APLASTIC ANEMIA 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., 1960Aplastic Anemia: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References / James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary, and index. ISBN: 0-597-84336-8 1. Aplastic Anemia-Popular works. I. Title.
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Disclaimer This publication is not intended to be used for the diagnosis or treatment of a health problem. It is sold with the understanding that the publisher, editors, and authors are not engaging in the rendering of medical, psychological, financial, legal, or other professional services. References to any entity, product, service, or source of information that may be contained in this publication should not be considered an endorsement, either direct or implied, by the publisher, editors, or authors. ICON Group International, Inc., the editors, and the authors are not responsible for the content of any Web pages or publications referenced in this publication.
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Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this book which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which produce publications on aplastic anemia. 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 APLASTIC ANEMIA ................................................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Aplastic Anemia............................................................................ 4 E-Journals: PubMed Central ....................................................................................................... 35 The National Library of Medicine: PubMed ................................................................................ 36 CHAPTER 2. NUTRITION AND APLASTIC ANEMIA ......................................................................... 83 Overview...................................................................................................................................... 83 Finding Nutrition Studies on Aplastic Anemia .......................................................................... 83 Federal Resources on Nutrition ................................................................................................... 87 Additional Web Resources ........................................................................................................... 87 CHAPTER 3. ALTERNATIVE MEDICINE AND APLASTIC ANEMIA ................................................... 89 Overview...................................................................................................................................... 89 National Center for Complementary and Alternative Medicine.................................................. 89 Additional Web Resources ........................................................................................................... 92 General References ....................................................................................................................... 93 CHAPTER 4. CLINICAL TRIALS AND APLASTIC ANEMIA ................................................................ 95 Overview...................................................................................................................................... 95 Recent Trials on Aplastic Anemia ............................................................................................... 95 Keeping Current on Clinical Trials ........................................................................................... 104 CHAPTER 5. PATENTS ON APLASTIC ANEMIA .............................................................................. 107 Overview.................................................................................................................................... 107 Patents on Aplastic Anemia....................................................................................................... 107 Patent Applications on Aplastic Anemia................................................................................... 114 Keeping Current ........................................................................................................................ 117 CHAPTER 6. BOOKS ON APLASTIC ANEMIA ................................................................................. 119 Overview.................................................................................................................................... 119 Book Summaries: Online Booksellers......................................................................................... 119 Chapters on Aplastic Anemia .................................................................................................... 120 CHAPTER 7. PERIODICALS AND NEWS ON APLASTIC ANEMIA .................................................... 123 Overview.................................................................................................................................... 123 News Services and Press Releases.............................................................................................. 123 Academic Periodicals covering Aplastic Anemia....................................................................... 125 CHAPTER 8. RESEARCHING MEDICATIONS .................................................................................. 127 Overview.................................................................................................................................... 127 U.S. Pharmacopeia..................................................................................................................... 127 Commercial Databases ............................................................................................................... 128 Researching Orphan Drugs ....................................................................................................... 128 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 133 Overview.................................................................................................................................... 133 NIH Guidelines.......................................................................................................................... 133 NIH Databases........................................................................................................................... 135 Other Commercial Databases..................................................................................................... 137 APPENDIX B. PATIENT RESOURCES ............................................................................................... 139 Overview.................................................................................................................................... 139 Patient Guideline Sources.......................................................................................................... 139 Associations and Aplastic Anemia............................................................................................. 144 Finding Associations.................................................................................................................. 145 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 147 Overview.................................................................................................................................... 147
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Preparation................................................................................................................................. 147 Finding a Local Medical Library................................................................................................ 147 Medical Libraries in the U.S. and Canada ................................................................................. 147 ONLINE GLOSSARIES................................................................................................................ 153 Online Dictionary Directories ................................................................................................... 153 APLASTIC ANEMIA DICTIONARY ........................................................................................ 155 INDEX .............................................................................................................................................. 215
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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 aplastic anemia 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 aplastic anemia, 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 aplastic anemia, 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 aplastic anemia. 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 aplastic anemia, 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 aplastic anemia. 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 APLASTIC ANEMIA Overview In this chapter, we will show you how to locate peer-reviewed references and studies on aplastic anemia.
The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and aplastic anemia, 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 “aplastic anemia” (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: •
Oral Manifestations in Patients with Aplastic Anemia Source: Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics. 92(5): 503-508. November 2001. Contact: Available from Mosby, Inc. 6277 Sea Harbor Drive, Orlando, FL 32887-4800. (800) 654-2452 or (407) 345-4000. Website: www.harcourthealth.com. Summary: Aplastic anemia is a serious hematologic disease characterized by hypocellular bone marrow and symptoms of fatigue, increased bruising epistaxis, and gingival hemorrhage. This article reports on a study undertaken to characterize the prevalence and risks of oral complications in aplastic anemia (AA). The study included 79 patients with AA (aged 37 years, plus or minus 17 years) and 66 control patients with schizophrenia (aged 33 years, plus or minus 12 years). Records were reviewed for
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demographic, clinical, and radiographic information. Prior medical therapy, laboratory values, disease duration, and medical treatment response were noted for patients with AA. Patients with AA presented more frequently with oral petechiae (tiny red spots), gingival hyperplasia (overgrowth of the gums), spontaneous gingival bleeding, and herpetic lesions. Prior cyclosporine use was associated with gingival hyperplasia. No other predictors for oral manifestations or treatment outcomes were found. The authors conclude that oral soft tissue changes and infections were more common in patients with AA. 3 tables. 15 references.
Federally Funded Research on Aplastic Anemia The U.S. Government supports a variety of research studies relating to aplastic anemia. 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 aplastic anemia. 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 aplastic anemia. The following is typical of the type of information found when searching the CRISP database for aplastic anemia: •
Project Title: ACTIVATION & PROLIFERATION OF HEMATOPOIETIC STEM CELLS Principal Investigator & Institution: Lansdorp, Peter M.; Associate Professor; British Columbia Cancer Research Centre 601 W 10Th Ave Vancouver, Timing: Fiscal Year 2002; Project Start 01-AUG-1990; Project End 31-MAY-2007 Summary: (provided by applicant): Hematopoietic stern cells (HSC), unlike e.g. embryonic stem cells, have a finite potential to divide. Limitations in the replication potential of HSC appear to be important in hematological disorders such as aplastic anemia and chronic myeloid leukemia. Such limitations could furthermore hamper the development of novel therapeutic strategies, including ex vivo stem cell expansion and gene therapy. Based on these considerations, studies that may help define and extend the replicative potential of HSC are important and a general interest. Previous studies with purified human "candidate" HSC funded by this grant have shown that the functional properties of HSC change dramatically during ontogeny and that the loss in HSC proliferative potential with age correlates with measurable shortening of telomeres. Here we propose to further examine the role of telomerase and telomeres in hematopoiesis. Specifically, we want to test the hypothesis that the replication history of HSC can be traced by studies of their telomere length. In order to test this hypothesis, we will examine the telomere length in subsets of purified HSC and their cultured
2 Healthcare projects are funded by the National Institutes of Health (NIH), Substance Abuse and Mental Health Services (SAMHSA), Health Resources and Services Administration (HRSA), Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDCP), Agency for Healthcare Research and Quality (AHRQ), and Office of Assistant Secretary of Health (OASH).
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progeny relative to defined populations of more mature cells using refined flow cytometry techniques developed in our laboratory. These techniques will also be used to further study the age related decline in telomere length in nucleated blood cells from normal individuals, patients with various hematological disorders and pedigrees of genotyped normal baboons. We will furthermore attempt to manipulate the telomere length in HSC using gene transfer and protein transduction strategies and study the functional properties of cells with extended telomeres in vitro and in vivo. The specific aims are:1) To study the telomere length in purified HSC and nucleated blood cells from normal individuals and patients with various hematological disorders before and after therapy.2) To study the telomere length in nucleated blood cells from baboons in relation to their age and genotype.3) To study the effect of artificial telomere elongation and telomerase inhibition on the proliferation, differentiation and replicative potential of purified "candidate" HSC in vitro and in vivo.Taken together, these studies will provide crucial baseline information on the role of telomeres in the biology of HSC. Such information is relevant for a basic understanding of hematopoiesis as well as applications of stem cells in and outside hematology. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ADDUCTS OF MITOMYCIN C WITH NUCLEOTIDES. Principal Investigator & Institution: Tomasz, Maria; Distinguished Professor; Chemistry; Hunter College Room E1424 New York, Ny 10021 Timing: Fiscal Year 2003; Project Start 01-JUL-1980; Project End 30-APR-2007 Summary: (provided by applicant): Mitomycin C (MC) is a natural antitumor antibiotic used in the clinic for cancer chemotherapy. MC generates six different DNA adducts in tumor cells. One of these is a DNA interstrand cross-link, as a result of bifunctional alkylation of the complementary DNA strands by MC, while the others are adducts of the drug, linked to only one strand of DNA (monoadducts and an intrastrand crosslink). The broad, long-range objective of the present proposal is to elucidate the relationship of each of the six adducts to the cytotoxicity/antitumor activity of MC. In addition, the putative toxic role of reactive oxygen species (ROS), generated by redox cycling of MC, will be examined using Fanconi's Anemia (FA) cells. The first aim of the proposal is to determine whether the known hypersensitivity of FA cells to MC is primarily due to ROS generation or to DNA adduct formation by the drug. These studies will better define the biochemical basis of the unique sensitivities of Faneoni's anemia cells, as well as providing insights into the activities of the mitomycins. The other specific aims serve to detect and characterize biochemical responses unique to the different DNA adducts of MC. In this context we shall investigate differential rates of repair of the adducts in living EMT6 tumor cells in cell culture. Differential modes of nucleotide excision repair of cross-link and monoadducts will be investigated in subcellular systems by constructing 91-mer oligonucleotide duplexes modified site-specifically with the various MC adducts, and using these as substrates for uvrABC excinuclease, or for the repair enzymes present in a mammalian whole cell extract. The same substrates will be used to search for "adduct binding proteins", specific for the cross-link, in cell extracts. Differential inhibition of lesion bypass by DNA polymerases by the different mitomycin monoadducts will also be investigated, using synthetic adduct-template-primer complexes as substrates. These latter experiments are aimed at identifying the basis for the unusually low cytotoxicity of the monoadducts 5 and 6. This research will lead to a better understanding of the molecular and biochemical basis of the antitumor activity and toxicology of MC and, more generally, of other DNA cross-linking agents, a major class of drugs currently used in cancer chemotherapy.
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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ADHESION MOLECULES MEDIATING SKIN TROPISM IN ACUTE GVHD Principal Investigator & Institution: Sackstein, Robert; Associate Professor; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2002; Project Start 01-MAY-2000; Project End 30-APR-2004 Summary: (Applicant's Abstract) Allogeneic hematopoietic stem cell transplantation (HSCT) is curative therapy for hematologic malignancies, aplastic anemia and a variety of genetic conditions; however, significant treatment-related morbidity and mortality results from the development of acute graft-versus-host disease (GVHD). Acute GVHD is caused by an immunological attack by donor effector cells against recipient tissues, particularly the skin, liver and intestines. In all cell-mediated inflammatory conditions, the migration of blood-borne effector cells into the involved sites is a highly specific and dynamic process, the first step of which is regulated by discrete adhesive interactions between circulating cells and target tissue endothelium. Utilizing an in vitro lymphocyte-skin adherence assay that is performed under shear conditions to mimic blood flow, the applicant has observed a highly specific adhesive interaction between human peripheral blood mononuclear cells (PBMC) and endothelium of papillary dermis in acute cutaneous GVHD. He hypothesizes that this adhesive interaction regulates in part the migration/recruitment of effector cells to skin in acute GVHD. The objective of this application is to elucidate, using human cells and skin specimens, the molecular basis of this PBMC-endothelial interaction, the cellular components of PBMC which bear the capacity to adhere to endothelium in acute GVHD, and the role of these adhesive interactions in the pathogenesis of acute GVHD. Specifically, he will: (1) Investigate the role of adhesion molecules known to mediate leukocyte-endothelial interactions and the structure of binding determinants which direct PBMC attachment to the dermal endothelium; (2) Test the binding capability of discrete subsets of PBMC and whether such subsets utilize similar adhesion molecules to bind to the endothelium cutaneous GVHD; (3) Examine the adherence of PBMC to dermal microvascular endothelial cells and determine the effects of inflammatory cytokines on the adherence capacity of the cultured cells; and (4) Establish a SCID Hu model of cutaneous GVHD to directly examine the role of adhesion molecules in the effector phase of cutaneous GVHD and the prevention of GVHD by use of reagents to block PBMC-endothelial adhesive interactions. The results of these studies should provide fundamental insights into the pathobiology of acute GVHD in humans. The identification of adhesion molecules mediating effector cell migration to target tissues may allow for therapeutic approaches to selectively interfere with the development of acute GVHD, thereby providing specific and efficient treatment for acute GVHD and preservation of beneficial alloreactivity, such as the graft-versus-leukemia effect, in patients undergoing allogeneic HSCT for hematologic malignancy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: BENZENE METABOLITES AND HEMATOTOXICITY Principal Investigator & Institution: Monks, Terrence J.; Professor and Chair; Div/Pharmoacology & Toxicology; University of Texas Austin 101 E. 27Th/Po Box 7726 Austin, Tx 78712 Timing: Fiscal Year 2002; Project Start 01-JUN-2000; Project End 31-MAY-2005
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Summary: (Adapted from applicant's abstract): Benzene, a major industrial chemical and environmental pollutant, causes a variety of hematological disorders in man, including aplastic anemia, myelodysplastic syndrome, and acute myelogenous leukemia. While it is clear that benzene must be metabolized to cause its acute hematotoxic effects, no single metabolite of benzene reproduces these effects in vivo. Coadministration of hydroquinone (HQ) and phenol (PHE), however, does lead to bone marrow suppression in rodents. A pharmacokinetic interaction between these two benzene metabolites results in increased concentrations of both metabolites in bone marrow. Peroxidase and/or phenoxy-radical mediated oxidation of HQ then initiates redox cycling and formation of the reactive electrophile, 1,4-benzoquinone, which is considered the ultimate hematotoxic metabolite of benzene. However, 1,4-benzoquinone readily undergoes glutathione (GSH) conjugation to form 2-(glutathion-Syl)hydroquinone, 2,5-bis-(glutathion-S-yl)hydroquinone, 2,6-bis-(glutathion-Syl)hydroquinone, and 2,3,5-tris-(glutathion-S-yl)hydroquinone. Preliminary data indicate that these GSH conjugates are present in the bone marrow of rats and mice following coadministration of hydroquinone and phenol. Moreover, the majority of HQGSH conjugates present in bone marrow are formed in situ and are metabolized to more reactive thiol conjugates via a previously unidentified mercapturic acid pathway. Because these quinol-thioether metabolites have enhanced capability to both redox cycle and arylate tissue macromolecules, we hypothesize that quinol-thioether metabolites contribute to benzene-mediated hematotoxicity and that the mechanism(s) likely involve the production of reactive oxygen species and/or interaction with proteins that specifically recognize GSH/cysteine and GSH/cysteine containing molecules. Such metabolite specific interactions interfere with growth- and differentiation-related signaling. We therefore propose to (i) assess the acute hematotoxicity of HQ-GSH conjugates in rodent hematopoietic tissue, (ii) determine changes in the production and/or function of hematopoietic growth factors in response to HQ-GSH conjugates, (iii) test the hypothesis that metabolite-induced changes in gamma-glutamyl transpeptidase activity (GGT), dipeptidase activity, cysteine transport, and GSH concentrations, precipitate sphingolipid turnover, the generation of ceramide and the induction of apoptosis, and (iv) test the hypothesis that specific proteins involved in the synthesis (GST), transport (GS-X pump), and metabolism (GGT, dipeptidases) of the peptidyl leukotrienes are targets of HQ-GSH conjugates and interfere with granulocytic cell differentiation. Because benzene reduces the number of myeloid stem cells in bone marrow and induces incomplete granulocytic differentiation, our studies will provide a comprehensive understanding of the mechanisms by which reactive polyphenolic metabolites of benzene cause perturbations in growth- and differentiation-related signaling and how such changes culminate in benzene-mediated hematotoxicity. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BONE MARROW FAILURE CLINICAL RESEARCH CENTER Principal Investigator & Institution: Maciejewski, Jaroslaw P.; Cleveland Clinic Foundation 9500 Euclid Ave Cleveland, Oh 44195 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-JUL-2008 Summary: (provided by applicant): Idiopathic bone marrow failure states and cytopenias (IBMFS&C) are rare disorders characterized by hematopoietic progenitor or stem cell failure resulting in deficient production of one, or all, blood cell lineages. Immune pathophysiology is a unifying factor in many cases of all these diseases. Prior collaborative trials have led to the improvement of effective medical therapy for aplastic anemia (AA), but ongoing multi-center studies are required to advance further the
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outcome for AA and especially the other bone IBMFS for which few useful treatment options exist. Here, we propose formation of the IBMFS&C Rare Disease Clinical Research Center (RDCRC) at The Cleveland Clinic Foundation (CCF) Cancer Center, encompassing a consortium of several specialized centers, patient advocacy group, and data and a collaboration with a data technology coordinating center (DTCC). The IBMFS&C RDCRC will focus on AA, paroxysmal nocturnal hemoglobinuria, singlelineage cytopenias including large granular lymphocyte leukemia and pure red cell aplasia, and various myelodysplastic syndromes. This application presents a multitargeted approach to improving the medical therapy for IBMFS&C that includes: 1) implementing treatment algorithms for each IBMFS that define standards of care, 2) systematically evaluating novel laboratory assays that may improve the diagnostic accuracy or understanding of pathophysiologic mechanisms, 3) enrolling patients into a longitudinal follow-up study to correlate new and established diagnostic variables with outcome, 4) comparing medical and transplant approaches for each relevant disorder, 5) developing experimental treatment protocols for disease subsets currently without good treatment options or without a standard treatment approach, 6) training of post-doctoral fellows to develop clinical trials and translational research projects for the IBMFS&C, 7) educating community physicians in the diagnosis and management of the IBMFS&C, and 8) improving outreach, education and referral resources for patients and physicians, in collaboration with the Aplastic Anemia & MDS International Foundation (AAMDSIF). Due to the expertise of the PI, together with the experience and size of CCF CC, CCF uniquely is positioned to serve as an RDCRC in IBMFS&C. A number of leading experts formed a consortium of medical centers that will be an integral part of the RDCRC. To support further its activities, additional infrastructure for this effort will include a formation of a rare disease office in each of the centers of the consortium, specialized laboratory testing sites, oversight of clinical trials, data management by the DTCC, and patient referral and education by the AAMDSIF. The IBMFS&C RDCRC and the consortium have developed a plan for educating fellows and community physicians about IBMFS&C. The success of these efforts will be evaluated in part by tracking referrals to the participating centers for standard treatment, or enrollment in the longitudinal and treatment protocols. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CLINICAL APPLICATIONS OF A NOVEL FANCONI ANEMIA ASSAY Principal Investigator & Institution: Shimamura, Akiko; Dana-Farber Cancer Institute 44 Binney St Boston, Ma 02115 Timing: Fiscal Year 2002; Project Start 05-JUL-2002; Project End 31-MAY-2007 Summary: Congenital bone marrow failure syndromes are characterized by abnormal hematopoietic cell growth, differentiation, and survival. Bone marrow transplant is the only available curative treatment, but is associated with significant side effects and limited by donor availability. The development of new therapeutic modalities calls for investigators with: 1. Expertise in bone marrow failure syndromes, 2. An understanding of the clinical implications of new molecular discoveries, 3. Experience in the design and implementation of clinical trials. Dr. Shimamura is a pediatric hematologist/oncologist with a molecular background in signal transduction and apoptosis. The proposed training program is designed to allow her to develop expertise in bone marrow failure syndromes and to gain experience in the design and implementation of patient-oriented research. Her long-term goal is to become an independent investigatory applying our understanding of molecular mechanisms of bone marrow failure to solve clinical
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problems. Dr. Shimamura will pursue her career development under the co- mentorship of Dr. Alan D'Andrea and Dr. David Nathan. Dr. D'Andrea's studies have uncovered a novel Fanconi anemia (FA) biochemical pathway. She proposes to study the clinical applications of these findings as follows: 1. Investigate the FANCD activation assay as a new functional screen for the FA pathway, 2. Screen for pharmacological agents that augment FANCD activation, and 3. Assess the effect of FA gene replacement therapy on the restoration of FANCD activity as part of the on-going Dana-Farber/Children's Hospital FA gene therapy project directed by Dr. Nathan. Dr. Shimamura has assembled a committee of expert advisors and collaborators to assist her in this project. Her project will be supported by several local core facilities and programs including the Fanconi Anemia Center, the Harvard Vector Laboratory, the Cell Manipulation and Gene Transfer Laboratories, the Clinical Gene Therapy Program, and the General Clinical Research Center at Children's Hospital. To complete her training, she will attend a bone marrow failure clinic at Children's Hospital, build a bone marrow failure repository for future independent studies, and complete course work on clinical research design, implementation and analysis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CORE--CYTOGENETICS Principal Investigator & Institution: Olson, Susan B.; Oregon Health & Science University Portland, or 972393098 Timing: Fiscal Year 2002 Summary: The Cytogenetics Core is of major significance to the success of Projects 1,2, 3 and the Core C Repository. Its expertise draws on 32 years of experience of the Research and Clinical Cytogenetics Laboratories at Oregon Health Sciences University. These laboratories are recognized internationally for the highest standards of academic cytogenetics excellence. Together, they have a staff of 14 technologists and research associates studying approximately 2,500 blood, bone marrow, solid tumor, amniotic fluid, chorionic villus and other solid tissue samples annually. Through their early efforts of test development, and more recently as the Cytogenetics Core for the current program project grant, these combined laboratories have become a national resource for Fanconi anemia testing. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CORE--MURINE HEMATOPATHOLOGY Principal Investigator & Institution: Aster, Jon C.; Associate Professor; Dana-Farber Cancer Institute 44 Binney St Boston, Ma 02115 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2007 Summary: (provided by applicant): To support the specific aims of the Projects in this application, the Murine Hematopathology Core will: 1. Provide gross pathology/autopsy service for murine models described in the Projects of the program. 2. Perform standard histological, immunohistochemical, and histochemical stains necessary to evaluate pathologic findings in murine models of aplastic anemia and leukemia. 3. Interpret the pathologic findings and render diagnoses. 4. Develop new paraffin-based immunohistochemical stains to improve the evaluation of disease phenotypes and the signaling events that underlie their pathogenesis. 5. Provide photographic services to document representative pathologic findings. In providing these services, the Core will interact directly with Projects. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CORRECTION OF CONGENITAL DISEASES BY STEM CELL THERAPY Principal Investigator & Institution: Nathan, David G.; Professor; Dana-Farber Cancer Institute 44 Binney St Boston, Ma 02115 Timing: Fiscal Year 2002 Summary: Gene replacement therapy of congenital bone marrow disorders is a long sought treatment goal and a great challenge to experimental hematology. In this project we focus on gene replacement for Fanconi Anemia and Diamond Blackfan Anemia. Both diseases require successful gene insertion and function in hematopoietic stem cells (HSC) and their progeny. Successful gene transfer into HSC requires selection of transfected and functioning HSC by the host. This will occur in Fanconi Anemia because HSC lacking the Fanconi gene die in the marrow. In Diamond Blackfan Anemia, the selection occurs at the level of the erythroid progenitor and precursor cells. We will use two classes of retrovirus vectors; moloney leukemia based vectors and HIV based lentivirus vectors. These will be tested in vitro and in two in vivo models; the NOD SCID mouse and in rhesus monkey. We have shown that it is imperative to utilize short incubations preferably in cold temperatures in order to protect the HSC from toxicity induced by the procedures themselves. These new incubation conditions will be tested in the experimental models. Appropriate vectors will be produced at very high concentrations in our GMP vector laboratory and the scale up to large human samples will be carried out in our GMP cell manipulation core laboratory. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CORRECTION OF RPS 19 DEFECTS IN DIAMOND BLACKFAN ANEMIA Principal Investigator & Institution: Sieff, Colin A.; Associate Professor; Dana-Farber Cancer Institute 44 Binney St Boston, Ma 02115 Timing: Fiscal Year 2002 Summary: Diamond Blackfan anemia (DBA) is a congenital anemia that develops at birth or soon after, and is due to failure of production of erythrocytes and their precursors, with normal or near normal myeloid and platelet lineages. It is inherited in about 10% of cases, mostly as an autosomal dominant. Recent genetic studies have led to the surprising identification of mutations in a ribosomal protein gene, RP219, on chromosome 19q13.2, in about 25% of both familial and sporadic cases (DBA1), and there is evidence for involvement of at least 2 other genes. Patients can remit completely on corticosteroids or may become resistant to treatment, and then require regular blood transfusions, or bone marrow transplant if a histocompatible sibling donor is available. The long term objective of this proposal is to develop preclinical data for a gene therapy protocol for severe DBA1 patients who are not eligible for matched sibling stem cell transplantation. Therefore the specific aims are (1) to identify RPS19 mutant patients by PCRT-based sequence analysis and by characterization of mutant proteins using antibodies to RPS19; (2) to further characterize the in vitro erythroid defect in these patients and then use abnormality in the erythroid progenitor cells and precursors; and (3), to "knock-in" to embryonic stem (ES) cells a mutation that has occurred independently in 6 unrelated families. The mutant ES cells will be injected into blastocysts and reimplanted into pseudopregnant females to generate chimeric animals for developing heterozygotes and breeding to homozygosity. Transmitting heterozygotes will be cross-bred to observe the consequences of mutation of both alleles in vivo. The major objective here is to create a DBA1 mouse that can be used to evaluate
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retrovirus and lentivirus RPS19 gene correction. Accomplishment of these goals will lead to further in vivo evaluation and a clinical protocol (not part of this project but part of the research program). In addition to the practical benefit to severely affected DBA1 patients, we hope to gain insight into how mutations in RPS19 lead to a block in the development of early erythroid cells. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ANEMIA
CYTOKINE-MEDIATED
PATHOPHYSIOLOGY
IN
FANCONI
Principal Investigator & Institution: Chen, Ming; Pediatrics; Weill Medical College of Cornell Univ New York, Ny 10021 Timing: Fiscal Year 2002; Project Start 21-AUG-2002 Summary: Fanconi anemia (FA) is an autosomal recessive disorder characterized by cellular hypersensitivity to DNA crosslinking agents such as mitomycin C (MMC) and diepoxybutane (DEB) (Auerbach 1993), bone marrow (BM) failure, diverse congenital anomalies, and a marked increased in the incidence of malignancies. Eight complementation groups (FA-A through FA-H) have been identified. The human genes defected in the FA-C, FA- A FA-G groups were recently cloned. Fancc-deficient mice have been created by targeted mutations of the murine Fancc gene. Cells from France -/mice showed hypersensitivity to MMC and DEB. Surprisingly, however, no gross hematologic defects or congenital anomalies were detected, although the homozygous mice showed decreased fertility. Evidence has been collected indicating that certain cytokines are involved in Fanconi anemia. TNF-alpha and IFN-gamma are inhibitory cytokines that can induced deregulated. Progenitor growth and apoptosis in Fancc-/hematopoietic progenitor cells (HPC). FANCC transgene protected HPC FANCC transgene protected HPC from Fas-mediated apoptosis. IL-6, TNF-alpha and IFNgamma, among others, are known to mediate immune-neuro-endocrine interactions. More recently, multiple endocrine abnormalities were discovered in FA patients, including deficiencies in growth hormone, thyroid and gonads function. We hypothesize that the endocrine abnormalities be due to aberrant response to cytokines, particularly TNF-alpha and IFN-gamma, in the endocrine glands. The proposed project will use Fancc-deficient mice and cell lines derived from endocrine glands, along with certain cytokines, to test this hypothesis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DEVELOPMENTAL BIOLOGY OF HEMATOPOIESIS Principal Investigator & Institution: Bahary, Nathan; Dana-Farber Cancer Institute 44 Binney St Boston, Ma 02115 Timing: Fiscal Year 2002; Project Start 15-JAN-1998; Project End 31-DEC-2002 Summary: (Adapted from applicants' abstract) Hematopoiesis in the vertebrate is characterized by the induction of ventral mesoderm to form hematopoietic stem cells and the eventual differentiation of these progenitors to form the final peripheral blood lineages. Several genes have been implicated in the differentiation and development of hematopoietic and vascular progenitor cells yet our understanding of the discrete steps involved in the induction of these cells from the ventral mesoderm is still incomplete. One method to delineate these processes is by the generation of hematopoietic mutants. In this regard, the zebrafish (Danio rerio) is an especially robust vertebrate system to both isolate and characterize such mutational events. Several hematopoietic mutants in zebrafish have been generated and characterized to date. The strength of the zebrafish
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system is illustrated by the fact that these hematopoietic mutants represent many of the proposed steps of both the primitive and definitive hematopoietic programs. One such gamma-induced mutation, b462B, has no blood formation in its homozygous state and is lethal at five days of embryogenesis. Whole embryo in-situ hybridization studies show diminished expression of Gata-1, Gata-2, Imo2, and cmyb, which are normally expressed early in hematopoiesis. This pattern of expression suggests that b462B is a gene that is critical for the early steps of hematopoiesis, and implies that b462B is the earliest hematopoietic mutant that has been obtained to date. In this application, the investigator plans to further characterize b462B, and to ultimately isolate the defective gene by either positional or phenotypic rescue methods. By characterizing and cloning this mutation, unique insights will be made into the genetic cascade that regulates hematopoiesis. This new knowledge has therapeutic value for bone marrow transplantation, stem cell gene therapy, aplastic anemia and myelodysplasia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DNA REPAIR DEFECT IN FANCONI ANEMIA, GROUP A Principal Investigator & Institution: Lambert, Muriel W.; Professor; Pathology and Lab Medicine; Univ of Med/Dent Nj Newark Newark, Nj 07103 Timing: Fiscal Year 2002; Project Start 01-JUL-1995; Project End 31-MAY-2003 Summary: The goal of this proposal is to delineate the relationship between the FAA and FAC gene products and the DNA repair defect in Fanconi anemia, complementation groups A (FA-A) and C (FA-C). It has been hypothesized that an underlying mechanism for this disorder may involve a DNA repair defect. We have isolated a DNA endonuclease complex from the nuclei of FA-A and FA-C cells and shown that it is defective in ability to incise DNA at sites of interstrand cross- links. Levels of a 230 kDa protein, associated with this complex and which binds to cross-linked DNA, are decreased in FA-A and FA-C cells. This protein has recently been identified as nonerythroid alpha spectrinllsigma* (alphaSpIIsigma*). The deficiency in alphaSpIIsigma* is corrected in FA-A cells transduced with a retroviral vector expressing the FAA cDNA, indicating that the FAA gene plays a role in its expression or stability. alphaSpIIsigma* also forms a complex with the FAA and FAC proteins in the nucleus which suggests that this complex may play role in DNA repair. It is possible that alphaSpllsigma* acts as a scaffold to help align or enhance interaction between proteins involved in the repair of interstrand cross-links and proteins that interact with FAA and FAC. The present proposal will address this by first determining the isoform of the alphaSpllsigma* we have identified and producing a recombinant protein that can be used in further studies. Exactly what proteins are associated with the FAA-FACalphaSpllsigma* complex, whether any of these proteins have binding affinity for DNA containing interstrand cross-links, and whether there is a deficiency in any of these proteins in FA-A and FA-C cells will be determined. The role of the FAA and FAC proteins in regulating the expression or stability of alphaSpllsigma* will be assessed as will the role of each of these three proteins in the repair of DNA interstrand cross-links. If alphaSpllsigma* is acting as a scaffolding protein, to help align and allow interactions between these as well as other proteins, this could have far reaching implications in a number of different processes, in addition to DNA repair, which have been associated with this protein, such as signal transduction and cell growth and development. A deficiency in alphaSpllsigma* in FA cells could thus ultimately affect hematopoietic differentiation and development. Isolation and identification of proteins associated with the FAA-FAC- alphaSpllsigma* complex and determination of their interactions with
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each other, other nuclear proteins, and DNA repair should help elucidate the basis of bone marrow failure and the development of aplastic anemia and leukemia in FA. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DYSREGULATION OF HEMATOPOIESIS IN FANCONI ANEMIA Principal Investigator & Institution: Bagby, Grover; Professor; Oregon Health & Science University Portland, or 972393098 Timing: Fiscal Year 2002 Summary: Over the past 4 years we have documented that hypersensitivity to mitotic inhibitory factors accounts, at least in part, for the apoptotic phenotype in FA cells. To date we have focused on elucidating the potential relationship between FANC and elements of the IFN-gamma pathway because of persuasive evidence that this cytokine plays a role in the pathogenesis of acquired aplastic anemia. Regarding the function of the FANC protein, we have made tow discoveries we believe to be of critical importance. First, FAN-C cells constitutively express IFN-dependent genes that induce mitotic arrest and apoptosis in hematopoietic progenitor cells and these mutant cells expresses these genes through signaling pathways that do not involve stat1. Transduction of FAN-C cells fail to phosphorylate stat1 after exposure to IFN-gamma because the normal FANC protein functions as a chaperone to deliver stat1 to the docking sites on the IFN- receptor alpha chain (IFNGR1). These two findings have converged with recently published findings on the anti-apoptotic function of hematopoietic growth factor receptors to lead us to hypothesize that Fanconi antiapoptotic function of hematopoietic growth factor receptors to lead us to hypothesize that Fanconi progenitor cells are apoptotic not only because of hypersensitivity to mitotic inhibitors, but because they cannot properly transduce anti-apoptotic signals through hematopoietic growth factor receptors. The studies described in this proposal are designed to test three hypotheses. First, that proper stat- mediated signal transduction via hematopoietic growth factors involves the delivery by the FANC protein, of stat molecules to specific receptor chains after ligand binding (this hypothesis forms the basis of Aim 1). Second, that the delivery of phosphorylated stat molecules to cognate binding sites on nuclear DNA also depends upon binding of stat-dimers to FANC protein (Aim 2). Third, that a specific stat1-independent signaling pathway governs; (a) the constitutive expression of p21wf1, IRF-1 and ISGF3-gamma in FAN-C cells and (b) same non-stat pathway accounts for the IFN/TNF/TGF sensitivity of FANC cells (Aim 3). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ENTRANCE INTO THE INTERNATIONAL FANCONI ANEMIA REGISTRY Principal Investigator & Institution: Auerbach, Arleen D.; Rockefeller University New York, Ny 100216399 Timing: Fiscal Year 2002 Summary: Fanconi anemia (FA) is a heterogeneous disease involving multiple organ systems including hematologic, skeletal, renal, neurologic and endocrine. Patients are predisposed to malignancies, particularly acute myelogenous leukemia (AML). Although the genes for two of the eight FA complementation groups, FANCC, FANCA and FANCG, (alias FAC, FAA, FAG) have been cloned, and mutations identified in both of these genes in affected individuals, the precise function of these genes has yet to be elucidated. It is the objective of this protocol to define the phenotypic spectrum of this
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rare syndrome by study of a large number of patients with diverse features. These patients will also provide a source of cells for molecular studies. It is an objective our study to extend our ability to define the FA genotype of all patients and to make genotype-phenotype correlations. This would enable physicians to better predict clinical outcome and aid decision-making regarding major therapeutic modalities for this clinically heterogeneous disorder. Understanding the genetic defect in FA should lead to a better understanding of birth defects and cancer predisposition in general, and the interaction of genetic and epigenetic factors in their pathogenesis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ETIOLOGY & PATHOGENESIS OF MURINE GRAFT VS-HOST DISEASE Principal Investigator & Institution: Korngold, Robert; Professor; Microbiology and Immunology; Thomas Jefferson University Office of Research Administration Philadelphia, Pa 191075587 Timing: Fiscal Year 2002; Project Start 01-JAN-1988; Project End 30-SEP-2004 Summary: Clinical allogeneic bone marrow transplantation is an important therapeutic treatment for several diseases including high risk leukemia, aplastic anemia, and severe combined immunodeficiency. In addition there is a wide range of metabolic and genetic disorders that can potentially be corrected by this approach. However, the usefulness of marrow transplantation continues to be limited by several important risk factors, the principal one being graft-versus-host disease (GVHD), an oftentimes lethal complication which occurs in a high proportion of transplants. The risk of GVHD can be reduced by HLA matching of the marrow donor and recipient, with a matched sibling being the primary choice. Yet, the risk of GVHD is still quite high due to disparity of non-HLA multiple minor histocompatibility antigens (miHA). In previous years we have clearly defined, in murine models, the relative etiological and pathological roles of both CD4+ and CD8+ T cell subsets in GVHD directed to miHA barriers. We have also found evidence for the oligoclonal, yet heterogeneous, nature of both T cell subset responses to miHA in vivo. The general aim of this current proposal is to continue our investigation of the immunobiology of lethal GVHD, with a focus on multiple miHA differences and how donor T cells develop the specific response to them. In this regard we will concentrate our efforts on the following specific aims: (1) the molecular and immunological analyses of the CD4+ T cell repertoire response to multiple miHA responsible for GVHD; (2) the molecular and immunological analyses of the CD8+ T cell repertoire response to multiple miHA responsible for GVHD; and (3) the utilization of the repertoire information to avoid GVHD and to retain optimal graft-versus-leukemia (GVL) responses. Insights generated from these studies on GVHD to miHA will hopefully lead to new approaches for overcoming one of the major obstacles for improved and expanded use of clinical allogeneic bone marrow transplantation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: EVALUATION OF GENETIC THERAPY IN FANC MICE Principal Investigator & Institution: Clapp, David W.; Associate Professor; Indiana Univ-Purdue Univ at Indianapolis 620 Union Drive, Room 618 Indianapolis, in 462025167 Timing: Fiscal Year 2002 Summary: Fanconi Anemia (FA) is an autosomal recessive syndrome characterized by progressive pancytopenia, diverse congenital abnormalities, and increased
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predisposition to malignancy. The only cure for FA has been HLA-matched bone marrow, and more recently umbilical cord blood, transplantation. The cloning of cDNAs for FA by functional complementation has opened up the possibility for correction of the disease by gene therapy. Our hypothesis is that hematopoietic stem and progenitor cells present in cord blood and bone marrow of patients with FA can be efficiently and stably transduced with retroviral- and adeno associated virus (AAV)- vectors containing the FA complementation C gene with correction of the growth patterns of these cells, and the enhanced sensitivity of FA cells to chromosome-breakage and kill by drugs. To this end the following aims are proposed: 1) Construct high titer retroviral- and AAVvectors containing the FA complementation C gene. 2) Compare vectors for high efficiency stable transduction of stem and progenitor cells in normal cord blood and later in normal bone marrow cells using first relatively unseparated cells present in a low-density fraction, then more highly purified cells. These comparisons will then be done in marrow and cord blood cells from patients with complementation C-FA to see if their growth characteristics, chromosomal fragility, and hypersensitivity to drugs can be corrected. 3) Evaluate stable integration of genes into the earliest subsets of hematopoietic stem/progenitor cells and compare this with integration into later more mature subsets of the cells by using a variety of in vitro and in vivo assays. In vitro assays include those for LTC-IC, HPP-CFC, CFU-GEMM, BFU-E and CFU-GM. Replating capacity of single HPP-CFC- and CFU-GEMM-colonies into secondary and subsequent plates will be used as an estimate of self-renewal capacity, and gene integration of sequentially replated colonies determined. For in vivo analysis of stable integration we will use human cell-inoculated SCID mice. 4) Compare stable gene integration, using retroviral and AAV- vectors pre- and post-cryopreservation of cord blood and before and after expansion of the stem and progenitor cells of these tissues sources. The information obtained could lead to a gene therapy approach to cure the FA syndrome by autologous stem/progenitor cell transplantation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: FAC IN STEM CELL FUNCTION AND OXYGEN SENSITIVITY Principal Investigator & Institution: Haneline, Laura S.; Pediatrics; Indiana Univ-Purdue Univ at Indianapolis 620 Union Drive, Room 618 Indianapolis, in 462025167 Timing: Fiscal Year 2002; Project Start 13-AUG-1999; Project End 31-JUL-2004 Summary: Fanconi anemia (FA) is a complex, autosomal recessive disorder characterized by bone marrow (BM) failure, increased incidence of malignancies, and hypersensitivity to bifunctional alkylating agents such as mitomycin C (MMC). There are eight complementation types of FA that have overlapping phenotypes inferring the existence of eight genes in a common biochemical pathway. It is clear that the hematopoietic progenitor compartment is affected by loss of Fanconi anemia complementation type C protein (FAC). However, no direct studies have been conducted evaluate whether the hematopoietic stem cell (HSC) compartment is similarly affected due to difficulties in assessing HSC function in the human system. The development of a murine model containing a homozygous disruption in the murine homologue (Fac) of FAC allows comprehensive evaluation of this question. Using this murine model, we showed that Fac -/- hematopoietic progenitors were hypersensitive to MMC, similar to FA patients. These data suggest that Fac -/- mice will be a good model system to study FA. Several lines of evidence suggest that FA proteins may have a role in maintaining normal oxidative metabolism. In addition, the recent observation in COS cells that FAC modulates NADPH:cytochrome p450 reductase (RED) activity, an important enzyme that generates oxygen radicals and activates several drugs such as
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MMC supports this hypothesis. The goals of this application are: 1) to determine whether loss of Fac affects HSC function, 2) to determine if Fac -/- hematopoietic cells have an increased sensitivity to oxidative stress, and 3) to evaluate whether overexpression of RED induces a hypersensitivity to oxidative stresss in Fac +/+ cells. These data will provide important information in elucidating the pathogenesis of BM failure and carcinogenesis in FA as well as investigate a distinct function of Fac in normal oxidative metabolism that could provide potential implications for modifying current treatment protocols for FA patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: FANCONI ANEMIA GENE PATHWAY IN RADIATION RESPONSES Principal Investigator & Institution: Thompson, Lawrence H.; Senior Scientist; Biology & Biotechnology Res; University of Calif-Lawrnc Lvrmr Nat Lab Lawrence Livermore National Lab Livermore, Ca 94550 Timing: Fiscal Year 2002; Project Start 24-JAN-2001; Project End 31-DEC-2004 Summary: The project's objective is to understand the molecular regulatory processes cells use to minimize genetic damage and genetic instability associated with reactive oxygen species (ROS) arising from endogenous processes or ionizing radiation (IR). This goal is addressed through studies of FANCG/XRCC9, the gene that is defective in. group G of the cancer-prone disorder Fanconi anemia (FA). Because FancG protein confers IR resistance in hamster cells, the human homolog is expected to participate in IR responses in human cells. Historically, a link between the FA genes and radiation responses has been unclear, with some studies suggesting that the primary defect in FA lies in removing DNA interstrand crosslinks. The general hypothesis to be tested is that the FANCG protein, as a member of a multiprotein complex, protects mammalian cells against endogenous and IR-generated oxidative damage and maintains genomic integrity by coordinating homeostasis processes that include regulation of ROS levels, apoptosis, and cell cycle progression. The proposed studies will provide a highly quantitative characterization of FANCG protein's contribution to biochemical and cellular endpoints associated with both normal cell proliferation and responses to IR exposure. Isogenic pairs of mutant and FANCG-complemented cells will be derived in both hamster CHO cells and human lymphoblasts. These pairs will be analyzed with respect to chromosomal aberrations, cell survival, hprt gene mutations, apoptosis, ROS, and cell cycle parameters with and without IR exposure. The FANCG-complemented FA-G lymphoblasts will be used to examine gene and protein regulation during the cell cycle as well as the subcellular localization of the protein with and without IR damage. Three proteins that are candidate interactors with FANCG from preliminary studies will be evaluated for possible involvement in the FA pathway. Finally, already identified high-frequency human allelic variants of FANCG in the US population will be evaluated for degree of dysfunction. The results of these studies will lead to more specific models of the nature of the FA protein "pathway" and its quantitative contributions to multiple biological effects associated with IR-mediated oxidative damage. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: FANCONI ANEMIA--ROLE OF THE C PROTEIN Principal Investigator & Institution: Hoatlin, Maureen E.; Medicine; Oregon Health & Science University Portland, or 972393098 Timing: Fiscal Year 2002; Project Start 01-MAY-1997; Project End 31-MAR-2004
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Summary: Fanconi anemia (FA) is a cancer susceptibility syndrome associated with developmental abnormalities and bone marrow failure. Because of the unique cellular hypersensitivity to DNA crosslinking agents FA is considered to be a DNA repair disorder. The first (of at least eight) of the known FA complementation group genes, FANCC, was cloned more than seven years ago. Despite substantial efforts to discover the function of the FANCC protein, and functions of the proteins encoded by the other more recently cloned FA genes (FANCA and FANCG), the basic defect is still unknown. We used a yeast two hybrid screen to identify a new POZ-zinc finger protein (termed FAZF) which interacts with FANCC. We recently showed that FAZF is a transcriptional repressor similar to the promyelocytic zinc finger protein (PLZF). PLZF represses transcription of target genes by recruitment of histone deacetylase through the SMRTmSin3-HDAC co-repressor complex and tethering the complex to specific DNA target sequences. The FANCC/FAZF interaction is intriguing because it suggests that the FANCC protein may be interacting with components of the histone deacetylase complex. We propose to investigate FAZF and its relationship to FA by: (1) Analyzing FAZF/FANCC interaction in response to DNA damage, determine if FAZF is an FA complementing protein, compare the expression of FAZF and FANCC in primary hematopoietic cells (2) Analyze the consequences of enforced expression of FAZF, identify FAZF's binding partners, determine if FAZF is phosphorylated in response to DNA damage (3) Produce and examine the phenotype of FAZF nullizygous mice. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: FAS/FASL MEDIATED APOPTOSIS IN GVHD AND APLASTIC ANEMIA Principal Investigator & Institution: Civin, Curt I.; Professor of Cancer Research; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-MAR-2003 Summary: The ability to stably transduce lympho-hematopoietic stem-progenitor cells (HSCs) allows us to genetically engineer HSCs and their progeny to serve as improved cellular tools to treat disease and complications. In Specific Aim 1, we propose preclinical studies in mouse and human models to confirm the concept and elucidate the principal cellular and molecular mechanisms by which Fas ligand-transduced (FasL*) dendritic cells (DCs) or HSCs may selectively kill the T and NK cells that mediate GVHD. The results of Aim 1 will also provide modeling information on the application of transduced FasL+ cells to reduce immune attack against HSCs in severe aplastic anemia (SAA) (Specific Aim 3). Since it is expected that transduced FasL+ cells may be toxic in potential future translational in vivo applications, we will investigate technologies to limit potential FasL toxicity, eg by eliminating the transduced cells (or their FasL expression) after tolerance to HSCs has been generated. A novel transduced FasL+ cell therapy approach to reduce effector lymphocytes attacking host cells in GVHD (Aim 1) and SAA (Aim 3) may eventually be used in transplants for SAA, PNH and other diseases, and a potential clinical trial is outlined in Aim 1. In addition, our accompanying mechanistic studies on apoptotic pathways in alloimmune cells will increase information on the fundamentals of the Fas pathway in the effector cells mediating GVHD (and SAA), which in turn, should increase understanding of death pathways in the biology of (a) alloimmune responses, (b) hematologic malignancies that evade immune surveillance, and (c) transplanted organs (or pluripotent stem cells). In Specific Aim 2, Projects 1, 2 and 4 will cooperate to investigate the potential role of the Fas pathway in the pathophysiology of HSCs from SANPNH patients. Specific Aim 1: To engineer FasL+ host DCs or HSCs to selectively kill the cellular effectors of GVHD.
