Streptococcus - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

STREPTOCOCCUS A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R E FERENCES J AMES...

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STREPTOCOCCUS 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., 1960Streptococcus: 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: 0-597-84639-1 1. Streptococcus-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.

Copyright Notice If a physician wishes to copy limited passages from this book for patient use, this right is automatically granted without written permission from ICON Group International, Inc. (ICON Group). However, all of ICON Group publications have copyrights. With exception to the above, copying our publications in whole or in part, for whatever reason, is a violation of copyright laws and can lead to penalties and fines. Should you want to copy tables, graphs, or other materials, please contact us to request permission (E-mail: [email protected]). ICON Group often grants permission for very limited reproduction of our publications for internal use, press releases, and academic research. Such reproduction requires confirmed permission from ICON Group International, Inc. The disclaimer above must accompany all reproductions, in whole or in part, of this book.

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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 streptococcus. 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 STREPTOCOCCUS ....................................................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Streptococcus ................................................................................ 5 E-Journals: PubMed Central ....................................................................................................... 61 The National Library of Medicine: PubMed ................................................................................ 94 CHAPTER 2. NUTRITION AND STREPTOCOCCUS ........................................................................... 143 Overview.................................................................................................................................... 143 Finding Nutrition Studies on Streptococcus ............................................................................. 143 Federal Resources on Nutrition ................................................................................................. 146 Additional Web Resources ......................................................................................................... 147 CHAPTER 3. ALTERNATIVE MEDICINE AND STREPTOCOCCUS..................................................... 149 Overview.................................................................................................................................... 149 National Center for Complementary and Alternative Medicine................................................ 149 Additional Web Resources ......................................................................................................... 165 General References ..................................................................................................................... 167 CHAPTER 4. DISSERTATIONS ON STREPTOCOCCUS....................................................................... 169 Overview.................................................................................................................................... 169 Dissertations on Streptococcus .................................................................................................. 169 Keeping Current ........................................................................................................................ 171 CHAPTER 5. PATENTS ON STREPTOCOCCUS ................................................................................. 173 Overview.................................................................................................................................... 173 Patents on Streptococcus ........................................................................................................... 173 Patent Applications on Streptococcus........................................................................................ 201 Keeping Current ........................................................................................................................ 231 CHAPTER 6. BOOKS ON STREPTOCOCCUS ..................................................................................... 233 Overview.................................................................................................................................... 233 Book Summaries: Federal Agencies............................................................................................ 233 Book Summaries: Online Booksellers......................................................................................... 235 Chapters on Streptococcus ......................................................................................................... 236 CHAPTER 7. PERIODICALS AND NEWS ON STREPTOCOCCUS ....................................................... 241 Overview.................................................................................................................................... 241 News Services and Press Releases.............................................................................................. 241 Newsletter Articles .................................................................................................................... 243 Academic Periodicals covering Streptococcus............................................................................ 244 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 247 Overview.................................................................................................................................... 247 NIH Guidelines.......................................................................................................................... 247 NIH Databases........................................................................................................................... 249 Other Commercial Databases..................................................................................................... 251 The Genome Project and Streptococcus ..................................................................................... 251 APPENDIX B. PATIENT RESOURCES ............................................................................................... 255 Overview.................................................................................................................................... 255 Patient Guideline Sources.......................................................................................................... 255 Finding Associations.................................................................................................................. 259 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 261 Overview.................................................................................................................................... 261 Preparation................................................................................................................................. 261 Finding a Local Medical Library................................................................................................ 261 Medical Libraries in the U.S. and Canada ................................................................................. 261

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ONLINE GLOSSARIES................................................................................................................ 267 Online Dictionary Directories ................................................................................................... 267 STREPTOCOCCUS DICTIONARY ........................................................................................... 269 INDEX .............................................................................................................................................. 351

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FORWARD In March 2001, the National Institutes of Health issued the following warning: "The number of Web sites offering health-related resources grows every day. Many sites provide valuable information, while others may have information that is unreliable or misleading."1 Furthermore, because of the rapid increase in Internet-based information, many hours can be wasted searching, selecting, and printing. Since only the smallest fraction of information dealing with streptococcus 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 streptococcus, 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 streptococcus, 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 streptococcus. 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 streptococcus, 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 streptococcus. The Editors

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From the NIH, National Cancer Institute (NCI): http://www.cancer.gov/cancerinfo/ten-things-to-know.

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CHAPTER 1. STUDIES ON STREPTOCOCCUS Overview In this chapter, we will show you how to locate peer-reviewed references and studies on streptococcus.

The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and streptococcus, 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 “streptococcus” (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: •

Streptococcus Milleri: A Cause of Pyogenic Liver Abscess Source: Journal of the National Medical Association. 93(7-8): 276-277. July-August 2001. Contact: Available from National Medical Association. 1012 Tenth Street, NW, Washington, DC 20001. (202) 347-1895, ext. 267. Website: www.NMAnet.org. Summary: Anemia, leukocytosis (high levels of white blood cells in the blood), elevated abnormal liver function enzymes, hypoalbuminemia (low levels of protein in the blood), fever, and right upper quadrand abdominal pain are common signs and symptoms of liver abscesses. Mortality is high: 100 percent without treatment, and 50 to 65 percent with medical treatment. The bacteria Streptococcus milleri has been found to be associated with liver abscesses significantly more frequently than any other streptococci. S. milleri is also a common cause of liver abscess in patients with Crohn's disease. This

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article reports a case of S. milleri in a 47 year old patient with a history of hypertension, alcohol abuse, and tobacco smoking. The authors stress that increased awareness of S. milleri has come from better isolation of Streptococci species. The clinical importance of this awareness is that S. milleri is resistant to metronidazole. Therefore, patients with liver abscesses who receive metronidazole may not respond if S. milleri is the infecting organism. Effective antibiotics include ampicillin, erythromycin, clindamycin, and the cephalosporins. 1 figure. 1 table. 3 references. •

Prognosis of Streptococcus Pneumoniae-Induced Hemolytic Uremic Syndrome Source: Pediatric Nephrology. 16(4): 362-365. April 2001. Contact: Available from Springer-Verlag. Service Center Secaucus, 44 Hartz Way, Secaucus, NJ 07094. (201) 348-4033. Summary: Streptococcus pneumoniae induced hemolytic uremic syndrome (HUS) is known to be a severe acute disease leading to death in one third of cases, but data regarding the long term followup are lacking. This article reports on a series of 11 patients with HUS induced by the bacteria Streptococcus pneumoniae; all patients had meningitis and pneumonia. Among 9 patients with a severe acute infectious disease, 3 died from meningitis (infection of the meninges, or outer membranes of the brain) and 1 from neurological sequelae after a partial recovery of renal (kidney) function. The mean duration of dialysis was 32 days in patients with acute renal failure (ARF) who survived the acute infectious period. Cortical necrosis (tissue death) was documented in five of six kidney specimens. Among the 7 surviving patients, 5 developed end stage renal disease (ESRD) between 4 and 17 years later. The authors note that S. pneumoniae induced HUS is a rare disease, and they recommend the use of a registry of patients, in order to follow prospectively a larger number of patients. 1 table. 21 references.

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Acute Otitis Media: Management and Surveillance in an Era of Pneumococcal Resistance-A Report from the Drug-Resistant Streptococcus Pneumoniae Therapeutic Working Group Source: Pediatric Infectious Disease Journal. 18(1): 1-9. January 1999. Contact: Available from Lippincott Williams and Wilkins. P.O. Box 350, Hagerstown, MD 21740-0350. Website: www.lww.com. Summary: This article summarizes the report of a therapeutic working group that was convened to provide consensus recommendations for the management of acute otitis media (AOM) and the surveillance of drug resistant Streptococcus pneumoniae (DRSP). Five areas were addressed, considering published and unpublished data from the scientific literature and from the experts present. Oral amoxicillin should remain the first line antimicrobial agent for treating AOM. In view of the increasing prevalence of DRSP, the safety of amoxicillin at higher than standard dosages and evidence that higher dosages of amoxicillin can achieve effective middle ear fluid concentrations, an increase in the dosage used for empiric treatment from 40 to 45 mg per kg per day to 80 to 90 mg per kg per day is recommended. For patients with clinically defined treatment failure after 3 days of therapy, useful alternative agents include oral amoxicillin clavulanate, cefuroxime axetil and intramuscular ceftriaxone. Many of the 13 other FDA approved otitis media drugs lack good evidence for efficacy against DRSP. Currently local surveillance data for pneumococcal resistance that are relevant for the clinical management of AOM are not available from most areas in the U.S. Recommendations to improve surveillance include establishing criteria for setting susceptibility breakpoints for clinically appropriate antimicrobials to ensure relevance for treating AOM, testing

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middle ear fluid or nasal swab isolates in addition to sterile site isolates and testing of drugs that are useful in treating AOM. The authors stress that these recommendations are intended to provide a framework for appropriate clinical and public health responses to this problem. 4 tables. 59 references. (AA-M). •

Streptococcus Mutans, Early Childhood Caries and New Opportunities Source: JADA. Journal of the American Dental Association. 130(12): 1787-1792. December 1999. Summary: This commentary article, written by the director of the National Institute of Dental and Craniofacial Research, discusses the prevalence of early childhood caries (cavities) and the role of Streptococcus mutans (a caries promoting bacteria). The author begins by reviewing epidemiological data that shows dental caries are at epidemic proportions among lower income children. The author contends that the condition of early childhood caries (ECC) results from a complication combination of factors, including human and microbial genetics, microbial ecology, and the complexities of pathogen, host, and environment interactions. One section describes the S. mutans bacteria in some detail, then discusses other factors related to caries susceptibility, including bottle habits, early dietary habits, and malnutrition. The author then turns to prevention strategies, including antimicrobial therapy, the oral application of genetically engineered antibodies, and fluoridation. Research studies continue to investigate the associations among strains of S. mutans, parent-child transmission, and susceptibility to ECC. The author reminds readers that educational interventions, combined with regular preventive care, can go a long way in helping to prevent ECC. One sidebar offers three resources through which readers can obtain additional information. 1 table. 25 references.

Federally Funded Research on Streptococcus The U.S. Government supports a variety of research studies relating to streptococcus. 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 streptococcus. 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 streptococcus. The following is typical of the type of information found when searching the CRISP database for streptococcus:

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Healthcare projects are funded by the National Institutes of Health (NIH), Substance Abuse and Mental Health Services (SAMHSA), Health Resources and Services Administration (HRSA), Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDCP), Agency for Healthcare Research and Quality (AHRQ), and Office of Assistant Secretary of Health (OASH).

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Project Title: AGE ASSOCIATED CHANGES IN B LYMPHOCYTE FUNCTION Principal Investigator & Institution: Bondada, Subbarao A.; Professor; Microbiology Immunology, and Molecular Genetics; University of Kentucky 109 Kinkead Hall Lexington, Ky 40506 Timing: Fiscal Year 2002; Project Start 01-AUG-1986; Project End 31-JUL-2006 Summary: (provided by applicant): Immune responses to pneumococcal polysaccharide antigens are important for protection against pneumococcal infections but are absent in neonates and are reduced in the aged. Using Pnu-Imune vaccine that is made up of 23 serotypes of pneumococcal polysaccharides and TNP-Ficoll, two type 2 thymus independent (TI)-2 antigens, we have shown that neonates and the aged have an accessory cell deficiency in addition to their B-cell defects. This deficiency is overcome by supplementation with accessory cell derived cytokines, IL-1 and IL-6. The neonatal macrophages make less IL-l and IL-12 in response to TI stimuli such as TNP-Ficoll and lipopolysaccharide. This application is directed at testing the molecular basis of accessory cell defects leading to B-cell unresponsiveness to polysaccharide antigens in the neonates and the aged. It is hypothesized that toll-like receptor (TLR) expression and/or TLR signaling pathways may be defective in neonatal macrophages. Also, B-cell macrophage interactions required for TI responses may involve the macrophage derived cytokine BLyS and its B-cell receptors, TACI and BCMA, which may be dysfunctional in the neonate. Towards this goal five specific aims are proposed. 1. To determine if the defect in neonatal and the aged macrophages is limited to IL-1 and IL-12 or is a general property of macrophages in the neonate and the aged. 2. To test the hypothesis that the molecular nature of the defect in neonatal accessory cells that contributes to TI-2 unresponsiveness is in TLR expression or in the TLR signaling pathway. 3. To determine the role of dendritic cells in neonatal and aged unresponsiveness to polysaccharide antigens. 4. To determine if the restoration of neonatal B-cell responses to polysaccharides is due to their ability to signal neonatal B-cells/accessory cells via TLR signaling pathway. 5. To determine the role of monocyte-derived TNF like molecule, BLyS and its receptor (TACI), in B-cell-macrophage interactions and to determine if neonates or aged have defects in this ligand receptor system. Results from these studies should in future allow us to design and test agents that can augment accessory cell function and in turn to develop more effective polysaccharide vaccines for the neonate and the aged. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ALCOHOL, APOPTOSIS AND LUNG OPPORTUNISTIC INFECTION Principal Investigator & Institution: D'souza, Nympha B.; Medicine; University of Kentucky 109 Kinkead Hall Lexington, Ky 40506 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2008 Summary: (provided by applicant): The long-term objective of this proposal is to elucidate the mechanisms by which chronic alcohol (EtOH) ingestion predisposes the host to pulmonary infections. In spite of years of extensive research, the precise mechanisms whereby pulmonary infections develop in alcoholics are not fully elucidated. Therefore, novel approaches need to be undertaken to further our understanding of how these infections develop. Based on the gaps in our understanding of why alcoholics have a greater propensity to acquire lung infections, and the recently discovered pivotal role for apoptosis in health and diseases, the project proposes to test three hypotheses: 1) EtOH alters basal rate of lung apoptosis. The primary targets of this EtOH effect are the alveolar macrophages (AM) and during an infection, also infiltrating

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cells; 2) EtOH alters apoptosis of lung immune cells by modulating the amount and interaction of apoptotic protein adapters; and 3) The EtOH-induced apoptotic death of lung cells overwhelms the inherent clearance mechanisms in the lung. As a result, the uncleared dead cells undergo secondary, necrosis leading to persistent lung inflammation. Accordingly, the proposal has four specific aims: 1) to determine the temporal relationship between EtOH-altered rate of lung apoptosis and severity of infection; 2) to determine the lung cell types undergoing apoptosis following EtOH ingestion and infection; 3) to determine the mechanism(s) underlying EtOH effects on lung immune cell apoptosis and 4) to determine the temporal relationship between EtOH-induced alterations in the kinetics of lung apoptosis and the ability of AM to remove apoptotic cells. To achieve these goals, mice will be fed EtOH for various periods and infected with Streptococcus pneumoniae (SP). These mice will be used to assess the apoptotic and pathologic state of the lung. To evaluate the potential deleterious effects of EtOH enhanced lung cell apoptosis, the lung propensity, to clear an SP infection, will be evaluated in presence and absence of apoptosis inhibitors. By applying biochemical, molecular and cell biology techniques, the steps of apoptotic signaling pathway where EtOH acts will be established. Finally, the project will determine if there is a correlation between EtOH-induced apoptosis, decreased phagocytosis, and increased inflammation. The project will provide essential and novel information to: 1) broaden our understanding of how EtOH increases the hosts' susceptibility to pulmonary infections and 2) pave the way to developing therapeutic interventions to control pulmonary infections. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ALTERNATIVE APPROACHES FOR E FAECALIS INFECTIONS Principal Investigator & Institution: Murray, Barbara E.; Professor of Medicine; Internal Medicine; University of Texas Hlth Sci Ctr Houston Box 20036 Houston, Tx 77225 Timing: Fiscal Year 2002; Project Start 01-AUG-2000; Project End 31-MAY-2005 Summary: (Adapted from the Applicant's Abstract): Enterococci are the 3rd most common cause of endocarditis, behind streptococci and staphylococci, and the 2nd or 3rd most common cause of hospital acquired infections, with Enterococcus faecalis being the predominant species isolated. Antimicrobial resistance likely facilitates the establishment of enterococci in nosocomial infections and certainly makes it more difficult to successfully treat patients, particularly those with endocarditis. The central hypothesis of this project is that by better understanding enterococci, new therapeutic or preventative modalities can be developed. Work during a previously funded grant identified and characterized a number of antigen encoding genes; a polysaccharide gene cluster (epa) that appears to influence virulence in mice; different adherence phenotypes, and a gene, ace, that appears to be involved in adherence; and a gene locus with homology to the accessory gene regulator (agr) locus of staphylococci that is involved in expression of an E. faecalis gelatinase and a serine protease that also influence virulence in mice. In this application, the investigators propose (1) to verify that the E. faecalis agr-like locus regulates gelE and sprE and determine if all are important for virulence; to investigate the distribution of these genes among E. faecalis; and to determine how the enterococcal agr-like locus is regulated and if it, like the staphylococcal agr, regulates other genes. They also plan (2) to test the hypothesis that Ace (a newly described adhesin for collagen of enterococci) is the cause of the adherence we have reported and is important for virulence; to explore the regulation of Ace production; and to determine the distribution and effect of variations in ace, if Ace elicits an antibody response in humans (using recombinant Ace and patient sera)

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infected by E. faecalis and if antibody made during infection, or antibody to recombinant Ace, is protective. In their third specific aim, they plan (3) to establish if the polysaccharide gene cluster is the cause of a recently described mucoid phenotype, to study its regulation, and to further test its contribution to adherence to foreign material, virulence and protection. They will also explore a system for constructing non-polar deletion mutants using counter-selection based on their prior work with the E. faecalis pyr genes, and to explore additional assays that would help to avoid lethality models. The investigators hope that results from this work will provide solid leads in the quest for methods to prevent, control, or combat E. faecalis infections. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ANALYSIS OF MGA PROTEIN FROM THE STREPTOCOCCUS PYOGENES Principal Investigator & Institution: Mciver, Kevin S.; Assistant Professor; Microbiology; University of Texas Sw Med Ctr/Dallas Dallas, Tx 753909105 Timing: Fiscal Year 2002; Project Start 30-SEP-2001; Project End 31-MAY-2005 Summary: (provided by applicant): The group A streptococcus (Streptococcus pyogenes, GAS) is a bacterial pathogen of enormous medical importance to humans, causing a variety of disease syndromes that range in severity from minor to lifethreatening. Mga is a DNA-binding protein of GAS that activates the transcription of several key virulence genes in response to changing environmental conditions, likely through interactions with other regulatory components in the cell. The Mga regulon encodes products essential for the survival of GAS in the host, including the antiphagocytic M protein, M-like immunoglobulin binding proteins, the secreted inhibitor of complement, a collagen-like protein, and a C5a peptidase. Thus, Mga provides an excellent model system to study global regulatory networks involved in GAS pathogenesis and how they may interact. However, we currently know very little about Mga, including what domains of the protein are critical for its function and how environmental signals control the Mga regulon. The specific aims of this project are: (1) To identify domains of Mga involved in DNA-binding and characterize their role in targeting specific promoters; (2) To determine a consensus Mga binding element for each of the known promoter sites through identification of specific Mga/nucleotide interactions; (3) To investigate whether domains of Mga interact directly with other bacterial components to transduce environmental signals (i.e., is Mga a two-component response regulator?); (4) To identify additional factors required for the environmental regulation of the Mga regulon and assess their role in global virulence regulation. An attractive feature of this proposal is our ability to study Mga both as a purified protein in vitro and as a native molecule in its GAS background. As such, we will be able to thoroughly address key questions of GAS pathogenesis associated closely with the environmental regulation of the Mga regulon. The overall objectives of this proposal are (A) to undertake a structure/function analysis of Mga and determine the mechanisms by which this key GAS virulence regulator contributes to streptococcal disease, and (B) improve our general understanding of regulatory pathways that broadly control virulence in these gram-positive pathogens. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ANTIBODY RESPONSE TO PNEUMOCOCCAL CARRIAGE IN HUMANS Principal Investigator & Institution: Mccool, Tera L.; Microbiology; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104

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Timing: Fiscal Year 2003; Project Start 01-JUN-2003; Project End 31-MAY-2006 Summary: (provided by applicant): An analysis of the immune response to pneumococcal proteins expressed during carriage in humans may reveal potential protein vaccine candidates. Half of the subjects in an experimental model of human carriage became colonized for 27-122 days; the other subjects were naturally resistant to colonization by the type 23F pneumococcus. IgG antibodies that recognized a 22 kD band (subsequently identified as the truncated N-terminus of pneumococcal surface protein A (PspA)) appeared after inoculation with pneumococcus in colonized subjects (6 of 7), while in all uncolonized subjects (7 of 7), PspA-specific antibodies were present prior to inoculation, suggesting a correlation between presence of PspA-specific IgG and resistance to colonization. The human serum and secretory antibody response to PspA was further elucidated by ELISA. This proposal examines the potential for PspA as a vaccine candidate against pneumococcal colonization and utilizes rational vaccine design based on the susceptibility to carriage in humans to identify novel vaccine candidates as well as to evaluate previously described vaccine antigens. In addition, the conservation of PspA expression in clinical isolates of pneumococcus will be examined to determine the effectiveness of a protein vaccine based soley on PspA. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ANTI-INFECTIVES WITH MULTI-DOMAIN RIBOSOMAL BINDING 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 15-JUN-2001; Project End 31-MAY-2003 Summary: Resistance to macrolide antibiotics has increased at alarming rates in recent years, driving the need to develop new and more effective antibiotics. The long term objective of this proposal is to develop a novel 16-membered macrolide antibiotic that is active against erythromycin-resistant Streptococcus pneumoniae and other Gram positive pathogens and which can be produced at reasonable cost. The proposed compound is designed to exhibit its potency through the novel mechanism of synergistic multi-domain ribosomal binding. Consequently, the compound should not induce macrolide resistance and evade all known efflux mechanisms that confer macrolide resistance. Phase I is a proof of principle project to produce a small series of derivatives of a 16- membered macrolide that is a readily available fermentation product, and determine whether the derivatives bind to domain II of the ribosomes and exhibit increased potency against macrolide-resistant strains. Phase II Specific Aims will be to optimize the derivatives to achieve oral bioavailability. Lead compounds will be examined in vitro and in animals for efficacy, toxicity and pharmacokinetics with the intent of advancing one or more to clinical development. PROPOSED COMMERCIAL APPLICATION: Clinical development candidates could be commericialized as antiinfective agents only after approval by the appropriate regulatory authorities. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: B7 COSTIMULATION RESPONSE TO EXTRACELLULAR BACTERIA Principal Investigator & Institution: Snapper, Clifford M.; Professor; Henry M. Jackson Fdn for the Adv Mil/Med Rockville, Md 20852 Timing: Fiscal Year 2002; Project Start 01-JUL-2000; Project End 31-MAR-2005 Summary: (Adapted from the Applicant's Abstract): Infections with extracellular, polysaccharide (PS)-encapsulated, bacteria represent a major source of morbidity and mortality in the U.S. Increasing antibiotic resistance to these agents, makes their control

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by immunotherapeutic means more compelling. Induction of PS- and protein-specific Ig play major roles in immunity to these bacteria. Preliminary results, using a model grampositive extracellular bacterium, Streptococcus pneumoniae (strain R36A), indicate that both PS- and protein-specific humoral responses to R36A are T cell-dependent and B7 ligand-dependent. Modulating B7 ligand interactions has therapeutic potential for modifying the ongoing immune response and for vaccine development, yet few studies have examined the role of these interactions during the T cell-dependent immune response to bacterial pathogens. This proposal will examine the role of B7 interactions during primary and memory Ig isotype responses to the PS and protein components of R36A. CD28 and CTLA-4 function will be examined using genetically deficient mice and blocking antibodies with the working hypothesis that these molecules differentially regulate the progression of the anti-PS and anti-protein response and that they may be useful targets for modifying this in vivo immune response, both at the initiation stage and subsequent to immunization. The individual roles of B7-1 and B7-2 will also be examined, and the specific APCs that provide B7-1 vs. B7-2-mediated costimulation will be identified using adoptive transfer experiments in genetically deficient mice. These experiments will provide insight into the mechanism of why B7-1 vs. B7-2 blockade differentially influences the R36A response. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BACTERIAL CONJUGATE VACCINES Principal Investigator & Institution: Madhi, Shabir; Univ of Witwaterstrand Johannesburg, Timing: Fiscal Year 2002; Project Start 01-JUN-2002; Project End 31-MAY-2007 Summary: Evaluation of quantitative and qualitative antibody responses to Streptococcus pneumoniae and Haemophilus influenzae type b conjugate vaccines The vertical transmission of HIV-1 infection from mother to infant can be reduced by at least two-thirds using simple perinatal anti-retroviral (ARV) drug regimens. Nevertheless, at least 10-12% of children born to HIV-1 infected mothers will still be HIV-1 infected. The management of these children through anti-retroviral treatment (ART) and prophylaxis against common opportunistic pathogens has been successful in developed countries. Implementation of such an intervention in resource-constrained countries will only be possible through novel strategies. Maj or causes of morbidity and mortality in HIV-1 infected children are infection by Pneumocystis carinii and bacteria, specifically Streptococcus pneumoniae and Haemophilus influenzae type b (Hib). Prophylaxis against these pathogens includes co-trirnoxazole and the new conjugate vaccines. This project will allow for an evaluation of the effectiveness of cotrimoxazole prophylaxis in HIV-1 infected children and its impact on selecting for antibiotic-resistant bacteria. Furthermore, the impact of ART on the immunogenicity of the conjugated pneumococcal and Hib vaccines will be evaluated in 250 HIV-1 infected children receiving ART and 125 who are not receiving ART at the time of their primary series of vaccines. These children will also be compared to HIV uninfected infants, born to seronegative (n = 125) and seropositive (n = 125) mothers. Both quantitative and qualitative antibody responses to these vaccines will be evaluated. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: BACTERIAL GENE EXPRESSION IN MODEL ORAL BIOFILMS Principal Investigator & Institution: Jacques, Nicholas A.; Principal Research Scientist; Institute of Dental Research 2 Chalmers St Sydney,

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Timing: Fiscal Year 2001; Project Start 20-SEP-1999; Project End 31-JUL-2004 Summary: It is now recognised that the transition of microbial species from a free-living, suspended or planktonic state to a component of an adherent community involves fundamental behavioural change. Both dental caries and periodontal diseases are essentially dependent on the polymicrobial plaque that develops with increasing complexity after the initial colonization of salivary components that coat the tooth surface. While there has been extensive analysis of the growth of dental plaque organisms as mixed communities in the planktonic state, to date there is little knowledge of interactions between adherent bacteria. The proposed studies will employ two powerful and complementary new technologies to monitor changes in gene expression occurring during initial colonisation and maturation of a model biofilm. Recognition of the factorial expansion of complexity in polymicrobial systems limits detailed analysis to two key microorganisms, Streptococcus gordonii as a major early coloniser of the acquired salivary pellicle and Streptococcus mutans which is strongly implicated as a major pathogen initiating dental caries. Both organisms can be genetically manipulated. The technique of In Biofilm Expression Technology (IBET) will enable comprehensive analysis of new gene expression patterns during biofilm formation on saliva-coated hydroxyapatite while Proteome analysis will facilitate recognition of altered protein profiles, particularly at the cell surface. Structural and time course analysis of altered gene expression patterns in situ will be enhanced by Confocal Laser Scanning Microscopy. Regulatory mechanisms relating to surface adhesins, the influence of extracellular sugar polymers, the response to unfavourable environments including acidic conditions and to the activity of key enzyme activities will be a focus. These parameters are highly pertinent and are the subject of study at the Institute. This program of research will provide essential data necessary for a therapeutic strategy aimed at the establishment and maintenance of a non-pathogenic dental plaque. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BACTERIAL VACCINE ANTIGEN DISCOVERY Principal Investigator & Institution: Paoletti, Lawrence C.; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2004; Project Start 01-APR-2004; Project End 31-MAR-2007 Summary: (provided by applicant): New directions in bacterial vaccine discovery may arise from studies of host-microbe interactions, particularly through the use of a newly described technology: the dynamic in vitro attachment and invasion system (DIVAS). DIVAS was developed to study bacterial attachment and invasion with cells held at specific and controlled conditions of growth, metabolism, and nutrient levels. Results from experiments performed with DIVAS and group B Streptococcus (GBS) type III strains substantiated earlier findings that capsular polysaccharide is not critical for invasion of respiratory epithelial cells. Moreover, GBS invaded these cells only when held at a fast as opposed to a relatively slower rate of growth and they expressed several proteins solely under growth conditions conducive for invasion. In this proposal, we seek to test the hypothesis that GBS proteins involved with invasion of eukaryotic cells are new and important targets of protective immunity. GBS is a major cause of neonatal sepsis and meningitis, and is increasingly prevalent among non-pregnant adults and the elderly with underlying illnesses. Preclinical and clinical trials have been successfully performed with protein conjugate vaccines prepared with GBS polysaccharides. GBS proteins with virulence properties have been described and some with vaccine potential have been tested preclinically. In this proposal, we will use DIVAS to identify

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physiological conditions conducive for bacterial attachment/invasion of eukaryotic cells using GBS as a model pathogen. We will isolate and identify GBS membrane proteins expressed solely under invasive conditions (Sp. Aim 1). GBS mutants lacking genes for these proteins will be constructed and tested for invasiveness in DIVAS and virulence in mice (Sp. Aim 1). Several of these proteins will be purified directly from GBS, or cloned and recombinantly expressed, and tested as vaccine candidates in mice (Sp. Aim 2). Findings from these studies utilizing this unique approach to vaccine antigen discovery could be directly applied to other bacterial pathogens. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BINDING ENDOCARDITIS

PROTEINS

AND

ORAL

STREPTOCOCCAL

Principal Investigator & Institution: Holt, Robert G.; Associate Professor; Meharry Medical College 1005-D B Todd Blvd Nashville, Tn 37208 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2007 Summary: Infective endocarditis is the most common serious and life-threatening cardiac infection in the United States. The number of cases is expected to increase because of the increasing numbers of intravenous drug users and elderly individuals with underlying valvular degenerative changes. Both groups are at risk for the development of the disease. Over 50% of all cases of infective endocarditis are caused by oral streptococci of the mitis group and the mutans group of streptococci, where historically many members were called viridans streptococci. The generally nonnivasive Streptococcus mutans is a member of the dental caries-causing mutans group streptococci and is the most frequent species of the mutans streptococci isolated from the oral cavity of humans. The long term goal of this study is to broaden the understanding of the pathogenesis of infective endocarditis caused by oral streptococci. We hypothesize that mutans streptococcal cells have specific receptors that bind extracellular matrix molecules and fibrinogen and this interaction functions to facilitate colonization of heart tissue in the pathogenesis of endocarditis caused by mutans streptococci. The goal of this project is to identify and characterize the bacterial cell surface molecules that are involved in the adherence of heart tissue by mutans streptococci. Binding studies in our laboratory have indicated that S. mutans cells have the ability to bind to the human extracellular matrix molecules, fibronectin, laminin, and collagen type I, and the plasma protein, fibrinogen. Also, we have determined that an isogenic antigen I/II (spaF)-deficient mutant strain of S. mutans has a reduced ability to bind fibronectin, collagen and fibrinogen which suggests that antigen I/II contributes to the interaction of S. mutans cells with these molecules. The specific aims of this study are: 1) to clone and characterize genes encoding proteins that mediate the interaction of S. mutans cells with extracellular matrix molecules (fibronectin, taminin and collagen) and fibrinogen; 2) to construct mutant S. mutans strains having defects in their ability to bind extmcellular matrix molecules and fibrinogen; 3) to evaluate using a rat model of experimental endocarditis the role of binding of S. mutans cells to extracellular matrix molecules and fibrinogen in the pathogenesis of infective endocarditis; and 4) to examine the virulence of an antigen I/II(P 1) mutant strain using the rat model of endocarditis. The results of these studies should identify candidate antigens for the production of protective immunity against infective endocarditis caused by oral streptococci as well as provide information on virulence mechanisms that function during infective endocarditis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: BIOMARKER OF NEUROTOXICITY IN MENINGITIS Principal Investigator & Institution: Mulchahey, James J.; Assistant Professor; Phase 2 Discovery, Inc. 3130 Highland Ave, 3Rd Fl Cincinnati, Oh 45219 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2003 Summary: (provided by applicant): The objective of this Phase I application is to develop a sensitive biomarker for quantifying neurotoxicity and neuroprotectant efficacy in meningitis. Previous research documents that brain injury caused by meningitis affects multiple brain areas with a heterogeneous distribution. We have previously shown that the cytoskeletal protein MAP-tau is cleavedin brain during axonal degeneration. We developed a sensitive ELISA that specifically quantifies this biomarker of neuronal degeneration, cleaved-tau (C-tau). Our preliminary studies demonstrate that levels of C-tau are increased over 300-fold in an animal model of group B streptococcus meningitis (GBM). We will use the well-documented neurotoxicity of GBM to validate the C-tau as a biomarker of neurotoxicity and a measure of neuroprotectant efficacy. Our Specific Aims are: Specific Aim 1: Determine whether GBM results in a time-dependent elevation in brain, plasma and CSF concentrations of C-tau. Specific Aim 2: Determine it C-tau levels in brain, CSF and plasma correlate with traditional measures of neuronal damage in GBM. Specific Aim 3: Determine whether perihperal tissues such as liver, kidney or spleen are potential sources of C-tau measured in GBM. Specific Aim 4: Determine whether a neuroprotectant intervention known to be effective in GBM has predictable effects on Ctau levels. PROPOSED COMMERCIAL APPLICATIONS: The C-tau ELISA may be used to quantify the severity of brain injury in meningitis and to quantify the effects of neuroprotectant interventions in basic science, preclinical and clinical research settings. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CARIES PREVENTION IN ALASKAN NATIVE INFANTS Principal Investigator & Institution: Grossman, David; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2003 Summary: Alaska Native children are disproportionately affected by early childhood caries, compared to all U.S. children. Dental care needs for adults and children in rural Alaska far exceed the acute care and prevention resources available. As a result, there is a high level of dental morbidity present among adults that likely contributes to early transmission of mutants streptococci (MS) from adult caregivers to infants in the household. Furthermore, the cultural practice of per- mastication of solid food for infant feeding amplifies the transmission of oral secretions from adult to child. The prevention of early MS acquisition and subsequent caries in infants and toddlers required efforts starting at birth. Since Alaska Natives are a rural population at high risk for caries, interruption of vertical transmission of MS using a combination of improved oral hygiene practice, and topical antimicrobials and bacteriostatic agents may be an ideal prevention strategy for childhood caries. Chlorhexidine and xylitol are two agents that have been shown to reduce dental decay and MS counts. The specific aim of this proposal is to conduct a community based, randomized blinded trial to determine if the serial use of chlorhexidine and xylitol in 250 mothers will reduce the vertical transmission of caries between Alaska Native mothers and infants. The YukonKuskokwim (YK) Delta of southwestern Alaska is the site of the study. We hypothesize that a two week period of twice-daily chlorhexidine mouthwash use prior to deliver followed by a subsequent two year period of maternal xylitol gum use, will lead to a

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significant reduction in the age-specific prevalence of early childhood caries at 12 and 24 months of age among the offspring of mothers in the intervention group, compared to control group mothers. We also hypothesize that, compared to controls, mothers and children in the intervention group will have significant reductions in oral MS counts at each follow-up interval. If proven successful, this intervention could have a significant impact on the prevalence of caries among young Alaska Native children and other population groups at high risk for childhood caries. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CD-18 DEPENDENT/INDEPENDENT WBC RESPONSES IN THE LUNG Principal Investigator & Institution: Doerschuk, Claire M.; Professor of Pediatrics and Pathology; Pediatrics; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2003; Project Start 01-AUG-1994; Project End 31-MAY-2008 Summary: (provided by applicant): Neutrophil emigration into the lungs can occur through at least two different pathways depending upon the stimulus, one that requires the CD11/CD18 adhesion complex, and one that does not. Our studies provide evidence that mice deficient in the NF-kappaB p65 (Rel A) subunit, mice deficient in both TNF R1 and IL-1R1, or mice with blockade of ICAM-1 have defects in E. coli-induced CD18dependent emigration. In contrast, mice deficient in the leukocyte non-receptor Src tyrosine kinases Lyn, Fgr, and Hck, in the small GTPase Rac2, or in interferon-(IFN-g) have defects in S. pneumoniae-induced CD18-independent but not E. coli-induced CD18-dependent emigration. Moreover, exogenous IFN-( switches CD18-dependent to CD18-independent emigration, whereas genetic deficiency of IFN-( switches CD18independent to CD18-dependent emigration. Studies comparing gene expression during these bacterial pneumonias also provided many new ideas. Our goal is, to understand the mechanisms, through which CD18-dependent and CD18-independent adhesion pathways are elicited and function; and to identify ways of modulating the acute inflammatory process to benefit the host. Our working hypothesis is that neutrophil emigration occurs through CD11/CD18-dependent pathways when early stages of host defense result in nuclear translocation of NF-kappaB, production of TNF-alpha and IL-1, and increased expression of ICAM-1 on pulmonary capillary endothelial cells, while CD11/CD18- independent mechanisms are selected when IFN-( is produced and the leukocyte Src kinases Lyn, Fgr, and Hck and the small GTPase Rac2 are activated. The proposed Aims will test this hypothesis and examine the role of each of these required molecules in the mechanisms of neutrophil emigration. Aim 1 will determine the role of NF-(B -mediated gene transcription and the function of TNF-alpha and IL-1 in CD18dependent and -independent neutrophil emigration. Aim 2 will determine the role of IFN-g in CD18- independent emigration. Aim 3 will determine the role of Lyn, Fgr, and Hck and of Rac2, and the functional relationships between these molecules and IFN-g in neutrophil recruitment and function. Aim 4 will determine the functional role of molecules identified by gene microarray technology to be differentially expressed in S. pneumoniae but not E. coli pneumonia. These studies will help to elucidate the molecular mechanisms of neutrophil recruitment and identify potential targets for therapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CHARACTERIZATION OF IRON TRANSPORT IN GBS Principal Investigator & Institution: Clancy, Kathryn A.; Children's Hospital and Reg Medical Ctr Box 5371, 4800 Sand Point Way Ne, Ms 6D-1 Seattle, Wa 98105 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2005 Summary: (provided by applicant): Group B streptococcus is the predominant etiological agent of neonatal bacteremia, sepsis and meningitis, and has been correlated with preterm membrane rupture and premature birth. While a limited number of GBS virulence determinants have been identified, the contribution of iron and iron acquisition to the pathogenesis of GBS infection is unknown. All pathogens require iron and a correlation between bacterial virulence and iron acquisition has been established. However, as the concentration of available iron in the human host (10 [-18]M) is well below that required by bacteria (10 [-8] M), successful pathogens express specific systems to acquire sufficient concentrations of intracellular iron. One such system involved in siderophore-mediated iron uptake, is the focus of this application. Siderophores are high-affinity iron chelators secreted from the bacterial cell to scavenge iron from host iron-binding proteins. Specialized uptake systems transport the siderophore-iron complex across the bacterial membrane. We have identified a putative siderophore-mediated iron transport system, the fhu operon, in GBS. The operon is comprised of four genes, fhuC, fhuD, fhuB, and fhuG, encoding a putative ATPhydrolysis protein, siderophore (ferrichrome)- iron receptor protein, and two permeases, respectively. In this application, the role of the fhu operon in iron acquisition by GBS will be examined. Basic information on the requirement of GBS for iron, the ability of GBS to utilize siderophores as an iron source, and whether the organism secretes siderophores to acquire iron will first be established. The biochemical characterization of an isogenic mutant strain deficient for fhu will examine the role of this operon in GBS siderophore-iron transport. In order to define the siderophore specificity of the fhu operon, the construction and biochemical characterization of isogenic mutant strains deficient for each gene is proposed. In addition, heterologous expression studies will provide further evidence for the role of the fhu-encoded proteins in siderophore-iron transport. These studies will provide a basic understanding of the molecular mechanism of iron acquisition in GBS and will allow us to design appropriate in vivo studies to determine the role of iron transport in GBS pathogenesis. The potential of identifying novel therapeutic targets to prevent or treat infections is also proposed. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CHEMISTRY AND IMMUNOLOGY OF STREPTOCOCCAL M PROTEINS Principal Investigator & Institution: Dale, James B.; Professor; Medicine; University of Tennessee Health Sci Ctr Memphis, Tn 38163 Timing: Fiscal Year 2002; Project Start 01-JUN-1996; Project End 31-MAY-2006 Summary: (provided by the applicant): The overall goal of this project is to develop a safe and broadly effective vaccine that will prevent group A streptococcal infections. Previous studies have shown that the surface M proteins, which are the major protective antigens, contain tissue-crossreactive epitopes as well as protective epitopes. The serotype-specific protective epitopes may be separated from potentially harmful autoimmune epitopes by using limited N-terminal peptides of M proteins. The protective M protein fragments representing multiple serotypes of group A streptococci may then be combined to form a multivalent vaccine. The specific aims of this proposal

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are: 1) To identify the primary structures of M proteins or other surface proteins that contain opsonic (protective) epitopes from serotypes of group A streptococci that are epidemiologically important and, therefore, necessary vaccine components, 2) To construct recombinant, multivalent vaccines that evoke optimal opsonic antibody responses in laboratory animals against 26 different serotypes of group A streptococci, 3) To test immune rabbit sera evoked by multivalent vaccines for opsonic and bactericidal antibodies against clinical isolates of group A streptococci collected from children with pharyngitis in 10 geographic sites in the U.S., 4) To develop strategies of intranasal delivery of multivalent M protein-based vaccines that result in secretory and systemic immune responses, and 5) To directly compare the protective immunogenicity of multivalent M protein-based vaccines delivered to mice via either the intramuscular or intranasal routes. In our preliminary studies, we have identified six epidemiologically important serotypes of group A streptococci that are not opsonized by antisera against the N-terminal M protein peptides. We propose a series of experiments to determine the covalent structures of the M proteins, M-like proteins, or other surface proteins that contain opsonic epitopes so that these M serotypes may be included in multivalent vaccines. We will construct a 26-valent vaccine composed of 4 different recombinant, hybrid proteins. The individual hybrid proteins will be tested for protective and tissuecrossreactive immunogenicity after intramuscular injection of rabbits. Because mucosal delivery of streptococcal vaccines may have both immunological and practical advantages over parenteral delivery, we will assess different strategies of intranasal delivery and then directly compare the protective efficacy of i.n. vs i.m. vaccines in mice. The studies should provide the detailed information needed to develop a safe and effective multivalent vaccine that could prevent the majority of streptococcal infections in North America and Western Europe. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CLINICAL CENTER IN COPD Principal Investigator & Institution: Bailey, William C.; Professor and Director; Medicine; University of Alabama at Birmingham Uab Station Birmingham, Al 35294 Timing: Fiscal Year 2003; Project Start 15-AUG-2003; Project End 31-JUL-2008 Summary: (provided by applicant): Chronic Obstructive Pulmonary Disease (COPD) is a serious public health problem responsible for more than 500, 000 hospitalizations, 100,000 deaths, and $15 billion in direct costs of medical care in the United States each year. We propose to form a collaborative COPD CRN Clinical Center at the University of Alabama at Birmingham (UAB) and the Birmingham Veterans Affairs Medical Center (BVAMC). The UAB/BVAMC Clinical Center will be headed by, Drs. William C. Bailey and J. Allen D. Cooper. The proposed investigators and their research staff have extensive experience in recruitment and retention for clinical trials, as well as study design and implementation. The collaborative effort between UAB and the BVAMC will allow us to quickly and efficiently recruit large numbers of COPD patients for clinical research studies. In addition, the UAB/BVAMC COPD Clinical Center will have access to a large network of experts at the University of Alabama at Birmingham who can assist in the design and implementation of clinical trials. The UAB/BVAMC Clinical Center proposes two studies aimed at enhancing treatment for moderate-to severe COPD. The first study will examine measures of inflammation and responsiveness to bronchodilator challenge, responsiveness to systemic steroid treatment, and responsiveness to inhaled steroid treatment. This study may provide a new method for identifying subgroups of COPD patients who are most likely to respond to inhaled corticosteroids. The second project will examine the causes of poor responsiveness to the

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pneumococcal vaccine with the long term goal of using this information to reduce pneumococcal infections and related exacerbations in COPD patients. The UAB/BVAMC Clinical Center also proposes a Clinical Research Skills Training Core. Dr. J. Allen D. Cooper, the Director for fellowship training in Pulmonary and Critical Care Medicine at UAB, will head this core. Trainees will be funded for a total of two years and will be required to enroll in one of the UAB K30 Clinical Research Curriculum Development Award components (either the Clinical Research Training Program or the Master's of Science in Public Health in Clinical Research). Trainees will also receive funding for a pilot project, which will be developed and conducted under the supervision of the Training Core Investigators. These Investigators have expertise in COPD, Clinical Research and Study Design, Behavioral Science, Epidemiology, and Statistics. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CLONING ANALYSIS OF S. MUTANS PUTATIVE COLLAGENASE Principal Investigator & Institution: Dao, My Lien L.; Biology; University of South Florida 4202 E Fowler Ave Tampa, Fl 33620 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-MAY-2005 Summary: Dental root decay is prevalent among older individuals as their gum recesses exposing Dental root surface to attack by cariogenic bacteria. In a study involving 449 subjects of an age range of 79-101 years, 96% had coronal decay experiences, and 64% had root caries experience with 23% of the group having untreated root caries (ADA News Releases, 2000). Streptococcus mutans, an etiologic agent in the development of coronal caries, has also been implicated in Dental root decay; data in support of this implication include the finding of S. mutans in Dental root section, its ability to bind collagen, and to degrade FALGPA, a known synthetic peptide substrate for collagenase. Bacterial collagenases are considered as virulence factors as they facilitate the invasion and destruction of host tissues by the pathogens. It is not yet known whether S. mutans produces a true collagenase enzyme. Considering the increase in incidence of Dental root caries as the population lives longer, the long-term goal of the current study is to develop effective and safe methods to control this disease, and improve the nutrition and quality of life of the population at risk. In order to determine whether the collagenolytic enzyme in S. mutans is a good candidate antigen for vaccine development, the Specific Aim of the current research is to learn more about the S. mutans enzyme in order to explore this avenue. A putative S. mutans collagenase gene has been obtained previously, and sequence analysis showed a high homology with the 35-kDa collagenase of various clinical isolates of Porphyromonas gingivalis, a bacterium causing periodontitis. The plan is to clone the 1.2 kbp putative collagenase coding sequence into an expression plasmid under the control of a strong promoter in order to obtain the corresponding protein, which in turn will be isolated and characterized by biochemical methods. Antibody will be prepared against the S. mutans enzyme and tested for the ability to block collagen binding and/or collagen degrading properties. The data obtained will be compared with other known bacterial collagenases. This information is essential in determining future directions for research on the role of S. mutans in Dental root caries, and other diseases that may involve collagen binding and collagen degrading activity such as periodontitis and endocarditis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: COMPLEMENT AS AN ADJUVANT IN POLYSACCHARIDE IMMUNITY Principal Investigator & Institution: Test, Samuel T.; Children's Hospital & Res Ctr at Oakland Research Center at Oakland Oakland, Ca 946091809 Timing: Fiscal Year 2002; Project Start 01-APR-2001; Project End 31-MAR-2004 Summary: (Adapted from Applicant's Abstract) The complement system plays a critical role in the antibody response to both thymus-dependent and thymus-independent antigens. Recently, the C3d fragment of complement C3 has been shown to have a profound adjuvant effect when coupled to a model T-dependent protein antigen and used to immunize mice. However, the utility of this approach for enhancing the humoral immune response to either T-independent or clinically relevant antigens has not been addressed. This project will test the hypothesis that C3d conjugated to the capsular polysaccharides of Streptococcus pneumoniae, clinically important Tindependent type 2 antigens, has an adjuvant effect similar to that seen for T-dependent antigens. Preliminary data show that conjugation of C3d to pneumococcal serotype 14 capsular polysaccharide results in a significant enhancement of the murine antibody response to this polysaccharide. The ultimate goal of these studies is to gain an understanding of the immune response to C3d-polysaccharide conjugates with proteinpolysaccharide conjugates in pneumococcal vaccines. The aims of this research are as follows. First to determine the effects of C3d conjugation on the humoral immune response to pneumococcal capsular polysaccharides as compared with the response to polysaccharides coupled to ovalbumin, a T-dependent protein carrier. The specific questions that will be addressed as part of this aim as follows: 1) Are there qualitative differences in the antibodies produced in response to immunization with the different types of polysaccharide conjugate? 2) What is the role of the complement system in the humoral immune response to the different conjugates? 3) What is the role of T lymphocytes in the antibody response to C3d-polysaccharide versus ovalbuminpolysaccharide conjugates? 4) Is the presence of a spleen necessary for mice to mount an effective humoral immune response to polysaccharide conjugates? 5) Within the spleen of immunized mice, how does the presence of C3d or ovalbumin coupled to pneumococcal polysaccharides influence the identity and distribution of the cells involved in the immune response? The second aim is to determine whether the adjuvant effect of C3d is a general phenomenon with respect to pneumococcal capsular polysaccharides. Conjugates of mouse C3d and capsular polysaccharide from serotypes 14, 6B and 23F S. pneumoniae will be prepared and evaluated in different strains of mice. These experiments should provide new insights into the immune response to conjugate vaccines and facilitate future efforts to improve vaccine efficacy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CONDITIONAL B INTEGRIN BLOCKADE, PMN TRAFFICKING Principal Investigator & Institution: Malik, Asrar B.; Distinguished Professor and Head; Pharmacology; University of Illinois at Chicago 1737 West Polk Street Chicago, Il 60612 Timing: Fiscal Year 2002; Project Start 10-JUL-2000; Project End 31-MAY-2005 Summary: Acute lung injury is characterized by polymorphonuclear leukocyte (PMN) accumulation in the pulmonary microcirculation and transalveolar PMNmigration, and resultant injury of the microvessel-alveolar barriers. The mechanisms of migration of PMN across both pulmonary microvessel endothelial and alveolar epithelial barriers and the role of transalveolar PMN migration in the pathogenesis of acute lung injury remain unclear. In the proposed studies, we will direct the expression of the selective

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anti-adhesive beta2 CD11/CD18 integrin binding protein, Neutrophil Inhibitory Factor (NIF), in a site- and inflammation- specific manner. NIF will be expressed in either pulmonary microvascular endothelium or type II alveolar epithelial cells using inducible cell-specific promoters. Constructs of NIF cDNA driven by the inducible endothelial cell-or type II alveolar epithelial cell-specific promoters (i.e., E-selectin and surfactant protein C promoters, respectively) will be introduced in mice to express NIF at endothelial and epithelial sites. Mice will be challenged with TNFalpha, or with gram negative or gram positive bacteria, E. coli or S. pneumoniae, administered intraperitioneally or directly into airway to simulate systemic or lung-localized infection. We will determine the effects of site- specific PMN beta2 integrin blockade in either microcirculation or alveolar space on the migration of PMN across microvessel- alveolar epithelial barriers and in the injury of these barriers. We will address the role of beta2 integrins in directing PMN traffic across the pulmonary microvessel endothelial and alveolar epithelial barriers and mechanism of injury of these barriers using a strategy based on cell-selective and inducible expression of beta2 integrin antagonist. In separate studies, we will determine using gene knockout mouse models the contributions of Lselectin (another PMN adhesion molecule involved in PMN migration) as well as ICAM-1 (a PMN beta2 integrin counter- receptor in endothelial and alveolar epithelial cells) and E- selectin (an endothelial cell-specific adhesion molecule) in the mechanisms of alveolar PMN migration and injury of microvessel and alveolar epithelial barriers. With the completion of these studies, new information will be obtained on the role of adhesion molecules in the mechanisms of PMN migration into the airspace and novel strategies will be developed to prevent acute lung injury based on the conditional and site-specific expression of a beta2 integrin antagonist. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CONSEQUENCES OF GROUP B STREPTOCOCCAL PROPHYLAXIS Principal Investigator & Institution: Sinha, Anushua; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2002; Project Start 30-SEP-2000; Project End 31-MAY-2005 Summary: (adapted from applicant's abstract): This application for a K23 award combines coursework, a research plan, and personal mentoring to train Anushua Sinha M.D., M.P.H. for independence as a clinical investigator. Dr. Sinha is boarded in Internal Medicine, Pediatrics, and Infectious Diseases. She currently holds an individual NRSA from NIAID to develop and use automated medical record linkage systems to assess the epidemiology of infections during the first 30 days of life. Dr. Richard Platt (Harvard Medical School) and Dr. Milton Weinstein (Harvard School of Public Health) will serve as research mentors. The research builds on Dr. Sinha's NIAID-funded work to investigate the impact of maternal antibiotic prophylaxis against neonatal group B streptococcus on non-GBS infectious outcomes of both infants and mothers. The adoption in the mid-199Os of prophylaxis during labor for approximately 25% of women greatly reduced the occurrence of neonatal GBS disease. However, little is known about its effects on other antibiotic susceptible and resistant infections of mothers and infants, or more generally on the emergence of antimicrobial resistance. It is important to elucidate these issues, and to ascertain patient utilities, to guide decisions about whether and how to use a GBS vaccine that is currently being developed at the investigator's institution (The Streptococcal Initiative, PI: D. Kasper, NO1-AI-75326). The study thus has 5 specific aims: Assess the impact of GBS prophylaxis on 1) neonatal nonGBS infections; 2) maternal non-GBS outcomes, 3) antibiotic resistant infections among prophylaxis recipients, and among newborns and postpartum women generally; and 4)

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Streptococcus

resource utilization. Aim 5 assesses the cost effectiveness of antibiotic prophylaxis compared to immunization. Dr. Sinha will address these issues using direct patient interviews together with data from an existing cohort of 15,532 deliveries from 10/1/90 to 3/31/98 for which she has linked extensive, automated inpatient and outpatient records. Case-control and cohort methods will be used to address aims 14, and decision analysis for aim 5. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CPG DNA ADJUVANTS AND VACCINES FOR ENCAPSULATED BACTERIA Principal Investigator & Institution: Harding, Clifford V.; Professor; Pathology; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2002; Project Start 29-SEP-2000; Project End 31-MAY-2005 Summary: (Adapted from the Applicant's Abstract): CpG oligodeoxynucleotides (ODN) have immunomodulatory effects that may be useful for many future vaccine applications. The goal of this proposal is to understand how CpG ODN alter antigen processing and presentation of peptides to T cells. The project will also investigate how CpG ODN alter humoral immunity to polysaccharide Ags, as induced by immunization with either unconjugated PS or PS-protein conjugate vaccines. Aim 1: To determine the effect of CpG ODN on the ability of Ag presenting cells to process Ag and stimulate T cell responses to protein Ags. It is hypothesized that CpG ODN enhance Ag processing by dendritic cells and B cells. Investigators will determine the effects of CpG ODN on the ability of these cells to process and present exogenous protein Ags, including CRM 197, the carrier protein for glycoconjugate vaccines studied in Aims 2 and 3. Mechanisms for these effects will be explored, including the influence of CpG ODN on factors such as MHC-II synthesis and expression, half-life of peptide:MHC-II complexes, and expression of Ag processing components. Aim 2: To explore the adjuvant effects of CpG ODN on responses to PS and peptide epitopes of glycoconjugate vaccines, primarily using an experimental vaccine for Streptococcus pneumoniae. It is suggested that CpG ODN will enhance Ab responses to PS epitopes of glycoconjugate vaccines and alter the Ab isotypes that are elicited (e.g., to induce IgG2a and IgG3 responses in mice). The mechanisms of these effects will be determined including the roles of cytokines and T cells. Aim 3: Experiments will test whether CpG ODN can act as effective adjuvants in concert with vaccines containing only unconjugated PS immunogen to enhance PSspecific IgM and IgG1 responses and induce PS-specific Ab of other isotypes. Mechanisms of these effects will be determined (e.g., roles of T cells and cytokines). Understanding the modulation of Ag presenting cells by CpG ODN would increase our understanding of the basic mechanisms of adjuvant function for CpG ODN. The ability of CpG ODN to enhance humoral immunity to PS Ags would allow the development of improved vaccines for encapsulated bacteria. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: DEGP PROTEINASE INHIBITORS: NOVEL ANTI-INFECTIVES Principal Investigator & Institution: Hruby, Dennis E.; Chief Scientific Officer; Siga Technologies, Inc. 420 Lexington Ave, Ste 620 New York, Ny 10170 Timing: Fiscal Year 2002; Project Start 01-AUG-2000; Project End 31-MAY-2004 Summary: (provided by applicant): The DegP (HtrA) protease is essential for virulence in several Gram-negative pathogens: S. typhimurium, B. melitensis, Y. enterocolitica and P. aeruginosa. The phenotype of a degP knockout in Escherichia coli, temperature and

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oxidative sensitivity, suggests a role in virulence. The DegP protease is a multifunctional protein essential for the removal of misfolded and aggregated proteins in the periplasm of Gram-negative bacteria. We have identified the major pilin subunit of the Pap pilus, PapA, as a native DegP substrate and demonstrate vigorous proteolysis of this substrate in vitro. The DegP cleavage site in PapA was mapped and an in vitro cleavage assay suitable for HTS was developed. Hits that arise from the HTS will be passed through a series of secondary screening assays and in vivo models to identify bioavailable inhibitors of DegP that display good selectivity. We recently identified DegP homologues in S. pyogenes and S. aureus and demonstrated that a degP knockout in S. pyogenes has reduced virulence. We propose to validate S. aureus DegP as a virulence factor and develop this target for screening. There is ample precedent for the efficacy of protease inhibitors as therapeutic agents. Moreover, nonessential virulence targets may be less prone to resistance development. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EFFECTS OF NATURAL AGENTS WITH FLUORIDE ON CARIES Principal Investigator & Institution: Koo, Hyun; Eastman Dentistry; University of Rochester Orpa - Rc Box 270140 Rochester, Ny 14627 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-MAY-2005 Summary: (provided by applicant): Apigenin and tt-farnesol, were identified as potentially novel natural anti-caries agents (Koo et al., 2002b; c). Both agents exhibited cariostatic properties in rats without significant effects on the animals' oral flora. Apigenin is a potent inhibitor of glucosyltransferases (GTFs), both in solution and on a surface (60-95% inhibition at 1.33mM), and without effect on bacterial growth, ttFarnesol, in contrast, affects the growth rate and metabolism of mutans streptococci biofilms by disrupting the membrane function. The aim of the proposed study is to evaluate the effects of the combination of apigenin, tt-farnesol and fluoride on the formation and composition of mutans streptococci biofilms in vitro, and on caries development in rats. Fluoride is a clinically proven anti-caries agent; its main effect is to interfere physicochemically with caries development. However, fluoride has antibacterial activity, and in addition, may interfere with GTF production (Bowen and Hewitt, 1974). Our hypothesis is that the association of the natural agents may enhance the anti-caries effect of fluoride by synergistically diminishing the virulence factors of mutans streptococci involved in the pathogenesis of dental caries. The rationale for this study is that the combination of the therapeutic agents will reduce the formation and virulence of cariogenic biofilms by (a) inhibiting the synthesis of glucans, e.g., inhibition of the activity and production of GTFs; Co) reducing the acid tolerance, e.g., inhibition of F-ATPase; (c) reducing the acidogenicity, e.g., enhancing the access of fluoride into cells by increasing the bacterial membrane permeability. We will test our hypothesis using a series of experiments as follows: I) In vitro- By determining the effects of the combination of agents on (1) formation, (2) viability, (3) pH, and (4) polysaccharide and inorganic composition of mutans streptococci biofilms. Streptococcus mutans biofllms formed on hydroxyapatite disks will be used in this part of the investigation. The polysaccharide composition will be determined by a series of colorimetric assays, liquid scintillation counting and gas chromatography/mass spectrometry. The concentrations of fluoride will be determined using a fluoride-selective electrode, calcium will be analyzed by atomic absorption spectrophotometry and phosphorus will be determined colorimetrically. The pH of the biofilms will be measured using a Beetrode pH electrode. II) In vivo - By evaluating the ability of combination(s) of agents (selected from in vitro analyses) to reduce dental caries, and to affect the pH and the composition of plaque

22

Streptococcus

using our rat model. The outcome of this study may lead to new and effective therapeutic combinations interventions to prevent dental caries, and possibly other plaque related diseases by using novel compounds in association with a well-known anti-caries agent. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EFFICACY OF DNA VERSUS PROTEIN VACCINE Principal Investigator & Institution: Dao, My Lien.; Associate Professor; Biology; University of South Florida 4202 E Fowler Ave Tampa, Fl 33620 Timing: Fiscal Year 2003; Project Start 15-JUL-2003; Project End 31-MAY-2005 Summary: (provided by applicant): Dental caries is an infectious disease caused by Streptococcus mutans. Despite fluoridation and improved Dental hygiene in industrialized countries, worldwide Dental cades is still a significant public health problem affecting 50-90 percent of the population 0Nodd Health Organization). In the United Sates of America, 59 percent of first graders have at least one cavity, one third of the adult population does not see a Dentist annually, and 24 percent of the elderly experience caries-associated tooth loss (Oral Health America). Animal studies demonstrated that this disease was preventable by immunization with so mutans antigens. Gene cloning technology was applied to produce recombinant bacteria, protein and peptide vaccines for active immunization, and antibody for passive immunization. Various levels of protection were achieved with these vaccines. Considering that the population at risk is mostly from low socioeconomic groups (Surgeon General's report, U.S. DHHS, 2000), it is desirable to find means to lower the costs of vaccine production for mass immunization. One possibility is to directly immunize with a plasmid DNA (cDNA) containing the gene(s) of interest and obtain expression of the target protein(s) in the host. Thus, expensive protein isolation from recombinant clones is avoided. The Long Term Goal of the current study is to prepare an efficacious, safe and economical Dental Cades vaccine. The Specific Aim for the proposed period is to explore the prospect of a DNA vaccine against S. mutans with special emphasis on comparing the efficacy, duration and costs with those of corresponding Protein Vaccine. As models, the S. mutans antigen A (AgA), a recognized candidate vaccine antigen, and its precursor the wall-associated protein A (WapA), a factor involved in colonization and buildup of Dental plaque, will be used. The work proposed is supported by the availability of the recombinant clones needed for the production of WapA and AgA protein vaccines, and wapA-pDNA and agApDNAvaccines, and by the expression of WapA and AgA in mammalian cells transfected with these pDNA constructs. The results obtained will determine the feasibility and cost-effectiveness of genetic immunization against Dental caries, and the work performed will serve as a model for vaccine research against other infectious agents invading the body through mucosal surfaces. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ELDERLY POLYSACCHARIDE

IMMUNE

RESPONSE

TO

PNEUMOCOCAL

Principal Investigator & Institution: Westerink, M a J.; Medicine; Medical College of Ohio at Toledo Research & Grants Admin. Toledo, Oh 436145804 Timing: Fiscal Year 2002; Project Start 01-APR-2000; Project End 31-MAR-2005 Summary: Infection is one of the leading causes of morbidity and mortality in the elderly. Streptococcus pneumoniae is the organism most commonly isolated from

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elderly patients with pneumonia. Increased susceptibility to infections that occur in the elderly has been attributed to deteriorating health, decreased pulmonary function and a functional decline of the immune system. The immune system is unique in that it may be manipulated to achieve a desirable response. Studies in aged mice demonstrate both quantitative and qualitative changes in the immune response to T-independent type 2 (TI-2) antigens. Reports indicate age related loss of affinity, fine specificity and protective immunity are associated with a molecular shift in V gene usage and changes in cytokine profile. Studies of the in vivo immune response in elderly have been limited to vaccine efficacy studies and quantitative analysis of the magnitude and duration of the post-vaccination antibody response. The results of these studies suggest that despite adequate quantitative immune response the elderly show decreased vaccine efficacy. Current knowledge concerning the aging immune response to TI-2 antigens is mostly based on animal models and may not be applicable to humans. Human studies are fragmented and address quantitative and qualitative immune response as separate issues. We propose to study and characterize the immune response to S. pneumoniae capsular polysaccharide in the elderly. We will focus on both quantitative and qualitative changes in the immune response on molecular and functional levels. The quantitative immune response, isotype and IgG subclass, will be correlated with opsonophagocytic activity. We hypothesize that the discrepancy between the quantitative and qualitative immune response in the elderly results from altered V region sequence. We will characterize the immunoglobulin gene usage pattern and V-DJ joint diversity of the antibody response to pneumococcal polysaccharides (PPS) of serotypes 4 and 14 in elderly and young adults. This will be accomplished by gene family specific ELISA and by isolating single responding cells and determining the sequence of the V chains. Second, we propose to evaluate the influence of soluble regulatory factors on the aging immune response. The reconstituted SCID mouse model will be used to study the aging human B cell response to PPS 4 and 14 in a controlled cytokine environment allowing us to differentiate altered response intrinsic to the B cells versus altered responses secondary to environmental factors such as cytokines. The results of these studies will form the essential baseline for the rational development of vaccine and adjuvant strategies for the elderly. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EXPERIMENTAL MODEL PREMATURITY

FOR CHORIOAMNIONITIS

AND

Principal Investigator & Institution: Gravett, Michael G.; Chief; None; Oregon Health & Science University Portland, or 972393098 Timing: Fiscal Year 2002; Project Start 01-SEP-1997; Project End 31-MAY-2006 Summary: Prematurity is the leading cause of neonatal morbidity and mortality in the United States. Intrauterine infections are an important, and potentially treatable cause of prematurity, and are associated with increased risk of neonatal white matter lesions of the brain and cerebral palsy. However, the mechanisms by which infection leads to prematurity and/or cerebral palsy remain speculative and treatment strategies untested largely because humans cannot be longitudinally studied following infection. We propose to use chronically instrumented pregnant rhesus monkeys at 120-130 day gestation with experimental intrauterine infection, as previously described (Gravett et al, Am J Obstet and Gynecol; 171:1660-1667,1994) to study the temporal and quantitative relationships among infection, cytokines, prostaglandins, steroid hormones, cytokine antagonists, preterm labor, and neonatal white matter lesions of the brain in order to develop effective interventional strategies. After postoperative stabilization in a tether,

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Streptococcus

we will; (1) inoculate Group B Streptococci (GBS) into the amniotic fluid to establish intrauterine infection and preterm labor. Uterine contractility will be continuously monitored and periodic samples of amniotic fluid and maternal and fetal blood (1-4 cc) will be obtained for assays of eicosanoids, steroid hormones, cytokines, matrix metalloproteinases and for microbial studies; (2) utilize antibiotics with and without potent inhibitors of proinflammatory cytokine production (dexamethasone,IL-10) o prostaglandin production (indomethacin) to ascertain the most effective intervention to down-regulate the cytokine/prostaglandin cascade and associated uterine activity; (3) infuse proinflammatory cytokine IL-1beta into the amniotic cavity through indwelling catheters in the absence of infection. Prior to infusion of IL-1beta in the absence of infection, specific novel proinflammatory cytokine inhibitors (IL-1ra and sTNF-R1 PEG) will be used to identify other potentially useful immunomodulators. Samples of the decidua, fetal membranes, tissues, and brain will be obtained at cesarean section for microbiologic, histopathologic studies, immunohistochemistry for cytokines, localization and quantitation of mRNA for cytokines and PGHS-2. Fetal brain will be examined for increased apoptosis associated with white matter lesions. Leukocytes in amniotic fluid and tracheal aspirates will be assessed by flow cytometry Postpartum, the mother will be treated with appropriate antibiotics to eradicate the GBS from the genital tract and returned to the colony. These studies will clarify the pathophysiology of infection-associated preterm labor and will suggest effective interventional strategies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: FUNCTIONAL DIFFERENTIATION IN B LYMPHOCYTES Principal Investigator & Institution: Rittenberg, Marvin B.; Professor; Molecular Microbiology and Immunology; Oregon Health & Science University Portland, or 972393098 Timing: Fiscal Year 2002; Project Start 01-JUL-1988; Project End 31-MAR-2004 Summary: (Adapted from the Investigator's abstract): The ability of somatic mutation to modify the course of a humoral immune response is well documented. However, the focus has been almost exclusively on the ability of this process to improve the functional characteristics of representative antibodies; the harmful effects have not been well characterized. Yet in terms of cell numbers, all evidence suggests that B-cell wastage caused by harmful somatic mutations probably far exceeds the number of cells whose antibodies are improved through mutation. The purpose of this project is to gain quantitative insight into the contribution of mutation to B-cell wastage and secondly to exploit the well-known power of harmful mutations, to illuminate function. The investigators have previously made and characterized in vitro the binding of a large number of mutants of the T15 antibody to the hapten, phosphocholine (PC). The hypothesis is that mutant Abs displaying defective Ag binding or secretion in vitro would lead to apoptosis and B-cell wastage if they were to occur in vivo. This hypothesis will be tested in three ways: 1) by examining the ability of mutant antibodies to recognize PC which is displayed in different structural contexts on the surfaces of the pathogenic organisms, Streptococcus pneumoniae, Ascaris suum and Trichinella spiralis as well as Proteus morganii; 2) by testing the ability of mutant antibodies to transmit antigen-induced signals to transfected B lymphoma cells, and 3) by examining apoptotic GC B-cells for mutations in the VH1 gene of T15 shown to be harmful in vitro. These studies bear on B-cell wastage and homeostasis and the causes of apoptosis in germinal centers where recent evidence has suggested some lymphoid tumors such as Hodgkin's disease may originate. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: GENETIC ANALYSIS OF ORAL STREPTOCOCCAL BIOFILM FORMATION Principal Investigator & Institution: Ganeshkumar, Nadarajah; Associate Professor; Molecular and Cell Biology; Boston University Medical Campus 715 Albany St, 560 Boston, Ma 02118 Timing: Fiscal Year 2002; Project Start 01-APR-2000; Project End 31-MAR-2004 Summary: Initial colonization of tooth surfaces by oral viridans streptococci, including Streptococcus gordonii, leads to the eventual formation of biofilms called dental plaque. The most common disease of man, caries and periodontal disease, result from imbalances in the oral microflora, which allow pathogenic species to dominate. Initial plaque formation is characterized by the adhesion of planktonic cells of bacteria such as streptococci to tooth surfaces via specific salivary proteins of the acquired pellicle. Subsequent growth of these initial colonizers and other bacteria on the abiotic surface leads to the formation of dental plaque. Studies have extensively characterized of the initial binding of the planktonic bacteria to saliva-coated/hydroxyapatite surfaces, but the prerequisite signals that trigger the transition from a planktonic to a sessile mode of life and the subsequent accumulation of dental biofilms are poorly understood. It is hypothesized that novel genes are required for initial dental biofilm formation, and identification of such genes and characterization of their expression will be crucial for the development of novel methods of dental plaque control. A simple, but effective method of microbial accumulation on polystyrene surfaces will be used in this study to characterize isolation of biofilm-defective mutants of S. gordonii using Tn916 transposan mutagenesis, (2) characterization of biofilm-defective mutants, and (3) cloning and genetic analyses of biofilm genes. These studies of biofilm formation in streptococci will provide valuable information on the initial stages of dental plaque formation. Understanding the mechanisms involved in biofilm formation will be crucial for the development of novel therapeutic strategies to modify the composition of dental biofilm flora towards that found in health. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: GENETIC ANALYSIS OF S. PYOGENES VIRULENCE FACTORS Principal Investigator & Institution: Scott, June R.; Professor; Microbiology and Immunology; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2003; Project Start 01-JUN-1984; Project End 31-JAN-2008 Summary: Streptococcus pyogenes, the group A streptococcus (GAS) is an important human pathogen causing frequent self-limiting diseases which may lead to serious sequelae. In addition, the GAS seems to be "reemerging" as a cause of life-threatening invasive disease. Because of the great diversity of syndromes produced by many strains of GAS, we wish to improve our understanding of the pathogenesis of this organism by focusing on the regulation of expression of its genes, which presumably occurs on interaction with the human host to determine disease outcome. This proposal focuses on the two major global regulators that alter expression of many GAS proteins, including virulence factors. The regulation of expression of Mga (Aim 1) and CovR/S (CsrR/S) (Aim 3) will be studied. The genes controlled by Mga and CovR/S and the mechanisms by which these regulatory proteins control expression of these genes will also be investigated (Aims 2 and 4). We hope these analyses will improve our understanding at the molecular level of the interactions of GAS with its human host and may identify new targets for development of therapies and vaccines. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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•

Streptococcus

Project Title: GENETIC FUNCTIONS OF AN ENTEROCOCCAL R FACTOR Principal Investigator & Institution: Dunny, Gary M.; Professor; Microbiology; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2002; Project Start 01-SEP-1992; Project End 31-MAR-2005 Summary: (Verbatim from Applicant's Abstract): The enterococci have become prevalent as causes of nosocomial infections. The high incidence of resistance of these organisms to the most efficacious antibiotics (e.g., vancomycin) causes major problems in treating enterococcal infections, and the tremendous reservoir of enterococcal resistance determinants serves as a vector for the spread of these genes to other, more pathogenic bacterial genera. This research is focused on dissection of a mechanism of horizontal genetic transfer of the antibiotic resistance plasmid pCF10 in Enterococcus faecalis. The most novel feature of this transfer system is that the pCF10-containing donor cell perceives the presence of potential recipients in its vicinity by sensing a small peptide signal (a sex pheromone called cCF10) excreted by the recipients. The donor cell only expresses genes required for plasmid transfer when exogenous cCF10 is detected in the growth medium. Both the donor cells response to exogenous pheromone, and the negative control system that prevents expression of transfer functions in the absence of exogenous pheromone, are complex processes that have been studied in detail. Enterococci produce a variety of peptide pheromones, consisting of hydrophobic peptides 7-8 amino acids in length. Different families of plasmids each encode a highly specific response to a single cognate pheromone. When a single cell carrying multiple pheromone plasmids is exposed to one pheromone, only the corresponding plasmid is transferred, even though the sensing systems are quite similar for all the plasmids examined to date. In the next funding period, the focus of the experiments will be on the molecular and genetic basis for the specificity of the pheromone response. The specific aims are: 1) Determine the molecular basis for specificity of pheromone cCF10 interactions with PrgZ (the extracellular pCF10-encoded pheromone binding protein), and with PrgX (the putative intracellular receptor for cCF10 believed to comprise the molecular switch involved in the intracellular phase of pheromone induction. 2) Determine the molecular basis for specific abolition of endogenous cCF10 activity in pCF10-containing donor cells by PrgY (a pCF10-encoded membrane protein), and by iCF10 (a plasmid-encoded peptide inhibitor of cCF10). 3) Determine the molecular basis for the activity and specificity of a novel regulatory RNA, Qa in blocking expression of conjugation in uninduced cells via its interaction with PrgX and with the Qs RNA encoded in the positive control region of pCF10. 4) Begin an experimental analysis of the genetic and molecular basis for specificity of the downstream steps in pheromone induction. These steps include post-transcriptional activation of transfer gene expression, and conjugative DNA processing. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: FIMBRIAE

GLYCOSYLATION

&

BIOGENESIS

OF

STREPTOCOCCAL

Principal Investigator & Institution: Wu, Hui; Microbiol & Molecular Genetics; University of Vermont & St Agric College 340 Waterman Building Burlington, Vt 05405 Timing: Fiscal Year 2003; Project Start 04-JUN-2003; Project End 31-MAY-2008 Summary: (provided by applicant): Dr. Wu's isolation and characterization of the Fap1 molecule, a glycosylated fimbrial structural subunit of Streptococcus parasanguis, was a significant breakthrough in understanding the basic for fimbrial biosynthesis and adhesion in Gram-positive bacteria. Fap1-like molecules and genes involved in Fapl

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glycosylation are not only highly conserved across oral streptococci but are also present in Streptococcus pneumoniae and in the staophlococci. Dr. Wu's current research on the glycoslylation of Fap1 is extremely exciting. It is likely that a universal glycosylation machinery is present in Gram-positive bacteria and the findings from these studies would be applicable to other organisms. Recently, he identified a gene cluster that is required for the glycosylation of Fap1. He is currently in the process of determining the biosynthetic pathway by which Fap1 is glycosylated using molecular genetic, structural biology, and biochemical approaches. With the support of a K22 award, Dr. Wu will take formal courses in mass spectrometry and bioinformatics and receive hands-on training in Mass spectrometry analysis of the carbohydrate structure and biochemical analysis of key enzymes involved in protein glycosylation. The support of a K22 will provide Dr. Wu with new skills and knowledge in carbohydrate biochemistry that will position him to pursue new avenues in the study of glycosylation of streptococcql adhesions. Dr. Wu is in a unique position to determine the mechanisms of prokaryotic glycosylation and Gram-positive fimbrial biogenesis as the explict genetic tools have been generated in Dr. Fives-Taylor's laboratory over the last 20 years. Dr. Wu's strength in molecular genetics coupled with the training in carbohydrate biochemistry specifically in mass spectrometry analysis and enzymology will enhance his career development in this exciting research area. The results of this proposal will help define the biosynthetic pathway for Fap1 glycosylation. New genes in the pathway may endow microbes with new effector functions or aid in the evasion of host defense, strategies that are important components of disease-causing capabilities of a number of bacterial pathogens. Therefore, elucidation of Fap1 glycosylation may provide a framework for understanding the role of glycoslyation in bacterial pathogenesis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GROUP B. STREPTOCOCCI AND TOLL-LIKE RECEPTORS Principal Investigator & Institution: Golenbock, Douglas T.; Chief, Division of Infectious Diseases &; Medicine; Univ of Massachusetts Med Sch Worcester Office of Research Funding Worcester, Ma 01655 Timing: Fiscal Year 2002; Project Start 15-AUG-2002; Project End 31-JUL-2007 Summary: (provided by applicant): Group B streptococci (GBS) are the leading cause of neonatal sepsis, the third most frequent cause of bacterial meningitis and an increasingly important cause of bacteremia and sepsis in adults in the United States today. Preliminary studies have identified a novel proinflammatory component of GBS, which we have designated GBS-factor (GBS-F). Based on experiments in mice with targeted genetic deletions in Toll-like receptor (TLR) expression and on experiments with engineered cell lines, we have determined that responses to GBS-F require expression of CD14, TLRs 2 and 6, and the Toll-adapter protein, MyD88. Activation of this receptor complex by GBS-F initiates important signaling events such as the activation of NF-kB, the phosphorylation of MAP kinases, the formation of proinflammatory cytokines, and the intracellular production of the toxic oxidant peroxynitrate. In contrast, although other components of GBS appear to engage TLRs, the exact identity of contributing TLRs is entirely unknown. The overall goal of this proposal is to identify and define components of GBS, focusing first on GBS-F, and their cognate Toll-like receptors (TLRs). We propose to characterize the structure of GBS-F and assess its function in vitro and in vivo. Furthermore, we will determine if TLR2, and related downstream signal transduction molecules, mediate a variety of important innate immune responses to GBS, including leukocyte chemotaxis and the intracellular killing of bacteria. Finally, we intend to determine what other TLRs, and associated

28

Streptococcus

signal transduction molecules, are involved in GBS recognition and response. The data learned from these studies should help in the development of rational therapeutic strategies to interfere with the deleterious hyperinflammation triggered by GBS and similar microbial organisms. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: IMMUNE RESPONSE TO THE GROUP A STREPTOCOCCAL CAPSULE Principal Investigator & Institution: Wessels, Michael R.; Professor; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2002; Project Start 01-JUL-1991; Project End 31-MAY-2005 Summary: Description (Adapted from applicant's abstract): A global increase in invasive group A Streptococcus (GAS) disease (bacteremia, necrotizing fasciitis, and streptococcal toxic shock syndrome) that began in the 1980's has continued through the present decade and has focused attention on investigation of mechanisms of GAS pathogenesis. During the previous funding period, work in their laboratory and others further documented the central role of the hyaluronic acid capsular polysaccharide in GAS virulence in experimental models of local and systemic infection. These studies showed that the capsule interferes with the phagocytic killing, prevents internalization of GAS by epithelial cells, modulates adherence mediated by other GAS surface molecules, and acts as a ligand for attachment of GAS to CD44 on pharyngeal keratinocytes. Despite these other advances, it remains undefined how the capsule or other virulence determinants control the processes of tissue invasion and persistent colonization in the host. During the next funding period, their objectives are to define the role of the hyaluronic acid capsule in invasion of GAS from an epithelial surface to deep tissue, to characterize the effects of capsule on intracellular trafficking of GAS in epithelial keratinocytes, and to determine how regulation of capsule expression in vivo contributes to pathogenesis of GAS infection. The proposed experiments will make use of primary keratinocyte cultures and a model system simulating intact human skin in conjunction with confocal fluorescence microscopy in order to study the tissue and cell biology of GAS translocation through human skin, the phenomenon of persistence within cells, and the regulation of capsule expression at various phases of the infection process. Results of these studies will elucidate the basic pathogenic mechanisms involved in GAS disease and may suggest strategies for intervention. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: IMMUNE RESPONSES TO PNEUMOCOCCAL ANTIGENS IN CHILDREN Principal Investigator & Institution: Kobrynski, Lisa J.; Pediatrics; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2002; Project Start 01-AUG-2000; Project End 31-JUL-2004 Summary: (Adapted from applicant's description): The objective of this proposal is to provide a period of mentored, multi-disciplinary training in clinical and laboratory research in pediatric immunology. CD 1 has recently been implicated in the antigen presentation of certain bacterial lipo-polysaccharides in a non-MHC dependent fashion. The applicant's data suggest that there is a role for CD1 restricted T cells in immune responses to pneumococcal polysaccharides and that a lack of these cells results in the inability to produce pneumococcal specific IgG. The proposed project will characterize these cells, delineate their role in polysaccharide antibody responses and ascertain

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whether patients in at-risk populations have alterations in this T cell subset. Identification of the precise role of these cells and the nature of the defect in susceptible hosts has the potential to lead to novel therapeutic regimes. This work has potentially broader applications in the immune responses to other polysaccharide antigens of common infectious agents. In addition, the applicant will pursue further training in study design and research methods, including didactic courses at the Rollins School of Public Health and the Graduate Division of Biological and Biomedical Sciences, at Emory. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: IMMUNITY TO PNEUMOCOCCAL SURFACE PROTEIN A AND C Principal Investigator & Institution: Briles, David E.; Professor; Microbiology; University of Alabama at Birmingham Uab Station Birmingham, Al 35294 Timing: Fiscal Year 2002; Project Start 01-AUG-1984; Project End 31-OCT-2002 Summary: (Adapted from the applicant's abstract): The proposal is aimed at continuing Dr. Briles' research efforts in the study of pneumococcal surface antigens. The application focuses on the first cell-associated protein described, PspA, as well as a second newly discovered protein, PspC. These two proteins may serve as vaccines themselves or as protein carriers for capsular polysaccharide-protein conjugates. PspA is present on all pneumococcal strains and can elicit protective immunity against sepsis and nasopharyngeal carriage in mice. PspC is related to PspA, but larger in size, and shows virtual identity with PspA in its C-terminal half. The proposed studies will determine whether PspC is a virulence factor and whether it can elicit protection. The relative roles of PspA and PspC in virulence and carriage in nonimmune animals will be examined. In addition, the relative roles of immunity against PspA and PspC in carriage, sepsis, and spread of pneumococci from the nasopharynx will be explored. The ability of human antibody to these molecules to protect mice from infection will be evaluated. Cross-reactive regions between the PspA and PspC proteins will be identified as well as the regions of each molecule most useful as a vaccine. Immunity to PspA and PspC will be evaluated to determine whether it involves opsonization, blocks virulence functions, or acts by other mechanisms. The data obtained will assist with the development of correlates of protective immunity for PspA and PspC that can be applied to vaccine development. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: IMMUNOCHEMISTRY POLYSACCHARIDES

OF

GROUP

B

STREPTOCOCCAL

Principal Investigator & Institution: Kasper, Dennis L.; Associate Director; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2001; Project Start 01-SEP-1985; Project End 31-JUL-2004 Summary: The major approach to the prevention of infection by encapsulated bacteria has been the use of vaccines consisting primarily of the polysaccharide capsules of these bacteria. The group B Streptococcus (GBS) is the most serious pathogen for the neonatal age group. Antibody to the capsular polysaccharides of GBS has been shown to be protective. Attempts to induce protective immunity to GBS utilizing polysaccharide capsules have met with only modest success due to the overall poor immunogenicity of these polysaccharide antigens in humans. The most effective approach to overcoming the problem of poor immunogenicity of polysaccharides has been covalent coupling to carrier proteins to produce conjugate vaccines, which have significantly enhanced

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immunogenicity. While it is clear that induction of T cell help is one important aspect of the enhanced immunogenicity of these conjugates, another factor, which we believe to be important, is the effect of conjugation on the polysaccharide epitope presentation and expression. Our studies of GBS polysaccharides have defined a unique system that allows the determination of how specific physicochemical characteristics, such as antigen conformation, affect the host recognition of polysaccharide antigens. Antibodies directed against these polysaccharides appear to recognize a conformational epitope that is fully expressed in higher-molecular-weight forms of the polysaccharide. Although a conjugate vaccine is likely to enhance the immune response by eliciting T cell help, conjugate designs that stabilize the conformational epitope may also increase the immune response by enhancing expression of this epitope. In this proposal we present a program to rigorously define model conjugate vaccines that allow the differentiation of the effects of conjugation in modifying polysaccharide epitope expression as distinct from the T cell dependent effects. Conjugation may modify particular structural features of the polysaccharide making it more immunogenic by changing the interaction of the polysaccharide and immune system. There are five specific aims in this proposal. In Specific Aims 1 and 2, oligosaccharides of differing length will be conjugated either at the reducing end or at multiple sites along the chain to determine what effect conformational stability has on the chain-length dependent epitope. The effect of single versus multisite coupling on T cell dependence will be studied. In Specific Aim 3,the effect on T cell dependence of the degree of cross-linking between the full length polysaccharide and the carrier protein molecules in a conjugate vaccine will be studied. In Specific Aims 4 and 5, specific chemical parameters which define conformation, NMR spectroscopy, and X-ray crystallography will define precisely how conformationally dependent polysaccharide epitopes interact directly with antibody. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: IMMUNOPROTEOMICS Principal Investigator & Institution: Boyle, Michael D.; Professor; Biology; Juniata College 1700 Moore St Huntingdon, Pa 16652 Timing: Fiscal Year 2002; Project Start 01-JUN-2002; Project End 31-MAY-2005 Summary: (provided by applicant): The proposed studies are designed to evaluate new methods using a mass spectral readout to provide sensitive, detection of selected proteins, as well as methods to monitor post-translational modification events of targeted antigens. The proposed assay involves an antigen capture step mediated by immobilized antibody (immuno) and an analytical step involving mass spectral analysis of bound antigen (proteomics). The goal of the project is to develop rapid sensitive methods of antigen capture from complex mixtures of unrelated proteins in a maimer that permits the subsequent precise molecular weight determination of the bound antigen using time of flight mass spectrometry. The ability to distinguish subtle variation in the size of a targeted antigen will allow analysis of post-translational modification events for any targeted antigen to be achieved. In addition, the ability to obtain semi-quantitative data based on the area under a specific molecular weight peak on the mass spectral read-out will be critically evaluated. The proof of concept studies will focus on a number of properties of the secreted streptococcal cysteine protease SpeB which is known to post-translationally modify the surface anti-phagocytic M protein, and degrade the secreted bacterial plasminogen activator SK. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: INHALED PARTICLES AND HOST DEFENSE IN THE PRIMED LUNG Principal Investigator & Institution: Kobzik, Lester; Associate Professor; Environmental Health; Harvard University (Sch of Public Hlth) Public Health Campus Boston, Ma 02115 Timing: Fiscal Year 2003; Project Start 07-JUL-2003; Project End 31-MAY-2008 Summary: (provided by applicant): The Problem: Hospital admissions for pneumonia are increased by elevated air particle levels. The mechanism(s) underlying particle effects on lung infection are unknown, but may reflect increased incidence of infection, increased severity of infection, or both. Hypothesis: The pathogenesis of the pneumococcal pneumonia (the most common variety and the disease we will study) suggests three possible mechanisms for particle effects: enhancement of lung cell 'receptors' used by bacteria for initial adhesion, damage to antimicrobial function of host cells (AMs and PMNs), and exaggerated inflammation in established infection leading to worse signs and symptoms. Hence, the central thesis of this research is that oxidant components of air particles mediate 1) dysfunction of host defenses against infection (incidence) and 2) increased inflammation in extant pneumonia (severity). Experimental Plan: Aim 1 will measure expression and function of pneumococcal 'receptors' (e.g., PAF receptor) used by pneumococcal for initial adhesion after exposure to concentrated ambient particles (CAPs) or control particles. Aim 2 will determine effects of air particles on pulmonary inflammation before and after onset of pneumococcal pneumonia. The hypothesis to be tested is that particles cause enhanced release of cytokine mediators by primed AMs, leading to increased inflammation and ultimately oxidant damage to both AM and PMN In vivo and in vitro studies will measure release of pro-inflammatory cytokines, cell influx and viability and severity of pneumonic inflammation. Aim 3 will test the hypothesis that particle exposure inhibits bacterial clearance via oxidantdependent damage of anti-microbial functions of AMs and PMNs. Component analysis will be performed using a panel of CAPs samples to provide links of particle constituents (e.g., metals, organics, endotoxin) with biologic effects. Rotated factor analysis will be used to correlate source types with CAPs toxicity. Specific intracellular oxidant pathways will be identified by measurement of oxidant production, intracellular levels of antioxidants, and the effect of a panel of anti-oxidants and other inhibitors. Significance: This research is relevant to the public health question of how inhaled particles cause pulmonary health effects and to the pathophysiology of lung host defense against environmental agents. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: INTERGENERIC SIGNALING MOLECULE OF STREPTOCOCCUS CRISTATUS Principal Investigator & Institution: Xie, Hua; Associate Professor; Meharry Medical College 1005-D B Todd Blvd Nashville, Tn 37208 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2007 Summary: Dental plaque (biofilm) has been implicated as a primary causative agent of adult periodontal disease. The key event leading to initiation of the disease is the transition from commensal dental biofilm to pathogenic biofilm. It is well known that the process of the transition is involved in the colonization of several specific periodontal pathogens such as Porphyromonas gingivalis. Our long-range goal is to understand events and factors leading to the transformation of healthy plaque to pathogenic plaque and to change the course of development of periodonpathogenic

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biofilm by preventing attachment of P. gingivalis. In our ongoing studies, we have identified several environmental factors that can influence expression of fimA gene, a virulence gene encoding a major protein unit (fimbrillin) of fimbriea. One of the striking findings is that the presence of Streptococcus cristatus molecule(s) could significantly repress fimA expression in P. gingivalis at the transcriptional level. As a result, S. cristatus could inhibit the formation of P. gingivalis biofilm in vitro. In this grant proposal, we will put our focus on characterization of S. ctristatus signaling molecule, biochemically and genetically. The hypothesis for this proposal is that S. cristatus plays an important role in impeding P. gingivalis' colonization on dental biofilm through intergenric signaling systems. To test this hypothesis, we will start with identification and purification the signaling molecule(s) of S. cristatus. The signaling molecule will be characterized in the terms of functional and genetic structures. We will also attempt to understand regulation of the signaling gene expression in oral biofilm. Therefore, the signaling gene of S. cristatus will be cloned. The promoter region of the gene will be fused with the reporter gene such as chloramphenical acetyltransferase gene, and level of the gene expression will be determined by measuring enzymatic activity. Finally the role of this molecule in the formation of pathogenic oral biofiim will be investigated. Studies will be initiated to determine the distribution of the signaling molecule in the dental plaques from healthy subjects and pedodontitis patients. Our ultimate goal is to convert the knowledge gained from these laboratory studies to practical technology that may be used to reprogram development of the dental biofilm and to reduce the incidence of adult periodontitis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: INTRARTICULAR SLPI THERAPY FOR RHEUMATOID ARTHRITIS Principal Investigator & Institution: Labhasetwar, Vinod D.; Associate Professor; Pharmaceutical Sciences; University of Nebraska Medical Center Omaha, Ne 681987835 Timing: Fiscal Year 2002; Project Start 28-SEP-2001; Project End 31-JUL-2003 Summary: (provided by applicant): Rheumatoid arthritis (RA) is a chronic inflammatory disease, characterized by the loss of joint structure and function, resulting in significant pain and morbidity. In this proposal, we plan to investigate a new therapeutic strategy for the treatment of RA. In normal joints, the cartilage matrix turnover is maintained due to a balance between the activities of proteases and protease inhibitors. This balance is lost in arthritic joints, resulting in a greater protease activity, leading to cartilage and bone degeneration. Secretory leukocyte protease inhibitor (SLPI) has been identified as an endogenous potent protease inhibitor that maintains the critical balance against the proteases in the joint. Since SLPI is not produced by the joint tissue and the arthritic joints loose their ability to sequester SLP1 from the blood, it is hypothesized that intra articular administration of SLPI in a sustained release formulation would be effective in reinstating the balance between the proteases and protease inhibitors, and in inhibiting the progression of the disease. SLPI is also considered to be involved in protecting the cartilage growth factor (Link N) in the joint from protease-mediated degradation. The link N promotes the synthesis of proteoglycan and collagen, which are required for maintaining normal cartilage composition in the joint. Therefore, localized SLPI therapy could also lead to regeneration of the cartilage matrix and restoration of joint functions. Therefore, the objective of the proposed studies is to determine the efficacy of sustained intra articular delivery of SLPI using an injectable thermo reversible (TR) gel system in RA. The specific aims of the research program are: (1) To formulate a sustained release TR gel system for SLP1 using biodegradable and biocompatible Polyethylene oxide-Poly (L-Lactide)-Polyethylene oxide copolymer, and to evaluate the gel for sustained protein

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release properties, (2) To investigate the kinetics of intra articularly injected SLPI-gel system to provide localized and sustained delivery of the protein, and to determine the therapeutic efficacy of the gel to inhibit the progression of the disease in a rat streptococcal. cell wall-induced model of inflammatory erosive arthritis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: LETHAL PNEUMOCOCCUS

SYNERGISM

BETWEEN

INFLUENZA

AND

Principal Investigator & Institution: Mccullers, Jonathan A.; Assistant Member; St. Jude Children's Research Hospital Memphis, Tn 381052794 Timing: Fiscal Year 2002; Project Start 01-APR-2001; Project End 31-MAR-2004 Summary: (provided by applicant): The K08 Award will provide an opportunity for the applicant to extend his virology training in the area of viral-bacterial interactions and to develop new expertise in pneumococcal pathogenesis in the setting of prior viral infection. These skills will enable the applicant to achieve his long term career goals by becoming a fully independent research scientist who can translate observations made at the bench into therapeutics and interventions at the bedside. Epidemiologic evidence suggests that there is a lethal synergism between influenza A virus and Streptococcus pneumonias accounting for excess mortality (average 20,000 influenza-related deaths per year in the US) during influenza epidemics. However, the pathogenic mechanisms underlying this interaction are poorly understood, and the lack of a suitable animal model of pneumonia following infection with both organisms has hampered study. The goal of the proposed research plan is to determine the role of receptor alterations engendered by influenza virus infection in the pathogenesis of pneumococcal pneumonia. A newly developed murine model of dual infection will be used to examine the relationships of timing and of infectious doses of influenza virus and pneumococcus to morbidity and mortality. Influenza viruses with different pathogenic features in the mouse will be utilized to determine how cytokine expression varies with different viruses. Expression of receptors permissive for pneumococcal adherence and invasion will be examined in the context of cytokine expression following influenza virus infection, and a correlation to development of pneumonia and in the murine model of dual infection will be made. Identification of specific pneumococcal proteins involved in this synergistic interaction will provide drug and vaccine targets for future intervention in human disease and death caused by pneumococcal superinfection following influenza. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: LUXS-MEDIATED QUORUM SENSING IN STREPTOCOCCUS MUTANS Principal Investigator & Institution: Wen, Zezhang; Oral Biology; University of Florida Gainesville, Fl 32611 Timing: Fiscal Year 2003; Project Start 15-JUN-2003; Project End 31-MAY-2005 Summary: (provided by applicant): Streptococcus mutans is recognized as the principal etiological agent of dental caries, the most prevalent infectious disease of humans. The ability to metabolize carbohydrates and generate acids, to survive acidic pH and other adverse conditions, and to adhere to and form tenacious biofilms on the tooth surface are believed to be critically associated with the cariogenicity of this human pathogen. Known for its high degree of acid tolerance (aciduricity) and its high capacity to produce acid (acidogenicity), S. mutans lives primarily on the tooth surface at high cell-

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Streptococcus

density in a high diversity ecosystem better known as dental plaque, the structure and composition of which is known to be largely influenced by such factors as the source and availability of nutrients, the pH in the oral cavity and by the ability of the biofilm organisms to adapt to the fluctuations in environmental conditions. Quorum sensing is a cell density--dependent regulatory mechanism that is known to be involved in regulation of a variety of physiologic processes and virulence in both Gram (+) and Gram (-) bacteria. We have recently generated evidence that the S. mutans possesses a gene encoding a functional homologue of the new family of autoinducer synthases (LuxS) that are responsible for production of autoinducers of the quorum sensing system 2, AI-2. This study is designed to yield novel information concerning LuxSmediated quorum sensing and virulence regulation in S. mutans, which will contribute to our understanding of the pathogenesis of this microorganism and the ecology of the oral flora. The Specific Aims of this proposed study are: 1) to investigate the role of luxS in acid tolerance by S. mutans. By using functional assays, reporter gene fusions, Northern hybridization, and proteomics, we will investigate acid tolerance and its regulation by luxS, and identify novel factors (proteins) that are involved in luxSregulated acid tolerance responses. 2). To use confocal laser scanning microscopy (CLSM) and mixed, known-species consortia to determine the impact of luxS of S. mutans on bacterial adherence by S. mutans and the inter- and intra-generic interactions between S. mutans and other oral bacteria in terms of biofilm initiation development and structure. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MATERNAL IMMUNIZATION TO PREVENT INFANT OTITIS MEDIA Principal Investigator & Institution: Ferrieri, Patricia; Professor; Pediatrics; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2006 Summary: (provided by applicant): Vaccine strategies to prevent childhood otitis media (OM) are being sought due to its major public health impact and the troubling increase in antibiotic resistant bacteria. The pneumococcus bacteria is a prime target for vaccine prevention. Maternal immunization is a strategy designed to prevent early infant OM, since it is one of the greatest risk determinants for recurrent and chronic OM. A recently licensed 7-valent pneumococcal conjugate vaccine (PCV7) is now given routinely to all infants beginning at age 2 months. This vaccine is highly protective against invasive pneumococcal disease after 7 months of age, has modest (6-9%) protection against all OM episodes between 7 and 24 months, and a 57% reduction in vaccine-type pneumococcal AOM. But it does not significantly reduce OM before 7 months. Thus, there remains a potentially important role for maternal pneumococcal immunization to prevent pneumococcal AOM in the first 6 months of life. Thus, it is important to test the hypothesis that maternal pneumococcal immunization during pregnancy does not produce immune interference in the infant, impairing response to the infant vaccine, before proceeding with a maternal vaccine OM efficacy trial. This Phase I/II trial will enroll 154 pregnant women and follow subjects and their infants to age 13 months. Primary aims are: (1) to determine if infants of women immunized with 9-valent PCV (PCV9) and infants of control women who receive placebo during the third trimester of pregnancy have equivalent anti-capsular polysaccharide (PS) IgG antibody responses to PCV7 measured one month after the third vaccine injection at 6 months of age, and (2) to compare local and systemic adverse events among women immunized with PCV9 or placebo. We will also investigate the hypotheses that (1) maternal immunization does

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not interfere with the infant's antibody subclass and pneumococcal opsonic responses to the primary PCV7 vaccine series or to booster PCV7 immunization at 12 months, (2) pregnant women have a significant antibody response to PCV9 vaccine compared to placebo vaccine and increased antibody persists 13 months after delivery, (3) anti-PS IgG and secretory IgA antibodies are present in the milk of immunized lactating women, and (4) maternal immunization does not interfere with the infants' antibody response to H. influenzae type b conjugate and diphtheria toxoid vaccines. Transplacental anti-PS IgG antibody transfer, the natural decline of two anti-PS antibodies against PS antigens in the maternal but not the infant vaccine, and the natural production of one anti-PS antibody not in either vaccine will be measured. The trial has enrolled and randomized 87 subjects to date with continuous, steady subject accrual since November 2000. Results of this trial will have a profound impact on the broad field of maternal immunization to prevent early infant disease caused by a variety of infant bacterial and viral pathogens. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MCP--STRUCTURE, MICROBIAL INTERACTIONS AND FUNCTION Principal Investigator & Institution: Atkinson, John P.; Professor of Medicine & Molecular Biolog; Medicine; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2002; Project Start 01-APR-1995; Project End 31-MAR-2005 Summary: (adapted from investigator's abstract): The complement system is ingeniously designed to prevent infections as well as to process immune complexes and damaged tissue. Strict control of its activation during innate and acquired humoral immune responses is critical to minimize damage to host tissue. Membrane cofactor protein (MCP; CD46) is widely expressed inhibitor of complement activation at the critical step of C3/C5 convertase generation. It serves as a cofactor for the serine protease factor I to cleave and thereby inactivate C3b and C4b that deposit on host tissue. Most cells and tissues express MCP as a family of four isoforms that differ in their O-glycosylation and cytoplasmic tails. MCP is a receptor for three human pathogens: measles virus, Streptococcus pyogenes and Neisseria. Attachment of the measles virus of Neisseria to MCP transmits signals for IL-12 down-regulation in monocytes or for calcium fluxes in epithelial cells, respectively. MCP has also been implicated in reproduction, in large part due to its dense expression on placental trophoblast and on the inner acrosome membrane of spermatozoa. Because of its potent complement regulator activity, MCP has been recombinantly produced for use as a soluble therapeutic agent and engineered into pigs whose organs are being employed for xenografting. In this grant application, we propose to continue our studies on the structure, microbial interactions and function of MCP. We postulated and later demonstrated during the prior grant period that each of four regularly expressed isoforms of MCP possesses functional advantages. In this renewal application we continue this focus while placing an increased emphasis on microbial connections and cell signaling. The active sites of MCP will be characterized by NMR spectroscopy and X-ray crystallography. We have recently demonstrated that in three cell types MCP is tyrosine phosphorylated on one of its two cytoplasmic tails. For this signaling event, we propose a systematic analysis of the site(s), responsible kinase(s), and related downstream events. Additionally, we will explore in depth the microbial interactions with MCP as they relate to binding sites, signaling events, and three-dimensional structure. We will characterize three strains of transgenic mice expressing human MCP. We anticipate these animals will be a valuable tissue source. We also propose a targeted disruption of the MCP mouse gene since MCP is expressed

