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

EOSINOPHILIA 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., 1960Eosinophilia: 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: 0-497-00406-2 1. Eosinophilia-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 eosinophilia. 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 EOSINOPHILIA........................................................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Eosinophilia................................................................................... 4 E-Journals: PubMed Central ....................................................................................................... 43 The National Library of Medicine: PubMed ................................................................................ 45 CHAPTER 2. NUTRITION AND EOSINOPHILIA ................................................................................. 91 Overview...................................................................................................................................... 91 Finding Nutrition Studies on Eosinophilia ................................................................................. 91 Federal Resources on Nutrition ................................................................................................... 93 Additional Web Resources ........................................................................................................... 94 CHAPTER 3. ALTERNATIVE MEDICINE AND EOSINOPHILIA........................................................... 95 Overview...................................................................................................................................... 95 National Center for Complementary and Alternative Medicine.................................................. 95 Additional Web Resources ........................................................................................................... 98 General References ....................................................................................................................... 99 CHAPTER 4. PATENTS ON EOSINOPHILIA ..................................................................................... 101 Overview.................................................................................................................................... 101 Patents on Eosinophilia.............................................................................................................. 101 Patent Applications on Eosinophilia.......................................................................................... 107 Keeping Current ........................................................................................................................ 109 CHAPTER 5. BOOKS ON EOSINOPHILIA ......................................................................................... 111 Overview.................................................................................................................................... 111 Book Summaries: Online Booksellers......................................................................................... 111 Chapters on Eosinophilia ........................................................................................................... 111 CHAPTER 6. PERIODICALS AND NEWS ON EOSINOPHILIA ........................................................... 115 Overview.................................................................................................................................... 115 News Services and Press Releases.............................................................................................. 115 Academic Periodicals covering Eosinophilia.............................................................................. 117 CHAPTER 7. RESEARCHING MEDICATIONS .................................................................................. 119 Overview.................................................................................................................................... 119 U.S. Pharmacopeia..................................................................................................................... 119 Commercial Databases ............................................................................................................... 120 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 123 Overview.................................................................................................................................... 123 NIH Guidelines.......................................................................................................................... 123 NIH Databases........................................................................................................................... 125 Other Commercial Databases..................................................................................................... 127 APPENDIX B. PATIENT RESOURCES ............................................................................................... 129 Overview.................................................................................................................................... 129 Patient Guideline Sources.......................................................................................................... 129 Finding Associations.................................................................................................................. 131 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 133 Overview.................................................................................................................................... 133 Preparation................................................................................................................................. 133 Finding a Local Medical Library................................................................................................ 133 Medical Libraries in the U.S. and Canada ................................................................................. 133 ONLINE GLOSSARIES................................................................................................................ 139 Online Dictionary Directories ................................................................................................... 139

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EOSINOPHILIA DICTIONARY................................................................................................. 141 INDEX .............................................................................................................................................. 203

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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 eosinophilia 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 eosinophilia, 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 eosinophilia, 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 eosinophilia. 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 eosinophilia, 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 eosinophilia. The Editors

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

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

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

Chronic Sinusitis: Relationship of Computed Tomographic Findings to Allergy, Asthma, and Eosinophilia Source: Journal of the American Medical Association. JAMA. 271(5): 363-367. February 2, 1994. Summary: This article reports on a study undertaken to develop a technique for evaluating the severity of chronic sinus disease and to examine the correlation with allergy, asthma, and eosinophilia. The study consisted of a survey of 104 patients undergoing surgery for chronic sinusitis at a university hospital ear, nose, and throat clinic. Outcome measures used included computed tomographic scans, serum samples, peripheral blood samples, and surgical biopsy specimens. Extensive disease was present in 39 percent of subjects and correlated well with asthma, specific IgE antibodies, and eosinophilia, but not with elevated total IgE. Among patients with peripheral

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eosinophilia, 87 percent had extensive disease. The authors present their system for quantitation of disease extent using computed tomographic scans of patients with chronic sinusitis. They conclude that the well-accepted associations of chronic sinusitis with asthma and allergy appear to be restricted to the group with extensive disease. 2 figures. 3 tables. 25 references. (AA-M).

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

Project Title: ASTHMA INDUCTION BY DENDRITIC CELLS AND TH2 CELLS Principal Investigator & Institution: Sung, Sun-Sang J.; Associate Professor; Internal Medicine; University of Virginia Charlottesville Box 400195 Charlottesville, Va 22904 Timing: Fiscal Year 2004; Project Start 01-JAN-2004; Project End 30-NOV-2007 Summary: (provided by applicant): Asthma is an important disease that afflicts 5% of the general population. Atopic asthma is caused by biased-T helper 2 (Th2) responses to allergens. In a mouse model, mice primed intratracheally with Ag-pulsed dendritic cells and challenged with Ag developed airway hyperresponsiveness, and lung eosinophilia and inflammation. Lungs have a more Th2-biased environment and primed T cells seem to divide faster in the lungs than lymph nodes in Ag-challenged mice, although the lymph node is believed to be the site of T cell activation and development. In this study, lung DC have been found to be composed of multiple subset. Studies on DC migration suggest that secondary lymphoid chemokine (SLC/CCL21) may be a key chemokine for DC migration to draining LN. In the lung but not lymph nodes of lung-immunized mice, large numbers of interferon-gamma-producing CD8+ T cells (Tc1) were present, resulting in a more Th2-baised environment in the lungs. These results support the hypothesis that: "a DC subset that presents antigen in lungs and mediates a Th2-biased response occurs in lungs. For T lymphocyte and DC migration to lymph nodes, SLC is a major mediator. Because Th1 and Tc1 cell numbers are very low in the inflammatory lungs, activated T cells readily develop into Th2 cells." In this proposal, experiments are designed to support this hypothesis. The aims consist of: (1) the isolation and functional studies of DC subsets in lungs; (2) the studies of CCR7/SLC interaction as a key

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

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chemokine receptor/chemokine interaction for lung DC and T cell migration to lymph nodes. The roles of other important candidate chemokine receptors such as CCR2 in mediating DC migration will also be examined; and (3) the studies of the migration of IFN-gamma-producing CD8+ T cells away from lungs during asthma pathogenesis. These studies will clarify the roles of DC and CD8+ T cells in the biased-Th2 lung response in asthma and provide a novel mechanism for Th2-biased responses during asthma pathogenesis. The results may provide additional therapeutic strategies in asthma by the interference of SLC functions and by regulating the migration of DC, Th1, and IFN-gamma-producing CD8+ T cells. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BIOCHEMICAL PATHWAYS OF 12 HETE AND 12 KETE METABOLISM Principal Investigator & Institution: Rokach, Joshua; Professor & Director; None; Florida Institute of Technology Box 1150, 150 W University Blvd Melbourne, Fl 32901 Timing: Fiscal Year 2002; Project Start 30-SEP-1992; Project End 30-NOV-2004 Summary: Psoriasis, asthma and inflammatory bowel disease (IBD) are characterized by a primary neutrophil and eosinophil infiltration at the inflammatory sites. 5-Oxo-ETE (5oxo-6E,8Z,11Z,14Z-eicosatetraenoic acid) is a potent activator of both neutrophils and eosinophils and among lipid mediators; it is the most active eosinophil chemoattractant so far tested. This raises the possibility that this compound is an important mediator of inflammation, especially in conditions associated with eosinophilia. The major focus of this application is the development of a variety of tools that will be used to investigate the biosynthesis, metabolism and physiological role of 5-oxo-ETE. A primary goal will be to synthesize affinity ligands and photoaffinity probes, based on 5-HETE, to permit the purification, labeling and ultimate cloning of 5-hydroxyeicosanoid dehydrogenase, the enzyme responsible for the formation of 5-oxo-ETE. Similar approaches will be used to develop affinity ligands related to 5-oxo-ETE. These will be used to characterize metabolic enzymes (5- oxo-eicosanoid-D6-reductase and 5-ketoreductase) as well as the 5-oxo-ETE receptor. We recently found that human platelets convert 5-oxo-ETE to a metabolite (5-oxo-12S-HETE) that antagonizes 5-oxo-ETE-induced calcium mobilization, and we propose to use this as a lead compound to develop more potent antagonists. Another major or goal is to investigate the metabolism of other oxo-eicosanoids, including 12-oxo-LTB4. We found that this compound is converted by keratinocytes in a highly stereospecific manner to a series of cysteinyl-containing metabolites c-LTB3, dLTB3 and e-LTB3, similar in structure to the potent cysteinyl-leukotrienes LTC4 and LTD4 and we propose to further investigate the mechanism for the formation of these compounds. In addition, we will investigate reductive pathways responsible for the conversion of 12-oxo-ETE to the potent proinflammatory agent 12-HETrE (12R-hydroxy5Z,8Z,14Z-eicosatrienoic acid). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CAMP CONTINUATION STUDY PHASE 2 (CAMPCS / 2) Principal Investigator & Institution: Strunk, Robert C.; Professor of Pediatrics; Pediatrics; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 30-JUN-2007 Summary: (provided by applicant): Childhood asthma can result in significant lung disease in adulthood and possibly the development of COPD. None of the long-term follow-up studies of childhood asthma have had the close follow-up needed to define

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determinants of outcomes in young adulthood. No study has examined the effects of intensive treatment with potent anti-inflammatory agents on outcomes. CAMP was a multicenter randomized clinical trial designed to determine the effects of three treatments (albuterol alone, albuterol with inhaled corticosteroid [ICS], albuterol with inhaled non-steroid) in 1,041 children (randomized at ages 5-12 years) with mild to moderate asthma on pulmonary function during a 3.5-5.5 year treatment phase. The cohort is being followed currently in a 4-year observational phase (CAMP Continuation Study, CAMPCS) to determine longer-term effects of the treatments on lung and somatic growth. 88% of the original cohort enrolled, with a missed visit rate of less than 1%. At the scheduled end of CAMPCS, only 70% of females and 38% of males will have achieved an age of likely maximal height and level of pulmonary function. Additional follow-up of the CAMP cohort, CAMPCS/2, is designed to follow the cohort for 4 additional years into early adulthood, when the patients will be 17-26 years (55% >greater than or equal too 21 years). We propose 5 specific aims. We will determine the effects of 3.5-5.5 years of ICS therapy started at ages 5 to 12 years on outcomes of pulmonary function, height, bone density, and the clinical course of asthma in young adulthood. Natural history aims will focus on 1) effects of lower respiratory symptoms, allergy, peripheral blood eosinophilia, and personal smoking on attained level lung function FEV1, FVC, FEV1/FVC) and airway reactivity in young adulthood, 2) effects of lung function, airway reactivity, allergy, peripheral blood eosinophilia, and personal smoking on lower respiratory symptoms in young adulthood, and 3) factors associated with a low FEV1/FVC ratio by comparison of FEV1/FVC and FEV1 and FVC in CAMP patients to three sets of pulmonary function values from normal. Genetic analyses will be done by Dr. Weiss and the Center for Genetics and Genomics at Harvard (without cost to this application) with comparison of the genetic data to the phenotypic data collected during CAMP, CAMPCS, and CAMPCS/2 will allow definitive determination of effect of ICS on these measures. CAMP is the largest and most completely characterized group of children with asthma. Follow-up of this cohort for another 4 years in CAMPCS/2 will provide valuable information about the natural history of this important childhood lung disease, and information on how the childhood illness affects adult lung health. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CHROMOSOME 5Q GENE VARIANTS AND ASTHMA-RELATED TRAITS Principal Investigator & Institution: Martinez, Fernando D.; Professor of Pediatrics; Pediatrics; University of Arizona P O Box 3308 Tucson, Az 857223308 Timing: Fiscal Year 2002; Project Start 30-SEP-2000; Project End 31-AUG-2005 Summary: Unraveling the complex genetic determinants of asthma may provide important new clues about its pathogenesis and novel therapeutic and preventive approaches. Both clinical phenotypes based on asthma symptoms and intermediate phenotypes for asthma have been found to be linked to markers in many areas of the genome. One area where several groups have found evidence for linkage independently is chromosome 5q. We found linkage between markers in chromosome 5q3 l and both eosinophilia and a composite "atopy" phenotype. The goal of this grant proposal is to identify the gene variants in 5q3 1-33 that are responsible for these two linkage signals. We will do so using the same population of families enrolled in the Tucson Children's Respiratory Study that have now been followed since the time of the birth of the index child approximately 18 years ago. In our first specific aim, we will identify gene variants having a frequency of 2% or more in a group of 25 known genes in chromosome 5q. We

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have selected these 25 genes among those that have been mapped to the 28cM interval that was tested for linkage in our previous studies. Our second specific aim is to perform linkage disequilibrium mapping using 100 known polymorphisms in the region of approximately 6.4cM that shows the highest likelihood of containing the gene variants responsible for either or both of the eosinophilia and atopy linkage signals. Detailed local mapping using both published and newly discovered polymorphisms in and around areas of positive signals will also be performed. Based on our previous experience in this same chromosomal region, we expect to find several association/linkage signals in chromosome 5q. This will allow to better understand the genetic influence that determine asthma risk. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CHRONIC HYPERPLASTIC SINUSITIS AND ASTHMA Principal Investigator & Institution: Borish, Larry C.; Associate Professor; University of Virginia Charlottesville Box 400195 Charlottesville, Va 22904 Timing: Fiscal Year 2002 Description (provided by applicant): This project will contribute to the overall objectives of this AADC by focusing on the contribution of sinusitis to the presence and severity of asthma. Sinusitis and asthma are very common conditions characterized by a similar inflammatory infiltrate, but the relationship between them is poorly understood. We have shown that extensive mucosal disease is a major independent risk factor for asthma. This finding could indicate that either the two conditions have a common cause or that one is dependent on the other. We will distinguish these possibilities by performing a prospective study on the relationship between sinusitis and asthma. Inherent in these studies is the critical need to develop and validate a methodology for objectively measuring the presence, severity, and clinical course of chronic hyperplastic sinusitis (CHS)/nasal polyposis (NP). As a disease of hyperplastic mucosal tissue with eosinophilia, we will show that the hyperplasia will be readily visualized and accurately quantified by CT scan. We will gain insights into the pathophysiology and interplay of these conditions by identifying changes in the nose and sinuses that correlate with increased inflammation in the lungs during experimental RV infection and nasal allergen challenges. Our proposed mechanism by which RV infection and allergen contribute to inflammation of the sinuses and lungs is that T cells primed in the nares and sinuses can act directly by localizing to the lungs. Alternatively, RV infection and allergen challenge may contribute to eosinophil influx into the airways, derived either from the bone marrow or locally from CD34+ve, IL5Ra+ precursors. Activated lymphocytes and eosinophil precursors, as well as newly generated bone marrowderived eosinophils, express VLA-4 and, in the presence of pre-existing VCAM-I, will localize in the lung where they will exacerbate inflammation. Finally, we will demonstrate that CHS/NP is characterized by the dysregulation of cysLTs and their receptors. CysLTs promote eosinophil-mediated inflammation, mucous gland secretion, the proliferation of epithelium and endothelium, and they contribute to remodeling and fibrosis. We hypothesize that the modulation of cysLT production and activity by aspirin desensitization will attenuate CHS/NP. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: COCKROACH ALLERGEN INDUCED AIRWAY INFLAMMATION Principal Investigator & Institution: Lukacs, Nicholas W.; Associate Professor of Pathology; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274

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Timing: Fiscal Year 2002 Summary: Despite a substantial increase in our understanding of the mechanism involved in the pathology of asthma, the mortality and morbidity rates continue to rise, especially in inner-city children. The etiology of many inner city asthmatics appears to be related to cockroach-delivered allergens. In the present proposal, we have detailed studies to assess specific mechanisms of a murine model of cockroach allergen-induced airway hyperreactivity which resemble atopic human asthmatics responses. The allergic responses in this model include significant increases in allergen-specific serum IgE, immediate release of histamine in the BAL, allergen-specific airway eosinophilia, and significantly altered airway physiology which correlates to the airway inflammation. The specific focus of the studies in this proposal will examine the mechanisms by which specific chemokines induce airway hyperreactivity at different stages of the cockroach allergen-induced responses. Differential responses at certain stages of allergic airway disease appears to center around the intensity of inflammation at the time of allergen rechallenge and the specific chemokine-mediated activation of local leukocyte populations. We hypothesize that specific CC chemokines which utilize specific receptors will be responsible for inducing airway hyperreactivity at different stages of cockroach allergen-induced airway responses. To test this postulate, the studies outlined in this proposal will examine two CC family chemokines, MCP-1 and eotaxin, which specifically bind to CCR2 and CCR3, respectively, and appear to mediate different responses leading to airway hyperreactivity. Our studies will include the following: 1) To characterize the inflammatory response and chemokine expression profiles at different stages of allergic response, 2) To examine the alteration of inflammation and airway physiology after depletion of the chemokines or in chemokine "knockout" (KO) on leukocyte populations during the development of allergic airway disease, 4) To determine the function of specific chemokine receptors in CCR2 and CCR3 KO mice, and 5) To elucidate the activational role of MCP-1 and eotaxin on specific leukocyte populations involved in the allergic airway responses. The development of these ideas will allow elucidation of the mechanistic activity of specific mediators and cell populations involved at different stages of cockroach allergen exacerbations of airway inflammation, leading to airway hyperreactivity and help define differences in disease progression within the allergic airway. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: COMPLEMENT REGULATION OF TH2 FUNCTIONS IN LUNG ALLERGY Principal Investigator & Institution: Drouin, Scott M.; None; University of Texas Hlth Sci Ctr Houston Box 20036 Houston, Tx 77225 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-AUG-2005 Summary: (provided by applicant): This career transition award will provide the necessary resources to assess the role of the complement system in asthma. Given that asthma is a major world-wide health problem, this research proposal will attempt to delineate the overall contribution of the complement system in the pathogenesis of asthma and, specifically, investigate the complement-mediated regulation of cell types that control asthma-associated responses. This hypothesis will be addressed through the use of an Aspergillus fumigatus animal model of pulmonary allergy utilizing mice that are deficient in the central component of the complement system C3 and the complement anaphylatoxin receptors which can contribute to airway hyperreactivity and inflammation. Furthermore, since Th2 and IgE responses are an important component of pulmonary allergy, and the role of complement has not been evaluated in

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regards to this facet, specific attention will be given to the ability of the complement system to regulate these asthma-associated responses. Collectively, this study will assess the expression, function, and participation of the complement system in airway inflammation during the course of asthma by evaluating asthma-associated responses such as airway hyperresponsiveness, lung eosinophilia, mucus hypersecretion, and Th2 and IgE responses in complement deficient and wild type animals. Moreover, results generated from this proposal will provide valuable insight into the contribution of the complement system in T cell regulation and allergy as well as pulmonary host defense and disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CONTROL OF EOSINOPHIL APOPTOSIS BY INTRACELLULAR SIGNALS Principal Investigator & Institution: Miesfeld, Roger L.; Professor; Biochem and Molecular Biophysics; University of Arizona P O Box 3308 Tucson, Az 857223308 Timing: Fiscal Year 2002; Project Start 01-APR-2000; Project End 31-MAR-2004 Summary: (Adapted from the Applicant's Abstract): One of the most efficacious treatments for chronic asthma is inhaled glucocorticoid therapy which reduces inflammation in the airways by inhibiting cytokine production and inducing eosinophil apoptosis. Although glucocorticoid therapy has proven to be effective for most asthmatics, there is a range of patient responsiveness, suggesting that variability may be due to underlying differences in intracellular signaling. The reduction for eosinophilia in asthmatics undergoing glucocorticoid therapy is strongly associated with improved airway functions, and glucocorticoids have been shown to induce apoptosis in human eosinophils in vitro and in vivo. Based on these observations, the investigators hypothesize that the quality and quantity of cytokine production in the lung, and differences in the eosinophil gene expression profile between individuals, are two key factors that modulate the potency of glucocorticoid therapy. Three specific aims are proposed to test this general hypothesis. 1) They have found that glucocorticoids induce human eosinophil apoptosis in primary cell cultures containing low levels of cytokines, but actually enhance eosinophil survival in cultures with high concentrations of cytokines. They will investigate the molecular basis for differential glucocorticoid effects in purified human eosinophils using cell extracts to monitor mitochondrial dysfunction, and kinase-specific inhibitors to determine which pathways contribute to this enhancement effect. 2) They will identify key signaling pathways required for anti- and pro-apoptotic signaling in the human eosinophil cell line model AML14.3D10. This will be done using molecular genetic approaches that exploit co-transfection assays containing the green fluorescent protein (GFP) gene and dominant negative gene variants of selected signaling molecules. 3) They will use cDNA microarray phenotyping of 20,000 human genes to identify and characterize expression patterns that associate with apoptotic sensitivity of primary human eosinophils, and with intracellular signaling pathways in AML14.3D10 cells grown under various culture conditions. This microarray analysis takes advantage of low-cost services and resources provided by the university-wide U. of Arizona Microarray Core Facility. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CYTOKINE REGULATION OF A MOUSE MODEL OF ASTHMA Principal Investigator & Institution: Finkelman, Fred D.; Professor; Internal Medicine; University of Cincinnati 2624 Clifton Ave Cincinnati, Oh 45221

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Timing: Fiscal Year 2002; Project Start 01-SEP-1999; Project End 31-JUL-2004 Summary: Asthma affects 3-6% of the general population of the United States and is an increasingly common cause of morbidity and mortality. The cytokine IL-4 has a central role in the pathogenesis of this disease: it stimulates the production of IgE and mucus, attracts eosinophils and other inflammatory cells to the lungs, stimulates the production of other asthma-associated cytokines, and, as shown by our preliminary data, increases smooth muscle responsiveness to cholinergic stimulation. This proposal will investigate the relative roles of the two receptors that bind IL-4 (the IL-4 receptor and the IL-13 receptors, in these processes. We will determine the mechanisms by which IL-4 and IL13 attract eosinophils to the lungs, the mechanism by which TGF-alpha acts synergistically with IL-4 to induce pulmonary eosinophilia and the mechanism by which IL-12 inhibits IL-4 induced pulmonary eosinophilia. In addition, we will perform experiments that investigate a noel observation that chronic exposure to IL-4 inhibits in vitro cyclic AMP responsiveness of pulmonary cell membranes to beta-adrenergic stimulation, to determine whether IL-4 similarly induces decreased pulmonary responsiveness to beta2-adrenergic stimulation in intact animals, whether this decrease in beta-adrenergic responsiveness can be induced also be allergen inhalation, whether this effect of IL-4 is also induced by IL-13, whether it is mediated by Stat6 signaling, whether it is associated with decreased pulmonary beta2-adrenergic receptor expression, whether it can be induced by other cytokines that enhance responsiveness to cholinergic stimulation, whether it requires the presence of inflammatory cells, and whether it is enhanced by TGF-alpha and opposed by IL-12. Our proposed studies will use transgenic mouse strains that over-express IL-4 in their lungs and that vary in their expression of IL-5, Stat6, and the IL-4 and IL-13 receptors; long acting forms of IL-4 and TGF-alpha that are administered nasally or systematically, and neutralizing antibodies specific for IL-4, the IL-4 receptor, and the IL-13 receptor. Pulmonary inflammation will be evaluated by microscopic examination of bronchoalveolar lavage cells and lung sections. In vitro assays will measure beta2-adrenergic receptor concentration and responsiveness in lung cell membranes, while responsiveness of intact mice to cholinergic and beta2-adrenergic stimulation will be determined by non-invasive barometric plethysmography with a Buxco apparatus. By clarifying the mechanisms by which cytokines induce pulmonary inflammation and airway responsiveness, the proposed studies will provide information important for rational therapy for asthma. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EFFECT OF IL-16 ON THE MURINE ALLERGIC AIRWAY RESPONSE Principal Investigator & Institution: Little, Frederic F.; Medicine; Boston University Medical Campus 715 Albany St, 560 Boston, Ma 02118 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2008 Summary: (provided by applicant): IL-16 is a pleiotropic cytokine which has been associated with allergic airway inflammation in humans and mice. It is constitutively synthesized by T-cells and is induced in the bronchial epithelium in allergic inflammation. The role of IL-16 as a CD4 ligand has been extensively studied. Stimulation of CD4+ T-cells with IL-16 results in phosphorylation of p56lck,expression of IL-2R-alpha and beta, and chemotaxis. IL-16 also downregulates TCR/CD3 mediated T-cell activation: it inhibits the mixed lymphocyte reaction, renders Tcells anergic, and abrogates activation by anti-CD3 stimulation. In murine models of allergic inflammation IL-16 downregulates antigen-driven T-cell activation. In these animal studies exogenous or transgenically expressed airway IL-16 decreases airway hyperresponsiveness (AHR) and eosinophilia, cardinal features of TH2 responses. This proposal is designed to

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elucidate the paracrine and autocrine effects of CD4+ T-cell derived IL-16 on allergic airway inflammation. We hypothesize that CD4+ T-cell IL-16 will inhibit antigen recognition by naive and sensitized T-cells; and that the effects of IL-16 are selective for TH2-mediated inflammation. I propose to use experimental models of allergic inflammation and bone marrow chimeras with knockout and transgenic mice to address the role of CD4+ T-cell IL-16 in the murine allergic airway response. Specifically, this proposal will address two major questions: 1) What is the contribution of T-cell derived IL-16 in the modulation of airway inflammation in TH2 cytokine overexpression and allergen exposure models of allergic airway inflammation? 2) What phases of the T cell immune response does IL-16 inhibit? These questions will be addressed by examining markers of T-cell activation in the lymph nodes and lung, antigen-specific immunoglobulins, airway inflammation and AHR in a murine model of allergic airway inflammation. These studies will provide direct training in transgenic technology, generation of bone marrow chimeric mice and manipulation of TH1 vs. TH2 responses and broader insights into the role of IL-16 in the allergic response. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EOSINOPHIL ACTIVITIES IN MURINE MODELS OF LUNG DISEASE Principal Investigator & Institution: Lee, James J.; Mayo Clinic Coll of Med, Mayo Clinic Az Sc Johnson Research Medical Building Scottsdale, Az 85259 Timing: Fiscal Year 2004; Project Start 30-SEP-2000; Project End 30-JUN-2008 Summary: (provided by applicant): The pulmonary eosinophilia accompanying the pathologies of asthma has been a correlative feature recognized even in the earliest studies investigating this disease. Innumerable investigations have confirmed and detailed this relationship, demonstrating that the presence of eosinophils is predictive of disease severity and occurs even in mild cases. The recruitment of eosinophils also occurs in animal models of allergen-mediated respiratory inflammation; the mouse, in particular, has been extensively studied. Despite the abundance of clinical studies and the availability of mouse models that correlate pulmonary eosinophilia with lung dysfunction, eosinophil effector functions are poorly understood and, indeed, questions remain as to the role(s), if any, of these leukocytes. We have created a novel line of mice genetically devoid of eosinophils. This ablation is accomplished through the specific expression of a suicide gene (i.e., Diphtheria Toxin A chain) exclusively in eosinophillineage committed cells of transgenic mice. The eosinophil ablation is absolute and specific as no effects are observed on other hematopoietically derived cells. This proposal utilizes our unique eosinophil-less line of mice, as well as other novel eosinophil-specific reagents/methodologies that we have developed, in two concurrent approaches testing the hypothesis that eosinophils have a causative role(s) in allergic airways disease (i.e., acute and chronic allergen-challenge protocols and genetic crosses with other established transgenic/gene knockout model systems). These objectives will be achieved by the completion of the following Specific Aims: (1) To determine unequivocally the contribution(s) of eosinophil effector functions to the pulmonary pathologies arising in an acute allergen sensitization/aerosol challenge model; (2) To define the role(s) of eosinophils in lung remodeling using a chronic model of allergenmediated inflammation; (3) To define eosinophil-dependent mechanism(s) leading to late phase bronchoconstriction following allergen provocation; (4) To determine the contribution(s) of eosinophils to the previously characterized pulmonary pathologies of lung-expressing IL-5 transgenic mice. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: EOSINOPHIL-AIRWAY EPITHELIAL FAS-FASL INTERACTIONS Principal Investigator & Institution: Hamann, Kimm J.; Associate Professor; Medicine; University of Chicago 5801 S Ellis Ave Chicago, Il 60637 Timing: Fiscal Year 2002; Project Start 25-SEP-2001; Project End 30-JUN-2005 Summary: Studies are proposed to examine the functional expression of Fas ligand (FasL) by airway epithelial cells and the induction of cell death in human eosinophils by this FasL. The central hypothesis is that epithelial FasL functions to help limit or resolve inflammatory cellular infiltrates such as eosinophils, and that in asthma this function is impaired contributing to persistent pulmonary eosinophilia. These studies will address molecular mechanisms which regulate the functional expression of FasL on airway epithelial cells in three specific aims: (1) Determine the role of NF-kappaB in the constitutive and inducible expression of Fas ligand (FasL) in human airway epithelial cells and the role of matrix (MMP) and disintegrin (ADAM) metalloproteases in the release of soluble FasL (sFasL) from these cells. Experiments will determine (a) constitutive expression of cytosolic and membrane-bound FasL; (b) the role of cytokines on the NF-kappaB-regulated expression of FasL on airway epithelial cells; and (c) the release of soluble (s)FasL and the roles of MMP-3 or -7, ADAM-17 or other epithelialexpressed MMP/ADAMS in this release. (2) Assess the Fas-mediated (apoptotic) killing of human and murine eosinophils and eosinophilic cell lines by airway epithelial FasL and the role of ICAM-1-mediated adherence of eosinophils to epithelial cells in these interactions. Experiments will (a) assess the epithelial cell-mediated killing of human or murine eosinophils and the necessity of cell-cell contact; (b) assess the effects of sFasL on induction of apoptosis of eosinophils by epithelial cells or agonistic anti-Fas; and the chemotactic activity of sFasL, and (c) determine the role of (NF-kappaB-regulated) ICAM-1 expression in promoting cell interactions; (3) Assess the physiological role of epithelial FasL in resolution of inflammation in vivo using a murine model of pulmonary eosinophilic inflammation. Experiments will (a) determine the in vitro effects of using epithelial cells and eosinophils from FasL-mutant (gld) and Fas-deficient (lpr) mice, respectively on eosinophil-epithelial cell interactions; (b) determine the in vitro effects of using cells from MMP and NF-kappaB knockout mice on these interactions and regulation of membrane(m)FasL and sFasL; and (c) determine the resolution of pulmonary eosinophilic inflammation in an in vivo model in lpr, gld, and MMP and NF-kappaB knockout and bone marrow chimeric mice compared to normal mice. Elucidation of the interactions of these interactions will lead to a better understanding of contributory Fas-mediated mechanisms of eosinophil clearance and to more specific therapies tailored to the chronic eosinophilic inflammatory nature of asthma. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: EOSINOPHILIC INFLAMMATION IN INTRINSIC ASTHMA Principal Investigator & Institution: Kita, Hirohito; Associate Professor; Mayo Clinic Coll of Medicine, Rochester 200 1St St Sw Rochester, Mn 55905 Timing: Fiscal Year 2002 Description (provided by applicant): Toward the achievement of the overall goal of this AADRC, Project 3 "Eosinophilic Inflammation in Intrinsic Asthma" will address why eosinophilia inflammation persists in the airways of patients with asthma and what significance eosinophil degranulation has in the disease process of human asthma. Bronchial mucosal abnormalities that characterize asthma, such as persistent airway eosinophilia and increased T cells producing IL-5, strongly suggest an ongoing T helper

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(Th)2-like immune response of the airways. Atopy and an IgE-mediated response to extrinsic antigens are the known and identifiable predisposing factors for asthma. However, many adult patients with asthma do not seem to be particularly atopic. The objective of this project is to elucidate the causes and pathophysiologic mechanisms of asthma in patients that are not demonstrably atopic, a condition commonly referred to a non-atopic or intrinsic asthma. We will test the hypothesis that bronchial asthma in patients with non-atopic asthma is caused by a chronic immunologic reaction to intrinsic antigen, namely fungi present in the airways, resulting in persistent IL-5 production and eosinophil activation in the airways. In Specific Aim 1, we will define the enhanced immunological responses, especially IL-5 and IFN-gamma production, of patients' immune cells to non-pathologic fungal organisms present in the airways. In Specific Aim 2, we will directly test whether fungal organisms present in the airways are involved in the disease process by removing the fungi from the airways by instillation of an antifungal agent. Conversely, the effects of an increased fungal antigen burden will be investigated by segmental broncho-provocation. In Specific Aim 3, we will use novel antibodies that recognize eosinophil degranulation activities to define the clinical relevance of eosinophil activation in human asthma by testing the hypothesis that enhanced eosinophil activation and degranulation in the airway lead to exacerbation of asthma symptoms in patients with non-atopic asthma. Elucidation of the causes and mechanisms of inflammation in non-atopic asthma will likely foster a better understanding of eosinophilia inflammation in human asthma and will enhance development of specific and effective therapies for this difficult disorder. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: FLT3-LIGAND, IMMUNOMODULATION AND THERAPY IN ASTHMA Principal Investigator & Institution: Agrawal, Devendra K.; Professor; Medicine; Creighton University 2500 California Plaza Omaha, Ne 68178 Timing: Fiscal Year 2004; Project Start 15-MAR-2004; Project End 28-FEB-2008 Summary: (provided by applicant): There is a direct association between type 2 Tlymphocyte profiles and allergic airway inflammation in asthma. One strategy for preventing type 2 responses to an allergen is to suppress the pro-allergic signals that antigen presenting cells (APCs) send to T-cells. The most potent APCs in the lung are dendritic cells (DCs), and recent studies have revealed phenotypic variability in this population, which can strongly polarize the developing T cells. FLT3 Ligand (FL) is a growth factor for DCs, and induces a type 1 T-cell response. We recently reported that FL prevented ovalbumin-induced allergic airway inflammation in mice and suppressed late allergic response (LAR) and airway hyperresponsiveness (AHR). Based on these studies, we developed the hypothesis that FL has therapeutic activity for hosts with asthma by the expansion of DC1 cells, production of IL-12 and induction of a type 1 T cell response that inhibits type 2 T-cell stimulation important in asthma. In Specific Aim 1, we will examine the ability of FL to reverse LAR, AHR, and eosinophilia in a mouse model of allergic airway inflammation and augment an antigen-specific, type 1T cell response to the inciting allergen. We will determine the dose-response for FL therapeutic activity and duration of effect. We will also examine the effect of FL on clinical correlates of asthma including baseline AHR in mice sensitized, but not challenged with the allergen. Further, we will examine the levels and isotype of antibodies to the allergen and cytokine levels in serum and lung washings, in addition to non-antigen and antigen-specific type 1 and 2 T cell responses by Elispot assays both systemically (spleen) and regionally (mediastinal lymph nodes and collagenase digested

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lungs). Non-specific therapeutic effect of FL will be examined in Schistoma mansoniinduced allergic airway inflammation model. In Specific Aim 2, we will investigate the ability of FL to reverse the airway remodeling associated with chronic asthma. We will study the ability of FL to reverse the histopathologic changes, including tracheal and bronchial epithelial thickness and sub-epithelial fibrosis, measure pro-fibrotic cytokines and chemokines and examine smooth muscle hyperplasia. In Specific Aim 3, we will study the mechanisms of FL therapeutic activity for acute and chronic asthma. We will determine the therapeutic activity of FL in wild type and IL-12( knock-out (KO) mice. As KO mice may have pre-existing compensatory mechanisms, we will also undertake studies examining the therapeutic activity of FL in animals given neutralizing antibodies to IL-12 during allergic airway inflammation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GALECTINS IN PATHOGENESIS OF ASTHMA: CHEMOTACTIC EFFECTS Principal Investigator & Institution: Liu, Fu-Tong; Professor and Chair; Scripps Research Institute Tpc7 La Jolla, Ca 92037 Timing: Fiscal Year 2002 Description (provided by applicant): Galectins are a protein family defined by their affinity for b-galactoside-containing sugars and consensus protein sequences. Galectin-3 has multiple functions, including chemotactic activity for monocytes, which has been demonstrated both in vitro and in vivo. This lectin also attracts eosinophils in vivo, probably through stimulation of various cell types to release eosinophil chemoattractants. Galectin-3 is expressed in airway epithelial cells and alveolar macrophages and is highly upregulated in the airways during allergic inflammation in a murine mode. Galectin-3-deficient mice develop a significantly lower level of eosinophil airway inflammation compared with wild-type mice, following airway antigen challenge. Other investigators have shown that galectin-9 is a potent eosinophil chemoattractant. In order to establish the role of galectin-3 and -9 in asthma through their chemotactic effects, we propose to: (1) detect galectin-9 in the airways and demonstrate its eosinophil chemoattractant activity in vitro. Whether galectin-9 is upregulated in the airways in asthmatic patients and represents a major eosinophil chemoattractant in BAL fluid will be determined. Whether galectin-9 can attract eosinophils when it is bound to extracellular matrix proteins, induce integrin expression, and, cause eosinophil transmigration through airway epithelial barrier will be determined; (2) establish the role of galectin-9 in asthma by using animal models. Whether administration of galectin-9 into the airways causes an eosinophil infiltration will be tested. The role of galectin-9 in eosinophilia airway inflammation will be established by using transgenic mice and specific inhibitors; (3) establish the chemotactic effect of galectin-3 in allergic airway inflammation. Whether galectin-3 is upregulated in the airways in asthmatic patients will be determined. Whether galectin-3 induces eosinophil chemokines in various cell types in vitro will be studied. The role of galectin3 in eosinophil infiltration in the murine model of asthma will be investigated using galectin-3-deficient mice; and (4) elucidate the signaling pathways responsible for galectins? chemotactic effects. Whether galectin-3 utilizes known chemokine receptors on monocytes will be determined. Whether galectin-3's chemotactic effect is mediated through protein tyrosine kinases, in addition to G-protein-coupled receptors, and whether it involves activation of protein kinase C, phosphoinositide 3-kinase and Rho ATPases will be investigated. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: GENETIC ANALYSIS OF MYELOPROLIFERATIVE DISEASE Principal Investigator & Institution: Cowell, John K.; Chairman, Department of Cancer Genetics; Roswell Park Cancer Institute Corp Buffalo, Ny 14263 Timing: Fiscal Year 2002; Project Start 01-APR-1999; Project End 31-JAN-2004 Summary: Myeloproliferative disorders (MPDs) result from the abnormal proliferation of myeloid precursor cells in the bone marrow. Understanding the genetic events which result in MPDs will not only improve our understanding of the disease process, but will also provide insights into the normal developmental control in early progenitor cells. A variant form of this disease is associated with T-cell leukemia/lymphoma and peripheral blood eosinophilia. The clinical course of the disease is particularly aggressive with rapid progression of the disease to acute myelogenous leukemia or stem cell leukemia. The involvement of both myeloid and T-cell lineages in this disease strongly suggest a primitive origin for the cells involved, before the commitment to a particular lineage. These tumors invariably show a highly specific, reciprocal chromosome translocation involving chromosomes 8 and 13. This specific translocation is always involved with this biphenotypic tumor indicating that genes located at the translocation breakpoints play an important role in disease development. The genes involved in this rearrangement have now been identified as FGFR1 in chromosome region 8p11 and a zinc finger gene, ZNF198, of unknown function, in 13q12. The molecular conequences of this rerrangement have been shown to be identical in all of the four cases we have analyzed. As a result of the rearrangement a fusion gene is generated which is under the control of the ZNF198 promoter. This novel gene carries the zinc finger motif of ZNF198 fused to the tyrosine kinase domain of FGFR1. Because of the highly specific nature of this rearrangement and its consistent presence in all of the tumors analyzed to date, this rearrangement must clearly be important in leukemogenesis in these patients. Our goals therefore are (1) to transform normal cells using the fusion gene in order to establish a functional assay in vitro, (2) to create a transgenic mouse line expressing the fusion protein and so establish an in vivo model to study the biological consequences of the translocation and (3) since the fusion gene may act as a dominant-negative we will also investigate the normal function of ZNF198 in order to compare its activity with that of the fusion gene. As a result of our improved understanding of the genetic events which give rise to this MPD, it may eventually be possible to design novel therapeutic approaches to this disease directed against the aberrant gene(s) and its product. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: IL3,IL5, AND GM-CSF SIGNALING AND ASTHMA Principal Investigator & Institution: Schindler, Christian W.; Associate Professor of Medicine and Micr; Microbiology; Columbia University Health Sciences Po Box 49 New York, Ny 10032 Timing: Fiscal Year 2002; Project Start 01-AUG-1996; Project End 30-JUN-2006 Summary: (provided by applicant): Interleukin (It)-5 is a member of a small family of cytokines (IL-3, IL-5, & GM-CSF) that play an important role in myeloid development. IL-5 however exhibits specificity for eosinophils, accounting for its unique role in promoting the eosinophilia that is seen in a number of human diseases, including asthma. IL-5, IL-3 and GM-CSF transduce signals through two members of the STAT (Signal Transducer and Activator of Transcription) family, Stat5a and Stat5b. Like other STATs, Stat5a and Sta5b transduce ligand specific signals from the receptor to the nucleus, where they promote the transcription of a specific set of genes. STATs share a

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number of structural motifs that are likely to contribute to their signaling fidelity. This includes an amino terminal four-bundle-helix domain of unknown function, a DNA binding domain, an SH2 domain and carboxy terminal transcriptional activation domain. Our preliminary studies indicate that the four-bundle-helix domain both regulates DNA binding activity and mediates association with a newly identified regulatory protein, StIP1 (Stat Interacting Protein). Stat5 is one of the more pleitrophic members of the STAT family and has been implicated in determining multiple cell fates in both myelocytes and lymphocytes. These studies suggest that the duration of Stat5 signaling is important in determining biological response. Whereas StIP1 and the fourbundle-helix domain appear to contribute to Stat5 activation, signal decay is also known to be tightly regulated. Consistent with this, constitutive activation of Stat5 has been shown to promote myeloid dysregulation. We plan to study how the four-bundle-helix and StIP1 regulate STAT activity and determine the significance of signal decay on the biological response transduced by Stat5. Specifically we propose to: 1. Further characterize StIP1. 2. Functionally characterize the STAT four-bundle-helix. 3. Explore the role of Stat5 signal decay in primary leukocytes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: IMMUNOBIOLOGY OF EXPERIMENTAL RSV INFECTION Principal Investigator & Institution: Braciale, Thomas J.; Director and Professor; Beirne Carter Center for Immunology Research; University of Virginia Charlottesville Box 400195 Charlottesville, Va 22904 Timing: Fiscal Year 2002; Project Start 30-SEP-1994; Project End 30-JUN-2003 Summary: (adapted from the applicant's abstract): The proposal investigates the interplay of host and viral factors involved in the development of the immune response to Respiratory Syncitial Virus (RSV) infection in mice. Preliminary data indicate that RSV-specific CD8+ T lymphocytes play an important regulatory role in directing the differentiation of RSV-specific memory CD4+ T lymphocytes into Th-1 or Th-2 effectors. In Aim 1, an in vitro model will be developed to investigate the role of CD8+ T cells in the development of effector CD4+ T cells. In particular, the roles of soluble and cell associated CD8 T lymphocyte gene products in driving Th-1 versus Th-2 responses to the RSV-G glycoprotein will be investigated. In Aim 2, subdominant Th epitopes will be identified to examine their contribution to Th-2 effector function and pulmonary eosinophil accumulation in response to RSV challenge. Finally in Aim 3, a combination of selective breeding and chromosomal DNA marker analysis will be used to identify host genetic loci that regulate the response of CD4+ T lymphocytes to RSV infection. These studies will provide new and potentially important information on the interaction of CD4+ and CD8+ T cells in the clearance of RSV infection. This information will be important for the development of an effective RSV vaccine. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: IMMUNOPATHOGENESIS OF AIRWAY INFLAMMATION Principal Investigator & Institution: Bottomly, Kim; Professor; Immunobiology; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2002; Project Start 10-DEC-1994; Project End 29-FEB-2004 Summary: The overall goal of this proposal is to understand how CD4 T lymphocytes and their associated cytokines regulate the chronic inflammatory disorder which is characteristic of asthma. Asthma airway inflammation involves eosinophils, lymphocytes and mast cells, all of which release chemical mediators in the local lung

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environment which are thought to cause the observed airway responses. There is considerable evidence that Th2 CD4 effector cells are associated with chronic airway inflammation. In this application, the direct role of Th2 cells and their associated cytokines in the induction of lung inflammatory responses to airway hyperresponsiveness will be tested. Underlying the proposal are 2 hypotheses: First, IL4, or int he absence of IL-4, IL-13 production by Th2 cells, and subsequent Stat6 signaling by lung endothelial cells are required for Th2 recruitment to the lung. Eosinophil recruitment depends on the presence of Th2 cells and the production of the Th2 cell associated cytokines, IL-4 and IL-5. Second, the appearance of eosinophils in the airway is IL-4 dependent in that in the absence of IL-4, eosinophils in the lung parenchyma do not migrate into the airway. The association of airway eosinophilia with airway responsiveness will be tested. These hypothesis will be tested in 3 Specific Aims: 1) To determine the role of IL-13 and Th2 cell recruitment to the lung; 2) to determine the mechanism by which Th2 derived IL-4 regulates lung and airway eosinophilia; and 3) to determine the cellular molecular and genetic factors that regulate airway eosinophilia following epicutaneous immunization. Using a newly established mouse model in which the Th2 cells and local lung environment can be independently genetically manipulated, the precise function of factors important in the induction of inflammation will be determined. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: INDUCTION OF RESPIRATORY TOLERANCE BY MUCOSAL CPG ODN Principal Investigator & Institution: Kline, Joel N.; Associate Professor; Internal Medicine; University of Iowa Iowa City, Ia 52242 Timing: Fiscal Year 2003; Project Start 10-DEC-1997; Project End 30-APR-2007 Summary: (provided by applicant): Asthma is characterized by Th2-cytokine-mediated airway-centered inflammation. Tolerance to inhaled antigens (Ag), as is seen in nonatopic individuals or following specific immunotherapy in atopic asthmatics, may be promoted by a variety of mechanisms. We have induced inhalation tolerance by mucosal immunotherapy with CpG-ODN (oligonucleotides containing unmethylated CpG dinucleotides) and Ag; neither stimulus alone was successful in suppressing the Th2-cytokine-mediated inflammation. Although stimulation with CpG-ODN induces strong Th1 responses, suppression of Th2 responses is only moderately reduced in the absence of Th1 cytokines such as IFN-gamma and IL-12; therefore, alteration of the balance between Th1 and Th2 responses does not explain the mechanisms through which CpG-ODN promote tolerance. We have found that mucosal immunotherapy promotes suppression of Ag-specific, to a much greater extent than Ag-non-specific, responses, and that cell-to-cell contact is necessary for maximal effect. Protection against airway eosinophilia can be adoptively transferred by antigen presenting cells (APC) treated with OVA+CpG-ODN. IL-10, and possibly TGF-beta, are involved in the tolerogenic effects of CpG-ODN. Based on these findings, we hypothesize: CpG-ODNinduced respiratory tolerance is mediated through interactions between dendritic cells and regulatory T-lymphocytes in the lung. In order to identify these interactions ultimately, we will first focus on the effects of CpG-ODN on each of these cell populations separately. We will explore this hypothesis in the context of these complementary Specific Aims: Aim 1: To evaluate whether anti-inflammatory effects of airway mucosal exposure to CpG-ODN are mediated through lung dendritic cells. Aim 2: To evaluate whether anti-inflammatory effects of airway mucosal exposure to CpGODN are mediated through regulatory T-lymphocytes.

