, 263 Defensins, 173, 186, 249, 254, 263 Deferoxamine, 166, 264 Degenerative, 264, 278 Dehydration, 169, 259, 264
Deletion, 37, 79, 251, 264 Dementia, 216, 264 Denaturation, 264, 298 Dendrites, 264, 291 Dendritic, 12, 264 Dendritic cell, 12, 264 Density, 42, 178, 264, 272, 285, 292, 298 Dental Care, 215, 264 Dental Caries, 217, 264 Dental Instruments, 17, 264 Dental Materials, 17, 264 Depolarization, 67, 264, 306 Depressive Disorder, 216, 264, 285 Dermal, 218, 264 Dermatitis, 21, 54, 118, 153, 172, 185, 234, 264 Dermatologist, 223, 264 Dermatology, 24, 101, 109, 118, 123, 144, 150, 151, 218, 265 Dermis, 218, 265, 284, 310 Detergents, 265, 309 Deuterium, 265, 279 Developed Countries, 182, 265 Diabetes Mellitus, 216, 265, 275, 278 Diagnostic procedure, 161, 222, 265 Dialysate, 265 Dialyzer, 216, 265, 277 Diapedesis, 29, 265 Diarrhea, 88, 205, 213, 218, 234, 265, 269, 270, 273, 281 Diarrhoea, 265, 274 Diathesis, 19, 265 Digestion, 31, 48, 248, 254, 255, 265, 283, 286, 308 Digestive system, 159, 265 Digoxigenin, 105, 265 Dihydrotestosterone, 265, 303 Dilatation, 247, 265, 299, 301, 314 Diphtheria, 14, 217, 251, 265 Diphtheria Toxin, 14, 265 Diploid, 266, 297 Direct, iii, 7, 16, 17, 20, 33, 46, 55, 163, 180, 192, 199, 200 Disaccharides, 20, 53, 266 Discitis, 127, 266 Discrete, 24, 27, 39, 266 Discrimination, 66, 70, 266 Disease Vectors, 266, 282 Disinfectant, 162, 193, 266, 270 Dissection, 18, 266 Dissociation, 248, 266, 283 Distal, 30, 266, 301
Index 321
Distemper, 172, 266 Distemper Virus, Canine, 266 Dopamine, 260, 266, 291 Dose-dependent, 45, 266 Double-blind, 131, 267 Drug Delivery Systems, 39, 267 Drug Resistance, 39, 46, 67, 102, 103, 180, 197, 267 Drug Tolerance, 267, 312 Duct, 267, 304, 310 Dura mater, 267, 288, 294 Dyskinesia, 216, 267 Dysphoric, 264, 267 E Edema, 14, 267, 284 Effector, 247, 261, 267 Efficacy, 14, 15, 16, 17, 19, 21, 28, 33, 34, 35, 71, 84, 129, 151, 158, 203, 267, 280 Egg Yolk, 192, 267 Elastic, 267, 310 Elastin, 260, 267, 271 Elective, 93, 267 Electrocoagulation, 260, 267 Electrolysis, 163, 250, 257, 267 Electrolyte, 218, 267, 299, 306 Electron microscope, 23, 267 Electrophoresis, 41, 61, 63, 66, 69, 70, 71, 72, 76, 84, 89, 99, 107, 112, 121, 123, 268, 280 Embryo, 247, 257, 267, 268, 281, 293 Emollient, 268, 275, 292 Emphysema, 40, 268 Empyema, 114, 268 Emulsion, 268, 272 Enamel, 264, 268, 284 Encapsulated, 18, 87, 268 Endemic, 74, 88, 98, 138, 259, 268, 307 Endocardium, 268 Endogenous, 18, 135, 142, 186, 252, 255, 266, 268 Endosomes, 32, 268 Endothelial cell, 81, 95, 137, 268, 311 Endothelium, 265, 268, 291, 297 Endothelium-derived, 268, 291 Endotoxin, 268, 313 End-stage renal, 121, 268 Enteric bacteria, 53, 268 Enteritis, 172, 268, 271 Enterocolitis, 269 Enterocytes, 53, 127, 269 Enteropeptidase, 269, 313
Enterotoxins, 14, 68, 69, 85, 104, 111, 114, 139, 171, 210, 213, 269 Environmental Exposure, 19, 269 Environmental Health, 140, 228, 230, 269 Enzymatic, 20, 50, 249, 256, 257, 261, 264, 269, 271, 278, 288, 298 Enzyme Inhibitors, 190, 269, 297 Eosinophilia, 269, 271 Eosinophils, 248, 269, 276, 285 Epidemic, 14, 61, 70, 72, 74, 77, 84, 88, 89, 94, 97, 100, 150, 180 Epidemiologic Factors, 217, 269 Epidemiological, 19, 72, 76, 85, 87, 89, 99, 123, 269, 271 Epidermal, 269, 284, 315 Epidermis, 25, 30, 184, 209, 210, 247, 255, 262, 265, 269, 279, 284, 295, 299, 302, 308 Epidural, 117, 266, 269 Epithelial, 29, 53, 75, 254, 269, 276, 278, 284, 294 Epithelial Cells, 29, 75, 254, 269, 278, 284 Epithelium, 75, 117, 253, 268, 269, 283, 294 Epitope, 23, 162, 269 ERV, 230, 270 Erythromycin, 98, 128, 142, 270 Esophagus, 265, 270, 296, 308 Ethanol, 106, 165, 270, 271 Excipient, 184, 270 Excisional, 38, 270 Excitation, 249, 270, 272, 291 Exfoliation, 30, 270 Exogenous, 32, 135, 268, 270 Exotoxin, 44, 167, 270, 308 Expiration, 270, 303 Expiratory, 270 Expiratory Reserve Volume, 270 Extensor, 270, 301 Extracellular Matrix, 77, 168, 189, 202, 262, 270, 271, 293 Extracellular Matrix Proteins, 168, 270 Extracellular Space, 270, 271 Exudate, 219, 271 F Family Planning, 229, 271 Fasciitis, 218, 271 Fat, 178, 255, 271, 285, 292, 304, 306, 310 Fatal Outcome, 271, 302 Fatty acids, 271, 275, 306 Febrile, 138, 271 Feline Panleukopenia, 266, 271 Fermentation, 33, 50, 182, 271, 273, 304 Fibrin, 21, 24, 255, 260, 271, 296, 297, 311