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Streptococcus

predominantly on the inner acrosomal membrane of mouse spermatozoa. The fertility of these mice will be assessed and they will be crossed with other deficient mice strains to explore the role of MCP in reproduction. Lastly, the mechanism of action of MCP in situ will be analyzed by quantitative methods developed during the prior granting period. We will address such questions as the role of membrane versus fluid phase inhibitors and contribution of MCP versus decay accelerating factor. The specific aims of this proposal outline a broad-based approach to increase our understanding of complement regulation by one if its major inhibitory proteins. Additionally, these experiments will expand our knowledge of the fascinating interactions of this complement regulator with three common infectious diseases and its role in cell signaling events and reproduction. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MECHANISMS OF CELL INJURY IN BURN COMPLICATED BY SEPSIS Principal Investigator & Institution: Horton, Jureta W.; Professor; Surgery; University of Texas Sw Med Ctr/Dallas Dallas, Tx 753909105 Timing: Fiscal Year 2002; Project Start 01-AUG-1999; Project End 31-JUL-2003 Summary: (adapted from applicant's abstract): Despite aggressive fluid resuscitation and topical antimicrobial therapy after burn trauma, sepsis frequently results from the loss of dermis; thus sepsis and resultant multiorgan failure are a major cause of death in the burn unit. Studies from the PI's lab and others' have shown that burn trauma and sepsis independently alter cardiocirculatory performance, and recent studies suggest that myocardial abnormalities after burn, trauma or sepsis are related to intracellular accumulation of calcium with subsequent cellular injury and dysfunction. Although this field has grown rapidly, much is still unknown about the cellular mechanisms underlying cardiac dysfunction after either trauma or sepsis. The PI's group have focused their attention on a clinically relevant model of burn injury complicated by sepsis (intratracheal administration of S. pneumoniae administered 24 hours postburn) and have shown progressive cardiocirculatory dysfunction in this two-hit model. Specific Aim 1a will determine if burn/sepsis exacerbates the increased [Ca2+] and [Na2+] shown to occur after burn alone and will determine the contribution of altered Na+/Ca2+ to cardiac contractile dysfunction. Specific aim 1b will determine the contribution of transient cellular acidosis and altered H+/Na+ exchange to increased [Na2+], and whether increased [Na+] in turn promotes Na+/Ca2+ exchange in [Ca2+] overload. Specific Aim 2 will determine the contribution of burn/ sepsis-mediated alterations in SR Ca2+ handling (SR Ca2+ efflux, Ca2+-ATPase activity, SERCA, and SR Ca content) to cellular Ca2+ and cardiac contractile deficits and determine the contribution of burn/sepsis induced myofilament Ca2+ insensitivity to cardiac contractile dysfunction. Studies in Specific Aim 3 will examine the role of PKC activation in intracellular Na+/Ca2+ accumulation and cardiac contractile dysfunction in burn sepsis. Studies in Specific Aim 4 will determine the contribution of increased [Ca2+] and reactive oxygen species to apoptosis in burn/sepsis and further determine the contribution of apoptosis to burn/sepsis-induced ionic derangements as well as cardiac contractile dysfunction. Only by understanding the cellular events involved in the postburn inflammatory cascade can adequate prevention and treatment modalities be designed to improve outcome. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MECHANISMS OF TANDEM REPEAT DELETION IN GROUP B STREP Principal Investigator & Institution: Puopolo, Karen M.; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2002; Project Start 07-FEB-2002; Project End 31-JAN-2007 Summary: (Provided by Applicant): Group B Streptococcus (GBS): is a leading cause of serious infection in newborns and pregnant women, and in adults immunologically impaired by liver disease, diabetes and malignancy. GBS contain a family of immunogenic surface proteins that are characterized by the presence of long tandemlyrepeated elements, the prototype of which is the alpha C protein. Previous work has demonstrated that variation in the number of tandem repeats in the gene for the alpha C protein (bca), alters the antigenicity of the protein and the virulence of the strain in the presence of specific antibody. Tandem repeat deletion in the alpha C protein allows antigenic variation and may thus serve as a virulence mechanism in GBS. The molecular mechanism by which excision of tandem repeat units in bca is accomplished is unknown. Identification of the molecular factors involved in tandem repeat deletion of broader interest as tandem repeat sequences of DNA are found in both prokaryotic and eukaryotic genomes, and variation in these sequences is associated both with changes in bacterial virulence and the genesis of inherited human diseases. Previous work by the applicant has demonstrated that inactivation of recA, the principal gene involved in bacterial homologous recombination, does not affect tandem repeat deletion in GBS. The scientific goals of this project are to identify genes involved in tandem repeat deletion in GBS, and to determine the role of conserved nucleotide sequences within repeats in directing tandem repeat deletion. To meet these goals, a plasmid -based reporter system will be constructed to complement studies of chromosomal tandem repeat deletion. The training goal of this project is to prepare the applicant for a career in bacterial genetic research by providing didactic education and the opportunity to develop laboratory expertise in this rapidly evolving field. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MOLECULAR DETERMINANTS OF HUMAN PNEUMOCOCCAL IMMUNITY Principal Investigator & Institution: Reason, Donald C.; Associate Scientist; Children's Hospital & Res Ctr at Oakland Research Center at Oakland Oakland, Ca 946091809 Timing: Fiscal Year 2002; Project Start 01-APR-2000; Project End 31-MAR-2005 Summary: Antibodies directed against the capsular polysaccharides of the pathogen Streptococcus pneumoniae protect humans against infection, and are elicited by vaccination with polysaccharide or polysaccharide conjugated to protein carriers. In the proposed study the variable region gene usage and junctional diversity of human antibodies specific for S. pneumoniae capsular serotypes 6B, 14, and 23F will be determined by repertoire cloning and sequence analysis. The influence of plain polysaccharide and polysaccharide-protein conjugate vaccine formulations on the expressed repertoire will be investigated, and the degree to which these thymusindependent and thymus-dependent forms of the vaccine induce somatic mutations and affinity maturation will be determined. The structural determinants of antipolysaccharide antibody affinity will be defined by sequence comparison, site directed mutagenesis, and molecular modeling. Sequence-defined Fab fragments will be expressed in vitro , their affinity and fine specificity determined, and the relationship between antibody affinity and protective efficacy established using an in vitro

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Streptococcus

opsonophagocytosis assay. Our overall hypothesis is that the quality of an oligoclonal antibody response, such as that seen in humans to bacterial capsular polysaccharides, is influenced to a greater degree by the affinities of the individual antibody binding domains than would be a polyclonal response. These differences in antibody affinity arise as a consequence of variable region gene usage, junctional diversity, and somatic mutation. The generation of affinity loss variants by somatic mutation could therefore leads a diminution of overall antibody quality. These studies will determine if antibodies to structurally distinct polysaccharides utilize the same or distinct variable region genes and the degree to which maturation of the response through somatic mutation determines overall affinity of the response. These studies will also determine if the same clonotypes occur in unrelated individuals, and if a single clonotype predominates the response to a given specificity. Defining the relationship between binding site affinity and antibody functional quality will provide better surrogate markers of protective immunity. Understanding the molecular mechanisms that shape the human antibody repertoire to pneumococcal polysaccharides may also suggest strategies that would facilitate the development of more efficacious vaccines. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOLECULAR INTERACTIONS BETWEEN SPEA AND THE TCR Principal Investigator & Institution: Collins, Carleen M.; Professor; Microbiology; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2002; Project Start 01-AUG-1998; Project End 31-JUL-2004 Summary: (Adapted from the applicant's abstract): In recent years in both this country and abroad, there has been a resurgence of acute, often life threatening infections due to Streptococcus pyogenes (group A streptococcus). Many patients experience symptoms mimicking this associated with staphylococcal toxic shock syndrome, and the designation streptococcal toxic shock syndrome (STSS) has been assigned to these invasive streptococcal infections. There is strong epidemiologic evidence implicating streptococcal pyrogenic exotoxin A (SpeA) in the pathogenesis of STSS. SpeA is a bacterial superantigen that is capable, in combination with class II major histocompatibility molecules, of activating a large fraction of T cells. The pathology of STSS and other bacterial superantigen mediated disease is believed to result from the massive and unregulated release of bioactive cytokines from the activated T cells. SpeA and other bacterial (and viral) proteins have been termed superantigens due to their unique mechanisms of interacting with the class II MHC expressing antigen-presenting cells and the T lymphocytes. Superantigens bind to class II MHC as intact molecules at sites distinct from the antigen-presenting groove. In addition to binding the class II MHC molecule, superantigens interact with the T cell receptor (TCR) in regions encoded by the V-gene segments. Each superantigen activates a specific set of V-beta chainencoding T cell, and thus is able to activate a much larger percentage of the T cell population than conventional peptide antigens. The goals of this grant proposal are to examine in detail the interaction between SpeA and the human TCR. The amino acid residues of SpeA needed for a productive TCR interaction will be defined. V-beta chains amino acids residues needed for a productive interaction with SpeA will be identified. These studies will include measurements of the affinities of the toxin- V-beta interactions. In addition, the X ray crystal structure of the toxin, mutant and allelic toxin forms, as well as the toxin completed with a human V-beta chain will be determined. These data will help characterize the interaction needed for activation of a T cell by the superantigen. In addition, the data obtained here are the first step in the design and development of compounds, such as TCR specific peptides, to interfere with the SpeA-

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TCR interaction, and in turn prevent SpeA from acting as a superantigen. It is possible that components that can specifically block the superantigenic capabilities of SpeA might prove useful as treatments to ameliorate and possibly prevent STSS in an infected individual. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOLECULAR COLONIZATION

MECHANISMS

OF

PNEUMOCOCCAL

Principal Investigator & Institution: Sebert, Michael E.; Microbiology; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 01-JUL-2002; Project End 31-MAR-2007 Summary: (provided by applicant): This application describes a 5-year program designed to provide training for Dr. Michael Sebert in the skills necessary to become an independent researcher in the field of microbial pathogenesis. Dr. Sebert is currently completing his fellowship training in pediatric infectious diseases. His present work in the laboratory of Dr. Jeffrey Weiser, his sponsor for this application, has provided preliminary exposure to the study of the molecular mechanisms of bacterial infection. The educational plan outlined herein consists of both a comprehensive didactic program intended to provide a solid foundation in molecular genetics, prokaryotic cell biology, immunology, and bacterial pathogenesis as well as a roadmap for the in-depth laboratory experience necessary for his maturation into a productive, independent investigator. Colonization of the upper respiratory tract by the major bacterial pathogen Streptococcus pneumoniae serves as the common first step in the pathogenesis of the wide range of disease processes caused by this organism. How S. pneumoniae senses and adapts to this environment is unknown. Genomic analyses of the pneumococcus have revealed over a dozen putative two-component signal transduction systems. PreliminaryInvestigations have revealed that one of these systems, CiaRH, is required for persistence of the organism in the infant rat nasopharynx and that a portion, but not all, of this failure to colonize effectively can be attributed to downregulation of a putative serine protease, HtrA. The hypothesis to be tested in the proposed research is that a set of genes is regulated by the CiaRH system that collectively account for the requirement of this system for effective carriage. The first specific aim toward this objective is the biochemical and molecular characterization of the HtrA protein in order to define its precise role in nasal carriage. The second specific aim of this project is the definition of the sequence elements upstream of htrA responsible for its regulation by CiaRH and the subsequent usage of this information to identify other genes under the control of CiaRH that contribute to colonization. Together these lines of investigation hold the potential to expand the understanding of the molecular basis of this critical step in the pathogenesis of S. pneumoniae. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NOVEL BIFUNCTIONAL MOLECULES FOR INTRAORAL DRUG DELIVERY Principal Investigator & Institution: Periathamby, Antony R.; Sullivan Professor; Periodontics; Marquette University P.O. Box 1881 Milwaukee, Wi 532011881 Timing: Fiscal Year 2002; Project Start 01-JUN-2002; Project End 31-MAY-2004 Summary: The goal of this innovative research project is to develop simple bifunctional molecules for intraoral delivery of antimicrobial agents. The bifunctional hybrid molecules will each be composed of a carrier sequence possessing high affinity for tooth

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and pellicle surfaces, and a natural antimicrobial peptide. These two sequences will be linked to each other with a biodegradable bond. With this linkage, antimicrobial sequences inherently linked to the carrier will be released efficiently from the tooth surface and in saliva through the oral physiological and microbial environment for a controlled and sustained release of the antimicrobial agent, thereby providing a novel and efficient method for intraoral drug delivery. This research project involves: 1) Synthesis of hybrid molecules by rationally selecting carrier sequences from salivary statherin, and antimicrobial sequences from bactenecins and defensins; 2) Determination of toxicity of hybrid molecules to ensure that they are cytotoxic only to microbes; 3) Delineation of the effect of whole saliva on the stability of hybrid molecules; 4) Assessment of the adsorption and desorption characteristics of hybrid molecules onto hydroxyapatite surfaces; 5) Determination of the extent of adherence of Candida albicans, Porphyromonas gingivalis, Actinobacillus actinomycetemcomitans, Streptococcus mutans, Streptococcus gordonii and Streptococcus sanguis onto the hybrid adsorbed hydroxyapatite surfaces. This proposed research will identify new, safe, and affordable hybrid molecules for the prevention and treatment of plaquerelated oral diseases. The hybrid molecules can be directly used as a topical rinse, or irrigant or they may be applied professionally to sub-gingival areas. The oral physiological and microbial environment will naturally induce the dissociation and the release of the antimicrobial peptide from the tooth surface into the site of oral infection. The hybrid molecules will serve as an efficient local drug delivery system and eliminate the discomfort and retention problems associated with the existing local delivery devices. The hybrid molecules will have a high potential for clinical and commercial application as anti-plaque agents. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NUCLEASE-RESISTANT OPSONIZATION

APTAMERS

FOR

ANTHRAX

Principal Investigator & Institution: Bruno, John G.; Operational Technologies Corporation Suite 230 San Antonio, Tx 78229 Timing: Fiscal Year 2004; Project Start 01-APR-2004; Project End 31-OCT-2004 Summary: (provided by investigator): The anti-phagocytic poly-D-glutamic acid (PDGA) capsule of Bacillus anthracis is a major virulence factor of inhalation anthrax. Although generation of antibodies to PDGA might be of value in opsonizing vegetative anthrax, such antibodies would require "humanization". A simpler and less expensive approach would be the development of nuclease-resistant ('shielded') DNA aptamers against PDGA with an Fc-TR or C3bR binding domain at the other end of a 'hybrid' aptamer. In Phase I, Operational Technologies (OpTech) in conjunction with the Biochemistry Department of the University of Texas at San Antonio (UTSA), proposes to develop 2'- amino pyrimidine modified shielded DNA aptamers against PDGA, murine Fc-yR, and C3bR by the SELEX process. OpTech will link the aptamers and compare phagocytosis of PDGA-conjugated microbeads by the RAW 264.7 macrophage-like cell line in the presence and absence of shielded aptamers and versus serum opsonized PDGA-conjugated microbeads. Since polyanionic PDGA appears to inhibit phagolysosome formation and killing of ingested bacteria, targeting PDGA with 2'amino-modified aptamers may serve to partially neutralize the polyanionic charge and enable bacterial killing by the respiratory burst. In Phase II, OpTech will clone and sequence all aptamers, then assess aptamer-opsonization and bacterial killing in RAW 264.7 cells with virulent anthrax at the Southwest Research Foundation. Since anthrax and some other infectious bacteria utilize capsules to evade phagocytosis, any

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inexpensive reagent that acts as an effective opsonin would be of tremendous value in the medical, veterinary or agricultural communities. If successful, OpTech will possess a pharmaceutical substance of great commercial value in the post-exposure treatment of anthrax. Further development of the concept for shielded aptamers against hyaluronic acid or other capsule materials, for example, would also lead to better treatments for many Streptococcus-related infections. Such shielded aptamers could even be used in inhalers to enhance alveolar macrophage phagocytosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PANDAS AND STREP INFECTION: ARE THEY LINKED? Principal Investigator & Institution: Kurlan, Roger M.; Professor; Neurology; University of Rochester Orpa - Rc Box 270140 Rochester, Ny 14627 Timing: Fiscal Year 2002; Project Start 25-SEP-2001; Project End 31-JUL-2005 Summary: Sydenham's chorea is the only accepted immune-mediated central nervous system manifestation of group A beta hemolytic streptococcal (GABHS) infection. Several lines of evidence now suggest that there may be a spectrum of post-GABHS immune- mediated neurobehavioral sequelae termed "Pediatric Autoimmune Neuropsychiatric Disorders after Streptococcal Infection (PANDAS)". Tics, including Tourette's syndrome (TS), and obsessive-compulsive disorder (OCD) have been reported as the characteristic features of PANDAS. Proposed is a multicenter prospective case control cohort study involving 40 cases of PANDAS and 40 matched controls with TS and/or OCD but without evidence of PANDAS. All subjects will undergo intensive clinical and laboratory prospective observation for 24 months to determine whether antecedent GABHS infection is: 1) temporally associated with exacerbations of PANDAS, 2) specifically associated with exacerbations of tics and OCD, and 3) a specific trigger for exacerbations of PANDAS. All determinations of case/control status, GABHS infection and clinical exacerbation will be determined independently by blinded review in order to limit selection and clinical biases. Establishing a post-infectious etiology for PANDAS would dramatically change our understanding of the causes of TS and OCD, alter our therapeutic approach and may have a critical public health implication of preventing potentially fatal rheumatic cardiac sequelae in affected children. Disproving the PANDAS hypothesis would prevent the use of expensive and potentially dangerous therapies (e.g., plasma exchange, immune globulin, antibiotics) that have been proposed for PANDAS patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PERA HELICASE AND REPLICATION OF DRUG RESISTANCE PLASMID Principal Investigator & Institution: Khan, Saleem A.; Professor; Molecular Genetics & Biochem; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2003; Project Start 15-APR-2003; Project End 31-MAR-2005 Summary: (provided by applicant): Plasmids that replicate by a rolling-circle (RC) mechanism are ubiquitous in Gram-positive bacteria and a vast majority of over 200 rolling-circle replicating (RCR) plasmids belong to four major families. Many RCR plasmids carry antibiotic resistance genes and evidence suggests that horizontal transfer of RCR plasmids is quite common. Many RCR plasmids also contain genes that are involved in plasmid mobilization and transfer. While some RCR plasmids are able to replicate stably only in their native hosts, many have a broad host range. RC replication involves synthesis of the leading strand that requires the PcrA helicase, single strand

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DNA binding protein and DNA polymerase III. Lagging strand replication requires primer RNA synthesis by the host RNA polymerase, and subsequently replication is carried out by DNA Pol I and DNA Pol III. PcrA helicase is required for plasmid RC replication as well as survival of Gram-positive organisms. The goal of this R21 application is to test the hypothesis that interaction between plasmid initiator proteins and the PcrA helicases is critical for efficient plasmid replication and may determine narrow versus broad host range replication ofRCR plasmids. No studies have been performed dealing with this issue and the exploratory/development nature of the current application is consistent with the R21 format. We plan to utilize a few plasmids with a relatively narrow host range and a few with broad host range in our study. We will study the replication of these plasmids in S. aureus, B. subtilis, B. cereus and S. pneumoniae. RCR plasmids defective in replication in a particular host will be complemented by a cloned copy of their cognate pcrA gene. We will purify the PcrA helicases from the above Gram-positive organisms and study their interactions with the plasmid initiator proteins. We will also study the in vitro replication of the above plasmids in cell free extracts made from S. aureus in the presence and absence of the various PcrA helicases. These studies should reveal whether PcrA is critical in determining the efficient replication and host range of RCR plasmids. These studies may facilitate the development of antimicrobial drugs targeting the PcrA helicase and/or the initiators of RCR plasmids. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PNEUMOCOCCAL EPIDEMIOLOGY

INFECTIONS

IN

SCD--PATHOLOGY

&

Principal Investigator & Institution: Tuomanen, Elaine I.; Chair, Professor; St. Jude Children's Research Hospital Memphis, Tn 381052794 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 31-MAR-2008 Summary: Patients with sickle cell disease experience a 400 fold increased risk of severe pneumococcal infection. This risk is not shared by other encapsulated pathogens or by other anemias suggesting that there is a potentially causal relationship between severity of pneumococcal disease and the SS phenotype. This application seeks to investigate two aspects of pneumococcal infection in sickle cell disease. First we will take advantage of the presence in this SS Center of a program in pneumococcal pathogenesis and expertise in creating an SS transplant mouse model (Project 4). These two programs will cooperate to characterize which step in pneumococcal invasion differs between wild type and SS mice. The steps of colonization and invasion will be dissected at the molecular level and intervention with specific receptor antagonists will be tested. We will further determine the level of protection from pneurnococcal disease afforded by progressive hematologic correction by transplantation. Second we will build on a strong history of this Center's study of the colonization of SS patients with antibiotic resistant pneumococci. The introduction of the new seven-valent conjugate pneumococcal vaccine into the SS population has not been studied. We will determine its effect on nasopharyngeal carriage with specific reference to antibiotic susceptibility and shifts away from vaccine serotypes. Further we will measure the prevalence of a new property of antibiotic tolerance emerging in clinical isolates. Tolerance prevents antibiotic killing of pneumococci and may adversely affect the outcome of infection. Spread of this property may have implications for the efficacy of continued penicillin prophylaxis in this at risk population. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PNEUMOLYSIN, INNATE AND ACQUIRED IMMUNITY TO PNEUMOCOCCI Principal Investigator & Institution: Malley, Richard; Assistant Professor; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2002; Project Start 15-APR-2002; Project End 31-MAR-2006 Summary: Streptococcus pneumoniae remains a major cause of morbidity and mortality worldwide. Two components of pneumococci are thought to be responsible for much of the deleterious inflammatory hot response, the thiol-activated secreted toxin pneumolysin and the peptidoglycan component of the ell wall. Both of these molecules have been shown to cause inflammatory changes in vitro studies in epithelial and neuronal cells, as well as activate monocytes and macrophages of the inactive immune system. Preliminary work in our laboratory supports the hypothesis that pneumolysin activates the innate arm of the immune system through a transmembrane receptor, Tolllike receptor 4 (TLR4), in synergy with peptidoglycan (a TLR2 ligand) and/or whole pneumococci. In addition, we have some preliminary data to suggest that the activation of the innate immune response by pneumolysin may greatly augment acquired immunity to pneumococcus as well. The scientific goals of this project are divided in two phases. In the first phase, the PI will study the TLR- dependent signaling pathway of pneumolysin, alone and in combination with peptidoglycan or whole pneumococci. Studies will be done to test the hypothesis that pneumolysin binds directly to TLR4. This phase will also include an intense didactic component, to complement the work in the laboratory. In the second phase, the PI will study the role of this pathway in the modulation of disease and acquired immunity to pneumococci. This phase of the project will test the hypothesis that TLR4-mediated cellular activation by pneumolysin plays an important role in the pathophysiology of pneumococcal disease. Pneumococci carrying mutations in the pneumolysin gene, with diminished or abrogated TLR4-signaling capability, will be studied both in vitro (in macrophages) and in vivo (in murine models of colonization and disease). The possible role of TLR4-mediated response to pneumolysin in the development of acquired immunity will be studied in the final aim of the proposal. The establishment of a link between the innate and the acquired arm of the immune response to pneumococcus may provide a better understanding of the mechanisms by which immunity to pneumococcus is acquired. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PREVENTION OF PNEUMOCOCCAL DISEASE IN HIV INFECTION Principal Investigator & Institution: Mcellistrem, Mary C.; Medicine; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2002; Project Start 30-SEP-2000; Project End 31-MAY-2005 Summary: (adapted from the application s abstract): A K24 award would afford the candidate the opportunity to attain the following objectives: 1) Short-term Objectives: Determine the epidemiology of Streptococcus pneumoniae infections in HIV-infected patients and establish the optimum clinical conditions necessary to facilitate utilization of an innovative, tailored, immunogenic and safe vaccine. 2) Long-term Objectives: The candidate has become proficient at pulse field gel electrophoresis (PFGE) and computer assisted gel analysis. This award will allow her to increase her current technical ability while realizing her aspiration of performing clinical trials. She will obtain her MPH in Epidemiology at the University of Pittsburgh School of Medicine s Program in Clinical Effectiveness/Evaluation Sciences and the Graduate School of Public Health with a focus on epidemiological methods, design of clinical trials, data management and

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Streptococcus

analyses. The candidate will be able to synthesize her technical expertise in bacterial subtyping with her desire to prevent bacterial disease in high risk populations. S. pneumoniae disease is associated with more deaths than any other vaccine- preventable bacterial pathogen. While the 23-valent pneumococcal polysaccharide vaccine covers the majority of invasive serotypes, this vaccine has inferior immunogenicity in HIV-infected patients with CD4 lymphocyte counts <500/mm3. Although the efficacy of one conjugate vaccine has been demonstrated among healthy infants, no efficacy data are available for high- risk populations. The candidate proposes a three tiered approach to preventing pneumococcal disease in HIV infected patients: 1) Using a regional database of over 2000 patients with invasive S. pneumoniae, the candidate will compare serotypes, antibiograms, and case fatality rates between HIV-infected and uninfected individuals. The effect of viral load, and CD4 count on the incidence of recurrent invasive disease will be assessed. The molecular epidemiology of recurrent disease will be performed by comparing PFGE subtypes with dendrograms of genetic relatedness. The HIV-infected patients she sees in the Pittsburgh Aids Center for Treatment (PACT) clinic will be the subjects for two randomized, double-blind vaccine trials. The effect of viral load and HAART on the immunogenicity of the pneumococcal polysaccharide and conjugate vaccines will be assessed. Pneumococcal antibody concentrations will be analyzed by logistic regression to assess the effect of initial viral load and CD4 lymphocyte count. All patients who exhibit a greater that 3-fold transient rise in HIV-1 RNA levels 2 and 4 weeks postimmunization will be evaluated by Fisher's Exact and McNemar's Tests. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PROPERTIES IN STREPTOCOCCAL M PROTEIN Principal Investigator & Institution: Fischetti, Vincent A.; Professor; Lab/Bacterial Pathogenesis & Immunology; Rockefeller University New York, Ny 100216399 Timing: Fiscal Year 2003; Project Start 01-APR-1997; Project End 31-MAR-2007 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PROSPECTIVE STUDY OF 'PANDAS' Principal Investigator & Institution: Goodman, Wayne K.; Professor and Chairman; Psychiatry; University of Florida Gainesville, Fl 32611 Timing: Fiscal Year 2002; Project Start 26-APR-2002; Project End 31-MAR-2007 Summary: The existence of PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcus) continues to be questioned. Confirmation of a relationship of this putative subtype of obsessive compulsive disorder (OCD) and Tourette's Syndrome (TS) to an antecedent Group A Streptococcal (GAS) has gained considerable practical importance because of implications for treatment and prevention interventions that are radically different from the standard practice of administering psychotropics (such as SRIs or neuroleptics) for symptomatic relief. In particular, a study showing the efficacy of plasmapheresis and intravenous immunoglobulin treatment in PANDAS has stimulated public and professional debate, with some parents demanding these interventions for their children and most clinician-scientists urging caution. The need for further research is clear, but no one study will address all the questions surrounding PANDAS. A series of studies designed to test specific aspects of the pathogen-triggered autoimmune hypothesis will be required. The primary specific aim of the present study is to evaluate whether episodes or exacerbations in

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obsessive-compulsive (OC) or tic symptoms in children with OCD or TS are significantly associated with antecedent GAS infection, as reflected in elevated serum antibody titers. Seventy-nine children (ages 4 to 12 years) with OCD, TS, or Chronic Multiple Tic Disorder (CMT) will participate in this study and be followed for approximately two and a half years, a 28-month period, at monthly intervals for clinical ratings of neuropsychiatric symptoms and serological testing for GAS infection (ASO and AntiDNAse B). The study will be conducted at two institutions, the University of Florida and the National Institute of Mental Health, using identical designs and procedures. In order to identify a cohort that exhibits the desired pattern of exacerbation/regression of symptoms and to allow for attrition, we estimate that approximately 180 patients will have to be enrolled over the five-year study. Blood samples will be obtained at each visit for GAS antibodies and for exploratory immunologic studies. Should clinical signs of pharyngitis develop, throat cultures will be ordered and, if positive for GAS, appropriate antibiotic treatment will be instituted. These cases, estimated at n = 45, may provide useful information on the effect of antibiotics to attenuate exacerbations or influence OC/tic symptom course. In this cohort with clinical GAS pharyngitis, the rate of exacerbations for the 6-months following treatment will be compared to the corresponding period prior to treatment. The proposed longitudinal study will furnish needed data on the validity of the PANDAS concept and help generate reliable operational criteria for identifying cases at risk of GAS-triggered OC or tic symptoms. The results will help determine if antimicrobial interventions are warranted in certain subtypes of pediatric OCD or TS. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: RAMAN STUDIES OF ENZYME COMPLEXES IN SOLUTION & CRYSTALS Principal Investigator & Institution: Carey, Paul R.; Professor; Biochemistry; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2002; Project Start 01-APR-1996; Project End 31-MAR-2004 Summary: (Verbatim from the Applicant's Abstract)The broad goal of this research is to provide new and detailed insights into the fundamentals of enzyme action by the approach of Raman spectroscopy. Technical innovations offer unprecedented opportunities for the development and application of the Raman method. These will be exploited here to investigate two main classes of enzymes, a dehalogenase that is of potential environmental import, since it degrades a chlorinated hydrocarbon; and flavoproteins, some of which are promising targets for drug design. In both areas, Raman difference spectroscopy will be used to obtain the Raman spectrum of a ligand bound to the enzyme in stable 1:1 complexes, or in reaction intermediates. Interpretation of the Raman data, aided by quantum mechanical calculations, will provide detailed information on the conformation, electron distribution and molecular interactions for the ligand. Preliminary studies reveal that several enzyme-ligand complexes exist in solution in more than one conformational state. The thermodynamic properties of these conformations will be defined by studying the variation of populations with temperature. Technical innovations also permit the construction of sensitive Raman microscopes that acquire the Raman spectrum of a sample using microscope optics. Preliminary experiments with the Raman microscope have shown that high-quality Raman spectra can be obtained from single protein crystals. Raman spectra of the flavoprotein parahydroxybenzoate hydroxylase were obtained from crystals in hanging drops in their growth chambers. The crystals were only 30 microns in dimensions. Both protein and flavin peaks could be seen in the crystal Raman spectra. Moreover, marker

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Streptococcus

bands for the buried or solvent-exposed flavin group could be discerned in two different enzyme-ligand complexes, each known to favor the buried or exposed conformation. Thus, for both dehalogenase and flavoproteins we are proposing to use Raman data to compare the details of ligand chemistry for complexes in solution versus single crystals. We will also make a careful comparison of conformational populations, where more than one conformational state is found. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: REGULATION OF IMMUNE RESPONSE IN THE ORAL CAVITY Principal Investigator & Institution: Michalek, Suzanne M.; Professor; Microbiology; University of Alabama at Birmingham Uab Station Birmingham, Al 35294 Timing: Fiscal Year 2002; Project Start 01-JUN-1988; Project End 31-MAY-2004 Summary: Public awareness of emerging infectious diseases and that infectious diseases continue to be the leading cause of morbidity and mortality worldwide has fostered a need to develop better means for prevention and treatment. The evidence that most infectious agents cause disease by colonization of or penetration through mucosal surfaces has prompted novel vaccination strategies that would lead to increased protection of the mucosae as well as surfaces bathe by mucosal secretion, e.g., teeth. Secretory IgA antibodies in saliva are important in protection against oral diseases, including Streptococcus mutans-induced dental caries, and are induced following stimulation of the common mucosal immune system (CMIS). However, little information in known about the human CMIS, especially with respect to salivary IgA responses. The overall goals of this grant is to evaluate compartmentalization within the human CMIS, especially with respect to the salivary IgA response, and to develop a human caries vaccine. The purpose of the present studies is to establish the effectiveness of the intranasal (IN) route of immunization for inducing human salivary IgA responses protective against infection with S. mutans. Specifically, we will: 1) Determine the immunization regimen for the effective induction of human salivary IgA responses after IN immunization of S. mutans antigens and mucosal adjuvants. The recombinant (r) S. mutans antigens to be used are the saliva-binding region (SBR) of the adhesin AgI/II and the catalytic domain (CAT) and glucan-binding domain (GLU) of glucosyltransferase. The adjuvants to be used are the B subunit of cholera toxin (rCTB) and monophosphoryl lipid A (MPL). Adult volunteers will be used in this aspect of the study. The quality and quantity of antibody in saliva, nasal wash, and serum and of circulating antibody-secreting cells will be measured at various times up to 6 months after IN immunization with each antigen alone, antigen and an adjuvant, or a combination of antigens and an adjuvant. The oral microflora will be assessed for the number of S. mutans/total streptococci. These results should determine the effectiveness of IN immunization with S. mutans antigens in inducing salivary IgA responses, the usefulness of adjuvants in promoting the response, and whether the response was protective. 2) Determine the longevity of the human salivary IgA response after IN immunization and evaluate memory in the CMIS in terms of salivary IgA responses after subsequent IN immunization. The immune responses in serum and secretion from adult subjects used in aim 1) will be followed to evaluate the duration of the response. When the response wanes, these subjects will be boosted with the original vaccine and immunologic and microbiologic parameters will be measured to establish the effectiveness of the immunization regimen for inducing prolonged salivary responses and to learn more about memory in the human CMIS. 3) Determine the effect of age on human salivary IgA responses after IN immunization with S. mutans antigens and mucosal adjuvants. Since dental caries is a childhood disease, it is important to learn

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if the information we are obtaining in adults regarding the human CMIS also applies to children. In this portion of the study, children will be immunized by the IN route with antigen alone or antigen with an adjuvant. By analysis over time of antibody activity in saliva, nasal wash, and serum, we will be able to define similarities/differences in the CMIS of children and adults. By monitoring the oral microflora, we will be able to tell if the induced response was effective in reducing the level of S. mutans and in preventing the colonization by S. mutans of erupting molars. The results of this study should establish the effectiveness of the IN route of immunization, the suitability of the rSBR, rCAT and rGLU proteins of S. mutans for a combination vaccine, and the benefit of a mucosal adjuvant (CTB or MPL) for inducing a human salivary response which affords immune protection against S. mutans infection. This study will provide valuable information on the human CMIS which will help in the development of mucosal vaccines and bring us closer to establishing a human caries vaccine. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: REGULATION OF STREPTOCOCCUS PYOGENES EXOPROTEINS Principal Investigator & Institution: Chaussee, Michael S.; Basic Biomedical Sciences; University of South Dakota 414 E Clark St Vermillion, Sd 57069 Timing: Fiscal Year 2004; Project Start 01-APR-2004; Project End 31-MAR-2008 Summary: (provided by applicant): Streptococcus pyogenes secretes several proteins to the extracellular environment that directly influence host-pathogen interactions and contribute to virulence. Many secreted proteins have been studied in detail; however, the functions of several others are unknown. The locus-designated rgg is required for the expression of streptococcal pyrogenic exotoxin B (SPE B), a secreted cysteine protease that contributes to virulence. Inactivation of rgg also altered the expression of additional secreted proteins. Results obtained from genetic and physiological analyses of the rgg mutant strain have led to the hypothesis that the composition of available catabolic substrates influences exoprotein expression in an Rgg-dependent manner. To test the hypothesis, the following aims are proposed: Specific Aim 1. Determine if the availability of nitrogen-containing catabolic substrates influences Rgg dependent expression of virulence-associated exoproteins. Quantitative RT-PCR will be used to identify changes in mf-1 and speB expression in response to the availability of catabolic substrates. Proteomics and metabolite analysis will be used to assess the influence of catabolic substrates on exoprotein expression. Specific Aim 2. Identify Rgg-regulated proteins. Differences in protein expression between wild-type strain NZ131 and an isogenic rgg mutant will be detected with two-dimensional gel electrophoresis and differentially expressed proteins identified with mass spectrometry. Specific Aim 3. Distinguish between Rgg-regulated proteins and changes in expression due to perturbations of other regulatory circuits. Changes in protein expression will be identified with proteomics following induction of rgg expression by using a nisininducible promoter. Specific Aim 4. Determine if Rgg binds to promoter regions of genes encoding exoproteins to control expression. Electrophoretic mobility-shift assays will be used to determine if Rgg binds to the promoter regions of mf-1 and speB. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: REGULATION OF THE S. MUTANS PHOSPHOTRANSFERASE SYSTEM Principal Investigator & Institution: Honeyman, Allen L.; Assistant Professor; Biomedical Sciences; Texas A&M University Health Science Ctr College Station, Tx 778433578

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Streptococcus

Timing: Fiscal Year 2002; Project Start 01-SEP-1994; Project End 31-JUL-2004 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ROLE OF B-1 LYMPHOCYTES IN ATHERGENESIS Principal Investigator & Institution: Witztum, Joseph L.; Professor; Medicine; University of California San Diego 9500 Gilman Dr, Dept. 0934 La Jolla, Ca 920930934 Timing: Fiscal Year 2002; Project Start 30-SEP-2001; Project End 31-JUL-2005 Summary: (provided by applicant): There is now much evidence to implicate the immune system in atherogenesis and the purpose of this grant is to explore the role of Blymphocyte associated immune mechanisms. We have shown that oxidation of LDL (OxLDL) renders it immunogenic and cloned spontaneously arising IgM autoantibodies (Abs) from spleens of apo +mice (EO Abs) that were selected for binding to OxLDL. All were subsequently shown to bind oxidized phospholipids (OxPL) present as free lipids or as adducts with proteins. We demonstrated that the EO Abs (such as EO6) bound to apoptotic cells, which are known to be under oxidative stress. EO6 blocked macrophage uptake of OxLDL, as well as phagocytosis of apoptotic cells. These data indicate that OxPL serve as ligands that mediate macrophage recognition of oxidatively modified cells and lipoproteins. To gain insight into the structure of these Abs, we cloned and sequenced their variable region genes and discovered a 100% homology of both VH/VL gene usage with T15 anti-phosphorylcholine (PC) Abs that have been extensively studied for over 30 years. T15 Abs bind to S. pneumonia, which contains PC on its cell wall polysaccharide, and confers "innate" protection against this pathogen. However, the T15 clone expands even in germ-free mice suggesting that it is selected based on an innate "housekeeping role," although the neo-antigens to which it binds had not been defined, prior to our studies. The fact that T15 B-cells are greatly expanded in the apoE/-mice suggests a specific immune response to oxidation-specific epitopes generated by their atherosclerotic burden. In this proposal, we will define the natural history of T15 Abs and T15 B-cells in plasma, lesions and B-cell compartments during the course of development of atherogenesis in murine models. We will determine their impact on atherogenesis through passive transfer experiments in mice, with T15/EO6 Abs themselves or B-1 cells. We will determine the impact of similar experiments in mice genetically unable to make the T15 clone and in mice that overexpress B-1 cell Abs. In addition, we will determine if humans develop anti OxLDL Abs following pneumococcal infection, or after pneumococcal vaccination, and determine experimentally in mice whether pneumococcal exposure or immunization impacts the atherogenic process. Finally, we will attempt to clone and characterize similar autoAbs in man. These data should provide novel information on T15 B-cell mediated mechanisms in atherogenesis and for the first time characterize oxidation-specific "neoself" ligands to which anti-OxLDL/T15 B cells respond. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ROLE OF ENTEROCOCCAL POLYSACCHARIDES IN VIRULENCE Principal Investigator & Institution: Huebner, Johannes; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-MAY-2007 Summary: (provided by applicant): The long-term goal of this study is to understand the molecular, biochemical, and immunologic factors that contribute to the pathogenesis of Enterococcus faecalis and Enterococcus faecium infections. The understanding of the

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interaction between bacteria and the human host defense system will be the basis for the development of new means of preventing otherwise untreatable enterococcal infections. The studies will provide new and clinically useful information because it has not previously been appreciated that enterococci possess a capsule which could be used as a vaccine antigen. The development of a serotyping system for enterococci will be the necessary basis for the application of these antigens to immunotherapy and immunoprophylaxis regimens. The molecular studies will focus on the role of capsular polysaccharides of enterococci in pathogenesis, using animal models relevant to important human enterococcal infections, and the genetic mechanisms involved in capsule production. The immunologic studies will focus on determining whether the isolated antigens are targets for protective immune responses. At the end of these studies, we expect to have a better understanding of the immunology of capsular polysaccharides of enterococci, a definition of their role in the pathogenesis of specific enterococcal infections, and their potential for the development of immunotherapies to prevent and/or treat infection in hospital patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ROLE OF ENTEROCOCCUS FAECALIS BIOFILMS DURING INFECTION Principal Investigator & Institution: Kristich, Christopher J.; Microbiology; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2005 Summary: (provided by applicant): Epidemiological evidence indicates that microbial biofilms play a role in indwelling device-associated bloodstream and urinary tract infections. However, direct evidence supporting this claim is lacking in most cases. The Gram-positive opportunistic pathogen Enterococcus faecalis is frequently implicated as a causative agent of urinary tract infections, bacteremia, and bacterial endocarditis. Each of these types of infections has been associated with organisms growing as a biofilm. E. faecalis is often isolated from biofilms on various indwelling devices. These observations lead to the hypothesis that biofilm growth is an important mechanism by which E. faecalis is able to persist in vivo and cause infection. The goal of this proposal is to evaluate the contribution of biofilm growth to E. faecalis persistence and proliferation in animal models of infection. The following approaches will be taken: identify the genes involved in biofilm formation, examine the regulation of those genes during biofilm development, analyze gene expression in biofilms grown in vivo, and assess mutants impaired in biofilm formation in in vivo models of infection. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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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

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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 •

Project Title: ROLE PATHOGENESIS

OF

OPACITY

VARIATION

IN

PNEUMOCOCCAL

Principal Investigator & Institution: Weiser, Jeffrey N.; Associate Professor; Microbiology; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 01-APR-1996; Project End 31-MAR-2005 Summary: (Adapted from the Applicant's Abstract): This is a continuation of a grant that has concentrated on Streptococcus pneumoniae and its ability to adapt to the nasopharynx with colonization as well as to produce invasive infection with bacteremia. Such adaptation has been shown to be correlated with the expression of two distinct phenotypes, the opaque and transparent colony forms. Opacity phenotype is associated with on-off switching of pyruvate oxidase (SpxB), that mediates the aerobic metabolism of pyruvate and results in the generation of H2O2. Pursuing the biochemical and genetic basis of opacity variation will continue with a focus on the ability of the pneumococcus to produce and tolerate unusually high levels of H2O2. The overall goal of the proposal is to define the effect of opacity phenotype on carriage, the important first step in the pathogenesis of pneumococcal disease. The specific aims are: (1) to define the contribution of H2O2 production and opacity variation to pneumococcal carriage; (2) to characterize the physiology of H2O2 production; (3) to define the mechanism for resistance to high-level H2O2 production. A genetic approach here will be used to attempt to isolate sequences contributing to the resistance to endogenously generated peroxide; and (4) to identify and characterize regulatory elements controlling opacity (phenotypic) variation. The hope here is to isolate transcription factors that may function as global regulators affecting pyruvate oxidase. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: S SANGUIS ADHESION--MOLECULAR BASIS OF SPECIFICITY Principal Investigator & Institution: Herzberg, Mark C.; Professor; Polymer Science & Engineering; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2002; Project Start 01-APR-1990; Project End 31-MAR-2004 Summary: Density-dependent surface growth may switch sessile phenotypes to planktonic. During years 08-13, sessile and planktonic S. sanguis and S. gordonii cells will be compared to test the hypothesis that expression of adhesin proteins is regulated by the process of adhesion. Specifically, we will (1) compare the adhesion specificities of PAAP+ S. sanguis and PAAP- S. gordonii in a biofilm model that facilitates adhesion, protein biosynthesis and growth at 37 C for 6 hours in chemically-defined synthetic medium. In this model, the two wild-type strains and selected mutants will tagged with different antibiotic resistance markers. The strains will be incubated alone or together to

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determine if adhesion is competitive when binding to saliva-coated hydroxyapatite in the presence or absence of specific antibodies against salivary antigens, or simulated pellicles formed from purified salivary macromolecules. Since preferred binding sites show discrete distributions on coated enamel chips, the two strains will be compared microscopically for topological distribution of binding. To learn if they express different adhesin phenotypes, (2) sessile and planktonic cells will be recovered periodically from the biofilm model and altered expression of streptococcal surface macromolecules will be analyzed by pulse-labeling, autoradiography and Western immunoblotting with antibodies against known proteins. Novel surface proteins regulated during adhesion will be analyzed by amino acid microsequencing, PCR synthesis of the target gene, insertional inactivation, analysis of the mutant for defects in adhesion and finally cloning and sequencing of the complete gene. Selected experiments will be simulated on enamel chips to determine the ultrastructural morphology of resultant biofilms. The specificity of adhesin proteins requires protection against oxidative stress. Preliminary data show partial cloning of the S. gordonii msrA gene, which encodes methionine sulfoxide reductase, a purported adhesin maintenance factor. To analyze posttranslational modification and functional maintenance of adhesin proteins, (3) an msrAnegative mutant will be constructed and the methionine-rich diversity region of the adhesin, antigen I/II (SspA/SspB) will be analyzed for altered structure and function. These studies will serve as a definitive test of the hypothesis that the process of adhesion regulates expression of required proteins in a biofilm model. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SALIARY IMMUNE RESPONSE TO COMMENSAL ORAL BACTERIA Principal Investigator & Institution: Cole, Michael F.; Professor; Microbiology and Immunology; Georgetown University Washington, Dc 20057 Timing: Fiscal Year 2002; Project Start 01-DEC-1988; Project End 31-MAY-2004 Summary: The indigenous microbiota of the mouth and other mucosal surfaces exists in homeostasis with the host except when perturbed, the mucosal surface damaged or the immune system compromised. Then, commensal bacteria are capable of causing severe opportunistic infections. Adaptive humoral immunity at mucosal surfaces principally is effected by secretory immunoglobulin A (SIgA) that is thought to play a role in the regulation of commensal bacteria. However, despite the fact that saliva contains SIgA antibodies reactive with commensal bacteria, these microorganisms colonize and persist on mucosal and tooth surfaces. This suggests that indigenous oral bacteria are unaffected by, not subjected to, or are able to avoid immune elimination by mucosal antibodies. This assertion is supported by data published by others showing that the acquisition and composition of the oral and intestinal indigenous microbiota of mice lacking mucosal SIgA and their litter mates do not differ, and that colonization of mice by commensal enteric bacteria appears to generate a self-limiting mucosal immune response resulting in a state of chronic hypo-responsiveness. During the previous funding period we have demonstrated, in a longitudinal study of human infants from birth to two years of age, that the commensal oral bacterium, S. mitis biovar 1, induces a limited antibody response in saliva with salivary SIgA antibodies reactive with this bacterium showing a significant decline from birth to two years of age. Furthermore, this bacterium demonstrated extensive genetic diversity and evidence of clonal replacement. Concomitantly, Western blots of envelope antigens of type strains of this bacterium showed a similar high degree of variability. In this competing continuation, the hypothesis to be tested is that commensal bacteria persist in the mouth by inducing a limited salivary SIgA antibody response due to antigenic variation mediated via clonal

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Streptococcus

replacement. Employing a longitudinal study of infants from birth to 12 months, the Specific Aims are to (1) analyze the clonal diversity of S. mitis biovar 1 obtained from shedding surfaces within the infants' mouth and (2) analyze the diversity of SIgA antibodies in each infants' saliva reactive with their own S. mitis biovar 1 isolates. This work should provide important information concerning colonization of the human mouth by pioneer bacteria and may demonstrate the ability of SIgA to influence the presence of specific bacterial clones. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SURFACES

SALIVA/GLUCOSYLTRANSFERASE

INTERACTIONS

ON

Principal Investigator & Institution: Bowen, William H.; Welcher Professor of Dentistry; Eastman Dentistry; University of Rochester Orpa - Rc Box 270140 Rochester, Ny 14627 Timing: Fiscal Year 2002; Project Start 01-DEC-1988; Project End 31-MAR-2004 Summary: The interaction of enzymatically active glucosyltransferase with host-derived constituents of the acquired enamel pellicle, as well as the products of GTF activity, may play a profound role in the formation and maturation of dental plaque. Glucosyltransferase adsorbs preferably to salivary-coated hydroxyapatite (sHA) in vitro and in vivo and expresses greatly enhanced glucan synthesizing ability. Results from studies in our laboratory indicate that glucosyltransferase expresses catalytic activity over a broad range of pH (4.5-7.5) and temperature when compared with the enzyme in solution. Glucan synthesized in situ adheres strongly to the sHA surface and provides binding sites for Streptococcus mutans and Streptococcus sobrinus. The clinical relevance of these data is enhanced by the observation that an amino alcohol which is without effect on the enzyme in solution effectively inhibits the enzyme adsorbed to a surface. To explore these important phenomena further, we propose to determine whether the different GTF enzymes produced by S. mutans (GTF-I, GTF-SI, GTF-S) differ in their ability to adhere to sHA. We will use enzymes prepared from an organism into which the genes have been cloned, thereby rendering purification of the enzymes less difficult. In addition, using gel electrophoresis and antibodies, we will examine specifically the constituents in saliva with which the GTF interacts. By means of crosslinking, we will attempt to identify the peptides in GTF that react with salivary constituents and use the information generated to biologically prepare peptides that can be used to compete with GTF for binding sites on sHA, thereby providing additional insight to the nature of these interactions and possibly pointing the way to development of antiplaque agents. We will examine the structure, molecular weight, and solubility of the glucans formed in situ. Such information may make it possible to design molecules which will compete with S. mutans and certain actinomyces for sites on glucan-coated pellicle. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

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

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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 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: SLS: MOLECULAR BASIS AND ROLE IN INVASIVE GAS DISEASE Principal Investigator & Institution: Nizet, Victor F.; Assistant Professor of Pediatrics; Pediatrics; University of California San Diego 9500 Gilman Dr, Dept. 0934 La Jolla, Ca 920930934 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2007 Summary: (provided by applicant): Group A Streptococcus (GAS) is a major human pathogen producing invasive infections including necrotizing fasciitis (NF). The virulence factors responsible for bacterial spread and tissue injury in GAS NF are poorly understood. GAS are recognized phenotypically by a zone of beta-hemolysis produced largely by the cytolytic toxin streptolysin S (SLS). Our laboratory has led a collaboration that elucidated the genetic basis for SLS production. The 9-gene sag operon is both necessary for GAS SLS production and sufficient to confer SLS activity to the nonpathogenic heterologous species Lactococcus lactis. Sequence features and homologies strongly suggest SLS belongs to the bacteriocin class of toxins, with sagA encoding the toxin precursor (pre-SLS) and downstream genes (sagB-I) encoding chemical modification, processing and export functions. Target mutagenesis of each gene in the sag operon results in an SLS-negative phenotype. In vivo testing of SLSnegative sag knockout mutants in a mouse model of GAS NF showed that SLS is required for virulence. SLS-negative mutants failed to produce the necrotic ulcer, diffuse neutrophilic infiltrate, and widespread dermal and fascial tissue injury observed with the parent GAS strains. Our discovery and genetic analysis of the sag locus for SLS production has generated powerful information and reagents to study the molecular basis, biologic activities, and virulence properties of this GAS exotoxin. We hypothesize that each gene in the sag operon is required for proper expression of SLS, and that the

54

Streptococcus

SagA precursor is chemically altered, exported and processed to yield a mature protein with modified amino acids and structural features of a bacteriocin. We further hypothesize that GAS is a multifunctional toxin with cytotoxic and proinflammatory activities on host cells. Finally, we hypothesize that SLS plays an important role in the pathogenesis of GAS NF, through direct cytotoxicity, stimulation of neutrophil inflammation and interference with phagocytosis, perhaps acting synergistically with other GAS factors such as M-protein and SPE-B. These hypotheses will be tested by molecular genetic studies, attempts protein purification and antibody development, and the use of targeted SLS mutants in in vitro assays of phagocytic function and our in vivo mouse model of GAS NF. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: STREPTOCOCCAL-ZEBRAFISH PATHOGENESIS

MODEL

OF

BACTERIAL

Principal Investigator & Institution: Neely, Melody N.; Assistant Professor; Immunology and Microbiology; Wayne State University 656 W. Kirby Detroit, Mi 48202 Timing: Fiscal Year 2003; Project Start 15-FEB-2003; Project End 31-JAN-2007 Summary: (provided by applicant): Streptococcal pathogens continue to evade concerted efforts to decipher clear-cut virulence mechanisms, although numerous genes have been implicated in pathogenesis. A single species can infect a diversity of tissues, suggesting the expression of specific virulence factors based on the local tissue environment or stage of infection. Our long-range goal is to identify the interactions that occur between the host and pathogen that lead to activation of virulence mechanisms and contribute to specific streptococcal disease states. The objective of this application is to characterize specific virulence mechanisms utilized within various tissues in vivo by employing a unique animal model, the zebrafish (Danio rerio). We will accomplish this by studying infection by two streptococcal species that represent two forms of streptococcal disease: a natural pathogen of both fish and humans, Streptococcus iniae, and a human-specific pathogen, Streptococcus pyogenes. While S. iniae primarily causes systemic disease in the zebrafish following intra-muscular injection, S. pyogenes causes a locally spreading necrotic disease confined to the muscle. By studying pathogens that are virulent for both fish and humans and that mediate disease states in the zebrafish that are identical to those found in human streptococcal infections, we will be able to identify common virulence strategies shared by a number of Gram positive pathogens. The central hypothesis is that streptococcal pathogens respond to their host by initiating specific virulence mechanisms based on the local tissue environment or host-specific factors expressed within that tissue. We propose to: (1) identify and characterize bacterial proteins that interact with the host in vivo to cause specific disease states and (2) characterize the role in pathogenesis of proteins previously implicated in virulence. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: STREPTOCOCCUS PNEUMONIAE ADHERENCE AND OTITIS MEDIA PATH Principal Investigator & Institution: Demaria, Thomas F.; Otolaryngology; Ohio State University 1960 Kenny Road Columbus, Oh 43210 Timing: Fiscal Year 2002; Project Start 01-AUG-1996; Project End 31-JUL-2005 Summary: (Adapted from the Investigator's Abstract) Otitis media (middle ear inflammation) ranks first among the most common diagnoses requiring a physician's

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office visit and recent estimates indicate that virtually all children (99%) will experience a least one episode of otitis media (OM) by age 2. The disease progresses in many children to recurrent infections and chronic inflammation, often with complications and sequalae that include persistent hearing loss nd communication disorders. Streptococcus pneumoniae (Spn), is one of the foremost human pathogens and is the primary nasopharynx, the initial event in the induction of OM and the mechanisms which effect the transition for a colonized state to invasion of the middle ear and the induction of the disease state by Spn are not known. The long term objectives of this proposal are to delineate the pathogenic mechanisms involved in Spn adherence, colonization, and invasion of the middle ear and to develop a scientific rationale for the design of novel diagnostic and prevention strategies. The specific aims of this proposal are: 1) To continue to define the role of Spn neuraminidase in the pathogenesis of OM and to assess whether it is a protective antigen and a potential protein-based vaccine candidate, and whether neuraminidase inhibitors are effective in the prevention of Spn nasopharyngeal colonization of OM. 2) To assess the efficacy of lacto-N-neotetraose, a Spn carbohydrate receptor analog, as an anti-infective for nasopharyngeal colonization. 3) To continue to define the mechanisms whereby influenza A virus affects Spn adherence, colonization, and OM. These aims are designed to delineate the initial interaction, adherence, and colonization which represents the first in a series of steps that culminates in otitis media. These studies may suggest avenues for blocking interaction of Spn with host cells either by immunization or direct intervention blockade with isolated receptor moieties or bacterial adhesin components. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: STRUCTURAL PHOSPHONATASE

AND

MECHANISTIC

STUDIES

OF

Principal Investigator & Institution: Allen, Karen N.; Associate Professor; Physiology and Biophysics; Boston University Medical Campus 715 Albany St, 560 Boston, Ma 02118 Timing: Fiscal Year 2002; Project Start 01-APR-2000; Project End 31-MAR-2005 Summary: ( applicant's abstract): The studies proposed in this new grant application will examine the structure and mechanism of action of the enzyme phosphonatase and extend structural and mechanistic studies to other members of the haloacid dehalogenase (HAD) enzyme superfamily. Each enzyme of this superfamily uses a conserved Asp residue to form either an acylphosphate-enzyme intermediate or an alkyl ester-enzyme intermediate. This chemistry is supported by a common structural scaffold. Phosphonatase catalyzes the hydrolysis of phosphonoacetaldehyde (P-Ald) to acetaldehyde and orthophosphate. In conjunction with 2-aminoethylphosphonate transaminase, phosphonatase functions in a two-step biodegradative pathway used to recycle P, N, and C from the ubiquitous natural phosphonate, 2aminoethylphosphonate. Despite the wide range of known biological activities associated with natural and synthetic phosphonates, the enzymology of phosphonate metabolism is poorly characterized. The goal of these studies is to derive an understanding of the process of enzyme catalyzed C-P bond cleavage using phosphonatase as the model system. The first set of experiments proposed will test mechanistic models based on the recently determined phosphonatase X-ray structure (Allen laboratory) and on previous mechanistic studies (Dunaway-Mariano laboratory). Site-directed mutagenesis coupled with transient kinetic analysis will be used to test the chemical steps of the models. Crystallographic structure determinations carried out on dead-end complexes formed using substrate analogues, enzyme mutants, and

56

Streptococcus

chemically modified enzymes will be used to capture the structures of proposed reaction intermediates. The second set of experiments proposed will examine the activesite diversification of the HAD enzyme superfamily. The ability of phosphonatase to catalyze the reactions of other family members will be determined and protein engineering will be used to swap catalytic activities of two family members. To further probe the catalytic plasticity of the superfamily, the structure and mechanism of betaphosphoglucomutase, a phosphotransferase from the HAD family will be examined. The goal of these studies is to derive an understanding of how the enzyme superfamily active site has been adapted to catalyze C-X, P-O and C-P bond cleavage in a variety of different substrate structures. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: STRUCTURAL STUDIES OF BACTERIAL COMPETENCE PROTEINS Principal Investigator & Institution: Cavanagh, John; Professor; Biochemistry; North Carolina State University Raleigh 2230 Stinson Drive Raleigh, Nc 27695 Timing: Fiscal Year 2003; Project Start 01-FEB-2003; Project End 31-JAN-2007 Summary: (provided by applicant): Bacteria have obtained a significant portion of their genetic diversity, metabolic fitness and lethality through the acquisition of nucleotide sequences from both closely and distantly related organisms. Horizontal gene transfer produces extremely dynamic genomes, in which substantial amounts of DNA are transferred between the chromosomes of different bacterial strains. Without question, such transfers have changed the ecological and pathogenic character of bacterial species. Transformation represents one of the main mechanisms by which DNA is incorporated into the recipients genome. It involves the uptake of naked DNA from the environment and has the potential to transmit DNA between distantly related organisms. For bacteria to be transformable, they must develop the physiological state referred to as competence. Genetic competence is defined as the ability of a cell to take up free DNA from the surrounding medium. If the cell is not competent, it cannot be transformed and its growth, survival and evolution are compromised. Research into the very nature of competence addresses both very fundamental and very practical questions and concerns. What mechanisms allow bacteria to incorporate new genes to develop novel, more sophisticated mechanisms for survival? By what means is genetic diversity provided, such that a microorganism can enlarge its own genomic complement? From a health related perspective, genetic transfer via competence is becoming more implicated in the development of the pathogenic character of bacteria. There is mounting evidence that virulent attributes and antibiotic resistance can be introduced and/or enhanced in this manner. The studies proposed here will focus on mechanistic characteristics of a set of interacting proteins that form the critical regulatory network initiating competence development in Bacillus subtilis. The goals of the research are to provide structural, dynamic and interaction information, in order to understand the regulatory effects of the proteins MecA, ComS, ClpP/C and ComK (and their complexes). This will be achieved by a combination of high-resolution NMR spectroscopy, electrospray mass spectrometry, surface plasmon resonance and other bioanalytical techniques, along with mutagenesis and protease foot-printing investigations. The results from these studies will provide a basis for the development of models to describe the mechanism of activation of competence, not only in B. subtilis, but also in other important grampositive (e.g. Streptococcus pneumoniae) and gram-negative (e.g. Neisseria gonorrhoeae and Haemophihts influenza) bacteria. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PROTEIN

STRUCTURE-FUNCTION

RELATIONSHIPS

OF

57

C-REACTIVE

Principal Investigator & Institution: Agrawal, Alok; Biochemistry; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-OCT-2002 Summary: (provided by applicant): C-reactive protein (CRP) is a major human acute phase protein and a component of the innate immune response. Its serum concentration is increased during inflammatory states, persists for the duration of the inflammatory process and returns to its normal low concentration following subsidence of inflammation. While CRP is felt to play a significant role in inflammation and host defense, the mechanisms by which CRP exerts its effects are unclear. In vitro, CRP binds to phosphocholine (PCh) moieties and can then bind to complement C1q and activate the classical complement pathway. In addition, binding of CRP to phagocytic cells via Fc receptors, with a variety of functional consequences, has been described. Recent publication of the crystal structures of CRP has provided insight into the amino acids that mediate binding of CRP to PCh, to Fc receptors, and to C1q, permitting generation of CRP mutants incapable of binding to PCh and to Fc receptors, as well as incapable of activating complement. Most known functional activities of CRP, in vitro, are associated with ligand-binding and subsequent complement activation or phagocytosis. Accordingly, we will employ such mutants to define the roles of binding to PCh and Fe receptors, and of complement activation in 2 model systems: a) the protective role of CRP in bacterial infections and b) the putative role of CRP in the pathogenesis of atherosclerosis resulting from its ability to bind to enzymatically-degraded LDL (ELDL). Our specific aims are: 1.To precisely define the ligand-binding sites on CRP required for binding to PCh, FcR and C1q and to generate mutants lacking these critical binding capabilities. 2. To define the role of these 3 binding capabilities in the protective effects of CRP in infection with Streptococcus pneumoniae, known to bind to CRP, and Salmonella typhimuriurn, which does not. We hypothesize that both complement activation and phagocytosis will be found to be involved in CRP-mediated protection of mice from bacterial infections. 3) To define the role of the 3 binding capabilities of interest on CRP-E-LDL interaction, and the role of such interaction in the pathogenesis of atherosclerosis. Our working hypothesis is that all 3 binding sites participate in the pathogenesis of atherosclerosis, by binding to E-LDL and initiating complement activation and uptake of E-LDL by macrophages. We will also determine the effects of injecting wild-type and mutant CRPs on the size of the atherosclerotic lesions formed in ApoE knock-out mice. These studies will provide substantial insight into the mechanisms by which this ancient protein may contribute to host defense, or alternatively, to pathogenesis of disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: TEM WITH DIGITAL AND CRYOPREPARATION SYSTEMS Principal Investigator & Institution: Evan, Andrew P.; Professor of Anatomy; Anatomy and Cell Biology; Indiana Univ-Purdue Univ at Indianapolis 620 Union Drive, Room 618 Indianapolis, in 462025167 Timing: Fiscal Year 2003; Project Start 01-JUN-2003; Project End 31-MAY-2004 Summary: (provided by applicant): The purpose of the application is to obtain funding to replace the existing Philips 400 TEM in the shared-user EM Center in the Department of Anatomy and Cell Biology with a state-of-the-art TEM, the JEOL 1230. The Philips 400 TEM was purchased with NSF funds in 1979 and has served over 40 different

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Streptococcus

researchers over the last 23 years, but this machine is presently unreliable and outdated. Since the acquisition of the Philips 400 TEM, significant technical advances have occurred in transmission electron microscopes which include ease of use and extended capabilities like digital image recording and ultracryo-microscopy. The new TEM will be housed in a 1789 sq. ft. laboratory dedicated to electron microscopy, supervised by a full-time faculty member, Dr. Vincent Gattone and managed by a full-time, highly qualified EM specialist, Ms. Caroline Miller. The microscope will be available to all investigators within the Indiana University-Purdue University campus at Indianapolis which includes Schools of Dentistry, Medicine, Science and Engineering & Technology. However, the majority of the research projects will come from ten (10) laboratories. These investigators have been identified as "major users" of the new instrument. Dr. Robert Bacallao will employ a variety of biochemical assays for protein sorting, immunohistochemical and ultrastructural analyses of Golgi complex dysfunction following ischemic injury. Dr. Andrew Evan will use imunohistochemical and digital imaging to precisely correlate sites of renal crystal deposition with known inhibitors of stone formation. Dr. Loren Field will use TEM to correlate structural changes in cardiomyocytes after specific pathological conditions. Dr. Lincoln Ford requires digital TEM images to accurately measure changes in smooth muscle thick filaments during contractility. Dr. Susan Gunst needs digital TEM images to evaluate the cellular mechanisms that regulate the response of airway smooth muscle to mechanical forces generated during breathing. Dr. James McAteer's studies require the high resolution of the TEM to detect subtle damage to the vascular endothelium induced by shock wave lithotripsy. Dr. Bruce Molitoris will employ immunohistochemistry to determine the cellular, biochemical and molecular mechanisms responsible for ischemia induced membrane changes. Dr. Carrie Phillips will use immunogold EM to evaluate the cellular localization of inversin protein in the inv mutant mouse model of PKD. Dr. Zao Xu will use TEM to investigate the nature of cell death, e.g. necrosis or apoptosis, in neostriatum of the rat after transient global schemia. Dr. Richard Gregory will employ immunohistochemistry to examine the role of a Streptococcus mutans 65 kDa fimbrial protein binding as a mechanism for the induction of dental carries. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: TREATMENT FOR GBS COLONIZATION IN PREGNANT WOMEN Principal Investigator & Institution: Bhatt, Bakul M.; Biomedical Development Corporation 500 Sandau, Ste 200 San Antonio, Tx 78216 Timing: Fiscal Year 2001; Project Start 20-SEP-1997; Project End 31-MAY-2004 Summary: (Adapted from Applicant's Abstract): The goal of this project is to further develop Iocide, a novel iodine-based antimicrobial technology, for use as a topical bacteriocide for group B streptococci (GBS) in the vaginal tract of pregnant women during the intrapartum period. GBS is the leading cause of neonatal bacterial disease and death, and most frequently occurs in neonates as sepsis, meningitis, and pneumonia. Despite clinical advances to date, GBS continues to be a major cause of illness and death among newborns. Due to the limitations of current clinical strategies, a need exists for alternate approaches to prevent GBS-related neonatal disease. The following specific aims have been designed to achieve this goal: 1) to optimize the formulation of the Iocide vaginal gel, 2) to determine the effective range of Iocide in vitro, 3) to demonstrate safety and efficacy to the Iocide in animals, and 4) to determine safety and efficacy of Iocide in human clinical trials. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: TYPE II ENTEROTOXINS AS MUCOSAL IMMUNOMODULATORS Principal Investigator & Institution: Connell, Terry D.; Associate Professor; Microbiology; State University of New York at Buffalo Suite 211 Ub Commons Buffalo, Ny 14228 Timing: Fiscal Year 2002; Project Start 15-APR-2001; Project End 31-MAR-2005 Summary: The objective of this application is to evaluate the mucosal adjuvant activities of the Escherichia coli Type II enterotoxins, LT-IIa and LT-IIb. Experiments in the laboratory of the applicant demonstrated that LT-IIa and LT-IIb induce different and distinctive patterns of enhanced immune responses, and that those patterns are profoundly different from those induced by cholera toxin (CT). For example, whereas CT used as an adjuvant induces predominantly a T helper 2-type response based on antibody isotype and cytokine patterns, Type II enterotoxins, particularly LT-IIb, induce both T helper 1 and T helper 2 responses. These data provide strong evidence that LTIIa, LT-IIb, and CT induce their adjuvant activities using different cellular and molecular mechanisms. As such, the Type II toxins provide an elegant set of tools for investigating the mechanisms of mucosal adjuvant induction. Although related in structure, LT-IIa, LT-IIb and CT bind to different sets of cell surface receptors. It is hypothesized that the distinctive adjuvant activities of the toxins are governed by their receptor-binding specificities. To test this hypothesis, the adjuvant activities of the Type II toxins will be analyzed in a mucosal mouse model using AgI/II of the oral pathogen Streptococcus mutans as a model antigen. Both antibody and cellular responses will be assessed. These studies will be facilitated by a collection of receptor-binding mutants, hybrid molecules, and chimeric toxins that are available in this laboratory. Immunization studies will be combined with immunohistological investigations of lymphoid tissue to begin to investigate the cellular component of toxin-induced adjuvant activity. Confocal microscopy will be used to identify the immunocompetent cells in the nasal lymphoid tissue and the draining lymph nodes that initially interact with the toxins after intranasal inoculation. As a further means to correlate adjuvant induction with toxin/cell interactions, immunocompetent cells taken from nasal lymphoid tissue will be classified for expression of toxin-specific surface receptors using flow cytometry analysis. Finally, the potential of non-toxic chimeric Type II proteins as adjuvant/antigen delivery vehicles will be evaluated. At the conclusion of these studies, the laboratory will be well positioned to evaluate the therapeutic potential of the Type II toxins as mucosal adjuvants in the subsequent production of new vaccines that will protect against pathogens that infect the oral, gastric and urogenital mucosae. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: VARIABLE SUSCEPTIBILITY

GENE

DEFECTS

AND

PNEUMOCOCCAL

Principal Investigator & Institution: Pirofski, Liise-Anne; Professor; Medicine; Yeshiva University 500 W 185Th St New York, Ny 10033 Timing: Fiscal Year 2002; Project Start 01-APR-2001; Project End 31-MAR-2006 Summary: (Adapted from Applicant's Abstract): The rationale for vaccination with pneumococcal capsular polysaccharide (PPS) vaccines is to induce opsonic antibodies to PPS, which are required for protection against Streptococcus pneumoniae. However, available PPS-based vaccines are poorly immunogenic in many patients at the highest risk for pneumococcal infection. Based on the following evidence we hypothesize that reduced expression of immunoglobulin genes from the VH3 subgroup translates into an impaired anti-PPS response: i) antibodies to PPS are oligoclonal and use genes from the

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VH3 subgroup; ii) reduced VH3 expression has been reported in patients at risk for pneumococcal infection that generate poor responses to PPS vaccines. This application proposes to determine structure-function relationships for human antibodies to serotype 3 S. pneumoniae, a cause of invasive pneumococcal infection in adults and children. The specific aims are: 1) To determine the molecular structure of human mAbs to PPS 3 generated in transgenic mice reconstituted with human immunoglobulin loci; 2) To characterize the infection in mice and as opsonic or non-opsonic in vitro; 3) To use mAbs with molecular structure as defined in Aim 1 and functional efficacy as defined in Aim 2 to select peptide mimics of PPS 3 epitopes, and to use the peptides to determine if PPSelicited antibodies in patients recognize protective, non-protective or disease-enhancing epitopes. Our studies will provide evidence to support or refute the hypothesis that pneumococcal vaccine failure results from an inability to produce antibodies to PPS epitopes with a certain molecular structure. This work will provide a new scientific knowledge base regarding structure-function relationships for antibodies to PPS 3 that can be used clinically to evaluate vaccine efficacy and to develop more immunogenic vaccines for patients at risk for pneumococcal infection. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ZOOCIN A AND ITS ASSOCIATED IMMUNITY FACTOR Principal Investigator & Institution: Sloan, Gary L.; Biological Sciences; University of Alabama in Tuscaloosa Tuscaloosa, Al 35487 Timing: Fiscal Year 2001; Project Start 01-APR-2001; Project End 31-MAR-2005 Summary: (Verbatim from Applicant's Abstract): The long-term goal of this research is to understand the control and transfer of information that allows some bacteria to produce toxic products to which they are not intrinsically resistant. The model systems being studied are lysostaphin, a plasmid-encoded staphylolytic glycylglycine endopeptidase produced by Staphylococcus simulans biovar staphylolyticus, which hydrolyzes the polyglycine cross bridges in the cell wall peptidoglycans of other staphylococci, and zoocin A, a chromosomally encoded streptococcolytic enzyme of unknown mechanism of action that is produced by Streptococcus equi subsp. zooepidemicus 4881. A comparison of the sequences of the genes for lysostaphin endopeptidase (end) and zoocin A (zooA) has revealed a high degree of similarity between these two enzymes; however, our preliminary investigations have revealed that zoocin A is most likely not simply an endopeptidase that hydrolyzes peptidoglycan cross bridges in susceptible streptococci. Both organisms carry resistance genes that also have a high degree of similarity (designated epr, for lysostaphin endopeptidase resistance and zif, for zoocin A immunity factor) immediately adjacent to the enzyme genes and oriented in the opposite direction to them. Both epr and zif have a high degree of similarity to femAB (factor essential for methicillin resistance) in staphylococci. The gene products for epr and femAB are known to be involved in the synthesis of cross bridges in the peptidoglycans of staphylococci; Epr specifies for the insertion of serines in these peptides whereas FemA and FemB specify for the insertion of glycines. Even though Zif is very similar to Epr, FemA, and FemB, our preliminary investigations have revealed that it is not involved in the biosynthesis of cross bridges. In addition, both end/epr and zooA/zif are bracketed by what appear to be transposable elements, suggesting that there may have been a horizontal transfer of DNA fragments containing these genes at some point in time. The specific aims of the proposed project are 1) to identify the site of action of zoocin A on the peptidoglycans of susceptible streptococci; 2) to identify the precise change made in streptococcal cell wall peptidoglycans by Zif and the cellular location of this protein; and 3) to determine if

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end/epr or zooA/zif can be transferred to other gram-positive organisms by natural mechanisms for genetic transfer. 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 “streptococcus” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for streptococcus in the PubMed Central database: •

16S Ribosomal DNA Sequence Analysis Distinguishes Biotypes of Streptococcus bovis: Streptococcus bovis Biotype II/2 Is a Separate Genospecies and the Predominant Clinical Isolate in Adult Males. by Clarridge JE III, Attorri SM, Zhang Q, Bartell J.; 2001 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=87968

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A binding-lipoprotein-dependent oligopeptide transport system in Streptococcus gordonii essential for uptake of hexa- and heptapeptides. by Jenkinson HF, Baker RA, Tannock GW.; 1996 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=177622

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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 High Incidence of Prophage Carriage among Natural Isolates of Streptococcus pneumoniae. by Ramirez M, Severina E, Tomasz A.; 1999 Jun 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=93836

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A New Alkaline pH-Adjusted Medium Enhances Detection of [beta]-Hemolytic Streptococci by Minimizing Bacterial Interference Due to Streptococcus salivarius. by Dierksen KP, Ragland NL, Tagg JR.; 2000 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=86167

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A Novel Erythromycin Resistance Methylase Gene (ermTR) in Streptococcus pyogenes. by Seppala H, Skurnik M, Soini H, Roberts MC, Huovinen P.; 1998 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105397

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A Novel Multiresistant Streptococcus pneumoniae Serogroup 19 Clone from Washington State Identified by Pulsed-Field Gel Electrophoresis and Restriction

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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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Fragment Length Patterns. by Luna VA, Jernigan DB, Tice A, Kellner JD, Roberts MC.; 2000 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=86493 •

A Response Regulator That Represses Transcription of Several Virulence Operons in the Group A Streptococcus. by Federle MJ, McIver KS, Scott JR.; 1999 Jun 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=93840

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A Serotype V Clone Is Predominant among Erythromycin-Resistant Streptococcus agalactiae Isolates in a Southwestern Region of Germany. by von Both U, Ruess M, Mueller U, Fluegge K, Sander A, Berner R.; 2003 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=154707

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A Shift from Oral to Blood pH Is a Stimulus for Adaptive Gene Expression of Streptococcus gordonii CH1 and Induces Protection against Oxidative Stress and Enhanced Bacterial Growth by Expression of msrA. by Vriesema AJ, Dankert J, Zaat SA.; 2000 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=97249

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AbiA, a Lactococcal Abortive Infection Mechanism Functioning in Streptococcus thermophilus. by Tangney M, Fitzgerald GF.; 2002 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=134376

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Ability of Lysozyme and 2-Deoxyglucose To Differentiate Human and Bovine Streptococcus bovis Strains. by Kurtovic A, Jarvis GN, Mantovani HC, Russell JB.; 2003 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=179835

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Absence of autolytic activity (peptidoglycan nicking) in penicillin-induced nonlytic death in a group A streptococcus. by McDowell TD, Lemanski CL.; 1988 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=211031

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Accumulation of 10 Fluoroquinolones by Wild-Type or Efflux Mutant Streptococcus pneumoniae. by Piddock LJ, Johnson MM.; 2002 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=127496

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Acquisition of Five High-Mr Penicillin-Binding Protein Variants during Transfer of High-Level [beta]-Lactam Resistance from Streptococcus mitis to Streptococcus pneumoniae. by Hakenbeck R, Konig A, Kern I, van der Linden M, Keck W, Billot-Klein D, Legrand R, Schoot B, Gutmann L.; 1998 Apr 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=107097

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Activities of Newer Fluoroquinolones against Streptococcus pneumoniae Clinical Isolates Including Those with Mutations in the gyrA, parC, and parE Loci. by Jorgensen JH, Weigel LM, Ferraro MJ, Swenson JM, Tenover FC.; 1999 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89072

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Activity of Gemifloxacin against Penicillin- and Ciprofloxacin-Resistant Streptococcus pneumoniae Displaying Topoisomerase- and Efflux-Mediated Resistance Mechanisms. by Heaton VJ, Goldsmith CE, Ambler JE, Fisher LM.; 1999 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89601

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Adaptation of Streptococcus mutans and Enterococcus hirae to acid stress in continuous culture. by Belli WA, Marquis RE.; 1991 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=182857

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Adherence of Streptococcus sanguis clinical isolates to smooth surfaces and interactions of the isolates with Streptococcus mutans glucosyltransferase. by Hamada S, Torii M, Kotani S, Tsuchitani Y.; 1981 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=350629

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Aerotolerance and Peroxide Resistance in Peroxidase and PerR Mutants of Streptococcus pyogenes. by King KY, Horenstein JA, Caparon MG.; 2000 Oct 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=110969

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All Detectable High-Molecular-Mass Penicillin-Binding Proteins Are Modified in a High-Level [beta]-Lactam-Resistant Clinical Isolate of Streptococcus mitis. by Amoroso A, Demares D, Mollerach M, Gutkind G, Coyette J.; 2001 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=90603

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Amino Acid Repetitions in the Dihydropteroate Synthase of Streptococcus pneumoniae Lead to Sulfonamide Resistance with Limited Effects on Substrate Km. by Haasum Y, Strom K, Wehelie R, Luna V, Roberts MC, Maskell JP, Hall LM, Swedberg G.; 2001 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=90378

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Amplified-Fragment Length Polymorphism Analysis versus Macro-Restriction Fragment Analysis for Molecular Typing of Streptococcus pneumoniae Isolates. by van Eldere J, Janssen P, Hoefnagels-Schuermans A, van Lierde S, Peetermans WE.; 1999 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=85030

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Analysis of Genetic Diversity of Streptococcus suis Clinical Isolates from Pigs in Spain by Pulsed-Field Gel Electrophoresis. by Vela AI, Goyache J, Tarradas C, Luque I, Mateos A, Moreno MA, Borge C, Perea JA, Dominguez L, Fernandez-Garayzabal JF.; 2003 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=156542

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Analysis of Immunoreactivity to a Streptococcus equi subsp. zooepidemicus M-Like Protein To Confirm an Outbreak of Poststreptococcal Glomerulonephritis, and Sequences of M-Like Proteins from Isolates Obtained from Different Host Species. by Nicholson ML, Ferdinand L, Sampson JS, Benin A, Balter S, Pinto SW, Dowell SF, Facklam RR, Carlone GM, Beall B.; 2000 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=87552

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Analysis of Loci Required for Determination of Serotype Antigenicity in Streptococcus mutans and Its Clinical Utilization. by Shibata Y, Ozaki K, Seki M, Kawato T, Tanaka H, Nakano Y, Yamashita Y.; 2003 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=193837

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Analysis of Penicillin-Binding Protein Genes of Clinical Isolates of Streptococcus pneumoniae with Reduced Susceptibility to Amoxicillin. by du Plessis M, Bingen E, Klugman KP.; 2002 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=127354

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Analysis of RogB-Controlled Virulence Mechanisms and Gene Expression in Streptococcus agalactiae. by Gutekunst H, Eikmanns BJ, Reinscheid DJ.; 2003 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=187362

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Analysis of the 5[prime prime or minute] Portion of the Type 19A Capsule Locus Identifies Two Classes of cpsC, cpsD, and cpsE Genes in Streptococcus pneumoniae. by Morona JK, Morona R, Paton JC.; 1999 Jun 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=93832

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Antibiotic Susceptibility and Mechanisms of Erythromycin Resistance in Clinical Isolates of Streptococcus agalactiae: French Multicenter Study. by De Mouy D, Cavallo JD, Leclercq R, Fabre R.; 2001 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=90666

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Antigenicity, Expression, and Molecular Characterization of Surface-Located Pullulanase of Streptococcus pneumoniae. by Bongaerts RJ, Heinz HP, Hadding U, Zysk G.; 2000 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=97827

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Antimicrobial Resistance and Serotype Distribution of Streptococcus pneumoniae Strains Causing Childhood Infections in Bangladesh, 1993 to 1997. by Saha SK, Rikitomi N, Ruhulamin M, Masaki H, Hanif M, Islam M, Watanabe K, Ahmed K, Matsumoto K, Sack RB, Nagatake T.; 1999 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=84560

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Antimicrobial Susceptibility and Serotype Distribution of Streptococcus pneumoniae and Molecular Characterization of Multidrug-Resistant Serotype 19F, 6B, and 23F Pneumococci in Northern Thailand. by Watanabe H, Asoh N, Hoshino K, Watanabe K, Oishi K, Kositsakulchai W, Sanchai T, Kunsuikmengrai K, Kahintapong S, Khantawa B, Tharavichitkul P, Sirisanthana T, Nagatake T.; 2003 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=193840

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Application of pbp1A PCR in Identification of Penicillin-Resistant Streptococcus pneumoniae. by du Plessis M, Smith AM, Klugman KP.; 1999 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=84499

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Associations of Streptococcus suis Serotype 2 Ribotype Profiles with Clinical Disease and Antimicrobial Resistance. by Rasmussen SR, Aarestrup FM, Jensen NE, Jorsal SE.; 1999 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=84321

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Autoinducer 2 Production by Streptococcusgordonii DL1 and the Biofilm Phenotype of a luxS Mutant Are Influenced by Nutritional Conditions. by Blehert DS, Palmer RJ Jr, Xavier JB, Almeida JS, Kolenbrander PE.; 2003 Aug 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=166464

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Barriers to Genetic Exchange between Bacterial Species: Streptococcus pneumoniae Transformation. by Majewski J, Zawadzki P, Pickerill P, Cohan FM, Dowson CG.; 2000 Feb 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=94378

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bca, Beta Gene, and Gene Product Divergency in Reference and Prototype Strains of Streptococcus agalactiae. by Maeland JA, Bevanger L, Iversen G, Lyng RV.; 1999 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=95811

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Biochemical characterization and evaluation of virulence of a fructosyltransferasedeficient mutant of Streptococcus mutans V403. by Schroeder VA, Michalek SM, Macrina FL.; 1989 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=259868

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Biology, immunology, and cariogenicity of Streptococcus mutans. by Hamada S, Slade HD.; 1980 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=373181

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Branched-Chain Amino Acid Biosynthesis Is Essential for Optimal Growth of Streptococcus thermophilus in Milk. by Garault P, Letort C, Juillard V, Monnet V.; 2000 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=92433

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Capsular Serotype and Antibiotic Resistance of Streptococcus pneumoniae Isolates in Two Chilean Cities. by Inostroza J, Trucco O, Prado V, Vinet AM, Retamal G, Ossa G, Facklam RR, Sorensen RU.; 1998 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=121354

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Capsule Biosynthesis and Basic Metabolism in Streptococcus pneumoniae Are Linked through the Cellular Phosphoglucomutase. by Hardy GG, Caimano MJ, Yother J.; 2000 Apr 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=101867

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Casein Utilization by Streptococcus thermophilus Results in a Diauxic Growth in Milk. by Letort C, Nardi M, Garault P, Monnet V, Juillard V.; 2002 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=123924

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Cell Density Modulates Acid Adaptation in Streptococcus mutans: Implications for Survival in Biofilms. by Li YH, Hanna MN, Svensater G, Ellen RP, Cvitkovitch DG.; 2001 Dec 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=95529

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Cell wall anchoring of the Streptococcus pyogenes M6 protein in various lactic acid bacteria. by Piard JC, Hautefort I, Fischetti VA, Ehrlich SD, Fons M, Gruss A.; 1997 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=179078

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Changes in Availability of Oxygen Accentuate Differences in Capsular Polysaccharide Expression by Phenotypic Variants and Clinical Isolates of Streptococcus pneumoniae. by Weiser JN, Bae D, Epino H, Gordon SB, Kapoor M, Zenewicz LA, Shchepetov M.; 2001 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98654

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Characteristics and cariogenicity of a fructanase-defective Streptococcus mutants strain. by Wexler DL, Penders JE, Bowen WH, Burne RA.; 1992 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=257376

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Characteristics of Streptococcus pyogenes Serotype M1 and M3 Isolates from Patients in Japan from 1981 to 1997. by Murase T, Suzuki R, Osawa R, Yamai S.; 1999 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=85898

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Characterization of a Genetic Element Carrying the Macrolide Efflux Gene mef(A) in Streptococcus pneumoniae. by Santagati M, Iannelli F, Oggioni MR, Stefani S, Pozzi G.; 2000 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=90116

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Characterization of a Novel Fucose-Regulated Promoter (PfcsK) Suitable for Gene Essentiality and Antibacterial Mode-of-Action Studies in Streptococcus pneumoniae. by Chan PF, O'Dwyer KM, Palmer LM, Ambrad JD, Ingraham KA, So C, Lonetto MA, Biswas S, Rosenberg M, Holmes DJ, Zalacain M.; 2003 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=150135

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Characterization of a Novel Type II Restriction-Modification System, Sth368I, Encoded by the Integrative Element ICESt1 of Streptococcus thermophilus CNRZ368. by Burrus V, Bontemps C, Decaris B, Guedon G.; 2001 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=92764

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Characterization of a P1-deficient strain of Streptococcus mutans that expresses the SpaA protein of Streptococcus sobrinus. by Kuykindoll RJ, Holt RG.; 1996 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=174277

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Characterization of an Isogenic Mutant of Streptococcus pyogenes Manfredo Lacking the Ability To Make Streptococcal Acid Glycoprotein. by Degnan BA, Fontaine MC, Doebereiner AH, Lee JJ, Mastroeni P, Dougan G, Goodacre JA, Kehoe MA.; 2000 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=97444

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Characterization of Antimicrobial Resistance in Streptococcus pyogenes Isolates from the San Francisco Bay Area of Northern California. by York MK, Gibbs L, PerdreauRemington F, Brooks GF.; 1999 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=84935

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Characterization of Blood Culture Isolates of Streptococcus dysgalactiae subsp. equisimilis Possessing Lancefield's Group A Antigen. by Brandt CM, Haase G, Schnitzler N, Zbinden R, Lutticken R.; 1999 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=85928

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Characterization of emb, a Gene Encoding the Major Adhesin of Streptococcus defectivus. by Manganelli R, van de Rijn I.; 1999 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=96276

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Characterization of Enterococcus faecalis Alkaline Phosphatase and Use in Identifying Streptococcus agalactiae Secreted Proteins. by Lee MH, Nittayajarn A, Ross RP, Rothschild CB, Parsonage D, Claiborne A, Rubens CE.; 1999 Sep 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=94101

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Characterization of group A Streptococcus strains recovered from Mexican children with pharyngitis by automated DNA sequencing of virulence-related genes: unexpectedly large variation in the gene (sic) encoding a complement-inhibiting protein. by Mejia LM, Stockbauer KE, Pan X, Cravioto A, Musser JM.; 1997 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=230151

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Characterization of Pit, a Streptococcus pneumoniae Iron Uptake ABC Transporter. by Brown JS, Gilliland SM, Ruiz-Albert J, Holden DW.; 2002 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=128127

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Characterization of Streptococcus agalactiae strains by randomly amplified polymorphic DNA analysis. by Chatellier S, Ramanantsoa C, Harriau P, Rolland K, Rosenau A, Quentin R.; 1997 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=230013

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Characterization of Streptococcus mutans Strains Deficient in EIIABMan of the Sugar Phosphotransferase System. by Abranches J, Chen YY, Burne RA.; 2003 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=169087

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Characterization of Streptococcus suis Genes Encoding Proteins Homologous to Sortase of Gram-Positive Bacteria. by Osaki M, Takamatsu D, Shimoji Y, Sekizaki T.; 2002 Feb 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=134807

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Characterization of the Tn916-like Transposon Tn3872 in a Strain of Abiotrophia defectiva (Streptococcus defectivus) Causing Sequential Episodes of Endocarditis in a Child. by Poyart C, Quesne G, Acar P, Berche P, Trieu-Cuot P.; 2000 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89770

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Cleavable-Complex Formation by Wild-Type and Quinolone-Resistant Streptococcus pneumoniae Type II Topoisomerases Mediated by Gemifloxacin and Other Fluoroquinolones. by Yague G, Morris JE, Pan XS, Gould KA, Fisher LM.; 2002 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=127068

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Clinical Isolates of Streptococcus pneumoniae with Different Susceptibilities to Ceftriaxone and Cefotaxime. by Karlowsky JA, Jones ME, Draghi DC, Sahm DF.; 2003 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=201161

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Clonal distribution of an atypical MRP +, EF*, and suilysin + phenotype of virulent Streptococcus suis serotype 2 strains in Brazil. by Martinez G, Pestana de Castro AF, Ribeiro Pagnani KJ, Nakazato G, Dias da Silveira W, Gottschalk M.; 2003 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=227027

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Clonal Relationship between U.S. and French Serotype V Group B Streptococcus Isolates. by Le Thomas-Bories I, Fitoussi F, Mariani-Kurkdjian P, Raymond J, Brahimi N, Bidet P, Lefranc V, Bingen E.; 2001 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=88579

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Cloning and Characterization of the Gene Encoding the Glutamate Dehydrogenase of Streptococcus suis Serotype 2. by Okwumabua O, Persaud JS, Reddy PG.; 2001 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=96045

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Cloning of the Streptococcus mutans Gene Encoding Glucan Binding Protein B and Analysis of Genetic Diversity and Protein Production in Clinical Isolates. by MattosGraner RO, Jin S, King WF, Chen T, Smith DJ, Duncan MJ.; 2001 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=100073

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Coaggregation of Streptococcus sanguis and other streptococci with Candida albicans. by Jenkinson HF, Lala HC, Shepherd MG.; 1990 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=258643

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Combined Contributions of Streptolysin O and Streptolysin S to Virulence of Serotype M5 Streptococcus pyogenes Strain Manfredo. by Fontaine MC, Lee JJ, Kehoe MA.; 2003 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=162000

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Comparative analysis of the localization of lipoteichoic acid in Streptococcus agalactiae and Streptococcus pyogenes. by Mattingly SJ, Johnston BP.; 1987 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=260717

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Comparison of the Gen-Probe Group A streptococcus Direct Test with culture and a rapid streptococcal antigen detection assay for diagnosis of streptococcal pharyngitis. by Heiter BJ, Bourbeau PP.; 1993 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=265698

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Competence Regulation by Oxygen Availability and by Nox Is Not Related to Specific Adjustment of Central Metabolism in Streptococcus pneumoniae. by Chapuy-Regaud S, Duthoit F, Malfroy-Mastrorillo L, Gourdon P, Lindley ND, Trombe MC.; 2001 May 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=99516

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Complete genome sequence and comparative genomic analysis of an emerging human pathogen, serotype V Streptococcus agalactiae. by Tettelin H, Masignani V, Cieslewicz MJ, Eisen JA, Peterson S, Wessels MR, Paulsen IT, Nelson KE, Margarit I, Read TD, Madoff LC, Wolf AM, Beanan MJ, Brinkac LM, Daugherty SC, DeBoy RT, Durkin AS, Kolonay JF, Madupu R, Lewis MR, Radune D, Fedorova NB, Scanlan D, Khouri H, Mulligan S, Carty HA, Cline RT, Van Aken SE, Gill J, Scarselli M, Mora M, Iacobini ET, Brettoni C, Galli G, Mariani M, Vegni F, Maione D, Rinaudo D, Rappuoli R, Telford JL, Kasper DL, Grandi G, Fraser CM.; 2002 Sep 17; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=129455

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Complete genome sequence of an M1 strain of Streptococcus pyogenes. by Ferretti JJ, McShan WM, Ajdic D, Savic DJ, Savic G, Lyon K, Primeaux C, Sezate S, Suvorov AN, Kenton S, Lai HS, Lin SP, Qian Y, Jia HG, Najar FZ, Ren Q, Zhu H, Song L, White J, Yuan X, Clifton SW, Roe BA, McLaughlin R.; 2001 Apr 10; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=31890

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Confirmation of Nontypeable Streptococcus pneumoniae-Like Organisms Isolated from Outbreaks of Epidemic Conjunctivitis as Streptococcus pneumoniae. by Carvalho MG, Steigerwalt AG, Thompson T, Jackson D, Facklam RR.; 2003 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=193841

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Conserved DegP Protease in Gram-Positive Bacteria Is Essential for Thermal and Oxidative Tolerance and Full Virulence in Streptococcus pyogenes. by Jones CH, Bolken TC, Jones KF, Zeller GO, Hruby DE.; 2001 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98667

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Construction and Analysis of a Streptococcus parasanguis recA Mutant: Homologous Recombination Is Not Required for Adhesion in an In Vitro Tooth Surface Model. by Froeliger EH, Tomich M, Fives-Taylor P.; 1999 Jan 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=103532

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Contribution of a Response Regulator to the Virulence of Streptococcus pneumoniae Is Strain Dependent. by Blue CE, Mitchell TJ.; 2003 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=166049

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Contribution of Fibronectin-Binding Protein to Pathogenesis of Streptococcus suis Serotype 2. by de Greeff A, Buys H, Verhaar R, Dijkstra J, van Alphen L, Smith HE.; 2002 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=127759

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Contribution of Mn-Cofactored Superoxide Dismutase (SodA) to the Virulence of Streptococcus agalactiae. by Poyart C, Pellegrini E, Gaillot O, Boumaila C, Baptista M, Trieu-Cuot P.; 2001 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98605

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Contribution of NADH Oxidase to Aerobic Metabolism of Streptococcus pyogenes. by Gibson CM, Mallett TC, Claiborne A, Caparon MG.; 2000 Jan 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=94295

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Contribution of Topoisomerase IV and DNA Gyrase Mutations in Streptococcus pneumoniae to Resistance to Novel Fluoroquinolones. by Pestova E, Beyer R, Cianciotto NP, Noskin GA, Peterson LR.; 1999 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89404

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Correlation of Activities of the Enzymes [alpha]-Phosphoglucomutase, UDPGalactose 4-Epimerase, and UDP-Glucose Pyrophosphorylase with Exopolysaccharide Biosynthesis by Streptococcus thermophilus LY03. by Degeest B, De Vuyst L.; 2000 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=92180

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Culture-Negative Childhood Empyema Is Usually Due to Penicillin-Sensitive Streptococcus pneumoniae Capsular Serotype 1. by Eltringham G, Kearns A, Freeman R, Clark J.; 2003 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=149645

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Defects in d-Alanyl-Lipoteichoic Acid Synthesis in Streptococcus mutans Results in Acid Sensitivity. by Boyd DA, Cvitkovitch DG, Bleiweis AS, Kiriukhin MY, Debabov DV, Neuhaus FC, Hamilton IR.; 2000 Nov 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=94739

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Deletions in the carboxyl-terminal region of Streptococcus gordonii glucosyltransferase affect cell-associated enzyme activity and sucrose-associated accumulation of growing cells. by Vickerman MM, Clewell DB.; 1997 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=168460

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Detection of Penicillin Susceptibility in Streptococcus pneumoniae by pbp2b PCRRestriction Fragment Length Polymorphism Analysis. by O'Neill AM, Gillespie SH, Whiting GC.; 1999 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=84195

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Development of a Multilocus Sequence Typing Scheme for the Pig Pathogen Streptococcus suis: Identification of Virulent Clones and Potential Capsular Serotype Exchange. by King SJ, Leigh JA, Heath PJ, Luque I, Tarradas C, Dowson CG, Whatmore AM.; 2002 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=130843

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Development of Specific Nested Oligonucleotide PCR Primers for the Streptococcus iniae 16S-23S Ribosomal DNA Intergenic Spacer. by Berridge BR, Fuller JD, de Azavedo J, Low DE, Bercovier H, Frelier PF.; 1998 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105208

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Differential Expression of Cytokine Genes and Inducible Nitric Oxide Synthase Induced by Opacity Phenotype Variants of Streptococcus pneumoniae during Acute Otitis Media in the Rat. by Long JP, Tong HH, Shannon PA, DeMaria TF.; 2003 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=201081

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Differentiation between Streptococcus gallolyticus Strains of Human Clinical and Veterinary Origins and Streptococcus bovis Strains from the Intestinal Tracts of Ruminants. by Devriese LA, Vandamme P, Pot B, Vanrobaeys M, Kersters K, Haesebrouck F.; 1998 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105232

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Dissemination of a Chloramphenicol- and Tetracycline-Resistant but PenicillinSusceptible Invasive Clone of Serotype 5 Streptococcus pneumoniae in Colombia. by Tamayo M, Sa-Leao R, Sanches IS, Castaneda E, de Lencastre H.; 1999 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=85154

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Dissemination of High-Level Penicillin-, Extended-Spectrum Cephalosporin-, and Erythromycin-Resistant Streptococcus pneumoniae Clones in Taiwan. by Hsueh PR, Teng LJ, Lee LN, Yang PC, Ho SW, Luh KT.; 1999 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=84215

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Dissemination of Streptococcus pneumoniae Clone Colombia5-19 in Latin America. by Gamboa L, Camou T, Hortal M, Castaneda E.; 2002 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=139718

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Dissemination of the Phage-Associated Novel Superantigen Gene speL in Recent Invasive and Noninvasive Streptococcus pyogenes M3/T3 Isolates in Japan. by Ikebe T, Wada A, Inagaki Y, Sugama K, Suzuki R, Tanaka D, Tamaru A, Fujinaga Y, Abe Y, Shimizu Y, Watanabe H.; 2002 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=128029

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Distribution of Environmentally Regulated Genes of Streptococcus suis Serotype 2 among S. suis Serotypes and Other Organisms. by de Greeff A, Buys H, Verhaar R, van Alphen L, Smith HE.; 2002 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=130683

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Distribution of the Intermedilysin Gene among the Anginosus Group Streptococci and Correlation between Intermedilysin Production and Deep-Seated Infection with Streptococcus intermedius. by Nagamune H, Whiley RA, Goto T, Inai Y, Maeda T, Hardie JM, Kourai H.; 2000 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=88699

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Distribution of the Mosaic Structured murM Genes among Natural Populations of Streptococcus pneumoniae. by Filipe SR, Severina E, Tomasz A.; 2000 Dec 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=111424

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Distribution of the SsuDAT1I Restriction-Modification System among Different Serotypes of Streptococcus suis. by Sekizaki T, Osaki M, Takamatsu D, Shimoji Y.; 2001 Sep 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=95429

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Diversity of PspA: Mosaic Genes and Evidence for Past Recombination in Streptococcus pneumoniae. by Hollingshead SK, Becker R, Briles DE.; 2000 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=101551

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Diversity of Streptococcus salivarius ptsH Mutants That Can Be Isolated in the Presence of 2-Deoxyglucose and Galactose and Characterization of Two Mutants Synthesizing Reduced Levels of HPr, a Phosphocarrier of the Phosphoenolpyruvate:Sugar Phosphotransferase System. by Thomas S, Brochu D, Vadeboncoeur C.; 2001 Sep 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=95391

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DNA Gyrase and Topoisomerase IV Are Dual Targets of Clinafloxacin Action in Streptococcus pneumoniae. by Pan XS, Fisher LM.; 1998 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105948

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drs (Distantly Related sic) Gene Polymorphisms among emm12-Type Streptococcus pyogenes Isolates. by Brandt CM, Haase G, Spellerberg B, Holland R, Lutticken R.; 2003 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=153900

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Dual Functions of Streptococcus salivarius Urease. by Chen YY, Weaver CA, Burne RA.; 2000 Aug 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=94645

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Effect of an Orphan Response Regulator on Streptococcus mutans SucroseDependent Adherence and Cariogenesis. by Idone V, Brendtro S, Gillespie R, Kocaj S, Peterson E, Rendi M, Warren W, Michalek S, Krastel K, Cvitkovitch D, Spatafora G.; 2003 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=166011

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Effect of growth conditions on levels of components of the phosphoenolpyruvate:sugar phosphotransferase system in Streptococcus mutans and Streptococcus sobrinus grown in continuous culture. by Vadeboncoeur C, Thibault L, Neron S, Halvorson H, Hamilton IR.; 1987 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=214049

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Effect of Heat Shock and Mutations in ClpL and ClpP on Virulence Gene Expression in Streptococcus pneumoniae. by Kwon HY, Kim SW, Choi MH, Ogunniyi AD, Paton JC, Park SH, Pyo SN, Rhee DK.; 2003 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=162022

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Effect of polyclonal and monoclonal antibodies on surface properties of Streptococcus sobrinus. by van Raamsdonk M, van der Mei HC, de Soet JJ, Busscher HJ, de Graaff J.; 1995 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=173212

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Effects of Compounds Found in Propolis on Streptococcus mutans Growth and on Glucosyltransferase Activity. by Koo H, Rosalen PL, Cury JA, Park YK, Bowen WH.; 2002 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=127145

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Effects of local immunization of hamsters with glucosyltransferase antigens on infection with Streptococcus sanguis. by Smith DJ, Taubman MA, Ebersole JL.; 1983 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=264537

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Effects of N-acetylglucosamine on carbohydrate fermentation by Streptococcus mutans NCTC 10449 and Streptococcus sobrinus SL-1. by Homer KA, Patel R, Beighton D.; 1993 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=302718

