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

LUNG

INFECTION 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., 1960Lung Infection: 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: 0-497-00684-7 1. Lung Infection-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 lung infection. 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 LUNG INFECTION ...................................................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Lung Infection............................................................................... 4 E-Journals: PubMed Central ....................................................................................................... 27 The National Library of Medicine: PubMed ................................................................................ 28 CHAPTER 2. ALTERNATIVE MEDICINE AND LUNG INFECTION...................................................... 55 Overview...................................................................................................................................... 55 National Center for Complementary and Alternative Medicine.................................................. 55 Additional Web Resources ........................................................................................................... 56 General References ....................................................................................................................... 57 CHAPTER 3. PATENTS ON LUNG INFECTION .................................................................................. 59 Overview...................................................................................................................................... 59 Patent Applications on Lung Infection........................................................................................ 59 Keeping Current .......................................................................................................................... 61 CHAPTER 4. PERIODICALS AND NEWS ON LUNG INFECTION ........................................................ 63 Overview...................................................................................................................................... 63 News Services and Press Releases................................................................................................ 63 Academic Periodicals covering Lung Infection ............................................................................ 65 CHAPTER 5. RESEARCHING MEDICATIONS .................................................................................... 67 Overview...................................................................................................................................... 67 U.S. Pharmacopeia....................................................................................................................... 67 Commercial Databases ................................................................................................................. 68 APPENDIX A. PHYSICIAN RESOURCES ............................................................................................ 71 Overview...................................................................................................................................... 71 NIH Guidelines............................................................................................................................ 71 NIH Databases............................................................................................................................. 73 Other Commercial Databases....................................................................................................... 75 APPENDIX B. PATIENT RESOURCES ................................................................................................. 77 Overview...................................................................................................................................... 77 Patient Guideline Sources............................................................................................................ 77 Finding Associations.................................................................................................................... 80 APPENDIX C. FINDING MEDICAL LIBRARIES .................................................................................. 83 Overview...................................................................................................................................... 83 Preparation................................................................................................................................... 83 Finding a Local Medical Library.................................................................................................. 83 Medical Libraries in the U.S. and Canada ................................................................................... 83 ONLINE GLOSSARIES.................................................................................................................. 89 Online Dictionary Directories ..................................................................................................... 89 LUNG INFECTION DICTIONARY ............................................................................................. 91 INDEX .............................................................................................................................................. 127

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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 lung infection 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 lung infection, 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 lung infection, 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 lung infection. 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 lung infection, 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 lung infection. The Editors

1 From

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

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

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

Floss or Die: Implications for Dental Professionals Source: Dentistry Today. 17(7): 76,78,80-82. July 1998. Contact: Available from Dentistry Today, Inc. 26 Park Street, Montclair, NJ 07042. (973) 783-3935. Summary: 'Floss or die' is a phrase coined by Dr. Raul Garcia, a research periodontist from Boston, Massachusetts, at a recent dental research conference. Since the original media attention, a number of newspapers and magazines have run related stories on the possible association of periodontal disease with a series of potentially life-threatening disorders. This article reviews current research in this area, summarizing the implications for practicing dental professionals. One study pointed to the possible causal relationship between certain plaque bacteria and aberrant blood platelet activity;

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such an interaction could result in an increased risk for blood clots, which are associated with myocardial infarction. A great deal of circumstantial evidence links untreated periodontal disease to endocarditis and lung infections in patients with chronic obstructive pulmonary disease. Furthermore, periodontal infection can affect the stability of type 1 diabetes and can weaken the host immune system. The authors report briefly on research that is looking for strategies to determine risk assessment for disease activity at susceptible sites in periodontal patients. Although there is much happening on the research front, the primary tool and most effective clinical treatment concept for periodontal disease management is still control of dental plaque. By suppressing plaque formation, the risk of destructive periodontal infection, with its attendant loss of supporting structure, is lowered. In addition, according to current research, dentists may also be lowering the risk of several potentially fatal diseases. The remainder of the article briefly reviews the equipment and supplies available for this plaque-fighting effort, including the role of toothbrushing and flossing. Statistics estimate that only 2 to 10 percent of the population flosses regularly and effectively; this patient noncompliance is an overriding consideration in establishing therapy. 9 figures. 13 references.

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

Project Title: AEROSOL INFECTION MOUSE MODEL FOR CYSTIC FIBROSIS Principal Investigator & Institution: Yu, Hongwei; Micro/Immunol/Molec Genetics; Marshall University Huntington, Wv 25701 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2004 Summary: Chronic respiratory infections with Pseudomonas aeruginosa are the primary causes of high morbidity and mortality in cystic fibrosis (CF). We have recently developed a unique pulmonary infection mouse model that depends on the artificially generated P. aeruginosa aerosol to cause a uniform whole-lung infection in mice. The focus of this revised proposal is to test a group of 90 clinical CF isolates of P. aeruginosa for innate lung clearance, cytokine profiles and histopathology in this aerosol infection

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

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model. The hypothesis to be tested here is that the hypervariable chromosomal restriction fragment length polymorphisms (RFLPs) of the clinical CF sputum isolates may contribute to i) variations in bacterial respiratory colonization capacity, ii) altered levels of cytokine production by the host, and iii) the different outcomes of lung pathology. This is based on our following recent observations. First, we have applied the technique of pulsed field gel electrophoresis (PFGE) to analyze a collection of 90 clinical CF isolates for their genomic profiles. We have established a database composed of 75 unique Spe-I restriction digest PFGE profiles. Out of 90 strains tested, we identified one isolate CF32 that had identical Spe-I, Xba-I and Dpn-I digest PFGE patterns as P. Aeruginosa PAO1, a standard reference strain of a wound origin. Secondly, we passed PAO1 and 3 other CF isolates including the PAO-1 like CF isolate through the aerosol infection system to test for the pulmonary clearance and production of tumor necrosis factor (TNF)-a. PA01 and CF32 showed a similar pattern of lung clearance and TNF-a induction in the C57BL/6J and BALB/cJ mice. However, the other 2 CF isolates were more resistant to the clearance by the BALB/cJ mice. One isolate (CF45) caused a significant induction of TNF-a by the murine lungs. These results indicate that the genomes of the CF isolates are highly diversified, and the genomic diversity may affect their intrinsic biological properties. More importantly, it's feasible to use the aerosol apparatus to assess the remaining CF isolates for their virulence properties. The future directions that this project may lead to include i) investigations of the novel Pseudomonas genes induced due to lung colonizations; ii) exploration of the novel DNA fragments missing in the PAO1 genome but present in a subset of the CF isolates; iii) DNA immunization and testing for protection, and iv) evaluation of some selected CF isolates in the aerosol mouse model. By achieving the research objective of this Academic Research Enhancement Award (AREA) that is to establish and infection database for the CF isolates in the aerosol model, we will have an essential base of knowledge from which to prepare a future R01 application to investigate the novel virulence mechanisms associated with the clinical CF isolates of P. aeruginosa. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

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 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

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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: ALVEOLAR MACROPHAGE AND MYCOBACTERIA Principal Investigator & Institution: Martin, William J.; Dean; Internal Medicine; University of Cincinnati 2624 Clifton Ave Cincinnati, Oh 45221 Timing: Fiscal Year 2003; Project Start 22-SEP-2003; Project End 31-AUG-2008 Summary: (provided by applicant): Profound immunosuppression as occurs in HIVinfected subjects is frequently associated with complicating mycobacterial infections. Mycobacterium tuberculosis is a worldwide pathogen and is a major cause of morbidity and mortality in both normal and immunosuppressed subjects. Non-tuberculous mycobacteria such as M. avium can be opportunistic infections that infect immunosuppressed individuals or subjects with underlying disorders such as pulmonary silicosis. Regardless of whether mycobacteria are acting as pathogens or opportunistic infectious organisms, mycobacteria in the lung first infect alveolar macrophages (AMs), the resident inflammatory cell of the alveolar spaces. AMs must be primed and activated by cytokines such as IFN-gamma or TNF-alpha to maximally respond to infectious organisms such as mycobacteria. Although it is recognized that AMs are central to the pathogenesis of mycobacterial disease, there are few studies that have examined the role of AMs in vivo in response to mycobacterial infection. We have developed a novel approach to "reconstitute" normal and activated AMs into the lungs of immunodeficient animals. We will use this new approach to test the hypothesis Deficiencies in the response of AMs to mycobacteria such as MAC or M. tuberculosis permit initial lung infection and subsequent dissemination during immunosuppression; conversely, correction of these AM deficiencies will restore alveolar immunity, control lung infection and prevent dissemination. We will examine the underlying mechanisms by which AMs respond in vivo to mycobacterial infection and will then use a variety of strategies to activate AMs for reconstitution to see if alveolar host defense is restored and infection eradicated. This will also test whether AMs activated by pro-inflammatory cytokines such as IFN-gamma mediate alveolar host defense to mycobacteria by AMderived TNF-alpha. These Specific Aims include: 1) to determine the mechanisms by which normal AMs reconstituted into the lungs of immunodeficient mice restore alveolar host defense to mycobacteria and prevent dissemination, 2) to determine if proinflammatory cytokines such as IFN-gamma are essential for alveolar host defense to mycobacteria and to prevent dissemination, 3) to determine if ex vivo gene therapy to

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reconstituted macrophages results in persistent overexpression of pro-inflammatory cytokines such as IFN-gamma in vivo and improves alveolar host defenses to mycobacteria and prevents dissemination, and 4) to determine if the effects of proinflammatory cytokines such as IFN-? on alveolar host defenses to mycobacteria are mediated by AM-derived TNF-alpha. This proposal will test hypotheses in vivo not possible by other means and will determine whether reconstitution of normal or activated AMs is sufficient to restore alveolar host defense to mycobacterial disease despite the presence of ongoing systemic immunosuppression. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ALVEOLAR MACROPHAGE INNATE IMMUNE FUNCTION IN HIV Principal Investigator & Institution: Koziel, Henry; Beth Israel Deaconess Medical Center St 1005 Boston, Ma 02215 Timing: Fiscal Year 2002; Project Start 02-MAR-2000; Project End 28-FEB-2005 Summary: The lungs remain a frequent target of HIV-related disease, although the mechanism(s) accounting for this increased susceptability are poorly understood. Alveolar macrophages (AM) are the predominant immune cell in the lungs, and serve a central role in mediating an effective "first-line" host response to infectious challenge. AM are infected with HIV, but evidence for effector cell dysfunction remains controversial. Preliminary data in this application demonstrate that HIV-1 infection impairs mannose receptor-mediated phagocytosis of P. carinii, an important pulmonary pathogen in the HIV+ host. The macrophage mannose receptor is a prototype of a host defense surface protein of innate immunity which mediates recognition of specific carbohydrate moities expressed on the surface of pathogens. In the context of AIDSrelated opportunistic infections, such pathogens include P. carinii, M. tuberculosis, MAC and C. neoformans. The Central Hypothesis is that HIV-1 and associated lung specific-factors dysregulate AM innate immune defense function, which in the setting of CD4+ T-lymphocyte depletion, predisposes the host to opportunistic lung infections. The goal of this project is to define the mechanism(s) underlying pulmonary innate immune cell dysregulation using the AM mannose receptor as the prototypic receptor of macrophage innate immunity. To test this hypothesis, experiments will address these Specific Aims: number 1) to characterize the expression and function of the cell membrane associated mannose receptor (mMR) comparing alveolar macrophages (AM) from healthy individuals to asymptomatic HIV-infected persons at high or low clinical risk for opportunistic pulmonary infections, and correlate with HIV-1 RNA and proviral DNA expression in the alveolar airspace; number 2) examine the mechanism of impaired mMR-mediated phagocytosis in AM in HIV-infected individuals by investigating the effects of in vitro HIV-1 infection, and the influence of specific exogenous and AAV vector-transduced structural and regulatory HIV-1 proteins on AM from healthy individuals; number 3) define the mMR-mediated signal transduction pathways comparing AM from healthy to HIV-infected individuals, and examine the influence of HIV-1 infection and HIV-1 gene products on Rho GTPase (Cdc42, Rac and Rho) and NF-kappaB/I-kappaB activity. Defining specific abnormalities in AM innate function will provide a rational basis for developing novel agents to augment local immune function, which could reduce the incidence or severity of pulmonary infections in patients with AIDS. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: BIOFILM DETACHMENT MECHANISMS IN CHRONIC LUNG INFECTIONS Principal Investigator & Institution: Singh, Pradeep; Internal Medicine; University of Iowa Iowa City, Ia 52242 Timing: Fiscal Year 2004; Project Start 01-AUG-2004; Project End 31-JUL-2008 Summary: (provided by applicant): P. aeruginosa biofilms cause many chronic infections including airway infections that afflict bronchiectasis patients, endotracheal tube colonization that leads to ventilator associated pneumonia, medical device infections, and others. In biofilms, bacteria live in matrix-encased group structures, and this growth mode produces physiologic changes that cause marked antibiotic resistance. In spite of the importance of biofilms in disease, no medical treatments have yet been developed to disrupt them. Interestingly, biofilm bacteria themselves possess active mechanisms to separate from biofilms; this process is known as detachment. Because detached bacteria regain sensitivity to killing, this process may be useful therapeutically. The goal of this work is to investigate a potential mechanism of P. aeruginosa biofilm detachment, and to study the pathological consequences of detachment using an airway biofilm infection model. We have discovered a P. aeruginosa variant strain with a hyper-detachment phenotype. This strain overproduces the bio-surfactant, rhamnolipid, which is required for its accelerated biofilm detachment. The following aims are proposed: 1. What is the mechanism of rhamnolipid-mediated biofilm detachment? We will examine the types of rhamnolipids produced by the wild type and variant strain, and use two independent methods to determine if rhamnolipids can, by themselves, cause biofilm detachment. Microarray analysis will be used to find other genes that may be needed for detachment. 2. What are the consequences of biofilm detachment in vivo? Using our airway biofilm infection model and isogenic hyper and hypo-detaching strains, we will investigate the potential risks of inducing detachment and determine if detachment improves clearance of the organisms by the host. 3. Will biofilm detachment in vivo increase the efficacy of antibiotic treatment? Using non-detaching strains, infections in the airway biofilm model are extremely resistant to treatment. In vitro, biofilm detachment restores antibiotic sensitivity. We will investigate whether detachment increases the efficacy of antibiotic treatment in vivo. These studies will model a treatment strategy that combines traditional antibiotics with induced biofilm detachment. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: C5A PNEUMONIA

IN

DEFENSE

AGAINST

MURINE

GRAM-NEGATIVE

Principal Investigator & Institution: Younger, John G.; Emergency Medicine; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2004; Project Start 01-JUL-2004; Project End 30-JUN-2009 Summary: (provided by applicant): This project is studying how the anaphylatoxin C5a, a protein generated by the immune system upon first interacting with invading microorganisms, helps support host defenses in the lung during acute Gram negative pneumonia. This disease is a serious threat to hospitalized, post-operative, and immunocompromised patients and the bacteria that cause it are increasingly resistant to broad-spectrum antibiotics. Using a murine model of lung infection, our goal is to better define the role of C5a so that improved therapies against Gram-negative pneumonia might be developed. The first aim of the project examines how C5a enhances the in vitro responses of alveolar macrophages to the clinically important

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pathogen Pseudomonas aeruginosa and will measure C5a's effect on phagocytosis, respiratory burst, bacterial killing, and release of proinflammatory mediators. Parallel studies will examine C5a's effect against this pathogen in whole blood. The second aim will study how structures on the surface of Gram-negative bacteria may alter the generation and ultimately the effectiveness of C5a. These studies take advantage of a mutant of a virulent strain of Klebsiella pneumoniae in which the gene responsible for initiating synthesis of the surface carbohydrate O-antigen has been deleted. Wild-type and mutant strains will be compared in terms of their ability to promote the generation of C5a and to alter the responses of alveolar macrophages. Parallel studies will be performed using a strain of E. coli which has been transformed to synthesize the Klebsiella O-antigen to determine if expression of this complement countermeasure can convey virulence to an otherwise nonpathogenic bacteria. The final aim of the proposal will examine 3 strategies to boost the level of C5a produced in the lung during acute infection. These experiments will examine intratracheal therapy with a protein derived from cobra venom which can generate C5a in the absence of an invading pathogen, an inhibitor of the enzyme carboxypeptidase-N (an important deactivator of C5a), and lastly recombinant murine C5a. It is hoped that the results will better define the role of C5a in host defense during Gram-negative lung infection, will increase understanding of how Gram-negative organisms evade complement-mediated lung defenses, and will determine whether novel C5a-enhancing therapies might be used to assist host defense during acute bacterial pneumonia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CELLULAR IMMUNITY TO P. AERUGINOSA CANDIDATE VACCINES Principal Investigator & Institution: Priebe, Gregory P.; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2002; Project Start 01-JUL-2001; Project End 30-JUN-2006 Summary: (provided by applicant): The central goal of this project is to understand the role of cellular immunity in infections caused by LPS-smooth strains of P. aeruginosa. These strains are significant pathogens for hospitalized patients and wearers of extended-use contact lenses. Recent evidence suggests that during the course of lung and eye infections, P. aeruginosa enters epithelial cells via the cystic fibrosis transmembrane conductance regulator. To study the immune response to the intracellular base of infection, live, attenuated P. aeruginosa strains having an unmarked deletion of the aroA gene have been constructed. Preliminary studies reveal that intranasal (IN) immunization with one such mutant protects against keratitis or lethal pneumonia in murine models. Splenic T cells from immunized mice can kill intracellular P. aeruginosa. Interestingly, passive transfer of antiserum is more protective against corneal infections than lung infections. The candidate will further define the cellular immunity to aroA deletion mutants of P. aeruginosa and test the following hypothesis: The protective efficacy of IN immunization with live, attenuated P. aeruginosa vaccine strains requires both humoral and cellular immune effecters, and the relative contribution of each effecter towards protection is different in different sites of infection. In Aim 1, the cellular immune effecters elicited by aroA deletants of P. aeruginosa will be delineated using immunomagnetic depletion coupled with assays for intracellular bacterial killing, T cell proliferation, and cytolysis. In Aim 2, P. aeruginosa specific T cell clones from IN-immunized mice will be derived and characterized. The candidate seeks an intensive, formal, mentored training to provide the necessary intellectual and technical tools to achieve independence as a scientist. As a specialist in pediatric critical

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Lung Infection

care and infectious diseases, his long-term goal is to develop effective immune-based interventions to prevent or ameliorate the consequences of P. aeruginosa infections. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENE EXPRESSION AND PATHOGENICITY OF P.AERUGINOSA Principal Investigator & Institution: Wiener-Kronish, Jeanine P.; Professor; Anesthesia & Perioperative Care; University of California San Francisco 3333 California Street, Suite 315 San Francisco, Ca 941430962 Timing: Fiscal Year 2004; Project Start 11-DEC-2003; Project End 30-NOV-2007 Summary: (provided by applicant): We are proposing a translational investigation, including clinical as well as basic scientists, to test the hypothesis that specific Pseudomonas virulence products determine whether lung infection occurs. The results from the proposed experiments will be used to develop diagnostic tools that can identify virulent Pseudomonas in patients. The results will also identify critical bacterial gene products involved in lung injury. The present application carefully dissects associations between bacterial virulence and lung injury so that future mechanistic investigations in patients can be proposed. Without the data from the proposed investigations, we do not have the information to proceed. We already have Pseudomonas strains obtained from a cohort of intubated, mechanically ventilated patients from another grant. Our first aim is to perform a genomic analysis of Pseudomonas strains obtained from 2 distinct patient populations; intubated, ventilated patients with signs of lung infections that have disseminated and intubated, ventilated patients who have no sign of disease. Using microarray analysis, we will determine the significantly different genes between the Pseudomonas strains found in these two patient groups and produce consensus primers to these genes. We will then utilize these consensus primers in a prospective investigation of 300 intubated, ventilated patients to confirm the prevalence of the genetic differences in colonized vs infected intubated, ventilated patients. The second aim is to compare the in vivo virulence gene expression of Pseudomonas strains obtained from colonized patients to the expression profile of the strains obtained from patients who have Pseudomonas lung infections Analysis of bacterial gene expression in vivo will be done using real-time PCR. The results of all these experiments will allow us to prove (or disprove) that there are different genes or different patterns of toxin gene expression between the Pseudomonas strains infecting patients and those colonizing patients. In the final aim, we will evaluate the interaction of type III toxin genes in vivo By utilizing an isogenic bacterial strain (PA103) that has each of the toxin genes added alone or in combination, we will be able to define the effects of each of the type III toxins as well as other genes we find of significance in the first two aims. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: GENETIC CONTROL OF HOST RESISTANCE TO AIRBORNE PATHOGENS Principal Investigator & Institution: Kramnik, Igor; Assistant Professor of Immunology & Infe; Harvard University (Sch of Public Hlth) Public Health Campus Boston, Ma 02115 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2008 Summary: Significant variation in human susceptibility to infections may be due in part to genetic heterogeneity within the host population. However, the genetic control of host resistance in immunocompetent individuals is polygenic and identification of polymorphic genes contributing to host resistance in human populations is a formidable task, because of epistatic gene interactions and the contribution of environmental

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factors. Animal models of human infections allow dissection of genetic factors contributing to host defense. Recently, we and others have identified several genetic loci controlling immunity to intracellular pathogens, some of which may control mechanisms of resistance that are common for several intracellular pathogens. Indeed, one of those loci (sst 1) controls both M. tuberculosis lung infection and systemic infections with F. tularensis and L. monocytogenes. We propose to study the genetic control of the early steps of pathogenesis caused by airborne infections with the two intracellular lung pathogens: M. tuberculosis and F. tularensis using mouse model. We will map genetic modifiers that counterbalance the detrimental effect of the sst 1 locus on lung tuberculosis and produce mouse strains congenic for those loci. We will establish an aerosol model of infection with a low dose of F. tularensis and determine which of the previously identified MTB-resistance loci are important in control of F. tularensis infection. We will test a panel of mouse inbred strains to find genetic variation in their ability to control early steps of disease caused by both pathogens and identify immunological correlates of host susceptibility using immunocompetent cells obtained from lung lesions. We will also test the role of host genetic variation in determining the efficiency of systemic vaccination against airborne infections with both pathogens. Understanding genetic risk factors for susceptibility to airborne infections should improve our ability to identify predisposed individuals and to develop optimal measures of protection and treatment in human populations. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GLUTATHIONE DEFICIENCY & IMMUNE DYSFUNCTION DURING AGING Principal Investigator & Institution: Liu, Rui-Ming; Environmental Health Sciences; University of Alabama at Birmingham Uab Station Birmingham, Al 35294 Timing: Fiscal Year 2002; Project Start 08-FEB-2002; Project End 30-NOV-2006 Summary: (provided by applicant) The function of alveolar macrophages (AM), a very important component of lung antibacterial and antiviral defense, decreases with age. Concomitantly, the incidence and the severity of infectious lung diseases increase with age and so does the sensitivity to the acute toxicity of 03 and NO2, two important environmental pollutants, which suppress AM function. The mechanisms underlying such age-associated decline in the immune function of AM and increase in sensitivity to 03 and NO2 toxicity, however, are not clear. Glutathione (GSH), an important antioxidant, plays a critical role in maintaining the optimal function of the immune system. GSH concentration decreases with age while GSH supplementation restores or improves the immune function, especially in the elderly, suggesting a potential involvement of GSH deficiency in age-associated dysfunction of the immune system. Our previous studies further suggest that decreased expression of gammaglutamylcysteine synthetase (GCS), the rate-limiting enzyme in de novo GSH synthesis, is at least partially responsible for age-associated decline in GSH content in rat tissues. However, does GSH content decrease with age in AM? If it does, what is the underlying mechanism? Most importantly, is decreased GSH content responsible for age-associated dysfunction of AM and increased susceptibility of the elderly to infectious lung diseases as well as 03 and NO2 toxicity? All these questions remain to be answered. The specific aims of this project are 1) To determine whether the GSH content in murine AM decreases with age and the potential underlying mechanism. 2) To test the hypothesis that decreased GCS gene expression is responsible for the age-associated decline in GSH content and dysfunction of AM as well as increased sensitivity of the elderly to infectious lung diseases. Tetracycline inducible, macrophage specific GCS sense and

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Lung Infection

antisense gene transgenic mouse models will be used to test this hypothesis. AM function as well as resistance of mice to pneumococci infection will be determined to see whether increasing GCS gene expression and GSH content will restore the function of AM from old mice as well as reduce their lung infection. 3) To determine whether increased sensitivity of the elderly to the acute toxicity caused by 03 or NO2 is due to a decreased GSH content and dysfunction of AM. The long-term objective of this project is to uncover the mechanism underlying dysfunction of AM and increased susceptibility to infectious lung diseases and O3/NO2 toxicity observed in the elderly and to provide therapeutic strategies for treatment of these diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GM-CSF & ALVEOLAR MACROPHAGE ANTIVIRAL LUNG DEFENSE Principal Investigator & Institution: Trapnell, Bruec C.; Associate Professor; Children's Hospital Med Ctr (Cincinnati) 3333 Burnet Ave Cincinnati, Oh 452293039 Timing: Fiscal Year 2002; Project Start 01-AUG-2001; Project End 31-JUL-2005 Summary: This application will test the hypothesis that granulocyte-macrophage-colony stimulating alveolar macrophage (AM) innate antiviral mechanisms and by limiting inflammation during viral lung infection. GM is a hematopoietic growth factor recently shown to be vital to lung homeostasis and host defense. The role of GM in early hematopoiesis appears to be redundant, however, its role in the lung is unique. While the mechanism(s) through which GM regulates lung host defense are unclear, GM modulates multiple, diverse function of AM. Based on our preliminary data and published reports, we propose that GM interacts with AM precursors in the lung, stimulating their terminal differentiation, and increases their capacity to internalize and degrade viral pathogens from the respiratory surface (i.e., GM increases intrinsic clearance of AM (ICAM). By increasing ICAM, GM increases primary pathogen clearance (i.e., by resident AM) thus reducing or obviating the need for chemotactic/proinflammatory cytokine signaling and secondary clearance (i.e., by recruited leukocytes). Murine models will be used in which the synthesis of GM is: 1) normal (GM+/+; 2) absent (GM-/-); 3) constitutively over- expressed in the lung (SPCGM/GM-/-); or 4) conditionally expressed in the lung under positive external control using a novel bitransgenic system (BTx-GM or BTx-GM/GM-/-. In the latter model, GM expression can be induced or extinguished, temporally, by addition or withdrawal of oral, aqueous doxycycline resulting in lung GM levels ranging from absence to overexpression. GM-deficient and replete mice will be used to study the in vivo role of GM in: (Aim 1) stimulating AM receptor expression and internalization of adenovirus; (Aim 2) trafficking and degradation of adenovirus in AM; and (Aim 3) limitation of inflammation during adenovirus infection of the respiratory tract. We will identify and characterize the mechanisms by which AM internalize and degrade adenovirus in vivo and in vitro. We will also discern the temporal relationship between GM expression in the lung and AM differentiation, ICAM (for adeno-virus), and the relationship between ICAM and limitation of lung inflammation. Our studies will help clarify the critical role of GM in modulating AM function, stimulation of innate lung host defense, and in limitation of lung inflammation and thus, will help establish the feasibility of the therapeutic use of recombinant GM for prevention or treatment of common acute and chronic lung infection and lung inflammation in various clinical disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: HOST-PATHOGEN INTERACTIONS IN CYSTIC FIBROSIS Principal Investigator & Institution: Moskowitz, Samuel M.; Pediatrics; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2002; Project Start 05-AUG-2001; Project End 31-JUL-2006 Summary: (provided by applicant): The goal of this application is to establish the independent research career of the candidate in the study of chronic lung disease, including that affecting individuals with cystic fibrosis (CF). The candidate is a pediatric pulmonary fellow with the career goal of developing an active program of diseaserelated basic research as a faculty member at a medical school. The training environments are the laboratory of the sponsor, Dr. Samuel Miller, at the University of Washington School of Medicine, and the CF Center at Children's Hospital and Regional Medical Center in Seattle, directed by the co-sponsor, Dr. Ronald Gibson. The proposed project seeks to clarify molecular mechanisms underlying chronic lung infection and inflammation in individuals with CF. The opportunistic pathogen Pseudomonas aeruginosa (PA) infects the lungs of most individuals with CF, frequently (but not invariably) causing severe progressive lung injury and premature death. Study of the interaction between PA and the CF lung is necessary to understand both the cellular processes that promote or permit CF lung infection, and the precise means by which PA interacts with lung cells to cause airway damage. The structure of lipopolysaccharide (LPS), the principal constituent of Gram-negative bacterial surfaces, appears to play a pivotal role in both microbial and human aspects of this interaction. The candidate's preliminary results indicate that resistance of laboratory and clinical isolates of PA to antimicrobial peptides (key components of host innate immunity) correlates with alterations in the structure of the lipid A moiety of LPS. Moreover, mutation of a PA locus that regulates LPS-modifying enzymes influences the antimicrobial peptide resistance phenotype. The microbiological phase of the project thus seeks to define PA genes necessary for this putative resistance mechanism, and to identify potential inhibitors using antimicrobial peptide-resistant strains. The human phase of the project builds on the clinical observation that some individuals with a severe CF genotype and chronic PA airway infection nevertheless have minimal lung disease. A case-control design will be utilized to test the hypothesis that polymorphisms in innate immune genes may limit CF lung disease. Those innate immune genes encoding the LPS receptor are leading candidates as CF modifier loci, based on the recent finding that CF-specific PA LPS structures have increased inflammatory activity. When prevalence of an LPS receptor variant differs in mild and severe CF lung disease, receptor function will be assayed in cell culture models of LPS signaling. Identifying innate immune genes as modifiers of the CF lung phenotype may suggest new avenues for treating the inflammatory consequences of CF airway infection. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: VIRULENCE

IMMUNOLOGIC

CONSEQUENCES

OF

M.

