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

GAUCHER DISEASE 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., 1960Gaucher Disease: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References / James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary, and index. ISBN: 0-497-00449-6 1. Gaucher Disease-Popular works. I. Title.

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Disclaimer This publication is not intended to be used for the diagnosis or treatment of a health problem. It is sold with the understanding that the publisher, editors, and authors are not engaging in the rendering of medical, psychological, financial, legal, or other professional services. References to any entity, product, service, or source of information that may be contained in this publication should not be considered an endorsement, either direct or implied, by the publisher, editors, or authors. ICON Group International, Inc., the editors, and the authors are not responsible for the content of any Web pages or publications referenced in this publication.

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

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Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this book which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which produce publications on Gaucher disease. 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 GAUCHER DISEASE ................................................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Gaucher Disease............................................................................ 4 E-Journals: PubMed Central ......................................................................................................... 9 The National Library of Medicine: PubMed ................................................................................ 10 CHAPTER 2. NUTRITION AND GAUCHER DISEASE ......................................................................... 57 Overview...................................................................................................................................... 57 Finding Nutrition Studies on Gaucher Disease........................................................................... 57 Federal Resources on Nutrition ................................................................................................... 58 Additional Web Resources ........................................................................................................... 59 CHAPTER 3. ALTERNATIVE MEDICINE AND GAUCHER DISEASE ................................................... 61 Overview...................................................................................................................................... 61 National Center for Complementary and Alternative Medicine.................................................. 61 Additional Web Resources ........................................................................................................... 63 General References ....................................................................................................................... 63 CHAPTER 4. PATENTS ON GAUCHER DISEASE................................................................................ 65 Overview...................................................................................................................................... 65 Patents on Gaucher Disease......................................................................................................... 65 Patent Applications on Gaucher Disease ..................................................................................... 68 Keeping Current .......................................................................................................................... 72 CHAPTER 5. BOOKS ON GAUCHER DISEASE ................................................................................... 73 Overview...................................................................................................................................... 73 Book Summaries: Federal Agencies.............................................................................................. 73 Chapters on Gaucher Disease....................................................................................................... 74 CHAPTER 6. PERIODICALS AND NEWS ON GAUCHER DISEASE ..................................................... 75 Overview...................................................................................................................................... 75 News Services and Press Releases................................................................................................ 75 Academic Periodicals covering Gaucher Disease ......................................................................... 77 CHAPTER 7. RESEARCHING MEDICATIONS .................................................................................... 79 Overview...................................................................................................................................... 79 U.S. Pharmacopeia....................................................................................................................... 79 Commercial Databases ................................................................................................................. 80 Researching Orphan Drugs ......................................................................................................... 80 APPENDIX A. PHYSICIAN RESOURCES ............................................................................................ 85 Overview...................................................................................................................................... 85 NIH Guidelines............................................................................................................................ 85 NIH Databases............................................................................................................................. 87 Other Commercial Databases....................................................................................................... 89 APPENDIX B. PATIENT RESOURCES ................................................................................................. 91 Overview...................................................................................................................................... 91 Patient Guideline Sources............................................................................................................ 91 Finding Associations.................................................................................................................... 93 APPENDIX C. FINDING MEDICAL LIBRARIES .................................................................................. 95 Overview...................................................................................................................................... 95 Preparation................................................................................................................................... 95 Finding a Local Medical Library.................................................................................................. 95 Medical Libraries in the U.S. and Canada ................................................................................... 95

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ONLINE GLOSSARIES................................................................................................................ 101 Online Dictionary Directories ................................................................................................... 102 GAUCHER DISEASE DICTIONARY........................................................................................ 105 INDEX .............................................................................................................................................. 137

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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 Gaucher disease 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 Gaucher disease, 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 Gaucher disease, 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 Gaucher disease. 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 Gaucher disease, 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 Gaucher disease. 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 GAUCHER DISEASE Overview In this chapter, we will show you how to locate peer-reviewed references and studies on Gaucher disease.

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

Nature and Extent of Jaw Involvement in Gaucher's Disease: Observations in a Series of 28 Patients Source: Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, Oral Endodontics. 85(2): 233-239. February 1998. Summary: This article outlines the nature and extent of jaw involvement in Gaucher disease. The authors report on a study undertaken to ascertain the nature and extent of mandibulo-maxillofacial pathosis in 28 patients with documented Gaucher disease by means of panoramic radiography. Twenty-five of 28 patients displayed radiographic evidence of jaw involvement. The most prevalent finding was gross widening of the marrow spaces; frank radiolucencies, endosteal scalloping, cortical thinning, root resorption, and inferior displacement of the mandibular canal or effacement of its cortices were also seen. A previously unreported finding was delayed eruption of

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permanent teeth, which was seen in more than half of the patients who were under 20 years of age. The authors conclude that osseous changes throughout the jaws may be more common than previously suspected and may alert the dentist to the presence of the disease. 4 figures. 2 tables. 25 references. (AA-M).

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

Project Title: A MOUSE MODEL OF GAUCHER DISEASE Principal Investigator & Institution: Beutler, Ernest N.; Chairman; Scripps Research Institute Tpc7 La Jolla, Ca 92037 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-JAN-2006 Summary: (provided by applicant): An animal model of Gaucher disease could be of great value in studying treatment strategies and some features of the pathogenesis of the disease. However, attempts to create such a model have been unsuccessful. The knockout mouse proved to be lethal at about the time of birth. We have now created a murine model of Gaucher disease by creating a chimeric mouse, transplanting wildtype mice with liver-derived hematopoietic stem cells from knockout fetuses. The peripheral blood and spleen from these animals is deficient in glucocerebrosidase activity and the amount of glucocerebroside in the liver and spleen is increased. Moreover, intravenous loading of the animals with glucocerebroside/albumin given intravenously increases the glucocerebroside levels further. We propose to further exploit this model by studying the natural history of glucocerebroside accumulation and by attempting to load these animals in a more convenient and possibly more physiologic manner. Such loading techniques might consist of intraperitoneal injection of glucocerebroside or the increase of blood cell turnover by the administration of G-CSF or phenylhydrazine. A "readout" that is more facile than chemical determination of glucocerebroside by HPLC will also be explored. In particular, electron microscopy and light microscopy will be used to attempt to demonstrate the development of Gaucher cells in the chimeric mice. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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

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Project Title: ANTIRESORPTIVE THERAPY FOR OSTEOPENIA IN GAUCHER DISEASE Principal Investigator & Institution: Wenstrup, Richard J.; Professor; Children's Hospital Med Ctr (Cincinnati) 3333 Burnet Ave Cincinnati, Oh 452293039 Timing: Fiscal Year 2003 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CLINICAL TRIAL OF GENE THERAPY OF GAUCHER DISEASE Principal Investigator & Institution: Barranger, John; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2002 Summary: The hypothesis of this study is that genetically corrected peripheral blood stem cells (PBSC) will result in a sustained reversal of the phenotype in patients with Gaucher disease. Specific aims to be achieved are the transfer of the human GC gene into PBSC obtained from patients with Gaucher disease, the transplantation of transduced PBSC autogously to patients and the measurement of carriage and expression of transferred gene and its duration in peripheral blood luekocytes (PBL) and the assessment of clinical effects of transplanting genetically corrected PBSC in patients with Gaucher disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CORE--GENE TRANSDUCTION AND GENE THERAPY Principal Investigator & Institution: Kohn, Donald B.; Professor of Pediatrics and Microbiology; Children's Hospital Los Angeles 4650 Sunset Blvd Los Angeles, Ca 900276062 Timing: Fiscal Year 2002 Summary: In the prior years of the grant, the Gene Transfer and Gene Therapy ore (GTAGTC) has produce retroviral vectors for the investigators of the projects. We have gained proficiency in the design, construction and packaging of HIV-1 based lentiviral vectors. The Core has also supported clinical gene therapy trials for Gaucher disease and ADA-deficient SCID. In the next funding period, the GTAGT Core will use current state-of-the- art vectors and packaging system to design, construct, package and perform initial characterization of retroviral and lentiviral vectors for investigators of the Projects to pursue their scientific objectives. Additionally, the Core will continue to perform transductions of patient HSC for clinical gene marking and gene therapy studies and molecular analyses of samples from clinical gene therapy trials to define the extents of gene transfer and expression. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: GLUCOCEREBROSIDASE GENE TRANSFER TO THE NERVOUS SYSTEM Principal Investigator & Institution: Becker, Pamela S.; Associate Professor of Medicine and Chie; Cancer Center; Univ of Massachusetts Med Sch Worcester Office of Research Funding Worcester, Ma 01655 Timing: Fiscal Year 2002; Project Start 07-AUG-2002; Project End 30-JUN-2004