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Effects of rodA and pbp2b Disruption on Cell Morphology and Oxidative Stress Response of Streptococcus thermophilus CNRZ368. by Thibessard A, Fernandez A, Gintz B, Leblond-Bourget N, Decaris B.; 2002 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=135019

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Emergence in France of Multiple Clones of Clinical Streptococcus pneumoniae Isolates with High-Level Resistance to Amoxicillin. by Doit C, Loukil C, Fitoussi F, Geslin P, Bingen E.; 1999 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89301

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Emergence of Penicillin-Nonsusceptible Streptococcus pneumoniae Invasive Clones in Canada. by Greenberg D, Speert DP, Mahenthiralingam E, Henry DA, Campbell ME, Scheifele DW.; 2002 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=120104

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Emergence of vancomycin resistance in the genus Streptococcus: characterization of a vanB transferable determinant in Streptococcus bovis. by Poyart C, Pierre C, Quesne G, Pron B, Berche P, Trieu-Cuot P.; 1997 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=163654

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Enhanced Exopolysaccharide Production by Metabolic Engineering of Streptococcus thermophilus. by Levander F, Svensson M, Radstrom P.; 2002 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=126717

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Enhanced Immunogenicity of a Genetic Chimeric Protein Consisting of Two Virulence Antigens of Streptococcus mutans and Protection against Infection. by Zhang P, Jespersgaard C, Lamberty-Mallory L, Katz J, Huang Y, Hajishengallis G, Michalek SM.; 2002 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=133010

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Epidemiological Analysis of Non-M-Typeable Group A Streptococcus Isolates from a Thai Population in Northern Thailand. by Pruksakorn S, Sittisombut N, Phornphutkul C, Pruksachatkunakorn C, Good MF, Brandt E.; 2000 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=86390

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Evaluation of Methods To Increase the Sensitivity and Timeliness of Detection of Streptococcus agalactiae in Pregnant Women. by Overman SB, Eley DD, Jacobs BE, Ribes JA.; 2002 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=139633

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Evaluation of Semiautomated Multiplex PCR Assay for Determination of Streptococcus pneumoniae Serotypes and Serogroups. by Lawrence ER, Griffiths DB, Martin SA, George RC, Hall LM.; 2003 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=149661

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Evaluation of the PASCO Strep Plus Broth Microdilution Antimicrobial Susceptibility Panels for Testing Streptococcus pneumoniae and Other Streptococcal Species. by Mohammed MJ, Tenover FC.; 2000 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=86569

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Expression of Efflux Pump Gene pmrA in Fluoroquinolone-Resistant and Susceptible Clinical Isolates of Streptococcus pneumoniae. by Piddock LJ, Johnson MM, Simjee S, Pumbwe L.; 2002 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=127475

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Expression of Green Fluorescent Protein in Streptococcus gordonii DL1 and Its Use as a Species-Specific Marker in Coadhesion with Streptococcus oralis 34 in SalivaConditioned Biofilms In Vitro. by Aspiras MB, Kazmerzak KM, Kolenbrander PE, McNab R, Hardegen N, Jenkinson HF.; 2000 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=92261

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Expression of the Secondary Sigma Factor [sigma]X in Streptococcus pyogenes Is Restricted at Two Levels. by Opdyke JA, Scott JR, Moran, Jr. CP.; 2003 Aug 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=165779

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Extremely High Incidence of Macrolide and Trimethoprim-Sulfamethoxazole Resistance among Clinical Isolates of Streptococcus pneumoniae in Taiwan. by Hsueh PR, Teng LJ, Lee LN, Yang PC, Ho SW, Luh KT.; 1999 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=88621

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Fibrinogen binding and resistance to phagocytosis of Streptococcus sanguis expressing cloned M protein of Streptococcus pyogenes. by Poirier TP, Kehoe MA, Whitnack E, Dockter ME, Beachey EH.; 1989 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=313036

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Fluoroquinolone Resistance in Clinical Isolates of Streptococcus pneumoniae: Contributions of Type II Topoisomerase Mutations and Efflux to Levels of Resistance. by Bast DJ, Low DE, Duncan CL, Kilburn L, Mandell LA, Davidson RJ, de Azavedo JC.; 2000 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=101601

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Fluoroquinolone Resistance Is a Poor Surrogate Marker for Type II Topoisomerase Mutations in Clinical Isolates of Streptococcus pneumoniae. by Millichap JJ, Pestova E, Siddiqui F, Noskin GA, Peterson LR.; 2001 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=88221

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Fluoroquinolone-Resistant Streptococcus pneumoniae in Spain: Activities of Garenoxacin against Clinical Isolates Including Strains with Altered Topoisomerases. by Morosini MI, Loza E, del Campo R, Almaraz F, Baquero F, Canton R.; 2003 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=166103

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Functional Analyses of the Promoters in the Lantibiotic Mutacin II Biosynthetic Locus in Streptococcus mutans. by Qi F, Chen P, Caufield PW.; 1999 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=91075

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Generation and Properties of a Streptococcus pneumoniae Mutant Which Does Not Require Choline or Analogs for Growth. by Yother J, Leopold K, White J, Fischer W.; 1998 Apr 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=107135

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Generation and Surface Localization of Intact M Protein in Streptococcus pyogenes Are Dependent on sagA. by Biswas I, Germon P, McDade K, Scott JR.; 2001 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=100083

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Genetic Alteration of Capsule Type but Not PspA Type Affects Accessibility of Surface-Bound Complement and Surface Antigens of Streptococcus pneumoniae. by Abeyta M, Hardy GG, Yother J.; 2003 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=143148

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Genetic Analysis and Functional Characterization of the Streptococcus pneumoniae vic Operon. by Wagner C, Saizieu AD, Schonfeld HJ, Kamber M, Lange R, Thompson CJ, Page MG.; 2002 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=130280

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Genetic and Biochemical Characterization of the F-ATPase Operon from Streptococcus sanguis 10904. by Kuhnert WL, Quivey, Jr. RG.; 2003 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=148061

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Genetic and Phenotypic Features of Streptococcus pyogenes Strains Isolated in Brazil That Harbor New emm Sequences. by Teixeira LM, Barros RR, Castro AC, Peralta JM, Da Gloria S. Carvalho M, Talkington DF, Vivoni AM, Facklam RR, Beall B.; 2001 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=88333

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Genetic and physiologic analysis of a formyl-tetrahydrofolate synthetase mutant of Streptococcus mutans. by Crowley PJ, Gutierrez JA, Hillman JD, Bleiweis AS.; 1997 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=178867

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Genetic Diversity and Clonal Patterns among Antibiotic-Susceptible and -Resistant Streptococcus pneumoniae Colonizing Children: Day Care Centers as Autonomous Epidemiological Units. by Sa-Leao R, Tomasz A, Sanches IS, Nunes S, Alves CR, Avo AB, Saldanha J, Kristinsson KG, de Lencastre H.; 2000 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=87554

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Genetic diversity and relationships among Streptococcus pyogenes strains expressing serotype M1 protein: recent intercontinental spread of a subclone causing episodes of invasive disease. by Musser JM, Kapur V, Szeto J, Pan X, Swanson DS, Martin DR.; 1995 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=173101

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Genetic Features of Streptococcus agalactiae Strains Causing Severe Neonatal Infections, as Revealed by Pulsed-Field Gel Electrophoresis and hylB Gene Analysis. by Rolland K, Marois C, Siquier V, Cattier B, Quentin R.; 1999 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=84979

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Genetic Inactivation of an Extracellular Cysteine Protease (SpeB) Expressed by Streptococcus pyogenes Decreases Resistance to Phagocytosis and Dissemination to Organs. by Lukomski S, Burns EH Jr, Wyde PR, Podbielski A, Rurangirwa J, MoorePoveda DK, Musser JM.; 1998 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=107969

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Genetic Loci for Coaggregation Receptor Polysaccharide Biosynthesis Streptococcus gordonii 38. by Xu DQ, Thompson J, Cisar JO.; 2003 Sep 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=193766

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Genetic Locus for Streptolysin S Production by Group A Streptococcus. by Nizet V, Beall B, Bast DJ, Datta V, Kilburn L, Low DE, De Azavedo JC.; 2000 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=101736

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Genetic Relatedness and Superantigen Expression in Group A Streptococcus Serotype M1 Isolates from Patients with Severe and Nonsevere Invasive Diseases. by Chatellier S, Ihendyane N, Kansal RG, Khambaty F, Basma H, Norrby-Teglund A, Low DE, McGeer A, Kotb M.; 2000 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=97638

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Genetic Relatedness of Levofloxacin-Nonsusceptible Streptococcus pneumoniae Isolates from North America. by Johnson CN, Benjamin, Jr. WH, Moser SA, Hollingshead SK, Zheng X, Crain MJ, Nahm MH, Waites KB.; 2003 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=156496

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Genetic Relatedness within Serotypes of Penicillin-Susceptible Streptococcus pneumoniae Isolates. by Overweg K, Bogaert D, Sluijter M, Yother J, Dankert J, de Groot R, Hermans PW.; 2000 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=87635

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Genetic Relationships between Clinical Isolates of Streptococcus pneumoniae, Streptococcus oralis, and Streptococcus mitis: Characterization of "Atypical" Pneumococci and Organisms Allied to S. mitis Harboring S. pneumoniae Virulence Factor-Encoding Genes. by Whatmore AM, Efstratiou A, Pickerill AP, Broughton K, Woodard G, Sturgeon D, George R, Dowson CG.; 2000 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=97291

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Genome sequence of a serotype M3 strain of group A Streptococcus: Phage-encoded toxins, the high-virulence phenotype, and clone emergence. by Beres SB, Sylva GL, Barbian KD, Lei B, Hoff JS, Mammarella ND, Liu MY, Smoot JC, Porcella SF, Parkins LD, Campbell DS, Smith TM, McCormick JK, Leung DY, Schlievert PM, Musser JM.; 2002 Jul 23; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=126627

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Genome-wide protective response used by group A Streptococcus to evade destruction by human polymorphonuclear leukocytes. by Voyich JM, Sturdevant DE, Braughton KR, Kobayashi SD, Lei B, Virtaneva K, Dorward DW, Musser JM, DeLeo FR.; 2003 Feb 18; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=149947

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Genotypic and Phenotypic Characterization of "Streptococcus milleri" Group Isolates from a Veterans Administration Hospital Population. by Clarridge JE III, Osting C, Jalali M, Osborne J, Waddington M.; 1999 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=85724

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Genotypic Heterogeneity of Streptococcus oralis and Distinct Aciduric Subpopulations in Human Dental Plaque. by Alam S, Brailsford SR, Adams S, Allison C, Sheehy E, Zoitopoulos L, Kidd EA, Beighton D.; 2000 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=92151

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Global differential gene expression in response to growth temperature alteration in group A Streptococcus. by Smoot LM, Smoot JC, Graham MR, Somerville GA, Sturdevant DE, Migliaccio CA, Sylva GL, Musser JM.; 2001 Aug 28; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=56975

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Global Transcriptional Analysis of clpP Mutations of Type 2 Streptococcus pneumoniae and Their Effects on Physiology and Virulence. by Robertson GT, Ng WL, Foley J, Gilmour R, Winkler ME.; 2002 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=135132

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Group A Streptococcus Gene Expression in Humans and Cynomolgus Macaques with Acute Pharyngitis. by Virtaneva K, Graham MR, Porcella SF, Hoe NP, Su H, Graviss EA, Gardner TJ, Allison JE, Lemon WJ, Bailey JR, Parnell MJ, Musser JM.; 2003 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=152081

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Growth of oral Streptococcus species and Actinomyces viscosus in human saliva. by de Jong MH, van der Hoeven JS, van OS JH, Olijve JH.; 1984 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=240009

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Growth-Phase-Dependent Expression of Virulence Factors in an M1T1 Clinical Isolate of Streptococcus pyogenes. by Unnikrishnan M, Cohen J, Sriskandan S.; 1999 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=96913

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Hemagglutination activities of group B, C, D, and G streptococci: demonstration of novel sugar-specific cell-binding activities in Streptococcus suis. by Kurl DN, Haataja S, Finne J.; 1989 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=313108

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High Rate of Tetracycline Resistance in Streptococcus pyogenes in Iran: an Epidemiological Study. by Jasir A, Tanna A, Noorani A, Mirsalehian A, Efstratiou A, Schalen C.; 2000 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=86737

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High Rate of Transmission of Penicillin-Resistant Streptococcus pneumoniae between Parents and Children. by Hoshino K, Watanabe H, Sugita R, Asoh N, Ntabaguzi SA, Watanabe K, Oishi K, Nagatake T.; 2002 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=139698

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High-Resolution Genotyping of Streptococcus pyogenes Serotype M1 Isolates by Fluorescent Amplified-Fragment Length Polymorphism Analysis. by Desai M, Efstratiou A, George R, Stanley J.; 1999 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=84992

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Household Transmission of Streptococcus pneumoniae among Siblings with Acute Otitis Media. by Shimada J, Yamanaka N, Hotomi M, Suzumoto M, Sakai A, Ubukata K, Mitsuda T, Yokota S, Faden H.; 2002 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=130916

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Humoral Immunity to Commensal Oral Bacteria in Human Infants: Salivary Secretory Immunoglobulin A Antibodies Reactive with Streptococcus mitis biovar 1, Streptococcus oralis, Streptococcus mutans, and Enterococcus faecalis during the First Two Years of Life. by Cole MF, Bryan S, Evans MK, Pearce CL, Sheridan MJ, Sura PA, Wientzen RL, Bowden GH.; 1999 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=96541

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Identification and Characterization of HtsA, a Second Heme-Binding Protein Made by Streptococcus pyogenes. by Lei B, Liu M, Voyich JM, Prater CI, Kala SV, DeLeo FR, Musser JM.; 2003 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=201091

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Identification and Characterization of the cps Locus of Streptococcus suis Serotype 2: the Capsule Protects against Phagocytosis and Is an Important Virulence Factor. by Smith HE, Damman M, van der Velde J, Wagenaar F, Wisselink HJ, StockhofeZurwieden N, Smits MA.; 1999 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=96524

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Identification and Molecular Analysis of PcsB, a Protein Required for Cell Wall Separation of Group B Streptococcus. by Reinscheid DJ, Gottschalk B, Schubert A, Eikmanns BJ, Chhatwal GS.; 2001 Feb 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=94990

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Identification of 113 conserved essential genes using a high-throughput gene disruption system in Streptococcus pneumoniae. by Thanassi JA, Hartman-Neumann SL, Dougherty TJ, Dougherty BA, Pucci MJ.; 2002 Jul 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=135739

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Identification of a Differentially Expressed Oligopeptide Binding Protein (OppA2) in Streptococcus uberis by Representational Difference Analysis of cDNA. by Taylor DL, Ward PN, Rapier CD, Leigh JA, Bowler LD.; 2003 Sep 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=181005

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Identification of a Streptolysin S-Associated Gene Cluster and Its Role in the Pathogenesis of Streptococcus iniae Disease. by Fuller JD, Camus AC, Duncan CL, Nizet V, Bast DJ, Thune RL, Low DE, de Azavedo JC.; 2002 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=128303

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Identification of an erm(A) Erythromycin Resistance Methylase Gene in Streptococcus pneumoniae Isolated in Greece. by Syrogiannopoulos GA, Grivea IN, Tait-Kamradt A, Katopodis GD, Beratis NG, Sutcliffe J, Appelbaum PC, Davies TA.; 2001 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=90289

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Identification of an Inducible Bacteriophage in a Virulent Strain of Streptococcus suis Serotype 2. by Harel J, Martinez G, Nassar A, Dezfulian H, Labrie SJ, Brousseau R, Moineau S, Gottschalk M.; 2003 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=201037

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Identification of Bacteriocin-Like Inhibitors from Rumen Streptococcus spp. and Isolation and Characterization of Bovicin 255. by Whitford MF, McPherson MA, Forster RJ, Teather RM.; 2001 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=92622

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Identification of Enterococcus, Streptococcus, and Staphylococcus by Multivariate Analysis of Proton Magnetic Resonance Spectroscopic Data from Plate Cultures. by Bourne R, Himmelreich U, Sharma A, Mountford C, Sorrell T.; 2001 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=88260

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Identification of Isolates of Streptococcus canis Infecting Humans. by Whatmore AM, Engler KH, Gudmundsdottir G, Efstratiou A.; 2001 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=88517

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Identification of Lipoprotein Homologues of Pneumococcal PsaA in the Equine Pathogens Streptococcus equi and Streptococcus zooepidemicus. by Harrington DJ, Greated JS, Chanter N, Sutcliffe IC.; 2000 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=101572

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Identification of Streptococcus bovis Biotype I Strains among S. bovis Clinical Isolates by PCR. by Songy WB, Ruoff KL, Facklam RR, Ferraro MJ, Falkow S.; 2002 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=120625

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Identification of Streptococcus sanguinis with a PCR-Generated Species-Specific DNA Probe. by Li Y, Pan Y, Qi F, Caufield PW.; 2003 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=179791

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Identification of the psaA Gene, Coding for Pneumococcal Surface Adhesin A, in Viridans Group Streptococci other than Streptococcus pneumoniae. by Jado I, Fenoll A, Casal J, Perez A.; 2001 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=96167

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Identification of Three Major Clones of Multiply Antibiotic-Resistant Streptococcus pneumoniae in Taiwanese Hospitals by Multilocus Sequence Typing. by Shi ZY, Enright MC, Wilkinson P, Griffiths D, Spratt BG.; 1998 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105231

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Immunoreactivity of Five Monoclonal Antibodies against the 37-Kilodalton Common Cell Wall Protein (PsaA) of Streptococcus pneumoniae. by Crook J, Tharpe JA, Johnson SE, Williams DB, Stinson AR, Facklam RR, Ades EW, Carlone GM, Sampson JS.; 1998 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=121359

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Impact of M49, Mrp, Enn, and C5a Peptidase Proteins on Colonization of the Mouse Oral Mucosa by Streptococcus pyogenes. by Ji Y, Schnitzler N, DeMaster E, Cleary P.; 1998 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=108676

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Impaired Temperature Stress Response of a Streptococcus thermophilus deoD Mutant. by Varcamonti M, Graziano MR, Pezzopane R, Naclerio G, Arsenijevic S, De Felice M.; 2003 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=143660

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In Utero Infection by Porcine Reproductive and Respiratory Syndrome Virus Is Sufficient To Increase Susceptibility of Piglets to Challenge by Streptococcus suis Type II. by Feng WH, Laster SM, Tompkins M, Brown T, Xu JS, Altier C, Gomez W, Benfield D, McCaw MB.; 2001 May 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=114243

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In Vitro Activities of Novel Des-Fluoro(6) Quinolone BMS-284756 against Mutants of Streptococcus pneumoniae, Streptococcus pyogenes, and Staphylococcus aureus Selected with Different Quinolones. by Schmitz FJ, Boos M, Mayer S, Kohrer K, Scheuring S.; 2002 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=127515

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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 Activity of the New Ketolide Telithromycin Compared with Those of Macrolides against Streptococcus pyogenes: Influences of Resistance Mechanisms and Methodological Factors. by Bemer-Melchior P, Juvin ME, Tassin S, Bryskier A, Schito GC, Drugeon HB.; 2000 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=101592

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In vitro method to differentiate isolates of type III Streptococcus agalactiae from symptomatic and asymptomatic patients. by Maurer JJ, Mattingly SJ.; 1988 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=266412

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In Vitro Selection of Resistance to Clinafloxacin, Ciprofloxacin, and Trovafloxacin in Streptococcus pneumoniae. by Nagai K, Davies TA, Pankuch GA, Dewasse BE, Jacobs MR, Appelbaum PC.; 2000 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=90145

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In Vivo Lysogenic Conversion of Tox[minus sign]Streptococcus pyogenes to Tox + with Lysogenic Streptococci or Free Phage. by Broudy TB, Fischetti VA.; 2003 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=161974

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Inactivation of the Streptococcus mutans wall-associated protein A gene (wapA) results in a decrease in sucrose-dependent adherence and aggregation. by Qian H, Dao ML.; 1993 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=281278

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Induction of natural competence in Streptococcus pneumoniae triggers lysis and DNA release from a subfraction of the cell population. by Steinmoen H, Knutsen E, Havarstein LS.; 2002 May 28; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=124321

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Inhibition of Human Peripheral Blood Mononuclear Cell Proliferation by Streptococcus pyogenes Cell Extract Is Associated with Arginine Deiminase Activity. by Degnan BA, Palmer JM, Robson T, Jones CE, Fischer M, Glanville M, Mellor GD, Diamond AG, Kehoe MA, Goodacre JA.; 1998 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=108312

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Inhibition of the expression of penicillin resistance in Streptococcus pneumoniae by inactivation of cell wall muropeptide branching genes. by Filipe SR, Tomasz A.; 2000 Apr 25; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=18328

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Inhibitory and Bactericidal Effects of Hydrogen Peroxide Production by Streptococcus pneumoniae on Other Inhabitants of the Upper Respiratory Tract. by Pericone CD, Overweg K, Hermans PW, Weiser JN.; 2000 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=101678

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Insertional Inactivation of Genes Responsible for the d-Alanylation of Lipoteichoic Acid in Streptococcus gordonii DL1 (Challis) Affects Intrageneric Coaggregations. by Clemans DL, Kolenbrander PE, Debabov DV, Zhang Q, Lunsford RD, Sakone H, Whittaker CJ, Heaton MP, Neuhaus FC.; 1999 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=115992

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Insertional Inactivation of pac and rmlB Genes Reduces the Release of Tumor Necrosis Factor Alpha, Interleukin-6, and Interleukin-8 Induced by Streptococcus mutans in Monocytic, Dental Pulp, and Periodontal Ligament Cells. by EngelsDeutsch M, Pini A, Yamashita Y, Shibata Y, Haikel Y, Scholler-Guinard M, Klein JP.; 2003 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=187322

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Intermedilysin, a novel cytotoxin specific for human cells secreted by Streptococcus intermedius UNS46 isolated from a human liver abscess. by Nagamune H, Ohnishi C, Katsuura A, Fushitani K, Whiley RA, Tsuji A, Matsuda Y.; 1996 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=174193

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Interspecies Recombination Contributes Minimally to Fluoroquinolone Resistance in Streptococcus pneumoniae. by Bast DJ, de Azavedo JC, Tam TY, Kilburn L, Duncan C, Mandell LA, Davidson RJ, Low DE.; 2001 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=90704

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Intracellular Survival of Streptococcus pyogenes in Polymorphonuclear Cells Results in Increased Bacterial Virulence. by Medina E, Rohde M, Chhatwal GS.; 2003 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=187312

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Intramolecular Regulation of the Opposing (p)ppGpp Catalytic Activities of RelSeq, the Rel/Spo Enzyme from Streptococcus equisimilis. by Mechold U, Murphy H, Brown L, Cashel M.; 2002 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=135074

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Introduction of New Clones of Penicillin-Nonsusceptible Streptococcus pneumoniae in Hong Kong. by Ip M, Lyon DJ, Yung RW, Tsang L, Cheng AF.; 2002 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=140348

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Invasive Streptococcus iniae Infections Outside North America. by Lau SK, Woo PC, Tse H, Leung KW, Wong SS, Yuen KY.; 2003 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=150295

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Involvement of Lsp, a Member of the LraI-Lipoprotein Family in Streptococcus pyogenes, in Eukaryotic Cell Adhesion and Internalization. by Elsner A, Kreikemeyer B, Braun-Kiewnick A, Spellerberg B, Buttaro BA, Podbielski A.; 2002 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=128222

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Linezolid and Vancomycin, Alone and in Combination with Rifampin, Compared with Moxifloxacin against a Multidrug-Resistant and a Vancomycin-Tolerant Streptococcus pneumoniae Strain in an In Vitro Pharmacodynamic Model. by Cha R, Rybak MJ.; 2003 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=155816

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Lmb, a Protein with Similarities to the LraI Adhesin Family, Mediates Attachment of Streptococcus agalactiae to Human Laminin. by Spellerberg B, Rozdzinski E, Martin S, Weber-Heynemann J, Schnitzler N, Lutticken R, Podbielski A.; 1999 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=96398

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Long-Range Mapping of the Streptococcus agalactiae Phylogenetic Lineage Restriction Digest Pattern Type III-3 Reveals Clustering of Virulence Genes. by Bohnsack JF, Whiting AA, Bradford RD, Van Frank BK, Takahashi S, Adderson EE.; 2002 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=127635

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LuxS-Based Signaling in Streptococcus gordonii: Autoinducer 2 Controls Carbohydrate Metabolism and Biofilm Formation with Porphyromonas gingivalis. by McNab R, Ford SK, El-Sabaeny A, Barbieri B, Cook GS, Lamont RJ.; 2003 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=141908

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M1 Protein Triggers a Phosphoinositide Cascade for Group A Streptococcus Invasion of Epithelial Cells. by Purushothaman SS, Wang B, Cleary PP.; 2003 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=201040

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Macrolide Resistance by Ribosomal Mutation in Clinical Isolates of Streptococcus pneumoniae from the PROTEKT 1999-2000 Study. by Farrell DJ, Douthwaite S, Morrissey I, Bakker S, Poehlsgaard J, Jakobsen L, Felmingham D.; 2003 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=155854

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Macrolide Resistance Gene mreA of Streptococcus agalactiae Encodes a Flavokinase. by Clarebout G, Villers C, Leclercq R.; 2001 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=90643

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Macrolide-Resistant Streptococcus pneumoniae and Streptococcus pyogenes in the Pediatric Population in Germany during 2000-2001. by Reinert RR, Lutticken R, Bryskier A, Al-Lahham A.; 2003 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=151724

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Macrolide-Resistant Streptococcus pneumoniae in Canada during 1998 --1999: Prevalence of mef(A) and erm(B) and Susceptibilities to Ketolides. by Hoban DJ, Wierzbowski AK, Nichol K, Zhanel GG.; 2001 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=90618

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Macrorestriction Fingerprinting of "Streptococcus milleri" Group Bacteria by PulsedField Gel Electrophoresis. by Bartie KL, Wilson MJ, Williams DW, Lewis MA.; 2000 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=86748

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Major Outbreak of Toxic Shock-Like Syndrome Caused by Streptococcus mitis. by Lu HZ, Weng XH, Zhu B, Li H, Yin YK, Zhang YX, Haas DW, Tang YW.; 2003 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=165286

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Mechanism of Fluoroquinolone Resistance Is an Important Factor in Determining the Antimicrobial Effect of Gemifloxacin against Streptococcus pneumoniae in an In Vitro Pharmacokinetic Model. by MacGowan AP, Bowker KE.; 2003 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=149284

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Mefloquine and New Related Compounds Target the F0 Complex of the F0F1 H +ATPase of Streptococcus pneumoniae. by Martin-Galiano AJ, Gorgojo B, Kunin CM, de la Campa AG.; 2002 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=127268

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Meningitis Due to Mixed Infection with Penicillin-Resistant and PenicillinSusceptible Strains of Streptococcus pneumoniae. by Chaves F, Campelo C, Sanz F, Otero JR.; 2003 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=149642

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Meningitis Due to Streptococcus salivarius. by Idigoras P, Valiente A, Iglesias L.; 2001 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=88286

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Metabolic Engineering of Acetaldehyde Production by Streptococcus thermophilus. by Chaves AC, Fernandez M, Lerayer AL, Mierau I, Kleerebezem M, Hugenholtz J.; 2002 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=129919

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Microarray-Based Identification of htrA, a Streptococcus pneumoniae Gene That Is Regulated by the CiaRH Two-Component System and Contributes to Nasopharyngeal Colonization. by Sebert ME, Palmer LM, Rosenberg M, Weiser JN.; 2002 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=128155

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M-Like Proteins of Streptococcus dysgalactiae. by Vasi J, Frykberg L, Carlsson LE, Lindberg M, Guss B.; 2000 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=97134

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Mode of action of a lysostaphin-like bacteriolytic agent produced by Streptococcus zooepidemicus 4881. by Simmonds RS, Pearson L, Kennedy RC, Tagg JR.; 1996 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=168280

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Molecular Analysis by Pulsed-Field Gel Electrophoresis and Antibiogram of Streptococcus pneumoniae Serotype 6B Isolates from Selected Areas within the United States. by Rudolph KM, Parkinson AJ, Roberts MC.; 1998 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105187

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Molecular Characterization of a Strain of Group A Streptococcus Isolated from a Patient with a Psoas Abscess. by Lau SK, Woo PC, Yim TC, To AP, Yuen KY.; 2003 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=254351

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Molecular Characterization of Equine Isolates of Streptococcus pneumoniae: Natural Disruption of Genes Encoding the Virulence Factors Pneumolysin and Autolysin. by Whatmore AM, King SJ, Doherty NC, Sturgeon D, Chanter N, Dowson CG.; 1999 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=96581

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Molecular Characterization of Multidrug-Resistant Streptococcus pneumoniae Isolates in Korea. by Song JH, Yang JW, Jin JH, Kim SW, Kim CK, Lee H, Peck KR, Kim S, Lee NY, Jacobs MR, Appelbaum PC.; 2000 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=86510

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Molecular Characterization of Penicillin-Resistant Streptococcus pneumoniae Isolates from Bulgaria. by Setchanova L, Tomasz A.; 1999 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=84503

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Molecular Epidemiology of Erythromycin Resistance in Streptococcus pneumoniae Isolates from Blood and Noninvasive Sites. by Amezaga MR, Carter PE, Cash P, McKenzie H.; 2002 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=130757

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Molecular Epidemiology of Penicillin-Nonsusceptible Streptococcus pneumoniae among Children in Greece. by Bogaert D, Syrogiannopoulos GA, Grivea IN, de Groot R, Beratis NG, Hermans PW.; 2000 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=87606

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Molecular Epidemiology of Penicillin-Resistant and Ciprofloxacin-Resistant Streptococcus pneumoniae in Canada. by Nichol KA, Zhanel GG, Hoban DJ.; 2003 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=151757

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Molecular Epidemiology of Penicillin-Resistant Streptococcus pneumoniae Isolates Recovered in Italy from 1993 to 1996. by Marchese A, Ramirez M, Schito GC, Tomasz A.; 1998 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105092

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Molecular Epidemiology of Streptococcus uberis Isolates from Dairy Cows with Mastitis. by Phuektes P, Mansell PD, Dyson RS, Hooper ND, Dick JS, Browning GF.; 2001 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=87955

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Molecular Evolution in a Multidrug-Resistant Lineage of Streptococcus pneumoniae: Emergence of Strains Belonging to the Serotype 6B Icelandic Clone That Lost Antibiotic Resistance Traits. by Vilhelmsson SE, Tomasz A, Kristinsson KG.; 2000 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=86448

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Mosaic Genes and Mosaic Chromosomes: Intra- and Interspecies Genomic Variation of Streptococcus pneumoniae. by Hakenbeck R, Balmelle N, Weber B, Gardes C, Keck W, de Saizieu A.; 2001 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98182

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MtsABC Is Important for Manganese and Iron Transport, Oxidative Stress Resistance, and Virulence of Streptococcus pyogenes. by Janulczyk R, Ricci S, Bjorck L.; 2003 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=153223

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MtuA, a Lipoprotein Receptor Antigen from Streptococcus uberis, Is Responsible for Acquisition of Manganese during Growth in Milk and Is Essential for Infection of the Lactating Bovine Mammary Gland. by Smith AJ, Ward PN, Field TR, Jones CL, Lincoln RA, Leigh JA.; 2003 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=187302

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Multicenter Study on Spreading of the tet(M) Gene in Tetracycline-Resistant Streptococcus Group G and C Isolates in Argentina. by Jeric PE, Lopardo H, Vidal P, Arduino S, Fernandez A, Orman BE, Sordelli DO, Centron D.; 2002 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=127005

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Multidrug-Resistant Streptococcus pneumoniae in Poland: Identification of Emerging Clones. by Overweg K, Hermans PW, Trzcinski K, Sluijter M, de Groot R, Hryniewicz W.; 1999 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=84938

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Multilocus analysis of extracellular putative virulence proteins made by group A Streptococcus: Population genetics, human serologic response, and gene transcription. by Reid SD, Green NM, Buss JK, Lei B, Musser JM.; 2001 Jun 19; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=34706

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Multilocus Sequence Typing of Streptococcus pyogenes and the Relationships between emm Type and Clone. by Enright MC, Spratt BG, Kalia A, Cross JH, Bessen DE.; 2001 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98174

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Multiple Mutations Modulate the Function of Dihydrofolate Reductase in Trimethoprim-Resistant Streptococcus pneumoniae. by Maskell JP, Sefton AM, Hall LM.; 2001 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=90431

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Multiplex PCR Assays for Simultaneous Detection of Six Major Serotypes and Two Virulence-Associated Phenotypes of Streptococcus suis in Tonsillar Specimens from Pigs. by Wisselink HJ, Joosten JJ, Smith HE.; 2002 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=120666

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Mutant Prevention Concentration of Gemifloxacin for Clinical Isolates of Streptococcus pneumoniae. by Hansen GT, Metzler K.; 2003 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=149038

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Mutation of luxS of Streptococcus pneumoniae Affects Virulence in a Mouse Model. by Stroeher UH, Paton AW, Ogunniyi AD, Paton JC.; 2003 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=155746

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Mutational Analysis of the Streptococcus pneumoniae Bimodular Class A PenicillinBinding Proteins. by Paik J, Kern I, Lurz R, Hakenbeck R.; 1999 Jun 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=93869

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NAD-Glycohydrolase Production and speA and speC Distribution in Group A Streptococcus (GAS) Isolates Do Not Correlate with Severe GAS Diseases in the Australian Population. by DelVecchio A, Maley M, Currie BJ, Sriprakash KS.; 2002 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=120539

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Nasal Carriage in Vietnamese Children of Streptococcus pneumoniae Resistant to Multiple Antimicrobial Agents. by Parry CM, Diep TS, Wain J, Hoa NT, Gainsborough M, Nga D, Davies C, Phu NH, Hien TT, White NJ, Farrar JJ.; 2000 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89715

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Nasopharyngeal Carriage of Penicillin-Resistant Streptococcus pneumoniae among Children with Acute Respiratory Tract Infections in Thailand: a Molecular Epidemiological Survey. by Dejsirilert S, Overweg K, Sluijter M, Saengsuk L, Gratten M, Ezaki T, Hermans PW.; 1999 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=84963

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Natural History of Streptococcus sanguinis in the Oral Cavity of Infants: Evidence for a Discrete Window of Infectivity. by Caufield PW, Dasanayake AP, Li Y, Pan Y, Hsu J, Hardin JM.; 2000 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=101685

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Nomenclature of Major Antimicrobial-Resistant Clones of Streptococcus pneumoniae Defined by the Pneumococcal Molecular Epidemiology Network. by McGee L, McDougal L, Zhou J, Spratt BG, Tenover FC, George R, Hakenbeck R, Hryniewicz W, Lefevre JC, Tomasz A, Klugman KP.; 2001 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=88185

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Novel Expansions of the Gene Encoding Dihydropteroate Synthase in TrimethoprimSulfamethoxazole-Resistant Streptococcus pneumoniae. by Padayachee T, Klugman KP.; 1999 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89451

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Novel Extracellular x-Prolyl Dipeptidyl-Peptidase (DPP) from Streptococcus gordonii FSS2: an Emerging Subfamily of Viridans Streptococcal x-Prolyl DPPs. by Goldstein JM, Banbula A, Kordula T, Mayo JA, Travis J.; 2001 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98662

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Novel Laminin-Binding Protein of Streptococcus pyogenes, Lbp, Is Involved in Adhesion to Epithelial Cells. by Terao Y, Kawabata S, Kunitomo E, Nakagawa I, Hamada S.; 2002 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=127702

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Novel Penicillin-, Cephalosporin-, and Macrolide-Resistant Clones of Streptococcus pneumoniae Serotypes 23F and 19F in Taiwan Which Differ from International Epidemic Clones. by Chiou CC, McEllistrem MC.; 2001 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=87890

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Novel Two-Component Regulatory System Involved in Biofilm Formation and Acid Resistance in Streptococcus mutans. by Li YH, Lau PC, Tang N, Svensater G, Ellen RP, Cvitkovitch DG.; 2002 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=151940

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Occurrence of mucoid M-18 Streptococcus pyogenes in a central Ohio pediatric population. by Marcon MJ, Hribar MM, Hosier DM, Powell DA, Brady MT, Hamoudi AC, Kaplan EL.; 1988 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=266656

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Opsonophagocytosis-Inhibiting Mac Protein of Group A Streptococcus: Identification and Characteristics of Two Genetic Complexes. by Lei B, DeLeo FR, Reid SD, Voyich JM, Magoun L, Liu M, Braughton KR, Ricklefs S, Hoe NP, Cole RL, Leong JM, Musser JM.; 2002 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=133040

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Optochin Revisited: Defining the Optimal Type of Blood Agar for Presumptive Identification of Streptococcus pneumoniae. by Gardam MA, Miller MA.; 1998 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=104639

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Oxygen sensitivity of sugar metabolism and interconversion of pyruvate formatelyase in intact cells of Streptococcus mutans and Streptococcus sanguis. by Takahashi N, Abbe K, Takahashi-Abbe S, Yamada T.; 1987 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=260389

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ParC and GyrA May Be Interchangeable Initial Targets of Some Fluoroquinolones in Streptococcus pneumoniae. by Varon E, Janoir C, Kitzis MD, Gutmann L.; 1999 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89068

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Peripartum Transmission of Penicillin-Resistant Streptococcus pneumoniae. by McDonald LC, Bryant K, Snyder J.; 2003 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=154670

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Peritoneal Culture Alters Streptococcus pneumoniae Protein Profiles and Virulence Properties. by Orihuela CJ, Janssen R, Robb CW, Watson DA, Niesel DW.; 2000 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=101580

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Persistence of Two Invasive Streptococcus pneumoniae Clones of Serotypes 1 and 5 in Comparison to That of Multiple Clones of Serotypes 6B and 23F among Children in Southern Israel. by Porat N, Trefler R, Dagan R.; 2001 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=88033

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Phenotypes and Genotypes of Erythromycin-Resistant Streptococcus pyogenes Strains in Italy and Heterogeneity of Inducibly Resistant Strains. by Giovanetti E, Montanari MP, Mingoia M, Varaldo PE.; 1999 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89394

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Phenotypic and Genotypic Characterization of Two Penicillin-Susceptible Serotype 6B Streptococcus pneumoniae Clones Circulating in Italy. by Gherardi G, Del Grosso M, Scotto d'Abusco A, D'Ambrosio F, Dicuonzo G, Pantosti A.; 2003 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=165367

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Phenotypic and Molecular Characterization of Tetracycline- and ErythromycinResistant Strains of Streptococcus pneumoniae. by Montanari MP, Cochetti I, Mingoia M, Varaldo PE.; 2003 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=161878

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Phenotypic Consequences Resulting from a Methionine-to-Valine Substitution at Position 48 in the HPr Protein of Streptococcus salivarius. by Plamondon P, Brochu D, Thomas S, Fradette J, Gauthier L, Vaillancourt K, Buckley N, Frenette M, Vadeboncoeur C.; 1999 Nov 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=94165

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Pigment Production by Streptococcus agalactiae in Quasi-Defined Media. by RosaFraile M, Sampedro A, Rodriguez-Granger J, Garcia-Pena ML, Ruiz-Bravo A, Haidour A.; 2001 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=92604

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Streptococcus

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Pneumococcal Surface Protein A Inhibits Complement Activation by Streptococcus pneumoniae. by Tu AH, Fulgham RL, McCrory MA, Briles DE, Szalai AJ.; 1999 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=96800

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Pneumolysin Detection Identifies Atypical Isolates of Streptococcus pneumoniae. by Kearns AM, Wheeler J, Freeman R, Seiders PR.; 2000 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=88616

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Population Dynamics of Streptococcus mitis in Its Natural Habitat. by Hohwy J, Reinholdt J, Kilian M.; 2001 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98734

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Postgenomic Analysis of Four Novel Antigens of Group A Streptococcus: Growth Phase-Dependent Gene Transcription and Human Serologic Response. by Reid SD, Green NM, Sylva GL, Voyich JM, Stenseth ET, DeLeo FR, Palzkill T, Low DE, Hill HR, Musser JM.; 2002 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=151937

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Prevalence of Antimicrobial Resistance in Respiratory Tract Isolates of Streptococcus pneumoniae: Results of a Canadian National Surveillance Study. by Zhanel GG, Karlowsky JA, Palatnick L, Vercaigne L, Low DE, Hoban DJ.; 1999 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89508

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Prevalence of Single Mutations in Topoisomerase Type II Genes among Levofloxacin-Susceptible Clinical Strains of Streptococcus pneumoniae Isolated in the United States in 1992 to 1996 and 1999 to 2000. by Davies TA, Evangelista A, Pfleger S, Bush K, Sahm DF, Goldschmidt R.; 2002 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=127004

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Production and Properties of Bacteriocin-Like Inhibitory Substances from the Swine Pathogen Streptococcus suis Serotype 2. by Melancon D, Grenier D.; 2003 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=169146

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Protective Immunity against Streptococcus mutans Infection in Mice after Intranasal Immunization with the Glucan-Binding Region of S. mutans Glucosyltransferase. by Jespersgaard C, Hajishengallis G, Huang Y, Russell MW, Smith DJ, Michalek SM.; 1999 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=97065

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Purification and Biochemical Characterization of Mutacin I from the Group I Strain of Streptococcus mutans, CH43, and Genetic Analysis of Mutacin I Biosynthesis Genes. by Qi F, Chen P, Caufield PW.; 2000 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=92137

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Purification and Characterization of Streptin, a Type A1 Lantibiotic Produced by Streptococcus pyogenes. by Wescombe PA, Tagg JR.; 2003 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=154524

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Purification of Mutacin III from Group III Streptococcus mutans UA787 and Genetic Analyses of Mutacin III Biosynthesis Genes. by Qi F, Chen P, Caufield PW.; 1999 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=99715

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Purification, Characterization, and Molecular Analysis of the Gene Encoding Glucosyltransferase from Streptococcus oralis. by Fujiwara T, Hoshino T, Ooshima T, Sobue S, Hamada S.; 2000 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=97449

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Purification, characterization, and nucleotide sequence of an intracellular maltotrioseproducing alpha-amylase from Streptococcus bovis 148. by Satoh E, Uchimura T, Kudo T, Komagata K.; 1997 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=168820

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Quinolone Resistance Mutations in Streptococcus pneumoniae GyrA and ParC Proteins: Mechanistic Insights into Quinolone Action from Enzymatic Analysis, Intracellular Levels, and Phenotypes of Wild-Type and Mutant Proteins. by Pan XS, Yague G, Fisher LM.; 2001 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=90795

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Rapid Pulsed-Field Gel Electrophoresis Method for Group B Streptococcus Isolates. by Benson JA, Ferrieri P.; 2001 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=88282

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Rapid Screening for Streptococcus agalactiae in Vaginal Specimens of Pregnant Women by Fluorescent In Situ Hybridization. by Artz LA, Kempf VA, Autenrieth IB.; 2003 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=154702

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Rapidly Increasing Prevalence of Penicillin-Resistant Streptococcus pneumoniae in Middle Tennessee: a 10-Year Clinical and Molecular Analysis. by Tang YW, Li H, Griffin JP, Haas DW, D'Agata EM.; 2002 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=153403

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Recovery of Streptococcus iniae from Diseased Fish Previously Vaccinated with a Streptococcus Vaccine. by Bachrach G, Zlotkin A, Hurvitz A, Evans DL, Eldar A.; 2001 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=93086

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RegG, a CcpA Homolog, Participates in Regulation of Amylase-Binding Protein A Gene (abpA) Expression in Streptococcus gordonii. by Rogers JD, Scannapieco FA.; 2001 Jun 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=99651

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Regulated Expression of the Streptococcus mutans dlt Genes Correlates with Intracellular Polysaccharide Accumulation. by Spatafora GA, Sheets M, June R, Luyimbazi D, Howard K, Hulbert R, Barnard D, el Janne M, Hudson MC.; 1999 Apr 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=93659

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Regulation and Physiological Significance of ClpC and ClpP in Streptococcus mutans. by Lemos JA, Burne RA.; 2002 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=151938

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Regulation of ATP-dependent P-(Ser)-HPr formation in Streptococcus mutans and Streptococcus salivarius. by Thevenot T, Brochu D, Vadeboncoeur C, Hamilton IR.; 1995 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=176946

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Regulation of d-Alanyl-Lipoteichoic Acid Biosynthesis in Streptococcus agalactiae Involves a Novel Two-Component Regulatory System. by Poyart C, Lamy MC, Boumaila C, Fiedler F, Trieu-Cuot P.; 2001 Nov 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=100127

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Streptococcus

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Regulation of Expression of the Fructan Hydrolase Gene of Streptococcus mutans GS5 by Induction and Carbon Catabolite Repression. by Burne RA, Wen ZT, Chen YY, Penders JE.; 1999 May 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=93730

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Relatedness of Streptococcus suis Isolates of Various Serotypes and Clinical Backgrounds as Evaluated by Macrorestriction Analysis and Expression of Potential Virulence Traits. by Allgaier A, Goethe R, Wisselink HJ, Smith HE, Valentin-Weigand P.; 2001 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=87757

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Relatedness of Streptococcus suis Serotype 2 Isolates from Different Geographic Origins as Evaluated by Molecular Fingerprinting and Phenotyping. by Chatellier S, Gottschalk M, Higgins R, Brousseau R, Harel J.; 1999 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=84308

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Relationship between Cell Surface Carbohydrates and Intrastrain Variation on Opsonophagocytosis of Streptococcus pneumoniae. by Kim JO, Romero-Steiner S, Sorensen UB, Blom J, Carvalho M, Barnard S, Carlone G, Weiser JN.; 1999 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=115974

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Relative contributions of hyaluronic acid capsule and M protein to virulence in a mucoid strain of the group A Streptococcus. by Moses AE, Wessels MR, Zalcman K, Alberti S, Natanson-Yaron S, Menes T, Hanski E.; 1997 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=174557

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Relative Roles of Genetic Background and Variation in PspA in the Ability of Antibodies to PspA To Protect against Capsular Type 3 and 4 Strains of Streptococcus pneumoniae. by Roche H, Ren B, McDaniel LS, Hakansson A, Briles DE.; 2003 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=166025

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Replacement of Histidine 340 with Alanine Inactivates the Group A Streptococcus Extracellular Cysteine Protease Virulence Factor. by Gubba S, Cipriano V, Musser JM.; 2000 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=97664

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Restriction fragment length polymorphism analysis of 16S ribosomal DNA of Streptococcus and Enterococcus species of bovine origin. by Jayarao BM, Dore JJ Jr, Oliver SP.; 1992 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=265485

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Rheumatic fever --associated Streptococcus pyogenes isolates aggregate collagen. by Dinkla K, Rohde M, Jansen WT, Kaplan EL, Chhatwal GS, Talay SR.; 2003 Jun 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=161421

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Role of CsrR, Hyaluronic Acid, and SpeB in the Internalization of Streptococcus pyogenes M Type 3 Strain by Epithelial Cells. by Jadoun J, Eyal O, Sela S.; 2002 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=127687

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Role of C-Terminal Domains in Surface Attachment of the Fructosyltransferase of Streptococcus salivarius ATCC 25975. by Rathsam C, Jacques NA.; 1998 Dec 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=107731

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Role of Manganese-Containing Superoxide Dismutase in Oxidative Stress and Virulence of Streptococcus pneumoniae. by Yesilkaya H, Kadioglu A, Gingles N, Alexander JE, Mitchell TJ, Andrew PW.; 2000 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=97493

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Role of Novel Choline Binding Proteins in Virulence of Streptococcus pneumoniae. by Gosink KK, Mann ER, Guglielmo C, Tuomanen EI, Masure HR.; 2000 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=101524

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Role of RegM, a Homologue of the Catabolite Repressor Protein CcpA, in the Virulence of Streptococcus pneumoniae. by Giammarinaro P, Paton JC.; 2002 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=128313

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Role of RopB in Growth Phase Expression of the SpeB Cysteine Protease of Streptococcus pyogenes. by Neely MN, Lyon WR, Runft DL, Caparon M.; 2003 Sep 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=181010

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Role of Streptococcus gordonii Amylase-Binding Protein A in Adhesion to Hydroxyapatite, Starch Metabolism, and Biofilm Formation. by Rogers JD, Palmer RJ Jr, Kolenbrander PE, Scannapieco FA.; 2001 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=100085

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Role of the dpr Product in Oxygen Tolerance in Streptococcus mutans. by Yamamoto Y, Higuchi M, Poole LB, Kamio Y.; 2000 Jul 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=94545

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Roles of Sortase in Surface Expression of the Major Protein Adhesin P1, SalivaInduced Aggregation and Adherence, and Cariogenicity of Streptococcus mutans. by Lee SF, Boran TL.; 2003 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=145395

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Selection of Recombinant Antibodies Specific for Pathogenic Streptococcus suis by Subtractive Phage Display. by de Greeff A, van Alphen L, Smith HE.; 2000 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=101672

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Selection of Virulence-Associated Determinants of Streptococcus suis Serotype 2 by In Vivo Complementation. by Smith HE, Buijs H, Wisselink HJ, Stockhofe-Zurwieden N, Smits MA.; 2001 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98113

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Self-Protection against Cell Wall Hydrolysis in Streptococcus milleri NMSCC 061 and Analysis of the Millericin B Operon. by Beukes M, Hastings JW.; 2001 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=93106

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Sensitive and Specific Method for Rapid Identification of Streptococcus pneumoniae Using Real-Time Fluorescence PCR. by McAvin JC, Reilly PA, Roudabush RM, Barnes WJ, Salmen A, Jackson GW, Beninga KK, Astorga A, McCleskey FK, Huff WB, Niemeyer D, Lohman KL.; 2001 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=88370

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Serotype Distribution and Antimicrobial Resistance of Streptococcus pneumoniae Isolated in Algiers, Algeria. by Ramdani-Bouguessa N, Rahal K.; 2003 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=151779

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Serotype Distribution and Antimicrobial Resistance of Streptococcus pneumoniae Isolates from Pediatric Patients in Singapore. by Soh SW, Poh CL, Lin RV.; 2000 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=90039

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Streptococcus

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Serum Opacity Factor (SOF) of Streptococcus pyogenes Evokes Antibodies That Opsonize Homologous and Heterologous SOF-Positive Serotypes of Group A Streptococci. by Courtney HS, Hasty DL, Dale JB.; 2003 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=187301

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SFS, a Novel Fibronectin-Binding Protein from Streptococcus equi, Inhibits the Binding between Fibronectin and Collagen. by Lindmark H, Guss B.; 1999 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=115982

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Strains of Streptococcus pyogenes from Severe Invasive Infections Bind HEp2 and HaCaT Cells More Avidly than Strains from Uncomplicated Infections. by Edwards ML, Fagan PK, Smith-Vaughan H, Currie BJ, Sriprakash KS.; 2003 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=179824

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Streptococcus gordonii Biofilm Formation: Identification of Genes that Code for Biofilm Phenotypes. by Loo CY, Corliss DA, Ganeshkumar N.; 2000 Mar 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=94426

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Streptococcus gordonii Strains Resistant to Fluorodeoxyuridine Contain Mutations in the Thymidine Kinase Gene and Are Deficient in Thymidine Kinase Activity. by Franke CA, Bolman TM, Ottum SA, Jones KF, Hruby DE.; 2000 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89769

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Streptococcus iniae, a Human and Animal Pathogen: Specific Identification by the Chaperonin 60 Gene Identification Method. by Goh SH, Driedger D, Gillett S, Low DE, Hemmingsen SM, Amos M, Chan D, Lovgren M, Willey BM, Shaw C, Smith JA.; 1998 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105023

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Streptococcus parasanguis pepO Encodes an Endopeptidase with Structure and Activity Similar to Those of Enzymes That Modulate Peptide Receptor Signaling in Eukaryotic Cells. by Froeliger EH, Oetjen J, Bond JP, Fives-Taylor P.; 1999 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=96872

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Streptococcus pneumoniae and Streptococcus pyogenes resistant to macrolides but sensitive to clindamycin: a common resistance pattern mediated by an efflux system. by Sutcliffe J, Tait-Kamradt A, Wondrack L.; 1996 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=163423

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Streptococcus pneumoniae Capsule Biosynthesis Protein CpsB Is a Novel Manganese-Dependent Phosphotyrosine-Protein Phosphatase. by Morona JK, Morona R, Miller DC, Paton JC.; 2002 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=139577

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Streptococcus pneumoniae PstS Production Is Phosphate Responsive and Enhanced during Growth in the Murine Peritoneal Cavity. by Orihuela CJ, Mills J, Robb CW, Wilson CJ, Watson DA, Niesel DW.; 2001 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98848

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Streptococcus salivarius Fimbriae Are Composed of a Glycoprotein Containing a Repeated Motif Assembled into a Filamentous Nondissociable Structure. by Levesque C, Vadeboncoeur C, Chandad F, Frenette M.; 2001 May 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=99487

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Streptococcus sinensis sp. nov., a Novel Species Isolated from a Patient with Infective Endocarditis. by Woo PC, Tam DM, Leung KW, Lau SK, Teng JL, Wong MK, Yuen KY.; 2002 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=120286

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Streptococcus suis Interactions with the Murine Macrophage Cell Line J774: Adhesion and Cytotoxicity. by Segura M, Gottschalk M.; 2002 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=128179

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Streptococcus-Escherichia coli shuttle vector pSA3 and its use in the cloning of streptococcal genes. by Dao ML, Ferretti JJ.; 1985 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=238354

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Streptococcus-Zebrafish Model of Bacterial Pathogenesis. by Neely MN, Pfeifer JD, Caparon M.; 2002 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=128100

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Structural Heterogeneity of the Streptococcal C5a Peptidase Gene in Streptococcus pyogenes. by Koroleva IV, Efstratiou A, Suvorov AN.; 2002 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=151962

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Surveillance of Invasive Streptococcus pneumoniae Infection in the Province of Quebec, Canada, from 1996 to 1998: Serotype Distribution, Antimicrobial Susceptibility, and Clinical Characteristics. by Jette LP, Delage G, Ringuette L, Allard R, De Wals P, Lamothe F, Loo V.; 2001 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=87807

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Survey of emm Gene Sequences from Pharyngeal Streptococcus pyogenes Isolates Collected in Spain and Their Relationship with Erythromycin Susceptibility. by Alberti S, Garcia-Rey C, Dominguez MA, Aguilar L, Cercenado E, Gobernado M, Garcia-Perea A.; 2003 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=156550

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Survey of Susceptibilities of Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis Isolates to 26 Antimicrobial Agents: a Prospective U.S. Study. by Thornsberry C, Ogilvie PT, Holley HP Jr, Sahm DF.; 1999 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89533

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Susceptibilities of Oral and Nasal Isolates of Streptococcus mitis and Streptococcus oralis to Macrolides and PCR Detection of Resistance Genes. by Ono T, Shiota S, Hirota K, Nemoto K, Tsuchiya T, Miyake Y.; 2000 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=89818

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Susceptibility to Telithromycin in 1,011 Streptococcus pyogenes Isolates from 10 Central and Eastern European Countries. by Nagai K, Appelbaum PC, Davies TA, Kelly LM, Hoellman DB, Andrasevic AT, Drukalska L, Hryniewicz W, Jacobs MR, Kolman J, Miciuleviciene J, Pana M, Setchanova L, Thege MK, Hupkova H, Trupl J, Urbaskova P.; 2002 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=127072

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Tandem Repeat Deletion in the Alpha C Protein of Group B Streptococcus Is recA Independent. by Puopolo KM, Hollingshead SK, Carey VJ, Madoff LC.; 2001 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98598

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The Autolytic Enzyme LytA of Streptococcus pneumoniae Is Not Responsible for Releasing Pneumolysin. by Balachandran P, Hollingshead SK, Paton JC, Briles DE.; 2001 May 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=95211

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The cps Genes of Streptococcus suis Serotypes 1, 2, and 9: Development of Rapid Serotype-Specific PCR Assays. by Smith HE, Veenbergen V, van der Velde J, Damman M, Wisselink HJ, Smits MA.; 1999 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=85514

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The CsrR /CsrS two-component system of group A Streptococcus responds to environmental Mg2 +. by Gryllos I, Levin JC, Wessels MR.; 2003 Apr 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=153075

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The Divergently Transcribed Streptococcus parasanguis Virulence-Associated fimA Operon Encoding an Mn2 +-Responsive Metal Transporter and pepO Encoding a Zinc Metallopeptidase Are Not Coordinately Regulated. by Oetjen J, Fives-Taylor P, Froeliger EH.; 2002 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=128308

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The In Vitro Interaction of Streptococcus pyogenes with Human Pharyngeal Cells Induces a Phage-Encoded Extracellular DNase. by Broudy TB, Pancholi V, Fischetti VA.; 2002 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=127989

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The Macrolide Efflux Genetic Assembly of Streptococcus pneumoniae Is Present in Erythromycin-Resistant Streptococcus salivarius. by Stadler C, Teuber M.; 2002 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=128751

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The pspC Gene of Streptococcus pneumoniae Encodes a Polymorphic Protein, PspC, Which Elicits Cross-Reactive Antibodies to PspA and Provides Immunity to Pneumococcal Bacteremia. by Brooks-Walter A, Briles DE, Hollingshead SK.; 1999 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=97064

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The Putative Proteinase Maturation Protein A of Streptococcus pneumoniae Is a Conserved Surface Protein with Potential To Elicit Protective Immune Responses. by Overweg K, Kerr A, Sluijter M, Jackson MH, Mitchell TJ, de Jong AP, de Groot R, Hermans PW.; 2000 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=101721

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The Regulator PerR Is Involved in Oxidative Stress Response and Iron Homeostasis and Is Necessary for Full Virulence of Streptococcus pyogenes. by Ricci S, Janulczyk R, Bjorck L.; 2002 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=128242

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The Specific Genes for Lantibiotic Mutacin II Biosynthesis in Streptococcus mutans T8 Are Clustered and Can Be Transferred En Bloc. by Chen P, Qi F, Novak J, Caufield PW.; 1999 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=91190

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The Streptococcus pneumoniae cia Regulon: CiaR Target Sites and Transcription Profile Analysis. by Mascher T, Zahner D, Merai M, Balmelle N, de Saizieu AB, Hakenbeck R.; 2003 Jan 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=141814

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The Streptococcus thermophilus Autolytic Phenotype Results from a Leaky Prophage. by Husson-Kao C, Mengaud J, Cesselin B, van Sinderen D, Benbadis L, Chapot-Chartier MP.; 2000 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=91863

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The Stress-Responsive dgk Gene from Streptococcus mutans Encodes a Putative Undecaprenol Kinase Activity. by Lis M, Kuramitsu HK.; 2003 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=152025

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The Three Major Spanish Clones of Penicillin-Resistant Streptococcus pneumoniae Are the Most Common Clones Recovered in Recent Cases of Meningitis in Spain. by Enright MC, Fenoll A, Griffiths D, Spratt BG.; 1999 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=85530

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Transcriptional Regulation and Signature Patterns Revealed by Microarray Analyses of Streptococcus pneumoniae R6 Challenged with Sublethal Concentrations of Translation Inhibitors. by Ng WL, Kazmierczak KM, Robertson GT, Gilmour R, Winkler ME.; 2003 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=141824

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Transcriptional Regulation in the Streptococcus pneumoniae rlrA Pathogenicity Islet by RlrA. by Hava DL, Hemsley CJ, Camilli A.; 2003 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=145342

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Transferability of macrolide, lincomycin, and streptogramin resistances between group A, B, and D streptococci, Streptococcus pneumoniae, and Staphylococcus aureus. by Engel HW, Soedirman N, Rost JA, van Leeuwen WJ, van Embden JD.; 1980 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=293990

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Transient Association of an Alternative Sigma Factor, ComX, with RNA Polymerase during the Period of Competence for Genetic Transformation in Streptococcus pneumoniae. by Luo P, Morrison DA.; 2003 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=141820

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Use of a Whole Genome Approach To Identify Vaccine Molecules Affording Protection against Streptococcus pneumoniae Infection. by Wizemann TM, Heinrichs JH, Adamou JE, Erwin AL, Kunsch C, Choi GH, Barash SC, Rosen CA, Masure HR, Tuomanen E, Gayle A, Brewah YA, Walsh W, Barren P, Lathigra R, Hanson M, Langermann S, Johnson S, Koenig S.; 2001 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98061

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Use of Clindamycin Disks To Detect Macrolide Resistance Mediated by ermB and mefE in Streptococcus pneumoniae Isolates from Adults and Children. by Waites K, Johnson C, Gray B, Edwards K, Crain M, Benjamin W Jr.; 2000 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=86572

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Use of Highly Encapsulated Streptococcus pneumoniae Strains in a Flow-Cytometric Assay for Assessment of the Phagocytic Capacity of Serotype-Specific Antibodies. by Jansen WT, Gootjes J, Zelle M, Madore DV, Verhoef J, Snippe H, Verheul AF.; 1998 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=95643

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Use of Ribotyping and Hemolysin Activity To Identify Highly Virulent Streptococcus suis Type 2 Isolates. by Staats JJ, Plattner BL, Nietfeld J, Dritz S, Chengappa MM.; 1998 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=124799

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uvrA Is an Acid-Inducible Gene Involved in the Adaptive Response to Low pH in Streptococcus mutans. by Hanna MN, Ferguson RJ, Li YH, Cvitkovitch DG.; 2001 Oct 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=99675

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Variable Sensitivity to Bacterial Methionyl-tRNA Synthetase Inhibitors Reveals Subpopulations of Streptococcus pneumoniae with Two Distinct Methionyl-tRNA Synthetase Genes. by Gentry DR, Ingraham KA, Stanhope MJ, Rittenhouse S, Jarvest RL, O'Hanlon PJ, Brown JR, Holmes DJ.; 2003 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=155832

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Viridans Group Streptococci Are Donors in Horizontal Transfer of Topoisomerase IV Genes to Streptococcus pneumoniae. by Balsalobre L, Ferrandiz MJ, Linares J, Tubau F, de la Campa AG.; 2003 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=161831

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ZmpB, a Novel Virulence Factor of Streptococcus pneumoniae That Induces Tumor Necrosis Factor Alpha Production in the Respiratory Tract. by Blue CE, Paterson GK, Kerr AR, Berge M, Claverys JP, Mitchell TJ.; 2003 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=187332

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 streptococcus, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “streptococcus” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for streptococcus (hyperlinks lead to article summaries): •

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A case of septicaemia, meningitis and pneumonia caused by Streptococcus bovis type II. Author(s): Namiduru M, Karaoglan I, Aktaran S, Dikensoy O, Baydar I. Source: Int J Clin Pract. 2003 October; 57(8): 735-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14627189

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.

Studies

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A common clone of erythromycin-resistant Streptococcus pneumoniae in Greece and the UK. Author(s): Fotopoulou N, Tassios PT, Beste DV, Ioannidou S, Efstratiou A, Lawrence ER, Papaparaskevas J, George RC, Legakis NJ. Source: Clinical Microbiology and Infection : the Official Publication of the European Society of Clinical Microbiology and Infectious Diseases. 2003 September; 9(9): 924-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14616680

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A fresh look at the definition of susceptibility of Streptococcus pneumoniae to betalactam antibiotics. Author(s): Musher DM, Bartlett JG, Doern GV. Source: Archives of Internal Medicine. 2001 November 26; 161(21): 2538-44. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11718584

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A highly sensitive immuno-PCR assay for detecting Group A Streptococcus. Author(s): Liang H, Cordova SE, Kieft TL, Rogelj S. Source: Journal of Immunological Methods. 2003 August; 279(1-2): 101-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12969551

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A quantitative LightCycler PCR to detect Streptococcus pneumoniae in blood and CSF. Author(s): van Haeften R, Palladino S, Kay I, Keil T, Heath C, Waterer GW. Source: Diagnostic Microbiology and Infectious Disease. 2003 October; 47(2): 407-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14522514

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Acquisition of host plasmin activity by the Swine pathogen Streptococcus suis serotype 2. Author(s): Jobin MC, Brassard J, Quessy S, Gottschalk M, Grenier D. Source: Infection and Immunity. 2004 January; 72(1): 606-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14688145

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Activities of a new oral streptogramin, XRP 2868, compared to those of other agents against Streptococcus pneumoniae and haemophilus species. Author(s): Pankuch GA, Kelly LM, Lin G, Bryskier A, Couturier C, Jacobs MR, Appelbaum PC. Source: Antimicrobial Agents and Chemotherapy. 2003 October; 47(10): 3270-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14506040

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Activities of cethromycin and telithromycin against recent North American isolates of Streptococcus pneumoniae. Author(s): Jorgensen JH, Crawford SA, McElmeel ML, Whitney CG. Source: Antimicrobial Agents and Chemotherapy. 2004 February; 48(2): 605-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14742216

96

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Activity of gemifloxacin against Streptococcus pneumoniae and Haemophilus influenzae. Author(s): Morrissey I, Tillotson G. Source: The Journal of Antimicrobial Chemotherapy. 2004 February; 53(2): 144-8. Epub 2004 January 16. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14729748

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Aggregated antibiograms and monitoring of drug-resistant Streptococcus pneumoniae. Author(s): Van Beneden CA, Lexau C, Baughman W, Barnes B, Bennett N, Cassidy PM, Pass M, Gelling L, Barrett NL, Zell ER, Whitney CG. Source: Emerging Infectious Diseases. 2003 September; 9(9): 1089-95. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14519245

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Alleles carried at positions -819 and -592 of the IL10 promoter affect transcription following stimulation of peripheral blood cells with Streptococcus pneumoniae. Author(s): Temple SE, Lim E, Cheong KY, Almeida CA, Price P, Ardlie KG, Waterer GW. Source: Immunogenetics. 2003 December; 55(9): 629-32. Epub 2003 November 06. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14605776

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An accessory sec locus of Streptococcus gordonii is required for export of the surface protein GspB and for normal levels of binding to human platelets. Author(s): Bensing BA, Sullam PM. Source: Molecular Microbiology. 2002 May; 44(4): 1081-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12010500

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An essential amino acid residue for catalytic activity of the dextranase of Streptococcus mutans. Author(s): Igarashi T, Morisaki H, Yamamoto A, Goto N. Source: Oral Microbiology and Immunology. 2002 June; 17(3): 193-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12030973

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Analysis of a viridans group strain reveals a case of bacteremia due to lancefield group G alpha-hemolytic Streptococcus dysgalactiae subsp equisimilis in a patient with pyomyositis and reactive arthritis. Author(s): Woo PC, Teng JL, Lau SK, Lum PN, Leung KW, Wong KL, Li KW, Lam KC, Yuen KY. Source: Journal of Clinical Microbiology. 2003 February; 41(2): 613-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12574255

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97

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Antenatal screening and intrapartum management of Group B Streptococcus in the UK. Author(s): Kenyon S, Brocklehurst P, Blackburn A, Taylor DJ. Source: Bjog : an International Journal of Obstetrics and Gynaecology. 2004 March; 111(3): 226-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14961883

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Antibiotic-resistant invasive pediatric Streptococcus pneumoniae clones in Israel. Author(s): Greenberg D, Dagan R, Muallem M, Porat N. Source: Journal of Clinical Microbiology. 2003 December; 41(12): 5541-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14662937

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Antibiotic-resistant Streptococcus pneumoniae in the heptavalent pneumococcal conjugate vaccine era: predictors of carriage in a multicommunity sample. Author(s): Finkelstein JA, Huang SS, Daniel J, Rifas-Shiman SL, Kleinman K, Goldmann D, Pelton SI, DeMaria A, Platt R. Source: Pediatrics. 2003 October; 112(4): 862-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14523178

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Array of M protein gene subtypes in 1064 recent invasive group A streptococcus isolates recovered from the active bacterial core surveillance. Author(s): Li Z, Sakota V, Jackson D, Franklin AR, Beall B; Active Bacterial Core Surveillance/Emerging Infections Program Network. Source: The Journal of Infectious Diseases. 2003 November 15; 188(10): 1587-92. Epub 2003 Nov 10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14624386

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Assessment of Streptococcus pyogenes microcolony formation in infected skin by confocal laser scanning microscopy. Author(s): Akiyama H, Morizane S, Yamasaki O, Oono T, Iwatsuki K. Source: Journal of Dermatological Science. 2003 September; 32(3): 193-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14507444

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Autolysin-targeted LightCycler assay including internal process control for detection of Streptococcus pneumoniae DNA in clinical samples. Author(s): Sheppard CL, Harrison TG, Morris R, Hogan A, George RC. Source: Journal of Medical Microbiology. 2004 March; 53(Pt 3): 189-95. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14970243

98

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Bacitracin-resistant clone of Streptococcus pyogenes isolated from pharyngitis patients in Belgium. Author(s): Malhotra-Kumar S, Wang S, Lammens C, Chapelle S, Goossens H. Source: Journal of Clinical Microbiology. 2003 November; 41(11): 5282-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14605184

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Bacteraemic Streptococcus pyogenes infection in the peri-partum period: now a rare disease and prior carriage by the patient may be important. Author(s): Barnham MR, Weightman NC. Source: The Journal of Infection. 2001 October; 43(3): 173-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11798254

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Bacteremia and meningitis caused by a macrolide-sensitive strain of Streptococcus pneumoniae during treatment with azithromycin. Author(s): Lisby G, Brasholt MS, Teglbjerg MS. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2001 August 1; 33(3): 415-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11438918

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Bacteremia due to beta-hemolytic Streptococcus group G: increasing incidence and clinical characteristics of patients. Author(s): Sylvetsky N, Raveh D, Schlesinger Y, Rudensky B, Yinnon AM. Source: The American Journal of Medicine. 2002 June 1; 112(8): 622-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12034411

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Bacteremia with group A Streptococcus associated with herpetic gingivostomatitis. Author(s): Amir J, Nussinovitch M, Straussberg R, Harel L. Source: The Pediatric Infectious Disease Journal. 2001 September; 20(9): 916-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11734779

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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 effect of delmopinol on attached and planktonic Streptococcus sanguinis cells. Author(s): Burgemeister S, Decker EM, Weiger R, Brecx M. Source: European Journal of Oral Sciences. 2001 December; 109(6): 425-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11767281

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99

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Bacteriological diagnosis of Streptococcus suis meningitis. Author(s): Durand F, Perino CL, Recule C, Brion JP, Kobish M, Guerber F, Croize J. Source: European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology. 2001 July; 20(7): 519-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11561816

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Beta-lactam resistance in Streptococcus mitis isolated from saliva of healthy subjects. Author(s): Nakayama A, Takao A. Source: Journal of Infection and Chemotherapy : Official Journal of the Japan Society of Chemotherapy. 2003 December; 9(4): 321-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14691653

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beta-Lactamase-producing Moraxella catarrhalis may prevent the emergence of penicillin-resistant Streptococcus pneumoniae in children with recurrent acute otitis media. Author(s): Joki-Erkkila VP, Aittoniemi J, Vuento R, Puhakka H. Source: International Journal of Pediatric Otorhinolaryngology. 2002 May 15; 63(3): 21922. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11997157

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Bilateral basal ganglia infarctions in a patient with Streptococcus pneumoniae meningitis. Author(s): Johkura K, Nishiyama T, Kuroiwa Y. Source: European Neurology. 2002; 48(2): 123-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12187007

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Bilateral cavernous sinus thromboses and intraorbital abscesses secondary to Streptococcus milleri. Author(s): Watkins LM, Pasternack MS, Banks M, Kousoubris P, Rubin PA. Source: Ophthalmology. 2003 March; 110(3): 569-74. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12623823

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Binding and agglutination of Streptococcus pneumoniae by human surfactant protein D (SP-D) vary between strains, but SP-D fails to enhance killing by neutrophils. Author(s): Jounblat R, Kadioglu A, Iannelli F, Pozzi G, Eggleton P, Andrew PW. Source: Infection and Immunity. 2004 February; 72(2): 709-16. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14742512

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Binding and invasion of HeLa and MRC-5 cells by Streptococcus agalactiae. Author(s): Tyrrell GJ, Kennedy A, Shokoples SE, Sherburne RK. Source: Microbiology (Reading, England). 2002 December; 148(Pt 12): 3921-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12480896

100

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Binding of a peptide from a Streptococcus dysgalactiae MSCRAMM to the Nterminal F1 module pair of human fibronectin involves both modules. Author(s): Schwarz-Linek U, Plevin MJ, Pickford AR, Hook M, Campbell ID, Potts JR. Source: Febs Letters. 2001 May 25; 497(2-3): 137-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11377428

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Binding of human C4BP to the hypervariable region of M protein: a molecular mechanism of phagocytosis resistance in Streptococcus pyogenes. Author(s): Berggard K, Johnsson E, Morfeldt E, Persson J, Stalhammar-Carlemalm M, Lindahl G. Source: Molecular Microbiology. 2001 October; 42(2): 539-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11703674

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Biochemical and functional properties of a pyruvate formate-lyase (PFL)-activating system in Streptococcus mutans. Author(s): Takahashi-Abbe S, Abe K, Takahashi N. Source: Oral Microbiology and Immunology. 2003 October; 18(5): 293-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12930520

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Both family 1 and family 2 PspA proteins can inhibit complement deposition and confer virulence to a capsular serotype 3 strain of Streptococcus pneumoniae. Author(s): Ren B, Szalai AJ, Thomas O, Hollingshead SK, Briles DE. Source: Infection and Immunity. 2003 January; 71(1): 75-85. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12496151

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Brain abscess due to Capnocytophaga species, Actinomyces species, and Streptococcus intermedius in a patient with cyanotic congenital heart disease. Author(s): Engelhardt K, Kampfl A, Spiegel M, Pfausler B, Hausdorfer H, Schmutzhard E. Source: European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology. 2002 March; 21(3): 236-7. Epub 2002 March 19. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11957031

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Brain abscess due to Streptococcus sanguis. Author(s): Dhawan B, Lyngdoh V, Mehta VS, Chaudhry R. Source: Neurology India. 2003 March; 51(1): 131-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12865554

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Carcinoma of the colon presenting as Streptococcus salivarius sepsis. Author(s): Afek S, Sperber AD, Almog Y. Source: Journal of Clinical Gastroenterology. 2004 January; 38(1): 86-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14679337

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Cell wall proteins of group B Streptococcus and low incidence of neonatal disease in southern Israel. Author(s): Marchaim D, Hallak M, Gortzak-Uzan L, Peled N, Riesenberg K, Schlaeffer F. Source: J Reprod Med. 2003 September; 48(9): 697-702. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14562634

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Central myonecrosis in a patient with group a beta-hemolytic streptococcus toxic shock syndrome. Author(s): Nichol P, Rod R, Corliss RF, Schurr M. Source: The Journal of Trauma. 2003 November; 55(5): 994-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14608183

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Changes in antibiotic-prescribing practices and carriage of penicillin-resistant Streptococcus pneumoniae: A controlled intervention trial in rural Alaska. Author(s): Hennessy TW, Petersen KM, Bruden D, Parkinson AJ, Hurlburt D, Getty M, Schwartz B, Butler JC. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2002 June 15; 34(12): 1543-50. Epub 2002 May 21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12032887

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Changes in enamel surface roughness and adhesion of Streptococcus mutans to enamel after vital bleaching. Author(s): Hosoya N, Honda K, Iino F, Arai T. Source: Journal of Dentistry. 2003 November; 31(8): 543-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14554071

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Characterization of an extracellular virulence factor made by group A Streptococcus with homology to the Listeria monocytogenes internalin family of proteins. Author(s): Reid SD, Montgomery AG, Voyich JM, DeLeo FR, Lei B, Ireland RM, Green NM, Liu M, Lukomski S, Musser JM. Source: Infection and Immunity. 2003 December; 71(12): 7043-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14638794

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Clarithromycin mediated the expression of polymorphonuclear granulocyte response against streptococcus pneumoniae strains with different patterns of susceptibility and resistance to penicillin and clarithromycin. Author(s): Cuffini AM, Tullio V, Mandras N, Roana J, Scalas D, Banche G, Carlone NA. Source: Int J Tissue React. 2002; 24(1): 37-44. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12013153

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Clinical manifestations and molecular epidemiology of necrotizing pneumonia and empyema caused by Streptococcus pneumoniae in children in Taiwan. Author(s): Hsieh YC, Hsueh PR, Lu CY, Lee PI, Lee CY, Huang LM. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2004 March 15; 38(6): 830-5. Epub 2004 February 27. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14999627

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Clinical profile of Streptococcus agalactiae native valve endocarditis. Author(s): Rollan MJ, San Roman JA, Vilacosta I, Sarria C, Lopez J, Acuna M, Bratos JL. Source: American Heart Journal. 2003 December; 146(6): 1095-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14661005

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Clinical significance of Streptococcus pneumoniae resistance reporting remains confusing. Author(s): Siegel RE. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2004 March 1; 38(5): 764-5; Author Reply 765-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14986267

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Clonal analysis of Streptococcus pneumoniae nonsusceptible to penicillin at day-care centers with index cases, in a region with low incidence of resistance: emergence of an invasive type 35B clone among carriers. Author(s): Henriqus Normark B, Christensson B, Sandgren A, Noreen B, Sylvan S, Burman LG, Olsson-Liljequist B. Source: Microbial Drug Resistance (Larchmont, N.Y.). 2003 Winter; 9(4): 337-44. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15008138

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Cloning and expression of hyaluronate lyase genes of Streptococcus intermedius and Streptococcus constellatus subsp. constellatus(1). Author(s): Takao A. Source: Fems Microbiology Letters. 2003 February 14; 219(1): 143-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12594036

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Colonization of Streptococcus mutans and Streptococcus sobrinus genotypes and caries development in children to mothers harboring both species. Author(s): Lindquist B, Emilson CG. Source: Caries Research. 2004 March-April; 38(2): 95-103. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14767165

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103

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Comparison of different techniques of quantitative PCR for determination of Streptococcus mutans counts in saliva samples. Author(s): Rupf S, Merte K, Kneist S, Al-Robaiy S, Eschrich K. Source: Oral Microbiology and Immunology. 2003 February; 18(1): 50-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12588459

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Comparison of five selective media for the growth and enumeration of Streptococcus mutans. Author(s): Wan AK, Seow WK, Walsh LJ, Bird PS. Source: Aust Dent J. 2002 March; 47(1): 21-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12035953

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Comparison of the Denka Seiken slide agglutination method to the quellung test for serogrouping of Streptococcus pneumoniae isolates. Author(s): Shutt CK, Samore M, Carroll KC. Source: Journal of Clinical Microbiology. 2004 March; 42(3): 1274-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15004092

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Constitutive expression of PcsB suppresses the requirement for the essential VicR (YycF) response regulator in Streptococcus pneumoniae R6. Author(s): Ng WL, Robertson GT, Kazmierczak KM, Zhao J, Gilmour R, Winkler ME. Source: Molecular Microbiology. 2003 December; 50(5): 1647-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14651645

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Contribution of glutathione peroxidase to the virulence of Streptococcus pyogenes. Author(s): Brenot A, King KY, Janowiak B, Griffith O, Caparon MG. Source: Infection and Immunity. 2004 January; 72(1): 408-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14688122

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Critical role of the complement system in group B streptococcus-induced tumor necrosis factor alpha release. Author(s): Levy O, Jean-Jacques RM, Cywes C, Sisson RB, Zarember KA, Godowski PJ, Christianson JL, Guttormsen HK, Carroll MC, Nicholson-Weller A, Wessels MR. Source: Infection and Immunity. 2003 November; 71(11): 6344-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14573654

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Current concepts in the pathogenesis of meningitis caused by Streptococcus pneumoniae. Author(s): Meli DN, Christen S, Leib SL, Tauber MG. Source: Current Opinion in Infectious Diseases. 2002 June; 15(3): 253-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12015459

104

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Decreased serum opsonic activity against Streptococcus pneumoniae in human immunodeficiency virus-infected Ugandan adults. Author(s): Takahashi H, Oishi K, Yoshimine H, Kumatori A, Moji K, Watanabe K, Nalwoga H, Tugume SB, Kebba A, Mugerwa R, Mugyenyi P, Nagatake T. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2003 December 1; 37(11): 1534-40. Epub 2003 November 06. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14614677

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Demineralization of dentin by Streptococcus mutans biofilms grown in the constant depth film fermentor. Author(s): Deng DM, ten Cate JM. Source: Caries Research. 2004 January-February; 38(1): 54-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14684978

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Demonstration of Streptococcus mutans with a cell wall polysaccharide specific to a new serotype, k, in the human oral cavity. Author(s): Nakano K, Nomura R, Nakagawa I, Hamada S, Ooshima T. Source: Journal of Clinical Microbiology. 2004 January; 42(1): 198-202. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14715753

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Detection of Group A beta-hemolytic Streptococcus employing three different detection methods: culture, rapid antigen detecting test, and molecular assay. Author(s): Santos O, Weckx LL, Pignatari AC, Pignatari SS. Source: The Brazilian Journal of Infectious Diseases : an Official Publication of the Brazilian Society of Infectious Diseases. 2003 October; 7(5): 297-300. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14552738

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Detection of penicillin-binding protein 2b gene alteration in Streptococcus mitis by polymerase chain reaction. Author(s): Usui H, Takao A, Nakayama A, Nagashima H, Sasaki F, Maeda N, Ishibashi K. Source: Journal of Infection and Chemotherapy : Official Journal of the Japan Society of Chemotherapy. 2004 February; 10(1): 19-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14991513

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Detection of Streptococcus anginosus and 8-hydroxydeoxyguanosine in saliva. Author(s): Sugano N, Yokoyama K, Oshikawa M, Kumagai K, Takane M, Tanaka H, Ito K. Source: J Oral Sci. 2003 December; 45(4): 181-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14763512

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105

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Detection of Streptococcus anginosus from saliva by real-time polymerase chain reaction. Author(s): Kumagai K, Sugano N, Takane M, Iwasaki H, Tanaka H, Yoshinuma N, Suzuki K, Ito K. Source: Letters in Applied Microbiology. 2003; 37(5): 370-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14633106

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Detection of tet(M), tet(O) and tet(S) in tetracycline/minocycline-resistant Streptococcus pyogenes bacteraemia isolates. Author(s): Hammerum AM, Nielsen HU, Agerso Y, Ekelund K, Frimodt-Moller N. Source: The Journal of Antimicrobial Chemotherapy. 2004 January; 53(1): 118-9. Epub 2003 December 04. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14657081

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Development of a diagnostic PCR assay targeting the Mn-dependent superoxide dismutase gene (sodA) for identification of Streptococcus gallolyticus. Author(s): Sasaki E, Osawa R, Nishitani Y, Whiley RA. Source: Journal of Clinical Microbiology. 2004 March; 42(3): 1360-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15004119

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Development of macrolide resistance by ribosomal protein L4 mutation in Streptococcus pyogenes during miocamycin treatment of an eight-year-old Greek child with tonsillopharyngitis. Author(s): Bozdogan B, Appelbaum PC, Ednie L, Grivea IN, Syrogiannopoulos GA. Source: Clinical Microbiology and Infection : the Official Publication of the European Society of Clinical Microbiology and Infectious Diseases. 2003 September; 9(9): 966-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14616688

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Diagnosis of invasive pneumococcal infection by PCR amplification of Streptococcus pneumoniae genomic fragments in blood: a multi-centre comparative study. Author(s): Sheppard CL, Harrison TG, Kearns AM, Guiver M, Creek M, Evans R, Smith MD, Eltringham G, Cartwright KA, George RC. Source: Commun Dis Public Health. 2003 September; 6(3): 221-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14708272

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Different polymerase chain reaction-based analyses for culture-negative endocarditis caused by Streptococcus pneumoniae. Author(s): Voldstedlund M, Pedersen LN, Fuursted K, Nielsen LP. Source: Scandinavian Journal of Infectious Diseases. 2003; 35(10): 757-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14606617

106

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Differentiation of Enterococcus faecium from Lactobacillus delbrueckii subsp. bulgaricus and Streptococcus thermophilus strains by PCR and dot-blot hybridisation. Author(s): Langa S, Fernandez A, Martin R, Reviriego C, Marin ML, Fernandez L, Rodriguez JM. Source: International Journal of Food Microbiology. 2003 December 1; 88(2-3): 197-200. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14596990

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Dissemination of emm28 erythromycin-, clindamycin- and bacitracin-resistant Streptococcus pyogenes in Spain. Author(s): Perez-Trallero E, Garcia C, Orden B, Marimon JM, Montes M. Source: European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology. 2004 February; 23(2): 1236. Epub 2004 January 08. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14712367

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Dissemination of macrolide-resistant Streptococcus pneumoniae isolates containing both erm(B) and mef(A) in South Korea. Author(s): Waites KB, Jones KE, Kim KH, Moser SA, Johnson CN, Hollingshead SK, Kang ES, Hong KS, Benjamin WH Jr. Source: Journal of Clinical Microbiology. 2003 December; 41(12): 5787-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14662984

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Distribution and characterization of hemolytic activity by an oral anaerobe from the Streptococcus milleri group. Author(s): Yamaguchi T, Koreeda H. Source: Oral Microbiology and Immunology. 2004 April; 19(2): 132-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14871356

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Drawbacks of antibiotic susceptibility of Streptococcus pneumoniae. Author(s): Pasticci MB, Baldelli F, Cardaccia A, Moretti A, Papili R, Stagni G. Source: Infez Med. 2003 December; 11(4): 213-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14988670

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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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107

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Dual infection with Streptococcus pneumoniae and Mycobacterium tuberculosis in HIV-seropositive patients with community acquired pneumonia. Author(s): Schleicher GK, Feldman C. Source: The International Journal of Tuberculosis and Lung Disease : the Official Journal of the International Union against Tuberculosis and Lung Disease. 2003 December; 7(12): 1207-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14677897

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Dynamics of Streptococcus agalactiae colonization in women during and after pregnancy and in their infants. Author(s): Hansen SM, Uldbjerg N, Kilian M, Sorensen UB. Source: Journal of Clinical Microbiology. 2004 January; 42(1): 83-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14715736

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Effect of clonal and serotype-specific properties on the invasive capacity of Streptococcus pneumoniae. Author(s): Sandgren A, Sjostrom K, Olsson-Liljequist B, Christensson B, Samuelsson A, Kronvall G, Henriques Normark B. Source: The Journal of Infectious Diseases. 2004 March 1; 189(5): 785-96. Epub 2004 February 16. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14976594

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Effect of new susceptibility breakpoints on reporting of resistance in Streptococcus pneumoniae--United States, 2003. Author(s): Centers for Disease Control and Prevention (CDC). Source: Mmwr. Morbidity and Mortality Weekly Report. 2004 February 27; 53(7): 152-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14985653

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Effect of the environment on genotypic diversity of Actinomyces naeslundii and Streptococcus oralis in the oral biofilm. Author(s): Paddick JS, Brailsford SR, Kidd EA, Gilbert SC, Clark DT, Alam S, Killick ZJ, Beighton D. Source: Applied and Environmental Microbiology. 2003 November; 69(11): 6475-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14602602

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Effects of RelA on key virulence properties of planktonic and biofilm populations of Streptococcus mutans. Author(s): Lemos JA, Brown TA Jr, Burne RA. Source: Infection and Immunity. 2004 March; 72(3): 1431-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14977948

108

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Effects of rhinovirus infection on the adherence of Streptococcus pneumoniae to cultured human airway epithelial cells. Author(s): Ishizuka S, Yamaya M, Suzuki T, Takahashi H, Ida S, Sasaki T, Inoue D, Sekizawa K, Nishimura H, Sasaki H. Source: The Journal of Infectious Diseases. 2003 December 15; 188(12): 1928-39. Epub 2003 Dec 03. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14673774

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Efficacy of extract of Pelargonium sidoides in children with acute non-group A betahemolytic streptococcus tonsillopharyngitis: a randomized, double-blind, placebocontrolled trial. Author(s): Bereznoy VV, Riley DS, Wassmer G, Heger M. Source: Alternative Therapies in Health and Medicine. 2003 September-October; 9(5): 6879. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14526713

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Efficacy of vancomycin plus levofloxacin combination therapy for refractory pericarditis due to multiresistant Streptococcus pneumoniae. Author(s): Safdar A. Source: International Journal of Infectious Diseases : Ijid : Official Publication of the International Society for Infectious Diseases. 2003 December; 7(4): 287. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14656421

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Embolic complications in streptococcus viridans endocarditis. Author(s): Mansi IA. Source: Journal of the American College of Cardiology. 2004 March 17; 43(6): 1133-4; Author Reply 1134. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15028385

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Emergence of fluoroquinolone-resistant Streptococcus pneumoniae in a South African child in a tuberculosis treatment facility. Author(s): von Gottberg A, Ludewick H, Bamber S, Govind C, Sturm AW, Klugman KP. Source: The Pediatric Infectious Disease Journal. 2003 November; 22(11): 1020-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14628774

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Emergence of high-level fluoroquinolone-resistant Streptococcus pneumoniae in Turkey. Author(s): Ak O O, Benzonana N, Ozer S, Eraksoy H. Source: International Journal of Infectious Diseases : Ijid : Official Publication of the International Society for Infectious Diseases. 2003 December; 7(4): 288-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14656422

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Emergence of penicillin-nonsusceptible Streptococcus pneumoniae invasive clones in Canada. Author(s): Greenberg D, Speert DP, Mahenthiralingam E, Henry DA, Campbell ME, Scheifele DW; CPS/LCDC IMPACT Monitoring Network. Source: Journal of Clinical Microbiology. 2002 January; 40(1): 68-74. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11773094

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Endogenous group G Streptococcus endophthalmitis following a dental procedure. Author(s): Ziakas NG, Tzetzi D, Boboridis K, Georgiadis NS. Source: Eur J Ophthalmol. 2004 January-February; 14(1): 59-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15005587

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Epidemiological and clinical features of group A Streptococcus pharyngitis in children. Author(s): Lin MH, Chang PF, Fong WK, Yen CW, Hung KL, Lin SJ. Source: Acta Paediatr Taiwan. 2003 September-October; 44(5): 274-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14964982

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Epidemiology of acute otitis media caused by Streptococcus pneumoniae before and after licensure of the 7-valent pneumococcal protein conjugate vaccine. Author(s): McEllistrem MC, Adams J, Mason EO, Wald ER. Source: The Journal of Infectious Diseases. 2003 December 1; 188(11): 1679-84. Epub 2003 November 10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14639539

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Epitope mapping of a protective monoclonal antibody against Pneumocystis carinii with shared reactivity to Streptococcus pneumoniae surface antigen PspA. Author(s): Wells J, Gigliotti F, Simpson-Haidaris PJ, Haidaris CG. Source: Infection and Immunity. 2004 March; 72(3): 1548-56. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14977961

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Erythromycin resistance in italian isolates of Streptococcus pyogenes and correlations with pulsed-field gel electrophoresis analysis. Author(s): Zampaloni C, Vitali LA, Prenna M, Toscano MA, Tempera G, Ripa S. Source: Microbial Drug Resistance (Larchmont, N.Y.). 2002 Spring; 8(1): 39-44. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12002648

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Evaluation of a new serotyping kit for Streptococcus pneumoniae. Author(s): Mudany MA, Kikuchi K, Totsuka K, Uchiyama T. Source: Journal of Medical Microbiology. 2003 November; 52(Pt 11): 975-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14532342

110

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Evaluation of PCR primers to screen for Streptococcus pneumoniae isolates and betalactam resistance, and to detect common macrolide resistance determinants. Author(s): Nagai K, Shibasaki Y, Hasegawa K, Davies TA, Jacobs MR, Ubukata K, Appelbaum PC. Source: The Journal of Antimicrobial Chemotherapy. 2001 December; 48(6): 915-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11733479

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Evaluation of semiautomated multiplex PCR assay for determination of Streptococcus pneumoniae serotypes and serogroups. Author(s): Lawrence ER, Griffiths DB, Martin SA, George RC, Hall LM. Source: Journal of Clinical Microbiology. 2003 February; 41(2): 601-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12574253

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Evolution of penicillin and erythromycin co-resistance in Streptococcus pneumoniae in Spain. Author(s): Garcia-Rey C, Bouza E, Aguilar L, Garcia-de-Lomas J, Baquero F; Spanish Surveillance Group for Respiratory Pathogens. Source: International Journal of Antimicrobial Agents. 2003 November; 22(5): 541-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14602376

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Factors associated with carriage of penicillin-resistant Streptococcus pneumoniae among Vietnamese children: a rural-urban divide. Author(s): Quagliarello AB, Parry CM, Hien TT, Farrar JJ. Source: J Health Popul Nutr. 2003 December; 21(4): 316-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15038586

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Factors associated with relative rates of antimicrobial resistance among Streptococcus pneumoniae in the United States: results from the TRUST Surveillance Program (1998-2002). Author(s): Karlowsky JA, Thornsberry C, Jones ME, Evangelista AT, Critchley IA, Sahm DF; TRUST Surveillance Program. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2003 April 15; 36(8): 963-70. Epub 2003 Apr 02. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12684907

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Failure of cefotaxime and meropenem to eradicate meningitis caused by an intermediately susceptible Streptococcus pneumoniae strain. Author(s): Vandecasteele SJ, Verhaegen J, Colaert J, Van Caster A, Devlieger H. Source: European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology. 2001 October; 20(10): 7512. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11757981

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Failure of macrolide antibiotic treatment in patients with bacteremia due to erythromycin-resistant Streptococcus pneumoniae. Author(s): Lonks JR, Garau J, Gomez L, Xercavins M, Ochoa de Echaguen A, Gareen IF, Reiss PT, Medeiros AA. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2002 September 1; 35(5): 556-64. Epub 2002 August 09. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12173129

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Fatal case of pneumonia caused by a nonhemolytic strain of Streptococcus pyogenes. Author(s): Taylor MB, Barkham T. Source: Journal of Clinical Microbiology. 2002 June; 40(6): 2311-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12037120

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Fatal necrotizing fasciitis due to Streptococcus pneumoniae after renal transplantation. Author(s): Imhof A, Maggiorini M, Zbinden R, Walter RB. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 2003 January; 18(1): 195-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12480983

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Fatal puerperal sepsis with necrotising fasciitis due to Streptococcus pneumoniae. Author(s): Clad A, Orlowska-Volk M, Karck U. Source: Bjog : an International Journal of Obstetrics and Gynaecology. 2003 February; 110(2): 213-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12618169

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Fate of Streptococcus pyogenes and epithelial cells following internalization. Author(s): Marouni MJ, Sela S. Source: Journal of Medical Microbiology. 2004 January; 53(Pt 1): 1-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14663098

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FcgammaRIIA polymorphisms in Streptococcus pneumoniae infection. Author(s): Yuan FF, Wong M, Pererva N, Keating J, Davis AR, Bryant JA, Sullivan JS. Source: Immunology and Cell Biology. 2003 June; 81(3): 192-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12752683

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Flow cytometric evaluation of adhesion of Streptococcus pyogenes to epithelial cells. Author(s): Sethman CR, Doyle RJ, Cowan MM. Source: Journal of Microbiological Methods. 2002 September; 51(1): 35-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12069888

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Fluoroquinolone resistance among clinical isolates of Streptococcus pneumoniae belonging to international multiresistant clones. Author(s): McGee L, Goldsmith CE, Klugman KP. Source: The Journal of Antimicrobial Chemotherapy. 2002 January; 49(1): 173-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11751784

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Fluoroquinolone resistance among Streptococcus pneumoniae in Hong Kong linked to the Spanish 23F clone. Author(s): Ho PL, Yam WC, Cheung TK, Ng WW, Que TL, Tsang DN, Ng TK, Seto WH. Source: Emerging Infectious Diseases. 2001 September-October; 7(5): 906-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11747711

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Fluoroquinolone resistance in Streptococcus pneumoniae in United States since 19941995. Author(s): Brueggemann AB, Coffman SL, Rhomberg P, Huynh H, Almer L, Nilius A, Flamm R, Doern GV. Source: Antimicrobial Agents and Chemotherapy. 2002 March; 46(3): 680-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11850248

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Fluoroquinolone-resistant Streptococcus pneumoniae in Spain: activities of garenoxacin against clinical isolates including strains with altered topoisomerases. Author(s): Morosini MI, Loza E, del Campo R, Almaraz F, Baquero F, Canton R. Source: Antimicrobial Agents and Chemotherapy. 2003 August; 47(8): 2692-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12878544

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Fluoroquinolone-resistant Streptococcus pneumoniae strains occur frequently in elderly patients in Japan. Author(s): Yokota S, Sato K, Kuwahara O, Habadera S, Tsukamoto N, Ohuchi H, Akizawa H, Himi T, Fujii N. Source: Antimicrobial Agents and Chemotherapy. 2002 October; 46(10): 3311-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12234869

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Formation of Streptococcus mutans biofilm following toothbrushing with regular and whitening toothpastes. Author(s): Steinberg D, Mor C, Dogan H, Kaufmann D, Rotstein I. Source: Am J Dent. 2003 February; 16(1): 58-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12744415

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Four antibiotic-resistant Streptococcus pneumoniae clones unrelated to the pneumococcal conjugate vaccine serotypes, including 2 new serotypes, causing acute otitis media in southern Israel. Author(s): Porat N, Barkai G, Jacobs MR, Trefler R, Dagan R. Source: The Journal of Infectious Diseases. 2004 February 1; 189(3): 385-92. Epub 2004 January 16. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14745695

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From ecological reservoir to disease: the nasopharynx, day-care centres and drugresistant clones of Streptococcus pneumoniae. Author(s): De Lencastre H, Tomasz A. Source: The Journal of Antimicrobial Chemotherapy. 2002 December; 50 Suppl S2: 75-81. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12556436

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Fulminant infection and toxic shock syndrome caused by Streptococcus pyogenes. Author(s): Fox KL, Born MW, Cohen MA. Source: The Journal of Emergency Medicine. 2002 May; 22(4): 357-66. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12113845

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Functional variation of the antigen I/II surface protein in Streptococcus mutans and Streptococcus intermedius. Author(s): Petersen FC, Assev S, van der Mei HC, Busscher HJ, Scheie AA. Source: Infection and Immunity. 2002 January; 70(1): 249-56. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11748190

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Genetic diversity of Streptococcus agalactiae strains colonizing the same pregnant woman. Author(s): Perez-Ruiz M, Rodriguez-Granger JM, Bautista-Marin MF, Romero-Noguera J, Rosa-Fraile M. Source: Epidemiology and Infection. 2004 April; 132(2): 375-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15061514

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Genetic relatedness, antibiotic susceptibility, and serotype distribution of Streptococcus pneumoniae responsible for meningitis in Poland, 1997-2001. Author(s): Skoczynska A, Hryniewicz W. Source: Microbial Drug Resistance (Larchmont, N.Y.). 2003 Summer; 9(2): 175-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12820803

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Genetic relationship between Streptococcus pneumoniae isolates from nasopharyngeal and cerebrospinal fluid of two infants with Pneumococcal Meningitis. Author(s): de Andrade AL, Pimenta FC, Brandileone MC, Laval CA, Guerra ML, de Andrade JG, Di Fabio JL. Source: Journal of Clinical Microbiology. 2003 August; 41(8): 3970-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12904432

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Genome-wide protective response used by group A Streptococcus to evade destruction by human polymorphonuclear leukocytes. Author(s): Voyich JM, Sturdevant DE, Braughton KR, Kobayashi SD, Lei B, Virtaneva K, Dorward DW, Musser JM, DeLeo FR. Source: Proceedings of the National Academy of Sciences of the United States of America. 2003 February 18; 100(4): 1996-2001. Epub 2003 Feb 06. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12574517

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Genomic location and variation of the gene for CRS, a complement binding protein in the M57 strains of Streptococcus pyogenes. Author(s): Binks M, McMillan D, Sriprakash KS. Source: Infection and Immunity. 2003 December; 71(12): 6701-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14638753

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Genotyping by amplified fragment length polymorphism analysis reveals persistence and recurrence of infection with Streptococcus anginosus group organisms. Author(s): Jacobs JA, Tjhie JH, Smeets MG, Schot CS, Schouls LM. Source: Journal of Clinical Microbiology. 2003 July; 41(7): 2862-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12843013

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Geographic distribution and clonal diversity of Streptococcus pneumoniae serotype 1 isolates. Author(s): Brueggemann AB, Spratt BG. Source: Journal of Clinical Microbiology. 2003 November; 41(11): 4966-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14605125

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Geographical difference of disease association in Streptococcus bovis bacteraemia. Author(s): Lee RA, Woo PC, To AP, Lau SK, Wong SS, Yuen KY. Source: Journal of Medical Microbiology. 2003 October; 52(Pt 10): 903-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12972586

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Glyceraldehyde-3-phosphate dehydrogenase of Streptococcus oralis functions as a coadhesin for Porphyromonas gingivalis major fimbriae. Author(s): Maeda K, Nagata H, Yamamoto Y, Tanaka M, Tanaka J, Minamino N, Shizukuishi S. Source: Infection and Immunity. 2004 March; 72(3): 1341-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14977937

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Granada agar sensitivity and detection of group B streptococcus. Author(s): De La Rosa-Fraile M. Source: Journal of Clinical Microbiology. 2003 August; 41(8): 4007. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12904446

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Group A streptococcus and streptococcal toxic shock syndrome: a postpartum case report. Author(s): Golden S. Source: Journal of Midwifery & Women's Health. 2003 September-October; 48(5): 357-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14526350

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Group A streptococcus bacteraemia complicated by osteomyelitis in an immunocompetent adult. Author(s): Akesson P, Linder A, Cronqvist J, Christensson B. Source: Scandinavian Journal of Infectious Diseases. 2004; 36(1): 63-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15000564

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Group a streptococcus spinal epidural abscess during varicella. Author(s): Quach C, Tapiero B, Noya F. Source: Pediatrics. 2002 January; 109(1): E14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11773582

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Group A Streptococcus tissue invasion by CD44-mediated cell signalling. Author(s): Cywes C, Wessels MR. Source: Nature. 2001 December 6; 414(6864): 648-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11740562

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Group B streptococcus carriage and vulvovaginal symptoms: causal or casual? A casecontrol study in a GUM clinic population. Author(s): Shaw C, Mason M, Scoular A. Source: Sexually Transmitted Infections. 2003 June; 79(3): 246-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12794214