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Specific Aim 2: To investigate the role of the Fas pathway in the pathogenesis of SAA and PNH. Specific Aim 3: To investigate whether FasL+ HSCs selectively kill autologous anti-HSC CTLs in SAA. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: FELINE LEUKEMIA VIRUS INDUCED RED CELL APLASIA Principal Investigator & Institution: Abkowitz, Janis L.; Associate Professor; Medicine; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2002; Project Start 01-DEC-1986; Project End 31-MAR-2004 Summary: Cats viremic with feline leukemia virus, subgroup C (FeLV-C) develop pure red cell aplasia (PRCA). This results from a block in BFU-E to CFU-E maturation. Although granulocytic and erythroid progenitors are infected, only erythroid differentiation is impaired. Thirty amino acids of variable region 1 (VR1) of the surface unit protein of the FeLV-C envelope are the genetic determinants of host cell infection, of retroviral interference, and of PRCA. We hypothesized that FeLV- C inhibits the cell surface expression (or function) of its receptor (via envelope-mediated interference), leading to PRCA. As a corollary, the receptor must have a critical role in normal erythropoiesis, but be redundant or non-essential for granulocytic differentiation. Using a retroviral vector cDNA library generated from cat (3201B) T cells, we have cloned the cDNA for the FeLV-C receptor (termed FLVCR). The predicted protein is comprised of 567 amino acids, has 12 membrane-spanning domains, and is likely a member of the major facilitator superfamily (MFS) of transporter proteins. There is significant homology with D-glucarate transporters in bacteria and C. elegans. The goals of this application are to study the physiology of FLVCR and to test our hypotheses. As Dglucarate (and other organic (sugar) anion) transport is not known to have any role in hematopoiesis, these studies should provide novel insights into the biology of early erythroid cell development, as well as the pathogenesis of PRCA. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: FLT3: ROLE AND REGULATION IN HSC Principal Investigator & Institution: Small, Donald; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-MAR-2003 Summary: Signaling stimulated through the FLT3 receptor by its ligand, FL, appears to play an important role in hematopoiesis. FL synergizes with other factors to enhance the proliferation/maintenance of human lymphohematopoietic stem-progenitor cells (HSC) in vitro. FL is part of most cocktails of cytokines and growth factors being used to culture human HSC ex vivo. FL also stimulates dendritic, B progenitor, and NK cell development. However, it is still unclear at this time whether or not FLT3 plays a role in proliferation, antiapoptosis, and differentiation of high quality HSC and/or low quality HSC. We have developed very potent, specific small molecule inhibitors ofFLT3 tyrosine kinase activity. Utilizing these inhibitors we can probe FLT3 function in different cell populations by shutting it offwhile still allowing other normal cellular processes to take place. These reagents might, in the future, be used to complement the cellular approaches to SAA and GVHD taking place in Projects 1 and 4. Within this project we will probe the biological function of FLT3 in both low and high quality HSC. For an identified set of candidate targets of FLT3 signaling, we will define the downstream gene expression pattern that is dependent on FLT3 activation in high and low quality HSC. Finally, FLT3 regulation in normal HSC will be studied in an attempt to
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understand why FLT3 is overexpressed in so many leukemias. Specific Aim 1: Define the role of FLT3-mediated signal transduction in high quality HSC and low quality HSC. Specific Aim 2: Determine the candidate gene expression profile dependent on FLT3 signaling in high and low quality HSC. Specific Aim 3: Identify enhancers and transcription factors which regulate the FLT3 gene in HSC. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: FUNCTION & PURIFICATION OF THE FANCONI ANEMIA PROTEIN C* Principal Investigator & Institution: Kupfer, Gary M.; Microbiology; University of Virginia Charlottesville Box 400195 Charlottesville, Va 22904 Timing: Fiscal Year 2002; Project Start 01-JUL-2002; Project End 31-MAY-2007 Summary: (provided by applicant): Fanconi anemia (FA) is a genetic disease with defects in development and hematopoiesis and propensity to cancer, indicating a vital and basic cell biology process at work. The hallmark of FA is genomic instability, evidenced bv gross chromosomal breakage and DNA alkylating agent hypersensitivity, which correlates with cancer susceptibility in general. Studies of FA are important in several ways. First, FA biology is involved across a spectrum of scientific disciplines. Including hematology oncology, and development. Second, since the known FA proteins are found only in mammalian cells and have no previously described protein domain, their study will yield the description of a novel pathway which promotes the maintenance of genomic stability. Third, work on other cancer susceptibility syndromes have proved to have wide applicability in science in general and cancer in particular, such as Li- Fraument syndrome (p53), ataxia telangiectasia (P13 kinase), and xeroderma pigmentosum (DNA nucleotide excision repair). Fourth, basic work on FA has already led to clinical use of reagents for diagnosis and genetic counseling, and gene therapy trials are currently underwav for treatment of FA. The focus of the grant is to determine the specific biochemical nature of the FA pathway. The emphasis is on the FA proteins, which are encoded by the FA genes, accounting for 5 of at least 7 complementation groups. The FA proteins bind together in a protein complex which forms and is nuclear in 6 of the 7 FA complementation groups, which indicates its importance in FA biology. Our hypothesis is that the FA nuclear protein complex functions as a multimeric complex which is regulated by postranslational phosphorylation. Specifically the purpose of this grant is to isolate the complex in order to purify additional binding proteins of the FA complex to lend an idea to the overall function of the FA complex. In my preliminary, studies I have isolated FA binding proteins whose interactions with FA proteins will be confirmed and whose hypothetical functions will be tested in the work proposed. In addition we will demonstrate how modifications of proteins and of the size of the FA protein complex regulates its function and localization. Our recent work has shown that the FancG protein becomes phosphorylated at mitosis and the entire complex exits condensed chromosomes. We will map the phosphorylation site, test for the kinase involved and assess the changes in complex size in response to multiple stimuli. Identification of new proteins and elucidation of FA pathway mechanisms promise to shed light on a novel area of cancer biology with the potential to provide direct clinical applicability. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GENE THERAPY IN HEMATOPOIETIC CELLS Principal Investigator & Institution: Kiem, Hans-Peter; Member; Fred Hutchinson Cancer Research Center Box 19024, 1100 Fairview Ave N Seattle, Wa 98109
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Timing: Fiscal Year 2002 Summary: The goal of this project is to develop hematopoietic stem cell gene therapy for diseases affecting the hematopoietic system. A recent study in children with X-linked serve combined immunodeficiency has shown the successful application of hematopoietic stem cell gene therapy. While these results were very encouraging for the gene therapy field, most genetic diseases do not have selective advantages for genecorrected cells, and are therefore not likely to be cured by currently available techniques. Further improvements in gene transfer efficiency and in the engraftment of transduced cells using less toxic non-myeloablative conditioning regimens will be required. We have used the dog model to study gene transfer into hematopoietic repopulating cells because of our long-standing experience with hematopoietic stem cell transplantation in this model and because of the availability of disease models. During the previous funding period, we have improved gene transfer into hematopoietic repopulating cells by (1) using a gibbon ape leukemia virus (GALV) envelope, (2) transducing CD34enriched cells in flasks coated with the human fibronectin fragments CH-296, and (3) using a growth factor combination which included canine stem cell factor (cSCF), canine granulocyte-colony stimulating factor (cG-CSF) and human FLT3-L. Although gene marking, especially in a non-myeloablative setting. Thus our objectives for this project are threefold. First, in Specific Aims 1-3, we propose to study techniques to further improve gene transfer rates in hematopoietic stem cells. Second, Specific Aims 4 and 5 will explore less toxic conditioning regimens in combination with immunosuppression and also investigate a novel in vivo selection system. Third, Specific Aims 6 and 7 will apply gene transfer techniques to disease models. Fanconi anemia has been chosen as the first target for hematopoietic stem cell gene therapy since gene-corrected stem cells in this disorder are thought to have a selective advantage over uncorrected stem cells. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENE TRANSFER OF HEMATOPOIETIC STEM CELLS Principal Investigator & Institution: Walsh, Christopher E.; Associate Professor; Medicine; University of North Carolina Chapel Hill Office of Sponsored Research Chapel Hill, Nc 27599 Timing: Fiscal Year 2002; Project Start 01-AUG-2001; Project End 10-NOV-2002 Summary: adapted from applicant's abstract): In order for efficient gene transfer of hematopoietic stem cells to be achieved we believe that the testing of new vectors and better defined stem cell populations are required. We have chosen Fanconi anemia (FA) as a model disease to facilitate improved gene transfer protocols of hematopoietic cells. FA is a rare autosomal recessive disorder characterized principally by bone marrow failure and the development of leukemia. The hematologic manifestations of FA are due to a disorder of stem cell function. The functions of the FANC proteins (FANC complementation groups A-H) are not understood but all FANC cells exhibit hypersensitivity to DNA crosslinkers and suggest a role in maintaining DNA stability. Although we demonstrated that a selective growth advantage exists in gene-corrected FA hematopoietic cells in a knockout model, the corrected stem cell population requires further characterization. Here we propose to identify and test gene transfer on isolated fractions of primitive hematopoietic stem cells based on physiologic rather than immunologic methods from both mouse and human. This purification scheme isolates the previously described novel side population fraction (SP) in both mouse and human hematopoietic cells. Our strategy is to isolate and transduce Fanconi anemia complementation group A (FANCA) and C (FANCC) knockout mice primitive stem cells. Recipient animals will be examined for their response to DNA damaging agents
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and cytokines and their ability to reconstitute hematopoiesis following gene transfer using moloney-murine retroviral and HIV, equine and feline-base lentiviral vectors. Isolation of human CD34+, CD34+/CD38- and SP fractions from FA patients will be tested for transduction by retroviral vectors using the NOD/scid immunodeficient mouse system. Currently we have an ongoing trial for FANCA patients. Information obtained from the planned studies will provide a better understanding of abnormal hematopoiesis in FA and better define therapeutic strategies important for designing future human clinical trials. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENETIC TARGETING OF HEMATOPOIETIC STEM CELLS Principal Investigator & Institution: Graubert, Timothy A.; Medicine; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2002; Project Start 01-JUL-1998; Project End 30-JUN-2003 Summary: A number of human diseases, including aplastic anemia and the myeloproliferative syndromes, are disorders of hematopoietic stem cells (HSC). The primary goal of this project is to develop a strategy for targeting gene expression to HSC in transgenic mice. This should provide a tool to study the molecular mechanisms important for normal and leukemic hematopoiesis. To accomplish this goal, we propose the following specific aims: (1) we will determine the genomic organization of the Ly-6 gene cluster in the region surrounding the mSca-1 locus, and (2) we will develop a system to target genes to the Sca-1+ compartment in mice using site-specific integration of a transgene, a via homologous recombination in embryonic stem (ES) cells. Sca-1 (Ly6A/E) is a member of the Ly-6 family, a tightly clustered group of highly homologous genes localized to murine chromosome 15. We and others have noted that mutations made in transgenic mice that leave a selectable marker and its promoter in a targeted locus can result in unanticipated effects on the expression of other tightly linked genes. For this reason, we will characterize the murine Ly-6 locus in the region linked to Sca-1. Specific reagents will be generated to analyze the expression of genes "neighboring" the site of integration into the Sca-1 locus. Characterization of the murine cluster will be complemented by analysis of a syntenic region on human chromosome 8, recently found to contain several potential homologs of mLy-6 genes. Sca-1 "knock-in" mice derived from correctly targeted ES clones should coexpress the integrated transgene with the endogenous Sca-1 allele. Since essentially all long- term bone marrow repopulating activity in the strains of mice under analysis resides in the Sca-1+ compartment, this strategy should result in HSC targeting in vivo. A mutated hCD4 reporter gene will be utilized in an initial proof of principle experiment to establish correct targeting with this vector. Subsequent experiments will include targeting the oncoproteins bcl-2 and PML/RAR alpha to HSC in order to study the mechanism of leukemic transformation of this compartment. This work will be conducted under the supervision of Dr. Timothy Ley. The laboratory has considerable expertise in transgenic technology and in the analysis of murine hematopoiesis. An advisory committee consisting of internationally recognized experimental hematologists has been assembled. Core facilities of the Washington University Cancer Center in addition to the scientific and clinical resources of Washington University Medical School and the Barnes-Jewish Hospital (an 1100 bed tertiary care center) will provide an appropriate environment to facilitate this candidate's transition to independent research. The long-term goal of this investigator is to study the molecular bases of hematopoiesis and leukemogenesis as an active member of a clinical Hematology/Bone Marrow Transplant Division. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Aplastic Anemia
Project Title: GROWTH FAILURE IN FANCONI ANEMIA Principal Investigator & Institution: Wajnrajch, Michael; Weill Medical College of Cornell Univ New York, Ny 10021 Timing: Fiscal Year 2002 Summary: Children with Fanconi anemia (FA) are being studied hormonally to determine the cause of their growth failure. Aspects of endocrine and somatic abnormality are being related to accumulated data regarding the mutations responsible for FA. Two papers relating to this protocol have been accepted for publication in peerreviewed journals. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: HORMONAL CONTROL OF HISTONE MODIFICATIONS IN ES CELLS Principal Investigator & Institution: Fritsch, Michael K.; Pathology and Lab Medicine; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2003; Project Start 01-MAR-2003; Project End 31-JAN-2008 Summary: (provided by applicant): The molecular aspects of the earliest steps in embryonic stem (ES) cell differentiation remain poorly understood. Our preliminary data suggest that global histone acetylation may be a critical first step in differentiation. The goals of this proposal are to establish whether global histone acetylation and/or methytation occurs during multiple hormonally induced methods of ES cell differentiation and establish the time frame in which these histone modifications occur using standard assays for histone modifications. Our model predicts that the bulk of these histone modifications probably occur in promoter regions and we will make use of novel CpG island arrays to confirm this. Studies are designed to determine whether the global histone modifications that occur during exit from the undifferentiated ES cell state are uniquely different from the gene-specific histone modifications induced by hormonal signaling to highly differentiated cells. The second specific aim is to explore the possible mechanisms leading to these unique global histone modifications early in ES cell differentiation by screening ES cell extracts for various enzymatic activities responsible for covalent modification of histories. The third specific aim is designed to test the functional significance of histone modifications in directly regulating ES cell differentiation. The histone deacetylase inhibitor, trichostatin A (TSA), will be used in conjunction with specific growth factors to increase the rate and proportion of cells directed to a specific committed cell fate. In addition, overexpression of specific gene products designed to inhibit histone acetyltransferase activity or increase histone deacetylase activity in ES cells will be assessed for effects on the rate of ES cell differentiation and overall cell fate commitment. The proposed studies are designed to understand early hormonally regulated ES cell differentiation with potential application for significantly improving the yield of lineage-specific differentiation in vitro. This would greatly facilitate the development of ES cell technology for potential transplantation of "pure" cell populations into patients with diseases such as Parkinson disease, aplastic anemia, etc. In addition, the model proposed within this application predicts that histone deacetylase inhibitors such as valproic acid (a known teratogen) and TSA may greatly potentiate the teratogenic effects of environmental compounds by altering the very early histone acetylation pattern required for normal lineage-specific differentiation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: IMAGING OF APOPTOSIS Principal Investigator & Institution: Ross, Brian D.; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2002; Project Start 14-JUN-2002; Project End 31-MAR-2007 Summary: (provided by applicant): The goal of the proposed project is to develop a transgenic rodent wherein activation of apoptosis can be imaged non-invasively. Strict coordination of proliferation and apoptosis is essential for normal physiology. An imbalance in these two opposing processes results in various diseases including AIDS, neurdegenerative disorders (Alzheimer's disease), myelodysplastic syndromes (Aplastic anemia, thalassemia), ischemia/reperfusion injury, cancer and autoimmune disease among others. Objective imaging of apoptosis will be a major advancement not only in the screening and validation of novel therapeutic molecules for the above diseases but also in the evaluation of therapeutic success or failure of current and future therapeutic treatment paradigms. We have over the last year of our P20 (pre-ICMIC) award developed a reporter cassette which when transfected into mammalian cells results in a polypeptide that has significantly attenuated levels of reporter activity. When this molecule is being expressed in cells undergoing apoptosis, a caspase (proteases activated during apoptosis) specific cleavage of the reporter gene occurs resulting in activation of the reporter thus enabling imaging of apoptosis. In the present proposal we will optimize this novel molecular construct and conduct in vitro (Specific Aim 1) and in vivo (Specific Aim 2) studies. Finally, a transgenic rodent model will be developed wherein the activation of apoptosis within the skin in response to sunlight can be imaged (Specific Aim 3). The ability to image apoptosis non-invasively and dynamically over time will be an invaluable resource to pharmaceutical industry and scientists for in vitro high throughput screening of compounds with pro- and anti-apoptotic activity and also for target validation in vivo. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: SYNDROME
IMMUNOTHERAPY
OF
LOW
RISK
MYELODYSPLASTIC
Principal Investigator & Institution: Molldrem, Jeffrey J.; Chief, Section of Transplant Immunology; Blood & Marrow Transplantation; University of Texas Md Anderson Can Ctr Cancer Center Houston, Tx 77030 Timing: Fiscal Year 2002; Project Start 01-APR-2001; Project End 31-MAR-2006 Summary: (Provided by applicant): Myelodysplastic syndrome (MDS) is a heterogeneous group of progressive, irreversible, hematopoietic stem cell disorders characterized by progressive cytopenia and for which there are no effective therapies. Experimental and clinical evidence indicates that lymphocytes from patients with MDS exert an inhibitory effect on autologous hematopoietic colony growth, and that this contributes to cytopenia. Immunosuppressive treatments that decrease the number of lymphocytes or suppress their function such as corticosteroids, cyclosporine, and antithymocyte globulin (ATG) have been shown to reverse that cytopenia, and in some cases to reduce the number of blasts in the marrow. How these lymphocytes recognize their target antigens and inhibit hematopoietic precursors is unknown. Identification of relevant hematopoietic target antigens, however, might lead to useful therapies for MDS, and would provide insight into other bone marrow failure states such as aplastic anemia where T lymphocytes are also thought to play a key role in the development of pancytopenia. As a strategy to search for those target antigens, we hypothesize that in myelodysplastic syndrome, lymphocyte inhibition of hematopoietic progenitors is
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Aplastic Anemia
mediated by clonal or oligoclonal activated T lymphocytes through MHC-restricted antigen recognition. The long-term goal of this project is to investigate whether clonal T cells associated with inhibition of marrow progenitors can be isolated from MDS patients and then used to further identify relevant target antigens. These clonal T cells could then be more specifically targeted in the treatment of MDS patients and identification of T cell target cells/antigens could help determine the proportional contribution of lymphocytes to the development of cytopenia in MDS. We have shown that patients with MDS who respond to ATG treatment have activated CD8+ lymphocytes that inhibit colony forming unit-granulocyte macrophage (CFU-GM) in a MHC class I-restricted manner. Dominant clonal and oligoclonal lymphocyte populations that are present in peripheral blood and bone marrow in some MDS patients are later replaced by a normal polyclonal distribution, which coincides with reestablishment of effective hematopoiesis after ATG treatment. The proposed studies will isolate and characterize clonal T cells from MDS patients, determine how these T cell clones suppress hematopoiesis, whether T cell-mediated inhibition of hematopoiesis is directed against dysplastic or normal progenitors, and whether additional T-celldirected immunosuppressive agents added to ATG treatment can enhance recovery from cytopenia in a randomized clinical trial. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: INTERACTIONS OF ENVIRONMENTAL TOXICANTS WITH LEUKOCYTES Principal Investigator & Institution: Trush, Michael A.; Professor; Environmental Health Sciences; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002; Project Start 15-JUN-1985; Project End 28-FEB-2004 Summary: (Adapted from the Investigator's Abstract)Polymorphonuclear (PMN's) and mononuclear leukocytes are important cells in host defense mechanisms. An alteration in either the production or function of these cells could result in suppressed host defenses against infection and neoplasms. A likely site at which such alterations could occur is in the bone marrow. Studies have shown that the oral administration of the environmental pollutant benzo(a)pyrene (BP) to Ah nonresponsive DBA/2 mice with an Ahd/Ahd genotype, results in acute and severe hematotoxicity, resembling aplastic anemia. This is of human relevance considering that diet is a major route of exposure to polycyclic aromatic hydrocarbons (PAHs). The overall aim of this project is to investigate biochemical and cellular mechanisms which could contribute to the altered production and function of PMNs and mononuclear cells by BP. It is the investigator's hypothesis that xenobiotic processing within specific bone marrow cell populations, such as the stromal microenvironment and committed myeloid progenitors, underlie their susceptibility for toxic reactions by BP and its metabolites. Enzymes that are pertinent to this investigation include cytochrome P-450, myeloperoxidase and those of the mitochondrial electron transport chain. Based on this hypothesis, the specific aims of this project will continue to: investigate biochemical and molecular interactions of BPderived quinones and BP-7,8-dihydrodiol (BP-diol) which occur as a result of their interactions with organelles and enzymes from bone marrow cells; investigate the mechanisms of toxicity of BP and its metabolites to DBA/2 bone marrow stromal cells in vitro and in vivo; examine the ability of BP and its metabolites to alter the differentiation of human myeloid cell lines, ML-1 and HL-60, and progenitor cells from DBA/2 mice; and evaluate if a peroxide-dependent mechanism is involved in the bioactivation of BPdiol in vitro and in vivo. Fulfillment of these aims will result in a greater understanding of biochemical and molecular interactions, determinants of cellular susceptibility, and
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mechanisms of potentiation which could contribute to the bone marrow toxic effects of BP. Knowledge of these mechanisms of toxicity within the bone marrow will contribute to the ability to develop biomarkers of effect to better assess the potential risk for hematotoxicity in humans exposed to PAHs through their diet, especially those that are Ah nonresponsive. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ISOLATION AND ANALYSIS OF CANDIDATE 7Q TUMOR SUPPRESSOR GENES Principal Investigator & Institution: Shannon, Kevin M.; Professor; University of Chicago 5801 S Ellis Ave Chicago, Il 60637 Timing: Fiscal Year 2002; Project Start 01-MAR-2001; Project End 28-FEB-2003 Summary: (Applicant's Description) Loss of chromosome 7 (monosomy 7) and deletion of a segment of the long arm (del(7q)) are recurring cytogenetic abnormalities that are strongly associated with secondary myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), as well as with cases of MDS and AML that arise in a number of other contexts including occupational exposure to mutagens, aplastic anemia, and certain inherited predispositions. Monosomy 7 and del(7q) frequently coexist with molecular alterations of the Ras signaling pathway in MDS/AML clones. The similar clinical and biologic features of patients with different antecedent risk factors implicate alterations of the same gene on 7q in the pathogenesis of all of these myeloid disorders. Cytogenetic and FISH analysis have been utilized to delineate two commonly deleted segments in patients with myeloid disorders characterized by a del(7q): one located in band q22 that accounts for most cases and a second segment in bands q32-33. These data are consistent with the hypothesis that recessive mutations which inactivate tumor suppressor genes within these commonly deleted segments contribute to leukemogenesis in patients with monosomy 7 or del(7q). The goal of this project is to identify and characterize the putative tumor-suppressor gene located on 7q22. Dr. Le Beau and her colleagues (Project 3) will employ cytogenetic techniques to narrow the commonly deleted segment on band q22 and we will utilize polymorphic markers that map within the critical region to investigate patient samples for submicroscopic deletions. We will use genomic DNA from the commonly deleted segment that is cloned in yeast artificial chromosomes and bacterial artificial chromosomes as probes for screening CDNA libraries and will also employ exon trapping and subtractive hybridization approaches to isolate new coding sequences that map within the commonly deleted segment. Finally, we will analyze bone marrow samples from patients with monosomy 7 or del(7q) for mutations in candidate genes that are identified by these approaches. This work will be facilitated by the large and diverse collection of specimens from adults and children with monosomy 7 and del(7q) maintained in our laboratory and at the University of Chicago, by a close interaction with Dr. Le Beau (Project 3), and by a collaboration with Dr. Eric Green whose laboratory is constructing a physical map of chromosome 7. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: LATE TRANSPLANTATION
EFFECTS
IN
SURVIVORS
OF
STEM
CELL
Principal Investigator & Institution: Baker, Kevin S.; Pediatrics; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2002; Project Start 01-AUG-2001; Project End 31-JUL-2006
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Aplastic Anemia
Summary: (Applicant's Description) K. Scott Baker, M.D. is a pediatric oncologist in the Blood and Marrow Transplant Program at the University of Minnesota, and holds an appointment as an Assistant Professor in the Department of Pediatrics. The candidates career goals are: 1) to develop clinical research expertise which has a solid foundation in clinical research methodology, epidemiology, and biostatistics, 2) to focus these activities on patient oriented research in the field of hematopoietic stem cell transplantation (SCT), specifically transplant related complications and late effects, 3) to utilize these newly acquired skills in order to achieve the status as an independent clinical investigator. The proposed career development plan will provide a comprehensive, multidisciplinary, closely mentored, patient oriented research experience. This will be accomplished in conjunction with formal didactic training in Clinical Research obtained by the candidate enrolling in the master's degree program in clinical research in the Division of Epidemiology. Under the mentorship of Dr. Leslie Robison and Dr. Norma Ramsay, the candidate will initiate investigations into the late effects seen in long-term survivors after SCT. The proposed research will establish prospective and retrospective, long-term follow-up studies of SCT survivors at the University of Minnesota for the systematic, protocol driven, evaluation of the incidence, risk factors, and characteristics of cardiopulmonary, renal, endocrine and reproductive late effects, quality of life outcomes, and second malignant neoplasms. Hypothesis driven investigations will also be undertaken in the current population of 1226 longterm survivors. These will include studies of the impact of different transplant conditioning regimens (total body irradiation, total lymphoid irradiation, and chemotherapy only) on subsequent late effects in children, an analysis of the spectrum and severity of treatment related sequelae which develop in the second decade of longterm follow-up, and an analysis of the impact that chronic graft-versus-host disease has on late effects and quality of life in SCT survivors. The candidate will also utilize data frorn the ongoing, multi-institutional, Childhood Cancer Survivor Study (Dr. Robison is Principal Investigator) for a comparative analysis of patients in that cohort receiving standard chemotherapy versus those who have undergone SCT as part of their therapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MOLECULAR ANALYSIS OF FANCONI'S ANEMIA C PROTEIN Principal Investigator & Institution: Plon, Sharon E.; Assistant Professor; Molecular and Human Genetics; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2002; Project Start 01-JUL-1995; Project End 30-JUN-2004 Summary: The long term goals of this project are to elucidate both the 'logic' and molecules involved in the genomic stability of hematopoietic cells through studies of Fanconi anemia (FA). Three FA genes have now been cloned, and the investigator is poised to ask precise questions about the organization and function of their protein products. Although the cellular phenotype of FA implicates these proteins in drugsensitive pathways as "gatekeepers" of genomic stability, their molecular functions remain incompletely understood. FANCC has a role in cellular detoxification by virtue of its interaction with NADPH cytochrome P-450 reductase (RED) and regulation of a pre-DNA damage step. FANCA is homologous to peroxidases, interacts with FANCG, and functions in the nucleus. Using cell culture yeast and mouse models, the investigator proposes to test the hypothesis that cytoplasmic FANCC-RED and nuclear FANCA-FANCG complexes perform detoxification functions in their respective cellular compartments. Thus, the investigator will (I) characterize the expression patterns of FA gene products during mouse embryogenesis, including hematopoietic and germ cell development, by in situ and biochemical strategies; (II) determine the oligomeric
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structure and regulation of FA proteins; (III) use genetic strategies to IocaIize the function of FA proteins to pre- or post-DNA damage steps, and, in this context, test the function of the FANCA peroxidase domain; and (IV) isolate genes that regulate the FANCC-RED pathway, and characterize the relationship of this pathway to that regulated by FANCA-FANCG. Our combined genetic, cellular and biochemical approaches should result in a comprehensive view of the regulation and function of FA gene products. Aside from improving our understanding of fundamental mechanisms of cellular detoxification and chromosomal stability relevant to hematopoiesis, the manipulation of drug-sensitive pathways controlled by FA genes will provide novel translational opportunities for chemosensitization of leukemias or solid tumors to bifunctional cross-linkers. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MOLECULAR GENETICS OF FANCONI ANEMIA Principal Investigator & Institution: Moses, Robb E.; Professor and Chair; Molecular and Medical Genetics; Oregon Health & Science University Portland, or 972393098 Timing: Fiscal Year 2002; Project Start 01-JUL-1994; Project End 30-JUN-2004 Summary: Fanconi anemia (FA) is an autosomal recessive disease which manifests increased risk of leukemia, regressive bone marrow failure, skeletal abnormalities, altered skin pigmentation and developmental delay. Therefore FA presents alterations in growth and development with anemia, and is an autosomal recessive disease with increased risk of cancer. There are eight complementation groups identified, indicating the involvement of multiple genes in the disease. This Program Project will use a molecular genetic approach to define the genetic elements causing Fanconi anemia and the function of the gene products in order to improve diagnosis and treatment. The concept of this project is to take a multi-disciplinary approach to the definition of the causes of Fanconi anemia at the molecular and cellular level. The clinical disciplines represented by the Investigators include medicine, pediatrics, medical genetics, hematology and oncology. The scientific areas of the investigations include molecular hematology, molecular genetics, mouse genetics, gene therapy, stem cell biology and DNA repair. The proposed project will have three investigative components and three core components: Project 1 will participate in cloning the FA-D group gene and analyze the function of the FA-D protein. Pathogenesis of FA as a result of crosslink repair defects will be tested in mouse models. Project 2 will participate in cloning FA-D and will build mouse models deficient in FA-D and FA-A gene products. Project3 will asess the apoptotic cytokine response defects in FA and define the molecular hematological defects in the mouse models. The Cytogenetics Core will test chromosome breakage in new Fanconi anemia cell line candidates and help map candidate Fanconi anemia genes. The Fanconi Anemia Cell Repository will identify Fanconi anemia cell lines for complementation testing and establish permanent cell lines for investigators as well as provide diagnostic procedures for FA patients and their providers. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: NONMYELOABLATIVE TRANSPLANTS FOR NONMALIGNANT DISORDERS Principal Investigator & Institution: Storb, Rainer F.; Member and Professor/ Program Head; Fred Hutchinson Cancer Research Center Box 19024, 1100 Fairview Ave N Seattle, Wa 98109 Timing: Fiscal Year 2002
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Aplastic Anemia
Summary: We propose to develop successful non-myeloablative hematopoietic stem cell transplant (HSCT) strategies using both related and unrelated donors in the treatment of patients with severe aplastic anemia, Fanconi anemia, other genetic and acquired disease, T-cell deficiency diseases, and autoimmune diseases. The strategies will vary depending on the underlying diseases for which HSCT is carried out. The unifying principle is to reduce the intensity of the conditioning regimens to levels which are not associated with pronounced pancytopenias and other common sort- and long-term toxicities of conventional conditioning regimens to levels which are not associated with pronounced pancytopenias and other common short- and long-term toxicities of conventional conditioning regimens. A novel aspect of the non- myeloablative HSCT is the use of post-grafting immunosuppression with the anti-metabolite mycophenolate mofetil and the T-cell activation blocker cyclosporine. Preclinical studies in a canine model have shown that the drug combination not only controlled graft-versus-host disease but also suppressed host-versus-graft reactions. The latter finding allowed the elimination of much of the high-dose suppressed host-versus-graft reactions. The latter finding allowed the elimination of much of the high dose-cytotoxic pre-transplant conditioning therapy, otherwise needed for stable allogeneic engraftment. Further canine studies have indicate that "creation of marrow space" by cytotoxic conditioning regimens is unnecessary for stable allogeneic engraftment. We have successfully applied the principles derived from the canine studies to treat elderly and medically infirm patients with hematological malignancies. Here we propose to extend the studies on non-myeloablative conditioning to include patients with non-malignant diseases. For most of the acquired and genetic diseases addressed in this project, persistence of some host immune or hematopoietic cells (mixed donor/host hematopoietic chimerism) would be acceptable without impairing the transplants' ability to cure the patients' underlying disease manifestations. For other patients, including those with autoimmune diseases, mixed chimerism may not suffice, and hematopoiesis may have to be converted to all-donor chimerism with the use of donor lymphocyte infusions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NQO1 IN PROTECTION AGAINST BENZENE TOXICICITY Principal Investigator & Institution: Ross, David; Professor; Pharmaceutical Sciences; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, Co 800450508 Timing: Fiscal Year 2003; Project Start 15-JUL-1998; Project End 30-NOV-2007 Summary: (provided by applicant): The homozygous NQO1*2 polymorphism results in a total lack of NQO1 activity due to accelerated degradation of the mutant NQO1*2 protein by the ubiquitin/proteasomal pathway. The NQO1*2 polymorphism has been found to be a risk factor for benzene-induced myeloid toxicity but also for childhood and adult de-novo leukemias and secondary leukemias arising as a result of chemotherapy. The mechanisms underlying the protective effects of NQO1 against benzene-induced myelotoxicity and both de-novo and secondary leukemias were puzzling since NQO1 was not expressed in aspirated human bone marrow cells or human bone marrow CD34+ progenitor cells, the target cell for induction of both aplastic anemia and leukemia. However, we observed that NQO1 was present in human bone marrow endothelial cells (HBMEC), which are not harvested by bone marrow aspiration. In the present application, we wish to explore the potential role of NQO1 in HBMEC in protection against benzene induced aplastic anemia and have established HBMEC cultures in our lab for this purpose. We propose a mechanism whereby HBMEC exposed to benzene metabolites produce increasing amounts of
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endothelial IL8 (elL8) which results in apoptosis of neighboring hematopoietic cells and myeloid progenitor cells resulting in aplastic anemia. We will also examine the mechanism underlying the lack of expression of NQO1 in human myeloid cells at the transcriptional level by characterizing cis acting DNA sequences and trans acting nuclear protein-DNA interactions that modulate NQO1 expression. One of the major tumor suppressor genes characterized in mammalian systems is p53 and a high percentage of leukemias contain mutations or allelic losses of p53. In preliminary data, we demonstrate that NQO1 forms a protein complex with wild type p53. We propose to examine whether the interaction of NQO1 and p53 is specific for wild type p53 and whether it has consequences for p53 stability and p53-dependent transcriptional activation of downstream genes. If NQO1 stabilizes p53 and the interaction has functional consequences, this would provide a mechanism for the increased incidence of leukemia of diverse origin that has been associated with a lack of NQO1 protein due to the NQO1*2 polymorphism. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PATHOPHYSIOLOGY OF PNH Principal Investigator & Institution: Brodsky, Robert A.; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-MAR-2007 Summary: Paroxysmal nocturnal hemoglobinuria (PNH) and aplastic anemia (AA) are closely related, life-threatening bone marrow stem cell disorders. AA results from an immune-mediated attack against hematopoietic stem cells. PNH is a clonal hematopoietic stem cell disorder caused by a somatic mutation of the PIGA gone and may arise de novo or evolve from AA. The biochemical consequence of PIGA mutations is a global loss of glycosylphosphatidyl-inositol (GPI) anchors. We have shown that the GPI-anchor is the receptor for the channel forming toxin aerolysin and that PNH cells are uniquely resistant to aerolysin. A novel diagnostic assay using aerolysin to detect PNH cells has demonstrated that the majority of AA patients harbor small populations of PNH cells. We have also shown that high-dose cyclophosphamide (CY) can lead to durable treatment-free remissions in the majority of patients with AA. The objective of these studies is to explore the relationship between AA and PNH and to elucidate the mechanism of clonal dominance in PNH. We will directly test whether PNH gains clonal dominance through immunologic escape or whether PIGA mutations themselves give HSCs an intrinsic survival advantage. The use of PNH as a model to study clonal expansion and clonal progression should give insight into other clonal hematopoietic diseases such as myelodysplastic syndromes and leukemogenesis. Specfici Aim 1: Detect PIGA mutations in normal human HSC. Specific Aim 2: Study the relationship between AA and PNH. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: POSITIONAL CLONING OF FANC GENES & MODELS OF FANCONI ANEMIA Principal Investigator & Institution: Grompe, Markus C.; Professor; Oregon Health & Science University Portland, or 972393098 Timing: Fiscal Year 2002 Summary: Fanconi Anemia (FA) is an autosomal recessive disease caused by deficiency of proteins in a cellular pathway which impacts chromosome stability, DNA cross-link response, embryonic development, cancer susceptibility and stem cell survival. At least
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eight different genes are known to exist and three of these have been isolated. However, the biochemical function(s) of the FANC proteins are currently not understood. In order to understand the pathway's function and develop improved therapy for this disease, we will clone additional FANC genes and develop knock- out mice of these already cloned. We have narrowed the location of the FA group D gene to <300 kb and together with Project 1 will complete its positional cloning. In addition, we will use microcellmediated chromosome transfer to map additional FA genes and positionally clone them in the future. We have generated knock-out mice for FA group C and will use these animals to study the role of FANCC in DNA cross-link responses in vivo, the biology of hematopoietic stem cells in FA and as a model FANCC in DNA cross-link responses in vivo, the biology of hematopoietic stem cells in FA and as a model for preclinical gene therapy. We will also generate knock-out mice for FA groups A and D. These mutants and their cells will be studied jointly with Projects 1 and 3. Mice doubly mutant in different FANC genes and genes involved in mammalian cross-link repair will be generated to study their cancer proneness hematopoiesis and responses to DNA damaging agents. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PROTO ONCOGENE PBX1 IN NORMAL HEMATOPOIETIC DEVELOPMENT Principal Investigator & Institution: Dimartino, Jorge F.; Pathology; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2002; Project Start 01-JUL-2001; Project End 30-JUN-2006 Summary: (Applicant's Description): The goal of this proposal is to further develop the research skills of the principal investigator by studying the role of the proto-oncogene Pbx1 in normal hematopoietic development. The candidate's predoctoral research experience in transcriptional regulation, and clinical interest in high-risk leukemia led him to the laboratory of Dr. Cleary at the Stanford University School of Medicine. This environment is highly conducive to the objectives of this proposal due to the existence of core facilities for making transgenic and knockout mice, as well as molecular genetic tools to study their phenotypes. Collaborators with expertise in these areas are readily available at Stanford and the nearby University of California, San Francisco. Through continued work with Dr. Cleary and consultants, the candidate will gain experience in the molecular genetic manipulation and differentiation of embryonic stem (ES) cells and in the use of mouse model systems for the study of hematopoietic disease. He will apply this knowledge in his future independent research career, which will focus on the use of ES cells and mouse model systems to study the biology of infant and leukemia. The focus of this application on Pbx1 arises from its involvement in chromosomal translocations in a subset of high-risk pediatric leukemia. Biochemical studies implicate Pbx1 as a cofactor of Hox proteins required for binding to specific DNA sequences. Our preliminary studies show that mice lacking Pbx1 fail to sustain definitive hematopoiesis during embryogenesis. To identify developmental pathways requiring Pbx1, hematopoietic progenitors from Pbx1 null mouse embryos will be transplanted into irradiated recipients and their contribution to hematopoiesis will be determined. In addition to transplantation experiments, the contribution of Pbx1 null ES cells to hematopoiesis will be studied in chimeric mice to identify defects in myeloid and lymphoid differentiation and self-renewal. The candidate proposes to develop a model system for the study of Pbx1/Hox cooperation in hematopoietic differentiation. The hematopoietic differentiation of Pbx1 null ES cells in vitro will be compared to that of normal ES cells. The effect of over- expressing Hox genes on the hematopoietic
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development of normal and Pbx1 deficient progenitors and ES cells will be studied. Differences between normal and Pbx1 deficient ES cells in terms of in vitro differentiation or susceptibility to Hox over-expression will form the basis of an assay for Pbx1/Hox function. By defining the specific requirements for Pbx1 function in normal hematopoiesis, these experiments will further our understanding of the molecular pathogenesis of leukemia, aplastic anemia and myelodysplasia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ROLE TRANSFORMATION
OF
THE
PNH
PHENOTYPE
IN
LEUKEMIC
Principal Investigator & Institution: Bessler, Monica; Barnes-Jewish Hospital Ms 90-94212 St. Louis, Mo 63110 Timing: Fiscal Year 2002; Project Start 20-JAN-2001; Project End 31-DEC-2005 Summary: (adapted from the applicant's abstract): Paroxysmal nocturnal hemoglobinuria (PNH) is a blood disorder, which is caused by the clonal expansion of a hematopoietic progenitor cell that carries a somatic mutation in the X-linked PIGA gene. It presented classically with hemoglobinuria due to intravascular hemolysis, thrombotic complications, and pancytopenia. The PIGA gene encodes a protein subunit of a glycosyltransferase essential in the synthesis of glycosyl phosphatidylinositol (GPI) anchor molecules. Patients with PNH therefore have a proportion of blood cells deficient in all GPI-linked surface molecules. PNH is frequently found in patients with aplastic anemia (AA) and in patients with myelodysplasia (MDS). Although not a neoplastic disease on its own, patients with PNH have an increased risk of developing acute myeloid leukemia (AML). Promoted by the clinical association of PNH with AA, MDS, and AML, we raised the hypothesis that a PIGA gene mutation alone does not cause clonal expansion or leukemic transformation. But due to their inability to like certain proteins to the cell surface through a GPI-anchor PNH cells escape immuno surveillance and cell death that causes bone marrow aplasia in AA and controls neoplastic cell growth in early leukemogenesis. In the proposed research we will use a mouse model that closely mimics the human disease and investigate the association of PNH with MDS and AML. We will obtain mice with blood cells lacking GPI-linked proteins by disrupting the murine Piga gene in early hematopoietic progenitor cells in the bone marrow using the Cre-loxP system. By this approach we will generate two types of mice, one with all blood cells deficient in GPI-linked proteins whereas the other will have both PIGA (+) and PIGA(-) circulating blood cells. We will then compare PIGA(+) and PIGA(-) hematopoiesis in these mice in vitro and in vivo under a variety of circumstances, including the administration of stimuli that trigger cell death along with agents known to cause leukemia transformation. Competition between cells expressing wild type Piga and those expressing the recombined Piga allele will enable us to uncover even subtle differences in cell death and proliferation in any stages of hematopoietic differentiation. These experiments will demonstrate whether PIGA(-) blood cells are more resistant to specific stimuli that activate apoptotic cell death and whether mice with PIGA(-) blood cells develop leukemia earlier and more frequent compared to mice with phenotypically normal blood cells. In this way we hope to identify the factors that differentially influence growth and death of PNH and normal hematopoietic progenitor cells and to elucidate mechanisms that may lead to leukemia transformation in patients with PNH. The availability of a mouse model for PNH will provide us with a powerful tool to test new therapeutic agents for the treatment of PNH, PNH/MDS, PNH,AML and possibly other clonal blood disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Aplastic Anemia
Project Title: SIGNAL TRANSDUCTION IN THE FANCONI ANEMIA PATHWAY Principal Investigator & Institution: D'andrea, Alan D.; Professor; Dana-Farber Cancer Institute 44 Binney St Boston, Ma 02115 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2007 Summary: (provided by applicant): The purpose of Project 5 is to further understand the signal transduction events in the Fanconi Anemia (FA) pathway. The grant is significant since a molecular understanding of FA may lead to a general understanding of aplastic anemia and cancer susceptibility in the general (non-FA) population. Also, FA is a candidate disease for gene therapy, based on the selective advantage of FA cDNA transduced hematopoietic progenitor cells. Our laboratory has recently determined that the six cloned FA genes (corresponding to subtypes A,C,D2,E,F, and G) interact in a novel signaling pathway, which regulates DNA repair and ultimately regulates normal blood cell production. Disruption of this pathway leads to the common clinical and cellular phenotype observed in FA. Specific Aim 1 for the five year study period will be to study the molecular interaction between the FA pathway and the Ataxia Telangiectasia Protein, ATM. Our preliminary data demonstrate that the FANCD2 protein is monoubiquitinated by the FA protein complex (A/C/E/F/G complex) and phosphorylated by ATM. In Specific Aim 2, we will develop murine models of FA (i.e., ATM/FANCG double knockout mice FANCD2 -/- mice) and will study hematopoiesis and leukemia susceptibility in these mice. In Specific Aim 3, we will use Drosophila genetics to validate various biochemical features of the FA pathway. Through the execution of these three specific aims, we plan extensive interactions with the four other projects in this Program Project and with the flow cytometry core and mouse pathology core. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: STEM CELL PRESERVATION WITH NONTOXIC SUGARS Principal Investigator & Institution: Walsh, John R.; Organ Recovery Systems, Inc. 701 E Bay St, Ste 433 Charleston, Sc 29403 Timing: Fiscal Year 2002; Project Start 25-SEP-2002; Project End 24-SEP-2003 Summary: (provided by applicant): Diseases of the bone marrow that may be treated with cryopreserved hemopoletic stem cell transplantation indude the leukemias, lymphomas and aplastic anemia. In the field of cryopreservation, current opinion is that cryoprotective agents should be removed prior to transplantation. In the case of dimethylsulfoxide (DM80), the most popular cryoprotectant, there are many documented effects at the cellular level along with frequent clinical reports of detrimental side effects in patients. The ability to use non-cytotoxic sugars should enable the avoidance of DMSO in currently employed cryopreservation procedures. Therefore, in this proposal we will use human stem/progenitor cells to develop preservation methods utilizing a new cell membrane permeabilization technology in combination with sugars that are normally impermeable. It is anticipated that cells cryopreserved by this technology will be directly infusible into patients. This technology may also be leveraged to provide stable long-term storage of a variety of cells, including mature blood cells, mesenchymal stem cells, cell-based biosensors and some medical therapies involving gene therapy. The following specific aims will be addressed in this Phase I research study: #1 Optimization of H5 pore and divalent metal ion (zinc for pore opening and dosing) concentrations; #2 Optimization of postpermeabilization pore removal; #3 Comparison of controlled rate cryopreservation at four cooling rates following permeabilization with trehalose or sucrose; and #4 Evaluation of residual H5
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cytotoxicity and the long-term hematopoietic potential of treated cells. These aims will be accomplished using human CD34+ cord blood cells and a panel of in vitro assays, and by transplantation in vivo into NOD/SCID mice. The technical innovations in this proposal are based upon the concept of reversible permeabilization of cell membranes using engineered pores to load the cells with disaccharides prior to freezing. The permeabilization technology employs a genetically engineered pore forming protein. The opening and dosing of the pore is regulated by divalent metal ions. Preliminary feasibility data is submitted demonstrating cryopreservation of a porated human hemopoietic progenitor cell line with trehalose. A Phase-Il SBIR study wilt be proposed to optimize hemopoletic stem and progenitor cell preservation if mice treated with porated human cells demonstrate good survival and hematopoietic reconstitution. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: THE RISK OF CANCER IN FANCONI ANEMIA HETEROZYGOTES Principal Investigator & Institution: Berwick, Marianne; Professor and Chief; SloanKettering Institute for Cancer Res New York, Ny 10021 Timing: Fiscal Year 2002; Project Start 01-APR-2001; Project End 31-MAR-2005 Summary: Fanconi anemia (FA) homozygotes have an increased cancer predisposition. In addition to the extraordinarily high frequency of AML in FA patients (actuarial risk of 52 percent for the development of MDS and/or AML by 40 years of age), FA patients exhibit malignancies of a variety of organ systems, most commonly gastrointestinal and gynecologic. The high incidence of nonhematologic malignancy in FA patients is especially striking because of the predicted early death from hematologic causes associated with the syndrome. Thus patients are unusually young when they develop cancer, and the incidence of malignancy probably would be considerably higher if patients had a longer life expectancy. There is evidence that heterozygote carriers of homozygous recessive familial cancer syndromes, such as Fanconi anemia, ataxia telangiectasia and xeroderma pigmentosum, are at increased risk for cancer. It is now possible to ascertain the carrier status by means of molecular tests rather than impute carrier status through probabilities, and thus it may be possible to arrive at a definitive answer to the role of heterozygosity among Fanconi anemia carriers. This study will directly address the etiology of cancer that involves the role of Fanconi anemia heterozygosity. The major aim of this retrospective cohort study will be to evaluate whether FA heterozygotes are at increased risk for developing cancer. In order to address this aim this study will use the extensive resources of the International Fanconi Anemia Registry at Rockefeller University. The sample will consist of 758 Fanconi anemia heterozygote grandparents of FA probands and 758 grandparents who do not carry an FA allele. Risk factor information will be obtained by questionnaire, blood will be collected for DNA analysis, and diagnostic pathology information will be collected using a systematic approach. Analyses will be undertaken to evaluate the role of Fanconi anemia heterozygosity for cancer. If carriers are found to be at increased risk, this information can be used to target individuals for cancer prevention strategies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: THERAPEUTIC USE OF STEM CELLS Principal Investigator & Institution: Jones, Richard J.; Professor of Oncology; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002
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Aplastic Anemia
Summary: The ability to isolate and expand lymphohematopoietic stem cells (HSC) should improve both the availability and outcome of clinical bone marrow transplantation (BMT). Moreover, clinical transplants with HSC are currently the only way to definitively prove that human HSC have been isolated. Although BMT is curative therapy for most hematologic malignancies and for a variety of fatal nonmalignant disorders that effect the lymphohematopoietic system, the majority of patients with these diseases are still not cured. This is, in large part, because patients with these diseases either are not eligible for, or fail, BMT. A graft containing HSC should also be an important method of eliminating (purging) tumor from autologous marrow grafts, especially in those diseases like CML and MDS where it has been difficult to eradicate tumor and simultaneously generate normal hematopoiesis. Transplantation of purified allogeneic HSC should be an important strategy for avoiding histocompatibility problems, graft-versus-host disease (GVHD) and graft rejection, associated with allogeneic BMT. Purified HSC may also be necessary for effective gene transfer therapy for lymphohematopoietic cells, as the rarity of these cells may make them inaccessible to present gene transfer techniques and these techniques may preferentially affect the more rapidly proliferating committed progenitors. The overall objective of this project is to study the use of HSC as treatment for a variety of disease. We will study the use of autologous HSC as treatment of stem failure disorders like MDS, severe aplastic anemia (SAA), and paroxysmal nocturnal hemoglobinuria (PNH). Our preliminary data suggest that the defect in most patients with aplastic anemia and MDS is at the level of a myeloid stem cell rather than the earliest HSC; further, many patients with aplastic anemia and MDS have relatively normal numbers of the earliest HSC. We will also study autologous HSC in the treatment for refractory, life-threatening autoimmune diseases like lupus. Finally, we will utilize isolated allogeneic HSC as a means to overcome histocompatibility problems associated with allogeneic BMT; specifically we will investigate in utero transplantation with allogeneic HSC to treat genetic diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TRANSCRIPTION FACTORS/ GENETIC SEQUENCES REQUIRED FOR CD34 IN EARLY HEMATOPOIESIS Principal Investigator & Institution: Krause, Diane S.; Associate Professor; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2002 Summary: The long-term goal of my research program is to define the molecular mechanisms that regulate nearly hematopoiesis. To do this I am using the murine CD34 gene as a model system. CD34 is the best characterized antigen that can be used to isolate hematopoietic reconstituting cells for human stem cell transplantation. It's expression is coordinately regulated with lineage commitment in hematopoietic differentiation such that CD34 is expressed on hematopoietic stem and progenitor cells, and as maturation progresses, expression decreases and all mature blood cells are CD34 negative. Forced over-expression of CD34 inhibits terminal differentiation suggesting that CD34 down-regulation is required for the differentiation process. In work to date, I have identified critical regions of the CD34 gene that enhance expression from the CD34 promoter in a tissue-specific manner. The aims presented in this proposal approach the study of early hematopoietic differentiation from several directions-1.) The isolation and identification of a potentially novel stem cell-specific transcription factor, 2.) The establishment of a family of genes that share the stage specific expression pattern of CD34, and therefore may be coordinately regulated, 3.) The isolation and identification
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of the DNA sequences required for position-independent, copy-number dependent, ell typed specific expression of CD34 in vivo, and 4.) Identification of these genes that are required for myeloid differentiation, but are inhibited when CD34 down-regulation is prevented. Each of this goals contributes to a better understanding of how hematopoietic stem cells are regulated. This increased understanding of how a stem cell "knows" to remain a stem cell, or to divide and differentiate into any of the mature cells in the peripheral blood has direct implications for the pathogenesis of leukemia and other hematopoietic disorders such as myelodysplasia and aplastic anemia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TUMOR SUPPRESSORS HEMATOPOIESIS AND LEUKEMIA Principal Investigator & Institution: Amatruda, James F.; Children's Hospital (Boston) Boston, Ma 021155737 Timing: Fiscal Year 2002; Project Start 13-AUG-1999; Project End 31-JUL-2004 Summary: Hematopoiesis and leukemogenesis are developmental phenomena, in which complex interactions of multiple genes give rise to orderly differentiation or to maturation arrest and uncontrolled proliferation. While many of the terminal events in these pathways have been elucidated by cellular, biochemical and transgenic mouse studies, the genes responsible for the most fundamental developmental decisions in hematopoiesis and leukemogenesis have been less well-defined. Tumor suppressor genes (TSGs), first identified in hereditary human cancers, are likely to be among this group of fundamental genes. TSGs are key elements of cellular pathways that regulate growth and differentiation. Specific TSGs have been shown to be mutated or deleted in primary human leukemias and leukemic cell lines. Mouse knock-out models and patients deficient in several of these genes demonstrate defective hematopoiesis or develop leukemias. To better understand the function of tumor suppressor genes in normal hematopoiesis and leukemogenesis we have chosen as a model the zebrafish (Danio rerio), a vertebrate system that combines physiology and development with powerful genetics. We plan to create zebrafish strains deficient in known TSGs and to characterize hematopoietic defects and the development of leukemia in these strains. A suppressor or enhancer screen for mutations that correct the defects or cure the leukemia will lead to the isolation of additional genes in these pathways. The experiments described in this proposal are likely to identify novel proteins that play key roles in the control of hematopoiesis and the genesis of leukemia. These proteins will be potential therapeutic targets for the treatment of aplastic anemia, myelodysplasia and leukemia in humans. 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
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.
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Aplastic Anemia
unrestricted.5 To search, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Pmc, and type “aplastic anemia” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for aplastic anemia in the PubMed Central database: •
Invasive Infection with Fusarium chlamydosporum in a Patient with Aplastic Anemia. by Segal BH, Walsh TJ, Liu JM, Wilson JD, Kwon-Chung KJ.; 1998 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=104919
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Molecular analysis and pathogenesis of the feline aplastic anemia retrovirus, feline leukemia virus C-Sarma. by Riedel N, Hoover EA, Gasper PW, Nicolson MO, Mullins JI.; 1986 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=253922
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Novel Human Erythrovirus Associated with Transient Aplastic Anemia. by Nguyen QT, Sifer C, Schneider V, Allaume X, Servant A, Bernaudin F, Auguste V, GarbargChenon A.; 1999 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=85263
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Pathogenic and host range determinants of the feline aplastic anemia retrovirus. by Riedel N, Hoover EA, Dornsife RE, Mullins JI.; 1988 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=280078
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Soft Tissue Infection with Absidia corymbifera in a Patient with Idiopathic Aplastic Anemia. by Cloughley R, Kelehan J, Corbett-Feeney G, Murray M, Callaghan J, Regan P, Cormican M.; 2002 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=153381
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Trichoderma longibrachiatum infection in a pediatric patient with aplastic anemia. by Munoz FM, Demmler GJ, Travis WR, Ogden AK, Rossmann SN, Rinaldi MG.; 1997 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=229611
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.
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. 6 PubMed was developed by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM) at the National Institutes of Health (NIH). The PubMed database was developed in conjunction with publishers of biomedical literature as a search tool for accessing literature citations and linking to full-text journal articles at Web sites of participating publishers. Publishers that participate in PubMed supply NLM with their citations electronically prior to or at the time of publication.