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Summary: (provided by applicant): The neuronopathic types of Gaucher disease still present a challenge for the treatment of the CNS symptoms. One approach would be gene therapy, but despite the fact that the glucocerebrosidase (GC) cDNA has been successfully transferred by retroviral vector to normal murine and human hematopoietic stem cells or by adeno-associated virus vector to muscle cells, and the transduced murine cells successfully transplanted in mice, the three clinical trials conducted to date resulted in either low levels of gene transfer, or a failure of engraftment after infusion, with a single exception. Gene transfer to neurons has been successfully demonstrated using retroviral, lentiviral, and other vectors. Engraftment of transduced neuronal and hematopoietic progenitors has been demonstrated in the brain of recipient animals. We hypothesize that transplantation of hematopoietic or neuronal progenitor cells transduced by retroviral and lentiviral vectors containing the cDNA for human glucocerebrosidase. This study will test the hypothesis that transplantation of hematopoietic or neuronal progenitor cells transduced by retroviral and lentiviral vectors containing the cDNA for human glucocerebrosidase will engraft in recipient Gaucher L444P mutant mice and lead to improved enzyme levels. Gene transfer to neurons has been successfully demonstrated with both retroviral and lentiviral vectors, and engraftment of transduced neuronal and hematopoietic progenitors has been attained in the brains of recipient animals. However, despite this success in animal models, the three clinical trials conducted to date have generally resulted in either low levels of gene transfer or a failure of engraftment after cell infusion. To accomplish this, we will: 1) characterize more completely the newly established Gaucher L444P mutant mouse; 2) intravenously administer retrovirally and lentivirally transduced hematopoietic progenitors to determine the extent of improved glucocerebrosidase enzyme levels in the tissues of the recipient mutant mice; and, 3) transplant by intrathecal administration ex vivo transduced hematopoietic or neuronal progenitors to determine if these cells will repopulate in brain and express glucocerebrosidase activity. At the completion of this study we will have determined whether lentiviral mediated gene transfer of human GC will result in sustained and improved enzyme levels in tissues, particularly brain, of recipient Gaucher mutant mice. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HYPOXEMIA AND PULMONARY HYPERTENSION IN GAUCHER DISEASE Principal Investigator & Institution: Dawson, Arthur D.; Scripps Research Institute Tpc7 La Jolla, Ca 92037 Timing: Fiscal Year 2002 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: NATURAL HISTORY AND TREATMENT OF GAUCHER DISEASE Principal Investigator & Institution: Kolodny, Edwin H.; New York University School of Medicine 550 1St Ave New York, Ny 10016 Timing: Fiscal Year 2002 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: NIEMANN-PICK DISEASE Principal Investigator & Institution: Wasserstein, Melissa P.; General Clinical Research Ctr; Mount Sinai School of Medicine of Nyu of New York University New York, Ny 10029 Timing: Fiscal Year 2002; Project Start 01-MAY-2001; Project End 30-APR-2006 Summary: Types A and B Niemann-Pick disease (NPD) are lysosomal storage disorders caused by deficient acid sphingomyelinase (ASM). Type A NPD is a severe neurodegenerative disease of infancy that typically causes death by three years of age. Type B NPD is characterized by the lack of neurological involvement and a phenotypic spectrum ranging from severe multisystem disease and early demise, to a milder condition of adulthood. The principal manifestations of Type B NPD include infiltrative pulmonary disease, hepatosplenomegaly, hyperlipidemia, and growth retardation and delayed puberty in children. The difficulty in differentiating between Types A and B NPD early in the disease course limits prognostic information, complicates family planning, and interferes with the selection of candidates for early therapeutic endeavors. Therefore, the ability to predict disease severity using information derived from empiric correlations between genotype and phenotype would be of significant value. Treatment for Types A and B NPD is primarily supportive, although bone marrow transplantation has been attempted with very limited success in Type B NPD patients. The therapeutic success of enzyme replacement therapy (ERT) in a related lysosomal storage disorder, Type I Gaucher disease, coupled with the demonstrated effectiveness of ERT in the Niemann-Pick mouse, provide the rationale for a clinical trial using recombinant ASM in patients with non-neuronopathic Type B NPD. The proposed studies will therefore focus on determining correlations between the clinical, radiographic and biochemical manifestations of Types A and B NPD and specific ASM mutations. In addition, the safety and effectiveness of ERT for Type B NPD will be evaluated. Thus the specific aims of the proposed research are: 1) to determine the natural history of Types A and B NPD and identify causative ASM mutations for genotype/phenotype correlations and 2) to evaluate the role of ERT for Type B NPD. An FDA-approved phase I/II clinical trial will be performed in Type B NPD patients to determine the safety and effectiveness of varying doses of intravenously administered recombinant human ASM. A series of clinical, biochemical, and pharmacological studies will be performed in order to evaluate the therapeutic effectiveness as well as the pharmacokinetics of the drug. In sum, these studies should provide important diagnostic and therapeutic information to improve the outcome of patients diagnosed with NPD. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: STUDIES OF GAUCHER DISEASE: A PROTOTYPE LIPIDOSIS Principal Investigator & Institution: Grabowski, Gregory A.; Professor and Director; Children's Hospital Med Ctr (Cincinnati) 3333 Burnet Ave Cincinnati, Oh 452293039 Timing: Fiscal Year 2002; Project Start 01-JAN-1986; Project End 30-JUN-2006 Summary: (provided by applicant): The overall objective of the proposed research is to delineate the molecular bases of the marked phenotypic variability in Gaucher disease (GD), a prototype inborn error of metabolism. The proposed studies address the hypotheses: 1) The mutations that predispose to GD are associated with disruptions of acid B-glucosidase [glucosylceramide (GC) glucohydrolase; UCase: GBA locus] structure and function leading to differential threshold levels of enzymatic activity in various patient tissues. Although this is a major basis of the phenotypic spectrum, intraand inter- locus sequence variants and polymorphisms may provide for additional

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contexts for phenotypic expression of disease-related mutations, e.g., altered substrate flux. To understand the interplay of such sequence variations, the determinants for the control of normal and mutant GCase enzyme activities will be evaluated with liposomal (in vitro) and lysosomal (ex vivo) membrane binding systems. 2) The in vivo levels of specific substrate synthesis and degradation, e.g., GC synthase (GCS) expression, and hydrolase activity, in selected inborn errors of glycosphingolipid (GSL) metabolism are primary determinants of their regional, tissue or cellular pathophysiology. The functional polymorphic variation at the GCS and GCase loci and the relationships of these variations to defined phenotypic parameters will be determined in patients with GD type 1. As a corollary, effective enzyme or gene therapy in GD, as a prototype, requires specific levels of enzyme in various organs. 3) The lack of adequate mouse models for GD have been a major impediment to continuing progress in pathophysiologic understanding and therapeutic developments, and their creation and characterization is a major focus of this proposal. We have developed conditional (tetracycline-on) and fixed (five specific point mutations) GCase expressing mice to simulate human GD variants. These alternative systems, together with the GCS KO heterozgyote mice will be used to address GC flux in relation to phenotype in vivo. These studies should provide insights into the pathophysiology and therapy of GD, and to over 20 glycolipid storage diseases that depend on the GCS synthetic and GCase degradative pathwavs. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: THE NATURAL HISTORY AND TREATMENT OF GAUCHER DISEASE Principal Investigator & Institution: Mistry, Pram; Mount Sinai School of Medicine of Cuny New York, Ny 10029 Timing: Fiscal Year 2002 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: TYPE 1 GAUCHER DISEASE: GENOTYPE/PHENOTYPE STUDIES Principal Investigator & Institution: Prakash-Cheng, Ainu; Human Genetics; Mount Sinai School of Medicine of Nyu of New York University New York, Ny 10029 Timing: Fiscal Year 2004; Project Start 15-JUL-2004; Project End 30-JUN-2009 Summary: (provided by applicant): The proposed Mentored Patient-Oriented Research Career Award is designed to provide the applicant with the didactic training, research skills, and mentored research experience needed to conduct high-quality clinical research on the genetic basis and treatment of inherited diseases. The didactic component will lead to an MS degree in Clinical Research in the K30 Clinical Research Curriculum offered at Mount Sinai. The mentored research focuses on Type 1 Gaucher disease (GD), the most common lysosomal storage disease, which is especially prevalent in individuals of Ashkenazi Jewish (AJ) descent. The deficient activity of acid 13glucosidase, encoded by mutations in its gene (GBA), results in the accumulation of glucosylceramide (GL-1), particularly in the macrophage-monocyte system. The disease phenotype has marked variability in patients with the N370S/N370S genotype (i.e., N370S homozygotes), ranging from severe hepatosplenomegaly, pancytopenia, and debilitating bone disease in childhood to overtly asymptomatic in late adulthood. Significant phenotypic diversity is also seen in N370S/"null" (N370S/84GG or N370S/IVS2 +1) patients. The proposed research will investigate the hypothesis that

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modifier genes are responsible for the markedly different phenotypes in AJ N370S homozygotes and N370S/null patients. The specific aims include: 1) characterizing and comparing the phenotypes in asymptomatic and symptomatic AJ N370S homozygotes, and mild and severe N370S/"null" patients, 2) identifying genes using microarrays that are markedly differentially expressed in blood monocytes isolated by fluorescenceactivated cell sorting (FACS) from symptomatic and severe N370S homozygotes and normal controls, 3) identifying/investigating candidate modifier genes, including two involved in GL-1 metabolism, as well as selected genes adjacent to and in linkage disequilibrium (LD) with GBA, for polymorphisms that correlate with phenotype. These studies should provide insight into modifier genes responsible for the marked phenotypic differences in N370S homozygotes. In addition, the proposed studies will provide the applicant with the skills and experience necessary to conduct independent, high-quality patient-oriented research. The applicant will have protected research time, dedicated laboratory space, and access to the General Clinical Research Center (GCRC) and core facilities. Her development will be fostered by the commitment of her CoMentors to guide her in the proposed studies and in the responsible conduct of research, and by the outstanding research and intellectual environment at Mount Sinai. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

E-Journals: PubMed Central3 PubMed Central (PMC) is a digital archive of life sciences journal literature developed and managed by the National Center for Biotechnology Information (NCBI) at the U.S. National Library of Medicine (NLM).4 Access to this growing archive of e-journals is free and unrestricted.5 To search, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Pmc, and type “Gaucher disease” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for Gaucher disease in the PubMed Central database: •

Complete correction of the enzymatic defect of type I Gaucher disease fibroblasts by retroviral-mediated gene transfer. by Sorge J, Kuhl W, West C, Beutler E.; 1987 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=304328

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Correction of glucocerebrosidase deficiency after retroviral-mediated gene transfer into hematopoietic progenitor cells from patients with Gaucher disease. by Fink JK, Correll PH, Perry LK, Brady RO, Karlsson S.; 1990 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=53681

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Cross-reacting material in Gaucher disease fibroblasts. by Beutler E, Kuhl W, Sorge J.; 1984 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=391953