TUBERCULOSIS

Principal Investigator & Institution: North, Robert J.; Member; Trudeau Institute, Inc. Saranac Lake, Ny 12983 Timing: Fiscal Year 2002; Project Start 01-JUN-1995; Project End 28-FEB-2006 Summary: (Adapted from the Applicant's Abstract): The proposed experiments are designed to investigate the limited protective value of the primary and secondary immune responses to airborne infection with virulent M. tuberculosis (Mtb) in mice. The secondary response will be studied in mice that possess a state of immunological

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Lung Infection

memory as a result of having been infected with avirulent or virulent live Mtb and later treated with chemotherapy to essentially abolish infection. Vaccinated and unvaccinated mice will be infected with virulent Mtb by aerosol and 5 mice sacrificed at progressive times of infection to follow the progression and subsequent immunological control of infection. Additional mice will be sacrificed to determine the kinetics of production in the draining tracheobronchial lymph node of Mtb-specific CD4 Th1 cells and CD8 T cells, identified and enumerated by their ability to secrete IFNgamma in response to Ag stimulation in the ELISPOT assay. The appearance of these T cells in the draining nodes will be compared with their appearance in blood and at sites in infection in the lungs. It will be determined, with the RNase protection assay and Western blotting, whether the onset of expression of immunity in the lung is associated with transcriptional activation of genes for Th1 cytokines needed for the mediation of immunity, and if iNOS needed for the expression of immunity by macrophages at infectious foci. The prediction that neither the primary, nor the secondary immune response will be capable of preventing the establishment of infection even with very small numbers of virulent Mtb, or even with a virulent Mtb, because of an intrinsic delay before immunity can be expressed in the lungs will be tested. The prediction that, once expressed, immunity will be unable to resolve even very low levels of infection, but will cause infection to become stationary, will also be tested by challenging mice with small numbers of Mtb, and by later reducing the number of Mtb in lesions with chemotherapy as immunity is being expressed. Whether the delay in expression of immunity is caused by a delay in the production of protective T cells, or a delay in the development of conditions at infectious foci necessary for the extravasation of T cells at these sites will be investigated by adoptive transfer studies. The inability of the secondary immune response to enable genetically susceptible mice to stop lung infection from progressing will be investigated. The possibility that genetically susceptible mice, will be incapable of stopping lethal regrowth of a greatly reduced level of lung infection following chemotherapy will also be investigated. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: IMPACT OF AIRWAY INFECTION ON ADENOVIRAL GENE TRANSFER Principal Investigator & Institution: Tosi, Michael; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2002 Summary: Among systems being developed for delivering and expressing the normal CFTR genes in the airways of CF patients, recombinant adenovirus (Ad) vectors are the farthest along in clinical trials in the United States. Chronic endobronchial inflammation associated with mucoid Pseudomonas infection afflicts most CF patients. However, the effects of this inflammatory airway environment in CF on gene delivery and expression by Ad vectors or other systems have not been carefully examined. Our major goals are to determine the effects of preexisting chronic airway inflammation on Ad-mediated gene delivery and expression in the lung, to identify mechanisms that mediate these effects, and to determine whether anti-inflammatory therapies can counter adverse effects of this inflammation on Ad-mediated gene transfer and expression. We hypothesize 1) that preexisting airway inflammation, as in CF, reduces Ad-mediated gene transfer and duration of transgene expression in the airways; 2) that this occurs directly by interference with Ad binding to epithelial cells, 3) that this also occurs indirectly by enhancement of specific immune responses that interfere with Admediated gene delivery and expression; and 4) that anti-inflammatory therapies can

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counter adverse effects of inflammation on Ad-mediated gene delivery and expression. Our specific aims are to: (1) Infect mice in the agarose bead model of chronic Pseudomonas lung infection, then determine if Ad-mediated gene transfer and duration of transgene expression in the airways are impaired. Cultural human airway epithelial cells in vitro will serve as a complementary method to examine the effects of CF sputum sol extracts or BAL fluid on Ad-mediated gene transfer (2) We will determine if CF secretions or their components interfere directly with Ad binding to epithelial cells and if this occurs by actions on the virus or the epithelial cells or both; (3) We will determine if chronically infected mice exhibit exaggerated Ad- specific humoral or cellular immune or inflammatory responses that reduce the extent or duration of transgene expression, and we will identify underlying mechanisms (.e.g. cytokine production or antigen presentation) whose enhancement may account for these exaggerated responses; 94) We will determine if treatment effective in reducing lung inflammation in chronically infected mice (i.e. antibodies to neutrophil and endothelial adhesion molecules or oral ibuprofen) will counter the adverse effects on inflammation on Ad-mediated gene transfer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: IN VIVO MOLECULAR ANALYSIS OF SIV LUNG INFECTIONS Principal Investigator & Institution: Reinhart, Todd A.; Associate Professor; Infectious Diseases and Microbiology; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2002; Project Start 30-SEP-1998; Project End 31-AUG-2004 Summary: The immunodeficiency inducing lentiviruses HIV-1 and SIV replicate in numerous tissues throughout the host, with early unchecked replication during the final stages of disease. The lung has been demonstrated in our previous studies to serve as a critical site of viral replication during the transition from clinical latency to AIDS in the SIV/macaque model of HIV-1 infection and disease induction in humans. This proposal outlines an experimental plan to comprehensively characterize the virologic and immunologic outcomes of infection in rhesus macaque lung tissues by SIV during the acute, clinically latent, and terminal stages of disease. Our hypothesis is that there are very specific virologic and immunologic events that occur in the lung immediately preceding the transition from clinical latency to AIDS, and we will seek to identify these events. For these in vivo analyses, cohorts of rhesus macaques will be inoculated intravenously with SlVdeltaB670 or biological and molecular clones derived therefrom, and in situ hybridization and immunohistochemical staining will be utilized to identify the numbers, locations, and types of productively infected cells in multiple parts of the lungs, in comparison to lymphoid tissues. In parallel, characterization of the composition of the lymphocytic and monocytic subsets will be performed. For these studies, lung tissue will be disaggregated and single cell suspensions generated to allow flow cytometric analyses of surface immunophenotype, in vitro killing analyses of SIVspecific cytotoxic T cell activities, and PCR/ heteroduplex mobility analyses of the T cell receptor Vbeta repertoire. In all experiments, investigations of lung tissues will be performed in comparison to bronchoalveolar lavage (BAL) cells, as the majority of existing data regarding the effects of HIV-1 on the immunologic environment in the lung are from BAL. These investigations will provide insight into the mechanisms by which primate lentiviruses alter the immunologic environment within the lung, leading to susceptibility to respiratory infections as well as systemic immunodeficiency. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: INFLAMMATORY RESPONSE TO PSEUDOMONAS IN CYSTIC FIBROSIS MICE AND CELLS Principal Investigator & Institution: Davis, Pamela B.; Professor; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2002 Summary: Patients with cystic fibrosis (CF) have a lesion in a gene which encodes a cAMP-regulated chloride channel, CFTR. This error is associated with abnormal regulation of other ion channels, abnormal glycosylation of secreted and cell surface molecules, and vulnerability to bacterial infection and inflammation in the lung. Lung infection and inflammation relentlessly progress to take the patients' lives. The exact mechanism(s) by which mutation in CFTR leads to lung infection and inflammation is not established, though this is critical in devising therapeutic strategies directed at the basic defect. Several hypotheses, not normally exclusive, which invoke different mechanisms, have been advanced to explain the connection. Studies using our human airway epithelial cell lines transfected with the R domain of CFTR and with mutant forms of CFTR support the hypothesis that the commonest infecting bacteria in CF, Pseudomonas aeruginosa, adhere to a greater extent to airway epithelial cells without functional CFTR than they do to normal cells because CF phenotype cells have increased surface asialo GM1, a receptor for Pseudomonas pili. Adherence of pili stimulates release of IL-8, a chemoattractant. However, we also found that the inflammatory response to pseudomonas delivered to the lung encased in agar beads (bypassing adherence and defensin killing) is excessive and lethal in CF mice. Thus, there must be a mechanism by which the CF host response becomes exaggerate din addition to a defect which allows a pristine CF lung to retain bacteria. In this proposal, we will investigate the inflammatory response of CF and non-CF mice, to pseudomonas encased in agar beads, including the contribution of CF genotype, pseudomonas adherence, and specific inflammatory cascades to the ultimate outcome. We will also investigate, at the cellular level, in human airway epithelial cells of normal and CF phenotype, the spectrum of inflammatory responses of the epithelial cell itself to pseudomonas and its products, including cytokines, eicosanoids, and the ability to support neutrophil migration. These studies should elucidate the relation of the CF genotype to the excessive inflammatory response and identify potential therapeutic targets in the inflammatory cascade. In addition. this project will supply samples to Dr. Berger's project and Dr. Prince project for studies of IL-10 and NF-kappaB respectively. 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

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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 •

Project Title: MAST CELLS AND THE HOST RESPONSE IN THE LUNG Principal Investigator & Institution: Wolters, Paul J.; Medicine; University of California San Francisco 3333 California Street, Suite 315 San Francisco, Ca 941430962 Timing: Fiscal Year 2004; Project Start 02-JUL-2004; Project End 30-JUN-2008 Summary: (provided by applicant): The long-term objective of our research is to determine the mechanisms by which mast cells regulate the host response to bacterial lung infections and to be able to modify how mast cells coordinate this response in ways that benefit the host. Recently, we made the discovery that the mast cell protease dipeptidyl peptidase I (DPPI) contributes to death of the host from septic peritonitis and that it appears to do so by regulating levels of mast cell IL-6. This suggests that mast cell DPPI, or other mast cell proteins regulated by DPPI, modify the host response to bacterial infection in ways that harm the host. Our central hypothesis is that: Mast cell proteases and cytokines coordinate lung defense against bacterial infections. While coordinating this defense, some of these mediators protect the host and improve survival while others harm the host and worsen survival. Specific aims are: #1. To determine the mechanism by which mast cell DPPI modulates the host response and survival from bacterial lung infections. This will be accomplished by applying a new method for creating mast cell-specific knockout mice and determining the physiologic mechanism for survival following inoculation with Klebsiella pneumoniae. #2. To define mechanisms by which mast cell proteases regulate cytokine levels during bacterial infections. We will test whether mast cell proteases hydrolyze cytokines by incubating cytokines with purified DPPI, tryptase or chymase and identifying cleavage products. Protease mediated cytokine production will be studied by measuring cytokines released by specific lung cells in response to DPPI, tryptase or chymase. #3. To determine whether mast cell TNF-alpha, IL-6, or IL-10 modulate the host response and survival from bacterial lung infections. We will use mast cell-specific-TNF-alpha, -IL-6, or -IL-10

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Lung Infection

knockout mice to test if mast cell sources of these cytokines play important roles in host defense. By understanding how specific mast cell mediators regulate host defense, we will gain greater insight into how these cells influence host survival. This knowledge can then be applied to the development of new treatments for bacterial pneumonia that modulate the activity of specific mast cells proteins in ways that improve survival. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MECHANISMS OF CELL GROWTH ARREST IN LATENT TUBERCULOSIS. Principal Investigator & Institution: Fontan, Patricia A.; Public Health Research Institute 225 Warren St Newark, Nj 071033535 Timing: Fiscal Year 2004; Project Start 01-APR-2004; Project End 31-MAR-2009 Summary: (provided by applicant): During the latent phase of tuberculosis the tubercle bacillus is believed to be metabolically active but in a slow or non-growing state which can resume bacterial replication at an opportune time later in life. However the mechanisms involved in the cessation of Mycobacterium tuberculosis (Mtb) division are unknown. There have been recent descriptions of bacterial possessing systems, resembling plasmid encoded toxin-antitoxin proteins that induce cell growth arrest when the microorganism is exposed to an environmental stress. We and other investigators have identified proteins resembling these putative toxin-antitoxin modules in Mtb. To provide evidence that these systems are cell growth arrest modules involved in the persistent phase of Mtb infection, we propose: 1-To demonstrate the inhibitory effect of the putative Mtb "toxin-antitoxin modules" on bacterial growth in vitro. 2-To determine the patterns of expression of the putative Mtb "toxin-antitoxin modules" during the persistent phase of bacterial infection in mice lung and guinea pig granulomas. 3-To analyze the regulatory mechanisms for the expression of the putative Mtb "toxin-antitoxin modules". 4-To determine the mechanism of action of the putative Mtb '_toxin-antitoxin modules". 5-To evaluate the role of the Mtb "toxin-antitoxin modules" in bacterial virulence, using a model of mouse lung infection. These studies will provide insight into the latent phase of tuberculosis and they will allow us to identify possible targets form the design of antimycobacterial drugs. During the research supported by this proposal the candidate will gain knowledge in the study of transcriptional regulation of Mtb under the mentorship of Dr. Issar Smith, who is an expert in the field. The candidate will obtain expertise in the management of State-ofthe-Art techniques at the Public Health Research Institute, an Institution with a high level of scientific achievement in the area of infectious diseases like TB. The completion of this proposal in this framework of scientific and institutional support will be fundamental for the candidate to establish herself as an independent investigator in the field of Mtb pathogenesis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: NMSO3: A NOVEL THERAPY FOR RESPIRATORY SYNCYTIAL VIRUS Principal Investigator & Institution: Bowlin, Terry L.; Microbiotix, Inc. Worcester, Ma 01605 Timing: Fiscal Year 2004; Project Start 01-MAR-2004; Project End 28-FEB-2006 Summary: (provided by applicant): There is a clinical need for a new cost-effective, nontoxic therapy to treat Respiratory Syncytial Virus (RSV) infections in young children and immunocompromised adults. Microbiotix, Inc. is developing NMSO3 as a treatment,

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intranasal delivery, for RSV infection. NMSO3 has been shown to be active in vitro (IC50 = 0.20mu/m) and in animals (Cotton Rat) against RSV infection (Kimura et al., 2000). We have extended those observations in our Phase I SBIR studies to confirm the antiRSV activity and mechanism of action. We have also produced gram quantities of compound, establish pharmacokinetic parameters and developed analytical techniques for NMSO3 detection. Based upon our bioavailability studies, we found NMSO3 was not taken up well by the oral route. However, we have now shown that when given by the intranasal route, NMSO3 eliminates detectable virus in the lung of RSV infected cotton rats. We have also now established that based upon sequencing of NMSO3 resistant mutants NMSO3 appears to inhibit RSV infection by interfering with the viral G protein. We are unaware of any other compound in development as a anti-RSV agent with this mechanism of action. We have also shown that NMSO3 can inhibit chemokine (MCP-1, RANTES, IP-10) production, induced by RSV in lung airway epithelial cells. It is our aim in the Phase II SBIR to expand the preclinical profile of NMSO3 and move the compound into IND enabling pharmacokinetic, toxicology and safety pharmacology studies. We will refine the optimum dosing regimen for treating RSV lung infections in cotton rats. Coupled with the pharmacokinetic profile and toxicological studies we will then establish a safety index based upon plasma drug concentrations. GMP quality NMSO3 will be prepared. The goal is to file an Investigational New Drug Application (IND) for NMSO3 to treat RSV infection within two years of initiation of the Phase II SBIR studies. Furthermore, we have recently shown NMSO3 to be active against human Metapneumovirus (hMPV) in vitro. Human MPV, which is closely related to human RSV, is also a significant respiratory pathogen. Our plan going forward is to continue to investigate the anti-hMPV activity of NMSO3. Anti-hMPV activity can be examined as part of our clinical Phase II studies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NOVEL PATHOGENESIS

CLASS

OF

PHOSPHOLIPASES--MOLECULAR

Principal Investigator & Institution: Vasil, Michael L.; Professor; Microbiology; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, Co 800450508 Timing: Fiscal Year 2002; Project Start 01-JUN-1993; Project End 25-SEP-2003 Summary: Pseudomonas aeruginosa is an important opportunistic pathogen both in terms of the morbidity and mortality of infections it causes. Most patients with cystic fibrosis (CF), are colonized at an early age with this organism and most CF patients ultimately succumb to a chronic lung infection from P. aeruginosa. The reason for the extraordinary pathogenicity of P. aeruginosa in these patients, as compared to other Pseudomonads for example, is not clear. It is highly probable that the myriad of virulence determinants P. aeruginosa produces contributes to its pathogenic potential. Unfortunately, the exact contribution of these factors, alone or in combination, to even the simplest kind of P. aeruginosa infection has not yet been elucidated. In the past few years studies using molecular, biochemical and genetic approaches have begun to elucidate the structure-function relationships and mechanisms of regulation of virulence determinants. This research is directed at understanding the role of phospholipase C (PLC) production in the pathogenesis of P. aeruginosa infections. PLC has become recognized in recent years as a critical enzyme in both eukaryotic and prokaryotic biology. In eukaryotic organisms it is a critical second messenger in cellular processes, particularly in the function of specific and nonspecific immune mechanisms. In prokaryotic organisms there has been a resurgence of interest in PLC as a critical

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virulence determinant, both in gram negative and gram positive infections. P. aeruginosa produces two distinct PLCs that could play a significant role in the pathogenesis of lung, as well a other kinds of infections. One PLC is cytolytic (PLC-H) on human erythrocytes and neutrophils, while the other is not (PLC-N) lytic to these kind of cells. These and other features suggest structure-functions relationships between PLC activity and cytolytic activity that will be investigated in this research project. A more complete understanding of the structure-function relationships of both PLCs will lead to better understanding of their role in the pathogenesis of P. aeruginosa, and could result in therapeutic interventions for P. aeruginosa lung infections that were not previously considered. We also propose that derivatives of the substrate products produced by the action of both PLCs on phosphatidylcholine, the major essential lipid in lung surfactant, significantly contribute to the pathogenesis of P. aeruginosa infections. We hypothesize that some of these derivatives are especially relevant to the survival of this organism in the lungs of CF patients. We will investigate how a class of compounds, known as osmoprotectants including, glycine betaine, are able to induce the synthesis of both PLCs in P. aeruginosa. This compound, derived from the one of substrate products of both PLCs, can provide for the survival of this organism in a high osmotic environment, such as found in the lungs of CF patients or in the urinary tract. We propose that understanding this unusual regulatory process could lead to the discovery of novel agents which might at least temper the pathogenic potential of P. aeruginosa, if not directly affect its ability to persist in the lungs of CF patients, or survive in the high osmotic environment of the urinary tract. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PATHOGENESIS AND VACCINE DEVELOPMENT FOR PLAGUE Principal Investigator & Institution: Straley, Susan C.; Professor; Duke University Durham, Nc 27710 Timing: Fiscal Year 2003; Project Start 04-SEP-2003; Project End 29-FEB-2008 Summary: This project proposes to identify large (> 50 kDa) surface proteins that are expressed during lung infection by the plague bacterium Yersinia pestis. These will be prioritized by conditions for expression, relative abundance, recognition by plague convalescent serum, and indications from homology with the databases of potential virulence function. Ten of these will be characterized for their necessity for virulence in a mouse model of pneumonic plague, amount that is surface-exposed, and their effects on adherence to a mouse alveolar macrophage cell line and to mouse lung explants. Four will then be chosen for detailed studies of immunogenicity and ability to protect against pneumonic plague. It is hoped that one or more of these will prove to be protective immunogens against pneumonic plague caused by a non-encapsulated strain against which vaccines currently in development will not protect adequately. Such vaccine candidates also will generate a protective immune globulin reagent for rapid protection of potentially exposed people, and a strong, specific antibody reagent might contribute to an improved multiplex detection method. Our findings will enhance our arsenal of means to protect against potential bioterrorism use of Yersinia pestis and also will improve our understanding of the pathogenesis of pneumonic plague. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PROTEOGLYCANS IN MICROBIAL PATHOGENESIS AND HOST DEFENSE Principal Investigator & Institution: Park, Pyong; Medicine; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030

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Timing: Fiscal Year 2002; Project Start 01-DEC-2001; Project End 30-NOV-2005 Summary: (provided by applicant) Microbial infection is a major public health threat that can be associated with high mortality, and that can also often amplify and lead to chronic inflammation, also resulting in serious complications. The current emergence of multi-drug resistant strains adds to the threat of infections. These features are especially evident in compromised patients in whom drug-resistant microbial pathogens infect with high mortality and morbidity. During infection, microbes exploit a variety of host components to promote their pathogenesis. Among these, cell surface heparan sulfate proteoglycans (HSPGs) are targeted by a wide spectrum of microbes. Cell surface HSPGs function as selective regulators of various molecular interactions, including those important to microbial pathogenesis and host defense. These HSPGS not only function at the cell surface, but also in the extracellular environment as soluble HSPGS because they can be shed as intact ectodomains in response to tissue injury, including those caused by infections. The long term objective of this research is to delineate how cell surface HSPGs regulate, in part, the highly complex host response to microbial infections. This proposal focuses on the role of syndecan-1, the predominant cell surface HSPG of epithelia. The goal of this application is to elucidate the molecular mechanisms that are responsible for exploitation of syndecan-1 shedding by bacterial pathogens to enhance their lung virulence. Three inter-related hypotheses will be tested in three aims: Specific Aim 1. Binding of certain virulence factors to their host receptors triggers signaling events that lead to activation of syndecan-1 shedding will be assessed by determining in molecular detail how LasA, a virulence factor for Pseudomonas aeruginosa lung infection, activates syndecan-1 shedding; Specific Aim 2. Syndecan-1 ectodomains regulate the host response by inhibiting innate defense mechanisms will be evaluated by establishing whether syndecan-1 ectodomains, via their specific structural features in their HS chains, inhibit the activity of cytokines and antimicrobials to enhance bacterial virulence in the lung; and Specific Aim 3. This mechanism is used by several major pulmonary bacterial pathogens will be probed by evaluating whether Staphylococcus aureus exploits syndecan-1 shedding to enhance its lung virulence. These studies, which delineate how cell surface HSPGs such as syndecan-1 are exploited by microbes for their pathogenesis, should provide a foundation for the development of novel prophylactic and therapeutic agents to combat infections caused by major opportunistic bacterial pathogens. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MUCOIDY

PSEUDOMONAS

IN

CYSTIC

FIBROSIS-REGULATION

OF

Principal Investigator & Institution: Deretic, Vojo P.; Professor; Molecular Genetics & Microbiol; University of New Mexico Albuquerque Controller's Office Albuquerque, Nm 87131 Timing: Fiscal Year 2002; Project Start 01-FEB-1992; Project End 31-JUL-2007 Summary: (provided by applicant): Pseudomonas aeruginosa is the major cause of chronic respiratory infections in cystic fibrosis (CF) leading to persistent inflammation, lung tissue damage and high morbidity and mortality in this most common inheritable disease in Caucasians. The initially invading strains of P. aeruginosa are nonmucoid, but concomitantly with the establishment of a chronic infection, mucoid mutants overproducing the exopolysaccharide alginate emerge. The chronic infection, and additional host and bacterial factors that are not fully understood, lead to increased inflammation and irreversible tissue damage. This laboratory has previously described the mechanism of conversion to mucoidy which occurs via muc mutations that lead to

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the activation of the alternative sigma factor AIgU, the P. aeruginosa ortholog of the bacterial extreme stress sigma factor sigma-E. While alginate overproduction plays a role in reducing pulmonary clearance, we hypothesize that additional factors, coexpressed with alginate upon activation of AlgU, may contribute to pathogenesis in CF, since sigma factors normally direct transcription of a large number of gene subsets. So far, we have identified 10 additional genes controlled by A1gU that are activated in muc mutants. Importantly, a significant portion of these genes encode lipoproteins. Since lipoproteins play a role in innate proinflammatory signaling, we additionally hypothesize that P. aeruginosa products co-expressed with mucoidy contribute to inflammation in CF via pattern recognition receptors. Here we propose to: 1.further identify P. aeruginosa genes whose expression is activated in mucoid cells using conventional methods and techniques of global expression profiling; 2.analyze P. aeruginosa proinflammatory products associated with conversion to mucoidy; 3. analyze the role of pattern recognition receptors and signaling pathways involved in innate host response to P. aeruginosa products; and 4. study proinflammatory signaling in CF in combination with altered responses in CF cells. The specific alms of this proposal are to: 1) Identify P. aeruginosa genes that are activated or otherwise affected during conversion to mucoidy. 2) Determine how products of mucoid P. aeruginosa contribute to inflammation in CF. 3) Examine how proinflammatory products of mucoid P. aeruginosa synergize with the basic defect in CF and its downstream physiological effects, leading to exacerbation of pulmonary disease. These studies are expected to improve our understanding of respiratory pathogenesis in CF, and lead to new treatments of presently incurable lung infections associated with this disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ROLE OF LYSOZYME IN AIRWAYS HOST DEFENSE Principal Investigator & Institution: Akinbi, Henry T.; Assistant Professor; Children's Hospital Med Ctr (Cincinnati) 3333 Burnet Ave Cincinnati, Oh 452293039 Timing: Fiscal Year 2002; Project Start 15-FEB-2002; Project End 31-JAN-2007 Summary: Lysozyme is a cationic protein of 146 amino acid residues (Mr approximately 14k) that is bactericidal against multiple gram-positive bacteria in vitro. Although lysozyme is the most abundant antimicrobial protein in airway surface fluid (ASL), its role in protecting the airways against infection, chronic colonization, and inflammation in vivo remains unproven. The results of preliminary studies reported in this application demonstrate a dose-dependent relationship between the level of lysozyme activity in bronchoalveolar lavage fluid and the rate of bacterial killing, of both gram positive and negative organisms, in acutely infected transgenic mice that overexpress lysozyme. Studies proposed in this application will test the central hypothesis that lysozyme is a critical component of airway host defense in vivo. Pathogen killing will be assessed in lysozyme (-/-) mice and lysozyme overexpressing mice following acute and chronic lung infection. The antimicrobial spectrum and potency of exogenouslyadministered recombinant lysozyme protein will also be assessed. These studies will provide insight into the role of lysozyme in airway host defense and provide a preliminary assessment of the therapeutic potential of exogenously administered lysozyme. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ROLE OF MMPL TRANSPORTERS IN M. TUBERCULOSIS VIRULENCE Principal Investigator & Institution: Cox, Jeffery S.; George Williams Hooper Fdn; University of California San Francisco 3333 California Street, Suite 315 San Francisco, Ca 941430962 Timing: Fiscal Year 2002; Project Start 15-SEP-2001; Project End 31-MAY-2006 Summary: (provided by applicant) Tuberculosis (TB) is a persistent lung infection that has plagued mankind for centuries and ranks as one of the most serious threats to world health today. The 2-3 million deaths attributed yearly to the disease, as well as the emergence of strains resistant to all of the available chemotherapeutic agents, urgently call for the development of new therapies to treat TB. For years, the identification of new drug targets has been hampered by the intractability of the bacillus to genetic analysis. Now with the advent of powerful genetic tools, combined with well-established mouse infection models, we have isolated novel M. tuberculosis mutants with lesions in individual genes that are required for normal growth during acute infection. Our initial results have led us to the hypothesis that M. tuberculosis influences host- pathogen contacts by utilizing the MmpL family of transporters to secrete biologically active lipids to the surface of the mycobacterial cell and ultimately into infected host cells. The studies proposed here give us the opportunity to test this model and thus understand the molecular details host- pathogen interactions critical during this stage of M.tuberculosis infection. Specifically, we will study a subset of Mmpls that are required for disease and identify the host-pathogen interactions mediated by these virulence molecules. We will determine the mechanism of transport of the cell wall lipid phthiocerol dimycocerosate (PDIM) by MmpL7 and seek to understand why this molecule is important for lung specificity of M. tuberculosis. Furthermore, we will identify the molecules transported by the other MmpL proteins identified by our genetic screens and determine their role in pathogenesis. Finally, we will determine if these molecules serve distinct roles in modifying the host for the benefit of the bacterium. Because members of the MmpL family of transporters are highly homologous to one another and to MmpL proteins of other mycobacterial pathogens, understanding the common mechanisms of their function may lead to the development of inhibitors that could be useful for treating a broad range of infectious diseases. The results from these studies will direct our long-term plans to understand the role secreted lipids play in the struggle between M. tuberculosis and the host. Ultimately, by understanding tuberculosis pathogenesis at the molecular level, we hope to aid in the discovery of new therapies to combat and eradicate this persistent infection. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ROLE OF SURFACTANT PROTEIN B IN INNATE AIRWAY DEFENSE Principal Investigator & Institution: Baatz, John E.; Assistant Professor; Pediatrics; Medical University of South Carolina P O Box 250854 Charleston, Sc 29425 Timing: Fiscal Year 2002; Project Start 01-JUL-2001; Project End 30-JUN-2005 Summary: (Applicant's Abstract): Surfactant protein B (SP-B) is essential for postnatal survival and normal surfactant function. SP-B is capable of reorganizing lipid bilayers and is fusigenic protein. Based on these characteristics and the similarity of SP-B's amino acid sequence to those of several antimicrobial peptides, we hypothesized that SP-B itself has antimicrobial properties. Preliminary data obtained by our laboratory have demonstrated he SP-B has in vitro antibacterial activity. The significance of this observation is three-fold. First SP-B is expressed solely in mammalian lungs where it is