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To generate your own bibliography of studies dealing with aplastic anemia, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “aplastic anemia” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for aplastic anemia (hyperlinks lead to article summaries): •
A retrospective analysis of long-term survival in severe aplastic anemia patients treated with allogeneic bone marrow transplantation or immunosuppressive therapy with antithymocyte globulin and cyclosporin A at a single institution. Author(s): Ellis RJ, Kahn Q, Skikne BS, Mayo MS, Allgood JW, Bodensteiner DM, Deauna-Limayo D, Cook JD. Source: Military Medicine. 2002 July; 167(7): 541-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12125844&dopt=Abstract
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Acquired aplastic anemia in children: incidence, prognosis and treatment options. Author(s): Locasciulli A. Source: Paediatric Drugs. 2002; 4(11): 761-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12390048&dopt=Abstract
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Acute graft-versus-host disease in patients with Fanconi anemia or acquired aplastic anemia undergoing bone marrow transplantation from HLA-identical sibling donors: risk factors and influence on outcome. Author(s): Guardiola P, Socie G, Li X, Ribaud P, Devergie A, Esperou H, Richard P, Traineau R, Janin A, Gluckman E. Source: Blood. 2004 January 1; 103(1): 73-7. Epub 2003 August 28. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12946993&dopt=Abstract
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Acute lymphoblastic leukemia in adult first manifested as severe aplastic anemia-role of molecular analysis in correct diagnosis. Author(s): Robak T, Bartkowiak J, Urbanska-Rys H, Szmigielska-Kaplon A, Strzelecka B, Chojnowski K. Source: Leukemia & Lymphoma. 2002 May; 43(5): 1147-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12148900&dopt=Abstract
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Allogeneic peripheral blood stem cell rescue of late graft failure after bone marrow transplantation in patients with aplastic anemia. Author(s): Chung IJ, Lee JJ, Park MR, Kook H, Cho SH, Hwang TJ, Kim HJ. Source: Journal of Korean Medical Science. 2002 August; 17(4): 468-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12172040&dopt=Abstract
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Allogeneic peripheral blood stem cell transplantation in the treatment of severe aplastic anemia and severe infection. Author(s): Wan L, Yan S, Wang C, Yang X, Zhou Z, Gao Y, Cai Q, Zhang B. Source: Chinese Medical Journal. 2003 May; 116(5): 676-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12875677&dopt=Abstract
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Antithymocyte globulin in the treatment of D-penicillamine-induced aplastic anemia. Author(s): Kondo H, Narita K. Source: International Journal of Hematology. 2002 May; 75(4): 385-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12041669&dopt=Abstract
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Antithymocyte globulin with or without cyclosporin A: 11-year follow-up of a randomized trial comparing treatments of aplastic anemia. Author(s): Frickhofen N, Heimpel H, Kaltwasser JP, Schrezenmeier H; German Aplastic Anemia Study Group. Source: Blood. 2003 February 15; 101(4): 1236-42. Epub 2002 October 10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12393680&dopt=Abstract
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Aplastic anemia and immunosuppression. Author(s): Nagy SM Jr, Fisher JJ. Source: Jama : the Journal of the American Medical Association. 2003 July 9; 290(2): 193; Author Reply 193. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12851270&dopt=Abstract
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Aplastic anemia associated with interferon beta-1a. Author(s): Aslam AK, Singh T. Source: American Journal of Therapeutics. 2002 November-December; 9(6): 522-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12424511&dopt=Abstract
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Aplastic anemia complicating systemic lupus erythematosus--report of a case and review of the literature. Author(s): Pavithran K, Raji NL, Thomas M. Source: Rheumatology International. 2002 November; 22(6): 253-5. Epub 2002 October 01. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12426665&dopt=Abstract
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Aplastic anemia evolving into overt myelodysplastic syndrome/acute myeloid leukemia with t(3;5)(p25;q31). Author(s): Kawata E, Kuroda J, Kimura S, Kamitsuji Y, Kobayashi Y, Yoshikawa T. Source: Cancer Genetics and Cytogenetics. 2002 September; 137(2): 91-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12393278&dopt=Abstract
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Aplastic anemia following administration of a tumor necrosis factor-alpha inhibitor. Author(s): Kuruvilla J, Leitch HA, Vickars LM, Galbraith PF, Li CH, Al-Saab S, Naiman SC. Source: European Journal of Haematology. 2003 November; 71(5): 396-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14667206&dopt=Abstract
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Aplastic anemia in Brazil: incidence and risk factors. Author(s): Maluf EM, Pasquini R, Eluf JN, Kelly J, Kaufman DW. Source: American Journal of Hematology. 2002 December; 71(4): 268-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12447955&dopt=Abstract
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Aplastic anemia in Down's syndrome. Author(s): Pavithran K, Raji NL. Source: American Journal of Hematology. 2003 July; 73(3): 213. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12827661&dopt=Abstract
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Aplastic anemia in Nijmegen breakage syndrome. Author(s): Pasic S. Source: The Journal of Pediatrics. 2002 November; 141(5): 742. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12410210&dopt=Abstract
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Aplastic anemia in the Orient. Author(s): Kojima S. Source: International Journal of Hematology. 2002 August; 76 Suppl 2: 173-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12430921&dopt=Abstract
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Aplastic anemia induced by phenytoin: a geriatric case with severe folic acid deficiency. Author(s): Blain H, Hamdan KA, Blain A, Jeandel C. Source: Journal of the American Geriatrics Society. 2002 February; 50(2): 396-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12028229&dopt=Abstract
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Aplastic anemia--low drug associations. Author(s): Issaragrisil S. Source: Curr Hematol Rep. 2003 January; 2(1): 1-2. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12901149&dopt=Abstract
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Autoantibodies frequently detected in patients with aplastic anemia. Author(s): Hirano N, Butler MO, Von Bergwelt-Baildon MS, Maecker B, Schultze JL, O'Connor KC, Schur PH, Kojima S, Guinan EC, Nadler LM. Source: Blood. 2003 December 15; 102(13): 4567-75. Epub 2003 August 28. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12947009&dopt=Abstract
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Bilateral macular hemorrhage caused by azathioprine-induced aplastic anemia in a corneal graft recipient. Author(s): Sudhir RR, Rao SK, Shanmugam MP, Padmanabhan P. Source: Cornea. 2002 October; 21(7): 712-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12352092&dopt=Abstract
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Biology and management of acquired severe aplastic anemia. Author(s): Brodsky RA. Source: Current Opinion in Oncology. 1998 March; 10(2): 95-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9555529&dopt=Abstract
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Bolous of methylprednisolone for aplastic anemia. Author(s): Sanz MA, Martinez JA, Besalduch J, Rafecas J. Source: Annals of Internal Medicine. 1982 January; 96(1): 124. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7053691&dopt=Abstract
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Bone marrow cytogenetic abnormalities of aplastic anemia. Author(s): Keung YK, Pettenati MJ, Cruz JM, Powell BL, Woodruff RD, Buss DH. Source: American Journal of Hematology. 2001 March; 66(3): 167-71. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11279622&dopt=Abstract
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Bone marrow fibroblasts from children with aplastic anemia exhibit reduced interleukin-6 production in response to cytokines and viral challenge. Author(s): Dilloo D, Vohringer R, Josting A, Habersang K, Scheidt A, Burdach S. Source: Pediatric Research. 1995 November; 38(5): 716-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8552439&dopt=Abstract
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Bone marrow samples from patients with aplastic anemia are not infected with parvovirus B19 and Mycobacterium tuberculosis. Author(s): Hsu HC, Lee YM, Su WJ, Huang CY, Yang CF, Ho CK, Ho CH, Wang SY, Liu WT. Source: American Journal of Clinical Pathology. 2002 January; 117(1): 36-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11789728&dopt=Abstract
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Bone marrow transplantation for aplastic anemia. Author(s): Storb R. Source: Cell Transplantation. 1993 September-October; 2(5): 365-79. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8162278&dopt=Abstract
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Bone marrow transplantation for leukemia and aplastic anemia: management of ABO incompatibility. Author(s): Curtis JE, Messner HA. Source: Can Med Assoc J. 1982 March 15; 126(6): 649-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7039802&dopt=Abstract
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Bone marrow transplantation for patients with acquired severe aplastic anemia using cyclophosphamide and antithymocyte globulin: the experience from a single center. Author(s): Abdelkefi A, Ben Othman T, Ladeb S, Torjman L, Hsairi M, Ben Abdeladhim A. Source: The Hematology Journal : the Official Journal of the European Haematology Association / Eha. 2003; 4(3): 208-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12764353&dopt=Abstract
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Bone marrow transplantation for pediatric patients with severe aplastic anemia in Taiwan. Author(s): Lin KH, Chen RL, Lin DT, Lui LT, Lin KS. Source: Transplantation Proceedings. 1993 August; 25(4 Suppl 3): 61-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8351722&dopt=Abstract
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Bone marrow transplantation for severe aplastic anemia from genotypically HLAnonidentical relatives. An update of the Seattle experience. Author(s): Wagner JL, Deeg HJ, Seidel K, Anasetti C, Doney K, Sanders J, Sullivan KM, Storb R. Source: Transplantation. 1996 January 15; 61(1): 54-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8560574&dopt=Abstract
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Bone marrow transplantation for severe aplastic anemia from HLA identical siblings. Author(s): Bacigalupo A. Source: Haematologica. 1999 January; 84(1): 2-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10091385&dopt=Abstract
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Bone marrow transplantation for severe aplastic anemia. Author(s): Lin KH, Chen YC, Lin DT, Lui LT, Wang CH, Lin KS. Source: J Formos Med Assoc. 1993 December; 92(12): 1070-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7911356&dopt=Abstract
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Bone marrow transplantation for severe aplastic anemia: has outcome improved? Author(s): Passweg JR, Socie G, Hinterberger W, Bacigalupo A, Biggs JC, Camitta BM, Champlin RE, Gale RP, Gluckman E, Gordon-Smith EC, Hows JM, Klein JP, Nugent ML, Pasquini R, Rowlings PA, Speck B, Tichelli A, Zhang MJ, Horowitz MM, Bortin MM. Source: Blood. 1997 July 15; 90(2): 858-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9226187&dopt=Abstract
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Bone marrow transplantation for severe aplastic anemia: the Barcelona Hospital Clinic experience. Author(s): Hernandez-Boluda JC, Marin P, Carreras E, Aguilar JL, Granena A, Rozman C, Montserrat E. Source: Haematologica. 1999 January; 84(1): 26-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10091390&dopt=Abstract
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Bone marrow transplantation for transfused patients with severe aplastic anemia using cyclophosphamide and total lymphoid irradiation as conditioning therapy: long-term follow-up from a single center. Author(s): Gaziev D, Giardini C, Galimberti M, Lucarelli G, Angelucci E, Polchi P, Baronciani D, Erer B, Sotti G. Source: Bone Marrow Transplantation. 1999 August; 24(3): 253-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10455362&dopt=Abstract
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Bone marrow transplantation in pediatric patients with severe aplastic anemia: cyclophosphamide and anti-thymocyte globulin conditioning followed by recombinant human granulocyte-macrophage colony stimulating factor. Author(s): Bunin N, Leahey A, Kamani N, August C. Source: Journal of Pediatric Hematology/Oncology : Official Journal of the American Society of Pediatric Hematology/Oncology. 1996 February; 18(1): 68-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8556374&dopt=Abstract
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Bone marrow transplantation in Taiwan: low incidence of acute GVHD in patients with hematologic malignancies and severe aplastic anemia. Author(s): Chen PM, Tzeng CH, Fan FS, Hsieh RK, Wei CH. Source: Bone Marrow Transplantation. 1994 June; 13(6): 709-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7920299&dopt=Abstract
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Bone marrow transplantation in the management of acquired aplastic anemia. Author(s): Gordon-Smith E, Marsh JC. Source: Journal of Hematotherapy. 1994 Fall; 3(3): 238-43. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7827873&dopt=Abstract
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Bone-marrow imaging with indium-111 chloride in aplastic anemia and myelofibrosis: concise communication. Author(s): Sayle BA, Helmer RE 3rd, Birdsong BA, Balachandran S, Gardner FH. Source: Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine. 1982 February; 23(2): 121-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7057252&dopt=Abstract
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CD34+ progenitor cell transplantation from two HLA-mismatched healthy fathers to two infants with severe aplastic anemia. Author(s): Yasui M, Park YD, Okamura T, Chayama K, Yoshimoto T, Inoue M, Yagi K, Kawa K. Source: International Journal of Hematology. 1998 January; 67(1): 15-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9594440&dopt=Abstract
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Changes in T-cell receptor VB repertoire in aplastic anemia: effects of different immunosuppressive regimens. Author(s): Kook H, Risitano AM, Zeng W, Wlodarski M, Lottemann C, Nakamura R, Barrett J, Young NS, Maciejewski JP. Source: Blood. 2002 May 15; 99(10): 3668-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11986222&dopt=Abstract
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Characterization of T-cell repertoire of the bone marrow in immune-mediated aplastic anemia: evidence for the involvement of antigen-driven T-cell response in cyclosporine-dependent aplastic anemia. Author(s): Zeng W, Nakao S, Takamatsu H, Yachie A, Takami A, Kondo Y, Sugimori N, Yamazaki H, Miura Y, Shiobara S, Matsuda T. Source: Blood. 1999 May 1; 93(9): 3008-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10216097&dopt=Abstract
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Chronic lymphocytic leukemia presenting in association with aplastic anemia. Author(s): Zonder JA, Keating M, Schiffer CA. Source: American Journal of Hematology. 2002 December; 71(4): 323-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12447965&dopt=Abstract
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Clinical relevance of the TNF-alpha promoter/enhancer polymorphism in patients with aplastic anemia. Author(s): Demeter J, Messer G, Schrezenmeier H. Source: Annals of Hematology. 2002 October; 81(10): 566-9. Epub 2002 October 11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12424537&dopt=Abstract
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Clostridium septicum myonecrosis presenting as a parapharyngeal abscess in a patient with aplastic anemia. Author(s): Fowler VG Jr, Hamilton CD, Ohl CA. Source: Infection. 1998 September-October; 26(5): 309-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9795792&dopt=Abstract
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Clozapine-induced aplastic anemia in a patient with Parkinson's disease. Author(s): Ziegenbein M, Steinbrecher A, Garlipp P. Source: Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie. 2003 June; 48(5): 352. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12866349&dopt=Abstract
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Comparative analysis of the in vitro proliferation and expansion of hematopoietic progenitors from patients with aplastic anemia and myelodysplasia. Author(s): Martinez-Jaramillo G, Flores-Figueroa E, Sanchez-Valle E, GutierrezEspindola G, Gomez-Morales E, Montesinos JJ, Flores-Guzman P, Chavez-Gonzalez A, Alvarado-Moreno JA, Mayani H. Source: Leukemia Research. 2002 October; 26(10): 955-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12163058&dopt=Abstract
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Comparative multi-color flow cytometric analysis of cell surface antigens in bone marrow hematopoietic progenitors between refractory anemia and aplastic anemia. Author(s): Otawa M, Kawanishi Y, Iwase O, Shoji N, Miyazawa K, Ohyashiki K. Source: Leukemia Research. 2000 April; 24(4): 359-66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10713334&dopt=Abstract
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Concentrations of thrombopoietin in bone marrow in normal subjects and in patients with idiopathic thrombocytopenic purpura, aplastic anemia, and essential thrombocythemia correlate with its mRNA expression of bone marrow stromal cells. Author(s): Hirayama Y, Sakamaki S, Matsunaga T, Kuga T, Kuroda H, Kusakabe T, Sasaki K, Fujikawa K, Kato J, Kogawa K, Koyama R, Niitsu Y. Source: Blood. 1998 July 1; 92(1): 46-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9639498&dopt=Abstract
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Consensus Conference on the Treatment of Aplastic Anemia. Author(s): Kojima S, Nakao S, Tomonaga M, Hows J, Marsh J, Gerard S, Bacigalupo A, Mizoguchi H. Source: International Journal of Hematology. 2000 July; 72(1): 118-23. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10979223&dopt=Abstract
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Constitutional (5;18) in a patient with aplastic anemia. Author(s): Keung YK, Suwanvecho S, Cobos E, Tonk V. Source: Cancer Genetics and Cytogenetics. 1999 July 15; 112(2): 184-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10686951&dopt=Abstract
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CsA-based post-graft immunosuppression: the main factor for improving outcome of allografted patients with acquired aplastic anemia. A retrospective survey by the Spanish Group of Hematopoietic Transplantation. Author(s): Arranz R, Conde E, Rodriguez-Salvanes F, Pajuelo FJ, Cabrera R, Sanz MA, Petit J, Bueno J, Maldonado J, Odriozola J, Conde JG, Brunet S, Carreras E, Iriondo A, Fernandez-Ranada JM, Marin P; Subcomite de Aplasia Medular del Grupo Espanol de Trasplante Hemopoyetico. Source: Bone Marrow Transplantation. 2002 February; 29(3): 205-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11859392&dopt=Abstract
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Cure from severe aplastic anemia in vivo and late effects. Author(s): Socie G, Gluckman E. Source: Acta Haematologica. 2000; 103(1): 49-54. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10705159&dopt=Abstract
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Current results of bone marrow transplantation in patients with acquired severe aplastic anemia. Report of the European Group for Blood and Marrow transplantation. On behalf of the Working Party on Severe Aplastic Anemia of the European Group for Blood and Marrow Transplantation. Author(s): Bacigalupo A, Oneto R, Bruno B, Socie G, Passweg J, Locasciulli A, Van Lint MT, Tichelli A, McCann S, Marsh J, Ljungman P, Hows J, Marin P, Schrezenmeier H. Source: Acta Haematologica. 2000; 103(1): 19-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10705155&dopt=Abstract
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Cutting edge: activation of the p38 mitogen-activated protein kinase signaling pathway mediates cytokine-induced hemopoietic suppression in aplastic anemia. Author(s): Verma A, Deb DK, Sassano A, Kambhampati S, Wickrema A, Uddin S, Mohindru M, Van Besien K, Platanias LC. Source: Journal of Immunology (Baltimore, Md. : 1950). 2002 June 15; 168(12): 5984-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12055203&dopt=Abstract
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Cyclophosphamide and antithymocyte globulin conditioning may be sufficient for Korean patients with early stage severe aplastic anemia transplanted with marrow from donors other than HLA-identical siblings. Author(s): Lee JH, Lee JH, Lee JS, Kim WK, Chi HS, Lee KH. Source: Haematologica. 2001 April; 86(4): 434-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11325653&dopt=Abstract
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Cyclophosphamide and antithymocyte globulin to condition patients with aplastic anemia for allogeneic marrow transplantations: the experience in four centers. Author(s): Storb R, Blume KG, O'Donnell MR, Chauncey T, Forman SJ, Deeg HJ, Hu WW, Appelbaum FR, Doney K, Flowers ME, Sanders J, Leisenring W. Source: Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation. 2001; 7(1): 39-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11215697&dopt=Abstract
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Cyclosporin A and short-term methotrexate versus cyclosporin A as graft versus host disease prophylaxis in patients with severe aplastic anemia given allogeneic bone marrow transplantation from an HLA-identical sibling: results of a GITMO/EBMT randomized trial. Author(s): Locatelli F, Bruno B, Zecca M, Van-Lint MT, McCann S, Arcese W, Dallorso S, Di Bartolomeo P, Fagioli F, Locasciulli A, Lawler M, Bacigalupo A. Source: Blood. 2000 September 1; 96(5): 1690-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10961865&dopt=Abstract
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Cyclosporine-induced encephalopathy predisposed by diltiazem in a patient with aplastic anemia. Author(s): Jiang TT, Huang W, Patel D. Source: The Annals of Pharmacotherapy. 1999 June; 33(6): 750-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10410193&dopt=Abstract
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Dapsone-induced aplastic anemia in a woman with bullous systemic lupus erythematosus. Author(s): Meyerson MA, Cohen PR. Source: Mayo Clinic Proceedings. 1994 December; 69(12): 1159-62. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7967777&dopt=Abstract
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Decreased expression of the Fas ligand on peripheral blood mononuclear cells and undetectable levels of soluble Fas ligand in the serum of patients with aplastic anemia and myelodysplastic syndrome. Author(s): Shinohara K, Takahahi T, Nawata R, Oeda E. Source: American Journal of Hematology. 1999 October; 62(2): 124-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10509009&dopt=Abstract
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Decreased rejection and improved survival of first and second marrow transplants for severe aplastic anemia (a 26-year retrospective analysis). Author(s): Stucki A, Leisenring W, Sandmaier BM, Sanders J, Anasetti C, Storb R. Source: Blood. 1998 October 15; 92(8): 2742-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9763558&dopt=Abstract
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Deficiency of CD34+ c-kit+ and CD34+38- hematopoietic precursors in aplastic anemia after immunosuppressive treatment. Author(s): Manz CY, Nissen C, Wodnar-Filipowicz A. Source: American Journal of Hematology. 1996 August; 52(4): 264-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8701944&dopt=Abstract
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Deficient proliferation of myeloid, erythroid, and multipotent progenitor cells in long-term marrow cultures from patients with aplastic anemia treated with immunosuppressive therapy. Author(s): Gomez-Morales E, Martinez-Jaramillo G, Sanchez-Valle E, Valencia-Plata I, Arana-Trejo RM, Castro MA, Pizzuto-Chavez J, Mayani H. Source: American Journal of Hematology. 1998 October; 59(2): 149-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9766800&dopt=Abstract
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Defunct hematopoietic progenitor growth and heterogeneous immunological phenotypes in acquired aplastic anemia of childhood: identification of subsets with decreased hematopoietic progenitors and increased IL15 or IL10 production. Author(s): Dirksen U, Asadi-Moghaddam K, Fuhrer M, Burdach S. Source: Klinische Padiatrie. 1998 July-August; 210(4): 167-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9743948&dopt=Abstract
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Delayed activation-induced T lymphocytes death in aplastic anemia: related with abnormal Fas system. Author(s): Kim SC, Min YH, Lee S, Chung SY, Yoo NC, Lee JW, Hahn JS, Ko YW. Source: Korean J Intern Med. 1998 February; 13(1): 41-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9538630&dopt=Abstract
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Delayed granulocyte response to G-CSF in aplastic anemia. Author(s): Higuchi T, Shimizu T, Okada S, Mori H, Niikura H, Omine M. Source: American Journal of Hematology. 1994 June; 46(2): 164-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7513497&dopt=Abstract
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Delivery after bone marrow transplantation with total lymphoid irradiation for severe aplastic anemia. Author(s): Ashida T, Tsubaki K, Hazu S, Ishikawa H, Urase F, Horiuchi A. Source: International Journal of Hematology. 1996 October; 64(3-4): 279-81. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8923792&dopt=Abstract
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Detection of myelodysplastic syndrome/ acute myeloid leukemia evolving from aplastic anemia in children, treated with recombinant human G-CSF. Author(s): Imashuku S, Hibi S, Bessho F, Tsuchida M, Nakahata T, Miyazaki S, Tsukimoto I, Hamajima N; Pediatric AA Follow-up Study Group in Japan. Source: Haematologica. 2003 November; 88(11): Ecr31. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14607763&dopt=Abstract
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Detection of small populations of CD59-deficient erythrocytes in patients with aplastic anemia or myelodysplastic syndrome and normal individuals. Author(s): Yamaguchi M, Machii T, Azenishi Y, Nishimura J, Shibano M, Kanakura Y, Kitani T. Source: Blood Cells, Molecules & Diseases. 2000 June; 26(3): 247-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10950945&dopt=Abstract
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Development of minimally differentiated acute myeloblastic leukemia with novel isochromosome 18p and antecedent aplastic anemia. Author(s): Keung YK, Cobos E, Morgan D, Tonk V. Source: Cancer Genetics and Cytogenetics. 1996 November; 92(1): 1-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8956860&dopt=Abstract
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Development of the glycosylphosphatitylinositol-anchoring defect characteristic for paroxysmal nocturnal hemoglobinuria in patients with aplastic anemia. Author(s): Schubert J, Vogt HG, Zielinska-Skowronek M, Freund M, Kaltwasser JP, Hoelzer D, Schmidt RE. Source: Blood. 1994 April 15; 83(8): 2323-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8161800&dopt=Abstract
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Diagnosis and management of aplastic anemia and myelodysplastic syndrome. Author(s): Paquette RL. Source: Oncology (Huntingt). 2002 September; 16(9 Suppl 10): 153-61. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12380966&dopt=Abstract
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Diagnostic and therapeutic thoracic surgery in leukemia and severe aplastic anemia. Author(s): Habicht JM, Gratwohl A, Tamm M, Drewe J, Proske M, Stulz P. Source: The Journal of Thoracic and Cardiovascular Surgery. 1997 June; 113(6): 982-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9202677&dopt=Abstract
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Disappearance of cytogenetic abnormalities induced by cyclosporine therapy in a case of aplastic anemia. Author(s): Takeshima M, Mochizuki Y, Yoshida T, Takamatsu H, Okumura H. Source: Blood. 1998 February 1; 91(3): 1094-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9457049&dopt=Abstract
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Distinct clinical outcomes for cytogenetic abnormalities evolving from aplastic anemia. Author(s): Maciejewski JP, Risitano A, Sloand EM, Nunez O, Young NS. Source: Blood. 2002 May 1; 99(9): 3129-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11964274&dopt=Abstract
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Donor-cell myelodysplastic syndrome developing 13 years after marrow grafting for aplastic anemia. Author(s): Haltrich I, Muller J, Szabo J, Kovacs G, Koos R, Poros A, Dobos M, Fekete G. Source: Cancer Genetics and Cytogenetics. 2003 April 15; 142(2): 124-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12699888&dopt=Abstract
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Double bone marrow transplantation for severe aplastic anemia after orthotopic liver transplantation: implications for clinical management and immune tolerance. Author(s): Stachel D, Schmid I, Lang T, Haas RJ, Otte JB. Source: Transplant International : Official Journal of the European Society for Organ Transplantation. 2002 January; 15(1): 39-44. Epub 2002 January 18. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11875612&dopt=Abstract
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Durable treatment-free remission after high-dose cyclophosphamide therapy for previously untreated severe aplastic anemia. Author(s): Brodsky RA, Sensenbrenner LL, Smith BD, Dorr D, Seaman PJ, Lee SM, Karp JE, Brodsky I, Jones RJ. Source: Annals of Internal Medicine. 2001 October 2; 135(7): 477-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11578150&dopt=Abstract
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Early ticlopidine-induced hepatic dysfunction, dermatitis and irreversible aplastic anemia after coronary artery stenting. Author(s): Ceylan C, Kirimli O, Akarsu M, Undar B, Guneri S. Source: American Journal of Hematology. 1998 November; 59(3): 260. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9798669&dopt=Abstract
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Early trilineage recovery by granulocyte colony-stimulating factor in a patient with aplastic anemia. Author(s): Hashimoto K, Kanakura Y, Yagura H, Mitsui H, Ogawa M, Horikawa Y, Nishiura T, Kanayama Y, Matsuzawa Y. Source: Acta Haematologica. 1995; 93(2-4): 110-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7543718&dopt=Abstract
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Ecthyma gangrenosum associated with aplastic anemia. Author(s): Chun WH, Kim YK, Kim LS, Ko YW, Bang D. Source: Journal of Korean Medical Science. 1996 February; 11(1): 64-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8703372&dopt=Abstract
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Effect of androgen therapy and anemia on serum erythropoietin levels in patients with aplastic anemia and myelodysplastic syndromes. Author(s): Piedras J, Hernandez G, Lopez-Karpovitch X. Source: American Journal of Hematology. 1998 February; 57(2): 113-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9462542&dopt=Abstract
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Effect of flt3 ligand on in vitro growth and expansion of colony-forming bone marrow cells from patients with aplastic anemia. Author(s): Wodnar-Filipowicz A, Chklovskaia E, Manz CY, Lyman SD, Nissen C. Source: Experimental Hematology. 1997 July; 25(7): 573-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9216732&dopt=Abstract
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Effect of interleukin 10 on the hematopoietic progenitor cells from patients with aplastic anemia. Author(s): Asano Y, Shibata S, Kobayashi S, Okamura S, Niho Y. Source: Stem Cells (Dayton, Ohio). 1999; 17(3): 147-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10342557&dopt=Abstract
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Effect of mixed chimerism on graft-versus-host disease, disease recurrence and survival after HLA-identical marrow transplantation for aplastic anemia or chronic myelogenous leukemia. Author(s): Huss R, Deeg HJ, Gooley T, Bryant E, Leisenring W, Clift R, Buckner CD, Martin P, Storb R, Appelbaum FR. Source: Bone Marrow Transplantation. 1996 October; 18(4): 767-76. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8899193&dopt=Abstract
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Effect of recombinant human granulocyte macrophage-colony stimulating factor in long-term marrow cultures from patients with aplastic anemia. Author(s): Martinez-Jaramillo G, Gomez-Morales E, Mayani H. Source: American Journal of Hematology. 1999 June; 61(2): 107-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10367789&dopt=Abstract
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Effectiveness of immunosuppressive therapy in older patients with aplastic anemia. European Group for Blood and Marrow Transplantation Severe Aplastic Anaemia Working Party. Author(s): Tichelli A, Socie G, Henry-Amar M, Marsh J, Passweg J, Schrezenmeier H, McCann S, Hows J, Ljungman P, Marin P, Raghavachar A, Locasciulli A, Gratwohl A, Bacigalupo A. Source: Annals of Internal Medicine. 1999 February 2; 130(3): 193-201. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10049197&dopt=Abstract
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Elevated levels of circulating procoagulant microparticles in patients with paroxysmal nocturnal hemoglobinuria and aplastic anemia. Author(s): Hugel B, Socie G, Vu T, Toti F, Gluckman E, Freyssinet JM, Scrobohaci ML. Source: Blood. 1999 May 15; 93(10): 3451-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10233897&dopt=Abstract
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Emphysematous gastritis and severe aplastic anemia. Author(s): Gutierrez O, Cantalapiedra A, Tabuyo MI, Del Villar R, Penarrubia MJ, Sales R, Garcia-Frade LJ. Source: The Hematology Journal : the Official Journal of the European Haematology Association / Eha. 2003; 4(1): 82-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12692527&dopt=Abstract
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Engraftment of allogeneic mesenchymal stem cells in the bone marrow of a patient with severe idiopathic aplastic anemia improves stroma. Author(s): Fouillard L, Bensidhoum M, Bories D, Bonte H, Lopez M, Moseley AM, Smith A, Lesage S, Beaujean F, Thierry D, Gourmelon P, Najman A, Gorin NC. Source: Leukemia : Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2003 February; 17(2): 474-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12592355&dopt=Abstract
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Enhanced response to basiliximab in a patient with aplastic anemia after treatment with standard immunosuppression. Author(s): Berman JA, Patel K, Caro J. Source: American Journal of Hematology. 2002 September; 71(1): 64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12221685&dopt=Abstract
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Epidemiology of aplastic anemia in Thailand. Thai Aplastic Anemia Study Group. Author(s): Issaragrisil S. Source: International Journal of Hematology. 1999 October; 70(3): 137-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10561905&dopt=Abstract
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Erythropoietin therapy for aplastic anemia. Author(s): Yoshida Y. Source: Intern Med. 1998 March; 37(3): 235. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9617855&dopt=Abstract
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Evaluation of case reports of aplastic anemia among patients treated with felbamate. Author(s): Kaufman DW, Kelly JP, Anderson T, Harmon DC, Shapiro S. Source: Epilepsia. 1997 December; 38(12): 1265-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9578520&dopt=Abstract
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Evaluation of immunoglobulin G and its subclasses in aplastic anemia. Author(s): Yagi T, Hasegawa M, Kageyama T, Teshima H, Fujii S, Tatsumi N. Source: Osaka City Med J. 2001 December; 47(2): 105-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11906122&dopt=Abstract
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Evolution of severe aplastic anemia to myelodysplasia with monosomy 7 following granulocyte colony-stimulating factor, erythropoietin and high-dose methylprednisolone combination therapy. Author(s): Ohsaka A, Sugahara Y, Imai Y, Kikuchi M. Source: Intern Med. 1995 September; 34(9): 892-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8580564&dopt=Abstract
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Excellent long-term survival after allogeneic marrow transplantation in patients with severe aplastic anemia. Author(s): Reiter E, Keil F, Brugger S, Kalhs P, Rabitsch W, Hinterberger W, Fischer G, Rosenmayr A, Haas O, Volc B, Lechner K, Greinix HT. Source: Bone Marrow Transplantation. 1997 June; 19(12): 1191-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9208112&dopt=Abstract
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Expansion of trisomy 8 and Sweet syndrome in a prolonged course of aplastic anemia. Author(s): Ohga S, Nomura A, Takada H, Terao H, Harada N, Hara T. Source: Journal of Pediatric Hematology/Oncology : Official Journal of the American Society of Pediatric Hematology/Oncology. 2002 January; 24(1): 64-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11902745&dopt=Abstract
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Factors predicting chronic graft-versus-host disease and survival after marrow transplantation for aplastic anemia. Author(s): Niederwieser D, Pepe M, Storb R, Witherspoon R, Longton G, Sullivan K. Source: Bone Marrow Transplantation. 1989 March; 4(2): 151-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2650784&dopt=Abstract
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Fanconi anemia: constitutional aplastic anemia. Author(s): Gordon-Smith EC, Rutherford TR. Source: Semin Hematol. 1991 April; 28(2): 104-12. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1876859&dopt=Abstract
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Fanconi aplastic anemia associated with beta-thalassemia trait. Author(s): Altay C, Gurgey A, Basak AN, Tadmouri GO, Schroeder-Kurt T. Source: American Journal of Hematology. 1996 July; 52(3): 239-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8756104&dopt=Abstract
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Fanconi's constitutional aplastic anemia. Author(s): Bhatnagar S, Chandra J, Narayan S, Jain V. Source: Indian Pediatrics. 1999 July; 36(7): 722-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10740314&dopt=Abstract
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Fatal acute hepatic failure induced by danazol in a patient with endometriosis and aplastic anemia. Author(s): Hayashi T, Takahashi T, Minami T, Akaike J, Kasahara K, Adachi M, Hinoda Y, Takahashi S, Hirayama T, Imai K. Source: Journal of Gastroenterology. 2001 November; 36(11): 783-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11757752&dopt=Abstract
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Fatal aplastic anemia associated with hepatitis B viral infection. Author(s): McSweeney PA, Carter JM, Green GJ, Romeril KR. Source: The American Journal of Medicine. 1988 August; 85(2): 255-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3400703&dopt=Abstract
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Fatal aplastic anemia caused by Epstein-Barr virus infection after autologous bone marrow transplantation for non-Hodgkin malignant lymphoma. Author(s): Inoue H, Shinohara K, Nomiyama J, Oeda E. Source: Intern Med. 1994 May; 33(5): 303-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7949635&dopt=Abstract
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Fatal aplastic anemia during treatment with ketoconazole. Author(s): Duman D, Turhal NS, Duman DG. Source: The American Journal of Medicine. 2001 December 15; 111(9): 737. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11747860&dopt=Abstract
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Fatal aplastic anemia following topical administration of ophthalmic chloramphenicol. Author(s): Fraunfelder FT, Bagby GC Jr, Kelly DJ. Source: American Journal of Ophthalmology. 1982 March; 93(3): 356-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7072798&dopt=Abstract
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Fatal aplastic anemia in a patient treated with carbamazepine. Author(s): Franceschi M, Ciboddo G, Truci G, Borri A, Canal N. Source: Epilepsia. 1988 September-October; 29(5): 582-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3409843&dopt=Abstract
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Fatal disseminated infection due to Exserohilum rostratum in a patient with aplastic anemia: case report and review. Author(s): Aquino VM, Norvell JM, Krisher K, Mustafa MM. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 1995 January; 20(1): 176-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7727648&dopt=Abstract
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Fatal outcome of a patient with severe aplastic anemia after treatment with metenolone acetate. Author(s): Tsukamoto N, Uchiyama T, Takeuchi T, Sato S, Naruse T, Nakazato Y. Source: Annals of Hematology. 1993 July; 67(1): 41-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8334198&dopt=Abstract
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Fatal post-transplant lymphoproliferative disorder following allogeneic bone marrow transplantation for aplastic anemia. Author(s): Rudzki Z, Werda L, Piatkowska-Jakubas B, Mensah P, Zazula M, Bialas M, Skotnicki AB, Stachura J. Source: Pol J Pathol. 2002; 53(1): 35-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12014224&dopt=Abstract
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F-blast is a useful marker for differentiating hypocellular refractory anemia from aplastic anemia. Author(s): Choi JW, Fujino M, Ito M. Source: International Journal of Hematology. 2002 April; 75(3): 257-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11999352&dopt=Abstract
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First report of a B cell lymphoproliferative disorder arising in a patient treated with immune suppressants for severe aplastic anemia. Author(s): Dorr V, Doolittle G, Woodroof J. Source: American Journal of Hematology. 1996 June; 52(2): 108-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8638630&dopt=Abstract
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Flowcytometric detection of PNH defect in Indian patients with aplastic anemia and myelodysplastic syndromes. Author(s): Varma N, Garewal G, Varma S, Vohra H. Source: American Journal of Hematology. 2000 November; 65(3): 264-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11074548&dopt=Abstract
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Flt3 ligand level reflects hematopoietic progenitor cell function in aplastic anemia and chemotherapy-induced bone marrow aplasia. Author(s): Wodnar-Filipowicz A, Lyman SD, Gratwohl A, Tichelli A, Speck B, Nissen C. Source: Blood. 1996 December 15; 88(12): 4493-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8977241&dopt=Abstract
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Fulminant hepatic failure following bone marrow transplantation for hepatitisassociated aplastic anemia. Author(s): Van Dam J, Farraye FA, Gale RP, Zeldis JB. Source: Bone Marrow Transplantation. 1990 January; 5(1): 57-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2105142&dopt=Abstract
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Fulminant hepatitis in aplastic anemia: hepatitis G or ALG? Author(s): Akan H, Konuk N, Fenkci S, Dilek I, Idilman R, Tuncer S. Source: Bone Marrow Transplantation. 1998 March; 21(5): 533. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9535049&dopt=Abstract
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Fusarium infections in patients with severe aplastic anemia: review and implications for management. Author(s): Girmenia C, Iori AP, Boecklin F, Torosantucci A, Chiani P, De Fabritiis P, Taglietti F, Cassone A, Martino P. Source: Haematologica. 1999 February; 84(2): 114-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10091408&dopt=Abstract
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Gamma interferon and aplastic anemia. Author(s): Young NS. Source: Blood. 1987 July; 70(1): 337-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3109525&dopt=Abstract
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gamma-Interferon gene expression in the bone marrow of patients with aplastic anemia. Author(s): Nistico A, Young NS. Source: Annals of Internal Medicine. 1994 March 15; 120(6): 463-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8311369&dopt=Abstract
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Gamma-interferon in aplastic anemia: inability to detect significant levels in sera or demonstrate hematopoietic suppressing activity. Author(s): Torok-Storb B, Johnson GG, Bowden R, Storb R. Source: Blood. 1987 February; 69(2): 629-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3099863&dopt=Abstract
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Gene expression profiling in CD34 cells to identify differences between aplastic anemia patients and healthy volunteers. Author(s): Zeng W, Chen G, Kajigaya S, Nunez O, Charrow A, Billings EM, Young NS. Source: Blood. 2004 January 1; 103(1): 325-32. Epub 2003 September 22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14504100&dopt=Abstract
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Genetic defects underlying paroxysmal nocturnal hemoglobinuria that arises out of aplastic anemia. Author(s): Nagarajan S, Brodsky RA, Young NS, Medof ME. Source: Blood. 1995 December 15; 86(12): 4656-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8541558&dopt=Abstract
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Gingival swelling as a manifestation of aplastic anemia. Author(s): Luker J, Scully C, Oakhill A. Source: Oral Surg Oral Med Oral Pathol. 1991 January; 71(1): 55-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1994323&dopt=Abstract
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Glucose intolerance, hyperinsulinemia and insulin resistance in aplastic anemia. Author(s): Issaragrisil S, Vannasaeng S, Piankijagum A. Source: Metabolism: Clinical and Experimental. 1989 March; 38(3): 204-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2918840&dopt=Abstract
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Gold induced aplastic anemia. Author(s): Adachi JD, Bensen WG, Ali M, Singal DP, Taylor S, Whitman L. Source: The Journal of Rheumatology. 1985 October; 12(5): 1011-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4087250&dopt=Abstract
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Gold induced aplastic anemia. Complete response to corticosteroids, plasmapheresis, and N-acetylcysteine infusion. Author(s): Hansen RM, Csuka ME, McCarty DJ, Saryan LA. Source: The Journal of Rheumatology. 1985 August; 12(4): 794-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4057204&dopt=Abstract
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Gold induced severe aplastic anemia: medullary autologous reconstitution after immunosuppression. Author(s): Salvarani C, Iori I, Prandi S, Rossi F, Filippi G. Source: The Journal of Rheumatology. 1985 April; 12(2): 387. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4032417&dopt=Abstract
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Gold-induced aplastic anemia. Author(s): Williame LM, Joos R, Proot F, Immesoete C. Source: Clinical Rheumatology. 1987 December; 6(4): 600-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3449312&dopt=Abstract
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Graft failure after an umbilical cord blood transplant in a patient with severe aplastic anemia. Author(s): Cancelas JA, Querol S. Source: Blood. 1995 November 1; 86(9): 3610. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7579471&dopt=Abstract
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Graft failure following bone marrow transplantation for severe aplastic anemia: risk factors and treatment results. Author(s): Champlin RE, Horowitz MM, van Bekkum DW, Camitta BM, Elfenbein GE, Gale RP, Gluckman E, Good RA, Rimm AA, Rozman C, et al. Source: Blood. 1989 February; 73(2): 606-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2644980&dopt=Abstract
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Graft-versus-host disease prophylaxis with methotrexate/cyclosporine in children with severe aplastic anemia treated with cyclophosphamide and HLA-identical marrow grafts. Author(s): Storb R, Sanders JE, Pepe M, Anasetti C, Appelbaum FR, Buckner CD, Deeg HJ, Doney K, Hansen J, Martin P, et al. Source: Blood. 1991 August 15; 78(4): 1144-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1868246&dopt=Abstract
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Granulocyte colony-stimulating factor (G-CSF) dependent hematopoiesis with monosomy 7 in a patient with severe aplastic anemia after ATG/CsA/G-CSF combined therapy. Author(s): Nishimura M, Yamada T, Andoh T, Tao T, Emoto M, Ohji T, Matsuda K, Kameda N, Satoh Y, Matsutani A, Azuno Y, Oka Y. Source: International Journal of Hematology. 1998 August; 68(2): 203-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9803678&dopt=Abstract
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Granulocyte colony-stimulating factor-supported combined immunosuppressive therapy (antilymphocyte globulin, cyclosporine, and methylprednisolone) in patients with aplastic anemia: tolerability, efficacy, and changes in the progenitor cell compartment. Author(s): Meidlinger P, Knobl P, Jager U, Gisslinger H, Pabinger I, Weltermann A, Lechner K, Geissler K. Source: Annals of Hematology. 1999 July; 78(7): 299-304. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10466441&dopt=Abstract
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Granulocyte-macrophage colony-stimulating factor in the sera of patients with aplastic anemia. Author(s): Schrezenmeier H, Raghavachar A, Heimpel H. Source: Clin Investig. 1993 February; 71(2): 102-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8461622&dopt=Abstract
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Granulopoietic effects of colony-stimulating factor obtained from urine of patients with aplastic anemia on normal and cyclophosphamide-treated mice. Author(s): Ishida Y, Azuno Y, Tanaka H, Tanaka M, Miyamura S, Kaneko T, Matsumoto N. Source: Acta Haematologica. 1988; 80(1): 1-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3135686&dopt=Abstract
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Growth in children after bone marrow transplantation for advanced neuroblastoma compared with growth after transplantation for leukemia or aplastic anemia. Author(s): Willi SM, Cooke K, Goldwein J, August CS, Olshan JS, Moshang T Jr. Source: The Journal of Pediatrics. 1992 May; 120(5): 726-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1578307&dopt=Abstract
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Guidelines for the treatment of severe aplastic anemia. Working Party on Severe Aplastic Anemia (WPSAA) of the European Group of Bone Marrow Transplantation (EBMT). Author(s): Bacigalupo A. Source: Haematologica. 1994 September-October; 79(5): 438-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7843630&dopt=Abstract
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Hematopoietic cell destruction by immune mechanisms in acquired aplastic anemia. Author(s): Young NS. Source: Semin Hematol. 2000 January; 37(1): 3-14. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10676907&dopt=Abstract
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Hematopoietic growth factors and marrow stroma in aplastic anemia. Author(s): Koijima S. Source: International Journal of Hematology. 1998 July; 68(1): 19-28. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9713165&dopt=Abstract
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Hematopoietic growth factors for the treatment of aplastic anemia. Author(s): Kumar M, Alter BP. Source: Current Opinion in Hematology. 1998 May; 5(3): 226-34. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9664165&dopt=Abstract
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Hematopoietic growth factors in the pathogenesis and for the treatment of aplastic anemia. Author(s): Marsh JC. Source: Semin Hematol. 2000 January; 37(1): 81-90. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10676913&dopt=Abstract
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Hematopoietic stem cell transplantation for high-risk adult patients with severe aplastic anemia; reduction of graft failure by enhancing stem cell dose. Author(s): Min CK, Kim DW, Lee JW, Han CW, Min WS, Kim CC. Source: Haematologica. 2001 March; 86(3): 303-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11255278&dopt=Abstract
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Hematopoietic stem cell transplantation for severe aplastic anemia--experience of an institute in Taiwan. Author(s): Bai LY, Chiou TJ, Liu JH, Yen CC, Wang WS, Yan MH, Hsiao LT, Chao TC, Chen PM. Source: Annals of Hematology. 2004 January; 83(1): 38-43. Epub 2003 October 03. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14530878&dopt=Abstract
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Hepatitis B virus-associated aplastic anemia followed by myelodysplastic syndrome. Author(s): Adachi Y, Yasui H, Yuasa H, Ishi Y, Imai K, Kato Y. Source: The American Journal of Medicine. 2002 March; 112(4): 330-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11893381&dopt=Abstract
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Hepatitis C virus infection in acquired aplastic anemia. Author(s): Paquette RL, Kuramoto K, Tran L, Sopher G, Nimer SD, Zeldis JB. Source: American Journal of Hematology. 1998 June; 58(2): 122-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9625579&dopt=Abstract
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Hepatitis-associated aplastic anemia and acute parvovirus B19 infection: a report of two cases and a review of the literature. Author(s): Pardi DS, Romero Y, Mertz LE, Douglas DD. Source: The American Journal of Gastroenterology. 1998 March; 93(3): 468-70. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9517662&dopt=Abstract
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Hepatitis-associated aplastic anemia and transfusion-transmitted virus infection. Author(s): Miyamoto M, Takahashi H, Sakata I, Adachi Y. Source: Intern Med. 2000 December; 39(12): 1068-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11197792&dopt=Abstract
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Hepatoma associated with androgen therapy for aplastic anemia. Author(s): Meadows AT, Naiman JL, Valdes-Dapena M. Source: The Journal of Pediatrics. 1974 January; 84(1): 109-10. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12119927&dopt=Abstract
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High incidence of transiently appearing complement-sensitive bone marrow precursor cells in patients with severe aplastic anemia--A possible role of high endogenous IL-2 in their suppression. Author(s): Nissen C, Tichelli A, Gratwohl A, Warthmann C, Moser Y, dalle Carbonare V, Sendelov S, Chklovskaia E, Jansen W, Wodnar-Filipowicz A, Sadallah S, Speck B. Source: Acta Haematologica. 1999; 101(4): 165-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10436296&dopt=Abstract
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High-dose cyclophosphamide for aplastic anemia and autoimmunity. Author(s): Brodsky RA. Source: Current Opinion in Oncology. 2002 March; 14(2): 143-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11880702&dopt=Abstract
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High-dose cyclophosphamide for treatment of aplastic anemia. Author(s): Young NS, Tisdale JF. Source: Annals of Internal Medicine. 2002 September 17; 137(6): 549-50; Author Reply 549-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12230370&dopt=Abstract
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High-dose cyclophosphamide in the treatment of severe aplastic anemia in children. Author(s): Jaime-Perez JC, Gonzalez-Llano O, Gomez-Almaguer D. Source: American Journal of Hematology. 2001 January; 66(1): 71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11426504&dopt=Abstract
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HLA-DR15 (DR2) is overrepresented in myelodysplastic syndrome and aplastic anemia and predicts a response to immunosuppression in myelodysplastic syndrome. Author(s): Saunthararajah Y, Nakamura R, Nam JM, Robyn J, Loberiza F, Maciejewski JP, Simonis T, Molldrem J, Young NS, Barrett AJ. Source: Blood. 2002 September 1; 100(5): 1570-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12176872&dopt=Abstract
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HLA-DR4-Ala74 beta is associated with risk and poor outcome of severe aplastic anemia. Author(s): Kapustin SI, Popova TI, Lyshchov AA, Imyanitov EN, Blinov MN, Abdulkadyrov KM. Source: Annals of Hematology. 2001 February; 80(2): 66-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11261326&dopt=Abstract
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HLA-DRB1*15 and pediatric aplastic anemia. Author(s): Oguz FS, Yalman N, Diler AS, Oguz R, Anak S, Dorak MT. Source: Haematologica. 2002 July; 87(7): 772-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12091130&dopt=Abstract
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Hospitalizations for aplastic anemia and agranulocytosis in Saskatchewan: incidence and associations with antecedent prescription drug use. Author(s): Rawson NS, Harding SR, Malcolm E, Lueck L. Source: Journal of Clinical Epidemiology. 1998 December; 51(12): 1343-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10086829&dopt=Abstract
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Human mesenchymal stem cells are not of donor origin in patients with severe aplastic anemia who underwent sex-mismatched allogeneic bone marrow transplant. Author(s): Stute N, Fehse B, Schroder J, Arps S, Adamietz P, Held KR, Zander AR. Source: Journal of Hematotherapy & Stem Cell Research. 2002 December; 11(6): 977-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12590713&dopt=Abstract
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Immune pathophysiology of aplastic anemia. Author(s): Maciejewski JP, Risitano A, Kook H, Zeng W, Chen G, Young NS. Source: International Journal of Hematology. 2002 August; 76 Suppl 1: 207-14. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12430855&dopt=Abstract
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Immunosuppressive therapy using antithymocyte globulin, cyclosporine, and danazol with or without human granulocyte colony-stimulating factor in children with acquired aplastic anemia. Author(s): Kojima S, Hibi S, Kosaka Y, Yamamoto M, Tsuchida M, Mugishima H, Sugita K, Yabe H, Ohara A, Tsukimoto I. Source: Blood. 2000 September 15; 96(6): 2049-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10979946&dopt=Abstract
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Immunosuppressive treatment of acquired aplastic anemia and immune-mediated bone marrow failure syndromes. Author(s): Young NS. Source: International Journal of Hematology. 2002 February; 75(2): 129-40. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11939258&dopt=Abstract
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Immunotherapy: an alternative for bone marrow transplantation (BMT) in severe acquired aplastic anemia? Author(s): Thomas M, Pavithran K, Potti N. Source: J Assoc Physicians India. 1997 April; 45(4): 257-60. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12521078&dopt=Abstract
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In aplastic anemia progenitor cells have a reduced sensitivity to the effects of growth factors. Author(s): Novitzky N, Jacobs P. Source: European Journal of Haematology. 1999 September; 63(3): 141-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10485268&dopt=Abstract
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Increased cytotoxic T cells with effector phenotype in aplastic anemia and myelodysplasia. Author(s): Kook H, Zeng W, Guibin C, Kirby M, Young NS, Maciejewski JP. Source: Experimental Hematology. 2001 November; 29(11): 1270-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11698122&dopt=Abstract
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Increased frequencies of glutathione S-transferase (GSTM1 and GSTT1) gene deletions in Korean patients with acquired aplastic anemia. Author(s): Lee KA, Kim SH, Woo HY, Hong YJ, Cho HC. Source: Blood. 2001 December 1; 98(12): 3483-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11719393&dopt=Abstract
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Increased frequency of HLA-DR2 in patients with paroxysmal nocturnal hemoglobinuria and the PNH/aplastic anemia syndrome. Author(s): Maciejewski JP, Follmann D, Nakamura R, Saunthararajah Y, Rivera CE, Simonis T, Brown KE, Barrett JA, Young NS. Source: Blood. 2001 December 15; 98(13): 3513-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11739151&dopt=Abstract
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Increased inducible nitric oxide synthase expression and nitric oxide concentration in patients with aplastic anemia. Author(s): Chung IJ, Lee JJ, Nam CE, Kim HN, Kim YK, Park MR, Cho SH, Kim HJ. Source: Annals of Hematology. 2003 February; 82(2): 104-8. Epub 2003 January 30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12601489&dopt=Abstract
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Induction of apoptosis by remoxipride metabolites in HL60 and CD34+/CD19- human bone marrow progenitor cells: potential relevance to remoxipride-induced aplastic anemia. Author(s): McGuinness SM, Johansson R, Lundstrom J, Ross D. Source: Chemico-Biological Interactions. 1999 August 1; 121(3): 253-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10462057&dopt=Abstract
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Induction of apoptosis in CD34+ cells by sera from patients with aplastic anemia. Author(s): Liu H, Mihara K, Kimura A, Tanaka K, Kamada N. Source: Hiroshima J Med Sci. 1999 June; 48(2): 57-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10434475&dopt=Abstract
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Induction of apoptosis of peripheral blood mononuclear cells by antithymocyte globulin (ATG) in aplastic anemia: an in vivo and in vitro study. Author(s): Dubey S, Srivastava A, Nityanand S. Source: Annals of Hematology. 2002 May; 81(5): 249-53. Epub 2002 April 27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12029533&dopt=Abstract
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Infections in patients with aplastic anemia: experience at a tertiary care cancer center. Author(s): Torres HA, Bodey GP, Rolston KV, Kantarjian HM, Raad II, Kontoyiannis DP. Source: Cancer. 2003 July 1; 98(1): 86-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12833460&dopt=Abstract
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Instability of chromosome 7 in colony forming cells of patients with aplastic anemia. Author(s): Ueda H, Tashiro S, Kojima S, Tanaka K, Eguchi M, Ueda K, Kamada N. Source: International Journal of Hematology. 1999 July; 70(1): 13-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10446489&dopt=Abstract
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Interleukin-10 inhibits in vitro hematopoietic suppression and production of interferon-gamma and tumor necrosis factor-alpha by peripheral blood mononuclear cells from patients with aplastic anemia. Author(s): Geissler K, Kabrna E, Kollars M, Ohler L, Berer A, Burgmann H, Winkler S, Willheim M, Hinterberger W, Lechner K. Source: The Hematology Journal : the Official Journal of the European Haematology Association / Eha. 2002; 3(4): 206-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12189567&dopt=Abstract
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Intracellular interferon-gamma in circulating and marrow T cells detected by flow cytometry and the response to immunosuppressive therapy in patients with aplastic anemia. Author(s): Sloand E, Kim S, Maciejewski JP, Tisdale J, Follmann D, Young NS. Source: Blood. 2002 August 15; 100(4): 1185-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12149196&dopt=Abstract
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Invasive cerebral aspergillosis in a patient with aplastic anemia. Response to liposomal amphotericin and surgery. Author(s): Rodriguez DL, Lopez CA, Cobos EB, Blanco AJ, Fernandez AF, Araujo LF. Source: Haematologica. 1999 August; 84(8): 758-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10457420&dopt=Abstract
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Invasive subglottal aspergillosis in a patient with severe aplastic anemia: a case report. Author(s): Nagasawa M, Itoh S, Tomizawa D, Kajiwara M, Sugimoto T, Kumagai J. Source: The Journal of Infection. 2002 April; 44(3): 198-201. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12099752&dopt=Abstract
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Investigation of SEN virus infection in patients with cryptogenic acute liver failure, hepatitis-associated aplastic anemia, or acute and chronic non-A-E hepatitis. Author(s): Umemura T, Tanaka E, Ostapowicz G, Brown KE, Heringlake S, Tassopoulos NC, Wang RY, Yeo AE, Shih JW, Orii K, Young NS, Hatzakis A, Manns MP, Lee WM, Kiyosawa K, Alter HJ. Source: The Journal of Infectious Diseases. 2003 November 15; 188(10): 1545-52. Epub 2003 October 28. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14624381&dopt=Abstract
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Is mitomycin C-induced chromosome breakage always required for the diagnosis of Fanconi aplastic anemia? Author(s): Ozsoylu S. Source: Pediatric Hematology and Oncology. 1999 May-June; 16(3): 271, 273. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10326228&dopt=Abstract
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Kaposi's Sarcoma of the intestine in an HIV-negative patient associated with immunosuppressive therapy for severe aplastic anemia. Author(s): Abhyankar SH, Burns RG, Godder KT, Pati AR, Henslee-Downey PJ. Source: Journal of Pediatric Hematology/Oncology : Official Journal of the American Society of Pediatric Hematology/Oncology. 1997 January-February; 19(1): 86-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9065726&dopt=Abstract
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Karyotype and in vitro-response to GM-CSF. Analysis of bone marrow cultures in leukemia, myelodysplasia and aplastic anemia. Author(s): Haase D, Fonatsch C. Source: Blut. 1990 March; 60(3): 192-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2180500&dopt=Abstract
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Ki-S1 and proliferating cell nuclear antigen expression of bone marrow macrophages. Immunohistochemical and morphometric study including reactive (inflammatory) myelitis, secondary aplastic anemia, AIDS, myelodysplastic syndromes and primary (idiopathic) osteomyelofibrosis. Author(s): Titius BR, Thiele J, Schaefer H, Kreipe H, Fischer R. Source: Acta Haematologica. 1994; 91(3): 144-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7522384&dopt=Abstract
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Lack of known hepatitis virus in hepatitis-associated aplastic anemia and outcome after bone marrow transplantation. Author(s): Safadi R, Or R, Ilan Y, Naparstek E, Nagler A, Klein A, Ketzinel-Gilaad M, Ergunay K, Danon D, Shouval D, Galun E. Source: Bone Marrow Transplantation. 2001 January; 27(2): 183-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11281388&dopt=Abstract
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Late clonal complications in older patients receiving immunosuppressive therapy for aplastic anemia. Author(s): Kami M, Machida U, Hirai H. Source: Annals of Internal Medicine. 1999 October 19; 131(8): 633-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10523237&dopt=Abstract
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Late clonal complications in severe aplastic anemia. Author(s): Tichelli A, Gratwohl A, Nissen C, Speck B. Source: Leukemia & Lymphoma. 1994 January; 12(3-4): 167-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8167549&dopt=Abstract
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Late clonal diseases of treated aplastic anemia. Author(s): Socie G, Rosenfeld S, Frickhofen N, Gluckman E, Tichelli A. Source: Semin Hematol. 2000 January; 37(1): 91-101. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10676914&dopt=Abstract
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Late complications following treatment for severe aplastic anemia (SAA) with highdose cyclophosphamide (Cy): follow-up of a randomized trial. Author(s): Tisdale JF, Maciejewski JP, Nunez O, Rosenfeld SJ, Young NS. Source: Blood. 2002 December 15; 100(13): 4668-70. Epub 2002 June 28. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12393567&dopt=Abstract
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Late graft failure 8 years after first bone marrow transplantation for severe acquired aplastic anemia. Author(s): Dufour C, Dallorso S, Casarino L, Corcione A, Pistoia V, Bacigalupo A, Morreale G, Dini G. Source: Bone Marrow Transplantation. 1999 April; 23(7): 743-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10218856&dopt=Abstract
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Late graft rejection following allogeneic bone marrow transplantation in aplastic anemia. Author(s): Rodriguez V, Khan SP. Source: Transplantation Proceedings. 2002 June; 34(4): 1307-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12072347&dopt=Abstract
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Limited heterogeneity of T cell receptor BV usage in aplastic anemia. Author(s): Zeng W, Maciejewski JP, Chen G, Young NS. Source: The Journal of Clinical Investigation. 2001 September; 108(5): 765-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11544283&dopt=Abstract
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Long-term follow-up of a randomized trial of graft-versus-host disease prevention by methotrexate/cyclosporine versus methotrexate alone in patients given marrow grafts for severe aplastic anemia. Author(s): Storb R, Leisenring W, Deeg HJ, Anasetti C, Appelbaum F, Bensinger W, Buckner CD, Clift R, Doney K, Hansen J, et al. Source: Blood. 1994 May 1; 83(9): 2749-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8167353&dopt=Abstract
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Long-term follow-up of allogeneic stem cell transplantation in patients with severe aplastic anemia after conditioning with cyclophosphamide plus antithymocyte globulin. Author(s): Kroger N, Zabelina T, Renges H, Kruger W, Kordes U, Rischewski J, Schrum J, Horstmann M, Ayuk F, Erttmann R, Kabisch H, Zander AR. Source: Annals of Hematology. 2002 November; 81(11): 627-31. Epub 2002 November 09. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12454700&dopt=Abstract
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Long-term follow-up of patients with aplastic anemia and refractory anemia responding to combination therapy with recombinant human granulocyte colonystimulating factor and erythropoietin. Author(s): Matsuda A, Kishimoto K, Yoshida K, Yagasaki F, Ito Y, Sakata T, Kawai N, Ino H, Hirashima K, Bessho M. Source: International Journal of Hematology. 2002 October; 76(3): 244-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12416735&dopt=Abstract
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Long-term interleukin-3 and intensive immunosuppression in the treatment of aplastic anemia. Author(s): Raghavachar A, Ganser A, Freund M, Heimpel H, Herrmann F, Schrezenmeier H. Source: Cytokines Mol Ther. 1996 December; 2(4): 215-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9384707&dopt=Abstract
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Long-term outcome after marrow transplantation for severe aplastic anemia. Author(s): Deeg HJ, Leisenring W, Storb R, Nims J, Flowers ME, Witherspoon RP, Sanders J, Sullivan KM. Source: Blood. 1998 May 15; 91(10): 3637-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9572999&dopt=Abstract
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Long-term outcome of 25 children and adolescents with severe aplastic anemia treated with antithymocyte globulin. Author(s): de-Medeiros CR, Ribeiro RC, Bittencourt MA, Zanis-Neto J, Pasquini R. Source: Brazilian Journal of Medical and Biological Research = Revista Brasileira De Pesquisas Medicas E Biologicas / Sociedade Brasileira De Biofisica. [et Al.]. 2000 May; 33(5): 553-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10775887&dopt=Abstract
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Long-term outcome of aplastic anemia in adults treated with antithymocyte globulin: comparison with bone marrow transplantation. Author(s): Paquette RL, Tebyani N, Frane M, Ireland P, Ho WG, Champlin RE, Nimer SD. Source: Blood. 1995 January 1; 85(1): 283-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7803802&dopt=Abstract
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Long-term production of pre-existing alloantibodies to E and c after allogenic BMT in a patient with aplastic anemia resulting in delayed hemolytic anemia. Author(s): Izumi N, Fuse I, Furukawa T, Uesugi Y, Tsuchiyama J, Toba K, Togashi K, Yamada K, Ohtake S, Saitoh Y, Yanagisawa N, Aizawa Y. Source: Transfusion. 2003 February; 43(2): 241-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12559020&dopt=Abstract
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Long-term results of the immunosuppressive treatment of patients with severe acquired aplastic anemia: a single institution study. Author(s): Ruiz-Arguelles GJ, Gomez-Rangel JD. Source: Acta Haematologica. 2003; 110(4): 184-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14663162&dopt=Abstract
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Low serum lipids suggest severe bone marrow failure in children with aplastic anemia. Author(s): Yokoyama M, Suto Y, Sato H, Arai K, Waga S, Kitazawa J, Maruyama H, Ito E. Source: Pediatrics International : Official Journal of the Japan Pediatric Society. 2000 December; 42(6): 613-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11192516&dopt=Abstract
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Lymphoproliferative disease of granular T lymphocytes presenting as aplastic anemia. Author(s): Go RS, Tefferi A, Li CY, Lust JA, Phyliky RL. Source: Blood. 2000 November 15; 96(10): 3644-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11071666&dopt=Abstract
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Lymphoproliferative disorder after immunosuppressive therapy for aplastic anemia. Author(s): Kumar S, Alperin JB, Kumar D, Pugh WC. Source: Blood. 1994 March 15; 83(6): 1706. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8123863&dopt=Abstract
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Magnetic resonance imaging of the bone marrow after bone marrow transplantation or immunosuppressive therapy in aplastic anemia. Author(s): Park JM, Jung HA, Kim DW, Lee JW, Kim CC, Hahn ST. Source: Journal of Korean Medical Science. 2001 December; 16(6): 725-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11748352&dopt=Abstract
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Management of patients with hematologic malignancies and aplastic anemia who are refractory to platelet transfusions. Author(s): Sandler SG. Source: Haematologia. 1998; 29(1): 1-11. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9704252&dopt=Abstract
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Marrow transplantation from unrelated donors for patients with severe aplastic anemia who have failed immunosuppressive therapy. Author(s): Deeg HJ, Seidel K, Casper J, Anasetti C, Davies S, Gajeweski JL, Territo M, Ramsay N, Harris RE, Catro-Malaspina H, Collins R, Champlin R, Schoch G, King R, Howe C. Source: Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation. 1999; 5(4): 243-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10465104&dopt=Abstract
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Marrow transplantation with or without donor buffy coat cells for 65 transfused aplastic anemia patients. Author(s): Storb R, Doney KC, Thomas ED, Appelbaum F, Buckner CD, Clift RA, Deeg HJ, Goodell BW, Hackman R, Hansen JA, Sanders J, Sullivan K, Weiden PL, Witherspoon RP. Source: Blood. 1982 February; 59(2): 236-46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7034811&dopt=Abstract
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Marrow transplants from unrelated donors for patients with aplastic anemia: minimum effective dose of total body irradiation. Author(s): Deeg HJ, Amylon ID, Harris RE, Collins R, Beatty PG, Feig S, Ramsay N, Territo M, Khan SP, Pamphilon D, Leis JF, Burdach S, Anasetti C, Hackman R, Storer B, Mueller B. Source: Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation. 2001; 7(4): 208-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11349807&dopt=Abstract
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Merkel cell carcinoma developing after antithymocyte globulin and cyclosporine therapy for aplastic anemia. Author(s): Takabayashi M, Sakai R, Sakamoto H, Iemoto Y, Kanamori H, Inayama Y, Ishigatsubo Y. Source: Anti-Cancer Drugs. 2003 March; 14(3): 251-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12634621&dopt=Abstract
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Mesalazine-associated severe aplastic anemia successfully treated with antithymocyte globulin, cyclosporine and granulocyte colony-stimulating factor. Author(s): Otsubo H, Kaito K, Sekita T, Shimada T, Kobayashi M, Hosoya T. Source: International Journal of Hematology. 1998 December; 68(4): 445-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9885444&dopt=Abstract
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Methimazole-induced aplastic anemia in third exposure: successful treatment with recombinant human granulocyte colony-stimulating factor. Author(s): Mezquita P, Luna V, Munoz-Torres M, Torres-Vela E, Lopez-Rodriguez F, Callejas JL, Escobar-Jimenez F. Source: Thyroid : Official Journal of the American Thyroid Association. 1998 September; 8(9): 791-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9777751&dopt=Abstract
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Modulation of macrocytosis in aplastic anemia. Author(s): Alter BP. Source: American Journal of Hematology. 1998 January; 57(1): 92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9423830&dopt=Abstract
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Multicenter prospective study of clonal complications in adult aplastic anemia patients following recombinant human granulocyte colony-stimulating factor (lenograstim) administration. Author(s): Bessho M, Hotta T, Ohyashiki K, Takahashi T, Mizoguchi H, Asano S, Ikeda Y, Sakurai M, Tojo A, Kizaki M, Iwanaga M, Tomonaga M, Hirashima K. Source: International Journal of Hematology. 2003 February; 77(2): 152-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12627850&dopt=Abstract
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Multiple hepatic adenomas caused by long-term administration of androgenic steroids for aplastic anemia in association with familial adenomatous polyposis. Author(s): Nakao A, Sakagami K, Nakata Y, Komazawa K, Amimoto T, Nakashima K, Isozaki H, Takakura N, Tanaka N. Source: Journal of Gastroenterology. 2000; 35(7): 557-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10905366&dopt=Abstract
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Mutations of the human telomerase RNA gene (TERC) in aplastic anemia and myelodysplastic syndrome. Author(s): Yamaguchi H, Baerlocher GM, Lansdorp PM, Chanock SJ, Nunez O, Sloand E, Young NS. Source: Blood. 2003 August 1; 102(3): 916-8. Epub 2003 April 03. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12676774&dopt=Abstract
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Myelodysplastic syndrome (MDS) with unbalanced t(1;7) after severe aplastic anemia (SAA) in childhood as a variant form of monosomy 7. Author(s): Kikuchi A, Ohashi H, Hanada R, Yamamoto K. Source: Leukemia : Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 1998 December; 12(12): 2036-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9844937&dopt=Abstract
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Myelodysplastic syndrome and aplastic anemia: distinct entities or diseases linked by a common pathophysiology? Author(s): Barrett J, Saunthararajah Y, Molldrem J. Source: Semin Hematol. 2000 January; 37(1): 15-29. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10676908&dopt=Abstract