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

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

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Heterogeneity in type I Gaucher disease demonstrated by restriction mapping of the gene. by Sorge J, Gelbart T, West C, Westwood B, Beutler E.; 1985 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=390585

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Identification of the second common Jewish Gaucher disease mutation makes possible population-based screening for the heterozygous state. by Beutler E, Gelbart T, Kuhl W, Sorge J, West C.; 1991 Dec 1; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=52965

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Mice with type 2 and 3 Gaucher disease point mutations generated by a single insertion mutagenesis procedure (SIMP). by Liu Y, Suzuki K, Reed JD, Grinberg A, Westphal H, Hoffmann A, Doring T, Sandhoff K, Proia RL.; 1998 Mar 3; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=19391

The National Library of Medicine: PubMed One of the quickest and most comprehensive ways to find academic studies in both English and other languages is to use PubMed, maintained by the National Library of Medicine.6 The advantage of PubMed over previously mentioned sources is that it covers a greater number of domestic and foreign references. It is also free to use. If the publisher has a Web site that offers full text of its journals, PubMed will provide links to that site, as well as to sites offering other related data. User registration, a subscription fee, or some other type of fee may be required to access the full text of articles in some journals. To generate your own bibliography of studies dealing with Gaucher disease, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “Gaucher disease” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for Gaucher disease (hyperlinks lead to article summaries): •

A case of type I Gaucher disease with cardiopulmonary amyloidosis and chitotriosidase deficiency. Author(s): Hrebicek M, Zeman J, Musilova J, Hodanova K, Renkema GH, Veprekova L, Ledvinova J, Hrebicek D, Sokolova J, Aerts JM, Elleder M. Source: Virchows Archiv : an International Journal of Pathology. 1996 November; 429(45): 305-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8972767

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A comparison of the pharmacological properties of carbohydrate remodeled recombinant and placental-derived beta-glucocerebrosidase: implications for clinical efficacy in treatment of Gaucher disease. Author(s): Friedman B, Vaddi K, Preston C, Mahon E, Cataldo JR, McPherson JM. Source: Blood. 1999 May 1; 93(9): 2807-16. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10216074

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

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A new gene-pseudogene fusion allele due to a recombination in intron 2 of the glucocerebrosidase gene causes Gaucher disease. Author(s): Cormand B, Diaz A, Grinberg D, Chabas A, Vilageliu L. Source: Blood Cells, Molecules & Diseases. 2000 October; 26(5): 409-16. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11112377

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A novel complex allele and two new point mutations in type 2 (acute neuronopathic) Gaucher disease. Author(s): Sinclair G, Choy FY, Humphries L. Source: Blood Cells, Molecules & Diseases. 1998 December; 24(4): 420-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9851895

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A novel mutation (V191G) in a German-British type 1 Gaucher disease patient. Mutations in brief no. 131. Online. Author(s): Choy FY, Humphries ML, Ben-Yoseph Y. Source: Human Mutation. 1998; 11(5): 411-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10206680

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Accuracy of ultrasonography in assessing spleen and liver size in patients with Gaucher disease: comparison to computed tomographic measurements. Author(s): Elstein D, Hadas-Halpern I, Azuri Y, Abrahamov A, Bar-Ziv Y, Zimran A. Source: Journal of Ultrasound in Medicine : Official Journal of the American Institute of Ultrasound in Medicine. 1997 March; 16(3): 209-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9166820

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Age estimate of the N370S mutation causing Gaucher disease in Ashkenazi Jews and European populations: A reappraisal of haplotype data. Author(s): Colombo R. Source: American Journal of Human Genetics. 2000 February; 66(2): 692-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10677327

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Alglucerase enzyme replacement therapy used safely and effectively throughout the whole pregnancy of a Gaucher disease patient. Author(s): Aporta Rodriguez R, Escobar Vedia JL, Navarro Castro AM, Aguilar Garcia G, Cabrera Torres A. Source: Haematologica. 1998 September; 83(9): 852-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9825582

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Alglucerase treatment of type 1 Gaucher disease with pulmonary involvement. Author(s): Martinez Odrizola P, Ferrero O, Jauregui I, Miguel F. Source: Respiratory Medicine. 1998 December; 92(12): 1370-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10197233

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Allogeneic bone marrow transplantation for Gaucher disease--a case report. Author(s): Yen CC, Chiou TJ, Lin CY, Wang NH, Chen PM. Source: Zhonghua Yi Xue Za Zhi (Taipei). 1997 June; 59(6): 372-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9294918

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ALP isoenzyme separation in type 1 Gaucher disease. Author(s): Ciana G, Tamaro G, Martini C, Ceschel S, Cuttini M, Bembi B. Source: Clinical Chemistry and Laboratory Medicine : Cclm / Fescc. 2000 May; 38(5): 479-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10952233

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Amyloidosis and gastric bleeding in a patient with Gaucher disease. Author(s): Elstein D, Rosenmann E, Reinus C, Paz J, Altarescu G, Zimran A. Source: Journal of Clinical Gastroenterology. 2003 September; 37(3): 234-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12960723

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An autopsy case of fetal Gaucher disease. Author(s): Adachi Y, Kobayashi Y, Ida H, Yasumizu R, Okamura A, Kayatani H, Teranishi N, Inaba M, Sugihara A, Genba H, Eto Y, Ikehara S. Source: Acta Paediatr Jpn. 1998 August; 40(4): 374-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9745785

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Anaesthetic management of children with type II and III Gaucher disease. Author(s): Dell'Oste C, Vincenti F. Source: Minerva Pediatr. 1997 October; 49(10): 495-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9557496

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Analysis and classification of 304 mutant alleles in patients with type 1 and type 3 Gaucher disease. Author(s): Koprivica V, Stone DL, Park JK, Callahan M, Frisch A, Cohen IJ, Tayebi N, Sidransky E. Source: American Journal of Human Genetics. 2000 June; 66(6): 1777-86. Epub 2000 May 04. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10796875

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Application of delayed extraction-matrix-assisted laser desorption ionization time-offlight mass spectrometry for analysis of sphingolipids in pericardial fluid, peritoneal fluid and serum from Gaucher disease patients. Author(s): Fujiwaki T, Yamaguchi S, Tasaka M, Sakura N, Taketomi T. Source: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences. 2002 August 25; 776(1): 115-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12127332

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Asymptomatic Gaucher disease implications for large-scale screening. Author(s): Azuri J, Elstein D, Lahad A, Abrahamov A, Hadas-Halpern I, Zimran A. Source: Genetic Testing. 1998; 2(4): 297-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10464607

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Audiometric abnormalities in children with Gaucher disease type 3. Author(s): Bamiou DE, Campbell P, Liasis A, Page J, Sirimanna T, Boyd S, Vellodi A, Harris C. Source: Neuropediatrics. 2001 June; 32(3): 136-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11521209

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Avascular necrosis of the sacroiliac joint in a patient with Gaucher disease. Author(s): Aharoni D, Mekhmandarov S, Itzchaki M, Hiller N, Elstein D. Source: Isr Med Assoc J. 2001 October; 3(10): 767-8. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11692553

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Beta-glucosidase activity in liver, spleen and brain in acute neuropathic Gaucher disease. Author(s): Takahashi T, Nishio H, Kodama S, Nakamura H. Source: Brain & Development. 1990; 12(2): 202-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2113779

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beta-Glucosidase isoenzymes in Epstein-Barr virus-transformed lymphoid cell lines from normal subjects and patients with type 1 Gaucher disease. Author(s): Maret A, Salvayre R, Samadi M, Douste-Blazy L. Source: Enzyme. 1987; 37(4): 208-17. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3038513

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Biochemical and ultrastructural findings in Epstein-Barr virus-transformed lymphoid cell lines from type 1 Gaucher disease. Author(s): Maret A, Salvayre R, Livni N, Icart J, Vuillaume M, Douste-Blazy L. Source: Biology of the Cell / under the Auspices of the European Cell Biology Organization. 1987; 59(1): 101-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3038233

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Biochemical markers of bone turnover as tools in the evaluation of skeletal involvement in patients with type 1 Gaucher disease. Author(s): Drugan C, Jebeleanu G, Grigorescu-Sido P, Caillaud C, Craciun AM. Source: Blood Cells, Molecules & Diseases. 2002 January-February; 28(1): 13-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11814307

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Biochemical properties of the tartrate-resistant acid phosphatase activity in Gaucher disease. Author(s): Lam KW, Desnick RJ. Source: Prog Clin Biol Res. 1982; 95: 267-78. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6750653

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Biochemical studies in a patient with subacute neuropathic Gaucher disease without visceral glucosylceramide storage. Author(s): Wenger DA, Roth S, Kudoh T, Grover WD, Tucker SH, Kaye EM, Ullman MD. Source: Pediatric Research. 1983 May; 17(5): 344-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6856396

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Bone and bone marrow changes in Gaucher disease: evaluation with quantitative CT. Author(s): Rosenthal DI, Mayo-Smith W, Goodsitt MM, Doppelt S, Mankin HJ. Source: Radiology. 1989 January; 170(1 Pt 1): 143-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2909087

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Bone and joint complications related to Gaucher disease. Author(s): Pastores GM, Patel MJ, Firooznia H. Source: Curr Rheumatol Rep. 2000 April; 2(2): 175-80. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11123056

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Bone complications in children with Gaucher disease. Author(s): Bembi B, Ciana G, Mengel E, Terk MR, Martini C, Wenstrup RJ. Source: The British Journal of Radiology. 2002; 75 Suppl 1: A37-44. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12036831

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Bone crises in Gaucher disease. Author(s): Cohen IJ. Source: Isr Med Assoc J. 2003 November; 5(11): 838-9. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14650121