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Group B Streptococcus colonization in male and nonpregnant female university students: a cross-sectional prevalence study. Author(s): Bliss SJ, Manning SD, Tallman P, Baker CJ, Pearlman MD, Marrs CF, Foxman B. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2002 January 15; 34(2): 184-90. Epub 2001 December 05. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11740706

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Group B streptococcus colonization of Greek pregnant women and neonates: prevalence, risk factors and serotypes. Author(s): Tsolia M, Psoma M, Gavrili S, Petrochilou V, Michalas S, Legakis N, Karpathios T. Source: Clinical Microbiology and Infection : the Official Publication of the European Society of Clinical Microbiology and Infectious Diseases. 2003 August; 9(8): 832-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14616704

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Group B streptococcus. Prevention of infection in the newborn. Author(s): Feldman R. Source: Pract Midwife. 2001 March; 4(3): 16-8. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12026655

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Group G streptococcus--a rare cause of osteomyelitis simulating bone tumour: a case report. Author(s): Tong SH, Tang WM, Wong JW. Source: Journal of Orthopaedic Surgery (Hong Kong). 2003 December; 11(2): 221-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14676352

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Guidelines direct treatment choices for group B streptococcus. Author(s): Scott K. Source: Pediatric Annals. 2003 September; 32(9): 632, 633, 636. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14508896

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Health care resource utilization associated with treatment of penicillin-susceptible and -nonsusceptible isolates of Streptococcus pneumoniae. Author(s): Klepser ME, Klepser DG, Ernst EJ, Brooks J, Diekema DJ, Mozaffari E, Hendrickson J, Doern GV. Source: Pharmacotherapy. 2003 March; 23(3): 349-59. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12627934

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Healthy elderly people lack neutrophil-mediated functional activity to type V group B Streptococcus. Author(s): Amaya RA, Baker CJ, Keitel WA, Edwards MS. Source: Journal of the American Geriatrics Society. 2004 January; 52(1): 46-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14687314

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Hemolytic uremic syndrome associated with group A beta-hemolytic streptococcus. Author(s): Shepherd AB, Palmer AL, Bigler SA, Baliga R. Source: Pediatric Nephrology (Berlin, Germany). 2003 September; 18(9): 949-51. Epub 2003 June 26. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12836092

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Hemolytic uremic syndrome attributable to Streptococcus pneumoniae infection: a novel cause for secondary protein N-glycan abnormalities. Author(s): de Loos F, Huijben KM, van der Kar NC, Monnens LA, van den Heuvel LP, Groener JE, de Moor RA, Wevers RA. Source: Clinical Chemistry. 2002 May; 48(5): 781-4. Erratum In: Clin Chem 2002 July; 48(7): 1142. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11978611

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Heptavalent pneumococcal vaccine conjugated to outer membrane protein of Neisseria meningitidis serogroup b and nasopharyngeal carriage of Streptococcus pneumoniae in infants. Author(s): Yeh SH, Zangwill KM, Lee H, Chang SJ, Wong VI, Greenberg DP, Ward JI. Source: Vaccine. 2003 June 2; 21(19-20): 2627-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12744899

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High burden of invasive Streptococcus agalactiae disease in South African infants. Author(s): Madhi SA, Radebe K, Crewe-Brown H, Frasch CE, Arakere G, Mokhachane M, Kimura A. Source: Annals of Tropical Paediatrics. 2003 March; 23(1): 15-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12648320

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High frequency of erythromycin A resistance and distribution of mefE and ermB genes in clinical isolates of Streptococcus pneumoniae in Japan. Author(s): Okamoto H, Tateda K, Ishii Y, Matsumoto T, Kobayashi T, Miyazaki S, Yamaguchi K. Source: Journal of Infection and Chemotherapy : Official Journal of the Japan Society of Chemotherapy. 2002 March; 8(1): 28-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11957116

118

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High incidence of oligozoospermia and teratozoospermia in human semen infected with the aerobic bacterium Streptococcus faecalis. Author(s): Mehta RH, Sridhar H, Vijay Kumar BR, Anand Kumar TC. Source: Reproductive Biomedicine Online. 2002 July-August; 5(1): 17-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12470540

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High level of resistance to levofloxacin of Streptococcus pneumoniae following fluoroquinolone therapy. Author(s): d'Escrivan T, Roussel-Delvallez M, Alfandari S, Guery B. Source: Infection. 2003 October; 31(5): 366. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14556066

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High prevalence of erythromycin resistance of Streptococcus pyogenes in Greek children. Author(s): Syrogiannopoulos GA, Grivea IN, Fitoussi F, Doit C, Katopodis GD, Bingen E, Beratis NG. Source: The Pediatric Infectious Disease Journal. 2001 September; 20(9): 863-8. Erratum In: Pediatr Infect Dis J 2001 December; 20(12): 1131. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11734765

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High rate of transmission of penicillin-resistant Streptococcus pneumoniae between parents and children. Author(s): Hoshino K, Watanabe H, Sugita R, Asoh N, Ntabaguzi SA, Watanabe K, Oishi K, Nagatake T. Source: Journal of Clinical Microbiology. 2002 November; 40(11): 4357-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12409431

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High rates of multiple antibiotic resistance in Streptococcus pneumoniae from healthy children living in isolated rural communities: association with cephalosporin use and intrafamilial transmission. Author(s): Samore MH, Magill MK, Alder SC, Severina E, Morrison-De Boer L, Lyon JL, Carroll K, Leary J, Stone MB, Bradford D, Reading J, Tomasz A, Sande MA. Source: Pediatrics. 2001 October; 108(4): 856-65. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11581436

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High-level penicillin-nonsusceptible Streptococcus pneumoniae bacteremia: identification of a low-risk subgroup. Author(s): Ruhe JJ, Myers L, Mushatt D, Hasbun R. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2004 February 15; 38(4): 508-14. Epub 2004 January 28. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14765343

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119

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Histidine and aspartic acid residues important for immunoglobulin G endopeptidase activity of the group A Streptococcus opsonophagocytosis-inhibiting Mac protein. Author(s): Lei B, Liu M, Meyers EG, Manning HM, Nagiec MJ, Musser JM. Source: Infection and Immunity. 2003 May; 71(5): 2881-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12704162

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Household transmission of invasive group A streptococcus with necrotizing fasciitis. Author(s): Laustrup HK, Justesen US, Pedersen C. Source: Scandinavian Journal of Infectious Diseases. 2003; 35(6-7): 414-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12953958

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Household transmission of Streptococcus pneumoniae among siblings with acute otitis media. Author(s): Shimada J, Yamanaka N, Hotomi M, Suzumoto M, Sakai A, Ubukata K, Mitsuda T, Yokota S, Faden H. Source: Journal of Clinical Microbiology. 2002 May; 40(5): 1851-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11980976

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HrcA is a negative regulator of the dnaK and groESL operons of Streptococcus pyogenes. Author(s): Woodbury R, Haldenwang WG. Source: Biochemical and Biophysical Research Communications. 2003 March 21; 302(4): 722-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12646229

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HtrA protease and processing of extracellular proteins of Streptococcus mutans. Author(s): Diaz-Torres ML, Russell RR. Source: Fems Microbiology Letters. 2001 October 16; 204(1): 23-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11682172

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Human immunoglobulin M memory B cells controlling Streptococcus pneumoniae infections are generated in the spleen. Author(s): Kruetzmann S, Rosado MM, Weber H, Germing U, Tournilhac O, Peter HH, Berner R, Peters A, Boehm T, Plebani A, Quinti I, Carsetti R. Source: The Journal of Experimental Medicine. 2003 April 7; 197(7): 939-45. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12682112

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Humans immunized with Streptococcus mutans antigens by mucosal routes. Author(s): Childers NK, Tong G, Li F, Dasanayake AP, Kirk K, Michalek SM. Source: Journal of Dental Research. 2002 January; 81(1): 48-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11820367

120

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Identification of NAD+ synthetase from Streptococcus sobrinus as a B-cellstimulatory protein. Author(s): Veiga-Malta I, Duarte M, Dinis M, Madureira P, Ferreira P, Videira A. Source: Journal of Bacteriology. 2004 January; 186(2): 419-26. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14702311

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Identification of new candidate vaccine antigens made by Streptococcus pyogenes: purification and characterization of 16 putative extracellular lipoproteins. Author(s): Lei B, Liu M, Chesney GL, Musser JM. Source: The Journal of Infectious Diseases. 2004 January 1; 189(1): 79-89. Epub 2003 December 22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14702157

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In situ reconstruction of septic aortic pseudoaneurysm due to Salmonella or Streptococcus microbial aortitis: long-term follow-up. Author(s): Luo CY, Ko WC, Kan CD, Lin PY, Yang YJ. Source: Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter. 2003 November; 38(5): 975-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14603203

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In vitro activity of telithromycin compared with macrolides and fluoroquinolones against Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis. Author(s): Kucukbasmaci O, Gonullu N, Aktas Z, Gurol D, Berkiten R. Source: International Journal of Antimicrobial Agents. 2003 November; 22(5): 497-501. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14602368

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In vitro activity of thiamphenicol against multiresistant Streptococcus pneumoniae, Haemophilus influenzae and Staphylococcus aureus in Italy. Author(s): Marchese A, Debbia EA, Tonoli E, Gualco L, Schito AM. Source: J Chemother. 2002 December; 14(6): 554-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12583545

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In vitro pharmacodynamic activity of gatifloxacin, gemifloxacin, moxifloxacin and levofloxacin against Streptococcus pneumoniae containing specific mutations in DNA gyrase and topoisomerase IV. Author(s): Garrison MW, Schimmels JA, Madaras-Kelly KJ. Source: Diagnostic Microbiology and Infectious Disease. 2003 December; 47(4): 587-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14711480

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Inactivation of srtA gene of Streptococcus mutans inhibits dextran-dependent aggregation by glucan-binding protein C. Author(s): Igarashi T, Asaga E, Sato Y, Goto N. Source: Oral Microbiology and Immunology. 2004 February; 19(1): 57-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14678475

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Infections in international pregnancy study: performance of the optical immunoassay test for detection of group B streptococcus. Author(s): Thinkhamrop J, Limpongsanurak S, Festin MR, Daly S, Schuchat A, Lumbiganon P, Zell E, Chipato T, Win AA, Perilla MJ, Tolosa JE, Whitney CG. Source: Journal of Clinical Microbiology. 2003 November; 41(11): 5288-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14605186

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Infective endocarditis caused by group G streptococcus with multiple cerebral emboli. Author(s): Erdem I, Goktas P, Demirtunc R, Erdem A. Source: Acta Medica (Hradec Kralove). 2003; 46(3): 125-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14677723

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Infective endocarditis due to Streptococcus bovis in a series of nonaddict patients: clinical and morphological characteristics of 20 cases and review of the literature. Author(s): Gonzalez-Juanatey C, Gonzalez-Gay MA, Llorca J, Testa A, Corredoira J, Vidan J, Mayo J, Gonzalez-Juanatey JR. Source: The Canadian Journal of Cardiology. 2003 September; 19(10): 1139-45. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14532939

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Inferring the potential success of pneumococcal vaccination in Italy: serotypes and antibiotic resistance of Streptococcus pneumoniae isolates from invasive diseases. Author(s): Pantosti A, Boccia D, D'Ambrosio F, Recchia S, Orefici G, Moro ML; National Surveillance of Bacterial Meningitis; Earss-Italia Study. Source: Microbial Drug Resistance (Larchmont, N.Y.). 2003; 9 Suppl 1: S61-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14633369

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Inhibition of Streptococcus mutans biofilm accumulation and polysaccharide production by apigenin and tt-farnesol. Author(s): Koo H, Hayacibara MF, Schobel BD, Cury JA, Rosalen PL, Park YK, VaccaSmith AM, Bowen WH. Source: The Journal of Antimicrobial Chemotherapy. 2003 November; 52(5): 782-9. Epub 2003 October 16. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14563892

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Inhibitory effect of water-soluble chitosan on growth of Streptococcus mutans. Author(s): Fujiwara M, Hayashi Y, Ohara N. Source: New Microbiol. 2004 January; 27(1): 83-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14964411

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Insight into the molecular basis of pathogen abundance: group A Streptococcus inhibitor of complement inhibits bacterial adherence and internalization into human cells. Author(s): Hoe NP, Ireland RM, DeLeo FR, Gowen BB, Dorward DW, Voyich JM, Liu M, Burns EH Jr, Culnan DM, Bretscher A, Musser JM. Source: Proceedings of the National Academy of Sciences of the United States of America. 2002 May 28; 99(11): 7646-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12032337

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Invasive M1T1 group A Streptococcus undergoes a phase-shift in vivo to prevent proteolytic degradation of multiple virulence factors by SpeB. Author(s): Aziz RK, Pabst MJ, Jeng A, Kansal R, Low DE, Nizet V, Kotb M. Source: Molecular Microbiology. 2004 January; 51(1): 123-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14651616

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Invasive properties of south Indian strains of Streptococcus pyogenes in a HEp-2 cell model. Author(s): Gladstone P, Jesudason MV, Sridharan G. Source: Clinical Microbiology and Infection : the Official Publication of the European Society of Clinical Microbiology and Infectious Diseases. 2003 October; 9(10): 1031-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14616747

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Invasive Streptococcus pneumoniae isolates from Argentinian children: serotypes, families of pneumococcal surface protein A (PspA) and genetic diversity. Author(s): Mollerach M, Regueira M, Bonofiglio L, Callejo R, Pace J, Di Fabio JL, Hollingshead S, Briles D; Streptococcus pneumoniae Working Group. Source: Epidemiology and Infection. 2004 April; 132(2): 177-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15061491

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Invasive Streptococcus pyogenes after allograft implantation--Colorado, 2003. Author(s): Centers for Disease Control and Prevention (CDC). Source: Mmwr. Morbidity and Mortality Weekly Report. 2003 December 5; 52(48): 11746. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14654764

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Ion release from copper phosphate cement and influence on Streptococcus mutans growth in vitro: a comparative study. Author(s): Foley J, Blackwell A. Source: Caries Research. 2003 November-December; 37(6): 416-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14571119

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ISSa4-based differentiation of Streptococcus agalactiae strains and identification of multiple target sites for ISSa4 insertions. Author(s): Dmitriev A, Shen A, Shen X, Yang Y. Source: Journal of Bacteriology. 2004 February; 186(4): 1106-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14762005

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Just the berries. Diagnosing and managing group A streptococcus pharyngitis. Author(s): Forward K. Source: Can Fam Physician. 2002 January; 48: 47-8. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11852611

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Kinetic properties of Streptococcus pneumoniae hyaluronate lyase. Author(s): Kelly SJ, Taylor KB, Li S, Jedrzejas MJ. Source: Glycobiology. 2001 April; 11(4): 297-304. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11358878

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Laboratory survey of antibiotic nonsusceptibility among Streptococcus pneumoniae isolates in South Carolina, 1998 versus 2000. Author(s): Dauner DG, Gibson JJ, Roberts DF, Kotchmar GS. Source: Southern Medical Journal. 2003 October; 96(10): 960-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14570339

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Lack of effect of chlorhexidine varnish on Streptococcus mutans transmission and caries in mothers and children. Author(s): Dasanayake AP, Wiener HW, Li Y, Vermund SV, Caufield PW. Source: Caries Research. 2002 July-August; 36(4): 288-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12218279

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Lack of vancomycin tolerance in Streptococcus pneumoniae strains isolated in Barcelona, Spain, from 1999 to 2001. Author(s): Ortega M, Marco F, Soriano A, Garcia E, Martinez JA, Mensa J. Source: Antimicrobial Agents and Chemotherapy. 2003 June; 47(6): 1976-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12760878

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Large chest wall abscess due to microaerophilic streptococcus. Author(s): Nakano N, Miyauchi K, Suzuki H, Kawachi K. Source: European Journal of Cardio-Thoracic Surgery : Official Journal of the European Association for Cardio-Thoracic Surgery. 2002 May; 21(5): 925. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12062289

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Large-scale identification of serotype 4 Streptococcus pneumoniae virulence factors. Author(s): Hava DL, Camilli A. Source: Molecular Microbiology. 2002 September; 45(5): 1389-406. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12207705

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Late antenatal carriage of group B Streptococcus by New Zealand women. Author(s): Grimwood K, Stone PR, Gosling IA, Green R, Darlow BA, Lennon DR, Martin DR. Source: The Australian & New Zealand Journal of Obstetrics & Gynaecology. 2002 May; 42(2): 182-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12069147

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Late infection of a total knee arthroplasty with Streptococcus bovis in association with carcinoma of the large intestine. Author(s): Vince KG, Kantor SR, Descalzi J. Source: The Journal of Arthroplasty. 2003 September; 18(6): 813-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14513461

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Late onset group B streptococcus endophthalmitis associated with conjunctival filtration bleb. Author(s): Tan TY, Escardo-Paton JA, Walters RF. Source: Eye (London, England). 2003 July; 17(5): 656-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12855980

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Latex assay for serotyping of group B Streptococcus isolates. Author(s): Slotved HC, Elliott J, Thompson T, Konradsen HB. Source: Journal of Clinical Microbiology. 2003 September; 41(9): 4445-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12958289

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lcd from Streptococcus anginosus encodes a C-S lyase with alpha,beta-elimination activity that degrades L-cysteine. Author(s): Yoshida Y, Nakano Y, Amano A, Yoshimura M, Fukamachi H, Oho T, Koga T. Source: Microbiology (Reading, England). 2002 December; 148(Pt 12): 3961-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12480900

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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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Levoflaxin and Streptococcus pneumoniae. Author(s): Mahgoub S, Hochstein L, Kopetz V, LaBombardi V, Leggiadro R, Glatt AE. Source: Chemotherapy. 2003 July; 49(4): 212; Author Reply 212. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12886059

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Limitations of the obstetric group B Streptococcus protocol. Author(s): Nemunaitis-Keller J, Gill P. Source: J Reprod Med. 2003 February; 48(2): 107-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12621794

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Linezolid and vancomycin, alone and in combination with rifampin, compared with moxifloxacin against a multidrug-resistant and a vancomycin-tolerant Streptococcus pneumoniae strain in an in vitro pharmacodynamic model. Author(s): Cha R, Rybak MJ. Source: Antimicrobial Agents and Chemotherapy. 2003 June; 47(6): 1984-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12760880

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Linezolid versus ceftriaxone/cefpodoxime in patients hospitalized for the treatment of Streptococcus pneumoniae pneumonia. Author(s): San Pedro GS, Cammarata SK, Oliphant TH, Todisco T; Linezolid Community-Acquired Pneumonia Study Group. Source: Scandinavian Journal of Infectious Diseases. 2002; 34(10): 720-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12477321

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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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Liver abscesses caused by Streptococcus milleri: an uncommon presenting sign of silent colonic cancer. Author(s): Tzur T, Liberman S, Felzenstein I, Cohen R, Rivkind AI, Almogy G. Source: Isr Med Assoc J. 2003 March; 5(3): 206-7. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12725147

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Long-range mapping of the Streptococcus agalactiae phylogenetic lineage restriction digest pattern type III-3 reveals clustering of virulence genes. Author(s): Bohnsack JF, Whiting AA, Bradford RD, Van Frank BK, Takahashi S, Adderson EE. Source: Infection and Immunity. 2002 January; 70(1): 134-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11748174

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Low antibody levels against cell wall-attached proteins of Streptococcus pyogenes predispose for severe invasive disease. Author(s): Akesson P, Rasmussen M, Mascini E, von Pawel-Rammingen U, Janulczyk R, Collin M, Olsen A, Mattsson E, Olsson ML, Bjorck L, Christensson B. Source: The Journal of Infectious Diseases. 2004 March 1; 189(5): 797-804. Epub 2004 February 18. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14976595

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Maternal carriage and antimicrobial resistance profile of group B Streptococcus. Author(s): Arisoy AS, Altinisik B, Tunger O, Kurutepe S, Ispahi C. Source: Infection. 2003 August; 31(4): 244-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14562949

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Meningitis and pneumonia in Guatemalan children: the importance of Haemophilus influenzae type b and Streptococcus pneumoniae. Author(s): Asturias EJ, Soto M, Menendez R, Ramirez PL, Recinos F, Gordillo R, Holt E, Halsey NA. Source: Revista Panamericana De Salud Publica = Pan American Journal of Public Health. 2003 December; 14(6): 377-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14769154

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Meningitis due to multiple-resistant penicillin- and cefotaxime-intermediate Streptococcus pneumoniae in a German child after bone marrow transplantation. Author(s): Buxmann H, Soerensen J, Koehl U, Schwabe D, Klingebiel T, Reinert RR, Schaefer V. Source: Infection. 2003 December; 31(6): 425-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14735387

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MgrA, an orthologue of Mga, Acts as a transcriptional repressor of the genes within the rlrA pathogenicity islet in Streptococcus pneumoniae. Author(s): Hemsley C, Joyce E, Hava DL, Kawale A, Camilli A. Source: Journal of Bacteriology. 2003 November; 185(22): 6640-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14594838

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Molecular characterization of Streptococcus pyogenes isolates collected during periods of increased acute rheumatic fever activity in Utah. Author(s): Miner LJ, Petheram SJ, Daly JA, Korgenski EK, Selin KS, Firth SD, Veasy LG, Hill HR, Bale JF Jr; The Post-Streptococcal Syndrome Stydy Team. Source: The Pediatric Infectious Disease Journal. 2004 January; 23(1): 56-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14743048

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Molecular epidemiology of multiresistant Streptococcus pneumoniae with both erm(B)- and mef(A)-mediated macrolide resistance. Author(s): Farrell DJ, Morrissey I, Bakker S, Morris L, Buckridge S, Felmingham D. Source: Journal of Clinical Microbiology. 2004 February; 42(2): 764-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14766850

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Molecular epidemiology of penicillin-susceptible non-beta-lactam-resistant Streptococcus pneumoniae isolates from Greek children. Author(s): Bogaert D, Hermans PW, Grivea IN, Katopodis GS, Mitchell TJ, Sluijter M, De Groot R, Beratis NG, Syrogiannopoulos GA. Source: Journal of Clinical Microbiology. 2003 December; 41(12): 5633-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14662953

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MtaR, a regulator of methionine transport, is critical for survival of group B streptococcus in vivo. Author(s): Shelver D, Rajagopal L, Harris TO, Rubens CE. Source: Journal of Bacteriology. 2003 November; 185(22): 6592-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14594832

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Multilocus sequence typing of serotype III group B streptococcus and correlation with pathogenic potential. Author(s): Davies HD, Jones N, Whittam TS, Elsayed S, Bisharat N, Baker CJ. Source: The Journal of Infectious Diseases. 2004 March 15; 189(6): 1097-102. Epub 2004 February 27. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14999614

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Multiple mycotic aortic aneurysms due to Streptococcus pneumoniae. Author(s): Coutu M, Blair JF. Source: Annals of Vascular Surgery. 2003 September; 17(5): 554-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14738083

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Nasopharyngeal carriage and susceptibility patterns of Streptococcus pneumoniae in Kumasi, Ghana. Author(s): Denno DM, Frimpong E, Gregory M, Steele RW. Source: West Afr J Med. 2002 July-September; 21(3): 233-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12744576

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Nasopharyngeal carriage of Streptococcus pneumoniae by adults and children in community and family settings. Author(s): Regev-Yochay G, Raz M, Dagan R, Porat N, Shainberg B, Pinco E, Keller N, Rubinstein E. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2004 March 1; 38(5): 632-9. Epub 2004 February 17. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14986245

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Nationwide surveillance of nasopharyngeal Streptococcus pneumoniae isolates from children with respiratory infection, Switzerland, 1998-1999. Author(s): Muhlemann K, Matter HC, Tauber MG, Bodmer T; Sentinel Working Group. Source: The Journal of Infectious Diseases. 2003 February 15; 187(4): 589-96. Epub 2003 January 29. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12599075

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Necrotizing pneumonia caused by Streptococcus pneumoniae in a child with systemic lupus erythematosus. Author(s): Chiu WJ, Kao HT, Huang JL. Source: Acta Paediatr Taiwan. 2002 September-October; 43(5): 291-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12607488

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Neonatal group B streptococcus infection in Taiwan: an increasing trend. Author(s): Huang FY. Source: Acta Paediatr Taiwan. 2002 November-December; 43(6): 312. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12632782

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Neonatal sepsis caused by Streptococcus bovis variant (biotype II/2): report of a case and review. Author(s): Gavin PJ, Thomson RB Jr, Horng SJ, Yogev R. Source: Journal of Clinical Microbiology. 2003 July; 41(7): 3433-5. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12843113

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New strategies to overcome antimicrobial resistance in Streptococcus pneumoniae with beta-lactam antibiotics. Author(s): Aguilar L, Gimenez MJ, Garcia-Rey C, Martin JE. Source: The Journal of Antimicrobial Chemotherapy. 2002 December; 50 Suppl S2: 93100. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12556439

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Non-tropical thoraco-abdominal pyomyositis caused by group A streptococcus in an immunocompetent adult. Author(s): Cherry C, Wiggins K, Mijch A, Ostergaard L. Source: Scandinavian Journal of Infectious Diseases. 2001; 33(11): 854-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11760169

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Novel genomic rearrangement that affects expression of the Streptococcus pyogenes streptolysin O (slo) gene. Author(s): Savic DJ, Ferretti JJ. Source: Journal of Bacteriology. 2003 March; 185(6): 1857-69. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12618450

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Novel vaccine strategies with protein antigens of Streptococcus pneumoniae. Author(s): Swiatlo E, Ware D. Source: Fems Immunology and Medical Microbiology. 2003 August 18; 38(1): 1-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12900048

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Obsessive-Compulsive disorder, Tourette's disorder, or pediatric autoimmune neuropsychiatric disorders associated with Streptococcus in an adolescent? Diagnostic and therapeutic challenges. Author(s): Gabbay V, Coffey B. Source: Journal of Child and Adolescent Psychopharmacology. 2003 Fall; 13(3): 209-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14642008

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Ophthalmia neonatorum caused by group B Streptococcus. Author(s): Poschl JM, Hellstern G, Ruef P, Bauer J, Linderkamp O. Source: Scandinavian Journal of Infectious Diseases. 2002; 34(12): 921-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12587626

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Opsonophagocytosis-inhibiting mac protein of group a streptococcus: identification and characteristics of two genetic complexes. Author(s): Lei B, DeLeo FR, Reid SD, Voyich JM, Magoun L, Liu M, Braughton KR, Ricklefs S, Hoe NP, Cole RL, Leong JM, Musser JM. Source: Infection and Immunity. 2002 December; 70(12): 6880-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12438365

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Oral colonization and immune responses to Streptococcus gordonii: Potential use as a vector to induce antibodies against respiratory pathogens. Author(s): Lee SF. Source: Current Opinion in Infectious Diseases. 2003 June; 16(3): 231-5. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12821813

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Oral condition, chemistry of saliva, and salivary levels of Streptococcus mutans in thalassemic patients. Author(s): Luglie PF, Campus G, Deiola C, Mela MG, Gallisai D. Source: Clinical Oral Investigations. 2002 December; 6(4): 223-6. Epub 2002 October 26. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12483237

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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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Outcome of penicillin-nonsusceptible Streptococcus pneumoniae meningitis: a nested case-control study. Author(s): Kellner JD, Scheifele DW, Halperin SA, Lebel MH, Moore D, Le Saux N, Ford-Jones EL, Law B, Vaudry W; Canadian Paediatric Society/Centre for Infectious Disease Prevention and Control Immunization Monitoring Program. Source: The Pediatric Infectious Disease Journal. 2002 October; 21(10): 903-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12394810

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Outcome of treatment of respiratory tract infections due to Streptococcus pneumoniae, including drug-resistant strains, with pharmacokinetically enhanced amoxycillin/clavulanate. Author(s): File TM Jr, Jacobs MR, Poole MD, Wynne B; 546, 547, 548, 549, 550, 551, 556, 557 and 592 Clinical Study Groups. Source: International Journal of Antimicrobial Agents. 2002 October; 20(4): 235-47. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12385678

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Oxidative stress tolerance is manganese (Mn(2+)) regulated in Streptococcus gordonii. Author(s): Jakubovics NS, Smith AW, Jenkinson HF. Source: Microbiology (Reading, England). 2002 October; 148(Pt 10): 3255-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12368459

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Oxygen regulates invasiveness and virulence of group B streptococcus. Author(s): Johri AK, Padilla J, Malin G, Paoletti LC. Source: Infection and Immunity. 2003 December; 71(12): 6707-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14638754

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Penicillin and vancomycin tolerance among clinical isolates of Streptococcus pneumoniae in Hong Kong. Author(s): Boost MV, Ko WM, O'Donoghue MM. Source: Hong Kong Medical Journal = Xianggang Yi Xue Za Zhi / Hong Kong Academy of Medicine. 2003 December; 9(6): 415-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14660808

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Penicillin susceptibility and molecular characteristics of clinical isolates of Streptococcus pneumoniae at the University of Malaya Medical Center, Kuala Lumpur, Malaysia. Author(s): Desa MN, Lin TK, Yasin RM, Parasakthi N. Source: International Journal of Infectious Diseases : Ijid : Official Publication of the International Society for Infectious Diseases. 2003 September; 7(3): 190-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14563222

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Persistent primary peritonitis due to group A streptococcus and E. coli. Author(s): Gavala A, Klimopulos S, Exarchos D, Konstantinidis K, Daniil Z, Zakynthinos SG, Zakynthinos E. Source: Intensive Care Medicine. 2002 December; 28(12): 1829-31. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12580167

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Phenotypic and genetic characterization of resistance against macrolides and lincosamides in Streptococcus gallolyticus strains isolated from pigeons and humans. Author(s): Kimpe A, Decostere A, Martel A, Devriese LA, Haesebrouck F. Source: Microbial Drug Resistance (Larchmont, N.Y.). 2003; 9 Suppl 1: S35-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14633365

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Pneumonia due to antibiotic resistant Streptococcus pneumoniae and Pseudomonas aeruginosa in the HAART era. Author(s): Allen SH, Brennan-Benson P, Nelson M, Asboe D, Bower M, Azadian B, Gazzard B, Stebbing J. Source: Postgraduate Medical Journal. 2003 December; 79(938): 691-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14707245

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Postantibiotic and sub-MIC effects of benzylpenicillin against Streptococcus pneumoniae with different susceptibilities for penicillin. Author(s): Odenholt I, Gustafsson I, Lowdin E. Source: Chemotherapy. 2003 December; 49(6): 287-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14671428

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Prevalence of antimicrobial resistance of Streptococcus pneumoniae in Chinese children: four hospitals surveillance. Author(s): Shen X, Lu Q, Ye Q, Zhang G, Yu S, Zhang H, Deng Q, Yang Y. Source: Chinese Medical Journal. 2003 September; 116(9): 1304-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14527353

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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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Pro-inflammatory cytokine and chemokine release by human brain microvascular endothelial cells stimulated by Streptococcus suis serotype 2. Author(s): Vadeboncoeur N, Segura M, Al-Numani D, Vanier G, Gottschalk M. Source: Fems Immunology and Medical Microbiology. 2003 January 21; 35(1): 49-58. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12589957

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Prophage induction and expression of prophage-encoded virulence factors in group A Streptococcus serotype M3 strain MGAS315. Author(s): Banks DJ, Lei B, Musser JM. Source: Infection and Immunity. 2003 December; 71(12): 7079-86. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14638798

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Quantitative detection of Streptococcus pneumoniae in nasopharyngeal secretions by real-time PCR. Author(s): Greiner O, Day PJ, Bosshard PP, Imeri F, Altwegg M, Nadal D. Source: Journal of Clinical Microbiology. 2001 September; 39(9): 3129-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11526140

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Quantitative relationship between salivary level of Streptococcus mutans and Candida albicans in children with Down's syndrome. Author(s): Linossier A, Vargas A, Villegas R, Chimenos E. Source: Medicina Oral : Organo Oficial De La Sociedad Espanola De Medicina Oral Y De La Academia Iberoamericana De Patologia Y Medicina Bucal. 2002 July-October; 7(4): 284-92. English, Spanish. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12134129

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Quantitative validation of media for transportation and storage of Streptococcus pneumoniae. Author(s): Charalambous BM, Batt SL, Peek AC, Mwerinde H, Sam N, Gillespie SH. Source: Journal of Clinical Microbiology. 2003 December; 41(12): 5551-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14662939

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Quinupristin-dalfopristin resistance in Streptococcus pneumoniae: novel L22 ribosomal protein mutation in two clinical isolates from the SENTRY antimicrobial surveillance program. Author(s): Jones RN, Farrell DJ, Morrissey I. Source: Antimicrobial Agents and Chemotherapy. 2003 August; 47(8): 2696-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12878545

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Rapid diagnosis of vaginal carriage of group B beta haemolytic streptococcus by an enrichment cum antigen detection test. Author(s): Das A, Ray P, Sharma M, Gopalan S. Source: The Indian Journal of Medical Research. 2003 June; 117: 247-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14748470

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Rate of nasopharyngeal carriage, antimicrobial resistance and serotype of Streptococcus pneumoniae among children in northern Taiwan. Author(s): Lo WT, Wang CC, Yu CM, Chu ML. Source: J Microbiol Immunol Infect. 2003 September; 36(3): 175-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14582561

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Regulation of protein H expression in M1 serotype isolates of Streptococcus pyogenes. Author(s): Smith TC, Sledjeski DD, Boyle MD. Source: Fems Microbiology Letters. 2003 February 14; 219(1): 9-15. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12594016

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Relevance of peptide uptake systems to the physiology and virulence of Streptococcus agalactiae. Author(s): Samen U, Gottschalk B, Eikmanns BJ, Reinscheid DJ. Source: Journal of Bacteriology. 2004 March; 186(5): 1398-408. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14973032

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Report from a WHO Working Group: standard method for detecting upper respiratory carriage of Streptococcus pneumoniae. Author(s): O'Brien KL, Nohynek H; World Health Organization Pneumococcal Vaccine Trials Carriage Working Group. Source: The Pediatric Infectious Disease Journal. 2003 February; 22(2): E1-11. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12586987

134

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Report from a WHO working group: standard method for detecting upper respiratory carriage of Streptococcus pneumoniae. Author(s): O'Brien KL, Nohynek H; World Health Organization Pneumococcal Vaccine Trials Carraige Working Group. Source: The Pediatric Infectious Disease Journal. 2003 February; 22(2): 133-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12586977

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Resistance among Streptococcus pneumoniae: Implications for drug selection. Author(s): Appelbaum PC. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2002 June 15; 34(12): 1613-20. Epub 2002 May 16. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12032897

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Resistance of group B streptococcus to selected antibiotics, including erythromycin and clindamycin. Author(s): Heelan JS, Hasenbein ME, McAdam AJ. Source: Journal of Clinical Microbiology. 2004 March; 42(3): 1263-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15004089

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Rhabdomyolysis as a result of Streptococcus pneumoniae: report of a case and review. Author(s): Blanco JR, Zabalza M, Salcedo J, San Roman J. Source: Clinical Microbiology and Infection : the Official Publication of the European Society of Clinical Microbiology and Infectious Diseases. 2003 September; 9(9): 944-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14616683

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Roles of Streptococcus mutans dextranase anchored to the cell wall by sortase. Author(s): Igarashi T, Asaga E, Goto N. Source: Oral Microbiology and Immunology. 2004 April; 19(2): 102-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14871349

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Serum and salivary IgA antibody responses to Saccharomyces cerevisiae, Candida albicans and Streptococcus mutans in orofacial granulomatosis and Crohn's disease. Author(s): Savage NW, Barnard K, Shirlaw PJ, Rahman D, Mistry M, Escudier MP, Sanderson JD, Challacombe SJ. Source: Clinical and Experimental Immunology. 2004 March; 135(3): 483-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15008983

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Similar inflammatory response in human whole blood to live Streptococcus pneumoniae of different serotypes. Author(s): Kragsbjerg P, Jurstrand M, Fredlund H. Source: Clinical Microbiology and Infection : the Official Publication of the European Society of Clinical Microbiology and Infectious Diseases. 2004 February; 10(2): 174-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14759244

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Stable isotope labeling of a Group A Streptococcus virulence factor using a chemically defined growth medium. Author(s): Vise PD, Kodali K, Hoe N, Paszczynski A, Musser JM, Daughdrill GW. Source: Protein Expression and Purification. 2003 December; 32(2): 232-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14965768

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Streptococcus pneumoniae as an uncommon cause of superinfected pancreatic pseudocysts. Author(s): Gubler C, Zinkernagel A, Ossola N, Bauerfeind P. Source: Infection. 2003 August; 31(4): 251-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14562951

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Streptococcus pneumoniae colonisation: the key to pneumococcal disease. Author(s): Bogaert D, De Groot R, Hermans PW. Source: The Lancet Infectious Diseases. 2004 March; 4(3): 144-54. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14998500

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Streptococcus pneumoniae empyema necessitatis. Author(s): Freeman AF, Ben-Ami T, Shulman ST. Source: The Pediatric Infectious Disease Journal. 2004 February; 23(2): 177-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14872190

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Streptococcus pneumoniae infections in the neonate. Author(s): Hoffman JA, Mason EO, Schutze GE, Tan TQ, Barson WJ, Givner LB, Wald ER, Bradley JS, Yogev R, Kaplan SL. Source: Pediatrics. 2003 November; 112(5): 1095-102. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14595052

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Streptococcus pneumoniae-associated arthritis of a lumbar facet joint in a 4-year-old boy. Author(s): Nishimura Y, Ishida H, Shin N, Mori K, Yoshihara T, Kasubuchi Y, Kin Y, Tamai K. Source: Pediatrics International : Official Journal of the Japan Pediatric Society. 2004 February; 46(1): 101-3. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15043677

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Streptococcus pyogenes meningitis complicating varicella in a 3-month-old child. Author(s): Brandt CM, Kitz R, Lutticken R, Brade V. Source: Scandinavian Journal of Infectious Diseases. 2003; 35(11-12): 876-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14723366

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Suppression of salivary Streptococcus mutans and lactobacilli by topical caries preventive agents. Author(s): Juric H, Dukic W, Jankovic B, Karlovic Z, Pavelic B. Source: Cent Eur J Public Health. 2003 December; 11(4): 219-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14768786

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Temporal association of the appearance of mucoid strains of Streptococcus pyogenes with a continuing high incidence of rheumatic fever in Utah. Author(s): Veasy LG, Tani LY, Daly JA, Korgenski K, Miner L, Bale J, Kaplan EL, Musser JM, Hill HR. Source: Pediatrics. 2004 March; 113(3 Pt 1): E168-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14993572

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The activity of levofloxacin and other antimicrobials against clinical isolates of Streptococcus pneumoniae collected worldwide during 1999-2002. Author(s): Jones ME, Blosser-Middleton RS, Thornsberry C, Karlowsky JA, Sahm DF. Source: Diagnostic Microbiology and Infectious Disease. 2003 December; 47(4): 579-86. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14711479

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The clinical significance of macrolide-resistant Streptococcus pneumoniae: it's all relative. Author(s): Nuermberger E, Bishai WR. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2004 January 1; 38(1): 99-103. Epub 2003 December 08. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14679455

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The effect of increasing copper content in phosphate-based glasses on biofilms of Streptococcus sanguis. Author(s): Mulligan AM, Wilson M, Knowles JC. Source: Biomaterials. 2003 May; 24(10): 1797-807. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12593962

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The effects of interferon-gamma and transforming growth factor-beta on adherence and survival of group B Streptococcus type III strains in ECV304 cells. Author(s): Santos GS, Miyazaki NH, Mattos-Guaraldi AL, Nagao PE. Source: International Journal of Molecular Medicine. 2003 March; 11(3): 401-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12579348

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137

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The in vitro interaction of Streptococcus pyogenes with human pharyngeal cells induces a phage-encoded extracellular DNase. Author(s): Broudy TB, Pancholi V, Fischetti VA. Source: Infection and Immunity. 2002 June; 70(6): 2805-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12010966

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The role of pneumolysin in the pathogenesis of Streptococcus pneumoniae infection. Author(s): Cockeran R, Anderson R, Feldman C. Source: Current Opinion in Infectious Diseases. 2002 June; 15(3): 235-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12015456

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Tolerability and immunogenicity of an eleven valent mixed carrier Streptococcus pneumoniae capsular polysaccharide-diphtheria toxoid or tetanus protein conjugate vaccine in Finnish and Israeli infants. Author(s): Dagan R, Kayhty H, Wuorimaa T, Yaich M, Bailleux F, Zamir O, Eskola J. Source: The Pediatric Infectious Disease Journal. 2004 February; 23(2): 91-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14872172

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Two novel superantigens found in both group A and group C Streptococcus. Author(s): Proft T, Webb PD, Handley V, Fraser JD. Source: Infection and Immunity. 2003 March; 71(3): 1361-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12595453

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Typing and molecular characterization of Streptococcus pneumoniae with reduced susceptibility to cefotaxime isolated in Latin America. Author(s): Castanheira M, Jones RN, Silbert S, Brandileone MC, Sader HS. Source: Microbial Drug Resistance (Larchmont, N.Y.). 2003 Winter; 9(4): 345-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15000740

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Unique regulation of SclB - a novel collagen-like surface protein of Streptococcus pyogenes. Author(s): Rasmussen M, Bjorck L. Source: Molecular Microbiology. 2001 June; 40(6): 1427-38. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11442840

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Universal antenatal group B streptococcus screening? The opinions of obstetricians and neonatologists within Australia. Author(s): McLaughlin K, Crowther C. Source: The Australian & New Zealand Journal of Obstetrics & Gynaecology. 2000 August; 40(3): 338-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11065044

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Up-regulation of ICAM-1, CD11a/CD18 and CD11c/CD18 on human THP-1 monocytes stimulated by Streptococcus suis serotype 2. Author(s): Al-Numani D, Segura M, Dore M, Gottschalk M. Source: Clinical and Experimental Immunology. 2003 July; 133(1): 67-77. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12823280

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Urinary detection of Streptococcus pneumoniae antigen for diagnosis of pneumonia. Author(s): Farina C, Arosio M, Vailati F, Moioli F, Goglio A. Source: New Microbiol. 2002 April; 25(2): 259-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12019736

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Use of a dynamic in vitro attachment and invasion system (DIVAS) to determine influence of growth rate on invasion of respiratory epithelial cells by group B Streptococcus. Author(s): Malin G, Paoletti LC. Source: Proceedings of the National Academy of Sciences of the United States of America. 2001 November 6; 98(23): 13335-40. Epub 2001 October 30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11687649

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Use of a whole genome approach to identify vaccine molecules affording protection against Streptococcus pneumoniae infection. Author(s): Wizemann TM, Heinrichs JH, Adamou JE, Erwin AL, Kunsch C, Choi GH, Barash SC, Rosen CA, Masure HR, Tuomanen E, Gayle A, Brewah YA, Walsh W, Barren P, Lathigra R, Hanson M, Langermann S, Johnson S, Koenig S. Source: Infection and Immunity. 2001 March; 69(3): 1593-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11179332

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Use of antiserum-coated latex particles for serotyping Streptococcus pneumoniae. Author(s): Arai S, Konda T, Wad A, Matsunaga Y, Okabe N, Watanabe H, Inouye S. Source: Microbiology and Immunology. 2001; 45(2): 159-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11293482

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Use of penicillin MICs to predict in vitro activity of other beta-lactam antimicrobial agents against Streptococcus pneumoniae. Author(s): Brueggemann AB, Pfaller MA, Doern GV. Source: Journal of Clinical Microbiology. 2001 January; 39(1): 367-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11136803

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Use of the NOW Streptococcus pneumoniae urinary antigen test in cerebrospinal fluid for rapid diagnosis of pneumococcal meningitis. Author(s): Samra Z, Shmuely H, Nahum E, Paghis D, Ben-Ari J. Source: Diagnostic Microbiology and Infectious Disease. 2003 April; 45(4): 237-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12729992

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Usefulness of betalactam therapy for community-acquired pneumonia in the era of drug-resistant Streptococcus pneumoniae: a randomized study of amoxicillinclavulanate and ceftriaxone. Author(s): Roson B, Carratala J, Tubau F, Dorca J, Linares J, Pallares R, Manresa F, Gudiol F. Source: Microbial Drug Resistance (Larchmont, N.Y.). 2001 Spring; 7(1): 85-96. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11310807

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Vaccination of day-care center attendees reduces carriage of Streptococcus pneumoniae among their younger siblings. Author(s): Givon-Lavi N, Fraser D, Dagan R. Source: The Pediatric Infectious Disease Journal. 2003 June; 22(6): 524-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12799509

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Vaccination with FimA from Streptococcus parasanguis protects rats from endocarditis caused by other viridans streptococci. Author(s): Kitten T, Munro CL, Wang A, Macrina FL. Source: Infection and Immunity. 2002 January; 70(1): 422-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11748213

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Vaccine development for group A streptococcus infections and associated disease. Author(s): Batzloff MR, Sriprakash KS, Good MF. Source: Current Drug Targets. 2004 January; 5(1): 57-69. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14738218

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Vaginal bacterial flora of pregnant women colonized with group B streptococcus. Author(s): Kubota T, Nojima M, Itoh S. Source: Journal of Infection and Chemotherapy : Official Journal of the Japan Society of Chemotherapy. 2002 December; 8(4): 326-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12525892

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Vaginal carriage of group B Streptococcus in infertile women. Author(s): Verghese S, Padmaja P, Asha M, Elizabeth SJ, Kundavi KM, Varma T. Source: Indian J Pathol Microbiol. 2001 January; 44(1): 37-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12561993

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Vancomycin-tolerant Streptococcus pneumoniae and its clinical significance. Author(s): Mitchell L, Tuomanen E. Source: The Pediatric Infectious Disease Journal. 2001 May; 20(5): 531-3. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11368113

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Various Streptococcus species isolated from infectious skin diseases. Author(s): Higaki S, Morohashi M, Yamagishi T. Source: Drugs Exp Clin Res. 2002; 28(4): 165-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12512235

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Viridans group streptococci are donors in horizontal transfer of topoisomerase IV genes to Streptococcus pneumoniae. Author(s): Balsalobre L, Ferrandiz MJ, Linares J, Tubau F, de la Campa AG. Source: Antimicrobial Agents and Chemotherapy. 2003 July; 47(7): 2072-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12821449

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Viridans streptococcus bacteremia in children on chemotherapy for cancer: an underestimated problem. Author(s): Ahmed R, Hassall T, Morland B, Gray J. Source: Pediatric Hematology and Oncology. 2003 September; 20(6): 439-44. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14631617

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Virulence control in group A Streptococcus by a two-component gene regulatory system: global expression profiling and in vivo infection modeling. Author(s): Graham MR, Smoot LM, Migliaccio CA, Virtaneva K, Sturdevant DE, Porcella SF, Federle MJ, Adams GJ, Scott JR, Musser JM. Source: Proceedings of the National Academy of Sciences of the United States of America. 2002 October 15; 99(21): 13855-60. Epub 2002 Oct 07. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12370433

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Waterhouse-Friderichsen syndrome after infection with group A streptococcus. Author(s): Karakousis PC, Page KR, Varello MA, Howlett PJ, Stieritz DD. Source: Mayo Clinic Proceedings. 2001 November; 76(11): 1167-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11702906

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Will resistance to ketolides develop in Streptococcus pneumoniae? Author(s): Leclercq R. Source: The Journal of Infection. 2002 February; 44 Suppl A: 11-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12150490

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Worldwide prevalence of antimicrobial resistance in Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis in the SENTRY Antimicrobial Surveillance Program, 1997-1999. Author(s): Hoban DJ, Doern GV, Fluit AC, Roussel-Delvallez M, Jones RN. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2001 May 15; 32 Suppl 2: S81-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11320449

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Xylitol-induced elevated expression of the gbpC gene in a population of Streptococcus mutans cells. Author(s): Sato Y, Yamamoto Y, Kizaki H. Source: European Journal of Oral Sciences. 2000 December; 108(6): 538-45. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11153929

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Zinc binding and dimerization of Streptococcus pyogenes pyrogenic exotoxin C are not essential for T-cell stimulation. Author(s): Swietnicki W, Barnie AM, Dyas BK, Ulrich RG. Source: The Journal of Biological Chemistry. 2003 March 14; 278(11): 9885-95. Epub 2002 December 08. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12473669

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CHAPTER 2. NUTRITION AND STREPTOCOCCUS Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and streptococcus.

Finding Nutrition Studies on Streptococcus 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 “streptococcus” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.

7

Adapted from http://ods.od.nih.gov. IBIDS is produced by the Office of Dietary Supplements (ODS) at the National Institutes of Health to assist the public, healthcare providers, educators, and researchers in locating credible, scientific information on dietary supplements. IBIDS was developed and will be maintained through an interagency partnership with the Food and Nutrition Information Center of the National Agricultural Library, U.S. Department of Agriculture.

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The following information is typical of that found when using the “Full IBIDS Database” to search for “streptococcus” (or a synonym): •

Antibacterial activity against cariogenic bacteria and inhibition of insoluble glucan production by free fatty acids obtained from dried Gloiopeltis furcata. Author(s): Hokkaido Univ., Hakodate (Japan). Faculty of Fisheries Source: Kurihara, H. Goto, Y. Aida, M. Hosokawa, M. Takahashi, K. Fisheries-Science (Japan). (February 1999). volume 65(1) page 129-132.

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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.

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Lactic acid bacteria, probiotics and immune system [Review]. Author(s): Univerzita Veterinarskeho Lekarstva, Kosice (Czech Republic). Ustav Patologickej Anatomie Source: Herich, R. Levkut, M. Veterinarni-Medicina-UZPI (Czech Republic). (June 2002). volume 47(6) page 169-180.

Additional physician-oriented references include: •

A case of retropharyngeal abscess caused by penicillin-resistant Streptococcus pneumoniae. Author(s): Department of Pediatrics, Kobe City General Hospital, Japan. [email protected] Source: Kobayashi, K I Haruta, T Kubota, M Nishio, T J-Infect. 2002 May; 44(4): 267-9 0163-4453

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A Streptococcus pneumoniae pathogenicity island encoding an ABC transporter involved in iron uptake and virulence. Author(s): Department of Infectious Diseases, Imperial College School of Medicine, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK. Source: Brown, J S Gilliland, S M Holden, D W Mol-Microbiol. 2001 May; 40(3): 572-85 0950-382X

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An outbreak of Streptococcus pyogenes infection associated with calcium oxalate urolithiasis in guineapigs (Cavia porcellus). Source: Okewole, P.A. Odeyemi, P.S. Oladunmade, M.A. Ajagbonna, B.O. Onah, J. Spencer, T. Lab-Anim. London : Royal Society of Medicine Services. April 1991. volume 25 (2) page 184-186. 0023-6772

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Analyses of Streptococcus mutans in saliva with species-specific monoclonal antibodies. Author(s): School of Dentistry and Dental Research Institute, University of California, Los Angeles, California 90095-1668, USA. Source: Gu, F Lux, R Anderson, M H del Aguila, M A Wolinsky, L Hume, W R Shi, W Hybrid-Hybridomics. 2002 August; 21(4): 225-32 1536-8599

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Chemical-biological interactions of NaF with three different cell lines and the caries pathogen Streptococcus sobrinus. Author(s): Department of Conservative Dentistry and Periodontology, Medical University Hannover, Germany.

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Source: Dogan, S Gunay, H Leyhausen, G Geurtsen, W Clin-Oral-Investig. 2002 June; 6(2): 92-7 1432-6981 •

Comparison of structural changes of cell surface carbohydrates in the eustachian tube epithelium of chinchillas infected with a Streptococcus pneumoniae neuraminidasedeficient mutant or its isogenic parent strain. Author(s): Division of Otologic Research, Department of Otolaryngology, Columbus, OH 43210, USA. Source: Tong, H H James, M Grants, I Liu, X Shi, G DeMaria, T F Microb-Pathog. 2001 December; 31(6): 309-17 0882-4010

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Effect of bifidobacterium Bb12 with or without Streptococcus thermophilus supplemented formula on nutritional status. Author(s): Research Center, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand. Source: Nopchinda, S Varavithya, W Phuapradit, P Sangchai, R Suthutvoravut, U Chantraruksa, V Haschke, F J-Med-Assoc-Thai. 2002 November; 85 Suppl 4: S1225-31 0125-2208

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Effect of date extract on growth and hemolytic activity of Streptococcus pyogenes. Author(s): Department of Preventive Dentistry, Faculty of Dentistry Jordan University of Science and Technology, Irbid. Source: Hammad, M Sallal, A K New-Microbiol. 2002 October; 25(4): 495-7 1121-7138

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Effect of molecular mass and degree of deacetylation of chitosan on adsorption of Streptococcus sobrinus 6715 to saliva treated hydroxyapatite. Author(s): Oral-Care Research Laboratories, Lion Corporation, 3-7 Honjo, 1-chome, Sumida-ku, Tokyo 130-8644, Japan. Source: Sano, H Shibasaki, K Matsukubo, T Takaesu, Y Bull-Tokyo-Dent-Coll. 2002 May; 43(2): 75-82 0040-8891

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Evaluation of teat germicides of low iodine concentration for prevention for bovine mastitis by Staphylococcus aureus and Streptococcus agalactiae. Source: Boddie, R.L. Nickerson, S.C. Dairy-Res-Rep-La-Agric-Exp-Stn. Homer, La. : The Station. 1992. page 93-97. 0459-8504

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In vitro antimicrobial activity of a chitooligosaccharide mixture against Actinobacillus actinomycetemcomitans and Streptococcus mutans. Author(s): Department of Oral Biology, College of Dentistry, Yonsei University, 134 Shinchon-Dong, Seodaemun-Gu, Seoul, South Korea. Source: Choi, B K Kim, K Y Yoo, Y J Oh, S J Choi, J H Kim, C Y Int-J-Antimicrob-Agents. 2001 December; 18(6): 553-7 0924-8579

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Inhibition of hyaluronan synthesis in Streptococcus equi FM100 by 4methylumbelliferone. Author(s): Departments of Biochemistry and Bacteriology, Hirosaki University School of Medicine, Hirosaki, Japan. Source: Kakizaki, I Takagaki, K Endo, Y Kudo, D Ikeya, H Miyoshi, T Baggenstoss, B A Tlapak Simmons, V L Kumari, K Nakane, A Weigel, P H Endo, M Eur-J-Biochem. 2002 October; 269(20): 5066-75 0014-2956

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Involvement of protein kinase C and tyrosin kinase in tumoricidal activation of macrophage induced by Streptococcus pneumoniae type II capsular polysaccharide. Author(s): Division of Immunopharmacology, College of Pharmacy, Sungkyunkwan University, Suwon, Kyunggi-do, South Korea.

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Source: Um, Sung Hee Rhee, Dong Kwon Pyo, Suhkneung Int-Immunopharmacol. 2002 January; 2(1): 129-37 1567-5769 •

Optimization of medium and cultivation conditions for capsular polysaccharide production by Streptococcus pneumoniae serotype 23F. Author(s): Centro de Biotechnologia, Instituto Butanan, Av. Vital Brasil, Sao Paulo, SP, Brazil. [email protected] Source: Goncalves, V M Zangirolami, T C Giordano, R L Raw, I Tanizaki, M M Giordano, R C Appl-Microbiol-Biotechnol. 2002 September; 59(6): 713-7 0175-7598

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Prevalence of salivary Streptococcus mutans in mothers and in their preschool children. Author(s): Public Dental Clinic, Varberg, Sweden. Source: Thorild, I Lindau Jonson, B Twetman, S Int-J-Paediatr-Dent. 2002 January; 12(1): 2-7 0960-7439

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Relationship between caries status, colony forming units (cfu) of Streptococcus mutans and Snyder caries activity test. Author(s): HOD Microbiology, RLT College of Science, Akola, India. Source: Ali, Y A Chandranee, N J Wadher, B J Khan, A Khan, Z H J-Indian-Soc-PedodPrev-Dent. 1998 June; 16(2): 56-60 0970-4388

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Synthesis of Streptococcus pneumoniae type 3 neoglycoproteins varying in oligosaccharide chain length, loading and carrier protein. Author(s): Bijvoet Center, Department of Bio-Organic Chemistry Utrecht University, The Netherlands. Source: Lefeber, D J Kamerling, J P Vliegenthart, J F Chemistry. 2001 October 15; 7(20): 4411-21 0947-6539

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The auxotrophic nature of Streptococcus uberis: The acquisition of essential amino acids from plasmin derived casein peptides. Source: Kitt, A.J. Streptococci and the host /. New York : Plenum Press, c1997. page 647650. ISBN: 0306456036

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The effect of indigenous Neem (Adirachta indica) mouth wash on Streptococcus mutans and lactobacilli growth. Author(s): Dept. of Pedodontics & Preventive Dentistry, College of Dental Surgery, Manipal 570 119, India. Source: Vanka, A Tandon, S Rao, S R Udupa, N Indian-J-Dent-Res. 2001 Jul-September; 12(3): 133-44 0970-9290

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Unusual Streptococcus suis type 2 disease on two farms feeding incorrectly formulated nursery feed. Source: Drum, S.D. Hoffman, L.J. Swine-health-prod. Perry, IA : American Association of Swine Practitioners. Sept/October 1998. volume 6 (5) page 217-218. 1066-4963

Federal Resources on Nutrition In addition to the IBIDS, the United States Department of Health and Human Services (HHS) and the United States Department of Agriculture (USDA) provide many sources of information on general nutrition and health. Recommended resources include: •

healthfinder®, HHS’s gateway to health information, including diet and nutrition: http://www.healthfinder.gov/scripts/SearchContext.asp?topic=238&page=0

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The United States Department of Agriculture’s Web site dedicated to nutrition information: www.nutrition.gov

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The Food and Drug Administration’s Web site for federal food safety information: www.foodsafety.gov

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The National Action Plan on Overweight and Obesity sponsored by the United States Surgeon General: http://www.surgeongeneral.gov/topics/obesity/

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The Center for Food Safety and Applied Nutrition has an Internet site sponsored by the Food and Drug Administration and the Department of Health and Human Services: http://vm.cfsan.fda.gov/

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Center for Nutrition Policy and Promotion sponsored by the United States Department of Agriculture: http://www.usda.gov/cnpp/

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Food and Nutrition Information Center, National Agricultural Library sponsored by the United States Department of Agriculture: http://www.nal.usda.gov/fnic/

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Food and Nutrition Service sponsored by the United States Department of Agriculture: http://www.fns.usda.gov/fns/

Additional Web Resources A number of additional Web sites offer encyclopedic information covering food and nutrition. The following is a representative sample: •

AOL: http://search.aol.com/cat.adp?id=174&layer=&from=subcats

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Family Village: http://www.familyvillage.wisc.edu/med_nutrition.html

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Google: http://directory.google.com/Top/Health/Nutrition/

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Healthnotes: http://www.healthnotes.com/

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Open Directory Project: http://dmoz.org/Health/Nutrition/

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Yahoo.com: http://dir.yahoo.com/Health/Nutrition/

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WebMDHealth: http://my.webmd.com/nutrition

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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html

The following is a specific Web list relating to streptococcus; 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 Crème Fraîche Source: Healthnotes, Inc.; www.healthnotes.com Guava Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,139,00.html

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Kefir Source: Healthnotes, Inc.; www.healthnotes.com Lhassi Source: Healthnotes, Inc.; www.healthnotes.com Milk Source: Healthnotes, Inc.; www.healthnotes.com Yogurt Source: Healthnotes, Inc.; www.healthnotes.com Yogurt Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,97,00.html Yogurt Cheese Source: Healthnotes, Inc.; www.healthnotes.com

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CHAPTER 3. STREPTOCOCCUS

ALTERNATIVE

MEDICINE

AND

Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to streptococcus. At the conclusion of this chapter, we will provide additional sources.

National Center for Complementary and Alternative Medicine The National Center for Complementary and Alternative Medicine (NCCAM) of the National Institutes of Health (http://nccam.nih.gov/) has created a link to the National Library of Medicine’s databases to facilitate research for articles that specifically relate to streptococcus and complementary medicine. To search the database, go to the following Web site: http://www.nlm.nih.gov/nccam/camonpubmed.html. Select “CAM on PubMed.” Enter “streptococcus” (or synonyms) into the search box. Click “Go.” The following references provide information on particular aspects of complementary and alternative medicine that are related to streptococcus: •

A capillary electrophoretic study on the specificity of beta-galactosidases from Aspergillus oryzae, Escherichia coli, Streptococcus pneumoniae, and Canavalia ensiformis (jack bean). Author(s): Zeleny R, Altmann F, Praznik W. Source: Analytical Biochemistry. 1997 March 1; 246(1): 96-101. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9056188

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A possible mechanism for the cellular coaggregation between Actinomyces viscosus ATCC 19246 and Streptococcus sanguis ATCC 10557. Author(s): Sato S, Koga T, Inoue M. Source: J Gen Microbiol. 1984 June; 130 ( Pt 6): 1351-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6481336

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A role for Lewis a antigens on salivary agglutinin in binding to Streptococcus mutans. Author(s): Ligtenberg AJ, Veerman EC, Nieuw Amerongen AV. Source: Antonie Van Leeuwenhoek. 2000 January; 77(1): 21-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10696874

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Accuracy of broth microdilution and E test methods for detecting chloramphenicol acetyl transferase mediated resistance in Streptococcus pneumoniae: Geographic variations in the prevalence of resistance in The SENTRY Antimicrobial Surveillance Program (1999). Author(s): Deshpande LM, Jones RN, Pfaller MA; SENTRY Program Participants Group (Americas and Europe). Source: Diagnostic Microbiology and Infectious Disease. 2001 April; 39(4): 267-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11404073

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Activation of granulocytes by phorbol-12-myristate-14-acetate (PMA) enhances phagocytosis of Streptococcus pyogenes. Author(s): Schnitzler N, Schweizer K, Podbielski A, Haase G, Spellerberg B, Holland R, Lutticken R. Source: Advances in Experimental Medicine and Biology. 1997; 418: 897-902. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9331794

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Activities of Chromolaena odorata (Compositae) leaf extract against Pseudomonas aeruginosa and Streptococcus faecalis. Author(s): Irobi ON. Source: Journal of Ethnopharmacology. 1992 August; 37(1): 81-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1453706

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Activities of trovafloxacin, gatifloxacin, clinafloxacin, sparfloxacin, levofloxacin, and ciprofloxacin against penicillin-resistant Streptococcus pneumoniae in an in vitro infection model. Author(s): Hershberger E, Rybak MJ. Source: Antimicrobial Agents and Chemotherapy. 2000 March; 44(3): 598-601. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10681324

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Adsorption of saliva-coated and just-harvested Streptococcus sanguis to saliva-coated hydroxyapatite beads. Author(s): Tamura M, Kuroda K, Ueda Y, Saito N, Hirano Y, Hayashi K. Source: J Nihon Univ Sch Dent. 1995 September; 37(3): 170-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7490611

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An In vitro microbial-caries model used to study the efficacy of antibodies to Streptococcus mutans surface proteins in preventing dental caries. Author(s): Fontana M, Buller TL, Dunipace AJ, Stookey GK, Gregory RL.

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Source: Clinical and Diagnostic Laboratory Immunology. 2000 January; 7(1): 49-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10618276 •

An oxygen-induced but protein F-independent fibronectin-binding pathway in Streptococcus pyogenes. Author(s): Lee JY, Caparon M. Source: Infection and Immunity. 1996 February; 64(2): 413-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8550185

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Anticariogenic activity of licorice and glycyrrhizine I: Inhibition of in vitro plaque formation by Streptococcus mutans. Author(s): Segal R, Pisanty S, Wormser R, Azaz E, Sela MN. Source: Journal of Pharmaceutical Sciences. 1985 January; 74(1): 79-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3981425

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Antimicrobial activity of calcium hydroxide liners on Streptococcus sanguis and S. mutans. Author(s): Barkhordar RA, Kempler D. Source: The Journal of Prosthetic Dentistry. 1989 March; 61(3): 314-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2921748

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Autolysin-targeted LightCycler assay including internal process control for detection of Streptococcus pneumoniae DNA in clinical samples. Author(s): Sheppard CL, Harrison TG, Morris R, Hogan A, George RC. Source: Journal of Medical Microbiology. 2004 March; 53(Pt 3): 189-95. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14970243

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Calcium-binding properties of SSP-5, the Streptococcus gordonii M5 receptor for salivary agglutinin. Author(s): Duan Y, Fisher E, Malamud D, Golub E, Demuth DR. Source: Infection and Immunity. 1994 December; 62(12): 5220-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7960097

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Characteristics of a protease of Streptococcus sanguis G9B which degrades the major salivary adhesin. Author(s): Lamont RJ, Rosan B. Source: Fems Microbiology Letters. 1989 March; 49(1): 101-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2656394

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Characterization of a rat salivary sialoglycoprotein complex which agglutinates Streptococcus mutans. Author(s): Brack CM, Reynolds EC.

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Source: Infection and Immunity. 1987 May; 55(5): 1264-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3570462 •

Characterization of acid phosphatase activities in the equine pathogen Streptococcus equi. Author(s): Hamilton A, Harrington D, Sutcliffe IC. Source: Systematic and Applied Microbiology. 2000 October; 23(3): 325-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11108009

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Characterization of extracellular beta-lactamases from penicillin G-resistant cells of Streptococcus thermophilus. Author(s): Chirica LC, Guray T, Gurakan GC, Bozoglu TF. Source: J Food Prot. 1998 July; 61(7): 896-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9678176

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Characterization of mechanisms involved in uptake of Streptococcus dysgalactiae by bovine mammary epithelial cells. Author(s): Calvinho LF, Oliver SP. Source: Veterinary Microbiology. 1998 October; 63(2-4): 261-74. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9851004

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Characterization of the interaction of bovine plasmin with Streptococcus uberis. Author(s): Lincoln RA, Leigh JA. Source: Journal of Applied Microbiology. 1998 June; 84(6): 1104-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9717296

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Cloning and expression of a Streptococcus sanguis surface antigen that interacts with a human salivary agglutinin. Author(s): Demuth DR, Davis CA, Corner AM, Lamont RJ, Leboy PS, Malamud D. Source: Infection and Immunity. 1988 September; 56(9): 2484-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3410546

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Cloning, over-expression, purification, and characterisation of N-acetylneuraminate synthase from Streptococcus agalactiae. Author(s): Suryanti V, Nelson A, Berry A. Source: Protein Expression and Purification. 2003 February; 27(2): 346-56. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12597896

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Coaggregation of Streptococcus salivarius with periodontopathogens: evidence for involvement of fimbriae in the interaction with Prevotella intermedia. Author(s): Levesque C, Lamothe J, Frenette M.

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Source: Oral Microbiology and Immunology. 2003 October; 18(5): 333-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12930529 •

Coaggregation of Streptococcus sanguis and other streptococci with Candida albicans. Author(s): Jenkinson HF, Lala HC, Shepherd MG. Source: Infection and Immunity. 1990 May; 58(5): 1429-36. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2182544

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Combination therapy with traditional Chinese medicines and Streptococcus pyogenes products (OK 432) for endogenous tumor necrosis factor therapy. A preliminary report. Author(s): Haranaka K, Sakurai A, Satomi N, Ono T, Haranaka R. Source: Cancer Biother. 1995 Summer; 10(2): 131-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7663572

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Comparative recovery of Streptococcus mutans on five isolation media, including a new simple selective medium. Author(s): Schaeken MJ, van der Hoeven JS, Franken HC. Source: Journal of Dental Research. 1986 June; 65(6): 906-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2940275

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Complete amino acid sequence and comparative molecular modelling of HPr from Streptococcus mutans Ingbritt. Author(s): Dashper SG, Kirszbaum L, Huq NL, Riley PF, Reynolds EC. Source: Biochemical and Biophysical Research Communications. 1994 March 30; 199(3): 1297-304. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8147873

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Covalent linkage between the capsular polysaccharide and the cell wall peptidoglycan of Streptococcus pneumoniae revealed by immunochemical methods. Author(s): Sorensen UB, Henrichsen J, Chen HC, Szu SC. Source: Microbial Pathogenesis. 1990 May; 8(5): 325-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2215183

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Cytoplasmic membrane lipoprotein LppC of Streptococcus equisimilis functions as an acid phosphatase. Author(s): Malke H. Source: Applied and Environmental Microbiology. 1998 July; 64(7): 2439-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9647812

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Detection of C-polysaccharide in serum of patients with Streptococcus pneumoniae bacteraemia. Author(s): Gillespie SH, Smith MD, Dickens A, Raynes JG, McAdam KP.

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Source: Journal of Clinical Pathology. 1995 September; 48(9): 803-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7490310 •

Development of a polymerase chain reaction assay to detect the presence of Streptococcus pneumoniae DNA. Author(s): Friedland LR, Menon AG, Reising SF, Ruddy RM, Hassett DJ. Source: Diagnostic Microbiology and Infectious Disease. 1994 December; 20(4): 187-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7705031

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Diagnosis of invasive pneumococcal infection by PCR amplification of Streptococcus pneumoniae genomic fragments in blood: a multi-centre comparative study. Author(s): Sheppard CL, Harrison TG, Kearns AM, Guiver M, Creek M, Evans R, Smith MD, Eltringham G, Cartwright KA, George RC. Source: Commun Dis Public Health. 2003 September; 6(3): 221-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14708272

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Effect of bifidobacterium Bb12 with or without Streptococcus thermophilus supplemented formula on nutritional status. Author(s): Nopchinda S, Varavithya W, Phuapradit P, Sangchai R, Suthutvoravut U, Chantraruksa V, Haschke F. Source: J Med Assoc Thai. 2002 November; 85 Suppl 4: S1225-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12549799

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Effect of tea polyphenols on glucan synthesis by glucosyltransferase from Streptococcus mutans. Author(s): Hattori M, Kusumoto IT, Namba T, Ishigami T, Hara Y. Source: Chemical & Pharmaceutical Bulletin. 1990 March; 38(3): 717-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2140716

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Effects of a mixture of organisms, Lactobacillus acidophilus or Streptococcus faecalis on cholesterol metabolism in rats fed on a fat- and cholesterol-enriched diet. Author(s): Fukushima M, Nakano M. Source: The British Journal of Nutrition. 1996 December; 76(6): 857-67. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9014654

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Effects of a mixture of organisms, Lactobacillus acidophilus or Streptococcus faecalis on delta6-desaturase activity in the livers of rats fed a fat- and cholesterol-enriched diet. Author(s): Fukushima M, Yamada A, Endo T, Nakano M. Source: Nutrition (Burbank, Los Angeles County, Calif.). 1999 May; 15(5): 373-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10355850

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Efficacy of extract of Pelargonium sidoides in children with acute non-group A betahemolytic streptococcus tonsillopharyngitis: a randomized, double-blind, placebocontrolled trial. Author(s): Bereznoy VV, Riley DS, Wassmer G, Heger M. Source: Alternative Therapies in Health and Medicine. 2003 September-October; 9(5): 6879. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14526713

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Efficacy of high-dose amoxicillin-clavulanate against experimental respiratory tract infections caused by strains of Streptococcus pneumoniae. Author(s): Woodnutt G, Berry V. Source: Antimicrobial Agents and Chemotherapy. 1999 January; 43(1): 35-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9869562

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Electric transmembrane potential mutation and resistance to the cationic and amphiphilic antitumoral drugs derived from pyridocarbazole, 2-Nmethylellipticinium and 2-N-methyl-9-hydroxyellipticinium, in Streptococcus pneumoniae. Author(s): Sautereau AM, Trombe MC. Source: J Gen Microbiol. 1986 September; 132 ( Pt 9): 2637-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3794659

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Encapsulation of Streptococcus uberis: influence of storage and cultural conditions. Author(s): Matthews KR, Jayarao BM, Guidry AJ, Erbe EF, Wergin WP, Oliver SP. Source: Veterinary Microbiology. 1994 April; 39(3-4): 361-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7518989

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Enhanced toxicity of copper for Streptococcus mutans under anaerobic conditions. Author(s): Evans SL, Tolbert C, Arceneaux JE, Byers BR. Source: Antimicrobial Agents and Chemotherapy. 1986 February; 29(2): 342-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3087278

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Expression of the hemolysin trait in a proteolytic transconjugant of Streptococcus faecalis. Author(s): Casas IA, Marquez E, Zimmerman LN. Source: Biochimie. 1988 February; 70(2): 283-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3134952

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Extract of Juglandaceae regia inhibits growth, in-vitro adherence, acid production and aggregation of Streptococcus mutans. Author(s): Jagtap AG, Karkera SG.

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Extraction, assay, and analysis of antimicrobials from plants with activity against dental pathogens (Streptococcus sp.) Author(s): Tichy J, Novak J. Source: Journal of Alternative and Complementary Medicine (New York, N.Y.). 1998 Spring; 4(1): 39-45. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9553834

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Glucosyltransferase mediates adhesion of Streptococcus gordonii to human endothelial cells in vitro. Author(s): Vacca-Smith AM, Jones CA, Levine MJ, Stinson MW. Source: Infection and Immunity. 1994 June; 62(6): 2187-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8188339

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Group B Streptococcus endogenous endophthalmitis : case reports and review of the literature. Author(s): Lee SY, Chee SP. Source: Ophthalmology. 2002 October; 109(10): 1879-86. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12359609

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High rates of multiple antibiotic resistance in Streptococcus pneumoniae from healthy children living in isolated rural communities: association with cephalosporin use and intrafamilial transmission. Author(s): Samore MH, Magill MK, Alder SC, Severina E, Morrison-De Boer L, Lyon JL, Carroll K, Leary J, Stone MB, Bradford D, Reading J, Tomasz A, Sande MA. Source: Pediatrics. 2001 October; 108(4): 856-65. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11581436

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Identification and analysis of a collagenolytic activity in Streptococcus mutans. Author(s): Jackson RJ, Lim DV, Dao ML. Source: Current Microbiology. 1997 January; 34(1): 49-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8939802

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Identification and characterisation of two extracellular proteases of Streptococcus mutans. Author(s): Harrington DJ, Russell RR. Source: Fems Microbiology Letters. 1994 August 15; 121(2): 237-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7926676

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Identification and characterization of a surface protein-releasing activity in Streptococcus mutans and other pathogenic streptococci. Author(s): Lee SF. Source: Infection and Immunity. 1992 October; 60(10): 4032-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1398915

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Identification and epidemiological characterization of Streptococcus uberis isolated from bovine mastitis using conventional and molecular methods. Author(s): Khan IU, Hassan AA, Abdulmawjood A, Lammler C, Wolter W, Zschock M. Source: Journal of Veterinary Science (Suwon-Si, Korea). 2003 December; 4(3): 213-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14685025

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Identification of a molecule of Porphyromonas gingivalis that binds to Streptococcus gordonii. Author(s): Lamont RJ, Hsiao GW, Gil S. Source: Microbial Pathogenesis. 1994 November; 17(5): 355-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7723662

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In vitro activity of propolis against Streptococcus pyogenes. Author(s): Bosio K, Avanzini C, D'Avolio A, Ozino O, Savoia D. Source: Letters in Applied Microbiology. 2000 August; 31(2): 174-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10972723

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In vitro antibacterial effect of RC-Prep components on Streptococcus sobrinus. Author(s): Steinberg D, Abid-el-Raziq D, Heling I. Source: Endodontics & Dental Traumatology. 1999 August; 15(4): 171-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10815566

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In vitro survival of Bacteroides intermedius in five transport media, alone or in the presence of Streptococcus sanguis. Author(s): Deveaux E, Delplanque P, Neut C, Charon J, Romond C. Source: Oral Microbiology and Immunology. 1990 December; 5(6): 320-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2129136

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In vitro susceptibilities of Shigella flexneri and Streptococcus pyogenes to inner gel of Aloe barbadensis Miller. Author(s): Ferro VA, Bradbury F, Cameron P, Shakir E, Rahman SR, Stimson WH. Source: Antimicrobial Agents and Chemotherapy. 2003 March; 47(3): 1137-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12604556

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Induction of an AP endonuclease activity in Streptococcus mutans during growth at low pH. Author(s): Hahn K, Faustoferri RC, Quivey RG Jr.

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Influence of monocytes and antibiotic treatment on tissue factor activity of endocardial vegetations in rabbits infected with Streptococcus sanguis. Author(s): Bancsi MJ, Veltrop MH, Bertina RM, Thompson J. Source: Infection and Immunity. 1996 February; 64(2): 448-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8550190

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Influence of protein kinase inhibitors on Streptococcus uberis internalization into bovine mammary epithelial cells. Author(s): Almeida RA, Calvinho LF, Oliver SP. Source: Microbial Pathogenesis. 2000 January; 28(1): 9-16. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10623559

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Inhibition of acid production by Streptococcus mutans NCTC 10449 by zinc and the effect of metal speciation. Author(s): Watson GK, Cummins D, van der Ouderaa FJ. Source: Caries Research. 1991; 25(6): 431-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1810655

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Inhibition of glucosyltransferase from Streptococcus mutans by oleanolic acid and ursolic acid. Author(s): Kozai K, Miyake Y, Kohda H, Kametaka S, Yamasaki K, Suginaka H, Nagasaka N. Source: Caries Research. 1987; 21(2): 104-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2949844

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Intrapulmonary bacterial clearance of type III group B streptococcus is reduced in preterm compared with term rabbits and occurs independent of antibody. Author(s): Hall SL, Sherman MP. Source: Am Rev Respir Dis. 1992 May; 145(5): 1172-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1586063

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In-vitro activity of the essential oil of Melaleuca alternifolia against Streptococcus spp. Author(s): Carson CF, Hammer KA, Riley TV. Source: The Journal of Antimicrobial Chemotherapy. 1996 June; 37(6): 1177-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8836821

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Involvement of protein kinase C and tyrosin kinase in tumoricidal activation of macrophage induced by Streptococcus pneumoniae type II capsular polysaccharide. Author(s): Um SH, Rhee DK, Pyo S.

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LiCl treatment releases a nickase implicated in genetic transformation of Streptococcus pneumoniae. Author(s): Fujii T, Naka D, Toyoda N, Seto H. Source: Journal of Bacteriology. 1987 November; 169(11): 4901-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2822653

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Mechanisms of platelet aggregation by Streptococcus sanguis, a causative organism in infective endocarditis. Author(s): Ford I, Douglas CW, Preston FE, Lawless A, Hampton KK. Source: British Journal of Haematology. 1993 May; 84(1): 95-100. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8338784

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Metal ion inactivation and chelator stimulation of Streptococcus mitis arginine aminopeptidase. Author(s): Hiraoka BY, Fukasawa K, Harada M. Source: Molecular and Cellular Biochemistry. 1987 February; 73(2): 111-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3104766

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Mitogenic factor secreted by Streptococcus pyogenes is a heat-stable nuclease requiring His122 for activity. Author(s): Iwasaki M, Igarashi H, Yutsudo T. Source: Microbiology (Reading, England). 1997 July; 143 ( Pt 7): 2449-55. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9245825

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Molecular mechanisms of resistance to commonly used non-betalactam drugs in Streptococcus pneumoniae. Author(s): Widdowson CA, Klugman KP. Source: Seminars in Respiratory Infections. 1999 September; 14(3): 255-68. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10501313

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Partial characterization of Streptococcus suis type 2 hemolysin. Author(s): Feder I, Chengappa MM, Fenwick B, Rider M, Staats J. Source: Journal of Clinical Microbiology. 1994 May; 32(5): 1256-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8051253

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PCR detection of Bifidobacterium strains and Streptococcus thermophilus in feces of human subjects after oral bacteriotherapy and yogurt consumption. Author(s): Brigidi P, Swennen E, Vitali B, Rossi M, Matteuzzi D.

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Peroxidase-catalyzed generation of catechin oligomers that inhibit glucosyltransferase from Streptococcus sobrinus. Author(s): Hamada S, Kontani M, Hosono H, Ono H, Tanaka T, Ooshima T, Mitsunaga T, Abe I. Source: Fems Microbiology Letters. 1996 September 15; 143(1): 35-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8807799

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Predominance of serotype V and frequency of erythromycin resistance in Streptococcus agalactiae in Ohio. Author(s): Croak A, Abate G, Goodrum K, Modrzakowski M. Source: American Journal of Obstetrics and Gynecology. 2003 May; 188(5): 1148-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12748459

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Prevention of dental caries by Oriental folk medicines--active principles of Zizyphi Fructus for inhibition of insoluble glucan formation by cariogenic bacterium Streptococcus mutans. Author(s): Kohda H, Kozai K, Nagasaka N, Miyake Y, Suginaka H, Hidaka K, Yamasaki K. Source: Planta Medica. 1986 April; (2): 119-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3725931

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Production of immunoglobulin A protease by Streptococcus pneumoniae from animals. Author(s): Proctor M, Manning PJ. Source: Infection and Immunity. 1990 September; 58(9): 2733-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2117567

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Properties of ATP-dependent protein kinase from Streptococcus pyogenes that phosphorylates a seryl residue in HPr, a phosphocarrier protein of the phosphotransferase system. Author(s): Reizer J, Novotny MJ, Hengstenberg W, Saier MH Jr. Source: Journal of Bacteriology. 1984 October; 160(1): 333-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6434522

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Protective effect of Plantago major L. Pectin polysaccharide against systemic Streptococcus pneumoniae infection in mice. Author(s): Hetland G, Samuelsen AB, Lovik M, Paulsen BS, Aaberge IS, Groeng EC, Michaelsen TE.

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Purification and characterization of a cell wall proteinase from Streptococcus lactis NCDO 763. Author(s): Monnet V, Le Bars D, Gripon JC. Source: The Journal of Dairy Research. 1987 May; 54(2): 247-55. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3110230

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Purification and characterization of a general aminopeptidase (St-PepN) from Streptococcus salivarius ssp. thermophilus CNRZ 302. Author(s): Rul F, Monnet V, Gripon JC. Source: Journal of Dairy Science. 1994 October; 77(10): 2880-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7836577

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Purification and characterization of a novel metalloendopeptidase from Streptococcus cremoris H61. A metalloendopeptidase that recognizes the size of its substrate. Author(s): Yan TR, Azuma N, Kaminogawa S, Yamauchi K. Source: European Journal of Biochemistry / Febs. 1987 March 2; 163(2): 259-65. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3545830

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Purification and characterization of an aminopeptidase from Streptococcus mitis ATCC 903. Author(s): Andersson C, Linder LE, Sund ML, Lonnies H. Source: Current Microbiology. 1992 November; 25(5): 261-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1369197

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Purification and characterization of an intracellular N-terminal exopeptidase from Streptococcus durans. Author(s): Machuga EJ. Source: Biochimica Et Biophysica Acta. 1984 July 30; 800(2): 127-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6430350

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Purification and immunological characterization of neuraminidase produced by Streptococcus pneumoniae. Author(s): Lock RA, Paton JC, Hansman D. Source: Microbial Pathogenesis. 1988 January; 4(1): 33-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3143891

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Purification and partial characterization of an intracellular aminopeptidase from Streptococcus salivarius subsp. thermophilus strain ACA-DC 114. Author(s): Tsakalidou E, Kalantzopoulos G.

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Purification and preliminary characterization of exo-beta-D-fructosidase in Streptococcus salivarius KTA-19. Author(s): Takahashi N, Mizuno F, Takamori K. Source: Infection and Immunity. 1985 January; 47(1): 271-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3965399

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Purification, characterization, and gene cloning of lysyl aminoeptidase from Streptococcus thermophilus YRC001. Author(s): Motoshima H, Shiraishi T, Tsukasaki F, Kaminogawa S. Source: Bioscience, Biotechnology, and Biochemistry. 2003 April; 67(4): 772-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12784617

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Relation between serum opsonic activity for Streptococcus pneumoniae and complement function in sickle cell disease. Author(s): Bjornson AB, Lobel JS, Harr KS. Source: The Journal of Infectious Diseases. 1985 October; 152(4): 701-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3930618

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Relationship between the uptake and cytotoxicity of celiptium in wild type and resistant mutants of the bacterium Streptococcus pneumoniae. Author(s): Sautereau AM, Tocanne JF, Trombe MC. Source: Biochemical and Biophysical Research Communications. 1987 June 15; 145(2): 927-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3593380

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Release of the component of Streptococcus faecalis Na(+)-ATPase from the membranes. Author(s): Kakinuma Y, Igarashi K. Source: Febs Letters. 1990 October 1; 271(1-2): 102-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2146151

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Screening of Taiwanese crude drugs for antibacterial activity against Streptococcus mutans. Author(s): Chen CP, Lin CC, Namba T. Source: Journal of Ethnopharmacology. 1989 December; 27(3): 285-95. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2615434

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Searching for acute poststreptococcal glomerulonephritis-associated Streptococcus pyogenes in Australian aboriginal communities. Author(s): Goodfellow AM, Gardiner DL.

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Simplified protocol for pulsed-field gel electrophoresis analysis of Streptococcus pneumoniae. Author(s): McEllistrem MC, Stout JE, Harrison LH. Source: Journal of Clinical Microbiology. 2000 January; 38(1): 351-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10618114

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Some features of the Streptococcus faecalis Na(+)-ATPase resemble those of the vacuolar-type ATPases. Author(s): Kakinuma Y, Igarashi K. Source: Febs Letters. 1990 October 1; 271(1-2): 97-101. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2146156

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Streptococcus thermophilus and its biosurfactants inhibit adhesion by Candida spp. on silicone rubber. Author(s): Busscher HJ, van Hoogmoed CG, Geertsema-Doornbusch GI, van der KuijlBooij M, van der Mei HC. Source: Applied and Environmental Microbiology. 1997 October; 63(10): 3810-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9327543

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Studies on dental caries prevention by traditional medicines. VIII. Inhibitory effect of various tannins on glucan synthesis by glucosyltransferase from Streptococcus mutans. Author(s): Kakiuchi N, Hattori M, Nishizawa M, Yamagishi T, Okuda T, Namba T. Source: Chemical & Pharmaceutical Bulletin. 1986 February; 34(2): 720-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2939967

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Studies on dental caries prevention by traditional medicines. X. Antibacterial action of phenolic components from mace against Streptococcus mutans. Author(s): Hattori M, Hada S, Watahiki A, Ihara H, Shu YZ, Kakiuchi N, Mizuno T, Namba T. Source: Chemical & Pharmaceutical Bulletin. 1986 September; 34(9): 3885-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3815609

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Synergism and mechanism of subinhibitory concentration of streptomycin on Streptococcus faecalis. Author(s): Fuursted K. Source: Apmis : Acta Pathologica, Microbiologica, Et Immunologica Scandinavica. 1989 January; 97(1): 27-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2492428

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The effect of betel nut extracts on dehydrogenase activity of Streptococcus mutans GS 5. Author(s): Koontongkaew S, Thaweboon B. Source: J Dent Assoc Thai. 1986 November-December; 36(6): 223-8. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3478385

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The effect of dietary fish oil on survival after infection with Klebsiella pneumoniae or Streptococcus pneumoniae. Author(s): Thors VS, Thorisdottir A, Erlendsdottir H, Einarsson I, Gudmundsson S, Gunnarsson E, Haraldsson A. Source: Scandinavian Journal of Infectious Diseases. 2004; 36(2): 102-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15061662

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The effect of indigenous Neem Azadirachta indica [correction of (Adirachta indica)] mouth wash on Streptococcus mutans and lactobacilli growth. Author(s): Vanka A, Tandon S, Rao SR, Udupa N, Ramkumar P. Source: Indian J Dent Res. 2001 July-September; 12(3): 133-44. Erratum In: Indian J Dent Res 2001 October-December; 12(4): 193. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11808064

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The growth inhibition of Streptococcus mutans by 5'-nucleotidase inhibitors from Areca catechu L. Author(s): Iwamoto M, Uchino K, Toukairin T, Kawaguchi K, Tatebayashi T, Ogawara H, Tonosaki Y. Source: Chemical & Pharmaceutical Bulletin. 1991 May; 39(5): 1323-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1914009

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The human polymeric immunoglobulin receptor binds to Streptococcus pneumoniae via domains 3 and 4. Author(s): Lu L, Lamm ME, Li H, Corthesy B, Zhang JR. Source: The Journal of Biological Chemistry. 2003 November 28; 278(48): 48178-87. Epub 2003 September 17. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=13679368

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Use of Gen-Probe AccuProbe Group B streptococcus test to detect group B streptococci in broth cultures of vaginal-anorectal specimens from pregnant women: comparison with traditional culture method. Author(s): Bourbeau PP, Heiter BJ, Figdore M. Source: Journal of Clinical Microbiology. 1997 January; 35(1): 144-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8968896

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Xanthorrhizol: a potential antibacterial agent from Curcuma xanthorrhiza against Streptococcus mutans. Author(s): Hwang JK, Shim JS, Baek NI, Pyun YR. Source: Planta Medica.

Additional Web Resources A number of additional Web sites offer encyclopedic information covering CAM and related topics. The following is a representative sample: •

Alternative Medicine Foundation, Inc.: http://www.herbmed.org/

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AOL: http://search.aol.com/cat.adp?id=169&layer=&from=subcats

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Chinese Medicine: http://www.newcenturynutrition.com/

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drkoop.com: http://www.drkoop.com/InteractiveMedicine/IndexC.html

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Family Village: http://www.familyvillage.wisc.edu/med_altn.htm

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Google: http://directory.google.com/Top/Health/Alternative/

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Healthnotes: http://www.healthnotes.com/

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MedWebPlus: http://medwebplus.com/subject/Alternative_and_Complementary_Medicine

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Open Directory Project: http://dmoz.org/Health/Alternative/

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HealthGate: http://www.tnp.com/

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WebMDHealth: http://my.webmd.com/drugs_and_herbs

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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html

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Yahoo.com: http://dir.yahoo.com/Health/Alternative_Medicine/

The following is a specific Web list relating to streptococcus; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: •

General Overview Diarrhea Source: Healthnotes, Inc.; www.healthnotes.com Ear Infection Source: Integrative Medicine Communications; www.drkoop.com Meningitis Source: Integrative Medicine Communications; www.drkoop.com Otitis Media Source: Integrative Medicine Communications; www.drkoop.com

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Ulcerative Colitis Source: Healthnotes, Inc.; www.healthnotes.com •

Herbs and Supplements Acidophilus and Other Probiotics Source: Prima Communications, Inc.www.personalhealthzone.com Barberry Alternative names: Berberis vulgaris Source: Healthnotes, Inc.; www.healthnotes.com Barberry Alternative names: Berberis vulgaris, Berberry Source: Integrative Medicine Communications; www.drkoop.com Berberis Vulgaris Source: Integrative Medicine Communications; www.drkoop.com Berberry Source: Integrative Medicine Communications; www.drkoop.com Betula Alternative names: Birch; Betula sp. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Cinnamomum Alternative names: Cinnamon; Cinnamomum zeylanicum Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Eucalyptus Alternative names: Eucalyptus globulus Source: Healthnotes, Inc.; www.healthnotes.com Eugenia Clove Alternative names: Cloves; Eugenia sp. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Glycyrrhiza Alternative names: Licorice; Glycyrrhiza glabra L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Goldenseal Alternative names: Hydrastis canadensis Source: Integrative Medicine Communications; www.drkoop.com Gymnema Alternative names: Gurmar; Gymnema sylvestre Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Hydrastis Canadensis Source: Integrative Medicine Communications; www.drkoop.com

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Melaleuca Alternative names: Tea Tree Oil; Melaleuca alternifolia Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Oregon Grape Alternative names: Berberis aquifolium Source: Healthnotes, Inc.; www.healthnotes.com Pygeum Alternative names: African Prune; Pygeum africanum Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Sambucus Alternative names: Black Elderberry; Sambucus nigra L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Sanguinaria Alternative names: Bloodroot; Sanguinaria canadensis L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Stevia Alternative names: Sweetleaf; Stevia rebaudiana Bertoni Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Thuja Plicata Alternative names: Western Red Cedar Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Zingiber Alternative names: Ginger; Zingiber officinale Roscoe Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Zizyphus Alternative names: Jujube; Ziziphus sp. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org

General References A good place to find general background information on CAM is the National Library of Medicine. It has prepared within the MEDLINEplus system an information topic page dedicated to complementary and alternative medicine. To access this page, go to the MEDLINEplus site at http://www.nlm.nih.gov/medlineplus/alternativemedicine.html. This Web site provides a general overview of various topics and can lead to a number of general sources.

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CHAPTER 4. DISSERTATIONS ON STREPTOCOCCUS Overview In this chapter, we will give you a bibliography on recent dissertations relating to streptococcus. 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 “streptococcus” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on streptococcus, we have not necessarily excluded nonmedical dissertations in this bibliography.

Dissertations on Streptococcus 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 streptococcus. 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: •

Adhesion and Internalization of Group A Streptococcus Isolates Found in Hawaii by Abe, Lucienne Merica; PhD from University of Hawai'i, 2003, 124 pages http://wwwlib.umi.com/dissertations/fullcit/3099050

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Characterization of a Secondary Sigma Factor from Streptococcus Pyogenes by Opdyke, Jason Alexander; PhD from Emory University, 2003, 175 pages http://wwwlib.umi.com/dissertations/fullcit/3080348

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Characterization of Potential Virulence Determinants in the Fish and Human Pathogen Streptococcus Iniae by Fuller, Jeffrey David; PhD from University of Toronto (Canada), 2003, 199 pages http://wwwlib.umi.com/dissertations/fullcit/NQ78389

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Effect of Interaction between Streptococcus Lactis and Aspergillus Flavus on the Production of Aflatoxin by Coallier-Ascah, Josée; PhD from Mcgill University (Canada), 1982 http://wwwlib.umi.com/dissertations/fullcit/NK58070

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Enzymatic and Structural Characterization of Choline Kinase and Ctp:phosphocholine Cytidylyltransferase from Streptococcus Pneumoniae by Campbell, Heidi Adams; PhD from University of Michigan, 2003, 145 pages http://wwwlib.umi.com/dissertations/fullcit/3096060

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Epidemiological Studies of Inflammatory Airway Disease in Horses (actinobacillus, Pasteurella, Mycoplasma Felis, Streptococcus Zooepidemicus) by Newton, J. Richard; PhD from Open University (United Kingdom), 2003 http://wwwlib.umi.com/dissertations/fullcit/f80289

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Etudes des Proteines de Streptococcus Suis Serotype 2 Associees a l'Etablissement de l'Infection (French and English Text) by Brassard, Julie; PhD from Universite De Montreal (Canada), 2003, 188 pages http://wwwlib.umi.com/dissertations/fullcit/NQ82720

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Hyaluronate Lyase Gene of Streptococcus Pyogenes: Molecular Characterization and Regulation by Walton, Sheryl Lynne; PhD from Old Dominion University, 2003, 168 pages http://wwwlib.umi.com/dissertations/fullcit/3090830

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Immunomodulation by an Anti-Streptococcus Mutans Monoclonal Antibody by Rhodin, Nikki R.; PhD from University of Florida, 2003, 132 pages http://wwwlib.umi.com/dissertations/fullcit/3096664

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Involvement of an Amino Acid Transporter in the Acid Tolerance of Streptococcus Mutans by Lackovic, Kresimir Petar; MSc from University of Toronto (Canada), 2003, 119 pages http://wwwlib.umi.com/dissertations/fullcit/MQ78520

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Modulation of Streptococcus Pneumoniae Capsule Production by Autophosphorylating Tyrosine Kinase Activity by Bender, Matthew Harry; PhD from The University of Alabama at Birmingham, 2003, 130 pages http://wwwlib.umi.com/dissertations/fullcit/3101527

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Peroxide Resistance in Streptococcus Pyogenes by King-Casas, Katherine Yudeh; PhD from Washington University, 2003, 167 pages http://wwwlib.umi.com/dissertations/fullcit/3095530

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Streptococcus Equi Studies on Vaccination and Adherence to Epithelial Cells of Horses by Srivastava, Satish Kumar; PhD from University of Guelph (Canada), 1982 http://wwwlib.umi.com/dissertations/fullcit/NK55572

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Streptococcus Sanguis Adhesins Mediating Attachment to Saliva-coated Hydroxyapatite Beads by Ganeshkumar, Nadarajah; PhD from The University of British Columbia (Canada), 1988 http://wwwlib.umi.com/dissertations/fullcit/NL47358

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Sublethal Heat Damage to Streptococcus Faecium Nrc 1261 by Duitschaever, Cyriel L; PhD from University of Guelph (Canada), 1975 http://wwwlib.umi.com/dissertations/fullcit/NK22690

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The Role of Hydrogen Peroxide Production in the Biology of Streptococcus Pneumoniae by Pericone, Christopher David; PhD from University of Pennsylvania, 2003, 174 pages http://wwwlib.umi.com/dissertations/fullcit/3087448

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The Role of Pneumococcal Surface Protein A in Virulence of a Capsular Serotype 3 Streptococcus Pneumoniae: Complement Attack Versus Bacterial Evasion by Ren, Bing; , PhD from The University of Alabama at Birmingham, 2003, 139 pages http://wwwlib.umi.com/dissertations/fullcit/3101546

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The Synthesis and Fate of Cyclic 3',5'-adenosine Monophosphate in Streptococcus Salivarius by Khandelwal, Ramji Lal; PhD from The University of Manitoba (Canada), 1972 http://wwwlib.umi.com/dissertations/fullcit/NK12670

Keeping Current Ask the medical librarian at your library if it has full and unlimited access to the ProQuest Digital Dissertations database. From the library, you should be able to do more complete searches via http://wwwlib.umi.com/dissertations.

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CHAPTER 5. PATENTS ON STREPTOCOCCUS Overview Patents can be physical innovations (e.g. chemicals, pharmaceuticals, medical equipment) or processes (e.g. treatments or diagnostic procedures). The United States Patent and Trademark Office defines a patent as a grant of a property right to the inventor, issued by the Patent and Trademark Office.8 Patents, therefore, are intellectual property. For the United States, the term of a new patent is 20 years from the date when the patent application was filed. If the inventor wishes to receive economic benefits, it is likely that the invention will become commercially available within 20 years of the initial filing. It is important to understand, therefore, that an inventor’s patent does not indicate that a product or service is or will be commercially available. The patent implies only that the inventor has “the right to exclude others from making, using, offering for sale, or selling” the invention in the United States. While this relates to U.S. patents, similar rules govern foreign patents. In this chapter, we show you how to locate information on patents and their inventors. If you find a patent that is particularly interesting to you, contact the inventor or the assignee for further information. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical patents that use the generic term “streptococcus” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on streptococcus, we have not necessarily excluded nonmedical patents in this bibliography.

Patents on Streptococcus By performing a patent search focusing on streptococcus, you can obtain information such as the title of the invention, the names of the inventor(s), the assignee(s) or the company that owns or controls the patent, a short abstract that summarizes the patent, and a few excerpts from the description of the patent. The abstract of a patent tends to be more technical in nature, while the description is often written for the public. Full patent descriptions contain much more information than is presented here (e.g. claims, references, figures, diagrams, etc.). We will tell you how to obtain this information later in the chapter. The following is an 8Adapted

from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.

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example of the type of information that you can expect to obtain from a patent search on streptococcus: •

Antibacterial chiral 8-(substituted piperidino)-benzo [i,j] quinolizines, processes, compositions and methods of treatment Inventor(s): Agarwal; Shiv Kumar (Aurangabad, IN), Bhawsar; Satish B (Aurangabad, IN), De Souza; Noel John (Mumbai, IN), Gupte; Shirkant V (Aurangabad, IN), Jafri; Mohammad A (Uttar Pradesh, IN), Patel; Mahesh Vithalbhai (Aurangabad, IN), Upadhyay; Dilip J (Mumbai, IN) Assignee(s): Wockhardt Limited (mumbai, In) Patent Number: 6,608,078 Date filed: May 7, 2001 Abstract: The present invention relates to optically pure 8-(substituted piperidino)benzo[i,j]quinolizines, their isomers, derivatives, salts, pseudopolymorphs, polymorphs prodrugs and hydrates thereof, to processes for their preparation, and to pharmaceutical compositions comprising 8-(substituted piperidino)-benzo[i,j]quinolizines their isomers, derivatives, salts, pseudopolymorphs, polymorphs and hydrates thereof. These compounds and compositions possess potent activity in treating local and systemic infections, particularly infections caused by sensitive and resistant Gram-positive organism infections, Gram-negative organism infections, mycobacterial infections and nosocomial pathogens, and particularly those belonging to the staphylococcus, streptococcus and enterococcus groups. Methods for treating the diseases and disorders arising from the foregoing infections in humans and animals are described by administering the compounds of the invention to said humans and animals. Excerpt(s): This invention relates to 8-(substituted piperidino)-benzo[i,j]quinolizines, to processes for their preparation and to pharmaceutical compositions comprising 8(substituted piperidino)-benzo[i,j]quinolizines. These compounds and compositions possess potent activity in treating local and systemic infections, particularly infections caused by sensitive and resistant Gram-positive organisms, Gram-negative organisms, mycobacteria and nosocomial pathogens, and particularly those belonging to the staphylococcus, streptococcus and enterococcus groups. Also, disclosed are methods for treating the diseases and disorders arising from the foregoing infections in humans and animals by administering the compounds of the invention to said humans and animals. Web site: http://www.delphion.com/details?pn=US06608078__

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Antisense RNA expression strategies effective against Streptococcus thermophilus bacteriophages Inventor(s): Klaenhammer; Todd Robert (Raleigh, NC), Sturino; Joseph Miland (Raleigh, NC) Assignee(s): North Carolina State University (raleigh, Nc) Patent Number: 6,686,192 Date filed: August 21, 2000 Abstract: Recombinant bacteria containing nucleotide sequences encoding Streptococcus thermophilus phage helicase and primase genes expressed in the antisense orientation and methods of making and using the same are disclosed.