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

Project Title: LEUCOCYTE ADHESION IN ALLERGIC INFLAMMATION Principal Investigator & Institution: Sriramarao, p; Professor & Head; La Jolla Inst for Molecular Medicine Molecular Medicine San Diego, Ca 921213074 Timing: Fiscal Year 2002; Project Start 01-JUN-1995; Project End 31-MAY-2005 Summary: Adherence of circulating eosinophil to vascular endothelium and their recruitment to extravascular sites in inflamed tissues is the hallmark of allergic inflammation. Recent studies have identified an important role for adhesion molecules and other mediators in the sequestration of eosinophils to sites of inflammation. In this competing renewal we first postulate that vascular cell adhesion molecule (VCAM-1) is a multifunctional cell adhesion molecule that supports initial rolling, activation dependent stable adhesion and chemokine mediated transmigration of eosinophils by interacting with different activation states of alpha4 integrins. Using VCAM-1 deficient heterozygous mice we will determine the tissue specific contribution of VCAM-1 to eosinophil recruitment to sites of allergic inflammation in the skin and peritoneum. Our studies have identified that CD44 may function as a novel rolling receptor for human eosinophils. Furthermore, C3a appears to function as a eosinophil active chemoattractant to mediate stable adhesion of rolling cells. We will therefore, examine the function of CD44 and C3a in eosinophil mediated allergic inflammation. Since matrix matalloproteinases (MMPs) play an important role in the migration of leukocytes within the extravascular space, we will examine the importance of eosinophil expressed MMP-9 as well as an inducible eosinophil-specific MMP, designated as MMP-E, in mediating eosinophil chemotaxis in vivo as part of the second specific aim. In addition monoclonal antibodies against MMP-E will be generated with a view to better understand the biochemical and functional regulation of MMP-E in the context of eosinophil recruitment and allergic inflammation. Since exposure to cytokines such as IL-5 leads to significant eosinophilia, in the third specific aim, the mechanisms of IL5/allergen-induced mobilization of hematopoietic progenitor/stem cell (HPSC) and eosinophil committed progenitors in the bone marrow will be investigated. We will also investigate how IL-5 modulates the trafficking/migration of HPSC from the bone marrow microenvironment (stromal and endothelial cells) to distal sites of allergic inflammation (lung endothelial cells under conditions of flow. Using in vivo techniques of intravital microscopy along with in vitro molecular and cellular tools, the proposed studies are intended to give a better understanding of the molecular mechanisms mediating eosinophil interactions in inflamed blood vessels and tissues and to provide a basis for developing novel therapeutic strategies for treatment of allergic inflammation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: LPA AND EDG RECEPTORS IN THE PULMONARY IMMUNE RESPOSE Principal Investigator & Institution: Georas, Steve N.; Associate Professor; Medicine; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2004; Project Start 01-JAN-2004; Project End 30-NOV-2007 Summary: (provided by applicant): The enzymatic metabolism of membrane glycerophospholipids generates bioactive lysophospholipids including lysophosphatidic acid (LPA). LPA is present in normal serum, and is increased in concentration upon physiologic activation of platelets and other cell types. LPA has well-known growth effects on endothelium and lung structural cells, but its effects on other cell types are

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poorly understood. It was only recently appreciated that LPA exerts its cellular effects by binding a family of cell-surface molecules termed the endothelial differentiation gene, or Edg, receptors. The present study was prompted by our observations that: (i) Edg receptor mRNA is highly expressed in T lymphocytes and dendritic cells, (ii) LPA strikingly enhances the secretion of interleukin 13 (IL-13) from sub maximally activated T cells, and (iii) the concentration of LPA was enhanced in bronchoalveolar lavage fluids after segmental allergen challenge of human subjects. In ongoing research, we found that LPA influences dendritic cell maturation to inhibit IL-12 production, and that coadministration of LPA at the time of allergen sensitization in mice markedly augments lung eosinophilia in response to airway allergen challenge. We have developed a novel method to measure picomolar quantities of LPA and show that activated dendritic cells can release extracellular LPA. In a new collaboration, we have been provided access to a panel of high-titer antibodies directed against the three LPA receptors, and mice bearing targeted deletions in each of the LPA receptor genes Ipa1, Ipa2, and Ipa3. We propose four aims to dissect the role of LPA and its receptors in the allergic pulmonary immune response. In Aim 1, we will define the molecular mechanisms by which LPA augments IL-13 expression in T cells, and test the hypothesis that this involves coupling of LPA receptors to MAPK and NF-kappaB activation. In Aim 2, we will test the hypothesis LPA augments the differentiation of Th2 cells from naive CD4+ precursors under conditions of limiting antigen availability. In Aim 3, we will use a mouse model of allergen sensitization and challenge and test the hypothesis that LPA and its receptors are required for T cell trafficking and pulmonary allergic inflammation. In Aim 4, we will test the hypothesis that LPA primes lung dendritic cells for a Th2-promoting phenotype in vivo. Taken together, these studies will provide the first comprehensive analysis of a novel lysophospholipid and signal transduction pathway in allergic inflammatory diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MECHANISM OF INHIBITION OF LUNG EOSINOPHILIA BY CPG DNA Principal Investigator & Institution: Sur, Sanjiv; Associate Professor of Internal Medicine; University of Texas Medical Br Galveston 301 University Blvd Galveston, Tx 77555 Timing: Fiscal Year 2002 Summary: There is a global increase in the morbidity and mortality from asthma, but a long-term therapy that prevents eosinophilic inflammation in patients with pre-existing asthma has not been described. Asthma is an eosinophil disease of the airways that is promoted by Th2 cytokines, and inhibited by Th1 cytokines such as IFN-gamma. Recent studies suggest the mammalian immune system recognizes unmethylated CpG motifs present in bacteria DNA as a "danger signal". This triggers rapid production of IFNgamma and Th1-inducing cytokines. These cytokines set up a lung milieu that is optimal for generation of Th1 cells and inhibition of eosinophil recruitment. In this proposal, the rapid and long-term effects of CpG ODN will be evaluated in a mouse model of asthma. The cells internalizing CpG ODN will be identified by confocal microscopy. The ability of these cells to produce IL-12, IL-18 and IFN-gamma will be demonstrated by quantitative RT-PCR and ELISA. The role of p38, JNK and ERK MAP kinases will be characterized by western blotting, immune complex kinase assays, and by using specific pharmacological or antisense oligonucleotide inhibitors of these pathways. The in vivo role of IFN-gamma, IL-12 and IL-18 will be demonstrated by using gene knockout animals, or by using neutralizing antibodies. The research proposal has important

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Eosinophilia

implications in the development of novel therapies for asthma, including those that provide long-term protection against eosinophilic inflammation and asthma attacks. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MECHANISMS OF CHEMOKINE EXPRESSION IN ASTHMA Principal Investigator & Institution: Lilly, Craig M.; Assistant Professor; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2002; Project Start 15-FEB-2000; Project End 31-JAN-2004 Summary: Asthma associated morbidity, disability effects 54 out of every 1000 Americans. This chronic recurrent disease is known to be directly associated with inflammation of the airways. Asthmatic airways are infiltrated with inflammatory cells including eosinophils which are present even in asymptomatic asthmatics with normal lung function. Eosinophils in asthmatic airways are activated and release preformed toxic granular proteins; they contain peroxidases which generate toxic oxygen metabolites, they generate lipid mediators and proinflammatory cytokines which can produce airway hyperresponsiveness-the cardinal physiological feature of asthma. The importance of eosinophils to asthma is suggested by studies that correlate the resolution of asthma symptoms with the resolution of airway eosinophilia. Defining the mechanisms that selectively recruit eosinophils to the airways has the potential to identify novel therapeutic targets relevant to eosinophil mediated diseases including asthma. While many substances are chemotactic for eosinophils far fewer have chemotactic effects that are selective for cell types assoicated with asthma. Eotaxin is one substance that selectively activates these cell types. The discovery of eotaxin in an animal model of asthma has led to investigations of its associations with human disease. Indeed we have recently found that eotaxin is mobilized in asthmatic lungs after segmental allergen challenge and airway levels correlate with the numbers of eosinophils recruited into the lungs. Eotaxin is detectable in human plasma and is directly and independently associated with asthma diagnosis, and inversely related to baseline lung function. Eotaxin levels are increased in asthma exacerbations and elevated levels are associated with worse outcomes from acute asthma care. Our long term goal is to understand the mechanisms that mobilize eotaxin and related chemokines that recruit eosinophils to the airways. We propose to study the mechanisms that are responsible for eotaxin mobilization by studying its mobilization in in vitro systems, and in cells from subjects with common eotaxin polymorphisms that impair eotaxin expression. Specifically we propose: (1) To determine the mechanism(s) by which a coding region polymorphism of the eotaxin gene reduces eotaxin expression. (2) To define the mechanisms that alter eotaxin mRNA expression. (3) To explore mechanisms common to eotaxin and MCP-4 mobilization and define regulatory elements critical for the coordinated expression of these chemokines. This work will lead to a better understanding of the mechanisms by which eotaxin and the CCR3 receptor contribute to the asthamtic diathesis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MECHANISMS OF CHEMOKINE-INDUCED INFLAMMATION IN HUMANS Principal Investigator & Institution: Beck, Lisa; Medicine; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002; Project Start 01-FEB-2001; Project End 31-JAN-2006

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Summary: Several members of the C-C branch of the chemokine family have been strongly implicated in the generation of tissue eosinophilia during allergic inflammation, due to their potent and selective chemoattractant activity on eosinophils. Since eosinophils are believed to be responsible for the tissue damage observed in allergic diseases, an improved understanding of the factors responsible for their recruitment in vivo is imperative. We have developed an in vivo chemokine challenge model with which we characterized the tissue response to RANTES in humans. We noted a profound delay in eosinophil recruitment in nonallergic subjects as compared to allergic subjects. Studies described in Aim 1 are designed to test whether the state of eosinophil priming or CCR3 expression or function explain this result. Studies in following Aims will follow up on our recent exciting discovery that epithelial (Aim 2) and endothelial (Aim 3) cells express a functional CCR3, which to date has only been described on leukocytes, mast cells and microglial cells. We will study the regulation of CCR3 expression focusing on cytokine families that are relevant for allergic diseases, namely Th1 and Th2 cytokines. Functional studies will focus on cell migration, induction of adhesion molecule expression, cytokine production and proliferation. To provide further insight into the biology of this receptor, we will determine whether epithelial or endothelial CCR3 expression varies depending on disease status (allergic vs nonallergic ) and whether allergen challenge modulates the baseline expression in allergic subjects. This grant proposal will test the overall hypothesis that chemokine responsiveness in vivo is dependent on several factors. including leukocyte priming and expression and function of relevant chemokine receptors on leukocytes and parenchymal cells (such as epithelial and endothelial cells). Results of these studies are likely to provide insights into the mechanisms by which chemokines induce cutaneous cell recruitment and will likely identify entirely new biological effects of C-C chemokines. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MECHANISMS OF EOSINOPHIL ACTIVATION BY RSV Principal Investigator & Institution: Garofalo, Roberto P.; Professor; University of Texas Medical Br Galveston 301 University Blvd Galveston, Tx 77555 Timing: Fiscal Year 2002 Summary: Eosinophils play a key role in the pathogenesis of respiratory syncytial virus (RSV)- induced airway inflammation and epithelial damage, which may predispose to allergic sensitization and development of asthma. We have shown that: 1) RSV infection of airway epithelial cells induces adhesion-dependent, degranulation of eosinophils; 2) The integral membrane glycoprotein, polymeric Ig receptor (pIgR), is up-regulated on RSV-infected airway epithelial cells and, in its secreted form (secretory component, SC), is a potent stimulus for eosinophil degranulation; 3) RSV is able to infect directly human eosinophils, which induces MAP kinase activity, activation of the potent transcription factor NF-kappaB, and production of chemokines. We hypothesize that pIgR expression on epithelial cells, activation of the Raf-1-MEK-MAP kinase pathway and nuclear translocation of NF-kappaB are critical events in the eosinophil activation during RSV infection. The following specific aims are proposed: 1) To characterize the role of pIgR in eosinophil degranulation induced by RSV-infected airway epithelial. The role pIgR in RSV- induced eosinophil degranulation will be studied by blocking the process using a panel of neutralizing monoclonal antibodies that recognized different epitopes of the pIgR, and by co-culture assays of eosinophils with epithelial cells stably transfected with the human pIgR. 2) To investigate the activation of NF-kappaB in RSV- infected human eosinophils and to determine its role in chemokine gene expression. The NF-kappaB

22

Eosinophilia

family members that are activated by eosinophils by RSV and the mechanisms of NFkappaB antisense oligonucleotides or double- stranded competitor oligonucleotides will be employed to determine their effect on RANTES and IL-8 secretion. 3) To study the Raf-1-MEK-MAP kinase pathway in RSV-infected eosinophils and to assess its importance in NF-kappaB activation and chemokine production. The mechanisms of Raf-1 activation in RSV-infected eosinophils, will be studied by examining the involvement of tyrosine kinases, protein kinase C, and p21 ras molecules in the activation of Raf-1 kinase. We will test the hypothesis that NF-kappaB activation and chemokine production (RANTES and IL-8) in RSV-stimulated eosinophils are linked to the activation of the Raf-1-MEK-MAP kinase pathway by the use of specific kinase inhibitors, antisense oligonucleotides, and dominant-negative mutants. Identification of critical molecules involved in eosinophil functions will help in identifying specific inhibitors for treatment of acute RSV infection and for prevention of its sequelae, including asthma. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MECHANISMS OF EOSINOPHILIA IN EXPERIMENTAL ASTHMA Principal Investigator & Institution: Rothenberg, Marc E.; Professor of Pediatrics, Director, Divis; Children's Hospital Med Ctr (Cincinnati) 3333 Burnet Ave Cincinnati, Oh 452293039 Timing: Fiscal Year 2002; Project Start 01-FEB-1998; Project End 31-JAN-2004 Summary: (Applicant's abstract): Asthma is a chronic debilitating inflammatory disease of the lungs whose incidence is on the rise especially among minority groups. Asthma is especially important during childhood when it accounts for the most common reason for a child's visit to the emergency room and hospitalization. Our goal is to provide the basis for developing novel therapeutic approaches for the treatment of asthma and other allergic disorders by elucidating mechanisms of peripheral blood and tissue eosinophilia. This application is based on the hypothesis that eosinophilic airway inflammation (characteristic of asthma) is mediated in part by eotaxin, a CC chemokine that specifically recruits and activates gene expression in eosinophils. Unlike all other eosinophil chemoattractants that have been extensively characterized, eotaxin is eosinophil specific. Using eotaxin deficient mice, this application will test the hypothesis that eotaxin plays a role in the pathogenesis of antigen-induced eosinophilic inflammation. Using mice that over-express eotaxin in combination with other eosinophil activating cytokines, the consequences of chronic eotaxin over-production will be examined. We will also test the hypothesis that recruited tissue eosinophils express unique gene products, some of which contribute to the inflammatory process and others which may provide markers for tissue eosinophils. The proposed studies will provide a scientific basis for the design of agents that target eotaxin. They will also identify gene products specifically expressed in eosinophils that have been recruited into the inflamed lung. These gene products will provide future targets for therapeutic intervention and add novel insight into the poorly understood function of eosinophils. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MECHANISMS OF HYPERREACTIVITY IN ATOPIC HOSTS Principal Investigator & Institution: Fryer, Allison D.; Professor; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002

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23

Summary: Under normal circumstances, the release of acetylcholine from airway parasympathetic nerves is limited by inhibitory M2 muscarinic receptors. The negative feedback normally provided by these receptors is decreased or lost in some humans with asthma and in animal models of asthma, leading to hyper-responsiveness. In antigen challenged guinea pigs, we have demonstrated that eosinophils causes M2 receptor dysfunction by releasing major basic protein, which is an allosteric antagonist at the M2 receptor. Hyper-responsiveness can be blocked by an antibody to major basic protein, and can be acutely characterized by airway eosinophilia. Hyper-responsiveness 2 and 3 days after ozone exposure is not blocked by eosinophil depletion, or reversed by heparin, unless the animals are previously sensitized to an antigen. It has recently been demonstrated that the inflammatory response of the lungs may vary depending on the atopic status of the host. It is our hypothesis that the inflammatory response of the lungs to injury, and the mechanisms by which the inflammation causes airway hyperresponsiveness and dysfunction of inhibitory M2 muscarinic receptors, depends upon whether the host is atopic. We postulate that in an animal model of atopy (sensitization to ovalbumin by intraperitoneal injection without inhalational challenge), subsequent ozone exposure will cause an influx of eosinophils. This will be accompanied by M2 receptor dysfunction and by hyper- responsiveness lasting a minimum of 3 days with characteristics more similar to those seen after antigen challenge (i.e., will be blocked by depletion of eosinophils, and will be reversed by heparin). In this grant we will also examine whether development of hyperresponsiveness to ozone in humans is dependent upon atopic status. These data will identify the mechanism behind the different responses of humans to ozone and possibly other air pollutants, thus allowing for better prediction of which individuals are at risk and the development of interventions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MECHANISMS OF PROGRAMED CELL DEATH IN EOSINOPHILS Principal Investigator & Institution: Zangrilli, James G.; Assistant Professor; Medicine; Thomas Jefferson University Office of Research Administration Philadelphia, Pa 191075587 Timing: Fiscal Year 2002; Project Start 01-JUL-1998; Project End 30-JUN-2004 Summary: (Adapted from applicants' abstract) Airway eosinophilia is a prominent feature of the inflammation in asthma, and current evidence suggests that these cells contribute significantly to asthma pathogenesis. The focus of the PI's research experience to date has been the study of the cellular and humoral events which take place in the asthmatic airway during IgE-mediated inflammation, using the model of segmental antigen challenge in humans. The motivation for writing this application is based upon several in vivo and in vitro observations derived from these studies, namely the presence of prolonged airway eosinophilia in late phase asthmatics, and the differential viability characteristics between airway and circulating eosinophils in culture. This suggests that apoptotic pathways are suppressed/ impaired during eosinophilic inflammation. The mechanisms by which the life span of an eosinophil is regulated at the site of allergic inflammation are unclear at present. They must include factors that promote cell survival initially, and factors that trigger the programmed cell death pathway, ultimately. Eosinophils spontaneously undergo apoptosis when removed from the circulation, but will respond to specific cytokines, such as IL-5, with a marked prolongation in viability. In contrast, programmed cell death in eosinophils is accelerated by treatment with glucocorticoids, or cross linking of surface Fas-antigen which these cells have recently been found to express. The molecular mechanisms

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Eosinophilia

underlying Fas- and glucocorticoid-mediated killing of eosinophils, and the extent to which they are active in vivo, are unknown. Significantly, killing by glucocorticoids, but not by Fas engagement, is antagonized by IL-5 suggesting that these agents act at different levels of the cell death pathway. Certain proteins have emerged as critical regulators of apoptosis and include the pro-apoptotic Ced-3-related cysteine proteases (caspases), and anti-apoptotic factors such as Bcl-2. The applicants hypothesize that substances which accelerate eosinophil apoptosis (i.e. glucocorticoids or Fas activation), act by altering the balance or the activity of these apoptotic regulators, particularly the cysteine proteases and associated molecules. They further hypothesize that because eosinophils are exquisitely sensitive to Fas-mediated killing, this must represent a physiologic mechanism by which eosinophilia is controlled during IgE-mediated inflammation in vivo. (End of Abstract) Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOLECULAR BIOLOGY AND FUNCTIONS OF EOSINOPHIL PROTEINS Principal Investigator & Institution: Ackerman, Steven J.; Professor; Biochem and Molecular Biology; University of Illinois at Chicago 1737 West Polk Street Chicago, Il 60612 Timing: Fiscal Year 2002; Project Start 01-JUL-1987; Project End 30-APR-2006 Summary: (Applicant's Abstract):This grant has focused on the molecular biology and functions of the eosinophil's granule-associated cationic and other proteins to elucidate key structure-function relationships for their potent inflammatory actions in allergic responses, host-parasite interactions, tissue damage and fibrosis. This renewal focuses on the Charcot-Leyden crystal (CLC) protein, which forms the distinctive bipyramidal crystals which are hallmarks of eosinophil (or basophil) participation in allergic and related inflammatory reactions. CLC protein was originally identified as eosinophil lysophospholipase (LPLase), but we have now shown it to be a member of the galectin superfamily of animal lectins based on amino acid sequence, 3D protein structure, lack of LPLase activity and gene structure. The physiologic/effector role this highly abundant eosinophil constituent is therefore unresolved. Quantitative considerations alone (CLC is 10 percent of eosinophil protein), but also its secretion by activated eosinophils, elevated blood levels in patients with eosinophilia, and increased levels in sputum and BAL of asthmatics, all argue for an important role in eosinophil function. Our cloning of the CLC cDNA and analyses of CLC amino acid sequence identified similarities to b-galactoside-binding animal galectins, but not to any LPLases or other lipolytic enzymes. Our X-ray crystal structure showed CLC protein to be nearly identical to human galectins-1, -2, -3 and -7, and to possess a carbohydrate recognition domain capable of binding mannose, but not standard b-galactoside sugars. We demonstrated that CLC protein is not eosinophil LPLase, which is likely identical to human pancreatic LPLase. The goal of this renewal is to investigate the mechanisms by which eosinophils, through their considerable LPLase activity or the lectin activities of CLC protein, function in allergic pulmonary inflammation. Three questions are addressed with regard to the structure and functions of CLC protein and eosinophil LPLase in terms of their pathophysiologic roles in acute and chronic allergic airways inflammation: (1) What is the biologically relevant glycoconjugate ligand for CLC protein and what does it tell us about CLC's role in eosinophil (or basophil) biology and function. We will identify the physiologically relevant ligand(s) for CLC protein; (2) What are the structure-function relationships for CLC protein's carbohydrate-binding "galectin-like" activities and ligand specificity? Site-specific mutagenesis will be used to

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25

characterize CLC protein's carbohydrate recognition domain and its mechanism of binding for the glycoconjugate ligands we define; (3) What is the role of eosinophil LPLase in allergic pulmonary inflammation involving eosinophils, and in asthma pathophysiology? We will determine whether eosinophil LPLase alters pulmonary surfactant function, resulting in decreased patency of distal airways in asthma, or modulates allergic pulmonary inflammation. We will analyze the effects of eosinophil LPLase on pulmonary surfactant function in vitro, and in vivo by determining the relationships between eosinophil recruitment and secretion of LPLase in the lung and its localization in distal airways in human asthma and murine allergic asthma models. We will analyze the effects of targeting overexpression of LPLase in the lung using transgenic approaches, and determine the effects of knocking out the eosinophil LPLase gene in murine models of eosinophilic airways inflammation. The proposed work should elucidate unique aspects of the structural biology and functions of CLC protein in eosinophils (and basophils), and the pathophysiologic actions of eosinophil LPLase in disease processes associated with eosinophilic inflammation in the lung and other tissues. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOLECULAR MECHANISMS OF CD30+ LYMPHOMA GROWTH Principal Investigator & Institution: Podack, Eckhard R.; Professor and Chairman; Microbiology and Immunology; University of Miami-Medical Box 248293 Coral Gables, Fl 33124 Timing: Fiscal Year 2002; Project Start 01-FEB-1999; Project End 31-DEC-2002 Summary: CD30 has long been recognized as a unique antigen on lymphomas of T or B origin of immature to the fully differentiated state. CD30 moreover has been found to be associated with disease progression in anaplastic large cell lymphoma. CD30 is expressed as a disease marker in allergic conditions and CD30 expression is associated with progression of HIV disease, with Epstein-Bar virus infection and transformation and with HTLV associated lymphomas. Finally, CD30 over-expression is found in Omenn's syndrome, a severe combined immunodeficiency of unknown etiology, characterized by high Il-5 levels, eosinophilia and IgE production. CD30 signaling functions via TRAF proteins have recently been elucidated. Similar to other members of the TNF-R family of receptors, CD30 signals have a dual role for activation, proliferation and anti-apoptosis; or for apoptosis. CD30 expression itself is favored by a TH2 environment and suppressed by Ifn-gamma. It is postulated and will be tested in this application that CD30 expressed on lymphomas provides a selective advantage to lymphomas or other CD30 positive cells through its co- stimulatory activity, by promoting proliferation and increasing resistance to apoptosis. This hypothesis will be examined 1. by analyzing pathways regulating TRAF2 activity which is primarily responsible for anti apoptotic signals through Jun-N-terminal kinase (JNK) and NFkappaB activation; 2. by CD30-L gene ablation to eliminate CD30-L triggered CD30 signals and signaling by CD30 induction on ongoing immune responses to tumors in vivo and in vitro. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MOUSE DYSFUNCTION

MODELS

OF

EOSINOPHIL-ASSOCIATED

LUNG

Principal Investigator & Institution: Lee, Nancy A.; Assistant Professor; Mayo Clinic Coll of Med, Mayo Clinic Az Sc Johnson Research Medical Building Scottsdale, Az 85259

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Eosinophilia

Timing: Fiscal Year 2003; Project Start 01-APR-1998; Project End 30-NOV-2006 Summary: (provided by applicant): The focus of this ongoing study is to define the relationship between pulmonary IL-5 expression, CD4+ T cell activities, and eosinophil effector functions. Our preliminary studies using transgenic mice demonstrated that IL5 and/or eosinophils have previously unrecognized activities which effect CD4+ T cell proliferation, activation, and/or Th2 differentiation. In this renewal, we propose to exploit these observations to test the hypothesis that IL-5 expression and/or eosinophil accumulation in the lung lead to T cell proliferation and activation. The activation of these lung T cells, in turn, elicits/regulates eosinophil effector functions that contribute to allergic pulmonary pathology. In the short term, the proposal seeks to accomplish three specific aims: (i) To define IL-5 and/or eosinophil mediated effects on CD4+ T cells and in particular, to determine the basis of the T cell proliferation in the lungs of IL5 transgenic mice. Moreover, to ask: are these T cells activated and is this proliferation/activation a direct consequence of IL-5 or an indirect result of IL-5 mediated eosinophil accumulation in the lung?; (ii) To determine whether T cellmediated activation of eosinophils is an underlying mechanism contributing to allergic respiratory inflammation. Our successful use of eosinophil adoptive transfer will be exploited to determine specific eosinophil-T cell signaling pathways leading to pulmonary pathology; (iii) To determine if a causative relationship exists between eosinophil recruitment and the development of airway pathologies. Specifically, using an eosinophil ablation strategy that we have developed, we will determine whether the pulmonary pathologies occurring in IL-5 transgenic mice, or the pathologies arising in ovalbumin sensitized/aerosol challenged wild type and gene knockout mice deficient of specific immune pathways are dependent on eosinophils. The transgenic and gone knockout approaches described in this proposal will help achieve these goals. Our longterm objective is to determine the causes of asthma and its associated morbidity that more effective strategies for diagnosis, prevention, and therapy might be developed. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MURINE CYTOMEGALOVIRUS MODULATES ALLERGIC AIRWAY DISEASE Principal Investigator & Institution: Wu, Carol A.; Assistant Professor; Medicine; University of Connecticut Sch of Med/Dnt Bb20, Mc 2806 Farmington, Ct 060302806 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 30-JUN-2006 Summary: (provided by applicant): Asthma is the most common chronic illness in developed countries. Despite advances in our understanding of its pathogenesis and therapy, the morbidity and mortality associated with asthma are increasing both in the United States and worldwide. Upper respiratory viral infections are a major cause of asthma exacerbations, accounting for 80 to 85 percent of asthma attacks in children and 40 percent in adults. While rhinovirus and respiratory syncytial virus are the most common precipitants, any virus capable of promoting an acute respiratory infection has the potential to exacerbate asthma. The mechanisms by which viruses induce the onset of asthma or increase its severity are poorly understood, vary among viruses, and are likely to involve multiple pathways. These include pathophysiologic changes in the respiratory epithelium and alterations in airway inflammation through the activation/recruitment of T lymphocytes with the subsequent release of proinflammatory cell mediators. In an OVA-induced murine model of allergic airway disease, we have observed an increase in lung eosinophils, Th2 cytokines, and mucus production, along with elevated serum IgE levels and hyperreactivity to methacholine challenge. Concomitant infection with murine cytomegalovirus (MCMV) an

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opportunistic respiratory pathogen, resulted in a decrease in lung eosinophils, altered lung Th1/Th2 cytokine expression, and enhanced mucus production in this model. Thus, concomitant infection with MCMV resulted in two distinct outcomes, attenuation of airway eosinophilia and enhanced mucus production, and both events appear to be influenced by the local cytokine environment. We hypothesize that the decrease in airway eosinophilia observed in MCMV/challenged mice is due to a shift in the balance of Th1/Th2 cytokines in the lung, resulting from induction of IL-12 and lL-18 by MCMV infected/activated alveolar macrophages. Furthermore, we hypothesize that enhanced mucus production is the result of the recruitment/proliferation of TCRgd cells, in response to MCMV infected respiratory epithelium, with the subsequent release of IL-l0. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NMR INTERLEUKIN 5

STUDIES

OF

ISOTOPICALLY

ENRICHED

HUMAN

Principal Investigator & Institution: Guiles, Ronald D.; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2002; Project Start 01-MAR-2002; Project End 28-FEB-2003 Summary: We have initiated a study directed at obtaining the solution structure of human interleukin-5. Interleukin-5 is a homodimeric protein with a molecular weight of 25 kDaltons. It is unique among the cytokines involved in hematopoesis in that it is essential in eosinsophil differentiation. It is induced upon presentation of foreign bodies or parasites. As such it has become a key target for drug design efforts in the alleviation of asthma, a condition which is often associated with eosinophilia and the inflammatory response. Although a crystal structure is known, we believe determining a complete set of assignments and a solution structure will facilitate the study of small molecule interactions with the protein in regions that site-directed mutagenesis experiments indicate are essential in receptor interaction. Our efforts initially focused on obtaining a high yield expression system for the protein using a synthetic gene approach utilizing optimized codon usage and a high yield expression vector. Using this system we have obtained sufficient quantities of doubly labeled interleukin-5 to begin triple resonance assignment and structure elucidation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: RESPONSE

PARASITIC

INFECTION

ALTERS

QUALITY

OF

IMMUNE

Principal Investigator & Institution: Boyer, Jean D.; Assistant Professor; Pathology and Lab Medicine; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 15-SEP-2002; Project End 31-AUG-2004 Summary: (provided by applicant): The AIDS epidemic in the Developing World represents a major global crisis. More than 95% of all HIV-infected people now live in the Developing World, and 95% percent of all HIV-1 related deaths have occurred among its people. Most who have died were in the prime of life, robbing their societies of their most productive workers severely taxing their infrastructures, and creating a large population of AIDS orphans. In these countries, chronic parasitic infection adds another level of complexity to AIDS vaccine development. Helminthic and protozoan infections are common in developing countries. The most conservative numbers suggest that approximately 1.5 billion people carry a parasitic burden. These persons exist in a constant state of immune activation that is characterized by a dominant Th2 type of cytokine profile, high IgE levels, and eosinophilia. Such an immune profile may have

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an adverse impact on the efficacy of vaccines in particular an HIV-1 vaccine. The impact of parasitic infection on vaccine effectiveness must be addressed to ensure that putative vaccines have the highest possible chance for field success. Currently there have been only a few studies of the effects of chronic parasitic infection on putative HIV-1 vaccines. The goal of my proposed project will be to study the impact of chronic parasitic infection and the resulting Th2 immune profile on an HIV-1 vaccine induced immune response. The model we will use is Leishmania major infection in Balb/c mice (there are several other excellent systems, including Schistosoma manosi, that may be used in subsequent studies). L. major infection in Balb/c mice leads to a Th2 immune profile mimicking what might be seen in the clinic in HIV-1 infected individuals. Following the establishment of chronic parasitic infection the mice will be immunized with a DNA HIV-1 vaccine (that has been reported to control viral replication and protect primates from CD4 loss). The level and quality of CD8 and CD4 responses against HIV-1 antigens will be assessed. Further, we will expand our studies to look at the effects of putative Th1 type cytokines in this model through co-administration of the HIV-1 vaccine and cytokine expressing plasmids. This proposal represents the initiation of a new and important area of research. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PATHOGENESIS & THERAPY OF 8P11 LEUKEMIA/LYMPHOMA Principal Investigator & Institution: Van Etten, Richard A.; Director, Hematologic Malignancies; New England Medical Center Hospitals 750 Washington St Boston, Ma 021111533 Timing: Fiscal Year 2004; Project Start 01-APR-2004; Project End 31-MAR-2009 Summary: (provided by applicant): 8p11 stem cell leukemia/lymphoma syndrome, also known as 8p11 myeloproliferative syndrome (EMS), is a novel hematological malignancy characterized by chronic myeloproliferative disease, eosiniphilia, and nonHodgkin's lymphoma. Current therapy for this disease is inadequate. The malignant cells from EMS patients have acquired chromosomal translocations involving the fibroblast growth factor receptor-1 (FGFR1) gene on 8p11 and express fusions of different N-terminal partner proteins with the tyrosine kinase domain of FGFR1. However, whether FGFR1 fusion proteins play a role in 8p11 syndrome and the molecular mechanisms underlying the pathogenesis of this disease are unknown. Recently, it has been demonstrated that different FGFR1 fusion proteins induce distinct leukemia/lymphoma syndromes in a mouse retroviral bone marrow transduction/transplantation model. These results implicate FGFR1 fusion tyrosine kinases as the direct cause of these malignancies and provide an accurate and quantitative animal model. In this application, this model system will be utilized to define the molecular pathogenesis of 8p11 leukemia/lymphoma syndrome and test targeted therapies for this disease. The first Aim will define the critical signaling pathways and the molecular mechanisms of induction of EMS-like disease in mice by the ZNF198-FGFR1 fusion tyrosine kinase, product of the (8;13) translocation in human 8pl 1 syndrome. This will be accomplished through biochemical analyses in Ba/F3 cells and primary leukemia cells from mice, studies with ZNF198-FGFR1 mutants, and use of mice with targeted mutations in signaling molecules. In the second Aim, the hematologic malignancies induced in mice by other FGFR1 fusions found in 8p11 syndrome, including FOP-FGFR1 and CEP110-FGFR1, will be characterized. The goal of the third Aim is preclinical testing of molecularly targeted therapeutic agents for 8p11 syndrome, comparing the antileukemic activity of several different FGFR1 kinase inhibitors in the mouse model of ZNF198-FGFR1- induced leukemia/lymphoma, and

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testing combinations of kinase inhibitors with drugs targeting essential downstream pathways identified in Aim 1. Collectively, these studies will yield important new knowledge about the pathogenesis and treatment of 8p11 syndrome that will also be valuable in extending targeted therapies to other hematologic malignancies and to solid tumors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: STATES.'

PEROXIDASE-BASED

TOXICITY

IN

HYPEREOSINOPHILIC

Principal Investigator & Institution: Slungaard, Arne; Medicine; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2002; Project Start 01-JUN-2002; Project End 31-MAY-2007 Summary: (provided by applicant): Eosinophi1 (EO) phagocytes destroy parasites but can also damage host tissue. Although allergies are the most common example of EOmediated pathology, the hypereosinophilic Syndrome (HES) is the most striking. HES is a systemic hematologic disorder characterized by multi-organ system involvement, preeminently a characteristic, usually lethal form of heart disease. Eosinophilic heart disease (EHD occurs in a variety of hypereosinophilic states, irrespective of their cause. Endocardial and myocardial deposition of EO specific granule proteins, of which eosinophil peroxidase (EPO) is the most abundant, is proposed to mediate cardiotoxicity in EHD. Despite the abundance of EPO and the vigor of the EO respiratory burst, little is known about the contribution of EPO-mediated oxidative damage to the pathology of eosinophilic inflammatory states. We find that three unusual substrates - bromide (Br-), nitrite (NO2-), and thiocyanate (SCN-) - compete for oxidation by EPO in physiologic fluids in the presence of H202, yielding, respectively, HOBr, NO2., and HOSCN. The relative toxicity of these oxidants for human cells is HOBr> NO2 >> HOSCN; yet EPO preferentially oxidizes SCN > NO2 - > Br-. We hypothesize that SCN "buffers" against generation by EPO of the more cytotoxic N02- and Br- based oxidants and consequently serum SCN- levels, which are dietarily determined, may modulate EPO toxicity. The overall goal of our proposed work is to examine the hypothesis that that EPO-generated oxidants impose damage in a substrate-determined manner to mammalian cells and tissue that contributes to the pathogenesis of EHD, which we propose as a paradigm for any organ damage occurring in eosinophil inflammatory states. The first specific aim is to test the hypothesis that whereas HOBr and N02 cause necrotic cell death by reacting with membrane components to destroy membrane integrity, HOSCN imposes sulfhydryl-targeted intracellular oxidative stress that can influence tissue factor gene expression and induce apoptosis. The second specific Aim is to test the hypothesis that an interleukin-5 (IL.5) transgenic mouse line will develop progressive functional, anatomic, and histologic manifestations of EHD with a parallel accumulation of EPOspecific protein oxidative damage as assessed by newly developed sensitive, substratespecific amino acid "biomarkers." The third specific aim is to test the hypothesis that EPO contributes to the pathogenesis of EHD in the IL.5 transgenic mouse line. We will compare EHD severity, longevity, and EPO biomarker levels in the IL-5 transgenic line with that of an IL-S transgenics crossbred with an EPO 'knockout" line. The fourth specific aim is test the hypothesis that increasing serum SCN- inhibits, and decreasing SCN- promotes, EPO-mediated protein oxidant damage and the severity of EHD in IL-5 transgenic mice. These studies, if successful, will establish a murine model for HES and EHD, prove a mole for EPO-mediated oxidant damage in the pathogenesis of EHD, and suggest a simple strategy fur its treatment, (i.e., dietary supplementation with

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inexpensive SCN-), that could be applied even in impoverished communities as well as against more common allergic diseases, such as asthma. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PILOT--BACTERIOCIDAL PERMEABILITY: INCREASING PROTEIN Principal Investigator & Institution: Furuta, Glenn T.; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2004 Summary: Tissues lined by squamous epithelial cells are regularly exposed to a large number of infectious and non-infectious insults. As a result, the protective epithelium has evolved a series of innate defense mechanisms to maintain an equilibrium between normal tissue function and unwarranted tissue destruction. An exquisite example is the esophagus. The esophageal mucosa utilizes a number of protective mechanisms including peristalsis, mucous secretion, and bicarbonate exchange to minimize the influence of potential injurious agents. In addition, the healthy squamous epithelium contains a number of immunocytes including mast cells, lymphocytes and dendritic cells. Conversely, esophageal diseases also lead to significant morbidity including gastroesophageal reflux disease (GERD) and esophageal cancer, with a disease frequency of nearly 25 million U.S. citizens per year. A common marker for esophageal inflammation is the accumulation of eosinophils. Our recent studies have examined the influenced of eosinophil derived granule protein major basic protein (MBP) can significantly influence epithelial structure and function. It is not known whether eosinophils represent a "friend" or "foe" in esophageal inflammation. To begin to address this issue, we utilized gene chip analysis and determined that MBP markedly induced the synthesis of an innate molecule of defense, bactericidal permeabilityincreasing protein (BPI), a potent anti-infective molecule with microbial killing and endotoxin-neutralizing functions, with previous expression attributed only to leukocytes. Ongoing and endotoxin-neutralizing functions, with previous expression attributed only to leukocytes. Ongoing studies have: a) revealed that squamous epithelial express BPI, b) identified the BPI gene promoter and it's expression in squamous epithelia, and c) identified a murine homolog of BPI expressed in mucosal epithelia. From these preliminary data, we hypothesize that squamous epithelial BPI is central to esophageal responses to eosinophilic disease. Two specific aims are directed at testing this hypothesis. Specific Aim 1: Define molecular mechanisms of BPI expression in squamous epithelia. Preliminary data indicate that epithelial BPI is functionally relevant in bacterial killing and in control of endotoxin responses in epithelia. At present, essentially nothing is known about the factor(s) which regulate BPI expression. Ongoing studies have identified and characterized the BPI gene promoter, and here we propose to gain insight into how squamous epithelial BPI expression is regulated at the molecular level. Specifically, we will elucidate molecular determinants of BPI promoter constructs. Specific Aim 2: Characterize squamous epithelial expression of the BPI homolog in healthy and eosinophilic diseased murine tissue. Until recently, it was believed that mice did not express BPI. New data from the Mouse Genome Project identified a BPI homolog on chromosome 1, and our ongoing work has revealed that mouse epithelia express BPI. In these studies, we will extend these preliminary findings to profile squamous epithelial BPI expression in the esophagus, define expression of BPI in murine esophagitis animals, and examine BPI expression in human patient esophageal tissue. The long-term goal of this research is to elucidate the role of epithelial BPI in health and disease. A better understanding of these principles provide the

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potential for therapies aimed at ameliorating symptoms associated with mucosal infection and inflammation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PULSE THERAPY TRIAL IN BETA INTERFERON RESISTANT ACTIVE Principal Investigator & Institution: Smith, Derek R.; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2002; Project Start 05-JUL-1999; Project End 30-JUN-2003 Summary: This will be a trial to test the clinical and radiographic efficacy of monthly pulse infusion therapy in beta-interferon-resistant active MS patients. While betainterferon medications have been shown to reduce disease activity in relapsing remitting MS patients, many patients continue to have active disease despite being on these medications. There is evidence that treatment of these patients with pulse methylprednisolone, pulse mitoxantrone or pulse cyclophosphamide may effectively reduce disease activity in these patients and potentially allow them to be stable maintained on beta-interferon therapy thereafter. This study is designed to randomize beta-interferon non-responsive patients for six months of treatment to either monthly intravenous pulse cyclophosphamide plus methylprednisolone or monthly intravenous pulse mitoxantrone plus methylprednisolone or monthly intravenous methylprednisolone alone. Patients will be maintained on beta-interferon and followed over 24 months. 20 patients will be enrolled per arm. MRI number of gadolinium enhancing lesions and T2 lesion volume will be the principal outcome measures while clinical scores and immunologic studies will be secondary outcome measures. Measurement of adverse events will also be an important component. Thus far the applicant's research has focused on immunologic studies in MS with the goal of understanding the mechanism of action of drugs used to treat the disease. We have found that the treatment of MS patients with some of these agents results in a number of changes, notably increases of IL-4 secretion associated with eosinophilia and decreases in IL-12. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: REGULATION OF EOSINOPHIL SURVIVAL Principal Investigator & Institution: Sperling, Anne I.; Assistant Professor; Medicine; University of Chicago 5801 S Ellis Ave Chicago, Il 60637 Timing: Fiscal Year 2002; Project Start 15-MAR-2000; Project End 28-FEB-2005 Summary: Asthma is a serious disease that can have debilitating and sometimes fatal effects on its sufferers. One of the hallmarks of the lung inflammation that occurs in asthma is the marked increase of eosinophils in the tissue as well as the airways. Since eosinophils are one of the major cell types involved in the pathology of asthma, the clearance of airway eosinophilia is an important step in the resolution of airway inflammation. Preliminary results have found that Fas (CD95), a cell surface receptor that when ligated can induce cell death via apoptosis, is an important mechanism of airway eosinophilia resolution. Although Fas and its ligand FasL were first defined as receptors on T lymphocytes, recently have bout been found to be expressed by various cells in the body. In the lungs, the Fas receptor has been found expressed on airway epithelium, smooth muscle, and inflammatory cells such as T cells, eosinophils, and neutrophils, while FasL expression is limited to T cells, monocytes, and airway epithelium. When murine BAL cells from mice with experimentally induce airway

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inflammation are cultured the eosinophils die rapidly via a Fas-dependent mechanism. This cell death can be countered, in part, by the addition of exogenous cytokines such as IL-5. In addition, in a murine model of allergic airway inflammation, we have recently found that mice that are deficient for the Fas receptor fail to resolve airway eosinophilia as fast as wild type controls. These data suggest that our results in vitro reflect in vivo mechanisms of airway inflammation resolution. Thus, the survival of eosinophils may be regulated by a balance between soluble factors that enhance survival and cell:cell interactions that lead to Fas- mediated cell death. The central hypothesis of this proposal is that T cells, which are major producers of these cytokines and express FasL upon activation, play a key role in the regulation of eosinophil survival. Therefore, the overall goal of this proposal will be to dissect the role of T cells in the regulation of airway eosinophilia through both in vitro and in vivo experimental systems. To address these goals the following studies are proposed. (1) It will be determined whether Fasmediated cell death is a major mechanism involved in the resolution of airway inflammation. (2) The role of T cells the Fas-induced apoptosis in vitro and in vivo will be determined. (3) The role of different T cell subsets and T cell cytokines the survival of death of eosinophils will be determined. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: REGULATION OF INTERLEUKIN-5 RECEPTOR SIGNALING Principal Investigator & Institution: Martinez-Moczygemba, Margarita; Medicine; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2004 Summary: (provided by applicant): Dr. Martinez-Moczygemba is a postdoctoral fellow whose research interest is to identify the molecular events mediating interleukin-5 (IL5)-induced signal termination. Understanding these mechanisms should provide novel targets for the modulation of IL-5-mediated inflammatory responses such as allergic inflammation and asthma. The Research Scholar Development Award (K22) will aid Dr. Martinez-Moczygemba to accomplish her research goals as well as to attain a tenuretrack assistant professor appointment. IL-5 specifically promotes the differentiation and survival of eosinophils and is critical to the pathobiology of eosinophilic inflammation in allergic disorders and asthma. IL-5 initiates its cellular effects by binding to a heterodimeric IL-5 receptor leading to the activation of the JAK!STAT, Ras/MAPK, and the PI3 kinase signaling pathways. The goal of this proposal is to delineate the molecular events that initiate, mediate, and modulate termination of IL-5 signal transduction. Aim I. Elucidate the molecular events that initiate proteasome termination of IL-5-induced signal transduction. We will determine if tyrosine or serine phosphorylation of betac is required for its proteasomal degradation by using specific inhibitors of these kinases, as well as making site-directed mutants of these beta-c phosphorylation sites. We will also determine if beta-c ubiquitination is necessary for its proteasomal degradation. Aim 2. Investigate the molecular mechanisms that mediate endocytosis and lysosomal degradation of the full length and truncated IL-5R following IL-5 stimulation. Potential endocytic consensus sequences in the cytoplasmic domains of beta-c and IL-5R-alpha will be evaluated for their role in ligand-induced endocytosis of the full-length receptors by targeted deletions and by site-directed mutagenesis. Aim 3. Determine if other shared cytokine signaling receptor chains are proteasomallyregulated. Other shared signaling receptor chains such as gamma- c / IL-4R-alpha will be analyzed for their susceptibility to degradation by proteasomes following ligand stimulation. Aim 4. Demonstrate the physiologic consequence of cytokine-induced heterotypic desensitization of beta-c receptors in vivo. GM-CSF and IL-3 over-

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expressing transgenic mice will be evaluated for their ability to develop eosinophilia following treatment with high doses of IL-5. In addition, eosinophils from IL-5 transgenic mice will be isolated and analyzed for their ability to be further stimulated by GM-CSF or IL-3 in vitro. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ROLE OF TH2 CELLS IN EOTAXIN REGULATION Principal Investigator & Institution: Mathew, Anuja; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2002; Project Start 01-MAY-2002 Summary: Asthma is a disease of airway inflammation in which airway eosinophilia is a prominent histologic feature. Eosinophils can release toxic mediators, lipids and proinflammatory cytokines that can induce airway hyper- responsiveness. Identifying the mechanisms that are involved in recruiting eosinophils to the site of injury are therefore critical in the understanding of pathogenesis of disease. Chemokines are a family of secreted proteins that play a critical role in directing different types of leukocytes to the site of infection of tissue damage. The aim of this proposal is to examine the role of Th2 cells in regulating the expression of eotaxin, a chemokine specific for eosinophils. We hope to identify and characterize molecules or factors released from Th2 cells that are responsible for affecting the expression of eotaxin at the mRNA and protein levels. We then hope to identify transcription factors that are important in promoting gene expression of eotaxin. The importance of these molecules will be examined in vivo using existing knockout animals. This work will lead to the greater understanding of the role of Th2 cells and eotaxin asthma. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: RSV AND ASTHMA Principal Investigator & Institution: Broide, David H.; Associate Professor of Medicine; Medicine; University of California San Diego La Jolla, Ca 920930934 Timing: Fiscal Year 2002; Project Start 01-MAR-1999; Project End 29-FEB-2004 Summary: Viral infections such as RSV are an important precipitant of childhood asthma. The overall objective of this grant proposal is therefore to understand the mechanism by which Respiratory Syncytial Virus (RSV) induces eosinophilic airway inflammation in atopic mice and to subsequently test the hypothesis that DNA immunization can inhibit RSV induced airway inflammation. In the first series of experiments we will demonstrate that viral infections such as RSV which are a frequent precipitant of childhood asthma induce eosinophilic inflammation in atopic mice by inducing the expression of IL-5 by CD8 + T cells and C chemokines by airway epithelium. The importance of the expression of these CC chemokines to eosinophil recruitment will be assessed in vivo in a mouse model of RSV infection of atopic mice pretreated with Ab to CC chemokines. To explore the possibility that a deficiency in functional CpG sequences in RSV promotes Th2 responses, we will infect mice with either RSV (? CpG suppressed), RSV and CpG, or Adenovirus (not CpG suppressed) to assess Th1 versus Th2 responses, eosinophilic airway inflammation and bronchial hyperreactivity. Additional experiments will determine which DNA based vaccine strategy (ISS alone, DNA-RSV-F alone, or the sequential combination) is the most effective in inhibiting eosinophilic inflammation, airway hyperreactivity and viral load in atopic mice challenged with RSV. To explore the mechanism of action of ISS in vivo, we will either use neutralizing Abs to individual cytokines (IL-12 and IFNs derived

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from NK cell and monocyte/macrophages) or neutralizing Ab to deplete NK cells to define the relative importance of either individual cytokines or NK cells to the mechanism of action of ISS in vivo. Overall these studies will contribute to our understanding of the mechanism of eosinophilic inflammation during RSV infection and suggest candidate vaccine strategies to inhibit RSV infection and airway inflammation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: RSV INDUCED PATTERN OF CYTOKINE EXPRESSION AND DISEASE Principal Investigator & Institution: Tang, Yi-Wei; Associate Professor of Medicine & Pathol; Medicine; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2002; Project Start 01-FEB-1994; Project End 29-FEB-2004 Summary: Respiratory Syncytial Virus (RSV) is the most important cause of severe lower respiratory tract disease in infants, rivaling influenza as a cause of excess mortality and morbidity in the elderly, and causing epidemics in bone marrow transplant units with fatality in the majority of cases. Adequate therapy and vaccines are not available, in part because of the unique immunologic features of RSV-induced disease. Formalin-inactivated whole virus vaccine (FI-RSV) did not protect against Infection and was associated with enhanced disease. Data from murine models and evidence from human studies suggest that selective induction of CD4+ T lymphocytes with a Type 2 cytokine expression pattern (dominant IL-4 production) by the FI-RSV vaccine is the basis for vaccine-enhanced illness. Severe RSV bronchiolitis in infants is also associated with Type 2 immune responses. The primary objective of this proposal is to define the mechanisms by which RSV promotes immune responses associated with Type 2 pattern of cytokine production. The specific alms are to: 1) Define the mechanisms by which the RSV G glycoprotein promotes eosinophilia, Th2-like immune responses, and enhanced illness, and 2) Define the mechanisms by which IL-4 delays virus clearance, inhibits CD8+ CTL induction, and promotes enhanced RSV-induced illness. The unique antigenic properties of RSV G will be studied using recombinant vaccinia viruses that express membrane-anchored G, secreted G, or produce both in equal amounts. We will define the role of G structure and antigen processing events on the IL-4 independent induction of IL-5 and eosinophils recently discovered in our laboratory. The mechanism of IL-4 inhibition of CD8+ CTL induction will be defined using recombinant vaccinia viruses constructed in our laboratory that co-express the RSV M2 protein and individual cytokines. The proposed studies will define viral and host factors responsible for patterns of immune response and disease expression after RSV infection. They will improve our basic understanding of how viruses cause disease, and how vaccine-induced immune responses are regulated, will have direct impact on new strategies for development of preventive vaccines and immunotherapeutics for RSV. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: STRUCTURAL BASIS OF CD28 REGULATION OF LUNG INFLAMMATION Principal Investigator & Institution: Green, Jonathan M.; Associate Professor; Internal Medicine; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2002; Project Start 15-FEB-2000; Project End 31-JAN-2004 Summary: (Adapted from the Applicant's Abstract): T lymphocytes are a major component of the inflammatory response and aberrant regulation of T cell activation

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and differentiation may be central to the pathogenesis of asthma. The CD28 costimulatory receptor is a critical regulator of T cell activation and differentiation, and thus may be an important target for therapy of immune mediated diseases. Manipulation of this receptor has been shown to alter the course of several animal models of disease, inducing models of antigen-induced airway inflammation. Accordingly, the primary goal of this proposal is to increase our understanding of the cellular and molecular basis by which CD28 modulates the T cell response to antigen. CD28 regulates multiple aspects of T cell functions, including proliferation, adhesion, T helper cell phenotype development and cell survival. The PI demonstrates that CD28 is essential for the development of antigen-induced inflammation in a murine model of airway disease. Sensitized CD28-deficient mice fail to develop airway inflammation or eosinophilia in response to antigen challenge. Examination of T helper cell phenotype in CD28 -/- mice demonstrates a defect in Th2 cytokine gene expression. The mechanism by which CD28 regulates these diverse aspects of T cell function is poorly understood, but likely involves multiple signaling pathways. Studies in transformed cell lines have implicated specific domains in the cytoplasmic trail of CD28 as important in signaling, but no consensus exists as to what is required for CD28 function in primary cells or in vivo responses. The data in primary T cells demonstrates a requirement for specific proline mediated interactions with the non-receptor tyrosine kinase lck in the regulation of T cell proliferation by CD28. The PI hypothesizes that multiple distinct structural domains of CD28 modulate specific features of T cell activation and differentiation. To address this, the following specific aims have been proposed: 1) determine the structural features of CD28 required for co-stimulation of primary T cells in vitro; and 2) characterize the specific cellular and molecular determinants by which CD28 regulates airway inflammation in vivo. These studies will provide critical data as to the regulation of T cell directed immune responses, and provide a rational basis for the development of new therapeutic strategies in the treatment of inflammatory lung disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: T CELL AND EOSINOPHIL RECRUITMENT IN LUNG FIBROSIS Principal Investigator & Institution: Tager, Andrew M.; Assistant in Medicine; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2002; Project Start 04-AUG-1999; Project End 31-JUL-2004 Summary: With the proposed Mentored Clinical Scientist Development Award, the applicant will build upon his prior experiences investigating the biology of inflammation in the lung. Based on very positive experiences in the laboratory to date, the applicant is firmly committed to a career in academic pulmonary and critical care medicine. The laboratory of Dr. Andrew D. Luster at the Massachusetts General Hospital will provide a rich intellectual environment to foster the candidate's scientific development toward his goal of independent investigation. The present proposal provides the applicant the opportunity to master a broad range of current laboratory techniques in molecular and cellular biology, supplemented by a program of didactic study of immunology. The research project proposed focuses on pathogenic mechanisms of pulmonary fibrosis. Pulmonary fibrotic disorders appear to be initiated by inflammation of the lower respiratory tract, which causes activation and proliferation of mesenchymal cells, and results in increased extracellular matrix deposition. Data both from patients and animal models indicate T cells and eosinophils participate in the inflammation of the lower respiratory tract, which causes activation and proliferation of mesenchymal cells, and results in increased extracellular matrix deposition. Data both

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from patients and animal models indicate T cells and eosinophils participate in the inflammation initiating at least some of these disorders. The research proposed is based on the hypotheses that the recruitment of T cells, their polarization toward the Th2 phenotype, and the consequent recruitment of eosinophils contribute to the pathogenesis of pulmonary fibrotic disorders The applicant specifically proposes to: (1) Investigate the role of the T cell chemoattractant IP-10 (interferon-induced protein of 10 kd) in T cell recruitment in BLM-induced fibrosis; (2) investigate the balance of Th1 versus Th2 responses in BLM-induced fibrosis, and the role of cytokines and costimulatory molecules in determining this balance; and (3) investigate the role of Th2 cytokines, and the eosinophil chemoattractants eotaxin and LTB4 (leukotriene B4), in eosinophil recruitment in BLM- induced fibrosis. The last area of the research proposed will include the generation of mice genetically deficient for the recently described murine LTB4 receptor. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: T CELL CONTROL OF AIRWAY MUCUS PRODUCTION Principal Investigator & Institution: Cohn, Lauren E.; Associate Professor; Internal Medicine; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2002; Project Start 01-APR-2000; Project End 31-MAR-2004 Summary: Mucus hyperproduction contributes to morbidity and mortality in patients with chronic airway diseases. In asthma, chronic bronchitis and cystic fibrosis, inflammation is believed to stimulate mucus production, despite their different characteristic airway pathologies. We have defined two inflammatory pathways that lead to mucus production, using a murine system we developed to study the inflammatory effects of Th1 and Th2 cells in the respiratory tract. Th2 cells activated in the airways of mice stimulate airway eosinophilia, airway hyperresponsiveness and mucus production; features found in asthmatic patients. We show that mucus induction by Th2 cells does not require IL-4, IL-5, eosinophils or mast cells, but depends on signaling through IL-4Ralpha, the common chain in IL-13 and IL-4 receptors. Thus, it appears that IL-13 stimulates mucus production induced by Th2 cells. We also show that mucus can be induced by a mechanism that is Th2-independent and associated with airway neutrophilia, suggesting some of the features in chronic bronchitis and cystic fibrosis. We present novel studies showing that Th1 cells, through the production of IFNgamma, inhibit mucus production induced by both Th1 and Th2 cells. Furthermore, IFNgamma produced by Th1 cells has the potential to reduce airway pathology in immunotherapy of asthma. Our goals in this proposal are to gain a more complete understanding of the cellular and molecular mechanisms that regulate mucus production. Our aims are to 1) determine the mechanism by which CD4 Th cells stimulate mucus production; 2) determine how airway epithelial mucus production is inhibited by IFNgamma 3) determine the extent of inhibitory effects of IFNgamma on mucus production. Using our established adoptive transfer system in which Th1 and Th2 cells and recipient mice can be independently genetically manipulated, the precise factors important in the control of mucus production will be determined. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: TCR CELLS PROMOTE TH2 LINEAGE COMMITMENT AND IGE PRODUC Principal Investigator & Institution: Puddington, Lynn A.; Associate Professor; Medicine; University of Connecticut Sch of Med/Dnt Bb20, Mc 2806 Farmington, Ct 060302806

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Timing: Fiscal Year 2002; Project Start 15-SEP-2000; Project End 31-JUL-2004 Summary: (Adapted from the Investigator's abstract): The overall goal of this project is to determine the cellular interface where TCR gamma/delta cells participate in the systemic immune response to a model protein antigen, Ovalbumin (OVA). They have striking results that TCR gamma/delta cells are potent contributors to the T- and B-cells systemic immune response to OVA from our studies using a mouse model of asthma. Ovalbumin-challenged wildtype mice demonstrate marked allergic inflammatory response, evidenced by airway eosinophilia and elevated serum IgE. These responses are attenuated in TCR gamma -/- animals and completely absent in TCR beta-/- mice. Airway responsiveness to aerosolized methacholine is also reduced in challenged TCR6r animals relative to challenged wildtype mice. This is true for mice lacking TCR gamma/delta cells throughout life, or in wildtype mice that are depleted of TCR gamma/delta cells only during the recall response to aerosol challenge. The application proposes that TCR gamma/delta cells function in the systemic immune response to OVA (administered i.p. with Alum) by promoting differentiation of CD4+ TCR alpha/beta cells. These OVA-specific CD4 + cells then promote B-cell differentiation and immunoglobulin class-switching. The visualization and enumeration of these events will suggest possible sites and molecular events whereby TCR gamma/delta cells can affect the immune response. The observations that TCR gamma/delta cells continue to impact on the magnitude of the cellular and humoral response following 2 or 3 immunization or challenges are more perplexing in light of what is known regarding the behavior of memory CD4+ TCR alpha/beta cells and B lymphocytes. This could imply that TCR gamma/delta cells are specific for OVA and that, like TCR alpha/beta B-cells, they exhibit functional memory responses. Alternatively, TCR gamma/delta cells have the same response to OVA upon each exposure, and the functional impact of that response is manifested in the same way irrespective of whether it occurs during the primary or recall response to antigen. These studies represent one of first model systems where all the reagents necessary have been assembled to begin to define the role of TCR gamma/delta cells in a "conventional" immune response. Specifically, they propose to: AIM 1. Determine the impact of TCR gamma/delta cells on commitment of CD4+ TCR alpha/beta cells to the Th2 lineage. AIM 2. Determine the impact of TCR gamma/delta cells in B-cell production of OVA-specific Ig. AIM 3. Determine if TCR gamma/delta Tcells represent innate or adaptive components of the systemic immune response to OVA. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: TH2-MEDIATED INFLAMMATORY RESPONSES IN THE SKIN AND LUNG Principal Investigator & Institution: Herrick, Christina A.; Assistant Professor of Dermatology; Dermatology; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2002; Project Start 30-SEP-2000; Project End 31-AUG-2004 Summary: (Adapted from Applicant's Abstract) This is a four year mentored training program under the direction of Dr. Kim Bottomly, Professor of Immunobiology at Yale School of Medicine. After completing a residency in Dermatology at Yale, I joined Dr. Bottomly's lab as a postdoctoral fellow, studying Th2-mediated lung inflammation in a mouse model of Asthma. My interest in this project was a natural outgrowth of my doctoral studies involving regulation of IgE responses and my clinical interest in atopic dermatitis. I established a novel method of inducing strongly biased Th2 responses in vivo by epicutaneously (e.c.) exposing mice to soluble protein. Upon airway challenge,