322
Staphylococcus aureus
Fibrinogen, 21, 24, 80, 81, 168, 171, 206, 271, 297, 311 Fibrinolytic, 21, 271 Fibroblasts, 81, 262, 271 Fibronectins, 271, 272 Fibrosarcoma, 271, 272 Fibrosis, 18, 101, 124, 132, 138, 272 Fistulas, 217, 272 Fixation, 200, 272 Flatus, 272, 273 Flow Cytometry, 76, 272 Fluorescence, 39, 48, 50, 69, 90, 111, 272 Fluorescent Dyes, 272 Folate, 50, 272, 273 Folic Acid, 272 Follicles, 194, 273 Food Preservatives, 175, 273 Foodborne Illness, 216, 273 Forearm, 255, 271, 273 Fosfomycin, 16, 114, 273 Fovea, 272, 273 Frameshift, 273, 313 Frameshift Mutation, 273, 313 Friction, 223, 273 Fructose, 273, 276 Fungi, 165, 173, 175, 177, 186, 203, 251, 261, 273, 276, 288, 289, 307, 315 Fungus, 173, 258, 273 G Gallate, 112, 144, 273 Gallbladder, 247, 254, 265, 273 Ganglia, 247, 273, 291, 295 Gangrene, 29, 218, 247, 273 Gangrenous, 218, 273, 305 Gas, 29, 249, 256, 270, 272, 273, 274, 279, 291, 292, 310, 314 Gas exchange, 274, 314 Gas Gangrene, 29, 274 Gastrin, 274, 279 Gastroenteritis, 218, 274, 304 Gastrointestinal, 175, 213, 217, 255, 256, 259, 262, 266, 270, 273, 274, 292, 309, 313, 314 Gastrointestinal tract, 213, 270, 274, 313 Gelatin, 263, 274, 275, 311 Gene Expression, 15, 54, 59, 68, 81, 84, 206, 207, 274 Gene Fusion, 60, 274 Genetic Code, 274, 292 Genetic Engineering, 255, 260, 274 Genetic testing, 274, 298
Genetics, 10, 17, 18, 32, 38, 52, 207, 261, 274 Genital, 259, 274, 283, 314 Genitourinary, 274, 291, 314 Genomics, 6, 43, 74, 176, 274 Genotype, 67, 121, 274, 296 Gestation, 274, 295 Gingivitis, 217, 274 Gland, 97, 171, 213, 214, 275, 286, 287, 294, 300, 304, 305, 308, 310, 311 Glomerular, 275 Glomeruli, 275 Glomerulonephritis, 19, 121, 123, 275 Glucocorticoid, 54, 275 Glucose, 255, 258, 265, 275, 276, 277, 282 Glucose Intolerance, 265, 275 Glucuronic Acid, 275, 278 Glutamic Acid, 273, 275, 291, 300 Glutamine, 67, 97, 190, 275 Glycerol, 44, 72, 275, 296 Glycerophospholipids, 275, 296 Glycine, 52, 62, 79, 249, 275, 287, 291, 305 Glycopeptides, 25, 49, 76, 80, 83, 87, 124, 275 Glycoprotein, 271, 275, 276, 279, 284, 290, 311, 313 Glycosaminoglycans, 53, 271, 275, 300 Glycoside, 20, 266, 276 Glycylglycine, 72, 276 Goblet Cells, 269, 276 Gonorrhea, 217, 276 Governing Board, 276, 299 Gp120, 276, 295 Graft, 276, 279 Grafting, 276, 281 Gram-Negative Bacteria, 28, 41, 53, 276 Gram-Positive Bacteria, 45, 53, 61, 136, 157, 180, 185, 205, 209, 276, 292, 294, 310 Gram-Positive Cocci, 276, 314 Granulocyte, 131, 276 Granuloma, 19, 217, 276, 286 Granuloma Inguinale, 217, 276, 286 Grasses, 273, 276, 278 Growth factors, 23, 276 Guanylate Cyclase, 277, 292 Gyrase, 13, 26, 41, 63, 78, 80, 81, 86, 89, 93, 277, 292 H Haemophilus, 184, 211, 219, 277 Haemophilus influenzae, 184, 211, 219, 277 Hair follicles, 194, 265, 277, 308
Index 323
Haploid, 277, 297 Haptens, 248, 277 Hay Fever, 249, 277 Headache, 234, 277, 282, 313 Headache Disorders, 277 Health Services, iv, 4, 15, 230, 277 Health Status, 216, 277 Hematogenous, 54, 92, 146, 277 Hematologic malignancies, 143, 277 Hematology, 135, 219, 277 Heme, 173, 277 Hemocytes, 173, 277 Hemodialysis, 146, 216, 265, 277, 284 Hemoglobin, 173, 277, 285 Hemolysins, 210, 278 Hemolysis, 269, 278 Hemolytic, 71, 98, 218, 271, 278, 281 Hemorrhage, 263, 267, 277, 278, 308 Hemostasis, 21, 278 Heparin, 53, 278 Hepatitis, 27, 217, 278 Hepatocytes, 278 Herbicides, 183, 278 Heredity, 274, 278 Heterodimers, 39, 278 Heterogeneity, 48, 76, 248, 278 Heterotrophic, 273, 278 Hip Prosthesis, 141, 