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Replication of bacteriophage infecting this bacterial cell, can be inhibited or decreased by constitutively expressing, the antisense oligonucleotide encoding for S. thermophilus phage helicase or primase. Excerpt(s): The present invention relates to bacteriophage resistant recombinant bacteria and their use in fermentation. The dairy industry has harnessed certain members of the heterogeneous group of lactic acid bacteria, including the thermophilic bacterium Streptococcus thermophilus, as starter cultures or culture adjuncts to drive the lactate fermentations in the manufacture of a variety of fermented products. This organism grows best at the high end of the mesophilic range, about 42-25.degree. C., thus it survives and produces acid at temperatures higher than can be tolerated by the mesophilic lactic acid bacteria. This characteristic makes S. thermophilus useful in the fermentation of dairy products, such as yogurt and Swiss and Italian cheeses, that are ordinarily manufactured or incubated at elevated temperatures. Pasteurized milk, the primary substrate for fermented products, and in some instances the starter cultures themselves, have been be shown to be a natural reservoir for virulent bacteriophages capable of infecting and, inevitably, lysing the starter culture(s) during product manufacture (Bruttin et al, Appl. Environ. Microbiol. 63:3144-3150 (1997); Moineau et al., J Dairy Sci. 79:2104-2111 (1996)). Depending upon the severity and temporal progression of the lytic infection, the concomitant loss of fermentative capacity associated with starter culture lysis can significantly retard or halt batch fermentations; thereby inflicting upon the dairy industry significant losses of time and production capital each year. With the advent of biotechnology, the dairy industry is seeking to identify novel phage defense strategies capable of extending the utility of industrial starter cultures. Web site: http://www.delphion.com/details?pn=US06686192__ •

Bactericide compositions prepared and obtained from microccus varians Inventor(s): Mollet; Beat (Mollie-Margot, CH), Peel; John (Lully, CH), Pridmore; David (Lausanne, CH), Rekhif; Nadji (Lausanne, CH), Suri; Bruno (Bubendorf, CH) Assignee(s): Nestec S.a. (vevey, Ch) Patent Number: 6,689,750 Date filed: August 6, 1996 Abstract: A bacteriocin is obtained by culturing cells of a strain of Micrococcus varians which, upon culturing in a culture medium, produces a bacteriocin which has agar well incubation inhibition test activity against at least one of Lactobacillus, Lactococcus, Streptococcus, Enterococcus, Listeria, Bacillus, Clostridia and Straphylococcus bacteria. The strain is cultured to obtain cultured cells in a concentration of from 10.sup.7 to 10.sup.11 organisms per ml of the medium, and the culture medium supernatant is separated from the cultured cells to obtain the supernatant which contains the bacteriocin, which is also identified by having an amino acid sequence from SEQ ID NO: 1 or a sequence differing from SEQ ID NO: 1 by from 1 to 4 amino acids. The supernatant, as is, or a concentrate thereof or a bacteriocin product isolated from the supernatant by dehydration or otherwise isolated and purified therefrom is added to a food or cosmetic product to inhibit the growth of bacteria against which agar well incubation inhibition test activity is exhibited by the bacteriocin. Excerpt(s): The present invention relates to a bacteriocin, to a strain which produces this bacteriocin, to a process for preparing this bacteriocin, and to the use of this bacteriocin and/or a strain producing this bacteriocin in the manufacture of foodstuffs and

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cosmetics. Bacteriocins have been isolated from numerous Gram-positive and Gramnegative bacteria. Bacteriocins are molecules which are essentially proteinaceous in nature and which possess a bactericidal effect and, for this reason, a bacteriocin provokes an antagonistic reaction between the bacterium which produces it and one or more different bacterial species. Furthermore, the inhibition spectrum of a bacteriocin is often limited to the species which are closely related to the bacterial species which produces it. Bacteriocins have, in particular, been demonstrated in lactic acid bacteria. For example, EP 0643136 (Societe des produits Nestle) describes the identification of two bacteriocins from Streptococcus thermophilus. Similarly, a bacteriocin has been isolated from Lactococcus lactis (App. and Env. Microbio. 58, 279-284, 1992; J. of Bio. Chem. 268, 16361-16368, 1993). Web site: http://www.delphion.com/details?pn=US06689750__ •

Bacteriostatic composition for salmonellae Inventor(s): Fukata; Tsuneo (Gifu, JP), Hirose; Kimio (Gifu, JP), Kito; Kyoji (Nagoya, JP), Ogawa; Takao (Ama-gun, JP) Assignee(s): Meito Sangyo Kabushiki Kaisha (aichi, Jp) Patent Number: 6,645,515 Date filed: May 25, 2001 Abstract: Provided is a bacteriostatic composition for salmonellae containing, as the active ingredient, a fermented broth obtained by effecting fermentation with the use of a lactic acid bacteriium belonging to the genus Leuconostoc, Streptococcus or Streptobacterium in a sucrose-containing medium, or a preparation originating in the supernatant obtained by subjecting the fermented broth to fractional precipitation from a water-miscible organic solvent. Excerpt(s): This invention relates to a bacteriostatic composition for salmonellae containing, as the active ingredient, a component originating in the fermented broth of a lactic acid bacterium. More specifically, the invention relates to a composition utilizable as a feed additive, or a medicine or a health food for prophylaxis or treatment a of salmonellosis. Some of animals are infected with salmonella when they are infants shortly after their birth, or even after they have grown to adults, due to change of the environment, etc. For preventing this, prophylaxis by administration of antibiotics, vaccines, various viable cell agents [for example, a product obtained by growth of a strain belonging to the genus Streptococcus or Lactobacillus, competitive exclusion of salmonellae (CE agent)] or the like, mannose (a kind of sugar) aggregating pathogens and inhibiting their adhesion to the intestinal wall, or oligosaccharides, etc. as health food has been tried. However, among these methods, antibiotics have the problems, for example that resistant strains are liable to occur, the normal bacterial flora advantageously acting on the living body is also excluded, and there is the possibility of movement and remaining of : the antibiotics in processed stock farm products ("Remaining of feed additives into stock farm products", Chikusan Handbook (Stock Raising Handbook), edited by Kentaro HIMENO et al., Kodansha Co., 1984, pp. 484485). Web site: http://www.delphion.com/details?pn=US06645515__

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C3 binding polypeptide of Streptococcus agalactiae group b Streptococcus Inventor(s): Ferrieri; Patricia (Minneapolis, MN), Smith; Beverly L. (Minneapolis, MN) Assignee(s): Regents of the University of Minnesota (minneapolis, Mn) Patent Number: 6,582,950 Date filed: July 1, 2000 Abstract: This invention relates to the identification of a human complement C3 binding polypeptide and the nucleic acid which encodes the polypeptide from Streptococcus agalactiae. The polypeptide binds C3 and may be implicated in S. agalactiae adhesion and/or virulence. The polypeptide is conserved in mass in a variety of streptococcal isolates and is recognized by antibodies produced by humans exposed to or colonized with Group B Streptococcus. Excerpt(s): This invention relates to Streptococcus agalactiae, Group B Streptococcus, and in particular this invention relates to the identification of a S. agalactiae polypeptide and a gene encoding it that may be implicated in Group B streptococcal adhesion and/or virulence. The S. agalactiae polypeptide according to the invention demonstrates binding of human complement C3. Streptococcus agalactiae, or group B Streptococcus (GBS), is a leading cause of infant mortality. GBS encompasses an estimated prevalence of several thousand cases per year resulting in an annual mortality rate in the United States between about 10% and 15% (Schuchat, Clin. Micro Rev., 11(3):497-513 (1998)). Although worldwide prevalence is known, insufficient specific epidemiological data is not readily available. Several virulence factors have been reported in GBS,. In addition to the streptococcal capsule, which is an important virulence factor, lipotechoic acid, a glycerol-phosphate polymer extending throughout the cell wall, is a virulence factor that may mediate adhesion (Teti et al., Infection and Immunity, 55(12):3057-3064 (1987)). Proteins such as hyaluronate lyase, cAMP factor, proteases, nucleases, hippuricase, neuraminidase, hemolysin, and C5a peptidase are expressed from GBS and many have been shown to be virulence factors (Nizet et al., Streptococcal Infections, Stevens D L and Kaplan E L, Eds. (2000); Bohnsack et al., Biochimica et Biophysica Acta, 1079:222-228 (1991)). In short, many studies are underway to define virulence factors molecularly by the mutation of genes encoding these proteins under question and the examination in assays for biological function. Web site: http://www.delphion.com/details?pn=US06582950__

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Composition for treatment of obesity Inventor(s): Bojrab; Gregory G. (Indianapolis, IN) Assignee(s): Lacpro Industries, Llc (indianapolis, In) Patent Number: 6,641,808 Date filed: December 7, 2000 Abstract: A probiotic composition and method for the treatment of obesity. The probiotic composition comprises a culture having Lactobacillus bulgaricus and Streptococcus thermophilus lactic acid bacteria and a carbohydrate enriched media, whereby the culture and media are combined and allowed to ferment until a desired ratio of the Lactobacillus bulgaricus and Streptococcus thermophilus organisms as well as a desired number of total organisms per dose are achieved. Once the desired ratios are achieved, the composition is concentrated and lyophilized. The method of the

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present invention comprises the steps of providing a probiotic composition of the present invention and administering the composition to a patient for the treatment of obesity. Excerpt(s): The present invention relates to the field of treatment of gastrointestinal disorders, hyperlipidemia, autoimmune diseases and obesity. More particularly, the present invention relates to a probiotic composition, and a method for treatment of obesity using the composition. Gastrointestinal disease includes many disorders, including but not limited to, inflammatory bowel diseases such as ulcerative colitis and Crohn's disease, infectious enteritis (viral, bacterial, parasitic), antibiotic associative diarrhea, clostridium difficile colitis, microscopic or lymphocytic colitis, collagenous colitis, colon polyps and familial polyp syndromes (e.g., familial polyposis syndrome, Gardner's Syndrome), helicobacter pylori, irritable bowel syndrome, nonspecific diarrheal illnesses, and intestinal cancers. Moreover, obesity is the most common and costly nutritional problem in the United States. The cause of many of these diseases is unknown. Such is the case with inflammatory bowel disease ("IBD"), the general term for diseases that cause inflammation in the intestines. For example, ulcerative colitis ("UC") is an IBD that causes inflammation of the mucosa lining of the large intestine. The inflammation usually occurs in the rectum and lower part of the colon, but it may affect the entire colon. Web site: http://www.delphion.com/details?pn=US06641808__ •

Compounds encoding the protective M-like protein of Streptococcus equi and assays therefor Inventor(s): Artiushin; Sergey (Lexington, KY), Timoney; John F. (Lexington, KY) Assignee(s): University of Kentucky Research Foundation (lexington, Ky) Patent Number: 6,458,358 Date filed: June 23, 1998 Abstract: The present invention relates generally to molecular compounds which encode the protective M-like protein of Streptococcus equi (SeM), the amino acid compound which is thereby encoded, and compositions of matter which incorporate either the encoding compounds or the cellular components for which they encode. For instance, vaccines which utilize the amino acid compounds or vectors and cell lines useful to make the amino acid compounds described herein are subjects of the present invention. The present invention provides methods to stimulate S. equi-specific immune response in horses. It also provides diagnostic assays for Streptococcus equi. Excerpt(s): Streptococcus equi, a Lancefield group C streptococcus, causes strangles, a highly contagious disease of the nasopharynx and draining lymph nodes of Equidae. The 58 kDa antiphagocytic M-like protein (SeM) is a major virulence factor and protective antigen and functions by limiting deposition of C3b on the bacterial surface and by directly binding fibrinogen. Boschwitz and Timoney, 17 Microbiol. Pathogenesis 121 (1994) and Boschwitz and Timoney, 62 Infect. Imnun. 3515 (1994). In the recent past, S. equi outbreaks on horse farms have been avoided and treated by quarantine of suspect animals; antiseptic handling of food, bedding and housing; and antibiotics when indicated. Vaccines comprising avirulent S. equi or fractions thereof have been described, but success rate has been low. U.S. Pat. No. 5,183,659 describes a vaccine which stimulated a nasopharyngeal antibody response in horses, but the vaccine had a

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limitation of many such vaccines, which is risk of reversion to virulence and occasional abcess development in vaccinated horses. Web site: http://www.delphion.com/details?pn=US06458358__ •

DNA encoding a plasminogen activating protein Inventor(s): Leigh; James A. (Newbury, GB), Rosey; Everett L. (Preston, CT), Yancey, Jr.; Robert J. (Salem, CT) Assignee(s): Pfizer, Inc. (new York, Ny) Patent Number: 6,485,904 Date filed: May 13, 1998 Abstract: The present invention provides polynucleotide molecules comprising nucleotide sequences encoding plasminogen activating (PauA) proteins from Streptococcus uberis, and substantially homologous polypeptides, peptide fragments, and fusion proteins thereof. The present invention further provides compositions and methods for recombinantly expressing the PauA proteins, substantially homologous polypeptides, peptide fragments and fusion proteins encoded by the polynucleotide molecules of the present invention. The present invention further provides a vaccine for protecting a member of a mammalian species against mastitis, comprising a PauA protein, substantially homologous polypeptide, peptide fragment, fusion protein, or polynucleotide molecule of the present invention. Excerpt(s): The present invention is in the field of animal health, and is directed to vaccine compositions and diagnostics for disease. More particularly, the present invention relates to vaccines against mastitis in mammals, and polynucleotide molecules having nucleotide sequences encoding plasminogen activating proteins useful in the production of said vaccines. Bovine mastitis causes significant loss of milk production in dairy cattle, resulting in severe economic impact on the dairy industry. Mastitis may be caused by one or more types of bacterial pathogens. Infection by Streptococcus is estimated to account for approximately 30% of all clinical cases of bovine mastitis. Infection by S. uberis, specifically, is estimated to account for approximately 20% of all clinical cases of bovine mastitis. Conventional methods for the prevention and treatment of mastitis in animals include the use of sanitary milking techniques and the administration of chemical antibiotics. The use of antibiotics, however, is limited by the fact that milk containing antibiotic residues is often not considered safe for human consumption and must be discarded. Specific approaches to the treatment or prevention of mastitis in animals include that of U.S. Pat. No. 5,198,214 to Stolle et al., which describes the use of polyvalent anti-mastitis vaccines comprising inactivated mastitiscausing pathogens cultivated from the milk of infected animals. In addition, U.S. Pat. No. 5,234,684 to Sordillo et al. describes a method of treating or preventing mastitis in cows, comprising administering bovine interferon gamma to the animals. Web site: http://www.delphion.com/details?pn=US06485904__

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DNA probes, method and kit for identifying antibiotic-resistant strains of bacteria Inventor(s): Hakenbeck; Regine (Fischbach, DE) Assignee(s): Max-planck-gesellschaft Zur Forderung Der Wissenschaften E.v. (munich, De) Patent Number: 6,713,254 Date filed: March 3, 2000 Abstract: The invention relates to a method for identifying antibiotic-resistant strains of bacteria, especially strains of Streptococcus pneumoniae. According to the invention, the method is based on a combination of hybridization experiments using sensitivityspecific and resistance-specific probes. The invention also relates to the DNA probes and to a kit for carrying out the inventive method. Excerpt(s): The present invention relates to DNA probes, a method and a kit for identifying antibiotic-resistant strains of bacteria. The occurrence of antibiotic-resistant strains of bacteria, particularly of streptococcus strains, represents an increasing problem. So far, antibiotic susceptibility tests have been carried out by isolating bacteria and establishing a culture to define the minimum antibiotic inhibitory concentration in a biological test. This method takes at least 1 to 2 days. Well-calculated and thus optimum treatment is not possible within this period. Therefore, there is a need for a faster identification of existing resistances. The object of the present invention consists in providing products and methods by means of which bacterial strains, particularly streptococcus strains, can be tested fast and reliably for existing antibiotic resistances. Web site: http://www.delphion.com/details?pn=US06713254__

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Facilitation of repair of neural injury with CM101/GBS toxin Inventor(s): Hellerqvist; Carl G. (Brentwood, TN), Wamil; Artur W. (Nashville, TN), Wamil; Barbara D. (Nashville, TN) Assignee(s): Vanderbilt University (nashville, Tn) Patent Number: 6,476,001 Date filed: July 29, 1999 Abstract: Neural injury may be advantageously treated with CM101, a polysaccharide toxin isolated from Group B.beta.-hemolytic Streptococcus bacteria. CM1O1 treatment aids in the re-establishment of neuronal connectivity, at least partially inhibits scar formation, and increases the probability of survival during the critical period following injury to the central nervous system. Preexisting neural injuries having scar tissue are ameliorated by surgical excision of the scar tissue in conjunction with administration of CM101. Excerpt(s): This invention relates to therapy for enhancing repair of neural injury in the central nervous system or the peripheral nervous system. Neural injury caused by physical trauma, ischemia, or disease can result in profound disability or death. Such disabilities, which may be physical and/or mental, include loss of movement, impaired sensory perception, loss of cognitive functions, seizures, and emotional and personality disorders. Given the incidence of death and the prevalence and possible severity of survivors' disabilities, neural injury takes a heavy toll on individuals and society. Accordingly, there is a need for treatments which facilitate the repair of damaged nerves and neuronal pathways. At present, there is no effective treatment for central nervous

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system (CNS) injuries. Brain physical trauma, spinal cord compression or transection, ischemia, or surgery cause hypoxia which initiates a cascade of molecular events leading to neural injury (Liu, X. Z. et al., Neuronal and glial apoptosis after traumatic spinal cord injury, J. Neurosci., 17:5395-5406 (1997); Olsson, Y. et al., Release of endogenous neurochemicals may increase vascular permeability, induce edema and influence cell changes in trauma to the spinal cord, Progress in Brain Res., 91:197-203 (1992); Crowe, M. J. et al., Apoptosis and delayed degeneration after spinal cord injury in rats and monkeys, Nature Med., 3:73-76 (1997)). Despite receiving medical attention, many patients die in the first few days following a serious CNS injury. For those patients that survive their injuries, prognosis depends on the ability of the remaining neurons to adapt new functions because, with current technology, neuronal connectivity is rarely restored. Because neural adaptation is slow and frequently incomplete, the potential benefit of a treatment which facilitates neural repair and the re-establishment of neuronal connectivity would be tremendous as would the benefit provided by a treatment that reduces the probability that a patient will die during the critical postinjury period. Web site: http://www.delphion.com/details?pn=US06476001__ •

Fibronectin binding protein compositions and methods of use Inventor(s): Hook; Magnus (Houston, TX), House-Pompeo; Karen L. (Valdesta, GA), Joh; Danny (Houston, TX), McGavin; Martin J. (Etobicoke, CA), Patti; Joseph M. (Cumming, GA), Speziale; Pietro (Pavia, IT) Assignee(s): The Texas A&m University System (college Station, Tx), University Degli Study DI Pavia (pavia, It), University of Manitoba (winnipeg, Ca) Patent Number: 6,685,943 Date filed: January 21, 1998 Abstract: Disclosed are antibodies that block the binding of fibronectin protein to fibronectin. Also disclosed are site specifically-mutated and truncated peptide epitopes derived from the fnbA and fnbB genes of Staphylococcus aureus, the fnba and fnbB genes of Streptococcus dysgalactiae, and the sfb gene of Streptococcus pyogenes, and nucleic acid segments encoding these peptides and epitopes. The anti-(fibronectin binding site) antibodies, peptides and epitopes that give rise to antibodies that block the binding of fibronectin binding proteins to fibronectin, and DNA segments encoding these proteins and are of use in various screening, diagnostic and therapeutic applications including active and passive immunization and methods for the prevention of streptococcal and staphylococcal colonization in animals or humans. These. DNA segments and the peptides derived therefrom are proposed to be of use directly in the preparation of vaccines and also for use as carrier proteins in vaccine formulations. Excerpt(s): The present invention relates generally to the field of molecular biology. More particularly, certain embodiments concern methods and compositions comprising DNA segments and proteins derived from bacterial species. More particularly, the invention provides fnibA nucleic acid and FnBPA amino acid compositions from Staphylococcus aureus. Also disclosed are peptide epitopes and protein sequences comprising site-specifically-modified or truncated fibronectin (Fn) binding site domains, and antibodies derived from immunization of animals with these peptide epitopes and binding site domains. Various methods for making and using these antibodies, peptides and DNA segments, peptides and nucleic acid segments encoding modified ligand binding site domains, and native and synthetic proteins are disclosed, such as, for

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example, the use of antibodies and/or DNA segments as diagnostic probes and templates for protein production, and the use of antibodies, proteins, fusion protein carriers, peptides and nucleic acid segments in various pharmacological and immunological applications. Bacterial adherence to host tissue involves specific microbial surface adhesins of which a subfamily termed MSCRAMMs specifically recognize extracellular matrix (ECM) components. Many pathogenic bacteria have been shown to specifically recognize and bind to various components of the extracellular matrix in an interaction which appears to represent a host tissue colonization mechanism. This adherence involves a group of bacterial proteins termed MSCRAMMs (microbial surface components recognizing adhesive matrix molecules) (Patti et al., 1994; Patti and Hook, 1994). Recombinant proteins corresponding to the repeat regions from the different Fn binding MSCRAMMs are all capable of inhibiting the binding of Fn to different Gram-positive bacteria, including S. aureus, S. dysgalactiae and S. pyogenes (Joh et al., 1994). Furthermore, studies using individual synthetic peptides revealed that a number of the repeat units retain Fn-binding activity, and interfere with binding of Fn by all of the Gram-positive species tested. These data suggest that the binding sites in Fn for the different MSCRAMMs are either overlapping or closely spaced on the matrix protein. Web site: http://www.delphion.com/details?pn=US06685943__ •

Glucan-containing compositions and paper Inventor(s): Nichols; Scott E. (Johnston, IA) Assignee(s): Pioneer Hi-bred International, Inc. (des Moines, Ia) Patent Number: 6,465,203 Date filed: December 19, 2000 Abstract: The present invention provides methods of making paper, utilizing glucans, produced by the glucosyltransferase B, C or D enzyme of the species Streptococcus mutans, instead of modified starches. The present glucans are functionally similar to currently utilized modified starches and are particularly useful in the coating step of paper manufacture. The present glucans also exhibit thermoplastic properties and impart gloss to the paper during the coating step. Excerpt(s): The present invention involves the field of paper manufacture. Specifically, the present invention provides sources alternative to modified starch in paper manufacture. There are three major phases in paper manufacture where starch is used as an ingredient. The first is the "wet end" where cellulose fibers are mixed with starch in a slurry, and the slurry is forced through a narrow opening onto a wire belt. Water is rapidly removed as the forming sheet travels the length of the belt. After a distance of typically five to fifteen meters on the belt, the sheet has had enough water removed from it so that it can support its own weight. The sheet travels through a number of foils and rolls wherein more water is removed. It is dried to about 11% moisture. The second phase in paper manufacturing involving starch is the "sizing step". Here, the paper goes through a sizing press where a slurry including starch is applied to the sheet. The sheet again goes through a series of foils and rolls. It is dried on rollers and can be taken off the press as a finished product. Web site: http://www.delphion.com/details?pn=US06465203__

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Human complement C3-degrading protein from Streptococcus pneumoniae Inventor(s): Dunny; Gary (St. Paul, MN), Hostetter; Margaret K. (New Haven, CT), Nandiwada; Lakshmi S. (Mendota Heights, MN) Assignee(s): Regents of the University of Minnesota (minneapolis, Mn) Patent Number: 6,676,943 Date filed: October 19, 1999 Abstract: The present invention relates to the identification and use of a family of human complement C3-degrading proteinases expressed by S. pneumoniae. The proteinase has a molecular weight of about 24 kD to about 34 kD as determined on a 10% SDS polyacrylamide gel. A preferred proteinase of this invention includes the amino acid sequence of SEQ ID NO:2. Excerpt(s): This invention relates to Streptococcus pneumoniae and in particular this invention relates to the identification of an S. pneumoniae protein that is capable of degrading human complement protein. C3. Respiratory infection with the bacterium Streptococcus pneumoniae (S. pneumoniae) leads to an estimated 500,000 cases of pneumonia and 47,000 deaths annually. Those persons at highest risk of bacteremic pneumococcal infection are infants under two years of age and the elderly. In these populations. S. pneumoniae is the leading cause of bacterial pneumonia and meningitis. Moreover, S. pneumoniae is the major bacterial cause of ear infections in children of all ages. Both children and the elderly share defects in the synthesis of protective antibodies to pneumococcal capsular polysaccharide after either bacterial colonization, local or systemic infection, or vaccination with purified polysaccharides. S. pneumoniae is the leading cause of invasive bacterial respiratory disease in both adults and children with HIV infection and produces hematogenous infection in these patients (Connor et al. Current Topics in AIDS 1987;1:185-209 and Janoff et al. Ann. Intern. Med 1992;117(4):314-324). Individuals who demonstrate the greatest risk for severe infection are not able to make antibodies to the current capsular polysaccharide vaccines. As a result, there are now four conjugate vaccines in clinical trial. Conjugate vaccines consist of pneumococcal capsular polysaccharides coupled to protein carriers or adjuvants in an attempt to boost the antibody response. However, there are other potential problems with conjugate vaccines currently in clinical trials. For example, pneumococcal serotypes that are most prevalent in the United States are different from the serotypes that are most common in places such as Israel. Western Europe, or Scandinavia. Therefore, vaccines that may be useful in one geographic locale may not be useful in another. The potential need to modify currently available capsular polysaccharide vaccines or to develop protein conjugates for capsular vaccines to suit geographic serotype variability entails prohibitive financial and technical complications. Thus, the search for immunogenic, surface-exposed proteins that are conserved worldwide among a variety of virulent serotypes is of prime importance to the prevention of pneumococcal infection and to the formulation of broadly protective pneumococcal vaccines. Moreover, the emergence of penicillin and cephalosporin-resistant pneumococci on a worldwide basis makes the need for effective vaccines even more exigent (Baquero et al. J. Antimicrob. Chemother. 1991;28S;31-8). Web site: http://www.delphion.com/details?pn=US06676943__

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lacR from Streptococcus pneumoniae Inventor(s): Chan; Pan Fong (Wayne, PA), Holmes; David J. (West Chester, PA), Lonetto; Michael A. (Wayne, PA), Traini; Christopher M. (Media, PA), Zalacain; Magdalena (West Chester, PA) Assignee(s): Smithkline Beecham Corporation (philadelphia, Pa) Patent Number: 6,548,273 Date filed: July 17, 2000 Abstract: The invention provides lacR polypeptides and polynucleotides encoding lacR polypeptides and methods for producing such polypeptides by recombinant techniques. Also provided are methods for utilizing lacR 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 lacR (repressor proteins) family, as well as their variants, herein referred to as "lacR," "lacR polynucleotide(s)," and "lacR polypeptide(s)" as the case may be. The Streptococci make up a medically important genera of microbes known to cause several types of disease in humans, including, for example, otitis media, conjunctivitis, pneumonia, bacteremia, meningitis, sinusitis, pleural empyema and endocarditis, and most particularly meningitis, such as for example infection of cerebrospinal fluid. Since its isolation more than 100 years ago, Streptococcus pneumoniae has been one of the more intensively studied microbes. For example, much of our early understanding that DNA is, in fact, the genetic material was predicated on the work of Griffith and of Avery, Macleod and McCarty using this microbe. Despite the vast amount of research with S. pneumoniae, many questions concerning the virulence of this microbe remain. It is particularly preferred to employ Streptococcal genes and gene products as targets for the development of antibiotics. The frequency of Streptococcus pneumoniae 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 Streptococcus pneumoniae strains that 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. Web site: http://www.delphion.com/details?pn=US06548273__

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Lactic acid bacteria species Inventor(s): Desachy; Patrice (Porsel FR, CH), Gaier; Walter (Chailly/Montreux, CH), Neeser; Jean-Richard (Savigny, CH), Pot; Bruno (Sint-Michiels Brugge, BE), Pridmore; David (Lausanne, CH), Stingele; Francesca (St-Prex, CH) Assignee(s): Nestec S.a. (vevey, Ch) Patent Number: 6,579,711 Date filed: April 13, 2000 Abstract: Strain of lactic acid bacterium, (1) whose 16S ribosomal RNA is characteristic of the genus Streptococcus, (2) whose total protein profile, obtained after migration of the total proteins on an SDS-PAGE electrophoresis gel, is characteristic of that of the

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strain of lactic acid bacterium CNCM I-1920 but distinct from those of the recognized species belonging to the genus Streptococcus, namely S. acidominimus, S. agalactiae, S. alactolyticus, S. anginosus, S. bovis, S. canis, S. caprinus, S. constellatus, S. cricetus, S. cristatus, S. difficile, S. downei, S. dysgalactiae ssp. dysgalactiae, S. dysgalactiae ssp. equisimilis, S. equi, S. equi ssp. equi, S. equi ssp. zooepidemicus, S. equinus, S. ferus, S. gallolyticus, S. gordonii, S. hyointestinalis, S. hyovaginalis, S. iniae, S. intermedius, S. intestinalis, S. macacae, S. mitis, S. mutans, S. oralis, S. parasanguinis, S. parauberis, S. phocae, S. pleomorphus, S. pneumoniae, S. porcinus, S. pyogenes, S. ratti, S. salivarius, S. sanguinis, S. shiloi, S. sobrinus, S. suis, S. thermophilus, S. thoraltensis, S. uberis, S. vestibularis, S. viridans. The invention also relates to the use of a strain of lactic acid bacterium according to the invention, or of a polysaccharide secreted by a strain according to the invention, for the preparation of a dietary composition, in particular an acidified milk or a fromage frais. The invention also relates to a dietary or pharmaceutical composition comprising a strain of lactic acid bacterium or a polysaccharide consisting of a succession of glucose, galactose and N-acetylglucosamine in a respective proportion of 3:2:1. In particular, strains CNCM I-1920, I-1921, I-1922, I1923, I-1924, I-1925 and I-1926. Excerpt(s): The present invention relates to new species of lactic acid bacteria belonging to the genus Streptococcus. The identification of lactic acid bacteria is essential in the dairy industry, and consists in differentiating distinctive morphological, physiological and/or genetic characteristics between several species. The distinctive physiological characteristics for a given species of lactic acid bacteria may be determined by various tests including, for example, analyzing their capacity to ferment various sugars and the migration profile of total proteins on an SDS-PAGE type electrophoresis gel (Pot et al., Taxonomy of lactic acid bacteria, in Bacteriocins of lactic acid bacteria, Microbiology, Genetics and Applications, L. De Vuyst, and E. J. Vandamme ed., Blackie Academic & Professional, London, 1994). Web site: http://www.delphion.com/details?pn=US06579711__ •

Lanthionine antibiotic compositions and method Inventor(s): Caufield; Page W. (Birmingham, AL), Novak; Jan (Birmingham, AL) Assignee(s): The Uab Research Foundation (birmingham, Al) Patent Number: 6,521,596 Date filed: September 10, 1998 Abstract: Certain bacteria indigenous to humans produce antimicrobial substances called bacteriocins which inhibit other bacteria, including members of their own species. Mutacins are a class of antibiotic substances made by Streptococcus mutans. Disclosed is the purification and biochemical characterization of a novel lanthionine-containing mutacin peptide from S. mutans. The purified peptide is pH- and temperature-stable and its amino acid composition indicates the presence of lanthionine and.beta.methyllanthionine. Also provided are methods of making and using the purified polypeptide. Excerpt(s): The invention relates to polypeptide antibiotics and to the identification of genetic loci associated with expression of the antibiotics. The invention particularly describes a purified lanthionine-containing antimicrobial agent, DNA encoding the protein, and methods and compositions for treatments employing the antibiotic. The phenotypic ally similar group of bacteria collectively known as the mutans streptococci

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are considered the major etiologic agents responsible for dental caries and have been implicated as major causative agents in other infectious and transmissible diseases, such as endocarditis. The species most commonly associated with dental caries is Streptococcus mutans. Attempts to better understand the genetic determinants that contribute to the cariogenic potential of this organism, as well as its natural history as an agent of an infectious disease, have only recently been explored. For example, a molecular approach has been employed to delineate the structure, function, and regulation of a number of different enzymes including the glucosyltransferases that are involved with sugar metabolism, an important virulence factor responsible for the metabolic conversion of sucrose to extracellular polymers to form critical mass and provide for fermentable substrates (Hamada, et al., 1986). The other two major factors thought to be involved with the pathogenicity of S. mutans are its acidogenic/aciduric properties (Caufield, et al., 1990A) and its ability to elaborate poorly characterized bacteriocin-like substances, generally known as mutacins, which may provide a selective force necessary for sustained colonization in a milieu of densely packed competing organisms found in plaque (Buchman, et al., 1988). Collectively called "mutacins" these agents kill other bacteria of the same or closely related species. The mutacins are only similar in name and host producer, as their properties differ widely. Mutacins associated with plasmid-containing strains of S. mutans have been designated as either Group I or II (mutacin I and mutacin II. Therefore, the production of mutacins is one characteristic of S. mutans that appears to contribute to its ability to colonize and be sustained, particularly in the oral cavity. In this regard, mutacins may be considered virulence factors. Web site: http://www.delphion.com/details?pn=US06521596__ •

Lantibiotic from Streptococcus mutans, method of production and use thereof Inventor(s): Lacroix; Christophe (Sillery, CA), Lapointe; Gisele (Ste-Foy, CA), Lavoie; Marc (Loretteville, CA), Mota-Meira; Marilaine (Loretteville, CA) Assignee(s): Universite Laval (quebec, Ca) Patent Number: 6,699,839 Date filed: October 19, 2000 Abstract: Mutacin are bactericidal substances of proteinaceous natures produced by Streptococcus mutans. Lantibiotics are antibacterial substances containing posttranslationnally modified amino acids such as lanthionine. The present invention teaches a simple method of purifying mutacin B-Ny266 from Streptococcus mutans strain Ny266 to homogeneity. The present invention further teaches the primary amino acid sequence of mutacin B-Ny266 as well as its proposed modified structure. Further, the present invention teaches compositions comprising mutacin B-Ny266 as well as methods for the treatment and/or prophylaxy of bacterial infections comprising an administration of a suitable dose of composition comprising mutacin B-Ny266. Excerpt(s): The present invention relates to a novel antibiotic produced by streptococcus mutans, salts thereof, pharmaceutical compositions containing same, and to methods for the production and extraction thereof. Bacteriocins produced by Gram-positive bacteria can be defined as inhibitory substances having a bactericidal mode of action and an essential protein moiety (Jack et al., 1995, Microbiol. Rev. 59:171-200). Bacteriocins produced by Streptococcus mutans were termed mutacins by Hamada and Ooshima (Hamada et al, 1975, Arch. Oral Biol. 20:641-648). Although there are many reports which show that S. mutans produces inhibitory substances, only a few such inhibitors

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have been isolated and characterized as mutacins (Chikindas et al., 1995, Antimicrob. Agents Chemother. 39:2656-2660; Delisle, 1986, Microbios 46:21-28; Fukushima et al., 1985, Arch. Oral Biol. 30:229-234; Hamada et al., 1986, Zentralbl. Bakteriol. Hyg. A. 261:287-298; Hillman et al., 1984, Infect. Immun. 44:141-144; Kurita et al., 1988, J. Gen. Microbiol. 134:213-220; Loyola-Rodriguez et al., 1992, J. Gen. Microbiol. 138:269-274; Novak et al., 1994, J. Bacteriol. 176:4316-4320; Novak et al., 1996, Anal. Biochem. 236:358360; Paul et al., 1975, Infect. Immun. 12:1375-1385; Takada et al., 1984, Infect. Immun. 44:370-378). The well studied mutacins include: RM-10 (Fukushima et al., 1985, Arch. Oral Biol. 30:229-234), C3603 (Takada et al., 1984, Infect. Immun. 44:370-378), JH 1000 (Hillman et al., 1984, Infect. Immun. 44:141-144), GS-5 (Paul et al., 1975, Infect. Immun. 12:1375-1385), MT 3791 and MT 6223 (Hamada et al., 1986, Zentralbl. Bakteriol. Hyg. A. 261:287-298;Loyola-Rodriguez et al., 1992, J. Gen. Microbiol. 138:269-274), mutacin-b (Delisle, 1986, Microbios 46:21-28), mutalipocins (Kurita et al., 1988, J. Gen. Microbiol. 134:213-220) and J-T8 (Chikindas et al., 1995, Antimicrob. Agents Chemother. 39:26562660; Novak et al., 1994, J. Bacteriol. 176:4316-4320;Novak et al., 1996, Anal. Biochem. 236:358-360). A preliminary classification of mutacins has been published previously (Morency et al., 1995, Can. J. Microbiol. 41:826-831), but a definitive classification will have to await the complete chemical characterization of these substances. Among the known mutacins, only T8, which belongs to group J (Morency et al., 1995, Can. J. Microbiol. 41:826-831), was identified as a lantibiotic and its first 8 N-terminal amino acid residues were determined by Novak et al. (Novak et al., 1994, J. Bacteriol. 176:43164320). Lantibiotics are defined as bacterium-derived ribosomally synthesized lanthionine-containing peptides with antibiotic activity (Jack et al., 1995, Microbiol. Rev. 59:171-200; Bierbaum et al., 1993, Zentralbl. Bakteriol. 278:1-22;Jack et al., 1995, Trends Biotechnol. 13:269-278). They generally contain unsaturated amino acids like 2,3didehydroalanine (dhA or U) (2)-2,3-didehydrobutyrine (dhB or O), and 2-aminobutyric acid (Abu). The lantibiotics are divided into two types (Jack et al., 1995, Microbiol. Rev. 59:171-200; Bierbaum et al., 1993, Zentralbl. Bakteriol. 278:1-22; Jack et al., 1995, Trends Biotechnol. 13:269-278; Jung, 1991, in: Nisin and Novel Lantibiotics., Jung et al., eds., pp. 1-34. ESCOM Science, Leiden). Type A comprises screw-shaped, amphipathic molecules with molecular masses between 2151 and 4635 Da and with 2 to 7 net positive charges. Type B consists of more globular molecules with molecular masses between 1825 and 2042 Da and with either no net charge or a net negative charge. They usually contain a higher proportion of modified amino acid residues than type A. Web site: http://www.delphion.com/details?pn=US06699839__ •

Method and means for the production of hyaluronic acid Inventor(s): St.ang.hl; Sten (Lund, SE) Assignee(s): Pharmacia AB (stockholm, Se) Patent Number: 6,537,795 Date filed: February 1, 2000 Abstract: A method for selecting streptococcus strains capable of producing hyaluronic acid with molecular weight exceeding six million includes the steps of cultivating strains of streptococci individually in culture medium which is free of metal ions which promote degradation of hyaluronic acid and which does not release from the reactor metal ions which promote the degradation of hyaluronic acid; and selecting a supercapsulated strain of a streptococcus, supercapsulated members thereof having a

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mucoid morphology and being capable of forming capsules having a diameter of greater than 4.mu.m. Excerpt(s): The present invention is related to a method for the production of high molecular weight hyaluronic acid by fermentation using supercapsulated strains of streptococci. The invention also relates to a method for the selection of supercapsulated mutants and to mutants producing such hyaluronic acid in high yield. Hyaluronic acid (HA) or hyaluronan is a glycosaminoglucan consisting of repeating disaccharides of alternating D-glucuronic acid and N-acetylglucosamine molecules. These molecules are joined by a.beta.(1,3)-D linkage while the glucosamine to glucuronic acid linkage is.beta.(1,4)-D. There are several sources of hyaluronic acid and its molecular weight varies considerably depending on the source. The HA found in synovial fluid has a molecular weight of about 1 to 8 million, that in human umbilical cord has a molecular weight around 3.6-4.5 million and HA in rooster combs may reach very high values, for instance up to 12-14 million, or even higher. The chemical composition of hyaluronic acid is the same regardless of its source and since it is non-immunogenic it has found several applications in medicine (Brimacombe and Webber (1964)). The effectiveness of HA is a result of an unique combination of elastic and viscous properties, which are correlated to the molecular weight. Therefore, there was early an interest in obtaining as high molecular weights as possible. Web site: http://www.delphion.com/details?pn=US06537795__ •

Method for detecting anti-Streptococcus pyogenes DNase B antibody in a test sample Inventor(s): Adams; Craig W. (Corona, CA), Belei; C. Marina (Anaheim, CA), Pang; Patty P. Y. (Rancho Cucamonga, CA) Assignee(s): Beckman Coulter, Inc. (fullerton, Ca) Patent Number: 6,632,614 Date filed: July 21, 1998 Abstract: The gene for Streptococcus pyogenes DNase B has been cloned and vectors incorporating the cloned DNA have been used to transform Escherichia coli, allowing efficient and rapid production of the DNase in E. coli without the necessity of growing large quantities of S. pyogenes. The enzyme can be produced with a leader peptide at its amino terminus. An improved method for the purification of naturally occurring S. pyogenes DNase B enzyme is also provided. The DNase B enzyme produced, either by purification of naturally occurring enzyme or by recombinant DNA techniques, can be used to generate antibodies and can also be used in immunochemical assays to detect the presence of anti-DNase B antibodies in serum as a marker of infection by S. pyogenes. Excerpt(s): This invention is directed to recombinant DNase B derived from the pathogenic bacterium Streptococcus pyogenes, methods for its production, and methods for its use. Despite advances in the prevention and treatment of bacterial infection, a number of bacterial pathogens remain serious problems in medical practice and continue to cause severe, even fatal disease. One of these pathogens is S. pyogenes. Among the diseases caused by S. pyogenes are streptococcal pharyngitis ("strep throat"), scarlet fever, and their suppurative complications, including cervical adenitis, otitis media, mastoiditis, peritonsillar abscesses, meningitis, pneumonitis, pneumonia, puerperal sepsis, cellulitis of the skin, impetigo, lymphangitis, erysipelas, acute glomerulonephritis, and rheumatic fever. Such infections often occur in hospitals

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(nosocomial infection), particularly in patients whose normal immune system functioning is suppressed. The latter category includes patients with AIDS, patients taking immunosuppressive drugs for cancer or to prevent transplant rejection, and patients having poor circulation, e.g., patients with diabetes. Web site: http://www.delphion.com/details?pn=US06632614__ •

Method for preparing food products by fermenting soy milk with streptococcus thermophilus Inventor(s): Boufassa; Corinne (Igny, FR), Tourancheau; Myriam (Palaiseau, FR) Assignee(s): Compagnie Gervais Danone (levallois-perr, Fr) Patent Number: 6,699,517 Date filed: July 2, 2002 Abstract: The invention provides a method for obtaining food products with reduced post-fermentation acidification, by fermenting mixtures of soy milk and either grain meal or almond milk with Streptococcus thermophilus and, optionally, other lactic acid bacteria. Excerpt(s): The invention relates to fermented products based on plant raw materials. It is known to use plant raw materials, in particular cereals, as substitutes or supplements for raw materials of milk origin in the manufacture of fermented food products, with the aim of combining the beneficial properties of these plant products with those of lactic ferments. For example, application EP 0,622,024 describes a product intended for early childhood feeding, consisting of 95% of yoghurt and 5% of a cereals meal mixture (oats, rice and wheat) and of soy extract, pasteurized beforehand and then fermented with Bifidobacterium infantis and optionally Streptococcus thermophilus, to a pH of about 4.6 to 4.7. It is indicated that this fermented supplement improves the nutritional value and the digestibility of the yoghurt, while providing nutrients which are essential for the growth of young children in a directly assimilable form, and that, in addition, the presence of the soy extract promotes the fermentative activity of Bifidobacterium infantis, and improves its viability. However, this document gives no precise information on the storage life of the fermented supplement or on that of the finished product (supplement+yoghurt), or on the effective rate of survival of the bacteria in the fermented supplement or in the final product. Web site: http://www.delphion.com/details?pn=US06699517__

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Method of immunization using a Group B Streptococcus type II and type III polysaccharide conjugate vaccine Inventor(s): Michon; Francis (Laurel, MD), Tai; Joseph Y. (Fort Washington, PA), Uitz; Catherine (Arlington, VA) Assignee(s): Baxter International Inc. (deerfield, Il) Patent Number: 6,602,508 Date filed: May 18, 2001 Abstract: The process for depolymerizing Group B Types II and III streptococcal polysaccharide is disclosed which results in polysaccharide fragments having a

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reducing end suitable for conjugating to protein. Conjugate molecules, vaccines and their use to immunize mammals including humans are also disclosed. Excerpt(s): The capsular polysaccharides from GBS bacteria are known to be important to GBS virulence and the development of protective immunity. See Kasper et al. U.S. Pat. No. 5,302,386. Moreover, the CP of recognized GBS types (I-V) are chemically related but antigenically distinct having repeating structures composed of galactose, glucose, N-acetyl glucosamine, and N-acetyl-neuraminic (sialic) acid. Infants and young children have poor immunogenic response to polysaccharide antigens. These responses are characterized as being T cell independent and therefore are not associated with important attributes such as memory, isotype switching, or affinity maturation, which are necessary for conferring long term immunologic protection against subsequent infection. To circumvent this lack of an effective immunogenic response in infants and young children to polysaccharides, the art has developed means of converting the T cell independent response to T cell dependent response by covalently coupling polysaccharide bacterial antigens to a carrier protein to form a conjugate molecule. See, Jennings et al. U.S. Pat. No. 4,356,170, which is incorporated herein by reference. Various procedures have been described in the art for conjugating capsular polysaccharides to proteins. For review, see Contributions to Microbiology and Immunology, vol 10, Conjugate Vaccines, volume editions J. M. Cruse and R. E. Lewis, Jr., 1989, which is incorporated herein by reference. In one method, polysaccharide is subjected to mild acid hydrolysis to produce reducing end groups capable of reacting with protein to form a covalent bond. Anderson, P. A., Infect. Immun., 39:233-238 (1983). However, the terminal sugar groups which participate in conjugating to protein exist in equilibrium between a hemiacetal and aldehyde and therefore couple to protein with poor efficiency. To overcome the poor reactivity of the terminal reducing sugar, the art turned to mild oxidation to introduce stable aldehyde groups at terminal positions of polysaccharides used to conjugate to protein. Jennings et al. U.S. Pat. No. 4,356,170, supra. Web site: http://www.delphion.com/details?pn=US06602508__ •

Method of isolating a peptide which immunologically mimics microbial carbohydrates including group B streptococcal carbohydrates and the use thereof in a vaccine Inventor(s): Pincus; Seth H. (Bozman, MT) Assignee(s): Research Development Institute, Inc. (bozeman, Mt) Patent Number: 6,444,787 Date filed: December 30, 1998 Abstract: This invention relates to new vaccines against microorganisms based on antigenically mimetic peptides. The invention also relates to methods of discovering such mimetic peptides by first screening peptide-display phage libraries with antibodies against the microbial carbohydrates(s) of interest to locate antigenically mimetic peptides. Vaccines against Group B Streptococcus, or Streptococcus Agalactiae, are preferably produced using this method. Excerpt(s): This invention relates to new vaccines against microorganisms based on antigenically mimetic peptides. The invention also relates to methods of discovering such mimetic peptides by screening peptide-display phage libraries with antibodies against the microbial carbohydrates(s) of interest to locate antigenically mimetic peptides. Vaccines against Group B Streptococcus, or Streptococcus Agalactiae, can be

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produced using this method. Vaccines against other microbial pathogens may also be produced using this method. Vaccines protect against disease by harnessing the body's innate ability to protect itself against foreign invading agents. During vaccination, the patient is injected with antigens, or DNA encoding antigens, which generate protective antibodies but which typically cannot cause severe disease themselves. For example, vaccination for bacterial diseases such as typhoid fever consists of injecting a patient with the bacterial agents of these diseases, after they have been disabled in some fashion to prevent them from causing disease. The patient's body recognizes these bacteria nonetheless and generates an antibody response against them. It is not always possible, however, to stimulate antibody formation merely by injecting the foreign agent which causes the disease. The foreign agent must be immunogenic, that is, it must be able to induce an immune response. Certain agents such as tetanus toxoid are innately immunogenic, and may be administered in vaccines. Other clinically important agents are not immunogenic, however, and must be converted into immunogenic molecules before they can induce an immune response. Successfully accomplishing this conversion for a variety of antigens is a major goal of a great deal of immunologic research. Web site: http://www.delphion.com/details?pn=US06444787__ •

Microorganisms useful in a method of producing.alpha.-halo-.alpha.,.beta.-saturated carbonyl compounds Inventor(s): Esaki; Nobuyoshi (Shiga, JP), Kamachi; Harumi (Chiba, JP), Kamachi; Motoaki (Chiba, JP), Yoneda; Tadashi (Chiba, JP) Assignee(s): Showa Denko Kabushiki Kaisha (tokyo, Jp) Patent Number: 6,645,752 Date filed: September 26, 2001 Abstract: A method of producing an.alpha.-halo-.alpha.,.beta.-saturated carbonyl compound from an.alpha.-halocarbonyl compound having an.alpha.,.beta.-carboncarbon double bond by reducing said.alpha.,.beta.-carbon-carbon double bond using a microorganism belonging to any one of the genera Acetobacter, Actinomyces, Acinetobacter, Agrobacterium, Aeromonas, Alcaligenes, Arthrobacter, Azotobacter, Bacillus, Brevibacterium, Burkholderia, Cellulomonas, Corynebacterium, Enterobacter, Enterococcus, Escherichia, Flavobacterium, Gluconobacter, Halobacteium, Halococccus, Klebsiella, Lactobacillus, Microbacterium, Micrococcus, Micropolyspora, Mycobacterium, Nocardia, Pseudomonas, Pseudonocardia, Rhodococcus, Rhodobacter, Serratia, Staphylococcus, Streptococcus and Streptomyces, Xanthomonas, or a microbial product thereof. Pseudomonas sp. SD810, SD811 and SD812, Burkholderia sp. SD 816, and mutants thereof having an activity of reducing the.alpha.,.beta.-carbon-carbon double bond of an.alpha.-halocarbonyl compound having an.alpha.,.beta.-carbon-carbon double bond. Excerpt(s): The present invention relates to a method of producing a corresponding.alpha.-halo-.alpha.,.beta.-saturated carbonyl compound from an.alpha.halocarbonyl compound having an.alpha.,.beta.-carbon-carbon double bond by hydrogenating the.alpha.,.beta.-carbon-carbon double bond using a microorganism belonging to the genus Acetobacter, Actinomyces, Acinetobacter, Agrobacterium, Aeromonas, Alcaligenes, Arthrobacter, Azotobacter, Bacillus, Brevibacterium, Burkholderia, Cellulomonas, Corynebacterium, Enterobacter, Enterococcus, Escherichia, Flavobacterium, Gluconobacter, Halobacteium, Halococccus, Klebsiella, Lactobacillus, Microbacterium, Micrococcus, Micropolyspora, Mycobacterium, Nocardia,

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Pseudomonas, Pseudonocardia, Rhodococcus, Rhodobacter, Serratia, Staphylococcus, Streptococcus, Streptomyces or Xanthomonas, preferably a microorganism belonging to the genus Pseudomonas or Burkholderia, more preferably Pseudomonas sp. SD810, Pseudomonas sp. SD811, Pseudomonas sp. SD812 or Burkholderia sp. SD816, or a microbial product thereof. The present invention also relates to novel microorganisms belonging to the genera Pseudomonas and Burkholderia, particularly Pseudomonas sp. SD810, Pseudomonas sp. SD811, Pseudomonas sp. SD812 and Burkholderia sp. SD816. Furthermore, the present invention relates to a method of producing a corresponding.alpha.-halo-.alpha.,.beta.-saturated carbonyl compound as an S form compound with respect to the.alpha.-position from an.alpha.-halocarbonyl compound having an.alpha.,.beta.-carbon-carbon double bond by hydrogenating the carbon-carbon double bond. This method can be used in the production of optically active carbonyl compounds such as various optically active (having an absolute S form configuration at the.alpha.-position) saturated carboxylic acids or amides. The optically active carbonyl compounds are a highly valuable chiral building block which is difficult to prepare by classical chemical processes, and are materials useful particularly as a raw material of medical or agricultural chemicals. In recent years, a method of producing various compounds, particularly optically active substances, by the reduction of a carbon--carbon double bond using a microorganism is drawing attention. To this effect, various methods of producing a corresponding.alpha.,.beta.-saturated carbonyl compound having a substituent at the.alpha.-position from a carbonyl compound having an.alpha.,.beta.-carbon-carbon double bond and having a substituent at the.alpha.-position by microbially reducing the carbon--carbon double bond have been reported (see, H. Simon, et al., Hoppe-Seyler's Z. Physiol. Chem., 362, 33 (1981), H. Giesel, et al., Arch. Microbiol., 135, 51 (1983), H. G. W. Leuenberger, et al., Helv. Chim. Acta., 62, 455 (1979), R. Matsuno, et al., J. Ferm. Bioeng., 84, 195 (1997)). However, for example, according to the method of using bacteria as the microorganism, an anaerobe such as Clostridium kluyveri (DSM-555) or Clostridium sp. La-1 (DSM-1460) is used. Therefore, the growing rate of the microorganism is slow, it is difficult to increase the cell concentration and accordingly, the reaction rate is not satisfactorily high. Thus, these methods have a problem in profitability and operability. Web site: http://www.delphion.com/details?pn=US06645752__ •

Modulating production of pneumococcal capsular polysaccharide Inventor(s): Weiser; Jeffrey N. (Merion, PA) Assignee(s): The Children's Hospital of Philadelphia (philadelphia, Pa) Patent Number: 6,642,017 Date filed: January 30, 2002 Abstract: The invention relates to methods of modulating capsular polysaccharide production in pneumococci such as Streptococcus pneumoniae. The invention further relates to methods of alleviating pneumococcal infections in animals, and to methods of identifying both agents capable of modulating pneumococcal capsular polysaccharide biosynthesis and agents useful for alleviating pneumococcal infections in animals. Excerpt(s): The invention relates broadly to production of capsular polysaccharide material from streptococcal organisms and to production of vaccines using such material. Streptococcus pneumoniae, sometimes designated pneumococcus, is generally a commensal organism colonizing the mucosal surface of the human nasopharynx. When host factors allow the organism access to the lower respiratory tract, a vigorous

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inflammatory response ensues, leading to a dense consolidation as alveolar air spaces fill with exudate. This condition is commonly referred to as pneumonia (Tuomanen et al., 1995). The most serious manifestation of pneumococcal infection is bacteremia, which can be complicated by sepsis, meningitis, or both. Bacteremia in adults is usually a complication of pneumonia (Raz et al., 1997). The ability of the pneumococcus to resist the major mechanism of clearance of the organism from the bloodstream (i.e. opsonophagocytosis) requires expression of the major virulence factor of the organism, which is a polysaccharide capsule (Avery et al., 1931; Watson et al., 1990). Pneumococci are capable of synthesizing no fewer than 90 structurally unique capsular polysaccharides (CPSs). Web site: http://www.delphion.com/details?pn=US06642017__ •

Multi oligosaccharide glycoconjugate bacterial meningitis vaccines Inventor(s): Chong; Pele (Richmond Hill, CA), Klein; Michel H. (Willowdale, CA), Lindberg; Alf (Lyons, FR) Assignee(s): Aventis Pasteur Limited (toronto, Ca) Patent Number: 6,656,472 Date filed: December 22, 2000 Abstract: Multivalent immunogenic molecules comprise a carrier molecule containing at least one functional T-cell epitope and multiple different carbonhydrate fragments each linked to the carrier molecule and each containing at least one functional B-cell epitope. The carrier molecule inparts enhanced immunogenicity to the multiple carbohydrate fragments. The carbohydrate fragments may be capsular oligosaccharide fragments from Streptococcus pneumoniae which may be serotypes (1, 4, 5, 6B, 9V, 14, 18C, 19F or 23F), or Neisseria meningitidis, which may be serotype (A, B, C) W-135 or Y. Such oligosaccharide fragments may be sized from about 2 to about 5 kDa. Alternatively, the carbohydrate fragments may be fragments of carbohydrate-based tumor antigens, such as Globo H, Le.sup.Y or STn. The multivalent molecules may be produced by random conjugation or site-directed conjugation of the carbohydrate fragments to the carrier molecule. The multivalent molecules may be employed in vaccines or in the generation of antibodies for diagnostic applications. Excerpt(s): The present invention is related to the field of vaccines and is particularly related to the development of novel glycoconjugation technologies which can be used to prepare glycoconjugates in which multi-oligosaccharides are covalently linked to the same carrier protein. Haemophilus influenzae type b (Hib), Neisseria meningitidis and Streptococcus pneumoniae are major causes of bacterial meningitis in children under five years of age. All these bacteria are protected from phagocytosis by a polysaccharidic capsule. Antibodies induced against the capsular polysaccharide (CPs) of the organism are protective in most cases. Effective Hib conjugate vaccines in which Hib CPs, PRP, is linked to different carrier proteins, such as diphtheria toxoid (PRP-D), tetanus toxoid (PRP-T), CRM 197 (HbOC) and the outer membrane proteins of N. meningitidis (PRPOMP), have been developed. Four Hib conjugate vaccines are now commercially available. New glycoconjugate vaccines against N. meningitidis and S. pneumoniae are highly recommended by the American College of Physicians. The development of multivalent pneumococcal vaccines for the prevention of both systemic and noninvasive pneumococcal diseases in infants, the elderly and immune-compromised individuals has gained increasing importance over the last decade. For more detailed reviews of pneumococcal disease, epidemiology, or the polysaccharide vaccine, numerous review

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articles are available (ref. 1, various references are referred to in parenthesis to more fully describe the state of the art to which this invention pertains. Full bibliographic information for each citation is found at the end of the specification, immediately preceding the claims. The disclosure of these references are hereby incorporated by reference into the present disclosure). Web site: http://www.delphion.com/details?pn=US06656472__ •

Nucleic acid and amino acid sequences relating to Streptococcus pneumoniae for diagnostics and therapeutics Inventor(s): Bush; David (Somerville, MA), Doucette-Stamm; Lynn (Framingham, MA), Houseweart; Chad Eric (Waltham, MA), Opperman; Timothy (Somerville, MA), Zeng; Qiandong (Waltham, MA) Assignee(s): Genome Therapeutics Corporation (waltham, Ma) Patent Number: 6,699,703 Date filed: May 26, 2000 Abstract: The invention provides isolated polypeptide and nucleic acid sequences derived from Streptococcus pneumoniae that are useful in diagnosis and therapy of pathological conditions; antibodies against the polypeptides; and methods for the production of the polypeptides. The invention also provides methods for the detection, prevention and treatment of pathological conditions resulting from bacterial infection. Excerpt(s): The invention relates to isolated nucleic acids and polypeptides derived from Streptococcus pneumoniae that are useful as molecular targets for diagnostics, prophylaxis and treatment of pathological conditions, as well as materials and methods for the diagnosis, prevention, and amelioration of pathological conditions resulting from bacterial infection. Streptococcus pneumoniae (S. pneumoniae) is a common, spherical, gram-positive bacterium. Worldwide it is a leading cause of illness among children, the elderly, and individuals with debilitating medical conditions (Breiman, R. F. et al., 1994, JAMA 271: 1831). S. pneumoniae is estimated to be the causal agent in 3,000 cases of meningitis, 50,000 cases of bacteremia, 500,000 cases of pneumonia, and 7,000,000 cases of otitis media annnually in the United States alone (Reichler, M. R. et al., 1992, J. Infect. Dis. 166: 1346; Stool, S. E. and Field, M. J., 1989 Pediatr. Infect. Dis J. 8: S11). In the United States alone, 40,000 deaths result annually from S. pneumoniae infections (Williams, W. W. et al., 1988 Ann. Intern. Med. 108: 616) with a death rate approaching 30% from bacteremia (Butler, J. C. et al., 1993, JAMA 270: 1826). Pneumococcal pneumonia is a serious problem among the elderly of industrialized nations (Kayhty, H. and Eskola, J., 1996 Emerg. Infect. Dis. 2: 289) and is a leading cause of death among children in developing nations (Kayhty, H. and Eskola, J., 1996 Emerg. Infect. Dis. 2: 289; Stansfield, S. K., 1987 Pediatr. Infect. Dis. 6: 622). Vaccines against S. pneumoniae have been available for a number of years. There are a large number of serotypes based on the polysaccharide capsule (van Dam, J. E., Fleer, A., and Snippe, H., 1990 Antonie van Leeuwenhoek 58: 1) although only a fraction of the serotypes seem to be associated with infections (Martin, D. R. and Brett, M. S., 1996 N. Z. Med. J. 109: 288). A multivalent vaccine against capsular polysaccharides of 23 serotypes (Smart, L. E., Dougall, A. J. and Gridwood, R. W., 1987 J. Infect. 14: 209) has provided protection for some groups but not for several groups at risk for pneumococcal infections, such as infants and the elderly (Makel, P. H. et al., 1980 Lancet 2: 547; Sankilampi, U., 1996 J. Infect. Dis. 173: 387). Conjugated pneumococcal capsular polysaccharide vaccines have somewhat

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improved efficacy, but are costly and, therefore, are not likely to be be in widespread use (Kayhty, H. and Eskola, J., 1996 Emerg. Infect. Dis. 2: 289). Web site: http://www.delphion.com/details?pn=US06699703__ •

Pneumococcal surface proteins and uses thereof Inventor(s): Briles; David E. (Birmingham, AL), Brooks-Walter; Alexis (Birmingham, AL), Crain; Marilyn J. (Birmingham, AL), Hollingshead; Susan (Birmingham, AL), McDaniel; Larry S. (Ridgland, MS), Swiatlo; Edwin (Birmingham, AL), Tart; Rebecca (Benson, NC), Yother; Janet (Birmingham, AL) Assignee(s): University of Alabama at Birmingham (birmingham, Al) Patent Number: 6,500,613 Date filed: September 16, 1996 Abstract: The present invention relates to pneumococcal genes, portions thereof, expression products therefrom and uses of such genes, portions and products; especially to genes of Streptococcus pneumoniae, e.g., the gene encoding pneumococcal surface protein A (PspA), i.e., the pspA gene, the gene encoding pneumococcal surface protein A-like proteins, such as pspA-like genes, e.g., the gene encoding pneumococcal surface protein C (PspC), i.e., the pspC gene, portions of such genes, expression products therefrom, and the uses of such genes, portions thereof and expression products therefrom. Excerpt(s): This invention relates to pneumococcal genes, portions thereof, expression products therefrom and uses of such genes, portions and products; especially to genes of Streptococcus pneumoniae, e.g., the gene encoding pneumococcal surface protein A (PspA) (said gene being "pspA"), pspA-like genes, pneumococcal surface protein C (PspC) (said gene being "pspC"), portions of such genes, expression products therefrom, and the uses of such genes, portions thereof and expression products therefrom. Such uses include uses of the genes and portions thereof for obtaining expression products by recombinant techniques, as well as for detecting the presence of Streptococcus pneumoniae or strains thereof by detecting DNA thereof by hybridization or amplification (e.g., PCR) and hybridization techniques (e.g., obtaining DNA-containing sample, contacting same with genes or fragment under PCR, amplification and/or hybridization conditions, and detecting presence of or isolating hybrid or amplified product). The expression product uses include use in preparing antigenic, immunological or vaccine compositions, for eliciting antibodies, an immunological response (other than or additional to antibodies) or a protective response (including antibody or other immunological response by administering composition to a suitable host); or, the expression product can be for use in detecting the presence of Streptococcus pneumoniae by detecting antibodies to Streptococcus pneumoniae protein(s) or antibodies to a portion thereof in a host, e.g., by obtaining an antibodycontaining sample from a relevant host, contacting the sample with expression product and detecting binding (for instance by having the product labeled); and, the antibodies generated by the aforementioned compositions are useful in diagnostic or detection kits or assays. Thus, the invention relates to varied compositions of matter and methods for use thereof. Streptococcus pneumoniae is an important cause of otitis media, meningitis, bacteremia and pneumonia. Despite the use of antibiotics and vaccines, the prevalence of pneumococcal infections has declined little over the last twenty-five years. It is generally accepted that immunity to Streptococcus pneumoniae can be mediated by specific antibodies against the polysaccharide capsule of the pneumococcus. However,

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neonates and young children fail to make an immune response against polysaccharide antigens and can have repeated infections involving the same capsular serotype. Web site: http://www.delphion.com/details?pn=US06500613__ •

Polypeptide fragments capable of competition with Streptococcus mutans antigen I/II Inventor(s): Kelly; Charles (London, GB), Lehner; Thomas (London, GB) Assignee(s): The Council of Governors of the United Medical & Dental School of Guy's and (gb) Patent Number: 6,500,433 Date filed: December 9, 1999 Abstract: Defined peptide subunits of Streptococcus mutans antigen I/II (SAI/II) are useful as agents to prevent and treat dental caries either by eliciting an immunological response or by preventing adhesion of S. mutans to the tooth. Excerpt(s): This invention relates to polypeptide fragments of the Streptococcus mutans I/II antigen that are useful in treating and preventing dental caries. Streptococcus mutans is the main etiological agent of dental caries, a disease which affects mammals including humans. The S. mutans I/II antigen (SA I/II) is a cell surface protein with an M.sub.r of about 185 kDa. It is believed to comprise several antigenic epitopes and to be at least partly responsible for S. mutans adhesion to teeth. Web site: http://www.delphion.com/details?pn=US06500433__

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Probe for diagnosing infectious diseases Inventor(s): Eda; Soji (Kyoto, JP), Keshi; Hiroyuki (Osaka, JP), Matsuhisa; Akio (Osaka, JP), Uehara; Hirotsugu (Takarazuka, JP), Ueyama; Hiroshi (Osaka, JP) Assignee(s): Fuso Pharmaceutical Industries, Ltd. (osaka, Jp) Patent Number: 6,660,852 Date filed: May 16, 1997 Abstract: A probe derived from bacteria of pneumonia, containing fragments of DNA which streptococcus pneumoniae essentially possesses, and useful for detecting and identifying causative bacteria of pneumonia is obtained by completely digesting the DNA with a restriction endonuclease PstI, followed by cloning into a suitable vector. Excerpt(s): The present invention relates to a probe which is useful for detecting and identifying the causative bacteria of infectious diseases, especially Streptococcus pneumoniae which is a representative causative bacterium of bacterial pneumonia. In pathology, infection is defined as an invasion and an establishment of an anchorage for growth in a host organism by a pathogenic organism (hereinafter referred to as "bacterium"). The outbreak of a disease caused by proliferation of a bacterium in vivo depends upon the interrelationship between the resistance of the host organism and the virulence of the bacterium. To improve therapeutic systems for treatment of infectious diseases, especially inflammatory diseases caused by Streptococcus pneumoniae and the like in pulmonary lobes and bronchia, namely bacterial pneumonia, among the infectious diseases, has been urgent problem in the field of this art. Such bacterial pneumonia is triggered by an attack with bacteria, e.g., Streptococcus pneumoniae,

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Staphylococcus aureus and the like which cause inflammation predominantly in alveoli. When suffered from bacterial pneumonia, generally from clinical aspect, inflammatory symptoms in upper airway followed by sudden chill and shiver attach, then crisis of high fever around 40.degree. C., and terrible cough, stethalgia and sputum have appeared. Web site: http://www.delphion.com/details?pn=US06660852__ •

Streptococcus and isoflavone-containing composition Inventor(s): Imaizumi; Kiyoko (Kurume, JP), Kumemura; Megumi (Kurume, JP), Masaki; Kyosuke (Kurume, JP), Shimizu; Seiichi (Tosu, JP), Uchiyama; Shigeto (Saga, JP), Ueno; Tomomi (Kurume, JP) Assignee(s): Otsuka Pharmaceutical Co., Ltd. (tokyo, Jp) Patent Number: 6,716,424 Date filed: February 8, 2000 Abstract: This invention provides a composition comprising a daidzein-containing substrate and a strain of micro-organism capable of metabolizing daidzein to equol as essential ingredients. This composition is effective in the prevention and alleviation of unidentified clinical syndrome inclusive of menopausal syndrome in middle-aged to elderly woman for which no effective means of prevention or alleviation has heretofore been available. Excerpt(s): The present invention relates to an isoflavone-containing composition and more particularly to a novel composition either comprising a daidzein-containing substance and a strain of microorganism capable of metabolizing daidzein to equol or comprising equol obtained by causing said strain of microorganism to act upon said daidzein-containing substance, which composition is useful for the prevention and alleviation of unidentified clinical syndrome and conditions associated with the menopause in middle-aged to elderly women. The documented collaborative research of National Cancer Center of Japan and Helsinki University (Finland) attributes the low incidence of gender-specific neoplastic diseases such as carcinoma of the prostate in men and carcinoma of the breast or ovary in women among the Japanese as compared with the European and American people to the greater intake by the Japanese of soybeanderived foods containing various isoflavonoids and the consequent well-coordinated balance of hormones (H. Adlercreutz, et al., (1992) Lancet, 339, 1233; H. Adlercreutz, et al., (1992) Lancet, 342, 1209-1210). Recently, there has been a mounting interest in the fact that isoflavonoids have estrogen (female hormone)-like activity (A. Molteni, et al.,(1995) J. Nutr., 125, 751S-756S), and it has been reported that these compounds are effective in osteoporosis which develops after the menopause when estrogen secretions have subsided or ceased (D. Agnusdei, et al., (1995) Bone and Mineral, 19 (Supple), S43S48) as well as in menopausal syndrome (D. D. Baird, et al., (1995) J. Clin. Endocrinol, Metab., 80, 1685-1690; A. L. Murkies, et al., (1995) Maturitas., 21, 195-198). Web site: http://www.delphion.com/details?pn=US06716424__

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Streptococcus pneumoniae antigens and vaccines Inventor(s): Barash; Steven C. (Rockville, MD), Choi; Gil H. (Rockville, MD), Dillon; Patrick J. (Carlsbad, CA), Dougherty; Brian (Killingworth, CT), 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: 6,573,082 Date filed: March 28, 2000 Abstract: The present invention relates to novel vaccines for the prevention or attenuation of infection by Streptococcus pneumoniae. The invention further relates to isolated nucleic acid molecules encoding antigenic polypeptides of Streptococcus pneumoniae. Antigenic polypeptides are also provided, as are vectors, host cells and recombinant methods for producing the same. The invention additionally relates to diagnostic methods for detecting Streptococcus nucleic acids, polypeptides and antibodies in a biological sample. Excerpt(s): The present invention relates to novel Streptococcus pneumoniae antigens for the detection of Streptococcus and for the prevention or of disease caused by Streptococcus. The invention further relates to isolated nucleic acid molecules encoding antigenic polypeptides of S. pneumoniae. Antigenic polypeptides are also provided, as are vectors, host cells and recombinant methods for producing the same. The invention additionally relates to diagnostic methods for detecting Streptococcus gene expression. Streptococcus pneumoniae has been one of the most extensively studied microorganisms since its first isolation in 1881. It was the object of many investigations that led to important scientific discoveries. In 1928, Griffith observed that when heatkilled encapsulated pneumococci and live strains constitutively lacking any capsule were concomitantly injected into mice, the nonencapsulated could be converted into encapsulated pneumococci with the same capsular type as the heat-killed strain. Years later, the nature of this "transforming principle," or carrier of genetic information, was shown to be DNA. (Avery, O. T., et al., J. Exp. Med., 79:137-157 (1944)). In spite of the vast number of publications on S. pneumoniae many questions about its virulence are still unanswered, and this pathogen remains a major causative agent of serious human disease, especially community-acquired pneumonia. (Johnston, R. B., et al., Rev. Infect. Dis. 13(Suppl. 6):S509-517 (1991)). In addition, in developing countries, the pneumococcus is responsible for the death of a large number of children under the age of 5 years from pneumococcal pneumonia. The incidence of pneumococcal disease is highest in infants under 2 years of age and in people over 60 years of age. Pneumococci are the second most frequent cause (after Haemophilus influenzae type b) of bacterial meningitis and otitis media in children. With the recent introduction of conjugate vaccines for H. influenzae type b, pneumococcal meningitis is likely to become increasingly prominent. S. pneumoniae is the most important etiologic agent of community-acquired pneumonia in adults and is the second most common cause of bacterial meningitis behind Neisseria meningitidis. Web site: http://www.delphion.com/details?pn=US06573082__

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Treatment of chronic inflammatory diseases with CM101/GBS toxin Inventor(s): Hellerqvist; Carl G. (Brentwood, TN), Wamil; Barbara D. (Nashville, TN) Assignee(s): Vanderbilt University (nashville, Tn) Patent Number: 6,476,002 Date filed: October 28, 1999 Abstract: A method of treating a chronic inflammatory disease such as rheumatoid arthritis or psoriasis includes treating a patient with a toxin derived from Group B.beta.hemolytic Streptococcus bacteria. The purified GBS toxin, or CM101, may be administered. intravenously to the patient in repeated doses. Excerpt(s): This invention relates to the treatment of chronic inflammatory diseases, including rheumatoid arthritis and psoriasis. Chronic inflammatory diseases such as rheumatoid arthritis (RA) and psoriasis are debilitating diseases affecting millions of people. In the initial stages of RA, the synovium of the affected joint becomes enlarged and inflamed. Expansion of the synovium is accompanied by angiogenesis and neovascularization. This, in turn, facilitates infiltration into the area by plasma cells, lymphocytes, and macrophages. As inflammatory cells accumulate within it, the synovium becomes edematous and hyperplastic. Neutrophils infiltrate the synovial fluid and cluster on the surface of the synovium. Fibrin deposition also occurs in the joint space. The synovial fluid increases in volume and turbidity with the accumulation of neutrophils, mononuclear cells and occasional red blood cells. Web site: http://www.delphion.com/details?pn=US06476002__

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Use of yacM and yqeJ, essential bacterial genes and polypeptides and their use Inventor(s): Fritz; Christian (Natick, MA), Guzman; Luz-Maria (Boston, MA), Youngman; Philip (Boston, MA) Assignee(s): Millennium Pharmaceuticals, Inc. (cambridge, Ma) Patent Number: 6,664,074 Date filed: February 23, 2001 Abstract: Disclosed are genes, termed "yacM" and "yqeJ," which are essential for survival for a wide range of bacteria, such as Streptococcus pneumoniae, Bacillus subtilis, and E. coli. These genes and the essential polypeptides they encode can be used to identify antibacterial agents for treating a broad spectrum of bacterial infections. Excerpt(s): The invention relates to the use of yacM and yqeJ, which are essential bacterial genes, in identifying antibacterial agents. Bacterial infections may be cutaneous, subcutaneous, or systemic. Opportunistic bacterial infections can be life threatening, especially in patients afflicted with AIDS or other diseases that compromise the immune system. Most bacteria that are pathogenic to humans are gram-positive bacteria. The bacterium Streptococcus pneumoniae, for example, typically infects the respiratory tract and can cause lobar pneumonia, as well as meningitis, sinusitis, and other infections. The invention is based on the discovery that the yacM and yqeJ genes of the gram positive bacterium Streptococcus pneumoniae, termed "S-yacM" and "SyqeJ," are essential for survival. Thus, the essential polypeptides that these genes encode are useful targets for identifying compounds that are inhibitors of the bacteria in which the polypeptides are expressed. Such inhibitors can inhibit bacterial growth by inhibiting the activity of an essential protein, or by inhibiting transcription of an

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essential gene or translation of the mRNA transcribed from the essential gene. The amino acid and nucleic acid sequences of the Streptococcus yacM and yqeJ polypeptides and genes are set forth in FIGS. 1 and 2, as summarized in Table 1. Web site: http://www.delphion.com/details?pn=US06664074__ •

Use of YLQF, YQEG, YYBQ, and YSXC, essential bacterial genes and polypeptides Inventor(s): Fritz; Christian (Natick, MA), Guzman; Luz-Maria (Boston, MA), Youngman; Philip (Boston, MA) Assignee(s): Millennium Pharmaceuticals, Inc. (cambridge, Ma) Patent Number: 6,638,729 Date filed: December 17, 2001 Abstract: Disclosed are genes found in Streptococcus pneumoniae that are essential for survival for a wide range of bacteria. These genes are termed "S-ylqF," "S-yqeG," "SyybQ," "S-yerL," and "S-ysxC." These genes and the polypeptides that they encode, as well as homologs and orthologs thereof can be used to identify antibacterial agents for treating a broad spectrum of bacterial infections. Excerpt(s): The invention relates to the use of ylqF, yqeG, yybQ, yerL, and ysxC, essential bacterial genes and polypeptides in identifying antibacterial agents. Bacterial infections may be cutaneous, subcutaneous, or systemic. Opportunistic bacterial infections proliferate, especially in patients afflicted with AIDS or other diseases that compromise the immune system. Most bacteria that are pathogenic to humans are gram positive bacteria. The bacterium Streptococcus pneumoniae, for example, typically infects the respiratory tract and can cause lobar pneumonia, as well as meningitis, sinusitis, and other infections. The invention is based on the identification of ten genes of the gram positive bacterium Streptococcus pneumoniae and of Bacillus subtilis as being essential for survival. The Streptococcus pneumoniae genes are termed "S-ylqF," "S-yqeG," "S-yybQ," "S-yerL," and "S-ysxC." The orthologs of these genes in Bacillus subtilis are termed "B-ylqF," "B-yqeG," "B-yybQ," "B-yerL," and "B-ysxC," respectively. The terms "ylqF," "yqeG," "yybQ," "yerL," and "ysxC" genes and polypeptides are used to refer to the Streptococcus pneumoniae and Bacillus subtilis genes and polypeptides, as well as their homologs and orthologs, collectively. While "homologs" are structurally similar genes contained within a species, "orthologs" are functionally equivalent genes from other species (within or outside of a given genus, e.g., from E. coli). These genes are considered "essential" genes, and their polypeptides are considered "essential" polypeptides. Each gene and polypeptide can be used in methods for identifying similar genes and polypeptides in pathogenic and non-pathogenic microorganisms. Each polypeptide can be used to identify compounds that are inhibitors of the pathogens in which the polypeptide (ylqF, yqeG, yybQ, yerL, or ysxC) is expressed. Such inhibitors attenuate bacterial growth by inhibiting the activity of ylqF, yqeG, yybQ, yerL, or ysxC polypeptide, or by inhibiting gene transcription or translation. Web site: http://www.delphion.com/details?pn=US06638729__

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•

Vaccine formulations comprising antiidiotypic antibodies which immunologically mimic group B streptococcal carbohydrates Inventor(s): Polonelli; Luciano (Parma, IT), Teti; Giuseppe (Messina, IT) Assignee(s): Chiron S.r.l. (siena, It) Patent Number: 6,676,938 Date filed: May 17, 2001 Abstract: The invention relates to peptide, oligopeptide or polypeptide compounds that are capable of eliciting a protective immune response against the capsular polysaccharide of group B Streptococcus (GBS), particularly type III GBS. Such compounds are useful in the development of vaccines that are effective against diseases caused by these pathogens. Excerpt(s): The present invention relates to compounds that are capable of eliciting a protective immune response against the capsular polysaccharide of group B Streptococcus (GBS), particularly type III GBS. Such compounds are useful in the development of vaccines that are effective against diseases caused by these pathogens. Group B streptococci (GBS) are recognised as a major cause of sepsis and meningitis in neonates and in susceptible adult patients such as those suffering from diabetes, cirrhosis and solid tumours. Although the use of antibiotics has had a dramatic impact on case fatality rate, the attack rates for infection have changed little. Indeed, even in industrialised countries, the incidence of mortality and permanent disability remains high in spite of appropriate therapy being applied. Immunisation of fertile women with a combination of type-antigens has been proposed as a strategy for the prevention of neonatal disease, with the rationale that specific antibodies passing through the placental barrier can prevent neonatal infection (Baker et al., 1981). Indeed, a significant correlation has been shown between GBS infection in neonates and low levels of maternal antibodies to the type-specific CHO (Baker et al., 1981; Baker et al., 1976). Web site: http://www.delphion.com/details?pn=US06676938__

Patent Applications on Streptococcus As of December 2000, U.S. patent applications are open to public viewing.9 Applications are patent requests which have yet to be granted. (The process to achieve a patent can take several years.) The following patent applications have been filed since December 2000 relating to streptococcus: •

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

9

This has been a common practice outside the United States prior to December 2000.

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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 •

Antibacterial compounds with activity against penicillin-resistant streptococcus pneumoniae Inventor(s): Djuric, Stevan; (Libertyville, IL), Ma, Zhenkun; (Dallas, TX), Marron, Thomas; (Libertyville, IL), Phelan, Kathleen; (Gurnee, IL), Yong, Hong; (Grayslake, IL), Zanze, Irini; (Lake Bluff, IL) Correspondence: Steven F. Weinstock; Abbott Laboratories; 100 Abbott Park Road; DEPT. 377/ap6a; Abbott Park; IL; 60064-6008; US Patent Application Number: 20040009932 Date filed: April 23, 2003 Abstract: Compounds which are useful as antibacterials for penicillin-resistant streptococcus pneumoniae and having formula (I) 1and formula (II) 2and 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 or treatment of bacterial infections using the compounds are disclosed. Excerpt(s): This application claims benefit of co-pending U.S. Provisional Application Ser. No. 60/375,652, filed Apr. 26, 2002, the specification of which is hereby incorporated by reference into this application. This invention is directed to compounds which have activity against penicillin-resistant streptococcus pneumoniae, processes for making the compounds and intermediates used the processes, compositions containing the compounds, and methods for prophylaxis or treatment of penicillin-resistant streptococcus pneumoniae using the compounds. Because the effectiveness of many drugs currently available for prophylaxis or treatment of penicillin-resistant

Patents 203

streptococcus pneumoniae is being compromised by drug-resistance, novel compounds with activity against penicillin-resistant streptococcus pneumoniae would be beneficial for their therapeutic value and their contribution to the antibacterial arts. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Antibody and immunoassay Inventor(s): Fukushima, Kazuo; (Tokyo, JP), Hanyu, Naohiro; (Tokyo, JP), Hirata, Kouichirou; (Tokyo, JP), Ukaji, Fumio; (Tokyo, JP) Correspondence: Oblon, Spivak, Mcclelland, Maier & Neustadt, P.C.; 1940 Duke Street; Alexandria; VA; 22314; US Patent Application Number: 20030124635 Date filed: December 17, 2002 Abstract: Streptococcus mutans in saliva or dental plaque collected from the oral cavity can be measured by the method of the present invention conveniently with high sensitivity without the performance of any complex procedure, such as culturing. The reactivity of the antibody of the present invention against Streptococcus mutans is 1000fold or more greater than its reactivity against each of Streptococcus gordonii, Streptococcus salivarius, Streptococcus oralis, Streptococcus mitis, and Streptococcus sanguis. Excerpt(s): The present invention relates to a polyclonal antibody which is specific for Streptococcus mutans, a method for producing the polyclonal antibody, a method for measuring a level of Streptococcus mutans, an immunoassay reagent and an immunochromatography test strip. Generally, a group of lactic acid producing bacteria referred to as mutans streptococci is known to be deeply associated with the onset of dental caries. The mutans streptococci is classified into 7 species which are serologically and genetically different: Streptococcus cricetus (S. cricetus, serotype a), Streptococcus rattus (S. rattus, serotype b), Streptococcus mutans (S. mutans, serotype c, e and f), Streptococcus ferus (S. ferus, serotype c), Streptococcus macacae (S. macacae, serotype c), Streptococcus sobrinus (S. sobrinus, serotype d and g) and Streptococcus downey (S. downey, serotype h). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

•

Choline binding proteins for anti-pneumococcal vaccines Inventor(s): Masure, H. Robert; (Germantown, TN), Rosenow, Carsten I.; (Redwood City, CA), Tuomanen, Elaine; (Germantown, TN), Wizemann, Theresa M.; (Germantown, MD) Correspondence: Klauber & Jackson; 411 Hackensack Avenue; Hackensack; NJ; 07601 Patent Application Number: 20030175293 Date filed: April 9, 2001 Abstract: The invention relates to bacterial choline binding proteins (CBPs) which bind choline. Such proteins are particularly desirable for vaccines against appropriate strains of Gram positive bacteria, particularly streptococcus, and more particularly pneumococcus. Also provided are DNA sequences encoding the bacterial choline binding proteins or fragment thereof, antibodies to the bacterial choline binding

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proteins, pharmaceutical compositions comprising the bacterial choline binding proteins, antibodies to the bacterial choline binding proteins suitable for use in passive immunization, and small molecule inhibitors of choline binding protein mediated adhesion. Methods for diagnosing the presence of the bacterial choline binding protein, or of the bacteria, are also provided. In a specific embodiment, a streptococcal choline binding protein is an enolase, which demonstrates strong affinity for fibronectin. Excerpt(s): The present application claims priority to Provisional Patent Application Serial No. 60/016,632, filed May 1, 1996, pursuant to 35 USC 119(e), the disclosure of which is incorporated herein by reference in its entirety. The present invention relates generally to choline binding proteins, methods for isolating choline binding proteins, and the genes encoding such proteins. The invention also relates to acellular vaccines to provide protection from bacterial infection using such proteins, and to antibodies against such proteins for use in diagnosis and passive immune therapy. In particular, the choline binding proteins of the invention are useful as vaccines against pneumococcus. Where a choline binding protein demonstrates activity as an adhesion protein, it is also useful as a competitive inhibitor of bacterial adhesion, or to discover small molecule antagonists of adhesion. Exported proteins in bacteria participate in many diverse and essential cell functions such as motility, signal transduction, macromolecular transport and assembly, and the acquisition of essential nutrients. For pathogenic bacteria, many exported proteins are virulence determinants that function as adhesions to colonize and thus infect the host or as toxins to protect the bacteria against the host's immune system [International Patent Publication No. WO 95/06732, published Mar. 9, 1995 by Masure et al., which is specifically incorporated herein by reference in its entirety, for a review, see Hoepelman and Tuomanen, Infect. Immun., 60:1729-33 (1992)]. However, other exported proteins may not directly mediate adhesion. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Compositions and methods immunogenic protein genes

for

detecting

streptococcus

agalactiae

surface

Inventor(s): Shah, Ketan; (San Diego, CA), Dattagupta, Nanibhushan; (San Diego, CA) Correspondence: Pennie And Edmonds; 1155 Avenue OF The Americas; New York; NY; 100362711 Patent Application Number: 20040009482 Date filed: July 9, 2002 Abstract: This invention relates generally to Group B streptococci (GBS) Streptococcus agalactiae detection. More specifically, the present invention provides for novel probes for a specific and sensitive diagnostic test of GBS. These GBS-specific probes hybridize with the the surface immunogenic protein (sip) gene. Arrays comprising the probes immobilized on a support for hybridization analysis and methods for GBS detection using the probes are also provided. Excerpt(s): This invention relates generally to Group B streptococci (GBS) detection. More specifically, the present invention provides for novel probes for a specific and sensitive diagnostic test for GBS. These GBS-specific probes hybridize with the surface immunogenic protein (sip) gene. Arrays comprising the novel probes immobilized on a support for hybridization analysis and methods for GBS detection using the probes are also provided. Life-threatening bacterial infections (bacteremia, pneumonia, and

Patents 205

meningitis) by Group B streptococci (also referred to herein as "GBS" or "Streptococcus agalactia") are the major cause of morbidity and mortality in neonates and very young infants (Schuchat, Clin. Microbiol. Rev. 11: 497-513 (1998)). Two to three of every 1,000 live births result in GBS infection. Approximately 75% of infections in infants occur in the first few days of life (early-onset infections), while late-onset infections typically occur in infants between 1 week and 3 months of age. Newborns with early-onset GBS disease usually acquire the organism from their GBS-colonized mothers during vaginal delivery. Therefore, prenatal screening for GBS is now recommended to reduce the incidence of early-onset GBS disease (see Committee on Infectious Diseases and Committee on Fetus and Newborn, Revised guidelines for prevention of early-onset group B streptococci (GBS) infection, Pediatrics, 99: 489-496 (1997)). Another problem associated with GBS is that the frequent use of antibiotics during the prenatal period has led to the emergence of an antibiotic-resistant strains of GBS. Furthermore, GBS infections also pose a significant danger of sepsis and menigitis in adults that are elderly, immunocompromised, or suffering from diabetes, cirrhosis, and malignancies. Early detection of GBS is thus critical among these patients to insure prompt and costeffective treatment to control the infection. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Detection of group a streptococcus Inventor(s): Uhl, James R.; (Rochester, MN), Cockerill, Franklin R.; (Rochester, MN) Correspondence: Fish & Richardson P.C.; 3300 Dain Rauscher Plaza; 60 South Sixth Street; Minneapolis; MN; 55402; US Patent Application Number: 20040014118 Date filed: June 19, 2003 Abstract: The invention provides methods to detect Group A Streptococcus (GAS) in biological samples using real-time PCR. Primers and probes for the detection of GAS are provided by the invention. Articles of manufacture containing such primers and probes for detecting GAS are further provided by the invention. Excerpt(s): This invention relates to bacterial diagnostics, and more particularly to detection of.beta.-hemolytic Group A Streptococcus (GAS). Streptococcus pyogenes is a group A streptococcal gram-positive bacterium that is the etiological agent of several diseases in humans, including pharyngitis and/or tonsillitis, skin infections (impetigo, erysipelas, and other forms of pyoderma), acute rheumatic fever (ARF), scarlet fever (SF), poststreptococcal glomerulonephritis (PSGN), and a toxic shock-like syndrome (TSLS). On a global basis, ARF is the most common cause of pediatric heart disease. For example, it is estimated that in India, more than six million school-aged children suffer from rheumatic heart disease. In the United States, "sore throat" is the third most common reason for physician office visits and S. pyogenes is recovered from about 30% of children with this complaint. There are about 25-35 million cases of streptococcal pharyngitis per year in the United States, responsible for about 1-2 billion dollars per year in health care costs. The invention provides for methods of identifying group A streptococcus (GAS) in a biological sample. Primers and probes for detecting GAS are provided by the invention, as are kits containing such primers and probes. Methods of the invention can be used to rapidly identify GAS nucleic acids from specimens for diagnosis of GAS infection. Using specific primers and probes, the methods include amplifying and monitoring the development of specific amplification products using real-time PCR.

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Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Diagnostic assay for antibiotic tolerance Inventor(s): Atkinson, Robyn M.; (Memphis, TN), Tuomanen, Elaine I.; (Germantown, TN) Correspondence: ST. Jude Children's Research Hospital; Office OF Technology Licensing; 332 N. Lauderdale; Memphis; TN; 38105; US Patent Application Number: 20030175796 Date filed: May 2, 2003 Abstract: Allelic variation in the vex2, pep27 and vncS genes of bacteria responsible for tolerance to antibiotics such as penicillin and vancomycin, is taught. Methods for identifying antibiotic tolerant bacteria and subjects infected with such bacteria, particularly antibiotic tolerant Streptococcus pneumoniae, are provided. Test kits and components useful for performing such methods, particularly including oligonucleotide primers, are also provided. Excerpt(s): This invention relates to the field of diagnostics based on DNA sequence information. Antimicrobial resistance to multiple antibiotics is a significant and well described clinical problem; however, a less well-characterized phenomenon, antimicrobial tolerance, has emerged in pathogenic isolates of Streptococcus pneumoniae with potentially serious effects on patient outcome. Tolerance describes the ability of bacteria to stop growing in the presence of an antibiotic, while surviving to resume growth once the antibiotic is removed. Incidence of tolerance to vancomycin, the antibiotic of last resort for Gram-positive infections, has increased to 8% in the past few years. Tolerance has also been implicated in poor patient outcome with pneumococcal meningitis, mortality 30% versus non-tolerant 5% (unpublished data). In 1997, a locus was identified that is believed to control the activation of the major pneumococcal autolytic enzyme LytA, which is the enzyme whose loss of function is associated with tolerance. Novak, R. B. et al, "Emergence of vancomycin tolerance in Streptococcus pneumoniae`, Nature 399:590-593 (1999). The operon, vex/pep27/vncr/s, encodes for a signal peptide, Pep27, that is transported out of the cell via the Vex dedicated transporter. Novak, R. et al., "Signal transduction by a death signal peptide: uncovering the mechanism of bacterial killing by penicillin", Molec Cell. 5:49-57 (2000). Pep27 is believed to be a quorum sensing peptide. Novak et al., id. (2000). Once it reaches a critical density in the supernatant, it signals through the two-component regulatory system, VncS and VncR, which subsequently induces activation of LytA. Novak et al., id. (2000). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

Patents 207

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Expression of sucrose phosphorylase in plants Inventor(s): Barry, Gerard Francis; (St. Louis, MO), de Weerd, Jan Willem; (Meridian, ID), Kishore, Ganesh Murthy; (Chesterfield, MO), Weldon, Marcia Lee; (Bonne Terre, MO) Correspondence: Catina Coy; Howrey Simon Arnold & White, Llp; 750 Bering Drive; Houston; TX; 77057-2198; US Patent Application Number: 20030110535 Date filed: November 5, 2002 Abstract: Introducing sucrose phosphorylase activity into plants by transformation with a gene for the enzyme increases the rate of sucrose hydrolysis, leading to increased starch, oil, and protein levels. The preferred gene is from Streptococcus mutans. Surprisingly, in potatoes transformed to express this gene in tubers, reduced bruise discoloration susceptibility and increased uniformity of starch deposition throughout the tuber are achieved. Excerpt(s): Recent advances in genetic engineering have provided the requisite tools to transform plants to contain foreign genes. It is now possible to produce plants which have unique characteristics of agronomic and crop processing importance. Certainly, one such advantageous trait is enhanced starch and/or solids content and quality in various crop plants. Another is enhanced oil and protein content of seeds of various crop plants. Sucrose is the carbon storage unit which is transported from the source tissues of most plants to the sink tissues. In sink tissues it is hydrolyzed and the components used to build other, more complex storage units, primarily starch, protein, and oil. The hydrolysis is primarily accomplished by sucrose synthase which produces UDPglucose and fructose. UDPglucose is converted to glucose 1-phosphate by UDPglucose pyrophosphorylase. The starch content of the sink tissues of various crop plants has been increased through the use of a gene encoding a bacterial ADPglucose pyrophosphorylase. See PCT Application WO 91/19806 (equivalent to U.S. Ser. No. 08/120,703, Kishore, incorporated herein by reference). This enzyme catalyzes the production of ADPglucose from glucose 1-phosphate. It has also been found that its expression during certain phases of seed development can decrease the oil content which is thought to be due to the shunting of raw material to the starch pathway with a concomitant decrease in its availability for oil production. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

•

Facilitation of wound healing with CM101/GBS toxin Inventor(s): Abramovitch, Rinat; (Mordechai, IL), Hellerqvist, Carl G.; (Brentwood, TN), Neeman, Michal; (Mazkeret Batya, IL), Wamil, Barbara D.; (Nashville, TN) Correspondence: Cooley Godward, Llp; 3000 EL Camino Real; 5 Palo Alto Square; Palo Alto; CA; 94306; US Patent Application Number: 20030180331 Date filed: March 24, 2003 Abstract: The method of the present invention provides a means of treating a patient having a wound, especially by minimizing scarring and accelerating wound healing, by administering CM101 or GBS toxin isolated from Group B.beta.-hemolytic streptococcus bacteria. The method of the present invention also includes administration of CM101 or

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GBS toxin to surgery patients having tumors in order to facilitate wound healing and minimize the likelihood of tumor progression. Excerpt(s): This invention relates to the facilitation of wound healing in patients, by minimizing scarring and accelerating healing. This invention also relates to the reduction of wound-related tumor progression. The normal process of healing a skin wound that has been surgically induced or is the result of trauma involves formation of a blood clot and, often, a scab. More particularly, first intention, or primary healing, generally occurs at clean incisions, whereas second intention, or secondary healing, occurs where wound edges are far apart. The protein fibrin holds the edges of the skin surrounding the wound together and the scab seals the wound and staves off infection. While an inflammatory response brings increased numbers of blood cells to the area to aid in the repair process, epithelial tissue regenerates and capillaries grow from blood vessels at the edges of the wound. The capillaries revascularize the area of the wound and contribute to the formation of granulation tissue which, in turn, causes scarring. Granulation tissue begins to form in the wound site and fills the site approximately five days after wound induction. Granulation tissue contains new collagen, fibroblasts, new blood vessels and inflammatory cells, especially macrophages (E. Rubin and J. L. Farber, Pathology, Lippincott, publ., pp. 85-95 (1994)). After seven to ten days, the wound has regained only 10% of the tissue's original strength. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Formulation and method for preventing antibiotics-induced diaper rash Inventor(s): Bartels, Jennifer F.; (Hammond, IA) Correspondence: Jennifer F. Bartels; 601 N. Hazel ST.; Hammond; IA; 70401; US Patent Application Number: 20030157067 Date filed: February 18, 2003 Abstract: A formulation and method for the prevention of antibiotics induced diaper rash comprising a) live active cultures selected from the group consisting of lactobacillus bulgaricus, streptococcus thermophilus, lactobacillus acidophilus, bifidus, and mixtures thereof; b) a pharmaceutically acceptable carrier; c) sugars or syrups selected from the group consisting of glucose, dextrose, fructose, sucrose, and derivatives and mixtures thereof, and d) flavorings. The pharmaceutically acceptable carrier is selected from the group consisting of purified water, soy milk, infant formula, juices, and mixtures thereof. The formulation might further comprise preservatives, diluents, fillers, starches and coloring. In its preferred embodiment, the formulation would be placed, poured or mixed into a dropper dispenser bottle for infant dosage. Excerpt(s): The present invention relates to a convenient liquid formulation for children and infants who are too young to chew probiotic tablets or consume probiotic drink mixes or persons who otherwise are unable to ingest other forms of probiotics due to age, illness, or disability. It has long been known that antibiotics dosages often cause diarrhea. The resulting diaper rash which invariably accompanies this diarrhea due to the intestinal flora imbalance caused by the antibiotics is a cause of great discomfort for both infants, patients, and caregivers. The present invention focuses on the diaper rash which results from intestinal flora imbalances that occur during antibiotic dosages. It is difficult to say that there is prior art relating to the diaper rash component of intestinal imbalances, since none of the many probiotics formulations found ever mentioned the problem of diaper rash.