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these e.c. sensitized mice develop lung inflammatory responses with features of human allergic asthma, including high numbers of eosinophils and mucus hypersecretion. We have shown that: 1) these e.c.- induced Th2 responses are IL-4 independent, but STAT6 dependent; 2) IL-4 independent Th2 responses in e.c. sensitized C57BL/6 mice are dependent on IL- 13; and 3) eosinophil migration from lung into airway in e.c. sensitized mice is IL-4 dependent in BALB/c, but not in C57BL/6, mice. It is our hypothesis that recruitment of eosinophils to the airway of e.c. sensitized mice is differentially regulated in these two strains because of differences in IL-13 production or receptivity. This will be tested in the following specific aims: 1) definition of the role of IL-13 during e.c. sensitization in BALB/c and C57BL/6 mice; and 2) determination of the cellular, molecular, and genetic factors that regulate airway eosinophilia in e.c. sensitized mice. In the third specific aim, the mechanisms put forth to explain the genetic difference in regulation of Th2 lung inflammation will be extended to the skin. This will involve establishing a new model of Th2-mediated skin inflammation by secondary antigen challenge in the skin (rather than the airway) of e.c. sensitized mice. Questions to be answered in this aim include: 1) is cutaneous inflammation governed by the same factors operating in the lung? 2) is eosinophil recruitment to skin IL-4 dependent in BALB/c mice, but not in C57BL/6 mice?; and 3) what is the role of IL-13 in skin inflammation? My plan is to continue working with Dr. Bottomly over the next several years to answer these questions. During this time, establishment of a novel model of Th2- mediated skin inflammation will provide me with a unique system in which to pursue future inquiries, facilitating my transition to an independent investigator. My goal is to continue basic science investigation of atopic skin disease as a junior faculty member in the Department of Dermatology at Yale School of Medicine. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: THE HYPEREOSINOPHILIC SYNDROMES AND MEPOLIZUMAB Principal Investigator & Institution: Gleich, Gerald J.; Professor of Medicine and Dermatology; Dermatology; University of Utah Salt Lake City, Ut 84102 Timing: Fiscal Year 2004; Project Start 15-JUN-2004; Project End 30-MAY-2008 Summary: (provided by applicant): The term, hypereosinophilic syndromes (HES), refers a spectrum of patients with elevated blood eosinophils. Over the past two decades, certain categories of patients have been recognized as HES subgroups. For example, the syndromes of episodic angioedema associated with eosinophilia, the syndrome of nodules, eosinophilia, rheumatism, dermatitis and swelling, HES associated with T cell clones, and the myeloproliferative variant have been recognized. Patients with T cell clones producing TH2 cytokines show evidence of L-5 production and IL-5 stimulates bone marrow production and activation of eosinophils. Mepolizumab is a high-affinity, specific, humanized monoclonal antibody to IL-5 which rapidly depletes eosinophils from the peripheral blood. This antibody has been administered to patients with several diseases, including asthma, and it is remarkably free of side-effects. The accompanying core clinical protocol describes a trial of mepolizumab for the treatment of HES; this mechanistic proposal seeks to understand the basic mechanisms underlying the response to mepolizumab. Specifically, we will: 1. Determine whether mepolizumab modulates T-cell functions, including their differentiation and cytokine production. 2. Test whether mepolizumab treatment suppresses eosinophil activation, cytokine production and expression of the IL-5 receptor on the eosinophils of treated patients. 3. Determine whether mepolizumab reveals heterogeneity in HES not heretofore recognized. Overall, this is a unique and unprecedented opportunity to conduct a multicenter study involving investigators with

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considerable experience to investigate the effects of anti-IL-5 administration and to determine which markers of eosinophil activation are best correlated with disease activity. Previous studies have largely been from single institutions, and this will be the first multicenter study. We anticipate the results will shed new light on this disease by defining essentially all HES subtypes and their frequencies, by determining the ability of anti-IL-5 to alter the immunological bases of HES, by identifying and investigating patients not responsive to anti-IL-5 and by identifying the characteristics of patients who can be effectively treated with anti-IL-5. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: THE ROLE OF CD11/CD INTEGRINS IN EXPERIMENTAL ASTHMA Principal Investigator & Institution: Prince, Joseph E.; Medicine; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2002; Project Start 30-SEP-2001; Project End 31-DEC-2002 Summary: (provided by applicant): Asthma, a common problem that exemplifies a pathologic inflammatory disease process, is characterized by episodic and reversible symptoms of airflow obstruction. The increasing prevalence both in the United States and worldwide reflects a growing public health problem. One recent estimate suggests the total annual cost of asthma to be $5.8 billion, with hospitalization accounting for over half of total expenditures. Traditional therapies of asthma have had limited success in reduction of morbidity and mortality, and it is clear that novel therapies will be needed. Over the last decade it has become widely accepted that asthma is an inflammatory disease and appears to result from activation and proliferation of Th2 lymphocytes. One potential target for therapy of asthma includes the selective inhibition of adhesive proteins responsible for recruitment of Th2 cells into the airway, the absence of which results in abolition of asthma in experimental models. Preliminary data strongly suggest that absence of CD18 results in complete loss of the experimental asthma phenotype in a murine model. CD11/CD18 integrins are heterodimeric, transmembrane proteins consisting of a variable alpha (CDlla, b, c, d) subunit coexpressed with the common beta-2 (CD18) subunit. CD11/CD18 integrins are expressed on a variety of leukocytes and mediate adhesive interactions with endothelium and extracellular matrix in recruiting leukocytes following exposure to any of numerous inflammatory stimuli. The aim of this project is to determine the role of CDll/CD18 integrins in a murine model of allergic airway disease, using mice deficient in CD18, mice singly deficient in each of the four CD11 subunits, and mice with combined deficiencies in multiple CD11 integrins. All genotypes of mice will be immunized with a hybrid antigen of ovalbumin and culture filtrate from Aspergillus fumigatus to induce the experimental asthma phenotype. Parameters to be measured will include airway response to intravenous acetylcholine, bronchoalveolar lavage eosinophilia, ovalbumin- specific IgE production, and goblet cell metaplasia. Enzymelinked immunospot (ELISPOT) assays will be used to quantitate IL-4 and IFN-gamma producing T cells in spleens and lungs of mutant and wild type mice to assess relative differences in Th2 cell emigration. Adoptive transfer of immunomagnetically purified CD4+ T cells from immunized mutant mice to lymphocyte deficient mice (RAG -/-) and to wild type mice will clarify the effects of specific gene deficiencies on Th2 lymphocyte trafficking to the lung. In vitro T cell stimulation will additionally be performed to determine the capacity for Th2 differentiation in the absence of each of the CD11 integrins. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: TRANSGENIC INVESTIGATIONS OF AIRWAY REMODELING Principal Investigator & Institution: Elias, Jack A.; Waldemar Von Zedtwitz Professor of Medic; Internal Medicine; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2002; Project Start 30-SEP-1999; Project End 17-MAY-2004 Summary: It is increasingly appreciated that the chronic inflammation underlying the asthmatic diathesis can cause impressive end organ alterations. These tissue effects, variously termed airway remodeling, include subepithelial fibrosis, mucus metaplasia, myocyte hypertrophy and hyperplasia and myofibroblast hyperplasia. However, our knowledge of the pathogenetic mechanisms and mediators that are responsible for these alterations, their degree of reversibility and their physiologic consequences have not been adequately investigated. To define the processes that mediate airway remodeling, we developed lung-specific constitutive and inducible / suppressive overexpression transgenic modeling systems and used these systems to characterize the in vivo effector profiles induced by asthma-relevant mediators. These studies demonstrated that interleukin-6-type cytokines and Th2-type cytokines induce remodeling responses that are similar in some ways and different in others. The IL-6-type cytokines caused impressive subepithelial fibrosis, hyaluronic acid (HA) deposition and myocyte and myofibroblast hyperplasia in the absence of eosinophilia or mucus metaplasia. The Th2type cytokines also caused subepithelial fibrosis with HA deposition. This response, however, was associated with eosinophilic inflammation and mucus metaplasia. HYPOTHESIS: The IL-6-type cytokines and Th2-type cytokines are important mediators of airway remodeling responses with overlapping and distinct effector properties. To test this hypothesis we propose to use constitutive and externally regulatable overexpression transgenic modeling systems. We will: (1) Characterize. the remodeling responses in transgenic mice that overexpress IL-6-type cytokines (IL-6, IL- 11, cardiotrophin-1) and Th2-type cytokines (IL-13, IL-9, IL-4). (2) Characterize the reversibility of the remodeling responses in transgenic mice that overexpress IL-6-type cytokines (IL-6, IL-11) and/or Th2-type cytokines (IL-13, IL-9). (3) Characterize the parameters of collagen metabolism in representative transgenic models and after chronic aeroallergen exposure. (4) Characterize the parameters of HA metabolism in representative transgenic models and after chronic aeroallergen exposure. (5) Characterize the role of the IL-6-type cytokines (IL-6, IL-11) and IL-13 in the induction of the collagen and HA responses in transgenic and antigen-driven models of airway remodeling. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: TRANSGENIC MOUSE MODEL FOR ADENOSINE-INDUCED ASTHMA Principal Investigator & Institution: Chan, Tehsheng; Microbiology and Immunology; University of Texas Medical Br Galveston 301 University Blvd Galveston, Tx 77555 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 30-JUN-2004 Summary: (provided by applicant): Adenosine deaminase (ADA) is a purine salvage enzyme that regulates the levels of adenosine and deoxyadenosine in mammalian tissues. Genetic deficiency of this enzyme is a cause of hereditary severe combined immune deficiency syndrome. A transgenic mouse model for adenosine deaminase deficiency has been produced that develops severe T cell deficiency. In addition, these transgenic mice manifest symptoms characteristic of asthma including eosinophilic inflammation of the lung, mucus overproduction, and airway obstruction. Since ample

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evidence ha previously shown that Th2 cells and their cytokines play a pivotal role in asthma pathogenesis, the asthma-like pathology present in our Th2-deficient mice points to some interesting Th2 cell-independent mechanism. To gain a better understanding of asthma pathogenesis in this novel animal model, we performed DNA microarray analyses. The results showed the absence of upregulation of Th2 cell-derived cytokines, and upregulation of a number of other cytokines/chemokines in the lung of ADA-negative mice. The genes that are expressed at the highest levels include TARC (thymus activated and regulated cytokine), JE/MCP- 1, KC/GRO 1, and eotaxin. Some of these genes are known to also play a role in allergic asthma, suggesting that adenosine-induced, Th2-independent asthma and Th2-mediated allergic asthma share common downstream pathways in disease pathogenesis. Our mouse model may also unmask certain mechanisms in allergic asthma, which were masked by the Th2dependent mechanism. Bronchial epithelial cells are known to produce TARC and other chemokines. In this application, we propose to test the hypothesis that adenosine, a well-documented signaling molecule, induces the production of TARC, JE/MCP-1 KC/GRO1 and eotaxin by lung epithelial cells. We will further test the hypotheses that these effector molecules are the pathogenic factors in the development of asthma-like disease in our mouse model and that adenosine receptor blocker could prevent the disease process. This transgenic mouse line provides a unique opportunity for studying the mechanism of Th2 cell-independent asthma-like disease, and has great potential for use in developing novel therapeutics. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: TSLP AND ALLERGIC INFLAMMATION Principal Investigator & Institution: Liu, Yong-Jun; Professor and Chairman; Immunology; University of Texas Md Anderson Can Ctr Cancer Center Houston, Tx 77030 Timing: Fiscal Year 2004; Project Start 01-MAY-2004; Project End 30-APR-2009 Summary: Thymic stromal lymphopoietin (TSLP) is a novel IL-7-like cytokine. Human TSLP (hTSLP) activates CD11+ dendritic cells (DCs) both to up-regulate MHC class II and costimulatory molecules CD40, CD80, and CD86 and to secrete the TH2-attracting chemokines TARC and MDC. TSLP-activated DCs induce the most marked antigenspecific CD4+, naive T-cell expansion, after which the T cells differentiate into TH2 effector cells that secrete high concentrations of interleukin (IL)-4, IL-5, IL-13, and tumor necrosis factor-alpha(TNF-alpha). hTSLP is mainly expressed by epithelial cells in allergic inflamed tissues. Our central hypothesis is that allergic insults caused by chemicals, microbes, and allergens initially trigger mucosal epithelial cells or skin keratinocytes, to produce TSLP. TSLP then activates Langerhans' cells (immature dendritic cells in epidermis), which migrate into the draining lymph nodes and prime allergen-specific na'fve T cells to expand and differentiate into proallergic TH2 effector cells. These TH2 effector T cells then produce IL-4, IL-5, and IL-13 that initiate an allergic inflammation by triggering immunoglobulin E (IgE) production, eosinophilia, and mucus production. Further investigation of the molecular mechanisms underlying the regulation of TSLP production by epithelial cells and TH2 differentiation induced by TSLP-activated DCs is essential for understanding the whole pathophysiological process underlying allergic responses, and hence for developing more effective therapies for allergic diseases. The specific aims of this proposal are: 1. To identify the molecular triggers of TSLP production by epithelial cells and the association of these triggers with human allergic diseases; 2. To identify the molecular regulation of TSLP receptor

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(TSLPR) and IL-7Ralpha co-expression; 3. To elicidate the molecular mechanisms by which TSLP-activated DCs induce TH2 differentiation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: VIRAL EXACERBATIONS OF ASTHMA Principal Investigator & Institution: Sanders, Scherer P.; Medicine; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002; Project Start 10-JUL-1998; Project End 30-JUN-2003 Summary: Up to 80 percent of asthma exacerbations are associated with the presence of an upper respiratory viral infection (URI), with human rhinoviruses (HRV) being the viral type most commonly associated with asthma attacks. This proposal will test the hypothesis that virus induced production of the eosinophil chemotactic and activating cytokines, eotaxin, RANTES, and granulocyte-macrophage colony stimulating factor (GM-CSF) from infected epithelial cells plays a central role in enhancing bronchial eosinophilia, and that this increase in activated eosinophils in the airway triggers disease exacerbations in asthmatics. Since exogenously administered nitric oxide (NO) inhibits HRV replication and virally induced cytokine production, we suggest that the capacity to cause asthma exacerbations depends upon virus reaching the lower airways in sufficient amounts to override the inhibitory host NO response and trigger epithelial cytokine production. Moreover, eosinophils must be "primed" to respond to the eosinophil chemoattractant cytokines. We suggest that this latter phenomenon occurs only in atopic individuals in response to circulating levels of priming cytokines (e.g. IL5). To test these hypotheses, and to further delineate the role of NO in regulating HRV infections, we will use both in vitro studies of infection of respiratory epithelial cells and in vivo HRV infection of normal, atopic and asthmatic subjects. We will determine if NO inhibits HRV replication by enhancing host antiviral responses and/or by inhibiting the actions of the important HRV protease 2A and 3C. We will also determine if viral replication and/or cytokine production is inhibited by NO via inhibition of mitochondrial enzymes that are important in energy metabolism. We will use cells transfected with cDNA coding for inducible nitric oxide synthase (iNOS) to determine if endogenously produced NO has the same effects as exogenously administered NO on HRV replication and cytokine production. We will infect normal, atopic and asthmatic subjects with HRV in vivo and will relate the presence of HRV in lower airway epithelial cells to epithelial expression of mRNA and protein for eotaxin, RANTES, GM-CSF and iNOS. We will test the hypothesis that atopic subjects whose eosinophils, isolated just prior to infection, show transepithelial migration to RANTES/eotaxin in vitro, will show enhanced nasal and bronchial eosinophilia in vivo, and will determine if inhibition of iNOS in vivo enhances HRV induced epithelial cytokine production. These studies should provide new insights into the pathogenesis of viral exacerbations of asthma and may provide the basis for improved therapeutic interventions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: VIRAL MODULATION OF EPITHELIAL FUNCTION Principal Investigator & Institution: Proud, David; Professor; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002 Summary: This Program Grant focuses on the hypothesis that chronic rhinosinusitis, a disease affects approximately 15% of Americans, is due to epithelial cell dysfunction. This dysfunction may arise from an inherent genetic defect(s), environmental influences,

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or most likely, a combination of the two. This project contributes to this hypothesis by testing whether viral infection is an important environmental stimulus in the development and exacerbation of chronic rhinosinusitis by triggering alterations in epithelial cell function, particularly increased production of pro- inflammatory cytokines, including IL-8, GM-CSF, RANTES and eotaxin. To examine the relationship between viral infection and chronic rhinosinusitis we will monitor subjects prospectively following endoscopic sinus surgery to determine if nasal and sinus secretions from subjects experiencing exacerbations of rhinosinusitis show a higher incidence of viral infection, detected by PCR, compared to secretions obtained from the same subjects during periods when disease activity is less severe. Given that nitric oxide (NO), is antiviral and inhibits epithelial cytokine production, we also will test the hypothesis that an inability of the sinus epithelium to increase production of NO, via the enzyme inducible NO synthase (iNOS), during viral infections is a risk factor for chronic rhinosinusitis. We will examine the mechanism of induction of iNOS by rhinovirus in cultured epithelial cells and will determine if subjects with chronic rhinosinusitis show lower induction of epithelial iNOS expression, and increased epithelial cytokine production and inflammation, compared to normal subjects during experimental rhinovirus infections. Intranasal glucocorticoids are currently advocated as an appropriate therapy to reduce disease recurrence in patients after sinus surgery. Despite widespread use for this identification, however, the efficacy, and mechanisms glucocorticoids versus placebo in subjects recruited after sinus injury to test the hypothesis, which is based upon in vitro data, that topical glucocorticoids will reduce epithelial expression of GM-CSF, RANTES, and eotaxin, and tissue eosinophilia in subjects but will have little effect on epithelial expression of IL-8 or on neutrophilic inflammation. We suggest that such an outcome will result in only a partial therapeutic effect. These studies should provide important insights into the pathogenesis of chronic rhinosinusitis and may lead to the development of improved therapies for the treatment of this major health problem. 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 “eosinophilia” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for eosinophilia in the PubMed Central database:

3 4

Adapted from the National Library of Medicine: http://www.pubmedcentral.nih.gov/about/intro.html.

With PubMed Central, NCBI is taking the lead in preservation and maintenance of open access to electronic literature, just as NLM has done for decades with printed biomedical literature. PubMed Central aims to become a world-class library of the digital age. 5 The value of PubMed Central, in addition to its role as an archive, lies in the availability of data from diverse sources stored in a common format in a single repository. Many journals already have online publishing operations, and there is a growing tendency to publish material online only, to the exclusion of print.

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Anti-IL-9 vaccination prevents worm expulsion and blood eosinophilia in Trichuris muris-infected mice. by Richard M, Grencis RK, Humphreys NE, Renauld JC, Van Snick J.; 2000 Jan 18; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=15405

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CCR3 is essential for skin eosinophilia and airway hyperresponsiveness in a murine model of allergic skin inflammation. by Ma W, Bryce PJ, Humbles AA, Laouini D, Yalcindag A, Alenius H, Friend DS, Oettgen HC, Gerard C, Geha RS.; 2002 Mar 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=150891

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Elevated Immunoglobulin E against Recombinant Brugia malayi [gamma]-Glutamyl Transpeptidase in Patients with Bancroftian Filariasis: Association with Tropical Pulmonary Eosinophilia or Putative Immunity. by Lobos E, Nutman TB, Hothersall JS, Moncada S.; 2003 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=145369

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Enhanced collagen synthesis and transcription by peak E, a contaminant of Ltryptophan preparations associated with the eosinophilia myalgia syndrome epidemic. by Takagi H, Ochoa MS, Zhou L, Helfman T, Murata H, Falanga V.; 1995 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=185860

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Enhanced Disease and Pulmonary Eosinophilia Associated with Formalin-Inactivated Respiratory Syncytial Virus Vaccination Are Linked to G Glycoprotein CX3CCX3CR1 Interaction and Expression of Substance P. by Haynes LM, Jones LP, Barskey A, Anderson LJ, Tripp RA.; 2003 Sep 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=224581

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Interleukin 5 is required for the blood and tissue eosinophilia but not granuloma formation induced by infection with Schistosoma mansoni. by Sher A, Coffman RL, Hieny S, Scott P, Cheever AW.; 1990 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=53199

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Interleukin-5 and the posttreatment eosinophilia in patients with onchocerciasis. by Limaye AP, Abrams JS, Silver JE, Awadzi K, Francis HF, Ottesen EA, Nutman TB.; 1991 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=295614

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Priming with a Secreted Form of the Fusion Protein of Respiratory Syncytial Virus (RSV) Promotes Interleukin-4 (IL-4) and IL-5 Production but Not Pulmonary Eosinophilia following RSV Challenge. by Bembridge GP, Lopez JA, Bustos R, Melero JA, Cook R, Mason H, Taylor G.; 1999 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=113060

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Priming with Secreted Glycoprotein G of Respiratory Syncytial Virus (RSV) Augments Interleukin-5 Production and Tissue Eosinophilia after RSV Challenge. by Johnson TR, Johnson JE, Roberts SR, Wertz GW, Parker RA, Graham BS.; 1998 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=109732

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Prior Exposure to Live Mycobacterium bovis BCG Decreases Cryptococcus neoformans-Induced Lung Eosinophilia in a Gamma Interferon-Dependent Manner. by Walzl G, Humphreys IR, Marshall BG, Edwards L, Openshaw PJ, Shaw RJ, Hussell T.; 2003 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=155718

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Protective immunity and eosinophilia in IgE-deficient SJA/9 mice infected with Nippostrongylus brasiliensis and Trichinella spiralis. by Watanabe N, Katakura K, Kobayashi A, Okumura K, Ovary Z.; 1988 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=280449

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Schistosoma japonicum-infected mice show reduced hepatic fibrosis and eosinophilia and selective inhibition of interleukin-5 secretion by CD4+ cells after treatment with anti-interleukin-2 antibodies. by Cheever AW, Xu Y, Sher A, Finkelman FD, Cox TM, Macedonia JG.; 1993 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=281360

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Secreted Respiratory Syncytial Virus G Glycoprotein Induces Interleukin-5 (IL-5), IL13, and Eosinophilia by an IL-4-Independent Mechanism. by Johnson TR, Graham BS.; 1999 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=112868

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Some enzymatic characteristics of eosinophil peroxidase from patients with eosinophilia and from healthy donors. by Bos AJ, Wever R, Hamers MN, Roos D.; 1981 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=351460

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

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A 20-year-old man with eosinophilia and easy bruisability. Author(s): Lim LC. Source: Singapore Med J. 1999 October; 40(10): 652-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10741194

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 case of angiolymphoid hyperplasia with eosinophilia treated with intralesional interferon alfa-2a. Author(s): Shenefelt PD, Rinker M, Caradonna S. Source: Archives of Dermatology. 2000 July; 136(7): 837-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10890984

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A rare vasoproliferative lesion: angiolymphoid hyperplasia with eosinophilia of the hand. Author(s): Krapohl BD, Machens HG, Reichert B, Mailander P. Source: British Journal of Plastic Surgery. 2003 March; 56(2): 168-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12791366

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Absence of association of peripheral blood eosinophilia or increased eosinophil cationic protein with bronchial hyperresponsiveness during asthma remission. Author(s): Koh YY, Kang H, Nah KM, Kim CK. Source: Annals of Allergy, Asthma & Immunology : Official Publication of the American College of Allergy, Asthma, & Immunology. 2003 September; 91(3): 297-302. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14533663

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Active human herpesvirus 6 infection in a patient with drug rash with eosinophilia and systemic symptoms. Author(s): Descamps V, Collot S, Mahe E, Houhou N, Crickx B, Ranger-Rogez S. Source: The Journal of Investigative Dermatology. 2003 July; 121(1): 215-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12839588

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Acute cerebral phaeohyphomycosis due to Wangiella dermatitidis accompanied by cerebrospinal fluid eosinophilia. Author(s): Chang CL, Kim DS, Park DJ, Kim HJ, Lee CH, Shin JH. Source: Journal of Clinical Microbiology. 2000 May; 38(5): 1965-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10790129

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Airway mast-cell activation in asthmatics is associated with selective sputum eosinophilia. Author(s): Bettiol J, Radermecker M, Sele J, Henquet M, Cataldo D, Louis R. Source: Allergy. 1999 November; 54(11): 1188-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10604555

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Angioedema associated with eosinophilia. Author(s): Yamabe H, Takanashi S, Osawa H, Nakamura N, Shirato K, Sugawara T, Nakamura M, Tamura M, Okumura K. Source: Intern Med. 2003 July; 42(7): 626. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12879960

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Angiolymphoid hyperplasia with eosinophilia arising from the facial artery. Author(s): Kimura Y, Tsutsumi T, Kuroishikawa Y, Kishimoto S. Source: The Journal of Laryngology and Otology. 2003 July; 117(7): 570-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12901818

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Angiolymphoid hyperplasia with eosinophilia involving the cubital nerve. Author(s): Martorell M, Perez-Valles A, Garcia-Garcia JA, Calabuig C, Aguilella L. Source: Acta Neuropathologica. 2004 April; 107(4): 372-6. Epub 2004 February 05. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14762674

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Angiolymphoid hyperplasia with eosinophilia of the orbit. Author(s): Kubo T, Hosokawa K, Kamiji T. Source: Annals of Plastic Surgery. 2000 June; 44(6): 683-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10884098

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Angiolymphoid hyperplasia with eosinophilia responsive to pulsed dye laser. Author(s): Abrahamson TG, Davis DA. Source: Journal of the American Academy of Dermatology. 2003 August; 49(2 Suppl Case Reports): S195-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12894122

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Angiolymphoid hyperplasia with eosinophilia showing characteristics of Kimura's disease. Author(s): Chung TS, Kim DK, Yoon MS, Yang WI. Source: The Journal of Dermatology. 2000 January; 27(1): 27-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10692821

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Angiolymphoid hyperplasia with eosinophilia successfully treated with a longpulsed tunable dye laser. Author(s): Rohrer TE, Allan AE. Source: Dermatologic Surgery : Official Publication for American Society for Dermatologic Surgery [et Al.]. 2000 March; 26(3): 211-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10759795

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Angiolymphoid hyperplasia with eosinophilia successfully treated with the flashlamp pulsed-dye laser. Author(s): Papadavid E, Krausz T, Chu AC, Walker NP. Source: The British Journal of Dermatology. 2000 January; 142(1): 192-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10819556

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Angiolymphoid hyperplasia with eosinophilia: a rare artery lesion. Author(s): Aurello P, Cicchini C, D'Angelo F, Di Gioia CR, D'Amati G. Source: Anticancer Res. 2003 May-June; 23(3C): 3069-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12926163

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Angiolymphoid hyperplasia with eosinophilia: F-18 FDG PET and MR demonstration. Author(s): Nguyen BD. Source: Clinical Nuclear Medicine. 2003 December; 28(12): 996-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14663329

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Angiolymphoid hyperplasia with eosinophilia: report of a lesion mimicking soft tissue tumor of extremely long duration. Author(s): Toth E, Orosz Z, Rahoty P. Source: Pathology, Research and Practice. 2000; 196(2): 99-101. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10707366

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Angiolymphoid hyperplasia with eosinophilia: successful treatment with the antiallergic agent suplatast tosilate. Author(s): Harada K, Kambe Y, Takeda H, Nakano H, Hanada K. Source: Dermatology (Basel, Switzerland). 2004; 208(2): 176-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15057015

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Asthma attacks with eosinophilia predict mortality from chronic obstructive pulmonary disease in a general population sample. Author(s): Hospers JJ, Schouten JP, Weiss ST, Rijcken B, Postma DS. Source: American Journal of Respiratory and Critical Care Medicine. 1999 December; 160(6): 1869-74. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10588599

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Bias or biology: evaluating the epidemiologic studies of L-tryptophan and the eosinophilia-myalgia syndrome. Author(s): Horwitz RI, Daniels SR. Source: J Rheumatol Suppl. 1996 October; 46: 60-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8895182

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Bilateral submandibular salivary gland swelling--a report of chronic sialodochitis with eosinophilia. Author(s): Darling MR, Phillips VM, Erasmus JH. Source: Sadj. 2002 March; 57(3): 104-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12061147

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Biochemical and immunologic characterization of a major IgE-inducing filarial antigen of Brugia malayi and implications for the pathogenesis of tropical pulmonary eosinophilia. Author(s): Lobos E, Ondo A, Ottesen EA, Nutman TB. Source: Journal of Immunology (Baltimore, Md. : 1950). 1992 November 1; 149(9): 302934. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1401928

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Biopsy eosinophilia as a predictor of renal graft dysfunction. Author(s): Jezior D, Boratynska M, Halon A, Kusztal M, Rabczynski J, Szyber P, Patrzalek D, Kaminska D, Klinger M. Source: Transplantation Proceedings. 2003 September; 35(6): 2182-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14529882

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Biotransformation of 3-(phenylamino)-1,2-propanediol to 3-(phenylamino)alanine: a chemical link between toxic oil syndrome and eosinophilia-myalgia syndrome. Author(s): Mayeno AN, Benson LM, Naylor S, Colberg-Beers M, Puchalski JT, Gleich GJ. Source: Chemical Research in Toxicology. 1995 October-November; 8(7): 911-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8555405

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Blood and bone marrow eosinophilia in malignant tumors. Role and nature of blood and tissue eosinophil colony-stimulating factor(s) in two patients. Author(s): Stefanini M, Claustro JC, Motos RA, Bendigo LL. Source: Cancer. 1991 August 1; 68(3): 543-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2065275

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Blood and graft eosinophilia as a rejection index in kidney transplant. Author(s): Almirall J, Campistol JM, Sole M, Andreu J, Revert L. Source: Nephron. 1993; 65(2): 304-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8247197

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Blood eosinophil number and activity in relation to lung function in patients with asthma and with eosinophilia. Author(s): Griffin E, Hakansson L, Formgren H, Jorgensen K, Peterson C, Venge P. Source: The Journal of Allergy and Clinical Immunology. 1991 February; 87(2): 548-57. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1847158

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Blood eosinophilia and degree of sensitization to house dust mites in preschool and school children with asthma. Author(s): Youroukova VF, Oddera S, Silvestri M, Spallarossa D, Rossi GA. Source: The Journal of Asthma : Official Journal of the Association for the Care of Asthma. 1998; 35(6): 489-96. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9751066

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Blood eosinophilia and FEV1. Cross-sectional and longitudinal analyses. Author(s): Frette C, Annesi I, Korobaeff M, Neukirch F, Dore MF, Kauffmann F. Source: Am Rev Respir Dis. 1991 May; 143(5 Pt 1): 987-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2024855

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Blood eosinophilia in atopic dermatitis. Author(s): Uehara M, Izukura R, Sawai T. Source: Clinical and Experimental Dermatology. 1990 July; 15(4): 264-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2208775

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Blood eosinophilia in Hodgkin's disease. A follow-up of 25 cases in Venezuela. Author(s): Desenne JJ, Acquatella G, Stern R, Muller A, Sanchez M, Somoza R. Source: Cancer. 1992 March 1; 69(5): 1248-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1739923

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Blood eosinophilia in tacrolimus-treated patients: an indicator of Pneumocystis carinii pneumonia. Author(s): Dickenmann MJ, Tamm M, Tsinalis D, Binet I, Thiel G, Steiger J. Source: Transplantation. 1999 November 27; 68(10): 1606-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10589963

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Blood eosinophilia, steroids, and rejection. Author(s): Lautenschlager I, von Willebrand E, Hayry P. Source: Transplantation. 1985 October; 40(4): 354-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3901441

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Bone marrow eosinophilia as a prognostic indicator in acute myelogenous leukemia with 8;21 translocation. Author(s): Hagihara M, Miyachi H, Kobayashi H, Ogawa T. Source: International Journal of Hematology. 1992 April; 55(2): 173-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1511166

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Borrelial fasciitis: diffuse fasciitis and peripheral eosinophilia associated with Borrelia infection. Author(s): Granter SR, Barnhill RL, Duray PH. Source: The American Journal of Dermatopathology. 1996 October; 18(5): 465-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8902092

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Bronchial eosinophilia in exacerbation of bronchitis: an allergic profile of inflammation? Author(s): Costabel U. Source: American Journal of Respiratory and Critical Care Medicine. 2001 July 1; 164(1): 3-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11435230

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Bronchial hyperresponsiveness, epithelial damage, and airway eosinophilia after single and repeated allergen exposure in a rat model of anhydride-induced asthma. Author(s): Cui ZH, Sjostrand M, Pullerits T, Andius P, Skoogh BE, Lotvall J. Source: Allergy. 1997 July; 52(7): 739-46. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9265989

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Bronchial responsiveness and airway inflammation in patients with nonallergic rhinitis with eosinophilia syndrome. Author(s): Leone C, Teodoro C, Pelucchi A, Mastropasqua B, Cavigioli G, Marazzini L, Foresi A. Source: The Journal of Allergy and Clinical Immunology. 1997 December; 100(6 Pt 1): 775-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9438486

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Bronchial responsiveness, eosinophilia, and short term exposure to air pollution. Author(s): Soyseth V, Kongerud J, Broen P, Lilleng P, Boe J. Source: Archives of Disease in Childhood. 1995 November; 73(5): 418-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8554358

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Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 12-2002. A 50-year-old man with eosinophilia and fluctuating hepatic lesions. Author(s): MacLean JD, Graeme-Cook FM. Source: The New England Journal of Medicine. 2002 April 18; 346(16): 1232-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11961153

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Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 19-2004. A 12-year-old boy with fatigue and eosinophilia. Author(s): Huang MS, Hasserjian RP. Source: The New England Journal of Medicine. 2004 June 17; 350(25): 2604-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15201418

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CCR3 is essential for skin eosinophilia and airway hyperresponsiveness in a murine model of allergic skin inflammation. Author(s): Ma W, Bryce PJ, Humbles AA, Laouini D, Yalcindag A, Alenius H, Friend DS, Oettgen HC, Gerard C, Geha RS. Source: The Journal of Clinical Investigation. 2002 March; 109(5): 621-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11877470

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Chemoattractant receptor-homologous molecule expressed on Th2 cells activation in vivo increases blood leukocyte counts and its blockade abrogates 13,14-dihydro-15keto-prostaglandin D2-induced eosinophilia in rats. Author(s): Shichijo M, Sugimoto H, Nagao K, Inbe H, Encinas JA, Takeshita K, Bacon KB, Gantner F. Source: The Journal of Pharmacology and Experimental Therapeutics. 2003 November; 307(2): 518-25. Epub 2003 September 15. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12975488

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CHIC2 deletion, a surrogate for FIP1L1-PDGFRA fusion, occurs in systemic mastocytosis associated with eosinophilia and predicts response to imatinib mesylate therapy. Author(s): Pardanani A, Ketterling RP, Brockman SR, Flynn HC, Paternoster SF, Shearer BM, Reeder TL, Li CY, Cross NC, Cools J, Gilliland DG, Dewald GW, Tefferi A. Source: Blood. 2003 November 1; 102(9): 3093-6. Epub 2003 July 03. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12842979

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Cholangiocellular carcinoma with an aggressive growth and eosinophilia, which showed multiple myeloma in autopsy. Author(s): Seki Y, Sato K, Isokawa O, Hasegawa G. Source: Intern Med. 2003 November; 42(11): 1149-50. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14686760

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Chronic cough.and tropical pulmonary eosinophilia. Author(s): Malavige GN. Source: Bmj (Clinical Research Ed.). 2003 May 10; 326(7397): 1036. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12749330

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Chronic eosinophilic leukaemia presenting with erythroderma, mild eosinophilia and hyper-IgE: clinical, immunological and cytogenetic features and therapeutic approach. A case report. Author(s): Granjo E, Lima M, Lopes JM, Doria S, Orfao A, Ying S, Barata LT, Miranda M, Cross NC, Bain BJ. Source: Acta Haematologica. 2002; 107(2): 108-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11919392

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Chronic myelocytic leukemia with eosinophilia, t(9;12)(q34;p13), and ETV6-ABL gene rearrangement: case report and review of the literature. Author(s): Keung YK, Beaty M, Steward W, Jackle B, Pettnati M. Source: Cancer Genetics and Cytogenetics. 2002 October 15; 138(2): 139-42. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12505259

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Chronic sinusitis in severe asthma is related to sputum eosinophilia. Author(s): ten Brinke A, Grootendorst DC, Schmidt JT, De Bruine FT, van Buchem MA, Sterk PJ, Rabe KF, Bel EH. Source: The Journal of Allergy and Clinical Immunology. 2002 April; 109(4): 621-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11941310

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Clarithromycin and pulmonary infiltration with eosinophilia. Author(s): Terzano C, Petroianni A. Source: Bmj (Clinical Research Ed.). 2003 June 21; 326(7403): 1377-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12816827

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Clinical and immunological features of patients with interleukin-5-producing T cell clones and eosinophilia. Author(s): Simon HU, Plotz SG, Simon D, Dummer R, Blaser K. Source: International Archives of Allergy and Immunology. 2001 January-March; 124(13): 242-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11306981

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Clonal T-helper lymphocytes and elevated IL-5 levels in episodic angioedema and eosinophilia (Gleich's syndrome). Author(s): Morgan SJ, Prince HM, Westerman DA, McCormack C, Glaspole I. Source: Leukemia & Lymphoma. 2003 September; 44(9): 1623-5. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14565669

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Cloning of the t(1;5)(q23;q33) in a myeloproliferative disorder associated with eosinophilia: involvement of PDGFRB and response to imatinib. Author(s): Wilkinson K, Velloso ER, Lopes LF, Lee C, Aster JC, Shipp MA, Aguiar RC. Source: Blood. 2003 December 1; 102(12): 4187-90. Epub 2003 August 07. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12907457

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Complete haematological and cytogenetic response to interferon alpha-2a of a myeloproliferative disorder with eosinophilia associated with a unique t(4;7) aberration. Author(s): Schoffski P, Ganser A, Pascheberg U, Busche G, Gaede B, Hertenstein B. Source: Annals of Hematology. 2000 February; 79(2): 95-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10741923

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Complex karyotype and absence of mutation in the c-kit receptor in aggressive mastocytosis presenting with pelvic osteolysis, eosinophilia and brain damage. Author(s): Jost E, Michaux L, Vanden Abeele M, Boland B, Latinne D, Godfraind C, Scheiff JM, Vaerman JL, Lecouvet F, Ferrant A. Source: Annals of Hematology. 2001 May; 80(5): 302-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11446735

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Correlations between exhaled nitric oxide levels, blood eosinophilia, and airway obstruction reversibility in childhood asthma are detectable only in atopic individuals. Author(s): Silvestri M, Sabatini F, Sale R, Defilippi AC, Fregonese L, Battistini E, Biraghi MG, Rossi GA. Source: Pediatric Pulmonology. 2003 May; 35(5): 358-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12687592

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Cryotherapy in the treatment of angiolymphoid hyperplasia with eosinophilia. Author(s): Wozniacka A, Omulecki A, Torzecka JD. Source: Medical Science Monitor : International Medical Journal of Experimental and Clinical Research. 2003 January; 9(1): Cs1-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12552249

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Cysteinyl leukotriene expression in chronic hyperplastic sinusitis-nasal polyposis: importance to eosinophilia and asthma. Author(s): Steinke JW, Bradley D, Arango P, Crouse CD, Frierson H, Kountakis SE, Kraft M, Borish L. Source: The Journal of Allergy and Clinical Immunology. 2003 February; 111(2): 342-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12589355

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Cytokine production from peripheral whole blood in atopic and nonatopic asthmatics: relationship with blood and sputum eosinophilia and serum IgE levels. Author(s): Bettiol J, Bartsch P, Louis R, De Groote D, Gevaerts Y, Louis E, Malaise M. Source: Allergy. 2000 December; 55(12): 1134-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11117270

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Decreased levels of CXCR3 transcripts in peripheral blood mononuclear cells from patients with atopic dermatitis and with cutaneous diseases associated with eosinophilia. Author(s): Hatano Y, Katagiri K, Takayasu S. Source: Archives of Dermatological Research. 2001 June; 293(6): 319-22. Erratum In: Arch Dermatol Res. 2002 July; 294(4): 203. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11480592

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Detection of interleukin-5 messenger RNA in Reed-Sternberg cells of Hodgkin's disease with eosinophilia. Author(s): Samoszuk M, Nansen L. Source: Blood. 1990 January 1; 75(1): 13-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2403816

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Development of diffuse fasciitis with eosinophilia during L-tryptophan treatment: demonstration of elevated type I collagen gene expression in affected tissues. A clinicopathologic study of four patients. Author(s): Varga J, Peltonen J, Uitto J, Jimenez S. Source: Annals of Internal Medicine. 1990 March 1; 112(5): 344-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2306063

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Diagnosis and treatment of postprandial nausea, allergy, and eosinophilia. Author(s): Coleman D, Guarderas JC, Scolapio JS, Cangemi JR. Source: Journal of Clinical Gastroenterology. 2004 March; 38(3): 260-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15128073

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Diagnostic complexity in a patient with asthma, pulmonary infiltrates, and eosinophilia. Author(s): Backman KS, Zull D, Patterson R. Source: Annals of Allergy, Asthma & Immunology : Official Publication of the American College of Allergy, Asthma, & Immunology. 1995 November; 75(5): 391-400. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7583860

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Diagnostic importance of serological methods and eosinophilia in tissue parasites. Author(s): Demirci M, Korkmaz M, Sakru N, Kaya S, Kuman A. Source: J Health Popul Nutr. 2002 December; 20(4): 352-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12659417

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Diagnostic significance of blood eosinophilia in returning travelers. Author(s): Schulte C, Krebs B, Jelinek T, Nothdurft HD, von Sonnenburg F, Loscher T. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2002 February 1; 34(3): 407-11. Epub 2001 December 19. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11753824

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Differential chemokine expression in tissues involved by Hodgkin's disease: direct correlation of eotaxin expression and tissue eosinophilia. Author(s): Teruya-Feldstein J, Jaffe ES, Burd PR, Kingma DW, Setsuda JE, Tosato G. Source: Blood. 1999 April 15; 93(8): 2463-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10194423

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Disseminated angiolymphoid hyperplasia with eosinophilia: a case report. Author(s): Zhang GY, Jiang J, Lin T, Wang QQ. Source: Cutis; Cutaneous Medicine for the Practitioner. 2003 October; 72(4): 323-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14604086

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Dissociation of airway hyperresponsiveness from immunoglobulin E and airway eosinophilia in a murine model of allergic asthma. Author(s): Wilder JA, Collie DD, Wilson BS, Bice DE, Lyons CR, Lipscomb MF. Source: American Journal of Respiratory Cell and Molecular Biology. 1999 June; 20(6): 1326-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10340953

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Dobutamine-induced eosinophilia. Author(s): El-Sayed OM, Abdelfattah RR, Barcelona R, Leier CV. Source: The American Journal of Cardiology. 2004 April 15; 93(8): 1078-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15081466

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Does peripheral blood eosinophilia predict allograft rejection in living-related liver transplantation? Author(s): Matsukura A, Kita Y, Harihara Y, Tanaka H, Ito M, Kawarasaki H, Kubota K, Takayama T, Hashizume K, Makuuchi M. Source: Transplantation Proceedings. 1999 November; 31(7): 2729-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10578267

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DRESS (drug rash with eosinophilia and systemic symptoms) syndrome associated with nevirapine therapy. Author(s): Bourezane Y, Salard D, Hoen B, Vandel S, Drobacheff C, Laurent R. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 1998 November; 27(5): 1321-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9827291

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Drug rash with eosinophilia and systemic symptoms (DRESS syndrome). Author(s): Tas S, Simonart T. Source: Acta Clin Belg. 1999 August; 54(4): 197-200. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10544509

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Drug rash with eosinophilia and systemic symptoms (DRESS) due to streptomycin. Author(s): Passeron T, Ndir MC, Aubron C, Hovette P. Source: Acta Dermato-Venereologica. 2004; 84(1): 92-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15040497

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Drug rash with eosinophilia and systemic symptoms caused by topical application of mercury. Author(s): Tschanz C, Prins C. Source: Dermatology (Basel, Switzerland). 2000; 201(4): 381-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11146363

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Drug rash with eosinophilia and systemic symptoms secondary to phenobarbitone. Author(s): Baruzzi A, Contin M, Barbara G, Cremon C, De Giorgio R, Patrizi A, Albani F, Corinaldesi R. Source: Clinical Neuropharmacology. 2003 July-August; 26(4): 177-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12897635

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Drug rash with eosinophilia and systemic symptoms syndrome and renal toxicity with a nevirapine-containing regimen in a pregnant patient with human immunodeficiency virus. Author(s): Knudtson E, Para M, Boswell H, Fan-Havard P. Source: Obstetrics and Gynecology. 2003 May; 101(5 Pt 2): 1094-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12738113

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Drug-induced eosinophilia and multisystemic failure with positive patch-test reaction to spironolactone: DRESS syndrome. Author(s): Ghislain PD, Bodarwe AD, Vanderdonckt O, Tennstedt D, Marot L, Lachapelle JM. Source: Acta Dermato-Venereologica. 2004; 84(1): 65-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15040482

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Drug-induced rash with eosinophilia and systemic symptoms syndrome with bupropion administration. Author(s): Bagshaw SM, Cload B, Gilmour J, Leung ST, Bowen TJ. Source: Annals of Allergy, Asthma & Immunology : Official Publication of the American College of Allergy, Asthma, & Immunology. 2003 May; 90(5): 572-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12775141

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Early diagnosis of primary biliary cirrhosis in type 1 diabetes: the possible role of eosinophilia. Author(s): Gazzaruso C, Giordanetti S, De Cata P, Poggi G, Fratino P. Source: Diabetes Care. 2003 October; 26(10): 2963-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14514618

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Eosinophilia and diseases: clinical revision of 1862 cases. Author(s): Lombardi C, Passalacqua G. Source: Archives of Internal Medicine. 2003 June 9; 163(11): 1371-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12796076

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Eosinophilia and hyperimmunoglobulinemia E as the presenting manifestations of Wegener's granulomatosis. Author(s): Kamali S, Kasapoglu E, Akturk F, Gul A, Inanc M, Ocal L, Aral O, Konice M. Source: Clinical Rheumatology. 2003 October; 22(4-5): 333-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14576994

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Eosinophilia and uterine leiomyosarcoma. Author(s): Pal L, Parkash V, Chambers JT. Source: Obstetrics and Gynecology. 2003 May; 101(5 Pt 2): 1130-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12738126

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Eosinophilia as a diagnostic value in patients suffering from schistosomiasis haematobium comparing to eosinophiluria and egg count in the urine. Author(s): Issa RM, Shalaby MA. Source: J Egypt Soc Parasitol. 1999 August; 29(2): 431-49. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10605495

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Eosinophilia at the time of respiratory syncytial virus bronchiolitis predicts childhood reactive airway disease. Author(s): Ehlenfield DR, Cameron K, Welliver RC. Source: Pediatrics. 2000 January; 105(1 Pt 1): 79-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10617708

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Eosinophilia correlates with the presence or development of chronic graft-versus-host disease in children. Author(s): Jacobsohn DA, Schechter T, Seshadri R, Thormann K, Duerst R, Kletzel M. Source: Transplantation. 2004 April 15; 77(7): 1096-100. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15087778

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Eosinophilia in nasal polyposis: its objective quantification and clinical relevance. Author(s): Gerstner AO, Gutsche M, Bucheler M, Machlitt J, Emmrich F, Sommerer F, Tarnok A, Bootz F. Source: Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology. 2004 January; 34(1): 65-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14720264

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Eosinophilia is associated with increased all-cause mortality after a follow-up of 30 years in a general population sample. Author(s): Hospers JJ, Schouten JP, Weiss ST, Postma DS, Rijcken B. Source: Epidemiology (Cambridge, Mass.). 2000 May; 11(3): 261-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10784241

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Eosinophilia presenting as acute coronary syndrome. Author(s): Huang CY, Lu TM, Hsu CP, Yang AH, Ding YA, Chiang CE. Source: American Journal of Hematology. 2004 May; 76(1): 94-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15114609

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Eosinophilia with aberrant T cells and elevated serum levels of interleukin-2 and interleukin-15. Author(s): Means-Markwell M, Burgess T, deKeratry D, O'Neil K, Mascola J, Fleisher T, Lucey D. Source: The New England Journal of Medicine. 2000 May 25; 342(21): 1568-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10824075

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Eosinophilia-preceded myelodysplastic syndrome associated with deletion of chromosome 20q and isochromosome 17q. Author(s): Takahashi T, Kamishima M, Yabana T, Hinoda Y, Imai K. Source: International Journal of Hematology. 1999 January; 69(1): 59-60. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10641446

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Eosinophils are derived from the neoplastic clone in patients with systemic mastocytosis and eosinophilia. Author(s): Pardanani A, Reeder T, Li CY, Tefferi A. Source: Leukemia Research. 2003 October; 27(10): 883-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12860006

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Eotaxin expression in oral squamous cell carcinomas with and without tumour associated tissue eosinophilia. Author(s): Lorena SC, Oliveira DT, Dorta RG, Landman G, Kowalski LP. Source: Oral Diseases. 2003 November; 9(6): 279-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14629326

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Epithelioid hemangioma (angiolymphoid hyperplasia with eosinophilia) in the oral mucosa. A case report and review of the literature. Author(s): Mariatos G, Gorgoulis VG, Laskaris G, Kittas C. Source: Oral Oncology. 1999 July; 35(4): 435-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10645412

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Erythema multiforme-type drug eruption due to ethambutol with eosinophilia and liver dysfunction. Author(s): Kurokawa I, Nakahigashi Y, Teramachi M. Source: International Journal of Antimicrobial Agents. 2003 June; 21(6): 596-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12791479

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Esophageal eosinophilia in children with dysphagia. Author(s): Cheung KM, Oliver MR, Cameron DJ, Catto-Smith AG, Chow CW. Source: Journal of Pediatric Gastroenterology and Nutrition. 2003 October; 37(4): 498503. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14508223

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Evaluation of blood eosinophilia and the eosinophil cationic protein (ECP) in the serum of asthmatic children with varying degree of severity. Author(s): Vila-Indurain B, Munoz-Lopez F, Martin-Mateos M. Source: Allergologia Et Immunopathologia. 1999 November-December; 27(6): 304-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10611555

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Extrapulmonary tuberculous infection manifested as peritoneal fluid eosinophilia in a continuous ambulatory peritoneal dialysis patient. Author(s): Hsu SC, Lan RR, Tseng CC, Lai CT, Huang JJ. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 2000 February; 15(2): 284-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10648689

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Facial swelling and eosinophilia in a 44-year-old woman. Author(s): Abraham D, Saltoun CA. Source: Annals of Allergy, Asthma & Immunology : Official Publication of the American College of Allergy, Asthma, & Immunology. 2002 December; 89(6): 561-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12487220

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Failure of sputum eosinophilia after eotaxin inhalation in asthma. Author(s): Bumbacea D, Scheerens J, Mann BS, Stirling RG, Chung KF. Source: Thorax. 2004 May; 59(5): 372-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15115860

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Failure to thrive in a 14-month-old boy with lymphopenia and eosinophilia. Author(s): Hartel C, Strunk T, Bucsky P, Schultz C. Source: Klinische Padiatrie. 2004 January-February; 216(1): 24-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14747967

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Familial analysis of eosinophilia caused by helminthic parasites. Author(s): Moro-Furlani AM, Krieger H. Source: Genetic Epidemiology. 1992; 9(3): 185-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1521780

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Familial eosinophilia maps to the cytokine gene cluster on human chromosomal region 5q31-q33. Author(s): Rioux JD, Stone VA, Daly MJ, Cargill M, Green T, Nguyen H, Nutman T, Zimmerman PA, Tucker MA, Hudson T, Goldstein AM, Lander E, Lin AY. Source: American Journal of Human Genetics. 1998 October; 63(4): 1086-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9758611

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Familial eosinophilia: a benign disorder? Author(s): Klion AD, Law MA, Riemenschneider W, McMaster ML, Brown MR, Horne M, Karp B, Robinson M, Sachdev V, Tucker E, Turner M, Nutman TB. Source: Blood. 2004 June 1; 103(11): 4050-5. Epub 2004 February 26. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14988154

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Familial eosinophilia: clinical and laboratory results on a U.S. kindred. Author(s): Lin AY, Nutman TB, Kaslow D, Mulvihill JJ, Fontaine L, White BJ, Knutsen T, Theil KS, Raghuprasad PK, Goldstein AM, Tucker MA. Source: American Journal of Medical Genetics. 1998 March 19; 76(3): 229-37. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9508242

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Familial peeling skin syndrome with eosinophilia: clinical, histologic, and ultrastructural study of three cases. Author(s): Janin A, Copin MC, Dubos JP, Rouland V, Delaporte E, Blanchet-Bardon C. Source: Archives of Pathology & Laboratory Medicine. 1996 July; 120(7): 662-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8757472

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Fatal eosinophilia myalgia syndrome in a marrow transplant patient attributed to total parenteral nutrition with a solution containing tryptophan. Author(s): de Oliveira JS, Auerbach SB, Sullivan KM, Sale GE. Source: Bone Marrow Transplantation. 1993 February; 11(2): 163-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8435665

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Fever, cough, pleuritic chest pain, and pleural fluid eosinophilia in a 30-year-old man. Author(s): Mortara L, Bayer AS. Source: Chest. 1994 March; 105(3): 918-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8131564

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Fever, lymphadenopathy, eosinophilia, lymphocytosis, hepatitis, and dermatitis. Author(s): Shapiro LE, Knowles SR, Shear NH. Source: Journal of the American Academy of Dermatology. 1998 January; 38(1): 132-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9448227

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Fever, lymphadenopathy, eosinophilia, lymphocytosis, hepatitis, and dermatitis: a severe adverse reaction to minocycline. Author(s): MacNeil M, Haase DA, Tremaine R, Marrie TJ. Source: Journal of the American Academy of Dermatology. 1997 February; 36(2 Pt 2): 347-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9039216

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Fever, refusal to walk and eosinophilia in a ten-month-old Samoan boy. Author(s): Maurer DM, Greene JP, Vincent JM, Demers DM, Pedersen RC, Sitenga NH, Burton BS. Source: The Pediatric Infectious Disease Journal. 2001 February; 20(2): 230-1, 232-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11224853

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Fibrogenic growth factors in the eosinophilia-myalgia syndrome and the toxic oil syndrome. Author(s): Kaufman LD, Gruber BL, Gomez-Reino JJ, Miller F. Source: Archives of Dermatology. 1994 January; 130(1): 41-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8285738

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Fibromyalgia, psychiatric disorders, and assessment of the longterm outcome of eosinophilia-myalgia syndrome. Author(s): Hudson JI, Pope HG Jr, Carter WP, Daniels SR. Source: J Rheumatol Suppl. 1996 October; 46: 37-42; Discussion 42-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8895180

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Fluconazole-induced agranulocytosis with eosinophilia. Author(s): Wong-Beringer A, Shriner K. Source: Pharmacotherapy. 2000 April; 20(4): 484-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10772380

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Fludarabine, as well as 2-chlorodeoxyadenosine, can induce eosinophilia during treatment of lymphoid malignancies. Author(s): Larfars G, Uden-Blohme AM, Samuelsson J. Source: British Journal of Haematology. 1996 September; 94(4): 709-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8826898

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Fludarabine-induced eosinophilia: case report. Author(s): Voutsadakis IA. Source: Annals of Hematology. 2002 May; 81(5): 292-3. Epub 2002 May 03. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12029541

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Foci of eosinophil-related necrosis in the liver: imaging findings and correlation with eosinophilia. Author(s): Lee WJ, Lim HK, Lim JH, Kim SH, Choi SH, Lee SJ. Source: Ajr. American Journal of Roentgenology. 1999 May; 172(5): 1255-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10227499

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Full thickness eosinophilia in oesophageal leiomyomatosis and idiopathic eosinophilic oesophagitis. A common allergic inflammatory profile? Author(s): Nicholson AG, Li D, Pastorino U, Goldstraw P, Jeffery PK. Source: The Journal of Pathology. 1997 October; 183(2): 233-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9390039