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Bone crisis in Gaucher disease--an update. Author(s): Yosipovitch Z, Katz K. Source: Isr J Med Sci. 1990 October; 26(10): 593-5. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2249941

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Bone density in Type 1 Gaucher disease. Author(s): Pastores GM, Wallenstein S, Desnick RJ, Luckey MM. Source: Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research. 1996 November; 11(11): 1801-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8915789

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Bone involvement in Gaucher disease. Author(s): Beighton P, Goldblatt J, Sacks S. Source: Prog Clin Biol Res. 1982; 95: 107-29. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7122630

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Bone marker alterations in patients with type 1 Gaucher disease. Author(s): Ciana G, Martini C, Leopaldi A, Tamaro G, Katouzian F, Ronfani L, Bembi B. Source: Calcified Tissue International. 2003 March; 72(3): 185-9. Epub 2003 January 15. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12522660

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Bone marrow relaxation times in Gaucher disease before and after enzyme replacement therapy. Author(s): Magnaldi S, Longo R, Ukmar M, Zanatta M, Bottega M, Sottocasa GL. Source: European Radiology. 1997; 7(4): 486-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9204325

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Bone marrow response in treated patients with Gaucher disease: evaluation by T1weighted magnetic resonance images and correlation with reduction in liver and spleen volume. Author(s): Terk MR, Dardashti S, Liebman HA. Source: Skeletal Radiology. 2000 October; 29(10): 563-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11127678

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Bone marrow transplantation as effective treatment of central nervous system disease in globoid cell leukodystrophy, metachromatic leukodystrophy, adrenoleukodystrophy, mannosidosis, fucosidosis, aspartylglucosaminuria, Hurler, Maroteaux-Lamy, and Sly syndromes, and Gaucher disease type III. Author(s): Krivit W, Peters C, Shapiro EG. Source: Current Opinion in Neurology. 1999 April; 12(2): 167-76. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10226749

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Bone marrow transplantation in Gaucher disease. Author(s): Rappeport JM, Barranger JA, Ginns EI. Source: Birth Defects Orig Artic Ser. 1986; 22(1): 101-9. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3516238

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Bone scans in the diagnosis of bone crisis in patients who have Gaucher disease. Author(s): Katz K, Mechlis-Frish S, Cohen IJ, Horev G, Zaizov R, Lubin E. Source: The Journal of Bone and Joint Surgery. American Volume. 1991 April; 73(4): 5137. Erratum In: J Bone Joint Surg Am 1991 June; 73(5): 791. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2013590

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Bone ultrasonometry, bone density, and turnover markers in type 1 Gaucher disease. Author(s): Fiore CE, Barone R, Pennisi P, Pavone V, Riccobene S. Source: Journal of Bone and Mineral Metabolism. 2002; 20(1): 34-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11810414

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Cardiovascular fibrosis, hydrocephalus, ophthalmoplegia, and visceral involvement in an American child with Gaucher disease. Author(s): Stone DL, Tayebi N, Coble C, Ginns EI, Sidransky E. Source: Journal of Medical Genetics. 2000 November; 37(11): E40. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11073549

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Carrier screening for Gaucher disease in couples of mixed ethnicity. Author(s): Wallerstein R, Starkman A, Jansen V. Source: Genetic Testing. 2001 Spring; 5(1): 61-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11336404

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Cessation of enzyme replacement therapy in Gaucher disease. Author(s): Grinzaid KA, Geller E, Hanna SL, Elsas LJ 2nd. Source: Genetics in Medicine : Official Journal of the American College of Medical Genetics. 2002 November-December; 4(6): 427-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12509713

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Changes in serum chitotriosidase activity with cessation of replacement enzyme (cerebrosidase) administration in Gaucher disease. Author(s): Czartoryska B, Tylki-Szymanska A, Lugowska A. Source: Clinical Biochemistry. 2000 March; 33(2): 147-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10751594

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Chemical chaperones increase the cellular activity of N370S beta -glucosidase: a therapeutic strategy for Gaucher disease. Author(s): Sawkar AR, Cheng WC, Beutler E, Wong CH, Balch WE, Kelly JW. Source: Proceedings of the National Academy of Sciences of the United States of America. 2002 November 26; 99(24): 15428-33. Epub 2002 Nov 14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12434014

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Children with type I Gaucher disease: growing into adulthood with and without enzyme therapy. Author(s): Zimran A, Abrahamov A, Elstein D. Source: Isr Med Assoc J. 2000 February; 2(2): 80-1. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10804921

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Cholelithiasis in patients with Gaucher disease. Author(s): Rosenbaum H, Sidransky E. Source: Blood Cells, Molecules & Diseases. 2002 January-February; 28(1): 21-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11987238

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Clinical and genetic studies of Japanese homozygotes for the Gaucher disease L444P mutation. Author(s): Ida H, Rennert OM, Iwasawa K, Kobayashi M, Eto Y. Source: Human Genetics. 1999 July-August; 105(1-2): 120-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10480365

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Clinical and molecular characteristics of Japanese Gaucher disease. Author(s): Eto Y, Ida H. Source: Neurochemical Research. 1999 February; 24(2): 207-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9972866

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Clinical quiz. Gaucher disease. Author(s): Yeung KA, Pinero-Carrero VM, Bornstein JA. Source: Journal of Pediatric Gastroenterology and Nutrition. 2001 August; 33(2): 182, 205. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11575304

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Clinically relevant therapeutic endpoints in type I Gaucher disease. Author(s): Hollak CE, Maas M, Aerts JM. Source: Journal of Inherited Metabolic Disease. 2001; 24 Suppl 2: 97-105; Discussion 87-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11758685

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Coagulopathy in Gaucher disease. Author(s): Ozturk G, Kocak U, Gursel T, Ezgu FS. Source: Indian J Pediatr. 1998 September-October; 65(5): 771-2. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10773938

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Coexistence of Gaucher disease type 1 and Joubert syndrome. Author(s): Boltshauser EJ, Maria BL. Source: Journal of Medical Genetics. 1999 November; 36(11): 870-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10636737

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Coexistence of Gaucher disease type 1 and Joubert syndrome. Author(s): van Royen-Kerkhof A, Poll-The BT, Kleijer WJ, van Diggelen OP, Aerts JM, Hopwood JJ, Beemer FA. Source: Journal of Medical Genetics. 1998 November; 35(11): 965-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9832051

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Commentary: low-dose high-frequency enzyme replacement therapy prevents fractures without complete suppression of painful bone crises in patients with severe juvenile onset type I Gaucher disease. Author(s): Elstein D, Abrahamov A, Itzchaki M, Zimran A. Source: Blood Cells, Molecules & Diseases. 1998 September; 24(3): 303-5; Discussion 3068. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10087988

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Commentary: the natural history of Gaucher disease. Author(s): Beutler E. Source: Blood Cells, Molecules & Diseases. 1998 March; 24(1): 82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9541480

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Comparative efficacy of dose regimens in enzyme replacement therapy of type I Gaucher disease. Author(s): Altarescu G, Schiffmann R, Parker CC, Moore DF, Kreps C, Brady RO, Barton NW. Source: Blood Cells, Molecules & Diseases. 2000 August; 26(4): 285-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11042029

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Corneal opacities in Gaucher disease. Author(s): Guemes A, Kosmorsky GS, Moodie DS, Clark B, Meisler D, Traboulsi EI. Source: American Journal of Ophthalmology. 1998 December; 126(6): 833-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9860012

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Correlation among genotype, phenotype, and biochemical markers in Gaucher disease: implications for the prediction of disease severity. Author(s): Whitfield PD, Nelson P, Sharp PC, Bindloss CA, Dean C, Ravenscroft EM, Fong BA, Fietz MJ, Hopwood JJ, Meikle PJ. Source: Molecular Genetics and Metabolism. 2002 January; 75(1): 46-55. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11825063

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Correlation of bone marrow response with hematological, biochemical, and visceral responses to enzyme replacement therapy of nonneuronopathic (type 1) Gaucher disease in 30 adult patients. Author(s): Poll LW, Koch JA, Willers R, Aerts H, Scherer A, Haussinger D, Modder U, vom Dahl S. Source: Blood Cells, Molecules & Diseases. 2002 March-April; 28(2): 209-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12064917

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D-dimer assay in Gaucher disease: correlation with severity of bone and lung involvement. Author(s): Shitrit D, Rudensky B, Zimran A, Elstein D. Source: American Journal of Hematology. 2003 August; 73(4): 236-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12879425

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Decrease of plasma taurine in Gaucher disease and its sustained correction during enzyme replacement therapy. Author(s): vom Dahl S, Monnighoff I, Haussinger D. Source: Amino Acids. 2000; 19(3-4): 585-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11140361

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Decreased salivary output in patients with Gaucher disease. Author(s): Dayan B, Elstein D, Zimran A, Nesher G. Source: Qjm : Monthly Journal of the Association of Physicians. 2003 January; 96(1): 53-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12509649

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Deficiency of steriod beta-glucosidase in Gaucher disease. Author(s): Kanfer JN, Raghavan SS, Mumford RA, Labow RS, Williamson DG, Layne DS. Source: Biochemical and Biophysical Research Communications. 1975 November 17; 67(2): 683-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1201047

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Deficient activity of glucocerebrosidase in urine from patients with type 1 Gaucher disease. Author(s): Aerts JM, Donker-Koopman WE, Koot M, Barranger JA, Tager JM, Schram AW. Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. 1986 July 30; 158(2): 155-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2943536

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Delayed growth and puberty in patients with Gaucher disease type 1: natural history and effect of splenectomy and/or enzyme replacement therapy. Author(s): Kauli R, Zaizov R, Lazar L, Pertzelan A, Laron Z, Galatzer A, Phillip M, Yaniv Y, Cohen IJ. Source: Isr Med Assoc J. 2000 February; 2(2): 158-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10804944