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secreted into the airway lining fluid by bronchial, bronchiolar and alveolar epithelial cells at relatively high concentrations. For that reason, it may act as a component of local mucosal immunity to prevent bacterial infections in these and other regions of the lung. Second, surfactant replacement preparations containing SP-B are presently used for safe treatment of neonatal respiratory distress syndrome, and such preparations do not elicit immunological responses. Third, SP-B is easily isolated or synthesized. Thus, there is potential for safe therapeutic use of SP-B for treatment of pulmonary bacterial infections. Use of SP-B to prevent or eradicate bacterial growth in the airway would be of particular importance in cystic fibrosis (CF), where progressive lung damage occurs as a result of persistent bacterial infection. Moreover, we have found aberrant forms of SP-B in bronchoalveolar lavage (BAL) of adult CF patients and that mature SP-B may be degraded or modified. We will test the hypothesis that SP-B is a component of the innate pulmonary immune system, protecting the human airway against bacterial infection, and this activity may be compromised in the airways of CF patients. The aims of this proposal are 1) to determine molecular forms and activity of SP-B in BAL from CF patients vs. those of normal humans, 2) to delineate the sites in the airway where SPB is found and in which it may play a defensive role, 3) to characterize the antibacterial activity of SP-B in vitro, and 4) to develop preparations containing native or synthetic SP-B for use as antibacterial agents in vivo. Results from the proposed experiments will lay the foundation for therapeutic use of SP-B for eradication of bacterial lung infections. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SMALL MOLECULE INHIBITOR OF QUORUM SENSING Principal Investigator & Institution: Wright, Susan C.; Senior Scientist; Panorama Research, Inc. 2462 Wyandotte St Mountain View, Ca 94043 Timing: Fiscal Year 2004; Project Start 01-MAR-2004; Project End 31-AUG-2004 Summary: (provided by applicant): The opportunistic human pathogen, Pseudomonas aeruginosa, utilizes acyl-homoserine lactones (acyI-HSL) as quorum sensing autoinducers to activate the expression of numerous virulence genes. Some virulence factors are directly toxic to host tissues while others promote formation of biofilms that then confer resistance to antibiotics in organisms enmeshed in these structures. This is a serious problem for cystic fibrosis patients who often develop chronic lung infections with P. aeruginosa that persist despite aggressive antibiotic therapy. Recent concern for the selection of antibiotic resistant bacteria has stimulated interest in the development of novel therapeutics that inhibit virulence factor production in various kinds of bacteria. The goal of this application is to develop novel small molecules that inhibit acyl-HSL quorum sensing in P. aeruginosa and thereby decrease production of virulence factors. Lead pyrrinone and furanone compounds having the desired activity have already been identified. Additional structurally related molecules will be synthesized and tested in vitro. The results of these assays will reveal which compounds are the most potent inhibitors of quorum sensing and virulence factor production. Active compounds will also be tested for inhibition of bacteria growth. Drugs that are not toxic to the bacteria may decrease the likely-hood for the selection of resistant bacteria variants. Drugs that show the best activity in in vitro assays will also be tested in a simple mouse model of P. aeruginosa lung infection. Future Phase II studies will test the lead drug candidate in animal models of Pseudomonas infection in lung, sepsis and burns. These studies may lead to the development of a new anti-Pseudomonas drug with a unique mechanism of action that may be especially useful for immunocompromised patients infected with antibiotic-resistant organisms.

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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SURFACTANT METABOLISM IN PNEUMOCYSTIS CARINII PNEUMONIA Principal Investigator & Institution: Beers, Michael F.; Associate Professor; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 15-MAY-2002; Project End 14-MAY-2003 Summary: Despite recent advances in its diagnosis, therapy, and prophylaxis, Pneumocystis carinii pneumonia (PCP) remains a leading cause of morbidity and mortality in patients with the Acquired Immunodeficiency Syndrome (AIDS). This lifethreatening opportunistic infection is associated with impaired gas exchange leading to clinically significant hypoxemia. The disease is caused by an enigmatic pathogen whose basic biology is poorly understood because of difficulty culturing the organism in vitro and cumbersome animal models of the infection. Surfactant abnormalities and pulmonary inflammation appear to have an important role in the pathogenesis of PCP and its associated hypoxemia; however the initiating and effector mechanisms for these events are not known. Because the hypoxic lung injury produced by PCP is associated with abnormalities in surfactant biophysics and lipid content, we hypothesize that: (i) severe disruption of normal pulmonary surfactant homeostasis is induced directly by P. carinii. The interaction of P. carinii with the distal alveolar epithelium is mediated by an abundant, immunogenic, cell-surface protein, glycoprotein A (gpA) found on the outer cell wall of the organism. These events include alteration in surfactant lipid metabolism and changes in the expression and cellular metabolism of surfactant specific proteins. (ii) Additional indirect mechanisms mediated via TNF-alpha produced by the host inflammatory response further disrupt surfactant homeostasis. We propose to characterize the role of gpA in the specific interaction of this organism with host epithelial cells and study mechanisms by which Pneumocystis mediates the severe lung injury seen with PCP using a murine model of infection. The specific aims are: (1) Define the cellular effects of Pneumocystis gp-A on lung surfactant metabolism in vitro; (2) Characterize changes in surfactant metabolism in an immunocompromised mouse model of PCP. To accomplish these aims, we will utilize in vivo animal systems to grow P. carinii as a source of purified gp-A and a well- controlled model of PCP infection. The project will combine elements derived from several thematic research programs to yield a comprehensive investigative proposal including: 1) A Principal Investigator with expertise in the major areas of surfactant biology; 2) a co-investigator experiences with P. carinii biology, gpA purification and animal models of PCP; 3) A consultant recognized as an authority on the scid mouse model of PCP. Results from these studies will further our understanding of the pathogenesis of P. carinii lung infection. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: SURFACTANT PROTEIN-A AND LUNG DEFENSE Principal Investigator & Institution: Korfhagen, Thomas R.; Professor of Pediatrics; Children's Hospital Med Ctr (Cincinnati) 3333 Burnet Ave Cincinnati, Oh 452293039 Timing: Fiscal Year 2002; Project Start 01-APR-1998; Project End 31-MAR-2003 Summary: (Adapted from applicant's abstract and specific aims): This application seeks to determine the role and the mechanism by which surfactant protein-A (SP-A) protects the lung from bacterial infection. SP-A is an abundant surfactant associated protein produced postnatally principally by two cellular compartments, the distal bronchiolar epithelium and alveolar Type II cells and the tracheal/bronchial glands. Its structural

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and functional resemblance to collections and the in vitro properties as an opsonin of bacterial pathogens strongly infer that SP-A is an important component of the innate immune system of the lung. This application, will test the hypothesis that SP-A protects the lung in vivo from bacterial infection and reduces septic spread from the lung by enhancing bacterial uptake and killing by alveolar macrophages and peripheral monocytes. The specific aims address: 1) the role and mechanism of SP-A during lung infection and prevention of septic spread of bacteria; 2) cellular sites and quantity of SPA synthesis required to protect the lungs from bacterial infection; and protection of the lung of SP-A -/- mice from infection by transtracheal replacement with SP-A. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SYNTHESIS OF P.AERUGINOSA LPS AND ITS ROLE IN INFECTION Principal Investigator & Institution: Goldberg, Joanna B.; Professor; Microbiology; University of Virginia Charlottesville Box 400195 Charlottesville, Va 22904 Timing: Fiscal Year 2002; Project Start 17-SEP-2001; Project End 30-APR-2005 Summary: (provided by the applicant): Pseudomonas aeruginosa is an opportunistic pathogen that can infect many different tissues. Similar to what has been observed in other Gram-negative bacteria, one of the virulence factors important for acute P. aeruginosa infections is lipopolysaccharide (LPS). In the case of P. aeruginosa, the O antigen portion is thought to be essential for systemic infections. Chronic lung infections in cystic fibrosis patients, on the other hand, are caused by P. aeruginosa strains that have a defective LPS with few or no O antigens; these infections remain localized to the lung. In other P. aeruginosa respiratory infections dissemination to the blood is also rare, suggesting that O antigen expression, which confers resistance to the action of normal human serum, may not be required for infections localized to the lung. Prior evaluations of P. aeruginosa LPS mutants in various infection models used either genetically or structurally undefined strains, or those with pleiotropic effects. Therefore the question as to the role of O antigen in P. aeruginosa pathogenesis clearly needs to be reevaluated. The objective of this proposal is to determine which portions of the LPS are critical for infections at particular sites. The genetic locus encoding the enzymes for the synthesis of P. aeruginosa serogroup O11 O antigen has been cloned from strain PA103. Previous work from a number of laboratories has shown PA103 to be highly virulent in many animal models of infection. The steps in the pathway of synthesis of this O antigen will be characterized through mutational, structural, and biochemical analysis of the genes of the O antigen locus (Specific Aim 1). The transcriptional organization of the O antigen gene locus will also be determined (Specific Aim 2). In order to ascertain which portions of the P. aeruginosa LPS are required for virulence, the genetically and structurally defined LPS mutants constructed here will be tested in two different mouse models of infection. In the intranasal infection model, infections can remain localized to the lung or can translocate from the lungs to the blood and other organs. In the corneal infection model, the P. aeruginosa infection remains localized to the eye after trauma (Specific Aim 3). The long-term goal of this research is to devise rational strategies to target LPS synthetic enzymes for the development of vaccines and antibacterial agents to inhibit infections caused by this important human pathogen. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: THE ROLE OF APOPTOSIS IN CF PSEUDOMONAL LUNG INFECTION Principal Investigator & Institution: Cannon, Carolyn L.; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115

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Timing: Fiscal Year 2002; Project Start 01-JUL-2000; Project End 30-JUN-2003 Summary: The clinical hallmark of the genetic disorder cystic fibrosis (CF) is chronic pulmonary infection, particularly with Pseudomonas aeruginosa. The global objective of the proposed project is to gain further insight into the link between defects in the CF gene product, the cystic fibrosis transmembrane conductance regulator (CFTR), and the pathogenesis of pulmonary infections with P. aeruginosa in CF patients. Preliminary studies in a CF cell culture model using the TUNEL assay indicates that P. aeruginosa induces apoptosis in normal, but not CF, lung cells. The specific objective of this project is to delineate the role of apoptosis in the interaction of P. aeruginosa with respiratory epithelium. The specific aims are twofold: 1) characterize the induction of apoptosis in cell culture and mouse models of CF following infection with P. aeruginosa, using TUNEL staining, FACS analysis and confocal microscopy of normal and CF lung cells, a. specifically, to detail the time-course of infection induced apoptosis, b. establish the role of internalization of P. aeruginosa in the induction of apoptosis, and c. determine the role of caspases in the infection-induced apoptosis, and 2) compare the expression of genes regulating apoptosis in lung cells expressing differing Cftr alleles, both before and after infection with P. aeruginosa, using DNA-microarray technology, a. specifically, to identify the expression levels of genes instrumental in orchestrating apoptosis in both wild-type and deltaF508 CFTR expressing lung cells after infection with P. aeruginosa, and b. determine the time course of expression of infection induced genes. This approach will allow simultaneous monitoring of the expression levels of hundreds of genes, potentially identifying and implicating cellular pathways previously unappreciated as participants in the process of respiratory cell-pseudomonal interaction. Thus, we propose to investigate the role of apoptosis in the pathogenesis of pseudomonal pulmonary infection in CF with the ultimate goal of perhaps formulating new treatment strategies based on the findings of these studies. Completion of this project promises to provide the experience necessary for the applicant to initiate a career as an independent investigator in the field of pseudomonal pathogensis, and to provide further insight in the pathogenesis of CF lung diseases. 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 “lung infection” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for lung infection in the PubMed Central database: •

Coinoculation with Hartmannella vermiformis enhances replicative Legionella pneumophila lung infection in a murine model of Legionnaires' disease. by Brieland

3 Adapted 4

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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J, McClain M, Heath L, Chrisp C, Huffnagle G, LeGendre M, Hurley M, Fantone J, Engleberg C.; 1996 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=174097 •

Host Cellular Immune Response to Pneumococcal Lung Infection in Mice. by Kadioglu A, Gingles NA, Grattan K, Kerr A, Mitchell TJ, Andrew PW.; 2000 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=97168

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In Vivo Regulation of Replicative Legionella pneumophila Lung Infection by Endogenous Interleukin-12. by Brieland JK, Remick DG, LeGendre ML, Engleberg NC, Fantone JC.; 1998 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=107859

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Pseudomonas aeruginosa lasR Transcription Correlates with the Transcription of lasA, lasB, and toxA in Chronic Lung Infections Associated with Cystic Fibrosis. by Storey DG, Ujack EE, Rabin HR, Mitchell I.; 1998 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=108233

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Reactivation of Chlamydia trachomatis lung infection in mice by cortisone. by Yang YS, Kuo CC, Chen WJ.; 1983 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=348001

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

6

A case of lung infection caused by an unusual strain of Nocardia farcinica. Author(s): Tsukamura M, Shimoide H, Kaneda K, Sakai R, Seino A. Source: Microbiology and Immunology. 1988; 32(5): 541-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3050378

PubMed was developed by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM) at the National Institutes of Health (NIH). The PubMed database was developed in conjunction with publishers of biomedical literature as a search tool for accessing literature citations and linking to full-text journal articles at Web sites of participating publishers. Publishers that participate in PubMed supply NLM with their citations electronically prior to or at the time of publication.

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•

A study of the taxonomy of the Mycobacterium nonchromogenicum complex and report of six cases of lung infection due to Mycobacterium nonchromogenicum. Author(s): Tsukamura M, Kita N, Otsuka W, Shimoide H. Source: Microbiology and Immunology. 1983; 27(3): 219-36. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6877101

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Adaptive resistance to tobramycin in Pseudomonas aeruginosa lung infection in cystic fibrosis. Author(s): Barclay ML, Begg EJ, Chambers ST, Thornley PE, Pattemore PK, Grimwood K. Source: The Journal of Antimicrobial Chemotherapy. 1996 June; 37(6): 1155-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8836818

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Adverse alterations in bone metabolism are associated with lung infection in adults with cystic fibrosis. Author(s): Aris RM, Stephens AR, Ontjes DA, Denene Blackwood A, Lark RK, Hensler MB, Neuringer IP, Lester GE. Source: American Journal of Respiratory and Critical Care Medicine. 2000 November; 162(5): 1674-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11069795

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Amyloid-related serum protein (SAA) as an indicator of lung infection in cystic fibrosis. Author(s): Marhaug G, Permin H, Husby G. Source: Acta Paediatr Scand. 1983 November; 72(6): 861-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6673488

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An unusual manifestation of staphylococcal lung infection. Author(s): Scammell AM, Heaf DP, Hart CA. Source: Br J Dis Chest. 1987 October; 81(4): 404-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3449124

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Anaerobic lung infection. Author(s): Gaur SN, Ramachandran S, Pant K, Chawla R, Thukral SS. Source: Indian J Chest Dis Allied Sci. 1987 October-December; 29(4): 223-6. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3451895

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Anaerobic lung infections treated with doxycycline. Author(s): Thadepalli H, Webb D, Huang JT. Source: Bull N Y Acad Med. 1978 February; 54(2): 165-76. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=272211

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Anaerobic lung infections. Author(s): Vincent MT, Goldman BS. Source: American Family Physician. 1994 June; 49(8): 1815-20. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8203319

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Analysis of restriction fragment length polymorphism and ribotyping of multiresistant Stenotrophomonas maltophilia isolated from persisting lung infection in a cystic fibrosis patient. Author(s): Wust J, Frei R, Gunthard H, Altwegg M. Source: Scandinavian Journal of Infectious Diseases. 1995; 27(5): 499-502. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8588142

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Antibody response to Pseudomonas aeruginosa in cystic fibrosis patients: a marker of therapeutic success?--A 30-year cohort study of survival in Danish CF patients after onset of chronic P. aeruginosa lung infection. Author(s): Johansen HK, Norregaard L, Gotzsche PC, Pressler T, Koch C, Hoiby N. Source: Pediatric Pulmonology. 2004 May; 37(5): 427-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15095326

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Antibody response to Pseudomonas aeruginosa surface protein antigens in a rat model of chronic lung infection. Author(s): Cochrane DM, Brown MR, Anwar H, Weller PH, Lam K, Costerton JW. Source: Journal of Medical Microbiology. 1988 December; 27(4): 255-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3143837

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Antilipopolysaccharide antibodies and differential diagnosis of chronic Pseudomonas aeruginosa lung infection in cystic fibrosis. Author(s): Fomsgaard A, Dinesen B, Shand GH, Pressler T, Hoiby N. Source: Journal of Clinical Microbiology. 1989 June; 27(6): 1222-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2502558

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Aspiration pneumonia and anaerobic lung infections. Author(s): Tuazon CU. Source: Primary Care. 1978 September; 5(3): 487-501. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=251325

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Augmentation therapy reduces frequency of lung infections in antitrypsin deficiency: a new hypothesis with supporting data. Author(s): Lieberman J. Source: Chest. 2000 November; 118(5): 1480-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11083705

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Bacterial diversity in cases of lung infection in cystic fibrosis patients: 16S ribosomal DNA (rDNA) length heterogeneity PCR and 16S rDNA terminal restriction fragment length polymorphism profiling. Author(s): Rogers GB, Hart CA, Mason JR, Hughes M, Walshaw MJ, Bruce KD. Source: Journal of Clinical Microbiology. 2003 August; 41(8): 3548-58. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12904354

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Bacteriological and radiographic features of lung infection by opportunist mycobacteris: a review. Author(s): Cook PL, Riddell RW, Simon G. Source: Tubercle. 1971 September; 52(3): 232-41. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4938218

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Bronchitis mimicking opportunistic lung infection in patients with human immunodeficiency virus infection/AIDS. Author(s): Chechani V, Allam AA, Smith PR, Webber CA, Kamholz SL. Source: N Y State J Med. 1992 July; 92(7): 297-300. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1518586

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Bronchopulmonary arterial malformation occurring in aspergillus lung infection complicating chronic granulomatous disease. Author(s): Wiseman NE, Reed MH. Source: Journal of Pediatric Surgery. 1981 August; 16(4): 457-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6168754

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Capofungin therapy for Aspergillus lung infection in a boy with chronic granulomatous disease. Author(s): Sallmann S, Heilmann A, Heinke F, Kerkmann ML, Schuppler M, Hahn G, Gahr M, Rosen-Wolff A, Roesler J. Source: The Pediatric Infectious Disease Journal. 2003 February; 22(2): 199-200. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12613459

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Cavitary lung infection caused by Mycobacterium flavescens. Author(s): Casimir MT, Fainstein V, Papadopolous N. Source: Southern Medical Journal. 1982 February; 75(2): 253-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7058379

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CFTR mutations and host susceptibility to Pseudomonas aeruginosa lung infection. Author(s): Pier GB. Source: Current Opinion in Microbiology. 2002 February; 5(1): 81-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11834374

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Changes in serum neopterin and serum beta 2-microglobulin in subjects with lung infections. Author(s): Carstens J, Andersen PL. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 1994 July; 7(7): 1233-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7925900

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Chlamydia trachomatis and Mycobacterium tuberculosis lung infection in an HIVpositive homosexual man. Author(s): Monno R, Maggi P, Carbonara S, Sibilio G, D'Aprile A, Costa D, Pastore G. Source: Aids Patient Care and Stds. 2001 December; 15(12): 607-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11788074

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Chlamydia trachomatis mouse pneumonitis lung infection in IL-18 and IL-12 knockout mice: IL-12 is dominant over IL-18 for protective immunity. Author(s): Lu H, Yang X, Takeda K, Zhang D, Fan Y, Luo M, Shen C, Wang S, Akira S, Brunham RC. Source: Molecular Medicine (Cambridge, Mass.). 2000 July; 6(7): 604-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10997341

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Cholestatic hepatitis in a patient who received clarithromycin therapy for a Mycobacterium chelonae lung infection. Author(s): Yew WW, Chau CH, Lee J, Leung CW. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 1994 June; 18(6): 1025-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8086541

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Chronic bullous disease of childhood and a paecilomyces lung infection in chronic granulomatous disease. Author(s): Sillevis Smitt JH, Leusen JH, Stas HG, Teeuw AH, Weening RS. Source: Archives of Disease in Childhood. 1997 August; 77(2): 150-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9301356

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Chronic granulomatous lung infection caused by the dimorphic fungus Emmonsia sp. Author(s): Wellinghausen N, Kern WV, Haase G, Rozdzinski E, Kern P, Marre R, Essig A, Hetzel J, Hetzel M. Source: International Journal of Medical Microbiology : Ijmm. 2003 December; 293(6): 441-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14760976

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Chronic lung infection in children. Author(s): Foster K, Alton H. Source: Paediatric Respiratory Reviews. 2003 September; 4(3): 225-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12880757

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Chronic Pseudomonas aeruginosa lung infection in cystic fibrosis. A longitudinal study of immune complex activity and inflammatory response in sputum sol-phase of cystic fibrosis patients with chronic Pseudomonas aeruginosa lung infections: influence of local steroid treatment. Author(s): Schiotz PO, Jorgensen M, Flensborg EW, Faero O, Husby S, Hoiby N, Jacobsen SV, Nielsen H, Svehag SE. Source: Acta Paediatr Scand. 1983 March; 72(2): 283-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6340415

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Ciprofloxacin-induced renal dysfunction in patients with mycobacterial lung infections. Author(s): Yew WW, Chau CH, Wong PC, Choi HY. Source: Tubercle and Lung Disease : the Official Journal of the International Union against Tuberculosis and Lung Disease. 1995 April; 76(2): 173-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7780103

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Clarithromycin in the treatment of Mycobacterium avium lung infections in patients without AIDS. Clarithromycin Study Group of France. Author(s): Dautzenberg B, Piperno D, Diot P, Truffot-Pernot C, Chauvin JP. Source: Chest. 1995 April; 107(4): 1035-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7705112

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Clindamycin vs penicillin for anaerobic lung infections. High rate of penicillin failures associated with penicillin-resistant Bacteroides melaninogenicus. Author(s): Gudiol F, Manresa F, Pallares R, Dorca J, Rufi G, Boada J, Ariza X, Casanova A, Viladrich PF. Source: Archives of Internal Medicine. 1990 December; 150(12): 2525-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1978771

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Coinoculation with Hartmannella vermiformis enhances replicative Legionella pneumophila lung infection in a murine model of Legionnaires' disease. Author(s): Brieland J, McClain M, Heath L, Chrisp C, Huffnagle G, LeGendre M, Hurley M, Fantone J, Engleberg C. Source: Infection and Immunity. 1996 July; 64(7): 2449-56. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8698466

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Colistin inhalation therapy in cystic fibrosis patients with chronic Pseudomonas aeruginosa lung infection. Author(s): Jensen T, Pedersen SS, Garne S, Heilmann C, Hoiby N, Koch C. Source: The Journal of Antimicrobial Chemotherapy. 1987 June; 19(6): 831-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3301785

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Comparative sensitivity of three methods for the diagnosis of cytomegalovirus lung infection. Author(s): Stirk PR, Griffiths PD. Source: Journal of Virological Methods. 1988 June; 20(2): 133-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2843557

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Comparison of efficacy and tolerance of intravenously and orally administered ciprofloxacin in cystic fibrosis patients with acute exacerbations of lung infection. Author(s): Strandvik B, Hjelte L, Lindblad A, Ljungberg B, Malmborg AS, Nilsson-Ehle I. Source: Scand J Infect Dis Suppl. 1989; 60: 84-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2756354

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Computed tomography in opportunistic lung infections. Author(s): Hartelius H. Source: Acta Radiologica (Stockholm, Sweden : 1987). 1988 March-April; 29(2): 171-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2833918

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Concurrent bacterial lung infection in patients with AIDS, PCP, and respiratory failure. Author(s): Peruzzi WT, Shapiro BA, Noskin GA, Currie DL, Skoutelis A, Murphy RL, Cane RD, Blake MJ. Source: Chest. 1992 May; 101(5): 1399-403. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1582304

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Correlation of interstitial pneumonia with human cytomegalovirus-induced lung infection and graft-versus-host disease after bone marrow transplantation. Author(s): Muller CA, Hebart H, Roos A, Roos H, Steidle M, Einsele H. Source: Medical Microbiology and Immunology. 1995 October; 184(3): 115-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8577311

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Cystic fibrosis lung infection cleared up? Author(s): Porteous D, Davidson D. Source: Nature Medicine. 1997 December; 3(12): 1317-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9396594

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Cystic fibrosis, lung infections, and a human tracheal antimicrobial peptide (hTAP). Author(s): Ko YH, Delannoy M, Pedersen PL. Source: Febs Letters. 1997 March 24; 405(2): 200-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9089291

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Deficiencies in lung surfactant proteins A and D are associated with lung infection in very premature neonatal baboons. Author(s): Awasthi S, Coalson JJ, Yoder BA, Crouch E, King RJ. Source: American Journal of Respiratory and Critical Care Medicine. 2001 February; 163(2): 389-97. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11179112

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Detection of nosocomial lung infection in ventilated patients. Author(s): Wunderink RG. Source: Am Rev Respir Dis. 1989 May; 139(5): 1302-4. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2712456

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Detection of nosocomial lung infection in ventilated patients. Use of a protected specimen brush and quantitative culture techniques in 147 patients. Author(s): Fagon JY, Chastre J, Hance AJ, Guiguet M, Trouillet JL, Domart Y, Pierre J, Gibert C. Source: Am Rev Respir Dis. 1988 July; 138(1): 110-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3144202

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Determination of IgG subclass antibodies to Pseudomonas aeruginosa outer membrane proteins in cystic fibrosis lung infection using immunoblotting and enzyme-linked immunosorbent assay. Author(s): Pressler T, Kronborg G, Shand GH, Mansa B, Hoiby N. Source: Medical Microbiology and Immunology. 1992; 181(6): 339-49. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1287420

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Diagnosis and treatment of anaerobic lung infections. Author(s): Thadepalli H, Webb DW. Source: Del Med J. 1979 June; 51(6): 327-30, 334-9. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=467749

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DNA vaccines against chronic lung infections by Pseudomonas aeruginosa. Author(s): Staczek J, Gilleland LB, van der Heyde HC, Gilleland HE. Source: Fems Immunology and Medical Microbiology. 2003 July 15; 37(2-3): 147-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12832118

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Doxycycline in the treatment of chronic lung infections. Author(s): Clendinnen IJ. Source: The Medical Journal of Australia. 1974 January 5; 1(1): 9-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4814429

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Early immune response in susceptible and resistant mice strains with chronic Pseudomonas aeruginosa lung infection determines the type of T-helper cell response. Author(s): Moser C, Hougen HP, Song Z, Rygaard J, Kharazmi A, Hoiby N. Source: Apmis : Acta Pathologica, Microbiologica, Et Immunologica Scandinavica. 1999 December; 107(12): 1093-100. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10660139

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Effect of ciprofloxacin in an in-vitro pharmacokinetic model against Pseudomonas aeruginosa isolated during cystic fibrosis lung infection. Author(s): Stevenson MI, Scott EM, Collier PS. Source: The Journal of Antimicrobial Chemotherapy. 1988 October; 22(4): 491-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3144524

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Efficacy and safety of sequential amoxicillin-clavulanate in the treatment of anaerobic lung infections. Author(s): Fernandez-Sabe N, Carratala J, Dorca J, Roson B, Tubau F, Manresa F, Gudiol F. Source: European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology. 2003 March; 22(3): 185-7. Epub 2003 March 05. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12649717