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Gallium uptake in eosinophilia myalgia syndrome. Author(s): Rao MG, Chauhan D, Mengel CE. Source: Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine. 1991 October; 32(10): 2026-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1919750

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Gastrointestinal conditions with eosinophilia. Author(s): Sinharay R. Source: Archives of Internal Medicine. 2004 April 12; 164(7): 805-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15078655

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Gastrointestinal involvement in L-tryptophan (L-Trp) associated eosinophiliamyalgia syndrome (EMS). Author(s): De Schryver-Kecskemeti K, Bennert KW, Cooper GS, Yang P. Source: Digestive Diseases and Sciences. 1992 May; 37(5): 697-701. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1563309

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Generalized exanthema, acute hepatitis with porphyrinuria and eosinophilia. Another clinical feature of Lyme disease? Author(s): Prinz A, Weiss P, Stanek G. Source: Zentralbl Bakteriol Mikrobiol Hyg [a]. 1987 February; 263(3): 389-91. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3591092

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Glial swelling with eosinophilia in human post-mortem brains: a change indicative of plasma extravasation. Author(s): Del Bigio MR, Deck JH, Davidson GS. Source: Acta Neuropathologica. 2000 December; 100(6): 688-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11078221

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Glucocorticosteroid treatment for cerebrospinal fluid eosinophilia in a patient with ventriculoperitonial shunt. Author(s): Tangsinmankong N, Nelson RP Jr, Good RA. Source: Annals of Allergy, Asthma & Immunology : Official Publication of the American College of Allergy, Asthma, & Immunology. 1999 October; 83(4): 341-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10541427

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Glucocorticosteroids inhibit mRNA expression for eotaxin, eotaxin-2, and monocytechemotactic protein-4 in human airway inflammation with eosinophilia. Author(s): Jahnsen FL, Haye R, Gran E, Brandtzaeg P, Johansen FE. Source: Journal of Immunology (Baltimore, Md. : 1950). 1999 August 1; 163(3): 1545-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10415058

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GM-CSF and eosinophil chemotactic factors in an acute lymphoblastic leukemia patient with eosinophilia. Author(s): Kita R, Enokihara H, Nagashima S, Tsunogake S, Yamato H, Saito K, Furusawa S, Shishido H, Fukushima Y, Fukuda T. Source: Acta Haematologica. 1993; 90(3): 144-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8291374

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Gnathostomiasis without eosinophilia led to a 5-year delay in diagnosis. Author(s): Slevogt H, Grobusch MP, Suttorp N. Source: Journal of Travel Medicine : Official Publication of the International Society of Travel Medicine and the Asia Pacific Travel Health Association. 2003 May-June; 10(3): 196. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12757699

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Graft eosinophilia in lung transplantation. Author(s): Yousem SA. Source: Human Pathology. 1992 October; 23(10): 1172-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1398645

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Granulocyte precursor cell studies in Schistosoma mansoni patients with eosinophilia. Author(s): Kamal KA, Skelly RR, Ahmed A. Source: Ann Clin Lab Sci. 1986 November-December; 16(6): 455-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3099624

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Granulocyte/macrophage-colony stimulating factor in allergen-induced rhinitis: cellular localization, relation to tissue eosinophilia and influence of topical corticosteroid. Author(s): Nouri-Aria KT, Masuyama K, Jacobson MR, Rak S, Lowhagen O, Schotman E, Hamid Q, Durham S. Source: International Archives of Allergy and Immunology. 1998 December; 117(4): 24854. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9876226

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Granulocyte-macrophage colony-stimulating factor and interleukin-5 concentrations in premature neonates with eosinophilia. Author(s): Calhoun DA, Sullivan SE, Lunoe M, Du Y, Christensen RD. Source: Journal of Perinatology : Official Journal of the California Perinatal Association. 2000 April-May; 20(3): 166-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10802841

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Granulocyte-macrophage colony-stimulating factor-related eosinophilia and Loeffler's endocarditis. Author(s): Donhuijsen K, Haedicke C, Hattenberger S, Hauswaldt C, Freund M. Source: Blood. 1992 May 15; 79(10): 2798. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1586727

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Granulomatous arteritis with massive eosinophilic leukocyte infiltration and transient peripheral eosinophilia subsequent to transarterial embolization therapy with a gelatin sponge. Author(s): Ishikura H, Sotozaki Y, Adachi H, Sato M, Yoshiki T. Source: Acta Pathol Jpn. 1991 August; 41(8): 618-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1750358

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Head and neck manifestations of eosinophilia-myalgia syndrome. Author(s): Levine B, Lanza DC, Ficco A, Freundlich B. Source: The Annals of Otology, Rhinology, and Laryngology. 1995 February; 104(2): 909. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7857025

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Helminthotoxic capacity of eosinophils in case of eosinophilia. Author(s): Mohamed NH, Makhlouf SA, Fahmy IA, Maklad KM, Makhlouf MA, elHosieny LM. Source: J Egypt Soc Parasitol. 1992 April; 22(1): 253-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1578172

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Hepatitis, hyperglycemia, pleural effusion, eosinophilia, hematuria and proteinuria occurring early in clozapine treatment. Author(s): Thompson J, Chengappa KN, Good CB, Baker RW, Kiewe RP, Bezner J, Schooler NR. Source: International Clinical Psychopharmacology. 1998 March; 13(2): 95-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9669191

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Hepatitis, rash and eosinophilia following trichloroethylene exposure: a case report and speculation on mechanistic similarity to halothane induced hepatitis. Author(s): Bond GR. Source: Journal of Toxicology. Clinical Toxicology. 1996; 34(4): 461-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8699563

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Heterogeneity in expression of cytokine mRNA in freshly isolated peripheral blood eosinophils of patients with cutaneous-disease-associated eosinophilia. Author(s): Hatano Y, Katagiri K, Takayasu S. Source: International Archives of Allergy and Immunology. 1999; 120 Suppl 1: 86-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10529612

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Heterogeneity of interleukin 5 genetic background in atopic dermatitis patients: significant difference between those with blood eosinophilia and normal eosinophil levels. Author(s): Yamamoto N, Sugiura H, Tanaka K, Uehara M. Source: Journal of Dermatological Science. 2003 November; 33(2): 121-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14581138

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High altitude climate therapy reduces peripheral blood T lymphocyte activation, eosinophilia, and bronchial obstruction in children with house-dust mite allergic asthma. Author(s): Simon HU, Grotzer M, Nikolaizik WH, Blaser K, Schoni MH. Source: Pediatric Pulmonology. 1994 May; 17(5): 304-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8058424

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High Eo-CSF activity in T-cell non-Hodgkin's lymphoma with eosinophilia. Author(s): Matsuzaki M, Shimamoto Y, Enokihara H, Yamaguchi M. Source: Clinical and Laboratory Haematology. 1992; 14(3): 251-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1451405

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High prevalence of eosinophilia in growth hormone-deficient children. Author(s): Kawada Y, Yamamoto Y, Noda M, Asayama K, Shirahata A. Source: Pediatrics International : Official Journal of the Japan Pediatric Society. 2001 April; 43(2): 141-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11285065

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High risk of eosinophilia in women treated with clozapine. Author(s): Banov MD, Tohen M, Friedberg J. Source: The Journal of Clinical Psychiatry. 1993 December; 54(12): 466-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8276737

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Histopathologic features of the L-tryptophan-related eosinophilia-myalgia (fasciitis) syndrome. Author(s): Winkelmann RK, Connolly SM, Quimby SR, Griffing WL, Lie JT. Source: Mayo Clinic Proceedings. 1991 May; 66(5): 457-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1709432

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HIV-1 infection and eosinophilia. Author(s): Caterino-de-Araujo A. Source: Immunology Today. 1994 October; 15(10): 498-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7945779

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Host factors and environmental determinants associated with skin test reactivity and eosinophilia in a community-based population study. Author(s): Mensinga TT, Schouten JP, Rijcken B, Weiss ST, van der Lende R. Source: Annals of Epidemiology. 1994 September; 4(5): 382-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7981846

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House dust mite-specific IgE antibodies in induced sputum are associated with sputum eosinophilia in mite-sensitive asthmatics. Author(s): Nahm DH, Kim HY, Park HS. Source: Annals of Allergy, Asthma & Immunology : Official Publication of the American College of Allergy, Asthma, & Immunology. 2000 August; 85(2): 129-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10982220

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House-dust mite allergy and eosinophilia in patients with asthma in Rangoon (Yangon). Author(s): Khin-Maung-U, Aung-Than-Batu. Source: The Journal of Asthma : Official Journal of the Association for the Care of Asthma. 1992; 29(6): 383-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1429392

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Human eotaxin is a specific chemoattractant for eosinophil cells and provides a new mechanism to explain tissue eosinophilia. Author(s): Garcia-Zepeda EA, Rothenberg ME, Ownbey RT, Celestin J, Leder P, Luster AD. Source: Nature Medicine. 1996 April; 2(4): 449-56. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8597956

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Hypereosinophilic syndrome with elevated serum tryptase versus systemic mast cell disease associated with eosinophilia: 2 distinct entities? Author(s): Tefferi A, Pardanani A, Li CY. Source: Blood. 2003 October 15; 102(8): 3073-4; Author Reply 3074. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14527892

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Hyper-IgE, eosinophilia, and immediate cutaneous hypersensitivity to insect antigens in the pruritic papular eruption of human immunodeficiency virus. Author(s): Rosatelli JB, Roselino AM. Source: Archives of Dermatology. 2001 May; 137(5): 672-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11346359

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Hypersensitivity pneumonitis and pulmonary vasculitis with eosinophilia in a patient taking an L-tryptophan preparation. Author(s): Travis WD, Kalafer ME, Robin HS, Luibel FJ. Source: Annals of Internal Medicine. 1990 February 15; 112(4): 301-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2297208

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Hypodense eosinophils and interleukin 5 activity in the blood of patients with the eosinophilia-myalgia syndrome. Author(s): Owen WF Jr, Petersen J, Sheff DM, Folkerth RD, Anderson RJ, Corson JM, Sheffer AL, Austen KF. Source: Proceedings of the National Academy of Sciences of the United States of America. 1990 November; 87(21): 8647-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2236076

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Iatrogenic eosinophilia. Author(s): Koga T, Aizawa H. Source: Archives of Internal Medicine. 2004 January 12; 164(1): 106; Author Reply 106. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14718332

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Idiopathic eosinophilia. Author(s): Suzuki R, Seto M, Nakaura S. Source: The New England Journal of Medicine. 2000 March 2; 342(9): 660; Author Reply 660-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10702059

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Idiopathic eosinophilia. Author(s): Roufosse F, Schandene L, Cogan E. Source: The New England Journal of Medicine. 2000 March 2; 342(9): 660; Author Reply 660-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10702058

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Idiopathic eosinophilia. Author(s): Guitart J. Source: The New England Journal of Medicine. 2000 March 2; 342(9): 659-60; Author Reply 660-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10702057

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IL-13 is sufficient for respiratory syncytial virus G glycoprotein-induced eosinophilia after respiratory syncytial virus challenge. Author(s): Johnson TR, Parker RA, Johnson JE, Graham BS. Source: Journal of Immunology (Baltimore, Md. : 1950). 2003 February 15; 170(4): 203745. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12574374

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Immunocytochemical localization of antigens recognised by tropical pulmonary eosinophilia and individuals with intestinal helminths antisera in microfilaria of Wuchereria bancrofti. Author(s): Alves LC, Brayner FA, Silva LF, Pimentel RC, Rocha A, Peixoto CA. Source: J Submicrosc Cytol Pathol. 2002 April; 34(2): 211-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12117283

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Immunophenotypic normalization of aberrant mast cells accompanies histological remission in imatinib-treated patients with eosinophilia-associated mastocytosis. Author(s): Elliott MA, Pardanani A, Li CY, Tefferi A. Source: Leukemia : Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2004 May; 18(5): 1027-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15014525

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In childhood asthma the degree of allergen-induced T-lymphocyte proliferation is related to serum IgE levels and to blood eosinophilia. Author(s): Silvestri M, Oddera S, Spallarossa D, Frangova Yourukova V, Rossi GA. Source: Annals of Allergy, Asthma & Immunology : Official Publication of the American College of Allergy, Asthma, & Immunology. 2000 April; 84(4): 426-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10795651

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Incidence and significance of peritoneal eosinophilia during peritoneal dialysisrelated peritonitis. Author(s): Fontan MP, Rodriguez-Carmona A, Galed I, Iglesias P, Villaverde P, GarciaUreta E. Source: Perit Dial Int. 2003 September-October; 23(5): 460-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14604198

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Incidence of peripheral blood eosinophilia and the threshold eosinophile count for indicating hypereosinophilia-associated diseases. Author(s): Kobayashi S, Inokuma S, Setoguchi K, Kono H, Abe K. Source: Allergy. 2002 October; 57(10): 950-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12269945

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Increased prostaglandin E2 concentrations and cyclooxygenase-2 expression in asthmatic subjects with sputum eosinophilia. Author(s): Profita M, Sala A, Bonanno A, Riccobono L, Siena L, Melis MR, Di Giorgi R, Mirabella F, Gjomarkaj M, Bonsignore G, Vignola AM. Source: The Journal of Allergy and Clinical Immunology. 2003 October; 112(4): 709-16. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14564348

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Inhibition of T helper 2-type responses, IgE production and eosinophilia by synthetic lipopeptides. Author(s): Akdis CA, Kussebi F, Pulendran B, Akdis M, Lauener RP, Schmidt-Weber CB, Klunker S, Isitmangil G, Hansjee N, Wynn TA, Dillon S, Erb P, Baschang G, Blaser K, Alkan SS. Source: European Journal of Immunology. 2003 October; 33(10): 2717-26. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14515255

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Intense eosinophilia with abnormal ultrastructure as presenting manifestation of acute lymphoblastic leukemia. Author(s): Ghosh K, Hiwase D, Muirhead D. Source: Haematologia. 2000; 30(2): 137-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10839566

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Interleukin-5 messenger RNA expression in peripheral blood mononuclear cells from patients with bronchial asthma and eosinophilia. Author(s): Ishizuka T, Ishizuka T, Iwamae S, Hisada T, Okayama Y, Tsukagoshi H, Dobashi K, Mori M. Source: Allergy and Asthma Proceedings : the Official Journal of Regional and State Allergy Societies. 2002 May-June; 23(3): 175-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12125504

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Interleukin-8 is a chemo-attractant for eosinophils purified from subjects with a blood eosinophilia but not from normal healthy subjects. Author(s): Sehmi R, Cromwell O, Wardlaw AJ, Moqbel R, Kay AB. Source: Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology. 1993 December; 23(12): 1027-36. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10779297

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Investigation of tropical eosinophilia; assessing a strategy based on geographical area. Author(s): Whetham J, Day JN, Armstrong M, Chiodini PL, Whitty CJ. Source: The Journal of Infection. 2003 April; 46(3): 180-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12643868

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Is eosinophilia helpful in diagnosing drug eruptions? Author(s): Berman B, Villa AM. Source: Skinmed. 2002 November-December; 1(2): 147-8. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14673343

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Is sputum eosinophilia a good or poor predictor of benefit from inhaled corticosteroid therapy in asthma? Author(s): Pizzichini MM. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 2002 December; 20(6): 1359-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12503688

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Is there any relationship between eosinophilia myalgia syndrome (EMS) and fibromyalgia syndrome (FMS)? An analysis of clinical and immunological data. Author(s): Barth H, Berg PA, Klein R. Source: Advances in Experimental Medicine and Biology. 1999; 467: 487-96. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10721092

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Isolated cerebrospinal fluid eosinophilia due to Streptococcus bovis meningitis in an infant. Author(s): Al-Arishi H, Frayha HH, Yaneza AL, Al Hifzi IS. Source: International Journal of Infectious Diseases : Ijid : Official Publication of the International Society for Infectious Diseases. 2002 December; 6(4): 323-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12725215

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Juvenile cases of restrictive cardiomyopathy without eosinophilia. Author(s): Izumi T, Masani F, Mitsuma S, Sasagawa Y, Kodama M, Okabe M, Tsuda T, Shibata A. Source: Heart Vessels Suppl. 1990; 5: 77-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2093720

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Juvenile temporal arteritis with eosinophilia: a distinct clinicopathological entity. Author(s): Fujimoto M, Sato S, Hayashi N, Wakugawa M, Tsuchida T, Tamaki K. Source: Dermatology (Basel, Switzerland). 1996; 192(1): 32-5. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8832949

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Kala-azar with peripheral eosinophilia. Author(s): Mishra M, Chaudhary RR. Source: J Assoc Physicians India. 1987 April; 35(4): 319. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3654541

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Kimura's disease (angiolymphoid hyperplasia with eosinophilia) associated with ulcerative colitis. Author(s): Shimamoto C, Takao Y, Hirata I, Ohshiba S. Source: Gastroenterol Jpn. 1993 April; 28(2): 298-303. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8486218

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Kimura's disease (angiolymphoid hyperplasia with eosinophilia) of the tympanic membrane. Author(s): Fitzgerald DC, Shmookler BM. Source: Ear, Nose, & Throat Journal. 1996 February; 75(2): 94-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8714421

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Kimura's disease and angiolymphoid hyperplasia with eosinophilia: clinical and histopathologic differences. Author(s): Chun SI, Ji HG. Source: Journal of the American Academy of Dermatology. 1992 December; 27(6 Pt 1): 954-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1479100

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Kimura's disease and angiolymphoid hyperplasia with eosinophilia: new observations from immunohistochemical studies of lymphocyte markers, endothelial antigens, and granulocyte proteins. Author(s): Helander SD, Peters MS, Kuo TT, Su WP. Source: Journal of Cutaneous Pathology. 1995 August; 22(4): 319-26. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7499571

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Kimura's disease and angiolymphoid hyperplasia with eosinophilia: two distinct histopathological entities. Author(s): Googe PB, Harris NL, Mihm MC Jr. Source: Journal of Cutaneous Pathology. 1987 October; 14(5): 263-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3680714

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Kimura's disease and its relation to angiolymphoid hyperplasia with eosinophilia: report of three cases and review of the literature. Author(s): Iguchi Y, Inoue T, Shimono M, Yamamura T, Shigematsu T, Takahashi S. Source: J Oral Pathol. 1986 March; 15(3): 132-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3084736

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Kimura's disease associated with bronchial asthma presenting eosinophilia and hyperimmunoglobulinemia E which were attenuated by suplatast tosilate (IPD1151T). Author(s): Tsukagoshi H, Nagashima M, Horie T, Oyama T, Yoshii A, Sato T, Iizuka K, Dobashi K, Mori M. Source: Intern Med. 1998 December; 37(12): 1064-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9932643

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Kimura's disease. Involvement of regional lymph nodes and distinction from angiolymphoid hyperplasia with eosinophilia. Author(s): Kuo TT, Shih LY, Chan HL. Source: The American Journal of Surgical Pathology. 1988 November; 12(11): 843-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2461103

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Kinetics of indium-III-labeled eosinophils in two patients with eosinophilia. Author(s): Yamauchi K, Suzuki Y. Source: European Journal of Nuclear Medicine. 1989; 15(5): 274-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2759129

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Kinetics of serum and cellular interleukin-5 in posttreatment eosinophilia of patients with lymphatic filariasis. Author(s): Limaye AP, Ottesen EA, Kumaraswami V, Abrams JS, Regunathan J, Vijayasekaran V, Jayaraman K, Nutman TB. Source: The Journal of Infectious Diseases. 1993 June; 167(6): 1396-400. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8501330

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Kinetics of the development and recovery of the lung from IgE-mediated inflammation: dissociation of pulmonary eosinophilia, lung injury, and eosinophilactive cytokines. Author(s): Shaver JR, Zangrilli JG, Cho SK, Cirelli RA, Pollice M, Hastie AT, Fish JE, Peters SP. Source: American Journal of Respiratory and Critical Care Medicine. 1997 February; 155(2): 442-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9032176

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Late appearance of t(1;19)(q11;q11) in myelodysplastic syndrome associated with dysplastic eosinophilia and pulmonary alveolar proteinosis. Author(s): Ando J, Tamayose K, Sugimoto K, Oshimi K. Source: Cancer Genetics and Cytogenetics. 2002 November; 139(1): 14-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12547151

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Late appearance of t(5;12)(q31;p12) in acute myeloid leukemia associated with eosinophilia. Author(s): Yahata N, Ohyashiki K, Ohyashiki JH, Kimura Y, Miyazawa K, Kodama A, Fukutake K, Toyama K. Source: Cancer Genetics and Cytogenetics. 1998 December; 107(2): 147-50. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9844611

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Latex allergy as a cause of eosinophilia in cerebrospinal fluid in a child with a ventricular shunt. Author(s): Niggemann B, Bauer A, Jendroska K, Wahn U. Source: The Journal of Allergy and Clinical Immunology. 1997 December; 100(6 Pt 1): 849-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9438497

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Levels of soluble IL-2 receptor in plasma from asthmatics. Correlations with blood eosinophilia, lung function, and corticosteroid therapy. Author(s): Lassalle P, Sergant M, Delneste Y, Gosset P, Wallaert B, Zandecki M, Capron A, Joseph M, Tonnel AB. Source: Clinical and Experimental Immunology. 1992 February; 87(2): 266-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1735191

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Local and systemic eosinophilia in patients undergoing endoscopic sinus surgery for chronic rhinosinusitis with and without polyposis. Author(s): Bryson JM, Tasca RA, Rowe-Jones JM. Source: Clinical Otolaryngology and Allied Sciences. 2003 February; 28(1): 55-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12580883

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Local and systemic eosinophilia in patients with carcinoma of the uterine cervix undergoing radiation therapy: correlation with radiation response. Author(s): Dalal BI, Das KC, Dutta TK, Malakar K. Source: Clin Oncol (R Coll Radiol). 1992 January; 4(1): 18-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1736974

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Localisation and distribution of Wuchereria bancrofti antigens recognised by antisera from tropical pulmonary eosinophilia and from individuals with intestinal helminths. Author(s): Peixoto CA, Alves LC, Ferreira Da Silva L, Pires ML, Rocha A. Source: J Submicrosc Cytol Pathol. 2003 January; 35(1): 61-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12762653

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Localized eosinophil degranulation mediates disease in tropical pulmonary eosinophilia. Author(s): O'Bryan L, Pinkston P, Kumaraswami V, Vijayan V, Yenokida G, Rosenberg HF, Crystal R, Ottesen EA, Nutman TB. Source: Infection and Immunity. 2003 March; 71(3): 1337-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12595450

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Localized soft tissue angiomatosis with subsequent development of angiolymphoid hyperplasia with eosinophilia. Author(s): Misago N, Tanaka T, Kodera H, Narisawa Y. Source: The Journal of Dermatology. 1999 January; 26(1): 48-55. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10063213

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Loffler's endocarditis presenting in 2 children as fever with eosinophilia. Author(s): Horenstein MS, Humes R, Epstein ML, Draper D. Source: Pediatrics. 2002 November; 110(5): 1014-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12415045

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Long-term follow-up of patients with diffuse fasciitis and eosinophilia associated with L-tryptophan ingestion. Author(s): Beko E, Pervaiz S, Nanda V, Dhawan S. Source: Cutis; Cutaneous Medicine for the Practitioner. 1993 April; 51(4): 266-70. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8477608

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L-tryptophan and eosinophilia-myalgia syndrome in New Mexico. Author(s): Eidson M, Philen RM, Sewell CM, Voorhees R, Kilbourne EM. Source: Lancet. 1990 March 17; 335(8690): 645-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1969024

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L-tryptophan and eosinophilia-myalgia syndrome. Author(s): Shapiro S. Source: Lancet. 1994 September 17; 344(8925): 817-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7916094

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L-tryptophan and eosinophilia-myalgia syndrome. Author(s): Shapiro S. Source: Lancet. 1994 April 23; 343(8904): 1035-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7909063

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L-tryptophan and the eosinophilia-myalgia syndrome: a clinical and laboratory study. Author(s): McKeon P, Swanwick G, Manley P. Source: Acta Psychiatrica Scandinavica. 1994 December; 90(6): 451-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7892779

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L-tryptophan: eosinophilia-myalgia syndrome. Author(s): D'Arcy PF. Source: Adverse Drug Reactions and Toxicological Reviews. 1995 Spring; 14(1): 37-43. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7612781

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L-tryptophan-induced eosinophilia-myalgia syndrome associated with primary cutaneous malignant fibrous histiocytoma and extraabdominal desmoid tumor. Author(s): Mainetti C, Masouye I, Salomon D, Chavaz P, Saurat JH. Source: Cancer. 1993 November 1; 72(9): 2712-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8402494

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L-tryptophan-related eosinophilia-myalgia syndrome possibly associated with a chronic B-lymphocytic leukemia. Author(s): Bohme A, Wolter M, Hoelzer D. Source: Annals of Hematology. 1998 November; 77(5): 235-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9858150

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Lymphocytic hypophysitis, pustulosis palmaris et plantaris and eosinophilia. Author(s): Yamaguchi T, Abe H, Matsui T, Kaji H, Fukase M, Tamaki N, Chihara K. Source: Intern Med. 1994 March; 33(3): 150-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8061391

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Management of drug rash with eosinophilia and systemic symptoms (DRESS syndrome): an update. Author(s): Tas S, Simonart T. Source: Dermatology (Basel, Switzerland). 2003; 206(4): 353-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12771485

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Marked airway eosinophilia prevents development of airway hyper-responsiveness during an allergic response in IL-5 transgenic mice. Author(s): Kobayashi T, Iijima K, Kita H. Source: Journal of Immunology (Baltimore, Md. : 1950). 2003 June 1; 170(11): 5756-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12759459

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Medullary CD30+ T cell lymphoma with eosinophilia and hyper-IgE supervening during the relentless course of pityriasis lichenoides. Author(s): Hermanns-Le T, Pierard GE. Source: Dermatology (Basel, Switzerland). 2000; 200(2): 170-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10773713

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Meloxicam-induced pulmonary infiltrates with eosinophilia: a case report. Author(s): Karakatsani A, Chroneou A, Koulouris NG, Orphanidou D, Jordanoglou J. Source: Rheumatology (Oxford, England). 2003 September; 42(9): 1112-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12923267

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Metastatic carcinoma presenting with concomitant eosinophilia and thromboembolism. Author(s): Fridlender ZG, Simon HU, Shalit M. Source: The American Journal of the Medical Sciences. 2003 August; 326(2): 98-101. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12920442

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Metastatic squamous cell carcinoma with marked blood eosinophilia and elevated serum interleukin-5 levels. Author(s): Walter R, Joller-Jemelka HI, Salomon F. Source: Experimental Hematology. 2002 January; 30(1): 1-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11823029

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Molecular monitoring of cerebrospinal fluid can predict clinical relapse in acute lymphoblastic leukemia with eosinophilia. Author(s): Nunez CA, Zipf TF, Roberts WM, Medeiros LJ, Hayes K, Bueso-Ramos CE. Source: Archives of Pathology & Laboratory Medicine. 2003 May; 127(5): 601-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12708906

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Montelukast reduces peripheral blood eosinophilia but not tissue eosinophilia or symptoms in a patient with eosinophilic gastroenteritis and esophageal stricture. Author(s): Daikh BE, Ryan CK, Schwartz RH. Source: Annals of Allergy, Asthma & Immunology : Official Publication of the American College of Allergy, Asthma, & Immunology. 2003 January; 90(1): 23-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12546333

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Morphometric analysis of the tumor associated tissue eosinophilia in the oral squamous cell carcinoma using different staining techniques. Author(s): Lorena SC, Dorta RG, Landman G, Nonogaki S, Oliveira DT. Source: Histology and Histopathology. 2003 July; 18(3): 709-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12792882

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Mucocutaneous pustules and erosions associated with ulcerative colitis, sclerosing cholangitis, and peripheral blood eosinophilia. Author(s): Lenczowski JM, Cronquist SD, Turner ML. Source: Journal of the American Academy of Dermatology. 2002 January; 46(1): 107-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11756954

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Nasal allergen provocation induces adhesion molecule expression and tissue eosinophilia in upper and lower airways. Author(s): Braunstahl GJ, Overbeek SE, Kleinjan A, Prins JB, Hoogsteden HC, Fokkens WJ. Source: The Journal of Allergy and Clinical Immunology. 2001 March; 107(3): 469-76. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11240947

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Nasal eosinophilia and IL-5 mRNA expression in seasonal allergic rhinitis induced by natural allergen exposure: effect of topical corticosteroids. Author(s): Masuyama K, Till SJ, Jacobson MR, Kamil A, Cameron L, Juliusson S, Lowhagen O, Kay AB, Hamid QA, Durham SR. Source: The Journal of Allergy and Clinical Immunology. 1998 October; 102(4 Pt 1): 6107. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9802369

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Nasal lavage cytometry in the diagnosis of nonallergic rhinitis with eosinophilia syndrome (NARES). Author(s): Schiavino D, Nucera E, Milani A, Della Corte AM, D'Ambrosio C, Pagliari G, Patriarca G. Source: Allergy and Asthma Proceedings : the Official Journal of Regional and State Allergy Societies. 1997 November-December; 18(6): 363-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9429670

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Neurologic, MR imaging, and MR spectroscopic findings in eosinophilia myalgia syndrome. Author(s): Haseler LJ, Sibbitt WL Jr, Sibbitt RR, Hart BL. Source: Ajnr. American Journal of Neuroradiology. 1998 October; 19(9): 1687-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9802492

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New reciprocal translocation t(6;10) (q27;q11) associated with idiopathic myelofibrosis and eosinophilia. Author(s): Cox MC, Panetta P, Venditti A, Abruzzese E, Del Poeta G, Cantonetti M, Amadori S. Source: Leukemia Research. 2001 April; 25(4): 349-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11248333

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New variant translocation in acute myelomonocytic leukemia with bone marrow eosinophilia. Author(s): Berger R, Dombret H. Source: Cancer Genetics and Cytogenetics. 1992 February; 58(2): 204-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1551091

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Nonasthmatic chronic cough: No effect of treatment with an inhaled corticosteroid in patients without sputum eosinophilia. Author(s): Pizzichini MM, Pizzichini E, Parameswaran K, Clelland L, Efthimiadis A, Dolovich J, Hargreave FE. Source: Can Respir J. 1999 July-August; 6(4): 323-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10463960

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Nonepisodic angioedema associated with eosinophilia: report of 4 cases and review of 33 young female patients reported in Japan. Author(s): Chikama R, Hosokawa M, Miyazawa T, Miura R, Suzuki T, Tagami H. Source: Dermatology (Basel, Switzerland). 1998; 197(4): 321-5. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9873168

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Non-L-tryptophan related eosinophilia-myalgia syndrome with hypoproteinemia and hypoalbuminemia. Author(s): Margolin L. Source: The Journal of Rheumatology. 2003 March; 30(3): 628-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12610828

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Norfloxacin-induced eosinophilia in a cirrhotic patient. Author(s): Mofredj A, Boudjema H, Cadranel JF. Source: The Annals of Pharmacotherapy. 2002 June; 36(6): 1107-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12058709

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On the treatment of the eosinophilia-myalgia syndrome. Author(s): Martinez-Osuna P, Espinoza LR. Source: Archives of Internal Medicine. 1991 June; 151(6): 1239. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2043034

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On-line HPLC-tandem mass spectrometry structural characterization of caseassociated contaminants of L-tryptophan implicated with the onset of eosinophilia myalgia syndrome. Author(s): Williamson BL, Johnson KL, Tomlinson AJ, Gleich GJ, Naylor S. Source: Toxicology Letters. 1998 October 15; 99(2): 139-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9817085

80

Eosinophilia

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Oral and maxillofacial pathology case of the month. Traumatic granuloma (traumatic ulcerative granuloma with stromal eosinophilia). Author(s): Newland JR. Source: Tex Dent J. 2003 June; 120(6): 530, 537. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12861908

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Oral angiolymphoid hyperplasia with eosinophilia. Author(s): Peters E, Altini M, Kola AH. Source: Oral Surg Oral Med Oral Pathol. 1986 January; 61(1): 73-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3456143

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Orally exhaled nitric oxide levels are related to the degree of blood eosinophilia in atopic children with mild-intermittent asthma. Author(s): Silvestri M, Spallarossa D, Frangova Yourukova V, Battistini E, Fregonese B, Rossi GA. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 1999 February; 13(2): 321-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10065675

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Orbital angiolymphoid hyperplasia with eosinophilia. Presentation as chalazion. Author(s): Archer KF, Hurwitz JJ, Heathcote G. Source: Ophthalmic Plastic and Reconstructive Surgery. 1991; 7(3): 208-21. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1911528

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Orbital involvement with angiolymphoid hyperplasia with eosinophilia--a benign condition for the practising ophthalmologist to be aware of. Author(s): Prasad TS, Suresh PS, Rodrigues G, Patel M, Moriarty AP. Source: Eye (London, England). 2000 June; 14 ( Pt 3A): 390-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11027009

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Osteogenesis imperfecta--an incidental diagnosis in a girl with tropical pulmonary eosinophilia. Author(s): Hamide A, Rani U, Prasad N, Dutta TK. Source: J Assoc Physicians India. 1993 September; 41(9): 619-20. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8307938

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Overlap of granulomatous vasculitis and sarcoidosis: presentation with uveitis, eosinophilia, leg ulcers, sinusitis, and past foot drop. Author(s): Petri M, Barr E, Cho K, Farmer E. Source: The Journal of Rheumatology. 1988 July; 15(7): 1171-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3172119

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Overlapping features of diffuse fasciitis with eosinophilia and scleroderma. Author(s): Mituszova M, Judak A, Poor G, Bely M. Source: Clin Exp Rheumatol. 1987 July-September; 5(3): 289-90. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3427843

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Palpable purpura in an asthmatic woman with eosinophilia. Author(s): Kim KH, Alapati U. Source: Archives of Dermatology. 2003 June; 139(6): 803-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12810518

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Peripheral blood eosinophilia in association with sarcoidosis. Author(s): Renston JP, Goldman ES, Hsu RM, Tomashefski JF Jr. Source: Mayo Clinic Proceedings. 2000 June; 75(6): 586-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10852419

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Peripheral eosinophilia and eosinophilic gastroenteritis after pediatric liver transplantation. Author(s): Romero R, Abramowsky CR, Pillen T, Smallwood GA, Heffron TG. Source: Pediatric Transplantation. 2003 December; 7(6): 484-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14870899

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Pleural fluid and serum eosinophilia: association with fluoxetine hydrochloride. Author(s): Behnia M, Dowdeswell I, Vakili S. Source: Southern Medical Journal. 2000 June; 93(6): 611-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10881782

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Pleural fluid eosinophilia with combined pharmacotherapy. Author(s): Chiles C, van Wattum PJ. Source: Psychosomatics. 2003 September-October; 44(5): 436-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12954922

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Positively labeled white blood cell scan with eosinophilia and absence of infection. Author(s): Vasanawala MS, Goris ML. Source: Clinical Nuclear Medicine. 2003 May; 28(5): 389-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12702935

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Presence of peak X and related compounds: the reported contaminant in case related 5-hydroxy-L-tryptophan associated with eosinophilia-myalgia syndrome. Author(s): Johnson KL, Klarskov K, Benson LM, Williamson BL, Gleich GJ, Naylor S. Source: The Journal of Rheumatology. 1999 December; 26(12): 2714-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10606395

82

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Primary biliary cirrhosis presented as peripheral eosinophilia in asymptomatic women with or without elevated alkaline phosphatase. Author(s): Zachou K, Rigopoulou E, Liaskos C, Patsiaoura K, Makri E, Stathakis N, Dalekos GN. Source: European Journal of Gastroenterology & Hepatology. 2004 April; 16(4): 425-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15028978

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Provocation with adenosine 5'-monophosphate, but not methacholine, induces sputum eosinophilia. Author(s): van den Berge M, Kerstjens HA, de Reus DM, Koeter GH, Kauffman HF, Postma DS. Source: Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology. 2004 January; 34(1): 71-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14720265

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Pulmonary infiltrates with eosinophilia syndromes in children. Author(s): Oermann CM, Panesar KS, Langston C, Larsen GL, Menendez AA, Schofield DE, Cosio C, Fan LL. Source: The Journal of Pediatrics. 2000 March; 136(3): 351-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10700692

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Quiz case 3. Traumatic ulcerative granuloma with stromal eosinophilia (TUGSE). Author(s): Littlefield PD, Syms MJ, Holtel MR. Source: Archives of Otolaryngology--Head & Neck Surgery. 2000 May; 126(5): 678, 6823. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10807343

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Rapid remission of severe pruritus from angiolymphoid hyperplasia with eosinophilia by pulsed dye laser therapy. Author(s): Nomura T, Sato-Matsumura KC, Kikuchi T, Abe M, Shimizu H. Source: Clinical and Experimental Dermatology. 2003 November; 28(6): 595-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14616822

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Rapidly evolving adult respiratory distress syndrome with eosinophilia of unknown cause in previously healthy active duty soldiers at an Army training center: report of two cases. Author(s): Giacoppe GN, Degler DA. Source: Military Medicine. 1999 December; 164(12): 911-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10628168

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Re: Lasso-de-la-Vega et al. gabapentin as a probable cause of hepatotoxicity and eosinophilia. Author(s): Hauben M. Source: The American Journal of Gastroenterology. 2002 August; 97(8): 2156-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12190207

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Recurrent angiolymphoid hyperplasia with eosinophilia mimicking temporal arteritis associated with nephrotic syndrome. Author(s): Sandstad E, Aksnes H, Sund S, Reinholt FP. Source: Clinical Nephrology. 2003 March; 59(3): 206-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12653265

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Recurrent central nervous system acute lymphoblastic leukemia associated with cerebrospinal fluid eosinophilia and basophilia: a proposed cytokine-mediated mechanism. Author(s): Fasipe F, Bestak M, Green NS. Source: Pediatric Hematology and Oncology. 2003 January-February; 20(1): 31-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12687751

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Recurrent eosinophilic cystitis with peripheral eosinophilia and hyperimmunoglobulinemia E. Author(s): Matsuura H, Sakurai M, Arima K. Source: Urologia Internationalis. 2003; 70(4): 327-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12740501

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Relationship between cutaneous allergen response and airway allergen-induced eosinophilia. Author(s): Boulay ME, Lemieux MC, Deschesnes F, Boulet LP. Source: Allergy. 2003 September; 58(9): 945-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12911426

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Relationship between exhaled NO, respiratory symptoms, lung function, bronchial hyperresponsiveness, and blood eosinophilia in school children. Author(s): Steerenberg PA, Janssen NA, de Meer G, Fischer PH, Nierkens S, van Loveren H, Opperhuizen A, Brunekreef B, van Amsterdam JG. Source: Thorax. 2003 March; 58(3): 242-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12612304

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Remitting fasciitis without eosinophilia: a new disease entity? A case report. Author(s): Ohno M, Nagaoka S, Onari K, Kitamura H, Hachiya M, Kondo S, Ishigatsubo Y. Source: Rheumatology (Oxford, England). 2001 December; 40(12): 1428-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11752527

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Rigorous new approach to constructing a gold standard for validating new diagnostic criteria, as exemplified by the eosinophilia-myalgia syndrome. Author(s): Hertzman PA, Clauw DJ, Duffy J, Medsger TA Jr, Feinstein AR. Source: Archives of Internal Medicine. 2001 October 22; 161(19): 2301-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11606145

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Sclerosing mucoepidermoid carcinoma with eosinophilia of the thyroid: a case report and review of the literature. Author(s): Shehadeh NJ, Vernick J, Lonardo F, Madan SK, Jacobs JR, Yoo GH, Kim HE, Ensley JF. Source: American Journal of Otolaryngology. 2004 January-February; 25(1): 48-53. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15011206

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Sclerosing mucoepidermoid carcinoma with eosinophilia of the thyroid--a case report. Author(s): Sharma K, Nigam S, Khurana N, Chaturvedi KU. Source: Indian J Pathol Microbiol. 2003 October; 46(4): 660-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15025372

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Second-hand smoke increases bronchial hyperreactivity and eosinophilia in a murine model of allergic aspergillosis. Author(s): Seymour BW, Schelegle ES, Pinkerton KE, Friebertshauser KE, Peake JL, Kurupd VP, Coffman RL, Gershwin LJ. Source: Clinical & Developmental Immunology. 2003 March; 10(1): 35-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14575156

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Severe eosinophilia during the course of toxic shock syndrome. Author(s): Ozaras R, Mert A, Tabak F, Bilir M, Ozturk R. Source: Southern Medical Journal. 2003 July; 96(7): 727-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12940337

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Smoking and atopy as determinants of sputum eosinophilia and bronchial hyperresponsiveness in adults with normal lung function. Author(s): Petays T, von Hertzen L, Metso T, Rytila P, Jousilahti P, Helenius I, Vartiainen E, Haahtela T. Source: Respiratory Medicine. 2003 August; 97(8): 947-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12924523

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Sputum eosinophilia in cough-variant asthma as a predictor of the subsequent development of classic asthma. Author(s): Kim CK, Kim JT, Kang H, Yoo Y, Koh YY. Source: Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology. 2003 October; 33(10): 1409-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14519148

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Stromal eosinophilia in colonic epithelial neoplasms. Author(s): Moezzi J, Gopalswamy N, Haas RJ Jr, Markert RJ, Suryaprasad S, Bhutani MS. Source: The American Journal of Gastroenterology. 2000 February; 95(2): 520-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10685761

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Structural characterization of case-associated contaminants peak C and FF in Ltryptophan implicated in eosinophilia-myalgia syndrome. Author(s): Naylor S, Williamson BL, Johnson KL, Gleich GJ. Source: Advances in Experimental Medicine and Biology. 1999; 467: 453-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10721088

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Subcutaneous T-cell lymphoma in a child with eosinophilia. Author(s): Taniguchi S, Kono T. Source: The British Journal of Dermatology. 2000 January; 142(1): 183-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10819548

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Successful management of spontaneous pneumothorax during general anaesthesia in a patient with eosinophilia. Author(s): Shah KA, Shetty A, Chaudhari LS. Source: Journal of Postgraduate Medicine. 1998 July-September; 44(3): 70-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10703575

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The development of a clinical syndrome of asymptomatic pancreatitis and eosinophilia after treatment with clozapine in schizophrenia: implications for clinical care, recognition and management. Author(s): Garlipp P, Rosenthal O, Haltenhof H, Machleidt W. Source: Journal of Psychopharmacology (Oxford, England). 2002 December; 16(4): 399400. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12503844

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The relationship between allergen-induced tissue eosinophilia and markers of repair and remodeling in human atopic skin. Author(s): Phipps S, Ying S, Wangoo A, Ong YE, Levi-Schaffer F, Kay AB. Source: Journal of Immunology (Baltimore, Md. : 1950). 2002 October 15; 169(8): 4604-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12370399

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Thyroid sclerosing mucoepidermoid carcinoma with eosinophilia: mimic of Hodgkin disease in nodal metastases. Author(s): Solomon AC, Baloch ZW, Salhany KE, Mandel S, Weber RS, LiVolsi VA. Source: Archives of Pathology & Laboratory Medicine. 2000 March; 124(3): 446-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10705405

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Time-course changes of eosinophil counts in premature infants: no effects of medical manipulation, except erythropoietin treatment, on eosinophilia. Author(s): Ehara A, Takeda Y, Kida T, Mizukami S, Hagisawa M, Yamada Y. Source: Pediatrics International : Official Journal of the Japan Pediatric Society. 2000 February; 42(1): 58-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10703236

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Tissue eosinophilia correlates strongly with poor prognosis in nodular sclerosing Hodgkin's disease, allowing for known prognostic factors. Author(s): von Wasielewski R, Seth S, Franklin J, Fischer R, Hubner K, Hansmann ML, Diehl V, Georgii A. Source: Blood. 2000 February 15; 95(4): 1207-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10666192

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Total and allergen-specific IgE levels in serum reflect blood eosinophilia and fractional exhaled nitric oxide concentrations but not pulmonary functions in allergic asthmatic children sensitized to house dust mites. Author(s): Sacco O, Sale R, Silvestri M, Serpero L, Sabatini F, Raynal ME, Biraghi M, Rossi GA. Source: Pediatric Allergy and Immunology : Official Publication of the European Society of Pediatric Allergy and Immunology. 2003 December; 14(6): 475-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14675476

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Transgenic overexpression of human IL-17E results in eosinophilia, B-lymphocyte hyperplasia, and altered antibody production. Author(s): Kim MR, Manoukian R, Yeh R, Silbiger SM, Danilenko DM, Scully S, Sun J, DeRose ML, Stolina M, Chang D, Van GY, Clarkin K, Nguyen HQ, Yu YB, Jing S, Senaldi G, Elliott G, Medlock ES. Source: Blood. 2002 October 1; 100(7): 2330-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12239140

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Transient eosinophilia by HIV infection. Author(s): Maeda Y, Miyatake J, Naiki Y, Nawata H, Sumimoto Y, Sono H, Sakaguchi M, Matsuda M, Kanamaru A. Source: Annals of Hematology. 2000 February; 79(2): 99-101. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10741924

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Tumor-associated tissue eosinophilia of penile cancer. Author(s): Ono Y, Ozawa M, Tamura Y, Suzuki T, Suzuki K, Kurokawa K, Fukabori Y, Yamanaka H. Source: International Journal of Urology : Official Journal of the Japanese Urological Association. 2002 February; 9(2): 82-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12028296

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Tumour-associated tissue eosinophilia as a prognostic factor in oral squamous cell carcinomas. Author(s): Dorta RG, Landman G, Kowalski LP, Lauris JR, Latorre MR, Oliveira DT. Source: Histopathology. 2002 August; 41(2): 152-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12147093

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Unilateral angiolymphoid hyperplasia with eosinophilia involving the left arm and hand. Author(s): Arnold M, Geilen CC, Coupland SE, Krengel S, Dippel E, Sproder J, Goerdt S, Orfanos CE. Source: Journal of Cutaneous Pathology. 1999 October; 26(9): 436-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10563499

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Unraveling the eosinophilia-myalgia syndrome. Author(s): Silver RM. Source: Archives of Dermatology. 1991 August; 127(8): 1214-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1863082

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Unusual eosinophilia not detected by an automated haematological analyser in a patient with liver cirrhosis. Author(s): Kabutomori O, Iwatani Y. Source: Journal of Clinical Pathology. 1997 November; 50(11): 967-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9462254

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Unusual leukocytosis with eosinophilia by an allergic disease. Author(s): Mohri H, Motomura S, Okubo T. Source: American Journal of Hematology. 1998 January; 57(1): 90-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9423828

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Unusual widespread type of angiolymphoid hyperplasia with eosinophilia mimicking prurigo nodularis. Author(s): Amagai N, Stolar E, Williams CM. Source: The Journal of Dermatology. 1993 October; 20(10): 660-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8277047

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Upper extremity contractures in a patient with eosinophilia-myalgia syndrome. Author(s): Marchman HB, Gleason CB, Shaw JC. Source: Archives of Physical Medicine and Rehabilitation. 1991 November; 72(12): 102930. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1953317

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Urine eosinophilia in bladder cancer. Author(s): Lowe D, Fletcher CD, Carpenter G. Source: Acta Cytol. 1985 March-April; 29(2): 187. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3856989

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Urticaria pigmentosa presenting with massive peripheral eosinophilia. Author(s): Stern RL, Manders SM, Buttress SH, Heymann WR. Source: Pediatric Dermatology. 1997 July-August; 14(4): 284-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9263309

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Urticarial lesions in a child with acute lymphoblastic leukemia and eosinophilia. Author(s): Hill A, Metry D. Source: Pediatric Dermatology. 2003 November-December; 20(6): 502-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14651570

•

Use of cyclosporin A in the eosinophilia myalgia syndrome. Author(s): Clauw DJ, Alloway JA, Katz P. Source: Annals of the Rheumatic Diseases. 1993 January; 52(1): 81-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8427523

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Variant translocation (3;inv(16)) in acute myelomonocytic leukemia with eosinophilia. Author(s): Thompson PW, Lucas GS, Davies MF, Whittaker JA. Source: Cancer Genetics and Cytogenetics. 1991 September; 55(2): 269-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1933831

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Vasculitis with eosinophilia and digital gangrene in a patient with acquired immunodeficiency syndrome. Author(s): Enelow RS, Hussein M, Grant K, Cupps TR, Druckman D, Mortazavi A, Villaflor ST, Glass-Royal M. Source: The Journal of Rheumatology. 1992 November; 19(11): 1813-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1491409

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Ventilation-perfusion scintiscanning in tropical pulmonary eosinophilia. Author(s): Ray D, Jayachandran CA. Source: Chest. 1993 August; 104(2): 497-500. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8339640

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Ventilatory functions in tropical pulmonary eosinophilia. Author(s): Singh RP, Narang RK, Bihari K, Jain VK. Source: J Assoc Physicians India. 1989 December; 37(12): 775-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2636584

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Ventricular cerebrospinal fluid eosinophilia in children with ventriculoperitoneal shunts. Author(s): Tung H, Raffel C, McComb JG. Source: Journal of Neurosurgery. 1991 October; 75(4): 541-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1885971

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Vernal keratoconjunctivitis: evidence for immunoglobulin E-dependent and immunoglobulin E-independent eosinophilia. Author(s): Ono SJ. Source: Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology. 2003 March; 33(3): 279-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12614438

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Vertebral compression and eosinophilia in a child with acute lymphatic leukemia. Author(s): Bjerregaard LL, Rosthooj S. Source: Journal of Pediatric Hematology/Oncology : Official Journal of the American Society of Pediatric Hematology/Oncology. 2002 May; 24(4): 313-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11972103

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Visual loss and eosinophilia after recombinant hepatitis B vaccine. Author(s): Brezin A, Lautier-Frau M, Hamedani M, Rogeaux O, Hoang PL. Source: Lancet. 1993 August 28; 342(8870): 563-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8102709

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Wegener's granulomatosis with peripheral eosinophilia. Atypical variant of a classic disease. Author(s): Krupsky M, Landau Z, Lifschitz-Mercer B, Resnitzky P. Source: Chest. 1993 October; 104(4): 1290-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8404215

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What factors cause bronchial hyperresponsiveness? Airway inflammation and eosinophilia are only part of the puzzle. Author(s): Townley RG. Source: Annals of Allergy, Asthma & Immunology : Official Publication of the American College of Allergy, Asthma, & Immunology. 2003 February; 90(2): 176-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12602661

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Widespread cutaneous vascular papules associated with peripheral blood eosinophilia and prominent inguinal lymphadenopathy. Author(s): Blauvelt A, Cobb MW, Turner ML. Source: Journal of the American Academy of Dermatology. 2000 October; 43(4): 698-700. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11004630

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Zosteriform angiolymphoid hyperplasia with eosinophilia. Author(s): Dowlati B, Nabai H, Mehregan DR, Mehregan DA, Khaleel J. Source: The Journal of Dermatology. 2002 March; 29(3): 178-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11990257

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CHAPTER 2. NUTRITION AND EOSINOPHILIA Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and eosinophilia.

Finding Nutrition Studies on Eosinophilia The National Institutes of Health’s Office of Dietary Supplements (ODS) offers a searchable bibliographic database called the IBIDS (International Bibliographic Information on Dietary Supplements; National Institutes of Health, Building 31, Room 1B29, 31 Center Drive, MSC 2086, Bethesda, Maryland 20892-2086, Tel: 301-435-2920, Fax: 301-480-1845, E-mail: [email protected]). The IBIDS contains over 460,000 scientific citations and summaries about dietary supplements and nutrition as well as references to published international, scientific literature on dietary supplements such as vitamins, minerals, and botanicals.7 The IBIDS includes references and citations to both human and animal research studies. As a service of the ODS, access to the IBIDS database is available free of charge at the following Web address: http://ods.od.nih.gov/databases/ibids.html. After entering the search area, you have three choices: (1) IBIDS Consumer Database, (2) Full IBIDS Database, or (3) Peer Reviewed Citations Only. Now that you have selected a database, click on the “Advanced” tab. An advanced search allows you to retrieve up to 100 fully explained references in a comprehensive format. Type “eosinophilia” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.

7 Adapted from http://ods.od.nih.gov. IBIDS is produced by the Office of Dietary Supplements (ODS) at the National Institutes of Health to assist the public, healthcare providers, educators, and researchers in locating credible, scientific information on dietary supplements. IBIDS was developed and will be maintained through an interagency partnership with the Food and Nutrition Information Center of the National Agricultural Library, U.S. Department of Agriculture.