278 Histamine, 250, 278 Histidine, 91, 156, 181, 278 Histocompatibility, 200, 213, 279 HLA, 46, 54, 56, 60, 279 Homeostasis, 40, 78, 279 Homologous, 26, 72, 79, 87, 170, 194, 263, 279, 290, 305, 310 Hormone, 185, 186, 262, 274, 279, 288, 304, 306, 310, 311 Horny layer, 269, 279 Host, 5, 7, 10, 12, 14, 15, 17, 18, 19, 21, 22, 23, 27, 29, 31, 32, 34, 36, 38, 39, 40, 41, 44, 45, 46, 54, 59, 62, 67, 75, 168, 171, 173, 179, 186, 189, 199, 200, 202, 206, 210, 212, 217, 218 Hybrid, 59, 260, 279 Hybridization, 66, 89, 90, 105, 177, 183, 211, 213, 279, 292, 308 Hybridomas, 14, 279 Hydration, 17, 279 Hydrogen, 11, 247, 253, 256, 257, 263, 264, 265, 270, 279, 285, 289, 291, 292, 293, 301, 311 Hydrogen Peroxide, 257, 279, 285
Hydrogenation, 279, 302 Hydrolysis, 8, 254, 258, 265, 279, 295, 296, 300, 302, 313 Hydrophilic, 265, 279, 309 Hydrophobic, 196, 265, 275, 279, 283, 285 Hydroxylysine, 260, 279 Hydroxyproline, 249, 260, 279 Hyperreflexia, 279, 311 Hypersensitivity, 249, 279, 304 Hypertension, 277, 280 Hysterectomy, 146, 280 I Id, 29, 154, 235, 242, 244, 280 Idiopathic, 19, 280 Imipenem, 61, 259, 280 Immune function, 12, 280 Immunity, 12, 14, 28, 29, 56, 70, 186, 193, 194, 205 Immunocompromised, 21, 30, 218, 280 Immunodeficiency, 12, 68, 196, 234, 280 Immunodiffusion, 156, 248, 280 Immunoelectrophoresis, 248, 280 Immunofluorescence, 7, 280 Immunogenic, 202, 280 Immunoglobulin, 135, 158, 250, 280, 289 Immunohistochemistry, 55, 280 Immunologic, 36, 54, 56, 258, 278, 280 Immunologic Factors, 278, 280 Immunology, 8, 10, 27, 36, 46, 152, 156 Immunomodulator, 97, 280, 286 Immunophilins, 280, 306 Immunosuppressant, 280, 281, 306 Immunosuppressive, 29, 275, 281, 310 Impairment, 267, 281, 288 Impetigo, 25, 30, 93, 95, 202, 234, 281 Implantation, 168, 281 In situ, 51, 111, 281 Incision, 281, 283, 284, 310 Incisional, 218, 281 Incubated, 36, 191, 212, 281 Incubation, 174, 192, 281 Indicative, 281, 294, 314 Induction, 7, 36, 37, 42, 48, 49, 60, 80, 94, 98, 173, 174, 206, 281 Infancy, 112, 281 Infarction, 262, 281, 288 Infection Control, 14, 15, 216 Infectious Diarrhea, 218, 281 Infiltration, 7, 275, 282 Influenza, 27, 127, 204, 282 Infusion, 192, 282 Ingestion, 250, 256, 282, 298
324
Staphylococcus aureus
Inhalation, 44, 248, 282, 298 Initiation, 7, 13, 15, 33, 39, 47, 48, 174, 282, 306 Inner ear, 282, 294, 314 Inoculum, 22, 43, 282 Inorganic, 165, 282, 290, 306 Inositol, 29, 282 Insecticides, 183, 282 Insight, 9, 22, 24, 25, 29, 30, 45, 52, 55, 282 Intensive Care, 70, 84, 110, 113, 123, 126, 137, 140, 201, 282 Intensive Care Units, 70, 123, 201, 282 Interferon, 141, 282 Interferon-alpha, 282 Intermittent, 282, 286, 295 Internal Medicine, 14, 31, 49, 102, 134, 185, 277, 282 Interstitial, 256, 271, 282 Intervertebral, 266, 283 Intestinal, 53, 249, 269, 283, 294 Intestine, 255, 268, 270, 283, 284, 308 Intoxication, 165, 213, 283 Intraperitoneal, 4, 283 Intravascular, 166, 219, 283 Intravenous, 15, 92, 120, 135, 157, 158, 168, 185, 223, 234, 282, 283 Intrinsic, 95, 110, 248, 253, 283 Invasive, 38, 53, 137, 163, 164, 168, 170, 176, 179, 181, 280, 283 Invertebrates, 186, 266, 277, 283 Involution, 214, 283 Ion Channels, 35, 283 Ionization, 283 Ionizing, 49, 249, 269, 283 Ions, 50, 153, 162, 175, 193, 203, 253, 266, 267, 279, 283, 301 Iris, 262, 283, 301 Isomerases, 28, 280, 283 Isoprenoid, 28, 283 J Joint, 7, 22, 54, 127, 200, 252, 259, 278, 283 K Kb, 228, 283 Keloid, 223, 259, 284 Keratectomy, 105, 284 Keratin, 214, 284 Keratinocytes, 54, 284 Keratitis, 78, 102, 105, 107, 125, 152, 156, 284 Keratolytic, 264, 284 Kidney Failure, 268, 284 Kinetic, 17, 24, 50, 283, 284