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Fiberoptic bronchoscopy in diagnosis of opportunistic lung infections: assessment of Sputa, Washings, Brushings and biopsy specimens. Author(s): Chopra SK, Mohsenifar Z. Source: The Western Journal of Medicine. 1979 July; 131(1): 4-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=483790

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Fungal lung infections treated by 5 flucytosine. Author(s): Symonds RP, Robertson AG, Stewart LM, Boyd G. Source: Scott Med J. 1982 July; 27(3): 244-6. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7112086

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Fungal pneumonia: the predominant lung infection causing death in children undergoing bone marrow transplantation. Author(s): Heurlin N, Bergstrom SE, Winiarski J, Ringden O, Ljungman P, Lonnqvist B, Andersson J. Source: Acta Paediatrica (Oslo, Norway : 1992). 1996 February; 85(2): 168-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8640044

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Ga-67 lung uptake in patients with adult respiratory distress syndrome. Association with lung infection and patients' prognosis. Author(s): Hardoff R, Bursztein-De Mytteraere S. Source: Clinical Nuclear Medicine. 1992 November; 17(11): 853-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1424372

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Gentamicin and tobramycin compared in the treatment of mucoid pseudomonas lung infections in cystic fibrosis. Author(s): Martin AJ, Smalley CA, George RH, Healing DE, Anderson CM. Source: Archives of Disease in Childhood. 1980 August; 55(8): 604-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7436516

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Glycosylation of alpha 1-acid glycoprotein in bacterial lung infections: distinct pattern in tuberculosis. Author(s): Fassbender K, Fassbender M, Schaberg T, Sobieska M, Muller W. Source: Clinical Chemistry. 1995 March; 41(3): 472-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7882529

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Good response to antibiotic treatment of lung infection due to Rhodococcus equi in a patient infected with human immunodeficiency virus. Author(s): Sasal M, Roig J, Cervantes M, Matas L, Segura F. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 1992 October; 15(4): 747-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1420703

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High frequency of hypermutable Pseudomonas aeruginosa in cystic fibrosis lung infection. Author(s): Oliver A, Canton R, Campo P, Baquero F, Blazquez J. Source: Science. 2000 May 19; 288(5469): 1251-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10818002

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Highly adherent small-colony variants of Pseudomonas aeruginosa in cystic fibrosis lung infection. Author(s): Haussler S, Ziegler I, Lottel A, von Gotz F, Rohde M, Wehmhohner D, Saravanamuthu S, Tummler B, Steinmetz I. Source: Journal of Medical Microbiology. 2003 April; 52(Pt 4): 295-301. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12676867

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Histological diagnosis of M. Kansasii lung infection: a case report. Author(s): Smith ER, Penman HG. Source: Pathology. 1971 April; 3(2): 93-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5094872

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Human immunodeficiency virus--associated lung infection: an overview. Author(s): Hopewell PC. Source: Seminars in Respiratory Infections. 1989 June; 4(2): 73-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2568670

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IgG subclasses and chronic bacterial infection. Subclass antibodies and the clinical course of chronic Pseudomonas aeruginosa lung infection in cystic fibrosis. Author(s): Pressler T. Source: Apmis. Supplementum. 1996; 66: 1-41. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8972694

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Imipenem in acute lung infections and bacterial re-exacerbations of chronic obstructive lung disease. Author(s): Pozzi E, De Rose V. Source: J Chemother. 1991 January; 3 Suppl 1: 213-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12041768

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Imipenem in the treatment of lung infections due to Mycobacterium fortuitum and Mycobacterium chelonae: further experience. Author(s): Yew WW, Lau KS, Tse WK, Wong CF. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 1992 December; 15(6): 1046-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1457638

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Imipenem/cilastatin treatment of multiresistant Pseudomonas aeruginosa lung infection in cystic fibrosis. Author(s): Pedersen SS, Pressler T, Hoiby N, Bentzon MW, Koch C. Source: The Journal of Antimicrobial Chemotherapy. 1985 November; 16(5): 629-35. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3935639

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Immune complexes in the sputum of patients with cystic fibrosis suffering from chronic Pseudomonas aeruginosa lung infection. Author(s): Schiotz PO, Nielsen H, Hoiby N, Glikmann G, Svehag SE. Source: Acta Pathol Microbiol Scand [c]. 1978 February; 86(1): 37-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=707104

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Immunology of the chronic lung infection. Author(s): Doring G. Source: Antibiot Chemother. 1991; 44: 80-4. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1801649

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In vitro cellular toxicity predicts Pseudomonas aeruginosa virulence in lung infections. Author(s): Sawa T, Ohara M, Kurahashi K, Twining SS, Frank DW, Doroques DB, Long T, Gropper MA, Wiener-Kronish JP. Source: Infection and Immunity. 1998 July; 66(7): 3242-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9632591

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Incidence and distribution of opportunistic lung infections in AIDS patients related to intravenous drug use: a study of bronchoalveolar lavage cytology by the Diff-Quik stain. Author(s): Kyriazis AP, Kyriazis AA. Source: Diagnostic Cytopathology. 1993 October; 9(5): 487-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7507027

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Influence of macrolide susceptibility on efficacies of clarithromycin and azithromycin against Streptococcus pneumoniae in a murine lung infection model. Author(s): Hoffman HL, Klepser ME, Ernst EJ, Petzold CR, Sa'adah LM, Doern GV. Source: Antimicrobial Agents and Chemotherapy. 2003 February; 47(2): 739-46. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12543686

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Intrauterine lung infection with Chlamydia trachomatis in a premature infant. Author(s): Mardh PA, Johansson PJ, Svenningsen N. Source: Acta Paediatr Scand. 1984 July; 73(4): 569-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6464746

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In-vitro investigation of the antibacterial activity of agents which may be used for the oral treatment of lung infections in CF patients. Author(s): Richards RM, Hamilton VE, Thomas MR. Source: The Journal of Antimicrobial Chemotherapy. 1998 August; 42(2): 171-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9738834

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Isolation and treatment of cystic fibrosis patients with lung infections caused by Pseudomonas (Burkholderia) cepacia and multiresistant Pseudomonas aeruginosa. Author(s): Hoiby N. Source: The Netherlands Journal of Medicine. 1995 June; 46(6): 280-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7643943

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Keep guard up against HIV-1-related lung infections, say experts. Author(s): McCarthy M. Source: Lancet. 1997 May 31; 349(9065): 1607. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9190488

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Lack of T-helper lymphocytes in BAL fluid from a HIV-negative patient with recurrent non-tuberculous mycobacterial lung infections. Author(s): Heurlin N, Bratel T, Andersson J, Christensson M, Christensson B. Source: Scandinavian Journal of Infectious Diseases. 1996; 28(6): 625-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9060068

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Lipopolysaccharide (LPS), LPS-immune complexes and cytokines as inducers of pulmonary inflammation in patients with cystic fibrosis and chronic Pseudomonas aeruginosa lung infection. Author(s): Kronborg G. Source: Apmis. Supplementum. 1995; 50: 1-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7756034

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Lipopolysaccharide is present in immune complexes isolated from sputum in patients with cystic fibrosis and chronic Pseudomonas aeruginosa lung infection. Author(s): Kronborg G, Shand GH, Fomsgaard A, Hoiby N. Source: Apmis : Acta Pathologica, Microbiologica, Et Immunologica Scandinavica. 1992 February; 100(2): 175-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1554493

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Longitudinal study of antibody response to lipopolysaccharides during chronic Pseudomonas aeruginosa lung infection in cystic fibrosis. Author(s): Fomsgaard A, Hoiby N, Shand GH, Conrad RS, Galanos C. Source: Infection and Immunity. 1988 September; 56(9): 2270-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3410536

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Lung infection and the diaphragm: placing basic research in clinical perspective. Author(s): Boczkowski J. Source: American Journal of Respiratory and Critical Care Medicine. 2004 March 15; 169(6): 662-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15003946

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Lung infection caused by Gordona aurantiaca (Rhodococcus aurantiacus). Author(s): Tsukamura M, Kawakami K. Source: Journal of Clinical Microbiology. 1982 October; 16(4): 604-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7153308

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Lung infection caused by Nocardia asteroides in a renal-transplant patient. Author(s): Natas OB, Willassen Y. Source: Scandinavian Journal of Infectious Diseases. 1983; 15(3): 317-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6359375

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Lung infection caused by Rhodococcus. Author(s): Hart DH, Peel MM, Andrew JH, Burdon JG. Source: Aust N Z J Med. 1988 October; 18(6): 790-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3242467

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Lung infection due to Mycobacterium xenopi: report of the first case in Japan. Author(s): Tsukamura M, Sekine K, Yokota A, Kuze A, Shibata M, Sato K. Source: Microbiology and Immunology. 1984; 28(1): 123-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6727712

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Lung infection with alginate-producing, mucoid Pseudomonas aeruginosa in cystic fibrosis. Author(s): Pedersen SS. Source: Apmis. Supplementum. 1992; 28: 1-79. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1449848

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Lung infection with anonymous mycobacteria. Author(s): Barter CE, Camens IM. Source: The Medical Journal of Australia. 1968 March 9; 1(10): 408-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4868828

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Lung infection with Burkholderia gladioli in a child with cystic fibrosis: acute clinical and spirometric deterioration. Author(s): Barker PM, Wood RE, Gilligan PH. Source: Pediatric Pulmonology. 1997 February; 23(2): 123-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9065952

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Lung infections associated with cystic fibrosis. Author(s): Lyczak JB, Cannon CL, Pier GB. Source: Clinical Microbiology Reviews. 2002 April; 15(2): 194-222. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11932230

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Lung infections in children. Author(s): Stark JM. Source: Current Opinion in Pediatrics. 1993 June; 5(3): 273-80. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8374645

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Lung infections in pediatric lung transplantation: experience in 49 cases. Author(s): Metras D, Viard L, Kreitmann B, Riberi A, Pannetier-Mille A, Garbi O, Marti JY, Geigle P. Source: European Journal of Cardio-Thoracic Surgery : Official Journal of the European Association for Cardio-Thoracic Surgery. 1999 April; 15(4): 490-4; Discussion 495. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10371127

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Lung infections. 1. Role of bacteria in the pathogenesis and progression of acute and chronic lung infection. Author(s): Stockley RA. Source: Thorax. 1998 January; 53(1): 58-62. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9577524

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Lung infections. 2. Branhamella catarrhalis: epidemiological and clinical aspects of a human respiratory tract pathogen. Author(s): Murphy TF. Source: Thorax. 1998 February; 53(2): 124-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9624298

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Lung infections. 3. Pseudomonas aeruginosa and other related species. Author(s): Wilson R, Dowling RB. Source: Thorax. 1998 March; 53(3): 213-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9659359

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Lung infections: role of apoptosis in host defense and pathogenesis of disease. Author(s): Behnia M, Robertson KA, Martin WJ 2nd. Source: Chest. 2000 June; 117(6): 1771-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10858414

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Management of Pseudomonas aeruginosa lung infection in Danish cystic fibrosis patients. Author(s): Pedersen SS, Jensen T, Hoiby N, Koch C, Flensborg EW. Source: Acta Paediatr Scand. 1987 November; 76(6): 955-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3425313

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Mechanism of Pseudomonas aeruginosa persistence during treatment with broadspectrum cephalosporins of lung infections in patients with cystic fibrosis. Author(s): Schryvers AB, Ogunariwo J, Chamberland S, Godfrey AJ, Rabin HR, Bryan LE. Source: Antimicrobial Agents and Chemotherapy. 1987 September; 31(9): 1438-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3118800

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Microbiology of cystic fibrosis lung infections: themes and issues. Author(s): Govan JR, Nelson JW. Source: Journal of the Royal Society of Medicine. 1993; 86 Suppl 20: 11-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7684788

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Microbiology of lung infection in cystic fibrosis. Author(s): Govan JR, Nelson JW. Source: British Medical Bulletin. 1992 October; 48(4): 912-30. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1281036

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Mucoid Pseudomonas aeruginosa growing in a biofilm in vitro are killed by opsonic antibodies to the mucoid exopolysaccharide capsule but not by antibodies produced during chronic lung infection in cystic fibrosis patients. Author(s): Meluleni GJ, Grout M, Evans DJ, Pier GB. Source: Journal of Immunology (Baltimore, Md. : 1950). 1995 August 15; 155(4): 2029-38. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7636254

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Murine model of BCG lung infection: dynamics of lymphocyte subpopulations in lung interstitium and tracheal lymph nodes. Author(s): Saxena RK, Weissman D, Simpson J, Lewis DM. Source: Journal of Biosciences. 2002 March; 27(2): 143-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11937685

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Mycobacterial lung infections. Author(s): Langdon DE. Source: Mayo Clinic Proceedings. 1999 July; 74(7): 744-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10405712

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Mycobacterium xenopi lung infection. Author(s): Wong CG, Harrison AC, Cornere M, Morris AJ. Source: N Z Med J. 1999 December 10; 112(1101): 476. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10678220

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New drugs for treating lung infection. Author(s): Nolan PE, Bass JB. Source: Chest. 1988 November; 94(5): 1076-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3053059

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Nocardia farcinica as a pathogen of lung infection. Author(s): Tsukamura M, Ohta M. Source: Microbiology and Immunology. 1980; 24(3): 237-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7412591

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Nocardia lung infection with hematogenous spread in a woman with adrenal cortical hyperfunction. Author(s): Pesce CM, Quaglia AC. Source: Eur J Respir Dis. 1984 November; 65(8): 613-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6394355

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Non-tuberculous mycobacterial lung infection complicated by chronic necrotising pulmonary aspergillosis. Author(s): Hafeez I, Muers MF, Murphy SA, Evans EG, Barton RC, McWhinney P. Source: Thorax. 2000 August; 55(8): 717-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10899252

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Non-tuberculous mycobacterial lung infection mimicking primary tuberculosis in non-immunocompromised children. Author(s): Levrey-Hadden H, Reix P, Louis D, Bellon G. Source: Acta Paediatrica (Oslo, Norway : 1992). 2002; 91(6): 725-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12162613

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Nosocomial lung infection and its diagnosis. Author(s): Tobin MJ, Grenvik A. Source: Critical Care Medicine. 1984 March; 12(3): 191-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6697743

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Ofloxacin and imipenem in the treatment of Mycobacterium fortuitum and Mycobacterium chelonae lung infections. Author(s): Yew WW, Kwan SY, Wong PC, Lee J. Source: Tubercle. 1990 June; 71(2): 131-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2219463

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Opportunist lung infections. Author(s): Lambert HP. Source: Journal of the Royal College of Physicians of London. 1979 January; 13(1): 29-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=33268

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Opportunistic lung infection caused by Rhodococcus (Corynebacterium) equi. Author(s): MacGregor JH, Samuelson WM, Sane DC, Godwin JD. Source: Radiology. 1986 July; 160(1): 83-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3715049

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Opportunistic lung infection due to "Pittsburgh Pneumonia Agent". Author(s): Myerowitz RL, Pasculle AW, Dowling JN, Pazin GJ Sr, Puerzer M, Yee RB, Rinaldo CR Jr, Hakala TR. Source: The New England Journal of Medicine. 1979 November 1; 301(18): 953-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=386116

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Opportunistic lung infection with Corynebacterium pseudodiphtheriticum after lung and heart transplantation. Author(s): Burke GJ, Malouf MA, Glanville AR. Source: The Medical Journal of Australia. 1997 April 7; 166(7): 362-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9137282

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Opportunistic lung infections in renal transplant patients: a comparison of Pittsburgh pneumonia agent and legionnaires' disease. Author(s): Taylor RJ, Schwentker FN, Hakala TR. Source: The Journal of Urology. 1981 March; 125(3): 289-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6259377

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Pedunculated malignant peripheral nerve-sheath tumour of the diaphragm presenting as recurrent lung infection: ultrasound diagnosis. Author(s): Ko SF, Ng SH, Lee TY, Sun PL, Lee SY, Hsiao CC. Source: The British Journal of Radiology. 2003 August; 76(908): 574-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12893703

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Pefloxacin versus imipenem in the therapy of nosocomial lung infections of intensive care unit patients. Author(s): Giamarellou H, Mandragos K, Bechrakis P, Pigas K, Bilalis D, Sfikakis P. Source: The Journal of Antimicrobial Chemotherapy. 1990 October; 26 Suppl B: 117-27. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2258339

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Peri-emphysematous lung infection. Author(s): Mahler DA, D'Esopo ND. Source: Clinics in Chest Medicine. 1981 January; 2(1): 51-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6914223

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Persistent lung infection due to Mycobacterium szulgai. Author(s): Collazos J, Diaz F, Rodriguez J, Ayarza R. Source: Tubercle and Lung Disease : the Official Journal of the International Union against Tuberculosis and Lung Disease. 1993 December; 74(6): 412-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8136500

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Piperacillin and tobramycin in the treatment of Pseudomonas lung infections in cystic fibrosis. Author(s): Hoogkamp-Korstanje JA, van der Laag J. Source: The Journal of Antimicrobial Chemotherapy. 1983 August; 12(2): 175-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6619055

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Pleuropulmonary lung infection by anaerobic bacteria. Author(s): Abeysundere RL, Hodson ME, Szawatkowski M, Noone P. Source: Br J Dis Chest. 1978 July; 72(3): 187-95. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=29654

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Potential of preventing Pseudomonas aeruginosa lung infections in cystic fibrosis patients: experimental studies in animals. Author(s): Johansen HK. Source: Apmis. Supplementum. 1996; 63: 5-42. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8944052

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Prevalence of Chlamydia trachomatis lung infection in patients with acquired immune deficiency syndrome. Author(s): Moncada JV, Schachter J, Wofsy C. Source: Journal of Clinical Microbiology. 1986 May; 23(5): 986. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3486881

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Prevention of lung infections associated with human immunodeficiency virus infection. Author(s): Hopewell PC. Source: Thorax. 1989 December; 44(12): 1038-44. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2575801

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Prevention of nosocomial lung infection in ventilated patients: use of an antimicrobial pharyngeal nonabsorbable paste. Author(s): Rodriguez-Roldan JM, Altuna-Cuesta A, Lopez A, Carrillo A, Garcia J, Leon J, Martinez-Pellus AJ. Source: Critical Care Medicine. 1990 November; 18(11): 1239-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2225893

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Production of N-acyl-L-homoserine lactones by P. aeruginosa isolates from chronic lung infections associated with cystic fibrosis. Author(s): Geisenberger O, Givskov M, Riedel K, Hoiby N, Tummler B, Eberl L. Source: Fems Microbiology Letters. 2000 March 15; 184(2): 273-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10713433

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Prone position for the prevention of lung infection. Author(s): Beuret P. Source: Minerva Anestesiol. 2002 April; 68(4): 266-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12024097

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Protection against Pseudomonas aeruginosa chronic lung infection in mice by genetic immunization against outer membrane protein F (OprF) of P. aeruginosa. Author(s): Price BM, Galloway DR, Baker NR, Gilleland LB, Staczek J, Gilleland HE Jr. Source: Infection and Immunity. 2001 May; 69(5): 3510-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11292786

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Protection of Cftr knockout mice from acute lung infection by a helper-dependent adenoviral vector expressing Cftr in airway epithelia. Author(s): Koehler DR, Sajjan U, Chow YH, Martin B, Kent G, Tanswell AK, McKerlie C, Forstner JF, Hu J. Source: Proceedings of the National Academy of Sciences of the United States of America. 2003 December 23; 100(26): 15364-9. Epub 2003 Dec 12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14673110

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Proteinases in chronic lung infection. Author(s): Stockley RA, Hill SL, Burnett D. Source: Annals of the New York Academy of Sciences. 1991; 624: 257-66. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2064226

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Proteus mirabilis as a cause of recurrent lung infection in a cystic fibrosis patient. Author(s): Ojeda-Vargas M, Pacheco A, Elia M, Villaverde R, Baquero F. Source: European Journal of Clinical Microbiology & Infectious Diseases: Official Publication of the European Society of Clinical Microbiology. 1990 March; 9(3): 234-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2186915

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Pseudomonas aeruginosa alginate is refractory to Th1 immune response and impedes host immune clearance in a mouse model of acute lung infection. Author(s): Song Z, Wu H, Ciofu O, Kong KF, Hoiby N, Rygaard J, Kharazmi A, Mathee K. Source: Journal of Medical Microbiology. 2003 September; 52(Pt 9): 731-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12909647

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Pseudomonas aeruginosa chromosomal beta-lactamase in patients with cystic fibrosis and chronic lung infection. Mechanism of antibiotic resistance and target of the humoral immune response. Author(s): Ciofu O. Source: Apmis. Supplementum. 2003; (116): 1-47. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14692154

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Pseudomonas aeruginosa lasR transcription correlates with the transcription of lasA, lasB, and toxA in chronic lung infections associated with cystic fibrosis. Author(s): Storey DG, Ujack EE, Rabin HR, Mitchell I. Source: Infection and Immunity. 1998 June; 66(6): 2521-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9596711

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Pyogenic lung infections. Author(s): Mwandumba HC, Beeching NJ. Source: Current Opinion in Pulmonary Medicine. 1999 May; 5(3): 151-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10228739

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Pyogenic lung infections: factors for predicting clinical outcome of lung abscess and thoracic empyema. Author(s): Mwandumba HC, Beeching NJ. Source: Current Opinion in Pulmonary Medicine. 2000 May; 6(3): 234-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10782709

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Radiographic patterns of opportunistic lung infections and Kaposi sarcoma in homosexual men. Author(s): McCauley DI, Naidich DP, Leitman BS, Reede DL, Laubenstein L. Source: Ajr. American Journal of Roentgenology. 1982 October; 139(4): 653-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6981922

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Rapid diagnosis of cytomegalovirus lung infection by DNA amplification in bronchoalveolar lavages. Author(s): Liesnard C, De Wit L, Motte S, Brancart F, Content J. Source: Molecular and Cellular Probes. 1994 August; 8(4): 273-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7870069

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Rapidly growing mycobacterial lung infection in association with esophageal disorders. Author(s): Hadjiliadis D, Adlakha A, Prakash UB. Source: Mayo Clinic Proceedings. 1999 January; 74(1): 45-51. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9987532

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Relapse of Paragonimus westermani lung infection after bithionol therapy. Author(s): Coleman DL, Barry M. Source: The American Journal of Tropical Medicine and Hygiene. 1982 January; 31(1): 71-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7058981

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Repeated lung infections. Scimitar syndrome. Author(s): Ziora D, Kozielski J, Glowacki J, Rycaj M, Niepsuj G. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 1994 March; 7(3): 617-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8013620

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Replicative Legionella pneumophila lung infection in intratracheally inoculated A/J mice. A murine model of human Legionnaires' disease. Author(s): Brieland J, Freeman P, Kunkel R, Chrisp C, Hurley M, Fantone J, Engleberg C. Source: American Journal of Pathology. 1994 December; 145(6): 1537-46. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7992856

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Respiratory syncytial virus lung infection in infants: immunoregulatory role of infected alveolar macrophages. Author(s): Midulla F, Villani A, Panuska JR, Dab I, Kolls JK, Merolla R, Ronchetti R. Source: The Journal of Infectious Diseases. 1993 December; 168(6): 1515-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8245538

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Rhodococcus equi pneumonia: highly active antiretroviral therapy helps but does not cure lung infection. Author(s): Sanz-Moreno J, Flores-Segovia J, Olmedilla-Arregui G, Gomez-Herruz P, Granell J. Source: Aids (London, England). 2002 February 15; 16(3): 509-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11834975

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Role of adherence in the pathogenesis of Pseudomonas aeruginosa lung infection in cystic fibrosis patients. Author(s): Woods DE, Bass JA, Johanson WG Jr, Straus DC. Source: Infection and Immunity. 1980 December; 30(3): 694-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7014444

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Role of exoenzyme S in chronic Pseudomonas aeruginosa lung infections. Author(s): Nicas TI, Frank DW, Stenzel P, Lile JD, Iglewski BH. Source: European Journal of Clinical Microbiology. 1985 April; 4(2): 175-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2988945

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Role of mutant CFTR in hypersusceptibility of cystic fibrosis patients to lung infections. Author(s): Pier GB, Grout M, Zaidi TS, Olsen JC, Johnson LG, Yankaskas JR, Goldberg JB. Source: Science. 1996 January 5; 271(5245): 64-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8539601

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Role of Pseudomonas aeruginosa exoenzymes in lung infections of patients with cystic fibrosis. Author(s): Doring G, Goldstein W, Roll A, Schiotz PO, Hoiby N, Botzenhart K. Source: Infection and Immunity. 1985 September; 49(3): 557-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3928491

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Serum antibodies to Pseudomonas aeruginosa outer-membrane proteins and ironregulated membrane proteins at different stages of chronic cystic fibrosis lung infection. Author(s): Shand GH, Pedersen SS, Brown MR, Hoiby N. Source: Journal of Medical Microbiology. 1991 April; 34(4): 203-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1902261

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Simultaneous lung infections in patients with acquired immunodeficiency syndrome. Author(s): Pierce JR Jr. Source: Archives of Internal Medicine. 1994 February 14; 154(3): 342. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8141901

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Staphylococcal lung infection in children. Author(s): Krishna Das MS, Guha DK, Geeta K. Source: Indian Pediatrics. 1977 July; 14(7): 545-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=924666

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Staphylococcus aureus capsular types and antibody response to lung infection in patients with cystic fibrosis. Author(s): Albus A, Fournier JM, Wolz C, Boutonnier A, Ranke M, Hoiby N, Hochkeppel H, Doring G. Source: Journal of Clinical Microbiology. 1988 December; 26(12): 2505-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3230130

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•

Successful elimination of an invasive Aspergillus nidulans lung infection by voriconazole after failure of a combination of caspofungin and liposomal amphotericin B in a boy with chronic granulomatous disease. Author(s): Rosen-Wolff A, Koch A, Friedrich W, Hahn G, Gahr M, Roesler J. Source: The Pediatric Infectious Disease Journal. 2004 June; 23(6): 584-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15194848

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The air crescent sign caused by Staphylococcus aureus lung infection in a neutropenic patient with leukemia. Author(s): Gold W, Vellend H, Brunton J. Source: Annals of Internal Medicine. 1992 June 1; 116(11): 910-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1580448

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The damaging role of bacteria in chronic lung infection. Author(s): Cole P. Source: The Journal of Antimicrobial Chemotherapy. 1997 December; 40 Suppl A: 5-10. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9484867

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The function of lung and blood neutrophils in patients with the adult respiratory distress syndrome. Implications for the pathogenesis of lung infections. Author(s): Martin TR, Pistorese BP, Hudson LD, Maunder RJ. Source: Am Rev Respir Dis. 1991 August; 144(2): 254-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1650151

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The glycosylation of airway mucins in cystic fibrosis and its relationship with lung infection by Pseudomonas aeruginosa. Author(s): Roussel P, Lamblin G. Source: Advances in Experimental Medicine and Biology. 2003; 535: 17-32. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14714886

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The immune response to chronic Pseudomonas aeruginosa lung infection in cystic fibrosis patients is predominantly of the Th2 type. Author(s): Moser C, Kjaergaard S, Pressler T, Kharazmi A, Koch C, Hoiby N. Source: Apmis : Acta Pathologica, Microbiologica, Et Immunologica Scandinavica. 2000 May; 108(5): 329-35. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10937769

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The innate immune response to pneumococcal lung infection: the untold story. Author(s): Kadioglu A, Andrew PW. Source: Trends in Immunology. 2004 March; 25(3): 143-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15036042

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The pathogenesis of Pseudomonas aeruginosa lung infections in cystic fibrosis. Author(s): Grimwood K. Source: Journal of Paediatrics and Child Health. 1992 February; 28(1): 4-11. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1554515

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The place of lung 99mTc DTPA aerosol transfer in the investigation of lung infections in HIV positive patients. Author(s): O'Doherty MJ, Page CJ, Bradbeer CS, Shahmanesh M, Edwards A, Barlow D, Nunan TO, Bateman NT. Source: Respiratory Medicine. 1989 September; 83(5): 395-401. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2694235

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The Pseudomonas aeruginosa alternative sigma factor PvdS controls exotoxin A expression and is expressed in lung infections associated with cystic fibrosis. Author(s): Hunt TA, Peng WT, Loubens I, Storey DG. Source: Microbiology (Reading, England). 2002 October; 148(Pt 10): 3183-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12368452

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The relation between respiratory illness in primary schoolchildren and the use of gas for cooking--III. Nitrogen dioxide, respiratory illness and lung infection. Author(s): Florey CV, Melia RJ, Chinn S, Goldstein BD, Brooks AG, John HH, Craighead IB, Webster X. Source: International Journal of Epidemiology. 1979 December; 8(4): 347-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=541157