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Myelodysplastic syndrome and aplastic anemia--diagnostic and conceptual uncertainties. Author(s): Barrett J. Source: Leukemia Research. 2000 July; 24(7): 595-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10867134&dopt=Abstract
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Myelodysplastic syndrome terminating in erythropoietic protoporphyria after 15 years of aplastic anemia. Author(s): Shirota T, Yamamoto H, Hayashi S, Fujimoto H, Harada Y, Hayashi T. Source: International Journal of Hematology. 2000 July; 72(1): 44-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10979208&dopt=Abstract
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Nasopharyngeal carcinoma, aplastic anemia, and various malignancies in a family: possible role of Epstein-Barr virus. Author(s): Schimke RN, Collins D, Cross D. Source: American Journal of Medical Genetics. 1987 May; 27(1): 195-202. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3037902&dopt=Abstract
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Neurological abnormalities in chronic benzene poisoning. A study of six patients with aplastic anemia and two with preleukemia. Author(s): Baslo A, Aksoy M. Source: Environmental Research. 1982 April; 27(2): 457-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7084168&dopt=Abstract
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Neutropenic colitis and aplastic anemia: a new association. Author(s): Mulholland MW, Delaney JP. Source: Annals of Surgery. 1983 January; 197(1): 84-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6848059&dopt=Abstract
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New approach of treatment of severe aplastic anemia. Cooperative Group on the Treatment of Aplastic Anemia. Author(s): Gluckman E, Bourdeau-Esperou H, Boogaerts M, Briere J, Navarro J, Leverger G, Leporrier M, Reiffers J, Janvier M, Michallet M, et al. Source: Bone Marrow Transplantation. 1991; 7 Suppl 2: 106-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1878666&dopt=Abstract
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New therapies for aplastic anemia. Author(s): Krantz SB. Source: The American Journal of the Medical Sciences. 1986 June; 291(6): 371-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3521274&dopt=Abstract
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Non-A non-B hepatitis induced aplastic anemia. Author(s): Pant A, Kale P, Harjai K, Shah M, Pathare AV. Source: Journal of Postgraduate Medicine. 1992 April-June; 38(2): 85-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1432838&dopt=Abstract
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Normal granulocyte function but impaired monocyte function in a patient with aplastic anemia. Author(s): Zabernigg A, Hilbe W, Reinisch N, Eisterer W, Thaler J, Spotl L, Konwalinka G. Source: Acta Haematologica. 1995; 94(2): 109-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7484011&dopt=Abstract
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Normal neurodevelopment in four young children treated with bone marrow transplantation for acute leukemia or aplastic anemia. Author(s): Kaleita TA, Shields WD, Tesler A, Feig SA. Source: Pediatrics. 1989 May; 83(5): 753-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2654868&dopt=Abstract
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Novel human erythrovirus associated with transient aplastic anemia. Author(s): Nguyen QT, Sifer C, Schneider V, Allaume X, Servant A, Bernaudin F, Auguste V, Garbarg-Chenon A. Source: Journal of Clinical Microbiology. 1999 August; 37(8): 2483-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10405389&dopt=Abstract
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N-RAS gene mutation in patients with aplastic anemia and aplastic anemia/ paroxysmal nocturnal hemoglobinuria during evolution to clonal disease. Author(s): Mortazavi Y, Tooze JA, Gordon-Smith EC, Rutherford TR. Source: Blood. 2000 January 15; 95(2): 646-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10627475&dopt=Abstract
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Ocular findings in aplastic anemia. Author(s): Mansour AM, Salti HI, Han DP, Khoury A, Friedman SM, Salem Z, Ibrahim K, Bazerbachi A, Saghir N. Source: Ophthalmologica. Journal International D'ophtalmologie. International Journal of Ophthalmology. Zeitschrift Fur Augenheilkunde. 2000; 214(6): 399-402. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11053999&dopt=Abstract
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Oligoclonal and polyclonal CD4 and CD8 lymphocytes in aplastic anemia and paroxysmal nocturnal hemoglobinuria measured by V beta CDR3 spectratyping and flow cytometry. Author(s): Risitano AM, Kook H, Zeng W, Chen G, Young NS, Maciejewski JP. Source: Blood. 2002 July 1; 100(1): 178-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12070025&dopt=Abstract
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Oral manifestations in patients with aplastic anemia. Author(s): Brennan MT, Sankar V, Baccaglini L, Pillemer SR, Kingman A, Nunez O, Young NS, Atkinson JC. Source: Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics. 2001 November; 92(5): 503-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11709685&dopt=Abstract
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Osteonecrosis of the hip in patients with aplastic anemia. Author(s): Park J, Jun J, Kim Y, Lee J, Kim C, Hahn S. Source: Journal of Korean Medical Science. 2002 December; 17(6): 806-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12483006&dopt=Abstract
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Outcome of 154 patients with severe aplastic anemia who received transplants from unrelated donors: the Japan Marrow Donor Program. Author(s): Kojima S, Matsuyama T, Kato S, Kigasawa H, Kobayashi R, Kikuta A, Sakamaki H, Ikuta K, Tsuchida M, Hoshi Y, Morishima Y, Kodera Y. Source: Blood. 2002 August 1; 100(3): 799-803. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12130489&dopt=Abstract
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Outcome of adult severe or very severe aplastic anemia treated with immunosuppressive therapy compared with bone marrow transplantation: multicenter trial. Author(s): Ahn MJ, Choi JH, Lee YY, Choi IY, Kim IS, Yoon SS, Park SY, Kim BK, Suh C, Son HJ, Jung CW, Lee JH, Sung JM, Im SA, Oh D, Jung SY, Yoon HJ, Cho KS, Lee JA, Yuh YJ, Kim SR, Ki M. Source: International Journal of Hematology. 2003 August; 78(2): 133-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12953807&dopt=Abstract
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Outcome of moderate aplastic anemia in children. Author(s): Khatib Z, Wilimas J, Wang W. Source: Am J Pediatr Hematol Oncol. 1994 February; 16(1): 80-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8311177&dopt=Abstract
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Outcome of pregnancy and disease course among women with aplastic anemia treated with immunosuppression. Author(s): Tichelli A, Socie G, Marsh J, Barge R, Frickhofen N, McCann S, Bacigalupo A, Hows J, Marin P, Nachbaur D, Symeonidis A, Passweg J, Schrezenmeier H; European Group for Blood and Marrow Transplantation Severe Aplastic Anaemia Working Party. Source: Annals of Internal Medicine. 2002 August 6; 137(3): 164-72. Summary for Patients In: http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12160364&dopt=Abstract
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Overproduction of inhibitory hematopoietic cytokines by lipopolysaccharideactivated peripheral blood mononuclear cells in patients with aplastic anemia. Author(s): Hsu HC, Tsai WH, Chen LY, Hsu ML, Ho CH, Lin CK, Wang SY. Source: Annals of Hematology. 1995 December; 71(6): 281-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8534759&dopt=Abstract
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Overuse of granulocyte colony-stimulating factor in acute myeloid leukemia, aplastic anemia and myelodysplastic syndrome. Author(s): Shinohara K. Source: Intern Med. 2000 January; 39(1): 82. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10674858&dopt=Abstract
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Paroxysmal nocturnal hemoglobinuria (membrane defect, pathogenesis, aplastic anemia, diagnosis). Author(s): Chrobak L. Source: Acta Medica (Hradec Kralove). 2000; 43(1): 3-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10934778&dopt=Abstract
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Pathophysiology and treatment of aplastic anemia. Author(s): Geissler K. Source: Wiener Klinische Wochenschrift. 2003 August 14; 115(13-14): 444-50. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13677262&dopt=Abstract
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Persistent remission after immunosuppressive therapy of hairy cell leukemia mimicking aplastic anemia: two case reports. Author(s): Sugimori C, Kaito K, Nakao S. Source: International Journal of Hematology. 2003 May; 77(4): 391-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12774930&dopt=Abstract
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Plasma thrombopoietin levels in patients with aplastic anemia and idiopathic thrombocytopenic purpura. Author(s): Ann Intern Med. 2002 Aug 6;137(3):I-34 Source: Chinese Medical Journal. 2002 July; 115(7): 983-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12160382
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Possible etiologic factors in 151 Turkish patients with aplastic anemia. Author(s): Alnigenis MN, Nalcaci M, Pekcelen Y, Atamer T, Sargin D. Source: American Journal of Hematology. 2001 September; 68(1): 60-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11559939&dopt=Abstract
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Pregnancy associated aplastic anemia: maternal and fetal outcome. Author(s): Deka D, Malhotra N, Sinha A, Banerjee N, Kashyap R, Roy KK. Source: The Journal of Obstetrics and Gynaecology Research. 2003 April; 29(2): 67-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12755524&dopt=Abstract
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Preliminary study of HLA-ABCDR antigens in CML, ANLL, thalassemia and severe aplastic anemia in Thais. Author(s): Chiewsilp P, Sujirachato K, Mongkolsuk T, Junpong S, Jootar S, Hathirat P. Source: J Med Assoc Thai. 2000 March; 83 Suppl 1: S130-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10865419&dopt=Abstract
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Prevalence of parvovirus B19 in liver tissue: no association with fulminant hepatitis or hepatitis-associated aplastic anemia. Author(s): Wong S, Young NS, Brown KE. Source: The Journal of Infectious Diseases. 2003 May 15; 187(10): 1581-6. Epub 2003 April 23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12721938&dopt=Abstract
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Pseudotumor cerebri in idiopathic aplastic anemia. Author(s): Nazir SA, Siatkowski RM. Source: J Aapos. 2003 February; 7(1): 71-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12690375&dopt=Abstract
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Pseudotumor cerebri in two adolescents with acquired aplastic anemia. Author(s): Jeng MR, Rieman M, Bhakta M, Helton K, Wang WC. Source: Journal of Pediatric Hematology/Oncology : Official Journal of the American Society of Pediatric Hematology/Oncology. 2002 December; 24(9): 765-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12468922&dopt=Abstract
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Quality of hematologic recovery in patients with aplastic anemia following cyclosporine therapy. Author(s): Yamaguchi M, Nakao S, Takamatsu H, Chuhjo T, Shiobara S, Matsuda T. Source: Experimental Hematology. 1995 April; 23(4): 341-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7534714&dopt=Abstract
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Quantitative analysis of cobblestone area-forming cells in bone marrow of patients with aplastic anemia by limiting dilution assay. Author(s): Schrezenmeier H, Jenal M, Herrmann F, Heimpel H, Raghavachar A. Source: Blood. 1996 December 15; 88(12): 4474-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8977239&dopt=Abstract
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Quantitative and qualitative assessment of reactive hematopoietic bone marrow in aplastic anemia using MR spectroscopy with variable echo times. Author(s): Amano Y, Kumazaki T. Source: Skeletal Radiology. 2002 January; 31(1): 19-24. Epub 2001 September 05. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11807588&dopt=Abstract
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Recombinant humanized anti-IL-2 receptor antibody (daclizumab) produces responses in patients with moderate aplastic anemia. Author(s): Maciejewski JP, Sloand EM, Nunez O, Boss C, Young NS. Source: Blood. 2003 November 15; 102(10): 3584-6. Epub 2003 July 24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12881307&dopt=Abstract
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Recovery of hematopoietic progenitor cells in patients with severe aplastic anemia who obtained good clinical response with a combination therapy of immunosuppressive agents and recombinant human granulocyte colony-stimulating factor. Author(s): Matsuo Y, Iwanaga M, Mori H, Yoshida S, Kawaguchi Y, Yakata Y, Murata K, Nagai K, Jinnai I, Matsuo T, Kuriyama K, Tomonaga M. Source: International Journal of Hematology. 2000 July; 72(1): 37-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10979207&dopt=Abstract
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Regional patterns in the incidence of aplastic anemia in Thailand. The Aplastic Anemia Study Group. Author(s): Issaragrisil S, Leaverton PE, Chansung K, Thamprasit T, Porapakham Y, Vannasaeng S, Piankijagum A, Kaufman DW, Anderson TE, Shapiro S, Young NS. Source: American Journal of Hematology. 1999 July; 61(3): 164-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10398308&dopt=Abstract
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Relationship between aplastic anemia and paroxysmal nocturnal hemoglobinuria. Author(s): Kinoshita T, Inoue N. Source: International Journal of Hematology. 2002 February; 75(2): 117-22. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11939256&dopt=Abstract
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Relationship between human parvovirus B19 infection and aplastic anemia. Author(s): Qian X, Zheng Y, Zhang G, Jiao X, Li Z. Source: Chinese Medical Sciences Journal = Chung-Kuo I Hsueh K'o Hsueh Tsa Chih / Chinese Academy of Medical Sciences. 2001 September; 16(3): 172-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12899333&dopt=Abstract
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Remission of severe aplastic anemia associated with hepatitis B virus infection after viral clearance: potential role of lamivudine. Author(s): Bozkaya H, Yurdaydin C, Toruner M, Arat M, Bozdayi AM, Erekul S, Cinar K, Koc H, Uzunalimoglu O. Source: Digestive Diseases and Sciences. 2002 August; 47(8): 1782-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12184530&dopt=Abstract
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Risk factors for cytomegalovirus retinitis following bone marrow transplantation from unrelated donors in patients with severe aplastic anemia or myelodysplasia. Author(s): Kuriyama K, Todo S, Ikushima S, Fujii N, Yoshihara T, Tsunamoto K, Naya M, Hojo M, Hibi S, Morimoto A, Imashuku S. Source: International Journal of Hematology. 2001 December; 74(4): 455-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11794704&dopt=Abstract
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Risk factors for evolution of acquired aplastic anemia into myelodysplastic syndrome and acute myeloid leukemia after immunosuppressive therapy in children. Author(s): Kojima S, Ohara A, Tsuchida M, Kudoh T, Hanada R, Okimoto Y, Kaneko T, Takano T, Ikuta K, Tsukimoto I; Japan Childhood Aplastic Anemia Study Group. Source: Blood. 2002 August 1; 100(3): 786-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12130487&dopt=Abstract
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Rubella-associated aplastic anemia treated by syngeneic stem cell transplantations. Author(s): Kook H, Kim GM, Kim HJ, Kim CJ, Yoon WS, Hwang TJ. Source: American Journal of Hematology. 2000 August; 64(4): 303-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10911384&dopt=Abstract
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Ruptured Klebsiella pneumoniae liver abscess after high-dose cyclophosphamide for severe aplastic anemia. Author(s): Lee JJ, Kim HJ, Chung IJ, Kook H, Park MR, Kim CJ, Shin DH, Hwang TJ. Source: American Journal of Hematology. 2000 July; 64(3): 218-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10861821&dopt=Abstract
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Screening for paroxysmal nocturnal hemoglobinuria (PNH) clone in Egyptian children with aplastic anemia. Author(s): Rizk S, Ibrahim IY, Mansour IM, Kandil D. Source: Journal of Tropical Pediatrics. 2002 June; 48(3): 132-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12164595&dopt=Abstract
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Second bone marrow transplantation for severe aplastic anemia: analysis of 34 cases. Author(s): de Medeiros CR, Bitencourt MA, Medeiros BC, Ioshizumi L, Pasquini R. Source: Bone Marrow Transplantation. 2001 November; 28(10): 941-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11753548&dopt=Abstract
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Severe aplastic anemia and allogeneic hematopoietic stem cell transplantation. Author(s): Myer SA, Oliva J. Source: Aacn Clinical Issues. 2002 May; 13(2): 169-91. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12011591&dopt=Abstract
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Severe aplastic anemia associated with thymic carcinoma and partial recovery of hematopoiesis after thymectomy. Author(s): Koizumi K, Nakao S, Haseyama Y, Kato H, Ohi M, Motohara T, Endo T, Sawada K, Koike T. Source: Annals of Hematology. 2003 June; 82(6): 367-70. Epub 2003 April 25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12715207&dopt=Abstract
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Soft tissue infection with Absidia corymbifera in a patient with idiopathic aplastic anemia. Author(s): Cloughley R, Kelehan J, Corbett-Feeney G, Murray M, Callaghan J, Regan P, Cormican M. Source: Journal of Clinical Microbiology. 2002 February; 40(2): 725-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11826008&dopt=Abstract
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Stem cell defect in aplastic anemia: reduced long term culture-initiating cells (LTCIC) in CD34+ cells isolated from aplastic anemia patient bone marrow. Author(s): Rizzo S, Scopes J, Elebute MO, Papadaki HA, Gordon-Smith EC, Gibson FM. Source: The Hematology Journal : the Official Journal of the European Haematology Association / Eha. 2002; 3(5): 230-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12391540&dopt=Abstract
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Stem cell transplantation for aplastic anemia. Author(s): Georges GE, Storb R. Source: International Journal of Hematology. 2002 February; 75(2): 141-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11939259&dopt=Abstract
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Successful bone marrow plus cord blood stem cell transplantation in a girl who developed myelodysplastic syndrome from hepatitis-associated aplastic anemia treated with long-term immunosuppressants and growth factors. Author(s): Shibuya A, Ishii S, Obinata K. Source: Hematology (Amsterdam, Netherlands). 2002 October; 7(5): 301-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12850817&dopt=Abstract
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Successful non-myeloablative stem cell transplantation for a heavily transfused woman with severe aplastic anemia complicated by heart failure. Author(s): Nishio M, Nakao S, Endo T, Fujimoto K, Takashima H, Sakai T, Bacigalupo A, Koike T, Sawada K. Source: Bone Marrow Transplantation. 2001 October; 28(8): 783-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11781631&dopt=Abstract
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Supplemental peripheral blood stem cells to decrease marrow rejection in adult patients with severe aplastic anemia. Author(s): Min CK, Kim DW, Lee JW, Han CW, Min WS, Kim CC. Source: American Journal of Hematology. 2002 January; 69(1): 15-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11835325&dopt=Abstract
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Telomerase activity and its correlation with the proliferative potential of bone marrow in aplastic anemia in children. Author(s): Shen JB, Tang JY, Zhao JC, Pan C, Chen J, Zhou X, Wang YP. Source: Acta Haematologica. 2002; 107(4): 208-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12053148&dopt=Abstract
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The relationship of aplastic anemia and PNH. Author(s): Young NS, Maciejewski JP, Sloand E, Chen G, Zeng W, Risitano A, Miyazato A. Source: International Journal of Hematology. 2002 August; 76 Suppl 2: 168-72. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12430920&dopt=Abstract
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The spectrum of PIG-A gene mutations in aplastic anemia/paroxysmal nocturnal hemoglobinuria (AA/PNH): a high incidence of multiple mutations and evidence of a mutational hot spot. Author(s): Mortazavi Y, Merk B, McIntosh J, Marsh JC, Schrezenmeier H, Rutherford TR; BIOMED II Pathophysiology and Treatment of Aplastic Anaemia Study Group. Source: Blood. 2003 April 1; 101(7): 2833-41. Epub 2002 November 07. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12424196&dopt=Abstract
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The treatment of severe aplastic anemia: outcomes of bone marrow transplantation and immunosuppressive therapy in a single institution of Korea. Author(s): Kim I, Yoon SS, Park S, Kim BK, Kim NK. Source: Journal of Korean Medical Science. 2003 June; 18(3): 365-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12808323&dopt=Abstract
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Therapeutic approaches to childhood acquired aplastic anemia. Author(s): Sugita K. Source: Curr Opin Investig Drugs. 2001 February; 2(2): 237-43. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11816837&dopt=Abstract
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Thrombopoietin is essential for the maintenance of normal hematopoiesis in humans: development of aplastic anemia in patients with congenital amegakaryocytic thrombocytopenia. Author(s): Ballmaier M, Germeshausen M, Krukemeier S, Welte K. Source: Annals of the New York Academy of Sciences. 2003 May; 996: 17-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12799278&dopt=Abstract
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Ticlopidine-induced aplastic anemia: two new case reports, review, and meta-analysis of 55 additional cases. Author(s): Symeonidis A, Kouraklis-Symeonidis A, Seimeni U, Galani A, Giannakoulas N, Fragopanagou E, Tiniakou M, Matsouka P, Zoumbos N. Source: American Journal of Hematology. 2002 September; 71(1): 24-32. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12221670&dopt=Abstract
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Treatment of aplastic anemia by the kidney-tonifying and mediating method. Author(s): Yu Y, Sun W, Cao K, Wang X. Source: J Tradit Chin Med. 2001 December; 21(4): 252-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12014121&dopt=Abstract
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Tumor necrosis factor-alpha levels in long-term marrow cultures from patients with aplastic anemia: modulation by granulocyte-macrophage colony-stimulating factor. Author(s): Martinez-Jaramillo G, Flores-Figueroa E, Gomez-Morales E, Sanchez-Valle E, Mayani H. Source: American Journal of Hematology. 2001 November; 68(3): 144-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11754394&dopt=Abstract
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Two cases of acute myeloblastic leukemia evolving from aplastic anemia. Author(s): Taguchi A, Tominaga T, Nakamori Y, Miyazaki M, Shinohara K. Source: International Journal of Hematology. 2003 June; 77(5): 471-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12841385&dopt=Abstract
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Ulcerative colitis associated with aplastic anemia. Author(s): Kishikawa H, Nishida J, Nakano M, Hirano E, Morishita T, Ishii H. Source: Digestive Diseases and Sciences. 2003 July; 48(7): 1376-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12870799&dopt=Abstract
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Umbilical cord blood transplantation from unrelated HLA-matched donor in an adult with severe aplastic anemia. Author(s): Mao P, Liao C, Zhu Z, Wang H, Wang S, Xu Y, Mo W, Ying Y, Li Q, Liu B. Source: Bone Marrow Transplantation. 2000 November; 26(10): 1121-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11108315&dopt=Abstract
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Unrelated donor marrow transplantation for severe acquired aplastic anemia using cyclophosphamide, antithymocyte globulin, and total body irradiation. Author(s): Kojima S, Inaba J, Kondo M, Kato K, Matsuyama T, Horikoshi Y, Mimaya J. Source: Blood. 1995 January 1; 85(1): 291-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7803804&dopt=Abstract
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Unrelated peripheral blood stem cell transplantation with 'megadoses' of purified CD34+ cells in three children with refractory severe aplastic anemia. Author(s): Schwinger W, Urban C, Lackner H, Kerbl R, Benesch M, Dornbusch HJ, Sovinz P, Schauenstein K, Schumm M, Handgretinger R. Source: Bone Marrow Transplantation. 2000 March; 25(5): 513-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10713628&dopt=Abstract
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Use of granulocyte colony-stimulating factor for treatment of aplastic anemia. Author(s): Kojima S. Source: Nagoya J Med Sci. 1999 November; 62(3-4): 77-82. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10689869&dopt=Abstract
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Use of hematopoietic growth factors for treatment of aplastic anemia. Author(s): Kojima S. Source: Bone Marrow Transplantation. 1996 December; 18 Suppl 3: S36-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8971406&dopt=Abstract
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Use of household pesticides and the risk of aplastic anaemia in Thailand. The Aplastic Anemia Study Group. Author(s): Kaufman DW, Issaragrisil S, Anderson T, Chansung K, Thamprasit T, Sirijirachai J, Piankijagum A, Porapakkham Y, Vannasaeng S, Leaverton PE, Shapiro S, Young NS. Source: International Journal of Epidemiology. 1997 June; 26(3): 643-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9222791&dopt=Abstract
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Use of human lymphoblastoid cells to detect the toxic effect of chloramphenicol and metabolites possibly involved in aplastic anemia in man. Author(s): Robbana-Barnat S, Decloitre F, Frayssinet C, Seigneurin JM, Toucas L, Lafarge-Frayssinet C. Source: Drug and Chemical Toxicology. 1997 August; 20(3): 239-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9292279&dopt=Abstract
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Use of lithium carbonate in the treatment of aplastic anemia. Author(s): Das KV, Thomas G. Source: J Assoc Physicians India. 1982 February; 30(2): 120-1. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6820365&dopt=Abstract
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Utility of blasts with a clear halo around the nucleolus as a predictive indicator for disease progression in patients with myelodysplastic syndromes and aplastic anemia. Author(s): Emura I, Chou T, Imai Y, Kakihara T, Asami K, Naito M, Ishiguro T, Yoshizawa H, Arakawa M. Source: Diagnostic Cytopathology. 2000 May; 22(5): 275-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10790232&dopt=Abstract
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Varicella-zoster virus infection after marrow transplantation for aplastic anemia or leukemia. Author(s): Atkinson K, Meyers JD, Storb R, Prentice RL, Thomas ED. Source: Transplantation. 1980; 29(1): 47-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6245486&dopt=Abstract
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Veno-occlusive disease of the liver after allogeneic bone marrow transplantation for severe aplastic anemia. Author(s): Lee JH, Lee KH, Choi SJ, Min YJ, Kim JG, Kim S, Lee JS, Kim SH, Park CJ, Chi HS, Kim WK. Source: Bone Marrow Transplantation. 2000 September; 26(6): 657-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11041568&dopt=Abstract
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Very low doses of GM-CSF administered alone or with erythropoietin in aplastic anemia. Author(s): Kurzrock R, Talpaz M, Gutterman JU. Source: The American Journal of Medicine. 1992 July; 93(1): 41-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1626572&dopt=Abstract
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Very severe aplastic anemia appearing after thymectomy. Author(s): Park CY, Kim HJ, Kim YJ, Park YH, Lee JW, Min WS, Kim CC. Source: Korean J Intern Med. 2003 March; 18(1): 61-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12760272&dopt=Abstract
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Very severe aplastic anemia following resection of lymphocytic thymoma: effectiveness of antilymphocyte globulin, cyclosporin A, and granulocyte-colony stimulating factor. Author(s): Dincol G, Saka B, Aktan M, Nalcaci M, Keskin H, Palanduz S, Ozturk S, Dincol K. Source: American Journal of Hematology. 2000 May; 64(1): 78-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10815795&dopt=Abstract
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Vibrio vulnificus septicemia in a patient with severe aplastic anemia. Author(s): Tsuzuki M, Ino T, Maruyama F, Okamoto M, Ezaki K, Hirano M. Source: International Journal of Hematology. 1998 February; 67(2): 175-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9631584&dopt=Abstract
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What is the definition of cure for aplastic anemia? Author(s): Camitta BM. Source: Acta Haematologica. 2000; 103(1): 16-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10705154&dopt=Abstract
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What is the most effective treatment of children with severe aplastic anemia who lack a matched sibling donor? Author(s): Johnson FL. Source: Bone Marrow Transplantation. 1996 December; 18 Suppl 3: S39-44. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8971407&dopt=Abstract
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CHAPTER 2. NUTRITION AND APLASTIC ANEMIA Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and aplastic anemia.
Finding Nutrition Studies on Aplastic Anemia 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 “aplastic anemia” (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 “aplastic anemia” (or a synonym): •
22 cases of chronic aplastic anemia treated with traditional Chinese medicine and large doses of androgen. Source: Qian, F W Ye, G Y Jiang, B R J-Tradit-Chin-Med. 1987 March; 7(1): 68 0254-6272
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A clinical and experimental study of herbal medicine in aplastic anemia. Author(s): Sino-Japanese Friendship Hospital, Beijing. Source: Xie, R Liao, J Ma, R J-Tradit-Chin-Med. 1993 September; 13(3): 211-6 0254-6272
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A patient with non-A, non-B, non-C hepatitis-associated aplastic anemia recovered promptly following immuno-suppressive therapy, including antithymocyte globulin. Author(s): Department of Internal Medicine, Japan Self-Defence Forces Central Hospital, Tokyo, Japan. Source: Kayashima, S Kondou, T Watanabe, Y Kobari, S Kagami, M Int-J-Hematol. 1998 June; 67(4): 403-9 0925-5710
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A study of aplastic anemia at the Department of Child Health, School of Medicine University of North Sumatera/Dr. Pirngadi Hospital, Medan. Author(s): Department of Child Health, School of Medicine, University of North Sumatera/Dr. Pirngadi Hospital, Medan. Source: Arif, A Sutjipto, A Paediatr-Indones. 1991 Sep-October; 31(9-10): 253-60 00309311
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Abnormalities of hematopoietic progenitor cells in patients with aplastic anemia after hematologic recovery. Source: Issaragrisil, S Piankijagum, A Tang Naitrisorana, Y J-Med-Assoc-Thai. 1989 November; 72(11): 643-8 0125-2208
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Acquired aplastic anemia in children: a review of 100 patients. Author(s): Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand. Source: Chuansumrit, A Hathirat, P Isarangkura, P Southeast-Asian-J-Trop-Med-PublicHealth. 1990 June; 21(2): 313-20 0038-3619
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An enzymologic study on bone marrow cells in patients with aplastic anemia treated by supplementing the kidney and removing blood stasis. Author(s): Affiliated Hospital to the Weifang Medical College, Shandong Province. Source: Wang, S Liu, J Li, J Zhang, S Hu, K Li, Z J-Tradit-Chin-Med. 2000 September; 20(3): 169-71 0254-6272
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Aplastic anemia associated with canthaxanthin ingested for 'tanning' purposes. Author(s): Department of Pharmacy, Vanderbilt University School of Medicine, Nashville, TN 37232-6602. Source: Bluhm, R Branch, R Johnston, P Stein, R JAMA. 1990 September 5; 264(9): 1141-2 0098-7484
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Bone marrow mast cell hyperplasia in dogs with aplastic anemia. Source: Walker, D. Cowell, R.L. Clinkenbeard, K.D. Feder, B. Meinkoth, J.H. Vet-clinpathol. Irvine, Calif : Fancy Publication Inc. 1997. volume 26 (3) page 106-111. 0275-6382
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Comparisons of the composition of fat cells obtained from the marrow of normal individuals or of subjects with aplastic anemia and from bone marrow cultures. Source: Malik, F Gordon, M Y Goldman, J M Gordon Smith, E C Exp-Hematol. 1984 March; 12(3): 191-7 0301-472X
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Contents of trace elements in the hair of aplastic anemia patients and their treatment based on an overall analysis of symptoms and signs. Author(s): Institute of Blood Disease, Langfang City, Hebei Province. Source: Wang, J Yang, S Chen, G Li, D Pang, A Tian, H J-Tradit-Chin-Med. 1994 June; 14(2): 98-100 0254-6272
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Cyclophosphamide and other new agents for the treatment of severe aplastic anemia. Author(s): Molecular and Clinical Hematology Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Source: Tisdale, J F Dunn, D E Maciejewski, J Semin-Hematol. 2000 January; 37(1): 102-9 0037-1963
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Double bone marrow transplantation for severe aplastic anemia after orthotopic liver transplantation: implications for clinical management and immune tolerance. Author(s): Department of Pediatrics, University of Erlangen-Nurnberg, Loschgestrasse 15, 91054 Erlangen, Germany.
[email protected] Source: Stachel, Daniel Schmid, Irene Lang, Thomas Haas, Rainer J Otte, Jean Bernard Transpl-Int. 2002 January; 15(1): 39-44 0934-0874
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Effect of androgen therapy and anemia on serum erythropoietin levels in patients with aplastic anemia and myelodysplastic syndromes. Author(s): Haematology-Oncology Department, Instituto Nacional de la Nutricion Salvador Zubiran, Tlalpan, Mexico. XLopezK%
[email protected] Source: Piedras, J Hernandez, G Lopez Karpovitch, X Am-J-Hematol. 1998 February; 57(2): 113-8 0361-8609
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Effects of Sheng-Mai injection on the PRPP synthetase activity in BFU-es and CFU-es from bone marrows of mice with benzene-induced aplastic anemia. Author(s): Research Laboratory of Blood Biochemistry, Hunan Medical University, Changsha, P.R.China. Source: Liu, L P Liu, J F Lu, Y Q Life-Sci. 2001 August 10; 69(12): 1373-9 0024-3205
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Further evidence for lymphokine overproduction in severe aplastic anemia. Author(s): Division of Hematology and Blood Coagulation, University of Vienna, Austria. Source: Hinterberger, W Adolf, G Aichinger, G Dudczak, R Geissler, K Hocker, P Huber, C Kalhs, P Knapp, W Koller, U et al. Blood. 1988 July; 72(1): 266-72 0006-4971
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High incidence of transiently appearing complement-sensitive bone marrow precursor cells in patients with severe aplastic anemia--A possible role of high endogenous IL-2 in their suppression. Author(s): Departments of Research and Internal Medicine, Division of Hematology, University Hospital, Basel, Switzerland.
[email protected] Source: Nissen, C Tichelli, A Gratwohl, A Warthmann, C Moser, Y dalle Carbonare, V Sendelov, S Chklovskaia, E Jansen, W Wodnar Filipowicz, A Sadallah, S Speck, B ActaHaematol. 1999; 101(4): 165-72 0001-5792
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IFN-gamma is not the only mediator of suppressed myelopoiesis produced by mononuclear cells from aplastic anemia patients. Author(s): Department of Immunology, Karolinska Institutet, Stockholm, Sweden. Source: Laskay, T Hansson, M Porwit, A Bjorkholm, M Berthold, W Kiessling, R J-BiolRegul-Homeost-Agents. 1987 Jan-March; 1(1): 37-44 0393-974X
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In vitro response of T cells from aplastic anemia patients to antilymphocyte globulin and phytohemagglutinin: colony-stimulating activity and lymphokine production. Author(s): Department of Hematology, San Martino Hospital, Genoa, Italy. Source: Tong, J Bacigalupo, A Piaggio, G Figari, O Sogno, G Marmont, A Exp-Hematol. 1991 June; 19(5): 312-6 0301-472X
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PHA for aplastic anemias: the alpha but not the omega of mitogen therapies. Author(s): JBMW Immunotherapeutics, Albuquerque, NM 87123-4255, USA. Source: Wimer, B M Cancer-Biother-Radiopharm. 1998 April; 13(2): 109-20 1084-9785
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Production of interleukin 3 and granulocyte-macrophage colony-stimulating factor from stimulated blood mononuclear cells in patients with aplastic anemia. Author(s): Department of Pediatrics, University of Tokushima, Japan. Source: Kawano, Y Takaue, Y Hirao, A Watanabe, T Abe, T Shimizu, T Sato, J Saito, S Kitamura, T Takaku, F et al. Exp-Hematol. 1992 October; 20(9): 1125-8 0301-472X
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Th activation in congenital hypoplastic anemia. Source: Herman, J H Shirey, R S Smith, B Kickler, T S Ness, P M Transfusion. 1987 MayJune; 27(3): 253-6 0041-1132
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Ticlopidine-associated aplastic anemia. A case report and review of literature. Author(s): Department of Internal Medicine, Veterans General Hospital-Kaoshiung, Taiwan, R.O.C. Source: Yeh, S P Hsueh, E J Wu, H Wang, Y C Ann-Hematol. 1998 February; 76(2): 87-90 0939-5555
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Treatment of acute aplastic anemia by traditional Chinese medicine combined with Western drugs. Source: Liang, B Gao, G H Tian, H B Liu, H F Xu, X Q Yang, J X Hou, W Yang, S L Sun, Y T Duan, Y et al. J-Tradit-Chin-Med. 1988 March; 8(1): 25-6 0254-6272
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Treatment of aplastic anemia by the kidney-tonifying and mediating method. Author(s): Department of Traditional Chinese Medicine, PLA 465 Hospital, Jilin Province, 132011. Source: Yu, Y Sun, W Cao, K Wang, X J-Tradit-Chin-Med. 2001 December; 21(4): 252-5 0254-6272
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Treatment of severe aplastic anemia with antilymphocyte globulin and androgens: a report on 33 patients. Author(s): Service des Maladies du Sang, Hopital Claude Huriez, C.H.U. Lille, France. Source: Facon, T Walter, M P Fenaux, P Morel, P Dupriez, B Gardin, C Jouet, J P Bauters, F Ann-Hematol. 1991 August; 63(2): 89-93 0939-5555
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Use of household pesticides and the risk of aplastic anaemia in Thailand. The Aplastic Anemia Study Group. Author(s): Stone Epidemiology Unit, School of Public Health, Boston University School of Medicine, Brookline, MA, USA. Source: Kaufman, D W Issaragrisil, S Anderson, T Chansung, K Thamprasit, T Sirijirachai, J Piankijagum, A Porapakkham, Y Vannasaeng, S Leaverton, P E Shapiro, S Young, N S Int-J-Epidemiol. 1997 June; 26(3): 643-50 0300-5771
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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 APLASTIC ANEMIA Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to aplastic anemia. 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 aplastic anemia 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 “aplastic anemia” (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 aplastic anemia: •
22 cases of chronic aplastic anemia treated with traditional Chinese medicine and large doses of androgen. Author(s): Qian FW, Ye GY, Jiang BR. Source: J Tradit Chin Med. 1987 March; 7(1): 68. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3613641&dopt=Abstract
•
A clinical and experimental study of herbal medicine in aplastic anemia. Author(s): Xie R, Liao J, Ma R. Source: J Tradit Chin Med. 1993 September; 13(3): 211-6. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8246600&dopt=Abstract
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Acquired aplastic anemia in children: incidence, prognosis and treatment options. Author(s): Locasciulli A.
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Source: Paediatric Drugs. 2002; 4(11): 761-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12390048&dopt=Abstract •
Acute childhood leukemia presenting as aplastic anemia: the response to corticosteroids. Author(s): Melhorn DK, Gross S, Newman AJ. Source: The Journal of Pediatrics. 1970 October; 77(4): 647-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5454711&dopt=Abstract
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An enzymologic study on bone marrow cells in patients with aplastic anemia treated by supplementing the kidney and removing blood stasis. Author(s): Wang S, Liu J, Li J, Zhang S, Hu K, Li Z. Source: J Tradit Chin Med. 2000 September; 20(3): 169-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11038975&dopt=Abstract
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Androst-4-ene-3 beta, 17 beta-diol dicyclopentylpropionate combined with traditional Chinese drugs in chronic aplastic anemia. Author(s): Zhang ZN, Wu YJ, Hou YH, Lei HP, Chen QQ, Guan MZ. Source: Chinese Medical Journal. 1981 October; 94(10): 669-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6797801&dopt=Abstract
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Aplastic anemia induced by an adulterated herbal medication. Author(s): Nelson L, Shih R, Hoffman R. Source: Journal of Toxicology. Clinical Toxicology. 1995; 33(5): 467-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7650772&dopt=Abstract
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Aplastic anemia induced by cyclohexylchloroethylnitrousurea. Author(s): Elis A, Lishner M, Savin H, Ravid M. Source: Anti-Cancer Drugs. 1994 February; 5(1): 105-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8186424&dopt=Abstract
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Bone marrow transplantation for aplastic anemia: recent advances and comparisons with alternative therapies. Author(s): Champlin RE. Source: Cancer Treat Res. 1990; 50: 185-99. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1976350&dopt=Abstract
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Contents of trace elements in the hair of aplastic anemia patients and their treatment based on an overall analysis of symptoms and signs. Author(s): Wang J, Yang S, Chen G, Li D, Pang A, Tian H.
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Source: J Tradit Chin Med. 1994 June; 14(2): 98-100. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7967704&dopt=Abstract •
Effects of Sheng-Mai injection on the PRPP synthetase activity in BFU-es and CFU-es from bone marrows of mice with benzene-induced aplastic anemia. Author(s): Liu LP, Liu JF, Lu YQ. Source: Life Sciences. 2001 August 10; 69(12): 1373-9. Erratum In: Life Sci 2001 October 12; 69(21): 2573. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11531161&dopt=Abstract
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Effects of zaizhang-I, a traditional Chinese medicine, on immunologically mediated aplastic anemia in mice. Author(s): Zhou JF, He MD, Li MZ, Yang W, Tang JZ, Sheng G, Zhu HF, Shao JF, Yang J. Source: J Tongji Med Univ. 1994; 14(3): 188-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7807608&dopt=Abstract
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Immunomodulating treatment in patients with aplastic anemia. Author(s): Guglielmo P, Giustolisi R, Cacciola E, Milone G. Source: The New England Journal of Medicine. 1983 June 2; 308(22): 1362-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6221194&dopt=Abstract
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Late complications following treatment for severe aplastic anemia (SAA) with highdose cyclophosphamide (Cy): follow-up of a randomized trial. Author(s): Tisdale JF, Maciejewski JP, Nunez O, Rosenfeld SJ, Young NS. Source: Blood. 2002 December 15; 100(13): 4668-70. Epub 2002 June 28. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12393567&dopt=Abstract
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Low drug attributability of aplastic anemia in Thailand. The Aplastic Anemia Study Group. Author(s): Issaragrisil S, Kaufman DW, Anderson T, Chansung K, Thamprasit T, Sirijirachai J, Piankijagum A, Porapakkham Y, Vannasaeng S, Leaverton PE, Shapiro S, Young NS. Source: Blood. 1997 June 1; 89(11): 4034-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9166842&dopt=Abstract
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Membrane changes and metabolic disorders in erythrocytes of patients and rat models with aplastic anemia. Author(s): Lu Y, Liu J. Source: Chinese Medical Journal. 1996 January; 109(1): 49-51. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8758365&dopt=Abstract
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Ocular findings in aplastic anemia. Author(s): Mansour AM, Salti HI, Han DP, Khoury A, Friedman SM, Salem Z, Ibrahim K, Bazerbachi A, Saghir N. Source: Ophthalmologica. Journal International D'ophtalmologie. International Journal of Ophthalmology. Zeitschrift Fur Augenheilkunde. 2000; 214(6): 399-402. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11053999&dopt=Abstract
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Stimulation of myelopoiesis in patients with aplastic anemia by recombinant human granulocyte-macrophage colony-stimulating factor. Author(s): Vadhan-Raj S, Buescher S, Broxmeyer HE, LeMaistre A, Lepe-Zuniga JL, Ventura G, Jeha S, Horwitz LJ, Trujillo JM, Gillis S, et al. Source: The New England Journal of Medicine. 1988 December 22; 319(25): 1628-34. Erratum In: N Engl J Med 1989 February 2; 320(5): 329. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3059191&dopt=Abstract
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Toxic chemical depression of the bone marrow and possible aplastic anemia explainable on a genetic basis. Author(s): Nebert DW, Jensen NM, Levitt RC, Felton JS. Source: Clin Toxicol. 1980 March; 16(1): 99-122. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7389284&dopt=Abstract
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Treatment of acute aplastic anemia by traditional Chinese medicine combined with Western drugs. Author(s): Liang B, Gao GH, Tian HB, Liu HF, Xu XQ, Yang JX, Hou W, Yang SL, Sun YT, Duan Y, et al. Source: J Tradit Chin Med. 1988 March; 8(1): 25-6. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3393016&dopt=Abstract
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Treatment of aplastic anemia by the kidney-tonifying and mediating method. Author(s): Yu Y, Sun W, Cao K, Wang X. Source: J Tradit Chin Med. 2001 December; 21(4): 252-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12014121&dopt=Abstract
Additional Web Resources A number of additional Web sites offer encyclopedic information covering CAM and related topics. The following is a representative sample: •
Alternative Medicine Foundation, Inc.: http://www.herbmed.org/
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AOL: http://search.aol.com/cat.adp?id=169&layer=&from=subcats
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Chinese Medicine: http://www.newcenturynutrition.com/
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drkoop.com®: http://www.drkoop.com/InteractiveMedicine/IndexC.html
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Family Village: http://www.familyvillage.wisc.edu/med_altn.htm
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Google: http://directory.google.com/Top/Health/Alternative/
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Healthnotes: http://www.healthnotes.com/
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MedWebPlus: http://medwebplus.com/subject/Alternative_and_Complementary_Medicine
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Open Directory Project: http://dmoz.org/Health/Alternative/
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HealthGate: http://www.tnp.com/
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WebMD®Health: http://my.webmd.com/drugs_and_herbs
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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html
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Yahoo.com: http://dir.yahoo.com/Health/Alternative_Medicine/
The following is a specific Web list relating to aplastic anemia; 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: •
Chinese Medicine Shengxue Wan Alternative names: Shengxue Pills; Shengxue Wan (Sheng Xue Wan) Source: Pharmacopoeia Commission of the Ministry of Health, People's Republic of China
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. CLINICAL TRIALS AND APLASTIC ANEMIA Overview In this chapter, we will show you how to keep informed of the latest clinical trials concerning aplastic anemia.
Recent Trials on Aplastic Anemia The following is a list of recent trials dedicated to aplastic anemia.8 Further information on a trial is available at the Web site indicated. •
A Study to Determine whether Therapy with Daclizumab Will Benefit Patients with Bone Marrow Failure Condition(s): Aplastic Anemia; Pure Red Cell Aplasia; Thrombocytopenic Purpura Study Status: This study is currently recruiting patients. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: Participants in this study are suffering from rare and serious blood disorders. In aplastic anemia, the bone marrow stops producing red blood cells, platelets, and white blood cells. In pure red cell aplasia, the bone marrow stops producing red cells, and in amegakaryocytic thrombocytopenic purpura, the bone marrow stops producing platelets. Current treatment approaches for these disorders include bone marrow transplant and/or immunosuppression. However, bone marrow transplant is not always possible, and immunosuppression has serious side effects. This study will investigate whether daclizumab can be used to treat these disorders. Daclizumab is a genetically engineered human antibody that blocks the interleukin-2 receptor on immune cells. It has been used successfully in many transplant patients to reduce the rate of organ rejection. Participants will undergo a complete history and physical examination. A bone marrow aspiration and biopsy will be performed to confirm the type of bone marrow failure. About 5 tablespoons of blood will be drawn for baseline tests and research purposes. Daclizumab will be administered every 2 weeks by vein in a 30-minute infusion. The first dose will be given at NIH and the next four may be given at NIH or by the participant's primary hematologist. The treatment
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These are listed at www.ClinicalTrials.gov.
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will last 8 weeks. Participants must also see their referring physician or NIH physicians every 2 weeks for blood counts. In the fourth and eighth weeks of the study and at the 3month follow-up visit, 2 tablespoons of blood will be drawn at NIH. At the 1-month follow-up visit to NIH, 5 tablespoons of blood will be drawn and another bone marrow aspiration and biopsy performed. Risks from bone marrow aspiration and biopsy and blood draws include discomfort. Daclizumab is usually well-tolerated; however, it may weaken immunity against certain bacteria and viruses. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001962 •
Collection of Biological Samples from Patients with Hepatitis-Associated Aplastic Anemia Condition(s): Aplastic Anemia Study Status: This study is currently recruiting patients. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: This study will collect samples of blood, stool, bone marrow, or other tissues from patients with hepatitis-associated aplastic anemia to investigate a possible association between exposure to viruses and the development of aplastic anemia in these patients. Cells from the samples obtained may be grown in the laboratory for future studies. Patients' samples may be used to: - Study abnormalities that occur in hepatitis-associated aplastic anemia; - Test for various viruses; - Test immune function; Measure factors related to the patients' disease or diseases they may be at risk for; Evaluate the effectiveness of current therapies, refine treatment approaches, and identify potential new therapies; - Identify possible measures for disease prevention; - Identify possible genetic factors associated with hepatitis-associated aplastic anemia. Patients 2 years of age and older with severe aplastic anemia that developed within 6 months of an episode of hepatitis may be eligible for this study. Participants will complete questionnaires and provide tissue samples as described below. Questionnaires All patients (or another respondent for the patient) will fill out a questionnaire including demographic information (age, gender, race, ethnic group, education level, state of residence), current symptoms, medications, medical history, and history of possible exposures to toxins or viruses. A second questionnaire, which includes questions related to mental health, sexual behavior, alcohol and drug use, is optional for participants age 21 and older. These questionnaires are designed to uncover features of hepatitisassociated aplastic anemia and possibly reveal a common cause of the disease. Sample Collections - Blood- will be collected at the time of the patient's initial evaluation or upon enrollment into the study and possibly periodically during the study. Blood will be drawn through a needle in an arm vein. - Bone marrow- may be collected as part of the patient's standard medical care or specifically for research purposes of this study. For this procedure, the skin over the hipbone and the outer surface of the bone itself are numbed with an injection of a local anesthesia. Then, a larger needle is inserted into the hipbone and marrow is drawn into a syringe. Marrow cells are suctioned two to six times during the 15-minute procedure. - Stool- will be provided by the patient. Livertissue may be biopsied as part of the patient's general medical care or for NIH patients, as part of their enrollment in a treatment protocol. Study Type: Observational
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Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00050115 •
Collection of Blood and Bone Marrow from Normal Volunteers and Patients for Research Purposes Condition(s): Aplastic Anemia; Fanconi's Anemia; Healthy; Hematologic Disease; Myelodysplastic Syndrome Study Status: This study is currently recruiting patients. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: This study is designed to provide bone marrow and/or blood cells for other research studies. Patients participating in this study will be asked to provide small amounts of medical information and undergo a limited physical examination designed to detect the presence of any obvious blood disease. A blood and bone marrow sample will be obtained to verify that the patient has normal blood cell production. Researchers plan to obtain bone marrow samples to be used in laboratory studies directed toward understanding the formation of blood cells. Bone marrow samples will be taken from the hip bone of patients and normal volunteers. These samples are valuable to many research studies within the Hematology Branch of the National Heart, Lung, and Blood Institute, including studies of normal and abnormal production of blood cells, the viral causes of blood diseases, and the role of the immune system in bone marrow failure and related conditions. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001627
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Collection of Blood from Patients with Pancytopenia Condition(s): Aplastic Anemia; Pancytopenia Study Status: This study is currently recruiting patients. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: Aplastic anemia is a condition in which the cells normally found in blood are greatly decreased. The normal levels of white blood cells, red blood cells, and platelets are much lower in patients with aplastic anemia. Because of these low levels of blood cells, patients with aplastic anemia have a variety of immune system abnormalities. However, low levels of blood cells make it difficult to collect specialized white blood cells (mononuclear cells) for research studies. This study was designed to collect lymphocytes from patients with low levels of all blood cells (pancytopenia) for use in research. Patients participating in the study will undergo a special procedure known as lymphapheresis. During lymphapheresis blood is taken from the patient in a manner similar to blood donation. The white blood cells are selectively removed by spinning (centrifugation), and the remaining red blood cells and platelets are placed back (re-infused) into the donor's blood stream. Patients participating in this study will not benefit directly from it. However, cells collected in this study may increase scientific knowledge and improve understanding and treatment for diseases like aplastic anemia. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001214
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Combination Chemotherapy and Bone Marrow Transplantation in Treating Patients With Aplastic Anemia or Hematologic Cancer Condition(s): childhood Hodgkin's lymphoma; childhood non-Hodgkin's lymphoma; hematopoietic and lymphoid cancer Study Status: This study is currently recruiting patients. Sponsor(s): Roswell Park Cancer Institute Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with bone marrow transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells. It is not yet known which regimen of combination chemotherapy followed by bone marrow transplantation is most effective for aplastic anemia or hematologic cancer. PURPOSE: Phase II/III trial to determine the effectiveness of different regimens of combination chemotherapy followed by bone marrow transplantation in treating patients who have aplastic anemia or hematologic cancer. Phase(s): Phase II; Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00003816
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Combination Chemotherapy Followed by Peripheral Stem Cell Transplantation in Treating Patients With Hematologic Cancer or Aplastic Anemia Condition(s): childhood Hodgkin's lymphoma; childhood non-Hodgkin's lymphoma; Gastrointestinal Cancer; hematopoietic and lymphoid cancer Study Status: This study is currently recruiting patients. Sponsor(s): Ireland Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Peripheral stem cell transplantation may be able to replace immune cells that were destroyed by chemotherapy used to kill cancer cells. PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy followed by peripheral stem cell transplantation in treating patients who have hematologic cancer or aplastic anemia. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00006379
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Combination Chemotherapy Followed By Umbilical Cord Blood Transplantation in Treating Patients With Hematologic Cancer or Severe Aplastic Anemia Condition(s): childhood Hodgkin's lymphoma; childhood non-Hodgkin's lymphoma; hematopoietic and lymphoid cancer Study Status: This study is currently recruiting patients. Sponsor(s): Ireland Cancer Center; National Cancer Institute (NCI)
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Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Umbilical cord blood transplantation may be able to replace cells destroyed by chemotherapy. PURPOSE: Phase I trial to study the effectiveness of combination chemotherapy followed by umbilical cord blood transplantation in treating patients who have hematologic cancer or severe aplastic anemia. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00054236 •
Improving Immunosuppressive Treatment for Patients with Severe Aplastic Anemia Condition(s): Aplastic Anemia Study Status: This study is currently recruiting patients. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: Immunosuppressive treatment (administering drugs that suppress the immune system) is often successful for people with severe aplastic anemia (SAA). However, SAA patients tend to be highly susceptible to relapse, even after successful immunosuppressive treatment. Research suggests that SAA is an autoimmune disease and thus may require longer immunosuppressive treatment with different drugs. The purpose of this study is to compare two immunosuppressive regimens with the goal of decreasing relapse in SAA patients. Study participants will be placed in one of two study groups. One group will receive a combined drug treatment of antithymocyte globulin (ATG), cyclosporine (CsA) and sirolimus for six months. The other group will receive a combined treatment of ATG and CsA for 6 months, followed by a slow taper of CsA over the next 18 months. Upon admission to NIH, patients will undergo several days of preliminary testing and receive the medications; they will be hospitalized during this period (7-10 days). Study participants will have blood drawn periodically during treatment. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00061360
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Investigating Voriconazole to Prevent Systemic Fungal Infection Condition(s): Neutropenia; Leukemia; Lymphoma; Aplastic Anemia Study Status: This study is currently recruiting patients. Sponsor(s): National Cancer Institute (NCI) Purpose - Excerpt: Children with a decreased ability to fight infection are at high risk for developing fungal infections. At present there are few medicines for treating fungal infections in children. Voriconazole is a new drug that is FDA approved to treat fungal infections in adults. The purpose of this study is to determine the safety, tolerability and pharmacokinetics (the body's handling of the drug) when it is given intravenously and orally to children younger than 12. Thirty-six children younger than 12 will participate in this study. Study participants will undergo the following evaluations: a physical
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exam, including an eye exam and an electrocardiogram; blood tests; and urinalysis. Participants will receive one or more different dosages of voriconazole intravenously, depending on when they enroll in the study. At the end of IV therapy, they will receive the drug as an oral solution two times a day. Investigators will obtain blood samples from participants on day 4, 8 and 12. Participants will remain hospitalized through day 8 of the study. On day 12, participants will undergo repeat evaluations from the beginning of the study. Their participation in this study will be last up to a maximum of 30 days. There will be two follow-up visits: at one month and at one year. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00062920 •
Peripheral Stem Cell Transplantation in Treating Patients With Hematologic Cancer or Aplastic Anemia Condition(s): childhood Hodgkin's lymphoma; chronic myeloproliferative disorders; Leukemia; Lymphoma; myelodysplastic and myeloproliferative diseases; plasma cell neoplasm Study Status: This study is currently recruiting patients. Sponsor(s): Roswell Park Cancer Institute; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Peripheral stem cell transplantation may be able to replace immune cells that were destroyed by chemotherapy used to kill cancer cells. PURPOSE: Phase II trial to study the effectiveness of chemotherapy followed by donor peripheral stem cell transplantation in treating patients who have hematologic cancer or aplastic anemia. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00053989
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Rabbit Antithymocyte Globulin Versus Campath-1H for Treating Severe Aplastic Anemia Condition(s): Aplastic Anemia Study Status: This study is currently recruiting patients. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: This study will compare two new treatments for people with severe aplastic anemia, a potentially fatal disease in which patients do not produce normal numbers of blood cells. Because they have too few red cells, patients may tire easily, have chest pains, and be short of breath even at rest. Too few white cells leave patients vulnerable to serious infections and possibly death. Too few platelets cause abnormal bleeding and easy bruising. Bleeding in the brain (stroke) can be fatal. Standard treatment with horse antithymocyte globulin (h-ATG), cyclosporine (CsA), and corticosteroids is effective, but patients often relapse. The treatments to be evaluated in this study are: 1) rabbit ATG (r-ATG) plus CsA plus corticosteroids; and 2) Campath-1H. r-ATG is made by injecting rabbits with white blood cells. The rabbit's immune system
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makes antibodies to destroy the foreign white cells. The antibodies are collected and purified to make r-ATG. CsA is commonly used to prevent rejection of donated tissue after bone marrow or organ transplantation and, in combination with h-ATG, for treating aplastic anemia. Corticosteroids suppress the immune system and are given to prevent or reduce the symptoms of serum sickness, which can develop in response to the rabbit proteins in the r-ATG. Campath-1H is a laboratory-made antibody currently used to treat chronic lymphocytic leukemia. It destroys white blood cells called lymphocytes that, in aplastic anemia, are responsible for destruction of bone marrow stem cells. Patients 15 years of age and older with severe aplastic anemia may be eligible for this study. Candidates will be screened with a medical history, physical examination, blood tests, and bone marrow biopsy. Participants are randomly assigned to one of two treatment groups: 1) r-ATG, CsA, and steroids, or 2) Campath-1H. For both treatments, it is suggested that a central venous line (large plastic tube) be placed in a large vein in the neck or chest. This tube can stay in the body and be used the entire treatment period to deliver the study drug and other medications, transfuse blood, and withdraw blood samples. Group 1 patients receive r-ATG by vein for 5 days, CsA by mouth as a liquid or capsule for 6 months, and a full dose of steroids by mouth for at least 2 weeks. After 2 weeks, when the risk of serum sickness-a reaction to the r-ATG-declines, the steroid dose is decreased. Group 2 patients receive Campath-1H by vein for 10 days. Because this drug suppresses the immune system, patients also take medicines to prevent herpes virus infection and Pneumocystis carinii-a type of pneumonia-and to treat cytomegalovirus infection, if it develops. All patients are hospitalized for the initial testing and treatment (about 2 weeks) when the risk of infection and seizures is highest. In addition to drug treatment, patients undergo the following procedures: - Blood tests: Throughout the hospital admission, blood samples are drawn daily to check drug side effects and the response to treatment. Samples are drawn less frequently for later tests. Bone marrow examination: A bone marrow sample is collected before beginning treatment, at 6 months, and then yearly. For this test, the area above the hip bone is numbed with a local anesthetic and a small sample of bone and marrow is withdrawn through a needle. - Chest x-ray may be done upon admission. - Other blood tests and xrays may be required to evaluate and treat symptoms that may develop. - Follow-up: Blood tests are done weekly by the patient's private doctor, and patients return to NIH for examinations at 3-month intervals. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00065260 •
Sargramostim in Reducing Graft-Versus-Host Disease in Patients Who Are Undergoing Donor Stem Cell Transplantation for Hematologic Cancer or Aplastic Anemia Condition(s): childhood Hodgkin's lymphoma; childhood non-Hodgkin's lymphoma; Graft Versus Host Disease; hematopoietic and lymphoid cancer Study Status: This study is currently recruiting patients. Sponsor(s): Roswell Park Cancer Institute; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Colony-stimulating factors such as sargramostim may increase the number of immune cells found in bone marrow or peripheral blood and may help a person's immune system recover from the side effects of chemotherapy or radiation therapy. Giving sargramostim to the stem cell donor and the patient may
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reduce the chance of developing graft-versus-host disease following stem cell transplantation. PURPOSE: Clinical trial to study the effectiveness of sargramostim in decreasing graft-versus-host disease in patients who are undergoing donor stem cell transplantation for hematologic cancer or aplastic anemia. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00053157 •
Stem Cell Mobilization Potential in Patients with Aplastic Anemia in remission Condition(s): Aplastic Anemia Study Status: This study is currently recruiting patients. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: This study will examine 1) whether it is possible to collect enough stem cells (cells produced by the bone marrow that mature into white and red blood cells and platelets) from patients with aplastic anemia to use for future treatment, and 2) whether patients who have been treated successfully and relapse will benefit from autologous stem cell transfusion (transfusion of their own stem cells). Patients 12 years of age or older with aplastic anemia who have been successfully treated with immunosuppressive drugs and are now in remission may be eligible for this study. Participants will undergo a complete history and physical examination, bone marrow biopsy (removal of a small sample of bone marrow from the hip bone) and blood tests, plus procedures to collect stem cells, as follows: -G-CSF (Filgrastim) administration - GCSF will be given by injection under the skin daily for up to 10 days. This drug causes stem cells to move from the marrow into the blood where they can be collected more easily. - Apheresis - Stem cells will be collected through apheresis, usually starting the 5th to 6th day of Filgrastin injections. For this procedure, whole blood is collected through a needle in an arm vein. The blood circulates through a cell separator machine where the white cells and stem cells are removed. The red cells, platelets and plasma are returned to the body through a second needle in the other arm. The procedure takes about 5 hours. Up to five procedures, done on consecutive days, may be required to collect enough cells for transplantation. If enough cells are collected, they will be purified (treated to remove the white blood cells) using an experimental device. Removing the lymphocytes may reduce the chance of relapse of aplastic anemia following the stem cell transplant. The stem cells will be frozen for later use, if needed. Follow-up - Participants are followed at NIH at 6-month intervals. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00011830
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Study of High Dose Cyclophosphamide in Patients with Severe Aplastic Anemia and Paroxysmal Nocturnal Hemoglobinuria Condition(s): Aplastic Anemia; Paroxysmal Hemoglobinuria, Nocturnal Study Status: This study is currently recruiting patients. Sponsor(s): Johns Hopkins Oncology Center
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Purpose - Excerpt: Objectives: I. Confirm the efficacy demonstrated in a pilot study using high dose cyclophosphamide in patients with severe aplastic anemia. II. Determine whether the addition of filgrastim (G-CSF) to high dose cyclophosphamide shortens the time to recovery in these patients. III. Determine whether this regimen is efficacious in treating paroxysmal nocturnal hemoglobinuria. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004464 •
T-cell Depleted Bone Marrow and G-CSF Stimulated Peripheral Stem Cell Transplantation From Related Donors in Treating Patients With Leukemia, Lymphoblastic Lymphoma, Myelodysplastic Syndrome, or Aplastic Anemia Condition(s): acute leukemia; atypical chronic myeloid leukemia; childhood lymphoblastic lymphoma; chronic leukemia; myelodysplastic and myeloproliferative disease; Non-Hodgkin's Lymphoma Study Status: This study is currently recruiting patients. Sponsor(s): Memorial Sloan-Kettering Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Bone marrow and peripheral stem cell transplantation may be able to replace immune cells that were destroyed by chemotherapy or radiation therapy used to kill cancer cells. PURPOSE: Phase II trial to study the effectiveness of Tcell depleted bone marrow and G-CSF stimulated peripheral stem cell transplantation in treating patients with leukemia, lymphoblastic lymphoma, myelodysplastic syndrome, or aplastic anemia. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00002718
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Umbilical Cord Blood and Placental Blood Transplantation in Treating Patients With Hematologic Cancer or Aplastic Anemia Condition(s): Langerhans cell histiocytosis; childhood Hodgkin's lymphoma; childhood non-Hodgkin's lymphoma; hematopoietic and lymphoid cancer Study Status: This study is currently recruiting patients. Sponsor(s): Herbert Irving Comprehensive Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Umbilical cord blood or placental blood transplantation may be able to replace immune cells that were destroyed by the chemotherapy or radiation therapy that was used to kill cancer cells. PURPOSE: Phase II trial to study the effectiveness of umbilical cord blood and placental blood transplantation in treating patients who have hematologic cancer or aplastic anemia. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00008164
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Umbilical Cord Blood Transplantation in Treating Patients With Severe Aplastic Anemia, Malignant Thymoma, or Myelodysplasia Condition(s): atypical chronic myeloid leukemia; myeloproliferative disease; Myelodysplastic Syndromes
myelodysplastic
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Study Status: This study is currently recruiting patients. Sponsor(s): Ireland Cancer Center; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Umbilical cord blood transplantation may allow doctors to give higher doses of chemotherapy or radiation therapy and kill more cancer cells. PURPOSE: Phase II trial to study the effectiveness of umbilical cord blood transplantation in treating patients who have severe aplastic anemia, malignantthymoma, or myelodysplasia. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00003336
Keeping Current on Clinical Trials The U.S. National Institutes of Health, through the National Library of Medicine, has developed ClinicalTrials.gov to provide current information about clinical research across the broadest number of diseases and conditions. The site was launched in February 2000 and currently contains approximately 5,700 clinical studies in over 59,000 locations worldwide, with most studies being conducted in the United States. ClinicalTrials.gov receives about 2 million hits per month and hosts approximately 5,400 visitors daily. To access this database, simply go to the Web site at http://www.clinicaltrials.gov/ and search by “aplastic anemia” (or synonyms). While ClinicalTrials.gov is the most comprehensive listing of NIH-supported clinical trials available, not all trials are in the database. The database is updated regularly, so clinical trials are continually being added. The following is a list of specialty databases affiliated with the National Institutes of Health that offer additional information on trials: •
For clinical studies at the Warren Grant Magnuson Clinical Center located in Bethesda, Maryland, visit their Web site: http://clinicalstudies.info.nih.gov/
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For clinical studies conducted at the Bayview Campus in Baltimore, Maryland, visit their Web site: http://www.jhbmc.jhu.edu/studies/index.html
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For cancer trials, visit the National Cancer Institute: http://cancertrials.nci.nih.gov/
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For eye-related trials, visit and search the Web page of the National Eye Institute: http://www.nei.nih.gov/neitrials/index.htm
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For heart, lung and blood trials, visit the Web page of the National Heart, Lung and Blood Institute: http://www.nhlbi.nih.gov/studies/index.htm
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For trials on aging, visit and search the Web site of the National Institute on Aging: http://www.grc.nia.nih.gov/studies/index.htm
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For rare diseases, visit and search the Web site sponsored by the Office of Rare Diseases: http://ord.aspensys.com/asp/resources/rsch_trials.asp
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For alcoholism, visit the National Institute on Alcohol Abuse and Alcoholism: http://www.niaaa.nih.gov/intramural/Web_dicbr_hp/particip.htm
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For trials on infectious, immune, and allergic diseases, visit the site of the National Institute of Allergy and Infectious Diseases: http://www.niaid.nih.gov/clintrials/
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For trials on arthritis, musculoskeletal and skin diseases, visit newly revised site of the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health: http://www.niams.nih.gov/hi/studies/index.htm
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For hearing-related trials, visit the National Institute on Deafness and Other Communication Disorders: http://www.nidcd.nih.gov/health/clinical/index.htm
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For trials on diseases of the digestive system and kidneys, and diabetes, visit the National Institute of Diabetes and Digestive and Kidney Diseases: http://www.niddk.nih.gov/patient/patient.htm
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For drug abuse trials, visit and search the Web site sponsored by the National Institute on Drug Abuse: http://www.nida.nih.gov/CTN/Index.htm
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For trials on mental disorders, visit and search the Web site of the National Institute of Mental Health: http://www.nimh.nih.gov/studies/index.cfm
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For trials on neurological disorders and stroke, visit and search the Web site sponsored by the National Institute of Neurological Disorders and Stroke of the NIH: http://www.ninds.nih.gov/funding/funding_opportunities.htm#Clinical_Trials
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CHAPTER 5. PATENTS ON APLASTIC ANEMIA Overview Patents can be physical innovations (e.g. chemicals, pharmaceuticals, medical equipment) or processes (e.g. treatments or diagnostic procedures). The United States Patent and Trademark Office defines a patent as a grant of a property right to the inventor, issued by the Patent and Trademark Office.9 Patents, therefore, are intellectual property. For the United States, the term of a new patent is 20 years from the date when the patent application was filed. If the inventor wishes to receive economic benefits, it is likely that the invention will become commercially available within 20 years of the initial filing. It is important to understand, therefore, that an inventor’s patent does not indicate that a product or service is or will be commercially available. The patent implies only that the inventor has “the right to exclude others from making, using, offering for sale, or selling” the invention in the United States. While this relates to U.S. patents, similar rules govern foreign patents. In this chapter, we show you how to locate information on patents and their inventors. If you find a patent that is particularly interesting to you, contact the inventor or the assignee for further information. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical patents that use the generic term “aplastic anemia” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on aplastic anemia, we have not necessarily excluded nonmedical patents in this bibliography.