L Labile, 261, 284 Laceration, 284, 311 Lactate Dehydrogenase, 87, 284 Lactation, 194, 214, 284 Laminin, 171, 253, 271, 284 Laparotomy, 144, 284 Large Intestine, 265, 283, 284, 303, 306 Lavage, 28, 45, 284 Laxative, 248, 284 Length of Stay, 131, 284 Lens, 105, 256, 284 Leprosy, 217, 284 Lethal, 14, 18, 34, 44, 51, 253, 265, 285 Leucine, 128, 285 Leukemia, 277, 285 Leukocytes, 12, 16, 56, 125, 253, 255, 258, 269, 282, 285, 313 Leukopenia, 266, 285 Levofloxacin, 102, 107, 111, 285 Library Services, 242, 285 Lidocaine, 253, 285 Life cycle, 273, 285 Ligands, 59, 150, 183, 257, 285 Ligation, 44, 285 Lincomycin, 259, 285 Linkage, 20, 24, 42, 46, 105, 258, 285 Lipid, 275, 285, 294 Lipid Peroxidation, 285, 294 Lipophilic, 285, 309 Lipopolysaccharide, 26, 131, 253, 276, 285 Lipoprotein, 276, 285 Liposomes, 42, 285 Lithium, 209, 285 Lithium Chloride, 209, 285 Liver, 123, 129, 139, 151, 247, 254, 265, 268, 273, 275, 278, 286 Liver Transplantation, 123, 286 Localization, 25, 30, 91, 280, 286 Localized, 24, 37, 38, 82, 168, 185, 202, 234, 247, 264, 265, 268, 272, 281, 284, 286, 293, 297, 304, 311, 313 Locomotion, 286, 297 Long-Term Care, 14, 140, 286 Loop, 13, 212, 286 Lucida, 284, 286 Lumbar, 266, 286 Lumbar puncture, 266, 286 Lung Transplantation, 28, 286 Lymph, 268, 286 Lymph node, 286
Index 325
Lymphatic, 205, 218, 268, 281, 286, 307, 311 Lymphatic system, 286, 307, 311 Lymphocyte, 5, 19, 172, 251, 286, 287 Lymphogranuloma Venereum, 276, 286 Lymphoid, 18, 55, 250, 262, 286, 287 Lymphoma, 277, 287 Lymphoproliferative, 200, 287 Lysine, 38, 279, 287, 313 Lysostaphin, 25, 82, 287 Lytic, 71, 79, 287, 305, 315 M Macrolides, 13, 33, 196, 287 Macrophage, 18, 75, 80, 117, 287 Major Histocompatibility Complex, 200, 213, 287 Malignancy, 287, 294 Malignant, 251, 271, 287, 291 Mammary, 75, 97, 171, 213, 287 Manic, 285, 287 Mannans, 273, 287 Mastitis, 87, 97, 98, 156, 171, 172, 181, 193, 194, 214, 255, 287, 305 Meat, 177, 178, 287 Mediastinitis, 138, 144, 287 Mediate, 16, 19, 29, 37, 49, 80, 213, 257, 266, 287 Mediator, 26, 287 MEDLINE, 229, 287 Meiosis, 287, 290, 310 Membrane Lipids, 287, 296 Membrane Proteins, 285, 288 Memory, 250, 264, 288 Meninges, 258, 263, 267, 288 Meningitis, 144, 288, 291 Menstruation, 187, 288 Mental, iv, 4, 159, 216, 228, 230, 235, 259, 264, 266, 288, 301 Mental Disorders, 159, 216, 288, 301 Mental Health, iv, 4, 159, 228, 230, 288, 301 Mercury, 175, 272, 288 Metabolite, 288, 299 Metastasis, 257, 288 Metastatic, 185, 288 Methicillin Resistance, 36, 42, 63, 73, 79, 80, 81, 85, 86, 96, 97, 101, 115, 123, 144, 288 Methionine, 43, 191, 288, 309 MI, 62, 97, 98, 118, 150, 167, 189, 190, 191, 192, 245, 288 Mice Minute Virus, 288, 294
Microbe, 5, 15, 27, 288, 312 Microbiological, 33, 115, 117, 172, 178, 288 Microcirculation, 289, 297 Microorganism, 173, 174, 175, 198, 260, 289, 294, 315 Micro-organism, 180, 264, 289, 305 Microscopy, 23, 39, 82, 96, 253, 289 Migration, 18, 32, 289 Mitosis, 47, 252, 289 Mobilization, 126, 289 Modification, 6, 28, 249, 274, 289 Molasses, 178, 289 Monitor, 4, 35, 47, 49, 289, 292 Monobactams, 204, 289 Monoclonal, 14, 53, 86, 91, 107, 162, 181, 188, 189, 201, 202, 279, 289 Monoclonal antibodies, 14, 53, 86, 91, 181, 189, 201, 202, 289 Monocyte, 116, 289 Monocytes, 40, 56, 135, 285, 290 Mononuclear, 56, 142, 271, 276, 289, 313 Morphological, 84, 210, 268, 273, 289 Morphology, 252, 277, 290 Mucins, 269, 276, 290, 304 Mucolytic, 256, 290 Mucosa, 41, 269, 290 Mucus, 205, 290 Multicenter study, 101, 290 Multidrug resistance, 46, 80, 200, 290 Multivalent, 203, 290 Mupirocin, 77, 82, 85, 117, 119, 129, 132, 133, 134, 140, 146, 151, 152, 183, 290 Musculoskeletal System, 290, 293 Myalgia, 282, 290 Myelography, 266, 290 Myeloid Cells, 18, 290 Myeloma, 53, 290 Myocarditis, 265, 290 Myocardium, 288, 290 N Naive, 22, 32, 37, 290 Nasal Cavity, 290 Nasal Mucosa, 41, 282, 290 Nasopharynx, 290, 291 Nausea, 274, 290 NCI, 1, 159, 227, 259, 290 Need, 3, 20, 34, 35, 39, 40, 46, 48, 168, 169, 176, 182, 213, 215, 218, 223, 236 Neisseria, 175, 219, 276, 291 Neisseria meningitidis, 219, 291 Neonatal, 84, 110, 120, 126, 137, 140, 291 Neoplasm, 291, 313
326
Staphylococcus aureus