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The relationship between malnutrition and lung infections. Author(s): Martin TR. Source: Clinics in Chest Medicine. 1987 September; 8(3): 359-72. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3117482

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The value of bronchoalveolar lavage in the immuno-compromised host with suspected opportunistic lung infection. Author(s): Holmes P, McLaughlin P, Garfield A, Tai E. Source: Panminerva Medica. 1986 April-June; 28(2): 107-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3774357

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Treatment of Pseudomonas aeruginosa lung infection in cystic fibrosis with high or conventional doses of ceftazidime. Author(s): De Boeck K, Breysem L. Source: The Journal of Antimicrobial Chemotherapy. 1998 March; 41(3): 407-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9578170

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Treatment of Pseudomonas lung infection in cystic fibrosis with piperacillin plus tobramycin versus ceftazidime monotherapy: preliminary communication. Author(s): De Boeck K, Smet M, Eggermont E. Source: Pediatric Pulmonology. 1989; 7(3): 171-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2508049

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Trimethoprim--sulphamethoxazole in intestinal and lung infections. Author(s): Kanaghinis T, Jordanoglou J, Gardikas C. Source: Chemotherapy. 1973; 18(3): 184-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4684645

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Tuberculosis, lung infections, and interstitial lung disease in AJRCCM 2000. Author(s): Tobin MJ. Source: American Journal of Respiratory and Critical Care Medicine. 2001 November 15; 164(10 Pt 1): 1774-88. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11734425

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Tuberculosis, lung infections, interstitial lung disease, and journalology in AJRCCM 2002. Author(s): Tobin MJ. Source: American Journal of Respiratory and Critical Care Medicine. 2003 February 1; 167(3): 345-55. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12554623

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Tuberculosis, lung infections, interstitial lung disease, and socioeconomic issues in AJRCCM 2001. Author(s): Tobin MJ. Source: American Journal of Respiratory and Critical Care Medicine. 2002 March 1; 165(5): 631-41. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11874809

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Tuberculosis, lung infections, interstitial lung disease, social issues and journalology in AJRCCM 2003. Author(s): Tobin MJ. Source: American Journal of Respiratory and Critical Care Medicine. 2004 January 15; 169(2): 288-300. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14718242

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Use of a mouse lung challenge model to identify antigens protective against Chlamydia pneumoniae lung infection. Author(s): Murdin AD, Dunn P, Sodoyer R, Wang J, Caterini J, Brunham RC, Aujame L, Oomen R. Source: The Journal of Infectious Diseases. 2000 June; 181 Suppl 3: S544-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10839756

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Use of immunoblot detection of serum antibodies in the diagnosis of chronic Pseudomonas aeruginosa lung infection in cystic fibrosis. Author(s): Shand GH, Pedersen SS, Tilling R, Brown MR, Hoiby N. Source: Journal of Medical Microbiology. 1988 November; 27(3): 169-77. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3143012

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Use of pulsed-field gel electrophoresis as an epidemiologic tool during an outbreak of Pseudomonas aeruginosa lung infections in an intensive care unit. Author(s): Talon D, Capellier G, Boillot A, Michel-Briand Y. Source: Intensive Care Medicine. 1995 December; 21(12): 996-1002. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8750124

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Usefulness of transtracheal puncture in the bacteriological diagnosis of lung infections in children. Author(s): Baran D, Cordier N. Source: Helv Paediatr Acta. 1973 November; 28(5): 391-9. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4589721

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Yersinia enterocolitica lung infection. Author(s): Bigler RD, Atkins RR, Wing EJ. Source: Archives of Internal Medicine. 1981 October; 141(11): 1529-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7283567

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CHAPTER 2. ALTERNATIVE MEDICINE AND LUNG INFECTION Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to lung infection. 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 lung infection 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 “lung infection” (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 lung infection: •

Edetate sodium aerosol in Pseudomonas lung infection in cystic fibrosis. Author(s): Brown J, Mellis CM, Wood RE. Source: Am J Dis Child. 1985 August; 139(8): 836-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3927708

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Effect of cytostatic agents on the number of alveolar phagocytes and the efficacy of ceftriaxone in an experimental murine lung infection. Author(s): Calame W, Mattie H. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 1991 March; 4(3): 340-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1864349

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Effects of Chinese medicinal herbs on a rat model of chronic Pseudomonas aeruginosa lung infection. Author(s): Song Z, Johansen HK, Moser C, Hoiby N. Source: Apmis : Acta Pathologica, Microbiologica, Et Immunologica Scandinavica. 1996 May; 104(5): 350-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8703440

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Gerimax ginseng regulates both humoral and cellular immunity during chronic Pseudomonas aeruginosa lung infection. Author(s): Song Z, Wu H, Mathee K, Hoiby N, Kharazmi A. Source: Journal of Alternative and Complementary Medicine (New York, N.Y.). 2002 August; 8(4): 459-66. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12230906

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Nutritional effects on host response to lung infections with mucoid Pseudomonas aeruginosa in mice. Author(s): van Heeckeren AM, Schluchter M, Xue L, Alvarez J, Freedman S, St George J, Davis PB. Source: Infection and Immunity. 2004 March; 72(3): 1479-86. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14977953

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/

Alternative Medicine 57

The following is a specific Web list relating to lung infection; 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 Cystic Fibrosis Source: Healthnotes, Inc.; www.healthnotes.com Cystic Fibrosis Source: Integrative Medicine Communications; www.drkoop.com Diarrhea Source: Healthnotes, Inc.; www.healthnotes.com Histoplasmosis Source: Integrative Medicine Communications; www.drkoop.com Radiation Damage Source: Integrative Medicine Communications; www.drkoop.com

•

Herbs and Supplements Panax Alternative names: Ginseng; Panax ginseng 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 3. PATENTS ON LUNG INFECTION 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.7 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 “lung infection” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on lung infection, we have not necessarily excluded non-medical patents in this bibliography.

Patent Applications on Lung Infection As of December 2000, U.S. patent applications are open to public viewing.8 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 lung infection:

7Adapted

from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm. 8 This has been a common practice outside the United States prior to December 2000.

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Method and system of diagnosing intrapulmonary infection using an electronic nose Inventor(s): Hanson, C. William III; (Radnor, PA) Correspondence: Akin Gump Strauss Hauer & Feld L.L.P.; One Commerce Square; 2005 Market Street, Suite 2200; Philadelphia; PA; 19103-7013; US Patent Application Number: 20030078511 Date filed: August 23, 2002 Abstract: The presence of a pathologic process in a lung of a mammal is detected by applying exhaled gas of a mammal to an electronic nose. Data derived from the electronic nose is used to determine whether a pathologic process is present in the lung of the mammal. The pathologic process may be a lung infection such as pneumonia. Excerpt(s): This application is a division of U.S. application Ser. No. 09/719,504 filed Feb. 9, 2001 (35 U.S.C.sctn.371 date) entitled "DIAGNOSING INTRAPULMONARY INFECTION AND ANALYZING NASAL SAMPLE, " the entire disclosure of which is incorporated herein by reference. The sense of smell has long been used as a diagnostic tool by medical clinicians. Because of its subjectivity and the lack of correlative monitors, smell, as a diagnostic tool, has never achieved significant prominence in modern medicine. "Electronic noses" or "electronic olfactory sensors" have recently been developed to provide objective measurements and analysis of aromas. One particular "electronic nose" which has achieved some commercial success, primarily in the area of quality control and environmental monitoring in particular industries such as the beverage, flavor, perfume and certain aspects of the food industries, is manufactured by Aromascan, Inc. of Hollis, N.H. The Aromascan product uses changes in an electrical property (specifically, impedance or resistance) of sensors in a sensor array made of a layer of a semi-conducting organic polymer, when exposed to particles in a gas for aroma analysis. The Aromascan product is disclosed in U.S. Pat. No. 4,887,455 (Payne et al.), the disclosure of which is incorporated herein by reference. The use of the Aromascan product permits the characterization and digital representation of aromas for the measurement, recording and objective analysis of aromas. In this manner, the Aromascan product emulates the performance of the human nose with discrimination, sensitivity and, most importantly, objective reproducibility. Details concerning the structure and operation of the Aromascan product are available from Aromascan and the above-cited patent. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Methods for treating lung infections and lung tumors and for treating and preventing lung metastases Inventor(s): Luhrmann, Anke; (Hannover, DE), Muhlradt, Peter; (Braunschweig, DE), Pabst, Reinhard; (Hannover, DE), Tschernig, Thomas; (Hildesheim, DE) Correspondence: Marshall, Gerstein & Borun Llp; 6300 Sears Tower; 233 S. Wacker Drive; Chicago; IL; 60606; US Patent Application Number: 20040127405 Date filed: April 11, 2003 Abstract: The invention relates to methods of treating lung infections and lung tumors and treating and preventing metastases of extrapulmonary tumors by administering lipopeptides or lipoproteins having the following formula (I): 1wherein:R.sub.1 and

Patents 61

R.sub.2, which may be the same or different from one another, denote C.sub.7-25 alkyl, C.sub.7-25 alkenyl, or C.sub.7-25 alkynyl,X denotes S, O, or CH.sub.2,W denotes CO or S(O).sub.n (where n=1 or 2),Y denotes a physiologically acceptable amino acid sequence, and* denotes an asymmetric carbon atom. Excerpt(s): This is a continuation-in-part of U.S. Ser. No. 10/(serial number not available) filed Apr. 2, 2003, which is the U.S. national phase of International Application No. PCT/EP01/11414, filed Oct. 2, 2001, the entire disclosure of which is hereby incorporated herein by reference. The invention relates to methods for treating lung infections and lung tumors, for treating and preventing lung metastases, for preventing lung inflammations, and for increasing lymphatic tissue in the bronchial mucosa, by administering lipopeptides or lipoproteins. It is known that lipopeptides, which were originally isolated from micro-organisms and which are available synthetically, activate macrophages (Baschang, C. 1989. Tetrahedron 45:6331-6360.). Variants of such lipopeptides from mycoplasmas are, by virtue of particular structural features, especially active (Muhlradt, P. F., M. Kie.beta., H. Meyer, R. Su.beta.muth, and G. Jung. 1997. J. Exp. Med. 185:1951-1958; Muhlradt, P. F., M. Kie.beta., H. Meyer, R. Su.beta.muth, and G. Jung. 1998. Infect. Immun. 66: 4804-4810). Such lipopeptides are obtainable synthetically (See, for example, Metzger, J. W., K-H. Wiesmuller and G. Jung. 1991. Int. J. Peptide Protein. Res. 38: 545-554, the entire disclosure of which is hereby incorporated herein by reference). At picogram per milliliter (pg/ml) concentrations in cell cultures, they are capable of stimulating various cells, including primarily macrophages, to synthesize proinflammatory cytokines (interleukin-1, interleukin-6, tumor necrosis factor) and chemokines (MIP-1, M1P-2, MCP-1, IL-8) (Deiters, U. and P. F. Muhlradt. 1999. Infect. Immun. 67: 3390-3398; Kaufmann, A., P. F. Muhlradt, D. Gemsa and H. Sprenger. 1999. Infect. Immun. 67: 6303-6308). 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 lung infection, you can access the U.S. Patent Office archive via the Internet at the following Web address: http://www.uspto.gov/patft/index.html. You will see two broad options: (1) Issued Patent, and (2) Published Applications. To see a list of issued patents, perform the following steps: Under “Issued Patents,” click “Quick Search.” Then, type “lung infection” (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 lung infection. You can also use this procedure to view pending patent applications concerning lung infection. 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 4. INFECTION

PERIODICALS

AND

NEWS

ON

LUNG

Overview In this chapter, we suggest a number of news sources and present various periodicals that cover lung infection.

News Services and Press Releases One of the simplest ways of tracking press releases on lung infection 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 “lung infection” (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 lung infection. 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 “lung infection” (or synonyms). The following was recently listed in this archive for lung infection: •

IgG levels do not explain lung infection susceptibility in HIV-infected patients Source: Reuters Medical News Date: February 26, 2001

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Antiproteolytic therapy reduces lung infections in antitrypsin deficiency Source: Reuters Industry Breifing Date: November 21, 2000

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Previous lung infections may be a factor in vaccine failure Source: Reuters Industry Breifing Date: November 06, 2000

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Ginseng effective in treating lung infection in mice Source: Reuters Health eLine Date: May 24, 2000

•

Smoking may impair protection against lung infection in HIV-positive individuals Source: Reuters Medical News Date: November 20, 1998

•

AIDS-related CMV lung infection can lead to pulmonary hypertension Source: Reuters Medical News Date: July 30, 1998 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 “lung infection” (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

Periodicals and News

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you can use this Web site’s general news search page at http://news.yahoo.com/. Type in “lung infection” (or synonyms). If you know the name of a company that is relevant to lung infection, 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 “lung infection” (or synonyms).

Academic Periodicals covering Lung Infection Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to lung infection. In addition to these sources, you can search for articles covering lung infection that have been published by any of the periodicals listed in previous chapters. To find the latest studies published, go to http://www.ncbi.nlm.nih.gov/pubmed, type the name of the periodical into the search box, and click “Go.” If you want complete details about the historical contents of a journal, you can also visit the following Web site: http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi. Here, type in the name of the journal or its abbreviation, and you will receive an index of published articles. At http://locatorplus.gov/, you can retrieve more indexing information on medical periodicals (e.g. the name of the publisher). Select the button “Search LOCATORplus.” Then type in the name of the journal and select the advanced search option “Journal Title Search.”

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CHAPTER 5. RESEARCHING MEDICATIONS Overview While a number of hard copy or CD-ROM resources are available for researching medications, a more flexible method is to use Internet-based databases. Broadly speaking, there are two sources of information on approved medications: public sources and private sources. We will emphasize free-to-use public sources.

U.S. Pharmacopeia Because of historical investments by various organizations and the emergence of the Internet, it has become rather simple to learn about the medications recommended for lung infection. One such source is the United States Pharmacopeia. In 1820, eleven physicians met in Washington, D.C. to establish the first compendium of standard drugs for the United States. They called this compendium the U.S. Pharmacopeia (USP). Today, the USP is a nonprofit organization consisting of 800 volunteer scientists, eleven elected officials, and 400 representatives of state associations and colleges of medicine and pharmacy. The USP is located in Rockville, Maryland, and its home page is located at http://www.usp.org/. The USP currently provides standards for over 3,700 medications. The resulting USP DI Advice for the Patient can be accessed through the National Library of Medicine of the National Institutes of Health. The database is partially derived from lists of federally approved medications in the Food and Drug Administration’s (FDA) Drug Approvals database, located at http://www.fda.gov/cder/da/da.htm. While the FDA database is rather large and difficult to navigate, the Phamacopeia is both user-friendly and free to use. It covers more than 9,000 prescription and over-the-counter medications. To access this database, simply type the following hyperlink into your Web browser: http://www.nlm.nih.gov/medlineplus/druginformation.html. To view examples of a given medication (brand names, category, description, preparation, proper use, precautions, side effects, etc.), simply follow the hyperlinks indicated within the United States Pharmacopeia (USP). Below, we have compiled a list of medications associated with lung infection. If you would like more information on a particular medication, the provided hyperlinks will direct you to ample documentation (e.g. typical dosage, side effects, drug-interaction risks, etc.). The

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following drugs have been mentioned in the Pharmacopeia and other sources as being potentially applicable to lung infection: Cefditoren •

Systemic - U.S. Brands: Spectracef http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/500329.html

Dornase Alfa •

Inhalation - U.S. Brands: Pulmozyme http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202710.html

Commercial Databases In addition to the medications listed in the USP above, a number of commercial sites are available by subscription to physicians and their institutions. Or, you may be able to access these sources from your local medical library.

Mosby’s Drug Consult Mosby’s Drug Consult database (also available on CD-ROM and book format) covers 45,000 drug products including generics and international brands. It provides prescribing information, drug interactions, and patient information. Subscription information is available at the following hyperlink: http://www.mosbysdrugconsult.com/. PDRhealth The PDRhealth database is a free-to-use, drug information search engine that has been written for the public in layman’s terms. It contains FDA-approved drug information adapted from the Physicians’ Desk Reference (PDR) database. PDRhealth can be searched by brand name, generic name, or indication. It features multiple drug interactions reports. Search PDRhealth at http://www.pdrhealth.com/drug_info/index.html. Other Web Sites Drugs.com (www.drugs.com) reproduces the information in the Pharmacopeia as well as commercial information. You may also want to consider the Web site of the Medical Letter, Inc. (http://www.medletter.com/) which allows users to download articles on various drugs and therapeutics for a nominal fee. If you have any questions about a medical treatment, the FDA may have an office near you. Look for their number in the blue pages of the phone book. You can also contact the FDA through its toll-free number, 1-888-INFO-FDA (1-888-463-6332), or on the World Wide Web at www.fda.gov.

69

APPENDICES

71

APPENDIX A. PHYSICIAN RESOURCES Overview In this chapter, we focus on databases and Internet-based guidelines and information resources created or written for a professional audience.

NIH Guidelines Commonly referred to as “clinical” or “professional” guidelines, the National Institutes of Health publish physician guidelines for the most common diseases. Publications are available at the following by relevant Institute9: •

Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm

•

National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/news/facts/

•

National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html

•

National Cancer Institute (NCI); guidelines available at http://www.cancer.gov/cancerinfo/list.aspx?viewid=5f35036e-5497-4d86-8c2c714a9f7c8d25

•

National Eye Institute (NEI); guidelines available at http://www.nei.nih.gov/order/index.htm

•

National Heart, Lung, and Blood Institute (NHLBI); guidelines available at http://www.nhlbi.nih.gov/guidelines/index.htm

•

National Human Genome Research Institute (NHGRI); research available at http://www.genome.gov/page.cfm?pageID=10000375

•

National Institute on Aging (NIA); guidelines available at http://www.nia.nih.gov/health/

9 These

publications are typically written by one or more of the various NIH Institutes.

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•

National Institute on Alcohol Abuse and Alcoholism (NIAAA); guidelines available at http://www.niaaa.nih.gov/publications/publications.htm

•

National Institute of Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/

•

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm

•

National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm

•

National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/

•

National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/

•

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm

•

National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html

•

National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm

•

National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/practitioners/index.cfm

•

National Institute of Neurological Disorders and Stroke (NINDS); neurological disorder information pages available at http://www.ninds.nih.gov/health_and_medical/disorder_index.htm

•

National Institute of Nursing Research (NINR); publications on selected illnesses at http://www.nih.gov/ninr/news-info/publications.html

•

National Institute of Biomedical Imaging and Bioengineering; general information at http://grants.nih.gov/grants/becon/becon_info.htm

•

Center for Information Technology (CIT); referrals to other agencies based on keyword searches available at http://kb.nih.gov/www_query_main.asp

•

National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/

•

National Center for Research Resources (NCRR); various information directories available at http://www.ncrr.nih.gov/publications.asp

•

Office of Rare Diseases; various fact sheets available at http://rarediseases.info.nih.gov/html/resources/rep_pubs.html

•

Centers for Disease Control and Prevention; various fact sheets on infectious diseases available at http://www.cdc.gov/publications.htm

Physician Resources

73

NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.10 Physician-oriented resources provide a wide variety of information related to the biomedical and health sciences, both past and present. The format of these resources varies. Searchable databases, bibliographic citations, full-text articles (when available), archival collections, and images are all available. The following are referenced by the National Library of Medicine:11 •

Bioethics: Access to published literature on the ethical, legal, and public policy issues surrounding healthcare and biomedical research. This information is provided in conjunction with the Kennedy Institute of Ethics located at Georgetown University, Washington, D.C.: http://www.nlm.nih.gov/databases/databases_bioethics.html

•

HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html

•

NLM Online Exhibitions: Describes “Exhibitions in the History of Medicine”: http://www.nlm.nih.gov/exhibition/exhibition.html. Additional resources for historical scholarship in medicine: http://www.nlm.nih.gov/hmd/hmd.html

•

Biotechnology Information: Access to public databases. The National Center for Biotechnology Information conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information for the better understanding of molecular processes affecting human health and disease: http://www.ncbi.nlm.nih.gov/

•

Population Information: The National Library of Medicine provides access to worldwide coverage of population, family planning, and related health issues, including family planning technology and programs, fertility, and population law and policy: http://www.nlm.nih.gov/databases/databases_population.html

•

Cancer Information: Access to cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html

•

Profiles in Science: Offering the archival collections of prominent twentieth-century biomedical scientists to the public through modern digital technology: http://www.profiles.nlm.nih.gov/

•

Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html

•

Clinical Alerts: Reports the release of findings from the NIH-funded clinical trials where such release could significantly affect morbidity and mortality: http://www.nlm.nih.gov/databases/alerts/clinical_alerts.html

•

Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html

•

MEDLINE: Bibliographic database covering the fields of medicine, nursing, dentistry, veterinary medicine, the healthcare system, and the pre-clinical sciences: http://www.nlm.nih.gov/databases/databases_medline.html

10

Remember, for the general public, the National Library of Medicine recommends the databases referenced in MEDLINEplus (http://medlineplus.gov/ or http://www.nlm.nih.gov/medlineplus/databases.html). 11 See http://www.nlm.nih.gov/databases/databases.html.

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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 Gateway12 The NLM (National Library of Medicine) Gateway is a Web-based system that lets users search simultaneously in multiple retrieval systems at the U.S. National Library of Medicine (NLM). It allows users of NLM services to initiate searches from one Web interface, providing one-stop searching for many of NLM’s information resources or databases.13 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “lung infection” (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 32726 111 1134 791 702 35464

HSTAT14 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.15 These documents include clinical practice guidelines, quickreference guides for clinicians, consumer health brochures, evidence reports and technology assessments from the Agency for Healthcare Research and Quality (AHRQ), as well as AHRQ’s Put Prevention Into Practice.16 Simply search by “lung infection” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

12

Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.

13

The NLM Gateway is currently being developed by the Lister Hill National Center for Biomedical Communications (LHNCBC) at the National Library of Medicine (NLM) of the National Institutes of Health (NIH). 14 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 15 16

The HSTAT URL is http://hstat.nlm.nih.gov/.

Other important documents in HSTAT include: the National Institutes of Health (NIH) Consensus Conference Reports and Technology Assessment Reports; the HIV/AIDS Treatment Information Service (ATIS) resource documents; the Substance Abuse and Mental Health Services Administration's Center for Substance Abuse Treatment (SAMHSA/CSAT) Treatment Improvement Protocols (TIP) and Center for Substance Abuse Prevention (SAMHSA/CSAP) Prevention Enhancement Protocols System (PEPS); the Public Health Service (PHS) Preventive Services Task Force's Guide to Clinical Preventive Services; the independent, nonfederal Task Force on Community Services’ Guide to Community Preventive Services; and the Health Technology Advisory Committee (HTAC) of the Minnesota Health Care Commission (MHCC) health technology evaluations.

Physician Resources

75

Coffee Break: Tutorials for Biologists17 Coffee Break is a general healthcare site that takes a scientific view of the news and covers recent breakthroughs in biology that may one day assist physicians in developing treatments. Here you will find a collection of short reports on recent biological discoveries. Each report incorporates interactive tutorials that demonstrate how bioinformatics tools are used as a part of the research process. Currently, all Coffee Breaks are written by NCBI staff.18 Each report is about 400 words and is usually based on a discovery reported in one or more articles from recently published, peer-reviewed literature.19 This site has new articles every few weeks, so it can be considered an online magazine of sorts. It is intended for general background information. You can access the Coffee Break Web site at the following hyperlink: http://www.ncbi.nlm.nih.gov/Coffeebreak/.

Other Commercial Databases In addition to resources maintained by official agencies, other databases exist that are commercial ventures addressing medical professionals. Here are some examples that may interest you: •

CliniWeb International: Index and table of contents to selected clinical information on the Internet; see http://www.ohsu.edu/cliniweb/.

•

Medical World Search: Searches full text from thousands of selected medical sites on the Internet; see http://www.mwsearch.com/.

17 Adapted 18

from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html.

The figure that accompanies each article is frequently supplied by an expert external to NCBI, in which case the source of the figure is cited. The result is an interactive tutorial that tells a biological story. 19 After a brief introduction that sets the work described into a broader context, the report focuses on how a molecular understanding can provide explanations of observed biology and lead to therapies for diseases. Each vignette is accompanied by a figure and hypertext links that lead to a series of pages that interactively show how NCBI tools and resources are used in the research process.

77

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 lung infection 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 lung infection. 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 lung infection. 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 “lung infection”:

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Cystic Fibrosis http://www.nlm.nih.gov/medlineplus/cysticfibrosis.html Fungal Infections http://www.nlm.nih.gov/medlineplus/fungalinfections.html Pneumonia http://www.nlm.nih.gov/medlineplus/pneumonia.html Respiratory Diseases http://www.nlm.nih.gov/medlineplus/respiratorydiseases.html Respiratory Syncytial Virus Infections http://www.nlm.nih.gov/medlineplus/respiratorysyncytialvirusinfections.html Tuberculosis http://www.nlm.nih.gov/medlineplus/tuberculosis.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 lung infection. 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: •

The Facts About AIDS and HIV for Teens Contact: South Carolina Department of Health and Environmental Control, Health Services, Bureau of Disease Control, PO Box 101106, Columbia, SC, 29211-0106, (803) 898-0752, http://www.scdhec.net/hs/diseasecont/disease.htm. Summary: This brochure provides factual information for adolescents about Acquired immunodeficiency syndrome (AIDS) and Human immunodeficiency virus (HIV) infection. It explains how HIV affects the immune system, and can lead to lung infection and skin cancer. It also discusses main routes of HIV transmission and casual contacts that do not transmit HIV, describes symptoms that are characteristic of AIDS, and antibody tests that can detect the presence of HIV. It lists preventive measures in sexual behavior and drug use to take to avoid HIV infection.

•

Chlamydia Contact: Public Health Seattle/King County, HIV/AIDS Programs, 400 Yesler Way 3rd Fl, Seattle, WA, 98104-2615, (206) 296-4649, http://www.metrokc.gov/health/apu.

Patient Resources

79

Summary: This brochure, written for the general public, provides information about chlamydia, a sexually transmitted disease (STD). Chlamydia is a bacterial STD that is spread through unprotected vaginal or anal sex. The vast majority of women and some men may not have any symptoms if they are infected with chlamydia; however, when symptoms occur they usually show up within three weeks of the initial infection. The brochure identifies common symptoms. The testing process involved in the diagnosis of chlamydia is described. Individuals can prevent or reduce their risks for chlamydia by practicing sexual abstinence, getting an STD check-up before having sex, using condoms during each sexual encounters, inspecting partners' genitals for symptoms, reducing their numbers of sex partners, and getting tested before having sex again if symptoms do occur. The brochure outlines the effects of chlamydia if left untreated. Chlamydia in women who are pregnant can lead to premature delivery; low birth weight; and eye, ear, or lung infections in the infant. Persons who are being treated for chlamydia should take all of their prescribed medicine, avoid sex during and for one week after treatment, tell all of their partners to get tested, and avoid douching or using an enema. The brochure provides contact information for services in the Seattle, Washington area from which individuals can learn more about chlamydia. 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 lung infection. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html. Additional Web Sources A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •

AOL: http://search.aol.com/cat.adp?id=168&layer=&from=subcats

•

Family Village: http://www.familyvillage.wisc.edu/specific.htm

•

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

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Lung Infection

Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to lung infection. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with lung infection. 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 lung infection. 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 “lung infection” (or a synonym), and you will receive information on all relevant organizations listed in the database. Health Hotlines directs you to toll-free numbers to over 300 organizations. You can access this database directly at http://www.sis.nlm.nih.gov/hotlines/. On this page, you are given the option to search by keyword or by browsing the subject list. When you have received your search results, click on the name of the organization for its description and contact information.

The Combined Health Information Database Another comprehensive source of information on healthcare associations is the Combined Health Information Database. Using the “Detailed Search” option, you will need to limit your search to “Organizations” and “lung infection”. 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 “lung infection” (or synonyms) into the “For these words:” box. You should check back periodically with this database since it is updated every three months.

Patient Resources

81

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 “lung infection” (or a synonym) into the search box, and click “Submit Query.”

83

APPENDIX C. FINDING MEDICAL LIBRARIES Overview In this Appendix, we show you how to quickly find a medical library in your area.

Preparation Your local public library and medical libraries have interlibrary loan programs with the National Library of Medicine (NLM), one of the largest medical collections in the world. According to the NLM, most of the literature in the general and historical collections of the National Library of Medicine is available on interlibrary loan to any library. If you would like to access NLM medical literature, then visit a library in your area that can request the publications for you.20

Finding a Local Medical Library The quickest method to locate medical libraries is to use the Internet-based directory published by the National Network of Libraries of Medicine (NN/LM). This network includes 4626 members and affiliates that provide many services to librarians, health professionals, and the public. To find a library in your area, simply visit http://nnlm.gov/members/adv.html or call 1-800-338-7657.