Patents on Aplastic Anemia By performing a patent search focusing on aplastic anemia, 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 9Adapted
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 aplastic anemia: •
HMVAB41 Inventor(s): Gallagher; Kathleen Theresa (Willow Grove, PA), Hurle; Mark R (Norristown, PA), Kikly; Kristine Kay (Linfield, PA) Assignee(s): Smithkline Beecham Corporation (philadelphia, Pa) Patent Number: 5,932,446 Date filed: November 26, 1997 Abstract: HMVAB41 polypeptides and polynucleotides and methods for producing such polypeptides by recombinant techniques are disclosed. Also disclosed are methods for utilizing HMVAB41 polypeptides and polynucleotides in the design of protocols for the treatment of cancer, inflammation, autoimmunity, allergy, asthma, rheumatoid arthritis, CNS inflammation, cerebellar degeneration, Alzheimer's disease, Parkison's disease, multiple sclerosis, amylotrophic lateral sclerosis, head injury damage, and other neurological abnormalities, septic shock, sepsis, stroke, osteoporosis, osteoarthritis, ischemia reperfusion injury, cardiovascular disease, kidney disease, liver disease, ischemic injury, myocardial infarction, hypotension, hypertension, AIDS, myelodysplastic syndromes and other hematologic abnormalities, aplastic anemia, male pattern bladness, and bacterial, fungal, protozoan and viral infections, among others, and diagnostic assays for such conditions. Excerpt(s): This invention relates to newly identified polynucleotides, polypeptides encoded by them and to the use of such polynucleotides and polypeptides, and to their production, hereinafter referred to as HMVAB41. The invention also relates to inhibiting or activating the action of such polynucleotides and polypeptides. The drug discovery process is currently undergoing a fundamental revolution as it embraces `functional genomics`, that is, high throughput genome- or gene-based biology. This approach is rapidly superceding earlier approaches based on `positional cloning`. A phenotype, that is a biological function or genetic disease, would be identified and this would then be tracked back to the responsible gene, based on its genetic map position. Functional genomics relies heavily on the various tools of bioinformatics to identify gene sequences of potential interest from the many molecular biology databases now available. There is a continuing need to identify and characterise further genes and their related polypeptides/proteins, as targets for drug discovery. This indicates that HMVAB41 related genes have an established, proven history as therapeutic targets. Clearly there is a need for identification and characterization of further members of this family which can play a role in preventing, ameliorating or correcting dysfunctions or diseases, including, but not limited to, cancer, inflammation, autoimmunity, allergy, asthma, rheumatoid arthritis, CNS inflammation, cerebellar degeneration, Alzheimer's disease, Parkinson's disease, multiple sclerosis, amylotrophic lateral sclerosis, head injury damage, and other neurological abnormalities, septic shock, sepsis, stroke, osteoporosis, osteoarthritis, ischemia reperfusion injury, cardiovascular disease, kidney disease, liver disease, ischemic injury, myocardial infarction, hypotension, hypertension, AIDS, myelodysplastic syndromes and other hematologic abnormalities, aplastic anemia, male pattern baldness, and bacterial, fungal, protozoan and viral infections. Web site: http://www.delphion.com/details?pn=US05932446__
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•
Human requiem Inventor(s): Gross; Mitchell S (Wayne, PA), Hurle; Mark Robert (Norristown, PA), Kikly; Kristine Kay (Linfield, PA) Assignee(s): Smithkline Beecham Corporation (philadelphia, Pa) Patent Number: 5,919,660 Date filed: June 24, 1997 Abstract: Human REQUIEM polypeptides and DNA (RNA) encoding such REQUIEM and a procedure for producing such polypeptides by recombinant techniques is disclosed. Also disclosed are methods for utilizing such REQUIEM for the treatment of a susceptibility to viral infection, tumorogenesis and to diseases and defects in the control embryogenesis and tissue homeostasis, and the nucleic acid sequences described above may be employed in an assay for ascertaining such susceptibility. Antagonists against such REQUIEM and their use as a therapeutic to treat Alzheimer's disease, Parkinson's disease, rheumatoid arthritis, septic shock, sepsis, stroke, CNS inflammation, osteoporosis, ischemia reperfusion injury, cell death associated with cardiovascular disease, polycystic kidney disease, apoptosis of endothelial cells in cardiovascular disease, degenerative liver disease, MS, ALS, cererbellar degeneration, ischemic injury, myocardial infarction, AIDS, myelodysplastic syndromes, aplastic anemia, male pattern baldness, and head injury damage are also disclosed. Also disclosed are diagnostic assays for detecting diseases related to mutations in the nucleic acid sequences and altered concentrations of the polypeptides. Also disclosed are diagnostic assays for detecting mutations in the polynucleotides encoding REQUIEM polypeptide and for detecting altered levels of the polypeptide in a host. Excerpt(s): This invention relates, in part, to newly identified polynucleotides and polypeptides; variants and derivatives of the polynucleotides and polypeptides; processes for making the polynucleotides and the polypeptides, and their variants and derivatives; agonists and antagonists of the polypeptides; and uses of the polynucleotides, polypeptides, variants, derivatives, agonists and antagonists. In particular, in these and in other regards, the invention relates to polynucleotides and polypeptides of a human homologue of murine requiem gene, hereinafter referred to as "REQUIEM". Hematopoietic stem cell proliferation, differentiation and apoptosis, are regulated by various growth factors and cytokines (Metcalf, D., Science 254, 529-531 (1992) and Vaux et al., Nature 335, 440-442 (1988)). Such cells committed to the myeloid lineage express high affinity receptors for GM-CSF1 and IL-3 (Miyajima et al., Blood 82,1960-1973 (1993)). Moreover, such cells develop a requirement for GM-CSF or IL-3 to survive and undergo apoptosis in response to GM-CSF or IL-3 deprivation (Williams et al., Nature 343, 76-79 (1990)). Hematopoietic cells are not unique in their requirement for growth factors for survival. Throughout development, cells of all lineages require proper signals to grow and differentiate. Failure to receive these signals often results in death of the cells by apoptosis. Even in the adult organism there is constant renewal and/or maintence of cells that requires growth factors and cytokines. Inappropriate cessation of signals from these growth factors may result in apoptosis thereby causing disfunction or disease. Web site: http://www.delphion.com/details?pn=US05919660__
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Human SDR2 cDNA clone Inventor(s): Albone; Earl Francis (Conshohocken, PA), Kikly; Kristine Kay (Linfield, PA) Assignee(s): Smithkline Beecham Corporation (philadelphia, Pa) Patent Number: 6,090,579 Date filed: December 16, 1997 Abstract: SDR2 polypeptides and polynucleotides and methods for producing such polypeptides by recombinant techniques are disclosed. Also disclosed are methods for utilizing SDR2 polypeptides and polynucleotides in the design of protocols for the treatment of cancer, inflammation, autoimmunity, allergy, asthma, rheumatoid arthritis, CNS inflamation, cerebellar degeneration, Alzheimer's disease, Parkinsons disease, multiple sclerosis, amylotrophic lateral sclerosis, head injury damage, and other neurological abnormalities, septic shock, sepsis, stroke, osteoporosis, osteoarthritis, ischemia reperfusion injury, cardiovascular disease, kidney disease, liver disease, ischemic injury, myocardial infarction, hypotension, hypertension, AIDS, myelodysplastic syndromes and other hematologic abnormalities, aplastic anemia, male pattern baldness, and bacterial, fungal, protozoan and viral infections, among others, and diagnostic assays for such conditions. Excerpt(s): This invention relates to newly identified polynucleotides, polypeptides encoded by them and to the use of such polynucleotides and polypeptides, and to their production. More particularly, the polynucleotides and polypeptides of the present invention relate to 6-TM family, hereinafter referred to as SDR2 (stromal-cell derived receptor). The invention also relates to inhibiting or activating the action of such polynucleotides and polypeptides. Murine SDR2 was cloned from a bone marrow stromal cell line using a signal sequence trap method (Shirozu, M., et al., Genomics 37:273-280, 1996). Murine SDR2 contains a signal sequence and has six putative transmembrane spanning domains. Other six transmembrane spanning proteins function as ion transporters (Becker, D., et al., PNAS 93:8123-8128, 1996), water channel proteins (Misaka, T., et al., FEBS Lett. 381:208-212, 199; Jung, J. S., et al., PNAS 91:1305213056, 1994), iron transporters (Dix, D. R., et al., JBC 269:26092-26099, 1994) or have been linked to cellular activation and division (Gaugitsch, H. W., et al., JBC 267:11267-11273, 1992). This indicates that the 6-TM family has an established, proven history as therapeutic targets. Clearly there is a need for identification and characterization of further members of 6-TM family which can play a role in preventing, ameliorating or correcting dysfunctions or diseases, including, but not limited to, cancer, inflammation, autoimmunity, allergy, asthma, rheumatoid arthritis, CNS inflammation, cerebellar degeneration, Alzheimer's disease, Parkinson's disease, multiple sclerosis, amylotrophic lateral sclerosis, head injury damage, and other neurological abnormalities, septic shock, sepsis, stroke, osteoporosis, osteoarthritis, ischemia reperfusion injury, cardiovascular disease, kidney disease, liver disease, ischemic injury, myocardial infarction, hypotension, hypertension, AIDS, myelodysplastic syndromes and other hematologic abnormalities, aplastic anemia, male pattern baldness, and bacterial, fungal, protozoan and viral infections. In one aspect, the invention relates to SDR2 polypeptides and recombinant materials and methods for their production. Another aspect of the invention relates to methods for using such SDR2 polypeptides and polynucleotides. Such uses include the treatment of cancer, inflammation, autoimmunity, allergy, asthma, rheumatoid arthritis, CNS inflammation, cerebellar degeneration, Alzheimer's disease, Parkinson's disease, multiple sclerosis, amylotrophic lateral sclerosis, head injury damage, and other neurological abnormalities, septic shock, sepsis, stroke, osteoporosis, osteoarthritis, ischemia reperfusion injury, cardiovascular disease, kidney
Patents 111
disease, liver disease, ischemic injury, myocardial infarction, hypotension, hypertension, AIDS, myelodysplastic syndromes and other hematologic abnormalities, aplastic anemia, male pattern baldness, and bacterial, fungal, protozoan and viral infections, among others. In still another aspect, the invention relates to methods to identify agonists and antagonists using the materials provided by the invention, and treating conditions associated with SDR2 imbalance with the identified compounds. Yet another aspect of the invention relates to diagnostic assays for detecting diseases associated with inappropriate SDR2 activity or levels. Web site: http://www.delphion.com/details?pn=US06090579__ •
Interleukin-1.beta. converting enzyme like apoptotic protease-6 Inventor(s): Dixit; Vishva M. (AnnArbor, MI), He; Wei-Wu (Columbia, MD), Kikly; Kristine K. (Linfield, PA), Ruben; Steven M. (Olney, MD) Assignee(s): Smithkline Beecham Corporation (philadelphia, Pa) Patent Number: 6,010,878 Date filed: May 8, 1997 Abstract: Human ICE LAP-6 polypeptides and DNA (RNA) encoding such ICE LAP-6 and a procedure for producing such polypeptides by recombinant techniques is disclosed. Also disclosed are methods for utilizing such ICE LAP-6 for the treatment of a susceptibility to viral infection, tumorogenesis and to diseases and defects in the control embryogenesis and tissue homeostasis, and the nucleic acid sequences described above may be employed in an assay for ascertaining such susceptibility. Antagonists against such ICE LAP-6 and their use as a therapeutic to treat Alzheimer's disease, Parkinson's disease, rheumatoid arthritis, septic shock, sepsis, stroke, chronic inflammation, acute inflammation, CNS inflammation, osteoporosis, ischemia reperfusion injury, cell death associated with cardiovascular disease, polycystic kidney disease, apoptosis of endothelial cells in cardiovascular disease, degenerative liver disease, MS, ALS, cererbellar degeneration, ischemic injury, myocardial infarction, AIDS, myelodysplastic syndromes, aplastic anemia, male pattern baldness, and head injury damage are also disclosed. Also disclosed are diagnostic assays for detecting diseases related to mutations in the nucleic acid sequences and altered concentrations of the polypeptides. Also disclosed are diagnostic assays for detecting mutations in the polynucleotides encoding the interleukin-1 beta converting enzyme apoptosis proteases and for detecting altered levels of the polypeptide in a host. Excerpt(s): This invention relates, in part, to newly identified polynucleotides and polypeptides; variants and derivatives of the polynucleotides and polypeptides; processes for making the polynucleotides and the polypeptides, and their variants and derivatives; agonists and antagonists of the polypeptides; and uses of the polynucleotides, polypeptides, variants, derivatives, agonists and antagonists. In particular, in these and in other regards, the invention relates to polynucleotides and polypeptides of human interleukin-1 beta converting enzyme apoptosis protease-6, hereinafter referred to as "ICE LAP-6". It has recently been discovered that an interleukin-1.beta. converting enzyme (ICE) is responsible for cleaving pro-IL-1.beta. into mature and active IL-1.beta. and is also responsible for programmed cell death (or apoptosis), which is a process through which organisms get rid of unwanted cells. In the nematode Caenorhabditis elegans, a genetic pathway of programmed cell death has been identified (Ellis, R. E., et al. Annu. Rev. Cell Biol., 7:663-698 (1991)). Two genes, ced-3 and ced-4, are essential for cells to undergo programmed cell death in C. elegans
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(Ellis, H. M., and Horvitz, H. R., Cell, 44:817-829 (1986)). It is becoming apparent that a class of cysteine proteases homologous to Caenorhabditis elegans Ced-3 play the role of "executioner" in the apoptotic mechanism (Martin, S. J., and Green, D. R. (1995) Cell 82, 349-352; Chinnaiyan, A. a. D., VM. (1996) Current Biology 6; Henkart, P. (1996) Immunity 4, 195-201). Recessive mutations that eliminate the function of these two genes prevent normal programmed cell death during the development of C. elegans. The known vertebrate counterpart to ced-3 protein is ICE. The overall amino acid identity between ced-3 and ICE is 28%, with a region of 115 amino acids (residues 246360 of ced-3 and 164-278 of ICE) that shows the highest identity (43%). This region contains a conserved pentapeptide, QACRG (SEQ ID NO:10) (residues 356-360 of ced-3), which contains a cysteine known to be essential for ICE function. Web site: http://www.delphion.com/details?pn=US06010878__ •
Interleukin-1 beta converting enzyme like apoptotic protease-7 Inventor(s): Dixit; Vishva M. (Ann Arbor, MI), Kikly; Kristine K. (Linfield, PA), Ni; Jian (Rockville, MD), Rosen; Craig A. (Laytonsville, MD), Ruben; Steven M. (Olney, MD) Assignee(s): Human Genome Sciences, Inc. (rockville, Md), Smithkline Beecham Corporation (philadelphia, Pa), The Regents of the University of Michigan (ann Arbor, Mi) Patent Number: 6,008,042 Date filed: May 7, 1997 Abstract: Human ICE LAP-7 polypeptides and DNA (RNA) encoding such ICE LAP-7 and a procedure for producing such polypeptides by recombinant techniques is disclosed. Also disclosed are methods for utilizing such ICE LAP-7 for the treatment of a susceptibility to viral infection, tumorogenesis and to diseases and defects in the control embryogenesis and tissue homeostasis, and the nucleic acid sequences described above may be employed in an assay for ascertaining such susceptibility. Antagonists against such ICE LAP-7 and their use as a therapeutic to treat Alzheimer's disease, Parkinson's disease, rheumatoid arthritis, septic shock, sepsis, stroke, chronic inflammation, acute inflammation, CNS inflammation, osteoporosis, ischemia reperfusion injury, cell death associated with cardiovascular disease, polycystic kidney disease, apoptosis of endothelial cells in cardiovascular disease, degenerative liver disease, MS, ALS, cererbellar degeneration, ischemic injury, myocardial infarction, AIDS, myelodysplastic syndromes, aplastic anemia, male pattern baldness, and head injury damage are also disclosed. Also disclosed are diagnostic assays for detecting diseases related to mutations in the nucleic acid sequences and altered concentrations of the polypeptides. Also disclosed are diagnostic assays for detecting mutations in the polynucleotides encoding the interleukin-1 beta converting enzyme apoptosis proteases and for detecting altered levels of the polypeptide in a host. Excerpt(s): Apoptosis, or programmed cell death (PCD), is a genetically regulated mechanism with a central role in both metazoan development and homeostasis. (Raff, 1992; Steller, 1995). The cell death machinery is conserved throughout evolution (Vaux et al., 1994) and is composed of several distinct parts including effectors, inhibitors and activators (Chinnaiyan and Dixit, 1996; Steller, 1995). Invertebrate model systems have been invaluable in identifying and characterizing the genes that control apoptosis. (Hengartner, 1996). While numerous candidate genes have been identified, how they interact to execute the apoptotic program is poorly understood. It is becoming apparent that cysteine proteases related to the Caenorhabditis elegans cell death gene ced-3
Patents 113
represent the effector components of the apoptotic machinery. The first mammalian homolog of CED-3 identified was interleukin-1.beta. converting enzyme (ICE). (Yuan et al., 1993). Overexpression of ICE or CED-3 in Rat-1 fibroblasts induced apoptosis, suggesting that ICE was functionally, as well as structurally, related to CED-3. (Miura et al., 1993). However, such evidence is only a correlation, as ectopic expression of a number of proteases, including chymotrypsin, proteinase K and trypsin, cause significant apoptosis. (Williams and Henkart, 1994). Further studies suggested that proteases related to ICE, rather than ICE itself, may play a more important role in the apoptotic mechanism. First, a number of cell types stably secrete mature IL-1.beta. without undergoing apoptosis. Second, ICE-deficient mice, although unable to generate active IL-1.beta., fail to exhibit a prominent cell death defective phenotype,(Kuida et al., 1995; Li et al., 1995). Third, in an in vitro model of apoptosis, condemned phase extracts prepared from chicken DU249 cells failed to cleave the primary substrate of ICE, pro-IL1b. (Lazebnik et al., 1994). Instead, a proteolytic activity in these extracts, termed prICE, cleaved the DNA repair enzyme poly (ADP-ribose) polymerase (PARP) into signature apoptotic fragments. (Lazebnik et al., 1994). Purified ICE failed to cleave PARP (Lazebnik et al., 1994; Tewari et al., 1995), suggesting that prICE was distinct from ICE. Web site: http://www.delphion.com/details?pn=US06008042__ •
Treatment of aluimmunization and refractoriness to platelet transfusion by protein A column therapy Inventor(s): Christie; Douglas J. (St. Paul, MN), Howe; Robert B. (Wayzata, MN) Assignee(s): Regents of the University of Minnesota (minneapolis, Mn) Patent Number: 5,277,701 Date filed: November 15, 1991 Abstract: The invention provides a therapeutic method for treating refractoriness to platelet transfusion by isolating blood serum from an alloimmunized patient undergoing platelet transfusion therapy, passing the serum through a bed comprising staphococcal protein A coupled to a solid support and returning the treated plasma to the patient. The method can be conducted by batch-type procedure or by continuously conducting the steps so that blood is withdrawn, passed through the bed, and returned to the patient as a continuous stream. The method is useful to treat alloimmunized patients suffering from leukemia, aplastic anemia, myelofibrosis, myelodysplastic syndrome, or in a bone marrow transplant patient. Excerpt(s): Refractoriness to platelet transfusion (RPT) is a serious complication of leukemia therapy, bone marrow transplantation, and other disorders where multiple infusions of platelets are required to prevent bleeding. Alloimmunization to HLA class I antigens is an important cause of RPT, with some estimates as high as 50-70% of patients receiving multiple platelet transfusions becoming alloimmunized to HLA antigens. (P. Daly et al., JAMA, 253:435 (1980); D. Hogge et al., Am. J. Hematol., 14:363 (1983); R. Kakaiya et al., Transfusion, 24:35 (1984); J. Eernisse et al., Exp. Hematol., 9:77 (1981); M. Murphy et al., Brit. J. Haematol., 60:409 (1985); and M. Murphy et al., Brit. J. Haematol., 62:529 (1986).) Additionally, antibodies directed against platelet-specific antigens, such as HPA-1a(=P1.sup.A1)*, HPA-1b(=P1.sup.A2) and HPA-3a(=Bak.sup.a), HPA2b(=Sib.sup.a), Nak.sup.a, and Gov.sup.a /Gov.sup.b have also been implicated in platelet transfusion failure. (R. Kickler et al., Transfusion, 30:622 (1990); F. Langenscheidt et al., Transfusion, 28:597 (1988); H. Saji et al., Vox Sang, 56:283 (1989), H. Ikeda et al., Vox Sang, 57:213 (1989); and J. Kelton et al., Blood, 75:2172 (1990).)
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Moreover, drug-dependent antibodies induced by vancomycin were recently found in association with RPT in two patients with leukemia. (D. Christie et al., Blood, 75:518 (1990).) Thus, it is apparent that a wide variety of different antibodies may contribute to shortened survival of transfused platelets. Standard transfusion strategies generally recommend that patients first receive pooled random donor platelets, followed by random single donor and HLA-matched single donor platelets once alloimmunization occurs. (J. Herman et al., Am. J. Ped. Hematol./Oncol., 9:272 (1987)). Although steroids, splenectomy, immunosuppressive therapy, IV IgG, and plasmapheresis have often proved successful in treating autoimmune thrombocytopenia (ATP), they have for the most part been ineffective in reducing RPT due to alloimmunization. (J. Herman et al., Am. J. Ped. Hematol./Oncol., 9:272 (1987); D. Hogge et al., Blood, 64:253 (1984); C. Schiffer et al., Blood, 64:937 (1984); and W. Bensinger et al., Transplantation, 41:602 (1986).) Several reports have shown marked increases in platelet counts in patients with ATP following reinfusion of autologous plasma that had been absorbed by immobilized protein A. (T. Guthrie et al, Sem. Hematol., 26(Suppl 1):3 (1989); K. Muroi et al., Sem. Hematol., 26(Suppl 1):10 (1989); A. Mittleman et al., Sem. Hematol., 26(Suppl 1):15 (1989); and H. Snyder, Jr. et al., Artif. Organ, 13:71 (1989).) In the present study, we investigated the effectiveness of protein A column therapy for improving platelet counts and transfusion refractoriness in 12 thrombocytopenic patients with histories of being unresponsive to platelet transfusion therapy. A therapeutic method is provided for treating refractoriness to platelet transfusion (RTP) in alloimmunized patients undergoing platelet transfusion therapy which permits the patients to sustain higher average daily platelet counts (2-10X higher than pretreatment) and to exhibit improved responsiveness to both random and HLA-matched platelet transfusion. The present method also decreases circulating platelet antibodies, which are responsible for alloimmunization. Web site: http://www.delphion.com/details?pn=US05277701__
Patent Applications on Aplastic Anemia As of December 2000, U.S. patent applications are open to public viewing.10 Applications are patent requests which have yet to be granted. (The process to achieve a patent can take several years.) The following patent applications have been filed since December 2000 relating to aplastic anemia: •
Androgen receptor modulators and methods for use thereof Inventor(s): Breslin, Michael J.; (Drexel Hill, PA), Duggan, Mark E.; (Schwenksville, PA), Halczenko, Wasyl; (Lansdale, PA), Harada, Shun-Ichi; (Ambler, PA), Hutchinson, John H.; (La Jolla, CA), Rodan, Gideon A.; (Bryn Mawr, PA), Sahoo, Soumya P.; (Old Bridge, NJ), Schmidt, Azriel; (Bryn Mawr, PA), Towler, Dwight A.; (Brentwood, MO) Correspondence: Merck And CO Inc; P O Box 2000; Rahway; NJ; 070650907 Patent Application Number: 20030065004 Date filed: July 25, 2002 Abstract: Compounds of structural formula (I) as herein defined are disclosed as useful in a method for modulating the androgen receptor in a tissue selective manner in a patient in need of such modulation, as well as in a method of agonizing the androgen
10
This has been a common practice outside the United States prior to December 2000.
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receptor in a patient, and in particular the method wherein the androgen receptor is antagonized in the prostate of a male patient or in the uterus of a female patient and agonized in bone and/or muscle tissue. These compounds are useful in the treatment of conditions caused by androgen deficiency or which can be ameliorated by androgen administration, including: osteoporosis, periodontal disease, bone fracture, bone damage following bone reconstructive surgery, sarcopenia, frailty, aging skin, male hypogonadism, post-menopausal symptoms in women, atherosclerosis, hypercholesterolemia, hyperlipidemia, aplastic anemia and other hematopoietic disorders, pancreatic cancer, renal cancer, arthritis and joint repair, alone or in combination with other active agents. In addition, these compounds are useful as pharmaceutical composition ingredients alone and in combination with other active agents. Excerpt(s): The present application claims priority of U.S. provisional application Serial No. 60/308,841, filed Jul. 31, 2001. Androgens play important roles in post-natal development that are most pronounced at adrenarche and pubarche. Androgen production promotes the musculoskeletal anabolism associated with the pubertal growth in both males and females. At puberty, ovarian and testicular androgens are responsible for pubertal hair, acne, and enhancement of libido. In males, exposure to 100-fold increased levels of endogenous androgens results in the gender dimorphism in bone mass, muscle mass (positive nitrogen balance), and upper body strength, and are required for normal sexual development (genitalia, spermatogenesis, prostate and seminal vesicle maturation). Delay in puberty decreases the peak bone mass achieved during adulthood. (Bhasin, S., et al., Eds. Pharmacology, Biology, and Clinical Applications of Androgens: Current Status and Future Prospects. Wiley-Liss, Inc.:New York, 1996). In women, natural menopause causes virtually complete loss of ovarian estrogen production and gradually reduces ovarian production of androgen by approximately 50%. The physiological consequences of reduced androgen production after menopause are evident in decreased energy and libido, and contribute significantly in many women to vasomotor symptoms. Decreased androgen output is also thought to contribute--along with declining pituitary growth hormone (GH) secretion and insulin derived growth factor 1 (IGF1) action--to age-dependent sarcopenia, negative nitrogen balance and loss of bone mass. (Vestergaard, et al., Effect of sex hormone replacement on the insulin-like growth factor system and bone mineral: a cross-sectional and longitudinal study in 595 perimenopausal women participating in the Danish Osteoporosis Prevention Study, J Clin Endocrinol Metab. 84:2286-90, 1999; and Bhasin, et al., Eds. Pharmacology, Biology, and Clinical Applications of Androgens: Current Status and Future Prospects, Wiley-Liss, Inc.:New York. 1996). Postmenopausal osteoporosis results mainly from estrogen deficiency. However, many women who received estrogen replacement therapy still lose bone with age and develop age--related osteoporotic fractures (albeit at a lower rate than those taking estrogens), indicating that both estrogens and androgens play important roles for bone health in both women and men. The simultaneous decreases in bone mass, muscle mass and muscle strength increase the risk of falls and especially of hip fractures in both men and women >65 years of age. In fact, one-third of all hip fractures occur in men. The androgen receptor (AR) belongs to the nuclear receptor superfamily and controls transcription in a ligand dependent manner (Brinkman, et al., Mechanisms of androgen receptor activation and function, J. Ster. Biochem. Mol. Biol. 69, 307-313, 1999). Upon androgen binding, AR binds directly to specific DNA sequences present in the promoter region of androgen responsive genes, termed androgen response elements (AREs), to stimulate transcription. Using ARE-dependent transcription as a criterion, agents that bind to AR and stimulate ARE-dependent transcription can be classified as agonists, and those that
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bind to AR and suppress ARE-dependent transcription are classified as antagonists. A number of natural or synthetic androgen agonists have been used for treatment of musculoskeletal or hematopoietic disorders and for hormone replacement therapy. In addition, AR antagonists, such as flutamide or bicalutamide, are used for treatment of prostate cancer. However, clinical use of these androgen agonists or antagonists have been limited because of undesirable effects, such as hirsutism and prostate enlargement for agonists, and bone loss, fracture, gynecomastia and sarcopenia for antagonists. It would be useful to have available androgens with tissue selective agonistic activity, which increase bone formation and muscle mass but do not induce the virilization. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Stimulation of hematopoiesis by ex vivo activated immune cells Inventor(s): Yang, Demao; (Mountain View, CA) Correspondence: Patterson, Thuente, Skaar & Christensen, P.A.; 4800 Ids Center; 80 South 8th Street; Minneapolis; MN; 55402-2100; US Patent Application Number: 20030223968 Date filed: May 29, 2002 Abstract: A protocol of activating and administering human blood cells so that bone marrow histology and/or blood cell counts of patients suffering from aplastic anemia approach normal. The protocol includes culturing the blood cells in the presence of a cytokine and an ionophore. It is emphasized that this abstract is provided to comply with the rules requiring an abstract that will allow a searcher or other reader to quickly ascertain the subject matter of the technical disclosure. It is submitted with the understanding that it will not be used to interpret or limit the scope or meaning of the claims. 37 C.F.R.sctn. 1.72(b). Excerpt(s): This invention relates to therapies for aplastic anemia, anemia and thrombocytopenic purpura. In particular, this invention relates to ex vivo activated immune cells as therapies for aplastic anemia, anemia and thrombocytopenic purpura. Furthermore, the invention relates to approaches to activate cells and corresponding cell culture approaches. Aplastic anemia is a disease characterized by ineffective hematopoiesis. Patients have varying degrees of abnormalities in production of all blood cell types. Although in most cases, the cause of the disease is unknown, radiation, benzene-based compounds, viruses (e.g., hepatitis), environmental toxins, and over the counter and prescription medications have been suspected to damage bone marrow, thereby leading to apoptosis of marrow stem cells. Regardless of the underlying causes, patients show similar clinical manifestations and disease progression courses. Aplastic anemia affects primarily young man and older persons of both the genders. Annually, two to six per million worldwide develop this disorder, with a prevalence of incidences in the Orient as compared to Europe or the United States. Several causal phenomena are hypothesized for aplastic anemia: congenital, pregnancy, viral, and drugs and chemicals. The most frequently cited causal agent of aplastic anemia is drugs or chemical exposure. Some agents, such as chloramphenicol, benzene, ionizing radiation, and antineoplastic agents, cause an aplasia that is dose-related in severity from personto-person. In these cases, marrow recovery usually occurs after withdrawal of the causal agent. Other agents, including pesticides and some anticonvulsants and antimicrobials, cause a reaction which is not dose-related and, therefore, cannot be predicted with hematological monitoring during administration. During administration of drugs, aplasias may occur even after cessation of drug therapy. In contrast to patients with
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idiopathic aplastic anemia, those with drug or toxin exposure exhibit similar clinical and demographic characteristics, have a similar prognosis, and a more-or-less uniform response to therapy. 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 aplastic anemia, 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 “aplastic anemia” (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 aplastic anemia. You can also use this procedure to view pending patent applications concerning aplastic anemia. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.
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CHAPTER 6. BOOKS ON APLASTIC ANEMIA Overview This chapter provides bibliographic book references relating to aplastic anemia. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on aplastic anemia 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 “aplastic anemia” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “aplastic anemia” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “aplastic anemia” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •
Aplastic Anemia : Pathophysiology and Treatment by Hubert Schrezenmeier (Editor), Andrea Bacigalupo (Editor); ISBN: 0521641012; http://www.amazon.com/exec/obidos/ASIN/0521641012/icongroupinterna
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Aplastic Anemia and Other Bone Marrow Failure Syndromes by Nasrollah T. Shahidi (Editor); ISBN: 0387970304; http://www.amazon.com/exec/obidos/ASIN/0387970304/icongroupinterna
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Aplastic Anemia and Other Bone Marrow Failure Syndromes; ISBN: 3540970304; http://www.amazon.com/exec/obidos/ASIN/3540970304/icongroupinterna
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Aplastic Anemia: Acquired and Inherited by Neal S. Young, Blanche P. Alter (Contributor); ISBN: 0721637027; http://www.amazon.com/exec/obidos/ASIN/0721637027/icongroupinterna
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Aplastic Anemia: Pathophysiology and Approaches to Therapy by Hermann Heimpel; ISBN: 0387097724; http://www.amazon.com/exec/obidos/ASIN/0387097724/icongroupinterna
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Aplastic Anemia: Stem Cell Biology and Advances in Treatment: Proceedings of the Third International Conference on Aplastic Anemia by International Conference on Aplastic Anemia, et al; ISBN: 0471834394; http://www.amazon.com/exec/obidos/ASIN/0471834394/icongroupinterna
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Ontogeny of Hematopoiesis, Aplastic Anemia by E. Gluckman (Editor), L. Coulombel (Editor); ISBN: 2855986265; http://www.amazon.com/exec/obidos/ASIN/2855986265/icongroupinterna
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Refractory anemia by Lawrence Kass; ISBN: 0398033412; http://www.amazon.com/exec/obidos/ASIN/0398033412/icongroupinterna
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The Drug Etiology of Agranulocytosis and Aplastic Anemia (Monographs in Epidemiology and Biostatistics, Vol. 18) by David W. Kaufman, et al; ISBN: 0195059832; http://www.amazon.com/exec/obidos/ASIN/0195059832/icongroupinterna
Chapters on Aplastic Anemia In order to find chapters that specifically relate to aplastic anemia, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and aplastic anemia 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 “aplastic anemia” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on aplastic anemia: •
Anaemia Source: in Scully, C. and Cawson, R.A. Medical Problems in Dentistry. 4th ed. Woburn, MA: Butterworth-Heinemann. 1998. p. 106-122. Contact: Available from Butterworth-Heinemann. 225 Wildwood Avenue, Woburn, MA 01801-2041. (800) 366-2665 or (781) 904-2500. Fax (800) 446-6520 or (781) 933-6333. E-mail:
[email protected]. Website: www.bh.com. PRICE: $110.00. ISBN: 0723610568. Summary: Anemia is not a disease in itself but may be a feature of many diseases. The essential feature of anemia is a hemoglobin level below normal for the age and sex of the patient. This chapter on anemia is from a text that covers the general medical and surgical conditions relevant to the oral health care sciences. Topics include the classification of anemias, laboratory investigations, general dental aspects of anemia, iron deficiency anemia, Vitamin B12 (cobalamin) deficiency, pernicious (Addisonian) anemia, folate (folic acid) deficiency, anemia associated with systemic disease, aplastic anemia, hemolytic anemia, sickle cell disease, the thalassemias, erythrocyte membrane defects, erythrocyte metabolic defects, and acquired hemolytic anemia. For each disorder, the authors discuss general aspects, diagnosis and management issues, dental aspects, and patient care strategies. The chapter includes a lengthy summary of the points covered. 1 appendix. 2 figures. 12 tables. 49 references.
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Orofacial Lesions in Major Medical Conditions Source: in Scully, C., et al. Color Atlas of Orofacial Health and Disease in Children and Adolescents. London, England: Martin Dunitz Ltd. 2002. p.201-224. Contact: Available from Martin Dunitz Ltd, The Livery House. 7-9 Pratt Street, London, England NW1 0AE. 4404074822202. Website: www.dunitz.co.uk. Email:
[email protected]. PRICE: $125.00 plus shipping and handling. ISBN: 1841841021. Summary: Orofacial lesions can be seen in many medical and surgical conditions, but this chapter highlights those most commonly seen in pediatric dental practice. These are mainly seen in immunocompromised patients or those with hemato-oncological problems. Oral diseases tend to be more frequent where poor oral hygiene, malnutrition, and tobacco use are present. The chapter is from a full-color atlas that covers the presentation of the common orofacial disorders and a wide range of less common and some rare disorders. Topics include AIDS and HIV-related disease, aplastic anemia, bone marrow transplantation, cerebral palsy, chemotherapy, congenital immunodeficiencies, cystic fibrosis, Down syndrome, Fallot's tetralogy, hemophilias, hyperparathyroidism, immunosuppressed patients, leukemias, learning disability, malnutrition, radiotherapy, solid organ transplantation, thrombocytopathy, and vitamin deficiencies. Full-color photographs are accompanied by brief text entries describing each condition and noting diagnostic and management considerations for each. 72 figures. 1 table.
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Gastrointestinal Complications in Stem Cell Transplantation Source: in Bayless, T.M. and Hanauer, S.B. Advanced Therapy of Inflammatory Bowel Disease. Hamilton, Ontario: B.C. Decker Inc. 2001. p. 649-654. Contact: Available from B.C. Decker Inc. 20 Hughson Street South, P.O. Box 620, L.C.D. 1 Hamilton, Ontario L8N 3K7. (905) 522-7017 or (800) 568-7281. Fax (905) 522-7839. Email:
[email protected]. Website: www.bcdecker.com. PRICE: $129.00 plus shipping and handling. ISBN: 1550091220. Summary: Stem cell transplantation (SCT) is the standard of care for the treatment of many hematologic (blood) malignancies, pediatric solid tumors, inherited disorders, and aplastic anemia (a deficiency of all the formed elements of blood). SCT also is being used to treat many autoimmune disorders in experimental situations. This chapter on gastrointestinal complications in SCT is from the second edition of a book devoted to the details of medical, surgical, and supportive management of patients with Crohn's disease (CD) and UC, together known as inflammatory bowel disease (IBD). Several patients with CD and leukemia have remitted or remained in remission after bone marrow transplantation. Complications related to SCT are becoming more widely recognized. Gastrointestinal complications of SCT result from preparative regimen toxicity, infection, and acute and chronic graft-versus-host (GVH) disease, which may be difficult to diagnostically separate and are therefore addressed in this chapter. Diarrhea related to toxicity induced by the preoperative regimen may last until day 15 after SCT. Infectious causes of diarrhea must be considered and can include bacterial and viral pathogens. Once infectious causes are ruled out, antidiarrheal agents (such as loperamide) may be initiated. Nausea, vomiting, and anorexia occur commonly during the preparative regimen; if they are severe, total parenteral (outside the GI tract) nutrition (TPN) must be used. At its simplest level, GVH disease arises from the recipient's immune recognition of minor antigenic differences between donor and recipient. Patients with gut GVH disease present with abdominal pain, nausea, and
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vomiting or diarrhea. The physical examination and history may include a rash on the hands, feet, and ears. In addition, significant GI bleeding may occur post transplant and contribute to higher mortality associated with SCT. 4 figures. 10 references.
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CHAPTER 7. PERIODICALS AND NEWS ON APLASTIC ANEMIA Overview In this chapter, we suggest a number of news sources and present various periodicals that cover aplastic anemia.
News Services and Press Releases One of the simplest ways of tracking press releases on aplastic anemia 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 “aplastic anemia” (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 aplastic anemia. 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 “aplastic anemia” (or synonyms). The following was recently listed in this archive for aplastic anemia: •
Immunosuppressive therapy for aplastic anemia often produces excellent results Source: Reuters Industry Breifing Date: March 06, 2003
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Low-dose cyclosporine effective in treating severe aplastic anemia Source: Reuters Industry Breifing Date: October 25, 2001
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High-dose cyclophosphamide shows promise as aplastic anemia treatment Source: Reuters Industry Breifing Date: October 01, 2001
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Aplastic anemia responds to drug treatment alone Source: Reuters Health eLine Date: October 01, 2001
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Bone marrow transplant is first choice for children with severe aplastic anemia Source: Reuters Medical News Date: December 12, 2000
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High-dose cyclophosphamide too toxic for patients with aplastic anemia Source: Reuters Industry Breifing Date: November 07, 2000
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Case Of Aplastic Anemia Induced By Fluoxetine Identified Source: Reuters Medical News Date: April 07, 1998
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Aplastic Anemia Linked To Prozac Source: Reuters Health eLine Date: April 07, 1998
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Hepatitis-Associated Aplastic Anemia Has Immunopathologic Etiology Source: Reuters Medical News Date: April 11, 1997
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Aplastic Anemia Linked To Fumes From Burning Oil: A Case Report Source: Reuters Medical News Date: July 19, 1995
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Combination Therapy Effective In Patients With Severe Aplastic Anemia Source: Reuters Medical News Date: June 05, 1995 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.
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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 “aplastic anemia” (or synonyms) into the search box, and click on “Search News.” As this service is technology oriented, you may wish to use it when searching for press releases covering diagnostic procedures or tests. Search Engines Medical news is also available in the news sections of commercial Internet search engines. See the health news page at Yahoo (http://dir.yahoo.com/Health/News_and_Media/), or you can use this Web site’s general news search page at http://news.yahoo.com/. Type in “aplastic anemia” (or synonyms). If you know the name of a company that is relevant to aplastic anemia, 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 “aplastic anemia” (or synonyms).
Academic Periodicals covering Aplastic Anemia Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to aplastic anemia. In addition to these sources, you can search for articles covering aplastic anemia 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 8. 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 aplastic anemia. One such source is the United States Pharmacopeia. In 1820, eleven physicians met in Washington, D.C. to establish the first compendium of standard drugs for the United States. They called this compendium the U.S. Pharmacopeia (USP). Today, the USP is a non-profit organization consisting of 800 volunteer scientists, eleven elected officials, and 400 representatives of state associations and colleges of medicine and pharmacy. The USP is located in Rockville, Maryland, and its home page is located at http://www.usp.org/. The USP currently provides standards for over 3,700 medications. The resulting USP DI® Advice for the Patient® can be accessed through the National Library of Medicine of the National Institutes of Health. The database is partially derived from lists of federally approved medications in the Food and Drug Administration’s (FDA) Drug Approvals database, located at http://www.fda.gov/cder/da/da.htm. While the FDA database is rather large and difficult to navigate, the Phamacopeia is both user-friendly and free to use. It covers more than 9,000 prescription and over-the-counter medications. To access this database, simply type the following hyperlink into your Web browser: http://www.nlm.nih.gov/medlineplus/druginformation.html. To view examples of a given medication (brand names, category, description, preparation, proper use, precautions, side effects, etc.), simply follow the hyperlinks indicated within the United States Pharmacopeia (USP).
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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.
Researching Orphan Drugs Although the list of orphan drugs is revised on a daily basis, you can quickly research orphan drugs that might be applicable to aplastic anemia by using the database managed by the National Organization for Rare Disorders, Inc. (NORD), at http://www.rarediseases.org/. Scroll down the page, and on the left toolbar, click on “Orphan Drug Designation Database.” On this page (http://www.rarediseases.org/search/noddsearch.html), type “aplastic anemia” (or synonyms) into the search box, and click “Submit Query.” When you receive your results, note that not all of the drugs may be relevant, as some may have been withdrawn from orphan status. Write down or print out the name of each drug and the relevant contact information. From there, visit the Pharmacopeia Web site and type the name of each orphan drug into the search box at http://www.nlm.nih.gov/medlineplus/druginformation.html. You may need to contact the sponsor or NORD for further information. NORD conducts “early access programs for investigational new drugs (IND) under the Food and Drug Administration’s (FDA’s) approval ‘Treatment INDs’ programs which allow for a limited number of individuals to receive investigational drugs before FDA marketing approval.” If the orphan product about which you are seeking information is approved for
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marketing, information on side effects can be found on the product’s label. If the product is not approved, you may need to contact the sponsor. The following is a list of orphan drugs currently listed in the NORD Orphan Drug Designation Database for aplastic anemia: •
Etiocholanedione http://www.rarediseases.org/nord/search/nodd_full?code=476
If you have any questions about a medical treatment, the FDA may have an office near you. Look for their number in the blue pages of the phone book. You can also contact the FDA through its toll-free number, 1-888-INFO-FDA (1-888-463-6332), or on the World Wide Web at www.fda.gov.
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APPENDICES
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APPENDIX A. PHYSICIAN RESOURCES Overview In this chapter, we focus on databases and Internet-based guidelines and information resources created or written for a professional audience.
NIH Guidelines Commonly referred to as “clinical” or “professional” guidelines, the National Institutes of Health publish physician guidelines for the most common diseases. Publications are available at the following by relevant Institute11: •
Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm
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National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/news/facts/
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National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html
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National Cancer Institute (NCI); guidelines available at http://www.cancer.gov/cancerinfo/list.aspx?viewid=5f35036e-5497-4d86-8c2c714a9f7c8d25
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National Eye Institute (NEI); guidelines available at http://www.nei.nih.gov/order/index.htm
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National Heart, Lung, and Blood Institute (NHLBI); guidelines available at http://www.nhlbi.nih.gov/guidelines/index.htm
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National Human Genome Research Institute (NHGRI); research available at http://www.genome.gov/page.cfm?pageID=10000375
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National Institute on Aging (NIA); guidelines available at http://www.nia.nih.gov/health/
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These publications are typically written by one or more of the various NIH Institutes.
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National Institute on Alcohol Abuse and Alcoholism (NIAAA); guidelines available at http://www.niaaa.nih.gov/publications/publications.htm
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National Institute of Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/
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National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm
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National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm
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National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/
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National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/
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National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm
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National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html
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National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm
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National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/practitioners/index.cfm
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National Institute of Neurological Disorders and Stroke (NINDS); neurological disorder information pages available at http://www.ninds.nih.gov/health_and_medical/disorder_index.htm
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National Institute of Nursing Research (NINR); publications on selected illnesses at http://www.nih.gov/ninr/news-info/publications.html
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National Institute of Biomedical Imaging and Bioengineering; general information at http://grants.nih.gov/grants/becon/becon_info.htm
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Center for Information Technology (CIT); referrals to other agencies based on keyword searches available at http://kb.nih.gov/www_query_main.asp
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National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/
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National Center for Research Resources (NCRR); various information directories available at http://www.ncrr.nih.gov/publications.asp
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Office of Rare Diseases; various fact sheets available at http://rarediseases.info.nih.gov/html/resources/rep_pubs.html
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Centers for Disease Control and Prevention; various fact sheets on infectious diseases available at http://www.cdc.gov/publications.htm
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NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.12 Physician-oriented resources provide a wide variety of information related to the biomedical and health sciences, both past and present. The format of these resources varies. Searchable databases, bibliographic citations, full-text articles (when available), archival collections, and images are all available. The following are referenced by the National Library of Medicine:13 •
Bioethics: Access to published literature on the ethical, legal, and public policy issues surrounding healthcare and biomedical research. This information is provided in conjunction with the Kennedy Institute of Ethics located at Georgetown University, Washington, D.C.: http://www.nlm.nih.gov/databases/databases_bioethics.html
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HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html
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NLM Online Exhibitions: Describes “Exhibitions in the History of Medicine”: http://www.nlm.nih.gov/exhibition/exhibition.html. Additional resources for historical scholarship in medicine: http://www.nlm.nih.gov/hmd/hmd.html
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Biotechnology Information: Access to public databases. The National Center for Biotechnology Information conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information for the better understanding of molecular processes affecting human health and disease: http://www.ncbi.nlm.nih.gov/
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Population Information: The National Library of Medicine provides access to worldwide coverage of population, family planning, and related health issues, including family planning technology and programs, fertility, and population law and policy: http://www.nlm.nih.gov/databases/databases_population.html
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Cancer Information: Access to cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html
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Profiles in Science: Offering the archival collections of prominent twentieth-century biomedical scientists to the public through modern digital technology: http://www.profiles.nlm.nih.gov/
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Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html
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Clinical Alerts: Reports the release of findings from the NIH-funded clinical trials where such release could significantly affect morbidity and mortality: http://www.nlm.nih.gov/databases/alerts/clinical_alerts.html
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Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html
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MEDLINE: Bibliographic database covering the fields of medicine, nursing, dentistry, veterinary medicine, the healthcare system, and the pre-clinical sciences: http://www.nlm.nih.gov/databases/databases_medline.html
12
Remember, for the general public, the National Library of Medicine recommends the databases referenced in MEDLINEplus (http://medlineplus.gov/ or http://www.nlm.nih.gov/medlineplus/databases.html). 13 See http://www.nlm.nih.gov/databases/databases.html.
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Toxicology and Environmental Health Information (TOXNET): Databases covering toxicology and environmental health: http://sis.nlm.nih.gov/Tox/ToxMain.html
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Visible Human Interface: Anatomically detailed, three-dimensional representations of normal male and female human bodies: http://www.nlm.nih.gov/research/visible/visible_human.html
The NLM Gateway14 The NLM (National Library of Medicine) Gateway is a Web-based system that lets users search simultaneously in multiple retrieval systems at the U.S. National Library of Medicine (NLM). It allows users of NLM services to initiate searches from one Web interface, providing one-stop searching for many of NLM’s information resources or databases.15 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “aplastic anemia” (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 11821 126 850 13 238 13048
HSTAT16 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.17 These documents include clinical practice guidelines, quickreference guides for clinicians, consumer health brochures, evidence reports and technology assessments from the Agency for Healthcare Research and Quality (AHRQ), as well as AHRQ’s Put Prevention Into Practice.18 Simply search by “aplastic anemia” (or synonyms) at the following Web site: http://text.nlm.nih.gov.
14
Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.
15
The NLM Gateway is currently being developed by the Lister Hill National Center for Biomedical Communications (LHNCBC) at the National Library of Medicine (NLM) of the National Institutes of Health (NIH). 16 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 17 18
The HSTAT URL is http://hstat.nlm.nih.gov/.
Other important documents in HSTAT include: the National Institutes of Health (NIH) Consensus Conference Reports and Technology Assessment Reports; the HIV/AIDS Treatment Information Service (ATIS) resource documents; the Substance Abuse and Mental Health Services Administration's Center for Substance Abuse Treatment (SAMHSA/CSAT) Treatment Improvement Protocols (TIP) and Center for Substance Abuse Prevention (SAMHSA/CSAP) Prevention Enhancement Protocols System (PEPS); the Public Health Service (PHS) Preventive Services Task Force's Guide to Clinical Preventive Services; the independent, nonfederal Task Force on Community Services’ Guide to Community Preventive Services; and the Health Technology Advisory Committee (HTAC) of the Minnesota Health Care Commission (MHCC) health technology evaluations.
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Coffee Break: Tutorials for Biologists19 Coffee Break is a general healthcare site that takes a scientific view of the news and covers recent breakthroughs in biology that may one day assist physicians in developing treatments. Here you will find a collection of short reports on recent biological discoveries. Each report incorporates interactive tutorials that demonstrate how bioinformatics tools are used as a part of the research process. Currently, all Coffee Breaks are written by NCBI staff.20 Each report is about 400 words and is usually based on a discovery reported in one or more articles from recently published, peer-reviewed literature.21 This site has new articles every few weeks, so it can be considered an online magazine of sorts. It is intended for general background information. You can access the Coffee Break Web site at the following hyperlink: http://www.ncbi.nlm.nih.gov/Coffeebreak/.
Other Commercial Databases In addition to resources maintained by official agencies, other databases exist that are commercial ventures addressing medical professionals. Here are some examples that may interest you: •
CliniWeb International: Index and table of contents to selected clinical information on the Internet; see http://www.ohsu.edu/cliniweb/.