Neoplastic, 279, 287, 291 Neopterin, 50, 291 Nerve, 250, 259, 264, 287, 291, 294, 299, 308, 312, 314 Nervous System, 216, 252, 258, 287, 291, 295, 302 Neurologic, 266, 291 Neuromuscular, 247, 291, 298 Neurons, 260, 264, 273, 291, 310 Neurophysiology, 264, 291 Neurotransmitter, 247, 249, 255, 266, 275, 278, 283, 291, 306, 309 Neutralization, 14, 135, 291 Neutrons, 249, 291, 302 Neutrophil, 19, 58, 83, 84, 94, 137, 291 Neutrophil Infiltration, 19, 291 Nisin, 51, 291 Nitric Oxide, 12, 54, 291 Nitrogen, 50, 178, 190, 204, 211, 248, 249, 270, 272, 275, 292, 313 Norfloxacin, 80, 93, 292 Nosocomial, 14, 41, 49, 52, 63, 72, 77, 86, 88, 152, 164, 168, 185, 197, 201 Nuclear, 261, 292 Nuclei, 249, 262, 274, 289, 291, 292, 301 Nucleic acid, 168, 172, 174, 177, 194, 196, 198, 211, 212, 213, 274, 279, 292, 302, 308 Nucleic Acid Hybridization, 279, 292 Nucleic Acid Probes, 90, 177, 292 Nucleus, 251, 253, 259, 263, 265, 269, 287, 289, 291, 292, 300, 301, 308 Nutritive Value, 178, 292 O Odour, 252, 292 Ofloxacin, 93, 102, 292 Ointments, 175, 292, 306 Oligo, 198, 292 Opacity, 264, 292 Operon, 68, 76, 83, 93, 97, 106, 293, 303 Ophthalmology, 102, 107, 272, 293 Opportunistic Infections, 198, 293 Oral Health, 293 Oral Hygiene, 234, 293 Oropharynx, 291, 293 Orthopaedic, 138, 146, 293 Osmosis, 293 Osmotic, 190, 293, 305 Ossification, 293 Osteoblasts, 7, 81, 94, 293 Osteogenesis, 11, 293 Osteomyelitis, 22, 60, 112, 127, 163, 168, 170, 171, 176, 179, 181, 185, 200, 206, 293
Osteoporosis, 11, 216, 293 Otolaryngology, 108, 132, 293 Overexpress, 45, 293 Oxacillin, 49, 61, 70, 72, 73, 82, 86, 87, 88, 89, 90, 93, 98, 206 Oxidation, 28, 247, 251, 263, 285, 293, 294 Oxidative Stress, 78, 87, 104, 293 Oxygen Consumption, 294, 303 P Pachymeningitis, 288, 294 Palliative, 294, 311 Palpation, 218, 294 Pancreas, 247, 254, 265, 294, 305, 313 Paneth Cells, 249, 269, 294 Papillomavirus, 27, 294 Par excellence, 14, 294 Parasite, 125, 294 Parasitic, 254, 294 Parvovirus, 127, 288, 294 Pathogenesis, 7, 10, 11, 12, 13, 19, 21, 22, 24, 26, 29, 30, 32, 34, 40, 43, 52, 54, 56, 62, 95, 156, 218, 294 Pathologic, 252, 254, 262, 279, 294, 301 Pathologic Processes, 252, 294 Pathologies, 208, 294 Pathophysiology, 19, 25, 218, 294 Patient Education, 234, 240, 242, 245, 294 Pefloxacin, 79, 98, 294 Pemphigus, 25, 247, 294 Penicillin, 8, 36, 37, 49, 51, 64, 67, 71, 78, 80, 82, 86, 87, 93, 95, 97, 98, 156, 183, 204 Penicillinase, 62, 78, 295 Pepsin, 178, 295 Peptide Fragments, 201, 295 Peptide T, 146, 295 Perforation, 82, 295 Pericarditis, 147, 295 Pericardium, 295 Perinatal, 84, 257, 295 Perineal, 185, 295 Perineum, 194, 295, 308 Periodontal disease, 217, 295 Periodontitis, 217, 275, 295 Perioperative, 139, 146, 295 Peripheral blood, 12, 54, 112, 142, 282, 295 Peripheral Nervous System, 291, 295, 309 Peritoneal, 3, 95, 101, 142, 151, 265, 283, 295 Peritoneal Cavity, 283, 295 Peritoneal Dialysis, 3, 95, 101, 142, 151, 265, 295 Peritoneum, 295, 296
Index 327
Peritonitis, 3, 21, 32, 44, 296 Phagocyte, 31, 296 Phagocytosis, 20, 28, 31, 58, 61, 87, 116, 131, 296 Phallic, 272, 296 Pharmaceutical Preparations, 258, 270, 274, 296 Pharmacodynamics, 126, 296 Pharmacokinetic, 34, 296 Pharmacologic, 250, 296, 312 Pharyngitis, 296, 304 Pharynx, 82, 132, 282, 290, 293, 296 Phenotype, 19, 25, 56, 62, 67, 91, 92, 130, 138, 164, 198, 199, 296 Pheromone, 34, 48, 194, 296 Phospholipases, 31, 296, 306 Phospholipids, 31, 84, 271, 282, 285, 287, 296 Phosphorus, 256, 296 Phosphorylated, 260, 296 Photocoagulation, 260, 296 Photodynamic therapy, 38, 296 Photosensitizer, 38, 296 Physical Examination, 217, 235, 297 Physiologic, 31, 288, 297, 302 Physiology, 6, 12, 26, 79, 183, 189, 202, 277, 291, 297, 309 Plague, 271, 297, 313 Plant Diseases, 268, 297 Plant Oils, 292, 297 Plasma cells, 250, 290, 297 Plasma protein, 297, 300, 305 Plasmid, 13, 16, 39, 47, 49, 51, 58, 61, 67, 70, 79, 81, 88, 92, 93, 99, 164, 193 Plasmin, 21, 297 Plasminogen, 21, 297 Plasminogen Activators, 21, 297 Platelet Activation, 16, 125, 297, 306 Platelet Aggregation, 16, 250, 292, 297 Platelets, 16, 59, 95, 125, 292, 297, 311 Platinum, 286, 298 Pleated, 284, 298 Pleural, 287, 298 Pneumonia, 9, 62, 63, 80, 106, 114, 127, 131, 158, 185, 202, 206, 262, 298 Polyethylene, 165, 298 Polymerase, 66, 67, 68, 69, 298, 303, 306 Polymerase Chain Reaction, 66, 67, 68, 69, 298 Polymers, 4, 6, 254, 298, 300 Polymorphic, 60, 65, 73, 89, 298