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Demonstration of feasibility of in vivo gene therapy for Gaucher disease using a chemically induced mouse model. Author(s): Marshall J, McEachern KA, Kyros JA, Nietupski JB, Budzinski T, Ziegler RJ, Yew NS, Sullivan J, Scaria A, van Rooijen N, Barranger JA, Cheng SH. Source: Molecular Therapy : the Journal of the American Society of Gene Therapy. 2002 August; 6(2): 179-89. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12161184

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Demonstration of the existence of a second, non-lysosomal glucocerebrosidase that is not deficient in Gaucher disease. Author(s): van Weely S, Brandsma M, Strijland A, Tager JM, Aerts JM. Source: Biochimica Et Biophysica Acta. 1993 March 24; 1181(1): 55-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8457606

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Detection and isolation of gene-corrected cells in Gaucher disease via a fluorescenceactivated cell sorter assay for lysosomal glucocerebrosidase activity. Author(s): Lorincz M, Herzenberg LA, Diwu Z, Barranger JA, Kerr WG. Source: Blood. 1997 May 1; 89(9): 3412-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9129049

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Development of safe and efficient retroviral vectors for Gaucher disease. Author(s): Havenga M, Fisher R, Hoogerbrugge P, Roberts B, Valerio D, van Es HH. Source: Gene Therapy. 1997 December; 4(12): 1393-400. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9472564

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Diagnosing Gaucher disease. Early recognition, implications for treatment, and genetic counseling. Author(s): Sidransky E, Tayebi N, Ginns EI. Source: Clinical Pediatrics. 1995 July; 34(7): 365-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7554686

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Diagnosis of adult Gaucher disease: use of a new chromogenic substrate, 2hexadecanoylamino-4-nitrophenyl-beta-D-glucopyranoside, in cultured skin fibroblasts. Author(s): Johnson WG, Gal AE, Miranda AF, Pentchev PG. Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. 1980 March 14; 102(1): 91-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7389109

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Differences in origin of the 1448C mutation in patients with Gaucher disease. Author(s): Iwasawa K, Ida H, Eto Y. Source: Acta Paediatr Jpn. 1997 August; 39(4): 451-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9316290

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Differential effects of enzyme supplementation therapy on manifestations of type 1 Gaucher disease. Author(s): Hollak CE, Corssmit EP, Aerts JM, Endert E, Sauerwein HP, Romijn JA, van Oers MH. Source: The American Journal of Medicine. 1997 September; 103(3): 185-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9316550

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Differentiation of the glucocerebrosidase gene from pseudogene by long-template PCR: implications for Gaucher disease. Author(s): Tayebi N, Cushner S, Sidransky E. Source: American Journal of Human Genetics. 1996 September; 59(3): 740-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8751878

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Disc gel electrophoresis of proteins of membranous cytoplasmic inclusion bodies from the spleen of the patient with Gaucher disease. Author(s): Abe T, Yamakawa T, Endou H, Nagashima K. Source: Jpn J Exp Med. 1978 April; 48(2): 177-81. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=213628

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Dixon quantitative chemical shift imaging is a sensitive tool for the evaluation of bone marrow responses to individualized doses of enzyme supplementation therapy in type 1 Gaucher disease. Author(s): Hollak C, Maas M, Akkerman E, den Heeten A, Aerts H. Source: Blood Cells, Molecules & Diseases. 2001 November-December; 27(6): 1005-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11831867

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Gaucher Disease

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DNA analysis of an uncommon missense mutation in a Gaucher disease patient of Jewish-Polish-Russian descent. Author(s): Choy FY, Wei C, Applegarth DA, McGillivray BC. Source: American Journal of Medical Genetics. 1994 June 1; 51(2): 156-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7916532

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Dosage-response in the treatment of Gaucher disease by enzyme replacement therapy. Author(s): Beutler E. Source: Blood Cells, Molecules & Diseases. 2000 August; 26(4): 303-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11042031

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Dose-dependent responses to macrophage-targeted glucocerebrosidase in a child with Gaucher disease. Author(s): Barton NW, Brady RO, Dambrosia JM, Doppelt SH, Hill SC, Holder CA, Mankin HJ, Murray GJ, Zirzow GC, Parker RI. Source: The Journal of Pediatrics. 1992 February; 120(2 Pt 1): 277-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1735829

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Early-onset severe neurological involvement and D409H homozygosity in Gaucher disease: outcome of enzyme replacement therapy. Author(s): Michelakakis H, Skardoutsou A, Mathioudakis J, Moraitou M, Dimitriou E, Voudris C, Karpathios T. Source: Blood Cells, Molecules & Diseases. 2002 January-February; 28(1): 1-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11814305

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Effectiveness of enzyme replacement therapy in 1028 patients with type 1 Gaucher disease after 2 to 5 years of treatment: a report from the Gaucher Registry. Author(s): Weinreb NJ, Charrow J, Andersson HC, Kaplan P, Kolodny EH, Mistry P, Pastores G, Rosenbloom BE, Scott CR, Wappner RS, Zimran A. Source: The American Journal of Medicine. 2002 August 1; 113(2): 112-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12133749

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Effects of enzyme replacement therapy in thirteen Japanese paediatric patients with Gaucher disease. Author(s): Ida H, Rennert OM, Kobayashi M, Eto Y. Source: European Journal of Pediatrics. 2001 January; 160(1): 21-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11195013

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Effects of imilglucerase withdrawal on an adult with Gaucher disease. Author(s): Schwartz IV, Karam S, Ashton-Prolla P, Michelin K, Coelho J, Pires RF, Pereira ML, Giugliani R. Source: British Journal of Haematology. 2001 June; 113(4): 1089. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11442517

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Elevated levels of M-CSF, sCD14 and IL8 in type 1 Gaucher disease. Author(s): Hollak CE, Evers L, Aerts JM, van Oers MH. Source: Blood Cells, Molecules & Diseases. 1997 August; 23(2): 201-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9236158

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Enzyme replacement therapy for Gaucher disease: critical investigations beyond demonstration of clinical efficacy. Author(s): Brady RO, Barton NW. Source: Biochemical Medicine and Metabolic Biology. 1994 June; 52(1): 1-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7917461

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Enzyme replacement therapy for Gaucher Disease: the only experience in Malaysia. Author(s): Chan LL, Lin HP. Source: Med J Malaysia. 2002 September; 57(3): 348-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12440275

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Enzyme replacement therapy in type III Gaucher disease. Author(s): Tylki-Szymanska A, Czartoryska B. Source: Journal of Inherited Metabolic Disease. 1999 April; 22(2): 203-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10234625

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Enzyme replacement therapy with imiglucerase in Taiwanese patients with type I Gaucher disease. Author(s): Hsu CC, Chien YH, Lai MY, Hwu WL. Source: J Formos Med Assoc. 2002 September; 101(9): 627-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12645190

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Enzyme therapy for Gaucher disease: the first 5 years. Author(s): Grabowski GA, Leslie N, Wenstrup R. Source: Blood Reviews. 1998 June; 12(2): 115-33. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9661800

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Enzyme therapy in Gaucher disease type 1: effect of neutralizing antibodies to acid beta-glucosidase. Author(s): Ponce E, Moskovitz J, Grabowski G. Source: Blood. 1997 July 1; 90(1): 43-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9207436

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Enzyme therapy in Gaucher disease type 2: an autopsy case. Author(s): Takahashi T, Yoshida Y, Sato W, Yano T, Shoji Y, Sawaishi Y, Sakuma I, Sashi T, Enomoto K, Ida H, Takada G. Source: The Tohoku Journal of Experimental Medicine. 1998 October; 186(2): 143-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10223617

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Enzyme therapy in type 1 Gaucher disease: comparative efficacy of mannoseterminated glucocerebrosidase from natural and recombinant sources. Author(s): Grabowski GA, Barton NW, Pastores G, Dambrosia JM, Banerjee TK, McKee MA, Parker C, Schiffmann R, Hill SC, Brady RO. Source: Annals of Internal Medicine. 1995 January 1; 122(1): 33-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7985893

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Enzyme therapy of Gaucher disease: clinical and biochemical changes during production of and tolerization for neutralizing antibodies. Author(s): Zhao H, Bailey LA, Grabowski GA. Source: Blood Cells, Molecules & Diseases. 2003 January-February; 30(1): 90-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12667990

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Ethical considerations for enzyme replacement therapy in neuronopathic Gaucher disease. Author(s): Elstein D, Abrahamov A, Zimran A. Source: Clinical Genetics. 1998 September; 54(3): 179-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9788718

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Ethical guidelines for enzyme therapy in neuronopathic Gaucher disease. Author(s): Elstein D, Steinberg A, Abrahamov A, Zimran A. Source: American Journal of Human Genetics. 1997 October; 61(4): A354. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11644969

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Ethics, policy, and rare genetic disorders: the case of Gaucher disease in Israel. Author(s): Gross ML. Source: Theoretical Medicine and Bioethics. 2002; 23(2): 151-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12400900

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Exhaustive screening of the acid beta-glucosidase gene, by fluorescence-assisted mismatch analysis using universal primers: mutation profile and genotype/phenotype correlations in Gaucher disease. Author(s): Germain DP, Puech JP, Caillaud C, Kahn A, Poenaru L. Source: American Journal of Human Genetics. 1998 August; 63(2): 415-27. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9683600

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Expansion of hematogones in a patient with Gaucher disease. Author(s): D'Arena G, Bisceglia M, Ladogana S, Carella AM, Carotenuto M, Paolucci P. Source: Medical and Pediatric Oncology. 2001 June; 36(6): 657-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11344501

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Extraordinary bone involvement in a Gaucher disease type I patient. Author(s): Barone R, Pavone V, Nigro F, Chabas A, Fiumara A. Source: British Journal of Haematology. 2000 March; 108(4): 838-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10792292