Medical Libraries in the U.S. and Canada In addition to the NN/LM, the National Library of Medicine (NLM) lists a number of libraries with reference facilities that are open to the public. The following is the NLM’s list and includes hyperlinks to each library’s Web site. These Web pages can provide information on hours of operation and other restrictions. The list below is a small sample of

20

Adapted from the NLM: http://www.nlm.nih.gov/psd/cas/interlibrary.html.

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Lung Infection

libraries recommended by the National Library of Medicine (sorted alphabetically by name of the U.S. state or Canadian province where the library is located)21: •

Alabama: Health InfoNet of Jefferson County (Jefferson County Library Cooperative, Lister Hill Library of the Health Sciences), http://www.uab.edu/infonet/

•

Alabama: Richard M. Scrushy Library (American Sports Medicine Institute)

•

Arizona: Samaritan Regional Medical Center: The Learning Center (Samaritan Health System, Phoenix, Arizona), http://www.samaritan.edu/library/bannerlibs.htm

•

California: Kris Kelly Health Information Center (St. Joseph Health System, Humboldt), http://www.humboldt1.com/~kkhic/index.html

•

California: Community Health Library of Los Gatos, http://www.healthlib.org/orgresources.html

•

California: Consumer Health Program and Services (CHIPS) (County of Los Angeles Public Library, Los Angeles County Harbor-UCLA Medical Center Library) - Carson, CA, http://www.colapublib.org/services/chips.html

•

California: Gateway Health Library (Sutter Gould Medical Foundation)

•

California: Health Library (Stanford University Medical Center), http://wwwmed.stanford.edu/healthlibrary/

•

California: Patient Education Resource Center - Health Information and Resources (University of California, San Francisco), http://sfghdean.ucsf.edu/barnett/PERC/default.asp

•

California: Redwood Health Library (Petaluma Health Care District), http://www.phcd.org/rdwdlib.html

•

California: Los Gatos PlaneTree Health Library, http://planetreesanjose.org/

•

California: Sutter Resource Library (Sutter Hospitals Foundation, Sacramento), http://suttermedicalcenter.org/library/

•

California: Health Sciences Libraries (University of California, Davis), http://www.lib.ucdavis.edu/healthsci/

•

California: ValleyCare Health Library & Ryan Comer Cancer Resource Center (ValleyCare Health System, Pleasanton), http://gaelnet.stmarysca.edu/other.libs/gbal/east/vchl.html

•

California: Washington Community Health Resource Library (Fremont), http://www.healthlibrary.org/

•

Colorado: William V. Gervasini Memorial Library (Exempla Healthcare), http://www.saintjosephdenver.org/yourhealth/libraries/

•

Connecticut: Hartford Hospital Health Science Libraries (Hartford Hospital), http://www.harthosp.org/library/

•

Connecticut: Healthnet: Connecticut Consumer Health Information Center (University of Connecticut Health Center, Lyman Maynard Stowe Library), http://library.uchc.edu/departm/hnet/

21

Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.

Finding Medical Libraries

85

•

Connecticut: Waterbury Hospital Health Center Library (Waterbury Hospital, Waterbury), http://www.waterburyhospital.com/library/consumer.shtml

•

Delaware: Consumer Health Library (Christiana Care Health System, Eugene du Pont Preventive Medicine & Rehabilitation Institute, Wilmington), http://www.christianacare.org/health_guide/health_guide_pmri_health_info.cfm

•

Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine, Wilmington), http://www.delamed.org/chls.html

•

Georgia: Family Resource Library (Medical College of Georgia, Augusta), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm

•

Georgia: Health Resource Center (Medical Center of Central Georgia, Macon), http://www.mccg.org/hrc/hrchome.asp

•

Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library, Honolulu), http://hml.org/CHIS/

•

Idaho: DeArmond Consumer Health Library (Kootenai Medical Center, Coeur d’Alene), http://www.nicon.org/DeArmond/index.htm

•

Illinois: Health Learning Center of Northwestern Memorial Hospital (Chicago), http://www.nmh.org/health_info/hlc.html

•

Illinois: Medical Library (OSF Saint Francis Medical Center, Peoria), http://www.osfsaintfrancis.org/general/library/

•

Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital, Lexington), http://www.centralbap.com/education/community/library.cfm

•

Kentucky: University of Kentucky - Health Information Library (Chandler Medical Center, Lexington), http://www.mc.uky.edu/PatientEd/

•

Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation, New Orleans), http://www.ochsner.org/library/

•

Louisiana: Louisiana State University Health Sciences Center Medical LibraryShreveport, http://lib-sh.lsuhsc.edu/

•

Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital, Farmington), http://www.fchn.org/fmh/lib.htm

•

Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center, Lewiston), http://www.cmmc.org/library/library.html

•

Maine: Hadley Parrot Health Science Library (Eastern Maine Healthcare, Bangor), http://www.emh.org/hll/hpl/guide.htm

•

Maine: Maine Medical Center Library (Maine Medical Center, Portland), http://www.mmc.org/library/

•

Maine: Parkview Hospital (Brunswick), http://www.parkviewhospital.org/

•

Maine: Southern Maine Medical Center Health Sciences Library (Southern Maine Medical Center, Biddeford), http://www.smmc.org/services/service.php3?choice=10

•

Maine: Stephens Memorial Hospital’s Health Information Library (Western Maine Health, Norway), http://www.wmhcc.org/Library/

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•

Manitoba, Canada: Consumer & Patient Health Information Service (University of Manitoba Libraries), http://www.umanitoba.ca/libraries/units/health/reference/chis.html

•

Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre, Winnipeg), http://www.deerlodge.mb.ca/crane_library/about.asp

•

Maryland: Health Information Center at the Wheaton Regional Library (Montgomery County, Dept. of Public Libraries, Wheaton Regional Library), http://www.mont.lib.md.us/healthinfo/hic.asp

•

Massachusetts: Baystate Medical Center Library (Baystate Health System), http://www.baystatehealth.com/1024/

•

Massachusetts: Boston University Medical Center Alumni Medical Library (Boston University Medical Center), http://med-libwww.bu.edu/library/lib.html

•

Massachusetts: Lowell General Hospital Health Sciences Library (Lowell General Hospital, Lowell), http://www.lowellgeneral.org/library/HomePageLinks/WWW.htm

•

Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital, Boston), http://www.nebh.org/health_lib.asp

•

Massachusetts: St. Luke’s Hospital Health Sciences Library (St. Luke’s Hospital, Southcoast Health System, New Bedford), http://www.southcoast.org/library/

•

Massachusetts: Treadwell Library Consumer Health Reference Center (Massachusetts General Hospital), http://www.mgh.harvard.edu/library/chrcindex.html

•

Massachusetts: UMass HealthNet (University of Massachusetts Medical School, Worchester), http://healthnet.umassmed.edu/

•

Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm

•

Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/

•

Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html

•

Michigan: Patient Education Resouce Center - University of Michigan Cancer Center (University of Michigan Comprehensive Cancer Center, Ann Arbor), http://www.cancer.med.umich.edu/learn/leares.htm

•

Michigan: Sladen Library & Center for Health Information Resources - Consumer Health Information (Detroit), http://www.henryford.com/body.cfm?id=39330

•

Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center, Missoula)

•

National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html

•

National: National Network of Libraries of Medicine (National Library of Medicine) provides library services for health professionals in the United States who do not have access to a medical library, http://nnlm.gov/

•

National: NN/LM List of Libraries Serving the Public (National Network of Libraries of Medicine), http://nnlm.gov/members/

Finding Medical Libraries

87

•

Nevada: Health Science Library, West Charleston Library (Las Vegas-Clark County Library District, Las Vegas), http://www.lvccld.org/special_collections/medical/index.htm

•

New Hampshire: Dartmouth Biomedical Libraries (Dartmouth College Library, Hanover), http://www.dartmouth.edu/~biomed/resources.htmld/conshealth.htmld/

•

New Jersey: Consumer Health Library (Rahway Hospital, Rahway), http://www.rahwayhospital.com/library.htm

•

New Jersey: Dr. Walter Phillips Health Sciences Library (Englewood Hospital and Medical Center, Englewood), http://www.englewoodhospital.com/links/index.htm

•

New Jersey: Meland Foundation (Englewood Hospital and Medical Center, Englewood), http://www.geocities.com/ResearchTriangle/9360/

•

New York: Choices in Health Information (New York Public Library) - NLM Consumer Pilot Project participant, http://www.nypl.org/branch/health/links.html

•

New York: Health Information Center (Upstate Medical University, State University of New York, Syracuse), http://www.upstate.edu/library/hic/

•

New York: Health Sciences Library (Long Island Jewish Medical Center, New Hyde Park), http://www.lij.edu/library/library.html

•

New York: ViaHealth Medical Library (Rochester General Hospital), http://www.nyam.org/library/

•

Ohio: Consumer Health Library (Akron General Medical Center, Medical & Consumer Health Library), http://www.akrongeneral.org/hwlibrary.htm

•

Oklahoma: The Health Information Center at Saint Francis Hospital (Saint Francis Health System, Tulsa), http://www.sfh-tulsa.com/services/healthinfo.asp

•

Oregon: Planetree Health Resource Center (Mid-Columbia Medical Center, The Dalles), http://www.mcmc.net/phrc/

•

Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center, Hershey), http://www.hmc.psu.edu/commhealth/

•

Pennsylvania: Community Health Resource Library (Geisinger Medical Center, Danville), http://www.geisinger.edu/education/commlib.shtml

•

Pennsylvania: HealthInfo Library (Moses Taylor Hospital, Scranton), http://www.mth.org/healthwellness.html

•

Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System, Pittsburgh), http://www.hsls.pitt.edu/guides/chi/hopwood/index_html

•

Pennsylvania: Koop Community Health Information Center (College of Physicians of Philadelphia), http://www.collphyphil.org/kooppg1.shtml

•

Pennsylvania: Learning Resources Center - Medical Library (Susquehanna Health System, Williamsport), http://www.shscares.org/services/lrc/index.asp

•

Pennsylvania: Medical Library (UPMC Health System, Pittsburgh), http://www.upmc.edu/passavant/library.htm

•

Quebec, Canada: Medical Library (Montreal General Hospital), http://www.mghlib.mcgill.ca/

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•

South Dakota: Rapid City Regional Hospital Medical Library (Rapid City Regional Hospital), http://www.rcrh.org/Services/Library/Default.asp

•

Texas: Houston HealthWays (Houston Academy of Medicine-Texas Medical Center Library), http://hhw.library.tmc.edu/

•

Washington: Community Health Library (Kittitas Valley Community Hospital), http://www.kvch.com/

•

Washington: Southwest Washington Medical Center Library (Southwest Washington Medical Center, Vancouver), http://www.swmedicalcenter.com/body.cfm?id=72

89

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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LUNG INFECTION DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. Abdominal Pain: Sensation of discomfort, distress, or agony in the abdominal region. [NIH] Aberrant: Wandering or deviating from the usual or normal course. [EU] Abscess: A localized, circumscribed collection of pus. [NIH] Acquired Immunodeficiency Syndrome: An acquired defect of cellular immunity associated with infection by the human immunodeficiency virus (HIV), a CD4-positive Tlymphocyte count under 200 cells/microliter or less than 14% of total lymphocytes, and increased susceptibility to opportunistic infections and malignant neoplasms. Clinical manifestations also include emaciation (wasting) and dementia. These elements reflect criteria for AIDS as defined by the CDC in 1993. [NIH] Acremonium: A mitosporic fungal genus with many reported ascomycetous teleomorphs. Cephalosporin antibiotics are derived from this genus. [NIH] Acyl: Chemical signal used by bacteria to communicate. [NIH] Adenovirus: A group of viruses that cause respiratory tract and eye infections. Adenoviruses used in gene therapy are altered to carry a specific tumor-fighting gene. [NIH] 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] Adverse Effect: An unwanted side effect of treatment. [NIH] Aerobic: In biochemistry, reactions that need oxygen to happen or happen when oxygen is present. [NIH] Aerosol: A solution of a drug which can be atomized into a fine mist for inhalation therapy. [EU]

Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among simple, uniform antigenic determinants such as haptens. Expressed as the association constant (K litres mole -1), which, owing to the heterogeneity of affinities in a population of antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU] Agar: A complex sulfated polymer of galactose units, extracted from Gelidium cartilagineum, Gracilaria confervoides, and related red algae. It is used as a gel in the preparation of solid culture media for microorganisms, as a bulk laxative, in making emulsions, and as a supporting medium for immunodiffusion and immunoelectrophoresis. [NIH]

Agarose: A polysaccharide complex, free of nitrogen and prepared from agar-agar which is produced by certain seaweeds (red algae). It dissolves in warm water to form a viscid

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solution. [NIH] Airway: A device for securing unobstructed passage of air into and out of the lungs during general anesthesia. [NIH] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alleles: Mutually exclusive forms of the same gene, occupying the same locus on homologous chromosomes, and governing the same biochemical and developmental process. [NIH] Allograft: An organ or tissue transplant between two humans. [NIH] Alternative medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used instead of standard treatments. Alternative medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] 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] 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] Anaerobic: 1. Lacking molecular oxygen. 2. Growing, living, or occurring in the absence of molecular oxygen; pertaining to an anaerobe. [EU] Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Anal: Having to do with the anus, which is the posterior opening of the large bowel. [NIH] Analgesic: An agent that alleviates pain without causing loss of consciousness. [EU] Analog: In chemistry, a substance that is similar, but not identical, to another. [NIH] 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] Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve

Dictionary 93

function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH] Animal model: An animal with a disease either the same as or like a disease in humans. Animal models are used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Antibacterial: A substance that destroys bacteria or suppresses their growth or reproduction. [EU] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]

Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] 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] Anti-infective: An agent that so acts. [EU] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Antilymphocyte Serum: Serum containing gamma-globulins which are antibodies for lymphocyte antigens. It is used both as a test for histocompatibility and therapeutically in transplantation. [NIH] Antimicrobial: Killing microorganisms, or suppressing their multiplication or growth. [EU] Antioxidant: A substance that prevents damage caused by free radicals. Free radicals are highly reactive chemicals that often contain oxygen. They are produced when molecules are split to give products that have unpaired electrons. This process is called oxidation. [NIH] Antiserum: The blood serum obtained from an animal after it has been immunized with a particular antigen. It will contain antibodies which are specific for that antigen as well as antibodies specific for any other antigen with which the animal has previously been immunized. [NIH] Antitoxin: A purified antiserum from animals (usually horses) immunized by injections of a toxin or toxoid, administered as a passive immunizing agent to neutralize a specific bacterial toxin, e.g., botulinus, tetanus or diphtheria. [EU] Antiviral: Destroying viruses or suppressing their replication. [EU]

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Anus: The opening of the rectum to the outside of the body. [NIH] Apoptosis: One of the two mechanisms by which cell death occurs (the other being the pathological process of necrosis). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA (DNA fragmentation) at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. [NIH] Aqueous: Having to do with water. [NIH] Arachidonic Acid: An unsaturated, essential fatty acid. It is found in animal and human fat as well as in the liver, brain, and glandular organs, and is a constituent of animal phosphatides. It is formed by the synthesis from dietary linoleic acid and is a precursor in the biosynthesis of prostaglandins, thromboxanes, and leukotrienes. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Artery: Vessel-carrying blood from the heart to various parts of the body. [NIH] 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] Aspergillosis: Infections with fungi of the genus Aspergillus. [NIH] Aspergillus: A genus of mitosporic fungi containing about 100 species and eleven different teleomorphs in the family Trichocomaceae. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Astrocytes: The largest and most numerous neuroglial cells in the brain and spinal cord. Astrocytes (from "star" cells) are irregularly shaped with many long processes, including those with "end feet" which form the glial (limiting) membrane and directly and indirectly contribute to the blood brain barrier. They regulate the extracellular ionic and chemical environment, and "reactive astrocytes" (along with microglia) respond to injury. Astrocytes have high- affinity transmitter uptake systems, voltage-dependent and transmitter-gated ion channels, and can release transmitter, but their role in signaling (as in many other functions) is not well understood. [NIH] Asymptomatic: Having no signs or symptoms of disease. [NIH] Attenuated: Strain with weakened or reduced virulence. [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] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Bacterial Infections: Infections by bacteria, general or unspecified. [NIH]

Dictionary 95

Bacterial toxin: A toxic substance, made by bacteria, that can be modified to kill specific tumor cells without harming normal cells. [NIH] Bactericidal: Substance lethal to bacteria; substance capable of killing bacteria. [NIH] 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] Bacterium: Microscopic organism which may have a spherical, rod-like, or spiral unicellular or non-cellular body. Bacteria usually reproduce through asexual processes. [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] Beta 2-Microglobulin: An 11 kDa protein associated with the outer membrane of many cells including lymphocytes. It is the small subunit of the MHC class I molecule. Association with beta 2-microglobulin is generally required for the transport of class I heavy chains from the endoplasmic reticulum to the cell surface. Beta 2-microglobulin is present in small amounts in serum, csf, and urine of normal people, and to a much greater degree in the urine and plasma of patients with tubular proteinemia, renal failure, or kidney transplants. [NIH] Beta-Lactamases: Enzymes found in many bacteria which catalyze the hydrolysis of the amide bond in the beta-lactam ring. Well known antibiotics destroyed by these enzymes are penicillins and cephalosporins. EC 3.5.2.6. [NIH] Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Bioavailability: The degree to which a drug or other substance becomes available to the target tissue after administration. [EU] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] 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] Biophysics: The science of physical phenomena and processes in living organisms. [NIH] Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body. [NIH] Biopsy specimen: Tissue removed from the body and examined under a microscope to determine whether disease is present. [NIH] Biopterin: A natural product that has been considered as a growth factor for some insects. [NIH]

Biosynthesis: The building up of a chemical compound in the physiologic processes of a living organism. [EU] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning

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technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Bioterrorism: The use of biological agents in terrorism. This includes the malevolent use of bacteria, viruses, or toxins against people, animals, or plants. [NIH] Bithionol: Halogenated anti-infective agent that is used against trematode and cestode infestations. [NIH] Bladder: The organ that stores urine. [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] Blot: To transfer DNA, RNA, or proteins to an immobilizing matrix such as nitrocellulose. [NIH]

Blotting, Western: Identification of proteins or peptides that have been electrophoretically separated by blotting and transferred to strips of nitrocellulose paper. The blots are then detected by radiolabeled antibody probes. [NIH] Body Fluids: Liquid components of living organisms. [NIH] 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] Broad-spectrum: Effective against a wide range of microorganisms; said of an antibiotic. [EU] Bronchi: The larger air passages of the lungs arising from the terminal bifurcation of the trachea. [NIH] Bronchial: Pertaining to one or more bronchi. [EU] Bronchiectasis: Persistent abnormal dilatation of the bronchi. [NIH] Bronchitis: Inflammation (swelling and reddening) of the bronchi. [NIH] Bronchoalveolar Lavage: Washing out of the lungs with saline or mucolytic agents for diagnostic or therapeutic purposes. It is very useful in the diagnosis of diffuse pulmonary infiltrates in immunosuppressed patients. [NIH] 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] Bronchoscopy: Endoscopic examination, therapy or surgery of the bronchi. [NIH] Bullous: Pertaining to or characterized by bullae. [EU] Burns: Injuries to tissues caused by contact with heat, steam, chemicals (burns, chemical), electricity (burns, electric), or the like. [NIH] Burns, Electric: Burns produced by contact with electric current or from a sudden discharge of electricity. [NIH]

Dictionary 97

Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. [NIH] Capsular: Cataract which is initiated by an opacification at the surface of the lens. [NIH] Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen are usually in the proportion to form water, (CH2O)n. The most important carbohydrates are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, 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] Carcinogenic: Producing carcinoma. [EU] Carcinogens: Substances that increase the risk of neoplasms in humans or animals. Both genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism, are included. [NIH] Cardiac: Having to do with the heart. [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] Caspases: A family of intracellular cysteine endopeptidases. They play a key role in inflammation and mammalian apoptosis. They are specific for aspartic acid at the P1 position. They are divided into two classes based on the lengths of their N-terminal prodomains. Caspases-1,-2,-4,-5,-8, and -10 have long prodomains and -3,-6,-7,-9 have short prodomains. EC 3.4.22.-. [NIH] Causal: Pertaining to a cause; directed against a cause. [EU] Ceftazidime: Semisynthetic, broad-spectrum antibacterial derived from cephaloridine and used especially for Pseudomonas and other gram-negative infections in debilitated patients. [NIH]

Ceftriaxone: Broad-spectrum cephalosporin antibiotic with a very long half-life and high penetrability to usually inaccessible infections, including those involving the meninges, eyes, inner ears, and urinary tract. [NIH] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell Division: The fission of a cell. [NIH] Cell membrane: Cell membrane = plasma membrane. The structure enveloping a cell, enclosing the cytoplasm, and forming a selective permeability barrier; it consists of lipids, proteins, and some carbohydrates, the lipids thought to form a bilayer in which integral proteins are embedded to varying degrees. [EU] Cell proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH] Cellular metabolism: The sum of all chemical changes that take place in a cell through

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which energy and basic components are provided for essential processes, including the synthesis of new molecules and the breakdown and removal of others. [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] Cephaloridine: A cephalosporin antibiotic. [NIH] Cephalosporins: A group of broad-spectrum antibiotics first isolated from the Mediterranean fungus Acremonium (Cephalosporium acremonium). They contain the betalactam moiety thia-azabicyclo-octenecarboxylic acid also called 7-aminocephalosporanic acid. [NIH] Cestode: A flatworm that is an endoparasite and belongs to the class Cestoda. [NIH] Check-up: A general physical examination. [NIH] Chemokines: Class of pro-inflammatory cytokines that have the ability to attract and activate leukocytes. They can be divided into at least three structural branches: C (chemokines, C), CC (chemokines, CC), and CXC (chemokines, CXC), according to variations in a shared cysteine motif. [NIH] Chemotactic Factors: Chemical substances that attract or repel cells or organisms. The concept denotes especially those factors released as a result of tissue injury, invasion, or immunologic activity, that attract leukocytes, macrophages, or other cells to the site of infection or insult. [NIH] Chemotherapeutic agent: A drug used to treat cancer. [NIH] Chemotherapy: Treatment with anticancer drugs. [NIH] Chlamydia: A genus of the family Chlamydiaceae whose species cause a variety of diseases in vertebrates including humans, mice, and swine. Chlamydia species are gram-negative and produce glycogen. The type species is Chlamydia trachomatis. [NIH] Chlorophyll: Porphyrin derivatives containing magnesium that act to convert light energy in photosynthetic organisms. [NIH] Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. [NIH] Chromatin: The material of chromosomes. It is a complex of DNA, histones, and nonhistone proteins (chromosomal proteins, non-histone) found within the nucleus of a cell. [NIH] Chromosomal: Pertaining to chromosomes. [EU] Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chronic Obstructive Pulmonary Disease: Collective term for chronic bronchitis and emphysema. [NIH] Cilastatin: A renal dehydropeptidase-I and leukotriene D4 dipeptidase inhibitor. Since the antibiotic, imipenem, is hydrolyzed by dehydropeptidase-I, which resides in the brush border of the renal tubule, cilastatin is administered with imipenem to increase its effectiveness. The drug also inhibits the metabolism of leukotriene D4 to leukeotriene E4. [NIH]

Ciprofloxacin: A carboxyfluoroquinoline antimicrobial agent that is effective against a wide range of microorganisms. It has been successfully and safely used in the treatment of resistant respiratory, skin, bone, joint, gastrointestinal, urinary, and genital infections. [NIH]

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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] 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] 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] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline, hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [NIH] Colloidal: Of the nature of a colloid. [EU] Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such

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as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Condoms: A sheath that is worn over the penis during sexual behavior in order to prevent pregnancy or spread of sexually transmitted disease. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Constipation: Infrequent or difficult evacuation of feces. [NIH] Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] Cornea: The transparent part of the eye that covers the iris and the pupil and allows light to enter the inside. [NIH] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [EU] Cortical: Pertaining to or of the nature of a cortex or bark. [EU] 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] Critical Care: Health care provided to a critically ill patient during a medical emergency or crisis. [NIH] Cryptosporidiosis: Parasitic intestinal infection with severe diarrhea caused by a protozoan, Cryptosporidium. It occurs in both animals and humans. [NIH] CSF: Cerebrospinal fluid. The fluid flowing around the brain and spinal cord. CSF is produced in the ventricles of the brain. [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 solidified with an agent such as agar or gelatin. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Cysteine: A thiol-containing non-essential amino acid that is oxidized to form cystine. [NIH] Cysteine Endopeptidases: Endopeptidases which have a cysteine involved in the catalytic process. This group of enzymes is inactivated by sulfhydryl reagents. EC 3.4.22. [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

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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] Cytosine: A pyrimidine base that is a fundamental unit of nucleic acids. [NIH] Cytostatic: An agent that suppresses cell growth and multiplication. [EU] Cytotoxic: Cell-killing. [NIH] De novo: In cancer, the first occurrence of cancer in the body. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Dementia: An acquired organic mental disorder with loss of intellectual abilities of sufficient severity to interfere with social or occupational functioning. The dysfunction is multifaceted and involves memory, behavior, personality, judgment, attention, spatial relations, language, abstract thought, and other executive functions. The intellectual decline is usually progressive, and initially spares the level of consciousness. [NIH] 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] Desensitization: The prevention or reduction of immediate hypersensitivity reactions by administration of graded doses of allergen; called also hyposensitization and immunotherapy. [EU] Diagnostic procedure: A method used to identify a disease. [NIH]

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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] Diphtheria: A localized infection of mucous membranes or skin caused by toxigenic strains of Corynebacterium diphtheriae. It is characterized by the presence of a pseudomembrane at the site of infection. Diphtheria toxin, produced by C. diphtheriae, can cause myocarditis, polyneuritis, and other systemic toxic effects. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Discrimination: The act of qualitative and/or quantitative differentiation between two or more stimuli. [NIH] Dissection: Cutting up of an organism for study. [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] 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] Douching: A jet or current of water, sometimes a dissolved medicating or cleansing agent, applied to a body part, organ or cavity for medicinal or hygienic purposes. [EU] Doxycycline: A synthetic tetracycline derivative with a range of antimicrobial activity and mode of action similar to that of tetracycline, but more effective against many species. Animal studies suggest that it may cause less tooth staining than other tetracyclines. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Drug Tolerance: Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from drug resistance wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from maximum tolerated dose and no-observed-adverse-effect level. [NIH] Duct: A tube through which body fluids pass. [NIH] Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [NIH] Effector cell: A cell that performs a specific function in response to a stimulus; usually used to describe cells in the immune system. [NIH] Efficacy: The extent to which a specific intervention, procedure, regimen, or service produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is based on the results of a randomized control trial. [NIH] 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] Elastic: Susceptible of resisting and recovering from stretching, compression or distortion applied by a force. [EU] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electrons: Stable elementary particles having the smallest known negative charge, present in all elements; also called negatrons. Positively charged electrons are called positrons. The

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numbers, energies and arrangement of electrons around atomic nuclei determine the chemical identities of elements. Beams of electrons are called cathode rays or beta rays, the latter being a high-energy biproduct of nuclear decay. [NIH] Electrophoresis: An electrochemical process in which macromolecules or colloidal particles with a net electric charge migrate in a solution under the influence of an electric current. [NIH]

Emaciation: Clinical manifestation of excessive leanness usually caused by disease or a lack of nutrition. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Emphysema: A pathological accumulation of air in tissues or organs. [NIH] Empyema: Presence of pus in a hollow organ or body cavity. [NIH] Emulsions: Colloids of two immiscible liquids where either phase may be either fatty or aqueous; lipid-in-water emulsions are usually liquid, like milk or lotion and water-in-lipid emulsions tend to be creams. [NIH] Encapsulated: Confined to a specific, localized area and surrounded by a thin layer of tissue. [NIH]

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] Endotoxins: Toxins closely associated with the living cytoplasm or cell wall of certain microorganisms, which do not readily diffuse into the culture medium, but are released upon lysis of the cells. [NIH] Enema: The injection of a liquid through the anus into the large bowel. [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]

Environmental Monitoring: The monitoring of the level of toxins, chemical pollutants, microbial contaminants, or other harmful substances in the environment or workplace by measuring the amounts of these toxicants in the bodies of people and animals in that environment, among other methods. It also includes the measurement of environmental exposure. Levels in humans and animals are used as indicators of toxic levels of undesirable chemicals. [NIH] Environmental Pollutants: Substances which pollute the environment. Use environmental pollutants in general or for which there is no specific heading. [NIH]

for

Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Enzyme-Linked Immunosorbent Assay: An immunoassay utilizing an antibody labeled