Polymorphism, 70, 86, 90, 107, 115, 298, 304 Polymyxin, 123, 152, 298 Polyneuritis, 265, 298 Polyposis, 104, 298 Population Dynamics, 30, 298 Postmenopausal, 293, 299 Postoperative, 138, 152, 299 Postsynaptic, 299, 306 Post-translational, 180, 299 Potassium, 299, 306 Potentiate, 39, 299 Potentiating, 39, 299 Potentiation, 299, 306 Practice Guidelines, 230, 299 Precipitation, 177, 299 Preclinical, 33, 299 Precursor, 266, 267, 269, 291, 297, 299, 300, 313 Presumptive, 73, 192, 299 Prevalence, 35, 51, 54, 89, 124, 126, 137, 139, 171, 201, 212, 299 Prickle, 247, 284, 299 Probe, 90, 112, 176, 177, 198, 299 Prodrug, 184, 299 Progeny, 261, 299 Progression, 12, 250, 299 Progressive, 41, 218, 257, 264, 267, 276, 283, 297, 299, 313 Projection, 263, 299 Proline, 78, 260, 279, 300 Promoter, 6, 42, 48, 59, 73, 81, 155, 207, 266, 300 Pronase, 192, 193, 300 Prone, 168, 223, 300 Prophase, 290, 300, 310 Prophylaxis, 134, 139, 196, 197, 300, 314 Proportional, 48, 300 Prospective Studies, 4, 300 Prospective study, 138, 141, 300 Prostate, 254, 300, 313 Prosthesis, 136, 200, 300 Protease, 10, 25, 30, 68, 83, 100, 192, 300 Protein C, 14, 107, 166, 249, 253, 260, 284, 285, 300 Protein Conformation, 249, 284, 300 Protein S, 14, 33, 183, 255, 265, 270, 274, 300, 304, 311 Protein Subunits, 14, 300 Proteoglycan, 53, 300 Proteolytic, 40, 49, 57, 153, 189, 202, 261, 269, 271, 297, 300
328
Staphylococcus aureus
Prothrombin, 24, 300, 311 Protocol, 16, 69, 112, 132, 301 Protons, 249, 279, 283, 301, 302 Protozoa, 261, 288, 289, 301, 307 Proximal, 266, 290, 301 Pseudomonas, 9, 16, 18, 38, 40, 152, 162, 173, 175, 177, 180, 193, 194, 208, 211, 217, 223 Psoriasis, 54, 301 Psychiatry, 101, 111, 272, 301, 314 Psychic, 288, 301 Public Health, 4, 10, 14, 16, 31, 152, 164, 178, 204, 230, 301 Public Policy, 229, 301 Pulmonary, 40, 92, 255, 256, 262, 284, 301, 310, 314 Pulmonary Emphysema, 40, 301 Pulsation, 214, 301 Pulse, 289, 301 Pupil, 262, 301 Purifying, 42, 170, 171, 190, 265, 301 Purines, 301, 305 Purulent, 147, 302 Pustular, 281, 302 Putrefaction, 273, 302 Pyogenic, 270, 293, 302, 305 Pyrimidines, 302, 305 Pyrophosphatases, 190, 302 Q Quinolones, 27, 42, 78, 80, 86, 96, 180, 302 R Rabies, 172, 302 Race, 289, 302 Radiation, 49, 269, 272, 283, 302, 315 Radioactive, 279, 281, 283, 289, 292, 302 Random Allocation, 302 Randomization, 28, 302 Randomized, 134, 158, 267, 302 Reagent, 86, 162, 206, 263, 302 Receptor, 5, 12, 18, 22, 25, 26, 32, 53, 54, 91, 156 Recombinant, 31, 33, 45, 163, 169, 170, 174, 176, 179, 189, 210, 212, 302, 303, 314 Recombinant Proteins, 31, 174, 303 Recombination, 64, 261, 303 Reconstitution, 27, 303 Rectum, 251, 255, 260, 265, 272, 273, 284, 300, 303 Red blood cells, 278, 303, 306 Reductase, 32, 60, 72, 144, 169, 190, 303, 311
Refer, 1, 261, 272, 273, 278, 286, 290, 291, 292, 303, 312 Refraction, 303, 307 Regeneration, 52, 303 Regimen, 208, 267, 303 Regulon, 6, 37, 63, 152, 303 Relapse, 7, 303 Reliability, 177, 303 Replicon, 206, 303 Repressor, 37, 44, 46, 49, 93, 100, 293, 303 Research Personnel, 47, 303 Respiration, 175, 256, 289, 303 Respiratory Physiology, 303, 314 Restoration, 303, 315 Retinoid, 207, 208, 303 Retrograde, 283, 303 Retrospective, 95, 107, 143, 304 Reversion, 51, 92, 304, 313 Rheumatism, 304 Rheumatoid, 22, 304 Rheumatoid arthritis, 22, 304 Rhinitis, 102, 304, 305 Ribonuclease, 55, 304 Ribosome, 304, 312 Ribotyping, 70, 89, 304 Rigidity, 297, 