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Factor IX deficiency in Gaucher disease. An in vitro phenomenon. Author(s): Boklan BF, Sawitsky A. Source: Archives of Internal Medicine. 1976 April; 136(4): 489-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1267559

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Failure of alglucerase infused into Gaucher disease patients to localize in marrow macrophages. Author(s): Beutler E, Kuhl W, Vaughan LM. Source: Molecular Medicine (Cambridge, Mass.). 1995 March; 1(3): 320-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8529110

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Failure of resting echocardiography and cardiac catheterization to identify pulmonary hypertension in two patients with type I Gaucher disease. Author(s): Sirrs S, Irving J, McCauley G, Gin K, Munt B, Pastores G, Mistry P. Source: Journal of Inherited Metabolic Disease. 2002 May; 25(2): 131-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12118528

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Familial sea-blue histiocytes with acid phosphatemia. A syndrome resembling Gaucher disease: the Lewis variant. Author(s): Blankenship RM, Greenburg BR, Lucas RN, Reynolds RD, Beutler E. Source: Jama : the Journal of the American Medical Association. 1973 July 2; 225(1): 54-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4123476

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Femoral neck fractures complicating Gaucher disease in children. Author(s): Goldman AB, Jacobs B. Source: Skeletal Radiology. 1984; 12(3): 162-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6494933

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First long-term results of imiglucerase therapy of type 1 Gaucher disease. Author(s): Niederau C, vom Dahl S, Haussinger D. Source: European Journal of Medical Research. 1998 February 21; 3(1-2): 25-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9512964

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First trimester diagnosis of Gaucher disease in a fetus with trisomy 21. Author(s): Besley GT, Ferguson-Smith ME, Frew C, Morris A, Gilmore DH. Source: Prenatal Diagnosis. 1988 July; 8(6): 471-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2974955

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Five new Gaucher disease mutations. Author(s): Beutler E, Gelbart T, Demina A, Zimran A, LeCoutre P. Source: Blood Cells, Molecules & Diseases. 1995; 21(1): 20-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7655857

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Fluorescent flow cytometric assay: a new diagnostic tool for measuring betaglucocerebrosidase activity in Gaucher disease. Author(s): Rudensky B, Paz E, Altarescu G, Raveh D, Elstein D, Zimran A. Source: Blood Cells, Molecules & Diseases. 2003 January-February; 30(1): 97-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12667991

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Focal changes of the spleen in one case of Gaucher disease--assessed by ultrasonography, CT, MRI and angiography. Author(s): Aspestrand F, Charania B, Scheel B, Kolmannskog F, Jacobsen M. Source: Der Radiologe. 1989 November; 29(11): 569-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2685891

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Fractures in children who have Gaucher disease. Author(s): Katz K, Cohen IJ, Ziv N, Grunebaum M, Zaizov R, Yosipovitch Z. Source: The Journal of Bone and Joint Surgery. American Volume. 1987 December; 69(9): 1361-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3440795

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Frequency of carriers of chronic (type I) Gaucher disease in Ashkenazi Jews. Author(s): Matoth Y, Chazan S, Cnaan A, Gelernter I, Klibansky C. Source: American Journal of Medical Genetics. 1987 July; 27(3): 561-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3631130

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Functional characterization of the novel mutation IVS 8 (-11delC) (-14T>A) in the intron 8 of the glucocerebrosidase gene of two Italian siblings with Gaucher disease type I. Author(s): Romano M, Danek GM, Baralle FE, Mazzotti R, Filocamo M. Source: Blood Cells, Molecules & Diseases. 2000 June; 26(3): 171-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10950936

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Gaucher disease and brucella: just a mere coincidence? Author(s): Turfaner Erturk N, Karter Y, Tungkale A, Sipahioglu F. Source: Genet Couns. 2003; 14(3): 363-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14577684

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Gaucher disease and parkinsonism: a phenotypic and genotypic characterization. Author(s): Tayebi N, Callahan M, Madike V, Stubblefield BK, Orvisky E, Krasnewich D, Fillano JJ, Sidransky E. Source: Molecular Genetics and Metabolism. 2001 August; 73(4): 313-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11509013

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Gaucher disease and the clinical experience with substrate reduction therapy. Author(s): Zimran A, Elstein D. Source: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences. 2003 May 29; 358(1433): 961-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12803930

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Gaucher disease associated with parkinsonism: four further case reports. Author(s): Varkonyi J, Rosenbaum H, Baumann N, MacKenzie JJ, Simon Z, AharonPeretz J, Walker JM, Tayebi N, Sidransky E. Source: American Journal of Medical Genetics. 2003 February 1; 116A(4): 348-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12522789

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Gaucher disease in a Turkish family. Author(s): Turfaner Erturk N, Karter Y, Tunckale A, Emre S, Erdogan C, Tasan E, Ozturk E. Source: Genet Couns. 2002; 13(3): 357-8. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12416646

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Gaucher disease in Romanian patients: incidence of the most common mutations and phenotypic manifestations. Author(s): Drugan C, Procopciuc L, Jebeleanu G, Grigorescu-Sido P, Dussau J, Poenaru L, Caillaud C. Source: European Journal of Human Genetics : Ejhg. 2002 September; 10(9): 511-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12173027

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Gaucher disease type I complicated with Parkinson's syndrome. Author(s): Varkonyi J, Simon Z, Soos K, Poros A. Source: Haematologia. 2002; 32(3): 271-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12611487

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Gaucher disease type I: analysis of two cases with thalassemic facies and pulmonary arteriovenous fistulas. Author(s): Gurakan F, Kocak N, Yuce A, Ozen H. Source: Turk J Pediatr. 2001 July-September; 43(3): 237-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11592516

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Gaucher disease with nephrotic syndrome: response to enzyme replacement therapy. Author(s): Santoro D, Rosenbloom BE, Cohen AH. Source: American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation. 2002 July; 40(1): E4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12087590

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Gaucher disease with parkinsonian manifestations: does glucocerebrosidase deficiency contribute to a vulnerability to parkinsonism? Author(s): Tayebi N, Walker J, Stubblefield B, Orvisky E, LaMarca ME, Wong K, Rosenbaum H, Schiffmann R, Bembi B, Sidransky E. Source: Molecular Genetics and Metabolism. 2003 June; 79(2): 104-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12809640

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Gaucher disease with pulmonary involvement in a 6-year-old girl: report of resolution of radiographic abnormalities on increasing dose of imiglucerase. Author(s): Lee SY, Mak AW, Huen KF, Lam ST, Chow CB. Source: The Journal of Pediatrics. 2001 December; 139(6): 862-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11743514

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Gaucher disease: from fundamental research to effective therapeutic interventions. Author(s): de Fost M, Aerts JM, Hollak CE. Source: The Netherlands Journal of Medicine. 2003 January; 61(1): 3-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12688562

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Gaucher disease: in vivo evidence for allele dose leading to neuronopathic and nonneuronopathic phenotypes. Author(s): Zhao H, Bailey LA, Elsas LJ 2nd, Grinzaid KA, Grabowski GA. Source: American Journal of Medical Genetics. 2003 January 1; 116A(1): 52-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12476451

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Gaucher disease: pediatric concerns. Author(s): Elstein D, Abrahamov A, Dweck A, Hadas-Halpern I, Zimran A. Source: Paediatric Drugs. 2002; 4(7): 417-26. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12083970

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Gaucher disease: Perspectives on a prototype lysosomal disease. Author(s): Zhao H, Grabowski GA. Source: Cellular and Molecular Life Sciences : Cmls. 2002 April; 59(4): 694-707. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12022475

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Gaucher disease: understanding the molecular pathogenesis of sphingolipidoses. Author(s): Cox TM. Source: Journal of Inherited Metabolic Disease. 2001; 24 Suppl 2: 106-21; Discussion 87-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11758671

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Gene rearrangements in the glucocerebrosidase-metaxin region giving rise to diseasecausing mutations and polymorphisms. Analysis of 25 Rec NciI alleles in Gaucher disease patients. Author(s): Diaz-Font A, Cormand B, Blanco M, Chamoles N, Chabas A, Grinberg D, Vilageliu L. Source: Human Genetics. 2003 April; 112(4): 426-9. Epub 2003 February 14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12589426

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Glucocerebrosidase level in the cerebrospinal fluid during enzyme replacement therapy--unsuccessful treatment of the neurological abnormality in type 2 Gaucher disease. Author(s): Migita M, Hamada H, Fujimura J, Watanabe A, Shimada T, Fukunaga Y. Source: European Journal of Pediatrics. 2003 July; 162(7-8): 524-5. Epub 2003 April 23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12845529

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Glucosylsphingosine accumulation in tissues from patients with Gaucher disease: correlation with phenotype and genotype. Author(s): Orvisky E, Park JK, LaMarca ME, Ginns EI, Martin BM, Tayebi N, Sidransky E. Source: Molecular Genetics and Metabolism. 2002 August; 76(4): 262-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12208131

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Glycolipid analysis of different tissues and cerebrospinal fluid in type II Gaucher disease. Author(s): Gornati R, Berra B, Montorfano G, Martini C, Ciana G, Ferrari P, Romano M, Bembi B. Source: Journal of Inherited Metabolic Disease. 2002 February; 25(1): 47-55. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11999980

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Haemostatic abnormalities and lupus anticoagulant activity in patients with Gaucher disease type I. Author(s): Barone R, Giuffrida G, Musso R, Carpinteri G, Fiumara A. Source: Journal of Inherited Metabolic Disease. 2000 June; 23(4): 387-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10896301

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Hematologic improvement in a patient with Gaucher disease on long-term enzyme replacement therapy: evidence for decreased splenic sequestration and improved red blood cell survival. Author(s): Parker RI, Barton NW, Read EJ, Brady RO. Source: American Journal of Hematology. 1991 October; 38(2): 130-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1951303