•
Medical World Search: Searches full text from thousands of selected medical sites on the Internet; see http://www.mwsearch.com/.
19 Adapted 20
from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html.
The figure that accompanies each article is frequently supplied by an expert external to NCBI, in which case the source of the figure is cited. The result is an interactive tutorial that tells a biological story. 21 After a brief introduction that sets the work described into a broader context, the report focuses on how a molecular understanding can provide explanations of observed biology and lead to therapies for diseases. Each vignette is accompanied by a figure and hypertext links that lead to a series of pages that interactively show how NCBI tools and resources are used in the research process.
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APPENDIX B. PATIENT RESOURCES Overview Official agencies, as well as federally funded institutions supported by national grants, frequently publish a variety of guidelines written with the patient in mind. These are typically called “Fact Sheets” or “Guidelines.” They can take the form of a brochure, information kit, pamphlet, or flyer. Often they are only a few pages in length. Since new guidelines on aplastic anemia 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 aplastic anemia. 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 aplastic anemia. 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 “aplastic anemia”:
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Other guides Anemia http://www.nlm.nih.gov/medlineplus/anemia.html Bone Marrow Diseases http://www.nlm.nih.gov/medlineplus/bonemarrowdiseases.html Bone Marrow Transplantation http://www.nlm.nih.gov/medlineplus/bonemarrowtransplantation.html Food Contamination and Poisoning http://www.nlm.nih.gov/medlineplus/foodcontaminationandpoisoning.html High Risk Pregnancy http://www.nlm.nih.gov/medlineplus/highriskpregnancy.html Sickle Cell Anemia http://www.nlm.nih.gov/medlineplus/sicklecellanemia.html Stem Cells and Stem Cell Transplantation http://www.nlm.nih.gov/medlineplus/stemcellsandstemcelltransplantation.html Ulcerative Colitis http://www.nlm.nih.gov/medlineplus/ulcerativecolitis.html
Within the health topic page dedicated to aplastic anemia, the following was listed: •
General/Overviews Anemia Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=DS00321 Anemia: When Low Iron Is the Cause Source: American Academy of Family Physicians http://familydoctor.org/009.xml
•
Diagnosis/Symptoms Ferritin Test Source: American Association for Clinical Chemistry http://www.labtestsonline.org/understanding/analytes/ferritin/test.html Hematocrit Source: American Association for Clinical Chemistry http://www.labtestsonline.org/understanding/analytes/hematocrit/test.html Hemoglobin Source: American Association for Clinical Chemistry http://www.labtestsonline.org/understanding/analytes/hemoglobin/test.html Serum Iron Test Source: American Association for Clinical Chemistry http://www.labtestsonline.org/understanding/analytes/serum_iron/test.html
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TIBC (Total Iron-Binding Capacity) & Transferrin Source: American Association for Clinical Chemistry http://www.labtestsonline.org/understanding/analytes/tibc/test.html Understanding Your Complete Blood Count Source: National Institutes of Health, Clinical Center http://www.cc.nih.gov/ccc/patient_education/pepubs/cbc97.pdf •
Treatment Blood and Marrow Stem Cell Transplantation Source: Leukemia & Lymphoma Society http://www.leukemia-lymphoma.org/all_mat_toc.adp?item_id=2443 Cord Blood FAQs Source: National Marrow Donor Program http://www.marrow.org/FAQS/cord_blood_faqs.html Epoetin Treatment Source: American Society of Clinical Oncology http://www.asco.org/ac/1%2C1003%2C_12-002214-00_18-0024517-00_19-002451800_20-001%2C00.asp How Is Fanconi Anemia Treated? Source: Fanconi Anemia Research Fund http://www.fanconi.org/TREATMENT.HTML
•
Nutrition Iron Source: National Institutes of Health, Office of Dietary Supplements http://www.cc.nih.gov/ccc/supplements/iron.html
•
Specific Conditions/Aspects Acquired Aplastic Anemia: Basic Explanations Source: Aplastic Anemia & MDS International Foundation http://www.aplastic.org/cgi-bin/byteserver.pl/pdfs/ACQUIRED-APLASTICANEMIA-BASIC-EXPLANATIONS.pdf Anemia (Normocytic Anemia) Source: American Academy of Family Physicians http://familydoctor.org/639.xml Anemia in Kidney Disease and Dialysis Source: National Kidney and Urologic Diseases Information Clearinghouse http://kidney.niddk.nih.gov/kudiseases/pubs/anemia/index.htm Aplastic Anemia Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=DS00322 Blood Donor Anemia: Causes? Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=HQ00328
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Diamond-Blackfan Anemia (DBA) Source: National Cancer Institute http://marrowfailure.cancer.gov/DBA.html Iron Deficiency Anemia Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=DS00323 Vitamin Deficiency Anemia Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=DS00325 What Is Fanconi Anemia and How Is It Diagnosed? Source: Fanconi Anemia Research Fund http://www.fanconi.org/WhatisFA.html •
Children About Anemia Source: Nemours Foundation http://kidshealth.org/kid/health_problems/blood/anemia.html Anemia Source: Nemours Foundation http://kidshealth.org/parent/medical/heart/anemia.html Anemia and Iron Status Source: Centers for Disease Control and Prevention http://www.cdc.gov/nccdphp/dnpa/anemiron.htm Iron-Deficiency Anemia Source: Nemours Foundation http://kidshealth.org/parent/medical/heart/ida.html Symptoms of Anemia Source: American Academy of Pediatrics http://www.medem.com/medlb/article_detaillb.cfm?article_ID=ZZZ6G06JL5C&s ub_cat=107 Thalassemia Source: March of Dimes Birth Defects Foundation http://www.marchofdimes.com/professionals/681_1229.asp
•
From the National Institutes of Health Thalassemia Source: National Heart, Lung, and Blood Institute http://www.nhlbi.nih.gov/health/dci/Diseases/Thalassemia/Thalassemia_WhatI s.html
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Organizations Fanconi Anemia Research Fund http://www.fanconi.org/ National Heart, Lung, and Blood Institute http://www.nhlbi.nih.gov/
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National Institute of Diabetes and Digestive and Kidney Diseases http://www.niddk.nih.gov/ •
Research Anemia Elevates Risk of Physical Decline in Older People Source: National Institute on Aging http://www.nih.gov/news/pr/jul2003/nia-25.htm Enzyme Discovery Sheds Light on Causes of Rare Disease, Cancer Source: National Institute on Aging http://www.nia.nih.gov/news/pr/2003/0914.htm
•
Statistics FASTATS: Anemia/Iron Deficiency Source: National Center for Health Statistics http://www.cdc.gov/nchs/fastats/anemia.htm
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Teenagers Understanding Anemia Source: Nemours Foundation http://kidshealth.org/teen/diseases_conditions/blood/anemia.html
•
Women Keeping the Blood and Lymphatic System Healthy Source: American Medical Women's Association http://www.amwa-doc.org/publications/WCHealthbook/bloodamwa-ch29.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. Healthfinder™ Healthfinder™ is sponsored by the U.S. Department of Health and Human Services and offers links to hundreds of other sites that contain healthcare information. This Web site is located at http://www.healthfinder.gov. Again, keyword searches can be used to find guidelines. The following was recently found in this database:
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FAQ: Aplastic Anemia, Myelodysplastic Syndromes, and Paroxysmal Nocturnal Hemoglobinuria (PNH) Summary: Answers questions about causes, symptoms, and therapies for aplastic anemia, myelodysplastic syndromes, and paroxysmal nocturnal hemoglobinuria. Source: Aplastic Anemia & MDS International Foundation, Inc. http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=7378 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 aplastic anemia. 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. PEDBASE Similar to NORD, PEDBASE covers relatively rare disorders, limited mainly to pediatric conditions. PEDBASE was designed by Dr. Alan Gandy. To access the database, which is more oriented to researchers than patients, you can view the current list of health topics covered at the following Web site: http://www.icondata.com/health/pedbase/pedlynx.htm. Additional Web Sources A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •
AOL: http://search.aol.com/cat.adp?id=168&layer=&from=subcats
•
Family Village: http://www.familyvillage.wisc.edu/specific.htm
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Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/
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Med Help International: http://www.medhelp.org/HealthTopics/A.html
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Open Directory Project: http://dmoz.org/Health/Conditions_and_Diseases/
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Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/
•
WebMD®Health: http://my.webmd.com/health_topics
Associations and Aplastic Anemia The following is a list of associations that provide information on and resources relating to aplastic anemia:
Patient Resources
•
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Aplastic Anemia and Myelodysplasia Association of Canada Telephone: (416) 235-0468 Toll-free: (888) 840-0039 Fax: (905) 780-1648 Web Site: http://www.aamac.ualberta.ca Background: The Aplastic Anemia and Myelodysplasia Association of Canada is a voluntary, not-for-profit organization founded in 1987 that is dedicated to the support of individuals with aplastic anemia or myelodysplasia and their family members. Aplastic anemia is a rare form of anemia in which there are abnormally low levels of red blood cells, white blood cells, and platelets in the blood. Myelodysplastic syndromes are a group of related bone marrow disorders. The Association disseminates information in understandable lay terminology and has a network of volunteers with personal experience with these conditions who are able to give guidance and support during times of need. In addition, the Association informs the public about aplastic anemia and myelodysplasia, supports the Canadian Red Cross blood programs and the Unrelated Bone Marrow Registry, and raises funds for medical research.
Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to aplastic anemia. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with aplastic anemia. 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 aplastic anemia. 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 “aplastic anemia” (or a synonym), and you will receive information on all relevant organizations listed in the database. Health Hotlines directs you to toll-free numbers to over 300 organizations. You can access this database directly at http://www.sis.nlm.nih.gov/hotlines/. On this page, you are given the option to search by keyword or by browsing the subject list. When you have received
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your search results, click on the name of the organization for its description and contact information. The Combined Health Information Database Another comprehensive source of information on healthcare associations is the Combined Health Information Database. Using the “Detailed Search” option, you will need to limit your search to “Organizations” and “aplastic anemia”. 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 “aplastic anemia” (or synonyms) into the “For these words:” box. You should check back periodically with this database since it is updated every three months. The National Organization for Rare Disorders, Inc. The National Organization for Rare Disorders, Inc. has prepared a Web site that provides, at no charge, lists of associations organized by health topic. You can access this database at the following Web site: http://www.rarediseases.org/search/orgsearch.html. Type “aplastic anemia” (or a synonym) into the search box, and click “Submit Query.”
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APPENDIX C. FINDING MEDICAL LIBRARIES Overview In this Appendix, we show you how to quickly find a medical library in your area.
Preparation Your local public library and medical libraries have interlibrary loan programs with the National Library of Medicine (NLM), one of the largest medical collections in the world. According to the NLM, most of the literature in the general and historical collections of the National Library of Medicine is available on interlibrary loan to any library. If you would like to access NLM medical literature, then visit a library in your area that can request the publications for you.22
Finding a Local Medical Library The quickest method to locate medical libraries is to use the Internet-based directory published by the National Network of Libraries of Medicine (NN/LM). This network includes 4626 members and affiliates that provide many services to librarians, health professionals, and the public. To find a library in your area, simply visit http://nnlm.gov/members/adv.html or call 1-800-338-7657.
Medical Libraries in the U.S. and Canada In addition to the NN/LM, the National Library of Medicine (NLM) lists a number of libraries with reference facilities that are open to the public. The following is the NLM’s list and includes hyperlinks to each library’s Web site. These Web pages can provide information on hours of operation and other restrictions. The list below is a small sample of
22
Adapted from the NLM: http://www.nlm.nih.gov/psd/cas/interlibrary.html.
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libraries recommended by the National Library of Medicine (sorted alphabetically by name of the U.S. state or Canadian province where the library is located)23: •
Alabama: Health InfoNet of Jefferson County (Jefferson County Library Cooperative, Lister Hill Library of the Health Sciences), http://www.uab.edu/infonet/
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Alabama: Richard M. Scrushy Library (American Sports Medicine Institute)
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Arizona: Samaritan Regional Medical Center: The Learning Center (Samaritan Health System, Phoenix, Arizona), http://www.samaritan.edu/library/bannerlibs.htm
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California: Kris Kelly Health Information Center (St. Joseph Health System, Humboldt), http://www.humboldt1.com/~kkhic/index.html
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California: Community Health Library of Los Gatos, http://www.healthlib.org/orgresources.html
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California: Consumer Health Program and Services (CHIPS) (County of Los Angeles Public Library, Los Angeles County Harbor-UCLA Medical Center Library) - Carson, CA, http://www.colapublib.org/services/chips.html
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California: Gateway Health Library (Sutter Gould Medical Foundation)
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California: Health Library (Stanford University Medical Center), http://wwwmed.stanford.edu/healthlibrary/
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California: Patient Education Resource Center - Health Information and Resources (University of California, San Francisco), http://sfghdean.ucsf.edu/barnett/PERC/default.asp
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California: Redwood Health Library (Petaluma Health Care District), http://www.phcd.org/rdwdlib.html
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California: Los Gatos PlaneTree Health Library, http://planetreesanjose.org/
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California: Sutter Resource Library (Sutter Hospitals Foundation, Sacramento), http://suttermedicalcenter.org/library/
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California: Health Sciences Libraries (University of California, Davis), http://www.lib.ucdavis.edu/healthsci/
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California: ValleyCare Health Library & Ryan Comer Cancer Resource Center (ValleyCare Health System, Pleasanton), http://gaelnet.stmarysca.edu/other.libs/gbal/east/vchl.html
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California: Washington Community Health Resource Library (Fremont), http://www.healthlibrary.org/
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Colorado: William V. Gervasini Memorial Library (Exempla Healthcare), http://www.saintjosephdenver.org/yourhealth/libraries/
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Connecticut: Hartford Hospital Health Science Libraries (Hartford Hospital), http://www.harthosp.org/library/
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Connecticut: Healthnet: Connecticut Consumer Health Information Center (University of Connecticut Health Center, Lyman Maynard Stowe Library), http://library.uchc.edu/departm/hnet/
23
Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.
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Connecticut: Waterbury Hospital Health Center Library (Waterbury Hospital, Waterbury), http://www.waterburyhospital.com/library/consumer.shtml
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Delaware: Consumer Health Library (Christiana Care Health System, Eugene du Pont Preventive Medicine & Rehabilitation Institute, Wilmington), http://www.christianacare.org/health_guide/health_guide_pmri_health_info.cfm
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Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine, Wilmington), http://www.delamed.org/chls.html
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Georgia: Family Resource Library (Medical College of Georgia, Augusta), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm
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Georgia: Health Resource Center (Medical Center of Central Georgia, Macon), http://www.mccg.org/hrc/hrchome.asp
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Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library, Honolulu), http://hml.org/CHIS/
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Idaho: DeArmond Consumer Health Library (Kootenai Medical Center, Coeur d’Alene), http://www.nicon.org/DeArmond/index.htm
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Illinois: Health Learning Center of Northwestern Memorial Hospital (Chicago), http://www.nmh.org/health_info/hlc.html
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Illinois: Medical Library (OSF Saint Francis Medical Center, Peoria), http://www.osfsaintfrancis.org/general/library/
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Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital, Lexington), http://www.centralbap.com/education/community/library.cfm
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Kentucky: University of Kentucky - Health Information Library (Chandler Medical Center, Lexington), http://www.mc.uky.edu/PatientEd/
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Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation, New Orleans), http://www.ochsner.org/library/
•
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
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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
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Maine: Maine Medical Center Library (Maine Medical Center, Portland), http://www.mmc.org/library/
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Maine: Parkview Hospital (Brunswick), http://www.parkviewhospital.org/
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Maine: Southern Maine Medical Center Health Sciences Library (Southern Maine Medical Center, Biddeford), http://www.smmc.org/services/service.php3?choice=10
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Maine: Stephens Memorial Hospital’s Health Information Library (Western Maine Health, Norway), http://www.wmhcc.org/Library/
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•
Manitoba, Canada: Consumer & Patient Health Information Service (University of Manitoba Libraries), http://www.umanitoba.ca/libraries/units/health/reference/chis.html
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Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre, Winnipeg), http://www.deerlodge.mb.ca/crane_library/about.asp
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Maryland: Health Information Center at the Wheaton Regional Library (Montgomery County, Dept. of Public Libraries, Wheaton Regional Library), http://www.mont.lib.md.us/healthinfo/hic.asp
•
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
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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/
•
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
•
National: National Network of Libraries of Medicine (National Library of Medicine) provides library services for health professionals in the United States who do not have access to a medical library, http://nnlm.gov/
•
National: NN/LM List of Libraries Serving the Public (National Network of Libraries of Medicine), http://nnlm.gov/members/
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Nevada: Health Science Library, West Charleston Library (Las Vegas-Clark County Library District, Las Vegas), http://www.lvccld.org/special_collections/medical/index.htm
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New Hampshire: Dartmouth Biomedical Libraries (Dartmouth College Library, Hanover), http://www.dartmouth.edu/~biomed/resources.htmld/conshealth.htmld/
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New Jersey: Consumer Health Library (Rahway Hospital, Rahway), http://www.rahwayhospital.com/library.htm
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New Jersey: Dr. Walter Phillips Health Sciences Library (Englewood Hospital and Medical Center, Englewood), http://www.englewoodhospital.com/links/index.htm
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New Jersey: Meland Foundation (Englewood Hospital and Medical Center, Englewood), http://www.geocities.com/ResearchTriangle/9360/
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New York: Choices in Health Information (New York Public Library) - NLM Consumer Pilot Project participant, http://www.nypl.org/branch/health/links.html
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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
•
Pennsylvania: Learning Resources Center - Medical Library (Susquehanna Health System, Williamsport), http://www.shscares.org/services/lrc/index.asp
•
Pennsylvania: Medical Library (UPMC Health System, Pittsburgh), http://www.upmc.edu/passavant/library.htm
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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/
•
Washington: Community Health Library (Kittitas Valley Community Hospital), http://www.kvch.com/
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Washington: Southwest Washington Medical Center Library (Southwest Washington Medical Center, Vancouver), http://www.swmedicalcenter.com/body.cfm?id=72
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ONLINE GLOSSARIES The Internet provides access to a number of free-to-use medical dictionaries. The National Library of Medicine has compiled the following list of online dictionaries: •
ADAM Medical Encyclopedia (A.D.A.M., Inc.), comprehensive medical reference: http://www.nlm.nih.gov/medlineplus/encyclopedia.html
•
MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp
•
Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/
•
Multilingual Glossary of Technical and Popular Medical Terms in Eight European Languages (European Commission) - Danish, Dutch, English, French, German, Italian, Portuguese, and Spanish: http://allserv.rug.ac.be/~rvdstich/eugloss/welcome.html
•
On-line Medical Dictionary (CancerWEB): http://cancerweb.ncl.ac.uk/omd/
•
Rare Diseases Terms (Office of Rare Diseases): http://ord.aspensys.com/asp/diseases/diseases.asp
•
Technology Glossary (National Library of Medicine) - Health Care Technology: http://www.nlm.nih.gov/nichsr/ta101/ta10108.htm
Beyond these, MEDLINEplus contains a very patient-friendly encyclopedia covering every aspect of medicine (licensed from A.D.A.M., Inc.). The ADAM Medical Encyclopedia can be accessed at http://www.nlm.nih.gov/medlineplus/encyclopedia.html. ADAM is also available on commercial Web sites such as drkoop.com (http://www.drkoop.com/) and Web MD (http://my.webmd.com/adam/asset/adam_disease_articles/a_to_z/a).
Online Dictionary Directories The following are additional online directories compiled by the National Library of Medicine, including a number of specialized medical dictionaries: •
Medical Dictionaries: Medical & Biological (World Health Organization): http://www.who.int/hlt/virtuallibrary/English/diction.htm#Medical
•
MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html
•
Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/
•
Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine
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APLASTIC ANEMIA DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Abdominal Pain: Sensation of discomfort, distress, or agony in the abdominal region. [NIH] Aberrant: Wandering or deviating from the usual or normal course. [EU] Abscess: A localized, circumscribed collection of pus. [NIH] Acceptor: A substance which, while normally not oxidized by oxygen or reduced by hydrogen, can be oxidized or reduced in presence of a substance which is itself undergoing oxidation or reduction. [NIH] 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] Acetylcysteine: The N-acetyl derivative of cysteine. It is used as a mucolytic agent to reduce the viscosity of mucous secretions. It has also been shown to have antiviral effects in patients with HIV due to inhibition of viral stimulation by reactive oxygen intermediates. [NIH] Acne: A disorder of the skin marked by inflammation of oil glands and hair glands. [NIH] Acute leukemia: A rapidly progressing cancer of the blood-forming tissue (bone marrow). [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, kidneys can recover from almost complete loss of function. [NIH] Adaptability: Ability to develop some form of tolerance to conditions extremely different from those under which a living organism evolved. [NIH] Adduct: Complex formed when a carcinogen combines with DNA or a protein. [NIH] Adolescence: The period of life beginning with the appearance of secondary sex characteristics and terminating with the cessation of somatic growth. The years usually referred to as adolescence lie between 13 and 18 years of age. [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
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synapse when a nerve impulse passes, i.e., the sympathetic fibres. [EU] Adverse Effect: An unwanted side effect of treatment. [NIH] Aerobic: In biochemistry, reactions that need oxygen to happen or happen when oxygen is present. [NIH] Aerobic Metabolism: A chemical process in which oxygen is used to make energy from carbohydrates (sugars). Also known as aerobic respiration, oxidative metabolism, or cell respiration. [NIH] Aerobic Respiration: A chemical process in which oxygen is used to make energy from carbohydrates (sugars). Also known as oxidative metabolism, cell respiration, or aerobic metabolism. [NIH] Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among 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] Agonists: Drugs that trigger an action from a cell or another drug. [NIH] Agranulocytosis: A decrease in the number of granulocytes (basophils, eosinophils, and neutrophils). [NIH] 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] Alkylating Agents: Highly reactive chemicals that introduce alkyl radicals into biologically active molecules and thereby prevent their proper functioning. Many are used as antineoplastic agents, but most are very toxic, with carcinogenic, mutagenic, teratogenic, and immunosuppressant actions. They have also been used as components in poison gases. [NIH]
Alkylation: The covalent bonding of an alkyl group to an organic compound. It can occur by a simple addition reaction or by substitution of another functional group. [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] Allo: A female hormone. [NIH] Allogeneic: Taken from different individuals of the same species. [NIH] Allogeneic bone marrow transplantation: A procedure in which a person receives stem cells, the cells from which all blood cells develop, from a compatible, though not genetically identical, donor. [NIH] Allografts: A graft of tissue obtained from the body of another animal of the same species but with genotype differing from that of the recipient; tissue graft from a donor of one genotype to a host of another genotype with host and donor being members of the same species. [NIH]
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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 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] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amnion: The extraembryonic membrane which contains the embryo and amniotic fluid. [NIH]
Amniotic Fluid: Amniotic cavity fluid which is produced by the amnion and fetal lungs and kidneys. [NIH] Anaemia: A reduction below normal in the number of erythrocytes per cu. mm., in the quantity of haemoglobin, or in the volume of packed red cells per 100 ml. of blood which occurs when the equilibrium between blood loss (through bleeding or destruction) and blood production is disturbed. [EU] Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Anal: Having to do with the anus, which is the posterior opening of the large bowel. [NIH] Analog: In chemistry, a substance that is similar, but not identical, to another. [NIH] Analytes: A component of a test sample the presence of which has to be demonstrated. The term "analyte" includes where appropriate formed from the analyte during the analyses. [NIH]
Anaphylatoxins: The family of peptides C3a, C4a, C5a, and C5a des-arginine produced in the serum during complement activation. They produce smooth muscle contraction, mast cell histamine release, affect platelet aggregation, and act as mediators of the local inflammatory process. The order of anaphylatoxin activity from strongest to weakest is C5a, C3a, C4a, and C5a des-arginine. The latter is the so-called "classical" anaphylatoxin but shows no spasmogenic activity though it contains some chemotactic ability. [NIH] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Androgenic: Producing masculine characteristics. [EU]
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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] Anemia, Sickle Cell: A disease characterized by chronic hemolytic anemia, episodic painful crises, and pathologic involvement of many organs. It is the clinical expression of homozygosity for hemoglobin S. [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] Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis. [NIH] Anomalies: Birth defects; abnormalities. [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] Antecedent: Existing or occurring before in time or order often with consequential effects. [EU]
Antiandrogens: Drugs used to block the production or interfere with the action of male sex hormones. [NIH] Antibacterial: A substance that destroys bacteria or suppresses their growth or reproduction. [EU] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]
Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] Anticonvulsant: An agent that prevents or relieves convulsions. [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
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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-inflammatory: Having to do with reducing inflammation. [NIH] Antineoplastic: Inhibiting or preventing the development of neoplasms, checking the maturation and proliferation of malignant cells. [EU] Antineoplastic Agents: Substances that inhibit or prevent the proliferation of neoplasms. [NIH]
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] Antithrombotic: Preventing or interfering with the formation of thrombi; an agent that so acts. [EU] Antithymocyte globulin: A protein used to reduce the risk of or to treat graft-versus-host disease. [NIH] Antiviral: Destroying viruses or suppressing their replication. [EU] Apheresis: Components plateletpheresis. [NIH]
being
separated
out,
as
leukapheresis,
plasmapheresis,
Aplasia: Lack of development of an organ or tissue, or of the cellular products from an organ or tissue. [EU] Aplastic anaemia: A form of anaemia generally unresponsive to specific antianaemia therapy, often accompanied by granulocytopenia and thrombocytopenia, in which the bone marrow may not necessarily be acellular or hypoplastic but fails to produce adequate numbers of peripheral blood elements. The term actually is all-inclusive and most probably encompasses several clinical syndromes. [EU] Aplastic anemia: A condition in which the bone marrow is unable to produce blood cells. [NIH]
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Apoptosis: One of the two mechanisms by which cell death occurs (the other being the pathological process of necrosis). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA (DNA fragmentation) at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. [NIH] Applicability: A list of the commodities to which the candidate method can be applied as presented or with minor modifications. [NIH] Aqueous: Having to do with water. [NIH] Arachidonic Acid: An unsaturated, essential fatty acid. It is found in animal and human fat as well as in the liver, brain, and glandular organs, and is a constituent of animal phosphatides. It is formed by the synthesis from dietary linoleic acid and is a precursor in the biosynthesis of prostaglandins, thromboxanes, and leukotrienes. [NIH] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Aromatic: Having a spicy odour. [EU] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arteriosclerosis: Thickening and loss of elasticity of arterial walls. Atherosclerosis is the most common form of arteriosclerosis and involves lipid deposition and thickening of the intimal cell layers within arteries. Additional forms of arteriosclerosis involve calcification of the media of muscular arteries (Monkeberg medial calcific sclerosis) and thickening of the walls of small arteries or arterioles due to cell proliferation or hyaline deposition (arteriolosclerosis). [NIH] Arteriovenous: Both arterial and venous; pertaining to or affecting an artery and a vein. [EU] Arteriovenous Fistula: An abnormal communication between an artery and a vein. [NIH] Arthralgia: Pain in the joint. [NIH] Articular: Of or pertaining to a joint. [EU] Ascorbic Acid: A six carbon compound related to glucose. It is found naturally in citrus fruits and many vegetables. Ascorbic acid is an essential nutrient in human diets, and necessary to maintain connective tissue and bone. Its biologically active form, vitamin C, functions as a reducing agent and coenzyme in several metabolic pathways. Vitamin C is considered an antioxidant. [NIH] Aspergillosis: Infections with fungi of the genus Aspergillus. [NIH] Aspiration: The act of inhaling. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Astrocytes: The largest and most numerous neuroglial cells in the brain and spinal cord. Astrocytes (from "star" cells) are irregularly shaped with many long processes, including those with "end feet" which form the glial (limiting) membrane and directly and indirectly contribute to the blood brain barrier. They regulate the extracellular ionic and chemical environment, and "reactive astrocytes" (along with microglia) respond to injury. Astrocytes have high- affinity transmitter uptake systems, voltage-dependent and transmitter-gated ion channels, and can release transmitter, but their role in signaling (as in many other functions) is not well understood. [NIH]
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Asymptomatic: Having no signs or symptoms of disease. [NIH] Ataxia: Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharnyx, larnyx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or peripheral nerve diseases. Motor ataxia may be associated with cerebellar diseases; cerebral cortex diseases; thalamic diseases; basal ganglia diseases; injury to the red nucleus; and other conditions. [NIH] Attenuated: Strain with weakened or reduced virulence. [NIH] Atypical: Irregular; not conformable to the type; in microbiology, applied specifically to strains of unusual type. [EU] Autoimmune disease: A condition in which the body recognizes its own tissues as foreign and directs an immune response against them. [NIH] Autoimmunity: Process whereby the immune system reacts against the body's own tissues. Autoimmunity may produce or be caused by autoimmune diseases. [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] 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] Bacteriophage: A virus whose host is a bacterial cell; A virus that exclusively infects bacteria. It generally has a protein coat surrounding the genome (DNA or RNA). One of the coliphages most extensively studied is the lambda phage, which is also one of the most important. [NIH] Bacterium: Microscopic organism which may have a spherical, rod-like, or spiral unicellular or non-cellular body. Bacteria usually reproduce through asexual processes. [NIH] Bacteriuria: The presence of bacteria in the urine with or without consequent urinary tract infection. Since bacteriuria is a clinical entity, the term does not preclude the use of urine/microbiology for technical discussions on the isolation and segregation of bacteria in the urine. [NIH] Basal Ganglia: Large subcortical nuclear masses derived from the telencephalon and located in the basal regions of the cerebral hemispheres. [NIH] Basal Ganglia Diseases: Diseases of the basal ganglia including the putamen; globus pallidus; claustrum; amygdala; and caudate nucleus. Dyskinesias (most notably involuntary movements and alterations of the rate of movement) represent the primary clinical manifestations of these disorders. Common etiologies include cerebrovascular disease; neurodegenerative diseases; and craniocerebral trauma. [NIH] Base: In chemistry, the nonacid part of a salt; a substance that combines with acids to form salts; a substance that dissociates to give hydroxide ions in aqueous solutions; a substance whose molecule or ion can combine with a proton (hydrogen ion); a substance capable of donating a pair of electrons (to an acid) for the formation of a coordinate covalent bond. [EU] Basophils: Granular leukocytes characterized by a relatively pale-staining, lobate nucleus and cytoplasm containing coarse dark-staining granules of variable size and stainable by basic dyes. [NIH]
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Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]
Benzene: Toxic, volatile, flammable liquid hydrocarbon biproduct of coal distillation. It is used as an industrial solvent in paints, varnishes, lacquer thinners, gasoline, etc. Benzene causes central nervous system damage acutely and bone marrow damage chronically and is carcinogenic. It was formerly used as parasiticide. [NIH] Benzo(a)pyrene: A potent mutagen and carcinogen. It is a public health concern because of its possible effects on industrial workers, as an environmental pollutant, an as a component of tobacco smoke. [NIH] Beta-Thalassemia: A disorder characterized by reduced synthesis of the beta chains of hemoglobin. There is retardation of hemoglobin A synthesis in the heterozygous form (thalassemia minor), which is asymptomatic, while in the homozygous form (thalassemia major, Cooley's anemia, Mediterranean anemia, erythroblastic anemia), which can result in severe complications and even death, hemoglobin A synthesis is absent. [NIH] Bicalutamide: An anticancer drug that belongs to the family of drugs called antiandrogens. [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] Binding Sites: The reactive parts of a macromolecule that directly participate in its specific combination with another molecule. [NIH] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biogenic Monoamines: Biogenic amines having only one amine moiety. Included in this group are all natural monoamines formed by the enzymatic decarboxylation of natural amino acids. [NIH] Biological response modifier: BRM. A substance that stimulates the body's response to infection and disease. [NIH] Biological therapy: Treatment to stimulate or restore the ability of the immune system to fight infection and disease. Also used to lessen side effects that may be caused by some cancer treatments. Also known as immunotherapy, biotherapy, or biological response modifier (BRM) therapy. [NIH] Biomarkers: Substances sometimes found in an increased amount in the blood, other body fluids, or tissues and that may suggest the presence of some types of cancer. Biomarkers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and GI tract cancers), and PSA (prostate cancer). Also called tumor markers. [NIH] Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body. [NIH] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Bladder: The organ that stores urine. [NIH] Blasts: Immature blood cells. [NIH] Blood Cell Count: A count of the number of leukocytes and erythrocytes per unit volume in
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a sample of venous blood. A complete blood count (CBC) also includes measurement of the hemoglobin, hematocrit, and erythrocyte indices. [NIH] Blood Glucose: Glucose in blood. [NIH] Blood Platelets: Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood transfusion: The administration of blood or blood products into a blood vessel. [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 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 aspiration: The removal of a small sample of bone marrow (usually from the hip) through a needle for examination under a microscope. [NIH] Bone marrow biopsy: The removal of a sample of tissue from the bone marrow with a needle for examination under a microscope. [NIH] Bone Marrow Cells: Cells contained in the bone marrow including fat cells, stromal cells, megakaryocytes, and the immediate precursors of most blood cells. [NIH] Bone Marrow Transplantation: The transference of bone marrow from one human or animal to another. [NIH] Bowel: The long tube-shaped organ in the abdomen that completes the process of digestion. There is both a small and a large bowel. Also called the intestine. [NIH] Bowel Movement: Body wastes passed through the rectum and anus. [NIH] Brachytherapy: A collective term for interstitial, intracavity, and surface radiotherapy. It uses small sealed or partly-sealed sources that may be placed on or near the body surface or within a natural body cavity or implanted directly into the tissues. [NIH] Bradykinin: A nonapeptide messenger that is enzymatically produced from kallidin in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from mast cells during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter. [NIH] Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]
Breeding: The science or art of changing the constitution of a population of plants or animals through sexual reproduction. [NIH] Buccal: Pertaining to or directed toward the cheek. In dental anatomy, used to refer to the buccal surface of a tooth. [EU] Bullous: Pertaining to or characterized by bullae. [EU]
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Bypass: A surgical procedure in which the doctor creates a new pathway for the flow of body fluids. [NIH] Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. [NIH] Callus: A callosity or hard, thick skin; the bone-like reparative substance that is formed round the edges and fragments of broken bone. [NIH] Canthaxanthin: A trans-carotenoid pigment widely distributed in nature. The compound is used as an oral suntanning agent and as a food and drug coloring agent. It is believed that it inhibits development of tumor cells and neoplastic transformation through its antioxidant properties. Oral ingestion of the compound causes canthaxanthin retinopathy. [NIH] Carbamazepine: An anticonvulsant used to control grand mal and psychomotor or focal seizures. Its mode of action is not fully understood, but some of its actions resemble those of phenytoin; although there is little chemical resemblance between the two compounds, their three-dimensional structure is similar. [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] Carcinogen: Any substance that causes cancer. [NIH] Carcinogenesis: The process by which normal cells are transformed into cancer cells. [NIH] Carcinogenic: Producing carcinoma. [EU] Carcinoma: Cancer that begins in the skin or in tissues that line or cover internal organs. [NIH]
Cardiac: Having to do with the heart. [NIH] Cardiopulmonary: Having to do with the heart and lungs. [NIH] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Cardiovascular disease: Any abnormal condition characterized by dysfunction of the heart and blood vessels. CVD includes atherosclerosis (especially coronary heart disease, which can lead to heart attacks), cerebrovascular disease (e.g., stroke), and hypertension (high blood pressure). [NIH] 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] Caspase: Enzyme released by the cell at a crucial stage in apoptosis in order to shred all cellular proteins. [NIH] Cations: Postively charged atoms, radicals or groups of atoms which travel to the cathode or negative pole during electrolysis. [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 Cycle: The complex series of phenomena, occurring between the end of one cell
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division and the end of the next, by which cellular material is divided between daughter 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 Extracts: Preparations of cell constituents or subcellular materials, isolates, or substances. [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 Respiration: The metabolic process of all living cells (animal and plant) in which oxygen is used to provide a source of energy for the cell. [NIH] Cell Size: The physical dimensions of a cell. It refers mainly to changes in dimensions correlated with physiological or pathological changes in cells. [NIH] Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. [NIH] Cell Transplantation: Transference of cells within an individual, between individuals of the same species, or between individuals of different species. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Centrifugation: A method of separating organelles or large molecules that relies upon differential sedimentation through a preformed density gradient under the influence of a gravitational field generated in a centrifuge. [NIH] Ceramide: A type of fat produced in the body. It may cause some types of cells to die, and is being studied in cancer treatment. [NIH] Cerebellar: Pertaining to the cerebellum. [EU] Cerebellum: Part of the metencephalon that lies in the posterior cranial fossa behind the brain stem. It is concerned with the coordination of movement. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebral Palsy: Refers to a motor disability caused by a brain dysfunction. [NIH] Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU] Cerebrum: The largest part of the brain. It is divided into two hemispheres, or halves, called the cerebral hemispheres. The cerebrum controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. [NIH] Character: In current usage, approximately equivalent to personality. The sum of the relatively fixed personality traits and habitual modes of response of an individual. [NIH]
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Chemotactic Factors: Chemical substances that attract or repel cells or organisms. The concept denotes especially those factors released as a result of tissue injury, invasion, or immunologic activity, that attract leukocytes, macrophages, or other cells to the site of infection or insult. [NIH] Chemotherapy: Treatment with anticancer drugs. [NIH] Chest Pain: Pressure, burning, or numbness in the chest. [NIH] Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. [NIH] Chromatin: The material of chromosomes. It is a complex of DNA, histones, and nonhistone proteins (chromosomal proteins, non-histone) found within the nucleus of a cell. [NIH] Chromosomal: Pertaining to chromosomes. [EU] Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chronic granulocytic leukemia: A slowly progressing disease in which too many white blood cells are made in the bone marrow. Also called chronic myelogenous leukemia or chronic myeloid leukemia. [NIH] Chronic leukemia: A slowly progressing cancer of the blood-forming tissues. [NIH] Chronic lymphocytic leukemia: A slowly progressing disease in which too many white blood cells (called lymphocytes) are found in the body. [NIH] Chronic myelogenous leukemia: CML. A slowly progressing disease in which too many white blood cells are made in the bone marrow. Also called chronic myeloid leukemia or chronic granulocytic leukemia. [NIH] Chronic renal: Slow and progressive loss of kidney function over several years, often resulting in end-stage renal disease. People with end-stage renal disease need dialysis or transplantation to replace the work of the kidneys. [NIH] Chymotrypsin: A serine endopeptidase secreted by the pancreas as its zymogen, chymotrypsinogen and carried in the pancreatic juice to the duodenum where it is activated by trypsin. It selectively cleaves aromatic amino acids on the carboxyl side. [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] Clear cell carcinoma: A rare type of tumor of the female genital tract in which the inside of the cells looks clear when viewed under a microscope. [NIH] Cleave: A double-stranded cut in DNA with a restriction endonuclease. [NIH] 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
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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] Coal: A natural fuel formed by partial decomposition of vegetable matter under certain environmental conditions. [NIH] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] Colitis: Inflammation of the colon. [NIH] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline, hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [NIH] Colony-Stimulating Factors: Glycoproteins found in a subfraction of normal mammalian plasma and urine. They stimulate the proliferation of bone marrow cells in agar cultures and the formation of colonies of granulocytes and/or macrophages. The factors include interleukin-3 (IL-3), granulocyte colony-stimulating factor (G-CSF), macrophage colonystimulating factor (M-CSF), and granulocyte-macrophage colony-stimulating factor (GMCSF). [NIH] Combination chemotherapy: Treatment using more than one anticancer drug. [NIH] Combination Therapy: Association of 3 drugs to treat AIDS (AZT + DDC or DDI + protease inhibitor). [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]
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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] Complementation: The production of a wild-type phenotype when two different mutations are combined in a diploid or a heterokaryon and tested in trans-configuration. [NIH] Complete remission: The disappearance of all signs of cancer. Also called a complete response. [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] Conjugated: Acting or operating as if joined; simultaneous. [EU] Conjugation: 1. The act of joining together or the state of being conjugated. 2. A sexual process seen in bacteria, ciliate protozoa, and certain fungi in which nuclear material is exchanged during the temporary fusion of two cells (conjugants). In bacterial genetics a form of sexual reproduction in which a donor bacterium (male) contributes some, or all, of its DNA (in the form of a replicated set) to a recipient (female) which then incorporates differing genetic information into its own chromosome by recombination and passes the recombined set on to its progeny by replication. In ciliate protozoa, two conjugants of separate mating types exchange micronuclear material and then separate, each now being a fertilized cell. In certain fungi, the process involves fusion of two gametes, resulting in union of their nuclei and formation of a zygote. 3. In chemistry, the joining together of two compounds to produce another compound, such as the combination of a toxic product with some substance in the body to form a detoxified product, which is then eliminated. [EU] 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] Constitutional: 1. Affecting the whole constitution of the body; not local. 2. Pertaining to the constitution. [EU] 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] 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
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pathologic involvement of them. [EU] Coronary heart disease: A type of heart disease caused by narrowing of the coronary arteries that feed the heart, which needs a constant supply of oxygen and nutrients carried by the blood in the coronary arteries. When the coronary arteries become narrowed or clogged by fat and cholesterol deposits and cannot supply enough blood to the heart, CHD results. [NIH] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Corpuscle: A small mass or body; a sensory nerve end bulb; a cell, especially that of the blood or the lymph. [NIH] Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [EU] Cortical: Pertaining to or of the nature of a cortex or bark. [EU] Corticosteroids: Hormones that have antitumor activity in lymphomas and lymphoid leukemias; in addition, corticosteroids (steroids) may be used for hormone replacement and for the management of some of the complications of cancer and its treatment. [NIH] Criterion: A standard by which something may be judged. [EU] Crossing-over: The exchange of corresponding segments between chromatids of homologous chromosomes during meiosia, forming a chiasma. [NIH] Cryofixation: Fixation of a tissue by localized cooling at very low temperature. [NIH] Cryopreservation: Preservation of cells, tissues, organs, or embryos by freezing. In histological preparations, cryopreservation or cryofixation is used to maintain the existing form, structure, and chemical composition of all the constituent elements of the specimens. [NIH]
Cryoprotective: Any substance added to a living tissue for improving its survival during frozen preservation. [NIH] Cryoprotective Agents: Substances that provide protection against the harmful effects of freezing temperatures. [NIH] Cultured cells: Animal or human cells that are grown in the laboratory. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Cutaneous: Having to do with the skin. [NIH] Cyclic: Pertaining to or occurring in a cycle or cycles; the term is applied to chemical compounds that contain a ring of atoms in the nucleus. [EU] 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] Cyclosporine: A drug used to help reduce the risk of rejection of organ and bone marrow transplants by the body. It is also used in clinical trials to make cancer cells more sensitive to anticancer drugs. [NIH] Cyproterone: An anti-androgen that, in the form of its acetate, also has progestational properties. It is used in the treatment of hypersexuality in males, as a palliative in prostatic carcinoma, and, in combination with estrogen, for the therapy of severe acne and hirsutism in females. [NIH]
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Cysteine: A thiol-containing non-essential amino acid that is oxidized to form cystine. [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]
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] Cytogenetics: A branch of genetics which deals with the cytological and molecular behavior of genes and chromosomes during cell division. [NIH] Cytokine: Small but highly potent protein that modulates the activity of many cell types, including T and B cells. [NIH] Cytomegalovirus: A genus of the family Herpesviridae, subfamily Betaherpesvirinae, infecting the salivary glands, liver, spleen, lungs, eyes, and other organs, in which they produce characteristically enlarged cells with intranuclear inclusions. Infection with Cytomegalovirus is also seen as an opportunistic infection in AIDS. [NIH] Cytomegalovirus Retinitis: Infection of the retina by cytomegalovirus characterized by retinal necrosis, hemorrhage, vessel sheathing, and retinal edema. Cytomegalovirus retinitis is a major opportunistic infection in AIDS patients and can cause blindness. [NIH] Cytopenia: A reduction in the number of blood cells. [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] Cytotoxic: Cell-killing. [NIH] Cytotoxicity: Quality of being capable of producing a specific toxic action upon cells of special organs. [NIH] Daclizumab: A monoclonal antibody that is being studied for treatment of adult T-cell leukemia. Also called dacliximab. Monoclonal antibodies are laboratory-produced substances that can locate and bind to cancer cells. [NIH] Danazol: A synthetic steroid with antigonadotropic and anti-estrogenic activities that acts as an anterior pituitary suppressant by inhibiting the pituitary output of gonadotropins. It possesses some androgenic properties. Danazol has been used in the treatment of endometriosis and some benign breast disorders. [NIH] Databases, Bibliographic: Extensive collections, reputedly complete, of references and citations to books, articles, publications, etc., generally on a single subject or specialized subject area. Databases can operate through automated files, libraries, or computer disks. The concept should be differentiated from factual databases which is used for collections of data and facts apart from bibliographic references to them. [NIH] De novo: In cancer, the first occurrence of cancer in the body. [NIH] Defense Mechanisms: Unconscious process used by an individual or a group of individuals
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in order to cope with impulses, feelings or ideas which are not acceptable at their conscious level; various types include reaction formation, projection and self reversal. [NIH] 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] Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other neurons. [NIH] Dendritic: 1. Branched like a tree. 2. Pertaining to or possessing dendrites. [EU] Dendritic cell: A special type of antigen-presenting cell (APC) that activates T lymphocytes. [NIH]
Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] Depolarization: The process or act of neutralizing polarity. In neurophysiology, the reversal of the resting potential in excitable cell membranes when stimulated, i.e., the tendency of the cell membrane potential to become positive with respect to the potential outside the cell. [EU] Depressive Disorder: An affective disorder manifested by either a dysphoric mood or loss of interest or pleasure in usual activities. The mood disturbance is prominent and relatively persistent. [NIH] Deprivation: Loss or absence of parts, organs, powers, or things that are needed. [EU] Dermal: Pertaining to or coming from the skin. [NIH] Dermatitis: Any inflammation of the skin. [NIH] DES: Diethylstilbestrol. A synthetic hormone that was prescribed from the early 1940s until 1971 to help women with complications of pregnancy. DES has been linked to an increased risk of clear cell carcinoma of the vagina in daughters of women who used DES. DES may also increase the risk of breast cancer in women who used DES. [NIH] Detoxification: Treatment designed to free an addict from his drug habit. [EU] Diabetes Mellitus: A heterogeneous group of disorders that share glucose intolerance in common. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Diarrhea: Passage of excessively liquid or excessively frequent stools. [NIH] Diastolic: Of or pertaining to the diastole. [EU] Diffusion: The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself throughout the available space; a major mechanism of biological transport. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Digestive system: The organs that take in food and turn it into products that the body can use to stay healthy. Waste products the body cannot use leave the body through bowel movements. The digestive system includes the salivary glands, mouth, esophagus, stomach, liver, pancreas, gallbladder, small and large intestines, and rectum. [NIH] Dihydrotestosterone: Anabolic agent. [NIH] Dilatation: The act of dilating. [NIH] Diltiazem: A benzothiazepine derivative with vasodilating action due to its antagonism of the actions of the calcium ion in membrane functions. It is also teratogenic. [NIH] Dilution: A diluted or attenuated medicine; in homeopathy, the diffusion of a given
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quantity of a medicinal agent in ten or one hundred times the same quantity of water. [NIH] Dimethyl: A volatile metabolite of the amino acid methionine. [NIH] Dipeptidases: Exopeptidases that specifically act on dipeptides. EC 3.4.13. [NIH] Dipeptides: Peptides composed of two amino acid units. [NIH] Diploid: Having two sets of chromosomes. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Disaccharides: Sugars composed of two monosaccharides linked by glycoside bonds. [NIH] Disease Progression: The worsening of a disease over time. This concept is most often used for chronic and incurable diseases where the stage of the disease is an important determinant of therapy and prognosis. [NIH] Disparity: Failure of the two retinal images of an object to fall on corresponding retinal points. [NIH] Dissociation: 1. The act of separating or state of being separated. 2. The separation of a molecule into two or more fragments (atoms, molecules, ions, or free radicals) produced by the absorption of light or thermal energy or by solvation. 3. In psychology, a defense mechanism in which a group of mental processes are segregated from the rest of a person's mental activity in order to avoid emotional distress, as in the dissociative disorders (q.v.), or in which an idea or object is segregated from its emotional significance; in the first sense it is roughly equivalent to splitting, in the second, to isolation. 4. A defect of mental integration in which one or more groups of mental processes become separated off from normal consciousness and, thus separated, function as a unitary whole. [EU] Dominance: In genetics, the full phenotypic expression of a gene in both heterozygotes and homozygotes. [EU] 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] Drive: A state of internal activity of an organism that is a necessary condition before a given stimulus will elicit a class of responses; e.g., a certain level of hunger (drive) must be present before food will elicit an eating response. [NIH] 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] Duodenum: The first part of the small intestine. [NIH] Dyspareunia: Painful sexual intercourse. [NIH] Ectopic: Pertaining to or characterized by ectopia. [EU] Edema: Excessive amount of watery fluid accumulated in the intercellular spaces, most commonly present in subcutaneous tissue. [NIH]
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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] Electrocardiogram: Measurement of electrical activity during heartbeats. [NIH] 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] Embolus: Bit of foreign matter which enters the blood stream at one point and is carried until it is lodged or impacted in an artery and obstructs it. It may be a blood clot, an air bubble, fat or other tissue, or clumps of bacteria. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Embryogenesis: The process of embryo or embryoid formation, whether by sexual (zygotic) or asexual means. In asexual embryogenesis embryoids arise directly from the explant or on intermediary callus tissue. In some cases they arise from individual cells (somatic cell embryoge). [NIH] Encapsulated: Confined to a specific, localized area and surrounded by a thin layer of tissue. [NIH]
Encephalopathy: A disorder of the brain that can be caused by disease, injury, drugs, or chemicals. [NIH] Endemic: Present or usually prevalent in a population or geographical area at all times; said of a disease or agent. Called also endemial. [EU] Endocrine Glands: Ductless glands that secrete substances which are released directly into the circulation and which influence metabolism and other body functions. [NIH] Endometrial: Having to do with the endometrium (the layer of tissue that lines the uterus). [NIH]
Endometriosis: A condition in which tissue more or less perfectly resembling the uterine mucous membrane (the endometrium) and containing typical endometrial granular and stromal elements occurs aberrantly in various locations in the pelvic cavity. [NIH] Endometrium: The layer of tissue that lines the uterus. [NIH] Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart. [NIH] Endothelium: A layer of epithelium that lines the heart, blood vessels (endothelium, vascular), lymph vessels (endothelium, lymphatic), and the serous cavities of the body. [NIH] Endothelium, Lymphatic: Unbroken cellular lining (intima) of the lymph vessels (e.g., the high endothelial lymphatic venules). It is more permeable than vascular endothelium, lacking selective absorption and functioning mainly to remove plasma proteins that have filtered through the capillaries into the tissue spaces. [NIH] Endothelium, Vascular: Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components
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from interstitium to lumen; this function has been most intensively studied in the blood capillaries. [NIH] Endothelium-derived: Small molecule that diffuses to the adjacent muscle layer and relaxes it. [NIH] Endotoxin: Toxin from cell walls of bacteria. [NIH] End-stage renal: Total chronic kidney failure. When the kidneys fail, the body retains fluid and harmful wastes build up. A person with ESRD needs treatment to replace the work of the failed kidneys. [NIH] Enhancer: Transcriptional element in the virus genome. [NIH] Enteropeptidase: A specialized proteolytic enzyme secreted by intestinal cells. It converts trypsinogen into its active form trypsin by removing the N-terminal peptide. EC 3.4.21.9. [NIH]
Environmental Exposure: The exposure to potentially harmful chemical, physical, or biological agents in the environment or to environmental factors that may include ionizing radiation, pathogenic organisms, or toxic chemicals. [NIH] Environmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health. [NIH]
Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Eosinophil: A polymorphonuclear leucocyte with large eosinophilic granules in its cytoplasm, which plays a role in hypersensitivity reactions. [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] Epidermis: Nonvascular layer of the skin. It is made up, from within outward, of five layers: 1) basal layer (stratum basale epidermidis); 2) spinous layer (stratum spinosum epidermidis); 3) granular layer (stratum granulosum epidermidis); 4) clear layer (stratum lucidum epidermidis); and 5) horny layer (stratum corneum epidermidis). [NIH] Epinephrine: The active sympathomimetic hormone from the adrenal medulla in most species. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. It is used in asthma and cardiac failure and to delay absorption of local anesthetics. [NIH] Epistaxis: Bleeding from the nose. [NIH] Epithelial: Refers to the cells that line the internal and external surfaces of the body. [NIH] Epithelial Cells: Cells that line the inner and outer surfaces of the body. [NIH] Epithelium: One or more layers of epithelial cells, supported by the basal lamina, which covers the inner or outer surfaces of the body. [NIH] Erythroblasts: Immature, nucleated erythrocytes occupying the stage of erythropoiesis that follows formation of erythroid progenitor cells and precedes formation of reticulocytes. Popularly called normoblasts. [NIH] Erythrocyte Indices: Quantification of size and cell hemoglobin content or concentration of the erythrocyte, usually derived from erythrocyte count, blood hemoglobin concentration, and hematocrit. Includes the mean cell volume (MCV), mean cell hemoglobin (MCH), and mean cell hemoglobin concentration (MCHC). Use also for cell diameter and thickness. [NIH]
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Erythrocyte Membrane: The semipermeable outer portion of the red corpuscle. It is known as a 'ghost' after hemolysis. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Erythroid Progenitor Cells: Committed, erythroid stem cells derived from myeloid stem cells. The progenitor cells develop in two phases: erythroid burst-forming units (BFU-E) followed by erythroid colony-forming units (CFU-E). BFU-E differentiate into CFU-E on stimulation by erythropoietin, and then further differentiate into erythroblasts when stimulated by other factors. [NIH] Erythropoiesis: The production of erythrocytes. [EU] 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] Erythrovirus: A genus of the family Parvoviridae, subfamily Parvovirinae, and containing one known species, human parvovirus B19. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]
Estrogen: One of the two female sex hormones. [NIH] Estrogen Replacement Therapy: The use of hormonal agents with estrogen-like activity in postmenopausal or other estrogen-deficient women to alleviate effects of hormone deficiency, such as vasomotor symptoms, dyspareunia, and progressive development of osteoporosis. This may also include the use of progestational agents in combination therapy. [NIH]
Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH] Excisional: The surgical procedure of removing a tumor by cutting it out. The biopsy is then examined under a microscope. [NIH] Excitation: An act of irritation or stimulation or of responding to a stimulus; the addition of energy, as the excitation of a molecule by absorption of photons. [EU] Exon: The part of the DNA that encodes the information for the actual amino acid sequence of the protein. In many eucaryotic genes, the coding sequences consist of a series of exons alternating with intron sequences. [NIH] External-beam radiation: Radiation therapy that uses a machine to aim high-energy rays at the cancer. Also called external radiation. [NIH] Extracellular: Outside a cell or cells. [EU] Extracellular Matrix: A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. [NIH] 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] Fat: Total lipids including phospholipids. [NIH] Fathers: Male parents, human or animal. [NIH] Fatigue: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli.