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The following information is typical of that found when using the “Full IBIDS Database” to search for “eosinophilia” (or a synonym): •

13-cis-retinoic acid-induced eosinophilia following autologous bone marrow transplantation for neuroblastoma. Author(s): Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut, USA. Source: Degar, B A Harrington, R D Rappeport, J M Woolfrey, A E Med-Pediatr-Oncol. 1999 April; 32(4): 308-10 0098-1532

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A rat model presenting eosinophilia in the airways, lung eosinophil activation, and pulmonary hyperreactivity. Author(s): Department of Pharmacology, Medical School, University of Sherbrooke, P.Q., Canada. Source: Carvalho, C Jancar, S Mariano, M Sirois, P Exp-Lung-Res. 1999 June; 25(4): 30316 0190-2148

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Allergen immunotherapy inhibits airway eosinophilia and hyperresponsiveness associated with decreased IL-4 production by lymphocytes in a murine model of allergic asthma. Author(s): Department of Pharmacology and Pathophysiology, Utrecht University, Utrecht, The Netherlands. [email protected] Source: Van Oosterhout, A J Van Esch, B Hofman, G Hofstra, C L Van Ark, I Nijkamp, F P Kapsenberg, M L Savelkoul, H F Weller, F R Am-J-Respir-Cell-Mol-Biol. 1998 October; 19(4): 622-8 1044-1549

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Correlation between blood eosinophilia and airways hyper-responsiveness in rats. Author(s): Beecham Pharmaceuticals Research Division, Epsom, Surrey, UK. Source: Spicer, B A Baker, R Laycock, S M Smith, H Agents-Actions. 1989 January; 26(12): 63-5 0065-4299

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Increased sensitivity to thyroid hormone replacement therapy followed by hyponatremia and eosinophilia in a patient with long-standing young-onset primary hypothyroidism. Author(s): Second Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Fukuoka City, Japan. Source: Fujikawa, M Okamura, K Sato, K Mizokami, T Shiratsuchi, M Fujishima, M JEndocrinol-Invest. 1999 June; 22(6): 476-80 0391-4097

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Inhibition of pulmonary eosinophilia in P-selectin- and ICAM-1-deficient mice. Author(s): Department of Medicine, University of California at San Diego, 92093-0635, USA. [email protected] Source: Broide, D H Sullivan, S Gifford, T Sriramarao, P Am-J-Respir-Cell-Mol-Biol. 1998 February; 18(2): 218-25 1044-1549

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Opposite effects of immunotherapy with ovalbumin and the immunodominant T-cell epitope on airway eosinophilia and hyperresponsiveness in a murine model of allergic asthma. Author(s): Department of Pharmacology and Pathophysiology, Faculty of Pharmacy, Institute of Infectious Diseases and Immunology, Utrecht University, Utrecht, The Netherlands. Source: Janssen, E M Wauben, M H Jonker, E H Hofman, G Van Eden, W Nijkamp, F P Van Oosterhout, A J Am-J-Respir-Cell-Mol-Biol. 1999 July; 21(1): 21-9 1044-1549

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Rapid HPLC screening method for contaminants found in implicated L-tryptophan associated with eosinophilia myalgia syndrome and adulterated rapeseed oil associated with toxic oil syndrome. Author(s): Department of Biochemistry and Molecular Biology, Mayo Clinic Foundation, Rochester, MN 55905, USA. Source: Williamson, B L Tomlinson, A J Hurth, K M Posada de la Paz, M Gleich, G J Naylor, S Biomed-Chromatogr. 1998 Sep-October; 12(5): 255-61 0269-3879

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Reduction of antigen-induced airway hyperreactivity and eosinophilia in ICAM-1deficient mice. Author(s): Department of Immunological Diseases, Research and Development Center, Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, Connecticut 06877, USA. wwolyniec@BI_pharm.com Source: Wolyniec, W W De Sanctis, G T Nabozny, G Torcellini, C Haynes, N Joetham, A Gelfand, E W Drazen, J M Noonan, T C Am-J-Respir-Cell-Mol-Biol. 1998 June; 18(6): 77785 1044-1549

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Regulation of T-helper type 2 cell and airway eosinophilia by transmucosal coadministration of antigen and oligodeoxynucleotides containing CpG motifs. Author(s): First Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan. Source: Shirota, H Sano, K Kikuchi, T Tamura, G Shirato, K Am-J-Respir-Cell-Mol-Biol. 2000 February; 22(2): 176-82 1044-1549

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Schistosoma mansoni induces the synthesis of IL-6 in pulmonary microvascular endothelial cells: role of IL-6 in the control of lung eosinophilia during infection. Author(s): Centre d'Immunologie et de Biologie Parasitaire, Inserm U547, Institut Pasteur de Lille, Lille, France. Source: Angeli, V Faveeuw, C Delerive, P Fontaine, J Barriera, Y Franchimont, N Staels, B Capron, M Trottein, F Eur-J-Immunol. 2001 September; 31(9): 2751-61 0014-2980

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The role of Mac-1 (CD11b/CD18) in antigen-induced airway eosinophilia in mice. Author(s): Speros P. Martel Laboratory of Leukocyte Biology, Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030, USA. [email protected] Source: Kanwar, S Smith, C W Shardonofsky, F R Burns, A R Am-J-Respir-Cell-Mol-Biol. 2001 August; 25(2): 170-7 1044-1549

Federal Resources on Nutrition In addition to the IBIDS, the United States Department of Health and Human Services (HHS) and the United States Department of Agriculture (USDA) provide many sources of information on general nutrition and health. Recommended resources include: •

healthfinder®, HHS’s gateway to health information, including diet and nutrition: http://www.healthfinder.gov/scripts/SearchContext.asp?topic=238&page=0

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The United States Department of Agriculture’s Web site dedicated to nutrition information: www.nutrition.gov

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The Food and Drug Administration’s Web site for federal food safety information: www.foodsafety.gov

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The National Action Plan on Overweight and Obesity sponsored by the United States Surgeon General: http://www.surgeongeneral.gov/topics/obesity/

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The Center for Food Safety and Applied Nutrition has an Internet site sponsored by the Food and Drug Administration and the Department of Health and Human Services: http://vm.cfsan.fda.gov/

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Center for Nutrition Policy and Promotion sponsored by the United States Department of Agriculture: http://www.usda.gov/cnpp/

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Food and Nutrition Information Center, National Agricultural Library sponsored by the United States Department of Agriculture: http://www.nal.usda.gov/fnic/

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Food and Nutrition Service sponsored by the United States Department of Agriculture: http://www.fns.usda.gov/fns/

Additional Web Resources A number of additional Web sites offer encyclopedic information covering food and nutrition. The following is a representative sample: •

AOL: http://search.aol.com/cat.adp?id=174&layer=&from=subcats

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Family Village: http://www.familyvillage.wisc.edu/med_nutrition.html

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Google: http://directory.google.com/Top/Health/Nutrition/

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Healthnotes: http://www.healthnotes.com/

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Open Directory Project: http://dmoz.org/Health/Nutrition/

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Yahoo.com: http://dir.yahoo.com/Health/Nutrition/

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WebMDHealth: http://my.webmd.com/nutrition

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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html

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CHAPTER 3. ALTERNATIVE MEDICINE AND EOSINOPHILIA Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to eosinophilia. 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 eosinophilia 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 “eosinophilia” (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 eosinophilia: •

A syndrome of lymphoblastic lymphoma, eosinophilia, and myeloid hyperplasia/malignancy associated with t(8;13)(p11;q11): description of a distinctive clinicopathologic entity. Author(s): Inhorn RC, Aster JC, Roach SA, Slapak CA, Soiffer R, Tantravahi R, Stone RM. Source: Blood. 1995 April 1; 85(7): 1881-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7661940

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Acute organic brain syndrome due to drug-induced eosinophilia. Author(s): Ng SC, Lee MK, Teh A. Source: Postgraduate Medical Journal. 1989 November; 65(769): 843-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2616421

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Angiolymphoid hyperplasia with eosinophilia. The disease and a comparison of treatment modalities. Author(s): Baum EW, Sams WM Jr, Monheit GD. Source: J Dermatol Surg Oncol. 1982 November; 8(11): 966-70. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6184389

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Autoantibodies in sera from patients with L-tryptophan-associated eosinophiliamyalgia syndrome. Demonstration of unique antigen-antibody specificities. Author(s): Kaufman LD, Varga J, Gomez-Reino JJ, Jimenez S, Targoff IN. Source: Clinical Immunology and Immunopathology. 1995 August; 76(2): 115-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7542184

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B-cell lymphoma associated with eosinophilia. Author(s): Watanabe K, Shinbo T, Kojima M, Naito M, Tanahashi N, Nara M. Source: Cancer. 1989 October 15; 64(8): 1682-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2477132

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Chorea, eosinophilia, and lupus anticoagulant associated with acute lymphoblastic leukemia. Author(s): Schiff DE, Ortega JA. Source: Pediatric Neurology. 1992 November-December; 8(6): 466-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1476578

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Eosinophilia associated with psyllium hydrophilic colloid ingestion. Author(s): Nelson AM, Taubin HL, Frank HD. Source: Jama : the Journal of the American Medical Association. 1980 January 25; 243(4): 329-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7351737

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Eosinophilia-myalgia syndrome case-associated contaminants in commercially available 5-hydroxytryptophan. Author(s): Klarskov K, Johnson KL, Benson LM, Gleich GJ, Naylor S. Source: Advances in Experimental Medicine and Biology. 1999; 467: 461-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10721089

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Hypereosinophilia induced by high-dose intratumoral and peritumoral mistletoe application to a patient with pancreatic carcinoma. Author(s): Huber R, Barth H, Schmitt-Graff A, Klein R. Source: Journal of Alternative and Complementary Medicine (New York, N.Y.). 2000 August; 6(4): 305-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10976976

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Hypereosinophilia, neurologic, and gastrointestinal symptoms after bee-pollen ingestion. Author(s): Lin FL, Vaughan TR, Vandewalker ML, Weber RW. Source: The Journal of Allergy and Clinical Immunology. 1989 April; 83(4): 793-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2708739

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Loffler's endomyocardial fibrosis with eosinophilia in association with acute lymphoblastic leukemia. Author(s): Blatt PM, Rothstein G, Miller HL, Cathey WJ. Source: Blood. 1974 October; 44(4): 489-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4547249

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Lymphoblastic leukemia with marked eosinophilia: a report of two cases. Author(s): Spitzer G, Garson OM. Source: Blood. 1973 September; 42(3): 377-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4516523

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Malignant histiocytosis in a patient presenting with leukocytosis, eosinophilia, and lymph node granuloma. Author(s): Ballard JO, Binder RA, Rath CE, Powell D. Source: Cancer. 1975 May; 35(5): 1444-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1122493

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Marked bone marrow eosinophilia at the time of relapse of acute myeloblastic leukaemia in association with the appearance of translocation t(12;20)(q24;q11). Author(s): Partridge F, Richardson W, Kearns P, Wilcox R, Majumdar G. Source: Leukemia & Lymphoma. 1996 June; 22(1-2): 181-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8724547

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Marked eosinophilia associated with acute lymphoblastic leukemia. Author(s): Rizzo SC, Fontana G, Marini G, Balduini CL. Source: Haematologica. 1976 March; 61(1): 81-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=820600

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Myeloproliferative disorder with profound hypereosinophilia associated with chemotherapy for breast cancer. Author(s): Soffer T, Chan WC, Brynes RK, Vogler WR, O'Neal S. Source: Cancer. 1984 December 1; 54(11): 2356-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6548657

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Persistent eosinophilia in an infant with probable intrauterine exposure to Ltryptophan-containing supplements. Author(s): Hatch DL, Garona JE, Goldman LR, Waller KO.

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Source: Pediatrics. 1991 October; 88(4): 810-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1896288 •

Reduced severity of eosinophilia-myalgia syndrome associated with the consumption of vitamin-containing supplements before illness. Author(s): Hatch DL, Goldman LR. Source: Archives of Internal Medicine. 1993 October 25; 153(20): 2368-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8215741

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Suppression by ingested eicosapentaenoic acid of the increases in nasal mucosal blood flow and eosinophilia of ryegrass-allergic reactions. Author(s): Rangi SP, Serwonska MH, Lenahan GA, Pickett WC, Blake VA, Sample S, Goetzl EJ. Source: The Journal of Allergy and Clinical Immunology. 1990 February; 85(2): 484-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2406326

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Toluene diisocyanate exposure induces laryngo-tracheal eosinophilia, which can be ameliorated by supplementation with antioxidant vitamins in guinea pigs. Author(s): Gu H, Itoh M, Matsuyama N, Hayashi S, Iimura A, Nakamura Y, Miki T, Takeuchi Y. Source: Acta Oto-Laryngologica. 2003 October; 123(8): 965-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14606601

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Treatment of angiolymphoid hyperplasia with eosinophilia. Author(s): Bonnetblanc JM, Bernard P, Malinvaud G. Source: Journal of the American Academy of Dermatology. 1985 October; 13(4): 668-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4078056

Additional Web Resources A number of additional Web sites offer encyclopedic information covering CAM and related topics. The following is a representative sample: •

Alternative Medicine Foundation, Inc.: http://www.herbmed.org/

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AOL: http://search.aol.com/cat.adp?id=169&layer=&from=subcats

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Chinese Medicine: http://www.newcenturynutrition.com/

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drkoop.com: http://www.drkoop.com/InteractiveMedicine/IndexC.html

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

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Google: http://directory.google.com/Top/Health/Alternative/

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Healthnotes: http://www.healthnotes.com/

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MedWebPlus: http://medwebplus.com/subject/Alternative_and_Complementary_Medicine

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Open Directory Project: http://dmoz.org/Health/Alternative/

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HealthGate: http://www.tnp.com/

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WebMDHealth: http://my.webmd.com/drugs_and_herbs

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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html

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Yahoo.com: http://dir.yahoo.com/Health/Alternative_Medicine/

The following is a specific Web list relating to eosinophilia; 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 Angioedema Source: Integrative Medicine Communications; www.drkoop.com Insomnia Source: Integrative Medicine Communications; www.drkoop.com Sleeplessness Source: Integrative Medicine Communications; www.drkoop.com

•

Herbs and Supplements 5-Hydroxytryptophan Source: Healthnotes, Inc.; www.healthnotes.com

General References A good place to find general background information on CAM is the National Library of Medicine. It has prepared within the MEDLINEplus system an information topic page dedicated to complementary and alternative medicine. To access this page, go to the MEDLINEplus site at http://www.nlm.nih.gov/medlineplus/alternativemedicine.html. This Web site provides a general overview of various topics and can lead to a number of general sources.

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CHAPTER 4. PATENTS ON EOSINOPHILIA Overview Patents can be physical innovations (e.g. chemicals, pharmaceuticals, medical equipment) or processes (e.g. treatments or diagnostic procedures). The United States Patent and Trademark Office defines a patent as a grant of a property right to the inventor, issued by the Patent and Trademark Office.8 Patents, therefore, are intellectual property. For the United States, the term of a new patent is 20 years from the date when the patent application was filed. If the inventor wishes to receive economic benefits, it is likely that the invention will become commercially available within 20 years of the initial filing. It is important to understand, therefore, that an inventor’s patent does not indicate that a product or service is or will be commercially available. The patent implies only that the inventor has “the right to exclude others from making, using, offering for sale, or selling” the invention in the United States. While this relates to U.S. patents, similar rules govern foreign patents. In this chapter, we show you how to locate information on patents and their inventors. If you find a patent that is particularly interesting to you, contact the inventor or the assignee for further information. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical patents that use the generic term “eosinophilia” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on eosinophilia, we have not necessarily excluded nonmedical patents in this bibliography.

Patents on Eosinophilia By performing a patent search focusing on eosinophilia, you can obtain information such as the title of the invention, the names of the inventor(s), the assignee(s) or the company that owns or controls the patent, a short abstract that summarizes the patent, and a few excerpts from the description of the patent. The abstract of a patent tends to be more technical in nature, while the description is often written for the public. Full patent descriptions contain much more information than is presented here (e.g. claims, references, figures, diagrams, etc.). We will tell you how to obtain this information later in the chapter. The following is an 8Adapted

from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.

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example of the type of information that you can expect to obtain from a patent search on eosinophilia: •

Activated immunoglobulin Inventor(s): Fukata; Yuriko (Hyogo, JP), Naiki; Mitsuru (Hyogo, JP), Yoshii; Haruo (Hyogo, JP) Assignee(s): Nippon Zoki Pharmaceutical Co., Ltd. (Osaka, JP) Patent Number: 6,627,194 Date filed: August 8, 1996 Abstract: Activated immunoglobulin which is useful as an eosinophilia-suppressing agent, immunomodulating agent, therapeutic agent for autoimmune diseases, anfiinflammatory agent and antiallergic agent is obtained by admixing immunoglobulin with a histamine component and then substantially or completely removing the histamine component. The histamine component may be removed or separated by dialysis, gel filtration, adsorption chromatography, ion exchange chromatography, or affinity chromatography. The method imparts pharmacological activity which is not inherently available in immunoglobulin of the natural type to immunoglobulin. The activated immunoglobulin of the present invention has an immunomodulating action which is clearly different from that of conventional immunosuppressive agents. It is useful as a therapeutic agent for autoimmune diseases such as chronic rheumatoid arthritis, systemic lupus erythematodes and multiple sclerosis as well as for various immunodeficiency syndromes wherein the immune system is not functioning properly. The activated immunoglobulin of the present invention may be also used as a pharmaceutical agent for eosinophilia caused by infectious diseases, parasitic diseases, diseases of respiratory organs, autoimmune diseases, malignant tumors, etc. In addition, the product of the invention may be used as an excellent antiinflammatory agent and antiallergic agent, and so is highly useful as a pharmaceutical. Excerpt(s): The present invention relates to a method for imparting pharmacological activities to immunoglobulin such as eosinophilia-suppressive action, immunomodulating action, therapeutic action for autoimmune disease, antiinflammatory action, antiallergic action, etc. which are not inherent to naturally occurring immunoglobulin. The present invention also relates to activated immunoglobulin obtained by said method and to pharmaceutical compositions containing said activated immunoglobulin. When a foreign substance invades a living organism, various reactions take place in the organism for removing the foreign substance. One of the reactions is the immune reaction whereby a specific protein (antibody) corresponding to the foreign substance (antigen) is produced. The immune reaction is a vital reaction for defending the organism against the invasion of foreign substances such as pathogens and various other proteins, polysaccharides, etc. The nature of the immune reaction is based upon an antigen-antibody reaction in which antibody is bonded to antigen in a specific manner. The main activity of an antibody is a binding activity which is specific to an antigen. When an antigen is in the form of particles such as bacteria, an agglutination reaction due to the formation of cross-linking of the antibody among the particles is induced. When an antigen has toxicity, enzymatic activity, etc., a neutralization reaction due to binding of the antibody or a hemolytic reaction, bacteriolytic reaction, immune adherence reaction, immunophagocytosis, etc. due to activation by binding of an antigen-antibody complex with complement

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components in the blood are induced. These reactions constitute immune response reactions in a living organism against the invasion of a foreign substance. Web site: http://www.delphion.com/details?pn=US06627194__ •

Drug preparation for oral administration Inventor(s): Yamazaki; Yuriko (Katoh-gun, JP), Yoshii; Haruo (Katoh-gun, JP) Assignee(s): Nippon Zoki Pharmaceutical Co., Ltd. (Osaka, JP) Patent Number: 6,187,803 Date filed: January 26, 1998 Abstract: A drug preparation for oral administration containing histamine-added immunoglobulin as an effective component may be used for prevention or treatment of allergic diseases such as bronchial asthma, allergic rhinitis, vasomotor rhinitis, urticaria, chronic eczema and atopic dermatitis; autoimmune diseases such as multiple sclerosis, chronic rheumatoid arthritis and systemic lupus erythematodes; various immunodeficiency syndromes; and also eosinophilia or various inflammatory diseases caused by infectious diseases, parasitic diseases, diseases of respiratory organs, autoimmune diseases, and malignant tumors. The drug preparation which can be administered orally can be taken by patients easier than an injectable preparation without loss of effectiveness. Therefore, the drug preparation for oral administration of the present invention is practical and highly useful. Excerpt(s): The present invention relates to a drug preparation for oral administration containing histamine-added immunoglobulin as an effective component. A complex of immunoglobulin and histamine has been known as a drug preparation, histamineadded immunoglobulin. It restores histamine fixing ability which is lowered in patients suffering from allergy and asthma. Accordingly, histamine-added immunoglobulin is used as an agent for nonspecific hyposensitizing therapy for bronchial asthma, allergic rhinitis, vasomotor rhinitis, and allergic skin diseases such as urticaria, chronic eczema, atopic dermatitis, etc. Histamine-added immunoglobulin also exhibits suppressive action to liberation of histamine. It does not exhibit side effects exhibited by antihistamines and adrenocortical hormones used as symptomatic remedies. It has therefore been widely used as a pharmaceutical agent with high safety. See pages 463 and 464 of "Drugs in Japan, Ethical Drugs," edited by Japan Pharmaceutical Information Center; published by Yakugyo Jiho Co., Ltd., Japan in October 1996. Histamine-added immunoglobulin is administered by a hypodermic injection because it is a proteinic preparation. There has been no report of its pharmaceutical effects by oral administration. Web site: http://www.delphion.com/details?pn=US06187803__

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Method of treating eosinophilia Inventor(s): Coffman; Robert L. (Portola Valley, CA), Rennick; Donna M. (Los Altos, CA) Assignee(s): Schering Corporation (Madison, NJ) Patent Number: 5,096,704 Date filed: July 23, 1990

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Abstract: A method of preventing eosinophilia associated with certain immune disorders is provided. The method comprises administering an effective amount of an antagonist to human interleukin-5. Preferably, the antagonist is a blocking monoclonal antibody specific for human interleukin-5, or a fragment or binding composition derived therefrom. Excerpt(s): The invention relates generally to a method for treating diseases associated with elevated populations of eosinophils, and more particularly, to a method of inhibiting eosinophil production and accumulation by blocking the stimulatory effects of interleukin-5 (IL-5). Eosinophils are white blood cells of the granulocytic lineage. Their normal function appears to be combating parasitic infections, particularly helminthic infections. However, their accumulation in tissues, a condition referred to as eosinophilia, is also associated with several disease states, most notably asthma, e.g. Frigas et al, J. Allergy and Clinical Immunol., Vol. 77, pgs. 527-537 (1986); Gleich, Hospital Practice (Mar. 15, 1988); and Weller, J. Allergy and Clinical Immunol., Vol. 73, pgs. 1-10 (1984). It is believed that the damage to the epithelial lining of the bronchial passages in severe asthmatic attacks is largely caused by the compounds released by degranulating eosinophils. Currently glucocorticoid steroids are the most effective drugs for treating the acute effects of allergic diseases, such as asthma. However, prolonged steroid treatment is associated with many deleterious side effects, Goodman and Gillman, The Pharmacological Basis of Therapeutics, 6th Ed. (MacMillan Publishing Company, New York, 1980). Moreover, the steroids apparently do not affect the production or accumulation of granulocytic cells, such as eosinophils, in the afflicted tissues. The availability of alternative or complementary approaches to the treatment of disorders associated with eosinophilia would have important clinical utility. Web site: http://www.delphion.com/details?pn=US05096704__ •

Method of treatment with IL-9 conjugate Inventor(s): Renauld; Jean Christophe (Kraainem, BE), Richard; Melisande (Brussels, BE), Van Snick; Jacques (Wezembeek-Oppem, BE) Assignee(s): Ludwig Institute for Cancer Research (New York, NY) Patent Number: 6,645,486 Date filed: January 25, 2000 Abstract: The methods of this invention relate to immunizing animals with conjugates of cytokines and a carrier to induce a prolonged high titre antibody response specific for the cytokine. This invention also relates to the treatment of pathological conditions, e.g., eosinophilia and allograft rejection, associated with the production of cytokines, in particular interleukins, e.g., IL-4, IL-5, IL-9, and IL-13, by immunization with the cytokine conjugates or by administration of antibodies specific for the cytokine. This invention also relates to compositions comprising the cytokine conjugates and the conjugates per se. Excerpt(s): This invention relates to methods for making cytokine specific antibodies. This invention also relates to methods for inducing in an animal a high titre antibody response specific for the cytokine. This invention further relates to the treatment of pathological conditions, e.g., eosinophilia, associated with the production of the cytokines. In addition, this invention relates to cytokine conjugates per se and compositions comprising the cytokine conjugates. Cytokines are involved in many biological functions and are major mediators of the immune response. They are

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associated with the initiation and progression of various autoimmune diseases. For example, tumor necrosis factor.alpha. (TNF.alpha.), interferon.gamma. (IFN.gamma.) and interleukin-1 (IL-1) have been associated with diabetes and the destruction of islet cells, the elevated production of Th2 cytokines have been associated with asthma, and interleukin-12 (IL-12) has been associated with rhuematoid arthritis. Interleukin-9 ("IL-9" hereafter), is a glycoprotein which has been isolated from both murine and human cells. See, e.g., U.S. Pat. No. 5,208,218, incorporated by reference. This reference also teaches isolated nucleic acid molecules encoding the protein portion of the molecule, and how to express it. Web site: http://www.delphion.com/details?pn=US06645486__ •

Methods and compositions for inhibiting tumor cell growth Inventor(s): Weller; Peter F. (Wellesley, MA), Wong; David T. W. (Newton, MA) Assignee(s): Beth Israel Deaconess Hospital, Inc. (Boston, MA) Patent Number: 6,264,948 Date filed: December 8, 1998 Abstract: A method of suppressing tumor cell growth, comprising administering to a mammal in need thereof an amount of an inhibitor of eosinophilia sufficient to result in suppression of tumor cell growth is disclosed. Excerpt(s): The invention relates in general to the field of cancer prevention and treatment. The inhibition of malignant cell induction and proliferation is the primary goal of cancer prevention and treatment. Physiological changes that are coincident with the occurrence of cancer may indicate phenomena that are either causative or protective with regard to the development and progression of the disease and are, therefore, of significant interest to clinical researchers. Eosinophils are granulocytic leukocytes with bi-lobed nuclei, named for their property of staining red in eosin dye. Their production from bone marrow stem cells, maturation and activation occur specifically in response to signals mediated by interleukin-5 (Weller, 1991, New England J. Med, 324: 1110-1118). These cells reside largely in epithelium-lined tissues that are in contact with the environment, such as the gastrointestinal- and lower genitourinary tracts, as well as the respiratory epithelium (Devos et al., 1995, J. Leuk. Biol., 57: 813-819; Weller, 1991, supra; Wong et al., 1990, J. Exp. Med., 172: 673-681). Web site: http://www.delphion.com/details?pn=US06264948__

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Murine interleukin-5 receptor Inventor(s): Murata; Yoshiyuki (Shimonoseki, JP), Takagi; Satoshi (Kumamoto, JP), Takatsu; Kiyoshi (301-32, Ishiharamachi, Kumamoto-shi, Kumamoto-ken, JP), Tominaga; Akiro (Kumamoto, JP) Assignee(s): Takatsu; Kiyoshi (JP) Patent Number: 5,453,491 Date filed: September 10, 1991 Abstract: The invention provides an isolated cDNA sequence coding for murine interleukin 5 receptor, murine secretory interleukin 5 receptor, human interleukin 5 receptor, and human secretory interleukin 5 receptor and products including murine

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interleukin 5 receptor, murine secretory interleukin 5 receptor, and human interleukin 5 receptor which are produced using the isolated cDNA sequence. These products may be useful for a therapeutic agent for autoimmune disorders and diseases with eosinophilia in which human IL-5 is believed to be involved. Excerpt(s): The present invention relates to isolated cDNA sequences coding for murine interleukin 5 receptors, murine secretory interleukin 5 receptors and human interleukin 5 recepters and to murine interleukin 5 receptors, murine secretory interleukin 5 receptors and human interleukin 5 receptors which are produced using the isolated cDNA sequences as well as to methods of producing the interleukin 5 receptors. Interleukin 5 (referred to as "IL-5", hereinafter) is a proliferation and differentiation factor for eosinophils and B lineage cells (Immunol. Rev. 102: 29, 107.,1988). It has been known that IL-5 is produced especially by T cells primed with Mycobacterium tuberculosis, parasites or allo-antigens (J. Immunol. 140: 1175, 1988; Nature, 324: 70, 1986). IL-5 has also been known to induce production of IgM class immunoglobulin including anti-DNA antibody. Recently, IL-5 has been suspected of involvement in autoimmune diseases and there is a report that IL-5 is closely associated with eosinophilia accompanied by autoantibody production, fascitis and myositis (Eosinophils, Oxford University Press, 1988). There are two types of IL-5 receptors (referred to as "IL-5R", hereinafter), namely, membrane bound IL-5R and secretory IL5R. Among them, mouse secretory IL-5R is able to bind to human IL-5 and therefore expected to serve as a therapeutic agent for diseases associated with IL-5. Web site: http://www.delphion.com/details?pn=US05453491__ •

Treatment of composition

refractory

Eosinophilia-Myalgia

Syndrome

with

L-tryptophan

Inventor(s): Caston; John C. (108 Cinder Ter., Spartanburg, SC 29302) Assignee(s): none reported Patent Number: 5,185,157 Date filed: May 2, 1990 Abstract: A method of treating a human patient with refractory Eosinophilia Myalgia Syndrome via oral administration of an effective dosage range of from 1000 mg. to 3000 mg. of a pharmaceutical composition, in unit dosage form, comprising a minor amount of a solid or liquid carrier and a major amount of the amino acid, pharmaceutical grade L-tryptophan, or its acid addition salt, with both of the carriers and the amino acid to be selected to exclude the zinc, magnesium, and calcium containing salts as adjuvants. Excerpt(s): This invention relates to the treatment of human Eosinophilia-Myalgia syndrome with selected amino acids. Eosinophilias are naturally occurring components in the mammalian blood which have activities like that of other white blood cells (lymphocytes). Eosinophilia means "an increase of such eosinophils circulating in the blood. The precise function of the eosinophils is not established, but they appear to be a first line of defense against parasitic invasions of the blood stream. They could also play a marked role in allergies and inflammation. Normally, a droplet of blood (e.g. a cubic millimeter) contains as many as 350 eosinophils. In patients with the ailment, EMS, there are 1,000-12,000 eosinophils per cubic millimeter. In the fall of 1989, medical investigators at the Federal Center for Disease Control reported discovery of the reason for a recent outbreak of the rare disease, EMS, apparently, it was linked to at least one source of the nutritional supplement, L-tryptophan, which had become contaminated in

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the manufacturing process. L-tryptophan (L-TTP) (chemically, 1-alpha-aminoindole-3propionic acid) is an essential amino acid, which is normally ingested as a constituent of dietary protein, but is not synthesized by the human body. It was first isolated from the milk protein, casein, early in this century. For many decades, L-tryptophan has been capable of laboratory synthesis by any of several routes, now well known in organic chemistry. Possibly, the once patented synthesis, starting with alpha-ketoglutaric acid phenylhydrazine, is the currently preferred mode of industrial-scale manufacture. Having a single asymmetric carbon atom, (alpha on the side chain), it is normally a mixture of two optically active antipodes. Web site: http://www.delphion.com/details?pn=US05185157__

Patent Applications on Eosinophilia As of December 2000, U.S. patent applications are open to public viewing.9 Applications are patent requests which have yet to be granted. (The process to achieve a patent can take several years.) The following patent applications have been filed since December 2000 relating to eosinophilia: •

Immunomodulating and antiinflammatory agent Inventor(s): Fukata, Yuriko; (Katoh-gun, JP), Yoshii, Haruo; (Katoh-gun, JP) Correspondence: Hollander Law Firm, P.L.C.; Suite 305; 10300 Eaton Place; Fairfax; VA; 22030 Patent Application Number: 20020004058 Date filed: April 23, 2001 Abstract: In the present invention, pharmaceutical compositions containing a histamineadded gamma-globulin as an effective component are used as an immunomodulating agent, a suppressive agent for eosinophilia, and as an antiinflammatory agent. The immunomodulating action is unexpectedly different from the action of conventional immunosuppressive agents. Accordingly, the compositions are useful as a pharmaceutical agent for the therapy of diseases associated with an abnormal immune system such as chronic articular rheumatism, systemic lupus erythematosus, multiple sclerosis, etc. and various types of immunodeficiency syndromes. In addition, the pharmaceutical compositions exhibit suppressive action upon hypereosinophilicity. They may be used as a therapeutic agent for infectious diseases, parasitic diseases, respiratory diseases, autoimmune diseases and eosinophilia caused by malignant tumors. The compositions are excellent antiinflammatory agents. Excerpt(s): This is a continuation-in-part application of application Ser. No. 08/941,565, filed Sep. 30, 1997, which is a divisional of application Ser. No. 08/287,249, filed Aug. 8, 1994, now U.S. Pat. No. 5,780,026, the disclosures of which are herein incorporated by reference in their entireties. The present invention relates to the use of a histamineadded gamma-globulin as pharmaceuticals. More particularly, it relates to an immunomodulating agent, a suppressive agent to hypereosinophilicity and an antiinflammatory agent containing the histamine-added gamma-globulin as an effective component. Histamine-added gamma-globulin restores histamine fixing ability which is lowered in patients suffering from allergy and asthma. It is used as an agent for

9

This has been a common practice outside the United States prior to December 2000.

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nonspecific hyposensitizing therapy for bronchial asthma, allergic rhinitis and allergic skin diseases such as urticaria, chronic eczema, atopic dermatitis, etc. Histamine-added gamma-globulin also exhibits suppressive action to liberation of histamine. It does not exhibit side effects exhibited by antihistamines and adrenocortical hormones used as symptomatic remedies. It has therefore been widely used as a pharmaceutical agent with high safety. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Method for making cytokine specific antibodies and uses thereof Inventor(s): Renauld, Jean Christophe; (Kraainem, BE), Richard, Melisande; (Bruxelles, BE), Van Snick, Jacques; (Wezembeek-Oppem, BE) Correspondence: Fulbright & Jaworski, Llp; 666 Fifth Ave; New York; NY; 10103-3198; US Patent Application Number: 20040028650 Date filed: August 8, 2003 Abstract: The methods of this invention relate to immunizing animals with conjugates of cytokines and a carrier to induce a prolonged high titre antibody response specific for the cytokine. This invention also relates to the treatment of pathological conditions, e.g., eosinophilia and allograft rejection, associated with the production of cytokines, in particular interleukins, e.g., IL-4, IL-5, IL-9, and IL-13, by immunization with the cytokine conjugates or by administration of antibodies specific for the cytokine. This invention also relates to compositions comprising the cytokine conjugates and the conjugates per se. Excerpt(s): This invention relates to methods for making cytokine specific antibodies. This invention also relates to methods for inducing in an animal a high titre antibody response specific for the cytokine. This invention further relates to the treatment of pathological conditions, e.g., eosinophilia, associated with the production of the cytokines. In addition, this invention relates to cytokine conjugates per se and compositions comprising the cytokine conjugates. Cytokines are involved in many biological functions and are major mediators of the immune response. They are associated with the initiation and progression of various autoimnimune diseases. For example, tumor necrosis factor.alpha. (TNF.alpha.), interferon.gamma. (IFN.gamma.) and interleukin-1 (IL-1) have been associated with diabetes and the destruction of islet cells, the elevated production of Th2 cytokines have been associated with asthma, and interleukin-12 (IL-12) has been associated with rhuematoid arthritis. Interleukin-9 ("IL-9" hereafter), is a glycoprotein which has been isolated from both murine and human cells. See, e.g., U.S. Pat. No. 5,208,218, incorporated by reference. This reference also teaches isolated nucleic acid molecules encoding the protein portion of the molecule, and how to express it. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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•

Method for treating inflammatory diseases using heat shock proteins Inventor(s): Gelfand, Erwin W.; (Englewood, CO), Haczku, Angela Francisca; (Princeton Junction, NJ), Lukacs, Katalin Veronika; (London, GB) Correspondence: Lee Crews; Fish & Richardson P.C.; 225 Franklin Street; Boston; MA; 02110-2804; US Patent Application Number: 20020006410 Date filed: August 17, 2001 Abstract: This invention relates to a method to protect a mammal from a disease associated with an inflammatory response, and in particular, from an inflammatory disease characterized by eosinophilia, airway hyperresponsiveness and/or a Th2-type immune response. The method includes administration of a heat shock protein to a mammal having such a disease. Formulations useful in the present method are also disclosed. Excerpt(s): The present invention relates to a method to protect a mammal from inflammatory diseases, and particularly, from diseases characterized by eosinophilia associated with an inflammatory response. Diseases involving inflammation are characterized by the influx of certain cell types and mediators, the presence of which can lead to tissue damage and sometimes death. Diseases involving inflammation are particularly harmful when they afflict the respiratory system, resulting in obstructed breathing, hypoxemia, hypercapnia and lung tissue damage. Obstructive diseases of the airways are characterized by airflow limitation (i.e., airflow obstruction or narrowing) due to constriction of airway smooth muscle, edema and hypersecretion of mucous leading to increased work in breathing, dyspnea, hypoxemia and hypercapnia. While the mechanical properties of the lungs during obstructed breathing are shared between different types of obstructive airway disease, the pathophysiology can differ. A variety of inflammatory agents can provoke airflow limitation including allergens, cold air, exercise, infections and air pollution. In particular, allergens and other agents in allergic or sensitized animals (i.e., antigens and haptens) cause the release of inflammatory mediators that recruit cells involved in inflammation. Such cells include lymphocytes, eosinophils, mast cells, basophils, neutrophils, macrophages, monocytes, fibroblasts and platelets. Inflammation results in airway hyperresponsiveness. A variety of studies have linked the degree, severity and timing of the inflammatory process with the degree of airway hyperresponsiveness. Thus, a common consequence of inflammation is airflow limitation and/or airway hyperresponsiveness. 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 eosinophilia, 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 “eosinophilia” (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 eosinophilia.

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You can also use this procedure to view pending patent applications concerning eosinophilia. 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 5. BOOKS ON EOSINOPHILIA Overview This chapter provides bibliographic book references relating to eosinophilia. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on eosinophilia include the Combined Health Information Database and the National Library of Medicine. Your local medical library also may have these titles available for loan.

Book Summaries: Online Booksellers Commercial Internet-based booksellers, such as Amazon.com and Barnes&Noble.com, offer summaries which have been supplied by each title’s publisher. Some summaries also include customer reviews. Your local bookseller may have access to in-house and commercial databases that index all published books (e.g. Books in Print). IMPORTANT NOTE: Online booksellers typically produce search results for medical and non-medical books. When searching for “eosinophilia” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “eosinophilia” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “eosinophilia” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •

Pulmonary Eosinophilia (Monographs in Developmental Biology) by Farokh Erach Udwadia; ISBN: 3805517394; http://www.amazon.com/exec/obidos/ASIN/3805517394/icongroupinterna

Chapters on Eosinophilia In order to find chapters that specifically relate to eosinophilia, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and eosinophilia using the “Detailed Search” option. Go to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find book chapters, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Book Chapter.” Type “eosinophilia” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on eosinophilia:

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•

Eosinophilia

Eosinophilic Gastroenteritis Source: in Feldman, M.; Friedman, L.S.; Sleisenger, M.H. Sleisenger and Fordtran's Gastrointestinal and Liver Disease: Pathophysiology/Diagnosis/Management. 7th ed. [2-volume set]. St. Louis, MO: Saunders. 2002. p. 1972-1982. Contact: Available from Elsevier. 11830 Westline Industrial Drive, St. Louis, MO 63146. (800) 545-2522. Fax (800) 568-5136. Website: www.us.elsevierhealth.com. PRICE: $229.00 plus shipping and handling. ISBN: 0721689736. Summary: Eosinophilic gastroenteritis is a disease characterized by tissue eosinophilia (an increase in a type of white blood cells) that can involve any layer or layers of the gut wall. This chapter on eosinophilic gastroenteritis is from a comprehensive and authoritative textbook that covers disorders of the gastrointestinal tract, biliary tree, pancreas, and liver, as well as the related topics of nutrition and peritoneal disorders. Topics include definition and incidence; pathogenesis; classification and clinical features; diagnostic considerations; differential diagnosis; treatment options, including diet, antihelminthics, sodium cromoglycate, glucocorticoids and immunosuppressive agents, and surgery; and prognosis. The chapter includes a mini-outline with page citations, illustrations, and extensive references. 4 figures. 1 table. 100 references.

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Diseases of the External Auditory Canal Source: in Canalis, R.F. and Lambert, P.R., eds. Ear: Comprehensive Otology. Philadelphia, PA: Lippincott Williams and Wilkins. 2000. p. 341-357. Contact: Available from Lippincott Williams and Wilkins. P.O. Box 1600, Hagerstown, MD 21741. (800) 638-3030. Fax (301) 223-2300. Website: www.lww.com. PRICE: $179.00 plus shipping and handling. ISBN: 078171558X. Summary: The external auditory canal (EAC) allows sound to reach the tympanic membrane and middle ear and protects those delicate structures. This chapter on diseases of the external auditory canal is from a textbook that offers complete coverage of the field of clinical otology (study of the ear). The book is oriented to serve both the otolaryngology resident as a practical learning tool and the practicing otolaryngologist as an updated reference source of clinical and basic information. This chapter covers the anatomy and physiology of the external auditory canal; hyperceruminosis (production of too much earwax, or cerumen); foreign bodies in the ear canal; dermatologic diseases, including essential pruritis and dermatitis; infectious diseases, including bacteria otitis externa, chronic stenosing external otitis (medial canal fibrosis), otomycosis, malignant external otitis, and furunculosis (acute localized otitis externa); trauma; acquired stenosis; tumor like lesions of the external auditory canal, including herniated temporomandibular joint soft tissue, inflammatory polyp, keratosis obturans, and cholesteatoma of the external auditory canal; benign tumors of the external auditory canal, including skin lesions, seborrheic keratosis, osteoma, exostosis, hemangioma, angiolymphoid hyperplasia with eosinophilia, and ceruminal gland adenoma; and malignant tumors of the external auditory canal, including basal cell carcinoma, squamous cell carcinoma, adenoidcystic carcinoma, and ceruminal gland adenocarcinoma. 24 figures. 1 table. 45 references.

•

Lymphoid Lesions Source: in Regezi, J.A. and Sciubba, J.J. Oral Pathology: Clinical Pathologic Correlations. 3rd ed. Philadelphia, PA: W.B. Saunders Company. 1999. p. 271-287.

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Contact: Available from W.B. Saunders Company. Book Order Fulfillment Department, 6277 Sea Harbor Drive, Orlando, FL 32821-9854. (800) 545-2522. Fax (800) 874-6418. Website: www.wbsaunders.com. PRICE: $63.95. ISBN: 0721677312. Summary: This chapter on lymphoid lesions is from a pathology textbook that presents current concepts of oral and maxillofacial pathology in order to enhance the reader's diagnostic skills through the use of differential diagnosis strategies. The text offers readers detailed guidance of etiology, pathogenesis, clinical features, histopathology, differential diagnosis, and treatment of oral diseases of the mucosa, submucosa, and bone. This chapter covers reactive lesions, including lymphoid hyperplasia, and angiolymphoid hyperplasia with eosinophilia (ALHE); developmental lesions, notably lymphoepithelial cyst; and neoplasms, including lymphoma (Hodgkin's lymphoma, non-Hodgkin's lymphoma, and Burkitt's lymphoma) and myeloma (plasmacytoma). The authors note that important in the discussion of lymphoid lesions involving the oral cavity and adjacent areas is the fact that many lesions, especially those arising in lymph nodes, are capable of simulating malignancy. 18 figures. 4 tables. 32 references.

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CHAPTER 6. PERIODICALS AND NEWS ON EOSINOPHILIA Overview In this chapter, we suggest a number of news sources and present various periodicals that cover eosinophilia.

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

Exhaled nitric oxide not linked to eosinophilia in asthma Source: Reuters Medical News Date: March 21, 2000

•

Early bronchiolitis and eosinophilia point to asthma in later childhood Source: Reuters Medical News Date: January 11, 2000

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•

Leukotriene D4 not tied to airway eosinophilia in asthma Source: Reuters Medical News Date: May 25, 1999

•

IL-5 Increases Airway Responsiveness And Eosinophilia In Asthma Source: Reuters Medical News Date: January 29, 1998

•

Regular Albuterol Use Increases Eosinophilia In Asthmatic Airways Source: Reuters Medical News Date: January 01, 1998

•

Inhaled Leukotriene D4 Induces Airway Eosinophilia In Asthmatics Source: Reuters Medical News Date: April 25, 1997

•

HIV May Induce Eosinophilia Directly Source: Reuters Medical News Date: September 13, 1996 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 “eosinophilia” (or synonyms) into the search box, and click on “Search News.” As this service is technology oriented, you may wish to use it when searching for press releases covering diagnostic procedures or tests. Search Engines Medical news is also available in the news sections of commercial Internet search engines. See the health news page at Yahoo (http://dir.yahoo.com/Health/News_and_Media/), or

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

Academic Periodicals covering Eosinophilia Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to eosinophilia. In addition to these sources, you can search for articles covering eosinophilia 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 7. 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 eosinophilia. 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 eosinophilia. 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 eosinophilia: Diethylcarbamazine •

Systemic - U.S. Brands: Hetrazan http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202192.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.

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APPENDICES

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

NIH Guidelines Commonly referred to as “clinical” or “professional” guidelines, the National Institutes of Health publish physician guidelines for the most common diseases. Publications are available at the following by relevant Institute10: •

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

•

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/

10

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

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•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

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NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.11 Physician-oriented resources provide a wide variety of information related to the biomedical and health sciences, both past and present. The format of these resources varies. Searchable databases, bibliographic citations, full-text articles (when available), archival collections, and images are all available. The following are referenced by the National Library of Medicine:12 •

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

•

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

•

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

11

Remember, for the general public, the National Library of Medicine recommends the databases referenced in MEDLINEplus (http://medlineplus.gov/ or http://www.nlm.nih.gov/medlineplus/databases.html). 12 See http://www.nlm.nih.gov/databases/databases.html.

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•

Toxicology and Environmental Health Information (TOXNET): Databases covering toxicology and environmental health: http://sis.nlm.nih.gov/Tox/ToxMain.html

•

Visible Human Interface: Anatomically detailed, three-dimensional representations of normal male and female human bodies: http://www.nlm.nih.gov/research/visible/visible_human.html

The NLM Gateway13 The NLM (National Library of Medicine) Gateway is a Web-based system that lets users search simultaneously in multiple retrieval systems at the U.S. National Library of Medicine (NLM). It allows users of NLM services to initiate searches from one Web interface, providing one-stop searching for many of NLM’s information resources or databases.14 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “eosinophilia” (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 18306 43 23 37 300 18709

HSTAT15 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.16 These documents include clinical practice guidelines, quickreference guides for clinicians, consumer health brochures, evidence reports and technology assessments from the Agency for Healthcare Research and Quality (AHRQ), as well as AHRQ’s Put Prevention Into Practice.17 Simply search by “eosinophilia” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

13

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

14

The NLM Gateway is currently being developed by the Lister Hill National Center for Biomedical Communications (LHNCBC) at the National Library of Medicine (NLM) of the National Institutes of Health (NIH). 15 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 16 17

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

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

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Coffee Break: Tutorials for Biologists18 Coffee Break is a general healthcare site that takes a scientific view of the news and covers recent breakthroughs in biology that may one day assist physicians in developing treatments. Here you will find a collection of short reports on recent biological discoveries. Each report incorporates interactive tutorials that demonstrate how bioinformatics tools are used as a part of the research process. Currently, all Coffee Breaks are written by NCBI staff.19 Each report is about 400 words and is usually based on a discovery reported in one or more articles from recently published, peer-reviewed literature.20 This site has new articles every few weeks, so it can be considered an online magazine of sorts. It is intended for general background information. You can access the Coffee Break Web site at the following hyperlink: http://www.ncbi.nlm.nih.gov/Coffeebreak/.

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

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

•

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

18 Adapted 19

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

The figure that accompanies each article is frequently supplied by an expert external to NCBI, in which case the source of the figure is cited. The result is an interactive tutorial that tells a biological story. 20 After a brief introduction that sets the work described into a broader context, the report focuses on how a molecular understanding can provide explanations of observed biology and lead to therapies for diseases. Each vignette is accompanied by a figure and hypertext links that lead to a series of pages that interactively show how NCBI tools and resources are used in the research process.

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APPENDIX B. PATIENT RESOURCES Overview Official agencies, as well as federally funded institutions supported by national grants, frequently publish a variety of guidelines written with the patient in mind. These are typically called “Fact Sheets” or “Guidelines.” They can take the form of a brochure, information kit, pamphlet, or flyer. Often they are only a few pages in length. Since new guidelines on eosinophilia 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 eosinophilia. 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 eosinophilia. 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 “eosinophilia”:

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Asthma http://www.nlm.nih.gov/medlineplus/asthma.html Asthma in Children http://www.nlm.nih.gov/medlineplus/asthmainchildren.html COPD http://www.nlm.nih.gov/medlineplus/copdchronicobstructivepulmonarydisease.t ml Dietary Supplements http://www.nlm.nih.gov/medlineplus/dietarysupplements.html Respiratory Diseases http://www.nlm.nih.gov/medlineplus/respiratorydiseases.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 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 eosinophilia. 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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Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to eosinophilia. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with eosinophilia. 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 eosinophilia. 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 “eosinophilia” (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 “eosinophilia”. 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 “eosinophilia” (or synonyms) into the “For these words:” box. You should check back periodically with this database since it is updated every three months.

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The National Organization for Rare Disorders, Inc. The National Organization for Rare Disorders, Inc. has prepared a Web site that provides, at no charge, lists of associations organized by health topic. You can access this database at the following Web site: http://www.rarediseases.org/search/orgsearch.html. Type “eosinophilia” (or a synonym) into the search box, and click “Submit Query.”

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

Preparation Your local public library and medical libraries have interlibrary loan programs with the National Library of Medicine (NLM), one of the largest medical collections in the world. According to the NLM, most of the literature in the general and historical collections of the National Library of Medicine is available on interlibrary loan to any library. If you would like to access NLM medical literature, then visit a library in your area that can request the publications for you.21

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

21

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

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libraries recommended by the National Library of Medicine (sorted alphabetically by name of the U.S. state or Canadian province where the library is located)22: •

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/

22

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

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•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

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•

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

•

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

•

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

•

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

•

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

•

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

•

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

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

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

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

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

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

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

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

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

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

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

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

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

Finding Medical Libraries

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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ONLINE GLOSSARIES The Internet provides access to a number of free-to-use medical dictionaries. The National Library of Medicine has compiled the following list of online dictionaries: •

ADAM Medical Encyclopedia (A.D.A.M., Inc.), comprehensive medical reference: http://www.nlm.nih.gov/medlineplus/encyclopedia.html

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MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp

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Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/

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Multilingual Glossary of Technical and Popular Medical Terms in Eight European Languages (European Commission) - Danish, Dutch, English, French, German, Italian, Portuguese, and Spanish: http://allserv.rug.ac.be/~rvdstich/eugloss/welcome.html

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On-line Medical Dictionary (CancerWEB): http://cancerweb.ncl.ac.uk/omd/

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Rare Diseases Terms (Office of Rare Diseases): http://ord.aspensys.com/asp/diseases/diseases.asp

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Technology Glossary (National Library of Medicine) - Health Care Technology: http://www.nlm.nih.gov/nichsr/ta101/ta10108.htm

Beyond these, MEDLINEplus contains a very patient-friendly encyclopedia covering every aspect of medicine (licensed from A.D.A.M., Inc.). The ADAM Medical Encyclopedia can be accessed at http://www.nlm.nih.gov/medlineplus/encyclopedia.html. ADAM is also available on commercial Web sites such as drkoop.com (http://www.drkoop.com/) and Web MD (http://my.webmd.com/adam/asset/adam_disease_articles/a_to_z/a).