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with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed. [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] Epidemiological: Relating to, or involving epidemiology. [EU] Epithelial: Refers to the cells that line the internal and external surfaces of the body. [NIH] Epithelial Cells: Cells that line the inner and outer surfaces of the body. [NIH] Epithelium: One or more layers of epithelial cells, supported by the basal lamina, which covers the inner or outer surfaces of the body. [NIH] Equipment and Supplies: Expendable and nonexpendable equipment, supplies, apparatus, and instruments that are used in diagnostic, surgical, therapeutic, scientific, and experimental procedures. [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] Esophageal: Having to do with the esophagus, the muscular tube through which food passes from the throat to the stomach. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]

Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Exotoxin: Toxic substance excreted by living bacterial cells. [NIH] Extracellular: Outside a cell or cells. [EU] Extravasation: A discharge or escape, as of blood, from a vessel into the tissues. [EU] Eye Infections: Infection, moderate to severe, caused by bacteria, fungi, or viruses, which occurs either on the external surface of the eye or intraocularly with probable inflammation, visual impairment, or blindness. [NIH] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Fat: Total lipids including phospholipids. [NIH] Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Flatus: Gas passed through the rectum. [NIH]

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Flucytosine: A fluorinated cytosine analog that is used as an antifungal agent. [NIH] Fold: A plication or doubling of various parts of the body. [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] 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] 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] Gas exchange: Primary function of the lungs; transfer of oxygen from inhaled air into the blood and of carbon dioxide from the blood into the lungs. [NIH] Gastric: Having to do with the stomach. [NIH] Gastric Acid: Hydrochloric acid present in gastric juice. [NIH] 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] 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 Therapy: The introduction of new genes into cells for the purpose of treating disease by restoring or adding gene expression. Techniques include insertion of retroviral vectors, transfection, homologous recombination, and injection of new genes into the nuclei of single cell embryos. The entire gene therapy process may consist of multiple steps. The new genes may be introduced into proliferating cells in vivo (e.g., bone marrow) or in vitro (e.g., fibroblast cultures) and the modified cells transferred to the site where the gene expression is required. Gene therapy may be particularly useful for treating enzyme deficiency diseases, hemoglobinopathies, and leukemias and may also prove useful in restoring drug sensitivity, particularly for leukemia. [NIH] Genital: Pertaining to the genitalia. [EU] Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Gingivitis: Inflammation of the gingivae. Gingivitis associated with bony changes is referred to as periodontitis. Called also oulitis and ulitis. [EU]

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Ginseng: An araliaceous genus of plants that contains a number of pharmacologically active agents used as stimulants, sedatives, and tonics, especially in traditional medicine. [NIH] Gland: An organ that produces and releases one or more substances for use in the body. Some glands produce fluids that affect tissues or organs. Others produce hormones or participate in blood production. [NIH] 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] Glycosylation: The chemical or biochemical addition of carbohydrate or glycosyl groups to other chemicals, especially peptides or proteins. Glycosyl transferases are used in this biochemical reaction. [NIH] Gonadal: Pertaining to a gonad. [EU] 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-versus-host disease: GVHD. A reaction of donated bone marrow or peripheral stem cells against a person's tissue. [NIH] Gram-negative: Losing the stain or decolorized by alcohol in Gram's method of staining, a primary characteristic of bacteria having a cell wall composed of a thin layer of peptidoglycan covered by an outer membrane of lipoprotein and lipopolysaccharide. [EU] Gram-positive: Retaining the stain or resisting decolorization by alcohol in Gram's method of staining, a primary characteristic of bacteria whose cell wall is composed of a thick layer of peptidologlycan with attached teichoic acids. [EU] Gram-Positive Bacteria: Bacteria which retain the crystal violet stain when treated by Gram's method. [NIH] Granulocyte: A type of white blood cell that fights bacterial infection. Neutrophils, eosinophils, and basophils are granulocytes. [NIH] Granulomas: Small lumps in tissues caused by inflammation. [NIH] Group Structure: The informal or formal organization of a group of people based on a network of personal relationships which is influenced by the size and composition, etc., of the group. [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] Heart Transplantation: The transference of a heart from one human or animal to another. [NIH]

Hematogenous: Originating in the blood or spread through the bloodstream. [NIH] Hematopoiesis: The development and formation of various types of blood cells. [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

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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] Hemoglobinopathies: A group of inherited disorders characterized by structural alterations within the hemoglobin molecule. [NIH] Heparan Sulfate Proteoglycan: A substance released by astrocytes, which is critical in stopping nervous fibers in their tracks. [NIH] Hepatitis: Inflammation of the liver and liver disease involving degenerative or necrotic alterations of hepatocytes. [NIH] Hepatocytes: The main structural component of the liver. They are specialized epithelial cells that are organized into interconnected plates called lobules. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] 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]

Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable. [NIH] Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Horseradish Peroxidase: An enzyme isolated from horseradish which is able to act as an antigen. It is frequently used as a histochemical tracer for light and electron microscopy. Its antigenicity has permitted its use as a combined antigen and marker in experimental immunology. [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] Hybridomas: Cells artificially created by fusion of activated lymphocytes with neoplastic cells. The resulting hybrid cells are cloned and produce pure or "monoclonal" antibodies or T-cell products, identical to those produced by the immunologically competent parent, and continually grow and divide as the neoplastic parent. [NIH] 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] Hydroxyproline: A hydroxylated form of the imino acid proline. A deficiency in ascorbic acid can result in impaired hydroxyproline formation. [NIH] Hygienic: Pertaining to hygiene, or conducive to health. [EU] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels

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are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hypoxemia: Deficient oxygenation of the blood; hypoxia. [EU] 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] Ibuprofen: A nonsteroidal anti-inflammatory agent with analgesic properties used in the therapy of rheumatism and arthritis. [NIH] Imipenem: Semisynthetic thienamycin that has a wide spectrum of antibacterial activity against gram-negative and gram-positive aerobic and anaerobic bacteria, including many multiresistant strains. It is stable to beta-lactamases. Clinical studies have demonstrated high efficacy in the treatment of infections of various body systems. Its effectiveness is enhanced when it is administered in combination with cilastatin, a renal dipeptidase inhibitor. [NIH] Immune function: Production and action of cells that fight disease or infection. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]

Immune Sera: Serum that contains antibodies. It is obtained from an animal that has been immunized either by antigen injection or infection with microorganisms containing the antigen. [NIH] Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] Immunization: Deliberate stimulation of the host's immune response. Active immunization involves administration of antigens or immunologic adjuvants. Passive immunization involves administration of immune sera or lymphocytes or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow). [NIH] Immunoassay: Immunochemical assay or detection of a substance by serologic or immunologic methods. Usually the substance being studied serves as antigen both in antibody production and in measurement of antibody by the test substance. [NIH] Immunoblotting: Immunologic methods for isolating and quantitatively measuring immunoreactive substances. When used with immune reagents such as monoclonal antibodies, the process is known generically as western blot analysis (blotting, western). [NIH]

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] Immunodeficiency syndrome: The inability of the body to produce an immune response. [NIH]

Immunodiffusion: Technique involving the diffusion of antigen or antibody through a semisolid medium, usually agar or agarose gel, with the result being a precipitin reaction. [NIH]

Immunoelectrophoresis: A technique that combines protein electrophoresis and double immunodiffusion. In this procedure proteins are first separated by gel electrophoresis (usually agarose), then made visible by immunodiffusion of specific antibodies. A distinct elliptical precipitin arc results for each protein detectable by the antisera. [NIH] Immunogenic: Producing immunity; evoking an immune response. [EU] Immunologic: The ability of the antibody-forming system to recall a previous experience

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with an antigen and to respond to a second exposure with the prompt production of large amounts of antibody. [NIH] Immunosuppression: Deliberate prevention or diminution of the host's immune response. It may be nonspecific as in the administration of immunosuppressive agents (drugs or radiation) or by lymphocyte depletion or may be specific as in desensitization or the simultaneous administration of antigen and immunosuppressive drugs. [NIH] Immunosuppressive: Describes the ability to lower immune system responses. [NIH] Immunosuppressive Agents: Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of suppressor T-cell populations or by inhibiting the activation of helper cells. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of interleukins and other cytokines are emerging. [NIH] Immunotherapy: Manipulation of the host's immune system in treatment of disease. It includes both active and passive immunization as well as immunosuppressive therapy to prevent graft rejection. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] In situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU] In Situ Hybridization: A technique that localizes specific nucleic acid sequences within intact chromosomes, eukaryotic cells, or bacterial cells through the use of specific nucleic acid-labeled probes. [NIH] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incision: A cut made in the body during surgery. [NIH] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]

Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH] Ingestion: Taking into the body by mouth [NIH] Inhalation: The drawing of air or other substances into the lungs. [EU]

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Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Inner ear: The labyrinth, comprising the vestibule, cochlea, and semicircular canals. [NIH] Insight: The capacity to understand one's own motives, to be aware of one's own psychodynamics, to appreciate the meaning of symbolic behavior. [NIH] Intensive Care: Advanced and highly specialized care provided to medical or surgical patients whose conditions are life-threatening and require comprehensive care and constant monitoring. It is usually administered in specially equipped units of a health care facility. [NIH]

Interleukin-1: A soluble factor produced by monocytes, macrophages, and other cells which activates T-lymphocytes and potentiates their response to mitogens or antigens. IL-1 consists of two distinct forms, IL-1 alpha and IL-1 beta which perform the same functions but are distinct proteins. The biological effects of IL-1 include the ability to replace macrophage requirements for T-cell activation. The factor is distinct from interleukin-2. [NIH] Interleukin-2: Chemical mediator produced by activated T lymphocytes and which regulates the proliferation of T cells, as well as playing a role in the regulation of NK cell activity. [NIH] Interleukin-6: Factor that stimulates the growth and differentiation of human B-cells and is also a growth factor for hybridomas and plasmacytomas. It is produced by many different cells including T-cells, monocytes, and fibroblasts. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intestinal: Having to do with the intestines. [NIH] Intestines: The section of the alimentary canal from the stomach to the anus. It includes the large intestine and small intestine. [NIH] Intoxication: Poisoning, the state of being poisoned. [EU] Intracellular: Inside a cell. [NIH] Intracellular Membranes: Membranes of subcellular structures. [NIH] Intravenous: IV. Into a vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]

Ion Channels: Gated, ion-selective glycoproteins that traverse membranes. The stimulus for channel gating can be a membrane potential, drug, transmitter, cytoplasmic messenger, or a mechanical deformation. Ion channels which are integral parts of ionotropic neurotransmitter receptors are not included. [NIH] 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] Keratitis: Inflammation of the cornea. [NIH] Kinetics: The study of rate dynamics in chemical or physical systems. [NIH] Labile: 1. Gliding; moving from point to point over the surface; unstable; fluctuating. 2. Chemically unstable. [EU] Latency: The period of apparent inactivity between the time when a stimulus is presented and the moment a response occurs. [NIH] Latent: Phoria which occurs at one distance or another and which usually has no

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troublesome effect. [NIH] Laxative: An agent that acts to promote evacuation of the bowel; a cathartic or purgative. [EU]

Lectin: A complex molecule that has both protein and sugars. Lectins are able to bind to the outside of a cell and cause biochemical changes in it. Lectins are made by both animals and plants. [NIH] 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] Lesion: An area of abnormal tissue change. [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] Lipid: Fat. [NIH] Lipid Bilayers: Layers of lipid molecules which are two molecules thick. Bilayer systems are frequently studied as models of biological membranes. [NIH] Lipopolysaccharide: Substance consisting of polysaccaride and lipid. [NIH] Liposomal: A drug preparation that contains the active drug in very tiny fat particles. This fat-encapsulated drug is absorbed better, and its distribution to the tumor site is improved. [NIH]

Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Localized: Cancer which has not metastasized yet. [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] Lung metastases: Cancer that has spread from the original (primary) tumor to the lung. [NIH]

Lung Transplantation: The transference of either one or both of the lungs from one human or animal to another. [NIH] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Lymph node: A rounded mass of lymphatic tissue that is surrounded by a capsule of connective tissue. Also known as a lymph gland. Lymph nodes are spread out along lymphatic vessels and contain many lymphocytes, which filter the lymphatic fluid (lymph). [NIH]

Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] Lymphatic system: The tissues and organs that produce, store, and carry white blood cells that fight infection and other diseases. This system includes the bone marrow, spleen, thymus, lymph nodes and a network of thin tubes that carry lymph and white blood cells. These tubes branch, like blood vessels, into all the tissues of the body. [NIH]

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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] Lymphocyte Depletion: Immunosuppression by reduction of circulating lymphocytes or by T-cell depletion of bone marrow. The former may be accomplished in vivo by thoracic duct drainage or administration of antilymphocyte serum. The latter is performed ex vivo on bone marrow before its transplantation. [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] Lytic: 1. Pertaining to lysis or to a lysin. 2. Producing lysis. [EU] Macrophage: A type of white blood cell that surrounds and kills microorganisms, removes dead cells, and stimulates the action of other immune system cells. [NIH] Malformation: A morphologic developmental process. [EU]

defect

resulting

from

an

intrinsically

abnormal

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]

Mannans: Polysaccharides consisting of mannose units. [NIH] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors. [NIH] Memory: Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. [NIH] Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] 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] 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] 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]

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Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [NIH] Milliliter: A measure of volume for a liquid. A milliliter is approximately 950-times smaller than a quart and 30-times smaller than a fluid ounce. A milliliter of liquid and a cubic centimeter (cc) of liquid are the same. [NIH] Mitochondrial Swelling: Increase in volume of mitochondria due to an influx of fluid; it occurs in hypotonic solutions due to osmotic pressure and in isotonic solutions as a result of altered permeability of the membranes of respiring mitochondria. [NIH] Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH] Mitosporic Fungi: A large and heterogenous group of fungi whose common characteristic is the absence of a sexual state. Many of the pathogenic fungi in humans belong to this group. [NIH]

Mobility: Capability of movement, of being moved, or of flowing freely. [EU] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] Monoclonal: An antibody produced by culturing a single type of cell. It therefore consists of a single species of immunoglobulin molecules. [NIH] Monoclonal antibodies: Laboratory-produced substances that can locate and bind to cancer cells wherever they are in the body. Many monoclonal antibodies are used in cancer detection or therapy; each one recognizes a different protein on certain cancer cells. Monoclonal antibodies can be used alone, or they can be used to deliver drugs, toxins, or radioactive material directly to a tumor. [NIH] Monocytes: Large, phagocytic mononuclear leukocytes produced in the vertebrate bone marrow and released into the blood; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles. [NIH] Mononuclear: A cell with one nucleus. [NIH] Monotherapy: A therapy which uses only one drug. [EU] Morphological: Relating to the configuration or the structure of live organs. [NIH] Mucins: A secretion containing mucopolysaccharides and protein that is the chief constituent of mucus. [NIH] Mucolytic: Destroying or dissolving mucin; an agent that so acts : a mucopolysaccharide or glycoprotein, the chief constituent of mucus. [EU] Mucosa: A mucous membrane, or tunica mucosa. [EU] Mucus: The viscous secretion of mucous membranes. It contains mucin, white blood cells, water, inorganic salts, and exfoliated cells. [NIH] Mycobacterial disease: Any disease caused by Mycobacterium other than M. tuberculosis, M. bovis, and M. avium. [NIH] Mycoplasma: A genus of gram-negative, facultatively anaerobic bacteria bounded by a

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plasma membrane only. Its organisms are parasites and pathogens, found on the mucous membranes of humans, animals, and birds. [NIH] Mycotic: Pertaining to a mycosis; caused by fungi. [EU] Myocardial infarction: Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Nebramycin: A complex of antibiotic substances produced by Streptomyces tenebrarius. [NIH]

Necrosis: A pathological process caused by the progressive degradative action of enzymes that is generally associated with severe cellular trauma. It is characterized by mitochondrial swelling, nuclear flocculation, uncontrolled cell lysis, and ultimately cell death. [NIH] Neonatal: Pertaining to the first four weeks after birth. [EU] Neoplasm: A new growth of benign or malignant tissue. [NIH] Neopterin: A pteridine derivative present in body fluids; elevated levels result from immune system activation, malignant disease, allograft rejection, and viral infections. (From Stedman, 26th ed) Neopterin also serves as a precursor in the biosynthesis of biopterin. [NIH] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU] 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] 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] 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

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next. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Opportunistic Infections: An infection caused by an organism which becomes pathogenic under certain conditions, e.g., during immunosuppression. [NIH] Organelles: Specific particles of membrane-bound organized living substances present in eukaryotic cells, such as the mitochondria; the golgi apparatus; endoplasmic reticulum; lysomomes; plastids; and vacuoles. [NIH] Osmosis: Tendency of fluids (e.g., water) to move from the less concentrated to the more concentrated side of a semipermeable membrane. [NIH] Osmotic: Pertaining to or of the nature of osmosis (= the passage of pure solvent from a solution of lesser to one of greater solute concentration when the two solutions are separated by a membrane which selectively prevents the passage of solute molecules, but is permeable to the solvent). [EU] Overexpress: An excess of a particular protein on the surface of a cell. [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] Oxygenation: The process of supplying, treating, or mixing with oxygen. No:1245 oxygenation the process of supplying, treating, or mixing with oxygen. [EU] Paecilomyces: A mitosporic fungal genus occasionally causing human diseases such as pulmonary infections, mycotic keratitis, endocarditis, and opportunistic infections. Its teleomorph is Byssochlamys. [NIH] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Particle: A tiny mass of material. [EU] Pathogen: Any disease-producing microorganism. [EU] Pathogenesis: The cellular events and reactions that occur in the development of disease. [NIH]

Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Pathologic Processes: The abnormal mechanisms and forms involved in the dysfunctions of

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tissues and organs. [NIH] Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Patient Education: The teaching or training of patients concerning their own health needs. [NIH]

Penicillin: An antibiotic drug used to treat infection. [NIH] 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] 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] 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] Periodontist: A specialist in the treatment of diseases of the gums. [NIH] Peripheral stem cells: Immature cells found circulating in the bloodstream. New blood cells develop from peripheral stem cells. [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] 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] 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] 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] Physical Examination: Systematic and thorough inspection of the patient for physical signs of disease or abnormality. [NIH] Physiologic: Having to do with the functions of the body. When used in the phrase "physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH]

Piperacillin: Semisynthetic, broad-spectrum, ampicillin-derived ureidopenicillin antibiotic proposed for pseudomonas infections. It is also used in combination with other antibiotics. [NIH]

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Plague: An acute infectious disease caused by Yersinia pestis that affects humans, wild rodents, and their ectoparasites. This condition persists due to its firm entrenchment in sylvatic rodent-flea ecosystems throughout the world. Bubonic plague is the most common form. [NIH] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plaque: A clear zone in a bacterial culture grown on an agar plate caused by localized destruction of bacterial cells by a bacteriophage. The concentration of infective virus in a fluid can be estimated by applying the fluid to a culture and counting the number of. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] Plasmid: An autonomously replicating, extra-chromosomal DNA molecule found in many bacteria. Plasmids are widely used as carriers of cloned genes. [NIH] Pneumoconiosis: Condition characterized by permanent deposition of substantial amounts of particulate matter in the lungs, usually of occupational or environmental origin, and by the tissue reaction to its presence. [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] 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] Polymers: Compounds formed by the joining of smaller, usually repeating, units linked by covalent bonds. These compounds often form large macromolecules (e.g., polypeptides, proteins, plastics). [NIH] Polymorphic: Occurring in several or many forms; appearing in different forms at different stages of development. [EU] Polymorphism: The occurrence together of two or more distinct forms in the same population. [NIH] Polypeptide: A peptide which on hydrolysis yields more than two amino acids; called tripeptides, tetrapeptides, etc. according to the number of amino acids contained. [EU] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] Posterior: Situated in back of, or in the back part of, or affecting the back or dorsal surface of the body. In lower animals, it refers to the caudal end of the body. [EU] Postnatal: Occurring after birth, with reference to the newborn. [EU] Potentiates: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the

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convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH] Preclinical: Before a disease becomes clinically recognizable. [EU] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] 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] Prophylaxis: An attempt to prevent disease. [NIH] Prospective study: An epidemiologic study in which a group of individuals (a cohort), all free of a particular disease and varying in their exposure to a possible risk factor, is followed over a specific amount of time to determine the incidence rates of the disease in the exposed and unexposed groups. [NIH] Prostaglandins: A group of compounds derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway. They are extremely potent mediators of a diverse group of physiological processes. [NIH] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation. [NIH] Protein Conformation: The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. Quaternary protein structure describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain). [NIH] Protein S: The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] Proteolytic: 1. Pertaining to, characterized by, or promoting proteolysis. 2. An enzyme that promotes proteolysis (= the splitting of proteins by hydrolysis of the peptide bonds with formation of smaller polypeptides). [EU] Protozoa: A subkingdom consisting of unicellular organisms that are the simplest in the animal kingdom. Most are free living. They range in size from submicroscopic to macroscopic. Protozoa are divided into seven phyla: Sarcomastigophora, Labyrinthomorpha, Apicomplexa, Microspora, Ascetospora, Myxozoa, and Ciliophora. [NIH] Pseudomonas: A genus of gram-negative, aerobic, rod-shaped bacteria widely distributed in

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nature. Some species are pathogenic for humans, animals, and plants. [NIH] Pseudomonas Infections: Infections with bacteria of the genus Pseudomonas. [NIH] Psychoactive: Those drugs which alter sensation, mood, consciousness or other psychological or behavioral functions. [NIH] Public Health: Branch of medicine concerned with the prevention and control of disease and disability, and the promotion of physical and mental health of the population on the international, national, state, or municipal level. [NIH] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] Publishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing. [NIH]

Pulmonary: Relating to the lungs. [NIH] Pulmonary hypertension: Abnormally high blood pressure in the arteries of the lungs. [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] Randomized: Describes an experiment or clinical trial in which animal or human subjects are assigned by chance to separate groups that compare different treatments. [NIH] Reagent: A substance employed to produce a chemical reaction so as to detect, measure, produce, etc., other substances. [EU] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Recombination: The formation of new combinations of genes as a result of segregation in crosses between genetically different parents; also the rearrangement of linked genes due to crossing-over. [NIH] Reconstitution: 1. A type of regeneration in which a new organ forms by the rearrangement of tissues rather than from new formation at an injured surface. 2. The restoration to original form of a substance previously altered for preservation and storage, as the restoration to a liquid state of blood serum or plasma that has been dried and stored. [EU] Rectum: The last 8 to 10 inches of the large intestine. [NIH] 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] Renal failure: Progressive renal insufficiency and uremia, due to irreversible and

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progressive renal glomerular tubular or interstitial disease. [NIH] Research Support: Financial support of research activities. [NIH] Respiratory Burst: A large increase in oxygen uptake by neutrophils and most types of tissue macrophages through activation of an NADPH-cytochrome b-dependent oxidase that reduces oxygen to a superoxide. Individuals with an inherited defect in which the oxidase that reduces oxygen to superoxide is decreased or absent (granulomatous disease, chronic) often die as a result of recurrent bacterial infections. [NIH] Respiratory distress syndrome: A lung disease that occurs primarily in premature infants; the newborn must struggle for each breath and blueing of its skin reflects the baby's inability to get enough oxygen. [NIH] Respiratory failure: Inability of the lungs to conduct gas exchange. [NIH] Retroviral vector: RNA from a virus that is used to insert genetic material into cells. [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] Ribotyping: Restriction fragment length polymorphism analysis of rRNA genes that is used for differentiating between species or strains. [NIH] Rickettsiae: One of a group of obligate intracellular parasitic microorganisms, once regarded as intermediate in their properties between bacteria and viruses but now classified as bacteria in the order Rickettsiales, which includes 17 genera and 3 families: Rickettsiace. [NIH]

Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Rod: A reception for vision, located in the retina. [NIH] Saline: A solution of salt and water. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [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] Schizoid: Having qualities resembling those found in greater degree in schizophrenics; a person of schizoid personality. [NIH] Schizophrenia: A mental disorder characterized by a special type of disintegration of the personality. [NIH] Schizotypal Personality Disorder: A personality disorder in which there are oddities of thought (magical thinking, paranoid ideation, suspiciousness), perception (illusions, depersonalization), speech (digressive, vague, overelaborate), and behavior (inappropriate affect in social interactions, frequently social isolation) that are not severe enough to characterize schizophrenia. [NIH] Screening: Checking for disease when there are no symptoms. [NIH]

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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] Semisynthetic: Produced by chemical manipulation of naturally occurring substances. [EU] Sensor: A device designed to respond to physical stimuli such as temperature, light, magnetism or movement and transmit resulting impulses for interpretation, recording, movement, or operating control. [NIH] Sepsis: The presence of bacteria in the bloodstream. [NIH] Septic: Produced by or due to decomposition by microorganisms; putrefactive. [EU] Sequencing: The determination of the order of nucleotides in a DNA or RNA chain. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Sexual Abstinence: Refraining from sexual intercourse. [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]

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] Sigma Factor: A protein which is a subunit of RNA polymerase. It effects initiation of specific RNA chains from DNA. [NIH] Signs and Symptoms: Clinical manifestations that can be either objective when observed by a physician, or subjective when perceived by the patient. [NIH] Silicosis: A type of pneumoconiosis caused by inhalation of particles of silica, quartz, ganister or slate. [NIH] Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] Sneezing: Sudden, forceful, involuntary expulsion of air from the nose and mouth caused by irritation to the mucous membranes of the upper respiratory tract. [NIH] Sodium: An element that is a member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23. With a valence of 1, it has a strong affinity for oxygen and other nonmetallic elements. Sodium provides the chief cation of the extracellular body fluids. Its salts are the most widely used in medicine. (From Dorland, 27th ed) Physiologically the sodium ion plays a major role in blood pressure regulation, maintenance of fluid volume, and electrolyte balance. [NIH] Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] Solvent: 1. Dissolving; effecting a solution. 2. A liquid that dissolves or that is capable of dissolving; the component of a solution that is present in greater amount. [EU] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH]

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Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Specificity: Degree of selectivity shown by an antibody with respect to the number and types of antigens with which the antibody combines, as well as with respect to the rates and the extents of these reactions. [NIH] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU] 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] Sputum: The material expelled from the respiratory passages by coughing or clearing the throat. [NIH] Steroid: A group name for lipids that contain a hydrogenated cyclopentanoperhydrophenanthrene ring system. Some of the substances included in this group are progesterone, adrenocortical hormones, the gonadal hormones, cardiac aglycones, bile acids, sterols (such as cholesterol), toad poisons, saponins, and some of the carcinogenic hydrocarbons. [EU] Stimulants: Any drug or agent which causes stimulation. [NIH] Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] Subacute: Somewhat acute; between acute and chronic. [EU] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] 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] Superoxide: Derivative of molecular oxygen that can damage cells. [NIH] Supplementation: Adding nutrients to the diet. [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]

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Suspensions: Colloids with liquid continuous phase and solid dispersed phase; the term is used loosely also for solid-in-gas (aerosol) and other colloidal systems; water-insoluble drugs may be given as suspensions. [NIH] Systemic: Affecting the entire body. [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] 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] Testicles: The two egg-shaped glands found inside the scrotum. They produce sperm and male hormones. Also called testes. [NIH] Tetanus: A disease caused by tetanospasmin, a powerful protein toxin produced by Clostridium tetani. Tetanus usually occurs after an acute injury, such as a puncture wound or laceration. Generalized tetanus, the most common form, is characterized by tetanic muscular contractions and hyperreflexia. Localized tetanus presents itself as a mild condition with manifestations restricted to muscles near the wound. It may progress to the generalized form. [NIH] Tetracycline: An antibiotic originally produced by Streptomyces viridifaciens, but used mostly in synthetic form. It is an inhibitor of aminoacyl-tRNA binding during protein synthesis. [NIH] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thoracic: Having to do with the chest. [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] 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] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tobramycin: An aminoglycoside, broad-spectrum antibiotic produced by Streptomyces tenebrarius. It is effective against gram-negative bacteria, especially the Pseudomonas species. It is a 10% component of the antibiotic complex, nebramycin, produced by the same species. [NIH] Tolerance: 1. The ability to endure unusually large doses of a drug or toxin. 2. Acquired drug tolerance; a decreasing response to repeated constant doses of a drug or the need for increasing doses to maintain a constant response. [EU] Tomography: Imaging methods that result in sharp images of objects located on a chosen plane and blurred images located above or below the plane. [NIH] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH]

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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] 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] Translocate: The attachment of a fragment of one chromosome to a non-homologous chromosome. [NIH] Translocation: The movement of material in solution inside the body of the plant. [NIH] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell to the other at the synapse. [NIH] Transplantation: Transference of a tissue or organ, alive or dead, within an individual, between individuals of the same species, or between individuals of different species. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Tubercle: A rounded elevation on a bone or other structure. [NIH] Tuberculosis: Any of the infectious diseases of man and other animals caused by species of Mycobacterium. [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]

Ureters: Tubes that carry urine from the kidneys to the bladder. [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]