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[NIH]
Feces: The excrement discharged from the intestines, consisting of bacteria, cells exfoliated from the intestines, secretions, chiefly of the liver, and a small amount of food residue. [EU] Femoral: Pertaining to the femur, or to the thigh. [EU] Femoral Neck Fractures: Fractures of the short, constricted portion of the thigh bone between the femur head and the trochanters. It excludes intertrochanteric fractures which are hip fractures. [NIH] Femur: The longest and largest bone of the skeleton, it is situated between the hip and the knee. [NIH] Ferritin: An iron-containing protein complex that is formed by a combination of ferric iron with the protein apoferritin. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [NIH] Fibronectin: An adhesive glycoprotein. One form circulates in plasma, acting as an opsonin; another is a cell-surface protein which mediates cellular adhesive interactions. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Filgrastim: A colony-stimulating factor that stimulates the production of neutrophils (a type of white blood cell). It is a cytokine that belongs to the family of drugs called hematopoietic (blood-forming) agents. Also called granulocyte colony-stimulating factor (G-CSF). [NIH] Flow Cytometry: Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake. [NIH] Fluorescence: The property of emitting radiation while being irradiated. The radiation emitted is usually of longer wavelength than that incident or absorbed, e.g., a substance can be irradiated with invisible radiation and emit visible light. X-ray fluorescence is used in diagnosis. [NIH] Fluorescent Dyes: Dyes that emit light when exposed to light. The wave length of the emitted light is usually longer than that of the incident light. Fluorochromes are substances that cause fluorescence in other substances, i.e., dyes used to mark or label other compounds with fluorescent tags. They are used as markers in biochemistry and immunology. [NIH] Flutamide: An antiandrogen with about the same potency as cyproterone in rodent and canine species. [NIH] Folate: A B-complex vitamin that is being studied as a cancer prevention agent. Also called folic acid. [NIH] Fold: A plication or doubling of various parts of the body. [NIH] Folic Acid: N-(4-(((2-Amino-1,4-dihydro-4-oxo-6-pteridinyl)methyl)amino)benzoyl)-Lglutamic acid. A member of the vitamin B family that stimulates the hematopoietic system. It is present in the liver and kidney and is found in mushrooms, spinach, yeast, green leaves,
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and grasses. Folic acid is used in the treatment and prevention of folate deficiencies and megaloblastic anemia. [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]
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] 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] Ganglion: 1. A knot, or knotlike mass. 2. A general term for a group of nerve cell bodies located outside the central nervous system; occasionally applied to certain nuclear groups within the brain or spinal cord, e.g. basal ganglia. 3. A benign cystic tumour occurring on a aponeurosis or tendon, as in the wrist or dorsum of the foot; it consists of a thin fibrous capsule enclosing a clear mucinous fluid. [EU] Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] Gasoline: Volative flammable fuel (liquid hydrocarbons) derived from crude petroleum by processes such as distillation reforming, polymerization, etc. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]
Gastritis: Inflammation of the stomach. [EU] Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [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 Deletion: A genetic rearrangement through loss of segments of DNA or RNA, bringing sequences which are normally separated into close proximity. This deletion may be detected using cytogenetic techniques and can also be inferred from the phenotype, indicating a deletion at one specific locus. [NIH] Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [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 Counseling: Advising families of the risks involved pertaining to birth defects, in order that they may make an informed decision on current or future pregnancies. [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]
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Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Genomics: The systematic study of the complete DNA sequences (genome) of organisms. [NIH]
Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Geriatric: Pertaining to the treatment of the aged. [EU] Gingival Hemorrhage: The flowing of blood from the marginal gingival area, particularly the sulcus, seen in such conditions as gingivitis, marginal periodontitis, injury, and ascorbic acid deficiency. [NIH] Gingival Hyperplasia: A pathological increase in the depth of the gingival crevice surrounding a tooth at the gum margin. [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] Glucose: D-Glucose. A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. [NIH] 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]
Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Glycoside: Any compound that contains a carbohydrate molecule (sugar), particularly any such natural product in plants, convertible, by hydrolytic cleavage, into sugar and a nonsugar component (aglycone), and named specifically for the sugar contained, as glucoside (glucose), pentoside (pentose), fructoside (fructose) etc. [EU] Gonadal: Pertaining to a gonad. [EU] Gonads: The gamete-producing glands, ovary or testis. [NIH] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to replace diseased or injured tissue removed from another part of the body. [NIH] Graft Rejection: An immune response with both cellular and humoral components, directed against an allogeneic transplant, whose tissue antigens are not compatible with those of the recipient. [NIH] Grafting: The operation of transfer of tissue from one site to another. [NIH] Graft-versus-host disease: GVHD. A reaction of donated bone marrow or peripheral stem cells against a person's tissue. [NIH] Granulocyte Colony-Stimulating Factor: A glycoprotein of MW 25 kDa containing internal disulfide bonds. It induces the survival, proliferation, and differentiation of neutrophilic granulocyte precursor cells and functionally activates mature blood neutrophils. Among the family of colony-stimulating factors, G-CSF is the most potent inducer of terminal differentiation to granulocytes and macrophages of leukemic myeloid cell lines. [NIH] Granulocyte-Macrophage Colony-Stimulating Factor: An acidic glycoprotein of MW 23 kDa with internal disulfide bonds. The protein is produced in response to a number of inflammatory mediators by mesenchymal cells present in the hemopoietic environment and at peripheral sites of inflammation. GM-CSF is able to stimulate the production of
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neutrophilic granulocytes, macrophages, and mixed granulocyte-macrophage colonies from bone marrow cells and can stimulate the formation of eosinophil colonies from fetal liver progenitor cells. GM-CSF can also stimulate some functional activities in mature granulocytes and macrophages. [NIH] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups: neutrophils, eosinophils, and basophils. [NIH] Granulocytopenia: A deficiency in the number of granulocytes, a type of white blood cell. [NIH]
Grasses: A large family, Gramineae, of narrow-leaved herbaceous monocots. Many grasses produce highly allergenic pollens and are hosts to cattle parasites and toxic fungi. [NIH] Growth: The progressive development of a living being or part of an organism from its earliest stage to maturity. [NIH] Growth factors: Substances made by the body that function to regulate cell division and cell survival. Some growth factors are also produced in the laboratory and used in biological therapy. [NIH] 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] Hairy cell leukemia: A type of chronic leukemia in which the abnormal white blood cells appear to be covered with tiny hairs when viewed under a microscope. [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] Heart attack: A seizure of weak or abnormal functioning of the heart. [NIH] Heart failure: Loss of pumping ability by the heart, often accompanied by fatigue, breathlessness, and excess fluid accumulation in body tissues. [NIH] Hemato: A selective mechanism opposing the passage of most large-molecular compounds from the blood to the cerebro-spinal fluid and brain tissue; offers some protection against intoxication. [NIH] Hematocrit: Measurement of the volume of packed red cells in a blood specimen by centrifugation. The procedure is performed using a tube with graduated markings or with automated blood cell counters. It is used as an indicator of erythrocyte status in disease. For example, anemia shows a low hematocrit, polycythemia, high values. [NIH] Hematologic malignancies: Cancers of the blood or bone marrow, including leukemia and lymphoma. Also called hematologic cancers. [NIH] Hematologist: A doctor who specializes in treating diseases of the blood. [NIH] Hematology: A subspecialty of internal medicine concerned with morphology, physiology, and pathology of the blood and blood-forming tissues. [NIH] Hematopoiesis: The development and formation of various types of blood cells. [NIH] Hematopoietic growth factors: A group of proteins that cause blood cells to grow and mature. [NIH] Hematopoietic Stem Cell Transplantation: The transference of stem cells from one animal or human to another (allogeneic), or within the same individual (autologous). The source for the stem cells may be the bone marrow or peripheral blood. Stem cell transplantation has been used as an alternative to autologous bone marrow transplantation in the treatment of a variety of neoplasms. [NIH]
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Hematopoietic Stem Cells: Progenitor cells from which all blood cells derive. [NIH] Hematopoietic tissue: Tissue in which new blood cells are formed. [NIH] Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. [NIH] Hemoglobin: One of the fractions of glycosylated hemoglobin A1c. Glycosylated hemoglobin is formed when linkages of glucose and related monosaccharides bind to hemoglobin A and its concentration represents the average blood glucose level over the previous several weeks. HbA1c levels are used as a measure of long-term control of plasma glucose (normal, 4 to 6 percent). In controlled diabetes mellitus, the concentration of glycosylated hemoglobin A is within the normal range, but in uncontrolled cases the level may be 3 to 4 times the normal conentration. Generally, complications are substantially lower among patients with Hb levels of 7 percent or less than in patients with HbA1c levels of 9 percent or more. [NIH] Hemoglobinuria: The presence of free hemoglobin in the urine. [NIH] Hemolysis: The destruction of erythrocytes by many different causal agents such as antibodies, bacteria, chemicals, temperature, and changes in tonicity. [NIH] Hemolytic: A disease that affects the blood and blood vessels. It destroys red blood cells, cells that cause the blood to clot, and the lining of blood vessels. HUS is often caused by the Escherichia coli bacterium in contaminated food. People with HUS may develop acute renal failure. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] 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] Hereditary: Of, relating to, or denoting factors that can be transmitted genetically from one generation to another. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Herpes: Any inflammatory skin disease caused by a herpesvirus and characterized by the formation of clusters of small vesicles. When used alone, the term may refer to herpes simplex or to herpes zoster. [EU] Herpes virus: A member of the herpes family of viruses. [NIH] Herpes Zoster: Acute vesicular inflammation. [NIH] 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]
Heterozygote: An individual having different alleles at one or more loci in homologous chromosome segments. [NIH] Hip Fractures: Fractures of the femur head, the femur neck, the trochanters, or the inter- or subtrochanteric region. Excludes fractures of the acetabulum and fractures of the femoral shaft below the subtrochanteric region. For the fractures of the femur neck the specific term femoral neck fractures is available. [NIH] Hirsutism: Excess hair in females and children with an adult male pattern of distribution. The concept does not include hypertrichosis, which is localized or generalized excess hair.
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[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] 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] Histocompatibility: The degree of antigenic similarity between the tissues of different individuals, which determines the acceptance or rejection of allografts. [NIH] Histology: The study of tissues and cells under a microscope. [NIH] Histone Deacetylase: Hydrolyzes N-acetyl groups on histones. [NIH] Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable. [NIH] Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] Homozygotes: An individual having a homozygous gene pair. [NIH] 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] Host: Any animal that receives a transplanted graft. [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] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [NIH] Hybridization: The genetic process of crossbreeding to produce a hybrid. Hybrid nucleic acids can be formed by nucleic acid hybridization of DNA and RNA molecules. Protein hybridization allows for hybrid proteins to be formed from polypeptide chains. [NIH] Hybridomas: Cells artificially created by fusion of activated lymphocytes with neoplastic cells. The resulting hybrid cells are cloned and produce pure or "monoclonal" antibodies or T-cell products, identical to those produced by the immunologically competent parent, and continually grow and divide as the neoplastic parent. [NIH] 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] Hypercholesterolemia: Abnormally high levels of cholesterol in the blood. [NIH] Hyperlipidemia: An excess of lipids in the blood. [NIH] Hyperplasia: An increase in the number of cells in a tissue or organ, not due to tumor
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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] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hypertrichosis: Localized or generalized excess hair. The concept does not include hirsutism, which is excess hair in females and children with an adult male pattern of distribution. [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] Hypogonadism: Condition resulting from or characterized by abnormally decreased functional activity of the gonads, with retardation of growth and sexual development. [NIH] Hypotension: Abnormally low blood pressure. [NIH] Id: The part of the personality structure which harbors the unconscious instinctive desires and strivings of the individual. [NIH] Ida: An alkylating agent. [NIH] Idiopathic: Describes a disease of unknown cause. [NIH] Immune function: Production and action of cells that fight disease or infection. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]
Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] Immune Tolerance: The specific failure of a normally responsive individual to make an immune response to a known antigen. It results from previous contact with the antigen by an immunologically immature individual (fetus or neonate) or by an adult exposed to extreme high-dose or low-dose antigen, or by exposure to radiation, antimetabolites, antilymphocytic serum, etc. [NIH] Immunity: Nonsusceptibility to the invasive or pathogenic microorganisms or to the toxic effect of antigenic substances. [NIH]
effects
of
foreign
Immunocompromised: Having a weakened immune system caused by certain diseases or treatments. [NIH] Immunodeficiency: The decreased ability of the body to fight infection and disease. [NIH] 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] Immunosuppressant: An agent capable of suppressing immune responses. [EU] Immunosuppressive: Describes the ability to lower immune system responses. [NIH] Immunosuppressive Agents: Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of suppressor T-cell populations or by inhibiting the activation of helper cells. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving
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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] 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 situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incontinence: Inability to control the flow of urine from the bladder (urinary incontinence) or the escape of stool from the rectum (fecal incontinence). [NIH] Incubation: The development of an infectious disease from the entrance of the pathogen to the appearance of clinical symptoms. [EU] Incubation period: The period of time likely to elapse between exposure to the agent of the disease and the onset of clinical symptoms. [NIH] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]
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]
Infusion: A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion. [NIH] Ingestion: Taking into the body by mouth [NIH] Inhalation: The drawing of air or other substances into the lungs. [EU] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a
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step in a carcinogenic process. [NIH] Inlay: In dentistry, a filling first made to correspond with the form of a dental cavity and then cemented into the cavity. [NIH] Inner ear: The labyrinth, comprising the vestibule, cochlea, and semicircular canals. [NIH] Inositol: An isomer of glucose that has traditionally been considered to be a B vitamin although it has an uncertain status as a vitamin and a deficiency syndrome has not been identified in man. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1379) Inositol phospholipids are important in signal transduction. [NIH] Insecticides: Pesticides designed to control insects that are harmful to man. The insects may be directly harmful, as those acting as disease vectors, or indirectly harmful, as destroyers of crops, food products, or textile fabrics. [NIH] Insight: The capacity to understand one's own motives, to be aware of one's own psychodynamics, to appreciate the meaning of symbolic behavior. [NIH] 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] Insulin-dependent diabetes mellitus: A disease characterized by high levels of blood glucose resulting from defects in insulin secretion, insulin action, or both. Autoimmune, genetic, and environmental factors are involved in the development of type I diabetes. [NIH] Insulin-like: Muscular growth factor. [NIH] Interferon: A biological response modifier (a substance that can improve the body's natural response to disease). Interferons interfere with the division of cancer cells and can slow tumor growth. There are several types of interferons, including interferon-alpha, -beta, and gamma. These substances are normally produced by the body. They are also made in the laboratory for use in treating cancer and other diseases. [NIH] Interferon-alpha: One of the type I interferons produced by peripheral blood leukocytes or lymphoblastoid cells when exposed to live or inactivated virus, double-stranded RNA, or bacterial products. It is the major interferon produced by virus-induced leukocyte cultures and, in addition to its pronounced antiviral activity, it causes activation of NK cells. [NIH] Interleukin-1: A soluble factor produced by monocytes, macrophages, and other cells which activates T-lymphocytes and potentiates their response to mitogens or antigens. IL-1 consists of two distinct forms, IL-1 alpha and IL-1 beta which perform the same functions but are distinct proteins. The biological effects of IL-1 include the ability to replace macrophage requirements for T-cell activation. The factor is distinct from interleukin-2. [NIH] Interleukin-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-3: A multilineage cell growth factor secreted by lymphocytes, epithelial cells, and astrocytes which stimulates clonal proliferation and differentiation of various types of blood and tissue cells. Also called multi-CSF, it is considered one of the hematopoietic colony stimulating factors. [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]
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Interleukins: Soluble factors which stimulate growth-related activities of leukocytes as well as other cell types. They enhance cell proliferation and differentiation, DNA synthesis, secretion of other biologically active molecules and responses to immune and inflammatory stimuli. [NIH] Internal Medicine: A medical specialty concerned with the diagnosis and treatment of diseases of the internal organ systems of adults. [NIH] Internal radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called brachytherapy, implant radiation, or interstitial radiation therapy. [NIH] Interphase: The interval between two successive cell divisions during which the chromosomes are not individually distinguishable and DNA replication occurs. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intestinal: Having to do with the intestines. [NIH] Intestine: A long, tube-shaped organ in the abdomen that completes the process of digestion. There is both a large intestine and a small intestine. Also called the bowel. [NIH] Intoxication: Poisoning, the state of being poisoned. [EU] Intracellular: Inside a cell. [NIH] Intramuscular: IM. Within or into muscle. [NIH] Intravascular: Within a vessel or vessels. [EU] Intravenous: IV. Into a vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]
Ion Transport: The movement of ions across energy-transducing cell membranes. Transport can be active or passive. Passive ion transport (facilitated diffusion) derives its energy from the concentration gradient of the ion itself and allows the transport of a single solute in one direction (uniport). Active ion transport is usually coupled to an energy-yielding chemical or photochemical reaction such as ATP hydrolysis. This form of primary active transport is called an ion pump. Secondary active transport utilizes the voltage and ion gradients produced by the primary transport to drive the cotransport of other ions or molecules. These may be transported in the same (symport) or opposite (antiport) direction. [NIH] Ionization: 1. Any process by which a neutral atom gains or loses electrons, thus acquiring a net charge, as the dissociation of a substance in solution into ions or ion production by the passage of radioactive particles. 2. Iontophoresis. [EU] Ionizing: Radiation comprising charged particles, e. g. electrons, protons, alpha-particles, etc., having sufficient kinetic energy to produce ionization by collision. [NIH] Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as cations; those with a negative charge are anions. [NIH] Irradiation: The use of high-energy radiation from x-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 from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive
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substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Irradiation is also called radiation therapy, radiotherapy, and x-ray therapy. [NIH] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Joint: The point of contact between elements of an animal skeleton with the parts that surround and support it. [NIH] Kb: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [NIH] Ketoconazole: Broad spectrum antifungal agent used for long periods at high doses, especially in immunosuppressed patients. [NIH] Kidney Disease: Any one of several chronic conditions that are caused by damage to the cells of the kidney. People who have had diabetes for a long time may have kidney damage. Also called nephropathy. [NIH] Kinetic: Pertaining to or producing motion. [EU] Labile: 1. Gliding; moving from point to point over the surface; unstable; fluctuating. 2. Chemically unstable. [EU] Lamivudine: A reverse transcriptase inhibitor and zalcitabine analog in which a sulfur atom replaces the 3' carbon of the pentose ring. It is used to treat HIV disease. [NIH] Large Intestine: The part of the intestine that goes from the cecum to the rectum. The large intestine absorbs water from stool and changes it from a liquid to a solid form. The large intestine is 5 feet long and includes the appendix, cecum, colon, and rectum. Also called colon. [NIH] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH] Lentivirus: A genus of the family Retroviridae consisting of non-oncogenic retroviruses that produce multi-organ diseases characterized by long incubation periods and persistent infection. Lentiviruses are unique in that they contain open reading frames (ORFs) between the pol and env genes and in the 3' env region. Five serogroups are recognized, reflecting the mammalian hosts with which they are associated. HIV-1 is the type species. [NIH] Lesion: An area of abnormal tissue change. [NIH] Lethal: Deadly, fatal. [EU] Leucocyte: All the white cells of the blood and their precursors (myeloid cell series, lymphoid cell series) but commonly used to indicate granulocytes exclusive of lymphocytes. [NIH]
Leukapheresis: The preparation of leukocyte concentrates with the return of red cells and leukocyte-poor plasma to the donor. [NIH] Leukemia: Cancer of blood-forming tissue. [NIH] Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [NIH] Leukotrienes: A family of biologically active compounds derived from arachidonic acid by oxidative metabolism through the 5-lipoxygenase pathway. They participate in host defense reactions and pathophysiological conditions such as immediate hypersensitivity and inflammation. They have potent actions on many essential organs and systems, including the cardiovascular, pulmonary, and central nervous system as well as the gastrointestinal tract and the immune system. [NIH] Libido: The psychic drive or energy associated with sexual instinct in the broad sense
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(pleasure and love-object seeking). It may also connote the psychic energy associated with instincts in general that motivate behavior. [NIH] Library Services: Services offered to the library user. They include reference and circulation. [NIH]
Life Expectancy: A figure representing the number of years, based on known statistics, to which any person of a given age may reasonably expect to live. [NIH] Ligament: A band of fibrous tissue that connects bones or cartilages, serving to support and strengthen joints. [EU] Linkages: The tendency of two or more genes in the same chromosome to remain together from one generation to the next more frequently than expected according to the law of independent assortment. [NIH] Lipid: Fat. [NIH] Lipid Peroxidation: Peroxidase catalyzed oxidation of lipids using hydrogen peroxide as an electron acceptor. [NIH] Lipopolysaccharide: Substance consisting of polysaccaride and lipid. [NIH] Liposomal: A drug preparation that contains the active drug in very tiny fat particles. This fat-encapsulated drug is absorbed better, and its distribution to the tumor site is improved. [NIH]
Lipoxygenase: An enzyme of the oxidoreductase class that catalyzes reactions between linoleate and other fatty acids and oxygen to form hydroperoxy-fatty acid derivatives. Related enzymes in this class include the arachidonate lipoxygenases, arachidonate 5lipoxygenase, arachidonate 12-lipoxygenase, and arachidonate 15-lipoxygenase. EC 1.13.11.12. [NIH] Lithium: An element in the alkali metals family. It has the atomic symbol Li, atomic number 3, and atomic weight 6.94. Salts of lithium are used in treating manic-depressive disorders. [NIH]
Lithium Carbonate: A lithium salt, classified as a mood-stabilizing agent. Lithium ion alters the metabolism of biogenic monoamines in the central nervous system, and affects multiple neurotransmission systems. [NIH] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Liver Transplantation: The transference of a part of or an entire liver from one human or animal to another. [NIH] Localization: The process of determining or marking the location or site of a lesion or disease. May also refer to the process of keeping a lesion or disease in a specific location or site. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Longitudinal study: Also referred to as a "cohort study" or "prospective study"; the analytic method of epidemiologic study in which subsets of a defined population can be identified who are, have been, or in the future may be exposed or not exposed, or exposed in different degrees, to a factor or factors hypothesized to influence the probability of occurrence of a given disease or other outcome. The main feature of this type of study is to observe large numbers of subjects over an extended time, with comparisons of incidence rates in groups that differ in exposure levels. [NIH] Loperamide: 4-(p-Chlorophenyl)-4-hydroxy-N.N-dimethyl-alpha,alpha-diphenyl-1piperidine butyramide hydrochloride. Synthetic anti-diarrheal agent with a long duration of action; it is not significantly absorbed from the gut, has no effect on the adrenergic system or
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central nervous system, but may antagonize histamine and interfere with acetylcholine release locally. [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] 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] Lymphoblastic: One of the most aggressive types of non-Hodgkin lymphoma. [NIH] Lymphoblasts: Interferon produced predominantly by leucocyte cells. [NIH] Lymphocyte: A white blood cell. Lymphocytes have a number of roles in the immune system, including the production of antibodies and other substances that fight infection and diseases. [NIH] Lymphocytic: Referring to lymphocytes, a type of white blood cell. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Lymphokine: A soluble protein produced by some types of white blood cell that stimulates other white blood cells to kill foreign invaders. [NIH] Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue. [NIH] Lymphoproliferative: Disorders characterized by proliferation of lymphoid tissue, general or unspecified. [NIH] Lysine: An essential amino acid. It is often added to animal feed. [NIH] 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] Malignancy: A cancerous tumor that can invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malnutrition: A condition caused by not eating enough food or not eating a balanced diet. [NIH]
Manic: Affected with mania. [EU] 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
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muscle; or (3) a substance released from cells as the result of the interaction of antigen with antibody or by the action of antigen with a sensitized lymphocyte. [EU] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Medullary: Pertaining to the marrow or to any medulla; resembling marrow. [EU] Megakaryocytes: Very large bone marrow cells which release mature blood platelets. [NIH] Megaloblastic: A large abnormal red blood cell appearing in the blood in pernicious anaemia. [EU] Melanin: The substance that gives the skin its color. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Memory: Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. [NIH] Menopause: Permanent cessation of menstruation. [NIH] Menstruation: The normal physiologic discharge through the vagina of blood and mucosal tissues from the nonpregnant uterus. [NIH] Mental Disorders: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. [NIH] Mental Health: The state wherein the person is well adjusted. [NIH] 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] Mesoderm: The middle germ layer of the embryo. [NIH] Meta-Analysis: A quantitative method of combining the results of independent studies (usually drawn from the published literature) and synthesizing summaries and conclusions which may be used to evaluate therapeutic effectiveness, plan new studies, etc., with application chiefly in the areas of research and medicine. [NIH] Metabolic disorder: A condition in which normal metabolic processes are disrupted, usually because of a missing enzyme. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] MI: Myocardial infarction. Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Mice Minute Virus: The type species of parvovirus prevalent in mouse colonies and found as a contaminant of many transplanted tumors or leukemias. [NIH] Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [NIH]
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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] Microscopy: The application of microscope magnification to the study of materials that cannot be properly seen by the unaided eye. [NIH] Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [NIH] Minor Histocompatibility Antigens: Allelic alloantigens often responsible for weak graft rejection in cases when (major) histocompatibility has been established by standard tests. In the mouse they are coded by more than 500 genes at up to 30 minor histocompatibility loci. The most well-known minor histocompatibility antigen in mammals is the H-Y antigen. [NIH]
Minor Histocompatibility Loci: Genetic loci responsible for the encoding of histocompatibility antigens other than those encoded by the major histocompatibility complex. The antigens encoded by these genes are often responsible for graft rejection in cases where histocompatibility has been established by standard tests. The location of some of these loci on the X and Y chromosomes explains why grafts from males to females may be rejected while grafts from females to males are accepted. In the mouse roughly 30 minor histocompatibility loci have been recognized, comprising more than 500 genes. [NIH] Mitochondria: Parts of a cell where aerobic production (also known as cell respiration) takes place. [NIH] Mitochondrial Swelling: Increase in volume of mitochondria due to an influx of fluid; it occurs in hypotonic solutions due to osmotic pressure and in isotonic solutions as a result of altered permeability of the membranes of respiring mitochondria. [NIH] Mitomycin: An antineoplastic antibiotic produced by Streptomyces caespitosus. It acts as a bi- or trifunctional alkylating agent causing cross-linking of DNA and inhibition of DNA synthesis. [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] Mitotic: Cell resulting from mitosis. [NIH] Mitotic inhibitors: Drugs that kill cancer cells by interfering with cell division (mitostis). [NIH]
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]
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Monocyte: A type of white blood cell. [NIH] Mononuclear: A cell with one nucleus. [NIH] Monosomy: The condition in which one chromosome of a pair is missing. In a normally diploid cell it is represented symbolically as 2N-1. [NIH] Morphological: Relating to the configuration or the structure of live organs. [NIH] Morphology: The science of the form and structure of organisms (plants, animals, and other forms of life). [NIH] Motion Sickness: Sickness caused by motion, as sea sickness, train sickness, car sickness, and air sickness. [NIH] Mucolytic: Destroying or dissolving mucin; an agent that so acts : a mucopolysaccharide or glycoprotein, the chief constituent of mucus. [EU] Mucosa: A mucous membrane, or tunica mucosa. [EU] 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] Mutagen: Any agent, such as X-rays, gamma rays, mustard gas, TCDD, that can cause abnormal mutation in living cells; having the power to cause mutations. [NIH] Mutagenic: Inducing genetic mutation. [EU] Mycophenolate mofetil: A drug that is being studied for its effectiveness in preventing graft-versus-host disease and autoimmune disorders. [NIH] Myelin: The fatty substance that covers and protects nerves. [NIH] Myelitis: Inflammation of the spinal cord. Relatively common etiologies include infections; autoimmune diseases; spinal cord; and ischemia (see also spinal cord vascular diseases). Clinical features generally include weakness, sensory loss, localized pain, incontinence, and other signs of autonomic dysfunction. [NIH] Myelodysplasia: Abnormal bone marrow cells that may lead to myelogenous leukemia. [NIH]
Myelodysplastic syndrome: Disease in which the bone marrow does not function normally. Also called preleukemia or smoldering leukemia. [NIH] Myelofibrosis: A disorder in which the bone marrow is replaced by fibrous tissue. [NIH] Myelogenous: Produced by, or originating in, the bone marrow. [NIH] Myeloid Cells: Cells which include the monocytes and the granulocytes. [NIH] Myeloid Progenitor Cells: One of the two stem cells derived from hematopoietic stem cells the other being the lymphoid progenitor cell. Derived from these myeloid progenitor cells are the erythroid progenitor cells and the myeloid cells (monocytes and granulocytes). [NIH] Myeloproliferative Disorders: Disorders in which one or more stimuli cause proliferation of hemopoietically active tissue or of tissue which has embryonic hemopoietic potential. [NIH] 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] Myocardial Reperfusion: Generally, restoration of blood supply to heart tissue which is ischemic due to decrease in normal blood supply. The decrease may result from any source including atherosclerotic obstruction, narrowing of the artery, or surgical clamping.
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Reperfusion can be induced to treat ischemia. Methods include chemical dissolution of an occluding thrombus, administration of vasodilator drugs, angioplasty, catheterization, and artery bypass graft surgery. However, it is thought that reperfusion can itself further damage the ischemic tissue, causing myocardial reperfusion injury. [NIH] Myocardial Reperfusion Injury: Functional, metabolic, or structural changes in ischemic heart muscle thought to result from reperfusion to the ischemic areas. Changes can be fatal to muscle cells and may include edema with explosive cell swelling and disintegration, sarcolemma disruption, fragmentation of mitochondria, contraction band necrosis, enzyme washout, and calcium overload. Other damage may include hemorrhage and ventricular arrhythmias. One possible mechanism of damage is thought to be oxygen free radicals. Treatment currently includes the introduction of scavengers of oxygen free radicals, and injury is thought to be prevented by warm blood cardioplegic infusion prior to reperfusion. [NIH]
Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Nausea: An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. [NIH] NCI: National Cancer Institute. NCI, part of the National Institutes of Health of the United States Department of Health and Human Services, is the federal government's principal agency for cancer research. NCI conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the NCI Web site at http://cancer.gov. [NIH] Necrosis: A pathological process caused by the progressive degradative action of enzymes that is generally associated with severe cellular trauma. It is characterized by mitochondrial swelling, nuclear flocculation, uncontrolled cell lysis, and ultimately cell death. [NIH] Need: A state of tension or dissatisfaction felt by an individual that impels him to action toward a goal he believes will satisfy the impulse. [NIH] 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] Nephropathy: Disease of the kidneys. [EU] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Neuroblastoma: Cancer that arises in immature nerve cells and affects mostly infants and children. [NIH] Neurologic: Having to do with nerves or the nervous system. [NIH] Neutrons: Electrically neutral elementary particles found in all atomic nuclei except light hydrogen; the mass is equal to that of the proton and electron combined and they are 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] Neutrophils: Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and
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stainable by neutral dyes. [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] 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] Nuclear Proteins: Proteins found in the nucleus of a cell. Do not confuse with nucleoproteins which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus. [NIH] Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the information (genetic code) for the transfer of genetic information from one generation to the next. [NIH] Nucleic Acid Hybridization: The process whereby two single-stranded polynucleotides form a double-stranded molecule, with hydrogen bonding between the complementary bases in the two strains. [NIH] Nucleolus: A small dense body (sub organelle) within the nucleus of eukaryotic cells, visible by phase contrast and interference microscopy in live cells throughout interphase. Contains RNA and protein and is the site of synthesis of ribosomal RNA. [NIH] Nucleoproteins: Proteins conjugated with nucleic acids. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Occupational Exposure: The exposure to potentially harmful chemical, physical, or biological agents that occurs as a result of one's occupation. [NIH] Odour: A volatile emanation that is perceived by the sense of smell. [EU] Ointments: Semisolid preparations used topically for protective emollient effects or as a vehicle for local administration of medications. Ointment bases are various mixtures of fats, waxes, animal and plant oils and solid and liquid hydrocarbons. [NIH] Oncogene: A gene that normally directs cell growth. If altered, an oncogene can promote or allow the uncontrolled growth of cancer. Alterations can be inherited or caused by an environmental exposure to carcinogens. [NIH] Oncogenic: Chemical, viral, radioactive or other agent that causes cancer; carcinogenic. [NIH] Oncologist: A doctor who specializes in treating cancer. Some oncologists specialize in a particular type of cancer treatment. For example, a radiation oncologist specializes in treating cancer with radiation. [NIH] Oncology: The study of cancer. [NIH]
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Opacity: Degree of density (area most dense taken for reading). [NIH] Open Reading Frames: Reading frames where successive nucleotide triplets can be read as codons specifying amino acids and where the sequence of these triplets is not interrupted by stop codons. [NIH] Operon: The genetic unit consisting of a feedback system under the control of an operator gene, in which a structural gene transcribes its message in the form of mRNA upon blockade of a repressor produced by a regulator gene. Included here is the attenuator site of bacterial operons where transcription termination is regulated. [NIH] Ophthalmic: Pertaining to the eye. [EU] Oral Health: The optimal state of the mouth and normal functioning of the organs of the mouth without evidence of disease. [NIH] Oral Hygiene: The practice of personal hygiene of the mouth. It includes the maintenance of oral cleanliness, tissue tone, and general preservation of oral health. [NIH] Oral Manifestations: Disorders of the mouth attendant upon non-oral disease or injury. [NIH]
Orderly: A male hospital attendant. [NIH] Organ Transplantation: Transference of an organ between individuals of the same species or between individuals of different species. [NIH] Organelles: Specific particles of membrane-bound organized living substances present in eukaryotic cells, such as the mitochondria; the golgi apparatus; endoplasmic reticulum; lysomomes; plastids; and vacuoles. [NIH] Orofacial: Of or relating to the mouth and face. [EU] Osteoarthritis: A progressive, degenerative joint disease, the most common form of arthritis, especially in older persons. The disease is thought to result not from the aging process but from biochemical changes and biomechanical stresses affecting articular cartilage. In the foreign literature it is often called osteoarthrosis deformans. [NIH] Osteoporosis: Reduction of bone mass without alteration in the composition of bone, leading to fractures. Primary osteoporosis can be of two major types: postmenopausal osteoporosis and age-related (or senile) osteoporosis. [NIH] Ovary: Either of the paired glands in the female that produce the female germ cells and secrete some of the female sex hormones. [NIH] Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]
Oxidative metabolism: A chemical process in which oxygen is used to make energy from carbohydrates (sugars). Also known as aerobic respiration, cell respiration, or aerobic metabolism. [NIH] 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] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior
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abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Pancreatic: Having to do with the pancreas. [NIH] Pancreatic cancer: Cancer of the pancreas, a salivary gland of the abdomen. [NIH] Pancreatic Juice: The fluid containing digestive enzymes secreted by the pancreas in response to food in the duodenum. [NIH] Pancytopenia: Deficiency of all three cell elements of the blood, erythrocytes, leukocytes and platelets. [NIH] Papilla: A small nipple-shaped elevation. [NIH] Papillary: Pertaining to or resembling papilla, or nipple. [EU] Paraffin: A mixture of solid hydrocarbons obtained from petroleum. It has a wide range of uses including as a stiffening agent in ointments, as a lubricant, and as a topical antiinflammatory. It is also commonly used as an embedding material in histology. [NIH] Parenteral: Not through the alimentary canal but rather by injection through some other route, as subcutaneous, intramuscular, intraorbital, intracapsular, intraspinal, intrasternal, intravenous, etc. [EU] Paroxysmal: Recurring in paroxysms (= spasms or seizures). [EU] Partial remission: The shrinking, but not complete disappearance, of a tumor in response to therapy. Also called partial response. [NIH] Particle: A tiny mass of material. [EU] Parvovirus: A genus of the family Parvoviridae, subfamily Parvovirinae, infecting a variety of vertebrates including humans. Parvoviruses are responsible for a number of important diseases but also can be non-pathogenic in certain hosts. The type species is mice minute virus. [NIH] Pathogen: Any disease-producing microorganism. [EU] Pathogenesis: The cellular events and reactions that occur in the development of disease. [NIH]
Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Pathologic Processes: The abnormal mechanisms and forms involved in the dysfunctions of tissues and organs. [NIH] Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Patient Advocacy: Promotion and protection of the rights of patients, frequently through a legal process. [NIH] Pediatrics: A medical specialty concerned with maintaining health and providing medical care to children from birth to adolescence. [NIH] Pelvic: Pertaining to the pelvis. [EU] Penicillamine: 3-Mercapto-D-valine. The most characteristic degradation product of the penicillin antibiotics. It is used as an antirheumatic and as a chelating agent in Wilson's disease. [NIH] Penicillin: An antibiotic drug used to treat infection. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of
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proteins. Peptides are combined to make proteins. [NIH] Pericardium: The fibroserous sac surrounding the heart and the roots of the great vessels. [NIH]
Perimenopausal: The time of a woman's life when menstrual periods become irregular. Refers to the time near menopause. [NIH] Periodontal disease: Disease involving the supporting structures of the teeth (as the gums and periodontal membranes). [NIH] Periodontitis: Inflammation of the periodontal membrane; also called periodontitis simplex. [NIH]
Peripheral blood: Blood circulating throughout the body. [NIH] Peripheral stem cell transplantation: A method of replacing blood-forming cells destroyed by cancer treatment. Immature blood cells (stem cells) in the circulating blood that are similar to those in the bone marrow are given after treatment to help the bone marrow recover and continue producing healthy blood cells. Transplantation may be autologous (an individual's own blood cells saved earlier), allogeneic (blood cells donated by someone else), or syngeneic (blood cells donated by an identical twin). Also called peripheral stem cell support. [NIH] Peripheral stem cells: Immature cells found circulating in the bloodstream. New blood cells develop from peripheral stem cells. [NIH] Pernicious: Tending to a fatal issue. [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] Pesticides: Chemicals used to destroy pests of any sort. The concept includes fungicides (industrial fungicides), insecticides, rodenticides, etc. [NIH] Petechiae: Pinpoint, unraised, round red spots under the skin caused by bleeding. [NIH] Petroleum: Naturally occurring complex liquid hydrocarbons which, after distillation, yield combustible fuels, petrochemicals, and lubricants. [NIH] Phagocyte: An immune system cell that can surround and kill microorganisms and remove dead cells. Phagocytes include macrophages. [NIH] Pharmacokinetic: The mathematical analysis of the time courses of absorption, distribution, and elimination of drugs. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of yeasts. [NIH] Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor of melanin, dopamine, noradrenalin, and thyroxine. [NIH] Phospholipases: A class of enzymes that catalyze the hydrolysis of phosphoglycerides or glycerophosphatidates. EC 3.1.-. [NIH] Phospholipids: Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides; glycerophospholipids) or sphingosine (sphingolipids). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not
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stored in large amounts in the system. [NIH] Phosphorus: A non-metallic element that is found in the blood, muscles, nevers, bones, and teeth, and is a component of adenosine triphosphate (ATP; the primary energy source for the body's cells.) [NIH] Phosphorylate: Attached to a phosphate group. [NIH] Phosphorylated: Attached to a phosphate group. [NIH] Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. [NIH] Photosensitivity: An abnormal cutaneous response involving the interaction between photosensitizing substances and sunlight or filtered or artificial light at wavelengths of 280400 mm. There are two main types : photoallergy and photoxicity. [EU] Physical Examination: Systematic and thorough inspection of the patient for physical signs of disease or abnormality. [NIH] Physiologic: Having to do with the functions of the body. When used in the phrase "physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH]
Physiology: The science that deals with the life processes and functions of organismus, their cells, tissues, and organs. [NIH] Pigment: A substance that gives color to tissue. Pigments are responsible for the color of skin, eyes, and hair. [NIH] Pilot study: The initial study examining a new method or treatment. [NIH] Placenta: A highly vascular fetal organ through which the fetus absorbs oxygen and other nutrients and excretes carbon dioxide and other wastes. It begins to form about the eighth day of gestation when the blastocyst adheres to the decidua. [NIH] Placental blood transplantation: The transfer of blood from a placenta to an individual whose own blood production system is suppressed. Placental blood contains high levels of stem cells needed to produce new blood cells. It is being studied in the treatment of cancer and severe blood disorders such as aplastic anemia. Also called umbilical cord blood transplant. [NIH] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] Plasmapheresis: Procedure whereby plasma is separated and extracted from anticoagulated whole blood and the red cells retransfused to the donor. Plasmapheresis is also employed for therapeutic use. [NIH] Plastids: Self-replicating cytoplasmic organelles of plant and algal cells that contain pigments and may synthesize and accumulate various substances. Plastids are used in phylogenetic studies. [NIH] Platelet Activation: A series of progressive, overlapping events triggered by exposure of the platelets to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to
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the formation of a stable hemostatic plug. [NIH] Platelet Aggregation: The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin, collagen) and is part of the mechanism leading to the formation of a thrombus. [NIH] Platelet Count: A count of the number of platelets per unit volume in a sample of venous blood. [NIH] Platelet Transfusion: The transfer of blood platelets from a donor to a recipient or reinfusion to the donor. [NIH] Plateletpheresis: The preparation of platelet concentrates with the return of red cells and platelet-poor plasma to the donor. [NIH] Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [NIH] Polycystic: An inherited disorder characterized by many grape-like clusters of fluid-filled cysts that make both kidneys larger over time. These cysts take over and destroy working kidney tissue. PKD may cause chronic renal failure and end-stage renal disease. [NIH] Polymerase: An enzyme which catalyses the synthesis of DNA using a single DNA strand as a template. The polymerase copies the template in the 5'-3'direction provided that sufficient quantities of free nucleotides, dATP and dTTP are present. [NIH] Polymorphic: Occurring in several or many forms; appearing in different forms at different stages of development. [EU] Polymorphism: The occurrence together of two or more distinct forms in the same population. [NIH] Polypeptide: A peptide which on hydrolysis yields more than two amino acids; called tripeptides, tetrapeptides, etc. according to the number of amino acids contained. [EU] 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] Postmenopausal: Refers to the time after menopause. Menopause is the time in a woman's life when menstrual periods stop permanently; also called "change of life." [NIH] Postnatal: Occurring after birth, with reference to the newborn. [EU] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Potentiate: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Potentiation: An overall effect of two drugs taken together which is greater than the sum of the effects of each drug taken alone. [NIH] Practicability: A non-standard characteristic of an analytical procedure. It is dependent on the scope of the method and is determined by requirements such as sample throughout and costs. [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,
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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] Predisposition: A latent susceptibility to disease which may be activated under certain conditions, as by stress. [EU] 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] Prenatal: Existing or occurring before birth, with reference to the fetus. [EU] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] Probe: An instrument used in exploring cavities, or in the detection and dilatation of strictures, or in demonstrating the potency of channels; an elongated instrument for exploring or sounding body cavities. [NIH] Progeny: The offspring produced in any generation. [NIH] Progesterone: Pregn-4-ene-3,20-dione. The principal progestational hormone of the body, secreted by the corpus luteum, adrenal cortex, and placenta. Its chief function is to prepare the uterus for the reception and development of the fertilized ovum. It acts as an antiovulatory agent when administered on days 5-25 of the menstrual cycle. [NIH] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Projection: A defense mechanism, operating unconsciously, whereby that which is emotionally unacceptable in the self is rejected and attributed (projected) to others. [NIH] Proliferating Cell Nuclear Antigen: Nuclear antigen with a role in DNA synthesis, DNA repair, and cell cycle progression. PCNA is required for the coordinated synthesis of both leading and lagging strands at the replication fork during DNA replication. PCNA expression correlates with the proliferation activity of several malignant and non-malignant cell types. [NIH] Promoter: A chemical substance that increases the activity of a carcinogenic process. [NIH] Promotor: In an operon, a nucleotide sequence located at the operator end which contains all the signals for the correct initiation of genetic transcription by the RNA polymerase holoenzyme and determines the maximal rate of RNA synthesis. [NIH] Prone: Having the front portion of the body downwards. [NIH] Proneness: Susceptibility to accidents due to human factors. [NIH] Prophylaxis: An attempt to prevent disease. [NIH] Proportional: Being in proportion : corresponding in size, degree, or intensity, having the same or a constant ratio; of, relating to, or used in determining proportions. [EU]
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Prospective study: An epidemiologic study in which a group of individuals (a cohort), all free of a particular disease and varying in their exposure to a possible risk factor, is followed over a specific amount of time to determine the incidence rates of the disease in the exposed and unexposed groups. [NIH] Prostate: A gland in males that surrounds the neck of the bladder and the urethra. It secretes a substance that liquifies coagulated semen. It is situated in the pelvic cavity behind the lower part of the pubic symphysis, above the deep layer of the triangular ligament, and rests upon the rectum. [NIH] 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 S: The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] Proteolytic: 1. Pertaining to, characterized by, or promoting proteolysis. 2. An enzyme that promotes proteolysis (= the splitting of proteins by hydrolysis of the peptide bonds with formation of smaller polypeptides). [EU] Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or vaccine dosages, length of study, routes of administration, who may participate, and other aspects of trial design. [NIH] Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] Protozoa: A subkingdom consisting of unicellular organisms that are the simplest in the animal kingdom. Most are free living. They range in size from submicroscopic to macroscopic. Protozoa are divided into seven phyla: Sarcomastigophora, Labyrinthomorpha, Apicomplexa, Microspora, Ascetospora, Myxozoa, and Ciliophora. [NIH] Psychic: Pertaining to the psyche or to the mind; mental. [EU] Psychomotor: Pertaining to motor effects of cerebral or psychic activity. [EU] Puberty: The period during which the secondary sex characteristics begin to develop and the capability of sexual reproduction is attained. [EU] Public Health: Branch of medicine concerned with the prevention and control of disease and disability, and the promotion of physical and mental health of the population on the international, national, state, or municipal level. [NIH] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] 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] Purpura: Purplish or brownish red discoloration, easily visible through the epidermis,
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caused by hemorrhage into the tissues. [NIH] Quality of Life: A generic concept reflecting concern with the modification and enhancement of life attributes, e.g., physical, political, moral and social environment. [NIH] Quinones: Hydrocarbon rings which contain two ketone moieties in any position. They can be substituted in any position except at the ketone groups. [NIH] Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radiation oncologist: A doctor who specializes in using radiation to treat cancer. [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] Radioimmunotherapy: Radiotherapy where cytotoxic radionuclides are linked to antibodies in order to deliver toxins directly to tumor targets. Therapy with targeted radiation rather than antibody-targeted toxins (immunotoxins) has the advantage that adjacent tumor cells, which lack the appropriate antigenic determinants, can be destroyed by radiation cross-fire. Radioimmunotherapy is sometimes called targeted radiotherapy, but this latter term can also refer to radionuclides linked to non-immune molecules (radiotherapy). [NIH] Radiolabeled: Any compound that has been joined with a radioactive substance. [NIH] 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] Reactive Oxygen Species: Reactive intermediate oxygen species including both radicals and non-radicals. These substances are constantly formed in the human body and have been shown to kill bacteria and inactivate proteins, and have been implicated in a number of diseases. Scientific data exist that link the reactive oxygen species produced by inflammatory phagocytes to cancer development. [NIH] 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]