304 Risk factor, 3, 12, 19, 30, 101, 123, 124, 300, 304 Ristocetin, 304, 314 Rod, 253, 270, 277, 301, 304 Rotavirus, 27, 304 S Salicylate, 47, 304 Saliva, 133, 304 Salivary, 217, 265, 304, 313 Salivary glands, 217, 265, 304, 313 Salmonella, 7, 27, 53, 156, 162, 175, 177, 178, 193, 194, 204, 205, 216, 218, 234 Scarlet Fever, 217, 304 Scleroderma, 271, 304 Scleroproteins, 284, 304 Screening, 4, 7, 39, 64, 65, 72, 73, 90, 93, 166, 176, 182, 188, 192, 196, 199, 212, 213 Sebaceous, 265, 304, 305 Sebaceous gland, 265, 305 Secretion, 34, 42, 278, 284, 290, 305 Secretory, 52, 192, 249, 305 Segregation, 42, 171, 303, 305 Selenomethionine, 191, 305 Self Care, 216, 305 Semisynthetic, 259, 280, 289, 305 Senile, 293, 305
Index 329
Sensor, 49, 305 Sepsis, 10, 22, 26, 32, 36, 55, 144, 171, 202, 204, 305 Septic, 22, 26, 45, 123, 138, 163, 170, 176, 179, 185, 202, 206, 252, 305 Septicaemia, 305 Septicemia, 168, 172, 181, 305 Sequence Homology, 295, 305 Sequencing, 65, 66, 73, 148, 180, 298, 305 Serine, 24, 25, 30, 63, 68, 72, 83, 196, 247, 256, 263, 305, 313 Serologic, 56, 75, 305 Serotypes, 162, 181, 305 Serum, 55, 56, 77, 92, 156, 170, 171, 189, 202 Serum Albumin, 256, 305 Side effect, 254, 305, 312 Sigma Factor, 6, 10, 97, 306 Signal Transduction, 26, 49, 72, 93, 282, 306 Signs and Symptoms, 303, 306 Silver Compounds, 203, 306 Sirolimus, 28, 281, 306 Skeleton, 247, 283, 306 Skin graft, 306, 308 Skin Manifestations, 30, 306 Skull, 263, 294, 306, 310 Sludge, 177, 178, 306 Small intestine, 269, 279, 283, 306, 313 Smooth muscle, 214, 249, 250, 262, 278, 306, 309 Soaps, 179, 180, 306, 309 Sodium, 21, 209, 306, 310 Soft tissue, 38, 132, 218, 255, 271, 272, 274, 306 Solvent, 165, 270, 275, 293, 307 Soma, 307 Somatic, 14, 287, 289, 295, 307 Somatic cells, 287, 289, 307 Specialist, 31, 236, 307, 314 Species Specificity, 30, 307 Specificity, 18, 24, 30, 52, 74, 89, 136, 156, 177, 248, 307 Spectroscopic, 17, 51, 307 Spectrum, 22, 25, 32, 45, 58, 77, 173, 174, 186, 200, 202, 208 Sperm, 259, 307 Sphenoid, 294, 307 Sphincter, 214, 307 Spinal cord, 258, 267, 269, 288, 290, 291, 294, 295, 307 Spinous, 269, 284, 307
Spirochete, 307, 310 Spleen, 55, 286, 307 Sporadic, 61, 74, 88, 94, 132, 307 Spores, 282, 307 Stabilization, 24, 43, 307 Staphylocoagulase, 24, 307 Staphylococcal Infections, 16, 22, 36, 57, 151, 157, 164, 189, 205, 234, 308 Staphylococcal Scalded Skin Syndrome, 24, 308 Steady state, 17, 308 Steel, 153, 308 Stents, 40, 308 Sterilization, 17, 112, 165, 308 Steroids, 262, 275, 308 Stimulus, 270, 283, 308, 311 Stomach, 247, 265, 270, 274, 279, 284, 290, 295, 296, 306, 307, 308 Strand, 11, 26, 39, 298, 308 Streptococcal, 201, 218, 285, 308 Streptococci, 122, 204, 218, 281, 290, 304, 308 Streptococcus, 6, 9, 57, 61, 78, 96, 173, 175, 184, 196, 211, 218, 223, 234 Streptococcus pneumoniae, 57, 78, 113, 131, 137, 139, 184, 211, 219, 234, 308 Stress, 16, 57, 63, 78, 87, 96, 97, 106, 144, 217, 253, 274, 290, 293, 304, 308 Stringency, 177, 308 Stroke, 159, 216, 228, 308 Structure-Activity Relationship, 35, 308 Subacute, 281, 286, 309 Subarachnoid, 277, 309 Subclinical, 172, 214, 281, 309 Subcutaneous, 22, 218, 258, 267, 273, 309 Subspecies, 307, 309 Substance P, 150, 270, 288, 303, 304, 305, 307, 309 Substrate, 8, 11, 13, 24, 38, 50, 52, 167, 175, 190, 192, 257, 269, 283, 309 Substrate Specificity, 52, 309 Sulbactam, 58, 78, 309 Sulfur, 270, 288, 309 Superantigens, 5, 44, 54, 62, 89, 124, 309 Superinfection, 127, 309 Superoxide, 63, 77, 98, 152, 309 Suppression, 82, 96, 200, 309 Suppressive, 196, 309 Surface-Active Agents, 44, 309 Surfactant, 28, 310, 315 Surgical Wound Infection, 22, 185, 310 Suspensions, 16, 310
330
Staphylococcus aureus