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Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] Urinary tract: The organs of the body that produce and discharge urine. These include the kidneys, ureters, bladder, and urethra. [NIH] Urine: Fluid containing water and waste products. Urine is made by the kidneys, stored in the bladder, and leaves the body through the urethra. [NIH] Vaccination: Administration of vaccines to stimulate the host's immune response. This includes any preparation intended for active immunological prophylaxis. [NIH] Vaccines: Suspensions of killed or attenuated microorganisms (bacteria, viruses, fungi, protozoa, or rickettsiae), antigenic proteins derived from them, or synthetic constructs, administered for the prevention, amelioration, or treatment of infectious and other diseases. [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] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venom: That produced by the poison glands of the mouth and injected by the fangs of poisonous snakes. [NIH] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [NIH] Virulent: A virus or bacteriophage capable only of lytic growth, as opposed to temperate phages establishing the lysogenic response. [NIH] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH] Visual Acuity: Acuteness or clearness of vision, especially of form vision, which is dependent mainly on the sharpness of the retinal focus. [NIH] Vitro: Descriptive of an event or enzyme reaction under experimental investigation occurring outside a living organism. Parts of an organism or microorganism are used together with artificial substrates and/or conditions. [NIH] Vivo: Outside of or removed from the body of a living organism. [NIH] Voriconazole: A drug that treats infections caused by fungi. [NIH] Vulva: The external female genital organs, including the clitoris, vaginal lips, and the opening to the vagina. [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]

Withdrawal: 1. A pathological retreat from interpersonal contact and social involvement, as

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may occur in schizophrenia, depression, or schizoid avoidant and schizotypal personality disorders. 2. (DSM III-R) A substance-specific organic brain syndrome that follows the cessation of use or reduction in intake of a psychoactive substance that had been regularly used to induce a state of intoxication. [EU] Xenograft: The cells of one species transplanted to another species. [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]

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INDEX A Abdominal Pain, 91, 116 Aberrant, 3, 24, 91 Abscess, 48, 91 Acquired Immunodeficiency Syndrome, 25, 50, 91 Acremonium, 91, 98 Acyl, 24, 47, 91 Adenovirus, 12, 14, 91 Adoptive Transfer, 14, 91 Adverse Effect, 14, 91, 121 Aerobic, 91, 108, 118 Aerosol, 4, 11, 14, 52, 55, 91, 123 Affinity, 91, 94, 121 Agar, 16, 91, 100, 108, 117 Agarose, 15, 91, 108 Airway, 8, 13, 14, 16, 19, 22, 24, 47, 51, 92 Algorithms, 92, 96 Alleles, 27, 92 Allograft, 92, 114 Alternative medicine, 64, 92 Amino acid, 22, 23, 61, 92, 93, 94, 100, 104, 106, 116, 117, 118, 122, 124 Amino Acid Sequence, 23, 61, 92, 93 Amoxicillin, 36, 92 Ampicillin, 92, 116 Amplification, 48, 92 Anaerobic, 29, 30, 33, 35, 36, 46, 92, 108, 113 Anaesthesia, 92, 109 Anal, 79, 92, 111 Analgesic, 92, 108 Analog, 92, 105 Anaphylatoxins, 92, 99 Anesthesia, 10, 92 Animal model, 11, 24, 25, 26, 93 Antibacterial, 11, 23, 26, 39, 93, 97, 108, 122 Antibiotic, 8, 24, 37, 48, 92, 93, 94, 96, 97, 98, 99, 104, 114, 116, 122, 123 Antibodies, 15, 30, 35, 38, 43, 50, 54, 93, 107, 108, 112, 113, 117 Antibody, 20, 30, 40, 50, 78, 91, 93, 96, 99, 103, 107, 108, 109, 113, 122 Antifungal, 93, 105 Antigen, 9, 15, 26, 91, 93, 99, 104, 107, 108, 109 Antigen-Antibody Complex, 93, 99

Anti-infective, 93, 96 Anti-inflammatory, 14, 93, 108 Antilymphocyte Serum, 93, 112 Antimicrobial, 13, 16, 22, 23, 29, 34, 35, 36, 38, 39, 43, 45, 46, 47, 51, 52, 93, 98, 102 Antioxidant, 11, 93, 115 Antiserum, 9, 93 Antitoxin, 18, 93 Antiviral, 11, 12, 93 Anus, 92, 94, 103, 110 Apoptosis, 5, 27, 42, 94, 97 Aqueous, 12, 94, 101, 103, 111 Arachidonic Acid, 94, 102, 118 Arterial, 31, 94, 107, 118 Arteries, 94, 96, 100, 112, 114, 119, 123 Artery, 94, 96, 100 Aspartic, 94, 97 Aspartic Acid, 94, 97 Aspergillosis, 44, 94 Aspergillus, 31, 51, 94 Assay, 14, 27, 94, 108 Astrocytes, 94, 107 Asymptomatic, 7, 94 Attenuated, 9, 94, 125 Azithromycin, 39, 94 B Bacillus, 18, 23, 94 Bacterial Infections, 17, 24, 94, 120 Bacterial toxin, 93, 95 Bactericidal, 22, 95 Bacteriophage, 95, 117, 124, 125 Bacterium, 20, 23, 95 Basophils, 95, 106, 111 Beta 2-Microglobulin, 32, 95 Beta-Lactamases, 95, 108 Bile, 95, 107, 111, 122 Bioavailability, 19, 95 Biochemical, 6, 19, 26, 92, 95, 96, 106, 111 Biofilms, 8, 24, 95 Biophysics, 25, 95 Biopsy, 36, 95 Biopsy specimen, 36, 95 Biopterin, 95, 114 Biosynthesis, 94, 95, 114 Biotechnology, 27, 28, 64, 73, 95 Bioterrorism, 20, 96 Bithionol, 49, 96 Bladder, 96, 124, 125

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Blood pressure, 96, 107, 119, 121 Blot, 96, 108 Blotting, Western, 96, 108 Body Fluids, 96, 102, 114, 121 Bone Marrow, 34, 37, 96, 105, 106, 108, 111, 112, 113 Bone Marrow Transplantation, 34, 37, 96 Bowel, 92, 96, 103, 111, 116 Broad-spectrum, 8, 43, 92, 96, 97, 98, 116, 123 Bronchi, 96 Bronchial, 24, 25, 61, 96 Bronchiectasis, 8, 96 Bronchitis, 31, 96, 98 Bronchoalveolar Lavage, 15, 22, 24, 39, 48, 52, 96 Bronchoalveolar Lavage Fluid, 22, 96 Bronchoscopy, 36, 96 Bullous, 32, 96 Burns, 24, 96 Burns, Electric, 96 C Calcium, 97, 99 Capsular, 50, 97 Carbohydrate, 7, 9, 97, 106, 117 Carbon Dioxide, 97, 105 Carcinogenic, 97, 110, 122 Carcinogens, 97, 115 Cardiac, 97, 103, 114, 122 Case report, 38, 97 Caspases, 27, 97 Causal, 3, 97 Ceftazidime, 52, 53, 97 Ceftriaxone, 55, 97 Cell Death, 94, 97, 114 Cell Division, 94, 97, 113, 117 Cell membrane, 7, 97 Cell proliferation, 9, 97 Cellular metabolism, 25, 97 Cellulose, 98, 105, 117 Cephaloridine, 97, 98 Cephalosporins, 43, 95, 98 Cestode, 96, 98 Check-up, 79, 98 Chemokines, 61, 98 Chemotactic Factors, 98, 99 Chemotherapeutic agent, 23, 98 Chemotherapy, 14, 29, 34, 36, 38, 39, 43, 45, 46, 51, 52, 53, 98 Chlamydia, 28, 32, 39, 46, 54, 78, 79, 98 Chlorophyll, 98, 105 Cholesterol, 95, 98, 122

Chromatin, 94, 98, 104 Chromosomal, 5, 48, 92, 98, 117 Chromosome, 98, 124 Chronic Obstructive Pulmonary Disease, 4, 98 Cilastatin, 38, 98, 108 Ciprofloxacin, 33, 34, 36, 98 Clarithromycin, 32, 33, 39, 99 Clinical trial, 4, 14, 73, 99, 119 Cloning, 95, 99 Collagen, 92, 99, 104, 105 Colloidal, 99, 103, 123 Complement, 9, 92, 99 Complementary and alternative medicine, 55, 57, 99 Complementary medicine, 55, 99 Computational Biology, 73, 100 Condoms, 79, 100 Connective Tissue, 96, 99, 100, 104, 105, 111, 120 Constipation, 100, 116 Contraindications, ii, 100 Cornea, 100, 110 Coronary, 100, 112, 114 Coronary Thrombosis, 100, 112, 114 Cortex, 100, 118 Cortical, 44, 100 Cortisone, 28, 100 Critical Care, 10, 29, 35, 40, 44, 47, 53, 100 Cryptosporidiosis, 94, 100 CSF, 12, 95, 100 Culture Media, 91, 100 Curative, 100, 123 Cysteine, 97, 98, 100 Cysteine Endopeptidases, 97, 100 Cytochrome, 100, 101, 120 Cytochrome b, 101, 120 Cytokine, 4, 12, 15, 17, 101 Cytomegalovirus, 34, 48, 101 Cytoplasm, 94, 95, 97, 101, 103, 104, 113 Cytosine, 101, 105 Cytostatic, 55, 101 Cytotoxic, 15, 101, 109 D De novo, 11, 101 Degenerative, 101, 107 Deletion, 9, 94, 101 Dementia, 91, 101 Dental Caries, 101 Dental Plaque, 4, 101 Dentists, 4, 101 Desensitization, 101, 109

129

Diagnostic procedure, 59, 64, 101 Diaphragm, 40, 45, 102 Diphtheria, 93, 102 Direct, iii, 22, 23, 67, 102, 119 Discrimination, 60, 102 Dissection, 11, 102 Distal, 25, 102 Dose-dependent, 22, 102 Douching, 79, 102 Doxycycline, 12, 29, 36, 102 Drug Interactions, 68, 102 Drug Tolerance, 102, 123 Duct, 102, 112, 120 E Effector, 7, 25, 99, 102 Effector cell, 7, 102 Efficacy, 8, 9, 34, 36, 55, 102, 108 Eicosanoids, 16, 102 Elastic, 102, 122 Electrolyte, 102, 121 Electrons, 93, 102, 115, 119 Electrophoresis, 5, 54, 103, 108 Emaciation, 91, 103 Embryo, 103, 109 Emphysema, 98, 103 Empyema, 48, 103 Emulsions, 91, 103 Encapsulated, 20, 103, 111 Endocarditis, 4, 103, 115 Endocardium, 103 Endogenous, 28, 102, 103, 115 Endotoxins, 99, 103 Enema, 79, 103 Environmental Exposure, 103 Environmental Health, 11, 16, 72, 74, 103 Environmental Monitoring, 60, 103 Environmental Pollutants, 11, 103 Enzymatic, 92, 97, 99, 101, 103 Enzyme, 9, 11, 19, 35, 102, 103, 105, 107, 117, 118, 122, 124, 125 Enzyme-Linked Immunosorbent Assay, 35, 103 Eosinophils, 104, 106, 111 Epidemiological, 42, 104 Epithelial, 9, 14, 16, 19, 24, 25, 104, 107 Epithelial Cells, 9, 14, 16, 19, 24, 25, 104, 107 Epithelium, 25, 27, 104 Equipment and Supplies, 4, 104 Erythrocytes, 20, 96, 104 Erythromycin, 94, 99, 104 Esophageal, 49, 104

Esophagus, 104, 122 Eukaryotic Cells, 104, 109, 115 Exogenous, 7, 103, 104 Exotoxin, 52, 104 Extracellular, 21, 94, 95, 100, 104, 121 Extravasation, 14, 104 Eye Infections, 9, 91, 104 F Family Planning, 73, 104 Fat, 94, 96, 104, 111, 120, 121, 122 Fibroblasts, 104, 110 Flatus, 104, 105 Flucytosine, 36, 105 Fold, 23, 105 Free Radicals, 93, 105 Fungi, 93, 94, 104, 105, 112, 113, 114, 125, 126 Fungus, 32, 98, 105 G Gas, 25, 52, 60, 97, 104, 105, 107, 114, 120, 123 Gas exchange, 25, 105, 120 Gastric, 92, 105 Gastric Acid, 92, 105 Gastrointestinal, 98, 105, 122 Gelatin, 100, 105, 106 Gene, 6, 7, 9, 10, 11, 14, 16, 22, 26, 27, 91, 92, 96, 105 Gene Expression, 10, 11, 105 Gene Therapy, 6, 91, 105 Genital, 98, 105, 125 Genotype, 13, 16, 105, 116 Gingivitis, 101, 105 Ginseng, 56, 57, 64, 106 Gland, 100, 106, 111, 121, 122 Glycine, 20, 92, 106, 114 Glycogen, 98, 106 Glycoprotein, 25, 37, 106, 113, 124 Glycosylation, 16, 37, 51, 106 Gonadal, 106, 122 Governing Board, 106, 117 Graft, 34, 106, 109 Graft-versus-host disease, 34, 106 Gram-negative, 8, 13, 26, 97, 98, 106, 108, 113, 118, 123 Gram-positive, 22, 106, 108 Gram-Positive Bacteria, 22, 106 Granulocyte, 12, 106 Granulomas, 18, 106 Group Structure, 8, 106 H Half-Life, 97, 106

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Heart Transplantation, 45, 106 Hematogenous, 44, 106 Hematopoiesis, 12, 106 Hemoglobin, 104, 106, 107 Hemoglobinopathies, 105, 107 Heparan Sulfate Proteoglycan, 21, 107 Hepatitis, 32, 107 Hepatocytes, 107 Heredity, 105, 107 Heterogeneity, 10, 31, 91, 107 Homeostasis, 12, 25, 107 Homologous, 23, 92, 105, 107, 124 Hormone, 100, 102, 107, 112, 118 Horseradish Peroxidase, 104, 107 Humoral, 9, 15, 48, 56, 107 Humour, 107 Hybridomas, 107, 110 Hydrogen, 97, 107, 113, 115 Hydroxyproline, 92, 99, 107 Hygienic, 102, 107 Hypertension, 107 Hypoxemia, 25, 108 Hypoxia, 108 Hypoxic, 25, 108 I Ibuprofen, 15, 108 Imipenem, 38, 44, 45, 98, 108 Immune function, 7, 11, 108, 109 Immune response, 9, 13, 14, 36, 48, 51, 93, 100, 108, 109, 122, 125 Immune Sera, 108 Immune system, 4, 8, 11, 24, 26, 78, 102, 108, 109, 112, 114, 116, 125 Immunization, 5, 9, 47, 91, 108, 109 Immunoassay, 103, 108 Immunoblotting, 35, 108 Immunocompromised, 8, 18, 24, 25, 44, 108 Immunodeficiency, 15, 31, 37, 38, 46, 78, 91, 108 Immunodeficiency syndrome, 78, 108 Immunodiffusion, 91, 108 Immunoelectrophoresis, 91, 108 Immunogenic, 25, 108 Immunologic, 15, 91, 98, 108 Immunosuppression, 6, 109, 112, 115 Immunosuppressive, 109 Immunosuppressive Agents, 109 Immunotherapy, 91, 101, 109 Impairment, 104, 109 In situ, 15, 109 In Situ Hybridization, 15, 109

In vitro, 7, 8, 12, 15, 17, 18, 19, 22, 23, 24, 25, 26, 39, 43, 105, 109 In vivo, 6, 8, 10, 12, 15, 17, 22, 24, 25, 26, 105, 109, 112, 115, 123 Incision, 109, 110 Induction, 5, 15, 27, 109 Infarction, 109 Ingestion, 5, 109 Inhalation, 34, 68, 91, 109, 121 Initiation, 19, 110, 121 Inner ear, 97, 110 Insight, 15, 18, 22, 27, 110 Intensive Care, 45, 54, 110 Interleukin-1, 28, 61, 110 Interleukin-2, 110 Interleukin-6, 61, 110 Interstitial, 34, 53, 96, 110, 120 Intestinal, 53, 100, 110 Intestines, 105, 110 Intoxication, 110, 126 Intracellular, 9, 11, 17, 97, 109, 110, 112, 120 Intracellular Membranes, 110, 112 Intravenous, 39, 110 Intrinsic, 5, 12, 14, 91, 110 Invasive, 51, 110 Ion Channels, 16, 94, 110 K Kb, 72, 110 Keratitis, 9, 110, 115 Kinetics, 6, 14, 110 L Labile, 99, 110 Latency, 15, 110 Latent, 15, 18, 110 Laxative, 91, 111 Lectin, 111, 112 Lens, 97, 111 Lesion, 16, 111, 121 Lethal, 9, 14, 16, 95, 111 Leukemia, 51, 105, 111 Leukocytes, 12, 95, 96, 98, 104, 111, 113, 124 Lipid, 13, 20, 23, 25, 103, 111 Lipid Bilayers, 23, 111 Lipopolysaccharide, 13, 26, 40, 106, 111 Liposomal, 51, 111 Liver, 94, 95, 101, 106, 107, 111 Localized, 26, 91, 101, 102, 103, 109, 111, 117, 123 Longitudinal study, 33, 40, 111 Lung metastases, 60, 61, 111

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Lung Transplantation, 42, 111 Lymph, 14, 43, 107, 111 Lymph node, 14, 43, 111 Lymphatic, 61, 109, 111, 122, 123 Lymphatic system, 111, 122, 123 Lymphocyte, 7, 43, 91, 93, 109, 112 Lymphocyte Count, 91, 112 Lymphocyte Depletion, 7, 109, 112 Lymphocytic, 15, 112 Lymphoid, 15, 93, 112 Lytic, 20, 112, 125 M Macrophage, 7, 11, 12, 20, 110, 112 Malformation, 31, 112 Malignant, 45, 91, 112, 114, 120 Malnutrition, 52, 112 Mannans, 105, 112 Mediate, 6, 14, 17, 112 MEDLINE, 73, 112 Membrane, 35, 47, 50, 94, 95, 97, 99, 104, 106, 110, 112, 113, 114, 115, 124 Membrane Proteins, 35, 50, 112 Memory, 14, 101, 112 Meninges, 97, 112 Mental, iv, 4, 72, 74, 101, 112, 119, 120 Mental Health, iv, 4, 72, 74, 112, 119 MI, 36, 89, 112 Microbe, 112, 123 Microorganism, 18, 112, 115, 125 Micro-organism, 61 Micro-organism, 101 Micro-organism, 112 Migration, 16, 113 Milliliter, 61, 113 Mitochondrial Swelling, 113, 114 Mitosis, 94, 113 Mitosporic Fungi, 94, 113 Mobility, 15, 113 Modification, 92, 113 Molecular, 6, 13, 15, 19, 21, 23, 24, 32, 48, 73, 75, 92, 95, 100, 113, 122, 124 Molecule, 23, 93, 95, 99, 102, 107, 111, 113, 115, 117, 119, 125 Monoclonal, 107, 108, 113 Monoclonal antibodies, 108, 113 Monocytes, 26, 110, 111, 113 Mononuclear, 113, 124 Monotherapy, 53, 113 Morphological, 103, 105, 113 Mucins, 51, 101, 113 Mucolytic, 96, 113 Mucosa, 61, 113

Mucus, 113 Mycobacterial disease, 6, 113 Mycoplasma, 61, 113 Mycotic, 114, 115 Myocardial infarction, 4, 100, 112, 114 Myocardium, 112, 114 N Nebramycin, 114, 123 Necrosis, 5, 94, 109, 112, 114 Neonatal, 24, 35, 114 Neoplasm, 114, 120, 124 Neopterin, 32, 114 Nerve, 45, 92, 114, 122, 124 Nervous System, 114, 122 Neural, 107, 114 Neurotransmitter, 92, 94, 106, 110, 114, 122 Neutrophil, 15, 16, 114 Nitrogen, 52, 91, 114 Nosocomial, 35, 44, 45, 47, 114 Nuclear, 37, 103, 104, 114 Nuclei, 103, 105, 113, 114 Nucleic acid, 101, 109, 114 Nucleus, 94, 95, 98, 101, 104, 113, 115 O Opportunistic Infections, 6, 7, 91, 115 Organelles, 101, 113, 115 Osmosis, 115 Osmotic, 20, 113, 115 Overexpress, 22, 115 Oxidants, 17, 115 Oxidation, 93, 100, 115 Oxidation-Reduction, 115 Oxygenation, 108, 115 P Paecilomyces, 32, 115 Palliative, 115, 123 Particle, 16, 115, 124 Pathogen, 6, 7, 9, 12, 13, 19, 22, 23, 24, 25, 26, 42, 44, 115 Pathogenesis, 6, 11, 16, 18, 19, 20, 21, 22, 23, 25, 26, 27, 42, 49, 51, 52, 115 Pathologic, 6, 60, 94, 95, 100, 115 Pathologic Processes, 94, 115 Pathophysiology, 17, 116 Patient Education, 78, 84, 86, 89, 116 Penicillin, 33, 92, 116 Penis, 100, 116 Peptide, 13, 35, 61, 92, 99, 116, 117, 118 Peptide Chain Elongation, 99, 116 Periodontal disease, 3, 116 Periodontist, 3, 116

132

Lung Infection

Peripheral stem cells, 106, 116 Peritoneum, 116 Peritonitis, 17, 116 Phagocyte, 115, 116 Phagocytosis, 6, 7, 9, 116 Pharmacokinetic, 19, 36, 116 Pharmacologic, 93, 106, 116, 123 Phenotype, 8, 13, 16, 116 Physical Examination, 98, 116 Physiologic, 8, 17, 95, 106, 116, 119 Piperacillin, 46, 53, 116 Plague, 20, 117 Plants, 94, 96, 97, 106, 111, 117, 119, 120, 124 Plaque, 3, 117 Plasma, 19, 93, 95, 97, 105, 106, 114, 117, 119 Plasma cells, 93, 117 Plasmid, 18, 117, 125 Pneumoconiosis, 117, 121 Pneumonia, 8, 9, 16, 18, 25, 30, 34, 37, 45, 49, 60, 78, 100, 117 Pneumonitis, 32, 117 Polymerase, 117, 121 Polymers, 95, 117, 118 Polymorphic, 10, 117 Polymorphism, 30, 31, 117, 120 Polypeptide, 92, 99, 117, 118 Polysaccharide, 91, 93, 98, 117 Posterior, 92, 117 Postnatal, 23, 117 Potentiates, 110, 117 Practice Guidelines, 74, 117 Preclinical, 19, 118 Precursor, 94, 102, 103, 114, 118 Prevalence, 10, 13, 46, 118 Progesterone, 118, 122 Progression, 14, 42, 93, 118 Progressive, 13, 14, 24, 101, 102, 114, 118, 119, 124 Prophylaxis, 25, 118, 125 Prospective study, 111, 118 Prostaglandins, 94, 102, 118 Protease, 17, 118 Protein C, 92, 95, 118 Protein Conformation, 92, 118 Protein S, 96, 99, 104, 118, 123 Proteolytic, 99, 118 Protozoa, 112, 118, 125 Pseudomonas Infections, 116, 119 Psychoactive, 119, 126 Public Health, 10, 16, 17, 18, 21, 74, 78, 119

Public Policy, 73, 119 Publishing, 27, 119 Pulmonary, 4, 5, 6, 7, 13, 17, 21, 22, 24, 25, 27, 40, 44, 48, 64, 96, 115, 119, 122 Pulmonary hypertension, 64, 119 R Race, 113, 119 Radiation, 57, 103, 105, 109, 119 Randomized, 102, 119 Reagent, 20, 119 Receptor, 7, 12, 13, 15, 16, 17, 93, 119 Recombinant, 9, 12, 14, 22, 119, 125 Recombination, 105, 119 Reconstitution, 6, 119 Rectum, 94, 104, 105, 119 Refer, 1, 99, 105, 114, 119, 124 Refraction, 119, 122 Refractory, 48, 119 Regeneration, 119 Regimen, 19, 102, 119 Renal failure, 95, 119 Research Support, 18, 120 Respiratory Burst, 9, 120 Respiratory distress syndrome, 24, 37, 51, 120 Respiratory failure, 34, 120 Retroviral vector, 105, 120 Rheumatism, 108, 120 Rheumatoid, 115, 120 Ribotyping, 30, 120 Rickettsiae, 120, 125 Risk factor, 11, 118, 120 Rod, 94, 95, 118, 120 S Saline, 96, 120 Salivary, 101, 120 Salivary glands, 101, 120 Saponins, 120, 122 Sarcoma, 48, 120 Schizoid, 120, 126 Schizophrenia, 120, 126 Schizotypal Personality Disorder, 120, 126 Screening, 99, 120 Secretion, 107, 113, 121 Semisynthetic, 92, 97, 99, 108, 116, 121 Sensor, 60, 121 Sepsis, 24, 121 Septic, 17, 26, 121 Sequencing, 19, 121 Serum, 20, 26, 29, 32, 50, 54, 91, 92, 93, 95, 99, 108, 116, 119, 121, 124 Sexual Abstinence, 79, 121

133

Shedding, 21, 121 Shock, 121, 124 Side effect, 67, 91, 121, 123 Sigma Factor, 22, 52, 121 Signs and Symptoms, 17, 121 Silicosis, 6, 121 Skull, 121, 123 Sneezing, 121 Sodium, 55, 121 Soft tissue, 96, 121 Solvent, 115, 121 Somatic, 107, 113, 121 Specialist, 9, 80, 116, 121 Species, 42, 94, 98, 102, 113, 119, 120, 122, 123, 124, 125, 126 Specificity, 23, 91, 122 Spectrum, 16, 21, 22, 108, 122 Spleen, 101, 111, 122 Sputum, 5, 15, 33, 39, 40, 122 Steroid, 33, 100, 120, 122 Stimulants, 106, 122 Stimulus, 102, 110, 122 Stomach, 104, 105, 107, 110, 122 Stress, 18, 22, 122 Subacute, 109, 122 Subclinical, 109, 122 Subspecies, 122 Substance P, 104, 119, 121, 122 Substrate, 20, 104, 122 Superoxide, 120, 122 Supplementation, 11, 122 Surfactant, 8, 20, 23, 25, 35, 122 Suspensions, 15, 123, 125 Systemic, 7, 11, 15, 26, 68, 96, 102, 109, 123, 124 T Teichoic Acids, 106, 123 Temporal, 5, 12, 123 Testicles, 123 Tetanus, 93, 123 Tetracycline, 11, 102, 123 Therapeutics, 24, 68, 123 Thoracic, 42, 48, 102, 112, 123 Thromboxanes, 94, 102, 123 Thymus, 108, 111, 123 Tobramycin, 29, 37, 46, 53, 123 Tolerance, 34, 123 Tomography, 34, 123 Toxic, iv, 18, 24, 95, 102, 103, 104, 123, 124 Toxicity, 11, 17, 39, 102, 123 Toxicology, 19, 74, 123 Toxin, 10, 18, 93, 102, 123, 124

Toxoid, 93, 124 Transduction, 7, 124 Transfection, 95, 105, 124 Transfer Factor, 108, 124 Transferases, 106, 124 Translation, 92, 104, 124 Translational, 10, 124 Translocate, 26, 124 Translocation, 99, 104, 124 Transmitter, 94, 110, 124 Transplantation, 93, 108, 112, 124 Trauma, 26, 114, 124 Tubercle, 18, 31, 33, 44, 46, 124 Tuberculosis, 6, 7, 11, 13, 18, 23, 32, 33, 37, 44, 46, 53, 78, 113, 124 Tumor Necrosis Factor, 5, 61, 124 Tumour, 45, 124 Tunica, 113, 124 U Ureters, 124, 125 Urethra, 116, 124, 125 Urinary, 20, 97, 98, 125 Urinary tract, 20, 97, 125 Urine, 43, 95, 96, 124, 125 V Vaccination, 11, 125 Vaccines, 20, 26, 35, 125 Vagina, 125 Vaginal, 79, 125 Vascular, 109, 125 Vector, 7, 47, 124, 125 Vein, 110, 114, 125 Venom, 9, 125 Veterinary Medicine, 73, 125 Viral, 12, 15, 19, 114, 124, 125 Virulence, 5, 9, 10, 18, 19, 20, 21, 23, 24, 26, 39, 94, 123, 125 Virulent, 9, 10, 13, 26, 125 Virus, 12, 15, 18, 31, 37, 38, 46, 49, 78, 91, 95, 117, 120, 124, 125 Visual Acuity, 125 Vitro, 19, 24, 25, 36, 39, 125 Vivo, 6, 8, 10, 12, 22, 28, 112, 125 Voriconazole, 51, 125 Vulva, 125 W White blood cell, 93, 106, 111, 112, 113, 114, 117, 125 Withdrawal, 12, 125 X Xenograft, 93, 126

134

Y

Lung Infection

Yeasts, 105, 116, 126

135

136

Lung Infection