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Hematological findings in the Norrbottnian type of Gaucher disease. Author(s): Tibblin E, Dreborg S, Erikson A, Hakansson G, Svennerholm L. Source: European Journal of Pediatrics. 1982 November; 139(3): 187-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7160406

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Hematologically important mutations: Gaucher disease. Author(s): Beutler E, Gelbart T. Source: Blood Cells, Molecules & Diseases. 1998 March; 24(1): 2-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9516376

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Hematologically important mutations: Gaucher disease. Author(s): Beutler E, Gelbart T. Source: Blood Cells, Molecules & Diseases. 1997; 23(1): 2-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9215746

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Hepatocellular carcinoma in a patient with Gaucher disease on enzyme supplementation therapy. Author(s): Erjavec Z, Hollak CE, de Vries EG. Source: Annals of Oncology : Official Journal of the European Society for Medical Oncology / Esmo. 1999 February; 10(2): 243. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10093697

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Hepatopulmonary syndrome in Gaucher disease with right-to-left shunt: evaluation and measurement using Tc-99m MAA. Author(s): Kim JH, Park CH, Pai MS, Hahn MH, Kim HJ. Source: Clinical Nuclear Medicine. 1999 March; 24(3): 164-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10069725

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Heterogeneity of mutations in the acid beta-glucosidase gene of Gaucher disease patients. Author(s): Latham TE, Theophilus BD, Grabowski GA, Smith FI. Source: Dna and Cell Biology. 1991 January-February; 10(1): 15-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1899336

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Heterologous expression and characterization of a rare Gaucher disease mutation (c.481C > T) from a Canadian aboriginal population using archival tissue samples. Author(s): Sinclair G, Choy FY, Ferreira P. Source: Molecular Genetics and Metabolism. 2001 November; 74(3): 345-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11708865

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High frequency of the Gaucher disease mutation at nucleotide 1226 among Ashkenazi Jews. Author(s): Zimran A, Gelbart T, Westwood B, Grabowski GA, Beutler E. Source: American Journal of Human Genetics. 1991 October; 49(4): 855-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1897529

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High level transcription of the glucocerebrosidase pseudogene in normal subjects and patients with Gaucher disease. Author(s): Sorge J, Gross E, West C, Beutler E. Source: The Journal of Clinical Investigation. 1990 October; 86(4): 1137-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1698821

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High prevalence of the 55-bp deletion (c.1263del55) in exon 9 of the glucocerebrosidase gene causing misdiagnosis (for homozygous N370S (c.1226A > G) mutation) in Spanish Gaucher disease patients. Author(s): Torralba MA, Alfonso P, Perez-Calvo JI, Cenarro A, Pastores GM, Giraldo P, Civeira F, Pocovi M. Source: Blood Cells, Molecules & Diseases. 2002 July-August; 29(1): 35-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12482401

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Gaucher Disease

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Home treatment with enzyme replacement therapy in a 5-year-old girl with type 2 Gaucher disease. Author(s): Migita M, Shimada T, Hayakawa J, Zhi CL, Morita T, Ohshiro K, Fukunaga Y. Source: Pediatrics International : Official Journal of the Japan Pediatric Society. 2003 June; 45(3): 363-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12828600

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Home treatment with intravenous enzyme replacement therapy for Gaucher disease: an international collaborative study of 33 patients. Author(s): Zimran A, Hollak CE, Abrahamov A, van Oers MH, Kelly M, Beutler E. Source: Blood. 1993 August 15; 82(4): 1107-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8353277

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Huge subcapsular splenic hematoma in a patient with Gaucher disease. Author(s): Aharoni D, Hadas-Halpern I, Elstein D, Zimran A. Source: Isr Med Assoc J. 2000 January; 2(1): 61-2. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10892378

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Human acid beta-glucosidase. Use of conduritol B epoxide derivatives to investigate the catalytically active normal and Gaucher disease enzymes. Author(s): Grabowski GA, Osiecki-Newman K, Dinur T, Fabbro D, Legler G, Gatt S, Desnick RJ. Source: The Journal of Biological Chemistry. 1986 June 25; 261(18): 8263-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3087971

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Human acid beta-glucosidase: affinity purification of the normal placental and Gaucher disease splenic enzymes on N-alkyl-deoxynojirimycin-sepharose. Author(s): Osiecki-Newman KM, Fabbro D, Dinur T, Boas S, Gatt S, Legler G, Desnick RJ, Grabowski GA. Source: Enzyme. 1986; 35(3): 147-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2944742

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Human acid beta-glucosidase: inhibition studies using glucose analogues and pH variation to characterize the normal and Gaucher disease glycon binding sites. Author(s): Osiecki-Newman K, Legler G, Grace M, Dinur T, Gatt S, Desnick RJ, Grabowski GA. Source: Enzyme. 1988; 40(4): 173-88. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3234317

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Human acid beta-glucosidase: Northern blot and S1 nuclease analysis of mRNA from HeLa cells and normal and Gaucher disease fibroblasts. Author(s): Graves PN, Grabowski GA, Ludman MD, Palese P, Smith FI. Source: American Journal of Human Genetics. 1986 December; 39(6): 763-74. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3026174

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Human acid beta-glucosidase: use of inhibitors, alternative substrates and amphiphiles to investigate the properties of the normal and Gaucher disease active sites. Author(s): Osiecki-Newman K, Fabbro D, Legler G, Desnick RJ, Grabowski GA. Source: Biochimica Et Biophysica Acta. 1987 September 2; 915(1): 87-100. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2956992

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Identification and characterization of a novel mutation c.1090G>T (G325W) and nine common mutant alleles leading to Gaucher disease in Spanish patients. Author(s): Torralba MA, Perez-Calvo JI, Pastores GM, Cenarro A, Giraldo P, Pocovi M. Source: Blood Cells, Molecules & Diseases. 2001 March-April; 27(2): 489-95. Erratum In: Blood Cells Mol Dis 2001 May-June; 27(3): 713. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11259172

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Identification and expression of acid beta-glucosidase mutations causing severe type 1 and neurologic type 2 Gaucher disease in non-Jewish patients. Author(s): Grace ME, Desnick RJ, Pastores GM. Source: The Journal of Clinical Investigation. 1997 May 15; 99(10): 2530-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9153297

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Identification of a 55-bp deletion in the glucocerebrosidase gene in Gaucher disease: phenotypic presentation and implications for mutation detection assays. Author(s): Mao R, O'Brien JF, Rao S, Schmitt E, Roa B, Feldman GL, Spence WC, Snow K. Source: Molecular Genetics and Metabolism. 2001 March; 72(3): 248-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11243731

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Identification of a novel three-nucleotide insertion mutation (c.841-842insTGA) in the acid beta-glucosidase gene of a Taiwan Chinese patient with type II Gaucher disease. Author(s): Wu JY, Wu MC, Lee CC, Tsai FJ. Source: Human Mutation. 2001 March; 17(3): 238. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11241851

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Gaucher Disease

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Identification of three additional genes contiguous to the glucocerebrosidase locus on chromosome 1q21: implications for Gaucher disease. Author(s): Winfield SL, Tayebi N, Martin BM, Ginns EI, Sidransky E. Source: Genome Research. 1997 October; 7(10): 1020-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9331372

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Identification of two novel and four uncommon missense mutations among chinese Gaucher disease patients. Author(s): Choy FY, Humphries ML, Shi H. Source: American Journal of Medical Genetics. 1997 August 8; 71(2): 172-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9217217

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Identification of two novel mutations, L105R and C342R, in Type I Gaucher disease. Author(s): Choy FY, Vaags A, Wong K, Macgregor D, Fernandez B, Prasad C. Source: Clinical Genetics. 2002 March; 61(3): 229-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12000368

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Iliopsoas hematoma in a young patient with type I Gaucher disease. Author(s): Jmoudiak M, Itzchaki M, Hadas-Halpern I, Hrebicek M, Hodanova K, Elstein D, Zimran A. Source: Isr Med Assoc J. 2003 September; 5(9): 673-4. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14509164

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Imaging and quantifying skeletal involvement in Gaucher disease. Author(s): Maas M, Poll LW, Terk MR. Source: The British Journal of Radiology. 2002; 75 Suppl 1: A13-24. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12036829

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Imino sugar therapy for type 1 Gaucher disease. Author(s): Priestman DA, Platt FM, Dwek RA, Butters TD. Source: Glycobiology. 2000 November; 10(11): Iv-Vi. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11221677

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Improvement of neurological symptoms by enzyme replacement therapy for Gaucher disease type IIIb. Author(s): Aoki M, Takahashi Y, Miwa Y, Iida S, Sukegawa K, Horai T, Orii T, Kondo N. Source: European Journal of Pediatrics. 2001 January; 160(1): 63-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11195024

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Improvement of splenomegaly and pancytopenia by enzyme replacement therapy against type 1 Gaucher disease: a report of sibling cases. Author(s): Tsuboi K, Iida S, Kato M, Hayami Y, Hanamura I, Miura K, Harada S, Komatsu H, Banno S, Wakita A, Nitta M, Ueda R. Source: International Journal of Hematology. 2001 April; 73(3): 356-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11345203

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Incidence of thrombophilia in patients with Gaucher disease. Author(s): Elstein D, Renbaum P, Levy-Lahad E, Zimran A. Source: American Journal of Medical Genetics. 2000 December 18; 95(5): 429-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11146461

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Increased operative bleeding during orthopaedic surgery in patients with type I Gaucher disease and bone involvement. Author(s): Katz K, Tamary H, Lahav J, Soudry M, Cohen IJ. Source: Bull Hosp Jt Dis. 1999; 58(4): 188-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10711366

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Insulin-like growth factors in childhood-onset Gaucher disease. Author(s): Rite S, Baldellou A, Giraldo P, Labarta JI, Giralt M, Rubio-Felix D, Guallar A, Perez-Calvo JI, Mayayo E, Ferrandez A, Pocovi M. Source: Pediatric Research. 2002 July; 52(1): 109-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12084856