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Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Recombination: The formation of new combinations of genes as a result of segregation in crosses between genetically different parents; also the rearrangement of linked genes due to crossing-over. [NIH] Reconstitution: 1. A type of regeneration in which a new organ forms by the rearrangement of tissues rather than from new formation at an injured surface. 2. The restoration to original form of a substance previously altered for preservation and storage, as the restoration to a liquid state of blood serum or plasma that has been dried and stored. [EU] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Recurrence: The return of a sign, symptom, or disease after a remission. [NIH] Red blood cells: RBCs. Cells that carry oxygen to all parts of the body. Also called erythrocytes. [NIH] Red Nucleus: A pinkish-yellow portion of the midbrain situated in the rostral mesencephalic tegmentum. It receives a large projection from the contralateral half of the cerebellum via the superior cerebellar peduncle and a projection from the ipsilateral motor cortex. [NIH] Reductase: Enzyme converting testosterone to dihydrotestosterone. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH] Refractory: Not readily yielding to treatment. [EU] Regeneration: The natural renewal of a structure, as of a lost tissue or part. [EU] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] 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] Remoxipride: An antipsychotic agent that is specific for dopamine D2 receptors. It has been shown to be effective in the treatment of schizophrenia. [NIH] Reperfusion: Restoration of blood supply to tissue which is ischemic due to decrease in normal blood supply. The decrease may result from any source including atherosclerotic obstruction, narrowing of the artery, or surgical clamping. It is primarily a procedure for treating infarction or other ischemia, by enabling viable ischemic tissue to recover, thus limiting further necrosis. However, it is thought that reperfusion can itself further damage the ischemic tissue, causing reperfusion injury. [NIH] Reperfusion Injury: Functional, metabolic, or structural changes, including necrosis, in ischemic tissues thought to result from reperfusion to ischemic areas of the tissue. The most common instance is myocardial reperfusion injury. [NIH] Repressor: Any of the specific allosteric protein molecules, products of regulator genes, which bind to the operator of operons and prevent RNA polymerase from proceeding into the operon to transcribe messenger RNA. [NIH] Research Design: A plan for collecting and utilizing data so that desired information can be obtained with sufficient precision or so that an hypothesis can be tested properly. [NIH]
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Resection: Removal of tissue or part or all of an organ by surgery. [NIH] Response Elements: Nucleotide sequences, usually upstream, which are recognized by specific regulatory transcription factors, thereby causing gene response to various regulatory agents. These elements may be found in both promotor and enhancer regions. [NIH] Restoration: Broad term applied to any inlay, crown, bridge or complete denture which restores or replaces loss of teeth or oral tissues. [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] Retinal: 1. Pertaining to the retina. 2. The aldehyde of retinol, derived by the oxidative enzymatic splitting of absorbed dietary carotene, and having vitamin A activity. In the retina, retinal combines with opsins to form visual pigments. One isomer, 11-cis retinal combines with opsin in the rods (scotopsin) to form rhodopsin, or visual purple. Another, all-trans retinal (trans-r.); visual yellow; xanthopsin) results from the bleaching of rhodopsin by light, in which the 11-cis form is converted to the all-trans form. Retinal also combines with opsins in the cones (photopsins) to form the three pigments responsible for colour vision. Called also retinal, and retinene1. [EU] Retinitis: Inflammation of the retina. It is rarely limited to the retina, but is commonly associated with diseases of the choroid (chorioretinitis) and of the optic nerve (neuroretinitis). The disease may be confined to one eye, but since it is generally dependent on a constitutional factor, it is almost always bilateral. It may be acute in course, but as a rule it lasts many weeks or even several months. [NIH] Retinopathy: 1. Retinitis (= inflammation of the retina). 2. Retinosis (= degenerative, noninflammatory condition of the retina). [EU] Retrospective: Looking back at events that have already taken place. [NIH] Retroviral vector: RNA from a virus that is used to insert genetic material into cells. [NIH] Retrovirus: A member of a group of RNA viruses, the RNA of which is copied during viral replication into DNA by reverse transcriptase. The viral DNA is then able to be integrated into the host chromosomal DNA. [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] Ribose: A pentose active in biological systems usually in its D-form. [NIH] Rickets: A condition caused by deficiency of vitamin D, especially in infancy and childhood, with disturbance of normal ossification. The disease is marked by bending and distortion of the bones under muscular action, by the formation of nodular enlargements on the ends and sides of the bones, by delayed closure of the fontanelles, pain in the muscles, and sweating of the head. Vitamin D and sunlight together with an adequate diet are curative, provided that the parathyroid glands are functioning properly. [EU] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Ristocetin: An antibiotic mixture of two components, A and B, obtained from Nocardia
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lurida (or the same substance produced by any other means). It is no longer used clinically because of its toxicity. It causes platelet agglutination and blood coagulation and is used to assay those functions in vitro. [NIH] Rodenticides: Substances used to destroy or inhibit the action of rats, mice, or other rodents. [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] Sargramostim: A colony-stimulating factor that stimulates the production of blood cells, especially platelets, during chemotherapy. It is a cytokine that belongs to the family of drugs called hematopoietic (blood-forming) agents. Also called GM-CSF. [NIH] Schizoid: Having qualities resembling those found in greater degree in schizophrenics; a person of schizoid personality. [NIH] Schizophrenia: A mental disorder characterized by a special type of disintegration of the personality. [NIH] Schizotypal Personality Disorder: A personality disorder in which there are oddities of thought (magical thinking, paranoid ideation, suspiciousness), perception (illusions, depersonalization), speech (digressive, vague, overelaborate), and behavior (inappropriate affect in social interactions, frequently social isolation) that are not severe enough to characterize schizophrenia. [NIH] Sclerosis: A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Sebaceous: Gland that secretes sebum. [NIH] Sebaceous gland: Gland that secretes sebum. [NIH] Secretion: 1. The process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. Any substance produced by secretion. [EU] Sediment: A precipitate, especially one that is formed spontaneously. [EU] Segregation: The separation in meiotic cell division of homologous chromosome pairs and their contained allelomorphic gene pairs. [NIH] Seizures: Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as epilepsy or "seizure disorder." [NIH] Semen: The thick, yellowish-white, viscid fluid secretion of male reproductive organs discharged upon ejaculation. In addition to reproductive organ secretions, it contains spermatozoa and their nutrient plasma. [NIH] Senile: Relating or belonging to old age; characteristic of old age; resulting from infirmity of old age. [NIH] Sensory loss: A disease of the nerves whereby the myelin or insulating sheath of myelin on
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the nerves does not stay intact and the messages from the brain to the muscles through the nerves are not carried properly. [NIH] Sepsis: The presence of bacteria in the bloodstream. [NIH] Septic: Produced by or due to decomposition by microorganisms; putrefactive. [EU] Septicemia: Systemic disease associated with the presence and persistence of pathogenic microorganisms or their toxins in the blood. Called also blood poisoning. [EU] Sequence Analysis: A multistage process that includes the determination of a sequence (protein, carbohydrate, etc.), its fragmentation and analysis, and the interpretation of the resulting sequence information. [NIH] 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] 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] Serum Sickness: Immune complex disease caused by the administration of foreign serum or serum proteins and characterized by fever, lymphadenopathy, arthralgia, and urticaria. When they are complexed to protein carriers, some drugs can also cause serum sickness when they act as haptens inducing antibody responses. [NIH] Sex Characteristics: Those characteristics that distinguish one sex from the other. The primary sex characteristics are the ovaries and testes and their related hormones. Secondary sex characteristics are those which are masculine or feminine but not directly related to reproduction. [NIH] Shock: The general bodily disturbance following a severe injury; an emotional or moral upset occasioned by some disturbing or unexpected experience; disruption of the circulation, which can upset all body functions: sometimes referred to as circulatory shock. [NIH]
Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the one sought to be benefited by its administration. [EU] Signal Transduction: The intercellular or intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GABA-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptormediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. [NIH] Signs and Symptoms: Clinical manifestations that can be either objective when observed by a physician, or subjective when perceived by the patient. [NIH] Skeletal: Having to do with the skeleton (boney part of the body). [NIH] Skeleton: The framework that supports the soft tissues of vertebrate animals and protects
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many of their internal organs. The skeletons of vertebrates are made of bone and/or cartilage. [NIH] Skin Pigmentation: Coloration of the skin. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Smoldering leukemia: Disease in which the bone marrow does not function normally. Also called preleukemia or myelodysplastic syndrome. [NIH] Social Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [NIH] Sodium: An element that is a member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23. With a valence of 1, it has a strong affinity for oxygen and other nonmetallic elements. Sodium provides the chief cation of the extracellular body fluids. Its salts are the most widely used in medicine. (From Dorland, 27th ed) Physiologically the sodium ion plays a major role in blood pressure regulation, maintenance of fluid volume, and electrolyte balance. [NIH] Sodium Channels: Cell membrane glycoproteins selective for sodium ions. Fast sodium current is associated with the action potential in neural membranes. [NIH] Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] Solid tumor: Cancer of body tissues other than blood, bone marrow, or the lymphatic system. [NIH] Solvent: 1. Dissolving; effecting a solution. 2. A liquid that dissolves or that is capable of dissolving; the component of a solution that is present in greater amount. [EU] Soma: The body as distinct from the mind; all the body tissue except the germ cells; all the axial body. [NIH] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] Somatic cells: All the body cells except the reproductive (germ) cells. [NIH] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Specificity: Degree of selectivity shown by an antibody with respect to the number and types of antigens with which the antibody combines, as well as with respect to the rates and the extents of these reactions. [NIH] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU] Sperm: The fecundating fluid of the male. [NIH] Spermatogenesis: Process of formation and development of spermatozoa, including spermatocytogenesis and spermiogenesis. [NIH] Spermatozoa: Mature male germ cells that develop in the seminiferous tubules of the testes. Each consists of a head, a body, and a tail that provides propulsion. The head consists
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mainly of chromatin. [NIH] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] Spinal Cord Vascular Diseases: Hypoxic-ischemic and hemorrhagic disorders of the spinal cord. Arteriosclerosis, emboli, and vascular malformations are potential causes of these conditions. [NIH] Spleen: An organ that is part of the lymphatic system. The spleen produces lymphocytes, filters the blood, stores blood cells, and destroys old blood cells. It is located on the left side of the abdomen near the stomach. [NIH] Splenectomy: An operation to remove the spleen. [NIH] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [EU] Stasis: A word termination indicating the maintenance of (or maintaining) a constant level; preventing increase or multiplication. [EU] 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 cell transplantation: A method of replacing immature blood-forming cells that were destroyed by cancer treatment. The stem cells are given to the person after treatment to help the bone marrow recover and continue producing healthy blood cells. [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] Sterility: 1. The inability to produce offspring, i.e., the inability to conceive (female s.) or to induce conception (male s.). 2. The state of being aseptic, or free from microorganisms. [EU] Steroid: A group name for lipids that contain a hydrogenated cyclopentanoperhydrophenanthrene ring system. Some of the substances included in this group are progesterone, adrenocortical hormones, the gonadal hormones, cardiac aglycones, bile acids, sterols (such as cholesterol), toad poisons, saponins, and some of the carcinogenic hydrocarbons. [EU] Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Stool: The waste matter discharged in a bowel movement; feces. [NIH] Strand: DNA normally exists in the bacterial nucleus in a helix, in which two strands are coiled together. [NIH] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] Stroke: Sudden loss of function of part of the brain because of loss of blood flow. Stroke may be caused by a clot (thrombosis) or rupture (hemorrhage) of a blood vessel to the brain. [NIH] Stroma: The middle, thickest layer of tissue in the cornea. [NIH] Stromal: Large, veil-like cell in the bone marrow. [NIH] Stromal Cells: Connective tissue cells of an organ found in the loose connective tissue. These are most often associated with the uterine mucosa and the ovary as well as the
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hematopoietic system and elsewhere. [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] 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] Subtrochanteric: Below a trochanter. [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] 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] Symphysis: A secondary cartilaginous joint. [NIH] Synaptic: Pertaining to or affecting a synapse (= site of functional apposition between neurons, at which an impulse is transmitted from one neuron to another by electrical or chemical means); pertaining to synapsis (= pairing off in point-for-point association of homologous chromosomes from the male and female pronuclei during the early prophase of meiosis). [EU] Systemic: Affecting the entire body. [NIH] Systemic disease: Disease that affects the whole body. [NIH] Systemic lupus erythematosus: SLE. A chronic inflammatory connective tissue disease marked by skin rashes, joint pain and swelling, inflammation of the kidneys, inflammation of the fibrous tissue surrounding the heart (i.e., the pericardium), as well as other problems. Not all affected individuals display all of these problems. May be referred to as lupus. [NIH] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] Telangiectasia: The permanent enlargement of blood vessels, causing redness in the skin or mucous membranes. [NIH] Telomerase: Essential ribonucleoprotein reverse transcriptase that adds telomeric DNA to the ends of eukaryotic chromosomes. Telomerase appears to be repressed in normal human somatic tissues but reactivated in cancer, and thus may be necessary for malignant transformation. EC 2.7.7.-. [NIH] Telomere: A terminal section of a chromosome which has a specialized structure and which is involved in chromosomal replication and stability. Its length is believed to be a few hundred base pairs. [NIH] Teratogen: A substance which, through immediate, prolonged or repeated contact with the skin may involve a risk of subsequent non-hereditable birth defects in offspring. [NIH]
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Teratogenic: Tending to produce anomalies of formation, or teratism (= anomaly of formation or development : condition of a monster). [EU] Testicular: Pertaining to a testis. [EU] Testis: Either of the paired male reproductive glands that produce the male germ cells and the male hormones. [NIH] Testosterone: A hormone that promotes the development and maintenance of male sex characteristics. [NIH] Thalamic: Cell that reaches the lateral nucleus of amygdala. [NIH] Thalamic Diseases: Disorders of the centrally located thalamus, which integrates a wide range of cortical and subcortical information. Manifestations include sensory loss, movement disorders; ataxia, pain syndromes, visual disorders, a variety of neuropsychological conditions, and coma. Relatively common etiologies include cerebrovascular disorders; craniocerebral trauma; brain neoplasms; brain hypoxia; intracranial hemorrhages; and infectious processes. [NIH] Thalassemia: A group of hereditary hemolytic anemias in which there is decreased synthesis of one or more hemoglobin polypeptide chains. There are several genetic types with clinical pictures ranging from barely detectable hematologic abnormality to severe and fatal anemia. [NIH] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thoracic: Having to do with the chest. [NIH] Thoracic Surgery: A surgical specialty concerned with diagnosis and treatment of disorders of the heart, lungs, and esophagus. Two major types of thoracic surgery are classified as pulmonary and cardiovascular. [NIH] Threshold: For a specified sensory modality (e. g. light, sound, vibration), the lowest level (absolute threshold) or smallest difference (difference threshold, difference limen) or intensity of the stimulus discernible in prescribed conditions of stimulation. [NIH] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] Thrombocytes: Blood cells that help prevent bleeding by causing blood clots to form. Also called platelets. [NIH] Thrombocytopenia: A decrease in the number of blood platelets. [NIH] Thrombomodulin: A cell surface glycoprotein of endothelial cells that binds thrombin and serves as a cofactor in the activation of protein C and its regulation of blood coagulation. [NIH]
Thrombopoietin: A humoral factor that controls blood platelet production through stimulation of megakaryocyte populations. Bone marrow megakaryocytes increase in both size and number in response to exposure to thrombopoietin. [NIH] Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thrombus: An aggregation of blood factors, primarily platelets and fibrin with entrapment of cellular elements, frequently causing vascular obstruction at the point of its formation. Some authorities thus differentiate thrombus formation from simple coagulation or clot formation. [EU] Thymoma: A tumor of the thymus, an organ that is part of the lymphatic system and is located in the chest, behind the breastbone. [NIH] Thymus: An organ that is part of the lymphatic system, in which T lymphocytes grow and
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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] Ticlopidine: Ticlopidine is an effective inhibitor of platelet aggregation. The drug has been found to significantly reduce infarction size in acute myocardial infarcts and is an effective antithrombotic agent in arteriovenous fistulas, aorto-coronary bypass grafts, ischemic heart disease, venous thrombosis, and arteriosclerosis. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tolerance: 1. The ability to endure unusually large doses of a drug or toxin. 2. Acquired drug tolerance; a decreasing response to repeated constant doses of a drug or the need for increasing doses to maintain a constant response. [EU] Tonicity: The normal state of muscular tension. [NIH] Topical: On the surface of the body. [NIH] Torsion: A twisting or rotation of a bodily part or member on its axis. [NIH] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxins: Specific, characterizable, poisonous chemicals, often proteins, with specific biological properties, including immunogenicity, produced by microbes, higher plants, or animals. [NIH] Trace element: Substance or element essential to plant or animal life, but present in extremely small amounts. [NIH] Trachea: The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi. [NIH] Transcriptase: An enzyme which catalyses the synthesis of a complementary mRNA molecule from a DNA template in the presence of a mixture of the four ribonucleotides (ATP, UTP, GTP and CTP). [NIH] 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] Transfusion: The infusion of components of blood or whole blood into the bloodstream. The blood may be donated from another person, or it may have been taken from the person earlier and stored until needed. [NIH] Translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell
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to the other at the synapse. [NIH] Transplantation: Transference of a tissue or organ, alive or dead, within an individual, between individuals of the same species, or between individuals of different species. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Treatment Outcome: Evaluation undertaken to assess the results or consequences of management and procedures used in combating disease in order to determine the efficacy, effectiveness, safety, practicability, etc., of these interventions in individual cases or series. [NIH]
Trisomy: The possession of a third chromosome of any one type in an otherwise diploid cell. [NIH]
Trypsin: A serine endopeptidase that is formed from trypsinogen in the pancreas. It is converted into its active form by enteropeptidase in the small intestine. It catalyzes hydrolysis of the carboxyl group of either arginine or lysine. EC 3.4.21.4. [NIH] 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] Tumor suppressor gene: Genes in the body that can suppress or block the development of cancer. [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] Ubiquitin: A highly conserved 76 amino acid-protein found in all eukaryotic cells. [NIH] Umbilical Arteries: Either of a pair of arteries originating from the internal iliac artery and passing through the umbilical cord to carry blood from the fetus to the placenta. [NIH] Umbilical Cord: The flexible structure, giving passage to the umbilical arteries and vein, which connects the embryo or fetus to the placenta. [NIH] Umbilical cord blood: Blood from the placenta (afterbirth) that contains high concentrations of stem cells needed to produce new blood cells. [NIH] Umbilical cord blood transplantation: The injection of umbilical cord blood to restore an individual's own blood production system suppressed by anticancer drugs, radiation therapy, or both. It is being studied in the treatment of cancer and severe blood disorders such as aplastic anemia. Cord blood contains high concentrations of stem cells needed to produce new blood cells. [NIH] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]
Urinalysis: Examination of urine by chemical, physical, or microscopic means. Routine
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urinalysis usually includes performing chemical screening tests, determining specific gravity, observing any unusual color or odor, screening for bacteriuria, and examining the sediment microscopically. [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, 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] Vaccine: A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. [NIH] 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] Valine: A branched-chain essential amino acid that has stimulant activity. It promotes muscle growth and tissue repair. It is a precursor in the penicillin biosynthetic pathway. [NIH]
Valproic Acid: A fatty acid with anticonvulsant properties used in the treatment of epilepsy. The mechanisms of its therapeutic actions are not well understood. It may act by increasing GABA levels in the brain or by altering the properties of voltage dependent sodium channels. [NIH] Vancomycin: Antibacterial obtained from Streptomyces orientalis. It is a glycopeptide related to ristocetin that inhibits bacterial cell wall assembly and is toxic to kidneys and the inner ear. [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vasodilators: Any nerve or agent which induces dilatation of the blood vessels. [NIH] 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] 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] Venous Thrombosis: The formation or presence of a thrombus within a vein. [NIH] Ventral: 1. Pertaining to the belly or to any venter. 2. Denoting a position more toward the belly surface than some other object of reference; same as anterior in human anatomy. [EU] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Villus: Cell found in the lining of the small intestine. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Virilization: The induction or development of male secondary sec characters, especially the induction of such changes in the female, including enlargement of the clitoris, growth of
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facial and body hair, development of a hairline typical of the male forehead, stimulation of secretion and proliferation of the sebaceous glands (often with acne), and deepening of the voice. Called also masculinization) [EU] Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [NIH] 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] Viscosity: A physical property of fluids that determines the internal resistance to shear forces. [EU] Vitamin A: A substance used in cancer prevention; it belongs to the family of drugs called retinoids. [NIH] Vitamin D: The vitamin that mediates intestinal calcium absorption, bone calcium metabolism, and probably muscle activity. It usually acts as a hormone precursor, requiring 2 stages of metabolism before reaching actual hormonal form. It is isolated from fish liver oils and used in the treatment and prevention of rickets. [NIH] Vitro: Descriptive of an event or enzyme reaction under experimental investigation occurring outside a living organism. Parts of an organism or microorganism are used together with artificial substrates and/or conditions. [NIH] Vivo: Outside of or removed from the body of a living organism. [NIH] Voriconazole: A drug that treats infections caused by fungi. [NIH] 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] Withdrawal: 1. A pathological retreat from interpersonal contact and social involvement, as may occur in schizophrenia, depression, or schizoid avoidant and schizotypal personality disorders. 2. (DSM III-R) A substance-specific organic brain syndrome that follows the cessation of use or reduction in intake of a psychoactive substance that had been regularly used to induce a state of intoxication. [EU] Womb: A hollow, thick-walled, muscular organ in which the impregnated ovum is developed into a child. [NIH] Xeroderma Pigmentosum: A rare, pigmentary, and atrophic autosomal recessive disease affecting all races. It is manifested as an extreme photosensitivity to ultraviolet light as the result of a deficiency in the enzyme that permits excisional repair of ultraviolet-damaged DNA. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH] X-ray therapy: The use of high-energy radiation from x-rays to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or
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brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. X-ray therapy is also called radiation therapy, radiotherapy, and irradiation. [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] Zalcitabine: A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by a hydrogen. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. The compound is a potent inhibitor of HIV replication at low concentrations, acting as a chainterminator of viral DNA by binding to reverse transcriptase. Its principal toxic side effect is axonal degeneration resulting in peripheral neuropathy. [NIH] Zoster: A virus infection of the Gasserian ganglion and its nerve branches, characterized by discrete areas of vesiculation of the epithelium of the forehead, the nose, the eyelids, and the cornea together with subepithelial infiltration. [NIH] Zygote: The fertilized ovum. [NIH] Zymogen: Inactive form of an enzyme which can then be converted to the active form, usually by excision of a polypeptide, e. g. trypsinogen is the zymogen of trypsin. [NIH]
215
INDEX A Abdominal, 121, 155, 195 Abdominal Pain, 121, 155 Aberrant, 11, 155 Abscess, 43, 76, 155 Acceptor, 155, 187, 194 Acetylcholine, 155, 188, 193 Acetylcysteine, 56, 155 Acne, 115, 155, 169, 213 Acute leukemia, 71, 103, 155, 199 Acute myelogenous leukemia, 7, 13, 155 Acute myeloid leukemia, 25, 31, 38, 47, 73, 76, 155 Acute nonlymphocytic leukemia, 155 Acute renal, 155, 180 Adaptability, 155, 165 Adduct, 5, 155 Adolescence, 155, 195 Adrenergic, 155, 159, 172, 174, 187 Adverse Effect, 156, 205 Aerobic, 156, 190, 194 Aerobic Metabolism, 156, 194 Aerobic Respiration, 156, 194 Affinity, 12, 109, 156, 160, 188, 206 Agonists, 109, 111, 115, 156 Agranulocytosis, 60, 120, 156 Algorithms, 8, 156, 162 Alimentary, 156, 195 Alkylating Agents, 15, 156 Alkylation, 5, 156 Alleles, 10, 156, 180 Allo, 67, 156 Allogeneic, 6, 14, 28, 34, 37, 45, 46, 51, 52, 54, 61, 65, 66, 77, 81, 156, 178, 179, 196 Allogeneic bone marrow transplantation, 14, 37, 46, 54, 65, 81, 156 Allografts, 156, 181 Alopecia, 157, 169 Alpha Particles, 157, 201 Alternative medicine, 125, 157 Ameliorated, 115, 157 Ameliorating, 108, 110, 157 Amino Acid Sequence, 157, 158, 175, 177 Amino Acids, 18, 112, 157, 162, 166, 177, 194, 195, 198, 200, 205, 208 Amnion, 157 Amniotic Fluid, 9, 157 Anaemia, 50, 73, 78, 120, 157, 159, 189
Anaesthesia, 157, 183 Anal, 157, 187 Analog, 157, 186 Analytes, 140, 141, 157 Anaphylatoxins, 157, 167 Anatomical, 157, 183, 204 Androgenic, 69, 157, 170 Androgens, 86, 115, 158 Anemia, Sickle Cell, 120, 158 Anesthesia, 96, 158 Anions, 158, 185 Anomalies, 11, 158, 209 Anorexia, 121, 158 Antagonism, 158, 171 Antecedent, 25, 48, 60, 158 Antiandrogens, 158, 162 Antibacterial, 158, 206, 212 Antibiotic, 5, 158, 190, 195, 203, 206 Antibodies, 10, 101, 113, 158, 170, 179, 180, 181, 188, 197, 201 Anticoagulant, 158, 200 Anticonvulsant, 158, 164, 212 Antifungal, 158, 186 Antigen, 24, 34, 43, 156, 158, 159, 167, 171, 181, 182, 183, 189, 190, 199 Antigen-Antibody Complex, 159, 167 Antigen-presenting cell, 159, 171 Anti-inflammatory, 159, 195 Antineoplastic, 116, 156, 159, 169, 190 Antineoplastic Agents, 116, 156, 159 Antioxidant, 159, 160, 164, 194 Antipsychotic, 159, 202 Antithrombotic, 159, 210 Antithymocyte globulin, 23, 37, 38, 41, 45, 61, 62, 66, 68, 80, 84, 99, 100, 159 Antiviral, 155, 159, 184 Apheresis, 102, 159 Aplasia, 8, 18, 31, 45, 54, 95, 116, 159 Aplastic anaemia, 80, 86, 159 Apoptosis, 7, 8, 11, 13, 16, 23, 29, 62, 109, 111, 112, 116, 160, 164 Applicability, 19, 160 Aqueous, 160, 161, 170 Arachidonic Acid, 160, 186 Arginine, 157, 160, 193, 211 Aromatic, 24, 160, 166, 196 Arterial, 160, 182, 200, 208 Arteries, 160, 163, 168, 169, 189, 191, 211
216
Aplastic Anemia
Arteriosclerosis, 160, 207, 210 Arteriovenous, 160, 210 Arteriovenous Fistula, 160, 210 Arthralgia, 160, 205 Articular, 160, 194 Ascorbic Acid, 160, 178 Aspergillosis, 63, 160 Aspiration, 96, 160 Assay, 6, 9, 29, 31, 75, 109, 111, 112, 160, 204 Astrocytes, 160, 184 Asymptomatic, 161, 162 Ataxia, 19, 32, 33, 161, 209 Attenuated, 23, 161, 171 Atypical, 103, 104, 161 Autoimmune disease, 23, 28, 34, 99, 161, 191 Autoimmunity, 60, 108, 110, 161 Autologous, 15, 18, 23, 34, 53, 56, 102, 114, 161, 179, 196 Autologous bone marrow transplantation, 53, 161, 179 Autonomic, 155, 159, 161, 191 Autopsy, 9, 161 B Bacteria, 18, 96, 158, 161, 168, 173, 174, 176, 180, 189, 190, 201, 205, 206, 210, 212 Bacteriophage, 161, 210 Bacterium, 161, 168, 180 Bacteriuria, 161, 212 Basal Ganglia, 159, 161, 177 Basal Ganglia Diseases, 161 Base, 21, 161, 171, 177, 186, 208 Basophils, 156, 161, 179, 186 Benign, 162, 170, 177, 192, 201 Benzene, 7, 28, 70, 85, 91, 116, 162 Benzo(a)pyrene, 24, 162 Beta-Thalassemia, 52, 162 Bicalutamide, 116, 162 Bile, 162, 177, 187, 207 Binding Sites, 13, 162 Biochemical, 5, 9, 15, 16, 19, 24, 26, 29, 30, 32, 35, 156, 162, 176, 194 Biogenic Monoamines, 162, 187 Biological response modifier, 162, 184 Biological therapy, 162, 179 Biomarkers, 25, 162 Biopsy, 95, 162, 175 Biotechnology, 16, 35, 36, 125, 135, 162 Bladder, 162, 183, 191, 200, 211, 212 Blasts, 23, 81, 162 Blood Cell Count, 116, 162, 179
Blood Glucose, 163, 180, 184 Blood Platelets, 163, 189, 198, 209 Blood pressure, 163, 164, 182, 190, 206 Blood transfusion, 10, 163 Blood vessel, 163, 164, 165, 173, 180, 186, 188, 189, 206, 207, 208, 209, 212 Body Fluids, 162, 163, 164, 206, 211 Bone marrow aspiration, 28, 95, 163 Bone marrow biopsy, 101, 102, 163 Bone Marrow Cells, 15, 24, 28, 50, 84, 90, 163, 167, 179, 189, 191 Bowel, 121, 157, 163, 171, 183, 185, 207 Bowel Movement, 163, 171, 207 Brachytherapy, 163, 185, 201, 214 Bradykinin, 163, 193 Branch, 84, 85, 97, 151, 163, 170, 188, 195, 200, 206, 209 Breeding, 10, 163 Buccal, 163, 188 Bullous, 46, 163 Bypass, 5, 164, 192, 210 C Calcium, 164, 167, 171, 192, 205, 213 Callus, 164, 173 Canthaxanthin, 84, 164 Carbamazepine, 53, 164 Carbohydrate, 164, 178, 198, 205 Carcinogen, 155, 162, 164 Carcinogenesis, 16, 164 Carcinogenic, 156, 162, 164, 184, 193, 199, 207 Carcinoma, 68, 70, 77, 164, 169 Cardiac, 164, 174, 192, 207 Cardiopulmonary, 26, 164 Cardiovascular, 48, 108, 109, 110, 111, 112, 164, 186, 209 Cardiovascular disease, 108, 109, 110, 111, 112, 164 Case report, 51, 53, 63, 73, 79, 86, 164 Caspase, 23, 164 Cations, 164, 185 Causal, 116, 164, 180 Cell Cycle, 16, 164, 199 Cell Death, 31, 109, 111, 112, 160, 165, 192 Cell Differentiation, 7, 22, 165, 205, 207 Cell Division, 161, 165, 170, 179, 185, 190, 197, 204 Cell Extracts, 5, 22, 165 Cell Lineage, 7, 165 Cell membrane, 32, 165, 171, 185, 196, 206 Cell proliferation, 16, 109, 160, 165, 185, 205
Index
Cell Respiration, 156, 165, 190, 194 Cell Size, 165, 176 Cell Survival, 16, 29, 165, 179 Cell Transplantation, 15, 40, 43, 98, 100, 101, 102, 103, 121, 140, 141, 165 Central Nervous System, 155, 162, 165, 177, 178, 186, 187, 188, 191 Centrifugation, 97, 165, 179 Ceramide, 7, 165 Cerebellar, 108, 110, 161, 165, 202 Cerebellum, 165, 202 Cerebral, 63, 121, 161, 165, 174, 200 Cerebral Palsy, 121, 165 Cerebrovascular, 161, 164, 165, 209 Cerebrum, 165 Character, 165, 171 Chemotactic Factors, 166, 167 Chemotherapy, 5, 26, 28, 54, 98, 99, 100, 101, 103, 104, 121, 166, 204 Chest Pain, 100, 166 Cholesterol, 162, 166, 169, 181, 207 Chromatin, 160, 166, 192, 207 Chromosomal, 15, 16, 19, 27, 30, 166, 203, 208 Chromosome, 10, 15, 21, 25, 27, 29, 63, 64, 166, 168, 180, 187, 191, 204, 208, 211 Chronic granulocytic leukemia, 166 Chronic leukemia, 103, 166, 179 Chronic lymphocytic leukemia, 43, 101, 166 Chronic myelogenous leukemia, 50, 166 Chronic renal, 166, 198 Chymotrypsin, 113, 166 CIS, 29, 166, 203 C-kit receptor, 166, 207 Clear cell carcinoma, 166, 171 Cleave, 113, 166 Clinical Medicine, 166, 199 Clinical trial, 4, 8, 17, 21, 95, 102, 104, 135, 166, 169, 200, 201 Clone, 30, 76, 110, 166 Cloning, 12, 15, 27, 30, 108, 162, 167 Coal, 162, 167 Cofactor, 30, 167, 200, 209 Colitis, 70, 79, 140, 167, 183 Collagen, 167, 176, 198 Colony-Stimulating Factors, 167, 178 Combination chemotherapy, 98, 99, 167 Combination Therapy, 52, 66, 75, 124, 167, 175 Complement, 18, 59, 85, 157, 167, 168, 177
217
Complementary and alternative medicine, 89, 93, 168 Complementary medicine, 89, 168 Complementation, 11, 12, 13, 15, 17, 19, 20, 27, 168 Complete remission, 168, 202 Computational Biology, 135, 168 Conjugated, 168, 170, 193 Conjugation, 7, 168 Connective Tissue, 160, 163, 167, 168, 176, 189, 203, 207, 208 Constitutional, 44, 52, 168, 203 Constriction, 168, 186 Contraindications, ii, 168 Coordination, 23, 165, 168, 191 Cornea, 39, 168, 207, 214 Coronary, 49, 164, 168, 169, 189, 191, 210 Coronary heart disease, 164, 169 Coronary Thrombosis, 169, 189, 191 Corpuscle, 169, 175 Cortex, 161, 169, 199, 202 Cortical, 169, 204, 209 Corticosteroids, 10, 23, 56, 90, 100, 169 Criterion, 115, 169 Crossing-over, 169, 202 Cryofixation, 169 Cryopreservation, 15, 32, 169 Cryoprotective, 32, 169 Cryoprotective Agents, 32, 169 Cultured cells, 6, 169 Curative, 6, 8, 34, 169, 203, 209 Cutaneous, 6, 169, 188, 197 Cyclic, 169, 179, 193 Cyclophosphamide, 29, 41, 42, 45, 49, 57, 60, 65, 66, 76, 80, 85, 91, 102, 103, 124, 169 Cyclosporine, 4, 23, 28, 43, 46, 48, 57, 61, 65, 68, 74, 99, 100, 124, 169 Cyproterone, 169, 176 Cysteine, 7, 112, 155, 170, 208 Cystine, 170 Cytochrome, 15, 24, 26, 170 Cytogenetics, 9, 27, 38, 44, 48, 49, 170 Cytokine, 13, 27, 45, 116, 170, 176, 204 Cytomegalovirus, 76, 101, 170 Cytomegalovirus Retinitis, 76, 170 Cytopenia, 23, 170 Cytoplasm, 160, 161, 165, 170, 174, 179, 192 Cytotoxic, 28, 32, 61, 170, 182, 201, 205 Cytotoxicity, 5, 33, 170
218
Aplastic Anemia
D Daclizumab, 75, 95, 170 Danazol, 53, 61, 170 Databases, Bibliographic, 135, 170 De novo, 29, 170 Defense Mechanisms, 24, 170 Degenerative, 109, 111, 112, 171, 180, 194, 203 Deletion, 25, 160, 171, 177 Dendrites, 171 Dendritic, 17, 18, 171 Dendritic cell, 17, 171 Density, 15, 165, 171, 176, 194 Depolarization, 171, 205 Depressive Disorder, 171, 187 Deprivation, 109, 171 Dermal, 6, 171 Dermatitis, 49, 171 DES, 86, 157, 171 Detoxification, 26, 171 Diabetes Mellitus, 171, 180 Diagnostic procedure, 27, 107, 125, 171 Diarrhea, 121, 171 Diastolic, 171, 182 Diffusion, 171, 183, 185 Digestion, 156, 162, 163, 171, 185, 187, 207, 212 Digestive system, 105, 171 Dihydrotestosterone, 171, 202 Dilatation, 171, 199, 212 Diltiazem, 46, 171 Dilution, 75, 171 Dimethyl, 172, 187 Dipeptidases, 7, 172 Dipeptides, 172 Diploid, 168, 172, 191, 197, 211 Direct, iii, 6, 15, 19, 35, 166, 172, 202 Disaccharides, 33, 172 Disease Progression, 81, 116, 172 Disparity, 14, 172 Dissociation, 156, 172, 185 Dominance, 29, 172 Dopamine, 159, 172, 196, 202 Drive, ii, vi, 3, 14, 15, 83, 172, 185, 186 Drug Interactions, 128, 172 Drug Tolerance, 172, 210 Duodenum, 162, 166, 172, 195, 207 Dyspareunia, 172, 175 E Ectopic, 113, 172 Edema, 170, 172, 192 Effector, 6, 17, 61, 113, 155, 167, 173
Effector cell, 6, 17, 173 Efficacy, 57, 103, 173, 211 Electrocardiogram, 100, 173 Electrons, 159, 161, 173, 185, 194, 201 Embolus, 173, 183 Embryo, 12, 157, 165, 173, 183, 189, 211 Embryogenesis, 12, 26, 30, 109, 111, 112, 173, 207 Encapsulated, 173, 187 Encephalopathy, 46, 173 Endemic, 173, 207 Endocrine Glands, 11, 173 Endometrial, 173 Endometriosis, 53, 170, 173 Endometrium, 173 Endothelial cell, 6, 28, 109, 111, 112, 173, 209 Endothelium, 6, 173, 174, 193 Endothelium, Lymphatic, 173 Endothelium, Vascular, 173 Endothelium-derived, 174, 193 Endotoxin, 174, 211 End-stage renal, 166, 174, 198 Enhancer, 35, 43, 174, 203 Enteropeptidase, 174, 211 Environmental Exposure, 174, 193 Environmental Health, 24, 134, 136, 174 Enzymatic, 22, 162, 164, 167, 174, 181, 203 Eosinophil, 174, 179 Epidemic, 174, 207 Epidermis, 174, 200 Epinephrine, 155, 172, 174, 211 Epistaxis, 3, 174 Epithelial, 174, 180, 184 Epithelial Cells, 174, 180, 184 Epithelium, 173, 174, 214 Erythroblasts, 174, 175 Erythrocyte Indices, 163, 174 Erythrocyte Membrane, 120, 175 Erythrocytes, 10, 48, 91, 157, 158, 162, 163, 174, 175, 180, 195, 202 Erythroid Progenitor Cells, 10, 174, 175, 191 Erythropoiesis, 18, 174, 175 Erythropoietin, 49, 51, 52, 66, 81, 85, 175 Erythrovirus, 36, 71, 175 Esophagus, 171, 175, 207, 209 Estrogen, 115, 169, 175 Estrogen Replacement Therapy, 115, 175 Eukaryotic Cells, 175, 193, 194, 211 Excisional, 175, 213 Excitation, 175, 176
Index
Exon, 25, 175 External-beam radiation, 175, 185, 201, 213 Extracellular, 160, 168, 175, 176, 206 Extracellular Matrix, 168, 175, 176 F Facial, 175, 213 Family Planning, 135, 175 Fat, 84, 160, 163, 165, 169, 173, 175, 187, 191, 203, 206 Fathers, 43, 175 Fatigue, 3, 175, 179 Feces, 176, 207 Femoral, 176, 180 Femoral Neck Fractures, 176, 180 Femur, 176, 180 Ferritin, 140, 176 Fetus, 175, 176, 182, 197, 199, 211, 212 Fibroblasts, 40, 113, 176, 184 Fibronectin, 20, 176 Fibrosis, 121, 176, 204 Filgrastim, 102, 103, 176 Flow Cytometry, 5, 32, 63, 72, 176 Fluorescence, 176 Fluorescent Dyes, 176 Flutamide, 116, 176 Folate, 120, 176, 177 Fold, 115, 176 Folic Acid, 39, 120, 176 Follow-Up Studies, 26, 177 Fungi, 158, 160, 168, 177, 179, 189, 190, 213, 214 G Gallbladder, 155, 171, 177 Gamma Rays, 177, 191, 201 Ganglion, 177, 214 Gas, 171, 177, 181, 191, 193, 212 Gasoline, 162, 177 Gastrin, 177, 181 Gastritis, 51, 177 Gastrointestinal, 33, 98, 121, 163, 174, 177, 186, 208, 211 Gastrointestinal tract, 177, 186, 211 Gene, 4, 9, 10, 11, 12, 15, 16, 18, 19, 20, 21, 22, 23, 25, 26, 27, 30, 31, 32, 34, 55, 62, 69, 71, 78, 108, 109, 112, 156, 162, 172, 177, 181, 193, 194, 203, 204 Gene Deletion, 62, 177 Gene Expression, 18, 21, 55, 177 Genetic Code, 177, 193 Genetic Counseling, 19, 177 Genetic Engineering, 162, 167, 177
219
Genetics, 26, 27, 32, 35, 38, 44, 48, 49, 70, 168, 170, 172, 178 Genomics, 108, 110, 178 Genotype, 5, 14, 24, 156, 178, 196 Geriatric, 39, 178 Gingival Hemorrhage, 3, 178 Gingival Hyperplasia, 4, 178 Gland, 178, 194, 195, 200, 204, 207, 210 Glucose, 56, 160, 163, 171, 178, 180, 184, 204 Glutamic Acid, 176, 178 Glycoprotein, 175, 176, 178, 188, 191, 209, 211 Glycoside, 172, 178, 204 Gonadal, 178, 207 Gonads, 11, 178, 182 Governing Board, 178, 199 Graft Rejection, 34, 65, 178, 190 Grafting, 28, 49, 178 Graft-versus-host disease, 6, 14, 26, 28, 34, 37, 50, 52, 57, 65, 102, 159, 178, 191 Granulocyte Colony-Stimulating Factor, 49, 52, 61, 66, 68, 69, 73, 75, 80, 167, 176, 178 Granulocyte-Macrophage ColonyStimulating Factor, 79, 86, 92, 167, 178 Granulocytes, 156, 167, 178, 179, 186, 191, 205, 213 Granulocytopenia, 159, 179 Grasses, 177, 179 Growth factors, 18, 22, 61, 77, 109, 179 Guanylate Cyclase, 179, 193 H Hairy cell leukemia, 73, 179 Haptens, 156, 179, 205 Heart attack, 164, 179 Heart failure, 78, 179 Hemato, 121, 179 Hematocrit, 140, 163, 174, 179 Hematologic malignancies, 6, 17, 34, 42, 67, 179 Hematologist, 8, 95, 179 Hematopoiesis, 4, 11, 18, 19, 21, 24, 27, 28, 30, 31, 32, 34, 35, 57, 77, 79, 116, 120, 179 Hematopoietic growth factors, 7, 13, 58, 80, 179 Hematopoietic Stem Cell Transplantation, 6, 20, 26, 77, 179 Hematopoietic Stem Cells, 10, 11, 20, 21, 29, 30, 35, 180, 191 Hematopoietic tissue, 7, 163, 180 Heme, 170, 180
220
Aplastic Anemia
Hemoglobin, 120, 140, 158, 162, 163, 174, 175, 180, 209 Hemoglobinuria, 8, 29, 31, 34, 48, 50, 55, 62, 71, 72, 73, 75, 76, 78, 102, 103, 144, 180 Hemolysis, 31, 175, 180 Hemolytic, 67, 120, 158, 180, 209 Hemorrhage, 39, 170, 180, 192, 201, 207 Hepatic, 49, 53, 54, 69, 180 Hepatitis, 53, 54, 55, 59, 63, 64, 71, 74, 76, 77, 84, 96, 116, 124, 180 Hepatocytes, 180 Hereditary, 35, 180, 196, 209 Heredity, 177, 178, 180 Herpes, 101, 180 Herpes virus, 101, 180 Herpes Zoster, 180 Heterogeneity, 65, 156, 180 Heterozygote, 33, 180 Hip Fractures, 115, 176, 180 Hirsutism, 116, 169, 180, 182 Histamine, 157, 159, 181, 188 Histiocytosis, 103, 181 Histocompatibility, 34, 181, 190 Histology, 116, 181, 195 Histone Deacetylase, 17, 22, 181 Homeostasis, 16, 109, 111, 112, 181 Homologous, 21, 26, 112, 156, 169, 180, 181, 204, 208 Homozygotes, 33, 172, 181 Hormonal, 22, 175, 181, 213 Hormone, 11, 115, 156, 169, 171, 174, 175, 177, 181, 184, 199, 203, 205, 209, 210, 213 Hormone Replacement Therapy, 116, 181 Host, 10, 17, 18, 24, 28, 36, 46, 101, 102, 109, 111, 112, 121, 156, 161, 181, 186, 203, 213 Humoral, 178, 181, 209 Hybrid, 17, 167, 181 Hybridization, 12, 25, 181 Hybridomas, 181, 184 Hydrogen, 155, 161, 164, 181, 187, 190, 192, 193, 194, 200, 214 Hydrolysis, 181, 185, 196, 198, 200, 211 Hypercholesterolemia, 115, 181 Hyperlipidemia, 115, 181 Hyperplasia, 4, 84, 181 Hypersensitivity, 5, 11, 13, 15, 17, 19, 20, 174, 182, 186, 203 Hypertension, 108, 110, 164, 182 Hypertrichosis, 180, 182 Hypertrophy, 182
Hypogonadism, 115, 182 Hypotension, 108, 110, 159, 182 I Id, 87, 92, 140, 141, 142, 144, 150, 152, 182 Ida, 142, 182 Idiopathic, 7, 36, 44, 51, 64, 73, 74, 77, 117, 182 Immune function, 96, 182 Immune response, 158, 159, 161, 178, 179, 182, 183, 208, 213 Immune system, 97, 99, 100, 101, 159, 161, 162, 173, 182, 186, 188, 191, 196, 212, 213 Immune Tolerance, 49, 85, 182 Immunity, 96, 112, 182 Immunocompromised, 121, 182 Immunodeficiency, 14, 20, 182 Immunoglobulin, 51, 158, 182, 190 Immunologic, 20, 29, 166, 182, 201 Immunology, 14, 23, 45, 85, 156, 176, 182 Immunosuppressant, 156, 182 Immunosuppressive Agents, 24, 75, 182 Immunosuppressive therapy, 37, 47, 50, 57, 61, 63, 64, 67, 68, 72, 73, 76, 78, 114, 123, 183 Impairment, 161, 183, 189 Implant radiation, 183, 185, 201, 213 In situ, 7, 26, 183 In vitro, 5, 6, 10, 15, 18, 22, 23, 24, 30, 31, 33, 44, 50, 62, 63, 64, 86, 113, 183, 204 In vivo, 5, 7, 10, 14, 15, 17, 20, 21, 23, 24, 30, 31, 33, 35, 45, 62, 183 Incontinence, 183, 191 Incubation, 10, 183, 186 Incubation period, 183, 186 Indicative, 119, 183, 195, 212 Induction, 7, 11, 28, 62, 158, 159, 183, 212 Infarction, 111, 183, 202, 210 Infiltration, 183, 214 Inflammatory bowel disease, 121, 183 Infusion, 56, 95, 183, 192, 210 Ingestion, 164, 183, 198 Inhalation, 183, 198 Initiation, 183, 199, 210 Inlay, 184, 203 Inner ear, 184, 212 Inositol, 29, 184 Insecticides, 184, 196 Insight, 11, 23, 29, 184 Insulator, 184, 191 Insulin, 56, 115, 184 Insulin-dependent diabetes mellitus, 184 Insulin-like, 115, 184
Index
Interferon, 38, 55, 63, 184, 188 Interferon-alpha, 184 Interleukin-1, 63, 111, 112, 113, 184 Interleukin-2, 95, 184 Interleukin-3, 66, 167, 184 Interleukin-6, 40, 184 Interleukins, 183, 185 Internal Medicine, 40, 49, 50, 55, 60, 64, 73, 84, 85, 86, 179, 185 Internal radiation, 185, 201, 213 Interphase, 185, 193 Interstitial, 163, 185, 213 Intestinal, 174, 185, 213 Intestine, 64, 163, 185, 186 Intoxication, 179, 185, 213 Intracellular, 63, 183, 185, 193, 205 Intramuscular, 185, 195 Intravascular, 31, 185 Intravenous, 183, 185, 195 Intrinsic, 29, 156, 185 Invasive, 36, 63, 182, 185 Ion Transport, 110, 185 Ionization, 185 Ionizing, 16, 116, 157, 174, 185, 201 Ions, 33, 161, 172, 181, 185, 206 Irradiation, 26, 42, 47, 68, 80, 185, 214 Ischemia, 23, 108, 109, 110, 111, 112, 186, 191, 192, 202 J Joint, 115, 160, 186, 194, 208 K Kb, 30, 134, 186 Ketoconazole, 53, 186 Kidney Disease, 85, 105, 108, 109, 110, 111, 112, 134, 141, 143, 186 Kinetic, 185, 186 L Labile, 167, 186 Lamivudine, 76, 186 Large Intestine, 171, 185, 186, 202, 206 Latent, 186, 199 Lentivirus, 10, 11, 186 Lesion, 5, 186, 187 Lethal, 12, 14, 186 Leucocyte, 174, 186, 188 Leukapheresis, 159, 186 Leukocytes, 24, 161, 162, 163, 166, 179, 184, 185, 186, 192, 195, 196, 211 Leukotrienes, 7, 160, 186 Libido, 115, 158, 186 Library Services, 150, 187 Life Expectancy, 33, 187
221
Ligament, 187, 200 Linkages, 180, 187, 214 Lipid, 160, 184, 187, 191, 194 Lipid Peroxidation, 187, 194 Lipopolysaccharide, 73, 187 Liposomal, 63, 187 Lipoxygenase, 186, 187 Lithium, 81, 159, 187 Lithium Carbonate, 81, 187 Liver Transplantation, 49, 85, 187 Localization, 16, 19, 187 Localized, 21, 155, 169, 173, 180, 182, 183, 187, 191, 197, 212 Longitudinal study, 115, 187 Loperamide, 121, 187 Lupus, 34, 188, 208 Lymph, 169, 173, 188, 205 Lymphadenopathy, 188, 205 Lymphatic, 143, 173, 183, 188, 189, 206, 207, 209 Lymphatic system, 188, 206, 207, 209 Lymphoblastic, 37, 103, 188 Lymphoblasts, 16, 188 Lymphocyte, 6, 8, 23, 28, 159, 188, 189 Lymphocytic, 81, 188 Lymphoid, 26, 30, 42, 47, 98, 101, 103, 158, 169, 186, 188, 191 Lymphokine, 85, 86, 188 Lymphoma, 37, 53, 65, 98, 99, 100, 101, 103, 141, 179, 188 Lymphoproliferative, 54, 67, 188 Lysine, 188, 211 M Macrophage, 24, 42, 50, 57, 167, 179, 184, 188 Macrophage Colony-Stimulating Factor, 57, 167, 188 Malignancy, 6, 15, 33, 188 Malignant, 26, 28, 34, 53, 104, 159, 181, 188, 192, 199, 201, 208 Malnutrition, 121, 188 Manic, 159, 187, 188 Mediate, 6, 11, 17, 172, 188 Mediator, 85, 184, 188 MEDLINE, 135, 189 Medullary, 56, 189 Megakaryocytes, 163, 189, 209 Megaloblastic, 177, 189 Melanin, 189, 196, 211 Memory, 158, 189 Menopause, 115, 189, 196, 198 Menstruation, 189
222
Aplastic Anemia
Mental Disorders, 105, 189 Mental Health, iv, 4, 96, 105, 134, 136, 189, 200 Mercury, 176, 189 Mesenchymal, 32, 51, 61, 178, 188, 189 Mesoderm, 11, 189 Meta-Analysis, 79, 189 Metabolic disorder, 91, 189 Metabolite, 7, 28, 172, 189 MI, 51, 111, 112, 153, 189 Mice Minute Virus, 189, 195 Microbe, 189, 210 Microbiology, 14, 19, 71, 77, 161, 189 Microorganism, 167, 190, 195, 213 Microscopy, 190, 193 Migration, 6, 190 Minor Histocompatibility Antigens, 14, 190 Minor Histocompatibility Loci, 190 Mitochondria, 190, 192, 194 Mitochondrial Swelling, 190, 192 Mitomycin, 5, 11, 15, 64, 190 Mitosis, 19, 160, 190 Mitotic, 13, 190 Mitotic inhibitors, 13, 190 Modeling, 17, 190 Modification, 22, 177, 190, 201, 214 Monitor, 190, 193 Monoclonal, 170, 181, 186, 190, 201, 214 Monocyte, 71, 188, 191 Mononuclear, 6, 24, 46, 62, 63, 73, 85, 86, 97, 188, 191, 211 Monosomy, 25, 52, 57, 69, 191 Morphological, 173, 191 Morphology, 179, 191 Motion Sickness, 191, 192 Mucolytic, 155, 191 Mucosa, 188, 191, 207 Multiple sclerosis, 108, 110, 191 Mutagen, 162, 191 Mutagenic, 156, 191 Mycophenolate mofetil, 28, 191 Myelin, 191, 204 Myelitis, 64, 191 Myelodysplasia, 12, 31, 35, 44, 52, 61, 64, 76, 104, 145, 191 Myelofibrosis, 42, 113, 191 Myelogenous, 191 Myeloid Cells, 29, 191 Myeloid Progenitor Cells, 29, 191 Myeloproliferative Disorders, 100, 191
Myocardial infarction, 108, 109, 110, 111, 112, 169, 189, 191 Myocardial Reperfusion, 191, 192, 202 Myocardial Reperfusion Injury, 192, 202 Myocardium, 189, 191, 192 N Nausea, 121, 159, 192 NCI, 1, 98, 99, 100, 101, 103, 104, 133, 166, 192 Necrosis, 79, 160, 170, 183, 189, 191, 192, 202 Need, 3, 108, 110, 114, 120, 128, 129, 145, 146, 156, 166, 192, 210 Neoplasia, 192 Neoplasm, 100, 192 Neoplastic, 31, 164, 181, 188, 192 Nephropathy, 186, 192 Nerve, 155, 158, 161, 169, 171, 177, 188, 191, 192, 198, 203, 204, 207, 210, 212, 214 Nervous System, 165, 188, 192, 208 Neuroblastoma, 58, 192 Neurologic, 13, 192 Neutrons, 157, 185, 192, 201 Neutrophils, 156, 176, 178, 179, 186, 192 Nitric Oxide, 62, 193 Nitrogen, 115, 158, 169, 193 Nuclear, 13, 19, 26, 29, 42, 115, 161, 168, 173, 175, 177, 192, 193, 199 Nuclear Proteins, 13, 193 Nuclei, 12, 157, 168, 173, 177, 190, 192, 193, 200 Nucleic acid, 109, 111, 112, 177, 181, 193, 214 Nucleic Acid Hybridization, 181, 193 Nucleolus, 81, 193 Nucleoproteins, 193 Nucleus, 12, 26, 160, 161, 166, 169, 170, 175, 177, 191, 192, 193, 200, 207, 209 O Occupational Exposure, 25, 193 Odour, 160, 193 Ointments, 193, 195 Oncogene, 30, 193, 207 Oncogenic, 186, 193 Oncologist, 8, 26, 193 Oncology, 19, 27, 33, 40, 42, 48, 52, 60, 64, 74, 85, 102, 141, 193 Opacity, 171, 194 Open Reading Frames, 186, 194 Operon, 194, 199, 202 Ophthalmic, 53, 194 Oral Health, 120, 194
Index
Oral Hygiene, 121, 194 Oral Manifestations, 3, 4, 194 Orderly, 35, 194 Organ Transplantation, 49, 101, 121, 194 Organelles, 24, 165, 170, 194, 197 Orofacial, 121, 194 Osteoarthritis, 108, 110, 194 Osteoporosis, 108, 109, 110, 111, 112, 115, 175, 194 Ovary, 178, 194, 207 Oxidation, 7, 155, 159, 170, 187, 194 Oxidative metabolism, 15, 156, 186, 194 Oxidative Stress, 16, 194 P Palliative, 169, 194, 209 Pancreas, 155, 162, 166, 171, 184, 194, 195, 211 Pancreatic, 115, 166, 195 Pancreatic cancer, 115, 195 Pancreatic Juice, 166, 195 Pancytopenia, 14, 23, 31, 97, 195 Papilla, 195 Papillary, 6, 195 Paraffin, 9, 195 Parenteral, 121, 195 Paroxysmal, 8, 29, 31, 34, 48, 50, 55, 62, 71, 72, 73, 75, 76, 78, 102, 103, 144, 195 Partial remission, 195, 202 Particle, 195, 210 Parvovirus, 40, 59, 74, 76, 175, 189, 195 Pathogen, 183, 195 Pathogenesis, 6, 9, 13, 14, 16, 18, 25, 27, 31, 35, 36, 58, 73, 195 Pathologic, 9, 158, 160, 162, 169, 182, 195 Pathologic Processes, 160, 195 Pathophysiology, 7, 17, 61, 70, 73, 78, 119, 120, 195 Patient Advocacy, 8, 195 Pediatrics, 11, 15, 25, 26, 27, 39, 52, 58, 59, 67, 71, 76, 85, 86, 90, 142, 195 Pelvic, 173, 195, 200 Penicillamine, 38, 195 Penicillin, 158, 195, 212 Peptide, 174, 195, 198, 200 Pericardium, 196, 208 Perimenopausal, 115, 196 Periodontal disease, 115, 196 Periodontitis, 178, 196 Peripheral blood, 6, 11, 24, 35, 37, 46, 62, 63, 73, 78, 80, 101, 159, 179, 184, 196, 199 Peripheral stem cell transplantation, 98, 100, 103, 196
223
Peripheral stem cells, 178, 196 Pernicious, 120, 189, 196 Peroxidase, 7, 27, 187, 196 Peroxide, 24, 187, 196 Pesticides, 80, 86, 116, 184, 196 Petechiae, 4, 196 Petroleum, 177, 195, 196 Phagocyte, 188, 196 Pharmacokinetic, 7, 196 Pharmacologic, 158, 196, 210 Phenotype, 13, 14, 17, 26, 32, 61, 108, 113, 168, 177, 196 Phenylalanine, 196, 211 Phospholipases, 196, 205 Phospholipids, 175, 184, 196 Phosphorus, 164, 197 Phosphorylate, 13, 197 Phosphorylated, 13, 17, 19, 32, 197 Phosphorylation, 19, 197 Photosensitivity, 197, 213 Physical Examination, 95, 97, 101, 102, 122, 197 Physiologic, 20, 189, 197, 201 Physiology, 18, 23, 35, 179, 197 Pigment, 164, 197 Pilot study, 103, 197 Placenta, 197, 199, 211 Placental blood transplantation, 103, 197 Plants, 163, 178, 191, 197, 204, 210 Plasma, 73, 100, 102, 113, 114, 158, 165, 167, 173, 176, 180, 186, 197, 198, 202, 204 Plasma cells, 158, 197 Plasmapheresis, 56, 114, 159, 197 Plastids, 194, 197 Platelet Activation, 197, 205 Platelet Aggregation, 157, 193, 198, 210 Platelet Count, 114, 198 Platelet Transfusion, 67, 113, 198 Plateletpheresis, 159, 198 Platelets, 95, 97, 100, 102, 113, 145, 193, 195, 197, 198, 204, 209 Poisoning, 70, 140, 185, 189, 192, 198, 205 Polycystic, 109, 111, 112, 198 Polymerase, 113, 198, 199, 202 Polymorphic, 25, 198 Polymorphism, 28, 43, 198 Polypeptide, 23, 109, 111, 112, 157, 167, 181, 198, 209, 214 Polyposis, 69, 198 Polysaccharide, 158, 198 Posterior, 157, 161, 165, 194, 198 Postmenopausal, 115, 175, 194, 198
224
Aplastic Anemia
Postnatal, 198, 207 Postsynaptic, 198, 205 Potentiate, 22, 198 Potentiation, 25, 198, 205 Practicability, 198, 211 Practice Guidelines, 136, 198 Preclinical, 10, 17, 28, 30, 199 Precursor, 10, 59, 85, 160, 169, 172, 173, 174, 178, 196, 199, 211, 212, 213 Predisposition, 14, 15, 33, 199 Preleukemia, 70, 191, 199, 206 Prenatal, 173, 199 Prevalence, 3, 74, 116, 199 Probe, 18, 199 Progeny, 5, 10, 17, 168, 199 Progesterone, 199, 207 Progression, 16, 29, 199 Progressive, 14, 23, 165, 166, 172, 175, 179, 192, 194, 197, 199 Projection, 171, 199, 202 Proliferating Cell Nuclear Antigen, 64, 199 Promoter, 21, 22, 34, 43, 115, 199 Promotor, 199, 203 Prone, 16, 199 Proneness, 30, 199 Prophylaxis, 46, 57, 199 Proportional, 24, 199 Prospective study, 69, 187, 200 Prostate, 115, 162, 200, 211 Protease, 111, 112, 167, 200 Protein C, 16, 19, 29, 32, 157, 161, 176, 200, 205 Protein S, 31, 162, 177, 200 Proteolytic, 113, 167, 174, 200 Protocol, 10, 13, 22, 26, 96, 116, 200 Protons, 157, 181, 185, 200, 201 Protozoa, 168, 190, 200 Psychic, 186, 200, 204 Psychomotor, 164, 200 Puberty, 115, 200 Public Health, 86, 136, 162, 200 Public Policy, 135, 200 Publishing, 36, 200 Pulmonary, 163, 186, 200, 209 Purpura, 44, 73, 95, 116, 200 Q Quality of Life, 26, 201 Quinones, 24, 201 R Race, 96, 190, 201
Radiation, 16, 101, 103, 104, 116, 174, 175, 176, 177, 182, 185, 193, 201, 211, 213 Radiation oncologist, 193, 201 Radiation therapy, 101, 103, 104, 175, 185, 201, 211, 214 Radioactive, 181, 183, 185, 193, 201, 214 Radioimmunotherapy, 201 Radiolabeled, 186, 201, 214 Radiotherapy, 121, 163, 186, 201, 214 Randomized, 24, 38, 46, 65, 91, 173, 201 Randomized clinical trial, 24, 201 Reactive Oxygen Species, 5, 7, 16, 201 Receptor, 13, 18, 29, 43, 65, 75, 95, 110, 114, 115, 159, 166, 172, 188, 201, 205 Recombinant, 12, 42, 47, 50, 66, 69, 75, 92, 108, 109, 110, 111, 112, 202, 212 Recombination, 21, 168, 202 Reconstitution, 33, 56, 202 Rectum, 163, 171, 177, 183, 186, 200, 202 Recurrence, 50, 202 Red blood cells, 95, 97, 102, 145, 175, 180, 202, 204 Red Nucleus, 161, 202 Reductase, 15, 26, 202 Refer, 1, 163, 167, 177, 180, 187, 192, 201, 202 Refraction, 202, 206 Refractory, 34, 44, 54, 66, 67, 80, 120, 202 Regeneration, 202 Regimen, 98, 103, 121, 173, 202 Relapse, 99, 100, 102, 202 Remission, 49, 73, 76, 102, 121, 202 Remoxipride, 62, 202 Reperfusion, 23, 108, 109, 110, 111, 112, 192, 202 Reperfusion Injury, 23, 108, 109, 110, 111, 112, 202 Repressor, 17, 194, 202 Research Design, 9, 202 Resection, 81, 203 Response Elements, 115, 203 Restoration, 9, 191, 202, 203 Retina, 170, 203 Retinal, 170, 172, 203 Retinitis, 170, 203 Retinopathy, 164, 203 Retrospective, 26, 33, 37, 45, 46, 203 Retroviral vector, 12, 18, 21, 203 Retrovirus, 10, 11, 36, 203 Rheumatism, 203 Rheumatoid, 108, 109, 110, 111, 112, 203
Index
Rheumatoid arthritis, 108, 109, 110, 111, 112, 203 Ribose, 113, 203 Rickets, 203, 213 Risk factor, 14, 25, 26, 28, 33, 37, 39, 57, 76, 200, 203 Ristocetin, 203, 212 Rodenticides, 196, 204 S Salivary, 170, 171, 195, 204 Salivary glands, 170, 171, 204 Saponins, 204, 207 Sargramostim, 101, 204 Schizoid, 204, 213 Schizophrenia, 3, 202, 204, 213 Schizotypal Personality Disorder, 204, 213 Sclerosis, 108, 110, 160, 191, 204 Screening, 22, 23, 25, 76, 166, 204, 212 Sebaceous, 204, 213 Sebaceous gland, 204, 213 Secretion, 115, 181, 184, 185, 204, 212, 213 Sediment, 204, 212 Segregation, 161, 202, 204 Seizures, 101, 164, 195, 204 Semen, 200, 204 Senile, 194, 204 Sensory loss, 191, 204, 209 Sepsis, 108, 109, 110, 111, 112, 205 Septic, 108, 109, 110, 111, 112, 205 Septicemia, 82, 205 Sequence Analysis, 10, 205 Serine, 166, 205, 211 Serous, 173, 205 Serum, 46, 49, 67, 85, 101, 113, 140, 157, 167, 182, 202, 205, 211 Serum Sickness, 101, 205 Sex Characteristics, 155, 158, 200, 205, 209 Shock, 108, 109, 110, 111, 112, 205, 211 Side effect, 8, 32, 95, 101, 127, 129, 156, 159, 162, 169, 205, 210, 214 Signal Transduction, 8, 12, 13, 19, 32, 184, 205 Signs and Symptoms, 202, 205 Skeletal, 13, 27, 75, 158, 205 Skeleton, 176, 186, 205 Skin Pigmentation, 27, 206 Small intestine, 172, 181, 185, 206, 211, 212 Smoldering leukemia, 191, 206 Social Environment, 201, 206 Sodium, 206, 212 Sodium Channels, 206, 212 Soft tissue, 4, 77, 163, 205, 206
225
Solid tumor, 9, 27, 121, 206 Solvent, 162, 206 Soma, 206 Somatic, 22, 29, 31, 155, 173, 181, 190, 206, 208 Somatic cells, 190, 206 Specialist, 145, 206 Species, 156, 165, 174, 175, 176, 181, 186, 189, 190, 194, 195, 201, 206, 211, 213 Specificity, 156, 199, 206 Spectrum, 13, 19, 26, 78, 186, 206 Sperm, 158, 166, 206 Spermatogenesis, 115, 206 Spermatozoa, 204, 206 Spinal cord, 160, 165, 166, 177, 191, 192, 207 Spinal Cord Vascular Diseases, 191, 207 Spleen, 170, 188, 207 Splenectomy, 114, 207 Sporadic, 10, 207 Stasis, 84, 90, 207 Stem Cell Factor, 20, 166, 207 Stem cell transplantation, 10, 32, 34, 37, 58, 59, 66, 76, 77, 78, 80, 98, 100, 102, 103, 121, 179, 207 Sterility, 169, 207 Steroid, 101, 170, 204, 207 Stimulus, 172, 173, 175, 207, 209 Stomach, 155, 171, 175, 177, 181, 192, 206, 207 Stool, 96, 183, 186, 207 Strand, 5, 198, 207 Stress, 192, 194, 199, 203, 207, 212 Stroke, 100, 105, 108, 109, 110, 111, 112, 134, 164, 207 Stroma, 51, 58, 207 Stromal, 24, 44, 110, 163, 173, 207 Stromal Cells, 24, 44, 163, 207 Subacute, 183, 208 Subclinical, 183, 204, 208 Subcutaneous, 172, 195, 208 Substance P, 189, 202, 204, 208 Substrate, 113, 208 Subtrochanteric, 180, 208 Sulfur, 186, 208 Suppression, 7, 45, 59, 63, 85, 208 Suppressive, 84, 208 Symphysis, 200, 208 Synaptic, 205, 208 Systemic, 38, 46, 99, 120, 163, 174, 183, 185, 201, 205, 208, 214 Systemic disease, 120, 205, 208
226
Aplastic Anemia
Systemic lupus erythematosus, 38, 46, 208 Systolic, 182, 208 T Telangiectasia, 19, 32, 33, 208 Telomerase, 4, 69, 78, 208 Telomere, 4, 208 Teratogen, 22, 208 Teratogenic, 22, 156, 171, 209 Testicular, 115, 209 Testis, 178, 209 Testosterone, 202, 209 Thalamic, 161, 209 Thalamic Diseases, 161, 209 Thalassemia, 23, 74, 142, 162, 209 Therapeutics, 38, 128, 209 Thoracic, 48, 209, 213 Thoracic Surgery, 48, 209 Threshold, 182, 209 Thrombin, 198, 200, 209 Thrombocytes, 198, 209 Thrombocytopenia, 79, 114, 159, 209 Thrombomodulin, 200, 209 Thrombopoietin, 44, 73, 79, 209 Thrombosis, 200, 207, 209 Thrombus, 169, 183, 192, 198, 209, 212 Thymoma, 81, 104, 209 Thymus, 188, 209 Thyroid, 11, 69, 210, 211 Ticlopidine, 49, 79, 86, 210 Tolerance, 17, 155, 210 Tonicity, 180, 210 Topical, 53, 195, 210 Torsion, 183, 210 Toxic, iv, 5, 17, 20, 24, 80, 92, 124, 156, 162, 168, 170, 174, 179, 182, 210, 212, 214 Toxicity, 10, 17, 24, 28, 121, 172, 189, 204, 210 Toxicology, 5, 6, 80, 90, 136, 210 Toxins, 96, 116, 158, 183, 201, 205, 210 Trace element, 85, 90, 210 Trachea, 210 Transcriptase, 186, 203, 208, 210, 214 Transcription Factors, 19, 203, 210 Transduction, 5, 13, 15, 21, 205, 210 Transfection, 162, 210 Transfusion, 59, 67, 86, 102, 113, 210 Translational, 8, 17, 27, 210 Transmitter, 155, 160, 172, 188, 210 Trauma, 161, 192, 209, 211 Treatment Outcome, 4, 211 Trisomy, 52, 211 Trypsin, 113, 166, 174, 211, 214
Tuberculosis, 40, 188, 211 Tumor marker, 162, 211 Tumor Necrosis Factor, 38, 63, 211 Tumor suppressor gene, 25, 29, 35, 211 Tyrosine, 18, 172, 211 U Ubiquitin, 28, 211 Umbilical Arteries, 211 Umbilical Cord, 15, 56, 98, 99, 103, 104, 197, 211 Umbilical cord blood, 15, 56, 80, 99, 103, 104, 197, 211 Umbilical cord blood transplantation, 80, 99, 104, 211 Unconscious, 170, 182, 211 Urethra, 200, 211, 212 Urinalysis, 100, 211 Urine, 57, 161, 162, 167, 180, 183, 211, 212 Urticaria, 205, 212 Uterus, 115, 173, 189, 199, 212 V Vaccine, 200, 212 Vacuoles, 194, 212 Vagina, 171, 189, 212 Valine, 195, 212 Valproic Acid, 22, 212 Vancomycin, 114, 212 Vascular, 11, 173, 183, 193, 197, 207, 209, 212 Vasodilators, 193, 212 Vasomotor, 115, 175, 212 Vector, 9, 10, 21, 210, 212 Vein, 95, 96, 101, 102, 160, 185, 193, 211, 212 Venous, 101, 160, 163, 198, 200, 210, 212 Venous blood, 163, 198, 212 Venous Thrombosis, 210, 212 Ventral, 11, 212 Veterinary Medicine, 135, 212 Villus, 9, 212 Viral, 40, 53, 76, 97, 108, 109, 110, 111, 112, 116, 121, 155, 193, 203, 210, 212, 214 Virilization, 116, 212 Virulence, 161, 210, 213 Virus, 15, 18, 20, 36, 53, 59, 63, 64, 70, 76, 81, 161, 174, 177, 184, 203, 210, 212, 213, 214 Viscera, 206, 213 Viscosity, 155, 213 Vitamin A, 184, 213 Vitamin D, 121, 142, 203, 213 Vitro, 5, 15, 23, 24, 31, 213
Index
Vivo, 4, 11, 15, 18, 23, 24, 30, 116, 213 Voriconazole, 99, 213 W White blood cell, 95, 97, 100, 102, 145, 158, 166, 176, 179, 186, 188, 191, 197, 213 Windpipe, 210, 213 Withdrawal, 116, 213 Womb, 212, 213 X Xeroderma Pigmentosum, 19, 33, 213
227
X-ray, 101, 176, 177, 185, 191, 193, 201, 213 X-ray therapy, 186, 213 Y Yeasts, 177, 196, 214 Z Zalcitabine, 186, 214 Zoster, 81, 214 Zygote, 168, 214 Zymogen, 166, 200, 214
228
Aplastic Anemia