Sweat, 265, 310 Sweat Glands, 265, 310 Symptomatic, 102, 310 Synaptic, 291, 306, 310 Synergistic, 208, 218, 310 Syphilis, 217, 310 Systemic, 19, 34, 44, 54, 56, 172, 200, 218, 255, 265, 281, 294, 304, 305, 310 T Tachycardia, 253, 310 Tachypnea, 253, 310 Tacrolimus, 28, 281, 310 Tardive, 216, 310 Tea Tree Oil, 151, 310 Teichoic Acids, 96, 276, 310 Teicoplanin, 80, 96, 101, 113, 117, 126, 180, 310 Temporal, 277, 294, 310 Terminator, 43, 310 Testicular, 40, 310 Testis, 310 Testosterone, 303, 310 Tetani, 311 Tetanic, 311 Tetanus, 14, 251, 311 Tetracycline, 59, 73, 98, 142, 206, 311 Therapeutics, 16, 110, 130, 181, 201, 311 Thermal, 92, 266, 291, 298, 311 Thioredoxin, 144, 311 Thoracic, 117, 135, 311, 315 Threonine, 52, 196, 295, 305, 311 Threshold, 217, 280, 311 Thrombin, 271, 297, 300, 311 Thrombocytes, 298, 311 Thrombolytic, 297, 311 Thrombomodulin, 300, 311 Thrombophlebitis, 163, 170, 176, 179, 311 Thrombosis, 300, 308, 311 Thrombus, 262, 281, 297, 311 Thymus, 286, 311 Thyroid, 216, 311 Tolerance, 26, 82, 97, 165, 275, 312 Tone, 293, 312 Tonsillitis, 304, 312 Tooth Preparation, 248, 312 Topical, 151, 252, 270, 279, 306, 310, 312 Topoisomerase inhibitors, 26, 312 Toxicity, 288, 304, 312 Toxicology, 8, 34, 35, 230, 312 Toxoid, 78, 251, 312 Trachea, 296, 311, 312 Transduction, 26, 49, 72, 93, 306, 312
Transfection, 255, 312 Translating, 113, 312 Translation, 190, 249, 270, 312 Translational, 180, 312 Translocation, 270, 312 Transmitter, 247, 266, 283, 287, 312 Transplantation, 15, 29, 129, 287, 312 Trauma, 15, 53, 88, 138, 175, 200, 205, 223, 313, 315 Treatment Failure, 147, 313 Trichuris, 192, 313 Trivalent, 203, 313 Trypsin, 172, 192, 193, 269, 313, 315 Tryptophan, 260, 313 Tuberculosis, Oral, 217, 313 Tularemia, 32, 217, 313 Tumor marker, 254, 313 Tumor Necrosis Factor, 80, 94, 313 Tumour, 142, 313 Tunica, 290, 313 Typhimurium, 53, 156, 194, 313 U Ulcer, 219, 258, 313 Unconscious, 250, 263, 280, 313 Universal Precautions, 216, 313 Ureters, 313 Urethra, 300, 313, 314 Urinary, 15, 38, 40, 118, 129, 166, 185, 212, 259, 274, 292, 294, 301, 313, 314 Urinary tract, 15, 38, 118, 129, 166, 185, 212, 294, 301, 313 Urinary tract infection, 15, 38, 118, 129, 185, 212, 294, 301, 313 Urine, 22, 118, 129, 212, 255, 292, 313, 314 Urogenital, 274, 276, 314 Urokinase, 186, 314 Uterus, 247, 280, 288, 314 V Vaccination, 171, 314 Vaccine, 16, 27, 56, 75, 119, 146, 168, 172, 181, 193, 194, 205, 213, 214, 301, 314, 315 Vagina, 187, 288, 314 Vaginal, 74, 146, 187, 314 Valves, 24, 40, 91, 127, 168, 314 Vancomycin Resistance, 59, 67, 76, 87, 93, 164, 314 Vascular, 40, 148, 168, 189, 202, 265, 268, 277, 281, 289, 291, 297, 311, 314 Vasodilators, 291, 314 Vector, 74, 207, 312, 314 Vein, 283, 292, 311, 314 Venereal, 291, 310, 314
Index 331
Venous, 40, 300, 314 Ventilation, 21, 314 Vertebral, 112, 314 Vesicular, 36, 252, 314 Veterinary Medicine, 27, 229, 314 Vibrio, 23, 156, 175, 204, 205, 216, 218, 259, 314 Vibrio cholerae, 204, 205, 218, 259, 314 Viral, 12, 14, 15, 27, 29, 172, 179, 218, 266, 272, 282, 291, 302, 312, 314, 315 Virologist, 29, 314 Virulence, 6, 10, 21, 32, 34, 36, 38, 42, 44, 46, 54, 55, 57, 65, 69, 70, 75, 77, 78, 79, 80, 84, 87, 88, 91, 92, 93, 95, 96, 100, 120, 141, 155, 156, 171, 185, 187, 221, 309, 312, 315 Virulent, 94, 96, 100, 128, 148, 315 Virus, 14, 27, 68, 162, 172, 177, 193, 196, 217, 234 Vitamin A, 282, 303, 315 Vitro, 4, 7, 11, 12, 16, 18, 27, 31, 32, 34, 35, 36, 38, 43, 45, 53, 54, 56, 58, 61, 64, 71, 73, 74, 75, 78, 79, 81, 93, 97, 98, 151, 182, 199
Vivo, 5, 7, 8, 9, 12, 15, 18, 31, 32, 34, 35, 36, 38, 43, 45, 52, 54, 71, 73, 74, 75, 79, 92, 182, 199 W War, 5, 84, 315 Warts, 172, 315 Wetting Agents, 309, 315 White blood cell, 250, 276, 281, 285, 286, 287, 289, 290, 291, 297, 315 Whole cell vaccine, 181, 315 Windpipe, 296, 311, 315 Wound Healing, 257, 259, 290, 315 Wound Infection, 22, 114, 116, 136, 181, 185, 202, 218, 315 X Xenograft, 250, 315 X-ray, 17, 39, 50, 52, 167, 183, 189, 190, 191, 272, 290, 292, 315 Y Yeasts, 186, 273, 296, 315 Z Zoonoses, 302, 315 Zygote, 262, 315 Zymogen, 24, 300, 315
332
Staphylococcus aureus