Online Dictionary Directories The following are additional online directories compiled by the National Library of Medicine, including a number of specialized medical dictionaries: •

Medical Dictionaries: Medical & Biological (World Health Organization): http://www.who.int/hlt/virtuallibrary/English/diction.htm#Medical

•

MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html

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Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/

•

Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine

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EOSINOPHILIA DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. 5-Hydroxytryptophan: Precursor of serotonin used as antiepileptic and antidepressant. [NIH] Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Abdominal Pain: Sensation of discomfort, distress, or agony in the abdominal region. [NIH] Aberrant: Wandering or deviating from the usual or normal course. [EU] Ablation: The removal of an organ by surgery. [NIH] Acanthocephala: A phylum of parasitic worms, closely related to tapeworms and containing two genera: Moniliformis, which sometimes infects man, and Macracanthorhynchus, which infects swine. [NIH] Acceptor: A substance which, while normally not oxidized by oxygen or reduced by hydrogen, can be oxidized or reduced in presence of a substance which is itself undergoing oxidation or reduction. [NIH] Acetylcholine: A neurotransmitter. Acetylcholine in vertebrates is the major transmitter at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. It is generally not used as an administered drug because it is broken down very rapidly by cholinesterases, but it is useful in some ophthalmological applications. [NIH] 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] Acute lymphoblastic leukemia: ALL. A quickly progressing disease in which too many immature white blood cells called lymphoblasts are found in the blood and bone marrow. Also called acute lymphocytic leukemia. [NIH] Acute lymphocytic leukemia: ALL. A quickly progressing disease in which too many immature white blood cells called lymphoblasts are found in the blood and bone marrow. Also called acute lymphoblastic leukemia. [NIH] Acute myelogenous leukemia: AML. A quickly progressing disease in which too many immature blood-forming cells are found in the blood and bone marrow. Also called acute myeloid leukemia or acute nonlymphocytic leukemia. [NIH] Acute myeloid leukemia: AML. A quickly progressing disease in which too many immature blood-forming cells are found in the blood and bone marrow. Also called acute myelogenous leukemia or acute nonlymphocytic leukemia. [NIH] Acute nonlymphocytic leukemia: A quickly progressing disease in which too many immature blood-forming cells are found in the blood and bone marrow. Also called acute myeloid leukemia or acute myelogenous leukemia. [NIH] Acute renal: A condition in which the kidneys suddenly stop working. In most cases,

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kidneys can recover from almost complete loss of function. [NIH] Acyl: Chemical signal used by bacteria to communicate. [NIH] Adaptability: Ability to develop some form of tolerance to conditions extremely different from those under which a living organism evolved. [NIH] Adenine: A purine base and a fundamental unit of adenine nucleotides. [NIH] Adenocarcinoma: A malignant epithelial tumor with a glandular organization. [NIH] Adenoma: A benign epithelial tumor with a glandular organization. [NIH] Adenosine: A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. [NIH] Adenosine Deaminase: An enzyme that catalyzes the hydrolysis of adenosine to inosine with the elimination of ammonia. Since there are wide tissue and species variations in the enzyme, it has been used as a tool in the study of human and animal genetics and in medical diagnosis. EC 3.5.4.4. [NIH] Adjuvant: A substance which aids another, such as an auxiliary remedy; in immunology, nonspecific stimulator (e.g., BCG vaccine) of the immune response. [EU] Adoptive Transfer: Form of passive immunization where previously sensitized immunologic agents (cells or serum) are transferred to non-immune recipients. When transfer of cells is used as a therapy for the treatment of neoplasms, it is called adoptive immunotherapy (immunotherapy, adoptive). [NIH] Adrenal Cortex: The outer layer of the adrenal gland. It secretes mineralocorticoids, androgens, and glucocorticoids. [NIH] Adrenergic: Activated by, characteristic of, or secreting epinephrine or substances with similar activity; the term is applied to those nerve fibres that liberate norepinephrine at a synapse when a nerve impulse passes, i.e., the sympathetic fibres. [EU] Adsorption: The condensation of gases, liquids, or dissolved substances on the surfaces of solids. It includes adsorptive phenomena of bacteria and viruses as well as of tissues treated with exogenous drugs and chemicals. [NIH] Adsorptive: It captures volatile compounds by binding them to agents such as activated carbon or adsorptive resins. [NIH] Adverse Effect: An unwanted side effect of treatment. [NIH] 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] Affinity Chromatography: In affinity chromatography, a ligand attached to a column binds specifically to the molecule to be purified. [NIH]

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Agonist: In anatomy, a prime mover. In pharmacology, a drug that has affinity for and stimulates physiologic activity at cell receptors normally stimulated by naturally occurring substances. [EU] Agranulocytosis: A decrease in the number of granulocytes (basophils, eosinophils, and neutrophils). [NIH] Air Pollutants: Substances which pollute the air. [NIH] Airway: A device for securing unobstructed passage of air into and out of the lungs during general anesthesia. [NIH] Alanine: A non-essential amino acid that occurs in high levels in its free state in plasma. It is produced from pyruvate by transamination. It is involved in sugar and acid metabolism, increases immunity, and provides energy for muscle tissue, brain, and the central nervous system. [NIH] Albumin: 1. Any protein that is soluble in water and moderately concentrated salt solutions and is coagulable by heat. 2. Serum albumin; the major plasma protein (approximately 60 per cent of the total), which is responsible for much of the plasma colloidal osmotic pressure and serves as a transport protein carrying large organic anions, such as fatty acids, bilirubin, and many drugs, and also carrying certain hormones, such as cortisol and thyroxine, when their specific binding globulins are saturated. Albumin is synthesized in the liver. Low serum levels occur in protein malnutrition, active inflammation and serious hepatic and renal disease. [EU] Albuterol: A racemic mixture with a 1:1 ratio of the r-isomer, levalbuterol, and s-albuterol. It is a short-acting beta 2-adrenergic agonist with its main clinical use in asthma. [NIH] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alimentary: Pertaining to food or nutritive material, or to the organs of digestion. [EU] Alkaline: Having the reactions of an alkali. [EU] Alkaline Phosphatase: An enzyme that catalyzes the conversion of an orthophosphoric monoester and water to an alcohol and orthophosphate. EC 3.1.3.1. [NIH] Alleles: Mutually exclusive forms of the same gene, occupying the same locus on homologous chromosomes, and governing the same biochemical and developmental process. [NIH] Allergen: An antigenic substance capable of producing immediate-type hypersensitivity (allergy). [EU] Allergic Rhinitis: Inflammation of the nasal mucous membrane associated with hay fever; fits may be provoked by substances in the working environment. [NIH] Allium: A genus of liliaceous herbs containing onions (Allium cepa), garlic (Allium sativum), and others; many produce pungent, often bacteriostatic and physiologically active compounds and are used as food, condiment, and medicament, the latter in traditional medicine. [NIH] Allo: A female hormone. [NIH] Allograft: An organ or tissue transplant between two humans. [NIH] Alopecia: Absence of hair from areas where it is normally present. [NIH] Alpha Particles: Positively charged particles composed of two protons and two neutrons, i.e., helium nuclei, emitted during disintegration of very heavy isotopes; a beam of alpha particles or an alpha ray has very strong ionizing power, but weak penetrability. [NIH] Alternative medicine: Practices not generally recognized by the medical community as

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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] Ameliorated: A changeable condition which prevents the consequence of a failure or accident from becoming as bad as it otherwise would. [NIH] Ameliorating: A changeable condition which prevents the consequence of a failure or accident from becoming as bad as it otherwise would. [NIH] Amine: An organic compound containing nitrogen; any member of a group of chemical compounds formed from ammonia by replacement of one or more of the hydrogen atoms by organic (hydrocarbon) radicals. The amines are distinguished as primary, secondary, and tertiary, according to whether one, two, or three hydrogen atoms are replaced. The amines include allylamine, amylamine, ethylamine, methylamine, phenylamine, propylamine, and many other compounds. [EU] Amino acid: 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 Motifs: Commonly observed structural components of proteins formed by simple combinations of adjacent secondary structures. A commonly observed structure may be composed of a conserved sequence which can be represented by a consensus sequence. [NIH]

Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Ammonia: A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. [NIH] Ampulla: A sac-like enlargement of a canal or duct. [NIH] 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] Analogous: Resembling or similar in some respects, as in function or appearance, but not in origin or development;. [EU] Anaphylatoxins: The family of peptides C3a, C4a, C5a, and C5a des-arginine produced in the serum during complement activation. They produce smooth muscle contraction, mast cell histamine release, affect platelet aggregation, and act as mediators of the local inflammatory process. The order of anaphylatoxin activity from strongest to weakest is C5a, C3a, C4a, and C5a des-arginine. The latter is the so-called "classical" anaphylatoxin but shows no spasmogenic activity though it contains some chemotactic ability. [NIH] Anaplasia: Loss of structural differentiation and useful function of neoplastic cells. [NIH] Anaplastic: A term used to describe cancer cells that divide rapidly and bear little or no resemblance to normal cells. [NIH]

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Anaplastic large cell lymphoma: A rare agressive form of lymphoma (cancer that begins in cells of the lymphatic system) that is usually of T-cell origin. [NIH] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Androgens: A class of sex hormones associated with the development and maintenance of the secondary male sex characteristics, sperm induction, and sexual differentiation. In addition to increasing virility and libido, they also increase nitrogen and water retention and stimulate skeletal growth. [NIH] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Anergic: 1. Characterized by abnormal inactivity; inactive. 2. Marked by asthenia or lack of energy. 3. Pertaining to anergy. [EU] Anergy: Absence of immune response to particular substances. [NIH] Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH] Angioedema: A vascular reaction involving the deep dermis or subcutaneous or submucal tissues, representing localized edema caused by dilatation and increased permeability of the capillaries, and characterized by development of giant wheals. [EU] Angiolymphoid Hyperplasia with Eosinophilia: Solitary or multiple benign cutaneous nodules comprised of immature and mature vascular structures intermingled with endothelial cells and a varied infiltrate of eosinophils, histiocytes, lymphocytes, and mast cells. [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] Anorexia: Lack or loss of appetite for food. Appetite is psychologic, dependent on memory and associations. Anorexia can be brought about by unattractive food, surroundings, or company. [NIH] Antagonism: Interference with, or inhibition of, the growth of a living organism by another living organism, due either to creation of unfavorable conditions (e. g. exhaustion of food supplies) or to production of a specific antibiotic substance (e. g. penicillin). [NIH] Antiallergic: Counteracting allergy or allergic conditions. [EU] Antibacterial: A substance that destroys bacteria or suppresses their growth or reproduction. [EU] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]

Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood

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thinner. [NIH] Antiepileptic: An agent that combats epilepsy. [EU] Antifungal: Destructive to fungi, or suppressing their reproduction or growth; effective against fungal infections. [EU] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Antigen-Antibody Complex: The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes immune complex diseases. [NIH] Antigen-presenting cell: APC. A cell that shows antigen on its surface to other cells of the immune system. This is an important part of an immune response. [NIH] Anti-infective: An agent that so acts. [EU] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Anti-Inflammatory Agents: Substances that reduce or suppress inflammation. [NIH] Antineoplastic: Inhibiting or preventing the development of neoplasms, checking the maturation and proliferation of malignant cells. [EU] Antioxidant: A substance that prevents damage caused by free radicals. Free radicals are highly reactive chemicals that often contain oxygen. They are produced when molecules are split to give products that have unpaired electrons. This process is called oxidation. [NIH] Antipsychotic: Effective in the treatment of psychosis. Antipsychotic drugs (called also neuroleptic drugs and major tranquilizers) are a chemically diverse (including phenothiazines, thioxanthenes, butyrophenones, dibenzoxazepines, dibenzodiazepines, and diphenylbutylpiperidines) but pharmacologically similar class of drugs used to treat schizophrenic, paranoid, schizoaffective, and other psychotic disorders; acute delirium and dementia, and manic episodes (during induction of lithium therapy); to control the movement disorders associated with Huntington's chorea, Gilles de la Tourette's syndrome, and ballismus; and to treat intractable hiccups and severe nausea and vomiting. Antipsychotic agents bind to dopamine, histamine, muscarinic cholinergic, a-adrenergic, and serotonin receptors. Blockade of dopaminergic transmission in various areas is thought to be responsible for their major effects : antipsychotic action by blockade in the mesolimbic and mesocortical areas; extrapyramidal side effects (dystonia, akathisia, parkinsonism, and tardive dyskinesia) by blockade in the basal ganglia; and antiemetic effects by blockade in the chemoreceptor trigger zone of the medulla. Sedation and autonomic side effects (orthostatic hypotension, blurred vision, dry mouth, nasal congestion and constipation) are caused by blockade of histamine, cholinergic, and adrenergic receptors. [EU] Antiviral: Destroying viruses or suppressing their replication. [EU] 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

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mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. [NIH] Arachidonic Acid: An unsaturated, essential fatty acid. It is found in animal and human fat as well as in the liver, brain, and glandular organs, and is a constituent of animal phosphatides. It is formed by the synthesis from dietary linoleic acid and is a precursor in the biosynthesis of prostaglandins, thromboxanes, and leukotrienes. [NIH] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Arteritis: Inflammation of an artery. [NIH] Artery: Vessel-carrying blood from the heart to various parts of the body. [NIH] Articular: Of or pertaining to a joint. [EU] Aspartic: The naturally occurring substance is L-aspartic acid. One of the acidic-amino-acids is obtained by the hydrolysis of proteins. [NIH] Aspartic Acid: One of the non-essential amino acids commonly occurring in the L-form. It is found in animals and plants, especially in sugar cane and sugar beets. It may be a neurotransmitter. [NIH] Aspergillosis: Infections with fungi of the genus Aspergillus. [NIH] Aspirin: A drug that reduces pain, fever, inflammation, and blood clotting. Aspirin belongs to the family of drugs called nonsteroidal anti-inflammatory agents. It is also being studied in cancer prevention. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Asthenia: Clinical sign or symptom manifested as debility, or lack or loss of strength and energy. [NIH] Astringents: Agents, usually topical, that cause the contraction of tissues for the control of bleeding or secretions. [NIH] Asymptomatic: Having no signs or symptoms of disease. [NIH] Atopic: Pertaining to an atopen or to atopy; allergic. [EU] Attenuated: Strain with weakened or reduced virulence. [NIH] Attenuation: Reduction of transmitted sound energy or its electrical equivalent. [NIH] Atypical: Irregular; not conformable to the type; in microbiology, applied specifically to strains of unusual type. [EU] Auditory: Pertaining to the sense of hearing. [EU] Autodigestion: Autolysis; a condition found in disease of the stomach: the stomach wall is digested by the gastric juice. [NIH] Autoimmune disease: A condition in which the body recognizes its own tissues as foreign and directs an immune response against them. [NIH] Autologous: Taken from an individual's own tissues, cells, or DNA. [NIH] Autologous bone marrow transplantation: A procedure in which bone marrow is removed from a person, stored, and then given back to the person after intensive treatment. [NIH]

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Autonomic: Self-controlling; functionally independent. [EU] Autopsy: Postmortem examination of the body. [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] 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] Bacteriostatic: 1. Inhibiting the growth or multiplication of bacteria. 2. An agent that inhibits the growth or multiplication of bacteria. [EU] Bacterium: Microscopic organism which may have a spherical, rod-like, or spiral unicellular or non-cellular body. Bacteria usually reproduce through asexual processes. [NIH] Basal cell carcinoma: A type of skin cancer that arises from the basal cells, small round cells found in the lower part (or base) of the epidermis, the outer layer of the skin. [NIH] Basal cells: Small, round cells found in the lower part (or base) of the epidermis, the outer layer of the skin. [NIH] Basement Membrane: Ubiquitous supportive tissue adjacent to epithelium and around smooth and striated muscle cells. This tissue contains intrinsic macromolecular components such as collagen, laminin, and sulfated proteoglycans. As seen by light microscopy one of its subdivisions is the basal (basement) lamina. [NIH] Basophil: A type of white blood cell. Basophils are granulocytes. [NIH] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]

Benign tumor: A noncancerous growth that does not invade nearby tissue or spread to other parts of the body. [NIH] Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Bile Acids: Acids made by the liver that work with bile to break down fats. [NIH] Bile duct: A tube through which bile passes in and out of the liver. [NIH] Biliary: Having to do with the liver, bile ducts, and/or gallbladder. [NIH] Biliary Tract: The gallbladder and its ducts. [NIH] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biological therapy: Treatment to stimulate or restore the ability of the immune system to fight infection and disease. Also used to lessen side effects that may be caused by some cancer treatments. Also known as immunotherapy, biotherapy, or biological response modifier (BRM) therapy. [NIH] Biomarkers: Substances sometimes found in an increased amount in the blood, other body fluids, or tissues and that may suggest the presence of some types of cancer. Biomarkers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and GI tract cancers), and PSA (prostate cancer). Also called tumor markers. [NIH]

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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] Biosynthesis: The building up of a chemical compound in the physiologic processes of a living organism. [EU] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Bladder: The organ that stores urine. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood Platelets: Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Body Fluids: Liquid components of living organisms. [NIH] Bone Density: The amount of mineral per square centimeter of bone. This is the definition used in clinical practice. Actual bone density would be expressed in grams per milliliter. It is most frequently measured by photon absorptiometry or x-ray computed tomography. [NIH] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bone Marrow Transplantation: The transference of bone marrow from one human or animal to another. [NIH] Bone scan: A technique to create images of bones on a computer screen or on film. A small amount of radioactive material is injected into a blood vessel and travels through the bloodstream; it collects in the bones and is detected by a scanner. [NIH] Bowel: The long tube-shaped organ in the abdomen that completes the process of digestion. There is both a small and a large bowel. Also called the intestine. [NIH] Brachytherapy: A collective term for interstitial, intracavity, and surface radiotherapy. It uses small sealed or partly-sealed sources that may be placed on or near the body surface or within a natural body cavity or implanted directly into the tissues. [NIH] Bradykinin: A nonapeptide messenger that is enzymatically produced from kallidin in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from mast cells during asthma attacks, from gut

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walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter. [NIH] Breeding: The science or art of changing the constitution of a population of plants or animals through sexual reproduction. [NIH] 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] Bronchial Hyperreactivity: Tendency of the smooth muscle of the tracheobronchial tree to contract more intensely in response to a given stimulus than it does in the response seen in normal individuals. This condition is present in virtually all symptomatic patients with asthma. The most prominent manifestation of this smooth muscle contraction is a decrease in airway caliber that can be readily measured in the pulmonary function laboratory. [NIH] Bronchioles: The tiny branches of air tubes in the lungs. [NIH] Bronchiolitis: Inflammation of the bronchioles. [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] Bronchoconstriction: Diminution of the caliber of a bronchus physiologically or as a result of pharmacological intervention. [NIH] Bronchus: A large air passage that leads from the trachea (windpipe) to the lung. [NIH] Buccal: Pertaining to or directed toward the cheek. In dental anatomy, used to refer to the buccal surface of a tooth. [EU] Buffers: A chemical system that functions to control the levels of specific ions in solution. When the level of hydrogen ion in solution is controlled the system is called a pH buffer. [NIH]

Bupropion: A unicyclic, aminoketone antidepressant. The mechanism of its therapeutic actions is not well understood, but it does appear to block dopamine uptake. The hydrochloride is available as an aid to smoking cessation treatment. [NIH] Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. [NIH] Callus: A callosity or hard, thick skin; the bone-like reparative substance that is formed round the edges and fragments of broken bone. [NIH] Capsules: Hard or soft soluble containers used for the oral administration of medicine. [NIH] Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen are usually in the proportion to form water, (CH2O)n. The most important carbohydrates are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, polyand heterosaccharides. [EU]

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Carbon Dioxide: A colorless, odorless gas that can be formed by the body and is necessary for the respiration cycle of plants and animals. [NIH] Carboxy: Cannabinoid. [NIH] 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] Carcinoma: Cancer that begins in the skin or in tissues that line or cover internal organs. [NIH]

Cardiac: Having to do with the heart. [NIH] Cardiomyopathy: A general diagnostic term designating primary myocardial disease, often of obscure or unknown etiology. [EU] 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] Catecholamine: A group of chemical substances manufactured by the adrenal medulla and secreted during physiological stress. [NIH] Causal: Pertaining to a cause; directed against a cause. [EU] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Cell Adhesion: Adherence of cells to surfaces or to other cells. [NIH] Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function which takes place during the development of the embryo and leads to the formation of specialized cells, tissues, and organs. [NIH] Cell Division: The fission of a cell. [NIH] Cell Lineage: The developmental history of cells as traced from the first division of the original cell or cells in the embryo. [NIH] Cell membrane: Cell membrane = plasma membrane. The structure enveloping a cell, enclosing the cytoplasm, and forming a selective permeability barrier; it consists of lipids, proteins, and some carbohydrates, the lipids thought to form a bilayer in which integral proteins are embedded to varying degrees. [EU] Cell proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH] Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH]

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Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebrospinal: Pertaining to the brain and spinal cord. [EU] Cerebrospinal fluid: CSF. The fluid flowing around the brain and spinal cord. Cerebrospinal fluid is produced in the ventricles in the brain. [NIH] Cerebrum: The largest part of the brain. It is divided into two hemispheres, or halves, called the cerebral hemispheres. The cerebrum controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. [NIH] Cerumen: The yellow or brown waxy secretions produced by vestigial apocrine sweat glands in the external ear canal. [NIH] Cervix: The lower, narrow end of the uterus that forms a canal between the uterus and vagina. [NIH] Chalazion: A non-neoplastic cyst of the meibomian glands of the eyelid. [NIH] Chemokines: Class of pro-inflammatory cytokines that have the ability to attract and activate leukocytes. They can be divided into at least three structural branches: C (chemokines, C), CC (chemokines, CC), and CXC (chemokines, CXC), according to variations in a shared cysteine motif. [NIH] Chemotactic Factors: Chemical substances that attract or repel cells or organisms. The concept denotes especially those factors released as a result of tissue injury, invasion, or immunologic activity, that attract leukocytes, macrophages, or other cells to the site of infection or insult. [NIH] Chemotaxis: The movement of cells or organisms toward or away from a substance in response to its concentration gradient. [NIH] Chemotherapy: Treatment with anticancer drugs. [NIH] Chest Pain: Pressure, burning, or numbness in the chest. [NIH] Chest wall: The ribs and muscles, bones, and joints that make up the area of the body between the neck and the abdomen. [NIH] Chimeras: Organism that contains a mixture of genetically different cells. [NIH] Cholangitis: Inflammation of a bile duct. [NIH] Cholesteatoma: A non-neoplastic keratinizing mass with stratified squamous epithelium, frequently occurring in the meninges, central nervous system, bones of the skull, and most commonly in the middle ear and mastoid region. [NIH] Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. [NIH] Cholinergic: Resembling acetylcholine in pharmacological action; stimulated by or releasing acetylcholine or a related compound. [EU] Chondrocytes: Polymorphic cells that form cartilage. [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] Chromatography, Ion Exchange: Separation technique in which the stationary phase consists of ion exchange resins. The resins contain loosely held small ions that easily exchange places with other small ions of like charge present in solutions washed over the resins. [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]

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Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chronic Disease: Disease or ailment of long duration. [NIH] Chronic Obstructive Pulmonary Disease: Collective term for chronic bronchitis and emphysema. [NIH] Cirrhosis: A type of chronic, progressive liver disease. [NIH] CIS: Cancer Information Service. The CIS is the National Cancer Institute's link to the public, interpreting and explaining research findings in a clear and understandable manner, and providing personalized responses to specific questions about cancer. Access the CIS by calling 1-800-4-CANCER, or by using the Web site at http://cis.nci.nih.gov. [NIH] C-kit receptor: A protein on the surface of some cells that binds to stem cell factor (a substance that causes certain types of cells to grow). Altered forms of this receptor may be associated with some types of cancer. [NIH] Clinical Medicine: The study and practice of medicine by direct examination of the patient. [NIH]

Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] Clone: The term "clone" has acquired a new meaning. It is applied specifically to the bits of inserted foreign DNA in the hybrid molecules of the population. Each inserted segment originally resided in the DNA of a complex genome amid millions of other DNA segment. [NIH]

Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH] Clozapine: A tricylic dibenzodiazepine, classified as an atypical antipsychotic agent. It binds several types of central nervous system receptors, and displays a unique pharmacological profile. Clozapine is a serotonin antagonist, with strong binding to 5-HT 2A/2C receptor subtype. It also displays strong affinity to several dopaminergic receptors, but shows only weak antagonism at the dopamine D2 receptor, a receptor commonly thought to modulate neuroleptic activity. Agranulocytosis is a major adverse effect associated with administration of this agent. [NIH] Codon: A set of three nucleotides in a protein coding sequence that specifies individual amino acids or a termination signal (codon, terminator). Most codons are universal, but some organisms do not produce the transfer RNAs (RNA, transfer) complementary to all codons. These codons are referred to as unassigned codons (codons, nonsense). [NIH] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] Cohort Studies: Studies in which subsets of a defined population are identified. These groups may or may not be exposed to factors hypothesized to influence the probability of the occurrence of a particular disease or other outcome. Cohorts are defined populations which, as a whole, are followed in an attempt to determine distinguishing subgroup characteristics. [NIH] Colitis: Inflammation of the colon. [NIH] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is

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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] Collapse: 1. A state of extreme prostration and depression, with failure of circulation. 2. Abnormal falling in of the walls of any part of organ. [EU] Colon: The long, coiled, tubelike organ that removes water from digested food. The remaining material, solid waste called stool, moves through the colon to the rectum and leaves the body through the anus. [NIH] 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 as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Computed tomography: CT scan. A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized tomography and computerized axial tomography (CAT) scan. [NIH]

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Computerized axial tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called CAT scan, computed tomography (CT scan), or computerized tomography. [NIH] Concomitant: Accompanying; accessory; joined with another. [EU] Congestive heart failure: Weakness of the heart muscle that leads to a buildup of fluid in body tissues. [NIH] Conjunctiva: The mucous membrane that lines the inner surface of the eyelids and the anterior part of the sclera. [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] Consciousness: Sense of awareness of self and of the environment. [NIH] Consensus Sequence: A theoretical representative nucleotide or amino acid sequence in which each nucleotide or amino acid is the one which occurs most frequently at that site in the different sequences which occur in nature. The phrase also refers to an actual sequence which approximates the theoretical consensus. A known conserved sequence set is represented by a consensus sequence. Commonly observed supersecondary protein structures (amino acid motifs) are often formed by conserved sequences. [NIH] Conserved Sequence: A sequence of amino acids in a polypeptide or of nucleotides in DNA or RNA that is similar across multiple species. A known set of conserved sequences is represented by a consensus sequence. Amino acid motifs are often composed of conserved sequences. [NIH] Constipation: Infrequent or difficult evacuation of feces. [NIH] Constriction: The act of constricting. [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] Coordination: Muscular or motor regulation or the harmonious cooperation of muscles or groups of muscles, in a complex action or series of actions. [NIH] Cornea: The transparent part of the eye that covers the iris and the pupil and allows light to enter the inside. [NIH] Corneum: The superficial layer of the epidermis containing keratinized cells. [NIH] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Corticosteroid: Any of the steroids elaborated by the adrenal cortex (excluding the sex hormones of adrenal origin) in response to the release of corticotrophin (adrenocorticotropic hormone) by the pituitary gland, to any of the synthetic equivalents of these steroids, or to angiotensin II. They are divided, according to their predominant biological activity, into three major groups: glucocorticoids, chiefly influencing carbohydrate, fat, and protein metabolism; mineralocorticoids, affecting the regulation of electrolyte and water balance; and C19 androgens. Some corticosteroids exhibit both types of activity in varying degrees, and others exert only one type of effect. The corticosteroids are used clinically for hormonal

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replacement therapy, for suppression of ACTH secretion by the anterior pituitary, as antineoplastic, antiallergic, and anti-inflammatory agents, and to suppress the immune response. Called also adrenocortical hormone and corticoid. [EU] Cowpox: A mild, eruptive skin disease of milk cows caused by cowpox virus, with lesions occurring principally on the udder and teats. Human infection may occur while milking an infected animal. [NIH] Cowpox Virus: A species of orthopoxvirus that is the etiologic agent of cowpox. It is closely related to but antigenically different from vaccina virus. [NIH] Critical Care: Health care provided to a critically ill patient during a medical emergency or crisis. [NIH] Cross-Sectional Studies: Studies in which the presence or absence of disease or other health-related variables are determined in each member of the study population or in a representative sample at one particular time. This contrasts with longitudinal studies which are followed over a period of time. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Cutaneous: Having to do with the skin. [NIH] Cyclic: Pertaining to or occurring in a cycle or cycles; the term is applied to chemical compounds that contain a ring of atoms in the nucleus. [EU] Cyclophosphamide: Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the liver to form the active aldophosphamide. It is used in the treatment of lymphomas, leukemias, etc. Its side effect, alopecia, has been made use of in defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer. [NIH] Cyst: A sac or capsule filled with fluid. [NIH] 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] Cysteinyl: Enzyme released by the cell at a crucial stage in apoptosis in order to shred all cellular proteins. [NIH] Cystine: A covalently linked dimeric nonessential amino acid formed by the oxidation of cysteine. Two molecules of cysteine are joined together by a disulfide bridge to form cystine. [NIH]

Cystitis: Inflammation of the urinary bladder. [EU] Cytochrome: Any electron transfer hemoprotein having a mode of action in which the transfer of a single electron is effected by a reversible valence change of the central iron atom of the heme prosthetic group between the +2 and +3 oxidation states; classified as cytochromes a in which the heme contains a formyl side chain, cytochromes b, which contain protoheme or a closely similar heme that is not covalently bound to the protein, cytochromes c in which protoheme or other heme is covalently bound to the protein, and cytochromes d in which the iron-tetrapyrrole has fewer conjugated double bonds than the hemes have. Well-known cytochromes have been numbered consecutively within groups and are designated by subscripts (beginning with no subscript), e.g. cytochromes c, c1, C2, . New cytochromes are named according to the wavelength in nanometres of the absorption maximum of the a-band of the iron (II) form in pyridine, e.g., c-555. [EU] Cytochrome b: Cytochromes (electron-transporting proteins) with protoheme or a related heme as the prosthetic group. The prosthetic group is not covalently bound to the protein moiety. [NIH]

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Cytokine: Small but highly potent protein that modulates the activity of many cell types, including T and B cells. [NIH] Cytomegalovirus: A genus of the family Herpesviridae, subfamily Betaherpesvirinae, infecting the salivary glands, liver, spleen, lungs, eyes, and other organs, in which they produce characteristically enlarged cells with intranuclear inclusions. Infection with Cytomegalovirus is also seen as an opportunistic infection in AIDS. [NIH] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a continuous aqueous solution (cytosol) and the organelles and inclusions suspended in it (phaneroplasm), and is the site of most of the chemical activities of the cell. [EU] Cytoskeleton: The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm. [NIH] Cytotoxic: Cell-killing. [NIH] Decarboxylation: The removal of a carboxyl group, usually in the form of carbon dioxide, from a chemical compound. [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] Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other neurons. [NIH] Dendritic: 1. Branched like a tree. 2. Pertaining to or possessing dendrites. [EU] Dendritic cell: A special type of antigen-presenting cell (APC) that activates T lymphocytes. [NIH]

Dermatitis: Any inflammation of the skin. [NIH] Dermatosis: Any skin disease, especially one not characterized by inflammation. [EU] Dermis: A layer of vascular connective tissue underneath the epidermis. The surface of the dermis contains sensitive papillae. Embedded in or beneath the dermis are sweat glands, hair follicles, and sebaceous glands. [NIH] Desensitization: The prevention or reduction of immediate hypersensitivity reactions by administration of graded doses of allergen; called also hyposensitization and immunotherapy. [EU] Desmoid tumor: A tumor of the tissue that surrounds muscles, usually in the abdomen. Desmoid tumors rarely metastasize. [NIH] Developed Countries: Countries that have reached a level of economic achievement through an increase of production, per capita income and consumption, and utilization of natural and human resources. [NIH] Developing Countries: Countries in the process of change directed toward economic growth, that is, an increase in production, per capita consumption, and income. The process of economic growth involves better utilization of natural and human resources, which results in a change in the social, political, and economic structures. [NIH] 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] Diarrhoea: Abnormal frequency and liquidity of faecal discharges. [EU] Diathesis: A constitution or condition of the body which makes the tissues react in special ways to certain extrinsic stimuli and thus tends to make the person more than usually susceptible to certain diseases. [EU] Diffusion: The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself throughout the available space; a major mechanism of biological transport. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Digestive tract: The organs through which food passes when food is eaten. These organs are the mouth, esophagus, stomach, small and large intestines, and rectum. [NIH] Dihydrotestosterone: Anabolic agent. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Discrete: Made up of separate parts or characterized by lesions which do not become blended; not running together; separate. [NIH] Dissociation: 1. The act of separating or state of being separated. 2. The separation of a molecule into two or more fragments (atoms, molecules, ions, or free radicals) produced by the absorption of light or thermal energy or by solvation. 3. In psychology, a defense mechanism in which a group of mental processes are segregated from the rest of a person's mental activity in order to avoid emotional distress, as in the dissociative disorders (q.v.), or in which an idea or object is segregated from its emotional significance; in the first sense it is roughly equivalent to splitting, in the second, to isolation. 4. A defect of mental integration in which one or more groups of mental processes become separated off from normal consciousness and, thus separated, function as a unitary whole. [EU] Dissociative Disorders: Sudden temporary alterations in the normally integrative functions of consciousness. [NIH] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU] Domesticated: Species in which the evolutionary process has been influenced by humans to meet their needs. [NIH] Dopamine: An endogenous catecholamine and prominent neurotransmitter in several systems of the brain. In the synthesis of catecholamines from tyrosine, it is the immediate precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of dopaminergic receptor subtypes mediate its action. Dopamine is used pharmacologically for its direct (beta adrenergic agonist) and indirect (adrenergic releasing) sympathomimetic effects including its actions as an inotropic agent and as a renal vasodilator. [NIH] Drug Design: The molecular designing of drugs for specific purposes (such as DNAbinding, enzyme inhibition, anti-cancer efficacy, etc.) based on knowledge of molecular properties such as activity of functional groups, molecular geometry, and electronic structure, and also on information cataloged on analogous molecules. Drug design is generally computer-assisted molecular modeling and does not include pharmacokinetics, dosage analysis, or drug administration analysis. [NIH] Drug Eruptions: Adverse cutaneous reactions caused by ingestion, parenteral use, or local

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application of a drug. These may assume various morphologic patterns and produce various types of lesions. [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] Duodenum: The first part of the small intestine. [NIH] Dura mater: The outermost, toughest, and most fibrous of the three membranes (meninges) covering the brain and spinal cord; called also pachymeninx. [EU] Dysphagia: Difficulty in swallowing. [EU] Dyspnea: Difficult or labored breathing. [NIH] Eczema: A pruritic papulovesicular dermatitis occurring as a reaction to many endogenous and exogenous agents (Dorland, 27th ed). [NIH] Edema: Excessive amount of watery fluid accumulated in the intercellular spaces, most commonly present in subcutaneous tissue. [NIH] Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [NIH] Effector cell: A cell that performs a specific function in response to a stimulus; usually used to describe cells in the immune system. [NIH] Efficacy: The extent to which a specific intervention, procedure, regimen, or service produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is based on the results of a randomized control trial. [NIH] Effusion: The escape of fluid into a part or tissue, as an exudation or a transudation. [EU] 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] Elastin: The protein that gives flexibility to tissues. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electrons: Stable elementary particles having the smallest known negative charge, present in all elements; also called negatrons. Positively charged electrons are called positrons. The numbers, energies and arrangement of electrons around atomic nuclei determine the chemical identities of elements. Beams of electrons are called cathode rays or beta rays, the latter being a high-energy biproduct of nuclear decay. [NIH] Emaciation: Clinical manifestation of excessive leanness usually caused by disease or a lack of nutrition. [NIH] Emboli: Bit of foreign matter which enters the blood stream at one point and is carried until it is lodged or impacted in an artery and obstructs it. It may be a blood clot, an air bubble, fat

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or other tissue, or clumps of bacteria. [NIH] Embolization: The blocking of an artery by a clot or foreign material. Embolization can be done as treatment to block the flow of blood to a tumor. [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] 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] Endocytosis: Cellular uptake of extracellular materials within membrane-limited vacuoles or microvesicles. Endosomes play a central role in endocytosis. [NIH] Endogenous: Produced inside an organism or cell. The opposite is external (exogenous) production. [NIH] Endomyocardial Fibrosis: A disease characterized by thickening of the endocardium, and frequently the inner third of the myocardium. The left ventricle is most frequently involved. Cardiomegaly and congestive heart failure may also be present. [NIH] Endoscope: A thin, lighted tube used to look at tissues inside the body. [NIH] Endoscopic: A technique where a lateral-view endoscope is passed orally to the duodenum for visualization of the ampulla of Vater. [NIH] Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart. [NIH] Endothelium: A layer of epithelium that lines the heart, blood vessels (endothelium, vascular), lymph vessels (endothelium, lymphatic), and the serous cavities of the body. [NIH] Endothelium, Lymphatic: Unbroken cellular lining (intima) of the lymph vessels (e.g., the high endothelial lymphatic venules). It is more permeable than vascular endothelium, lacking selective absorption and functioning mainly to remove plasma proteins that have filtered through the capillaries into the tissue spaces. [NIH] Endothelium, Vascular: Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components from interstitium to lumen; this function has been most intensively studied in the blood capillaries. [NIH] Endothelium-derived: Small molecule that diffuses to the adjacent muscle layer and relaxes it. [NIH] 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] Environmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health. [NIH]

Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Eosinophil: A polymorphonuclear leucocyte with large eosinophilic granules in its

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cytoplasm, which plays a role in hypersensitivity reactions. [NIH] Eosinophilic: A condition found primarily in grinding workers caused by a reaction of the pulmonary tissue, in particular the eosinophilic cells, to dust that has entered the lung. [NIH] Eosinophilic Gastroenteritis: Infection and swelling of the lining of the stomach, small intestine, or large intestine. The infection is caused by white blood cells (eosinophils). [NIH] Epidemic: Occurring suddenly in numbers clearly in excess of normal expectancy; said especially of infectious diseases but applied also to any disease, injury, or other healthrelated event occurring in such outbreaks. [EU] Epidemiologic Studies: Studies designed to examine associations, commonly, hypothesized causal relations. They are usually concerned with identifying or measuring the effects of risk factors or exposures. The common types of analytic study are case-control studies, cohort studies, and cross-sectional studies. [NIH] Epidermal: Pertaining to or resembling epidermis. Called also epidermic or epidermoid. [EU] Epidermis: Nonvascular layer of the skin. It is made up, from within outward, of five layers: 1) basal layer (stratum basale epidermidis); 2) spinous layer (stratum spinosum epidermidis); 3) granular layer (stratum granulosum epidermidis); 4) clear layer (stratum lucidum epidermidis); and 5) horny layer (stratum corneum epidermidis). [NIH] Epidermoid carcinoma: A type of cancer in which the cells are flat and look like fish scales. Also called squamous cell carcinoma. [NIH] Epigastric: Having to do with the upper middle area of the abdomen. [NIH] Epinephrine: The active sympathomimetic hormone from the adrenal medulla in most species. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. It is used in asthma and cardiac failure and to delay absorption of local anesthetics. [NIH] Epithelial: Refers to the cells that line the internal and external surfaces of the body. [NIH] Epithelial Cells: Cells that line the inner and outer surfaces of the body. [NIH] Epithelium: One or more layers of epithelial cells, supported by the basal lamina, which covers the inner or outer surfaces of the body. [NIH] Epitope: A molecule or portion of a molecule capable of binding to the combining site of an antibody. For every given antigenic determinant, the body can construct a variety of antibody-combining sites, some of which fit almost perfectly, and others which barely fit. [NIH]

Erythema: Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of causes. [NIH] Erythema Infectiosum: Contagious infection with human B19 Parvovirus most commonly seen in school age children and characterized by fever, headache, and rashes of the face, trunk, and extremities. It is often confused with rubella. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Erythropoietin: Glycoprotein hormone, secreted chiefly by the kidney in the adult and the liver in the fetus, that acts on erythroid stem cells of the bone marrow to stimulate proliferation and differentiation. [NIH] Esophageal: Having to do with the esophagus, the muscular tube through which food passes from the throat to the stomach. [NIH] Esophageal Stricture: A narrowing of the esophagus often caused by acid flowing back

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from the stomach. This condition may require surgery. [NIH] Esophagitis: Inflammation, acute or chronic, of the esophagus caused by bacteria, chemicals, or trauma. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]

Evoke: The electric response recorded from the cerebral cortex after stimulation of a peripheral sense organ. [NIH] Exanthema: Diseases in which skin eruptions or rashes are a prominent manifestation. Classically, six such diseases were described with similar rashes; they were numbered in the order in which they were reported. Only the fourth (Duke's disease), fifth (erythema infectiosum), and sixth (exanthema subitum) numeric designations survive as occasional synonyms in current terminology. [NIH] Exocrine: Secreting outwardly, via a duct. [EU] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] External-beam radiation: Radiation therapy that uses a machine to aim high-energy rays at the cancer. Also called external radiation. [NIH] Extracellular: Outside a cell or cells. [EU] Extracellular Matrix: A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. [NIH] Extracellular Matrix Proteins: Macromolecular organic compounds that contain carbon, hydrogen, oxygen, nitrogen, and usually, sulfur. These macromolecules (proteins) form an intricate meshwork in which cells are embedded to construct tissues. Variations in the relative types of macromolecules and their organization determine the type of extracellular matrix, each adapted to the functional requirements of the tissue. The two main classes of macromolecules that form the extracellular matrix are: glycosaminoglycans, usually linked to proteins (proteoglycans), and fibrous proteins (e.g., collagen, elastin, fibronectins and laminin). [NIH] Extracellular Space: Interstitial space between cells, occupied by fluid as well as amorphous and fibrous substances. [NIH] Extravasation: A discharge or escape, as of blood, from a vessel into the tissues. [EU] Extravascular: Situated or occurring outside a vessel or the vessels. [EU] Extremity: A limb; an arm or leg (membrum); sometimes applied specifically to a hand or foot. [EU] Facial: Of or pertaining to the face. [EU] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Fasciitis: Inflammation of the fascia. There are three major types: 1) Eosinophilic fasciitis, an inflammatory reaction with eosinophilia, producing hard thickened skin with an orangepeel configuration suggestive of scleroderma and considered by some a variant of scleroderma; 2) Necrotizing fasciitis, a serious fulminating infection (usually by a beta hemolytic Streptococcus) causing extensive necrosis of superficial fascia; 3) Nodular/Pseudosarcomatous/Proliferative fasciitis, characterized by a rapid growth of fibroblasts with mononuclear inflammatory cells and proliferating capillaries in soft tissue, often the forearm; it is not malignant but is sometimes mistaken for fibrosarcoma. [NIH]

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Fat: Total lipids including phospholipids. [NIH] Fatigue: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. [NIH]

Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fibroblast Growth Factor: Peptide isolated from the pituitary gland and from the brain. It is a potent mitogen which stimulates growth of a variety of mesodermal cells including chondrocytes, granulosa, and endothelial cells. The peptide may be active in wound healing and animal limb regeneration. [NIH] Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [NIH] Fibronectins: Glycoproteins found on the surfaces of cells, particularly in fibrillar structures. The proteins are lost or reduced when these cells undergo viral or chemical transformation. They are highly susceptible to proteolysis and are substrates for activated blood coagulation factor VIII. The forms present in plasma are called cold-insoluble globulins. [NIH] Fibrosarcoma: A type of soft tissue sarcoma that begins in fibrous tissue, which holds bones, muscles, and other organs in place. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Filariasis: Infections with nematodes of the superfamily Filarioidea. The presence of living worms in the body is mainly asymptomatic but the death of adult worms leads to granulomatous inflammation and permanent fibrosis. Organisms of the genus Elaeophora infect wild elk and domestic sheep causing ischaemic necrosis of the brain, blindness, and dermatosis of the face. [NIH] Filtration: The passage of a liquid through a filter, accomplished by gravity, pressure, or vacuum (suction). [EU] Fixation: 1. The act or operation of holding, suturing, or fastening in a fixed position. 2. The condition of being held in a fixed position. 3. In psychiatry, a term with two related but distinct meanings : (1) arrest of development at a particular stage, which like regression (return to an earlier stage), if temporary is a normal reaction to setbacks and difficulties but if protracted or frequent is a cause of developmental failures and emotional problems, and (2) a close and suffocating attachment to another person, especially a childhood figure, such as one's mother or father. Both meanings are derived from psychoanalytic theory and refer to 'fixation' of libidinal energy either in a specific erogenous zone, hence fixation at the oral, anal, or phallic stage, or in a specific object, hence mother or father fixation. 4. The use of a fixative (q.v.) to preserve histological or cytological specimens. 5. In chemistry, the process whereby a substance is removed from the gaseous or solution phase and localized, as in carbon dioxide fixation or nitrogen fixation. 6. In ophthalmology, direction of the gaze so that the visual image of the object falls on the fovea centralis. 7. In film processing, the chemical removal of all undeveloped salts of the film emulsion, leaving only the developed silver to form a permanent image. [EU] Fluoxetine: The first highly specific serotonin uptake inhibitor. It is used as an antidepressant and often has a more acceptable side-effects profile than traditional antidepressants. [NIH] Follow-Up Studies: Studies in which individuals or populations are followed to assess the outcome of exposures, procedures, or effects of a characteristic, e.g., occurrence of disease. [NIH]

Foramen: A natural hole of perforation, especially one in a bone. [NIH]

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Forearm: The part between the elbow and the wrist. [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] Furunculosis: An infection where furuncles are present over a period of weeks to months. Species of Staphylococcus are usually the causative agents. [NIH] Gadolinium: An element of the rare earth family of metals. It has the atomic symbol Gd, atomic number 64, and atomic weight 157.25. Its oxide is used in the control rods of some nuclear reactors. [NIH] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Gamma Rays: Very powerful and penetrating, high-energy electromagnetic radiation of shorter wavelength than that of x-rays. They are emitted by a decaying nucleus, usually between 0.01 and 10 MeV. They are also called nuclear x-rays. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] Gangrene: Death and putrefaction of tissue usually due to a loss of blood supply. [NIH] 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] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]

Gastroenteritis: An acute inflammation of the lining of the stomach and intestines, characterized by anorexia, nausea, diarrhoea, abdominal pain, and weakness, which has various causes, including food poisoning due to infection with such organisms as Escherichia coli, Staphylococcus aureus, and Salmonella species; consumption of irritating food or drink; or psychological factors such as anger, stress, and fear. Called also enterogastritis. [EU] Gastroesophageal Reflux: Reflux of gastric juice and/or duodenal contents (bile acids, pancreatic juice) into the distal esophagus, commonly due to incompetence of the lower esophageal sphincter. Gastric regurgitation is an extension of this process with entry of fluid into the pharynx or mouth. [NIH] Gastroesophageal Reflux Disease: Flow of the stomach's contents back up into the esophagus. Happens when the muscle between the esophagus and the stomach (the lower esophageal sphincter) is weak or relaxes when it shouldn't. May cause esophagitis. Also called esophageal reflux or reflux esophagitis. [NIH] Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH]

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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 Rearrangement: The ordered rearrangement of gene regions by DNA recombination such as that which occurs normally during development. [NIH] Genetic Code: The specifications for how information, stored in nucleic acid sequence (base sequence), is translated into protein sequence (amino acid sequence). The start, stop, and order of amino acids of a protein is specified by consecutive triplets of nucleotides called codons (codon). [NIH] Genetic Engineering: Directed modification of the gene complement of a living organism by such techniques as altering the DNA, substituting genetic material by means of a virus, transplanting whole nuclei, transplanting cell hybrids, etc. [NIH] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Giant Cells: Multinucleated masses produced by the fusion of many cells; often associated with viral infections. In AIDS, they are induced when the envelope glycoprotein of the HIV virus binds to the CD4 antigen of uninfected neighboring T4 cells. The resulting syncytium leads to cell death and thus may account for the cytopathic effect of the virus. [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] Glucocorticoid: A compound that belongs to the family of compounds called corticosteroids (steroids). Glucocorticoids affect metabolism and have anti-inflammatory and immunosuppressive effects. They may be naturally produced (hormones) or synthetic (drugs). [NIH] Glucuronic Acid: Derivatives of uronic acid found throughout the plant and animal kingdoms. They detoxify drugs and toxins by conjugating with them to form glucuronides in the liver which are more water-soluble metabolites that can be easily eliminated from the body. [NIH] Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid (glutamate) is the most common excitatory neurotransmitter in the central nervous system. [NIH]

Glycerol: A trihydroxy sugar alcohol that is an intermediate in carbohydrate and lipid metabolism. It is used as a solvent, emollient, pharmaceutical agent, and sweetening agent. [NIH]

Glycerophospholipids: Derivatives of phosphatidic acid in which the hydrophobic regions are composed of two fatty acids and a polar alcohol is joined to the C-3 position of glycerol through a phosphodiester bond. They are named according to their polar head groups, such as phosphatidylcholine and phosphatidylethanolamine. [NIH] Glycine: A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter. [NIH]

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Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Glycosaminoglycans: Heteropolysaccharides which contain an N-acetylated hexosamine in a characteristic repeating disaccharide unit. The repeating structure of each disaccharide involves alternate 1,4- and 1,3-linkages consisting of either N-acetylglucosamine or Nacetylgalactosamine. [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] Grade: The grade of a tumor depends on how abnormal the cancer cells look under a microscope and how quickly the tumor is likely to grow and spread. Grading systems are different for each type of cancer. [NIH] Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to replace diseased or injured tissue removed from another part of the body. [NIH] Graft Rejection: An immune response with both cellular and humoral components, directed against an allogeneic transplant, whose tissue antigens are not compatible with those of the recipient. [NIH] Graft-versus-host disease: GVHD. A reaction of donated bone marrow or peripheral stem cells against a person's tissue. [NIH] Granule: A small pill made from sucrose. [EU] Granulocyte: A type of white blood cell that fights bacterial infection. Neutrophils, eosinophils, and basophils are granulocytes. [NIH] Granuloma: A relatively small nodular inflammatory lesion containing grouped mononuclear phagocytes, caused by infectious and noninfectious agents. [NIH] Groin: The external junctural region between the lower part of the abdomen and the thigh. [NIH]

Growth factors: Substances made by the body that function to regulate cell division and cell survival. Some growth factors are also produced in the laboratory and used in biological therapy. [NIH] Guanylate Cyclase: An enzyme that catalyzes the conversion of GTP to 3',5'-cyclic GMP and pyrophosphate. It also acts on ITP and dGTP. (From Enzyme Nomenclature, 1992) EC 4.6.1.2. [NIH] Guinea Pigs: A common name used for the family Caviidae. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research. [NIH]

Haematological: Relating to haematology, that is that branch of medical science which treats of the morphology of the blood and blood-forming tissues. [EU] Haematology: The science of the blood, its nature, functions, and diseases. [NIH] Haptens: Small antigenic determinants capable of eliciting an immune response only when coupled to a carrier. Haptens bind to antibodies but by themselves cannot elicit an antibody response. [NIH] Hay Fever: A seasonal variety of allergic rhinitis, marked by acute conjunctivitis with lacrimation and itching, regarded as an allergic condition triggered by specific allergens. [NIH]

Headache: Pain in the cranial region that may occur as an isolated and benign symptom or as a manifestation of a wide variety of conditions including subarachnoid hemorrhage; craniocerebral trauma; central nervous system infections; intracranial hypertension; and

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other disorders. In general, recurrent headaches that are not associated with a primary disease process are referred to as headache disorders (e.g., migraine). [NIH] Heart failure: Loss of pumping ability by the heart, often accompanied by fatigue, breathlessness, and excess fluid accumulation in body tissues. [NIH] Helminths: Commonly known as parasitic worms, this group includes the acanthocephala, nematoda, and platyhelminths. Some authors consider certain species of leeches that can become temporarily parasitic as helminths. [NIH] Hematologic malignancies: Cancers of the blood or bone marrow, including leukemia and lymphoma. Also called hematologic cancers. [NIH] Hematopoiesis: The development and formation of various types of blood cells. [NIH] Hematuria: Presence of blood in the urine. [NIH] Hemolytic: A disease that affects the blood and blood vessels. It destroys red blood cells, cells that cause the blood to clot, and the lining of blood vessels. HUS is often caused by the Escherichia coli bacterium in contaminated food. People with HUS may develop acute renal failure. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hemostasis: The process which spontaneously arrests the flow of blood from vessels carrying blood under pressure. It is accomplished by contraction of the vessels, adhesion and aggregation of formed blood elements, and the process of blood or plasma coagulation. [NIH]

Heparin: Heparinic acid. A highly acidic mucopolysaccharide formed of equal parts of sulfated D-glucosamine and D-glucuronic acid with sulfaminic bridges. The molecular weight ranges from six to twenty thousand. Heparin occurs in and is obtained from liver, lung, mast cells, etc., of vertebrates. Its function is unknown, but it is used to prevent blood clotting in vivo and vitro, in the form of many different salts. [NIH] Hepatic: Refers to the liver. [NIH] Hepatitis: Inflammation of the liver and liver disease involving degenerative or necrotic alterations of hepatocytes. [NIH] Hepatocytes: The main structural component of the liver. They are specialized epithelial cells that are organized into interconnected plates called lobules. [NIH] Hepatotoxicity: How much damage a medicine or other substance does to the liver. [NIH] Hereditary: Of, relating to, or denoting factors that can be transmitted genetically from one generation to another. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Herniated: Protrusion of a degenerated or fragmented intervertebral disc into the intervertebral foramen compressing the nerve root. [NIH] Heterodimers: Zippered pair of nonidentical proteins. [NIH] Heterogeneity: The property of one or more samples or populations which implies that they are not identical in respect of some or all of their parameters, e. g. heterogeneity of variance. [NIH]

Heterotrophic: Pertaining to organisms that are consumers and dependent on other organisms for their source of energy (food). [NIH] Histamine: 1H-Imidazole-4-ethanamine. A depressor amine derived by enzymatic decarboxylation of histidine. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter. [NIH]

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Histidine: An essential amino acid important in a number of metabolic processes. It is required for the production of histamine. [NIH] Histiocytosis: General term for the abnormal appearance of histiocytes in the blood. Based on the pathological features of the cells involved rather than on clinical findings, the histiocytic diseases are subdivided into three groups: Langerhans cell histiocytosis, nonLangerhans cell histiocytosis, and malignant histiocytic disorders. [NIH] Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] Hormonal: Pertaining to or of the nature of a hormone. [EU] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Hormone Replacement Therapy: Therapeutic use of hormones to alleviate the effects of hormone deficiency. [NIH] Humoral: Of, relating to, proceeding from, or involving a bodily humour - now often used of endocrine factors as opposed to neural or somatic. [EU] Humour: 1. A normal functioning fluid or semifluid of the body (as the blood, lymph or bile) especially of vertebrates. 2. A secretion that is itself an excitant of activity (as certain hormones). [EU] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [NIH] 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] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hydrophobic: Not readily absorbing water, or being adversely affected by water, as a hydrophobic colloid. [EU] Hydroxylysine: A hydroxylated derivative of the amino acid lysine that is present in certain collagens. [NIH] Hydroxyproline: A hydroxylated form of the imino acid proline. A deficiency in ascorbic acid can result in impaired hydroxyproline formation. [NIH] Hypercapnia: A clinical manifestation of abnormal increase in the amount of carbon dioxide in arterial blood. [NIH] Hypereosinophilic Syndrome: A heterogeneous group of disorders with the common feature of prolonged eosinophilia of unknown cause and associated organ system dysfunction, including the heart, central nervous system, kidneys, lungs, gastrointestinal tract, and skin. There is a massive increase in the number of eosinophils in the blood, mimicking leukemia, and extensive eosinophilic infiltration of the various organs. It is often referred to as idiopathic. [NIH]

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Hyperglycemia: Abnormally high blood sugar. [NIH] Hyperplasia: An increase in the number of cells in a tissue or organ, not due to tumor formation. It differs from hypertrophy, which is an increase in bulk without an increase in the number of cells. [NIH] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hypertrophy: General increase in bulk of a part or organ, not due to tumor formation, nor to an increase in the number of cells. [NIH] Hypodermic: Applied or administered beneath the skin. [EU] Hypothyroidism: Deficiency of thyroid activity. In adults, it is most common in women and is characterized by decrease in basal metabolic rate, tiredness and lethargy, sensitivity to cold, and menstrual disturbances. If untreated, it progresses to full-blown myxoedema. In infants, severe hypothyroidism leads to cretinism. In juveniles, the manifestations are intermediate, with less severe mental and developmental retardation and only mild symptoms of the adult form. When due to pituitary deficiency of thyrotropin secretion it is called secondary hypothyroidism. [EU] 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] Idiopathic: Describes a disease of unknown cause. [NIH] Idiopathic myelofibrosis: A progressive disease in which the bone marrow is replaced by fibrous tissue and is unable to produce red blood cells; the cause is unknown. [NIH] Immune Adherence Reaction: A method for the detection of very small quantities of antibody in which the antigen-antibody-complement complex adheres to indicator cells, usually primate erythrocytes or nonprimate blood platelets. The reaction is dependent on the number of bound C3 molecules on the C3b receptor sites of the indicator cell. [NIH] Immune Complex Diseases: Group of diseases mediated by the deposition of large soluble complexes of antigen and antibody with resultant damage to tissue. Besides serum sickness and the arthus reaction, evidence supports a pathogenic role for immune complexes in many other systemic immunologic diseases including glomerulonephritis, systemic lupus erythematosus and polyarteritis nodosa. [NIH] Immune 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] 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.