Patents 209

Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Genes and proteins, and their use Inventor(s): Dobson, Richard James; (Berkshire, GB), Dougan, Gordon; (London, GB), Everest, Paul; (Dumbartonshire, GB), Feldman, Robert; (Berkshire, GB), Hughes, Martin John Glenton; (Berkshire, GB), Lane, Jonathan Douglas; (Berkshire, GB), Moore, Joanne Christine; (Berkshire, GB), Santangelo, Joseph David; (Berkshire, GB), Wilson, Rebecca Kerry; (London, GB) Correspondence: Saliwanchik Lloyd & Saliwanchik; A Professional Association; 2421 N.W. 41st Street; Suite A-1; Gainesville; FL; 326066669 Patent Application Number: 20030104000 Date filed: March 11, 2002 Abstract: A protein from Group B Streptococcus is shown to be an outer surface protein and is a useful target for antimicrobial therapy. Excerpt(s): This Application is a continuation-in-part of U.S. Ser. No. 09/868,352, filed on Jun. 15, 2001. This invention relates to the identification of a bacterial gene and protein, and its use. More particularly, it relates to its use in therapy, for immunisation and in screening for drugs. Early Onset Neonatal Infection. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Hyaluronate synthase gene and uses thereof Inventor(s): DeAngelis, Paul L.; (Galveston, TX), Papaconstantinou, John; (Galveston, TX), Weigel, Paul H.; (League City, TX) Correspondence: Dunlap, Codding & Rogers, P.C.; Suite 420; 9400 North Broadway; Oklahoma City; OK; 73114; US Patent Application Number: 20030104415 Date filed: April 15, 2002 Abstract: Disclosed are DNA sequences encoding hyaluronic acid synthase that are employed to construct recombinant cells useful in the production of hyaluronate synthase and hyaluronic acid (HA). In preferred aspects, chromosomal DNA encoding the HA synthase gene, hasA, was cloned from a Streptococcus pyogenes genomic library. These vectors were used to transform host cells such as E. coli and acapsular Streptococci to produce hyaluronic acid. Resultant transformants were screened to identify colonies which have incorporated HA synthase DNA in a form that is being actively transcribed into the corresponding HA synthase enzyme. These colonies were selected and employed in the production of hyaluronic acid. Excerpt(s): The present invention relates to a nucleic acid encoding the enzyme hyaluronate synthase, and to the use of this nucleic acid in the preparation of recombinant cells for the production of the hyaluronate synthase enzyme and hyaluronic acid. Hyaluronate is also known as hyaluronic acid or hyaluronan. The incidence of streptococcal infections is a major health and economic problem worldwide, particularly in developing countries (Rotta, 1988). One reason for this is due to the ability of Streptococcal bacteria to grow undetected by the body's phagocytic cells (i.e., macrophages and polymorphonuclear cells (PMNs). These cells are responsible for

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recognizing and engulfing foreign microorganisms. One effective way the bacteria evade surveillance is by coating themselves with polysaccharide capsules, such as hyaluronic acid (HA) capsules. (Kendall et al., 1937). Since HA is generally nonimmunogenic (Quinn and Singh, 1957), the encapsulated bacteria do not elicit an immune response and are, therefore, not targeted for destruction. Moreover, the capsule exerts an antiphagocytic effect on PMNs in vitro (Hirsch, et al., 1960) and prevents attachment of Streptococcus to macrophages (Whitnack, et al., 1981). Precisely because of this, in group A and group C Streptococci, the HA capsules are major virulence factors in natural and experimental infections (Kass, et al., 1944; Wessels, et al., 1991). Group A Streptococcus are responsible for numerous human diseases including pharyngitis, impetigo, deep tissue infections, rheumatic fever and a toxic shock-like syndrome (Schaechter, et al., 1989). The group C Streptococcus equisimilis is responsible for osteomyelitis (Barson, 1986), pharyngitis (Benjamin, et al., 1976), brain abscesses (Dinn, 1971), and pneumonia (Rizkallah, et al., 1988; Siefkin, et al., 1983). Structurally, HA is a high molecular weight linear polysaccharide of repeating disaccharide units consisting of N-acetylglucosamine (GlcNAc) and glucuronic acid (GlcA) (Laurent and Fraser, 1992). HA is the only glycosaminoglycan synthesized by both mammalian and bacterial cells particularly groups A and C Streptococci. Some Streptococcus strains make HA which is secreted into the medium as well as HA capsules. The mechanism by which these bacteria synthesize HA is of interest since the production of the HA capsule is a very efficient and clever way that Streptococci use to evade surveillance by the immune system. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Immunization of dairy cattle with chimeric GapC protein against streptococcus infection Inventor(s): Fontaine, Michael; (Saskatoon, CA), Perez-Casal, Jose; (Saskatoon, CA), Potter, Andrew A.; (Saskatoon, CA) Correspondence: Robins & Pasternak; 1731 Embarcadero Road; Suite 230; Palo Alto; CA; 94303; US Patent Application Number: 20040062774 Date filed: August 27, 2003 Abstract: The recombinant production of Gap4, a chimeric GapC plasmin binding protein comprising the entire amino acid sequence of the Streptococcus dysgalactiae GapC protein in addition to unique amino acid sequences from the Streptococcus parauberis and Streptococcus agalactiae GapC proteins, is described. Also described is the use of Gap4 chimeric GapC protein in vaccine compositions to prevent or treat streptococcal infections in general and mastitis in particular. Excerpt(s): This application is related to provisional patent application serial No. 60/211,247, filed Jun. 12, 2000, from which application priority is claimed under 35 USC.sctn.119(e)(1) and which application is incorporated herein by reference in its entirety. The present invention relates generally to bacterial antigens and genes encoding the same. More particularly, the present invention pertains to the construction of a chimeric plasmin binding protein gene comprising the entire S. dysgalactiae gapC coding sequence as well as coding sequences for unique regions from several Streptococcus bacteria species, and the use of the same in vaccine compositions. Mastitis, an infection of the mammary gland usually caused by bacteria or fungus, results in major economic losses to the dairy industry yearly. Among the bacterial

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species most commonly associated with mastitis are various species of the genus Streptococcus, including S. aureus, S. uberis, (untypeable), S. agalactiae (Lancefield group B), S. dysgalactiae (Lancefield group C), S. zooepidemicus, and the Lancefield groups D, G., L and N streptococci. Some of those species are contagions (e.g. S. agalactiae), while others are considered environmental pathogens (e.g. S. dysgalactiae and S. uberis). The environmental pathogen S. uberis is responsible for about 20% of all clinical cases of mastitis (Bramley, A. J. and Dodd, F. H. (1984) J. Dairy Res. 51:481-512; Bramley, A. J. (1987) Animal Health Nutrition 42:12-16; Watts, J. L. (1988) J. Dairy Sci. 71:1616-1624); it is the predominant organism isolated from mammary glands during the non-lactating period (Bramley, A. J. (1984) Br. Vet. J 140:328-335; Bramley and Dodd (1984) J. Dairy Res. 51:481-512; Oliver, S. P. (1988) Am. J. Vet. Res. 49:1789-1793). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Immunization of dairy cattle with GapC protein against Streptococcus infection Inventor(s): Bolton, Alexandra J.; (Calgary, CA), Fontaine, Michael; (West Lothian, GB), Perez-Casal, Jose; (Saskatoon, CA), Potter, Andrew A.; (Saskatoon, CA) Correspondence: Cooley Godward, Llp; 3000 EL Camino Real; 5 Palo Alto Square; Palo Alto; CA; 94306; US Patent Application Number: 20030165524 Date filed: April 26, 2002 Abstract: The GapC plasmin binding protein genes of Streptococcus dysgalactiae (S. dysgalactiae), Streptococcus agalactiae (S. agalactiae), Streptococcus uberis (S. uberis), Streptococcus parauberis (S. parauberis), and Streptococcus iniae (S. iniae) are described, as well as the recombinant production of the GapC proteins therefrom. Also described is the use of the GapC proteins from those species in vaccine compositions to prevent or treat bacterial infections in general, and mastitis in particular. Excerpt(s): This application is a continuation-in-part of U.S. patent application Ser. No. 09/878,781, filed Jun. 11, 2001, from which application priority is claimed under 35 USC.sctn.120, which is related to provisional patent application serial No. 60/211,022, filed Jun. 12, 2000, from which application priority is claimed under 35 USC.sctn.119(e)(1), and which applications are incorporated herein by reference in their entireties. The present invention relates generally to bacterial antigens and genes encoding the same. More particularly, the present invention pertains to the cloning, expression and characterization of the GapC plasmin-binding proteins from Streptococcus dysgalactiae, Streptococcus agalactiae, Streptococcus uberis, Streptococcus parauberis, and Streptococcus iniae, and the use of the same in vaccine compositions. Mastitis is an infection of the mammary gland usually caused by bacteria or fungus. The inflammatory response following infection results in decreased milk yield as well as quality, and causes major annual economic losses to the dairy industry. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Immunogen adherence inhibitor directed to lactic acid producing organisms and method of making and using it Inventor(s): Mitteness, Bradley M.; (Ghent, MN), Nash, Peter; (Eden Prairie, MN) Correspondence: Gray, Plant, Mooty, Mooty & Bennett, P.A.; P.O. Box 2906; Minneapolis; MN; 55402-0906; US Patent Application Number: 20040043020 Date filed: September 8, 2003 Abstract: A microbial adherence inhibitor specific to lactic acid producing microorganisms, in the form of fowl egg antibodies is disclosed, along with the method of making it and methods of using it. The inhibitor functions by substantially preventing the attachment or adherence of colony-forming immunogens in the rumen and intestinal tracts of host food animals. The inhibitor is made by inoculating female birds with the immunogen, allowing time for an immune response in the female bird and then harvesting the eggs that contain antibodies to the immunogen. The egg contents can be dried or used as a liquid and added to the feed or water for the host animals. Dependent upon the particular immunogen with which the female bird is inoculated, the egg antibody is used to promote the growth of food animals by improving feed conversion rates by decreasing the lactic acid production caused by the presence of certain colonyforming organisms in the animals, and to substantially reduce or eliminate the incidence of species that have been linked to very high production of lactic acid which can result in reduced performance and in acute situations, dangerously low rumen pH levels. When high levels of lactic acid are present in the rumen, rumen ulcers can form. When rumen ulcers are present other bacteria such as Fusobacterium necrophorum can escape the rumen and cause liver abscesses or laminitis, which further reduce feed conversion efficiency. Colony forming immunogens such as Streptococcus bovis (a major lactic acid producer) and Fusobacterium necrophorum can both be targeted by antibodies to enhance feed efficiency. Excerpt(s): This application is a continuation-in-part of U.S. application Ser. No. 10/038,260 filed on Jan. 7, 2002, which is a divisional application of Ser. No. 09/616,843 filed Jul. 14, 2000 which is a non-provisional application related to provisional application Serial No. 60/201,268 filed on May 2, 2000 and provisional application Serial No. 60/143,985, filed on Jul. 15, 1999. This invention is directed to microbial adherence inhibitors in the form of fowl egg antibodies for substantially preventing the attachment or adherence of colony-forming immunogens or haptens in the rumen and intestinal tract of host food animals, to the method of producing each adherence inhibitors, and to the methods of using such inhibitors to: (1) promote the growth of food animals by improving feed conversion rates by decreasing the lactic acid production organisms in food animals, and (2) to substantially reduce or eliminate the microorganisms that reduce pH and cause problems in the liver and rumen, and erratic feed intake and (3) to reduce the incidence of microorganisms that can escape the rumen and cause liver abscesses and laminitis. Certain common bacterial immunogens in the rumen can produce large amounts of lactic acid. These include but are not limited to Streptococcus bovis and Lactobacillus spp. As the host consumes starch in the diet, these deleterious organisms produce very high amounts of lactic acid that can result in reduced performance and, in acute situations, dangerously low pH rumen levels. Once the pH lowers in the rumen, these bacterial species become the primary etiologic agents in rumen abscesses. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Immunogenic pneumococcal protein and vaccine compositions thereof Inventor(s): Adamou, John E.; (Germantown, MD), Johnson, Leslie S.; (Germantown, MD), Koenig, Scott; (Rockville, MD) Correspondence: Carella, Byrne, Bain, Gilfillan, Cecchi,; Stewart & Olstein; 6 Becker Farm Road; Roseland; NJ; 07068; US Patent Application Number: 20030166844 Date filed: April 27, 2001 Abstract: The present invention relates to novel immunogenic polypeptides, and therapeutically active fragments thereof, and vaccines, and vaccine compositions, for the prevention and treatment of streptococcal infection, especially by Streptococcus pneumoniae. The invention also relates to antibodies against the disclosed polypeptides, as well as methods of disease prevention and/or treatment. Excerpt(s): This application claims the priority of U.S. Provisional Application No. 60/200,074, filed Apr. 27, 2000, the disclosure of which is hereby incorporated by reference in its entirety. This invention relates to the field of bacterial surface proteins and their use as components in vaccines and vaccine compositions for protection against bacterial infections. Streptococcus pneumoniae (S. pneumoniae; pneumococcus) is a gram positive bacterium that is also a major causative agent of invasive infections in animals and humans, including such diseases as sepsis, menningitis, otitis media, and lobar pneumonia. (Tuomanen et al, New Engl. J. Med., 322:1280-1284 (1995)) As part of the infective process, pneumococci readily bind to non-inflamed human epithelial cells of the upper and lower respiratory tract by binding to eukaryotic carbohydrates in a lectin-like manner (Cundell et al, Micro. Path., 17:361-374 (1994)). Conversion to invasive pneumococcal infections for bound bacteria may involve the local generation of inflammatory factors that may activate the epithelial cells to change the number and type of receptors on their surfaces. (Cundell et al, Nature, 377:435-438 (1995)) It has been suggested that one such receptor, platelet activating factor (PAF), is engaged by the pneumococcal bacteria and, within a short period of time, perhaps as short as minutes later, following appearance of PAF, the pneumococcal organisms exhibit strongly enhanced adherence to, and invasion of, tissue. Certain soluble receptor analogs have been shown to prevent the progression of pneumococcal infections (Idanpaan-Heikkila et al, J. Inf. Dis., 176:704-712 (1997)). Other proteins have been suggested as being involved in the pathogenicity of S. pneumoniae, but the majority of the gene products have not been characterized. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Lactic acid bacteria producing polysaccharide similar to those in human milk and corresponding gene Inventor(s): Desachy, Patrice; (Porsel, CH), Gaier, Walter; (Chailly-Montreux, CH), Neeser, Jean-Richard; (Savigny, CH), Pot, Bruno; (Sint-Michiels Brugge, BE), Pridmore, David; (Lausanne, CH), Stingele, Francesca; (St-Prex, CH) Correspondence: Winston & Strawn; Patent Department; 1400 L Street, N.W.; Washington; DC; 20005-3502; US Patent Application Number: 20040023361 Date filed: June 16, 2003

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Abstract: A lactic acid bacterium having a 16S ribosomal RNA characteristic of the genus Streptococcus, cocci morphology, a growth optimum in the range of about 28.degree. C. to about 45.degree. C., having the ability to ferment D-galactose, D-glucose, D-fructose, D-mannose, and N-acetyl (D)-glucosamine, salicin, cellobiose, maltose, lactose, sucrose and raffinose, and imparting a viscosity of greater than 100 mPa.s at a shear rate of about 293 s.sup.-1. The strain often produces an exopolysaccharide comprising a chain of glucose, galactose and N-acetylglucosamine in a proportion of 3:2:1 respectively. The new strain is identified as Streptococcus macedonicus. Other characteristics include a total protein profile obtained after culture in an MRS medium for 24 h at 28.degree. C., extraction of the total proteins and migration of the proteins on an SDS-PAGE electrophoresis gel, exhibits a degree of Pearson correlation of at least 78 with respect to bacterium CNCM I-1920 or I-1926. The strain and its secreted polysaccharides can be used in preparing dietary compositions. The present invention further relates to a new exopolysaccharide synthesis operon and the genes thereof isolated from the new species and to transformed cells having inserted nucleotides that encode proteins of the EPS operon or at least one gene thereof. Excerpt(s): This application is a continuation-in-part of U.S. patent application Ser. No. 09/548,606, filed Apr. 13, 2000, which is a continuation of the U.S. national phase of International Application No. PCT/EP98/06636, filed Oct. 9, 1998, the content of both of which is expressly incorporated herein by reference thereto and claim priority to Swiss Patent Application No. 97203245.2 filed Oct. 17, 1997. The present invention relates to new species of lactic acid bacteria belonging to the genus Streptococcus, identified herein as Streptococcus macedonicus and its use in the production of food compositions. The present invention further relates to a new exopolysaccharide synthesis operon isolated from the new species Streptococcus macedonicus and transformed microorganisms containing the operon or genes thereof. The identification of lactic acid bacteria is essential in the dairy industry, and consists of differentiating distinctive morphological, physiological and/or genetic characteristics between several species. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Lubrication composition Inventor(s): Lewis, Pam; (San Antonio, TX), Siegel, Phyllis B.; (San Antonio, TX), Veach, Tom C.; (San Antonio, TX) Correspondence: John Lezdey & Associates; Suite 302; 4625 East Bay Drive; Clearwater; FL; 33764; US Patent Application Number: 20030211173 Date filed: May 8, 2002 Abstract: An aqueous acidic lubricating composition for use in the mucosal areas of the human body, that provides at least 30 ppm of available iodine. There is also provided a method of treating vaginitis preventing STD and group B streptococcus. Excerpt(s): The present invention relates to an antimicrobial lubricant which can be used in the mucosal areas of the human body. More particularly, there is provided an antimicrobial lubricating composition in gel form or as a liquid which can be utilized in the vaginal cavity. One of the main disciplines of medicine is the treatment of the female reproductive system for the prevention, treatment, mitigation, diagnosis, and cure of diseases, and the prevention of conception. Usually, this involves the delivery of active

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agents to the vaginal cavity and its environs. Systems to affect the delivery of such agents are usually in the form of gels, foams, creams, or suppositories and quick dissolving tablets. The vaginal cavity is subject to conditions which render it as a target for disease and infection; however, it is extremely difficult to deliver an active agent to this area for an extended period of time. The vaginal cavity exhibits an aqueous environment containing secreting glands whose fluids create an acidic pH in the range of 3.5 to 5.5. The environment of the vagina is conducive to the growth of bacteria, fungi, yeast and other microorganisms since it is warm, moist, and dark. It is also the vestibule for menstrual debris and residual seminal fluid from sexual intercourse. The crevices of the vaginal cavity facilitate the retention of undesirable bacteria, fungi, yeast, and other microorganisms as well as the debris from menstruation and sexual intercourse. The vaginal cavity is also subject to considerable physical deformation, such as during sexual intercourse or the insertion of tampons. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Method for inducing an immune response to polysaccharide bacterial antigens and to protein structures of virus capsides Inventor(s): Reynaud, Claude-Agnes; (Paris Cedex, FR), Weill, Jean-Claude; (Paris Cedex, FR) Correspondence: Oppedahl And Larson Llp; P O Box 5068; Dillon; CO; 80435-5068; US Patent Application Number: 20040043039 Date filed: July 22, 2003 Abstract: The invention concerns an immunogenic composition, in a pharmaceutically acceptable carrier, for specifically stimulating a sub-population of B M.sup.+D.sup.+CD27.sup.+ cells so as to provide T-independent anti-bacterial response in said cells. The invention also concerns the use for producing T-independent antibacterial immune responses in subjects infected or susceptible of being infected by polysaccharide bacteria (streptococcus, meningococcus, pneumococcus, hemophilus influenza) or by protein capsid viruses (poliovirus, encephalomyocarditis virus, influenza virus). Excerpt(s): The present invention pertains to the field of immunization of warm-blooded animals, including man, against infectious agents. More specifically, it relates to means of triggering and/or reinforcing immune responses to infections and diseases caused by encapsulated bacteria with polysaccharide functions and/or by protein structures of virus capsids. The immune response to polysaccharide antigens develops gradually during the early years of life (H. Hidalgo et al., "Pre- and postimmunization antibody titers in children with recurrent infections," Ann. All. Asthma. Immunol. 76 (1996), 341346) and involves chiefly the IgG2s. Children under 2 years of age and elderly persons lack defenses against encapsulated bacteria with polysaccharide functions, whereas such individuals are able to respond to T-dependent (protein) antigens. This phenomenon, which has clinical implications, has not been completely elucidated to date. Now, pneumococcus, meningococcus, Haemophilus influenzae and the streptococci are genera with polysaccharide capsule and functions varying according to the strain. By way of example, 84 different serotypes of Pneumococcus have been identified. Now this agent is the principal cause of bacterial pneumopathy, meningitis, sinusitis and otitis. Among these conditions, pneumococcic pneumonia accounts for nearly 5000 deaths per year in France, 90% of them in persons over 65 years of age, and 1 million deaths per year worldwide in children under 5 years (Lancet 354 [1999], editorial, 2011; F. Shann,

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"Pneumococcal vaccine: Time for another controlled trial," Lancet 351 [1998], 1600-1601; G. R. Siber, "Pneumococcal disease: Prospects for a new generation of vaccines," Science 265 [1994], 1385-1387). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Methods for production of hyaluronic acid and isolated strains of supercapsulated streptococci Inventor(s): Stahl, Sten; (Lund, SE) Correspondence: Dinsmore & Shohl, Llp; 1900 Chemed Center; 255 East Fifth Street; Cincinnati; OH; 45202; US Patent Application Number: 20030134393 Date filed: January 29, 2003 Abstract: Isolated strains of supercapsulated streptococci bend at a density of no greater than 1.03 g/cm.sup.3 in a Percoll gradient and are capable of producing hyaluronic acid with molecular weight exceeding 6 million Da. Methods of producing high molecular weight hyaluronic acid employ a supercapsulated strain of streptococcus which bands at a density of no greater than 1.03 g/cm.sup.3 in a Percoll gradient. Methods of selecting streptococcus strains capable of producing hyaluronic acid with a molecular weight exceeding 6 million Da comprise, inter alia, cultivating supercapsulated strains of streptococci which band at a density of no greater than 1.03 g/cm.sup.3 in a Percoll gradient. Excerpt(s): This application is a continuation of Ser. No. 09/496,149 filed Feb. 1, 2000, which is a divisional of Ser. No. 08/737,408 filed Jan. 7, 1997, now U.S. Pat. No. 6,090,596, which is a 371 of PCT/SE95/00585 filed May 24, 1995. The present invention is related to a method for the production of high molecular weight hyaluronic acid by fermention using supercapsulated strains of streptococci. The invention also relates to a method for the selection of supercapsulated mutants and to mutants producing such hyaluronic acid in high yield. Hyaluronic acid (HA) or hyaluronan is a glycosaminoglucan consisting of repeating disaccharides of alternating D-glucuronic acid and N-acetylglucosamine molecules. These molecules are joined by a.beta. (1,3)-D linkage while the glucosamine to glucuronic acid linkage is.beta. (1,4)-D. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Methods of use of gemifloxacin compounds against fluoroquinolone resistant streptococcus pneumoniae bacteria Inventor(s): Bast, Darrin; (Hamilton, CA), Davidson, Ross J.; (Halifax, CA), DeAzavedo, Joyce; (Toronto, CA), Low, Donald E.; (Toronto, CA) Correspondence: Glaxosmithkline; Corporate Intellectual Property - Uw2220; P.O. Box 1539; King OF Prussia; PA; 19406-0939; US Patent Application Number: 20030105127 Date filed: December 18, 2002 Abstract: This invention relates, in part, to newly identified methods of using quinolone antibiotics, particularly a gemifloxacin compound against certain pathogenic bacteria.

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Excerpt(s): This invention relates, in part, to newly identified methods of using quinolone antibiotics, particularly a gemifloxacin compound against Streptococcus pneumonia bacteria, such as fluoroquinolone resistant S. pneumoniae, especially ciprofloxacin or trovafloxacin resistant S. pneumoniae. Quinolones have been shown to be effective to varying degrees against a range of bacterial pathogens. However, as diseases caused by these pathogens are on the rise, there exists a need for antimicrobial compounds that are more potent than the present group of quinolones. PCT/KR98/00051 discloses (R;S)-7-(3-aminomethyl-4-syn-methoxyimino-- pyrrolidin-1yl)-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid methanesulfonate and hydrates thereof including the sesquihydrate. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Novel fibronectin-binding protein Inventor(s): Frykberg, Lars; (Uppsala, SE), Guss, Bengt; (Uppsala, SE), Jacobsson, Karin; (Uppsala, SE), Lindmark, Hans; (Uppsala, SE) Correspondence: Birch Stewart Kolasch & Birch; PO Box 747; Falls Church; VA; 220400747; US Patent Application Number: 20030165527 Date filed: October 11, 2002 Abstract: The present invention is concerned with a novel fibronectin-binding protein of Streptococcus equi, to a DNA fragment encoding this protein, to host cells and vectors containing said DNA fragment and to methods to produce said protein based on recombinant DNA technology.The invention is also related to use of said protein in the preparation of a vaccine, to a vaccine containing said protein, to antibodies specific for said protein and to polyvalent antisera containing such antibodies. Excerpt(s): This application is the national phase under 35 U.S.C.sctn.371 of PCT International Application No. PCT/SE99/02448 which has an International filing date of Dec. 21, 1999, which designated the United States of America. The present invention is generally related to a novel protein, methods to produce said protein and use thereof, e.g. for immunization purposes. More specifically, the present invention is related to a novel fibronectin-binding protein derived from a bacterium belonging to the genus Streptococcus, to a DNA sequence encoding said protein, recombinant DNA methods for the production of said protein, and use of said protein per se or a fragment thereof as an immunogenic protein or antigenic polypeptide or peptide, e.g. for use as an active component in a vaccine, or to produce antisera. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Novel group B streptococcus antigens Inventor(s): Boyer, Martine; (Beauport, CA), Brodeur, Bernard R.; (Sillery, CA), Charlebois, Isabelle; (St-Nicolas, CA), Hamel, Josee; (Sillery, CA), Martin, Denis; (StAugustin-de-Desmaures, CA), Rioux, Clement; (Ville de Cap rouge, CA) Correspondence: Millen, White, Zelano & Branigan, PC; 2200 Clarendon Blvd; Suite 1400; Arlington; VA; 22201; US Patent Application Number: 20030228323 Date filed: January 13, 2003 Abstract: Group B streptococcus (GBS) proteins and polynucleotides encoding them are disclosed. Said proteins are antigenic and therefore useful vaccine components for the prophylaxis or therapy of streptococcus infection in animals. Also disclosed are recombinant methods of producing the protein antigens as well as diagnostic assays for detecting streptococcus bacterial infection. Excerpt(s): The present invention is related to antigens, more particularly protein antigens of group B streptococcus (GBS) bacterial pathogen which are useful as vaccine components for therapy and/or prophylaxis. Streptococcus are gram (+) bacteria that are differentiated by group specific carbohydrate antigens A through 0 found on their cell surface. Streptococcus groups are further distinguished by type-specific capsular polysaccharide antigens. Several serotypes have been identified for the Group B streptococcus (GBS): Ia, Ib, II, III, IV, V, VI, VII and VIII. GBS also contains antigenic proteins known as "C-proteins" (alpha, beta, gamma and delta), some of which have been cloned. Although GBS is a common component of the normal human vaginal and colonic flora this pathogen has long been recognized as a major cause of neonatal sepsis and meningitis, late-onset meningitis in infants, postpartum endometritis as well as mastitis in dairy herds. Expectant mothers exposed to GBS are at risk of postpartum infection and may transfer the infection to their baby as the child passes through the birth canal. Although the organism is sensitive to antibiotics, the high attack rate and rapid onset of sepsis in neonates and meningitis in infants results in high morbidity and mortality. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Nucleic acids and proteins from group B streptococcus Inventor(s): Hanniffy, Sean Bosco; (Cambridge, GB), Le Page, Richard William Falla; (London, GB), Wells, Jeremy Mark; (Norwich, GB) Correspondence: Hunton & Williams; Intellectual Property Department; 1900 K Street, N.W.; Suite 1200; Washington; DC; 20006-1109; US Patent Application Number: 20030138775 Date filed: January 26, 2001 Abstract: Novel protein antigens from Group B Streptococcus are described, together with nucleic acid sequences encoding them. Their use in vaccines and screening methods is also described. Excerpt(s): This application is based on Provisional Application No. 60/125,163 filed Mar. 19, 1999 and is a continuation of International Application PCT/GB99/02444 filed Jul. 27, 1999, the disclosure of each being incorporated herein by reference in its entirety. The present invention relates to proteins derived from Streptococcus agalactiae, nucleic

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acid molecules encoding such proteins, and the use of the proteins as antigens and/or immunogens and in detection/diagnosis. It also relates to a method for the rapid screening of bacterial genomes to isolate and characterise bacterial cell envelope associated or secreted proteins. The Group B Streptococcus (GBS) (Streptococcus agalactiae) is an encapsulated bacterium which emerged in the 1970s as a major pathogen of humans causing sepsis and meningitis in neonates as well as adults. The incidence of early onset neonatal infection during the first 5 days of life varies from 0.7 to 3.7 per 1000 live births and causes mortality in about 20% of cases. Between 25-50% of neonates surviving early onset infections frequently suffer neurological sequalae. Late onset neonatal infections occur from 6 days to three months of age at a rate of about 0.51.0 per 1000 live births. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Nucleic acids and proteins from Streptococcus pneumoniae Inventor(s): Hanniffy, Sean Bosco; (Cambridge, GB), Hansbro, Philip Michael; (Newcastle, AU), Le Page, Richard William Falla; (London, GB), Wells, Jeremy Mark; (Norwich, GB) Correspondence: Brobeck, Phleger & Harrison, Llp; Attn: Intellectual Property Department; 1333 H Street, N.W. Suite 800; Washington; DC; 20005; US Patent Application Number: 20030134407 Date filed: January 26, 2001 Abstract: Novel proteins from Streptococcus pneumoniae are described, together with nucleic acid sequences encoding them. Their use in vaccines and in screening methods is also described. Excerpt(s): The present invention relates to proteins derived from Streptococcus pneumoniae, nucleic acid molecules encoding such proteins, the use of the nucleic acid and/or proteins as antigens/immunogens and in detection/diagnosis, as well as methods for screening the proteins/nucleic acid sequences as potential anti-microbial targets. Streptococcus pneumoniae, commonly referred to as the pneumococcus, is an important pathogenic organism. The continuing significance of Streptoccocus pneumoniae infections in relation to human disease in developing and developed countries has been authoritatively reviewed (Fiber, G. R., Science, 265: 1385-1387 (1994)). That indicates that on a global scale this organism is believed to be the most common bacterial cause of acute respiratory infections, and is estimated to result in 1 million childhood deaths each year, mostly in developing countries (Stansfield, S. K., Pediatr. Infect. Dis., 6: 622 (1987)). In the USA it has been suggested (Breiman et al, Arch. Intern. Med., 150: 1401 (1990)) that the pneumococcus is still the most common cause of bacterial pneumonia, and that disease rates are particularly high in young children, in the elderly, and in patients with predisposing conditions such as asplenia, heart, lung and kidney disease, diabetes, alcoholism, or with immunosupressive disorders, especially AIDS. These groups are at higher risk of pneumococcal septicaemia and hence meningitis and therefore have a greater risk of dying from pneumococcal infection. The pneumococcus is also the leading cause of otitis media and sinusitis, which remain prevalent infections in children in developed countries, and which incur substantial costs. The need for effective preventative strategies against pneumococcal infection is highlighted by the recent emergence of penicillin-resistant pneumococci. It has been reported that 6.6% of pneumoccal isolates in 13 US hospitals in 12 states were found to be resistant to penicillin and some isolates were also resistant to other antibiotics

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including third generation cyclosporins (Schappert, S. M., Vital and Health Statistics of the Centres for Disease Control/National Centre for Health Statistics, 214:1 (1992)). The rates of penicillin resistance can be higher (up to 20%) in some hospitals (Breiman et al, J. Am. Med. Assoc., 271: 1831 (1994)). Since the development of penicillin resistance among pneumococci is both recent and sudden, coming after decades during which penicillin remained an effective treatment, these findings are regarded as alarming. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Pneumococcus polysaccharide conjugates for use as vaccine against tetanus an diphtheria Inventor(s): Schultz, Dominique; (Lyon, FR) Correspondence: Mcdonnell Boehnen Hulbert & Berghoff; 300 South Wacker Drive; Suite 3200; Chicago; IL; 60606; US Patent Application Number: 20030099672 Date filed: September 17, 2002 Abstract: The invention relates to the use of a composition comprising n Streptococcus pneumoniae polysaccharides conjugated to the tetanus toxoid and p Streptococcus pneumoniae polysaccharides conjugated to the diphtheria toxoid, for manufacturing a vaccine which protects against Clostridium tetani and/or Corynebacterium diphtheriae infections in which:(1) n and p are other than 1, with p being, however,.ltoreq.15,(2) 2.ltoreq.n+p.ltoreq.38,(3) the total amount of conjugated toxoid present in one vaccine dose is sufficient to induce protection against Clostridium tetani and/or Corynebacterium diphtheriae infections. Excerpt(s): The present invention relates to the use of vaccine combinations for preventing tetanus and/or diphtheria. In multivalent vaccine compositions, although there are many advantages in mutually combining the antigens so as to confer protection against several pathogens, negative interactions between the antigens may exist, the consequence of which is a relative drop in the immunogenicity of one or more components. This risk is all the greater given that the number of antigens, also called "valences", is considerable. Multivalent vaccines are known which comprise in particular diphtheria and tetanus valencies. Combining diphtheria, tetanus and whooping cough antigens with those of the polio virus leads to a decrease in the immune response to whooping cough. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Polynucleotide primers and probes for rapid detection of Group B streptococcal (GBS) Inventor(s): Kurnool, Purnima; (Canton, MI), Wu, Betty; (Canton, MI) Correspondence: Klauber & Jackson; 411 Hackensack Avenue; Hackensack; NJ; 07601 Patent Application Number: 20030207273 Date filed: March 20, 2002 Abstract: Highly specific oligonucleotide primers and probes useful in a rapid and specific method for detecting the presence of Group B Streptococcal (GBS) or Streptococcus agalactiae infection in a biological sample.

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Excerpt(s): This invention relates to methods for detecting Group B streptococci (GBS) infections, particularly to methods allowing a rapid and accurate diagnosis to prevent and treat neonatal GBS infections. Group B streptococci (GBS) are responsible for a broad range of severe human diseases, predominantly the life-threatening bacterial infections in neonates and very young infants. Approximately 70 to 80% of infant infections occur in the first few days of life, so-called early-onset disease, while lateonset infections occur in infants between 1 week and 3 months of age. Newborns with early-onset GBS disease usually acquire the organism during delivery from their GBScolonized mothers, manifesting in sepsis and meningitis which cause not only illness and death, but long term disabilities such as hearing loss, impaired vision, developmental problems, and cerebral palsy. In order to substantially reduce the incidence of early-onset GBS disease, prenatal screening for GBS and intrapartum antimicrobial prophylaxis are now highly recommended in the United States. However, since these strategies require the frequent use of antibiotics, antibiotic resistant GBS or other bacterial agents might emerge during the perinatal period. In addition, these measures are unlikely to prevent late-onset infections, prematurity, and stillbirths related to GBS, while obviously not addressing GBS disease in nonpregnant adults. GBS are increasingly recognized as a frequent cause of invasive infections in pregnant women and clinically ill and older adults, such as those suffering from diabetes, cirrhosis, malignancies and immunodifciencies. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Recombinant protective protein from streptococcus pneumoniale Inventor(s): Green, Bruce A.; (Pittsford, NY), Masi, Amy W.; (Caledonia, NY) Correspondence: Paul F Fehlner; Darby & Darby; Post Office Box 5257; New York; NY; 10150-5257; US Patent Application Number: 20040052816 Date filed: May 29, 2003 Abstract: The present invention discloses amino acid sequences and nucleic acid sequences relating to a Streptococcus Pneumoniae surface associated Pneumo Protective Protein (PPP) having a molecular weight of about 20 kilo Daltons (kDa). The PPP exhibits the ability to reduce colonization of pneumococcal bacteria. Thus the present invention also pertains to compositions for the treatment and prophylaxis of infection or inflammation associated with bacterial infection. Excerpt(s): This application claims priority under 35 U.S.C.sctn. 119 from U.S. Provisional Patent Application Serial No. 60/258,841, filed Dec. 28, 2000; which is hereby incorporated by reference in its entirety. The present invention provides amino acid sequences and nucleic acid sequences relating to a protein of Streptococcus pneumoniae having a molecular weight of 20 kilo Daltons (kDa). The present invention also pertains to compositions for the treatment and prophylaxis of infection or inflammation associated with bacterial infection. The middle ear is a sterile, air-filled cavity separated from the outer ear by the eardrum. Attached to the eardrum are three ear bones that vibrate when sound waves strike the eardrum. Vibrations are transmitted to the inner ear, which generates nerve impulses that are sent to the brain. Air may enter the middle ear through the Eustachian tube, which opens in the walls of the nasopharynx. 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 •

Streptoccal inhibitor of complement-mediated lysis, protein SIC Inventor(s): Akesson, Per; (Lund, SE), Bjorck, Lars; (Lund, SE), Sjoholm, Anders; (Lund, SE) Correspondence: Kalow & Springut Llp; 488 Madison Avenue; 19th Floor; New York; NY; 10022; US Patent Application Number: 20040010117 Date filed: February 26, 2003 Abstract: A protein from Streptococcus pyogenes, serotype M1 has been characterized. This protein, called protein SIC, plays a role in S. pyogenes pathogenicity and virulence. It inhibits hemolysis by interacting with the plasma proteins clusterin, and members of the cystatin protein super family such as histidine rich glycoprotein (HRG). The protein, comprises at least one of the following partial amino acid sequences: (a) glu thr tyr thr ser arg asn phe; (b) asp trp ser gly asp asp trp pro glu asp asp trp; (c) arg ser gly val gly leu ser gln tyr gly trp ser; (d) trp ser ser asp lys lys asp glu thr glu asp lys thr; (e) gly thr gly tyr glu lys arg asp asp trp gly gly pro gly; (f) lys arg asp asp trp arg gly pro gly his ile pro lys pro. The protein and antibodies specific for the protein can be used in analytical procedures for determining the presence of virulent Streptococcus pyogenes in a sample. The protein can also be used in vaccine compositions. Excerpt(s): The present invention relates to a new protein, protein SIC, that can be derived from Streptococcus pyogenes strains of serotypes M1 and M57. Methods for analysis and purification and pharmaceutical preparations including vaccine compositions related to the protein as well as specific antibodies are also claimed. Streptococcus pyogenes is an important human pathogen causing a number of acute suppurative infections such as erysipelas, necrotizing fasciitis, and pharyngitis. These

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Gram-positive bacteria also cause a serious toxic shock-like syndrome, whereas glomreulonephritis and rheumatic fever are serious poststreptococcal sequelae. To elude the host defence and establish an infection, S. pyogenes has developed multiple molecular mechanisms. Some of these are dependent on genes located in a chromosomal region designated the mga locus according to a recent agreement, which is under the control of the positive regulator gene mga, previously called mry (Caparon and Scott, 1987: Proc. Natl. Acad. Sci. U.S.A. 84, 8677-8681) or virR (Simpson et al., 1990: J. Bacteriol. 172, 696-700). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Streptococcal C5a peptidase vaccine Inventor(s): Cleary, Paul Patrick; (Shoreview, MN), Stafslien, Deborah K.; (Madison, WI) Correspondence: Schwegman, Lundberg, Woessner & Kluth, P.A.; P.O. Box 2938; Minneapolis; MN; 55402; US Patent Application Number: 20040052801 Date filed: April 11, 2003 Abstract: Novel vaccines for use against.beta.-hemolytic Streptococcus colonization or infection are disclosed. The vaccines contain an immunogenic amount of a variant of streptococcal C5a peptidase (SCP). Also disclosed is a method of protecting a susceptible mammal against.beta.-hemolytic Streptococcus colonization or infection by administering such a vaccine. Enzymatically inactive SCP, and polynucleotides encoding these SCP proteins are further disclosed. Excerpt(s): This application is a continuation of U.S. application Ser. No. 09/870,122, filed May 30, 2001, which is a continuation of International Patent Application No. PCT/US99/28826, filed Dec. 3, 1999, which published in English on Jun. 15, 2000 as WO 00/34487, which applications and publication are incorporated by reference herein. There are several different.beta.-hemolytic streptococcal species that have been identified. Streptococcus pyogenes, also called group A streptococci, is a common bacterial pathogen of humans. Primarily a disease of children, it causes a variety of infections including pharyngitis, impetigo and sepsis in humans. Subsequent to infection, autoimmune complications such as rheumatic fever and acute glomerulonephritis can occur in humans. This pathogen also causes severe acute diseases such as scarlet fever, necrotizing fasciitis and toxic shock. Sore throat caused by group A streptococci, commonly called "strep throat," accounts for at least 16% of all office calls in a general medical practice, depending on the season. Hope-Simpson, E., "Streptococcus pyogenes in the throat: A study in a small population, 1962-1975," J. Hyg. Camb., 87:109-129 (1981). This species is also the cause of the recent resurgence in North America and four other continents of toxic shock associated with necrotizing fasciitis. Stevens, D. L., "Invasive group A streptococcus infections," Clin. Infect. Dis., 14:2-13 (1992). Also implicated in causing strep throat and occasionally in causing toxic shock are groups C and G streptococci. Hope-Simpson, E., "Streptococcus pyogenes in the throat: A study in a small population, 1962-1975," J. Hyg. Camb., 87:109-129 (1981). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Streptococcus antigens Inventor(s): Blais, Normand; (Ste-Foy, CA), Brodeur, Bernard R.; (Sillery, CA), Charland, Nathalie; (Breakeyville, CA), Hamel, Josee; (Sillery, CA), Labbe, Steve; (Ile d'Orleans, CA), Martin, Denis; (St-Augustin-de-Desmaures, CA), Ouellet, Catherine; (St-Jean Chrisostome, CA) Correspondence: Mcdermott, Will & Emery; 600 13th Street, N.W.; Washington; DC; 20005-3096; US Patent Application Number: 20030232976 Date filed: December 20, 2002 Abstract: The present invention relates to polypeptides of Streptococcus pneumoniae which may be used for prophylaxis, diagnostic and/or therapy purposes. Excerpt(s): The present invention is related to polypeptides, antigens, epitopes and antibodies directed to these epitopes, more particularly polypeptide antigens of Streptococcus pneumoniae pathogen which may be useful for prophylaxis, diagnostic or treatment of streptococcal infection. S. pneumoniae is an important agent of disease in man especially among infants, the elderly and immunocompromised persons. It is a bacterium frequently isolated from patients with invasive diseases such as bacteraemia/septicaemia, pneumonia, meningitis with high morbidity and mortality throughout the world. Even with appropriate antibiotic therapy, pneumococcal infections still result in many deaths. Although the advent of antimicrobial drugs has reduced the overall mortality from pneumococcal disease, the presence of resistant pneumococcal organisms has become a major problem in the world today. Effective pneumococcal vaccines could have a major impact on the morbidity and mortality associated with S. pneumoniae disease. Such vaccines would also potentially be useful to prevent otitis media in infants and young children. Efforts to develop a pneumococcal vaccine have generally concentrated on generating immune responses to the pneumococcal capsular polysaccharide. More than 80 pneumococcal capsular serotypes have been identified on the basis of antigenic differences. The currently available pneumococcal vaccine, comprising 23 capsular polysaccharides that most frequently caused disease, has significant shortcomings related primarily to the poor immunogenicity of some capsular polysaccharides, the diversity of the serotypes and the differences in the distribution of serotypes over time, geographic areas and age groups. In particular, the failure of existing vaccines and capsular conjugate vaccines currently in development to protect young children against all serotypes spurres evaluation of other S. pneumoniae components. Although immunogenicity of capsular polysaccharides can be improved, serotype specificity will still represent a major limitation of polysaccharide-based vaccines. The use of a antigenically conserved immunogenic pneumococcal protein antigen, either by itself or in combination with additional components, offers the possibility of a protein-based pneumococcal vaccine. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Streptococcus pneumoniale 37-kDa surface adhesion a protein Inventor(s): Ades, Edwin W.; (Atlanta, GA), Carlone, George M.; (Stone Mountain, GA), Russell, Harold; (Efland, NC), Sampson, Jacquelyn; (College Park, GA), Tharpe, Jean A.; (Lithonia, GA) Correspondence: Shari J. Corin, PH.D.; Needle & Rosenberg, P.C.; The Candler Building, Suite 1200; 127 Peachtree Street, N.E.; Atlanta; GA; 30303-1811; US Patent Application Number: 20030105307 Date filed: January 3, 2001 Abstract: The invention provides a nucleic acid encoding the 37-kDa protein from Streptococcus pneumoniae. Also provided are isolated nucleic acids comprising a unique fragment of at least 10 nucleotides of the 37-kDa protein. The invention also provides purified polypeptides encoded by the nucleic acid encoding the 37-kDa protein from and the nucleic acids comprising a unique fragment of at least 10 nucleotides of the 37-kDa protein. Also provided are antibodies which selectively binds the polypeptides encoded by the nucleic acid encoding the 37-kDa protein and the nucleic acids comprising a unique fragment of at least 10 nucleotides of the 37-kDa protein. Also provided are vaccines comprising immunogenic polypeptides encoded by the nucleic acid encoding the 37-kDa protein and the nucleic acids comprising a unique fragment of at least 10 nucleotides of the 37-kDa protein. Further provided is a method of detecting the presence of Streptococcus pneumoniae in a sample comprising the steps of contacting a sample suspected of containing Streptococcus pneumoniae with nucleic acid primers capable of hybridizing to a nucleic acid comprising a portion of the nucleic acid encoding the 37-kDa protein, amplifying the nucleic acid and detecting the presence of an amplification product, the presence of the amplification product indicating the presence of Streptococcus pneumoniae in the sample. Further provided are methods of detecting the presence of Streptococcus pneumoniae in a sample using antibodies or antigens, methods of preventing and treating Streptococcus pneumoniae infection in a subject. Excerpt(s): This application is a continuation-in-part of Ser. No. 08/222,179, filed Apr. 4, 1994, which is a continuation-in-part of Ser. No. 07/791,377, filed Sep. 17, 1991, now U.S. Pat. No. 5,422,427, both of which are hereby incorporated by reference in their entirety. This invention relates to the 37-kDa Streptococcus pneumoniae surface adhesin A protein. Specifically, the invention relates to an isolated nucleic acid encoding the 37kDa protein of Streptococcus pneumoniae, to unique fragments of the nucleic acid encoding the 37-kDa protein of Streptococcus pneumoniae, and to the polypeptides encoded by those nucleic acids. The invention further relates to antibodies to those polypeptides, and to methods of detecting the presence of Streptococcus pneumoniae, methods of preventing Streptococcus pneumoniae infection, and methods of treating a Streptococcus pneumoniae infection. Pneumococcal disease continues to be a leading cause of sickness and death in the United States and throughout the world. Both the lack of efficacy of the currently used polysaccharide vaccines in children under 2 years of age and their variable serotype-specific efficacy among vaccinated individuals, have prompted manufacturers to investigate alternative vaccine formulations that do not require the use of multiple capsular polysaccharides. One current approach under consideration is the use of immunogenic species-common proteins as vaccine candidates. These proteins could be used in combination with other immunogenic proteins or as protein carriers in a protein-polysaccharide or oligosaccharide conjugate vaccine. An effective vaccine that included a common protein could eliminate the need for formulations based on multiple capsular polysaccharides (as in the 23-valent

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polysaccharide vaccine) by offering a broader range of protection against a greater number of serotypes. Additionally, a protein-based vaccine would be T-cell dependent and provide a memory response, resulting in a more efficacious vaccine. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Streptococcus pyogenes antigens Inventor(s): Boyer, Martine; (Ste-Foy, CA), Brodeur, Bernard; (Sillery, CA), Hamel, Josee; (Sillery, CA), Martin, Denis; (St Augustin, CA), Rioux, Stephane; (Beauport, CA) Correspondence: Millen, White, Zelano & Branigan, P.C.; 2200 Clarendon BLVD.; Suite 1400; Arlington; VA; 22201; US Patent Application Number: 20030165528 Date filed: April 22, 2003 Abstract: The present invention relates to antigens, more particularly an antigen of Streptococcus pygenes (also called group A Streptococcus (GAS)) bacterial pathogen which is useful as vaccine component for therapy and/or prophylaxis. Excerpt(s): The present invention is related to antigens, more particularly a polypeptide antigen of Streptococcus pyogenes (also called group A Streptococcus (GAS)) bacterial pathogen which may be useful for prophylaxis, diagnostic and/or therapy of streptococcal infection. Streptococci are gram (+) bacteria which are differentiated by group specific carbohydrate antigens A through O which are found at the cell surface. Streptococcus pyogenes isolates are further distinguished by type-specific M protein antigens. M proteins are important virulence factors which are highly variable both in molecular weights and in sequences. Indeed, more than 80-M protein types have been identified on the basis of antigenic differences. Streptococcus pyogenes is responsible for many diverse infection types, including pharyngitis, erysipelas and impetigo, scarlet fever, and invasive diseases such as bacteremia and necrotizing fasciitis and also toxic shock. A resurgence of invasive disease in recent years has been documented in many countries, including those in North America and Europe. Although the organism is sensitive to antibiotics, the high attack rate and rapid onset of sepsis results in high morbidity and mortality. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Streptococcus pyogenes DNase B leader peptide and methods for its use Inventor(s): Adams, Craig W.; (Corona, CA), Belei, C. Marina; (Anaheim, CA), Pang, Patty P.Y.; (Rancho Cucamonga, CA) Correspondence: Attention OF William J. Wood; Gates & Cooper Llp; Howard Hughes Center; 6701 Center Drive West, Suite 1050; Los Angeles; CA; 90045; US Patent Application Number: 20040023305 Date filed: June 3, 2003 Abstract: The gene for Streptococcus pyogenes DNase B has been cloned and vectors incorporating the cloned DNA have been used to transform Escherichia coli, allowing efficient and rapid production of the DNase in E. coli without the necessity of growing large quantities of S. pyogenes. The enzyme can be produced with a leader peptide at its amino terminus. An improved method for the purification of naturally occurring S.

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pyogenes DNase B enzyme is also provided. The DNase B enzyme produced, either by purification of naturally occurring enzyme or by recombinant DNA techniques, can be used to generate antibodies and can also be used in immunochemical assays to detect the presence of anti-DNase B antibodies in serum as a marker of infection by S. pyogenes. Excerpt(s): This invention is directed to recombinant DNase B derived from the pathogenic bacterium Streptococcus pyogenes, methods for its production, and methods for its use. Despite advances in the prevention and treatment of bacterial infection, a number of bacterial pathogens remain serious problems in medical practice and continue to cause severe, even fatal disease. One of these pathogens is S. pyogenes. Among the diseases caused by S. pyogenes are streptococcal pharyngitis ("strep throat"), scarlet fever, and their suppurative complications, including cervical adenitis, otitis media, mastoiditis, peritonsillar abscesses, meningitis, pneumonitis, pneumonia, puerperal sepsis, cellulitis of the skin, impetigo, lymphangitis, erysipelas, acute glomerulonephritis, and rheumatic fever. Such infections often occur in hospitals (nosocomial infection), particularly in patients whose normal immune system functioning is suppressed. The latter category includes patients with AIDS, patients taking immunosuppressive drugs for cancer or to prevent transplant rejection, and patients having poor circulation, e.g., patients with diabetes. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Synthesis of complex carbohydrates Inventor(s): Jennings, Harold J; (Gloucester, CA), Zou, Wei; (Gloucester, CA) Correspondence: W Charles Kent; Ridout & Maybee; 150 Metcalfe Street 19th Floor; Ottawa; ON; K2p 1p1; CA Patent Application Number: 20030170828 Date filed: February 19, 2003 Abstract: A tailor-assembly approach is employed for synthesis of complex carbohydrates wherein a polysaccharide is degraded and the shorter product obtained from the degradation is subjected to enzymatic modification to add a sugar moiety. The products may be useful in the preparation of a cancer vaccine. In one example, oligosaccharides of the type Ia group B Streptococcus (GBSIa) capsular polysaccharide and multivalent sialyl Le.sup.x antigens are specifically described. GBSIa polysaccharide was depolymerized by partial Smith degradation to fragments representing asialo core repeating units. Enzymatic sialylation of these oligomers furnished GBSIa repeating units (from monomer to pentamer). Fucosylation on GlcNAc residues of GBSIa oligomers afforded oligosaccharides that carry multiple sialyl Le.sup.x epitopes. Excerpt(s): The invention relates to the field of synthesis of complex carbohydrates. The development of carbohydrate-based anticancer and antibacterial vaccines has lead to a need for more efficient methods for the synthesis of complex carbohydrate antigens. Although notable progress has been made in chemical and chemo-enzymatic synthesis (e.g. Zou, Carbohydr.Res, 1998, 309,297), solid-phase synthesis (e.g. Zheng, Angew.Chem., (Int. Ed. Engl.), 1998, 37, 786-788) and programmed robotic synthesis (e.g. Zhang, J.Am.Chem.Soc., 1999, 121, 734.), complex carbohydrates of biological significance are still very difficult to make. This difficulty is compounded by the fact that most biological interactions between carbohydrates and proteins are multivalent, thus requiring for maximum efficiency the synthesis and presentation of multiple

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carbohydrate epitopes with defined structures. Multivalent carbohydrate epitopes can be chemically or chemo-enzymatically synthesised. However, the methods widely used for the synthesis of oligosaccharides are time consuming, difficult, and expensive. Current methods share a common strategy wherein the oligosaccharide is built up step by step from monosaccharides and/or other small building blocks. The multiple steps involved in obtaining various monovalent carbohydrate epitopes limits their efficient synthesis, and obtaining them in a multivalent form adds a further degree of difficulty. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Use of ylqF, yqeG, yybQ, yerL, and ysxC, essential bacterial genes and polypeptides Inventor(s): Fritz, Christian; (Natick, MA), Guzman, Luz-Maria; (Boston, MA), Youngman, Philip; (Boston, MA) Correspondence: Fish & Richardson PC; 225 Franklin ST; Boston; MA; 02110; US Patent Application Number: 20030228643 Date filed: April 25, 2003 Abstract: Disclosed are genes found in Streptococcus pneumoniae that are essential for survival for a wide range of bacteria. These genes are termed "S-ylqF," "S-yqeG," "SyybQ," "S-yerL," and "S-ysxC." These genes and the polypeptides that they encode, as well as homologs and orthologs thereof can be used to identify antibacterial agents for treating a broad spectrum of bacterial infections. Excerpt(s): The invention relates to the use of ylqF, yqeG, yybQ, yerL, and ysxC, essential bacterial genes and polypeptides in identifying antibacterial agents. Bacterial infections may be cutaneous, subcutaneous, or systemic. Opportunistic bacterial infections proliferate, especially in patients afflicted with AIDS or other diseases that compromise the immune system. Most bacteria that are pathogenic to humans are gram positive bacteria. The bacterium Streptococcus pneumoniae, for example, typically infects the respiratory tract and can cause lobar pneumonia, as well as meningitis, sinusitis, and other infections. The invention is based on the identification of ten genes of the gram positive bacterium Streptococcus pneumoniae and of Bacillus subtilis as being essential for survival. The Streptococcus pneumoniae genes are termed "S-ylqF," "S-yqeG," "S-yybQ," "S-yerL," and "S-ysxC." The orthologs of these genes in Bacillus subtilis are termed "B-ylqF," "B-yqeG," "B-ybQ," "B-yerL," and "B-ysxC," respectively. The terms "ylqF," "yqeG," "yybQ," "yerL," and "ysxC" genes and polypeptides are used to refer to the Streptococcus pneumoniae and Bacillus subtilis genes and polypeptides, as well as their homologs and orthologs, collectively. While "homologs" are structurally similar genes contained within a species, "orthologs" arefunctionally equivalent genes from other species (within or outside of a given genus, e.g., from E. coli). These genes are considered "essential" genes, and their polypeptides are considered "essential" polypeptides. Each gene and polypeptide can be used in methods for identifying similar genes and polypeptides in pathogenic and non-pathogenic microorganisms. Each polypeptide can be used to identify compounds that are inhibitors of the pathogens in which the polypeptide (ylqF, yqeG, yybQ, yerL, or ysxC) is expressed. Such inhibitors attenuate bacterial growth by inhibiting the activity of ylqF, yqeG, yybQ, yerL, or ysxC polypeptide, or by inhibiting gene transcription or translation. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Vaccine against streptococcus pneumoniae capsular polysaccharides Inventor(s): Capiau, Carine; (Rixensart, BE), Deschamps, Marguerite; (Rixensart, BE), Desmons, Pierre Michel; (Rixensart, BE), Laferriere, Craig Antonyjoseph; (Rixensart, BE), Poolman, Jan; (Rixensart, BE), Prieels, Jean-Paul; (Rixensart, BE) Correspondence: Glaxosmithkline; Corporate Intellectual Property - Uw2220; P.O. Box 1539; King OF Prussia; PA; 19406-0939; US Patent Application Number: 20030147922 Date filed: August 26, 2002 Abstract: The present invention relates to the field of bacterial polysaccharide antigen vaccines. In particular, the present invention relates to specific advantageous pnumococcal polysaccharide conjugates adjuvanted with 3D-MPL and substantially devoid aluminium-based adjuvant. Excerpt(s): The present invention relates to bacterial polysaccharide antigen vaccines, their manufacture and the use of such polysaccharides in medicines. In particular the present invention relates to three inter-related aspects: A--vaccines comprising a pneumococcal polysaccharide antigen, typically a pneumococcal polysaccharide conjugate antigen, formulated with a protein antigen from Streptococcus pneumoniae and optionally a Th1 inducing adjuvant; B--specific, advantageous pneumococcal polysaccharide conjugates adjuvanted with a Th1 adjuvant; and C--bacterial polysaccharide conjugates in general conjugated to protein D from H. influenzae. Streptococcus pneumoniae is a Gram-positive bacteria responsible for considerable morbidity and mortality (particularly in the young and aged), causing invasive diseases such as pneumonia, bacteremia and meningitis, and diseases associated with colonisation, such as acute Otitis media. The rate of pneumococcal pneumonia in the U.S. for persons over 60 years of age is estimated to be 3 to 8 per 100,000. In 20% of cases this leads to bacteremia, and other manifestations such as meningitis, with a mortality rate close to 30% even with antibiotic treatment. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Vaccine compositions comprising streptococcus pneumoniae polypeptides having selected structural motifs Inventor(s): Adamou, John E.; (New Milford, CT), Johnson, Leslie S.; (Darnestown, MD) Correspondence: Alan J. Grant, ESQ.; C/o Carella, Byrne, Bain, Gilfillan, Cecchi,; Stewart & Olstein; 6 Becker Farm Road; Roseland; NJ; 07068; US Patent Application Number: 20040001836 Date filed: April 14, 2003 Abstract: A vaccine composition is disclosed that comprises polypeptides and fragments of polypeptides containing histidine triad residues or coiled-coil regions, some of which polypeptides or fragments lie between 80 and 680 residues in length. Also disclosed are processes for preventing infection caused by S. pneumoniae comprising administering of vaccine compositions. Excerpt(s): This application is based on U.S. Provisional Application No. 60/113,048, filed Dec. 21, 1998, which is hereby incorporated in its entirety. This invention relates generally to the field of bacterial antigens and their use, for example, as immunogenic agents in humans and animals to stimulate an immune response. More specifically, it

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relates to the vaccination of mammalian species with a polypeptide comprising at least one conserved histidine triad residue (HxxHxH) and at least one helix-forming polypeptide obtained from Streptococcus pneumoniae as a mechanism for stimulating production of antibodies that protect the vaccine recipient against infection by a wide range of serotypes of pathogenic S. pneumoniae. Further, the invention relates to antibodies against such polypeptides useful in diagnosis and passive immune therapy with respect to diagnosing and treating such pneumococcal infections. In a particular aspect, the present invention relates to the prevention and treatment of pneumococcal infections such as infections of the middle ear, nasopharynx, lung and bronchial areas, blood, CSF, and the like, that are caused by pneumococcal bacteria. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Virulence of Streptococci Inventor(s): Smith, Hilda Elizabeth; (Lelystad, NL) Correspondence: Trask Britt; P.O. Box 2550; Salt Lake City; UT; 84110; US Patent Application Number: 20040009192 Date filed: May 9, 2003 Abstract: The invention relates to the field of diagnosis of and vaccination against Streptococcal infections and to the detection of virulence markers of Streptococci. The invention discloses a method for modulating virulence of a Streptococcus comprising modifying a genomic fragment of Streptococcus wherein the genomic fragment comprises at least a functional part of a fragment identifiable by hybridization in Streptococcus suis to a nucleic acid or fragment thereof as shown in FIG. 5. Excerpt(s): This application is a continuation of PCT/NL01/00805, filed Nov. 6, 2001, designating the United States of America, corresponding to PCT International Publication WO 02/38597 (published in English on May 16, 2002), the contents of which are incorporated herein in its entirety. The invention relates to the field of diagnosis of and vaccination against Streptococcal infections and to the detection of virulence markers of Streptococci. Streptococcus species, of which there are a large variety of that cause infections in domestic animals and man, are often grouped according to Lancefield's groups. Typing according to Lancefield occurs on the basis of serological determinants or antigens that are, among others, present in the capsule of the bacterium and, thus, allows for an approximate determination. Often bacteria from a different group show cross-reactivity with each other, while other Streptococci cannot be assigned a specific group-determinant at all. Within groups, further differentiation is often possible on the basis of serotyping. These serotypes further contribute to the large antigenic variability of Streptococci, a fact that creates an array of difficulties within diagnosis of and vaccination against Streptococcal infections. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

Keeping Current In order to stay informed about patents and patent applications dealing with streptococcus, 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,

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and (2) Published Applications. To see a list of issued patents, perform the following steps: Under “Issued Patents,” click “Quick Search.” Then, type “streptococcus” (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 streptococcus. You can also use this procedure to view pending patent applications concerning streptococcus. 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 STREPTOCOCCUS Overview This chapter provides bibliographic book references relating to streptococcus. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on streptococcus include the Combined Health Information Database and the National Library of Medicine. Your local medical library also may have these titles available for loan.

Book Summaries: Federal Agencies The Combined Health Information Database collects various book abstracts from a variety of healthcare institutions and federal agencies. To access these summaries, go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. You will need to use the “Detailed Search” option. To find book summaries, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer. For the format option, select “Monograph/Book.” Now type “streptococcus” (or synonyms) into the “For these words:” box. You should check back periodically with this database which is updated every three months. The following is a typical result when searching for books on streptococcus: •

Pregnancy After a Loss: A Guide to Pregnancy After a Miscarriage, Stillbirth, or Infant Death Source: New York, NY: Berkley Books/Penguin Putnam, Inc. 1999. 391 p. Contact: Available from Berkley Books/Penguin Putnam, Inc., 375 Hudson Street, New York, NY 10014. (800) 788-6262 (orders), (800) 631-8571 (customer service hotline), (800) 227-9604 (Fax), [email protected] (E-mail), http://www.penguinputnam.com (Web Site). $14.95. ISBN 0-425-17047-0. Summary: This book, written by a woman who lost her son, Patrick, to an umbilical cord problem on her due date, is designed to give hope and practical information to other women who have suffered a pregnancy loss. The author interviewed nearly 100 women while writing this book, all of whom made it through pregnancy after a loss and now have one or more healthy babies. The book focuses on the feelings that are unique to women who have suffered a pregnancy loss, and provides advice on reducing anxiety.

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Medical aspects of pregnancy loss are described in simple, straightforward language. Chapter 1 takes readers down the road that a bereaved mother would travel to find out why her baby died. This chapter covers the followup visit with the obstetrician, which is when the parents discuss the autopsy and any genetic testing that was done on the baby. If these do not provide an answer, the doctor may suggest that the mother be tested for autoimmune disorders, uterine abnormalities, genetic disorders, viral and bacterial infections, and hormone imbalances. Other common reasons for pregnancy loss are described (i.e., neural tube defects, placental problems, umbilical cord problems, incompetent cervix, and maternal illness) as are common reasons for early infant death: congenital problems, streptococcus infection, and sudden infant death syndrome. Chapter 2 discusses the subject of getting ready to get pregnant again, both physically and emotionally. This chapter covers the advantages and disadvantages of getting pregnant right away, factors that will affect one's decision to get pregnant, when partners disagree on the timing of another pregnancy, and where to find support and guidance during the decision-making process. Even if a woman has waited 6 months or a year to get pregnant again, there are certain things she should do to prepare for the pregnancy. Mothers to be should get a thorough physical exam; get into shape; take folic acid; keep track of her periods; and avoid drugs, alcohol, and cigarettes. This chapter also covers the pros and cons of choosing a new doctor or staying with the old one, questions one should ask each doctor under consideration, the stress of not getting pregnant right away, infertility problems and treatment, and when the pregnancy is a surprise. Chapter 4 focuses on the first trimester of a new pregnancy, including concerns over telling others about the pregnancy, suggestions for alleviating the anxiety, what to expect during the prenatal visits, tests one can have done at this time, and the signs of an impending miscarriage. Chapter 5 focuses on the second trimester, including concerns about answering awkward questions, the gender of the baby, delivering too early, exercising, and sexual intercourse. Feelings that may be common during this trimester are panic over the baby's movements, reluctance to bond with the baby, anxiety about surpassing the anniversary of the previous baby's death, superstitions about the pregnancy, and fear. Prenatal tests that can be offered at this time and symptoms that are not normal during the second trimester also are covered. Chapter 6 examines the concerns mothers are likely to have during the third trimester regarding early delivery, setting up the nursery, baby shower offers, choosing a name, and excessive weight gain. Feelings that may be common during this time include obsession over the baby's movements, constant worry, and being annoyed by unsolicited advice. Tips for alleviating the anxiety include taking a prepared childbirth class, writing a birth plan, getting a doula, calling the doctor frequently, insisting on frequent prenatal visits, eliminating unnecessary stress, and practicing relaxation techniques. The nature of prenatal visits during the third trimester, tests that are usually done at this time, monitoring the baby's kicks, and danger signals in late pregnancy also are discussed. Chapter 7 deals with the truly high-risk pregnancy. Common reasons for high-risk status are a history of preterm labor or delivery, incompetent cervix, impending multiple birth, history of placental problems, history of two or more miscarriages, genetic problems, chronic medical conditions, and pregnancy after age 35. Bed rest is a commonly prescribed treatment in high-risk pregnancies. This chapter provides suggestions for surviving extended bed rest as well as a chart of activities to help mothers and their OB/GYNs mutually define what she can and can't do. Other topics that are discussed include hospitalization, the impact of that and bed rest on family and career, selective reduction in cases of multiples, feelings that are common among mothers during bed rest, and tips for relieving the anxiety. The signs and treatment of preterm labor also are discussed. Chapter 8 deals with labor and delivery, including fetal monitoring during labor, bonding with the baby, feelings commonly reported after

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birth, what to expect if your baby goes to the NICU, and tips for relieving anxiety. Chapter 9 talks about the consequences of pregnancy loss on parenting the subsequent child. It is common for parents to feel anxious and overprotective, but their loss also may make them exceptional parents. There is often continued sadness and introspection and a totally changed outlook on life. This chapter also reviews some of the private and public ways in which parents have chosen to remember their infants who died. Chapter 10 looks at pregnancy after a loss from a father's perspective, including feelings that are common to fathers who are expecting again and ways in which the mother can ease her spouse's anxiety. A list of resources includes support organizations for pregnancy and infant loss, high-risk pregnancy, subsequent pregnancy, infertility, and pregnancy/childbirth; publishers of relevant books; and internet resources. •

A Holistic Protocol for the Immune System Contact: Tree of Life Publications, PO Box 126, Joshua Tree, CA, 92252. Summary: This self-help manual presents a holistic approach, or natural healing process, for patients with a compromised immune system. The author outlines a fourstage protocol to treat AIDS and HIV, kill the body's parasites, rebuild the adrenal and thyroid glands, rid the body of bacteria and fungi, and repair the immune system. Each phase of this protocol will last approximately four to six weeks. Following the introduction, the author provides detailed descriptions of the holistic protocols and products, and an overview of AIDS, HIV, herpes, hepatitis, chronic fatigue syndrome, candidiasis, Kaposi's sarcoma, cytomegalovirus, Pneumocystis carinii pneumonia (PCP), and staphylococcus and streptococcus infections.

Book Summaries: Online Booksellers Commercial Internet-based booksellers, such as Amazon.com and Barnes&Noble.com, offer summaries which have been supplied by each title’s publisher. Some summaries also include customer reviews. Your local bookseller may have access to in-house and commercial databases that index all published books (e.g. Books in Print). IMPORTANT NOTE: Online booksellers typically produce search results for medical and non-medical books. When searching for “streptococcus” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “streptococcus” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “streptococcus” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •

Molecular Microbiology and Immunobiology of Streptococcus Mutans by Shigeyuki Hamada (Editor); ISBN: 0444807683; http://www.amazon.com/exec/obidos/ASIN/0444807683/icongroupinterna

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Streptococcal disease and the community : proceedings of the fifth International Symposium on Streptococcus Pyogenes, Amsterdam, 27 August-1 September, 1972; ISBN: 044415101X; http://www.amazon.com/exec/obidos/ASIN/044415101X/icongroupinterna

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The Official Patient's Sourcebook on Group B Streptococcus Infection: A Revised and Updated Directory for the Internet Age by Icon Health Publications; ISBN: 0597833222; http://www.amazon.com/exec/obidos/ASIN/0597833222/icongroupinterna

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Chapters on Streptococcus In order to find chapters that specifically relate to streptococcus, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and streptococcus 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 “streptococcus” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on streptococcus: •

Use of Probiotics in Inflammatory Bowel Disease Source: in Williams, C.N., et al., eds. Trends in Inflammatory Bowel Disease Therapy 1999. Boston, MA: Kluwer Academic Publishers. 2000. p. 252-258. Contact: Available from Kluwer Academic Publishers. Customer Service Deparment, P.O. Box 358, Accord Station, Hingham, MA 02018-0358. (781) 871-6600. Fax (781) 6819045. E-mail: [email protected]. Website: www.wkap.nl. PRICE: 145.00 plus shipping and handling. ISBN: 0792387627. Summary: A body of evidence from clinical and experimental observations indicates a role for intestinal microflora in the pathogenesis of inflammatory bowel disease (IBD). Probiotics are defined as 'living organisms, which upon ingestion in certain numbers, exert health benefits beyond inherent basic nutrition.' This chapter on the use of probiotics in IBD is from a monograph that reprints the presentations given at the Trends in Inflammatory Bowel Disease Therapy Symposium, held in Vancouver, British Columbia, Canada, in August 1999. The general objective of the conference was to provide an update in the etiology, pathogenesis, and treatment of inflammatory bowel disease (IBD), including ulcerative colitis (UC) and CD. In this chapter, the authors review recent evidence supports the potential role of probiotics in IBD therapy. The authors' experience focuses on the use of a new probiotic preparation (VSL number 3) containing 300 billion per gram of viable lyophilized (freeze dried) bacteria of four strains of lactobacilli, three strains of bifidobacteria, and one strain of Streptococcus salivarius subspecies thermophilus. Twenty patients received 6 grams a day of VSL3 for 12 months and were periodically assessed. Microbiological determination showed a significant increase in concentration of lactobacilli, bifidobacteria, and Streptococcus salivarius subspecies thermophilus, fecal pH was significantly reduced, and the great majority of patients (75 percent) remained in remission. Subsequent efficacy of this new oral probiotic preparation was tested versus placebo in 40 patients with chronic relapsing pouchitis. Of the 20 patients who received placebo, all relapsed, whereas 17 of the 20 patients treated with VSL3 were still in remission after 9 months. All these 17 patients, after suspension of the treatment, had a relapse within 4 months. A controlled study evaluating the efficacy of treatment with antibiotics and probiotics versus mesalazine in the prevention of postoperative recurrence in patients with Crohn' disease is now in progress. The authors conclude that these findings suggest that probiotics may be of therapeutic benefit in maintenance treatment of IBD. 4 figures. 27 references.

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Infection-Associated Glomerulonephritis Source: in Catto, G.R.D. New Clinical Applications-Nephrology: Glomerulonephritis. Hingham, MA: Kluwer Academic Publishers. p. 69-95. 1990.

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Contact: Available from Kluwer Academic Publishers. P.O. Box 358, Accord Station, Hingham, MA 02018-0358. (617) 871-6600. PRICE: $54. ISBN: 0746201095. Summary: Infections with many organisms may produce glomerular lesions. This review concentrates on the glomerular consequences of infection with specific organisms. Separate detailed attention is given to each specific source of infection, covering viral (hepatitis B, cytomegalovirus, HIV), bacterial (Streptococcus, Staphylococcus, Treponema pallidum, Mycobacterium leprae), and parasitic (Plasmodium malariae, Schistosoma mansoni) infections. Rarer types of infection also are discussed. It is concluded that, in most patients, the glomerular changes are induced by an immune mechanism as a consequence of exposure to a foreign antigen or by modification of a host protein, making it antigenic with a subsequent autologous response. Since organisms (even of the same species) vary with respect to their nephritogenic potential and the response obtained is governed by a wide variety of patient characteristics (including genetic and nutritional), it not surprising that a uniform glomerular response is seldom obtained following a specific infection. 72 references. •

Rheumatic Fever Source: in Maddison, P.J.; et al., Eds. Oxford Textbook of Rheumatology. Volume 2. New York, NY: Oxford University Press, Inc. 1993. p. 613-620. Contact: Available from Oxford University Press, Inc., New York, NY. Summary: This chapter for health professionals presents an overview of rheumatic fever. The classical ways in which rheumatic fever may manifest itself are outlined. The epidemiology and pathogenesis are discussed. The role of group A streptococcus and genetics in the disease process of rheumatic fever is examined. Theories on the pathological mechanisms of group A streptococcus in rheumatic fever are presented. The clinical features of acute rheumatic fever are described, including arthritis, carditis, rheumatic heart disease, chorea, subcutaneous nodules, and erythema marginatum. The minor manifestations of rheumatic fever are identified, including fever, abdominal pain, epistaxis, and rheumatic pneumonia. The use of laboratory tests in the diagnosis of rheumatic fever is discussed. The clinical course and treatment of rheumatic fever is explained, and the use of antibiotic prophylaxis following resolution of the acute episode is considered. 56 references, 1 figure, and 3 tables.

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Unreplicated Trials Source: in Manu, P. Pharmacotherapy of Common Functional Syndromes: EvidenceBased Guidelines for Primary Care Practice. Binghamton, NY: Haworth Medical Press. 2000. p. 169-174. Contact: Available from Haworth Medical Press, an imprint of Haworth Press, Inc. 10 Alice Street, Binghamton, New York 13904-1580. (800) HAWORTH or (800) 429-6784. Outside United States and Canada (607) 722-5857. Fax (800) 895-0582. E-mail: [email protected]. Website: www.haworthpressinc.com. PRICE: $69.95 plus shipping and handling. ISBN: 0789005883. Summary: This chapter is from a book that evaluates drug therapies for each of the four major functional disorders: chronic fatigue syndrome, fibromyalgia, irritable bowel syndrome (IBS), and premenstrual syndrome. In this chapter, the fifth of six short chapters that focuses on IBS, the author introduces and reviews unreplicated research trials on therapies for the condition. These trials include Streptococcus faecium, not

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substantially better than placebo for any of the symptoms evaluated; fedotozine (a drug used to block colonic pain), with which a high dose (30 mg daily) was better than placebo with regard to the severity of abdominal pain and abdominal distention; Chinese herbal medicine, which offered encouraging results (44 percent with treatment improved, compared to 22 percent taking placebo) that need replicating; and Indian herbal medicine, which was no better than placebo with respect to the proportions of patients reporting improvement in the severity of abdominal pain, constipation, gaseousness, and altered bowel habits (diarrhea and constipation). The Indian herbal mixture was effective in reducing the severity of diarrhea and that of symptoms of anxiety and depression, but this limited benefit does not support widespread use of Indian herbal medicine as a therapeutic modality for patients with IBS. •

Cholecystitis and Mirizzi Syndrome Source: in Okuda, K., ed.,et al. Hepatobiliary Diseases: Pathophysiology and Imaging. Malden, MA: Blackwell Science, Inc. 2001. p. 682-695. Contact: Available from Blackwell Science, Inc. 350 Main Street, Commerce Place, Malden, MA 02148. (800) 215-1000 or (617) 388-8250. Fax (617) 388-8270. E-mail: [email protected]. Website: www.blackwell- science.com. PRICE: $275.00. ISBN: 0632055421. Summary: This chapter on cholecystitis and Mirizzi syndrome is from a textbook that familiarizes the reader with various imaging modalities, the information they provide, and the merits of each, in order to facilitate the combined use of different imaging techniques in the diagnosis and management of hepatobiliary (liver and bile tract) diseases. Acute calculous cholecystitis is an acute inflammation of the gallbladder precipitated by obstruction of the neck of the gallbladder or cystic duct by a gallstone. Acute cholecystitis is the most common complication of gallbladder stones, causing the patient severe pain and illness. Emphysematous cholecystitis is rare and characterized by the gallbladder being infected by gas-forming bacteria, including Clostridia, Escherichia coli, and Staphylococcus and Streptococcus species. Chronic cholecystitis is almost always associated with gallstones, whether or not the patient has had symptoms. Xanthogranulomatous cholecystitis is characterized by multiple, yellowish brown intraluminal nodules, proliferative fibrosis, and foamy histiocytic infiltration (bile within the gallbladder wall). Porcelain gallbladder is defined as diffuse calcification of the wall of the organ. Milk of calcium bile, or limy bile, is formed by the precipitation of calcium carbonate, calcium phosphate, and calcium bilirubinate in the gallbladder, resulting in a semifluid or putty like material. Mirizzi syndrome is an uncommon complication of long standing gallstone disease that occurs in 0.7 to 1.4 percent of all cholecystectomies (gallbladder removals) performed. Mirizzi syndrome includes stricture (narrowing) of the common hepatic (liver) bile duct due to inflammation of the gallbladder and fistula after erosion of the impacted stone into the common hepatic duct. For each condition, the author discusses pathogenesis, pathology, clinical presentation, diagnostic imaging, and treatment options. 23 figures. 19 references.

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Streptococcal Toxic Shock Syndrome Associated With Necrotizing Fasciitis Source: in Coggins, C.H.; Hancock, E.W.; Levitt, L.J., eds. Annual Review of Medicine, Volume 51, 2000. Palo Alto, CA: Annual Reviews, Inc. 2000. p. 271-288. Contact: Available from Annual Reviews. 4139 El Camino Way, P.O. Box 10139, Palo Alto, CA 94303-0139. (650) 493-4400. E-mail: [email protected]. Website: www.AnnualReviews.org.

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Summary: This chapter provides health professionals with information on the demographics, symptoms, signs, diagnosis, clinical course, and treatment of streptococcal toxic shock syndrome (strep TSS) with associated necrotizing fasciitis. Strep TSS is the early onset of shock and organ failure associated with any infection caused by Streptococcus pyogenes. It is a rapidly progressive process that kills 30 to 60 percent of patients in 72 to 96 hours. The initial symptoms of strep TSS depend largely on the site of primary infection. Of all patients with strep TSS, 20 percent experience an influenza like syndrome characterized by fever, chills, myalgia, and diarrhea. In patients who develop deep soft tissue infections, such as necrotizing fasciitis or intrauterine infection, severe pain is the most common initial symptom of strep TSS. Violaceous bullae, hypotension, fever, and evidence of organ failure are late clinical manifestations. Diagnosis is not difficult when all the clinical features of strep TSS are manifest; however, the signs and symptoms may be quite subtle early in the course of illness, and laboratory tests may provide valuable clues to the diagnosis. The challenge to clinicians is to make an early diagnosis and to intervene with aggressive fluid replacement, emergent surgical debridement, and general supportive measures. Superantigens such as pyrogenic exotoxin A interact with monocytes and T lymphocytes in unique ways, resulting in T cell proliferation and watershed production of monokines and lymphokines. Penicillin, though efficacious in mild S. pyogenes infection, is less effective in severe infections because of its short postantibiotic effect, inoculum effect, and reduced activity against stationary phase organisms. Emerging treatments for strep TSS include clindamycin and intravenous gamma globulin. 2 tables and 81 references. (AA-M). •

Chapter 174: Infections of the Skin and Underlying Tissue Source: in Berkow, R., ed. The Merck Manual of Medical Information: Home Edition (online version). Rahway, NJ: Merck and Company, Inc. 2000. 6 p. Contact: Available online from Merck and Company, Inc. (800) 819-9456. Website: www.merck.com/pubs/mmanual_home/contents.htm. Also available from your local book store. PRICE: $29.95 plus shipping. Summary: This chapter provides the general public and people who have infections of the skin and underlying tissue with information on the symptoms, diagnosis, and treatment of cellulitis, necrotizing fasciitis, skin gangrene, lymphadenitis, acute lymphangitis, and skin abscesses. Cellulitis is a spreading bacterial infection in the skin and underlying tissues, usually in the legs. Although many different bacteria can cause cellulitis, Streptococcus is the most common. Initial symptoms include redness and tenderness over a small area of skin. As the infection spreads, the lymph nodes may become enlarged and tender. Other symptoms include fever, chills, a rapid heart rate, headache, and low blood pressure. Diagnosis is based on analysis of samples taken from the blood, skin, pus, or an open wound. Treatment involves taking antibiotics; keeping the affected part of the body immobile and elevated; and applying cool, wet dressings to the infected area. Necrotizing fasciitis is a severe form of cellulitis that destroys infected tissue under the skin. A strain of Streptococcus causes this infection. Symptoms include fever, rapid heart rate, and mental deterioration. Treatment is antibiotic therapy and surgical removal of dead tissue. Skin gangrene is the death of tissue followed by bacterial invasion. The type of bacteria most commonly involved in skin gangrene is Clostridia. Major injuries can interrupt the supply of blood and oxygen to an injured area, creating a situation that allows clostridia to grow. Infection with clostridia makes the skin warm. Skin changes in color from pale to red or bronze and finally to green. Diagnosis is based on symptoms and imaging and laboratory tests. Treatment involves

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taking antibiotics and having the destroyed tissue surgically removed. High pressure oxygen therapy may also be used. Lymphadenitis is an inflammation of the lymph nodes caused by infection from any type of organism. Symptoms include enlarged tender and painful lymph nodes. Treatment depends on the organism causing the infection. Acute lymphangitis is an inflammation of lymphatic vessels that is usually caused by a streptococcal infection. Symptoms include red, irregular, warm, tender streaks under the skin; enlarged and tender lymph nodes; fever; chills; rapid heart rate; and headache. Antibiotics are used to treat this disease. Skin abscesses are collections of pus caused by a bacterial infection. Symptoms include swelling, pain, and tenderness. Treatment usually involves cutting the abscess open and draining the pus. Antibiotics may be needed if the infection has spread or if the abscess is on the middle or upper part of the face. •

Meanings Source: in Curtis, E. Hand to Mouth: Essays on the Art of Dentistry. Chicago, IL: Quintessence Publishing Co, Inc. 2002. p. 52-89. Contact: Available from Quintessence Publishing Co, Inc. 551 Kimberly Drive, Carol Stream, IL 60188-9981. (800) 621-0387 or (630) 682-3223. Fax (630) 682-3288. E-mail: [email protected]. Website: www.quintpub.com. PRICE: $38.00 plus shipping and handling. ISBN: 0867154098. Summary: This section of essays is from a textbook for dental students that offers a humanistic approach to delivery of dental care. The text includes a series of dental vignettes filtered through the humanities and popular culture, with the goal of entertaining, instructing, and inspiring students training to become dentists. The author emphasizes that dentistry is as much about people as procedures, and writing ties them together. Through writing these stories, the author can help sensitize students to the nonscientific needs of their patients. In this section, the author includes ten essays covering the history of where dentistry was delivered (town versus country) and by whom; dental jargon and slang; stereotypes of what a dentist looks like; cost considerations, including billing for dental services; the development of microscopy and the resulting discovery of Streptococcus mutans as a caries causing bacteria; saliva and the development of salivary diagnostic tests; tooth color and discoloration; dental pain and its elimination; and measuring cultural meaning in missing teeth. The chapter is illustrated with cartoons, line drawings, historical advertisements, and artistic renditions of dentistry-related themes.

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CHAPTER 7. PERIODICALS AND NEWS ON STREPTOCOCCUS Overview In this chapter, we suggest a number of news sources and present various periodicals that cover streptococcus.

News Services and Press Releases One of the simplest ways of tracking press releases on streptococcus 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 “streptococcus” (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 streptococcus. 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 “streptococcus” (or synonyms). The following was recently listed in this archive for streptococcus: •

Group A streptococcus vaccine shows promise in animal model Source: Reuters Industry Breifing Date: May 28, 2003

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Multi-drug resistant Streptococcus pneumoniae a growing concern Source: Reuters Industry Breifing Date: April 02, 2003

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FDA approves Bayer's Avelox for penicillin-resistant streptococcus Source: Reuters Industry Breifing Date: March 03, 2003

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Sexual activity tied to transmission of group B Streptococcus Source: Reuters Medical News Date: September 12, 2002

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Vaccines against types IV and VII group B Streptococcus effective in animals Source: Reuters Industry Breifing Date: July 10, 2002

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Bacteriophage enzyme rapidly kills Streptococcus pneumoniae Source: Reuters Industry Breifing Date: December 06, 2001

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Antimicrobial-resistant isolates of Streptococcus pneumoniae up sharply Source: Reuters Medical News Date: July 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 “streptococcus” (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

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you can use this Web site’s general news search page at http://news.yahoo.com/. Type in “streptococcus” (or synonyms). If you know the name of a company that is relevant to streptococcus, you can go to any stock trading Web site (such as http://www.etrade.com/) and search for the company name there. News items across various news sources are reported on indicated hyperlinks. Google offers a similar service at http://news.google.com/. BBC Covering news from a more European perspective, the British Broadcasting Corporation (BBC) allows the public free access to their news archive located at http://www.bbc.co.uk/. Search by “streptococcus” (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 “streptococcus” (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 streptococcus: •

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.

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Academic Periodicals covering Streptococcus Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to streptococcus. In addition to these sources, you can search for articles covering streptococcus that have been published by any of the periodicals listed in previous chapters. To find the latest studies published, go to http://www.ncbi.nlm.nih.gov/pubmed, type the name of the periodical into the search box, and click “Go.” If you want complete details about the historical contents of a journal, you can also visit the following Web site: http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi. Here, type in the name of the journal or its abbreviation, and you will receive an index of published articles. At http://locatorplus.gov/, you can retrieve more indexing information on medical periodicals (e.g. the name of the publisher). Select the button “Search LOCATORplus.” Then type in the name of the journal and select the advanced search option “Journal Title Search.”

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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 Institute10: •

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

•

National Institute on Aging (NIA); guidelines available at http://www.nia.nih.gov/health/

10

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.11 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:12 •

Bioethics: Access to published literature on the ethical, legal, and public policy issues surrounding healthcare and biomedical research. This information is provided in conjunction with the Kennedy Institute of Ethics located at Georgetown University, Washington, D.C.: http://www.nlm.nih.gov/databases/databases_bioethics.html

•

HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html

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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

•

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

11

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). 12 See http://www.nlm.nih.gov/databases/databases.html.

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•

Toxicology and Environmental Health Information (TOXNET): Databases covering toxicology and environmental health: http://sis.nlm.nih.gov/Tox/ToxMain.html

•

Visible Human Interface: Anatomically detailed, three-dimensional representations of normal male and female human bodies: http://www.nlm.nih.gov/research/visible/visible_human.html

The NLM Gateway13 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.14 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “streptococcus” (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 59028 261 901 841 71 61102

HSTAT15 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.16 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.17 Simply search by “streptococcus” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

13

Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.

14

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). 15 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 16 17

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 Biologists18 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.19 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.20 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/.

The Genome Project and Streptococcus In the following section, we will discuss databases and references which relate to the Genome Project and streptococcus. Online Mendelian Inheritance in Man (OMIM) The Online Mendelian Inheritance in Man (OMIM) database is a catalog of human genes and genetic disorders authored and edited by Dr. Victor A. McKusick and his colleagues at Johns Hopkins and elsewhere. OMIM was developed for the World Wide Web by the National Center for Biotechnology Information (NCBI).21 The database contains textual information, pictures, and reference information. It also contains copious links to NCBI’s Entrez database of MEDLINE articles and sequence information. 18 Adapted 19

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. 20 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. 21 Adapted from http://www.ncbi.nlm.nih.gov/. Established in 1988 as a national resource for molecular biology information, NCBI creates public databases, conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information--all for the better understanding of molecular processes affecting human health and disease.

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To search the database, go to http://www.ncbi.nlm.nih.gov/Omim/searchomim.html. Type “streptococcus” (or synonyms) into the search box, and click “Submit Search.” If too many results appear, you can narrow the search by adding the word “clinical.” Each report will have additional links to related research and databases. In particular, the option “Database Links” will search across technical databases that offer an abundance of information. The following is an example of the results you can obtain from the OMIM for streptococcus: •

Streptococcus, Group A, Severity of Infection by Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=607395 Genes and Disease (NCBI - Map)

The Genes and Disease database is produced by the National Center for Biotechnology Information of the National Library of Medicine at the National Institutes of Health. This Web site categorizes each disorder by system of the body. Go to http://www.ncbi.nlm.nih.gov/disease/, and browse the system pages to have a full view of important conditions linked to human genes. Since this site is regularly updated, you may wish to revisit it from time to time. The following systems and associated disorders are addressed: •

Cancer: Uncontrolled cell division. Examples: Breast and ovarian cancer, Burkitt lymphoma, chronic myeloid leukemia, colon cancer, lung cancer, malignant melanoma, multiple endocrine neoplasia, neurofibromatosis, p53 tumor suppressor, pancreatic cancer, prostate cancer, Ras oncogene, RB: retinoblastoma, von Hippel-Lindau syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Cancer.html

•

Immune System: Fights invaders. Examples: Asthma, autoimmune polyglandular syndrome, Crohn’s disease, DiGeorge syndrome, familial Mediterranean fever, immunodeficiency with Hyper-IgM, severe combined immunodeficiency. Web site: http://www.ncbi.nlm.nih.gov/disease/Immune.html

•

Metabolism: Food and energy. Examples: Adreno-leukodystrophy, atherosclerosis, Best disease, Gaucher disease, glucose galactose malabsorption, gyrate atrophy, juvenile-onset diabetes, obesity, paroxysmal nocturnal hemoglobinuria, phenylketonuria, Refsum disease, Tangier disease, Tay-Sachs disease. Web site: http://www.ncbi.nlm.nih.gov/disease/Metabolism.html

•

Muscle and Bone: Movement and growth. Examples: Duchenne muscular dystrophy, Ellis-van Creveld syndrome, Marfan syndrome, myotonic dystrophy, spinal muscular atrophy. Web site: http://www.ncbi.nlm.nih.gov/disease/Muscle.html

•

Nervous System: Mind and body. Examples: Alzheimer disease, amyotrophic lateral sclerosis, Angelman syndrome, Charcot-Marie-Tooth disease, epilepsy, essential tremor, fragile X syndrome, Friedreich’s ataxia, Huntington disease, Niemann-Pick disease, Parkinson disease, Prader-Willi syndrome, Rett syndrome, spinocerebellar atrophy, Williams syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Brain.html

•

Signals: Cellular messages. Examples: Ataxia telangiectasia, Cockayne syndrome, glaucoma, male-patterned

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baldness, SRY: sex determination, tuberous sclerosis, Waardenburg syndrome, Werner syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Signals.html •

Transporters: Pumps and channels. Examples: Cystic fibrosis, deafness, diastrophic dysplasia, Hemophilia A, long-QT syndrome, Menkes syndrome, Pendred syndrome, polycystic kidney disease, sickle cell anemia, Wilson’s disease, Zellweger syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Transporters.html Entrez

Entrez is a search and retrieval system that integrates several linked databases at the National Center for Biotechnology Information (NCBI). These databases include nucleotide sequences, protein sequences, macromolecular structures, whole genomes, and MEDLINE through PubMed. Entrez provides access to the following databases: •

3D Domains: Domains from Entrez Structure, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo

•

Books: Online books, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=books

•

Genome: Complete genome assemblies, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Genome

•

NCBI’s Protein Sequence Information Survey Results: Web site: http://www.ncbi.nlm.nih.gov/About/proteinsurvey/

•

Nucleotide Sequence Database (Genbank): Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Nucleotide

•

OMIM: Online Mendelian Inheritance in Man, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=OMIM

•

PopSet: Population study data sets, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Popset

•

ProbeSet: Gene Expression Omnibus (GEO), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo

•

Protein Sequence Database: Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Protein

•

PubMed: Biomedical literature (PubMed), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed

•

Structure: Three-dimensional macromolecular structures, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Structure

•

Taxonomy: Organisms in GenBank, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Taxonomy

To access the Entrez system at the National Center for Biotechnology Information, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=genome, and then select the database that you would like to search. The databases available are listed in the

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drop box next to “Search.” Enter “streptococcus” (or synonyms) into the search box and click “Go.” Jablonski’s Multiple Congenital Anomaly/Mental Retardation (MCA/MR) Syndromes Database22 This online resource has been developed to facilitate the identification and differentiation of syndromic entities. Special attention is given to the type of information that is usually limited or completely omitted in existing reference sources due to space limitations of the printed form. At http://www.nlm.nih.gov/mesh/jablonski/syndrome_toc/toc_a.html, you can search across syndromes using an alphabetical index. Search by keywords at http://www.nlm.nih.gov/mesh/jablonski/syndrome_db.html. The Genome Database23 Established at Johns Hopkins University in Baltimore, Maryland in 1990, the Genome Database (GDB) is the official central repository for genomic mapping data resulting from the Human Genome Initiative. In the spring of 1999, the Bioinformatics Supercomputing Centre (BiSC) at the Hospital for Sick Children in Toronto, Ontario assumed the management of GDB. The Human Genome Initiative is a worldwide research effort focusing on structural analysis of human DNA to determine the location and sequence of the estimated 100,000 human genes. In support of this project, GDB stores and curates data generated by researchers worldwide who are engaged in the mapping effort of the Human Genome Project (HGP). GDB’s mission is to provide scientists with an encyclopedia of the human genome which is continually revised and updated to reflect the current state of scientific knowledge. Although GDB has historically focused on gene mapping, its focus will broaden as the Genome Project moves from mapping to sequence, and finally, to functional analysis. To access the GDB, simply go to the following hyperlink: http://www.gdb.org/. Search “All Biological Data” by “Keyword.” Type “streptococcus” (or synonyms) into the search box, and review the results. If more than one word is used in the search box, then separate each one with the word “and” or “or” (using “or” might be useful when using synonyms).

22

Adapted from the National Library of Medicine: http://www.nlm.nih.gov/mesh/jablonski/about_syndrome.html. 23 Adapted from the Genome Database: http://gdbwww.gdb.org/gdb/aboutGDB.html - mission.

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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 streptococcus 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 streptococcus. 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 streptococcus. 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 “streptococcus”:

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Cellulitis http://www.nlm.nih.gov/medlineplus/cellulitis.html Meningitis http://www.nlm.nih.gov/medlineplus/meningitis.html Staphylococcal Infections http://www.nlm.nih.gov/medlineplus/staphylococcalinfections.html Streptococcal Infections http://www.nlm.nih.gov/medlineplus/streptococcalinfections.html Throat Disorders http://www.nlm.nih.gov/medlineplus/throatdisorders.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 streptococcus. 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: •

Impetigo Source: KidsHealth. October 2002. 2 p. Contact: Nemours Foundation. Website: www.kidshealth.org. Summary: This fact sheet is written for parents of children who have impetigo, a highly contagious blistering disease of the skin caused by either Group A streptococcus or Staphylococcus aureas. It usually affects preschool and school-age children and can be spread from one area of the body to another or from one child to another. If it is caused by Group A streptococcus it appears as tiny blisters. These blisters burst revealing wet red patches of skin that weep fluid. Staphylococcus aureas causes larger blisters that tend to stay intact. Impetigo may itch and can be spread by scratching. An antibiotic ointment is used to treat impetigo. The doctor may prescribe an oral antibiotic if the infection has spread to many areas of the body or if the ointment is not working. The infected skin should be cleansed daily with antiseptic soap and covered with clean gauze. It is not necessary to remove any layers of crust that have formed over the wet patches of skin. Healing should begin within 2 to 3 days of starting treatment, and children can return to school in about 48 hours after the treatment is started; they will no longer be contagious. Good hygiene practices, including regular hand washing and keeping the fingernails clipped, can prevent the spread of impetigo. If one family

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member has impetigo, towels, bed linens, and clothing should be kept separate from that of other family members and washed in hot water. •

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 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.

•

Erythema Nodosum Source: Kirksville, MO: American Osteopathic College of Dermatology (AOCD). 2001. 2 p. Contact: Available online from American Osteopathic College of Dermatology. 1501 East Illinois Street, P.O. Box 7525, Kirksville, MO 63501. (800) 449-2623 or (660) 665-2184. Fax (660) 627-2623. E-mail: [email protected]. Website: www.aocd.org/skin/dermatologic_diseases/ index.html. Summary: This pamphlet provides people who have erythema nodosum with information on the etiology, symptoms, and treatment of this inflammation of the subcutaneous fat tissue. Erythema nodosum occurs three times more often in women than in men and most often affects people between the ages of 15 and 30. The causes of erythema nodosum include medications, such as sulfa drugs and some brands of oral contraceptives, and infection with streptococcus and tuberculosis. The skin lesions of erythema nodosum, which are painful, are usually slightly raised and bright red, and as they fade, they get a yellowish color. They can range in size from one half inch to several inches. The differential diagnosis includes insect bites, bruises, pancreatitis, and phlebitis. A biopsy and other diagnostic tests are used in diagnosing the disease. The most effective treatment is to eliminate the cause. Other modalities include drugs and bed rest. 2 figures.

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Healthfinder™ Healthfinder™ is sponsored by the U.S. Department of Health and Human Services and offers links to hundreds of other sites that contain healthcare information. This Web site is located at http://www.healthfinder.gov. Again, keyword searches can be used to find guidelines. The following was recently found in this database: •

FAQ - About Group B Streptococcal Infections Summary: Answers to consumers' most commonly asked questions about Group B streptococcus (GBS) -- a type of bacterium that causes illness in newborn babies, pregnant women, the elderly, and adults with other Source: National Center for Infectious Diseases, Centers for Disease Control and Prevention http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=3038

•

Group A Streptococcal Infections Summary: A general overview of Group A Streptococcal Infections and some of the streptococcal illnesses for which the group A streptococcus bacterium is responsible. Source: National Institute of Allergy and Infectious Diseases, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=236

•

Group B Streptococcus (GBS) Disease Home Page - National Center for Infectious Diseases/CDC Summary: Information and resources about Group B streptococcus (GBS) that includes fact sheets, slide set, a video for pregnant women and more. Source: National Center for Infectious Diseases, Centers for Disease Control and Prevention http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=3037 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 streptococcus. 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.

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Additional Web Sources A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •

AOL: http://search.aol.com/cat.adp?id=168&layer=&from=subcats

•

Family Village: http://www.familyvillage.wisc.edu/specific.htm

•

Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/

•

Med Help International: http://www.medhelp.org/HealthTopics/A.html

•

Open Directory Project: http://dmoz.org/Health/Conditions_and_Diseases/

•

Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/

•

WebMDHealth: http://my.webmd.com/health_topics

Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to streptococcus. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with streptococcus. 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 streptococcus. 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 “streptococcus” (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

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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 “streptococcus”. 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 “streptococcus” (or synonyms) into the “For these words:” box. You should check back periodically with this database since it is updated every three months. The National Organization for Rare Disorders, Inc. The National Organization for Rare Disorders, Inc. has prepared a Web site that provides, at no charge, lists of associations organized by health topic. You can access this database at the following Web site: http://www.rarediseases.org/search/orgsearch.html. Type “streptococcus” (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.24

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

24

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)25: •

Alabama: Health InfoNet of Jefferson County (Jefferson County Library Cooperative, Lister Hill Library of the Health Sciences), http://www.uab.edu/infonet/

•

Alabama: Richard M. Scrushy Library (American Sports Medicine Institute)

•

Arizona: Samaritan Regional Medical Center: The Learning Center (Samaritan Health System, Phoenix, Arizona), http://www.samaritan.edu/library/bannerlibs.htm

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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

•

California: Consumer Health Program and Services (CHIPS) (County of Los Angeles Public Library, Los Angeles County Harbor-UCLA Medical Center Library) - Carson, CA, http://www.colapublib.org/services/chips.html

•

California: Gateway Health Library (Sutter Gould Medical Foundation)

•

California: Health Library (Stanford University Medical Center), http://wwwmed.stanford.edu/healthlibrary/

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California: Patient Education Resource Center - Health Information and Resources (University of California, San Francisco), http://sfghdean.ucsf.edu/barnett/PERC/default.asp

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California: Redwood Health Library (Petaluma Health Care District), http://www.phcd.org/rdwdlib.html

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California: Los Gatos PlaneTree Health Library, http://planetreesanjose.org/

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California: Sutter Resource Library (Sutter Hospitals Foundation, Sacramento), http://suttermedicalcenter.org/library/

•

California: Health Sciences Libraries (University of California, Davis), http://www.lib.ucdavis.edu/healthsci/

•

California: ValleyCare Health Library & Ryan Comer Cancer Resource Center (ValleyCare Health System, Pleasanton), http://gaelnet.stmarysca.edu/other.libs/gbal/east/vchl.html

•

California: Washington Community Health Resource Library (Fremont), http://www.healthlibrary.org/

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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/

25

Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.

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•

Connecticut: Waterbury Hospital Health Center Library (Waterbury Hospital, Waterbury), http://www.waterburyhospital.com/library/consumer.shtml

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Delaware: Consumer Health Library (Christiana Care Health System, Eugene du Pont Preventive Medicine & Rehabilitation Institute, Wilmington), http://www.christianacare.org/health_guide/health_guide_pmri_health_info.cfm

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Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine, Wilmington), http://www.delamed.org/chls.html

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Georgia: Family Resource Library (Medical College of Georgia, Augusta), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm

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Georgia: Health Resource Center (Medical Center of Central Georgia, Macon), http://www.mccg.org/hrc/hrchome.asp

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Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library, Honolulu), http://hml.org/CHIS/

•

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

•

Maine: Stephens Memorial Hospital’s Health Information Library (Western Maine Health, Norway), http://www.wmhcc.org/Library/

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Manitoba, Canada: Consumer & Patient Health Information Service (University of Manitoba Libraries), http://www.umanitoba.ca/libraries/units/health/reference/chis.html

•

Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre, Winnipeg), http://www.deerlodge.mb.ca/crane_library/about.asp

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Maryland: Health Information Center at the Wheaton Regional Library (Montgomery County, Dept. of Public Libraries, Wheaton Regional Library), http://www.mont.lib.md.us/healthinfo/hic.asp

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Massachusetts: Baystate Medical Center Library (Baystate Health System), http://www.baystatehealth.com/1024/

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Massachusetts: Boston University Medical Center Alumni Medical Library (Boston University Medical Center), http://med-libwww.bu.edu/library/lib.html

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Massachusetts: Lowell General Hospital Health Sciences Library (Lowell General Hospital, Lowell), http://www.lowellgeneral.org/library/HomePageLinks/WWW.htm

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Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital, Boston), http://www.nebh.org/health_lib.asp

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Massachusetts: St. Luke’s Hospital Health Sciences Library (St. Luke’s Hospital, Southcoast Health System, New Bedford), http://www.southcoast.org/library/

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Massachusetts: Treadwell Library Consumer Health Reference Center (Massachusetts General Hospital), http://www.mgh.harvard.edu/library/chrcindex.html

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Massachusetts: UMass HealthNet (University of Massachusetts Medical School, Worchester), http://healthnet.umassmed.edu/

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Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm

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Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/

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Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html

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Michigan: Patient Education Resouce Center - University of Michigan Cancer Center (University of Michigan Comprehensive Cancer Center, Ann Arbor), http://www.cancer.med.umich.edu/learn/leares.htm

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Michigan: Sladen Library & Center for Health Information Resources - Consumer Health Information (Detroit), http://www.henryford.com/body.cfm?id=39330

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Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center, Missoula)

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National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html

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National: National Network of Libraries of Medicine (National Library of Medicine) provides library services for health professionals in the United States who do not have access to a medical library, http://nnlm.gov/

•

National: NN/LM List of Libraries Serving the Public (National Network of Libraries of Medicine), http://nnlm.gov/members/

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Nevada: Health Science Library, West Charleston Library (Las Vegas-Clark County Library District, Las Vegas), http://www.lvccld.org/special_collections/medical/index.htm

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New Hampshire: Dartmouth Biomedical Libraries (Dartmouth College Library, Hanover), http://www.dartmouth.edu/~biomed/resources.htmld/conshealth.htmld/

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New Jersey: Consumer Health Library (Rahway Hospital, Rahway), http://www.rahwayhospital.com/library.htm

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New Jersey: Dr. Walter Phillips Health Sciences Library (Englewood Hospital and Medical Center, Englewood), http://www.englewoodhospital.com/links/index.htm

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New Jersey: Meland Foundation (Englewood Hospital and Medical Center, Englewood), http://www.geocities.com/ResearchTriangle/9360/

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New York: Choices in Health Information (New York Public Library) - NLM Consumer Pilot Project participant, http://www.nypl.org/branch/health/links.html

•

New York: Health Information Center (Upstate Medical University, State University of New York, Syracuse), http://www.upstate.edu/library/hic/

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New York: Health Sciences Library (Long Island Jewish Medical Center, New Hyde Park), http://www.lij.edu/library/library.html

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New York: ViaHealth Medical Library (Rochester General Hospital), http://www.nyam.org/library/

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Ohio: Consumer Health Library (Akron General Medical Center, Medical & Consumer Health Library), http://www.akrongeneral.org/hwlibrary.htm

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Oklahoma: The Health Information Center at Saint Francis Hospital (Saint Francis Health System, Tulsa), http://www.sfh-tulsa.com/services/healthinfo.asp

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Oregon: Planetree Health Resource Center (Mid-Columbia Medical Center, The Dalles), http://www.mcmc.net/phrc/

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Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center, Hershey), http://www.hmc.psu.edu/commhealth/

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Pennsylvania: Community Health Resource Library (Geisinger Medical Center, Danville), http://www.geisinger.edu/education/commlib.shtml

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Pennsylvania: HealthInfo Library (Moses Taylor Hospital, Scranton), http://www.mth.org/healthwellness.html

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Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System, Pittsburgh), http://www.hsls.pitt.edu/guides/chi/hopwood/index_html

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Pennsylvania: Koop Community Health Information Center (College of Physicians of Philadelphia), http://www.collphyphil.org/kooppg1.shtml

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Pennsylvania: Learning Resources Center - Medical Library (Susquehanna Health System, Williamsport), http://www.shscares.org/services/lrc/index.asp

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Pennsylvania: Medical Library (UPMC Health System, Pittsburgh), http://www.upmc.edu/passavant/library.htm

•

Quebec, Canada: Medical Library (Montreal General Hospital), http://www.mghlib.mcgill.ca/

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South Dakota: Rapid City Regional Hospital Medical Library (Rapid City Regional Hospital), http://www.rcrh.org/Services/Library/Default.asp

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Texas: Houston HealthWays (Houston Academy of Medicine-Texas Medical Center Library), http://hhw.library.tmc.edu/

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Washington: Community Health Library (Kittitas Valley Community Hospital), http://www.kvch.com/

•

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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STREPTOCOCCUS DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. 1-phosphate: A drug that halts cell suicide in human white blood cells. [NIH] Abdomen: That portion of the body that lies between the thorax and the pelvis. [NIH] Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Abdominal Pain: Sensation of discomfort, distress, or agony in the abdominal region. [NIH] Abscess: A localized, circumscribed collection of pus. [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] ACE: Angiotensin-coverting enzyme. A drug used to decrease pressure inside blood vessels. [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] Acetylglucosamine: The N-acetyl derivative of glucosamine. [NIH] Acid Phosphatase: An enzyme that catalyzes the conversion of an orthophosphoric monoester and water to an alcohol and orthophosphate. EC 3.1.3.2. [NIH] Acidity: The quality of being acid or sour; containing acid (hydrogen ions). [EU] Acidosis: A pathologic condition resulting from accumulation of acid or depletion of the alkaline reserve (bicarbonate content) in the blood and body tissues, and characterized by an increase in hydrogen ion concentration. [EU] Acremonium: A mitosporic fungal genus with many reported ascomycetous teleomorphs. Cephalosporin antibiotics are derived from this genus. [NIH] Acrosome: Cap-like structure covering the nucleus and anterior part of the sperm head. [NIH]

Acrylonitrile: A highly poisonous compound used widely in the manufacture of plastics, adhesives and synthetic rubber. [NIH] Actinobacillus: A genus of Pasteurellaceae described as gram-negative, nonsporeforming, nonmotile, facultative anaerobes. Most members are found both as pathogens and commensal organisms in the respiratory, alimentary, and genital tracts of animals. [NIH] Actinomyces: A genus of gram-positive, rod-shaped bacteria whose organisms are nonmotile. Filaments that may be present in certain species are either straight or wavy and may have swollen or clubbed heads. [NIH] Acute Disease: Disease having a short and relatively severe course. [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]

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Adaptability: Ability to develop some form of tolerance to conditions extremely different from those under which a living organism evolved. [NIH] Adaptation: 1. The adjustment of an organism to its environment, or the process by which it enhances such fitness. 2. The normal ability of the eye to adjust itself to variations in the intensity of light; the adjustment to such variations. 3. The decline in the frequency of firing of a neuron, particularly of a receptor, under conditions of constant stimulation. 4. In dentistry, (a) the proper fitting of a denture, (b) the degree of proximity and interlocking of restorative material to a tooth preparation, (c) the exact adjustment of bands to teeth. 5. In microbiology, the adjustment of bacterial physiology to a new environment. [EU] Adenine: A purine base and a fundamental unit of adenine nucleotides. [NIH] Adenitis: Inflammation of a gland. [EU] Adenosine: A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. [NIH] Adenylate Cyclase: An enzyme of the lyase class that catalyzes the formation of cyclic AMP and pyrophosphate from ATP. EC 4.6.1.1. [NIH] Adhesions: Pathological processes consisting of the union of the opposing surfaces of a wound. [NIH] Adjustment: The dynamic process wherein the thoughts, feelings, behavior, and biophysiological mechanisms of the individual continually change to adjust to the environment. [NIH] Adjuvant: A substance which aids another, such as an auxiliary remedy; in immunology, nonspecific stimulator (e.g., BCG vaccine) of the immune response. [EU] Adoptive Transfer: Form of passive immunization where previously sensitized immunologic agents (cells or serum) are transferred to non-immune recipients. When transfer of cells is used as a therapy for the treatment of neoplasms, it is called adoptive immunotherapy (immunotherapy, adoptive). [NIH] Adsorption: The condensation of gases, liquids, or dissolved substances on the surfaces of solids. It includes adsorptive phenomena of bacteria and viruses as well as of tissues treated with exogenous drugs and chemicals. [NIH] Adsorptive: It captures volatile compounds by binding them to agents such as activated carbon or adsorptive resins. [NIH] Aerobic: In biochemistry, reactions that need oxygen to happen or happen when oxygen is present. [NIH] Aerobic Metabolism: A chemical process in which oxygen is used to make energy from carbohydrates (sugars). Also known as aerobic respiration, oxidative metabolism, or cell respiration. [NIH] Aerobic Respiration: A chemical process in which oxygen is used to make energy from carbohydrates (sugars). Also known as oxidative metabolism, cell respiration, or aerobic metabolism. [NIH] Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among

Dictionary 271

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] Agalactia: Absence or failure of the secretion of milk; called also agalactosis. [EU] Agar: A complex sulfated polymer of galactose units, extracted from Gelidium cartilagineum, Gracilaria confervoides, and related red algae. It is used as a gel in the preparation of solid culture media for microorganisms, as a bulk laxative, in making emulsions, and as a supporting medium for immunodiffusion and immunoelectrophoresis. [NIH]

Age Groups: Persons classified by age from birth (infant, newborn) to octogenarians and older (aged, 80 and over). [NIH] Aged, 80 and Over: A person 80 years of age and older. [NIH] Agonists: Drugs that trigger an action from a cell or another drug. [NIH] Air Pressure: The force per unit area that the air exerts on any surface in contact with it. Primarily used for articles pertaining to air pressure within a closed environment. [NIH] Air Sacs: Thin-walled sacs or spaces which function as a part of the respiratory system in birds, fishes, insects, and mammals. [NIH] Airway: A device for securing unobstructed passage of air into and out of the lungs during general anesthesia. [NIH] Albumin: 1. Any protein that is soluble in water and moderately concentrated salt solutions and is coagulable by heat. 2. Serum albumin; the major plasma protein (approximately 60 per cent of the total), which is responsible for much of the plasma colloidal osmotic pressure and serves as a transport protein carrying large organic anions, such as fatty acids, bilirubin, and many drugs, and also carrying certain hormones, such as cortisol and thyroxine, when their specific binding globulins are saturated. Albumin is synthesized in the liver. Low serum levels occur in protein malnutrition, active inflammation and serious hepatic and renal disease. [EU] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alimentary: Pertaining to food or nutritive material, or to the organs of digestion. [EU] Alkaline: Having the reactions of an alkali. [EU] Allantois: An embryonic diverticulum of the hindgut of reptiles, birds, and mammals; in man its blood vessels give rise to those of the umbilical cord. [NIH] Allograft: An organ or tissue transplant between two humans. [NIH] Alpha-1: A protein with the property of inactivating proteolytic enzymes such as leucocyte collagenase and elastase. [NIH] Alpha-Amylase: An enzyme that catalyzes the endohydrolysis of 1,4-alpha-glycosidic linkages in starch, glycogen, and related polysaccharides and oligosaccharides containing 3 or more 1,4-alpha-linked D-glucose units. EC 3.2.1.1. [NIH] Alpha-Defensins: Defensins found in azurophilic granules of neutrophils and in the secretory granules of intestinal paneth cells. [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,

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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] Amebiasis: Infection with any of various amebae. It is an asymptomatic carrier state in most individuals, but diseases ranging from chronic, mild diarrhea to fulminant dysentery may occur. [NIH] Ameliorated: A changeable condition which prevents the consequence of a failure or accident from becoming as bad as it otherwise would. [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] 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] Amnion: The extraembryonic membrane which contains the embryo and amniotic fluid. [NIH]

Amniotic Fluid: Amniotic cavity fluid which is produced by the amnion and fetal lungs and kidneys. [NIH] Amoxicillin: A broad-spectrum semisynthetic antibiotic similar to ampicillin except that its resistance to gastric acid permits higher serum levels with oral administration. [NIH] Ampicillin: Semi-synthetic derivative of penicillin that functions as an orally active broadspectrum antibiotic. [NIH] Amplification: The production of additional copies of a chromosomal DNA sequence, found as either intrachromosomal or extrachromosomal DNA. [NIH] Amylase: An enzyme that helps the body digest starches. [NIH] Anaerobic: 1. Lacking molecular oxygen. 2. Growing, living, or occurring in the absence of molecular oxygen; pertaining to an anaerobe. [EU] Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Anal: Having to do with the anus, which is the posterior opening of the large bowel. [NIH] Analog: In chemistry, a substance that is similar, but not identical, to another. [NIH] Analogous: Resembling or similar in some respects, as in function or appearance, but not in origin or development;. [EU] Analytes: A component of a test sample the presence of which has to be demonstrated. The term "analyte" includes where appropriate formed from the analyte during the analyses. [NIH]

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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] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Anchorage: In dentistry, points of retention of fillings and artificial restorations and appliances. [NIH] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Anergy: Absence of immune response to particular substances. [NIH] Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH] Angiogenesis: Blood vessel formation. Tumor angiogenesis is the growth of blood vessels from surrounding tissue to a solid tumor. This is caused by the release of chemicals by the tumor. [NIH] 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]

Anorectal: Pertaining to the anus and rectum or to the junction region between the two. [EU] Antecedent: Existing or occurring before in time or order often with consequential effects. [EU]

Anthrax: An acute bacterial infection caused by ingestion of bacillus organisms. Carnivores may become infected from ingestion of infected carcasses. It is transmitted to humans by contact with infected animals or contaminated animal products. The most common form in humans is cutaneous anthrax. [NIH] Antibacterial: A substance that destroys bacteria or suppresses their growth or reproduction. [EU] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]

Antibiotic Prophylaxis: Use of antibiotics before, during, or after a diagnostic, therapeutic, or surgical procedure to prevent infectious complications. [NIH] Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH]

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Antibody Affinity: A measure of the binding strength between antibody and a simple hapten or antigen determinant. It depends on the closeness of stereochemical fit between antibody combining sites and antigen determinants, on the size of the area of contact between them, and on the distribution of charged and hydrophobic groups. It includes the concept of "avidity," which refers to the strength of the antigen-antibody bond after formation of reversible complexes. [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] Antimicrobial: Killing microorganisms, or suppressing their multiplication or growth. [EU] Antimycotic: Suppressing the growth of fungi. [EU] Antineoplastic: Inhibiting or preventing the development of neoplasms, checking the maturation and proliferation of malignant cells. [EU] 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] Anus: The opening of the rectum to the outside of the body. [NIH] Anxiety: Persistent feeling of dread, apprehension, and impending disaster. [NIH] Aorta: The main trunk of the systemic arteries. [NIH] Aortic Aneurysm: Aneurysm of the aorta. [NIH] Aortitis: Inflammation of the wall of the aorta. [NIH] Apolipoproteins: The protein components of lipoproteins which remain after the lipids to

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which the proteins are bound have been removed. They play an important role in lipid transport and metabolism. [NIH] Apoptosis: One of the two mechanisms by which cell death occurs (the other being the pathological process of necrosis). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA (DNA fragmentation) at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. [NIH] Approximate: Approximal [EU] Aqueous: Having to do with water. [NIH] Arachidonic Acid: An unsaturated, essential fatty acid. It is found in animal and human fat as well as in the liver, brain, and glandular organs, and is a constituent of animal phosphatides. It is formed by the synthesis from dietary linoleic acid and is a precursor in the biosynthesis of prostaglandins, thromboxanes, and leukotrienes. [NIH] 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] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Arteriovenous: Both arterial and venous; pertaining to or affecting an artery and a vein. [EU] 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] Aspartic: The naturally occurring substance is L-aspartic acid. One of the acidic-amino-acids is obtained by the hydrolysis of proteins. [NIH] Aspartic Acid: One of the non-essential amino acids commonly occurring in the L-form. It is found in animals and plants, especially in sugar cane and sugar beets. It may be a neurotransmitter. [NIH] 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] Asymptomatic: Having no signs or symptoms of disease. [NIH] Ataxia: Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharnyx, larnyx, and other structures.

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Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or peripheral nerve diseases. Motor ataxia may be associated with cerebellar diseases; cerebral cortex diseases; thalamic diseases; basal ganglia diseases; injury to the red nucleus; and other conditions. [NIH] Atrophy: Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. [NIH] Attenuation: Reduction of transmitted sound energy or its electrical equivalent. [NIH] Atypical: Irregular; not conformable to the type; in microbiology, applied specifically to strains of unusual type. [EU] Auditory: Pertaining to the sense of hearing. [EU] Autacoids: A chemically diverse group of substances produced by various tissues in the body that cause slow contraction of smooth muscle; they have other intense but varied pharmacologic activities. [NIH] Autoantibodies: Antibodies that react with self-antigens (autoantigens) of the organism that produced them. [NIH] Autoantigens: Endogenous tissue constituents that have the ability to interact with autoantibodies and cause an immune response. [NIH] Autodigestion: Autolysis; a condition found in disease of the stomach: the stomach wall is digested by the gastric juice. [NIH] Autoimmune disease: A condition in which the body recognizes its own tissues as foreign and directs an immune response against them. [NIH] Autoimmune Hepatitis: A liver disease caused when the body's immune system destroys liver cells for no known reason. [NIH] Autologous: Taken from an individual's own tissues, cells, or DNA. [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 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] Autopsy: Postmortem examination of the body. [NIH] Autoradiography: A process in which radioactive material within an object produces an image when it is in close proximity to a radiation sensitive emulsion. [NIH] Avidity: The strength of the interaction of an antiserum with a multivalent antigen. [NIH] Axonal: Condition associated with metabolic derangement of the entire neuron and is manifest by degeneration of the distal portion of the nerve fiber. [NIH] Azithromycin: A semi-synthetic macrolide antibiotic structurally related to erythromycin. It has been used in the treatment of Mycobacterium avium intracellulare infections, toxoplasmosis, and cryptosporidiosis. [NIH] Bacillus: A genus of Bacillaceae that are spore-forming, rod-shaped cells. Most species are saprophytic soil forms with only a few species being pathogenic. [NIH] Bacteraemia: The presence of bacteria in the blood. [EU]

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Bacteremia: The presence of viable bacteria circulating in the blood. Fever, chills, tachycardia, and tachypnea are common acute manifestations of bacteremia. The majority of cases are seen in already hospitalized patients, most of whom have underlying diseases or procedures which render their bloodstreams susceptible to invasion. [NIH] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Bacterial Adhesion: Physicochemical property of fimbriated and non-fimbriated bacteria of attaching to cells, tissue, and nonbiological surfaces. It is a factor in bacterial colonization and pathogenicity. [NIH] Bacterial Infections: Infections by bacteria, general or unspecified. [NIH] Bacterial Physiology: Physiological processes and activities of bacteria. [NIH] Bacterial Proteins: Proteins found in any species of bacterium. [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] Basal Ganglia: Large subcortical nuclear masses derived from the telencephalon and located in the basal regions of the cerebral hemispheres. [NIH] Basal Ganglia Diseases: Diseases of the basal ganglia including the putamen; globus pallidus; claustrum; amygdala; and caudate nucleus. Dyskinesias (most notably involuntary movements and alterations of the rate of movement) represent the primary clinical manifestations of these disorders. Common etiologies include cerebrovascular disease; neurodegenerative diseases; and craniocerebral trauma. [NIH] Base: In chemistry, the nonacid part of a salt; a substance that combines with acids to form salts; a substance that dissociates to give hydroxide ions in aqueous solutions; a substance whose molecule or ion can combine with a proton (hydrogen ion); a substance capable of donating a pair of electrons (to an acid) for the formation of a coordinate covalent bond. [EU] Basement Membrane: Ubiquitous supportive tissue adjacent to epithelium and around smooth and striated muscle cells. This tissue contains intrinsic macromolecular components such as collagen, laminin, and sulfated proteoglycans. As seen by light microscopy one of its subdivisions is the basal (basement) lamina. [NIH] Basophils: Granular leukocytes characterized by a relatively pale-staining, lobate nucleus and cytoplasm containing coarse dark-staining granules of variable size and stainable by basic dyes. [NIH] Bed Rest: Confinement of an individual to bed for therapeutic or experimental reasons. [NIH] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]

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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] Bifidobacterium: A rod-shaped, gram-positive, non-acid-fast, non-spore-forming, nonmotile bacterium that is a genus of the family Actinomycetaceae. It inhabits the intestines and feces of humans as well as the human vagina. [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] Bile Acids: Acids made by the liver that work with bile to break down fats. [NIH] Bile Acids and Salts: Steroid acids and salts. The primary bile acids are derived from cholesterol in the liver and usually conjugated with glycine or taurine. The secondary bile acids are further modified by bacteria in the intestine. They play an important role in the digestion and absorption of fat. They have also been used pharmacologically, especially in the treatment of gallstones. [NIH] Bile duct: A tube through which bile passes in and out of the liver. [NIH] Biliary: Having to do with the liver, bile ducts, and/or gallbladder. [NIH] Biliary Tract: The gallbladder and its ducts. [NIH] Bilirubin: A bile pigment that is a degradation product of heme. [NIH] Binding Sites: The reactive parts of a macromolecule that directly participate in its specific combination with another molecule. [NIH] Bioavailability: The degree to which a drug or other substance becomes available to the target tissue after administration. [EU] Bioavailable: The ability of a drug or other substance to be absorbed and used by the body. Orally bioavailable means that a drug or other substance that is taken by mouth can be absorbed and used by the body. [NIH] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biofilms: Films of bacteria or other microbial organisms, usually embedded in extracellular polymers such as implanted medical devices, which adhere to surfaces submerged in, or subjected to, aquatic environments (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed). Biofilms consist of multilayers of microbial cells glued together to form microbial communities which are highly resistant to both phagocytes and antibiotics. [NIH] Biogenesis: The origin of life. It includes studies of the potential basis for life in organic compounds but excludes studies of the development of altered forms of life through mutation and natural selection, which is evolution. [NIH] Biological response modifier: BRM. A substance that stimulates the body's response to infection and disease. [NIH] Biomolecular: A scientific field at the interface between advanced computing and biotechnology. [NIH]

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Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body. [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] Biotype: A group of individuals having the same genotype. [NIH] Bladder: The organ that stores urine. [NIH] Blastocyst: The mammalian embryo in the post-morula stage in which a fluid-filled cavity, enclosed primarily by trophoblast, contains an inner cell mass which becomes the embryonic disc. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Blot: To transfer DNA, RNA, or proteins to an immobilizing matrix such as nitrocellulose. [NIH]

Body Fluids: Liquid components of living organisms. [NIH] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bone Marrow Transplantation: The transference of bone marrow from one human or animal to another. [NIH] 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] Broad-spectrum: Effective against a wide range of microorganisms; said of an antibiotic. [EU] Bronchi: The larger air passages of the lungs arising from the terminal bifurcation of the trachea. [NIH]

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Bronchial: Pertaining to one or more bronchi. [EU] 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] Bronchoconstriction: Diminution of the caliber of a bronchus physiologically or as a result of pharmacological intervention. [NIH] Bronchodilator: A drug that relaxes the smooth muscles in the constricted airway. [NIH] Bypass: A surgical procedure in which the doctor creates a new pathway for the flow of body fluids. [NIH] Calcification: Deposits of calcium in the tissues of the breast. Calcification in the breast can be seen on a mammogram, but cannot be detected by touch. There are two types of breast calcification, macrocalcification and microcalcification. Macrocalcifications are large deposits and are usually not related to cancer. Microcalcifications are specks of calcium that may be found in an area of rapidly dividing cells. Many microcalcifications clustered together may be a sign of cancer. [NIH] Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. [NIH] Calcium Carbonate: Carbonic acid calcium salt (CaCO3). An odorless, tasteless powder or crystal that occurs in nature. It is used therapeutically as a phosphate buffer in hemodialysis patients and as a calcium supplement. [NIH] Calcium Hydroxide: Ca(OH)2. A white powder that has many therapeutic uses. Because of its ability to stimulate mineralization, it is found in many dental formulations. [NIH] Calcium Oxalate: The calcium salt of oxalic acid, occurring in the urine as crystals and in certain calculi. [NIH] Calculi: An abnormal concretion occurring mostly in the urinary and biliary tracts, usually composed of mineral salts. Also called stones. [NIH] Cancer vaccine: A vaccine designed to prevent or treat cancer. [NIH] Candidiasis: Infection with a fungus of the genus Candida. It is usually a superficial infection of the moist cutaneous areas of the body, and is generally caused by C. albicans; it most commonly involves the skin (dermatocandidiasis), oral mucous membranes (thrush, def. 1), respiratory tract (bronchocandidiasis), and vagina (vaginitis). Rarely there is a systemic infection or endocarditis. Called also moniliasis, candidosis, oidiomycosis, and formerly blastodendriosis. [EU] Candidosis: An infection caused by an opportunistic yeasts that tends to proliferate and become pathologic when the environment is favorable and the host resistance is weakened. [NIH]

Capillary: Any one of the minute vessels that connect the arterioles and venules, forming a network in nearly all parts of the body. Their walls act as semipermeable membranes for the interchange of various substances, including fluids, between the blood and tissue fluid;

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called also vas capillare. [EU] Capillary Fragility: The lack of resistance, or susceptibility, of capillaries to damage or disruption under conditions of increased stress. [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] Carboxy: Cannabinoid. [NIH] Carboxylic Acids: Organic compounds containing the carboxy group (-COOH). This group of compounds includes amino acids and fatty acids. Carboxylic acids can be saturated, unsaturated, or aromatic. [NIH] Carcinogen: Any substance that causes cancer. [NIH] Carcinogenic: Producing carcinoma. [EU] Carcinoma: Cancer that begins in the skin or in tissues that line or cover internal organs. [NIH]

Cardiac: Having to do with the heart. [NIH] Cardiovirus: A genus of the family Picornaviridae causing encephalitis and myocarditis in rodents. Encephalomyocarditis virus is the type species. [NIH] Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes. [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] Catalyse: To speed up a chemical reaction. [EU] Catalytic Domain: The region of an enzyme that interacts with its substrate to cause the enzymatic reaction. [NIH] Catechin: Extracted from Uncaria gambier, Acacia catechu and other plants; it stabilizes collagen and is therefore used in tanning and dyeing; it prevents capillary fragility and abnormal permeability, but was formerly used as an antidiarrheal. [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] Caudate Nucleus: Elongated gray mass of the neostriatum located adjacent to the lateral ventricle of the brain. [NIH] Causal: Pertaining to a cause; directed against a cause. [EU] Cause of Death: Factors which produce cessation of all vital bodily functions. They can be analyzed from an epidemiologic viewpoint. [NIH] Cecum: The beginning of the large intestine. The cecum is connected to the lower part of the small intestine, called the ileum. [NIH]

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Cefotaxime: Semisynthetic broad-spectrum cephalosporin. [NIH] Ceftriaxone: Broad-spectrum cephalosporin antibiotic with a very long half-life and high penetrability to usually inaccessible infections, including those involving the meninges, eyes, inner ears, and urinary tract. [NIH] Cefuroxime: Broad-spectrum cephalosporin antibiotic resistant to beta-lactamase. It has been proposed for infections with gram-negative and gram-positive organisms, gonorrhea, and haemophilus. [NIH] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Cell Adhesion: Adherence of cells to surfaces or to other cells. [NIH] Cell 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] 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] Cellobiose: A disaccharide consisting of two glucose units in beta (1-4) glycosidic linkage. Obtained from the partial hydrolysis of cellulose. [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]

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Cerebellar: Pertaining to the cerebellum. [EU] Cerebellar Diseases: Diseases that affect the structure or function of the cerebellum. Cardinal manifestations of cerebellar dysfunction include dysmetria, gait ataxia, and muscle hypotonia. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebral Cortex: The thin layer of gray matter on the surface of the cerebral hemisphere that develops from the telencephalon and folds into gyri. It reaches its highest development in man and is responsible for intellectual faculties and higher mental functions. [NIH] Cerebral Palsy: Refers to a motor disability caused by a brain dysfunction. [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] Cerebrum: The largest part of the brain. It is divided into two hemispheres, or halves, called the cerebral hemispheres. The cerebrum controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. [NIH] Cervical: Relating to the neck, or to the neck of any organ or structure. Cervical lymph nodes are located in the neck; cervical cancer refers to cancer of the uterine cervix, which is the lower, narrow end (the "neck") of the uterus. [NIH] Cervix: The lower, narrow end of the uterus that forms a canal between the uterus and vagina. [NIH] Cesarean Section: Extraction of the fetus by means of abdominal hysterotomy. [NIH] Character: In current usage, approximately equivalent to personality. The sum of the relatively fixed personality traits and habitual modes of response of an individual. [NIH] Chemotactic Factors: Chemical substances that attract or repel cells or organisms. The concept denotes especially those factors released as a result of tissue injury, invasion, or immunologic activity, that attract leukocytes, macrophages, or other cells to the site of infection or insult. [NIH] Chemotaxis: The movement of cells or organisms toward or away from a substance in response to its concentration gradient. [NIH] Chemotherapy: Treatment with anticancer drugs. [NIH] Chest Pain: Pressure, burning, or numbness in the chest. [NIH] Chest wall: The ribs and muscles, bones, and joints that make up the area of the body between the neck and the abdomen. [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] Chlorhexidine: Disinfectant and topical anti-infective agent used also as mouthwash to prevent oral plaque. [NIH] Chlorophyll: Porphyrin derivatives containing magnesium that act to convert light energy in photosynthetic organisms. [NIH] Cholecystitis: Inflammation of the gallbladder. [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

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unless quickly treated. [NIH] Cholera Toxin: The enterotoxin from Vibrio cholerae. It is a protein that consists of two major components, the heavy (H) or A peptide and the light (L) or B peptide or choleragenoid. The B peptide anchors the protein to intestinal epithelial cells, while the A peptide, enters the cytoplasm, and activates adenylate cyclase, and production of cAMP. Increased levels of cAMP are thought to modulate release of fluid and electrolytes from intestinal crypt cells. [NIH] Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. [NIH] Cholesterol Esters: Fatty acid esters of cholesterol which constitute about two-thirds of the cholesterol in the plasma. The accumulation of cholesterol esters in the arterial intima is a characteristic feature of atherosclerosis. [NIH] Choline: A basic constituent of lecithin that is found in many plants and animal organs. It is important as a precursor of acetylcholine, as a methyl donor in various metabolic processes, and in lipid metabolism. [NIH] Chorea: Involuntary, forcible, rapid, jerky movements that may be subtle or become confluent, markedly altering normal patterns of movement. Hypotonia and pendular reflexes are often associated. Conditions which feature recurrent or persistent episodes of chorea as a primary manifestation of disease are referred to as choreatic disorders. Chorea is also a frequent manifestation of basal ganglia diseases. [NIH] Chorion: The outermost extraembryonic membrane. [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 Fatigue Syndrome: Fatigue caused by the combined effects of different types of prolonged fatigue. [NIH] Chronic renal: Slow and progressive loss of kidney function over several years, often resulting in end-stage renal disease. People with end-stage renal disease need dialysis or transplantation to replace the work of the kidneys. [NIH] Chylomicrons: A class of lipoproteins that carry dietary cholesterol and triglycerides from the small intestines to the tissues. [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] 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] Cirrhosis: A type of chronic, progressive liver disease. [NIH] Clarithromycin: A semisynthetic macrolide antibiotic derived from erythromycin that is active against a variety of microorganisms. It can inhibit protein synthesis in bacteria by reversibly binding to the 50S ribosomal subunits. This inhibits the translocation of aminoacyl transfer-RNA and prevents peptide chain elongation. [NIH]

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Clear cell carcinoma: A rare type of tumor of the female genital tract in which the inside of the cells looks clear when viewed under a microscope. [NIH] Cleave: A double-stranded cut in DNA with a restriction endonuclease. [NIH] Clindamycin: An antibacterial agent that is a semisynthetic analog of lincomycin. [NIH] Clinical Medicine: The study and practice of medicine by direct examination of the patient. [NIH]

Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] Clone: The term "clone" has acquired a new meaning. It is applied specifically to the bits of inserted foreign DNA in the hybrid molecules of the population. Each inserted segment originally resided in the DNA of a complex genome amid millions of other DNA segment. [NIH]

Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH] Clostridium: A genus of motile or nonmotile gram-positive bacteria of the family Bacillaceae. Many species have been identified with some being pathogenic. They occur in water, soil, and in the intestinal tract of humans and lower animals. [NIH] Clostridium difficile: A common inhabitant of the colon flora in human infants and sometimes in adults. It produces a toxin that causes pseudomembranous enterocolitis in patients receiving antibiotic therapy. [NIH] 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] Cochlea: The part of the internal ear that is concerned with hearing. It forms the anterior part of the labyrinth, is conical, and is placed almost horizontally anterior to the vestibule. [NIH]

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] Colitis: Inflammation of the colon. [NIH] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline, hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [NIH] Collagenases: Enzymes that catalyze the degradation of collagen by acting on the peptide bonds. EC 3.4.24.-. [NIH]

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Collagenous Colitis: A type of colitis. Caused by an abnormal band of collagen, a threadlike protein. [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] Colon Polyps: Small, fleshy, mushroom-shaped growths in the colon. [NIH] Colonic flora: The bacteria normally residing within the colon. [EU] Combination Therapy: Association of 3 drugs to treat AIDS (AZT + DDC or DDI + protease inhibitor). [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] Common Bile Duct: The largest biliary duct. It is formed by the junction of the cystic duct and the hepatic duct. [NIH] Communication Disorders: Disorders of verbal and nonverbal communication caused by receptive or expressive language disorders, cognitive dysfunction (e.g., mental retardation), psychiatric conditions, and hearing disorders. [NIH] Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complement Activation: The sequential activation of serum components C1 through C9, initiated by an erythrocyte-antibody complex or by microbial polysaccharides and properdin, and producing an inflammatory response. [NIH] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH]

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Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complete remission: The disappearance of all signs of cancer. Also called a complete response. [NIH] Compulsions: In psychology, an irresistible urge, sometimes amounting to obsession to perform a particular act which usually is carried out against the performer's will or better judgment. [NIH] Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Conception: The onset of pregnancy, marked by implantation of the blastocyst; the formation of a viable zygote. [EU] Concomitant: Accompanying; accessory; joined with another. [EU] Cone: One of the special retinal receptor elements which are presumed to be primarily concerned with perception of light and color stimuli when the eye is adapted to light. [NIH] Congestion: Excessive or abnormal accumulation of blood in a part. [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 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] Consciousness: Sense of awareness of self and of the environment. [NIH] Constipation: Infrequent or difficult evacuation of feces. [NIH] Constriction: The act of constricting. [NIH] Consumption: Pulmonary tuberculosis. [NIH]

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Contamination: The soiling or pollution by inferior material, as by the introduction of organisms into a wound, or sewage into a stream. [EU] Contractility: Capacity for becoming short in response to a suitable stimulus. [EU] Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] Control group: In a clinical trial, the group that does not receive the new treatment being studied. This group is compared to the group that receives the new treatment, to see if the new treatment works. [NIH] Controlled study: An experiment or clinical trial that includes a comparison (control) group. [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] Corpus: The body of the uterus. [NIH] Corpus Striatum: Striped gray and white matter consisting of the neostriatum and paleostriatum (globus pallidus). It is located in front of and lateral to the thalamus in each cerebral hemisphere. The gray substance is made up of the caudate nucleus and the lentiform nucleus (the latter consisting of the globus pallidus and putamen). The white matter is the internal capsule. [NIH] Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [EU] Cortical: Pertaining to or of the nature of a cortex or bark. [EU] 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] Cortisone: A natural steroid hormone produced in the adrenal gland. It can also be made in the laboratory. Cortisone reduces swelling and can suppress immune responses. [NIH] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU] Craniocerebral Trauma: Traumatic injuries involving the cranium and intracranial structures (i.e., brain; cranial nerves; meninges; and other structures). Injuries may be classified by whether or not the skull is penetrated (i.e., penetrating vs. nonpenetrating) or whether there is an associated hemorrhage. [NIH] Crossing-over: The exchange of corresponding segments between chromatids of homologous chromosomes during meiosia, forming a chiasma. [NIH] Cryptosporidiosis: Parasitic intestinal infection with severe diarrhea caused by a protozoan, Cryptosporidium. It occurs in both animals and humans. [NIH] 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

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solidified with an agent such as agar or gelatin. [NIH] Cultured cells: Animal or human cells that are grown in the laboratory. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Cutaneous: Having to do with the skin. [NIH] Cyclic: Pertaining to or occurring in a cycle or cycles; the term is applied to chemical compounds that contain a ring of atoms in the nucleus. [EU] Cyclosporins: A group of closely related cyclic undecapeptides from the fungi Trichoderma polysporum and Cylindocarpon lucidum. They have some antineoplastic and antifungal action and significant immunosuppressive effects. Cyclosporins have been proposed as adjuvants in tissue and organ transplantation to suppress graft rejection. [NIH] Cystic Duct: The tube that carries bile from the gallbladder into the common bile duct and the small intestine. [NIH] Cytochrome: Any electron transfer hemoprotein having a mode of action in which the transfer of a single electron is effected by a reversible valence change of the central iron atom of the heme prosthetic group between the +2 and +3 oxidation states; classified as cytochromes a in which the heme contains a formyl side chain, cytochromes b, which contain protoheme or a closely similar heme that is not covalently bound to the protein, cytochromes c in which protoheme or other heme is covalently bound to the protein, and cytochromes d in which the iron-tetrapyrrole has fewer conjugated double bonds than the hemes have. Well-known cytochromes have been numbered consecutively within groups and are designated by subscripts (beginning with no subscript), e.g. cytochromes c, c1, C2, . New cytochromes are named according to the wavelength in nanometres of the absorption maximum of the a-band of the iron (II) form in pyridine, e.g., c-555. [EU] Cytochrome b: Cytochromes (electron-transporting proteins) with protoheme or a related heme as the prosthetic group. The prosthetic group is not covalently bound to the protein moiety. [NIH] Cytokine: Small but highly potent protein that modulates the activity of many cell types, including T and B cells. [NIH] Cytomegalovirus: A genus of the family Herpesviridae, subfamily Betaherpesvirinae, infecting the salivary glands, liver, spleen, lungs, eyes, and other organs, in which they produce characteristically enlarged cells with intranuclear inclusions. Infection with Cytomegalovirus is also seen as an opportunistic infection in AIDS. [NIH] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a continuous aqueous solution (cytosol) and the organelles and inclusions suspended in it (phaneroplasm), and is the site of most of the chemical activities of the cell. [EU] Cytoskeleton: The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm. [NIH] Cytotoxic: Cell-killing. [NIH] Cytotoxicity: Quality of being capable of producing a specific toxic action upon cells of special organs. [NIH] Dairy Products: Raw and processed or manufactured milk and milk-derived products. These are usually from cows (bovine) but are also from goats, sheep, reindeer, and water buffalo. [NIH] Decidua: The epithelial lining of the endometrium that is formed before the fertilized ovum reaches the uterus. The fertilized ovum embeds in the decidua. If the ovum is not fertilized, the decidua is shed during menstruation. [NIH]

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Defense Mechanisms: Unconscious process used by an individual or a group of individuals in order to cope with impulses, feelings or ideas which are not acceptable at their conscious level; various types include reaction formation, projection and self reversal. [NIH] Defensins: Family of antimicrobial peptides that have been identified in humans, animals, and plants. They are thought to play a role in host defenses against infections, inflammation, wound repair, and acquired immunity. Based on the disulfide pairing of their characteristic six cysteine residues, they are divided into alpha-defensins and beta-defensins. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Dehydration: The condition that results from excessive loss of body water. [NIH] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Delivery of Health Care: The concept concerned with all aspects of providing and distributing health services to a patient population. [NIH] 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 Plaque: A film that attaches to teeth, often causing dental caries and gingivitis. It is composed of mucins, secreted from salivary glands, and microorganisms. [NIH] Dentists: Individuals licensed to practice dentistry. [NIH] 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] 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]

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] DES: Diethylstilbestrol. A synthetic hormone that was prescribed from the early 1940s until 1971 to help women with complications of pregnancy. DES has been linked to an increased

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risk of clear cell carcinoma of the vagina in daughters of women who used DES. DES may also increase the risk of breast cancer in women who used DES. [NIH] Deuterium: Deuterium. The stable isotope of hydrogen. It has one neutron and one proton in the nucleus. [NIH] Developed Countries: Countries that have reached a level of economic achievement through an increase of production, per capita income and consumption, and utilization of natural and human resources. [NIH] Developing Countries: Countries in the process of change directed toward economic growth, that is, an increase in production, per capita consumption, and income. The process of economic growth involves better utilization of natural and human resources, which results in a change in the social, political, and economic structures. [NIH] Dexamethasone: (11 beta,16 alpha)-9-Fluoro-11,17,21-trihydroxy-16-methylpregna-1,4diene-3,20-dione. An anti-inflammatory glucocorticoid used either in the free alcohol or esterified form in treatment of conditions that respond generally to cortisone. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Diaper Rash: A type of irritant dermatitis localized to the area in contact with a diaper and occurring most often as a reaction to prolonged contact with urine, feces, or retained soap or detergent. [NIH] Diaphragm: The musculofibrous partition that separates the thoracic cavity from the abdominal cavity. Contraction of the diaphragm increases the volume of the thoracic cavity aiding inspiration. [NIH] Diarrhea: Passage of excessively liquid or excessively frequent stools. [NIH] Diastolic: Of or pertaining to the diastole. [EU] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Dihydrotestosterone: Anabolic agent. [NIH] Dilatation: The act of dilating. [NIH] Dimerization: The process by which two molecules of the same chemical composition form a condensation product or polymer. [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] 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] Discrete: Made up of separate parts or characterized by lesions which do not become blended; not running together; separate. [NIH] Disease Progression: The worsening of a disease over time. This concept is most often used for chronic and incurable diseases where the stage of the disease is an important determinant of therapy and prognosis. [NIH] Dispenser: Glass, metal or plastic shell fitted with valve from which a pressurized formulation is dispensed; an instrument for atomizing. [NIH] 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

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molecule into two or more fragments (atoms, molecules, ions, or free radicals) produced by the absorption of light or thermal energy or by solvation. 3. In psychology, a defense mechanism in which a group of mental processes are segregated from the rest of a person's mental activity in order to avoid emotional distress, as in the dissociative disorders (q.v.), or in which an idea or object is segregated from its emotional significance; in the first sense it is roughly equivalent to splitting, in the second, to isolation. 4. A defect of mental integration in which one or more groups of mental processes become separated off from normal consciousness and, thus separated, function as a unitary whole. [EU] Dissociative Disorders: Sudden temporary alterations in the normally integrative functions of consciousness. [NIH] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU] Distention: The state of being distended or enlarged; the act of distending. [EU] Dose-dependent: Refers to the effects of treatment with a drug. If the effects change when the dose of the drug is changed, the effects are said to be dose dependent. [NIH] 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] Drive: A state of internal activity of an organism that is a necessary condition before a given stimulus will elicit a class of responses; e.g., a certain level of hunger (drive) must be present before food will elicit an eating response. [NIH] Dross: Residue remaining in an opium pipe which has been smoked; contains 50 % of the morphine present in the original drug. [NIH] Drug Design: The molecular designing of drugs for specific purposes (such as DNAbinding, enzyme inhibition, anti-cancer efficacy, etc.) based on knowledge of molecular properties such as activity of functional groups, molecular geometry, and electronic structure, and also on information cataloged on analogous molecules. Drug design is generally computer-assisted molecular modeling and does not include pharmacokinetics, dosage analysis, or drug administration analysis. [NIH] Drug Tolerance: Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from drug resistance wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from maximum tolerated dose and no-observed-adverse-effect level. [NIH] Duct: A tube through which body fluids pass. [NIH] Duodenum: The first part of the small intestine. [NIH] Dura mater: The outermost, toughest, and most fibrous of the three membranes (meninges) covering the brain and spinal cord; called also pachymeninx. [EU] Dysplasia: Cells that look abnormal under a microscope but are not cancer. [NIH] Dystrophy: Any disorder arising from defective or faulty nutrition, especially the muscular dystrophies. [EU] Eardrum: A thin, tense membrane forming the greater part of the outer wall of the tympanic cavity and separating it from the external auditory meatus; it constitutes the boundary between the external and middle ear. [NIH] Ecosystem: A dynamic complex of plant, animal and micro-organism communities and their non-living environment interacting as a functional unit. [NIH]

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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] Ego: The conscious portion of the personality structure which serves to mediate between the demands of the primitive instinctual drives, (the id), of internalized parental and social prohibitions or the conscience, (the superego), and of reality. [NIH] Eicosanoids: A class of oxygenated, endogenous, unsaturated fatty acids derived from arachidonic acid. They include prostaglandins, leukotrienes, thromboxanes, and hydroxyeicosatetraenoic acid compounds (HETE). They are hormone-like substances that act near the site of synthesis without altering functions throughout the body. [NIH] Ejaculation: The release of semen through the penis during orgasm. [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] Electrode: Component of the pacing system which is at the distal end of the lead. It is the interface with living cardiac tissue across which the stimulus is transmitted. [NIH] Electrolytes: Substances that break up into ions (electrically charged particles) when they are dissolved in body fluids or water. Some examples are sodium, potassium, chloride, and calcium. Electrolytes are primarily responsible for the movement of nutrients into cells, and the movement of wastes out of cells. [NIH] 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] 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]

Emboli: Bit of foreign matter which enters the blood stream at one point and is carried until it is lodged or impacted in an artery and obstructs it. It may be a blood clot, an air bubble, fat or other tissue, or clumps of bacteria. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Emollient: Softening or soothing; called also malactic. [EU] Empiric: Empirical; depending upon experience or observation alone, without using scientific method or theory. [EU] 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

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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]

Encephalocele: Cerebral tissue herniation through a congenital or acquired defect in the skull. The majority of congenital encephaloceles occur in the occipital or frontal regions. Clinical features include a protuberant mass that may be pulsatile. The quantity and location of protruding neural tissue determines the type and degree of neurologic deficit. Visual defects, psychomotor developmental delay, and persistent motor deficits frequently occur. [NIH]

Encephalomyelitis: A general term indicating inflammation of the brain and spinal cord, often used to indicate an infectious process, but also applicable to a variety of autoimmune and toxic-metabolic conditions. There is significant overlap regarding the usage of this term and encephalitis in the literature. [NIH] Encephalomyocarditis Virus: The type species of cardiovirus causing encephalomyelitis and myocarditis in rodents, pigs, and monkeys. Infection in man has been reported with CNS involvement but without myocarditis. [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] Endometrium: The layer of tissue that lines the uterus. [NIH] Endopeptidases: A subclass of peptide hydrolases. They are classified primarily by their catalytic mechanism. Specificity is used only for identification of individual enzymes. They comprise the serine endopeptidases, EC 3.4.21; cysteine endopeptidases, EC 3.4.22; aspartic endopeptidases, EC 3.4.23, metalloendopeptidases, EC 3.4.24; and a group of enzymes yet to be assigned to any of the above sub-classes, EC 3.4.99. EC 3.4.-. [NIH] Endophthalmitis: Suppurative inflammation of the tissues of the internal structures of the eye; not all layers of the uvea are affected. Fungi, necrosis of intraocular tumors, and retained intraocular foreign bodies often cause a purulent endophthalmitis. [NIH] Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart. [NIH] Endothelium: A layer of epithelium that lines the heart, blood vessels (endothelium, vascular), lymph vessels (endothelium, lymphatic), and the serous cavities of the body. [NIH] Endothelium, Lymphatic: Unbroken cellular lining (intima) of the lymph vessels (e.g., the high endothelial lymphatic venules). It is more permeable than vascular endothelium, lacking selective absorption and functioning mainly to remove plasma proteins that have filtered through the capillaries into the tissue spaces. [NIH] Endothelium, Vascular: Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components

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from interstitium to lumen; this function has been most intensively studied in the blood capillaries. [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 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] 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 Induction: An increase in the rate of synthesis of an enzyme due to the presence of an inducer which acts to derepress the gene responsible for enzyme synthesis. [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] Enzyme Repression: The interference in synthesis of an enzyme due to the elevated level of an effector substance, usually a metabolite, whose presence would cause depression of the gene responsible for enzyme synthesis. [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] 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]

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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] Epinephrine: The active sympathomimetic hormone from the adrenal medulla in most species. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. It is used in asthma and cardiac failure and to delay absorption of local anesthetics. [NIH] Epistaxis: Bleeding from the nose. [NIH] Epithelial: Refers to the cells that line the internal and external surfaces of the body. [NIH] Epithelial Cells: Cells that line the inner and outer surfaces of the body. [NIH] Epithelium: One or more layers of epithelial cells, supported by the basal lamina, which covers the inner or outer surfaces of the body. [NIH] Epitope: A molecule or portion of a molecule capable of binding to the combining site of an antibody. For every given antigenic determinant, the body can construct a variety of antibody-combining sites, some of which fit almost perfectly, and others which barely fit. [NIH]

ERV: The expiratory reserve volume is the largest volume of gas that can be expired from the end-expiratory level. [NIH] Erysipelas: An acute infection of the skin caused by species of streptococcus. This disease most frequently affects infants, young children, and the elderly. Characteristics include pink-to-red lesions that spread rapidly and are warm to the touch. The commonest site of involvement is the face. [NIH] Erythema: Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of causes. [NIH] Erythema Nodosum: An erythematous eruption commonly associated with drug reactions or infection and characterized by inflammatory nodules that are usually tender, multiple, and bilateral. These nodules are located predominantly on the shins with less common occurrence on the thighs and forearms. They undergo characteristic color changes ending in temporary bruise-like areas. This condition usually subsides in 3-6 weeks without scarring or atrophy. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Erythromycin: A bacteriostatic antibiotic substance produced by Streptomyces erythreus. Erythromycin A is considered its major active component. In sensitive organisms, it inhibits protein synthesis by binding to 50S ribosomal subunits. This binding process inhibits peptidyl transferase activity and interferes with translocation of amino acids during translation and assembly of proteins. [NIH] Essential Tremor: A rhythmic, involuntary, purposeless, oscillating movement resulting from the alternate contraction and relaxation of opposing groups of muscles. [NIH] Estrogen: One of the two female sex hormones. [NIH] Ethanol: A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in alcoholic beverages. [NIH] Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH]

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Eustachian tube: The middle ear cavity is in communication with the back of the nose through the Eustachian tube, which is normally closed, but opens on swallowing, in order to maintain equal air pressure. [NIH] Evacuation: An emptying, as of the bowels. [EU] Evoke: The electric response recorded from the cerebral cortex after stimulation of a peripheral sense organ. [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] Excitation: An act of irritation or stimulation or of responding to a stimulus; the addition of energy, as the excitation of a molecule by absorption of photons. [EU] Excitatory: When cortical neurons are excited, their output increases and each new input they receive while they are still excited raises their output markedly. [NIH] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Exotoxin: Toxic substance excreted by living bacterial cells. [NIH] 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 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] Extraction: The process or act of pulling or drawing out. [EU] Exudate: Material, such as fluid, cells, or cellular debris, which has escaped from blood vessels and has been deposited in tissues or on tissue surfaces, usually as a result of inflammation. An exudate, in contrast to a transudate, is characterized by a high content of protein, cells, or solid materials derived from cells. [EU] Fallopian tube: The oviduct, a muscular tube about 10 cm long, lying in the upper border of the broad ligament. [NIH] Familial polyposis: An inherited condition in which numerous polyps (tissue masses) develop on the inside walls of the colon and rectum. It increases the risk for colon cancer. [NIH]

Family Planning: Programs or services designed to assist the family in controlling

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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] Fathers: Male parents, human or animal. [NIH] Fatigue: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. [NIH]

Fatty acids: A major component of fats that are used by the body for energy and tissue development. [NIH] Feces: The excrement discharged from the intestines, consisting of bacteria, cells exfoliated from the intestines, secretions, chiefly of the liver, and a small amount of food residue. [EU] Fermentation: An enzyme-induced chemical change in organic compounds that takes place in the absence of oxygen. The change usually results in the production of ethanol or lactic acid, and the production of energy. [NIH] Ferrichrome: A cyclic peptide consisting of three residues of delta-N-hydroxy-delta-Nacetylornithine. It acts as an iron transport agent in Ustilago sphaerogena. [NIH] Fetal Blood: Blood of the fetus. Exchange of nutrients and waste between the fetal and maternal blood occurs via the placenta. The cord blood is blood contained in the umbilical vessels at the time of delivery. [NIH] Fetal Development: Morphologic and physiologic growth and development of the mammalian embryo or fetus. [NIH] Fetal Membranes: Thin layers of tissue which surround the embryo or fetus and provide for its nutrition, respiration, excretion and protection; they are the yolk sac, allantois, amnion, and chorion. [NIH] Fetal Monitoring: Physiologic or biochemical monitoring of the fetus. It is usually done during labor and may be performed in conjunction with the monitoring of uterine activity. It may also be performed prenatally as when the mother is undergoing surgery. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fibrin: A protein derived from fibrinogen in the presence of thrombin, which forms part of the blood clot. [NIH] 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]

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Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [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] Filtration: The passage of a liquid through a filter, accomplished by gravity, pressure, or vacuum (suction). [EU] Fistula: Abnormal communication most commonly seen between two internal organs, or between an internal organ and the surface of the body. [NIH] 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] Fluoridation: The addition of fluorine usually as a fluoride to something, as the adding of a fluoride to drinking water or public water supplies for prevention of tooth decay in children. [NIH] Fluorine: A nonmetallic, diatomic gas that is a trace element and member of the halogen family. It is used in dentistry as flouride to prevent dental caries. [NIH] Folate: A B-complex vitamin that is being studied as a cancer prevention agent. Also called folic acid. [NIH] Fold: A plication or doubling of various parts of the body. [NIH] Folic Acid: N-(4-(((2-Amino-1,4-dihydro-4-oxo-6-pteridinyl)methyl)amino)benzoyl)-Lglutamic acid. A member of the vitamin B family that stimulates the hematopoietic system. It is present in the liver and kidney and is found in mushrooms, spinach, yeast, green leaves, and grasses. Folic acid is used in the treatment and prevention of folate deficiencies and megaloblastic anemia. [NIH] Forearm: The part between the elbow and the wrist. [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

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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] Free Radicals: Highly reactive molecules with an unsatisfied electron valence pair. Free radicals are produced in both normal and pathological processes. They are proven or suspected agents of tissue damage in a wide variety of circumstances including radiation, damage from environment chemicals, and aging. Natural and pharmacological prevention of free radical damage is being actively investigated. [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] Functional Disorders: Disorders such as irritable bowel syndrome. These conditions result from poor nerve and muscle function. Symptoms such as gas, pain, constipation, and diarrhea come back again and again, but there are no signs of disease or damage. Emotional stress can trigger symptoms. Also called motility disorders. [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] Galactosidases: A family of galactoside hydrolases that hydrolyze compounds with an Ogalactosyl linkage. EC 3.2.1.-. [NIH] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Gallstones: The solid masses or stones made of cholesterol or bilirubin that form in the gallbladder or bile ducts. [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] Gastric: Having to do with the stomach. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]

Gastritis: Inflammation of the stomach. [EU] Gastroenteritis: An acute inflammation of the lining of the stomach and intestines,

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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] Gelatin: A product formed from skin, white connective tissue, or bone collagen. It is used as a protein food adjuvant, plasma substitute, hemostatic, suspending agent in pharmaceutical preparations, and in the manufacturing of capsules and suppositories. [NIH] Gelatinase A: A secreted endopeptidase homologous with interstitial collagenase, but which possesses an additional fibronectin-like domain. EC 3.4.24.24. [NIH] Gels: Colloids with a solid continuous phase and liquid as the dispersed phase; gels may be unstable when, due to temperature or other cause, the solid phase liquifies; the resulting colloid is called a sol. [NIH] Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]

Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Gene Fusion: Fusion of structural genes to analyze protein behavior or fusion of regulatory sequences with structural genes to determine mechanisms of regulation. [NIH] Gene Library: A large collection of cloned DNA fragments from a given organism, tissue, organ, or cell type. It may contain complete genomic sequences (genomic library) or complementary DNA sequences, the latter being formed from messenger RNA and lacking intron sequences. [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] Genetics, Microbial: A branch of genetics which deals with the genetic mechanisms and processes of microorganisms. [NIH] Genital: Pertaining to the genitalia. [EU] Genitourinary: Pertaining to the genital and urinary organs; urogenital; urinosexual. [EU] Genomic Library: A form of gene library containing the complete DNA sequences present in the genome of a given organism. It contrasts with a cDNA library which contains only sequences utilized in protein coding (lacking introns). [NIH] Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Germ Cells: The reproductive cells in multicellular organisms. [NIH] Germ-free: Free of bacteria, disease-causing viruses, and other organisms that can cause

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infection. [NIH] Germinal Center: The activated center of a lymphoid follicle in secondary lymphoid tissue where B-lymphocytes are stimulated by antigens and helper T cells (T-lymphocytes, helperinducer) are stimulated to generate memory cells. [NIH] Gestation: The period of development of the young in viviparous animals, from the time of fertilization of the ovum until birth. [EU] Giardiasis: An infection of the small intestine caused by the flagellated protozoan Giardia lamblia. It is spread via contaminated food and water and by direct person-to-person contact. [NIH] Gingivitis: Inflammation of the gingivae. Gingivitis associated with bony changes is 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] Glomerulus: A tiny set of looping blood vessels in the nephron where blood is filtered in the kidney. [NIH] Glucans: Polysaccharides composed of repeating glucose units. They can consist of branched or unbranched chains in any linkages. [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] Glucosyltransferases: Enzymes that catalyze the transfer of glucose from a nucleoside diphosphate glucose to an acceptor molecule which is frequently another carbohydrate. EC 2.4.1.-. [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] Glucuronides: Glycosides of glucuronic acid formed by the reaction of uridine diphosphate glucuronic acid with certain endogenous and exogenous substances. Their formation is important for the detoxification of drugs, steroid excretion and bilirubin metabolism to a more water-soluble compound that can be eliminated in the urine and bile. [NIH] Glutamate: Excitatory neurotransmitter of the brain. [NIH] Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid (glutamate) is the most common excitatory neurotransmitter in the central nervous system. [NIH]

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Glutathione Peroxidase: An enzyme catalyzing the oxidation of 2 moles of glutathione in the presence of hydrogen peroxide to yield oxidized glutathione and water. EC 1.11.1.9. [NIH]

Glycerol: A trihydroxy sugar alcohol that is an intermediate in carbohydrate and lipid metabolism. It is used as a solvent, emollient, pharmaceutical agent, and sweetening agent. [NIH]

Glycerophospholipids: Derivatives of phosphatidic acid in which the hydrophobic regions are composed of two fatty acids and a polar alcohol is joined to the C-3 position of glycerol through a phosphodiester bond. They are named according to their polar head groups, such as phosphatidylcholine and phosphatidylethanolamine. [NIH] Glycine: A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter. [NIH] Glycogen: A sugar stored in the liver and muscles. It releases glucose into the blood when cells need it for energy. Glycogen is the chief source of stored fuel in the body. [NIH] Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Glycosaminoglycan: A type of long, unbranched polysaccharide molecule. Glycosaminoglycans are major structural components of cartilage and are also found in the cornea of the eye. [NIH] Glycoside: Any compound that contains a carbohydrate molecule (sugar), particularly any such natural product in plants, convertible, by hydrolytic cleavage, into sugar and a nonsugar component (aglycone), and named specifically for the sugar contained, as glucoside (glucose), pentoside (pentose), fructoside (fructose) etc. [EU] Glycosidic: Formed by elimination of water between the anomeric hydroxyl of one sugar and a hydroxyl of another sugar molecule. [NIH] Glycosylation: The chemical or biochemical addition of carbohydrate or glycosyl groups to other chemicals, especially peptides or proteins. Glycosyl transferases are used in this biochemical reaction. [NIH] Glycylglycine: N-Glycylglycine. The simplest of all peptides. It functions as a gammaglutamyl acceptor. [NIH] Goats: Any of numerous agile, hollow-horned ruminants of the genus Capra, closely related to the sheep. [NIH] Gonadal: Pertaining to a gonad. [EU] Gonorrhea: Acute infectious disease characterized by primary invasion of the urogenital tract. The etiologic agent, Neisseria gonorrhoeae, was isolated by Neisser in 1879. [NIH] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to replace diseased or injured tissue removed from another part of the body. [NIH] Graft Rejection: An immune response with both cellular and humoral components, directed against an allogeneic transplant, whose tissue antigens are not compatible with those of the recipient. [NIH] 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-positive: Retaining the stain or resisting decolorization by alcohol in Gram's method

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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] Granulation Tissue: A vascular connective tissue formed on the surface of a healing wound, ulcer, or inflamed tissue. It consists of new capillaries and an infiltrate containing lymphoid cells, macrophages, and plasma cells. [NIH] Granulocyte: A type of white blood cell that fights bacterial infection. Neutrophils, eosinophils, and basophils are granulocytes. [NIH] Granulomatous Disease, Chronic: A recessive X-linked defect of leukocyte function in which phagocytic cells ingest but fail to digest bacteria, resulting in recurring bacterial infections with granuloma formation. [NIH] Grasses: A large family, Gramineae, of narrow-leaved herbaceous monocots. Many grasses produce highly allergenic pollens and are hosts to cattle parasites and toxic fungi. [NIH] Growth: The progressive development of a living being or part of an organism from its earliest stage to maturity. [NIH] Gyrase: An enzyme that causes negative supercoiling of E. coli DNA during replication. [NIH]

Habitual: Of the nature of a habit; according to habit; established by or repeated by force of habit, customary. [EU] 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] Half-Life: The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity. [NIH] Haploid: An organism with one basic chromosome set, symbolized by n; the normal condition of gametes in diploids. [NIH] Haptens: Small antigenic determinants capable of eliciting an immune response only when coupled to a carrier. Haptens bind to antibodies but by themselves cannot elicit an antibody response. [NIH] Headache: Pain in the cranial region that may occur as an isolated and benign symptom or as a manifestation of a wide variety of conditions including subarachnoid hemorrhage; craniocerebral trauma; central nervous system infections; intracranial hypertension; and other disorders. In general, recurrent headaches that are not associated with a primary disease process are referred to as headache disorders (e.g., migraine). [NIH] Headache Disorders: Common conditions characterized by persistent or recurrent headaches. Headache syndrome classification systems may be based on etiology (e.g., vascular headache, post-traumatic headaches, etc.), temporal pattern (e.g., cluster headache, paroxysmal hemicrania, etc.), and precipitating factors (e.g., cough headache). [NIH] Health Care Costs: The actual costs of providing services related to the delivery of health

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care, including the costs of procedures, therapies, and medications. It is differentiated from health expenditures, which refers to the amount of money paid for the services, and from fees, which refers to the amount charged, regardless of cost. [NIH] Health Expenditures: The amounts spent by individuals, groups, nations, or private or public organizations for total health care and/or its various components. These amounts may or may not be equivalent to the actual costs (health care costs) and may or may not be shared among the patient, insurers, and/or employers. [NIH] Hearing Disorders: Conditions that impair the transmission or perception of auditory impulses and information from the level of the ear to the temporal cortices, including the sensorineural pathways. [NIH] Helicobacter: A genus of gram-negative, spiral-shaped bacteria that is pathogenic and has been isolated from the intestinal tract of mammals, including humans. [NIH] Helicobacter pylori: A spiral bacterium active as a human gastric pathogen. It is a gramnegative, urease-positive, curved or slightly spiral organism initially isolated in 1982 from patients with lesions of gastritis or peptic ulcers in Western Australia. Helicobacter pylori was originally classified in the genus Campylobacter, but RNA sequencing, cellular fatty acid profiles, growth patterns, and other taxonomic characteristics indicate that the microorganism should be included in the genus Helicobacter. It has been officially transferred to Helicobacter gen. nov. (see Int J Syst Bacteriol 1989 Oct;39(4):297-405). [NIH] Hematogenous: Originating in the blood or spread through the bloodstream. [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 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] Hemoglobinuria: The presence of free hemoglobin in the urine. [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]

Hepatic: Refers to the liver. [NIH] Hepatitis: Inflammation of the liver and liver disease involving degenerative or necrotic alterations of hepatocytes. [NIH]

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Hepatitis, Chronic: A collective term for a clinical and pathological syndrome which has several causes and is characterized by varying degrees of hepatocellular necrosis and inflammation. Specific forms of chronic hepatitis include autoimmune hepatitis, chronic hepatitis B, chronic hepatitis C, chronic hepatitis D, indeterminate chronic viral hepatitis, cryptogenic chronic hepatitis, and drug-related chronic hepatitis. [NIH] Hepatocellular: Pertaining to or affecting liver cells. [EU] Hepatocytes: The main structural component of the liver. They are specialized epithelial cells that are organized into interconnected plates called lobules. [NIH] Hereditary: Of, relating to, or denoting factors that can be transmitted genetically from one generation to another. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Herpes: Any inflammatory skin disease caused by a herpesvirus and characterized by the formation of clusters of small vesicles. When used alone, the term may refer to herpes simplex or to herpes zoster. [EU] Herpes Zoster: Acute vesicular inflammation. [NIH] Heterodimers: Zippered pair of nonidentical proteins. [NIH] Heterogeneity: The property of one or more samples or populations which implies that they are not identical in respect of some or all of their parameters, e. g. heterogeneity of variance. [NIH]

Heterotrophic: Pertaining to organisms that are consumers and dependent on other organisms for their source of energy (food). [NIH] Histamine: 1H-Imidazole-4-ethanamine. A depressor amine derived by enzymatic decarboxylation of histidine. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter. [NIH] Histidine: An essential amino acid important in a number of metabolic processes. It is required for the production of histamine. [NIH] Histocompatibility: The degree of antigenic similarity between the tissues of different individuals, which determines the acceptance or rejection of allografts. [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] Hormonal: Pertaining to or of the nature of a hormone. [EU] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Horny layer: The superficial layer of the epidermis containing keratinized cells. [NIH] Host: Any animal that receives a transplanted graft. [NIH] Housekeeping: The care and management of property. [NIH] Humoral: Of, relating to, proceeding from, or involving a bodily humour - now often used of endocrine factors as opposed to neural or somatic. [EU] Humour: 1. A normal functioning fluid or semifluid of the body (as the blood, lymph or bile) especially of vertebrates. 2. A secretion that is itself an excitant of activity (as certain hormones). [EU]

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Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [NIH] Hybridization: The genetic process of crossbreeding to produce a hybrid. Hybrid nucleic acids can be formed by nucleic acid hybridization of DNA and RNA molecules. Protein hybridization allows for hybrid proteins to be formed from polypeptide chains. [NIH] Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H, atomic number 1, and atomic weight 1. It exists, under normal conditions, as a colorless, odorless, tasteless, diatomic gas. Hydrogen ions are protons. Besides the common H1 isotope, hydrogen exists as the stable isotope deuterium and the unstable, radioactive isotope tritium. [NIH] Hydrogen 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] Hydrolases: Any member of the class of enzymes that catalyze the cleavage of the substrate and the addition of water to the resulting molecules, e.g., esterases, glycosidases (glycoside hydrolases), lipases, nucleotidases, peptidases (peptide hydrolases), and phosphatases (phosphoric monoester hydrolases). EC 3. [NIH] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] 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] Hyperlipidemia: An excess of lipids in the blood. [NIH] Hyperreflexia: Exaggeration of reflexes. [EU] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hypotension: Abnormally low blood pressure. [NIH] Hypothermia: Lower than normal body temperature, especially in warm-blooded animals; in man usually accidental or unintentional. [NIH] Hypoxia: Reduction of oxygen supply to tissue below physiological levels despite adequate perfusion of the tissue by blood. [EU] Hypoxic: Having too little oxygen. [NIH] Hysterotomy: An incision in the uterus, performed through either the abdomen or the vagina. [NIH] Id: The part of the personality structure which harbors the unconscious instinctive desires and strivings of the individual. [NIH] Immune Complex Diseases: Group of diseases mediated by the deposition of large soluble complexes of antigen and antibody with resultant damage to tissue. Besides serum sickness

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and the arthus reaction, evidence supports a pathogenic role for immune complexes in many other systemic immunologic diseases including glomerulonephritis, systemic lupus erythematosus and polyarteritis nodosa. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]

Immune Sera: Serum that contains antibodies. It is obtained from an animal that has been immunized either by antigen injection or infection with microorganisms containing the antigen. [NIH] Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] Immunity: Nonsusceptibility to the invasive or pathogenic microorganisms or to the toxic effect of antigenic substances. [NIH]

effects

of

foreign

Immunization: Deliberate stimulation of the host's immune response. Active immunization involves administration of antigens or immunologic adjuvants. Passive immunization involves administration of immune sera or lymphocytes or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow). [NIH] Immunoassay: Immunochemical assay or detection of a substance by serologic or immunologic methods. Usually the substance being studied serves as antigen both in antibody production and in measurement of antibody by the test substance. [NIH] Immunocompromised: Having a weakened immune system caused by certain diseases or treatments. [NIH] Immunodeficiency: The decreased ability of the body to fight infection and disease. [NIH] Immunodiffusion: Technique involving the diffusion of antigen or antibody through a semisolid medium, usually agar or agarose gel, with the result being a precipitin reaction. [NIH]

Immunoelectrophoresis: A technique that combines protein electrophoresis and double immunodiffusion. In this procedure proteins are first separated by gel electrophoresis (usually agarose), then made visible by immunodiffusion of specific antibodies. A distinct elliptical precipitin arc results for each protein detectable by the antisera. [NIH] Immunogen: A substance that is capable of causing antibody formation. [NIH] Immunogenic: Producing immunity; evoking an immune response. [EU] Immunoglobulin: A protein that acts as an antibody. [NIH] Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents. [NIH] Immunologic: The ability of the antibody-forming system to recall a previous experience with an antigen and to respond to a second exposure with the prompt production of large amounts of antibody. [NIH] 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] Immunosuppressive: Describes the ability to lower immune system responses. [NIH] Immunosuppressive therapy: Therapy used to decrease the body's immune response, such as drugs given to prevent transplant rejection. [NIH] Immunotherapy: Manipulation of the host's immune system in treatment of disease. It includes both active and passive immunization as well as immunosuppressive therapy to

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prevent graft rejection. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] 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] Impotence: The inability to perform sexual intercourse. [NIH] In situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incision: A cut made in the body during surgery. [NIH] Incontinence: Inability to control the flow of urine from the bladder (urinary incontinence) or the escape of stool from the rectum (fecal incontinence). [NIH] Incubated: Grown in the laboratory under controlled conditions. (For instance, white blood cells can be grown in special conditions so that they attack specific cancer cells when returned to the body.) [NIH] Incubation: The development of an infectious disease from the entrance of the pathogen to the appearance of clinical symptoms. [EU] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU] Indomethacin: A non-steroidal anti-inflammatory agent (NSAID) that inhibits the enzyme cyclooxygenase necessary for the formation of prostaglandins and other autacoids. It also inhibits the motility of polymorphonuclear leukocytes. [NIH] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] Infant Mortality: Perinatal, neonatal, and infant deaths in a given population. [NIH] Infant, Newborn: An infant during the first month after birth. [NIH] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]

Infertility: The diminished or absent ability to conceive or produce an offspring while sterility is the complete inability to conceive or produce an offspring. [NIH]

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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] Inflammatory bowel disease: A general term that refers to the inflammation of the colon and rectum. Inflammatory bowel disease includes ulcerative colitis and Crohn's disease. [NIH]

Influenza: An acute viral infection involving the respiratory tract. It is marked by inflammation of the nasal mucosa, the pharynx, and conjunctiva, and by headache and severe, often generalized, myalgia. [NIH] Infuse: To pour (a liquid) into something. [EU] 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] Initiator: A chemically reactive substance which may cause cell changes if ingested, inhaled or absorbed into the body; the substance may thus initiate a carcinogenic process. [NIH] Inlay: In dentistry, a filling first made to correspond with the form of a dental cavity and then cemented into the cavity. [NIH] Inner ear: The labyrinth, comprising the vestibule, cochlea, and semicircular canals. [NIH] 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] Insertional: A technique in which foreign DNA is cloned into a restriction site which occupies a position within the coding sequence of a gene in the cloning vector molecule. Insertion interrupts the gene's sequence such that its original function is no longer expressed. [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] Insomnia: Difficulty in going to sleep or getting enough sleep. [NIH] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose. It is also an important regulator of protein and lipid metabolism. Insulin is used as a drug to control insulin-dependent diabetes mellitus. [NIH] Integrins: A family of transmembrane glycoproteins consisting of noncovalent heterodimers. They interact with a wide variety of ligands including extracellular matrix glycoproteins, complement, and other cells, while their intracellular domains interact with the cytoskeleton. The integrins consist of at least three identified families: the cytoadhesin receptors, the leukocyte adhesion receptors, and the very-late-antigen receptors. Each family contains a common beta-subunit combined with one or more distinct alpha-subunits. These receptors participate in cell-matrix and cell-cell adhesion in many physiologically important processes, including embryological development, hemostasis, thrombosis, wound healing, immune and nonimmune defense mechanisms, and oncogenic transformation. [NIH] Interferon: A biological response modifier (a substance that can improve the body's natural

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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] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Interstitial Collagenase: A member of the metalloproteinase family of enzymes that is principally responsible for cleaving fibrillar collagen. It can degrade interstitial collagens, types I, II and III. EC 3.4.24.7. [NIH] Intestinal: Having to do with the intestines. [NIH] Intestinal Flora: The bacteria, yeasts, and fungi that grow normally in the intestines. [NIH] Intestine: A long, tube-shaped organ in the abdomen that completes the process of digestion. There is both a large intestine and a small intestine. Also called the bowel. [NIH] Intracellular: Inside a cell. [NIH] Intracellular Membranes: Membranes of subcellular structures. [NIH] Intramuscular: IM. Within or into muscle. [NIH] Intramuscular injection: IM. Injection into a muscle. [NIH] Intraocular: Within the eye. [EU] Intravenous: IV. Into a vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Introns: Non-coding, intervening sequences of DNA that are transcribed, but are removed from within the primary gene transcript and rapidly degraded during maturation of messenger RNA. Most genes in the nuclei of eukaryotes contain introns, as do mitochondrial and chloroplast genes. [NIH] Introspection: Examination by a person of his own feelings, thoughts, and mental state. [NIH]

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]

Involuntary: Reaction occurring without intention or volition. [NIH] Iodine: A nonmetallic element of the halogen group that is represented by the atomic symbol I, atomic number 53, and atomic weight of 126.90. It is a nutritionally essential element, especially important in thyroid hormone synthesis. In solution, it has anti-infective properties and is used topically. [NIH] Ionizing: Radiation comprising charged particles, e. g. electrons, protons, alpha-particles, etc., having sufficient kinetic energy to produce ionization by collision. [NIH] Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as cations; those with a negative charge are anions. [NIH] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Islet: Cell producing insulin in pancreas. [NIH]

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Isotope Labeling: Techniques for labeling a substance with a stable or radioactive isotope. It is not used for articles involving labeled substances unless the methods of labeling are substantively discussed. Tracers that may be labeled include chemical substances, cells, or microorganisms. [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] 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] Keratin: A class of fibrous proteins or scleroproteins important both as structural proteins and as keys to the study of protein conformation. The family represents the principal constituent of epidermis, hair, nails, horny tissues, and the organic matrix of tooth enamel. Two major conformational groups have been characterized, alpha-keratin, whose peptide backbone forms an alpha-helix, and beta-keratin, whose backbone forms a zigzag or pleated sheet structure. [NIH] Keratinocytes: Epidermal cells which synthesize keratin and undergo characteristic changes as they move upward from the basal layers of the epidermis to the cornified (horny) layer of the skin. Successive stages of differentiation of the keratinocytes forming the epidermal layers are basal cell, spinous or prickle cell, and the granular cell. [NIH] Keratolytic: An agent that promotes keratolysis. [EU] Keto: It consists of 8 carbon atoms and within the endotoxins, it connects poysaccharide and lipid A. [NIH] Kidney Disease: Any one of several chronic conditions that are caused by damage to the cells of the kidney. People who have had diabetes for a long time may have kidney damage. Also called nephropathy. [NIH] Kidney stone: A stone that develops from crystals that form in urine and build up on the inner surfaces of the kidney, in the renal pelvis, or in the ureters. [NIH] Kinetic: Pertaining to or producing motion. [EU] Labile: 1. Gliding; moving from point to point over the surface; unstable; fluctuating. 2. Chemically unstable. [EU] Labyrinth: The internal ear; the essential part of the organ of hearing. It consists of an osseous and a membranous portion. [NIH] Laceration: 1. The act of tearing. 2. A torn, ragged, mangled wound. [EU] Lactobacillus: A genus of gram-positive, microaerophilic, rod-shaped bacteria occurring widely in nature. Its species are also part of the many normal flora of the mouth, intestinal tract, and vagina of many mammals, including humans. Pathogenicity from this genus is rare. [NIH] Lactobacillus acidophilus: A species of gram-positive, rod-shaped bacteria isolated from the intestinal tract of humans and animals, the human mouth, and vagina. This organism produces the fermented product, acidophilus milk. [NIH] 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]

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Language Disorders: Conditions characterized by deficiencies of comprehension or expression of written and spoken forms of language. These include acquired and developmental disorders. [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]

LCD: Low-calorie diet. Caloric restriction of about 800 to 1,500 calories (approximately 12 to 15 kcal/kg of body weight) per day. [NIH] Lectin: A complex molecule that has both protein and sugars. Lectins are able to bind to the outside of a cell and cause biochemical changes in it. Lectins are made by both animals and plants. [NIH] 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] Lethal: Deadly, fatal. [EU] Leukemia: Cancer of blood-forming tissue. [NIH] Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [NIH] Leukocytosis: A transient increase in the number of leukocytes in a body fluid. [NIH] Leukotrienes: A family of biologically active compounds derived from arachidonic acid by oxidative metabolism through the 5-lipoxygenase pathway. They participate in host defense reactions and pathophysiological conditions such as immediate hypersensitivity and inflammation. They have potent actions on many essential organs and systems, including the cardiovascular, pulmonary, and central nervous system as well as the gastrointestinal tract and the immune system. [NIH] Levofloxacin: A substance used to treat bacterial infections. It belongs to the family of drugs called quinolone antibiotics. [NIH] Library Services: Services offered to the library user. They include reference and circulation. [NIH]

Life cycle: The successive stages through which an organism passes from fertilized ovum or spore to the fertilized ovum or spore of the next generation. [NIH] Ligament: A band of fibrous tissue that connects bones or cartilages, serving to support and strengthen joints. [EU] Ligands: A RNA simulation method developed by the MIT. [NIH] 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

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electron acceptor. [NIH] Lipopolysaccharide: Substance consisting of polysaccaride and lipid. [NIH] Lipoprotein: Any of the lipid-protein complexes in which lipids are transported in the blood; lipoprotein particles consist of a spherical hydrophobic core of triglycerides or cholesterol esters surrounded by an amphipathic monolayer of phospholipids, cholesterol, and apolipoproteins; the four principal classes are high-density, low-density, and very-lowdensity lipoproteins and chylomicrons. [EU] Liquor: 1. A liquid, especially an aqueous solution containing a medicinal substance. 2. A general term used in anatomical nomenclature for certain fluids of the body. [EU] Lithotripsy: The destruction of a calculus of the kidney, ureter, bladder, or gallbladder by physical forces, including crushing with a lithotriptor through a catheter. Focused percutaneous ultrasound and focused hydraulic shock waves may be used without surgery. Lithotripsy does not include the dissolving of stones by acids or litholysis. Lithotripsy by laser is laser lithotripsy. [NIH] Litter: Appliance consisting of an oblong frame over which is stretched a canvas or other material, used for carrying an injured or disabled person. [NIH] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Localization: The process of determining or marking the location or site of a lesion or disease. May also refer to the process of keeping a lesion or disease in a specific location or site. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Locomotion: Movement or the ability to move from one place or another. It can refer to humans, vertebrate or invertebrate animals, and microorganisms. [NIH] Longitudinal study: Also referred to as a "cohort study" or "prospective study"; the analytic method of epidemiologic study in which subsets of a defined population can be identified who are, have been, or in the future may be exposed or not exposed, or exposed in different degrees, to a factor or factors hypothesized to influence the probability of occurrence of a given disease or other outcome. The main feature of this type of study is to observe large numbers of subjects over an extended time, with comparisons of incidence rates in groups that differ in exposure levels. [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] Low-density lipoprotein: Lipoprotein that contains most of the cholesterol in the blood. LDL carries cholesterol to the tissues of the body, including the arteries. A high level of LDL increases the risk of heart disease. LDL typically contains 60 to 70 percent of the total serum cholesterol and both are directly correlated with CHD risk. [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] Lupus: A form of cutaneous tuberculosis. It is seen predominantly in women and typically involves the nasal, buccal, and conjunctival mucosa. [NIH] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Lymph node: A rounded mass of lymphatic tissue that is surrounded by a capsule of

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connective tissue. Also known as a lymph gland. Lymph nodes are spread out along lymphatic vessels and contain many lymphocytes, which filter the lymphatic fluid (lymph). [NIH]

Lymphadenitis: Inflammation of the lymph nodes. [NIH] Lymphangitis: Inflammation of a lymphatic vessel or vessels. Acute lymphangitis may result from spread of bacterial infection (most commonly beta-haemolytic streptococci) into the lymphatics, manifested by painful subcutaneous red streaks along the course of the vessels. [EU] 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] Lymphocyte Count: A count of the number of lymphocytes in the blood. [NIH] Lymphocytic: Referring to lymphocytes, a type of white blood cell. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Lymphokines: Soluble protein factors generated by activated lymphocytes that affect other cells, primarily those involved in cellular immunity. [NIH] Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue. [NIH] 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] Malabsorption: Impaired intestinal absorption of nutrients. [EU] 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] Malnutrition: A condition caused by not eating enough food or not eating a balanced diet. [NIH]

Mammary: Pertaining to the mamma, or breast. [EU] Mammogram: An x-ray of the breast. [NIH] Manifest: Being the part or aspect of a phenomenon that is directly observable : concretely expressed in behaviour. [EU] Mannans: Polysaccharides consisting of mannose units. [NIH] Mastication: The act and process of chewing and grinding food in the mouth. [NIH]

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Mastitis: Inflammatory disease of the breast, or mammary gland. [NIH] Mastoiditis: Inflammation of the cavity and air cells in the mastoid part of the temporal bone. [NIH] Matrix metalloproteinase: A member of a group of enzymes that can break down proteins, such as collagen, that are normally found in the spaces between cells in tissues (i.e., extracellular matrix proteins). Because these enzymes need zinc or calcium atoms to work properly, they are called metalloproteinases. Matrix metalloproteinases are involved in wound healing, angiogenesis, and tumor cell metastasis. [NIH] Measles Virus: The type species of morbillivirus and the cause of the highly infectious human disease measles, which affects mostly children. [NIH] Meatus: A canal running from the internal auditory foramen through the petrous portion of the temporal bone. It gives passage to the facial and auditory nerves together with the auditory branch of the basilar artery and the internal auditory veins. [NIH] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] Medical Record Linkage: The creation and maintenance of medical and vital records in multiple institutions in a manner that will facilitate the combined use of the records of identified individuals. [NIH] Medicament: A medicinal substance or agent. [EU] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Megaloblastic: A large abnormal red blood cell appearing in the blood in pernicious anaemia. [EU] Meiosis: A special method of cell division, occurring in maturation of the germ cells, by means of which each daughter nucleus receives half the number of chromosomes characteristic of the somatic cells of the species. [NIH] Melanin: The substance that gives the skin its color. [NIH] Melanocytes: Epidermal dendritic pigment cells which control long-term morphological color changes by alteration in their number or in the amount of pigment they produce and store in the pigment containing organelles called melanosomes. Melanophores are larger cells which do not exist in mammals. [NIH] Melanoma: A form of skin cancer that arises in melanocytes, the cells that produce pigment. Melanoma usually begins in a mole. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Membrane 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 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]

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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] Menopause: Permanent cessation of menstruation. [NIH] Menstrual Cycle: The period of the regularly recurring physiologic changes in the endometrium occurring during the reproductive period in human females and some primates and culminating in partial sloughing of the endometrium (menstruation). [NIH] 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 Health: The state wherein the person is well adjusted. [NIH] Mental Processes: Conceptual functions or thinking in all its forms. [NIH] Mental Retardation: Refers to sub-average general intellectual functioning which originated during the developmental period and is associated with impairment in adaptive behavior. [NIH]

Mentors: Senior professionals who provide guidance, direction and support to those persons desirous of improvement in academic positions, administrative positions or other career development situations. [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] Mesoderm: The middle germ layer of the embryo. [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] 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] Metronidazole: Antiprotozoal used in amebiasis, trichomoniasis, giardiasis, and as treponemacide in livestock. It has also been proposed as a radiation sensitizer for hypoxic cells. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985, p133), this substance may reasonably be anticipated to be a carcinogen (Merck, 11th ed). [NIH] MI: Myocardial infarction. Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [NIH] Microcalcifications: Tiny deposits of calcium in the breast that cannot be felt but can be detected on a mammogram. A cluster of these very small specks of calcium may indicate

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that cancer is present. [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] Mineralization: The action of mineralizing; the state of being mineralized. [EU] Minocycline: A semisynthetic staphylococcus infections. [NIH]

antibiotic

effective

against

tetracycline-resistant

Miocamycin: A macrolide antibiotic that has a wide antimicrobial spectrum and is particularly effective in respiratory and genital infections. [NIH] Miscarriage: Spontaneous expulsion of the products of pregnancy before the middle of the second trimester. [NIH] Miscible: Susceptible of being mixed. [EU] 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] Mobility: Capability of movement, of being moved, or of flowing freely. [EU] Mobilization: The process of making a fixed part or stored substance mobile, as by separating a part from surrounding structures to make it accessible for an operative procedure or by causing release into the circulation for body use of a substance stored in the body. [EU] Modeling: A treatment procedure whereby the therapist presents the target behavior which the learner is to imitate and make part of his repertoire. [NIH] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecular mass: The sum of the atomic masses of all atoms in a molecule, based on a scale in which the atomic masses of hydrogen, carbon, nitrogen, and oxygen are 1, 12, 14, and 16, respectively. For example, the molecular mass of water, which has two atoms of hydrogen and one atom of oxygen, is 18 (i.e., 2 + 16). [NIH] Molecular Structure: The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds. [NIH] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] Monitor: An apparatus which automatically records such physiological signs as respiration,

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pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH] Monoclonal: An antibody produced by culturing a single type of cell. It therefore consists of a single species of immunoglobulin molecules. [NIH] Monoclonal antibodies: Laboratory-produced substances that can locate and bind to cancer cells wherever they are in the body. Many monoclonal antibodies are used in cancer detection or therapy; each one recognizes a different protein on certain cancer cells. Monoclonal antibodies can be used alone, or they can be used to deliver drugs, toxins, or radioactive material directly to a tumor. [NIH] Monocyte: A type of white blood cell. [NIH] Monokines: Soluble mediators of the immune response that are neither antibodies nor complement. They are produced largely, but not exclusively, by monocytes and macrophages. [NIH] Mononuclear: A cell with one nucleus. [NIH] Morbillivirus: A genus of the family Paramyxoviridae (subfamily Paramyxovirinae) where all the virions have hemagglutinin but not neuraminidase activity. All members produce both cytoplasmic and intranuclear inclusion bodies. MEASLES VIRUS is the type species. [NIH]

Morphological: Relating to the configuration or the structure of live organs. [NIH] Morphology: The science of the form and structure of organisms (plants, animals, and other forms of life). [NIH] Motility: The ability to move spontaneously. [EU] Mucins: A secretion containing mucopolysaccharides and protein that is the chief constituent of mucus. [NIH] Mucociliary: Pertaining to or affecting the mucus membrane and hairs (including eyelashes, nose hair, .): mucociliary clearing: the clearance of mucus by ciliary movement ( particularly in the respiratory system). [EU] 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] Multivalent: Pertaining to a group of 5 or more homologous or partly homologous chromosomes during the zygotene stage of prophase to first metaphasis in meiosis. [NIH] Muscle Fibers: Large single cells, either cylindrical or prismatic in shape, that form the basic unit of muscle tissue. They consist of a soft contractile substance enclosed in a tubular sheath. [NIH] Muscular Atrophy: Derangement in size and number of muscle fibers occurring with aging, reduction in blood supply, or following immobilization, prolonged weightlessness, malnutrition, and particularly in denervation. [NIH] Muscular Dystrophies: A general term for a group of inherited disorders which are characterized by progressive degeneration of skeletal muscles. [NIH] Myalgia: Pain in a muscle or muscles. [EU] Mycosis: Any disease caused by a fungus. [EU] Mycotic: Pertaining to a mycosis; caused by fungi. [EU]

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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] Myotonic Dystrophy: A condition presenting muscle weakness and wasting which may be progressive. [NIH] Myristate: Pharmacological activator of protein kinase C. [NIH] Nasal Mucosa: The mucous membrane lining the nasal cavity. [NIH] Nasopharynx: The nasal part of the pharynx, lying above the level of the soft palate. [NIH] Natural selection: A part of the evolutionary process resulting in the survival and reproduction of the best adapted individuals. [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] Need: A state of tension or dissatisfaction felt by an individual that impels him to action toward a goal he believes will satisfy the impulse. [NIH] Neonatal: Pertaining to the first four weeks after birth. [EU] Neonatorum: Patchy or generalized progressive hardening of the subcutaneous fat, often with fatal outcome, occurring in infants predisposed by reason of prematurity, marasmus, hypothermia, gastro-intestinal or respiratory infection, or gross malformations. [NIH] Neoplasia: Abnormal and uncontrolled cell growth. [NIH] Neoplasm: A new growth of benign or malignant tissue. [NIH] Neoplastic: Pertaining to or like a neoplasm (= any new and abnormal growth); pertaining to neoplasia (= the formation of a neoplasm). [EU] Neostriatum: The phylogenetically newer part of the corpus striatum consisting of the caudate nucleus and putamen. It is often called simply the striatum. [NIH] Nephropathy: Disease of the kidneys. [EU] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Networks: Pertaining to a nerve or to the nerves, a meshlike structure of interlocking fibers or strands. [NIH] Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU] Neural tube defects: These defects include problems stemming from fetal development of the spinal cord, spine, brain, and skull, and include birth defects such as spina bifida, anencephaly, and encephalocele. Neural tube defects occur early in pregnancy at about 4 to 6 weeks, usually before a woman knows she is pregnant. Many babies with neural tube defects have difficulty walking and with bladder and bowel control. [NIH] Neuraminidase: An enzyme that catalyzes the hydrolysis of alpha-2,3, alpha-2,6-, and alpha-2,8-glycosidic linkages (at a decreasing rate, respectively) of terminal sialic residues in oligosaccharides, glycoproteins, glycolipids, colominic acid, and synthetic substrate. (From Enzyme Nomenclature, 1992) EC 3.2.1.18. [NIH] Neuronal: Pertaining to a neuron or neurons (= conducting cells of the nervous system). [EU]

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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] Neurotoxicity: The tendency of some treatments to cause damage to 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] Neutrophil: A type of white blood cell. [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] 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] Nonverbal Communication: Transmission of emotions, ideas, and attitudes between individuals in ways other than the spoken language. [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] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nutritional Status: State of the body in relation to the consumption and utilization of nutrients. [NIH] Obsession: A recurrent, persistent thought, image, or impulse that is unwanted and distressing (ego-dystonic) and comes involuntarily to mind despite attempts to ignore or suppress it. Common obsessions involve thoughts of violence, contamination, and selfdoubt. [EU] Obsessive-Compulsive Disorder: An anxiety disorder characterized by recurrent, persistent obsessions or compulsions. Obsessions are the intrusive ideas, thoughts, or images that are experienced as senseless or repugnant. Compulsions are repetitive and seemingly purposeful behavior which the individual generally recognizes as senseless and from which

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the individual does not derive pleasure although it may provide a release from tension. [NIH] Office Visits: Visits made by patients to health service providers' offices for diagnosis, treatment, and follow-up. [NIH] Oleanolic Acid: Occurs in leaves of Olea europaea, Viscum album L., and other higher plants. It is also the aglycone component of many saponins. [NIH] Oligosaccharides: Carbohydrates consisting of between two and ten monosaccharides connected by either an alpha- or beta-glycosidic link. They are found throughout nature in both the free and bound form. [NIH] Oncogene: A gene that normally directs cell growth. If altered, an oncogene can promote or allow the uncontrolled growth of cancer. Alterations can be inherited or caused by an environmental exposure to carcinogens. [NIH] Oncogenic: Chemical, viral, radioactive or other agent that causes cancer; carcinogenic. [NIH] Opacity: Degree of density (area most dense taken for reading). [NIH] Operon: The genetic unit consisting of a feedback system under the control of an operator gene, in which a structural gene transcribes its message in the form of mRNA upon blockade of a repressor produced by a regulator gene. Included here is the attenuator site of bacterial operons where transcription termination is regulated. [NIH] 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] Organ Transplantation: Transference of an organ between individuals of the same species or between individuals of different species. [NIH] Orgasm: The crisis of sexual excitement in either humans or animals. [NIH] Orofacial: Of or relating to the mouth and face. [EU] 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] Otitis: Inflammation of the ear, which may be marked by pain, fever, abnormalities of hearing, hearing loss, tinnitus, and vertigo. [EU] Otitis Media: Inflammation of the middle ear. [NIH] Outer ear: The pinna and external meatus of the ear. [NIH] Outpatient: A patient who is not an inmate of a hospital but receives diagnosis or treatment in a clinic or dispensary connected with the hospital. [NIH] Ovalbumin: An albumin obtained from the white of eggs. It is a member of the serpin superfamily. [NIH] Ovaries: The pair of female reproductive glands in which the ova, or eggs, are formed. The ovaries are located in the pelvis, one on each side of the uterus. [NIH] Ovary: Either of the paired glands in the female that produce the female germ cells and secrete some of the female sex hormones. [NIH]

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Overexpress: An excess of a particular protein on the surface of a cell. [NIH] Ovum: A female germ cell extruded from the ovary at ovulation. [NIH] Ovum Implantation: Endometrial implantation of the blastocyst. [NIH] Oxalate: A chemical that combines with calcium in urine to form the most common type of kidney stone (calcium oxalate stone). [NIH] Oxalic Acid: A strong dicarboxylic acid occurring in many plants and vegetables. It is produced in the body by metabolism of glyoxylic acid or ascorbic acid. It is not metabolized but excreted in the urine. It is used as an analytical reagent and general reducing agent. [NIH] Oxidants: Oxidizing agents or electron-accepting molecules in chemical reactions in which electrons are transferred from one molecule to another (oxidation-reduction). In vivo, it appears that phagocyte-generated oxidants function as tumor promoters or cocarcinogens rather than as complete carcinogens perhaps because of the high levels of endogenous antioxidant defenses. It is also thought that oxidative damage in joints may trigger the autoimmune response that characterizes the persistence of the rheumatoid disease process. [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]

Oxidation-Reduction: A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471). [NIH] Oxidative metabolism: A chemical process in which oxygen is used to make energy from carbohydrates (sugars). Also known as aerobic respiration, cell respiration, or aerobic metabolism. [NIH] Oxidative Stress: A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi). [NIH] Pachymeningitis: Inflammation of the dura mater of the brain, the spinal cord or the optic nerve. [NIH] Palate: The structure that forms the roof of the mouth. It consists of the anterior hard palate and the posterior soft palate. [NIH] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Palsy: Disease of the peripheral nervous system occurring usually after many years of increased lead absorption. [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] Pancreatic: Having to do with the pancreas. [NIH] Pancreatic cancer: Cancer of the pancreas, a salivary gland of the abdomen. [NIH] Pancreatic Pseudocyst: Cyst-like space not lined by epithelium and contained within the

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pancreas. [NIH] Pancreatitis: Acute or chronic inflammation of the pancreas, which may be asymptomatic or symptomatic, and which is due to autodigestion of a pancreatic tissue by its own enzymes. It is caused most often by alcoholism or biliary tract disease; less commonly it may be associated with hyperlipaemia, hyperparathyroidism, abdominal trauma (accidental or operative injury), vasculitis, or uraemia. [EU] Panic: A state of extreme acute, intense anxiety and unreasoning fear accompanied by disorganization of personality function. [NIH] Paranasal Sinuses: Air-filled extensions of the respiratory part of the nasal cavity into the frontal, ethmoid, sphenoid, and maxillary cranial bones. They vary in size and form in different individuals and are lined by the ciliated mucous membranes of the nasal cavity. [NIH]

Parasite: An animal or a plant that lives on or in an organism of another species and gets at least some of its nutrition from that other organism. [NIH] Parasitic: Having to do with or being a parasite. A parasite is an animal or a plant that lives on or in an organism of another species and gets at least some of its nutrients from it. [NIH] Parenteral: Not through the alimentary canal but rather by injection through some other route, as subcutaneous, intramuscular, intraorbital, intracapsular, intraspinal, intrasternal, intravenous, etc. [EU] Parietal: 1. Of or pertaining to the walls of a cavity. 2. Pertaining to or located near the parietal bone, as the parietal lobe. [EU] Paroxysmal: Recurring in paroxysms (= spasms or seizures). [EU] Partial remission: The shrinking, but not complete disappearance, of a tumor in response to therapy. Also called partial response. [NIH] Pathogen: Any disease-producing microorganism. [EU] Pathogenesis: The cellular events and reactions that occur in the development of disease. [NIH]

Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Pathologic Processes: The abnormal mechanisms and forms involved in the dysfunctions of tissues and organs. [NIH] Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Patient Education: The teaching or training of patients concerning their own health needs. [NIH]

Pelvic: Pertaining to the pelvis. [EU] Pelvis: The lower part of the abdomen, located between the hip bones. [NIH] Penicillin: An antibiotic drug used to treat infection. [NIH] Penicillin Resistance: Nonsusceptibility of an organism to the action of penicillins. [NIH] Penis: The external reproductive organ of males. It is composed of a mass of erectile tissue enclosed in three cylindrical fibrous compartments. Two of the three compartments, the corpus cavernosa, are placed side-by-side along the upper part of the organ. The third compartment below, the corpus spongiosum, houses the urethra. [NIH] Peptic: Pertaining to pepsin or to digestion; related to the action of gastric juices. [EU] Peptic Ulcer: An ulceration of the mucous membrane of the esophagus, stomach or

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duodenum, caused by the action of the acid gastric juice. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Peptide Chain Elongation: The process whereby an amino acid is joined through a substituted amide linkage to a chain of peptides. [NIH] Peptide Fragments: Partial proteins formed by partial hydrolysis of complete proteins. [NIH] Perception: The ability quickly and accurately to recognize similarities and differences among presented objects, whether these be pairs of words, pairs of number series, or multiple sets of these or other symbols such as geometric figures. [NIH] Percutaneous: Performed through the skin, as injection of radiopacque material in radiological examination, or the removal of tissue for biopsy accomplished by a needle. [EU] Perfusion: Bathing an organ or tissue with a fluid. In regional perfusion, a specific area of the body (usually an arm or a leg) receives high doses of anticancer drugs through a blood vessel. Such a procedure is performed to treat cancer that has not spread. [NIH] 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] 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]

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] Periplasm: The space between the inner and outer membranes of a cell that is shared with the cell wall. [NIH] Peritoneum: Endothelial lining of the abdominal cavity, the parietal peritoneum covering the inside of the abdominal wall and the visceral peritoneum covering the bowel, the mesentery, and certain of the organs. The portion that covers the bowel becomes the serosal layer of the bowel wall. [NIH] Peritonitis: Inflammation of the peritoneum; a condition marked by exudations in the peritoneum of serum, fibrin, cells, and pus. It is attended by abdominal pain and tenderness, constipation, vomiting, and moderate fever. [EU] Peroxide: Chemical compound which contains an atom group with two oxygen atoms tied to each other. [NIH] Personality Disorders: A major deviation from normal patterns of behavior. [NIH]

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Pertussis: An acute, highly contagious infection of the respiratory tract, most frequently affecting young children, usually caused by Bordetella pertussis; a similar illness has been associated with infection by B. parapertussis and B. bronchiseptica. It is characterized by a catarrhal stage, beginning after an incubation period of about two weeks, with slight fever, sneezing, running at the nose, and a dry cough. In a week or two the paroxysmal stage begins, with the characteristic paroxysmal cough, consisting of a deep inspiration, followed by a series of quick, short coughs, continuing until the air is expelled from the lungs; the close of the paroxysm is marked by a long-drawn, shrill, whooping inspiration, due to spasmodic closure of the glottis. This stage lasts three to four weeks, after which the convalescent stage begins, in which paroxysms grow less frequent and less violent, and finally cease. Called also whooping cough. [EU] PH: The symbol relating the hydrogen ion (H+) concentration or activity of a solution to that of a given standard solution. Numerically the pH is approximately equal to the negative logarithm of H+ concentration expressed in molarity. pH 7 is neutral; above it alkalinity increases and below it acidity increases. [EU] 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] Pharmaceutical Preparations: Drugs intended for human or veterinary use, presented in their finished dosage form. Included here are materials used in the preparation and/or formulation of the finished dosage form. [NIH] Pharmacokinetic: The mathematical analysis of the time courses of absorption, distribution, and elimination of drugs. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] 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] Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor of melanin, dopamine, noradrenalin, and thyroxine. [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] Phlebitis: Inflammation of a vein. [NIH] Phorbol: Class of chemicals that promotes the development of tumors. [NIH] Phosphoglucomutase: An enzyme that catalyzes the conversion of alpha D-glucose 1phosphate to alpha D-glucose 6-phosphate. EC 5.4.2.2. [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]

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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] Phosphorylase: An enzyme of the transferase class that catalyzes the phosphorylysis of a terminal alpha-1,4-glycosidic bond at the non-reducing end of a glycogen molecule, releasing a glucose 1-phosphate residue. Phosphorylase should be qualified by the natural substance acted upon. EC 2.4.1.1. [NIH] Phosphorylase a: The phosphorylated and more active form of phosphorylase that functions as a regulatory enzyme during glycogen breakdown. The phosphate groups are hydrolytically removed by phosphorylase phosphatase to form phosphorylase B and orthophosphate. EC 2.4.1.-. [NIH] Phosphorylase Phosphatase: An enzyme that deactivates glycogen phosphorylase a by releasing inorganic phosphate and phosphorylase b, the inactive form. EC 3.1.3.17. [NIH] Phosphorylated: Attached to a phosphate group. [NIH] Phosphorylates: Attached to a phosphate group. [NIH] Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. [NIH] Phosphorylcholine: Calcium and magnesium salts used therapeutically in hepatobiliary dysfunction. [NIH] Physical Examination: Systematic and thorough inspection of the patient for physical signs of disease or abnormality. [NIH] Physicochemical: Pertaining to physics and chemistry. [EU] 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] Placenta: A highly vascular fetal organ through which the fetus absorbs oxygen and other nutrients and excretes carbon dioxide and other wastes. It begins to form about the eighth day of gestation when the blastocyst adheres to the decidua. [NIH] Plant Diseases: Diseases of plants. [NIH] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plaque: A clear zone in a bacterial culture grown on an agar plate caused by localized destruction of bacterial cells by a bacteriophage. The concentration of infective virus in a fluid can be estimated by applying the fluid to a culture and counting the number of. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] Plasma Exchange: Removal of plasma and replacement with various fluids, e.g., fresh frozen plasma, plasma protein fractions (PPF), albumin preparations, dextran solutions, saline. Used in treatment of autoimmune diseases, immune complex diseases, diseases of excess plasma factors, and other conditions. [NIH]

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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] Plasmapheresis: Procedure whereby plasma is separated and extracted from anticoagulated whole blood and the red cells retransfused to the donor. Plasmapheresis is also employed for therapeutic use. [NIH] 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] Plasticity: In an individual or a population, the capacity for adaptation: a) through gene changes (genetic plasticity) or b) through internal physiological modifications in response to changes of environment (physiological plasticity). [NIH] Platelet Activating Factor: A phospholipid derivative formed by platelets, basophils, neutrophils, monocytes, and macrophages. It is a potent platelet aggregating agent and inducer of systemic anaphylactic symptoms, including hypotension, thrombocytopenia, neutropenia, and bronchoconstriction. [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. 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]

Pleura: The thin serous membrane enveloping the lungs and lining the thoracic cavity. [NIH] Pleural: A circumscribed area of hyaline whorled fibrous tissue which appears on the surface of the parietal pleura, on the fibrous part of the diaphragm or on the pleura in the interlobar fissures. [NIH] Pneumococcal Infections: Infections with bacteria of the species Streptococcus pneumoniae. [NIH]

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Pneumococcal Vaccines: Vaccines or candidate vaccines used to prevent infections with Streptococcus pneumoniae. [NIH] Pneumonia: Inflammation of the lungs. [NIH] Pneumonitis: A disease caused by inhaling a wide variety of substances such as dusts and molds. Also called "farmer's disease". [NIH] Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [NIH] Polycystic: An inherited disorder characterized by many grape-like clusters of fluid-filled cysts that make both kidneys larger over time. These cysts take over and destroy working kidney tissue. PKD may cause chronic renal failure and end-stage renal disease. [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] Polyneuritis: Inflammation of several peripheral nerves at the same time. [NIH] Polyp: A growth that protrudes from a mucous membrane. [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] Polyvalent: Having more than one valence. [EU] Posterior: Situated in back of, or in the back part of, or affecting the back or dorsal surface of the body. In lower animals, it refers to the caudal end of the body. [EU] 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] Potentiation: An overall effect of two drugs taken together which is greater than the sum of the effects of each drug taken alone. [NIH]

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Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH] 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] Premenstrual: Occurring before menstruation. [EU] Premenstrual Syndrome: A syndrome occurring most often during the last week of the menstrual cycle and ending soon after the onset of menses. Some of the symptoms are emotional instability, insomnia, headache, nausea, vomiting, abdominal distension, and painful breasts. [NIH] Prenatal: Existing or occurring before birth, with reference to the fetus. [EU] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] Prickle: Several layers of the epidermis where the individual cells are connected by cell bridges. [NIH] Probe: An instrument used in exploring cavities, or in the detection and dilatation of strictures, or in demonstrating the potency of channels; an elongated instrument for exploring or sounding body cavities. [NIH] 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] Progesterone: Pregn-4-ene-3,20-dione. The principal progestational hormone of the body, secreted by the corpus luteum, adrenal cortex, and placenta. Its chief function is to prepare the uterus for the reception and development of the fertilized ovum. It acts as an antiovulatory agent when administered on days 5-25 of the menstrual cycle. [NIH] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Proline: A non-essential amino acid that is synthesized from glutamic acid. It is an essential component of collagen and is important for proper functioning of joints and tendons. [NIH] Promoter: A chemical substance that increases the activity of a carcinogenic process. [NIH] Prone: Having the front portion of the body downwards. [NIH] 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] Propolis: Resinous substance obtained from beehives; contains many different substances which may have antimicrobial or antimycotic activity topically; its extracts are called