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[NIH]

Immunoglobulin: A protein that acts as an antibody. [NIH] Immunologic: The ability of the antibody-forming system to recall a previous experience with an antigen and to respond to a second exposure with the prompt production of large amounts of antibody. [NIH] Immunology: The study of the body's immune system. [NIH] 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] Immunosuppressive therapy: Therapy used to decrease the body's immune response, such as drugs given to prevent transplant rejection. [NIH] Immunotherapy: Manipulation of the host's immune system in treatment of disease. It includes both active and passive immunization as well as immunosuppressive therapy to prevent graft rejection. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] Implant radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called [NIH] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incidental: 1. Small and relatively unimportant, minor; 2. Accompanying, but not a major part of something; 3. (To something) Liable to occur because of something or in connection with something (said of risks, responsibilities, .) [EU] Incision: A cut made in the body during surgery. [NIH] Incompetence: Physical or mental inadequacy or insufficiency. [EU] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] 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

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microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]

Infiltration: The diffusion or accumulation in a tissue or cells of substances not normal to it or in amounts of the normal. Also, the material so accumulated. [EU] Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH] Inflammatory bowel disease: A general term that refers to the inflammation of the colon and rectum. Inflammatory bowel disease includes ulcerative colitis and Crohn's disease. [NIH]

Influenza: An acute viral infection involving the respiratory tract. It is marked by inflammation of the nasal mucosa, the pharynx, and conjunctiva, and by headache and severe, often generalized, myalgia. [NIH] Infusion: A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion. [NIH] Ingestion: Taking into the body by mouth [NIH] Inguinal: Pertaining to the inguen, or groin. [EU] Inhalation: The drawing of air or other substances into the lungs. [EU] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Initiator: A chemically reactive substance which may cause cell changes if ingested, inhaled or absorbed into the body; the substance may thus initiate a carcinogenic process. [NIH] Inorganic: Pertaining to substances not of organic origin. [EU] Insight: The capacity to understand one's own motives, to be aware of one's own psychodynamics, to appreciate the meaning of symbolic behavior. [NIH] Instillation: . [EU] Insulator: Material covering the metal conductor of the lead. It is usually polyurethane or silicone. [NIH] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose. It is also an important regulator of protein and lipid metabolism. Insulin is used as a drug to control insulin-dependent diabetes mellitus. [NIH] Integrins: A family of transmembrane glycoproteins consisting of noncovalent heterodimers. They interact with a wide variety of ligands including extracellular matrix glycoproteins, complement, and other cells, while their intracellular domains interact with the cytoskeleton. The integrins consist of at least three identified families: the cytoadhesin receptors, the leukocyte adhesion receptors, and the very-late-antigen receptors. Each family contains a common beta-subunit combined with one or more distinct alpha-subunits. These receptors participate in cell-matrix and cell-cell adhesion in many physiologically important processes, including embryological development, hemostasis, thrombosis, wound healing, immune and nonimmune defense mechanisms, and oncogenic transformation. [NIH] Interferon: A biological response modifier (a substance that can improve the body's natural response to disease). Interferons interfere with the division of cancer cells and can slow tumor growth. There are several types of interferons, including interferon-alpha, -beta, and gamma. These substances are normally produced by the body. They are also made in the laboratory for use in treating cancer and other diseases. [NIH]

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Interferon Alfa-2a: A recombinant alfa interferon consisting of 165 amino acids with lysine at position 23 and histidine at position 34. It is used extensively as an antiviral and antineoplastic agent. [NIH] Interferon-alpha: One of the type I interferons produced by peripheral blood leukocytes or lymphoblastoid cells when exposed to live or inactivated virus, double-stranded RNA, or bacterial products. It is the major interferon produced by virus-induced leukocyte cultures and, in addition to its pronounced antiviral activity, it causes activation of NK cells. [NIH] Interleukin-1: A soluble factor produced by monocytes, macrophages, and other cells which activates T-lymphocytes and potentiates their response to mitogens or antigens. IL-1 consists of two distinct forms, IL-1 alpha and IL-1 beta which perform the same functions but are distinct proteins. The biological effects of IL-1 include the ability to replace macrophage requirements for T-cell activation. The factor is distinct from interleukin-2. [NIH] Interleukin-12: A heterodimeric cytokine that stimulates the production of interferon gamma from T-cells and natural killer cells, and also induces differentiation of Th1 helper cells. It is an initiator of cell-mediated immunity. [NIH] Interleukin-15: Cytokine that stimulates the proliferation of T-lymphocytes and shares biological activities with IL-2. IL-15 also can induce B-lymphocyte proliferation and differentiation. [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-5: Factor promoting eosinophil differentiation and activation in hematopoiesis. It also triggers activated B-cells for a terminal differentiation into Ig-secreting cells. [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] Interleukins: Soluble factors which stimulate growth-related activities of leukocytes as well as other cell types. They enhance cell proliferation and differentiation, DNA synthesis, secretion of other biologically active molecules and responses to immune and inflammatory stimuli. [NIH] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Internal radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called brachytherapy, implant radiation, or interstitial radiation therapy. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intervertebral: Situated between two contiguous vertebrae. [EU] Intestinal: Having to do with the intestines. [NIH] Intestine: A long, tube-shaped organ in the abdomen that completes the process of digestion. There is both a large intestine and a small intestine. Also called the bowel. [NIH] Intracellular: Inside a cell. [NIH] Intramuscular: IM. Within or into muscle. [NIH] Intraperitoneal: IP. Within the peritoneal cavity (the area that contains the abdominal organs). [NIH] Intravenous: IV. Into a vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU]

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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 Exchange: Reversible chemical reaction between a solid, often an ION exchange resin, and a fluid whereby ions may be exchanged from one substance to another. This technique is used in water purification, in research, and in industry. [NIH] Ion Exchange Resins: High molecular weight, insoluble polymers which contain functional groups that are capable of undergoing exchange reactions (ion exchange) with either cations or anions. [NIH] Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as cations; those with a negative charge are anions. [NIH] Islet: Cell producing insulin in pancreas. [NIH] Karyotype: The characteristic chromosome complement of an individual, race, or species as defined by their number, size, shape, etc. [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] Keratin: A class of fibrous proteins or scleroproteins important both as structural proteins and as keys to the study of protein conformation. The family represents the principal constituent of epidermis, hair, nails, horny tissues, and the organic matrix of tooth enamel. Two major conformational groups have been characterized, alpha-keratin, whose peptide backbone forms an alpha-helix, and beta-keratin, whose backbone forms a zigzag or pleated sheet structure. [NIH] Keratinocytes: Epidermal cells which synthesize keratin and undergo characteristic changes as they move upward from the basal layers of the epidermis to the cornified (horny) layer of the skin. Successive stages of differentiation of the keratinocytes forming the epidermal layers are basal cell, spinous or prickle cell, and the granular cell. [NIH] Keratoconjunctivitis: Simultaneous inflammation of the cornea and conjunctiva. [NIH] Keratosis: Any horny growth such as a wart or callus. [NIH] Keto: It consists of 8 carbon atoms and within the endotoxins, it connects poysaccharide and lipid A. [NIH] Labile: 1. Gliding; moving from point to point over the surface; unstable; fluctuating. 2. Chemically unstable. [EU] Laminin: Large, noncollagenous glycoprotein with antigenic properties. It is localized in the basement membrane lamina lucida and functions to bind epithelial cells to the basement membrane. Evidence suggests that the protein plays a role in tumor invasion. [NIH] Large Intestine: The part of the intestine that goes from the cecum to the rectum. The large intestine absorbs water from stool and changes it from a liquid to a solid form. The large intestine is 5 feet long and includes the appendix, cecum, colon, and rectum. Also called colon. [NIH] Laser therapy: The use of an intensely powerful beam of light to kill cancer cells. [NIH] Lavage: A cleaning of the stomach and colon. Uses a special drink and enemas. [NIH] Lectin: A complex molecule that has both protein and sugars. Lectins are able to bind to the outside of a cell and cause biochemical changes in it. Lectins are made by both animals and plants. [NIH] Leiomyosarcoma: A tumor of the muscles in the uterus, abdomen, or pelvis. [NIH]

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Lesion: An area of abnormal tissue change. [NIH] Lethal: Deadly, fatal. [EU] Lethargy: Abnormal drowsiness or stupor; a condition of indifference. [EU] Leucocyte: All the white cells of the blood and their precursors (myeloid cell series, lymphoid cell series) but commonly used to indicate granulocytes exclusive of lymphocytes. [NIH]

Leukaemia: An acute or chronic disease of unknown cause in man and other warm-blooded animals that involves the blood-forming organs, is characterized by an abnormal increase in the number of leucocytes in the tissues of the body with or without a corresponding increase of those in the circulating blood, and is classified according of the type leucocyte most prominently involved. [EU] Leukemia: Cancer of blood-forming tissue. [NIH] Leukocyte Count: A count of the number of white blood cells per unit volume in venous blood. A differential leukocyte count measures the relative numbers of the different types of white cells. [NIH] Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [NIH] Leukocytosis: A transient increase in the number of leukocytes in a body fluid. [NIH] Life cycle: The successive stages through which an organism passes from fertilized ovum or spore to the fertilized ovum or spore of the next generation. [NIH] Ligaments: Shiny, flexible bands of fibrous tissue connecting together articular extremities of bones. They are pliant, tough, and inextensile. [NIH] Ligands: A RNA simulation method developed by the MIT. [NIH] Linkage: The tendency of two or more genes in the same chromosome to remain together from one generation to the next more frequently than expected according to the law of independent assortment. [NIH] Linkage Disequilibrium: Nonrandom association of linked genes. This is the tendency of the alleles of two separate but already linked loci to be found together more frequently than would be expected by chance alone. [NIH] Lipid: Fat. [NIH] Lipid Peroxidation: Peroxidase catalyzed oxidation of lipids using hydrogen peroxide as an electron acceptor. [NIH] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Liver Cirrhosis: Liver disease in which the normal microcirculation, the gross vascular anatomy, and the hepatic architecture have been variably destroyed and altered with fibrous septa surrounding regenerated or regenerating parenchymal nodules. [NIH] Liver scan: An image of the liver created on a computer screen or on film. A radioactive substance is injected into a blood vessel and travels through the bloodstream. It collects in the liver, especially in abnormal areas, and can be detected by the scanner. [NIH] Liver Transplantation: The transference of a part of or an entire liver from one human or animal to another. [NIH] Localization: The process of determining or marking the location or site of a lesion or disease. May also refer to the process of keeping a lesion or disease in a specific location or site. [NIH]

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Localized: Cancer which has not metastasized yet. [NIH] Lower Esophageal Sphincter: The muscle between the esophagus and stomach. When a person swallows, this muscle relaxes to let food pass from the esophagus to the stomach. It stays closed at other times to keep stomach contents from flowing back into the esophagus. [NIH]

Lung Transplantation: The transference of either one or both of the lungs from one human or animal to another. [NIH] Lupus: A form of cutaneous tuberculosis. It is seen predominantly in women and typically involves the nasal, buccal, and conjunctival mucosa. [NIH] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Lymph node: A rounded mass of lymphatic tissue that is surrounded by a capsule of 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]

Lymphadenopathy: Disease or swelling of the lymph nodes. [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] Lymphoblasts: Interferon produced predominantly by leucocyte cells. [NIH] Lymphocyte: A white blood cell. Lymphocytes have a number of roles in the immune system, including the production of antibodies and other substances that fight infection and diseases. [NIH] Lymphocyte Count: A count of the number of lymphocytes in the blood. [NIH] Lymphocytic: Referring to lymphocytes, a type of white blood cell. [NIH] Lymphocytosis: Excess of normal lymphocytes in the blood or in any effusion. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue. [NIH] Lymphomatoid Papulosis: Clinically benign, histologically malignant, recurrent cutaneous eruption characterized by an infiltration of large atypical cells surrounded by inflammatory cells. The atypical cells resemble Reed-Sternberg cells of Hodgkin's disease or the malignant cells of cutaneous T-cell lymphoma. In some cases, lymphomatoid papulosis progresses to lymphomatous conditions including mycosis fungoides, Hodgkin's disease, cutaneous T-cell lymphoma, or Ki-1 lymphoma. [NIH] Lymphopenia: Reduction in the number of lymphocytes. [NIH] Lysine: An essential amino acid. It is often added to animal feed. [NIH] Lysophospholipase: An enzyme that catalyzes the hydrolysis of a single fatty acid ester bond in lysoglycerophosphatidates with the formation of glyceryl phosphatidates and a fatty acid. EC 3.1.1.5. [NIH] Lysophospholipids: Derivatives of phosphatidic acids that lack one of its fatty acyl chains due to its hydrolytic removal. [NIH]

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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] Macrophage Colony-Stimulating Factor: A mononuclear phagocyte colony-stimulating factor synthesized by mesenchymal cells. The compound stimulates the survival, proliferation, and differentiation of hematopoietic cells of the monocyte-macrophage series. M-CSF is a disulfide-bonded glycoprotein dimer with a MW of 70 kDa. It binds to a specific high affinity receptor (receptor, macrophage colony-stimulating factor). [NIH] Maculopapular: Both macular and papular, as an eruption consisting of both macules and papules; sometimes erroneously used to designate a papule that is only slightly elevated. [EU]

Magnetic Resonance Imaging: Non-invasive method of demonstrating internal anatomy based on the principle that atomic nuclei in a strong magnetic field absorb pulses of radiofrequency energy and emit them as radiowaves which can be reconstructed into computerized images. The concept includes proton spin tomographic techniques. [NIH] Malignancy: A cancerous tumor that can invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malignant fibrous histiocytoma: A sarcoma that usually begins in soft tissue. It usually appears as an enlarging, painful mass that can cause fracture due to destruction of the bone by a spreading tumor. [NIH] Malignant tumor: A tumor capable of metastasizing. [NIH] Manifest: Being the part or aspect of a phenomenon that is directly observable : concretely expressed in behaviour. [EU] Mastocytosis: A group of diseases resulting from proliferation of mast cells. [NIH] Meatus: A canal running from the internal auditory foramen through the petrous portion of the temporal bone. It gives passage to the facial and auditory nerves together with the auditory branch of the basilar artery and the internal auditory veins. [NIH] Medial: Lying near the midsaggital plane of the body; opposed to lateral. [NIH] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] Mediator: An object or substance by which something is mediated, such as (1) a structure of the nervous system that transmits impulses eliciting a specific response; (2) a chemical substance (transmitter substance) that induces activity in an excitable tissue, such as nerve or muscle; or (3) a substance released from cells as the result of the interaction of antigen with antibody or by the action of antigen with a sensitized lymphocyte. [EU] Medicament: A medicinal substance or agent. [EU] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Meibomian: A series of simple, branched, alveolar, sebaceous glands, located in the tarso of the eyelids, whose ducts empty into the eyelid margins in line with and lateral to the lacrimal puncta. [NIH] Meibomian Glands: The sebaceous glands situated on the inner surface of the eyelids between the tarsal plates and conjunctiva. [NIH] Melanin: The substance that gives the skin its color. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH]

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Memory: Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. [NIH] Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] Meningitis: Inflammation of the meninges. When it affects the dura mater, the disease is termed pachymeningitis; when the arachnoid and pia mater are involved, it is called leptomeningitis, or meningitis proper. [EU] Mental: Pertaining to the mind; psychic. 2. (L. mentum chin) pertaining to the chin. [EU] Mental Health: The state wherein the person is well adjusted. [NIH] Mental Processes: Conceptual functions or thinking in all its forms. [NIH] Mercury: A silver metallic element that exists as a liquid at room temperature. It has the atomic symbol Hg (from hydrargyrum, liquid silver), atomic number 80, and atomic weight 200.59. Mercury is used in many industrial applications and its salts have been employed therapeutically as purgatives, antisyphilitics, disinfectants, and astringents. It can be absorbed through the skin and mucous membranes which leads to mercury poisoning. Because of its toxicity, the clinical use of mercury and mercurials is diminishing. [NIH] Mesenchymal: Refers to cells that develop into connective tissue, blood vessels, and lymphatic tissue. [NIH] Mesentery: A layer of the peritoneum which attaches the abdominal viscera to the abdominal wall and conveys their blood vessels and nerves. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] Metaplasia: A condition in which there is a change of one adult cell type to another similar adult cell type. [NIH] Metastasis: The spread of cancer from one part of the body to another. Tumors formed from cells that have spread are called "secondary tumors" and contain cells that are like those in the original (primary) tumor. The plural is metastases. [NIH] Metastasize: To spread from one part of the body to another. When cancer cells metastasize and form secondary tumors, the cells in the metastatic tumor are like those in the original (primary) tumor. [NIH] Methylprednisolone: (6 alpha,11 beta)-11,17,21-Trihydroxy-6-methylpregna-1,4-diene-3,2dione. A prednisolone derivative which has pharmacological actions similar to prednisolone. [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] Microcirculation: The vascular network lying between the arterioles and venules; includes capillaries, metarterioles and arteriovenous anastomoses. Also, the flow of blood through this network. [NIH] Microfilaria: The prelarval stage of Filarioidea in the blood and other tissues of mammals and birds. They are removed from these hosts by blood-sucking insects in which they metamorphose into mature larvae. [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]

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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] Millimeter: A measure of length. A millimeter is approximately 26-times smaller than an inch. [NIH] Mineralocorticoids: A group of corticosteroids primarily associated with the regulation of water and electrolyte balance. This is accomplished through the effect on ion transport in renal tubules, resulting in retention of sodium and loss of potassium. Mineralocorticoid secretion is itself regulated by plasma volume, serum potassium, and angiotensin II. [NIH] Minocycline: A semisynthetic staphylococcus infections. [NIH]

antibiotic

effective

against

tetracycline-resistant

Minority Groups: A subgroup having special characteristics within a larger group, often bound together by special ties which distinguish it from the larger group. [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] Mitoxantrone: An anthracenedione-derived antineoplastic agent. [NIH] Mobilization: The process of making a fixed part or stored substance mobile, as by separating a part from surrounding structures to make it accessible for an operative procedure or by causing release into the circulation for body use of a substance stored in the body. [EU] Modeling: A treatment procedure whereby the therapist presents the target behavior which the learner is to imitate and make part of his repertoire. [NIH] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] Monitor: An apparatus which automatically records such physiological signs as respiration, pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH] Monoclonal: An antibody produced by culturing a single type of cell. It therefore consists of a single species of immunoglobulin molecules. [NIH] Monoclonal antibodies: Laboratory-produced substances that can locate and bind to cancer cells wherever they are in the body. Many monoclonal antibodies are used in cancer detection or therapy; each one recognizes a different protein on certain cancer cells. Monoclonal antibodies can be used alone, or they can be used to deliver drugs, toxins, or radioactive material directly to a tumor. [NIH] Monocyte: A type of white blood cell. [NIH]

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Mononuclear: A cell with one nucleus. [NIH] Monophosphate: So called second messenger for neurotransmitters and hormones. [NIH] Morphology: The science of the form and structure of organisms (plants, animals, and other forms of life). [NIH] Motion Sickness: Sickness caused by motion, as sea sickness, train sickness, car sickness, and air sickness. [NIH] Mucociliary: Pertaining to or affecting the mucus membrane and hairs (including eyelashes, nose hair, .): mucociliary clearing: the clearance of mucus by ciliary movement ( particularly in the respiratory system). [EU] Mucolytic: Destroying or dissolving mucin; an agent that so acts : a mucopolysaccharide or glycoprotein, the chief constituent of mucus. [EU] Mucosa: A mucous membrane, or tunica mucosa. [EU] Mucus: The viscous secretion of mucous membranes. It contains mucin, white blood cells, water, inorganic salts, and exfoliated cells. [NIH] Multicenter study: A clinical trial that is carried out at more than one medical institution. [NIH]

Multiple Myeloma: A malignant tumor of plasma cells usually arising in the bone marrow; characterized by diffuse involvement of the skeletal system, hyperglobulinemia, Bence-Jones proteinuria, and anemia. [NIH] Multiple sclerosis: A disorder of the central nervous system marked by weakness, numbness, a loss of muscle coordination, and problems with vision, speech, and bladder control. Multiple sclerosis is thought to be an autoimmune disease in which the body's immune system destroys myelin. Myelin is a substance that contains both protein and fat (lipid) and serves as a nerve insulator and helps in the transmission of nerve signals. [NIH] Mutagenesis: Process of generating genetic mutations. It may occur spontaneously or be induced by mutagens. [NIH] Mutagens: Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes. [NIH] Myalgia: Pain in a muscle or muscles. [EU] Myelin: The fatty substance that covers and protects nerves. [NIH] Myelodysplastic syndrome: Disease in which the bone marrow does not function normally. Also called preleukemia or smoldering leukemia. [NIH] Myelogenous: Produced by, or originating in, the bone marrow. [NIH] Myeloma: Cancer that arises in plasma cells, a type of white blood cell. [NIH] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myositis: Inflammation of a voluntary muscle. [EU] Nasal Cavity: The proximal portion of the respiratory passages on either side of the nasal septum, lined with ciliated mucosa, extending from the nares to the pharynx. [NIH] Nasal Mucosa: The mucous membrane lining the nasal cavity. [NIH] Natural killer cells: NK cells. A type of white blood cell that contains granules with enzymes that can kill tumor cells or microbial cells. Also called large granular lymphocytes (LGL). [NIH]

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Nausea: An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. [NIH] NCI: National Cancer Institute. NCI, part of the National Institutes of Health of the United States Department of Health and Human Services, is the federal government's principal agency for cancer research. NCI conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the NCI Web site at http://cancer.gov. [NIH] Necrolysis: Separation or exfoliation of tissue due to necrosis. [EU] 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] Nematoda: A class of unsegmented helminths with fundamental bilateral symmetry and secondary triradiate symmetry of the oral and esophageal structures. Many species are parasites. [NIH] Neoplasia: Abnormal and uncontrolled cell growth. [NIH] Neoplasm: A new growth of benign or malignant tissue. [NIH] Neoplastic: Pertaining to or like a neoplasm (= any new and abnormal growth); pertaining to neoplasia (= the formation of a neoplasm). [EU] Nephrosis: Descriptive histopathologic term for renal disease without an inflammatory component. [NIH] Nephrotic: Pertaining to, resembling, or caused by nephrosis. [EU] Nephrotic Syndrome: Clinical association of heavy proteinuria, hypoalbuminemia, and generalized edema. [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] Neuroblastoma: Cancer that arises in immature nerve cells and affects mostly infants and children. [NIH] Neuroleptic: A term coined to refer to the effects on cognition and behaviour of antipsychotic drugs, which produce a state of apathy, lack of initiative, and limited range of emotion and in psychotic patients cause a reduction in confusion and agitation and normalization of psychomotor activity. [EU] Neurologic: Having to do with nerves or the nervous system. [NIH] Neuromuscular: Pertaining to muscles and nerves. [EU] Neuromuscular Junction: The synapse between a neuron and a muscle. [NIH] 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]

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Neutralization: An act or process of neutralizing. [EU] Neutrons: Electrically neutral elementary particles found in all atomic nuclei except light hydrogen; the mass is equal to that of the proton and electron combined and they are unstable when isolated from the nucleus, undergoing beta decay. Slow, thermal, epithermal, and fast neutrons refer to the energy levels with which the neutrons are ejected from heavier nuclei during their decay. [NIH] Neutrophil: A type of white blood cell. [NIH] Nevirapine: A potent, non-nucleoside reverse transcriptase inhibitor used in combination with nucleoside analogues for treatment of HIV infection and AIDS. [NIH] Niacin: Water-soluble vitamin of the B complex occurring in various animal and plant tissues. Required by the body for the formation of coenzymes NAD and NADP. Has pellagra-curative, vasodilating, and antilipemic properties. [NIH] Nitric Oxide: A free radical gas produced endogenously by a variety of mammalian cells. It is synthesized from arginine by a complex reaction, catalyzed by nitric oxide synthase. Nitric oxide is endothelium-derived relaxing factor. It is released by the vascular endothelium and mediates the relaxation induced by some vasodilators such as acetylcholine and bradykinin. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic guanylate cyclase and thus elevates intracellular levels of cyclic GMP. [NIH]

Nitrogen: An element with the atomic symbol N, atomic number 7, and atomic weight 14. Nitrogen exists as a diatomic gas and makes up about 78% of the earth's atmosphere by volume. It is a constituent of proteins and nucleic acids and found in all living cells. [NIH] Noel: The highest dose level of a chemical that, in a given toxicity test, causes no observable adverse effect in the test animals. [NIH] Non-nucleoside: A member of a class of compounds, including delavirdine, loviride and nevirapine, that acts to directly combine with and block the action of HIV's reverse transcriptase. [NIH] Norepinephrine: Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic. [NIH] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the information (genetic code) for the transfer of genetic information from one generation to the next. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Ocular: 1. Of, pertaining to, or affecting the eye. 2. Eyepiece. [EU] Oesophagitis: Inflammation of the esophagus. [EU] Onchocerciasis: Infection with nematodes of the genus Onchocerca. Characteristics include

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the presence of firm subcutaneous nodules filled with adult worms, pruritus, and ocular lesions. [NIH] Oncogenic: Chemical, viral, radioactive or other agent that causes cancer; carcinogenic. [NIH] Oncology: The study of cancer. [NIH] Ophthalmologist: A medical doctor specializing in the diagnosis and medical or surgical treatment of visual disorders and eye disease. [NIH] Opportunistic Infections: An infection caused by an organism which becomes pathogenic under certain conditions, e.g., during immunosuppression. [NIH] Orbit: One of the two cavities in the skull which contains an eyeball. Each eye is located in a bony socket or orbit. [NIH] Osteolysis: Dissolution of bone that particularly involves the removal or loss of calcium. [NIH]

Otitis: Inflammation of the ear, which may be marked by pain, fever, abnormalities of hearing, hearing loss, tinnitus, and vertigo. [EU] Otolaryngology: A surgical specialty concerned with the study and treatment of disorders of the ear, nose, and throat. [NIH] Otology: The branch of medicine which deals with the diagnosis and treatment of the disorders and diseases of the ear. [NIH] Ovalbumin: An albumin obtained from the white of eggs. It is a member of the serpin superfamily. [NIH] Ovary: Either of the paired glands in the female that produce the female germ cells and secrete some of the female sex hormones. [NIH] Overexpress: An excess of a particular protein on the surface of a cell. [NIH] Oxidants: Oxidizing agents or electron-accepting molecules in chemical reactions in which electrons are transferred from one molecule to another (oxidation-reduction). In vivo, it appears that phagocyte-generated oxidants function as tumor promoters or cocarcinogens rather than as complete carcinogens perhaps because of the high levels of endogenous antioxidant defenses. It is also thought that oxidative damage in joints may trigger the autoimmune response that characterizes the persistence of the rheumatoid disease process. [NIH]

Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]

Oxidation-Reduction: A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471). [NIH] Oxidative Stress: A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi). [NIH] Oxygenation: The process of supplying, treating, or mixing with oxygen. No:1245 oxygenation the process of supplying, treating, or mixing with oxygen. [EU]

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Pachymeningitis: Inflammation of the dura mater of the brain, the spinal cord or the optic nerve. [NIH] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Pancreatic: Having to do with the pancreas. [NIH] Pancreatic Juice: The fluid containing digestive enzymes secreted by the pancreas in response to food in the duodenum. [NIH] Pancreatitis: Acute or chronic inflammation of the pancreas, which may be asymptomatic or symptomatic, and which is due to autodigestion of a pancreatic tissue by its own enzymes. It is caused most often by alcoholism or biliary tract disease; less commonly it may be associated with hyperlipaemia, hyperparathyroidism, abdominal trauma (accidental or operative injury), vasculitis, or uraemia. [EU] Parapsoriasis: The term applied to a group of relatively uncommon inflammatory, maculopapular, scaly eruptions of unknown etiology and resistant to conventional treatment. Eruptions are both psoriatic and lichenoid in appearance, but the diseases are distinct from psoriasis, lichen planus, or other recognized dermatoses. Proposed nomenclature divides parapsoriasis into two distinct subgroups, pityriasis lichenoides and parapsoriasis en plaques (small- and large-plaque parapsoriasis). [NIH] Parasite: An animal or a plant that lives on or in an organism of another species and gets at least some of its nutrition from that other organism. [NIH] Parasitic: Having to do with or being a parasite. A parasite is an animal or a plant that lives on or in an organism of another species and gets at least some of its nutrients from it. [NIH] Parasitic Diseases: Infections or infestations with parasitic organisms. They are often contracted through contact with an intermediate vector, but may occur as the result of direct exposure. [NIH] Parenchyma: The essential elements of an organ; used in anatomical nomenclature as a general term to designate the functional elements of an organ, as distinguished from its framework, or stroma. [EU] Parenteral: Not through the alimentary canal but rather by injection through some other route, as subcutaneous, intramuscular, intraorbital, intracapsular, intraspinal, intrasternal, intravenous, etc. [EU] Parenteral Nutrition: The administering of nutrients for assimilation and utilization by a patient who cannot maintain adequate nutrition by enteral feeding alone. Nutrients are administered by a route other than the alimentary canal (e.g., intravenously, subcutaneously). [NIH] Parietal: 1. Of or pertaining to the walls of a cavity. 2. Pertaining to or located near the parietal bone, as the parietal lobe. [EU] Parotid: The space that contains the parotid gland, the facial nerve, the external carotid artery, and the retromandibular vein. [NIH] Partial remission: The shrinking, but not complete disappearance, of a tumor in response to therapy. Also called partial response. [NIH] Particle: A tiny mass of material. [EU] Patch: A piece of material used to cover or protect a wound, an injured part, etc.: a patch

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over the eye. [NIH] Pathogen: Any disease-producing microorganism. [EU] Pathogenesis: The cellular events and reactions that occur in the development of disease. [NIH]

Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Pathologic Processes: The abnormal mechanisms and forms involved in the dysfunctions of tissues and organs. [NIH] Pathologies: The study of abnormality, especially the study of diseases. [NIH] Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Pelvic: Pertaining to the pelvis. [EU] Pelvis: The lower part of the abdomen, located between the hip bones. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Perfusion: Bathing an organ or tissue with a fluid. In regional perfusion, a specific area of the body (usually an arm or a leg) receives high doses of anticancer drugs through a blood vessel. Such a procedure is performed to treat cancer that has not spread. [NIH] Peripheral blood: Blood circulating throughout the body. [NIH] Peripheral stem cells: Immature cells found circulating in the bloodstream. New blood cells develop from peripheral stem cells. [NIH] Peristalsis: The rippling motion of muscles in the intestine or other tubular organs characterized by the alternate contraction and relaxation of the muscles that propel the contents onward. [NIH] Peritoneal: Having to do with the peritoneum (the tissue that lines the abdominal wall and covers most of the organs in the abdomen). [NIH] Peritoneal Cavity: The space enclosed by the peritoneum. It is divided into two portions, the greater sac and the lesser sac or omental bursa, which lies behind the stomach. The two sacs are connected by the foramen of Winslow, or epiploic foramen. [NIH] Peritoneal Dialysis: Dialysis fluid being introduced into and removed from the peritoneal cavity as either a continuous or an intermittent procedure. [NIH] Peritoneum: Endothelial lining of the abdominal cavity, the parietal peritoneum covering 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] Peroxidase: A hemeprotein from leukocytes. Deficiency of this enzyme leads to a hereditary disorder coupled with disseminated moniliasis. It catalyzes the conversion of a donor and peroxide to an oxidized donor and water. EC 1.11.1.7. [NIH] Peroxide: Chemical compound which contains an atom group with two oxygen atoms tied to each other. [NIH] PH: The symbol relating the hydrogen ion (H+) concentration or activity of a solution to that of a given standard solution. Numerically the pH is approximately equal to the negative

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logarithm of H+ concentration expressed in molarity. pH 7 is neutral; above it alkalinity increases and below it acidity increases. [EU] Phagocyte: An immune system cell that can surround and kill microorganisms and remove dead cells. Phagocytes include macrophages. [NIH] Pharmaceutical Preparations: Drugs intended for human or veterinary use, presented in their finished dosage form. Included here are materials used in the preparation and/or formulation of the finished dosage form. [NIH] Pharmacokinetics: Dynamic and kinetic mechanisms of exogenous chemical and drug absorption, biotransformation, distribution, release, transport, uptake, and elimination as a function of dosage, and extent and rate of metabolic processes. It includes toxicokinetics, the pharmacokinetic mechanism of the toxic effects of a substance. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Pharmacotherapy: A regimen of using appetite suppressant medications to manage obesity by decreasing appetite or increasing the feeling of satiety. These medications decrease appetite by increasing serotonin or catecholamine—two brain chemicals that affect mood and appetite. [NIH] Pharynx: The hollow tube about 5 inches long that starts behind the nose and ends at the top of the trachea (windpipe) and esophagus (the tube that goes to the stomach). [NIH] Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of yeasts. [NIH] Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor of melanin, dopamine, noradrenalin, and thyroxine. [NIH] Phosphatidic Acids: Fatty acid derivatives of glycerophosphates. They are composed of glycerol bound in ester linkage with 1 mole of phosphoric acid at the terminal 3-hydroxyl group and with 2 moles of fatty acids at the other two hydroxyl groups. [NIH] Phosphorus: A non-metallic element that is found in the blood, muscles, nevers, bones, and teeth, and is a component of adenosine triphosphate (ATP; the primary energy source for the body's cells.) [NIH] Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. [NIH] Physiologic: Having to do with the functions of the body. When used in the phrase "physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH]

Physiology: The science that deals with the life processes and functions of organismus, their cells, tissues, and organs. [NIH] Pituitary Gland: A small, unpaired gland situated in the sella turcica tissue. It is connected to the hypothalamus by a short stalk. [NIH] Pityriasis: A name originally applied to a group of skin diseases characterized by the formation of fine, branny scales, but now used only with a modifier. [EU] Pityriasis Lichenoides: A subgroup of parapsoriasis itself divided into acute and chronic forms. The acute form is characterized by the abrupt onset of a generalized, reddish-brown, maculopapular eruption. Lesions may be vesicular, hemorrhagic, crusted, or necrotic. Histologically the disease is characterized by epidermal necrolysis. The chronic form shows milder skin changes with necrosis. An important variant of the chronic form is lymphomatoid papulosis. [NIH]

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Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] Plasmacytoma: Any discrete, presumably solitary, mass of neoplastic plasma cells either in bone marrow or various extramedullary sites. [NIH] Plasmids: Any extrachromosomal hereditary determinant. Plasmids are self-replicating circular molecules of DNA that are found in a variety of bacterial, archaeal, fungal, algal, and plant species. [NIH] Platelet Aggregation: The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin, collagen) and is part of the mechanism leading to the formation of a thrombus. [NIH] Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Platyhelminths: A phylum of acoelomate, bilaterally symmetrical flatworms, without a definite anus. It includes three classes: Cestoda, Turbellaria, and Trematoda. [NIH] Plethysmography: Recording of change in the size of a part as modified by the circulation in it. [NIH] Pleura: The thin serous membrane enveloping the lungs and lining the thoracic cavity. [NIH] Pleural: A circumscribed area of hyaline whorled fibrous tissue which appears on the surface of the parietal pleura, on the fibrous part of the diaphragm or on the pleura in the interlobar fissures. [NIH] Pleural cavity: A space enclosed by the pleura (thin tissue covering the lungs and lining the interior wall of the chest cavity). It is bound by thin membranes. [NIH] Pleural Effusion: Presence of fluid in the pleural cavity resulting from excessive transudation or exudation from the pleural surfaces. It is a sign of disease and not a diagnosis in itself. [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] Pneumothorax: Accumulation of air or gas in the space between the lung and chest wall, resulting in partial or complete collapse of the lung. [NIH] Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [NIH] Pollen: The male fertilizing element of flowering plants analogous to sperm in animals. It is released from the anthers as yellow dust, to be carried by insect or other vectors, including wind, to the ovary (stigma) of other flowers to produce the embryo enclosed by the seed. The pollens of many plants are allergenic. [NIH] Polymorphism: The occurrence together of two or more distinct forms in the same population. [NIH] Polyp: A growth that protrudes from a mucous membrane. [NIH]

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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] Polyposis: The development of numerous polyps (growths that protrude from a mucous membrane). [NIH] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] 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] Postprandial: Occurring after dinner, or after a meal; postcibal. [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 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] Prednisolone: A glucocorticoid with the general properties of the corticosteroids. It is the drug of choice for all conditions in which routine systemic corticosteroid therapy is indicated, except adrenal deficiency states. [NIH] Preleukemia: Conditions in which the abnormalities in the peripheral blood or bone marrow represent the early manifestations of acute leukemia, but in which the changes are not of sufficient magnitude or specificity to permit a diagnosis of acute leukemia by the usual clinical criteria. [NIH] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] Prickle: Several layers of the epidermis where the individual cells are connected by cell bridges. [NIH] Primary Biliary Cirrhosis: A chronic liver disease. Slowly destroys the bile ducts in the liver. This prevents release of bile. Long-term irritation of the liver may cause scarring and cirrhosis in later stages of the disease. [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] Prognostic factor: A situation or condition, or a characteristic of a patient, that can be used to estimate the chance of recovery from a disease, or the chance of the disease recurring (coming back). [NIH] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or

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severity. [EU] Progressive disease: Cancer that is increasing in scope or severity. [NIH] Proline: A non-essential amino acid that is synthesized from glutamic acid. It is an essential component of collagen and is important for proper functioning of joints and tendons. [NIH] Promoter: A chemical substance that increases the activity of a carcinogenic process. [NIH] 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] Prostate: A gland in males that surrounds the neck of the bladder and the urethra. It secretes a substance that liquifies coagulated semen. It is situated in the pelvic cavity behind the lower part of the pubic symphysis, above the deep layer of the triangular ligament, and rests upon the rectum. [NIH] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] 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] Proteinuria: The presence of protein in the urine, indicating that the kidneys are not working properly. [NIH] Proteoglycans: Glycoproteins which have a very high polysaccharide content. [NIH] Proteolytic: 1. Pertaining to, characterized by, or promoting proteolysis. 2. An enzyme that promotes proteolysis (= the splitting of proteins by hydrolysis of the peptide bonds with formation of smaller polypeptides). [EU] Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or vaccine dosages, length of study, routes of administration, who may participate, and other aspects of trial design. [NIH] Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] Protozoa: A subkingdom consisting of unicellular organisms that are the simplest in the animal kingdom. Most are free living. They range in size from submicroscopic to macroscopic. Protozoa are divided into seven phyla: Sarcomastigophora,

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Labyrinthomorpha, Apicomplexa, Microspora, Ascetospora, Myxozoa, and Ciliophora. [NIH] Protozoal: Having to do with the simplest organisms in the animal kingdom. Protozoa are single-cell organisms, such as ameba, and are different from bacteria, which are not members of the animal kingdom. Some protozoa can be seen without a microscope. [NIH] Protozoan: 1. Any individual of the protozoa; protozoon. 2. Of or pertaining to the protozoa; protozoal. [EU] Protozoan Infections: Infections with unicellular organisms of the subkingdom Protozoa. [NIH]

Pruritic: Pertaining to or characterized by pruritus. [EU] Pruritus: An intense itching sensation that produces the urge to rub or scratch the skin to obtain relief. [NIH] Psychiatric: Pertaining to or within the purview of psychiatry. [EU] Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders. [NIH] Psychology: The science dealing with the study of mental processes and behavior in man and animals. [NIH] Psyllium: Dried, ripe seeds of Plantago psyllium, P. indica, and P. ovata (Plantaginaceae). Plantain seeds swell in water and are used as demulcents and bulk laxatives. [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 Eosinophilia: A disease characterized by pulmonary infiltrations of eosinophils and blood eosinophilia. [NIH] Pulmonary Fibrosis: Chronic inflammation and progressive fibrosis of the pulmonary alveolar walls, with steadily progressive dyspnea, resulting finally in death from oxygen lack or right heart failure. [NIH] Pulmonary Ventilation: The total volume of gas per minute inspired or expired measured in liters per minute. [NIH] Pulse: The rhythmical expansion and contraction of an artery produced by waves of pressure caused by the ejection of blood from the left ventricle of the heart as it contracts. [NIH]

Purines: A series of heterocyclic compounds that are variously substituted in nature and are known also as purine bases. They include adenine and guanine, constituents of nucleic acids, as well as many alkaloids such as caffeine and theophylline. Uric acid is the metabolic end product of purine metabolism. [NIH] Purpura: Purplish or brownish red discoloration, easily visible through the epidermis, caused by hemorrhage into the tissues. [NIH] Putrefaction: The process of decomposition of animal and vegetable matter by living organisms. [NIH]

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Pyrimidines: A family of 6-membered heterocyclic compounds occurring in nature in a wide variety of forms. They include several nucleic acid constituents (cytosine, thymine, and uracil) and form the basic structure of the barbiturates. [NIH] 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] Racemic: Optically inactive but resolvable in the way of all racemic compounds. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radiation therapy: The use of high-energy radiation from x-rays, gamma rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body in the area near cancer cells (internal radiation therapy, implant radiation, or brachytherapy). Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Also called radiotherapy. [NIH] Radioactive: Giving off radiation. [NIH] Radiolabeled: Any compound that has been joined with a radioactive substance. [NIH] Radiotherapy: The use of ionizing radiation to treat malignant neoplasms and other benign conditions. The most common forms of ionizing radiation used as therapy are x-rays, gamma rays, and electrons. A special form of radiotherapy, targeted radiotherapy, links a cytotoxic radionuclide to a molecule that targets the tumor. When this molecule is an antibody or other immunologic molecule, the technique is called radioimmunotherapy. [NIH] Randomized: Describes an experiment or clinical trial in which animal or human subjects are assigned by chance to separate groups that compare different treatments. [NIH] Randomized clinical trial: A study in which the participants are assigned by chance to separate groups that compare different treatments; neither the researchers nor the participants can choose which group. Using chance to assign people to groups means that the groups will be similar and that the treatments they receive can be compared objectively. At the time of the trial, it is not known which treatment is best. It is the patient's choice to be in a randomized trial. [NIH] Receptivity: The condition of the reproductive organs of a female flower that permits effective pollination. [NIH] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Recombination: The formation of new combinations of genes as a result of segregation in crosses between genetically different parents; also the rearrangement of linked genes due to crossing-over. [NIH] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Recurrence: The return of a sign, symptom, or disease after a remission. [NIH] Red blood cells: RBCs. Cells that carry oxygen to all parts of the body. Also called erythrocytes. [NIH] Reductase: Enzyme converting testosterone to dihydrotestosterone. [NIH]

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Refer: To send or direct for treatment, aid, information, de decision. [NIH] Reflux: The term used when liquid backs up into the esophagus from the stomach. [NIH] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH] Refractory: Not readily yielding to treatment. [EU] Regeneration: The natural renewal of a structure, as of a lost tissue or part. [EU] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Regional lymph node: In oncology, a lymph node that drains lymph from the region around a tumor. [NIH] Regurgitation: A backward flowing, as the casting up of undigested food, or the backward flowing of blood into the heart, or between the chambers of the heart when a valve is incompetent. [EU] Relapse: The return of signs and symptoms of cancer after a period of improvement. [NIH] Remission: A decrease in or disappearance of signs and symptoms of cancer. In partial remission, some, but not all, signs and symptoms of cancer have disappeared. In complete remission, all signs and symptoms of cancer have disappeared, although there still may be cancer in the body. [NIH] Respiration: The act of breathing with the lungs, consisting of inspiration, or the taking into the lungs of the ambient air, and of expiration, or the expelling of the modified air which contains more carbon dioxide than the air taken in (Blakiston's Gould Medical Dictionary, 4th ed.). This does not include tissue respiration (= oxygen consumption) or cell respiration (= cell respiration). [NIH] Respiratory Burst: A large increase in oxygen uptake by neutrophils and most types of tissue macrophages through activation of an NADPH-cytochrome b-dependent oxidase that reduces oxygen to a superoxide. Individuals with an inherited defect in which the oxidase that reduces oxygen to superoxide is decreased or absent (granulomatous disease, chronic) often die as a result of recurrent bacterial infections. [NIH] 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 System: The tubular and cavernous organs and structures, by means of which pulmonary ventilation and gas exchange between ambient air and the blood are brought about. [NIH] Restrictive cardiomyopathy: Heart muscle disease in which the muscle walls become stiff and lose their flexibility. [NIH] Retina: The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outer-most layer is pigmented, whereas the inner nine layers are transparent. [NIH] Rheumatism: A group of disorders marked by inflammation or pain in the connective tissue structures of the body. These structures include bone, cartilage, and fat. [NIH] Rheumatoid: Resembling rheumatism. [EU] Rheumatoid arthritis: A form of arthritis, the cause of which is unknown, although infection, hypersensitivity, hormone imbalance and psychologic stress have been suggested as possible causes. [NIH]

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Rhinitis: Inflammation of the mucous membrane of the nose. [NIH] Rhinovirus: A genus of Picornaviridae inhabiting primarily the respiratory tract of mammalian hosts. It includes the human strains associated with common colds. [NIH] Ribose: A pentose active in biological systems usually in its D-form. [NIH] 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] Rods: One type of specialized light-sensitive cells (photoreceptors) in the retina that provide side vision and the ability to see objects in dim light (night vision). [NIH] Saline: A solution of salt and water. [NIH] Saliva: The clear, viscous fluid secreted by the salivary glands and mucous glands of the mouth. It contains mucins, water, organic salts, and ptylin. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [NIH] 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] Sarcoidosis: An idiopathic systemic inflammatory granulomatous disorder comprised of epithelioid and multinucleated giant cells with little necrosis. It usually invades the lungs with fibrosis and may also involve lymph nodes, skin, liver, spleen, eyes, phalangeal bones, and parotid glands. [NIH] Sarcoma: A connective tissue neoplasm formed by proliferation of mesodermal cells; it is usually highly malignant. [NIH] Scans: Pictures of structures inside the body. Scans often used in diagnosing, staging, and monitoring disease include liver scans, bone scans, and computed tomography (CT) or computerized axial tomography (CAT) scans and magnetic resonance imaging (MRI) scans. In liver scanning and bone scanning, radioactive substances that are injected into the bloodstream collect in these organs. A scanner that detects the radiation is used to create pictures. In CT scanning, an x-ray machine linked to a computer is used to produce detailed pictures of organs inside the body. MRI scans use a large magnet connected to a computer to create pictures of areas inside the body. [NIH] Schizophrenia: A mental disorder characterized by a special type of disintegration of the personality. [NIH] Sclera: The tough white outer coat of the eyeball, covering approximately the posterior fivesixths of its surface, and continuous anteriorly with the cornea and posteriorly with the external sheath of the optic nerve. [EU] Scleroderma: A chronic disorder marked by hardening and thickening of the skin. Scleroderma can be localized or it can affect the entire body (systemic). [NIH] Sclerosis: A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. [NIH]

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Screening: Checking for disease when there are no symptoms. [NIH] Secretion: 1. The process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. Any substance produced by secretion. [EU] Secretory: Secreting; relating to or influencing secretion or the secretions. [NIH] Segmental: Describing or pertaining to a structure which is repeated in similar form in successive segments of an organism, or which is undergoing segmentation. [NIH] Segmentation: The process by which muscles in the intestines move food and wastes through the body. [NIH] Semisynthetic: Produced by chemical manipulation of naturally occurring substances. [EU] Sensibility: The ability to receive, feel and appreciate sensations and impressions; the quality of being sensitive; the extend to which a method gives results that are free from false negatives. [NIH] Sensitization: 1. Administration of antigen to induce a primary immune response; priming; immunization. 2. Exposure to allergen that results in the development of hypersensitivity. 3. The coating of erythrocytes with antibody so that they are subject to lysis by complement in the presence of homologous antigen, the first stage of a complement fixation test. [EU] Serine: A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from glycine or threonine. It is involved in the biosynthesis of purines, pyrimidines, and other amino acids. [NIH] Serotonin: A biochemical messenger and regulator, synthesized from the essential amino acid L-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (receptors, serotonin) explain the broad physiological actions and distribution of this biochemical mediator. [NIH] Serous: Having to do with serum, the clear liquid part of blood. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] 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]

Shunt: A surgically created diversion of fluid (e.g., blood or cerebrospinal fluid) from one area of the body to another area of the body. [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] Signs and Symptoms: Clinical manifestations that can be either objective when observed by a physician, or subjective when perceived by the patient. [NIH] Sinusitis: An inflammatory process of the mucous membranes of the paranasal sinuses that occurs in three stages: acute, subacute, and chronic. Sinusitis results from any condition causing ostial obstruction or from pathophysiologic changes in the mucociliary transport mechanism. [NIH] Skeletal: Having to do with the skeleton (boney part of the body). [NIH] Skin test: A test for an immune response to a compound by placing it on or under the skin.

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[NIH]

Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Smallpox: A generalized virus infection with a vesicular rash. [NIH] Smoking Cessation: Discontinuation of the habit of smoking, the inhaling and exhaling of tobacco smoke. [NIH] Smoldering leukemia: Disease in which the bone marrow does not function normally. Also called preleukemia or myelodysplastic syndrome. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]

Sodium: An element that is a member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23. With a valence of 1, it has a strong affinity for oxygen and other nonmetallic elements. Sodium provides the chief cation of the extracellular body fluids. Its salts are the most widely used in medicine. (From Dorland, 27th ed) Physiologically the sodium ion plays a major role in blood pressure regulation, maintenance of fluid volume, and electrolyte balance. [NIH] Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] Solid tumor: Cancer of body tissues other than blood, bone marrow, or the lymphatic system. [NIH] Solvent: 1. Dissolving; effecting a solution. 2. A liquid that dissolves or that is capable of dissolving; the component of a solution that is present in greater amount. [EU] Soma: The body as distinct from the mind; all the body tissue except the germ cells; all the axial body. [NIH] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Specificity: Degree of selectivity shown by an antibody with respect to the number and types of antigens with which the antibody combines, as well as with respect to the rates and the extents of these reactions. [NIH] Spectroscopic: The recognition of elements through their emission spectra. [NIH] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU] Sperm: The fecundating fluid of the male. [NIH] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] Spinous: Like a spine or thorn in shape; having spines. [NIH]

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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] Squamous: Scaly, or platelike. [EU] Squamous cell carcinoma: Cancer that begins in squamous cells, which are thin, flat cells resembling fish scales. Squamous cells are found in the tissue that forms the surface of the skin, the lining of the hollow organs of the body, and the passages of the respiratory and digestive tracts. Also called epidermoid carcinoma. [NIH] Squamous cell carcinoma: Cancer that begins in squamous cells, which are thin, flat cells resembling fish scales. Squamous cells are found in the tissue that forms the surface of the skin, the lining of the hollow organs of the body, and the passages of the respiratory and digestive tracts. Also called epidermoid carcinoma. [NIH] Squamous cells: Flat cells that look like fish scales under a microscope. These cells cover internal and external surfaces of the body. [NIH] Squamous Epithelium: Tissue in an organ such as the esophagus. Consists of layers of flat, scaly cells. [NIH] Staging: Performing exams and tests to learn the extent of the cancer within the body, especially whether the disease has spread from the original site to other parts of the body. [NIH]

Staphylococcus: A genus of gram-positive, facultatively anaerobic, coccoid bacteria. Its organisms occur singly, in pairs, and in tetrads and characteristically divide in more than one plane to form irregular clusters. Natural populations of Staphylococcus are membranes of warm-blooded animals. Some species are opportunistic pathogens of humans and animals. [NIH] Stem Cell Factor: Hematopoietic growth factor and the ligand of the c-kit receptor CD117 (proto-oncogene protein C-kit). It is expressed during embryogenesis and provides a key signal in multiple aspects of mast-cell differentiation and function. [NIH] Stem Cells: Relatively undifferentiated cells of the same lineage (family type) that retain the ability to divide and cycle throughout postnatal life to provide cells that can become specialized and take the place of those that die or are lost. [NIH] Stenosis: Narrowing or stricture of a duct or canal. [EU] Sterility: 1. The inability to produce offspring, i.e., the inability to conceive (female s.) or to induce conception (male s.). 2. The state of being aseptic, or free from microorganisms. [EU] Steroid: A group name for lipids that contain a hydrogenated cyclopentanoperhydrophenanthrene ring system. Some of the substances included in this group are progesterone, adrenocortical hormones, the gonadal hormones, cardiac aglycones, bile acids, sterols (such as cholesterol), toad poisons, saponins, and some of the carcinogenic hydrocarbons. [EU] Stimulant: 1. Producing stimulation; especially producing stimulation by causing tension on muscle fibre through the nervous tissue. 2. An agent or remedy that produces stimulation. [EU]

Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH]

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Streptomycin: O-2-Deoxy-2-(methylamino)-alpha-L-glucopyranosyl-(1-2)-O-5- deoxy-3-Cformyl-alpha-L-lyxofuranosyl-(1-4)-N,N'-bis(aminoiminomethyl)-D-streptamine. Antibiotic substance produced by the soil actinomycete Streptomyces griseus. It acts by inhibiting the initiation and elongation processes during protein synthesis. [NIH] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] Stricture: The abnormal narrowing of a body opening. Also called stenosis. [NIH] Stroma: The middle, thickest layer of tissue in the cornea. [NIH] Stromal: Large, veil-like cell in the bone marrow. [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] Subcutaneous: Beneath the skin. [NIH] Submandibular: Four to six lymph glands, located between the lower jaw and the submandibular salivary gland. [NIH] Subspecies: A category intermediate in rank between species and variety, based on a smaller number of correlated characters than are used to differentiate species and generally conditioned by geographical and/or ecological occurrence. [NIH] Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of pain, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses. [NIH]

Substrate: A substance upon which an enzyme acts. [EU] Suction: The removal of secretions, gas or fluid from hollow or tubular organs or cavities by means of a tube and a device that acts on negative pressure. [NIH] Sulfur: An element that is a member of the chalcogen family. It has an atomic symbol S, atomic number 16, and atomic weight 32.066. It is found in the amino acids cysteine and methionine. [NIH] Superoxide: Derivative of molecular oxygen that can damage cells. [NIH] Supplementation: Adding nutrients to the diet. [NIH] Suppositories: A small cone-shaped medicament having cocoa butter or gelatin at its basis and usually intended for the treatment of local conditions in the rectum. [NIH] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Suppressive: Tending to suppress : effecting suppression; specifically : serving to suppress activity, function, symptoms. [EU] Surfactant: A fat-containing protein in the respiratory passages which reduces the surface tension of pulmonary fluids and contributes to the elastic properties of pulmonary tissue. [NIH]

Sweat: The fluid excreted by the sweat glands. It consists of water containing sodium chloride, phosphate, urea, ammonia, and other waste products. [NIH] Sweat Glands: Sweat-producing structures that are embedded in the dermis. Each gland consists of a single tube, a coiled body, and a superficial duct. [NIH]

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Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] Synapse: The region where the processes of two neurons come into close contiguity, and the nervous impulse passes from one to the other; the fibers of the two are intermeshed, but, according to the general view, there is no direct contiguity. [NIH] Systemic: Affecting the entire body. [NIH] Systemic lupus erythematosus: SLE. A chronic inflammatory connective tissue disease marked by skin rashes, joint pain and swelling, inflammation of the kidneys, inflammation of the fibrous tissue surrounding the heart (i.e., the pericardium), as well as other problems. Not all affected individuals display all of these problems. May be referred to as lupus. [NIH] Tacrolimus: A macrolide isolated from the culture broth of a strain of Streptomyces tsukubaensis that has strong immunosuppressive activity in vivo and prevents the activation of T-lymphocytes in response to antigenic or mitogenic stimulation in vitro. [NIH] Temporal: One of the two irregular bones forming part of the lateral surfaces and base of the skull, and containing the organs of hearing. [NIH] Testosterone: A hormone that promotes the development and maintenance of male sex characteristics. [NIH] Tetracycline: An antibiotic originally produced by Streptomyces viridifaciens, but used mostly in synthetic form. It is an inhibitor of aminoacyl-tRNA binding during protein synthesis. [NIH] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thermal: Pertaining to or characterized by heat. [EU] Threonine: An essential amino acid occurring naturally in the L-form, which is the active form. It is found in eggs, milk, gelatin, and other proteins. [NIH] Threshold: For a specified sensory modality (e. g. light, sound, vibration), the lowest level (absolute threshold) or smallest difference (difference threshold, difference limen) or intensity of the stimulus discernible in prescribed conditions of stimulation. [NIH] Thrombocytes: Blood cells that help prevent bleeding by causing blood clots to form. Also called platelets. [NIH] Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thromboxanes: Physiologically active compounds found in many organs of the body. They are formed in vivo from the prostaglandin endoperoxides and cause platelet aggregation, contraction of arteries, and other biological effects. Thromboxanes are important mediators of the actions of polyunsaturated fatty acids transformed by cyclooxygenase. [NIH] Thymus: An organ that is part of the lymphatic system, in which T lymphocytes grow and multiply. The thymus is in the chest behind the breastbone. [NIH] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH] Thyrotropin: A peptide hormone secreted by the anterior pituitary. It promotes the growth of the thyroid gland and stimulates the synthesis of thyroid hormones and the release of thyroxine by the thyroid gland. [NIH] Tinnitus: Sounds that are perceived in the absence of any external noise source which may take the form of buzzing, ringing, clicking, pulsations, and other noises. Objective tinnitus refers to noises generated from within the ear or adjacent structures that can be heard by other individuals. The term subjective tinnitus is used when the sound is audible only to the affected individual. Tinnitus may occur as a manifestation of cochlear diseases;

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vestibulocochlear nerve diseases; intracranial hypertension; craniocerebral trauma; and other conditions. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Titre: The quantity of a substance required to produce a reaction with a given volume of another substance, or the amount of one substance required to correspond with a given amount of another substance. [EU] 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] Topical: On the surface of the body. [NIH] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxin: A poison; frequently used to refer specifically to a protein produced by some higher plants, certain animals, and pathogenic bacteria, which is highly toxic for other living organisms. Such substances are differentiated from the simple chemical poisons and the vegetable alkaloids by their high molecular weight and antigenicity. [EU] Trachea: The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi. [NIH] Transcriptase: An enzyme which catalyses the synthesis of a complementary mRNA molecule from a DNA template in the presence of a mixture of the four ribonucleotides (ATP, UTP, GTP and CTP). [NIH] Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process. [NIH] Transduction: The transfer of genes from one cell to another by means of a viral (in the case of bacteria, a bacteriophage) vector or a vector which is similar to a virus particle (pseudovirion). [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Transfer Factor: Factor derived from leukocyte lysates of immune donors which can transfer both local and systemic cellular immunity to nonimmune recipients. [NIH] 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] 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]