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propolis resin or balsam. Synonyms: bee bread; hive dross; bee glue. [NIH] Proportional: Being in proportion : corresponding in size, degree, or intensity, having the same or a constant ratio; of, relating to, or used in determining proportions. [EU] Prospective study: An epidemiologic study in which a group of individuals (a cohort), all free of a particular disease and varying in their exposure to a possible risk factor, is followed over a specific amount of time to determine the incidence rates of the disease in the exposed and unexposed groups. [NIH] Prostaglandin: Any of a group of components derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway that are extremely potent mediators of a diverse group of physiologic processes. The abbreviation for prostaglandin is PG; specific compounds are designated by adding one of the letters A through I to indicate the type of substituents found on the hydrocarbon skeleton and a subscript (1, 2 or 3) to indicate the number of double bonds in the hydrocarbon skeleton e.g., PGE2. The predominant naturally occurring prostaglandins all have two double bonds and are synthesized from arachidonic acid (5,8,11,14-eicosatetraenoic acid) by the pathway shown in the illustration. The 1 series and 3 series are produced by the same pathway with fatty acids having one fewer double bond (8,11,14-eicosatrienoic acid or one more double bond (5,8,11,14,17-eicosapentaenoic acid) than arachidonic acid. The subscript a or ß indicates the configuration at C-9 (a denotes a substituent below the plane of the ring, ß, above the plane). The naturally occurring PGF's have the a configuration, e.g., PGF2a. All of the prostaglandins act by binding to specific cell-surface receptors causing an increase in the level of the intracellular second messenger cyclic AMP (and in some cases cyclic GMP also). The effect produced by the cyclic AMP increase depends on the specific cell type. In some cases there is also a positive feedback effect. Increased cyclic AMP increases prostaglandin synthesis leading to further increases in cyclic AMP. [EU] Prostaglandins A: (13E,15S)-15-Hydroxy-9-oxoprosta-10,13-dien-1-oic acid (PGA(1)); (5Z,13E,15S)-15-hydroxy-9-oxoprosta-5,10,13-trien-1-oic acid (PGA(2)); (5Z,13E,15S,17Z)-15hydroxy-9-oxoprosta-5,10,13,17-tetraen-1-oic acid (PGA(3)). A group of naturally occurring secondary prostaglandins derived from PGE. PGA(1) and PGA(2) as well as their 19hydroxy derivatives are found in many organs and tissues. [NIH] Prostate: A gland in males that surrounds the neck of the bladder and the urethra. It secretes a substance that liquifies coagulated semen. It is situated in the pelvic cavity behind the lower part of the pubic symphysis, above the deep layer of the triangular ligament, and rests upon the rectum. [NIH] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Protease Inhibitors: Compounds which inhibit or antagonize biosynthesis or actions of proteases (endopeptidases). [NIH] Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific proteinbinding measures are often used as assays in diagnostic assessments. [NIH] Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation. [NIH] Protein Conformation: The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. Quaternary protein structure describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain). [NIH]

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Protein Engineering: Procedures by which nonrandom single-site changes are introduced into structural genes (site-specific mutagenesis) in order to produce mutant genes which can be coupled to promoters that direct the synthesis of a specifically altered protein, which is then analyzed for structural and functional properties and then compared with the predicted and sought-after properties. The design of the protein may be assisted by computer graphic technology and other advanced molecular modeling techniques. [NIH] Protein S: The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] 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] 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] Psoriasis: A common genetically determined, chronic, inflammatory skin disease characterized by rounded erythematous, dry, scaling patches. The lesions have a predilection for nails, scalp, genitalia, extensor surfaces, and the lumbosacral region. Accelerated epidermopoiesis is considered to be the fundamental pathologic feature in psoriasis. [NIH] Psychiatric: Pertaining to or within the purview of psychiatry. [EU] Psychic: Pertaining to the psyche or to the mind; mental. [EU] Psychology: The science dealing with the study of mental processes and behavior in man and animals. [NIH] Public Health: Branch of medicine concerned with the prevention and control of disease and disability, and the promotion of physical and mental health of the population on the international, national, state, or municipal level. [NIH] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] Pulmonary: Relating to the lungs. [NIH] Pulmonary Artery: The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs. [NIH] 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]

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Purifying: Respiratory equipment whose function is to remove contaminants from otherwise wholesome air. [NIH] Purines: A series of heterocyclic compounds that are variously substituted in nature and are known also as purine bases. They include adenine and guanine, constituents of nucleic acids, as well as many alkaloids such as caffeine and theophylline. Uric acid is the metabolic end product of purine metabolism. [NIH] Purulent: Consisting of or containing pus; associated with the formation of or caused by pus. [EU] Pustular: Pertaining to or of the nature of a pustule; consisting of pustules (= a visible collection of pus within or beneath the epidermis). [EU] Putamen: The largest and most lateral of the basal ganglia lying between the lateral medullary lamina of the globus pallidus and the external capsule. It is part of the neostriatum and forms part of the lentiform nucleus along with the globus pallidus. [NIH] Putrefaction: The process of decomposition of animal and vegetable matter by living organisms. [NIH] Pyoderma: Any purulent skin disease (Dorland, 27th ed). [NIH] Pyogenic: Producing pus; pyopoietic (= liquid inflammation product made up of cells and a thin fluid called liquor puris). [EU] Pyridoxal: 3-Hydroxy-5-(hydroxymethyl)-2-methyl-4- pyridinecarboxaldehyde. [NIH] 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] Pyrogenic: Inducing fever. [EU] Quality of Life: A generic concept reflecting concern with the modification and enhancement of life attributes, e.g., physical, political, moral and social environment. [NIH] Quinolones: Quinolines which are substituted in any position by one or more oxo groups. These compounds can have any degree of hydrogenation, any substituents, and fused ring systems. [NIH] Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radioactive: Giving off radiation. [NIH] Raffinose: A trisaccharide occurring in Australian manna (from Eucalyptus spp, Myrtaceae) and in cottonseed meal. [NIH] Randomized: Describes an experiment or clinical trial in which animal or human subjects are assigned by chance to separate groups that compare different treatments. [NIH] Reactive Oxygen Species: Reactive intermediate oxygen species including both radicals and non-radicals. These substances are constantly formed in the human body and have been shown to kill bacteria and inactivate proteins, and have been implicated in a number of diseases. Scientific data exist that link the reactive oxygen species produced by inflammatory phagocytes to cancer development. [NIH] Reagent: A substance employed to produce a chemical reaction so as to detect, measure, produce, etc., other substances. [EU]

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Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Recombination: The formation of new combinations of genes as a result of segregation in crosses between genetically different parents; also the rearrangement of linked genes due to crossing-over. [NIH] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Recurrence: The return of a sign, symptom, or disease after a remission. [NIH] Red blood cells: RBCs. Cells that carry oxygen to all parts of the body. Also called erythrocytes. [NIH] Red Nucleus: A pinkish-yellow portion of the midbrain situated in the rostral mesencephalic tegmentum. It receives a large projection from the contralateral half of the cerebellum via the superior cerebellar peduncle and a projection from the ipsilateral motor cortex. [NIH] Reductase: Enzyme converting testosterone to dihydrotestosterone. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH] Refractory: Not readily yielding to treatment. [EU] 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] Relaxation Techniques: The use of muscular relaxation techniques in treatment. [NIH] Remission: A decrease in or disappearance of signs and symptoms of cancer. In partial remission, some, but not all, signs and symptoms of cancer have disappeared. In complete remission, all signs and symptoms of cancer have disappeared, although there still may be cancer in the body. [NIH] Renal failure: Progressive renal insufficiency and uremia, due to irreversible and progressive renal glomerular tubular or interstitial disease. [NIH] 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] Repressor Proteins: Proteins which are normally bound to the operator locus of an operon, thereby preventing transcription of the structural genes. In enzyme induction, the substrate of the inducible enzyme binds to the repressor protein, causing its release from the operator and freeing the structural genes for transcription. In enzyme repression, the end product of the enzyme sequence binds to the free repressor protein, the resulting complex then binds to the operator and prevents transcription of the structural genes. [NIH] Reproductive system: In women, this system includes the ovaries, the fallopian tubes, the

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uterus (womb), the cervix, and the vagina (birth canal). The reproductive system in men includes the prostate, the testes, and the penis. [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 Burst: A large increase in oxygen uptake by neutrophils and most types of tissue macrophages through activation of an NADPH-cytochrome b-dependent oxidase that reduces oxygen to a superoxide. Individuals with an inherited defect in which the oxidase that reduces oxygen to superoxide is decreased or absent (granulomatous disease, chronic) often die as a result of recurrent bacterial infections. [NIH] Restoration: Broad term applied to any inlay, crown, bridge or complete denture which restores or replaces loss of teeth or oral tissues. [NIH] Resuscitation: The restoration to life or consciousness of one apparently dead; it includes such measures as artificial respiration and cardiac massage. [EU] Retinoblastoma: An eye cancer that most often occurs in children younger than 5 years. It occurs in hereditary and nonhereditary (sporadic) forms. [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] Rhinovirus: A genus of Picornaviridae inhabiting primarily the respiratory tract of mammalian hosts. It includes the human strains associated with common colds. [NIH] Ribose: A pentose active in biological systems usually in its D-form. [NIH] Ribosome: A granule of protein and RNA, synthesized in the nucleolus and found in the cytoplasm of cells. Ribosomes are the main sites of protein synthesis. Messenger RNA attaches to them and there receives molecules of transfer RNA bearing amino acids. [NIH] 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] Root Caries: Dental caries involving the tooth root, cementum, or cervical area of the tooth. [NIH]

Rubber: A high-molecular-weight polymeric elastomer derived from the milk juice (latex) of Hevea brasiliensis and other trees. It is a substance that can be stretched at room temperature to atleast twice its original length and after releasing the stress, retractrapidly,

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and recover its original dimensions fully. Synthetic rubber is made from many different chemicals, including styrene, acrylonitrile, ethylene, propylene, and isoprene. [NIH] Rural Population: The inhabitants of rural areas or of small towns classified as rural. [NIH] Saccule: The smaller of the 2 sacs within the vestibule of the ear. [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] Salivary Proteins: Proteins found in saliva and the salivary glands. These proteins show some enzymatic activity, but their composition varies in different individuals. [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] Salmonellosis: Infection by salmonellae. [NIH] Sanitary: Relating or belonging to health and hygiene; conductive to the restoration or maintenance of health. [NIH] Saponins: Sapogenin glycosides. A type of glycoside widely distributed in plants. Each consists of a sapogenin as the aglycon moiety, and a sugar. The sapogenin may be a steroid or a triterpene and the sugar may be glucose, galactose, a pentose, or a methylpentose. Sapogenins are poisonous towards the lower forms of life and are powerful hemolytics when injected into the blood stream able to dissolve red blood cells at even extreme dilutions. [NIH] Sarcoma: A connective tissue neoplasm formed by proliferation of mesodermal cells; it is usually highly malignant. [NIH] Scarlet Fever: Infection with group A streptococci that is characterized by tonsillitis and pharyngitis. An erythematous rash is commonly present. [NIH] Scintillation Counting: Detection and counting of scintillations produced in a fluorescent material by ionizing radiation. [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] Sclerosis: A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Sebaceous: Gland that secretes sebum. [NIH] 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] Seizures: Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include

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abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as epilepsy or "seizure disorder." [NIH] Semen: The thick, yellowish-white, viscid fluid secretion of male reproductive organs discharged upon ejaculation. In addition to reproductive organ secretions, it contains spermatozoa and their nutrient plasma. [NIH] Semicircular canal: Three long canals of the bony labyrinth of the ear, forming loops and opening into the vestibule by five openings. [NIH] Seminal fluid: Fluid from the prostate and other sex glands that helps transport sperm out of the man's body during orgasm. Seminal fluid contains sugar as an energy source for sperm. [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] Sensory loss: A disease of the nerves whereby the myelin or insulating sheath of myelin on the nerves does not stay intact and the messages from the brain to the muscles through the nerves are not carried properly. [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] Sequence Analysis: A multistage process that includes the determination of a sequence (protein, carbohydrate, etc.), its fragmentation and analysis, and the interpretation of the resulting sequence information. [NIH] Sequencing: The determination of the order of nucleotides in a DNA or RNA chain. [NIH] Sequester: A portion of dead bone which has become detached from the healthy bone tissue, as occurs in necrosis. [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] Serous: Having to do with serum, the clear liquid part of blood. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Sex Determination: The biological characteristics which distinguish human beings as female or male. [NIH] Shedding: Release of infectious particles (e. g., bacteria, viruses) into the environment, for example by sneezing, by fecal excretion, or from an open lesion. [NIH] 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]

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Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the one sought to be benefited by its administration. [EU] Signal Transduction: The intercellular or intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GABA-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptormediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. [NIH] Signs and Symptoms: Clinical manifestations that can be either objective when observed by a physician, or subjective when perceived by the patient. [NIH] Sinusitis: An inflammatory process of the mucous membranes of the paranasal sinuses that occurs in three stages: acute, subacute, and chronic. Sinusitis results from any condition causing ostial obstruction or from pathophysiologic changes in the mucociliary transport mechanism. [NIH] Skeleton: The framework that supports the soft tissues of vertebrate animals and protects many of their internal organs. The skeletons of vertebrates are made of bone and/or cartilage. [NIH] Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]

Sneezing: Sudden, forceful, involuntary expulsion of air from the nose and mouth caused by irritation to the mucous membranes of the upper respiratory tract. [NIH] Social Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [NIH] Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] Solid tumor: Cancer of body tissues other than blood, bone marrow, or the lymphatic system. [NIH] Solvent: 1. Dissolving; effecting a solution. 2. A liquid that dissolves or that is capable of dissolving; the component of a solution that is present in greater amount. [EU] 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 mutations: Alterations in DNA that occur after conception. Somatic mutations can occur in any of the cells of the body except the germ cells (sperm and egg) and therefore are

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not passed on to children. These alterations can (but do not always) cause cancer or other diseases. [NIH] Sound wave: An alteration of properties of an elastic medium, such as pressure, particle displacement, or density, that propagates through the medium, or a superposition of such alterations. [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] 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] Spectrophotometry: The art or process of comparing photometrically the relative intensities of the light in different parts of the spectrum. [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] Sperm Head: The anterior, usually ovoid, nucleus-containing part of spermatozoa. [NIH] Spina bifida: A defect in development of the vertebral column in which there is a central deficiency of the vertebral lamina. [NIH] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] Spinal Cord Compression: Acute and chronic conditions characterized by external mechanical compression of the spinal cord due to extramedullary neoplasm; epidural abscess; spinal fractures; bony deformities of the vertebral bodies; and other conditions. Clinical manifestations vary with the anatomic site of the lesion and may include localized pain, weakness, sensory loss, incontinence, and impotence. [NIH] Spinal Fractures: Broken bones in the vertebral column. [NIH] Spinal Nerves: The 31 paired peripheral nerves formed by the union of the dorsal and ventral spinal roots from each spinal cord segment. The spinal nerve plexuses and the spinal roots are also included. [NIH] Spinous: Like a spine or thorn in shape; having spines. [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] Sputum: The material expelled from the respiratory passages by coughing or clearing the throat. [NIH] Stabilization: The creation of a stable state. [EU]

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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] Stenosis: Narrowing or stricture of a duct or canal. [EU] Sterile: Unable to produce children. [NIH] Sterility: 1. The inability to produce offspring, i.e., the inability to conceive (female s.) or to induce conception (male s.). 2. The state of being aseptic, or free from microorganisms. [EU] Steroid: A group name for lipids that contain a hydrogenated cyclopentanoperhydrophenanthrene ring system. Some of the substances included in this group are progesterone, adrenocortical hormones, the gonadal hormones, cardiac aglycones, bile acids, sterols (such as cholesterol), toad poisons, saponins, and some of the carcinogenic hydrocarbons. [EU] Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Stool: The waste matter discharged in a bowel movement; feces. [NIH] Strand: DNA normally exists in the bacterial nucleus in a helix, in which two strands are coiled together. [NIH] Streptococcal: Caused by infection due to any species of streptococcus. [NIH] Streptococcal Infections: Infections with bacteria of the genus Streptococcus. [NIH] Streptococcal Vaccines: Vaccines or candidate vaccines used to prevent streptococcal infections. [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 agalactiae: A bacterium which causes mastitis in cattle and occasionally in man. [NIH] Streptococcus mutans: A polysaccharide-producing species of Streptococcus isolated from human dental plaque. [NIH] Streptococcus pneumoniae: A gram-positive organism found in the upper respiratory tract, inflammatory exudates, and various body fluids of normal and/or diseased humans and, rarely, domestic animals. [NIH] Streptomycin: O-2-Deoxy-2-(methylamino)-alpha-L-glucopyranosyl-(1-2)-O-5- deoxy-3-Cformyl-alpha-L-lyxofuranosyl-(1-4)-N,N'-bis(aminoiminomethyl)-D-streptamine. Antibiotic substance produced by the soil actinomycete Streptomyces griseus. It acts by inhibiting the initiation and elongation processes during protein synthesis. [NIH]

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Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] Striatum: A higher brain's domain thus called because of its stripes. [NIH] Stricture: The abnormal narrowing of a body opening. Also called stenosis. [NIH] Styrene: A colorless, toxic liquid with a strong aromatic odor. It is used to make rubbers, polymers and copolymers, and polystyrene plastics. [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] Suction: The removal of secretions, gas or fluid from hollow or tubular organs or cavities by means of a tube and a device that acts on negative pressure. [NIH] 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] Superoxide Dismutase: An oxidoreductase that catalyzes the reaction between superoxide anions and hydrogen to yield molecular oxygen and hydrogen peroxide. The enzyme protects the cell against dangerous levels of superoxide. EC 1.15.1.1. [NIH] Superstitions: A belief or practice which lacks adequate basis for proof; an embodiment of fear of the unknown, magic, and ignorance. [NIH] Supplementation: Adding nutrients to the diet. [NIH] Suppositories: A small cone-shaped medicament having cocoa butter or gelatin at its basis and usually intended for the treatment of local conditions in the rectum. [NIH]

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Surface Plasmon Resonance: A biosensing technique in which biomolecules capable of binding to specific analytes or ligands are first immobilized on one side of a metallic film. Light is then focused on the opposite side of the film to excite the surface plasmons, that is, the oscillations of free electrons propagating along the film's surface. The refractive index of light reflecting off this surface is measured. When the immobilized biomolecules are bound by their ligands, an alteration in surface plasmons on the opposite side of the film is created which is directly proportional to the change in bound, or adsorbed, mass. Binding is measured by changes in the refractive index. The technique is used to study biomolecular interactions, such as antigen-antibody binding. [NIH] Surfactant: A fat-containing protein in the respiratory passages which reduces the surface tension of pulmonary fluids and contributes to the elastic properties of pulmonary tissue. [NIH]

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] Symphysis: A secondary cartilaginous joint. [NIH] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] Synaptic: Pertaining to or affecting a synapse (= site of functional apposition between neurons, at which an impulse is transmitted from one neuron to another by electrical or chemical means); pertaining to synapsis (= pairing off in point-for-point association of homologous chromosomes from the male and female pronuclei during the early prophase of meiosis). [EU] Synergistic: Acting together; enhancing the effect of another force or agent. [EU] Synovial: Of pertaining to, or secreting synovia. [EU] Synovial Fluid: The clear, viscous fluid secreted by the synovial membrane. It contains mucin, albumin, fat, and mineral salts and serves to lubricate joints. [NIH] Synovial Membrane: The inner membrane of a joint capsule surrounding a freely movable joint. It is loosely attached to the external fibrous capsule and secretes synovial fluid. [NIH] Systemic: Affecting the entire body. [NIH] Systemic disease: Disease that affects the whole body. [NIH] Systemic lupus erythematosus: SLE. A chronic inflammatory connective tissue disease marked by skin rashes, joint pain and swelling, inflammation of the kidneys, inflammation of the fibrous tissue surrounding the heart (i.e., the pericardium), as well as other problems. Not all affected individuals display all of these problems. May be referred to as lupus. [NIH] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] Tachycardia: Excessive rapidity in the action of the heart, usually with a heart rate above 100 beats per minute. [NIH] Tachypnea: Rapid breathing. [NIH] Tandem Repeat Sequences: Copies of DNA sequences which lie adjacent to each other in the same orientation (direct tandem repeats) or in the opposite direction to each other (inverted tandem repeats). [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] Telangiectasia: The permanent enlargement of blood vessels, causing redness in the skin or

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mucous membranes. [NIH] Telencephalon: Paired anteriolateral evaginations of the prosencephalon plus the lamina terminalis. The cerebral hemispheres are derived from it. Many authors consider cerebrum a synonymous term to telencephalon, though a minority include diencephalon as part of the cerebrum (Anthoney, 1994). [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] Testosterone: A hormone that promotes the development and maintenance of male sex characteristics. [NIH] Tetani: Causal agent of tetanus. [NIH] Tetanic: Having the characteristics of, or relating to tetanus. [NIH] Tetanus: A disease caused by tetanospasmin, a powerful protein toxin produced by Clostridium tetani. Tetanus usually occurs after an acute injury, such as a puncture wound or laceration. Generalized tetanus, the most common form, is characterized by tetanic muscular contractions and hyperreflexia. Localized tetanus presents itself as a mild condition with manifestations restricted to muscles near the wound. It may progress to the generalized form. [NIH] 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] Thalamic: Cell that reaches the lateral nucleus of amygdala. [NIH] Thalamic Diseases: Disorders of the centrally located thalamus, which integrates a wide range of cortical and subcortical information. Manifestations include sensory loss, movement disorders; ataxia, pain syndromes, visual disorders, a variety of neuropsychological conditions, and coma. Relatively common etiologies include cerebrovascular disorders; craniocerebral trauma; brain neoplasms; brain hypoxia; intracranial hemorrhages; and infectious processes. [NIH] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thermal: Pertaining to or characterized by heat. [EU] Thiamphenicol: A methylsulfonyl analog of chloramphenicol. It is an antibiotic and immunosuppressive agent. [NIH] Thorax: A part of the trunk between the neck and the abdomen; 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] Thrombocytopenia: A decrease in the number of blood 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

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serves as a cofactor in the activation of protein C and its regulation of blood coagulation. [NIH]

Thromboses: The formation or presence of a blood clot within a blood vessel during life. [NIH]

Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thromboxanes: Physiologically active compounds found in many organs of the body. They are formed in vivo from the prostaglandin endoperoxides and cause platelet aggregation, contraction of arteries, and other biological effects. Thromboxanes are important mediators of the actions of polyunsaturated fatty acids transformed by cyclooxygenase. [NIH] Thrombus: An aggregation of blood factors, primarily platelets and fibrin with entrapment of cellular elements, frequently causing vascular obstruction at the point of its formation. Some authorities thus differentiate thrombus formation from simple coagulation or clot formation. [EU] Thrush: A disease due to infection with species of fungi of the genus Candida. [NIH] Thymus: An organ that is part of the lymphatic system, in which T lymphocytes grow and multiply. The thymus is in the chest behind the breastbone. [NIH] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH] Thyroid Gland: A highly vascular endocrine gland consisting of two lobes, one on either side of the trachea, joined by a narrow isthmus; it produces the thyroid hormones which are concerned in regulating the metabolic rate of the body. [NIH] Thyroid Hormones: Hormones secreted by the thyroid gland. [NIH] Tic: An involuntary compulsive, repetitive, stereotyped movement, resembling a purposeful movement because it is coordinated and involves muscles in their normal synergistic relationships; tics usually involve the face and shoulders. [EU] Tinnitus: Sounds that are perceived in the absence of any external noise source which may take the form of buzzing, ringing, clicking, pulsations, and other noises. Objective tinnitus refers to noises generated from within the ear or adjacent structures that can be heard by other individuals. The term subjective tinnitus is used when the sound is audible only to the affected individual. Tinnitus may occur as a manifestation of cochlear diseases; vestibulocochlear nerve diseases; intracranial hypertension; craniocerebral trauma; and other conditions. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] 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] Tonicity: The normal state of muscular tension. [NIH] Tonsillitis: Inflammation of the tonsils, especially the palatine tonsils. It is often caused by a bacterium. Tonsillitis may be acute, chronic, or recurrent. [NIH] Tonsils: Small masses of lymphoid tissue on either side of the throat. [NIH] Tooth Loss: The failure to retain teeth as a result of disease or injury. [NIH]

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Tooth Preparation: Procedures carried out with regard to the teeth or tooth structures preparatory to specified dental therapeutic and surgical measures. [NIH] Topical: On the surface of the body. [NIH] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] 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] Toxoplasmosis: The acquired form of infection by Toxoplasma gondii in animals and man. [NIH]

Trachea: The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi. [NIH] Transaminase: Aminotransferase (= a subclass of enzymes of the transferase class that catalyse the transfer of an amino group from a donor (generally an amino acid) to an acceptor (generally 2-keto acid). Most of these enzymes are pyridoxal-phosphate-proteins. [EU]

Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process. [NIH] Transduction: The transfer of genes from one cell to another by means of a viral (in the case of bacteria, a bacteriophage) vector or a vector which is similar to a virus particle (pseudovirion). [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Transfer Factor: Factor derived from leukocyte lysates of immune donors which can transfer both local and systemic cellular immunity to nonimmune recipients. [NIH] Transferases: Transferases are enzymes transferring a group, for example, the methyl group or a glycosyl group, from one compound (generally regarded as donor) to another compound (generally regarded as acceptor). The classification is based on the scheme "donor:acceptor group transferase". (Enzyme Nomenclature, 1992) EC 2. [NIH] Translation: The process whereby the genetic information present in the linear sequence of ribonucleotides in mRNA is converted into a corresponding sequence of amino acids in a protein. It occurs on the ribosome and is unidirectional. [NIH] Translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Translocation: The movement of material in solution inside the body of the plant. [NIH] Transplantation: Transference of a tissue or organ, alive or dead, within an individual, between individuals of the same species, or between individuals of different species. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock,

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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] Trees: Woody, usually tall, perennial higher plants (Angiosperms, Gymnosperms, and some Pterophyta) having usually a main stem and numerous branches. [NIH] Tremor: Cyclical movement of a body part that can represent either a physiologic process or a manifestation of disease. Intention or action tremor, a common manifestation of cerebellar diseases, is aggravated by movement. In contrast, resting tremor is maximal when there is no attempt at voluntary movement, and occurs as a relatively frequent manifestation of Parkinson disease. [NIH] Triad: Trivalent. [NIH] Trichomoniasis: An infection with the protozoan parasite Trichomonas vaginalis. [NIH] Trophoblast: The outer layer of cells of the blastocyst which works its way into the endometrium during ovum implantation and grows rapidly, later combining with mesoderm. [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] Tuberous Sclerosis: A rare congenital disease in which the essential pathology is the appearance of multiple tumors in the cerebrum and in other organs, such as the heart or kidneys. [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] Typhoid fever: The most important member of the enteric group of fevers which also includes the paratyphoids. [NIH] Typhoid fever: The most important member of the enteric group of fevers which also includes the paratyphoids. [NIH] Tyrosine: A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine, thyroid hormones, and melanin. [NIH] Ulcer: A localized necrotic lesion of the skin or a mucous surface. [NIH] Ulcerative colitis: Chronic inflammation of the colon that produces ulcers in its lining. This condition is marked by abdominal pain, cramps, and loose discharges of pus, blood, and mucus from the bowel. [NIH] Umbilical Arteries: Either of a pair of arteries originating from the internal iliac artery and passing through the umbilical cord to carry blood from the fetus to the placenta. [NIH] Umbilical Cord: The flexible structure, giving passage to the umbilical arteries and vein, which connects the embryo or fetus to the placenta. [NIH]

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Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Uraemia: 1. An excess in the blood of urea, creatinine, and other nitrogenous end products of protein and amino acids metabolism; more correctly referred to as azotemia. 2. In current usage the entire constellation of signs and symptoms of chronic renal failure, including nausea, vomiting anorexia, a metallic taste in the mouth, a uraemic odour of the breath, pruritus, uraemic frost on the skin, neuromuscular disorders, pain and twitching in the muscles, hypertension, edema, mental confusion, and acid-base and electrolyte imbalances. [EU]

Urea: A compound (CO(NH2)2), formed in the liver from ammonia produced by the deamination of amino acids. It is the principal end product of protein catabolism and constitutes about one half of the total urinary solids. [NIH] Urease: An enzyme that catalyzes the conversion of urea and water to carbon dioxide and ammonia. EC 3.5.1.5. [NIH] Uremia: The illness associated with the buildup of urea in the blood because the kidneys are not working effectively. Symptoms include nausea, vomiting, loss of appetite, weakness, and mental confusion. [NIH] Ureter: One of a pair of thick-walled tubes that transports urine from the kidney pelvis to the bladder. [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]

Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] Urinary tract: The organs of the body that produce and discharge urine. These include the kidneys, ureters, bladder, and urethra. [NIH] Urinary tract infection: An illness caused by harmful bacteria growing in the urinary tract. [NIH]

Urine: Fluid containing water and waste products. Urine is made by the kidneys, stored in the bladder, and leaves the body through the urethra. [NIH] Urogenital: Pertaining to the urinary and genital apparatus; genitourinary. [EU] Urolithiasis: Stones in the urinary system. [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] Uvea: The middle coat of the eyeball, consisting of the choroid in the back of the eye and the ciliary body and iris in the front of the eye. [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] Vaginitis: Inflammation of the vagina characterized by pain and a purulent discharge. [NIH] Vancomycin: Antibacterial obtained from Streptomyces orientalis. It is a glycopeptide related to ristocetin that inhibits bacterial cell wall assembly and is toxic to kidneys and the inner ear. [NIH]

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Vancomycin Resistance: Nonsusceptibility of bacteria, especially gram-positive cocci, to the action of vancomycin, an inhibitor of cell wall synthesis. [NIH] Varicella: Chicken pox. [EU] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vasculitis: Inflammation of a blood vessel. [NIH] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH] Vegetative: 1. Concerned with growth and with nutrition. 2. Functioning involuntarily or unconsciously, as the vegetative nervous system. 3. Resting; denoting the portion of a cell cycle during which the cell is not involved in replication. 4. Of, pertaining to, or characteristic of plants. [EU] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venous: Of or pertaining to the veins. [EU] Ventricle: One of the two pumping chambers of the heart. The right ventricle receives oxygen-poor blood from the right atrium and pumps it to the lungs through the pulmonary artery. The left ventricle receives oxygen-rich blood from the left atrium and pumps it to the body through the aorta. [NIH] Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Vertebrae: A bony unit of the segmented spinal column. [NIH] Vertebral: Of or pertaining to a vertebra. [EU] Vertigo: An illusion of movement; a sensation as if the external world were revolving around the patient (objective vertigo) or as if he himself were revolving in space (subjective vertigo). The term is sometimes erroneously used to mean any form of dizziness. [EU] Vestibule: A small, oval, bony chamber of the labyrinth. The vestibule contains the utricle and saccule, organs which are part of the balancing apparatus of the ear. [NIH] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Vibrio: A genus of Vibrionaceae, made up of short, slightly curved, motile, gram-negative rods. Various species produce cholera and other gastrointestinal disorders as well as abortion in sheep and cattle. [NIH] Vibrio cholerae: The etiologic agent of cholera. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Viral Hepatitis: Hepatitis caused by a virus. Five different viruses (A, B, C, D, and E) most commonly cause this form of hepatitis. Other rare viruses may also cause hepatitis. [NIH] Viral Load: The quantity of measurable virus in the blood. Change in viral load, measured in plasma, is used as a surrogate marker in HIV disease progression. [NIH] Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [NIH] Virulent: A virus or bacteriophage capable only of lytic growth, as opposed to temperate phages establishing the lysogenic response. [NIH] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH]

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Viscosity: A physical property of fluids that determines the internal resistance to shear forces. [EU] Vitro: Descriptive of an event or enzyme reaction under experimental investigation occurring outside a living organism. Parts of an organism or microorganism are used together with artificial substrates and/or conditions. [NIH] Vivo: Outside of or removed from the body of a living organism. [NIH] Vulgaris: An affection of the skin, especially of the face, the back and the chest, due to chronic inflammation of the sebaceous glands and the hair follicles. [NIH] Weight Gain: Increase in body weight over existing weight. [NIH] White blood cell: A type of cell in the immune system that helps the body fight infection and disease. White blood cells include lymphocytes, granulocytes, macrophages, and others. [NIH]

Whooping Cough: A respiratory infection caused by Bordetella pertussis and characterized by paroxysmal coughing ending in a prolonged crowing intake of breath. [NIH] Whooping Cough: A respiratory infection caused by Bordetella pertussis and characterized by paroxysmal coughing ending in a prolonged crowing intake of breath. [NIH] Windpipe: A rigid tube, 10 cm long, extending from the cricoid cartilage to the upper border of the fifth thoracic vertebra. [NIH] Womb: A hollow, thick-walled, muscular organ in which the impregnated ovum is developed into a child. [NIH] Wound Healing: Restoration of integrity to traumatized tissue. [NIH] Xenograft: The cells of one species transplanted to another species. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH] 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] Yolk Sac: An embryonic membrane formed from endoderm and mesoderm. In reptiles and birds it incorporates the yolk into the digestive tract for nourishing the embryo. In placental mammals its nutritional function is vestigial; however, it is the source of most of the intestinal mucosa and the site of formation of the germ cells. It is sometimes called the vitelline sac, which should not be confused with the vitelline membrane of the egg. [NIH] Zebrafish: A species of North American fishes of the family Cyprinidae. They are used in embryological studies and to study the effects of certain chemicals on development. [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]

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INDEX 1 1-phosphate, 207, 269, 326, 327 A Abdomen, 269, 279, 283, 307, 311, 314, 323, 324, 339, 340, 343 Abdominal, 3, 129, 237, 238, 269, 283, 291, 301, 323, 324, 325, 330, 346 Abdominal Pain, 3, 237, 238, 269, 301, 325, 346 Abscess, 3, 79, 82, 100, 115, 124, 144, 240, 269, 339 Acceptor, 269, 302, 303, 314, 323, 345 ACE, 7, 269 Acetylcholine, 269, 284, 321 Acetylglucosamine, 71, 185, 188, 210, 214, 216, 269 Acid Phosphatase, 152, 153, 269 Acidity, 269, 326 Acidosis, 36, 269 Acremonium, 269, 282 Acrosome, 35, 269 Acrylonitrile, 269, 336 Actinobacillus, 40, 145, 170, 269 Actinomyces, 52, 75, 100, 107, 149, 191, 269 Acute Disease, 4, 224, 269 Acute renal, 4, 269, 305 Adaptability, 270, 282 Adaptation, 50, 62, 65, 181, 270, 328 Adenine, 270, 333 Adenitis, 188, 228, 270 Adenosine, 171, 270, 327 Adenylate Cyclase, 270, 284 Adhesions, 27, 204, 270 Adjustment, 68, 270 Adjuvant, 18, 20, 23, 46, 59, 230, 270, 301 Adoptive Transfer, 10, 270 Adsorption, 40, 145, 150, 270 Adsorptive, 270 Aerobic, 50, 69, 118, 270, 323 Aerobic Metabolism, 50, 69, 270, 323 Aerobic Respiration, 270, 323 Affinity, 15, 23, 37, 39, 190, 204, 270 Agalactia, 205, 271 Agar, 85, 115, 175, 271, 289, 308, 327 Age Groups, 225, 271 Aged, 80 and Over, 271 Agonists, 184, 271

Air Pressure, 271, 297 Air Sacs, 271, 272 Airway, 19, 49, 58, 108, 170, 197, 271, 280 Albumin, 271, 322, 327, 328, 342 Algorithms, 271, 279 Alimentary, 269, 271, 324 Alkaline, 61, 66, 269, 271, 272, 280 Allantois, 271, 298 Allograft, 122, 271 Alpha-1, 271, 327 Alpha-Amylase, 87, 271 Alpha-Defensins, 271, 290 Alternative medicine, 149, 167, 242, 271 Alveoli, 197, 272 Amber, 272, 309 Amebiasis, 272, 317 Ameliorated, 180, 272 Amino Acid Sequence, 153, 175, 183, 186, 194, 210, 221, 223, 272, 273, 301 Ammonia, 272, 342, 347 Amnion, 272, 298 Amniotic Fluid, 24, 272 Amoxicillin, 4, 63, 72, 139, 155, 272 Ampicillin, 4, 272 Amplification, 105, 154, 195, 205, 222, 226, 272 Amylase, 87, 89, 272 Anaerobic, 155, 272, 304, 336, 340 Anaesthesia, 272, 309 Anal, 187, 272, 314 Analog, 55, 272, 285, 343 Analogous, 272, 292, 345 Analytes, 272, 342 Anaphylatoxins, 273, 286 Anatomical, 273, 283, 294, 309, 314, 336 Anchorage, 196, 273 Anemia, 3, 253, 273, 299 Anergy, 273, 341 Anesthesia, 271, 273 Angiogenesis, 199, 273, 316 Animal model, 13, 23, 33, 49, 54, 241, 273 Anions, 271, 273, 311, 341 Annealing, 273, 329 Anorectal, 164, 273 Antecedent, 41, 44, 273 Anthrax, 40, 273 Antibiotic Prophylaxis, 19, 237, 273 Antibody Affinity, 37, 274

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Anticoagulant, 274, 331 Antifungal, 274, 289 Antigen-Antibody Complex, 274, 286 Antigen-presenting cell, 38, 274, 290 Anti-infective, 9, 55, 274, 283, 307, 311 Anti-Infective Agents, 9, 274 Anti-inflammatory, 274, 291, 302, 309 Antimycotic, 274, 330 Antineoplastic, 274, 289 Antioxidant, 274, 323 Antiseptic, 178, 256, 274 Antiserum, 138, 274, 276 Anus, 272, 273, 274, 279, 286, 325 Anxiety, 233, 238, 274, 321, 324 Aorta, 274, 348 Aortic Aneurysm, 127, 274 Aortitis, 120, 274 Apolipoproteins, 274, 314 Apoptosis, 6, 24, 36, 58, 181, 275 Approximate, 231, 275 Aqueous, 214, 215, 275, 277, 289, 293, 307, 313, 314 Arachidonic Acid, 275, 293, 313, 331 Archaea, 275, 317 Arginine, 79, 159, 273, 275 Aromatic, 275, 281, 326, 341 Arterial, 275, 284, 307, 332, 342 Arteries, 274, 275, 279, 288, 314, 317, 344, 346 Arterioles, 275, 279, 280, 318 Arteriovenous, 275, 318 Artery, 275, 288, 293, 316, 332, 346 Arthroplasty, 124, 275 Articular, 32, 275 Aspartic, 119, 275, 294 Aspartic Acid, 119, 275 Aspiration, 43, 275 Assay, 21, 30, 38, 61, 68, 72, 93, 151, 154, 156, 206 Asymptomatic, 78, 272, 275, 324 Ataxia, 252, 275, 283, 343 Atrophy, 252, 276, 296 Attenuation, 198, 276 Atypical, 67, 75, 86, 276 Auditory, 276, 292, 305, 316 Autacoids, 276, 309 Autoantibodies, 48, 276 Autoantigens, 276 Autodigestion, 276, 324 Autoimmune disease, 178, 276, 327 Autoimmune Hepatitis, 276, 306 Autologous, 237, 276

Autonomic, 269, 276, 325 Autonomic Nervous System, 276, 325 Autopsy, 234, 276 Autoradiography, 51, 276 Avidity, 274, 276 Axonal, 13, 276 Azithromycin, 98, 276 B Bacillus, 40, 56, 175, 191, 199, 200, 223, 229, 273, 276 Bacteraemia, 105, 114, 115, 153, 225, 276 Bacteremia, 15, 27, 28, 49, 50, 52, 92, 184, 193, 194, 195, 204, 227, 230 Bacterial Adhesion, 204, 277 Bacterial Physiology, 270, 277 Bacterial Proteins, 54, 182, 277 Bactericidal, 16, 49, 79, 98, 176, 186, 277, 296 Bacteriocins, 176, 185, 186, 277 Bacteriophage, 77, 175, 242, 277, 327, 336, 345, 348 Bacteriostatic, 13, 176, 277, 296 Basal Ganglia, 99, 276, 277, 284, 333 Basal Ganglia Diseases, 276, 277, 284 Base, 37, 58, 60, 105, 228, 270, 277, 290, 299, 301, 312, 343, 346, 347 Basement Membrane, 277, 297, 312 Basophils, 277, 304, 313, 328 Bed Rest, 234, 257, 277 Benign, 277, 304, 320 Beta-Defensins, 278, 290 Beta-Lactam Resistance, 110, 278 Beta-Lactamases, 152, 278 Bifidobacterium, 145, 154, 159, 189, 278 Bilateral, 99, 278, 296 Bile, 238, 278, 289, 300, 302, 306, 314, 340 Bile Acids, 278, 340 Bile Acids and Salts, 278 Bile duct, 238, 278, 300 Biliary, 278, 280, 286, 324 Biliary Tract, 278, 280, 324 Bilirubin, 271, 278, 300, 302 Binding Sites, 35, 51, 52, 57, 182, 278 Bioavailability, 9, 278 Bioavailable, 21, 278 Biofilms, 21, 25, 33, 49, 51, 65, 72, 104, 136, 278 Biogenesis, 27, 278 Biological response modifier, 278, 310 Biomolecular, 278, 342 Biopsy, 257, 279, 325

353

Biotechnology, 61, 94, 162, 175, 242, 249, 251, 252, 253, 278, 279 Biotype, 61, 77, 128, 279 Biotypes, 61, 304 Bladder, 279, 309, 314, 320, 331, 347 Blastocyst, 279, 287, 323, 327, 346 Blood Coagulation, 279, 280, 335, 344 Blood pressure, 239, 279, 307, 319 Blood vessel, 208, 269, 271, 273, 279, 283, 294, 297, 302, 305, 311, 315, 325, 338, 342, 344, 348 Blot, 106, 279 Body Fluids, 279, 280, 292, 293, 340 Bone Marrow, 126, 279, 308, 315, 338 Bone Marrow Transplantation, 126, 279 Bowel, 178, 236, 237, 272, 279, 295, 300, 310, 311, 313, 320, 325, 340, 346 Bowel Movement, 279, 340 Bradykinin, 279, 328 Branch, 265, 279, 301, 315, 316, 324, 332, 339, 343 Breakdown, 279, 291, 300, 327 Broad-spectrum, 272, 279, 282 Bronchi, 279, 280, 296, 345 Bronchial, 231, 280, 306 Bronchioles, 272, 280 Bronchoalveolar Lavage, 49, 280 Bronchoalveolar Lavage Fluid, 49, 280 Bronchoconstriction, 280, 328 Bronchodilator, 16, 280 Bypass, 53, 280 C Calcification, 238, 280 Calcium, 21, 35, 36, 144, 151, 238, 280, 286, 293, 316, 317, 323, 327, 338 Calcium Carbonate, 238, 280 Calcium Hydroxide, 151, 280 Calcium Oxalate, 144, 280, 323 Calculi, 280 Cancer vaccine, 228, 280 Candidiasis, 235, 280 Candidosis, 280 Capillary, 14, 149, 279, 280, 281, 348 Capillary Fragility, 281 Capsules, 29, 40, 188, 210, 281, 301 Carbohydrate, 27, 55, 71, 80, 177, 193, 218, 227, 228, 281, 302, 303, 329, 337 Carbon Dioxide, 281, 327, 335, 347 Carboxy, 281 Carboxylic Acids, 192, 281 Carcinogen, 281, 317 Carcinogenic, 281, 310, 322, 330, 340

Carcinoma, 100, 124, 197, 281 Cardiac, 12, 36, 41, 281, 293, 294, 296, 320, 335, 340 Cardiovirus, 281, 294 Carrier Proteins, 29, 181, 193, 281, 328 Case report, 115, 116, 156, 281, 298 Catalyse, 281, 345 Catalytic Domain, 46, 281 Catechin, 160, 281 Catheter, 257, 281, 314 Cations, 281, 311 Caudate Nucleus, 277, 281, 288, 320 Causal, 42, 115, 194, 281, 305, 337, 343 Cause of Death, 36, 194, 281 Cecum, 281, 313 Cefotaxime, 67, 110, 126, 137, 282 Ceftriaxone, 4, 67, 125, 139, 282 Cefuroxime, 4, 282 Cell Adhesion, 80, 282, 310 Cell Death, 58, 275, 282 Cell Differentiation, 282, 338 Cell Division, 252, 277, 282, 316, 318, 327, 330, 336 Cell membrane, 281, 282, 290, 326 Cell proliferation, 239, 282, 338 Cell Respiration, 270, 282, 323, 335 Cell Size, 282, 299 Cellobiose, 214, 282 Cellulitis, 98, 188, 228, 239, 256, 282 Cellulose, 182, 282, 300, 327 Central Nervous System, 41, 180, 269, 276, 282, 300, 302, 304, 313 Central Nervous System Infections, 282, 304 Cephalosporins, 4, 278, 282 Cerebellar, 276, 283, 334, 346 Cerebellar Diseases, 276, 283, 346 Cerebral, 23, 121, 221, 276, 277, 283, 288, 294, 296, 297, 343 Cerebral Cortex, 276, 283, 297 Cerebral Palsy, 23, 221, 283 Cerebrospinal, 114, 138, 184, 283 Cerebrospinal fluid, 114, 138, 184, 283 Cerebrum, 283, 343, 346 Cervical, 188, 228, 283, 335 Cervix, 234, 283, 335 Cesarean Section, 24, 283 Character, 56, 283, 290 Chemotactic Factors, 283, 286 Chemotaxis, 27, 283 Chest Pain, 257, 283 Chest wall, 124, 283

354

Streptococcus

Chin, 283, 317 Chlorhexidine, 13, 123, 283 Chlorophyll, 283, 295, 300 Cholecystitis, 238, 283 Cholera, 46, 59, 283, 284, 337, 348 Cholera Toxin, 46, 59, 284 Cholesterol, 154, 278, 284, 300, 314, 316, 340 Cholesterol Esters, 284, 314 Choline, 73, 89, 170, 203, 204, 284 Chorea, 41, 237, 284 Chorion, 284, 298 Chromatin, 275, 284, 295 Chromosomal, 37, 53, 209, 224, 272, 284, 328 Chromosome, 284, 287, 304, 313, 336 Chronic, 6, 16, 32, 34, 45, 49, 51, 55, 199, 234, 235, 236, 237, 238, 252, 272, 284, 291, 295, 306, 309, 312, 324, 329, 332, 336, 338, 339, 341, 342, 344, 346, 347, 349 Chronic Fatigue Syndrome, 235, 237, 284 Chronic renal, 284, 329, 347 Chylomicrons, 284, 314 Cicatrix, 284, 312 Cicatrix, Hypertrophic, 284, 312 Ciprofloxacin, 62, 78, 82, 150, 217, 284 Cirrhosis, 201, 205, 221, 284 Clarithromycin, 101, 284 Clear cell carcinoma, 285, 291 Cleave, 35, 285 Clindamycin, 4, 90, 93, 106, 134, 239, 285 Clinical Medicine, 285, 330 Clinical trial, 5, 11, 16, 43, 58, 183, 249, 285, 288, 292, 332, 333 Clone, 12, 17, 40, 48, 53, 61, 62, 70, 75, 82, 83, 95, 98, 102, 112, 285 Cloning, 22, 25, 37, 51, 67, 91, 102, 152, 162, 196, 211, 279, 285, 310 Clostridium, 178, 192, 220, 285, 343 Clostridium difficile, 178, 285 Clot Retraction, 285, 328 Coagulation, 279, 285, 305, 328, 344 Cochlea, 285, 310 Cofactor, 35, 285, 332, 344 Coliphages, 277, 285 Colitis, 166, 178, 236, 285, 286 Collagenases, 17, 285 Collagenous Colitis, 178, 286 Colloidal, 271, 286, 293 Colon, 100, 178, 252, 285, 286, 297, 310, 313, 346 Colon Polyps, 178, 286

Colonic flora, 218, 286 Combination Therapy, 108, 286 Commensal, 31, 51, 76, 192, 269, 286 Common Bile Duct, 286, 289 Communication Disorders, 55, 248, 286 Complement Activation, 35, 57, 86, 273, 286 Complementary and alternative medicine, 149, 167, 286 Complementary medicine, 149, 287 Complete remission, 287, 334 Compulsions, 287, 321 Computational Biology, 249, 251, 287 Conception, 214, 287, 298, 338, 340 Concomitant, 175, 207, 287 Cone, 287, 341 Congestion, 287, 296 Conjugated, 10, 18, 30, 37, 40, 117, 194, 220, 230, 278, 287, 289 Conjugation, 18, 26, 30, 53, 193, 287 Conjunctiva, 287, 310 Conjunctivitis, 68, 184, 287 Connective Tissue, 279, 282, 285, 287, 290, 299, 300, 301, 304, 312, 315, 332, 335, 336, 342 Consciousness, 287, 292, 335 Constipation, 238, 287, 300, 325 Constriction, 287, 311 Consumption, 159, 179, 287, 291, 301, 321, 335 Contamination, 288, 321 Contractility, 24, 58, 288 Contraindications, ii, 288 Control group, 14, 288 Controlled study, 236, 288 Cornea, 288, 303 Corneum, 288, 295 Coronary, 288, 317 Coronary Thrombosis, 288, 317 Corpus, 288, 320, 324, 330 Corpus Striatum, 288, 320 Cortex, 288, 322, 330, 334 Cortical, 4, 288, 297, 336, 343 Corticosteroids, 16, 288, 302 Cortisone, 288, 291 Cranial, 288, 304, 324, 325 Craniocerebral Trauma, 277, 288, 304, 343, 344 Crossing-over, 288, 334 Cryptosporidiosis, 276, 288 Culture Media, 271, 288 Cultured cells, 175, 289

355

Curative, 289, 343 Cutaneous, 199, 200, 229, 273, 280, 289, 314 Cyclic, 171, 270, 289, 298, 331 Cyclosporins, 220, 289 Cystic Duct, 238, 286, 289 Cytochrome, 289, 335 Cytochrome b, 289, 335 Cytokine, 6, 23, 31, 33, 59, 69, 132, 289 Cytomegalovirus, 235, 237, 289 Cytoplasm, 275, 277, 282, 284, 289, 295, 335 Cytoskeleton, 289, 310 Cytotoxic, 40, 54, 289, 338 Cytotoxicity, 54, 91, 162, 289 D Dairy Products, 175, 289 Decidua, 24, 289, 327 Defense Mechanisms, 290, 310 Defensins, 40, 271, 278, 290 Degenerative, 12, 290, 305 Dehydration, 175, 283, 290 Deletion, 8, 37, 91, 275, 290 Delivery of Health Care, 290, 305 Denaturation, 290, 329 Dendrites, 290, 321 Dendritic, 6, 20, 290, 316 Dendritic cell, 6, 20, 290 Density, 34, 50, 65, 206, 216, 290, 299, 314, 322, 339 Dental Care, 240, 290 Dental Caries, 5, 11, 12, 21, 33, 46, 150, 160, 163, 186, 196, 203, 290, 299 Dental Plaque, 11, 25, 32, 34, 52, 75, 203, 290, 340 Dentists, 240, 290 Depolarization, 290, 338 Dermal, 53, 290 Dermatitis, 257, 290, 291 Dermatologist, 243, 290 Dermis, 36, 290, 312, 342 DES, 40, 176, 182, 273, 290 Deuterium, 291, 307 Developed Countries, 10, 219, 291 Developing Countries, 198, 209, 219, 291 Dexamethasone, 24, 291 Diagnostic procedure, 173, 242, 291 Diaper Rash, 208, 291 Diaphragm, 291, 328 Diarrhea, 165, 178, 208, 238, 239, 257, 272, 288, 291, 295, 300 Diastolic, 291, 307

Digestion, 271, 278, 279, 291, 311, 314, 324, 340 Dihydrotestosterone, 291, 334 Dilatation, 291, 330 Dimerization, 141, 291 Diphtheria, 35, 137, 193, 220, 291 Diploid, 291, 327 Direct, iii, 16, 18, 20, 49, 54, 55, 68, 116, 285, 291, 302, 307, 314, 332, 334, 342 Disaccharides, 188, 216, 291 Discrete, 51, 84, 291 Disease Progression, 291, 348 Dispenser, 208, 291 Dissection, 26, 291 Dissociation, 40, 270, 291 Dissociative Disorders, 292 Distal, 276, 292, 293 Distention, 238, 292 Dose-dependent, 49, 292 Double-blind, 44, 108, 155, 292 Drive, ii, vi, 56, 57, 143, 175, 240, 292 Dross, 292, 331 Drug Design, 45, 292 Drug Tolerance, 292, 344 Duct, 238, 286, 292, 336, 340, 342 Duodenum, 278, 292, 325, 340 Dura mater, 292, 317, 323 Dysplasia, 253, 292 Dystrophy, 252, 292 E Eardrum, 221, 292 Ecosystem, 34, 292 Edema, 181, 293, 347 Effector, 27, 269, 286, 293, 295 Efficacy, 4, 9, 13, 16, 18, 21, 22, 23, 32, 34, 37, 42, 44, 55, 58, 60, 108, 150, 155, 195, 226, 236, 292, 293 Ego, 293, 321 Eicosanoids, 24, 293 Ejaculation, 293, 337 Elastic, 188, 293, 339, 342 Elastin, 285, 293, 297 Electrode, 21, 293 Electrolytes, 278, 284, 293 Electron microscope, 58, 293 Electrophoresis, 43, 47, 52, 61, 63, 74, 81, 82, 87, 109, 163, 184, 185, 214, 293, 308 Emboli, 121, 293 Embryo, 272, 279, 282, 293, 298, 309, 317, 346, 349 Emollient, 293, 303 Empiric, 4, 293

356

Streptococcus

Empyema, 69, 102, 135, 184, 293 Emulsion, 276, 293 Enamel, 51, 52, 101, 290, 294, 312 Encapsulated, 9, 20, 29, 42, 93, 198, 210, 215, 219, 294 Encephalocele, 294, 320 Encephalomyelitis, 294 Encephalomyocarditis Virus, 215, 294 Endemic, 283, 294, 339 Endocarditis, 7, 12, 17, 49, 52, 67, 91, 102, 105, 108, 121, 139, 159, 184, 186, 280, 294 Endocardium, 294 Endogenous, 26, 32, 109, 153, 156, 181, 276, 293, 294, 302, 323, 331, 345 Endometrium, 289, 294, 317, 346 Endopeptidases, 294, 331 Endophthalmitis, 109, 124, 156, 294 Endothelial cell, 14, 19, 130, 132, 156, 294, 343 Endothelium, 19, 58, 294, 328 Endothelium, Lymphatic, 294 Endothelium, Vascular, 294 Endotoxin, 31, 295, 346 End-stage renal, 284, 295, 329 Enteric bacteria, 51, 295 Enteritis, 178, 295 Enterococcus, 7, 26, 48, 49, 52, 62, 66, 76, 77, 88, 106, 144, 174, 175, 191, 222, 295 Enterocolitis, 285, 295 Enterotoxins, 59, 295 Environmental Exposure, 295, 322 Environmental Health, 31, 248, 250, 295 Enzymatic, 32, 87, 170, 228, 272, 280, 281, 286, 290, 295, 306, 316, 329, 336 Enzyme Induction, 295, 334 Enzyme Inhibitors, 295, 328 Enzyme Repression, 295, 334 Eosinophilia, 295, 298 Eosinophils, 295, 304, 313 Epidemic, 5, 68, 84, 295, 339 Epidemiological, 5, 43, 49, 72, 74, 76, 84, 109, 157, 170, 177, 295, 298 Epidermal, 295, 312, 316 Epidermis, 202, 288, 290, 295, 306, 312, 330, 333 Epidural, 115, 296, 339 Epinephrine, 296, 321, 346 Epistaxis, 237, 296 Epithelial, 11, 18, 28, 35, 43, 80, 84, 88, 152, 158, 170, 208, 213 Epithelial Cells, 11, 19, 28, 35, 80, 84, 88, 152, 158, 170, 213

Epithelium, 145, 277, 294, 296, 323 Epitope, 30, 109, 193, 296 ERV, 250, 296, 297 Erysipelas, 188, 205, 223, 227, 228, 296 Erythema, 237, 257, 296 Erythema Nodosum, 257, 296 Erythrocytes, 273, 279, 296, 305, 334 Erythromycin, 4, 9, 61, 62, 64, 70, 77, 82, 85, 91, 92, 160 Essential Tremor, 252, 296 Estrogen, 197, 296 Ethanol, 296, 298 Eukaryotic Cells, 11, 90, 296 Eustachian tube, 145, 221, 297 Evacuation, 287, 297, 313 Evoke, 16, 297, 340 Excipient, 202, 297 Excitation, 297, 299, 321 Excitatory, 297, 302 Exogenous, 14, 20, 26, 270, 294, 297, 302, 331 Exotoxin, 38, 47, 53, 141, 239, 297 Expiratory, 296, 297 Expiratory Reserve Volume, 296, 297 Extensor, 297, 332 Extracellular, 9, 11, 12, 26, 47, 74, 83, 84, 88, 92, 152, 156, 182, 186 Extracellular Matrix, 12, 182, 287, 297, 299, 310, 316 Extracellular Matrix Proteins, 297, 316 Extracellular Space, 297 Extraction, 156, 186, 214, 283, 297 Exudate, 193, 297 F Fallopian tube, 297, 334 Familial polyposis, 178, 297 Family Planning, 249, 297 Fasciitis, 28, 53, 111, 119, 223, 224, 227, 238, 239, 298 Fat, 154, 257, 275, 278, 279, 293, 298, 313, 320, 335, 338, 342 Fatal Outcome, 298, 320 Fathers, 235, 298 Fatigue, 235, 237, 284, 298 Fatty acids, 144, 271, 281, 293, 298, 303, 331, 344 Feces, 159, 278, 287, 291, 298, 340 Fermentation, 9, 71, 175, 176, 188, 189, 298, 336 Ferrichrome, 15, 298 Fetal Blood, 24, 298 Fetal Development, 298, 320

357

Fetal Membranes, 24, 298 Fetal Monitoring, 234, 298 Fetus, 205, 283, 298, 327, 330, 346, 347 Fibrin, 199, 208, 279, 285, 298, 325, 328, 343, 344 Fibrinogen, 12, 73, 178, 298, 328, 343 Fibroblasts, 208, 298, 299 Fibrosarcoma, 298, 299 Fibrosis, 238, 253, 299, 336 Filtration, 124, 299 Fistula, 238, 299 Flatus, 299, 300 Flow Cytometry, 24, 59, 299 Fluorescence, 28, 89, 299 Fluorescent Dyes, 299 Fluoridation, 5, 22, 299 Fluorine, 299 Folate, 299 Fold, 13, 42, 44, 203, 299 Folic Acid, 234, 299 Forearm, 279, 298, 299 Frameshift, 299, 346 Frameshift Mutation, 299, 346 Free Radicals, 274, 292, 300 Friction, 243, 300 Fructose, 207, 208, 214, 300, 303 Functional Disorders, 237, 300 Fungi, 215, 235, 274, 287, 289, 294, 300, 304, 311, 317, 318, 319, 339, 344, 349 Fungus, 210, 211, 280, 282, 300, 319 G Galactosidases, 149, 300 Gallbladder, 238, 269, 278, 283, 289, 300, 314 Gallstones, 238, 278, 300 Ganglia, 269, 277, 300, 320, 325 Gangrene, 239, 300 Gangrenous, 300, 337 Gas, 21, 238, 272, 281, 296, 299, 300, 307, 321, 341 Gastric, 59, 272, 276, 300, 305, 306, 324, 325 Gastrin, 300, 306 Gastritis, 300, 305 Gastroenteritis, 300, 336 Gastrointestinal, 178, 279, 284, 296, 301, 313, 341, 348 Gelatin, 289, 301, 303, 341, 343 Gelatinase A, 7, 301 Gels, 215, 301 Gene Expression, 11, 14, 26, 32, 49, 62, 63, 71, 75, 198, 253, 301 Gene Fusion, 34, 301

Gene Library, 301 Genetic Code, 301, 321 Genetic Engineering, 207, 279, 285, 301 Genetic testing, 234, 301, 329 Genetics, 5, 6, 26, 27, 39, 41, 83, 185, 237, 287, 301 Genetics, Microbial, 5, 301 Genital, 24, 269, 284, 285, 301, 318, 347 Genitourinary, 301, 347 Genomic Library, 209, 301 Genotype, 279, 301, 326 Germ Cells, 301, 316, 322, 338, 349 Germ-free, 48, 301 Germinal Center, 24, 302 Gestation, 23, 302, 325, 327 Giardiasis, 302, 317 Gingivitis, 290, 302 Gland, 83, 210, 211, 270, 288, 302, 315, 316, 323, 331, 336, 340, 342, 344 Glomerular, 237, 302, 334 Glomeruli, 302 Glomerulonephritis, 63, 162, 188, 205, 224, 228, 236, 302, 308 Glomerulus, 302 Glucans, 21, 52, 182, 302 Glucocorticoid, 291, 302 Glucose, 69, 185, 190, 207, 208, 214, 252, 271, 282, 302, 303, 305, 310, 326, 327, 336 Glucosyltransferases, 21, 186, 302 Glucuronic Acid, 188, 210, 216, 302 Glucuronides, 302 Glutamate, 67, 302 Glutamic Acid, 40, 299, 302, 321, 330 Glutathione Peroxidase, 103, 303 Glycerol, 177, 303, 326 Glycerophospholipids, 303, 326 Glycine, 272, 278, 303, 315, 321, 337 Glycogen, 271, 303, 327 Glycoprotein, 66, 90, 223, 298, 303, 312, 319, 343, 346 Glycosaminoglycan, 210, 303 Glycoside, 291, 303, 307, 336 Glycosidic, 271, 282, 303, 320, 322, 327 Glycosylation, 27, 35, 303 Glycylglycine, 60, 303 Goats, 289, 303 Gonadal, 303, 340 Gonorrhea, 282, 303 Governing Board, 303, 330 Graft, 289, 303, 306, 309 Graft Rejection, 289, 303, 309 Grafting, 303, 309

358

Streptococcus

Gram-negative, 20, 56, 174, 176, 269, 282, 303, 304, 305, 336, 348 Gram-Positive Bacteria, 49, 67, 68, 199, 285, 304 Gram-Positive Cocci, 304, 348 Granulation Tissue, 208, 304 Granulocyte, 101, 304 Granulocytes, 150, 304, 338, 349 Granulomatous Disease, Chronic, 304, 335 Grasses, 299, 304 Growth, 11, 21, 25, 26, 32, 45, 49, 50, 56, 62, 65, 71, 73, 75, 76, 83, 86, 89, 90, 145, 146, 155, 157, 164, 175, 176, 189, 196, 199, 200, 206, 212, 214, 215, 229, 252 Gyrase, 69, 70, 78, 120, 304 H Habitual, 283, 304 Haemophilus, 10, 91, 95, 96, 120, 126, 140, 193, 198, 202, 215, 222, 282, 304 Haemophilus influenzae, 10, 91, 96, 120, 126, 140, 193, 198, 202, 215, 222, 304 Hair follicles, 290, 304, 340, 349 Half-Life, 20, 282, 304 Haploid, 304, 327 Haptens, 212, 271, 304 Headache, 239, 257, 304, 310, 330 Headache Disorders, 304 Health Care Costs, 205, 304, 305 Health Expenditures, 305 Hearing Disorders, 286, 305 Helicobacter, 178, 305 Helicobacter pylori, 178, 305 Hematogenous, 183, 305 Hemodialysis, 280, 305 Hemoglobin, 273, 296, 305 Hemoglobinuria, 252, 305 Hemolysis, 53, 223, 295, 305 Hemolytic, 4, 41, 61, 145, 155, 180, 199, 205, 207, 224 Hemorrhage, 288, 304, 305 Hemostasis, 305, 310 Hepatic, 238, 271, 286, 305 Hepatitis, 235, 237, 305, 306, 348 Hepatitis, Chronic, 235, 306 Hepatocellular, 306 Hepatocytes, 305, 306 Hereditary, 306, 335 Heredity, 301, 306 Herpes, 235, 306 Herpes Zoster, 306 Heterodimers, 306, 310 Heterogeneity, 75, 85, 91, 271, 306

Heterotrophic, 300, 306 Histamine, 273, 306 Histidine, 88, 119, 223, 230, 231, 306 Histocompatibility, 38, 306 Homeostasis, 24, 51, 92, 306 Homologous, 37, 67, 68, 90, 179, 288, 301, 306, 319, 336, 342 Hormonal, 276, 306 Hormone, 197, 234, 288, 290, 293, 296, 300, 306, 310, 311, 316, 330, 335, 338, 343, 344 Horny layer, 295, 306 Housekeeping, 48, 306 Humoral, 10, 18, 20, 24, 35, 51, 76, 303, 306 Humour, 306 Hybrid, 16, 39, 40, 59, 144, 195, 285, 307 Hybridization, 34, 87, 180, 195, 204, 222, 231, 307 Hydrogen, 79, 170 Hydrogen Peroxide, 79, 170, 303, 307, 313, 341 Hydrogenation, 307, 333 Hydrolases, 294, 300, 307 Hydrolysis, 15, 55, 89, 190, 207, 275, 278, 282, 307, 320, 325, 326, 332 Hydrophobic, 26, 274, 303, 307, 314 Hydroxylysine, 285, 307 Hydroxyproline, 272, 285, 307 Hyperlipidemia, 178, 307 Hyperreflexia, 307, 343 Hypersensitivity, 307, 313, 335 Hypertension, 4, 304, 307, 344, 347 Hypotension, 239, 307, 328 Hypothermia, 307, 320 Hypoxia, 181, 307, 343 Hypoxic, 307, 317 Hysterotomy, 283, 307 I Id, 147, 165, 206, 252, 259, 264, 266, 293, 307 Immune Complex Diseases, 274, 307, 327 Immune response, 6, 9, 10, 16, 18, 23, 24, 27, 28, 30, 35, 43, 46, 48, 49, 51, 57, 59, 130, 178, 191, 196, 201, 210, 212, 215, 220, 225, 230, 270, 273, 274, 276, 288, 303, 304, 308, 319, 341, 347, 348 Immune Sera, 308 Immunoassay, 121, 203, 308 Immunocompromised, 205, 225, 308 Immunodeficiency, 104, 252, 257, 308 Immunodiffusion, 271, 308 Immunoelectrophoresis, 271, 308 Immunogen, 20, 212, 308

359

Immunoglobulin, 8, 23, 44, 51, 59, 76, 119, 160, 164, 273, 308, 319 Immunohistochemistry, 24, 58, 308 Immunologic, 45, 46, 48, 190, 191, 270, 283, 308 Immunologic Factors, 48, 308 Immunology, 6, 24, 25, 28, 39, 44, 49, 51, 54, 65, 151, 153, 157, 161, 190 Immunosuppressive, 189, 228, 289, 302, 308, 343 Immunosuppressive therapy, 308 Immunotherapy, 49, 270, 308 Impairment, 275, 309, 317 Impetigo, 188, 205, 210, 224, 227, 228, 256, 309 Implantation, 122, 287, 309, 323 Impotence, 309, 339 In situ, 11, 36, 52, 120, 309 In vitro, 8, 9, 11, 21, 24, 27, 31, 32, 37, 42, 43, 49, 52, 54, 57, 58, 60, 78, 145, 150, 151, 156, 157, 210 In vivo, 10, 15, 21, 23, 24, 27, 28, 31, 43, 49, 52, 53, 54, 122, 127, 140, 196, 309, 323, 344 Incision, 307, 309, 311 Incontinence, 309, 339 Incubated, 50, 175, 223, 309 Incubation, 175, 309, 326 Indicative, 235, 309, 324, 348 Indomethacin, 24, 309 Induction, 10, 26, 30, 46, 47, 53, 55, 58, 59, 79, 88, 132, 157, 208, 309 Infant Mortality, 177, 309 Infant, Newborn, 271, 309 Infarction, 288, 309, 317 Infertility, 234, 309 Infiltration, 199, 238, 302, 310 Inflammatory bowel disease, 178, 236, 310 Influenza, 33, 55, 56, 215, 239, 310 Infuse, 24, 310 Infusion, 24, 310 Ingestion, 6, 236, 273, 310, 329 Inhalation, 40, 310, 329 Initiation, 10, 31, 34, 53, 310, 340, 345 Initiator, 42, 310 Inlay, 310, 335 Inner ear, 221, 282, 310, 347 Inoculum, 239, 310 Inorganic, 21, 310, 319, 327 Insertional, 51, 79, 310 Insight, 10, 24, 48, 50, 52, 57, 122, 310 Insomnia, 310, 330

Insulin, 310, 311 Integrins, 19, 310 Interferon, 14, 136, 179, 310, 311 Interferon-alpha, 311 Interstitial, 280, 297, 301, 311, 334 Interstitial Collagenase, 301, 311 Intestinal, 51, 69, 176, 178, 208, 212, 236 Intestinal Flora, 208, 311 Intestine, 178, 278, 279, 295, 311, 313, 340 Intracellular, 15, 26, 27, 28, 31, 36, 80, 87, 161, 309, 310, 311, 316, 331, 338 Intracellular Membranes, 311, 316 Intramuscular, 4, 16, 311, 324 Intramuscular injection, 16, 311 Intraocular, 294, 311 Intravenous, 12, 44, 239, 243, 257, 310, 311, 324 Intrinsic, 23, 271, 277, 311 Introns, 301, 311 Introspection, 235, 311 Involuntary, 277, 284, 296, 311, 320, 338, 344 Iodine, 58, 145, 214, 311 Ionizing, 295, 311, 336 Ions, 187, 269, 277, 292, 293, 307, 311, 318 Ischemia, 58, 180, 276, 311 Islet, 93, 127, 311 Isotope Labeling, 135, 312 J Joint, 23, 32, 135, 199, 275, 284, 312, 342 K Kb, 248, 312 Keloid, 243, 284, 312 Keratin, 312 Keratinocytes, 28, 312 Keratolytic, 290, 312 Keto, 312, 345 Kidney Disease, 219, 248, 253, 312 Kidney stone, 312, 323 Kinetic, 55, 123, 311, 312 L Labile, 286, 312 Labyrinth, 285, 310, 312, 337, 348 Laceration, 312, 343 Lactobacillus, 106, 154, 175, 176, 177, 191, 208, 212, 312 Lactobacillus acidophilus, 154, 208, 312 Laminin, 12, 80, 84, 277, 297, 312 Language Disorders, 286, 313 Large Intestine, 124, 178, 281, 311, 313, 334, 338 Lavage, 49, 313

360

Streptococcus

Laxative, 271, 313 LCD, 124, 313 Lectin, 213, 313, 316 Lens, 281, 313 Lethal, 33, 277, 313 Leukemia, 252, 313 Leukocytes, 24, 75, 114, 277, 279, 283, 295, 309, 311, 313, 346 Leukocytosis, 3, 313 Leukotrienes, 275, 293, 313 Levofloxacin, 74, 86, 108, 118, 120, 136, 150, 313 Library Services, 264, 313 Life cycle, 300, 313 Ligament, 79, 297, 313, 331 Ligands, 48, 310, 313, 342 Lincomycin, 93, 285, 313 Linkage, 19, 40, 153, 188, 216, 282, 300, 313, 325 Lipid, 46, 275, 284, 303, 310, 312, 313, 314, 323 Lipid Peroxidation, 313, 323 Lipopolysaccharide, 6, 125, 277, 303, 314 Lipoprotein, 61, 77, 80, 83, 153, 303, 314 Liquor, 314, 333 Lithotripsy, 58, 314 Litter, 51, 314 Localization, 24, 58, 67, 73, 308, 314 Localized, 19, 32, 257, 269, 290, 291, 294, 309, 312, 314, 322, 327, 336, 339, 343, 346 Locomotion, 314, 327 Longitudinal study, 45, 51, 314 Loop, 223, 314 Low-density lipoprotein, 314 Lucida, 312, 314 Lumbar, 135, 314 Lupus, 314, 342 Lymph, 59, 178, 239, 283, 294, 306, 314, 315 Lymph node, 59, 178, 239, 283, 314, 315 Lymphadenitis, 239, 315 Lymphangitis, 188, 228, 239, 315 Lymphatic, 240, 294, 309, 314, 315, 338, 339, 344 Lymphatic system, 314, 315, 338, 339, 344 Lymphocyte, 44, 48, 274, 315 Lymphocyte Count, 44, 315 Lymphocytic, 178, 315 Lymphoid, 24, 59, 273, 288, 302, 304, 315, 344 Lymphokines, 239, 315 Lymphoma, 24, 252, 315

Lysostaphin, 60, 81, 315 Lytic, 175, 315, 337, 348 M Macrolides, 78, 90, 91, 120, 131, 315 Macrophage, 6, 40, 48, 91, 145, 158, 315 Malabsorption, 252, 315 Malignancy, 37, 315 Malignant, 252, 274, 298, 315, 320, 336 Malnutrition, 5, 271, 276, 315, 319 Mammary, 83, 152, 158, 210, 211, 315, 316 Mammogram, 280, 315, 317 Manifest, 237, 239, 276, 315 Mannans, 300, 315 Mastication, 13, 315 Mastitis, 82, 145, 157, 179, 210, 211, 218, 316, 337, 340 Mastoiditis, 188, 228, 316 Matrix metalloproteinase, 24, 316 Measles Virus, 35, 316 Meatus, 292, 316, 322 Mediate, 12, 27, 31, 48, 54, 57, 177, 204, 293, 316 Medical Record Linkage, 19, 316 Medicament, 316, 341 MEDLINE, 249, 251, 253, 316 Megaloblastic, 299, 316 Meiosis, 316, 319, 342 Melanin, 316, 326, 346 Melanocytes, 316 Melanoma, 252, 316 Membrane Lipids, 316, 326 Membrane Proteins, 12, 193, 316 Memory, 10, 46, 119, 190, 227, 302, 316 Meninges, 4, 282, 288, 292, 316, 317 Meningitis, 4, 11, 13, 15, 27, 58, 81, 93, 165, 183, 184, 188, 193, 194, 195, 198, 199, 200, 201, 205, 206, 215, 218, 219, 221, 225, 228, 229, 230, 256 Menopause, 197, 317, 329 Menstrual Cycle, 317, 330 Menstruation, 215, 289, 317, 330 Mental, iv, 5, 45, 180, 239, 248, 250, 254, 257, 283, 286, 292, 298, 311, 316, 317, 332, 347 Mental Health, iv, 5, 45, 248, 250, 317, 332 Mental Processes, 292, 317, 332 Mental Retardation, 254, 286, 317 Mentors, 19, 317 Mercury, 299, 317 Mesoderm, 317, 346, 349 Metabolite, 47, 295, 317, 330 Metastasis, 316, 317

361

Methicillin Resistance, 60, 317 Methionine, 51, 85, 127, 317, 341 Metronidazole, 4, 317 MI, 73, 112, 220, 234, 267, 317 Microbe, 11, 184, 317, 345 Microcalcifications, 280, 317 Microcirculation, 18, 318, 328 Microorganism, 34, 56, 191, 197, 285, 318, 324, 349 Micro-organism, 197, 290, 292, 305, 318, 337 Microscopy, 11, 28, 34, 58, 59, 97, 240, 277, 318 Migration, 14, 18, 184, 185, 214, 318 Mineralization, 280, 318 Minocycline, 105, 318 Miocamycin, 105, 318 Miscarriage, 233, 234, 318 Miscible, 176, 318 Mitosis, 275, 318 Mobility, 47, 318 Mobilization, 41, 318 Modeling, 37, 140, 292, 318, 332 Modification, 30, 51, 53, 66, 70, 228, 237, 272, 301, 318, 333 Molecular mass, 145, 187, 318 Molecular Structure, 60, 318 Molecule, 6, 8, 19, 26, 29, 32, 38, 157, 179, 190, 193, 204, 274, 277, 278, 286, 292, 293, 296, 297, 302, 303, 307, 310, 313, 318, 321, 323, 327, 328, 332, 334, 338, 348 Monitor, 11, 30, 318, 321 Monoclonal, 71, 78, 109, 144, 170, 319 Monoclonal antibodies, 71, 144, 319 Monocyte, 6, 319 Monokines, 239, 319 Mononuclear, 79, 199, 298, 319, 346 Morbillivirus, 316, 319 Morphological, 121, 185, 214, 293, 300, 316, 319 Morphology, 51, 71, 188, 214, 275, 319 Motility, 204, 300, 309, 319 Mucins, 290, 319, 336 Mucociliary, 319, 338 Mucolytic, 280, 319 Mucosa, 78, 178, 295, 314, 319, 349 Mucus, 319, 346 Multivalent, 15, 193, 194, 220, 228, 276, 319 Muscle Fibers, 319 Muscular Atrophy, 252, 319 Muscular Dystrophies, 292, 319

Myalgia, 239, 310, 319 Mycosis, 319 Mycotic, 127, 319 Myocarditis, 281, 291, 294, 320 Myocardium, 317, 320 Myotonic Dystrophy, 252, 320 Myristate, 150, 320 N Nasal Mucosa, 310, 320 Nasopharynx, 29, 39, 50, 55, 113, 178, 192, 221, 231, 320 Natural selection, 278, 320 Nausea, 301, 320, 330, 347 Neonatal, 6, 11, 15, 19, 23, 27, 29, 58, 74, 101, 128, 201, 209, 218, 219, 221, 309, 320 Neonatorum, 129, 320 Neoplasia, 252, 320 Neoplasm, 320, 336, 339, 346 Neoplastic, 197, 315, 320 Neostriatum, 58, 281, 288, 320, 333 Nephropathy, 312, 320 Nerve, 221, 273, 276, 283, 290, 300, 320, 323, 329, 336, 339, 340, 344 Nervous System, 41, 180, 181, 252, 276, 282, 320, 321, 325, 348 Networks, 8, 320 Neural, 180, 234, 294, 306, 320 Neural tube defects, 234, 320 Neuraminidase, 55, 145, 161, 177, 319, 320 Neuronal, 13, 43, 180, 320 Neurons, 181, 290, 297, 300, 320, 321, 342 Neurotoxicity, 13, 321 Neurotransmitter, 269, 270, 272, 275, 279, 302, 303, 306, 321, 338, 341 Neutrophil, 14, 19, 54, 117, 130, 321 Nisin, 47, 187, 321 Nitrogen, 47, 222, 297, 318, 321, 346 Nonverbal Communication, 286, 321 Nosocomial, 7, 26, 174, 189, 228, 321 Nuclear, 14, 277, 287, 296, 321 Nuclei, 287, 301, 311, 318, 321, 332 Nucleic Acid Hybridization, 307, 321 Nutritional Status, 145, 154, 321 O Obsession, 234, 287, 321 Obsessive-Compulsive Disorder, 41, 321 Office Visits, 205, 322 Oleanolic Acid, 158, 322 Oligosaccharides, 30, 176, 193, 228, 229, 271, 320, 322 Oncogene, 252, 322 Oncogenic, 310, 322

362

Streptococcus

Opacity, 50, 69, 90, 290, 322 Operon, 15, 53, 73, 89, 92, 206, 214, 322, 334 Opportunistic Infections, 51, 322 Oral Health, 22, 322 Oral Hygiene, 13, 257, 322 Organ Transplantation, 289, 322 Orgasm, 293, 322, 337 Orofacial, 134, 322 Osteomyelitis, 115, 116, 210, 322 Osteoporosis, 197, 322 Otitis, 4, 34, 54, 69, 76, 165, 184, 188, 194, 195, 198, 213, 215, 219, 225, 228, 230 Otitis Media, 4, 34, 55, 69, 76, 165, 184, 188, 194, 195, 198, 213, 219, 225, 228 Outer ear, 221, 322 Outpatient, 20, 322 Ovalbumin, 18, 322 Ovaries, 322, 334 Ovary, 197, 322, 323 Overexpress, 48, 50, 323 Ovum, 289, 302, 313, 323, 330, 346, 349 Ovum Implantation, 323, 346 Oxalate, 144, 323 Oxalic Acid, 280, 323 Oxidants, 31, 323 Oxidation, 48, 190, 269, 274, 289, 303, 313, 323 Oxidation-Reduction, 323 Oxidative metabolism, 270, 313, 323 Oxidative Stress, 48, 51, 62, 71, 83, 89, 92, 323 P Pachymeningitis, 317, 323 Palate, 320, 323 Palliative, 323, 343 Palsy, 23, 221, 323 Pancreas, 269, 310, 311, 323, 324 Pancreatic, 135, 252, 323, 324 Pancreatic cancer, 252, 323 Pancreatic Pseudocyst, 135, 323 Pancreatitis, 257, 324 Panic, 234, 324 Paranasal Sinuses, 324, 338 Parasite, 324, 346 Parasitic, 178, 237, 288, 324 Parenteral, 16, 324 Parietal, 324, 325, 328 Paroxysmal, 252, 304, 324, 326, 349 Partial remission, 324, 334 Pathologic, 7, 269, 275, 279, 280, 288, 307, 324, 332

Pathologic Processes, 275, 324 Pathophysiology, 24, 31, 43, 238, 324 Patient Education, 256, 262, 264, 267, 324 Pelvic, 324, 331 Pelvis, 269, 312, 314, 322, 324, 347 Penicillin Resistance, 79, 220, 324 Penis, 293, 324, 335 Peptic, 305, 324 Peptic Ulcer, 305, 324 Peptide, 17, 20, 22, 26, 38, 40, 52, 60, 90, 179, 181, 185, 188, 190, 196, 201, 206, 217, 227 Peptide Chain Elongation, 284, 325 Peptide Fragments, 179, 325 Perception, 180, 287, 305, 325 Percutaneous, 314, 325 Perfusion, 307, 325 Pericarditis, 108, 325 Pericardium, 325, 342 Perinatal, 10, 221, 309, 325 Perineum, 325, 340 Periodontal disease, 11, 25, 31, 325 Periodontitis, 17, 32, 302, 325 Peripheral blood, 96, 311, 325 Peripheral Nervous System, 180, 321, 323, 325, 341 Periplasm, 21, 325 Peritoneum, 325 Peritonitis, 131, 325 Peroxide, 50, 63, 79, 170, 325 Personality Disorders, 180, 325 Pertussis, 326, 349 PH, 160, 326 Phagocyte, 323, 326 Phagocytosis, 7, 40, 48, 54, 57, 73, 74, 76, 100, 150, 193, 326 Pharmaceutical Preparations, 223, 282, 296, 301, 326 Pharmacokinetic, 81, 326 Pharmacologic, 273, 276, 304, 326, 345 Pharyngitis, 16, 45, 66, 68, 75, 98, 109, 123, 188, 205, 210, 223, 224, 227, 228, 326, 336 Pharynx, 310, 320, 326 Phenotype, 8, 20, 42, 50, 53, 64, 67, 69, 75, 93, 326 Phenylalanine, 326, 346 Pheromone, 26, 53, 326 Phlebitis, 257, 326 Phorbol, 150, 326 Phosphoglucomutase, 56, 65, 69, 326 Phospholipases, 326, 338 Phospholipids, 48, 298, 314, 316, 326

363

Phosphorus, 21, 280, 327 Phosphorylase, 207, 327 Phosphorylase a, 207, 327 Phosphorylase Phosphatase, 327 Phosphorylated, 35, 327 Phosphorylates, 160, 327 Phosphorylation, 27, 327 Phosphorylcholine, 48, 327 Physical Examination, 257, 327 Physicochemical, 30, 277, 327 Physiologic, 34, 74, 298, 304, 317, 327, 331, 334, 346 Physiology, 50, 55, 75, 133, 327, 341 Placenta, 298, 327, 330, 346 Plant Diseases, 295, 327 Plants, 156, 207 Plaque, 11, 21, 22, 25, 31, 34, 40, 52, 75, 151, 186, 203, 283, 327 Plasma, 12, 13, 41, 48, 199, 223, 271, 273, 282, 284, 294, 298, 301, 304, 305, 327, 328, 337, 348 Plasma cells, 199, 273, 304, 327 Plasma Exchange, 41, 327 Plasma protein, 12, 223, 271, 294, 327, 328 Plasmapheresis, 44, 328 Plasmid, 17, 22, 26, 37, 41, 53, 60, 186, 328, 348 Plasmin, 95, 146, 152, 210, 211, 328 Plasminogen, 30, 179, 328 Plasminogen Activators, 328 Plasticity, 56, 328 Platelet Activating Factor, 213, 328 Platelet Activation, 328, 338 Platelet Aggregation, 159, 273, 328, 344 Platelets, 96, 328, 343, 344 Platinum, 314, 328 Pleura, 328 Pleural, 184, 328 Pneumococcal Infections, 6, 17, 192, 194, 195, 213, 225, 231, 328 Pneumococcal Vaccines, 18, 183, 193, 203, 225, 329 Pneumonitis, 188, 228, 329 Poisoning, 301, 317, 320, 329, 336 Polycystic, 253, 329 Polymerase, 42, 93, 104, 105, 154, 329, 334 Polymerase Chain Reaction, 104, 105, 154, 329 Polymers, 11, 186, 278, 329, 332, 341 Polymorphic, 66, 92, 329 Polymorphism, 63, 69, 76, 88, 114, 329 Polyneuritis, 291, 329

Polyp, 178, 329 Polyposis, 178, 329 Polyvalent, 179, 217, 329 Posterior, 272, 276, 323, 329 Postmenopausal, 322, 329 Postoperative, 23, 236, 329 Postsynaptic, 329, 338 Post-translational, 30, 51, 329 Potentiation, 329, 338 Practice Guidelines, 250, 330 Precipitation, 176, 238, 330 Preclinical, 11, 13, 330 Precursor, 22, 53, 275, 284, 293, 295, 326, 328, 330, 346 Premenstrual, 237, 330 Premenstrual Syndrome, 237, 330 Prenatal, 205, 221, 234, 293, 330 Prevalence, 4, 5, 14, 42, 81, 86, 87, 116, 118, 132, 140, 146, 150, 177, 180, 195, 223, 330 Prickle, 312, 330 Probe, 56, 68, 77, 164, 196, 330 Prodrug, 202, 330 Progeny, 287, 330 Progesterone, 330, 340 Progression, 10, 32, 175, 208, 213, 273, 330 Progressive, 36, 42, 239, 282, 284, 292, 304, 319, 320, 328, 330, 334, 346 Proline, 285, 307, 330 Promoter, 8, 17, 32, 47, 53, 66, 96, 330 Prone, 21, 243, 330 Prophase, 319, 330, 342 Prophylaxis, 10, 19, 42, 176, 194, 202, 218, 221, 225, 227, 237, 330, 347 Propolis, 71, 157, 330 Proportional, 331, 342 Prospective study, 314, 331 Prostaglandin, 24, 331, 344 Prostaglandins A, 309, 331 Prostate, 197, 252, 331, 335, 337 Protease, 7, 20, 30, 32, 35, 39, 47, 56, 68, 74, 88, 89, 119, 151, 160, 286, 331 Protease Inhibitors, 21, 32, 331 Protein Binding, 58, 331 Protein Conformation, 272, 312, 331 Protein Engineering, 56, 332 Protein S, 58, 181, 215, 223, 253, 279, 284, 296, 301, 331, 332, 335, 340, 343 Proteoglycan, 32, 332 Proteolytic, 122, 155, 271, 286, 298, 328, 332 Protocol, 125, 163, 235, 332 Protons, 307, 311, 332, 333

364

Streptococcus

Protozoa, 287, 318, 332, 339 Psoriasis, 199, 332 Psychiatric, 286, 332 Psychic, 317, 332, 337 Psychology, 287, 292, 332 Public Health, 5, 16, 19, 22, 29, 31, 34, 41, 43, 105, 126, 136, 154, 250, 332 Public Policy, 249, 332 Pulmonary, 6, 14, 16, 18, 23, 31, 196, 279, 280, 287, 313, 332, 342, 348 Pulmonary Artery, 279, 332, 348 Pulse, 43, 51, 319, 332 Purifying, 186, 333 Purines, 333, 337 Purulent, 294, 333, 347 Pustular, 309, 333 Putamen, 277, 288, 320, 333 Putrefaction, 300, 333 Pyoderma, 205, 333 Pyogenic, 3, 322, 333, 337 Pyridoxal, 333, 345 Pyrimidines, 333, 337 Pyrogenic, 38, 47, 141, 239, 333 Q Quality of Life, 17, 333 Quinolones, 78, 217, 333 R Race, 318, 333 Radiation, 276, 295, 299, 300, 311, 317, 333, 336, 349 Radioactive, 276, 304, 307, 309, 312, 319, 321, 322, 333 Raffinose, 214, 333 Randomized, 13, 35, 44, 108, 139, 155, 293, 333 Reactive Oxygen Species, 36, 333 Reagent, 41, 203, 323, 333 Receptor, 6, 14, 15, 19, 26, 27, 31, 33, 35, 38, 42, 43, 55, 59, 74, 83, 90, 151, 164, 213 Recombination, 37, 68, 70, 79, 287, 334 Rectum, 178, 273, 274, 279, 286, 297, 299, 300, 309, 310, 313, 331, 334, 341 Recurrence, 114, 236, 334 Red blood cells, 199, 296, 305, 334, 336 Red Nucleus, 276, 334 Reductase, 51, 83, 334 Refer, 1, 200, 229, 286, 300, 306, 314, 321, 334, 345 Refraction, 334, 339 Refractory, 108, 334 Regeneration, 32, 334 Regimen, 46, 293, 334

Regulon, 8, 92, 334 Relapse, 236, 334 Relaxation Techniques, 234, 334 Remission, 236, 334 Renal failure, 4, 334 Repressor, 89, 127, 184, 322, 334 Repressor Proteins, 184, 334 Reproductive system, 214, 334 Respiration, 281, 298, 318, 335 Respiratory Burst, 40, 335 Restoration, 6, 32, 335, 336, 349 Resuscitation, 36, 335 Retinoblastoma, 252, 335 Reversion, 179, 335, 346 Rheumatism, 335 Rheumatoid, 32, 199, 323, 335 Rheumatoid arthritis, 32, 199, 335 Rhinitis, 335, 337 Rhinovirus, 108, 335 Ribose, 270, 335 Ribosome, 335, 345 Rigidity, 327, 335 Risk factor, 116, 331, 335 Ristocetin, 335, 347 Rod, 101, 269, 276, 277, 278, 304, 312, 335, 336 Root Caries, 17, 335 Rubber, 163, 269, 335 Rural Population, 13, 336 S Saccule, 336, 348 Saliva, 11, 25, 40, 46, 51, 52, 72, 75, 89, 144, 145, 150, 170, 203, 240 Salivary, 11, 25, 40, 46, 51, 52, 76, 146, 150, 151, 152, 240 Salivary glands, 289, 290, 336 Salivary Proteins, 25, 336 Salmonella, 57, 120, 176, 257, 301, 336 Salmonellosis, 176, 336 Sanitary, 179, 336 Saponins, 322, 336, 340 Sarcoma, 235, 299, 336 Scarlet Fever, 188, 205, 224, 227, 228, 336 Scintillation Counting, 21, 336 Scleroderma, 298, 336 Sclerosis, 252, 253, 336 Screening, 21, 87, 97, 137, 162, 181, 184, 190, 205, 209, 218, 219, 221, 285, 336 Sebaceous, 290, 336, 349 Sebaceous gland, 290, 336, 349 Secretion, 24, 46, 271, 306, 319, 336, 337 Secretory, 9, 16, 32, 35, 46, 51, 76, 271, 336

365

Segregation, 334, 336 Seizures, 180, 324, 336 Semen, 118, 293, 331, 337 Semicircular canal, 310, 337 Seminal fluid, 215, 337 Semisynthetic, 272, 282, 284, 285, 318, 337 Senile, 322, 337 Sensory loss, 337, 339, 343 Sepsis, 11, 15, 27, 29, 36, 58, 188, 193, 201, 205, 213, 218, 219, 221, 224, 227, 228 Septic, 120, 337 Septicaemia, 94, 219, 225, 337 Sequence Analysis, 17, 37, 61, 337 Sequencing, 51, 66, 305, 329, 337 Sequester, 32, 337 Serine, 7, 35, 39, 294, 337 Serologic, 83, 86, 308, 337 Serotypes, 6, 15, 18, 23, 37, 42, 44, 70, 72, 75, 83, 84, 85, 88, 90, 92, 110, 113, 116, 121, 122, 135, 183, 193, 194, 215, 218, 223, 225, 227, 231, 337 Serous, 294, 328, 337 Sex Determination, 253, 337 Shedding, 52, 337 Shock, 28, 38, 58, 71, 81, 101, 113, 115, 205, 210, 224, 227, 238, 239, 314, 337, 345 Side effect, 338, 345 Signal Transduction, 27, 39, 204, 338 Signs and Symptoms, 3, 31, 239, 334, 338, 347 Sinusitis, 184, 199, 200, 215, 219, 229, 338 Skeleton, 312, 331, 338 Skull, 288, 294, 320, 338, 343 Small intestine, 281, 284, 289, 292, 295, 302, 306, 311, 338 Smooth muscle, 58, 273, 276, 280, 306, 338, 341 Sneezing, 326, 337, 338 Social Environment, 333, 338 Soft tissue, 239, 279, 298, 299, 338 Solid tumor, 273, 338 Solvent, 46, 176, 296, 303, 338 Soma, 338 Somatic, 24, 37, 306, 316, 318, 325, 338 Somatic mutations, 24, 37, 338 Sound wave, 221, 339 Specialist, 58, 259, 339 Specificity, 15, 23, 26, 37, 51, 149, 225, 271, 294, 339 Spectrophotometry, 21, 339 Spectrum, 41, 45, 50, 70, 176, 199, 200, 229, 318, 339

Sperm, 269, 284, 337, 338, 339 Sperm Head, 269, 339 Spina bifida, 320, 339 Spinal cord, 181, 282, 283, 284, 292, 294, 296, 316, 320, 323, 325, 339 Spinal Cord Compression, 181, 339 Spinal Fractures, 339 Spinal Nerves, 325, 339 Spinous, 295, 312, 339 Spleen, 13, 18, 119, 289, 315, 339 Sporadic, 335, 339 Spores, 310, 339 Sputum, 197, 339 Stabilization, 23, 339 Staphylococcus aureus, 61, 78, 93, 145, 181, 197, 202, 222, 243, 257 Stenosis, 340, 341 Sterile, 5, 221, 340 Sterility, 309, 340 Steroid, 16, 23, 278, 288, 302, 336, 340 Stimulus, 14, 62, 288, 292, 293, 297, 340, 343 Stomach, 269, 276, 300, 301, 306, 313, 320, 324, 326, 338, 339, 340 Stool, 194, 286, 309, 313, 340 Strand, 41, 329, 340 Streptococcal Infections, 15, 38, 54, 177, 209, 210, 256, 258, 340 Streptococcal Vaccines, 16, 340 Streptomycin, 163, 340 Stress, 4, 5, 62, 78, 93, 234 Striatum, 320, 341 Stricture, 238, 340, 341 Styrene, 336, 341 Subacute, 309, 338, 341 Subarachnoid, 304, 341 Subclinical, 309, 336, 341 Subcutaneous, 199, 200, 229, 237, 257, 282, 293, 300, 315, 320, 324, 341 Subspecies, 236, 339, 341 Substance P, 144, 296, 317, 335, 336, 340, 341 Substrate, 17, 21, 55, 63, 161, 175, 197, 281, 295, 307, 320, 334, 341 Suction, 299, 341 Sulfur, 297, 317, 341 Superantigens, 38, 137, 239, 341 Superinfection, 33, 341 Superoxide, 68, 89, 105, 335, 341 Superoxide Dismutase, 68, 89, 105, 341 Superstitions, 234, 341 Supplementation, 6, 341

366

Streptococcus

Suppositories, 215, 301, 341 Surface Plasmon Resonance, 56, 342 Surfactant, 19, 99, 342 Sweat, 290, 342 Sweat Glands, 290, 342 Symphysis, 283, 331, 342 Symptomatic, 44, 78, 324, 342 Synaptic, 321, 338, 342 Synergistic, 9, 33, 342, 344 Synovial, 188, 199, 342 Synovial Fluid, 188, 199, 342 Synovial Membrane, 342 Systemic disease, 54, 342 Systemic lupus erythematosus, 128, 308, 342 Systolic, 307, 342 T Tachycardia, 277, 342 Tachypnea, 277, 342 Tandem Repeat Sequences, 37, 342 Teichoic Acids, 304, 342 Telangiectasia, 252, 342 Telencephalon, 277, 283, 343 Temporal, 7, 23, 136, 175, 304, 305, 316, 343 Testosterone, 334, 343 Tetani, 220, 343 Tetanic, 343 Tetanus, 137, 191, 193, 220, 343 Tetracycline, 70, 76, 83, 85, 105, 318, 343 Thalamic, 276, 343 Thalamic Diseases, 276, 343 Therapeutics, 33, 125, 194, 343 Thermal, 68, 292, 329, 343 Thiamphenicol, 120, 343 Thorax, 269, 314, 343 Threonine, 337, 343 Threshold, 307, 343 Thrombin, 298, 328, 331, 343 Thrombocytes, 328, 343 Thrombocytopenia, 328, 343 Thrombolytic, 328, 343 Thrombomodulin, 331, 343 Thromboses, 99, 344 Thrombosis, 310, 332, 344 Thromboxanes, 275, 293, 344 Thrombus, 288, 309, 328, 343, 344 Thrush, 280, 344 Thymus, 6, 18, 37, 308, 315, 344 Thyroid, 235, 311, 344, 346 Thyroid Gland, 235, 344 Thyroid Hormones, 344, 346

Tic, 45, 344 Tinnitus, 322, 344 Tolerance, 21, 33, 42, 68, 89, 123, 130, 131, 170, 206, 270, 344 Tone, 322, 323, 344 Tonicity, 305, 344 Tonsillitis, 205, 336, 344 Tonsils, 344 Tooth Loss, 22, 344 Tooth Preparation, 270, 345 Topical, 13, 36, 40, 58, 136, 283, 296, 307, 345 Toxicity, 9, 31, 40, 155, 317, 335, 345 Toxicology, 250, 345 Toxin, 38, 43, 46, 53, 59, 180, 199, 207, 285, 291, 295, 343, 344, 345 Toxoid, 35, 137, 191, 193, 220, 345 Toxoplasmosis, 276, 345 Trachea, 279, 326, 344, 345 Transaminase, 55, 345 Transcription Factors, 50, 345 Transduction, 28, 39, 204, 206, 338, 345 Transfection, 279, 345 Transfer Factor, 308, 345 Transferases, 303, 345 Translation, 93, 200, 229, 272, 296, 345 Translational, 30, 51, 345 Translocation, 14, 28, 284, 296, 345 Transplantation, 42, 111, 284, 308, 345 Trauma, 36, 101, 180, 208, 243, 324, 345 Treatment Failure, 4, 346 Trees, 272, 335, 346 Tremor, 252, 346 Triad, 230, 231, 346 Trichomoniasis, 317, 346 Trophoblast, 35, 279, 346 Tryptophan, 285, 346 Tuberous Sclerosis, 253, 346 Tumor Necrosis Factor, 79, 94, 103, 153, 346 Tumour, 116, 346 Tunica, 319, 346 Typhimurium, 20, 346 Typhoid fever, 191, 346 Tyrosine, 14, 35, 170, 346 U Ulcer, 53, 282, 304, 346 Ulcerative colitis, 178, 236, 310, 346 Umbilical Arteries, 346 Umbilical Cord, 188, 233, 271, 346 Unconscious, 290, 307, 347 Uraemia, 324, 347

367

Urea, 342, 347 Urease, 71, 305, 347 Uremia, 334, 347 Ureter, 314, 347 Urethra, 324, 331, 347 Urinary, 49, 138, 223, 280, 282, 284, 301, 309, 347 Urinary tract, 49, 223, 282, 347 Urinary tract infection, 49, 223, 347 Urine, 223, 279, 280, 291, 302, 305, 309, 312, 323, 347 Urogenital, 59, 301, 303, 347 Urolithiasis, 144, 347 Uterus, 283, 288, 289, 294, 307, 317, 322, 330, 335, 347 Uvea, 294, 347 V Vaccination, 23, 37, 46, 48, 59, 121, 139, 170, 183, 191, 231, 347 Vagina, 215, 278, 280, 283, 291, 307, 312, 317, 335, 347 Vaginal, 58, 87, 133, 139, 164, 205, 214, 218, 347 Vaginitis, 214, 280, 347 Vancomycin, 26, 72, 80, 108, 123, 125, 131, 139, 206, 347, 348 Vancomycin Resistance, 72, 348 Varicella, 115, 136, 348 Vascular, 58, 120, 127, 181, 290, 294, 304, 309, 318, 327, 328, 344, 348 Vasculitis, 324, 348 Vector, 26, 91, 130, 196, 310, 345, 348 Vegetative, 40, 348 Vein, 275, 311, 321, 326, 346, 348 Venous, 275, 332, 348 Ventricle, 281, 332, 342, 348 Venules, 279, 280, 294, 318, 348 Vertebrae, 339, 348 Vertebral, 339, 348

Vertigo, 322, 348 Vestibule, 215, 285, 310, 336, 337, 348 Veterinary Medicine, 249, 348 Vibrio, 283, 284, 348 Vibrio cholerae, 283, 284, 348 Viral, 33, 35, 38, 44, 178, 234, 237, 306, 310, 322, 345, 348 Viral Hepatitis, 306, 348 Viral Load, 44, 348 Virulent, 40, 54, 56, 67, 69, 77, 93, 175, 183, 223, 348 Virus, 33, 35, 55, 78, 104, 215, 220, 257, 277, 281, 282, 301, 311, 327, 345, 348 Viscosity, 214, 349 Vitro, 21, 24, 37, 43, 57, 68, 72, 78, 80, 81, 92, 155, 158 Vivo, 10, 15, 21, 23, 24, 27, 28, 31, 43, 49, 50, 52, 54, 79, 89, 196, 349 Vulgaris, 166, 349 W Weight Gain, 234, 349 White blood cell, 3, 269, 273, 304, 309, 313, 315, 319, 321, 327, 349 Whooping Cough, 220, 326, 349 Windpipe, 326, 344, 349 Womb, 335, 347, 349 Wound Healing, 207, 208, 284, 310, 316, 349 X Xenograft, 273, 349 X-ray, 30, 35, 55, 299, 315, 321, 349 Y Yeasts, 280, 300, 311, 326, 349 Yolk Sac, 298, 349 Z Zebrafish, 54, 91, 349 Zygote, 287, 349 Zymogen, 331, 349

368

Streptococcus

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