Dictionary 199

Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Trichloroethylene: A highly volatile inhalation anesthetic used mainly in short surgical procedures where light anesthesia with good analgesia is required. It is also used as an industrial solvent. Prolonged exposure to high concentrations of the vapor can lead to cardiotoxicity and neurological impairment. [NIH] Tryptophan: An essential amino acid that is necessary for normal growth in infants and for nitrogen balance in adults. It is a precursor serotonin and niacin. [NIH] Tuberculosis: Any of the infectious diseases of man and other animals caused by species of Mycobacterium. [NIH] Tumor marker: A substance sometimes found in an increased amount in the blood, other body fluids, or tissues and which may mean that a certain type of cancer is in the body. Examples of tumor markers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and gastrointestinal tract cancers), and PSA (prostate cancer). Also called biomarker. [NIH] Tumor Necrosis Factor: Serum glycoprotein produced by activated macrophages and other mammalian mononuclear leukocytes which has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. It mimics the action of endotoxin but differs from it. It has a molecular weight of less than 70,000 kDa. [NIH] Tumour: 1. Swelling, one of the cardinal signs of inflammations; morbid enlargement. 2. A new growth of tissue in which the multiplication of cells is uncontrolled and progressive; called also neoplasm. [EU] Tunica: A rather vague term to denote the lining coat of hollow organs, tubes, or cavities. [NIH]

Tympanic membrane: A thin, tense membrane forming the greater part of the outer wall of the tympanic cavity and separating it from the external auditory meatus; it constitutes the boundary between the external and middle ear. [NIH] Tyrosine: A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine, thyroid hormones, and melanin. [NIH] Ulcerative colitis: Chronic inflammation of the colon that produces ulcers in its lining. This condition is marked by abdominal pain, cramps, and loose discharges of pus, blood, and mucus from the bowel. [NIH] Uraemia: 1. An excess in the blood of urea, creatinine, and other nitrogenous end products of protein and amino acids metabolism; more correctly referred to as azotemia. 2. In current usage the entire constellation of signs and symptoms of chronic renal failure, including nausea, vomiting anorexia, a metallic taste in the mouth, a uraemic odour of the breath, pruritus, uraemic frost on the skin, neuromuscular disorders, pain and twitching in the muscles, hypertension, edema, mental confusion, and acid-base and electrolyte imbalances. [EU]

Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]

Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] 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] Urticaria: A vascular reaction of the skin characterized by erythema and wheal formation due to localized increase of vascular permeability. The causative mechanism may be allergy,

200

Eosinophilia

infection, or stress. [NIH] Uterus: The small, hollow, pear-shaped organ in a woman's pelvis. This is the organ in which a fetus develops. Also called the womb. [NIH] Uvea: The middle coat of the eyeball, consisting of the choroid in the back of the eye and the ciliary body and iris in the front of the eye. [NIH] Uveitis: An inflammation of part or all of the uvea, the middle (vascular) tunic of the eye, and commonly involving the other tunics (the sclera and cornea, and the retina). [EU] 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]

Vaccinia: The cutaneous and occasional systemic reactions associated with vaccination using smallpox (variola) vaccine. [NIH] Vaccinia Virus: The type species of Orthopoxvirus, related to cowpox virus, but whose true origin is unknown. It has been used as a live vaccine against smallpox. It is also used as a vector for inserting foreign DNA into animals. Rabbitpox virus is a subspecies of vaccinia virus. [NIH] Vacuoles: Any spaces or cavities within a cell. They may function in digestion, storage, secretion, or excretion. [NIH] Vagina: The muscular canal extending from the uterus to the exterior of the body. Also called the birth canal. [NIH] Variola: A generalized virus infection with a vesicular rash. [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vasculitis: Inflammation of a blood vessel. [NIH] Vasodilator: An agent that widens blood vessels. [NIH] Vasomotor: 1. Affecting the calibre of a vessel, especially of a blood vessel. 2. Any element or agent that effects the calibre of a blood vessel. [EU] VE: The total volume of gas either inspired or expired in one minute. [NIH] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venous: Of or pertaining to the veins. [EU] Venous blood: Blood that has given up its oxygen to the tissues and carries carbon dioxide back for gas exchange. [NIH] Ventricle: One of the two pumping chambers of the heart. The right ventricle receives oxygen-poor blood from the right atrium and pumps it to the lungs through the pulmonary artery. The left ventricle receives oxygen-rich blood from the left atrium and pumps it to the body through the aorta. [NIH] Ventricular: Pertaining to a ventricle. [EU] Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Vertigo: An illusion of movement; a sensation as if the external world were revolving

Dictionary 201

around the patient (objective vertigo) or as if he himself were revolving in space (subjective vertigo). The term is sometimes erroneously used to mean any form of dizziness. [EU] Vesicular: 1. Composed of or relating to small, saclike bodies. 2. Pertaining to or made up of vesicles on the skin. [EU] 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] Viral Load: The quantity of measurable virus in the blood. Change in viral load, measured in plasma, is used as a surrogate marker in HIV disease progression. [NIH] Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [NIH] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH] Viscera: Any of the large interior organs in any one of the three great cavities of the body, especially in the abdomen. [NIH] Visceral: , from viscus a viscus) pertaining to a viscus. [EU] 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] Wart: A raised growth on the surface of the skin or other organ. [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]

Windpipe: A rigid tube, 10 cm long, extending from the cricoid cartilage to the upper border of the fifth thoracic vertebra. [NIH] Wound Healing: Restoration of integrity to traumatized tissue. [NIH] Xenograft: The cells of one species transplanted to another species. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH] 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]

203

INDEX 5 5-Hydroxytryptophan, 96, 99, 141 A Abdominal, 141, 158, 164, 172, 177, 183, 184, 199 Abdominal Pain, 141, 164, 184, 199 Aberrant, 15, 34, 59, 69, 141 Ablation, 11, 25, 26, 141 Acanthocephala, 141, 167 Acceptor, 141, 174, 182 Acetylcholine, 23, 39, 141, 152, 180, 181 Acquired Immunodeficiency Syndrome, 89, 141 Acute lymphoblastic leukemia, 64, 70, 77, 83, 88, 96, 97, 141 Acute lymphocytic leukemia, 141 Acute myelogenous leukemia, 15, 50, 141 Acute myeloid leukemia, 74, 141 Acute nonlymphocytic leukemia, 141 Acute renal, 141, 167 Acyl, 142, 175 Adaptability, 142, 151 Adenine, 142, 189 Adenocarcinoma, 112, 142 Adenoma, 112, 142 Adenosine, 40, 82, 142, 185 Adenosine Deaminase, 40, 142 Adjuvant, 142, 165 Adoptive Transfer, 26, 36, 142 Adrenal Cortex, 142, 155, 187 Adrenergic, 10, 142, 143, 146, 158, 161 Adsorption, 102, 142 Adsorptive, 142 Adverse Effect, 142, 153, 181, 193 Aerosol, 11, 26, 37, 142 Affinity, 5, 14, 38, 102, 142, 143, 153, 176, 194 Affinity Chromatography, 102, 142 Agonist, 143, 158 Agranulocytosis, 62, 143, 153 Air Pollutants, 23, 143 Alanine, 49, 143 Albumin, 143, 182 Albuterol, 6, 116, 143 Algorithms, 143, 149 Alimentary, 143, 183 Alkaline, 82, 143, 144, 150 Alkaline Phosphatase, 82, 143

Alleles, 143, 174 Allergen, 7, 8, 10, 11, 13, 18, 19, 20, 21, 41, 51, 65, 69, 78, 83, 86, 92, 143, 157, 193 Allergic Rhinitis, 78, 103, 108, 143, 166 Allium, 63, 143 Allo, 106, 143 Allograft, 56, 104, 108, 143 Alopecia, 143, 156 Alpha Particles, 143, 190 Alternative medicine, 116, 143 Ameliorated, 98, 144 Ameliorating, 31, 144 Amine, 144, 167 Amino Acid Motifs, 144, 155 Amino Acid Sequence, 24, 144, 145, 155, 165 Ammonia, 142, 144, 196 Ampulla, 144, 160 Anaesthesia, 85, 144, 170 Anal, 144, 161, 163 Analogous, 144, 158, 186, 198 Anaphylatoxins, 144, 154 Anaplasia, 144 Anaplastic, 25, 144, 145 Anaplastic large cell lymphoma, 25, 145 Anatomical, 145, 170, 183, 192 Androgens, 142, 145, 155 Anemia, 145, 179 Anergic, 10, 145 Anergy, 145 Anesthesia, 143, 145, 199 Angioedema, 38, 46, 53, 79, 99, 145 Animal model, 8, 11, 14, 20, 23, 28, 35, 41, 145 Anorexia, 145, 164, 199 Antagonism, 145, 153 Antiallergic, 48, 102, 145, 156 Antibacterial, 145, 194 Antibiotic, 145, 178, 194, 196, 197 Antibodies, 3, 10, 13, 19, 45, 67, 104, 108, 145, 166, 168, 169, 175, 178, 186 Anticoagulant, 96, 145, 188 Antiepileptic, 141, 146 Antifungal, 13, 146 Antigen-Antibody Complex, 102, 146, 154 Antigen-presenting cell, 146, 157 Anti-infective, 30, 146

204

Eosinophilia

Anti-inflammatory, 6, 17, 146, 147, 156, 165 Anti-Inflammatory Agents, 6, 146, 147, 156 Antineoplastic, 146, 156, 172, 178 Antioxidant, 98, 146, 182 Antipsychotic, 146, 153, 180 Antiviral, 42, 43, 146, 172 Apoptosis, 9, 12, 23, 25, 29, 31, 146, 151, 156 Arachidonic Acid, 147, 159, 188 Arginine, 144, 147, 181 Arterial, 147, 168, 188 Arteries, 147, 149, 155, 177, 197 Arterioles, 147, 149, 177 Arteritis, 65, 71, 83, 147 Artery, 47, 48, 147, 149, 155, 159, 160, 176, 183, 189, 200 Articular, 107, 147, 174 Aspartic, 147, 151 Aspartic Acid, 147, 151 Aspergillosis, 84, 147 Aspirin, 7, 147 Assay, 15, 147 Asthenia, 145, 147 Astringents, 147, 177 Asymptomatic, 20, 82, 86, 147, 163, 183 Atopic, 4, 8, 13, 17, 23, 33, 37, 42, 50, 54, 66, 80, 86, 103, 108, 147 Attenuated, 37, 73, 147, 200 Attenuation, 27, 147 Atypical, 90, 147, 153, 175 Auditory, 112, 147, 176, 199 Autodigestion, 147, 183 Autoimmune disease, 102, 103, 105, 106, 107, 147, 179 Autologous, 92, 147 Autologous bone marrow transplantation, 92, 147 Autonomic, 141, 146, 148, 181 Autopsy, 52, 148 B Bacteria, 19, 102, 112, 142, 145, 146, 148, 160, 162, 177, 189, 192, 194, 195, 198, 200 Bacterial Infections, 148, 191 Bactericidal, 30, 148 Bacteriophage, 148, 198 Bacteriostatic, 143, 148 Bacterium, 148, 167 Basal cell carcinoma, 112, 148 Basal cells, 148 Basement Membrane, 148, 162, 173

Basophil, 24, 148 Benign, 61, 80, 112, 142, 145, 148, 166, 175, 180, 190 Benign tumor, 112, 148 Bile, 148, 152, 164, 168, 174, 187, 195 Bile Acids, 148, 164, 195 Bile duct, 148, 152, 187 Biliary, 82, 112, 148, 183 Biliary Tract, 148, 183 Biochemical, 18, 28, 49, 143, 148, 150, 173, 193 Biological therapy, 148, 166 Biomarkers, 29, 148 Biopsy, 3, 49, 149 Biopsy specimen, 3, 149 Biosynthesis, 5, 147, 149, 193 Biotechnology, 43, 45, 116, 125, 149 Bladder, 88, 149, 156, 179, 188, 199 Blood Coagulation, 149, 150, 163 Blood Platelets, 149, 169, 193 Blood pressure, 149, 178, 194 Blood vessel, 18, 149, 160, 167, 174, 175, 177, 184, 194, 197, 200 Body Fluids, 148, 149, 159, 194, 199 Bone Density, 6, 149 Bone Marrow Transplantation, 61, 149 Bone scan, 149, 192 Bowel, 144, 149, 171, 172, 184, 199 Brachytherapy, 149, 172, 190 Bradykinin, 149, 181 Breeding, 16, 150 Bronchi, 150, 161, 198 Bronchial, 10, 12, 14, 33, 41, 42, 46, 51, 66, 70, 73, 83, 84, 85, 90, 103, 104, 108, 150, 167 Bronchial Hyperreactivity, 33, 84, 150 Bronchioles, 150 Bronchiolitis, 34, 58, 115, 150 Bronchitis, 36, 51, 150, 153 Bronchoalveolar Lavage, 10, 19, 39, 150 Bronchoalveolar Lavage Fluid, 19, 150 Bronchoconstriction, 11, 150 Bronchus, 150 Buccal, 150, 175 Buffers, 29, 150 Bupropion, 57, 150 C Calcium, 5, 106, 150, 154, 182 Callus, 150, 173 Capsules, 150, 165 Carbohydrate, 24, 150, 155, 165, 187

205

Carbon Dioxide, 151, 157, 163, 164, 168, 191, 200 Carboxy, 16, 151 Carcinogenic, 151, 171, 182, 188, 195 Carcinogens, 151, 182 Carcinoma, 52, 74, 77, 84, 86, 96, 112, 151 Cardiac, 151, 160, 161, 179, 195 Cardiomyopathy, 151 Case report, 52, 53, 56, 59, 62, 66, 77, 84, 151 Caspases, 24, 151 Catecholamine, 151, 158, 185 Causal, 151, 161 Cell Adhesion, 18, 151, 171 Cell Death, 12, 23, 29, 31, 146, 151, 165, 180 Cell Differentiation, 37, 151, 195 Cell Division, 148, 151, 166, 178, 186 Cell Lineage, 15, 151 Cell membrane, 10, 151 Cell proliferation, 26, 35, 151, 172 Cell Survival, 23, 35, 151, 166 Central Nervous System, 83, 141, 143, 151, 152, 153, 164, 165, 166, 168, 179, 193 Cerebral, 46, 152, 161, 162 Cerebrospinal, 46, 64, 71, 74, 77, 83, 89, 152, 193 Cerebrospinal fluid, 46, 64, 71, 74, 77, 83, 89, 152, 193 Cerebrum, 152 Cerumen, 112, 152 Cervix, 74, 152 Chalazion, 80, 152 Chemokines, 8, 14, 20, 21, 33, 41, 152 Chemotactic Factors, 64, 152, 154 Chemotaxis, 10, 18, 152 Chemotherapy, 97, 152 Chest Pain, 61, 152 Chest wall, 152, 186 Chimeras, 11, 152 Cholangitis, 78, 152 Cholesteatoma, 112, 152 Cholesterol, 148, 152, 195 Cholinergic, 10, 146, 152 Chondrocytes, 152, 163 Chromatin, 146, 152 Chromatography, Ion Exchange, 102, 152 Chromosomal, 7, 16, 28, 61, 152 Chromosome, 6, 15, 30, 59, 152, 173, 174 Chronic Disease, 153, 174 Chronic Obstructive Pulmonary Disease, 48, 153 Cirrhosis, 82, 153, 187

CIS, 92, 153 C-kit receptor, 54, 153, 195 Clinical Medicine, 153, 187 Clinical trial, 4, 125, 153, 179, 188, 190 Clone, 59, 153 Cloning, 5, 24, 53, 149, 153 Clozapine, 66, 67, 86, 153 Codon, 27, 153, 165 Cofactor, 153, 188 Cohort Studies, 153, 161 Colitis, 153 Collagen, 40, 44, 55, 144, 148, 153, 162, 163, 165, 186, 188 Collapse, 154, 186 Colon, 65, 153, 154, 171, 173, 199 Complement, 8, 102, 144, 154, 165, 169, 171, 173, 193 Complementary and alternative medicine, 95, 99, 154 Complementary medicine, 95, 154 Computational Biology, 125, 154 Computed tomography, 149, 154, 155, 192 Computerized axial tomography, 154, 155, 192 Concomitant, 26, 77, 155 Congestive heart failure, 155, 160 Conjunctiva, 155, 171, 173, 176 Connective Tissue, 149, 153, 155, 157, 163, 164, 165, 175, 177, 191, 192, 197 Consciousness, 155, 157, 158 Consensus Sequence, 32, 144, 155 Conserved Sequence, 144, 155 Constipation, 146, 155, 184 Constriction, 109, 155 Contraindications, ii, 155 Coordination, 155, 179 Cornea, 155, 173, 192, 196, 200 Corneum, 155, 161 Coronary, 59, 155, 177 Coronary Thrombosis, 155, 177 Corticosteroid, 6, 65, 71, 74, 79, 155, 187 Cowpox, 156, 200 Cowpox Virus, 156, 200 Critical Care, 35, 48, 51, 73, 156 Cross-Sectional Studies, 156, 161 Curative, 156, 181, 197 Cutaneous, 21, 38, 54, 56, 66, 68, 72, 75, 76, 83, 87, 90, 145, 156, 158, 175, 200 Cyclic, 10, 156, 166, 181 Cyclophosphamide, 31, 156 Cyst, 113, 152, 156 Cysteine, 24, 151, 152, 156, 196

206

Eosinophilia

Cysteine Endopeptidases, 151, 156 Cysteinyl, 5, 54, 156 Cystine, 156 Cystitis, 83, 156 Cytochrome, 156, 191 Cytochrome b, 156, 191 Cytokine, 9, 10, 13, 17, 21, 27, 32, 34, 35, 38, 41, 42, 43, 54, 61, 66, 83, 104, 108, 157, 172 Cytomegalovirus, 26, 157 Cytoplasm, 146, 151, 157, 160, 161 Cytoskeleton, 157, 171 Cytotoxic, 29, 157, 170, 190 D Decarboxylation, 157, 167 Degenerative, 157, 167 Deletion, 52, 59, 146, 157 Dementia, 141, 146, 157 Dendrites, 157 Dendritic, 4, 13, 17, 19, 30, 41, 157 Dendritic cell, 4, 13, 17, 19, 30, 41, 157 Dermatitis, 37, 38, 50, 54, 61, 62, 66, 103, 108, 112, 157, 159 Dermatosis, 157, 163 Dermis, 145, 157, 196 Desensitization, 7, 32, 157, 170 Desmoid tumor, 76, 157 Developed Countries, 26, 157 Developing Countries, 27, 157 Diagnostic procedure, 101, 116, 157 Diaphragm, 158, 186 Diarrhoea, 158, 164 Diathesis, 20, 40, 158 Diffusion, 158, 171 Digestion, 143, 148, 149, 158, 172, 174, 195, 200 Digestive tract, 158, 194, 195 Dihydrotestosterone, 158, 190 Direct, iii, 11, 13, 17, 26, 28, 34, 55, 119, 153, 158, 183, 191, 197 Discrete, 158, 186 Dissociation, 56, 73, 142, 158 Dissociative Disorders, 158 Distal, 18, 25, 158, 164 Domesticated, 158, 166 Dopamine, 146, 150, 153, 158, 180, 185 Drug Design, 27, 158 Drug Eruptions, 71, 158 Drug Interactions, 120, 159 Drug Tolerance, 159, 198 Duct, 144, 159, 162, 192, 195, 196 Duodenum, 148, 159, 160, 183, 195

Dura mater, 159, 177, 183 Dysphagia, 60, 159 Dyspnea, 109, 159, 189 E Eczema, 103, 108, 159 Edema, 109, 145, 159, 180, 199 Effector, 11, 16, 17, 24, 26, 40, 41, 141, 154, 159 Effector cell, 17, 41, 159 Efficacy, 28, 31, 43, 158, 159 Effusion, 159, 175 Eicosanoids, 5, 159 Elastic, 159, 196 Elastin, 154, 159, 162 Electrolyte, 155, 159, 178, 194, 199 Electrons, 146, 159, 173, 182, 190 Emaciation, 141, 159 Emboli, 65, 159, 160 Embolization, 65, 160 Embryo, 151, 160, 170, 186 Emphysema, 153, 160 Endocarditis, 65, 75, 160 Endocardium, 160 Endocytosis, 32, 160 Endogenous, 158, 159, 160, 182, 198 Endomyocardial Fibrosis, 97, 160 Endoscope, 160 Endoscopic, 43, 74, 160 Endothelial cell, 17, 18, 21, 93, 145, 160, 163 Endothelium, 7, 18, 39, 160, 181 Endothelium, Lymphatic, 160 Endothelium, Vascular, 160 Endothelium-derived, 160, 181 Endotoxins, 154, 160, 173 Environmental Health, 124, 126, 160 Enzymatic, 18, 45, 102, 144, 150, 154, 160, 167 Enzyme, 5, 39, 40, 43, 142, 143, 156, 158, 159, 160, 166, 175, 184, 188, 190, 196, 198, 201 Eosinophilic Gastroenteritis, 77, 81, 112, 161 Epidemic, 27, 44, 161 Epidemiologic Studies, 48, 161 Epidermal, 161, 173, 185 Epidermis, 41, 148, 155, 157, 161, 173, 187, 189 Epidermoid carcinoma, 161, 195 Epigastric, 161, 183 Epinephrine, 142, 158, 161, 180, 181, 199

207

Epithelial, 12, 14, 21, 30, 36, 41, 42, 51, 85, 104, 142, 161, 167, 173 Epithelial Cells, 12, 14, 21, 30, 41, 42, 43, 161, 167, 173 Epithelium, 7, 10, 26, 30, 31, 33, 43, 105, 148, 160, 161 Epitope, 92, 161 Erythema, 59, 161, 162, 199 Erythema Infectiosum, 161, 162 Erythrocytes, 145, 149, 161, 169, 190, 193 Erythropoietin, 86, 161 Esophageal, 30, 60, 77, 161, 164, 180 Esophageal Stricture, 77, 161 Esophagitis, 30, 162, 164 Esophagus, 30, 158, 161, 162, 164, 175, 181, 185, 191, 195 Evoke, 162, 195 Exanthema, 63, 162 Exocrine, 162, 183 Exogenous, 10, 32, 142, 159, 160, 162, 185 External-beam radiation, 162, 190 Extracellular, 14, 19, 35, 39, 155, 160, 162, 163, 171, 194 Extracellular Matrix, 14, 35, 39, 155, 162, 163, 171 Extracellular Matrix Proteins, 14, 162 Extracellular Space, 162 Extravasation, 63, 162 Extravascular, 18, 162 Extremity, 88, 162 F Facial, 47, 60, 162, 176, 183 Family Planning, 125, 162 Fasciitis, 50, 55, 67, 75, 81, 84, 162 Fat, 147, 149, 155, 159, 163, 174, 179, 191, 194, 196 Fatigue, 51, 163, 167 Fetus, 161, 163, 200 Fibroblast Growth Factor, 28, 163 Fibroblasts, 109, 162, 163, 172 Fibronectins, 162, 163 Fibrosarcoma, 162, 163 Fibrosis, 7, 14, 24, 36, 40, 45, 112, 163, 189, 192 Filariasis, 44, 73, 163 Filtration, 102, 163 Fixation, 163, 193 Fluoxetine, 81, 163 Follow-Up Studies, 5, 163 Foramen, 163, 167, 176, 184 Forearm, 149, 162, 164 Free Radicals, 146, 158, 164

Fungi, 13, 146, 147, 164, 177, 200, 201 Furunculosis, 112, 164 G Gadolinium, 31, 164 Gallbladder, 141, 148, 164 Gamma Rays, 164, 190 Ganglia, 141, 146, 164, 180 Gangrene, 89, 164 Gas, 144, 151, 158, 164, 168, 181, 186, 189, 191, 196, 200 Gas exchange, 164, 191, 200 Gastric, 147, 164, 167 Gastrin, 164, 168 Gastroenteritis, 112, 164 Gastroesophageal Reflux, 30, 164 Gastroesophageal Reflux Disease, 30, 164 Gastrointestinal, 63, 97, 105, 112, 150, 161, 164, 168, 193, 196, 199 Gastrointestinal tract, 112, 164, 168, 193, 199 Gelatin, 65, 165, 196, 197 Gene, 6, 9, 11, 15, 16, 19, 20, 21, 22, 24, 25, 26, 27, 28, 29, 30, 33, 35, 39, 53, 55, 61, 143, 149, 165 Gene Expression, 9, 21, 22, 29, 33, 35, 55, 165 Gene Rearrangement, 53, 165 Genetic Code, 165, 181 Genetic Engineering, 149, 153, 165 Genetics, 6, 15, 53, 61, 73, 74, 79, 89, 142, 165 Genotype, 165, 185 Giant Cells, 165, 192 Gland, 7, 48, 112, 142, 165, 175, 183, 185, 188, 193, 195, 196, 197 Glucocorticoid, 9, 24, 104, 165, 187 Glucuronic Acid, 165, 167 Glutamic Acid, 165, 180, 188 Glycerol, 165, 185 Glycerophospholipids, 18, 165 Glycine, 144, 165, 180, 193 Glycoprotein, 16, 21, 34, 44, 45, 69, 105, 108, 161, 165, 166, 173, 176, 179, 199 Glycosaminoglycans, 162, 166 Gonadal, 166, 195 Governing Board, 166, 187 Grade, 106, 166 Graft, 49, 58, 64, 166, 170 Graft Rejection, 166, 170 Graft-versus-host disease, 58, 166 Granule, 24, 29, 30, 166 Granulocyte, 42, 64, 65, 72, 166

208

Eosinophilia

Granuloma, 44, 80, 82, 97, 166 Groin, 166, 171 Growth factors, 62, 166 Guanylate Cyclase, 166, 181 Guinea Pigs, 23, 98, 166 H Haematological, 53, 88, 166 Haematology, 62, 66, 166 Haptens, 109, 142, 166 Hay Fever, 143, 166 Headache, 161, 166, 171 Heart failure, 167, 189 Helminths, 69, 74, 167, 180 Hematologic malignancies, 28, 167 Hematopoiesis, 167, 172 Hematuria, 66, 167 Hemolytic, 102, 162, 167 Hemorrhage, 166, 167, 189 Hemostasis, 167, 171, 193 Heparin, 23, 167 Hepatic, 45, 51, 143, 167, 174 Hepatitis, 61, 62, 63, 66, 90, 167 Hepatocytes, 167 Hepatotoxicity, 83, 167 Hereditary, 40, 167, 184, 186 Heredity, 165, 167 Herniated, 112, 167 Heterodimers, 167, 171 Heterogeneity, 38, 66, 142, 167 Heterotrophic, 164, 167 Histamine, 8, 102, 103, 107, 144, 146, 167, 168 Histidine, 167, 168, 172 Histiocytosis, 97, 168 Homologous, 52, 143, 168, 193 Hormonal, 155, 168 Hormone, 66, 92, 143, 155, 159, 161, 164, 168, 171, 187, 191, 197 Hormone Replacement Therapy, 92, 168 Humoral, 23, 37, 166, 168 Humour, 168 Hybrid, 39, 153, 168 Hybridomas, 168, 172 Hydrogen, 141, 144, 150, 162, 168, 174, 178, 181, 182, 184, 188 Hydrolysis, 142, 147, 168, 175, 187, 188 Hydrophobic, 165, 168 Hydroxylysine, 154, 168 Hydroxyproline, 144, 154, 168 Hypercapnia, 109, 168 Hypereosinophilic Syndrome, 38, 168 Hyperglycemia, 66, 169

Hyperplasia, 7, 14, 40, 46, 47, 48, 54, 56, 59, 72, 73, 75, 80, 82, 83, 87, 88, 90, 95, 96, 98, 112, 113, 145, 169 Hypersensitivity, 68, 143, 157, 161, 169, 191, 193 Hypertrophy, 40, 169 Hypodermic, 103, 169 Hypothyroidism, 92, 169 Hypoxemia, 109, 169 Hypoxia, 169 I Idiopathic, 63, 68, 69, 78, 168, 169, 192 Idiopathic myelofibrosis, 78, 169 Immune Adherence Reaction, 102, 169 Immune Complex Diseases, 146, 169 Immune function, 169, 170 Immune Sera, 169 Immune system, 19, 102, 107, 146, 148, 159, 169, 170, 175, 176, 179, 185, 201 Immunization, 17, 33, 37, 104, 108, 142, 169, 170, 193 Immunodeficiency, 25, 57, 68, 102, 103, 107, 141, 169 Immunodeficiency syndrome, 102, 103, 107, 169 Immunoglobulin, 37, 41, 44, 56, 89, 102, 103, 106, 145, 170, 178 Immunologic, 13, 31, 34, 49, 142, 152, 169, 170, 190 Immunosuppression, 170, 182 Immunosuppressive, 102, 107, 112, 156, 165, 170, 197 Immunosuppressive Agents, 102, 107, 112, 170 Immunosuppressive therapy, 170 Immunotherapy, 17, 36, 92, 142, 148, 157, 170 Impairment, 170, 199 Implant radiation, 170, 172, 190 In vitro, 9, 10, 12, 14, 15, 16, 18, 20, 23, 25, 32, 33, 35, 39, 42, 43, 170, 197 In vivo, 9, 12, 14, 15, 18, 19, 21, 23, 25, 32, 33, 35, 37, 40, 42, 52, 167, 170, 182, 197 Incidental, 80, 170 Incision, 170, 173 Incompetence, 164, 170 Induction, 12, 13, 17, 21, 25, 27, 28, 34, 36, 40, 43, 105, 145, 146, 170 Infarction, 155, 170, 177 Infiltration, 5, 14, 53, 65, 168, 171, 175 Inflammatory bowel disease, 5, 171 Influenza, 34, 171

209

Infusion, 31, 171 Ingestion, 75, 96, 97, 158, 171, 186 Inguinal, 90, 171 Inhalation, 10, 17, 60, 142, 171, 186, 199 Initiation, 28, 105, 108, 171, 196, 198 Initiator, 171, 172 Inorganic, 171, 179 Insight, 9, 21, 22, 30, 171 Instillation, 13, 171 Insulator, 171, 179 Insulin, 171, 173 Integrins, 18, 39, 171 Interferon, 4, 31, 36, 44, 46, 53, 105, 108, 171, 172, 175 Interferon Alfa-2a, 46, 172 Interferon-alpha, 171, 172 Interleukin-1, 59, 105, 108, 172 Interleukin-12, 105, 108, 172 Interleukin-15, 59, 172 Interleukin-2, 45, 59, 172 Interleukin-5, 27, 29, 32, 44, 45, 53, 55, 65, 70, 73, 77, 104, 105, 172 Interleukin-6, 40, 172 Interleukins, 104, 108, 170, 172 Intermittent, 80, 172, 184 Internal radiation, 172, 190 Interstitial, 149, 150, 162, 172 Intervertebral, 167, 172 Intestinal, 69, 74, 172 Intestine, 149, 172, 173, 184 Intracellular, 9, 29, 151, 170, 171, 172, 181, 192 Intramuscular, 172, 183 Intraperitoneal, 23, 172 Intravenous, 31, 39, 171, 172, 183 Intrinsic, 12, 142, 148, 172 Invasive, 10, 173, 176 Ion Exchange, 152, 173 Ion Exchange Resins, 152, 173 Ions, 150, 152, 158, 159, 168, 173 Islet, 105, 108, 173 K Karyotype, 54, 173 Kb, 124, 173 Keratin, 173 Keratinocytes, 5, 41, 173 Keratoconjunctivitis, 89, 173 Keratosis, 112, 173 Keto, 52, 173 L Labile, 154, 173 Laminin, 148, 162, 173

Large Intestine, 158, 161, 172, 173, 190, 194 Laser therapy, 82, 173 Lavage, 78, 173 Lectin, 14, 24, 173 Leiomyosarcoma, 58, 173 Lesion, 31, 46, 48, 166, 174 Lethal, 29, 148, 174 Lethargy, 169, 174 Leucocyte, 160, 174, 175 Leukaemia, 52, 97, 174 Leukemia, 15, 28, 53, 59, 69, 76, 78, 79, 89, 97, 167, 168, 174, 187 Leukocyte Count, 52, 174 Leukocytes, 11, 16, 18, 21, 30, 33, 39, 105, 149, 152, 172, 174, 184, 199 Leukocytosis, 88, 97, 174 Life cycle, 164, 174 Ligaments, 155, 174 Ligands, 5, 25, 171, 174 Linkage, 6, 174, 185 Linkage Disequilibrium, 7, 174 Lipid, 5, 20, 165, 171, 173, 174, 179, 182 Lipid Peroxidation, 174, 182 Liver Cirrhosis, 88, 174 Liver scan, 174, 192 Liver Transplantation, 56, 81, 174 Localization, 25, 65, 69, 174 Localized, 75, 112, 145, 163, 170, 173, 175, 186, 192, 199 Lower Esophageal Sphincter, 164, 175 Lung Transplantation, 64, 175 Lupus, 96, 102, 103, 175, 197 Lymph, 4, 11, 13, 41, 61, 62, 90, 97, 113, 160, 168, 175, 191, 192, 196 Lymph node, 4, 11, 13, 41, 97, 113, 175, 191, 192 Lymphadenopathy, 61, 62, 90, 175 Lymphatic, 73, 89, 145, 160, 171, 175, 177, 194, 195, 197 Lymphatic system, 145, 175, 194, 195, 197 Lymphoblasts, 141, 175 Lymphocyte, 4, 10, 13, 16, 39, 66, 69, 72, 87, 141, 146, 170, 172, 175, 176 Lymphocyte Count, 141, 175 Lymphocytic, 76, 175 Lymphocytosis, 61, 62, 175 Lymphoid, 4, 62, 112, 113, 145, 174, 175 Lymphoma, 15, 28, 53, 66, 77, 85, 95, 96, 97, 113, 145, 167, 175 Lymphomatoid Papulosis, 175, 185 Lymphopenia, 60, 175 Lysine, 168, 172, 175

210

Eosinophilia

Lysophospholipase, 24, 175 Lysophospholipids, 18, 175 M Macrophage, 42, 65, 172, 176 Macrophage Colony-Stimulating Factor, 65, 176 Maculopapular, 176, 183, 185 Magnetic Resonance Imaging, 176, 192 Malignancy, 28, 95, 113, 176 Malignant fibrous histiocytoma, 76, 176 Malignant tumor, 49, 102, 103, 107, 112, 176, 179 Manifest, 40, 176 Mastocytosis, 52, 54, 59, 69, 176 Meatus, 176, 199 Medial, 112, 176 Mediate, 8, 18, 29, 32, 39, 40, 158, 176 Mediator, 4, 5, 172, 176, 193 Medicament, 143, 176, 196 MEDLINE, 125, 176 Meibomian, 152, 176 Meibomian Glands, 152, 176 Melanin, 176, 185, 199 Memory, 16, 37, 145, 157, 177 Meninges, 151, 152, 159, 177 Meningitis, 71, 177 Mental, iv, 4, 124, 126, 157, 158, 163, 169, 170, 177, 189, 192, 199 Mental Health, iv, 4, 124, 126, 177, 189 Mental Processes, 158, 177, 189 Mercury, 57, 177 Mesenchymal, 35, 176, 177 Mesentery, 177, 184 Metabolite, 5, 177 Metaplasia, 39, 40, 177 Metastasis, 177 Metastasize, 157, 177 Methylprednisolone, 31, 177 MI, 139, 177 Microbe, 177, 198 Microcirculation, 174, 177 Microfilaria, 69, 177 Microorganism, 153, 177, 184, 201 Migration, 4, 18, 21, 38, 42, 178 Milliliter, 149, 178 Millimeter, 106, 178 Mineralocorticoids, 142, 155, 178 Minocycline, 62, 178 Minority Groups, 22, 178 Mitochondrial Swelling, 178, 180 Mitosis, 147, 178 Mitoxantrone, 31, 178

Mobilization, 5, 18, 20, 178 Modeling, 40, 158, 178 Modification, 144, 165, 178 Molecular, 9, 12, 15, 17, 18, 19, 23, 24, 27, 28, 30, 32, 35, 36, 37, 38, 41, 56, 77, 93, 125, 127, 149, 154, 158, 167, 173, 178, 196, 198, 199 Monitor, 9, 43, 54, 178, 181 Monoclonal, 18, 21, 38, 104, 168, 178, 190 Monoclonal antibodies, 18, 21, 178 Monocyte, 34, 64, 176, 178 Mononuclear, 54, 70, 162, 166, 176, 179, 199 Monophosphate, 82, 179 Morphology, 166, 179 Motion Sickness, 179, 180 Mucociliary, 179, 193 Mucolytic, 150, 179 Mucosa, 30, 59, 113, 175, 179 Mucus, 9, 10, 26, 36, 38, 40, 41, 179, 199 Multicenter study, 38, 179 Multiple Myeloma, 52, 179 Multiple sclerosis, 102, 103, 107, 179 Mutagenesis, 24, 27, 32, 179 Mutagens, 179 Myelin, 179 Myelodysplastic syndrome, 59, 73, 179, 194 Myelogenous, 179 Myeloma, 113, 179 Myocardium, 160, 177, 179 Myositis, 106, 179 N Nasal Cavity, 179 Nasal Mucosa, 98, 171, 179 Natural killer cells, 172, 179 Nausea, 55, 146, 164, 180, 199 NCI, 1, 123, 153, 180 Necrolysis, 180, 185 Necrosis, 63, 146, 162, 163, 170, 177, 180, 185, 192 Nematoda, 167, 180 Neoplasia, 180 Neoplasm, 180, 192, 199 Neoplastic, 59, 144, 152, 168, 175, 180, 186 Nephrosis, 180 Nephrotic, 83, 180 Nephrotic Syndrome, 83, 180 Nerve, 47, 142, 145, 157, 167, 176, 179, 180, 183, 191, 192, 195, 198 Nervous System, 151, 176, 180, 196 Neural, 168, 180

211

Neuroblastoma, 92, 180 Neuroleptic, 146, 153, 180 Neurologic, 78, 97, 180 Neuromuscular, 141, 180, 199 Neuromuscular Junction, 141, 180 Neurotransmitter, 141, 142, 144, 147, 150, 158, 165, 167, 180, 181, 196 Neutralization, 102, 181 Neutrons, 143, 181, 190 Neutrophil, 5, 181 Nevirapine, 56, 57, 181 Niacin, 181, 199 Nitric Oxide, 42, 43, 54, 80, 86, 115, 181 Nitrogen, 144, 145, 156, 162, 163, 181, 199 Noel, 10, 181 Non-nucleoside, 181 Norepinephrine, 142, 158, 180, 181 Nuclear, 21, 48, 63, 73, 81, 159, 164, 180, 181 Nuclei, 105, 143, 159, 165, 176, 178, 181, 188 Nucleic acid, 105, 108, 165, 179, 181, 189, 190 Nucleus, 15, 146, 152, 156, 157, 164, 179, 181, 188 O Ocular, 181, 182 Oesophagitis, 63, 181 Onchocerciasis, 44, 181 Oncogenic, 171, 182 Oncology, 59, 83, 89, 182, 191 Ophthalmologist, 80, 182 Opportunistic Infections, 141, 182 Orbit, 47, 182 Osteolysis, 54, 182 Otitis, 112, 182 Otolaryngology, 74, 82, 84, 112, 182 Otology, 47, 65, 112, 182 Ovalbumin, 13, 23, 26, 37, 39, 92, 182 Ovary, 45, 182, 186 Overexpress, 40, 182 Oxidants, 29, 182 Oxidation, 29, 141, 146, 156, 174, 182 Oxidation-Reduction, 182 Oxidative Stress, 29, 182 Oxygenation, 169, 182 P Pachymeningitis, 177, 183 Palliative, 183, 197 Pancreas, 112, 141, 148, 171, 173, 183, 199 Pancreatic, 24, 96, 164, 183 Pancreatic Juice, 164, 183

Pancreatitis, 86, 183 Parapsoriasis, 183, 185 Parasite, 24, 183 Parasitic, 27, 102, 103, 104, 106, 107, 141, 167, 183, 192 Parasitic Diseases, 102, 103, 107, 183 Parenchyma, 17, 183 Parenteral, 61, 158, 183 Parenteral Nutrition, 61, 183 Parietal, 183, 184, 186 Parotid, 183, 192 Partial remission, 183, 191 Particle, 183, 198 Patch, 57, 183 Pathogen, 27, 184 Pathogenesis, 5, 6, 8, 10, 21, 22, 23, 26, 28, 29, 33, 35, 36, 41, 42, 43, 49, 112, 113, 184 Pathologic, 13, 39, 112, 147, 149, 155, 169, 184 Pathologic Processes, 147, 184 Pathologies, 11, 26, 36, 184 Pathophysiology, 7, 25, 92, 109, 112, 184 Pelvic, 54, 184, 188 Pelvis, 173, 184, 200 Peptide, 144, 163, 173, 184, 187, 188, 197 Perfusion, 89, 169, 184 Peripheral blood, 3, 6, 15, 22, 38, 46, 54, 56, 66, 70, 77, 78, 81, 90, 172, 184, 187 Peripheral stem cells, 166, 184 Peristalsis, 30, 184 Peritoneal, 60, 69, 112, 172, 184 Peritoneal Cavity, 172, 184 Peritoneal Dialysis, 60, 69, 184 Peritoneum, 18, 177, 184 Peritonitis, 69, 184 Peroxidase, 29, 45, 174, 184 Peroxide, 174, 184 PH, 50, 83, 149, 184 Phagocyte, 176, 182, 185 Pharmaceutical Preparations, 165, 185 Pharmacokinetics, 158, 185 Pharmacologic, 145, 185, 198 Pharmacotherapy, 62, 79, 81, 185 Pharynx, 164, 171, 179, 185 Phenotype, 6, 19, 35, 36, 39, 185 Phenylalanine, 185, 199 Phosphatidic Acids, 175, 185 Phosphorus, 150, 185 Phosphorylation, 10, 32, 185 Physiologic, 18, 24, 29, 32, 40, 143, 149, 185, 190 Physiology, 8, 71, 80, 112, 185

212

Eosinophilia

Pituitary Gland, 155, 163, 185 Pityriasis, 77, 183, 185 Pityriasis Lichenoides, 77, 183, 185 Plants, 147, 150, 151, 173, 179, 181, 186, 192, 198 Plasma, 20, 63, 74, 143, 145, 151, 160, 163, 165, 167, 178, 179, 186, 201 Plasma cells, 145, 179, 186 Plasmacytoma, 113, 186 Plasmids, 28, 186 Platelet Aggregation, 144, 181, 186, 197 Platelets, 5, 18, 109, 181, 186, 197 Platyhelminths, 167, 186 Plethysmography, 10, 186 Pleura, 186 Pleural, 61, 66, 81, 186 Pleural cavity, 186 Pleural Effusion, 66, 186 Pneumonia, 50, 155, 186 Pneumonitis, 68, 186 Pneumothorax, 85, 186 Poisoning, 164, 177, 180, 186 Pollen, 97, 186 Polymorphism, 20, 186 Polyp, 112, 186 Polypeptide, 144, 153, 155, 187, 188 Polyposis, 7, 54, 58, 74, 187 Polysaccharide, 146, 187, 188 Posterior, 144, 183, 187, 192 Postnatal, 187, 195 Postprandial, 55, 187 Potentiates, 172, 187 Practice Guidelines, 126, 187 Preclinical, 28, 187 Precursor, 15, 64, 141, 147, 156, 158, 159, 160, 181, 185, 187, 199 Prednisolone, 177, 187 Preleukemia, 179, 187, 194 Prevalence, 39, 66, 187 Prickle, 173, 187 Primary Biliary Cirrhosis, 57, 187 Progesterone, 187, 195 Prognostic factor, 86, 87, 187 Progression, 8, 15, 25, 105, 108, 145, 187, 201 Progressive, 29, 151, 153, 157, 159, 169, 180, 187, 188, 189, 199 Progressive disease, 169, 188 Proline, 35, 154, 168, 188 Promoter, 15, 30, 188 Prophylaxis, 188, 200 Prospective study, 7, 188

Prostaglandins, 147, 159, 188 Prostate, 148, 188, 199 Protease, 42, 188 Protein C, 143, 144, 148, 153, 173, 188 Protein Conformation, 144, 173, 188 Protein S, 14, 24, 149, 155, 165, 188, 196, 197 Proteinuria, 66, 179, 180, 188 Proteoglycans, 148, 162, 188 Proteolytic, 154, 188 Protocol, 38, 188 Protons, 143, 168, 188, 190 Protozoa, 177, 188, 189, 200 Protozoal, 189 Protozoan, 27, 189 Protozoan Infections, 27, 189 Pruritic, 68, 159, 189 Pruritus, 82, 182, 189, 199 Psychiatric, 62, 189 Psychiatry, 67, 163, 189 Psychology, 158, 189 Psyllium, 96, 189 Public Health, 39, 126, 189 Public Policy, 125, 189 Publishing, 43, 104, 189 Pulmonary, 6, 8, 10, 11, 12, 16, 19, 24, 26, 35, 44, 49, 52, 53, 55, 68, 69, 73, 74, 75, 77, 80, 82, 86, 89, 92, 93, 111, 149, 150, 161, 189, 191, 196, 200 Pulmonary Eosinophilia, 10, 11, 12, 44, 49, 52, 69, 73, 74, 75, 80, 89, 92, 111, 189 Pulmonary Fibrosis, 35, 189 Pulmonary Ventilation, 189, 191 Pulse, 31, 178, 189 Purines, 189, 193 Purpura, 81, 189 Putrefaction, 164, 189 Pyrimidines, 190, 193 R Race, 143, 173, 178, 190 Racemic, 143, 190 Radiation, 74, 162, 164, 170, 172, 190, 192, 201 Radiation therapy, 74, 162, 172, 190 Radioactive, 149, 168, 170, 172, 174, 178, 181, 182, 190, 192 Radiolabeled, 190 Radiotherapy, 149, 190 Randomized, 6, 159, 190 Randomized clinical trial, 6, 190 Receptivity, 38, 190 Recombinant, 34, 44, 90, 172, 190, 200

213

Recombination, 165, 190 Rectum, 154, 158, 164, 171, 173, 188, 190, 196 Recurrence, 43, 190 Red blood cells, 161, 167, 169, 190, 192 Reductase, 5, 190 Refer, 1, 150, 154, 163, 164, 174, 180, 181, 191, 198 Reflux, 164, 191 Refraction, 191, 194 Refractory, 106, 191 Regeneration, 163, 191 Regimen, 57, 159, 185, 191 Regional lymph node, 73, 191 Regurgitation, 164, 191 Relapse, 77, 97, 191 Remission, 46, 69, 82, 190, 191 Respiration, 151, 178, 191 Respiratory Burst, 29, 191 Respiratory distress syndrome, 82, 191 Respiratory System, 109, 179, 191 Restrictive cardiomyopathy, 71, 191 Retina, 191, 192, 200 Rheumatism, 38, 107, 191 Rheumatoid, 102, 103, 182, 191 Rheumatoid arthritis, 102, 103, 191 Rhinitis, 51, 65, 78, 103, 192 Rhinovirus, 26, 43, 192 Ribose, 142, 192 Rickettsiae, 192, 200 Risk factor, 7, 43, 161, 188, 192 Rods, 164, 192 S Saline, 150, 192 Saliva, 192 Salivary, 48, 157, 192, 196 Salivary glands, 157, 192 Saponins, 192, 195 Sarcoidosis, 80, 81, 192 Sarcoma, 163, 176, 192 Scans, 3, 192 Schizophrenia, 86, 192 Sclera, 155, 192, 200 Scleroderma, 81, 162, 192 Sclerosis, 179, 192 Screening, 93, 153, 193 Secretion, 7, 19, 22, 24, 30, 31, 45, 156, 167, 168, 169, 172, 178, 179, 193, 200 Secretory, 21, 105, 106, 193 Segmental, 13, 19, 20, 23, 193 Segmentation, 193 Semisynthetic, 178, 193

Sensibility, 144, 193 Sensitization, 11, 19, 21, 23, 38, 49, 193 Serine, 32, 193 Serotonin, 141, 146, 153, 163, 180, 185, 193, 199 Serous, 160, 186, 193 Shock, 84, 109, 193, 199 Shunt, 64, 74, 193 Side effect, 103, 104, 108, 119, 142, 146, 148, 156, 193, 198 Signs and Symptoms, 191, 193, 199 Sinusitis, 3, 7, 53, 54, 80, 193 Skeletal, 145, 179, 193 Skin test, 67, 193 Skull, 152, 182, 194, 197 Small intestine, 159, 161, 168, 172, 194 Smallpox, 194, 200 Smoking Cessation, 150, 194 Smoldering leukemia, 179, 194 Smooth muscle, 10, 14, 31, 109, 144, 150, 167, 194, 196 Sodium, 112, 178, 194, 196 Soft tissue, 48, 75, 112, 149, 162, 163, 176, 194 Solid tumor, 29, 194 Solvent, 165, 194, 199 Soma, 194 Somatic, 6, 168, 178, 194 Specialist, 131, 194 Specificity, 15, 24, 142, 187, 194 Spectroscopic, 78, 194 Spectrum, 38, 194 Sperm, 145, 152, 186, 194 Spinal cord, 151, 152, 159, 177, 180, 183, 194 Spinous, 161, 173, 194 Spleen, 13, 157, 175, 192, 195 Sputum, 24, 46, 53, 54, 60, 67, 70, 71, 79, 82, 85, 195 Squamous, 30, 59, 77, 87, 112, 152, 161, 195 Squamous cell carcinoma, 59, 77, 87, 112, 161, 195 Squamous cells, 195 Squamous Epithelium, 30, 152, 195 Staging, 192, 195 Staphylococcus, 164, 178, 195 Stem Cell Factor, 153, 195 Stem Cells, 105, 161, 184, 195 Stenosis, 112, 195, 196 Sterility, 156, 195 Steroid, 6, 104, 192, 195 Stimulant, 167, 195

214

Eosinophilia

Stimulus, 17, 21, 43, 150, 159, 195, 197 Stomach, 141, 147, 158, 161, 162, 164, 168, 173, 175, 180, 184, 185, 191, 194, 195 Streptomycin, 56, 196 Stress, 151, 164, 180, 182, 191, 196, 200 Stricture, 195, 196 Stroma, 183, 196 Stromal, 18, 41, 80, 82, 85, 196 Subacute, 170, 193, 196 Subclinical, 170, 196 Subcutaneous, 85, 145, 159, 182, 183, 196 Submandibular, 48, 196 Subspecies, 194, 196, 200 Substance P, 44, 177, 193, 196 Substrate, 29, 196 Suction, 163, 196 Sulfur, 162, 196 Superoxide, 191, 196 Supplementation, 29, 98, 196 Suppositories, 165, 196 Suppression, 17, 98, 105, 156, 196 Suppressive, 40, 102, 103, 107, 196 Surfactant, 25, 196 Sweat, 152, 157, 196 Sweat Glands, 152, 157, 196 Symptomatic, 103, 108, 150, 183, 197 Synapse, 142, 180, 197, 198 Systemic lupus erythematosus, 107, 169, 197 T Tacrolimus, 50, 197 Temporal, 71, 83, 176, 197 Testosterone, 190, 197 Tetracycline, 178, 197 Therapeutics, 41, 52, 104, 120, 197 Thermal, 158, 181, 197 Threonine, 193, 197 Threshold, 70, 197 Thrombocytes, 186, 197 Thrombosis, 171, 188, 197 Thromboxanes, 147, 159, 197 Thymus, 41, 169, 175, 197 Thyroid, 84, 86, 92, 169, 197, 199 Thyrotropin, 169, 197 Tinnitus, 182, 197 Titre, 104, 108, 198 Tolerance, 17, 142, 198 Tomography, 154, 155, 198 Topical, 43, 57, 65, 78, 147, 198 Toxic, iv, 20, 33, 49, 62, 84, 93, 185, 198 Toxicity, 29, 57, 102, 159, 177, 181, 198 Toxicology, 49, 66, 79, 126, 198

Toxin, 11, 198 Trachea, 150, 185, 197, 198 Transcriptase, 181, 198 Transcription Factors, 33, 198 Transduction, 19, 28, 32, 198 Transfection, 9, 149, 198 Transfer Factor, 169, 198 Translation, 144, 198 Translocation, 15, 21, 28, 50, 78, 79, 89, 97, 198 Transmitter, 141, 158, 176, 181, 198 Transplantation, 28, 49, 50, 56, 58, 60, 81, 169, 198 Trauma, 112, 162, 166, 180, 183, 198, 199 Trichloroethylene, 66, 199 Tryptophan, 44, 48, 55, 61, 63, 67, 68, 75, 76, 79, 81, 85, 93, 96, 97, 106, 154, 193, 199 Tuberculosis, 106, 175, 199 Tumor marker, 148, 199 Tumor Necrosis Factor, 41, 105, 108, 199 Tumour, 59, 87, 199 Tunica, 179, 199 Tympanic membrane, 72, 112, 199 Tyrosine, 14, 15, 22, 28, 32, 35, 158, 199 U Ulcerative colitis, 72, 78, 171, 199 Uraemia, 183, 199 Urethra, 188, 199 Urinary, 156, 199 Urine, 58, 88, 149, 167, 188, 199 Urticaria, 88, 103, 108, 199 Uterus, 152, 173, 187, 200 Uvea, 200 Uveitis, 80, 200 V Vaccination, 44, 200 Vaccines, 28, 34, 200, 201 Vaccinia, 34, 200 Vaccinia Virus, 34, 200 Vacuoles, 160, 200 Vagina, 152, 200 Variola, 200 Vascular, 18, 90, 145, 157, 160, 170, 171, 174, 177, 181, 199, 200 Vasculitis, 68, 80, 89, 183, 200 Vasodilator, 150, 158, 167, 200 Vasomotor, 103, 200 VE, 7, 200 Vector, 27, 183, 198, 200 Vein, 172, 181, 183, 200 Venous, 174, 188, 200

215

Venous blood, 174, 200 Ventricle, 160, 189, 200 Ventricular, 74, 89, 200 Venules, 149, 160, 177, 200 Vertigo, 182, 200 Vesicular, 185, 194, 200, 201 Veterinary Medicine, 125, 201 Viral, 16, 26, 28, 33, 34, 42, 43, 163, 165, 171, 182, 198, 201 Viral Load, 33, 201 Virulence, 147, 198, 201 Virus, 16, 21, 25, 26, 33, 34, 42, 44, 45, 57, 58, 68, 69, 141, 148, 156, 165, 172, 194, 198, 200, 201 Viscera, 177, 194, 201 Visceral, 184, 201

Vitro, 10, 12, 14, 32, 42, 167, 201 Vivo, 12, 14, 18, 21, 24, 32, 33, 35, 42, 201 W Wart, 173, 201 White blood cell, 81, 104, 106, 112, 141, 145, 148, 161, 166, 174, 175, 176, 178, 179, 181, 186, 201 Windpipe, 150, 185, 197, 201 Wound Healing, 163, 171, 201 X Xenograft, 145, 201 X-ray, 24, 149, 154, 155, 164, 181, 190, 192, 201 Y Yeasts, 164, 185, 201

216

Eosinophilia