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Interruption in enzyme replacement therapy for Gaucher disease. Author(s): Weinreb NJ. Source: British Journal of Haematology. 2001 June; 113(4): 1087-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11442515

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Involvement of the foot and ankle in patients with Gaucher disease. Author(s): Katz K, Kornreich L, Horev G, Ziv N, Soudry M, Cohen IJ. Source: Foot & Ankle International / American Orthopaedic Foot and Ankle Society [and] Swiss Foot and Ankle Society. 1999 February; 20(2): 104-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10063978

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Is it possible to identify siblings by studying bone marrow under a microscope? Two unusual cases of Gaucher disease. Author(s): Papla B, Machaczka M, Skotnicki AB. Source: Pol J Pathol. 2002; 53(2): 87-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12140872

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Gaucher Disease

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Is the perinatal lethal form of Gaucher disease more common than classic type 2 Gaucher disease? Author(s): Stone DL, van Diggelen OP, de Klerk JB, Gaillard JL, Niermeijer MF, Willemsen R, Tayebi N, Sidransky E. Source: European Journal of Human Genetics : Ejhg. 1999 May-June; 7(4): 505-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10352942

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Is there a correlation between degree of splenomegaly, symptoms and hypersplenism? A study of 218 patients with Gaucher disease. Author(s): Gielchinsky Y, Elstein D, Hadas-Halpern I, Lahad A, Abrahamov A, Zimran A. Source: British Journal of Haematology. 1999 September; 106(3): 812-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10468878

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Juvenile Gaucher disease simulating osteomyelitis. Author(s): Miller JH, Ortega JA, Heisel MA. Source: Ajr. American Journal of Roentgenology. 1981 October; 137(4): 880-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6974991

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Late-infantile Gaucher disease in a child with myoclonus and bulbar signs: neuropathological and neurochemical findings. Author(s): Conradi N, Kyllerman M, Mansson JE, Percy AK, Svennerholm L. Source: Acta Neuropathologica. 1991; 82(2): 152-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1718128

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Lessons learned from the development of enzyme therapy for Gaucher disease. Author(s): Barranger JA, O'Rourke E. Source: Journal of Inherited Metabolic Disease. 2001; 24 Suppl 2: 89-96; Discussion 87-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11758684

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Leukocyte beta-glucosidase in homozygotes and heterozygotes for Gaucher disease. Author(s): Raghavan SS, Topol J, Kolodny EH. Source: American Journal of Human Genetics. 1980 March; 32(2): 158-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6770675

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Life-threatening splenic hemorrhage in two patients with Gaucher disease. Author(s): Stone DL, Ginns EI, Krasnewich D, Sidransky E. Source: American Journal of Hematology. 2000 June; 64(2): 140-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10814997

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Linkage disequilibrium of common Gaucher disease mutations with a polymorphic site in the pyruvate kinase (PKLR) gene. Author(s): Rockah R, Narinsky R, Frydman M, Cohen IJ, Zaizov R, Weizman A, Frisch A. Source: American Journal of Medical Genetics. 1998 July 7; 78(3): 233-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9677056

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Linkage of the PvuII polymorphism with the common Jewish mutation for Gaucher disease. Author(s): Zimran A, Gelbart T, Beutler E. Source: American Journal of Human Genetics. 1990 May; 46(5): 902-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1971142

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Littoral cell angioma of the spleen in a patient with Gaucher disease. Author(s): Gupta MK, Levin M, Aguilera NS, Pastores GM. Source: American Journal of Hematology. 2001 September; 68(1): 61-2. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11559940

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Liver scintigraphy in a patient with Gaucher disease. Author(s): Ohta H, Komibuchi T, Takeda H, Taniguchi T, Mihara Y, Nakano T, Shintaku M, Fujimoto M, Nasu K, Oki S, et al. Source: Ann Nucl Med. 1993 May; 7(2): 115-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8318347

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Long-term follow-up of the first successful bone marrow transplantation in Gaucher disease. Author(s): Ringden O, Groth CG, Erikson A, Backman L, Granqvist S, Mansson JE, Svennerholm L. Source: Transplantation. 1988 July; 46(1): 66-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3134756

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Low-dose high-frequency enzyme replacement therapy for very young children with severe Gaucher disease. Author(s): Zimran A, Hadas-Halpern I, Zevin S, Levy-Lahad E, Abrahamov A. Source: British Journal of Haematology. 1993 December; 85(4): 783-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7918044

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Low-dose high-frequency enzyme replacement therapy prevents fractures without complete suppression of painful bone crises in patients with severe juvenile onset type I Gaucher disease. Author(s): Cohen IJ, Katz K, Kornreich L, Horev G, Frish A, Zaizov R. Source: Blood Cells, Molecules & Diseases. 1998 September; 24(3): 296-302. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10087987

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Gaucher Disease

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Low-dose low-frequency imiglucerase as a starting regimen of enzyme replacement therapy for patients with type I Gaucher disease. Author(s): Elstein D, Abrahamov A, Hadas-Halpern I, Meyer A, Zimran A. Source: Qjm : Monthly Journal of the Association of Physicians. 1998 July; 91(7): 483-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9797931

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Low-dose N-butyldeoxynojirimycin (OGT 918) for type I Gaucher disease. Author(s): Heitner R, Elstein D, Aerts J, Weely S, Zimran A. Source: Blood Cells, Molecules & Diseases. 2002 March-April; 28(2): 127-33. Erratum In: Blood Cells Mol Dis. 2003 Mar-Apr; 28(2): 301. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12064906

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Lower frequency of Gaucher disease carriers among Tay-Sachs disease carriers. Author(s): Peleg L, Frisch A, Goldman B, Karpaty M, Narinsky R, Bronstein S, Frydman M. Source: European Journal of Human Genetics : Ejhg. 1998 March-April; 6(2): 185-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9781065

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Magnetic resonance imaging of bone marrow changes in Gaucher disease during enzyme replacement therapy: first German long-term results. Author(s): Poll LW, Koch JA, vom Dahl S, Willers R, Scherer A, Boerner D, Niederau C, Haussinger D, Modder U. Source: Skeletal Radiology. 2001 September; 30(9): 496-503. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11587517

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Management of Gaucher disease in a post-communist transitional health care system: Croatian experience. Author(s): Mrsic M, Stavljenic-Rukavina A, Fumic K, Labar B, Bogdanic V, Potocki K, Kardum-Skelin I, Rovers D. Source: Croatian Medical Journal. 2003 October; 44(5): 606-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14515422

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Management of neuronopathic Gaucher disease: a European consensus. Author(s): Vellodi A, Bembi B, de Villemeur TB, Collin-Histed T, Erikson A, Mengel E, Rolfs A, Tylki-Szymanska A; Neuronopathic Gaucher Disease Task Force of the European Working Group on Gaucher Disease. Source: Journal of Inherited Metabolic Disease. 2001 June; 24(3): 319-27. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11486896

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Management of neutralizing antibody to Ceredase in a patient with type 3 Gaucher disease. Author(s): Brady RO, Murray GJ, Oliver KL, Leitman SF, Sneller MC, Fleisher TA, Barton NW. Source: Pediatrics. 1997 December; 100(6): E11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9382912

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Marked elevation of the chemokine CCL18/PARC in Gaucher disease: a novel surrogate marker for assessing therapeutic intervention. Author(s): Boot RG, Verhoek M, de Fost M, Hollak CE, Maas M, Bleijlevens B, van Breemen MJ, van Meurs M, Boven LA, Laman JD, Moran MT, Cox TM, Aerts JM. Source: Blood. 2004 January 1; 103(1): 33-9. Epub 2003 September 11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12969956

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Massive splenomegaly and Epstein-Barr virus-associated infectious mononucleosis in a patient with Gaucher disease. Author(s): Eapen M, Hostetter M, Neglia JP. Source: Journal of Pediatric Hematology/Oncology : Official Journal of the American Society of Pediatric Hematology/Oncology. 1999 January-February; 21(1): 47-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10029812

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Metaphyseal undertubulation in Gaucher disease: resolution at MRI in a patient undergoing enzyme replacement therapy. Author(s): Kelman CG, Disler DG. Source: Journal of Computer Assisted Tomography. 2000 January-February; 24(1): 173-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10667678

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Methotrexate selectable retroviral vectors for Gaucher disease. Author(s): Havenga MJ, Werner AB, Valerio D, van Es HH. Source: Gene Therapy. 1998 October; 5(10): 1379-88. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9930344

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Mice with type 2 and 3 Gaucher disease point mutations generated by a single insertion mutagenesis procedure. Author(s): Liu Y, Suzuki K, Reed JD, Grinberg A, Westphal H, Hoffmann A, Doring T, Sandhoff K, Proia RL. Source: Proceedings of the National Academy of Sciences of the United States of America. 1998 March 3; 95(5): 2503-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9482915

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Molecular analysis and clinical findings in the Spanish Gaucher disease population: putative haplotype of the N370S ancestral chromosome. Author(s): Cormand B, Grinberg D, Gort L, Chabas A, Vilageliu L. Source: Human Mutation. 1998; 11(4): 295-305. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9554746

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Molecular biology of glucocerebrosidase and the treatment of Gaucher disease. Author(s): Barranger JA, Tomich J, Weiler S, Sakallah S, Sansieri C, Mifflin T, Bahnson A, Wei FS, Wei JF, Vallor M, et al. Source: Cytokines Mol Ther. 1995 September; 1(3): 149-63. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9384672

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Multiple hypoechoic hepatic lesions in a patient with Gaucher disease. Author(s): Patlas M, Hadas-Halpern I, Reinus C, Zimran A, Elstein D. Source: Journal of Ultrasound in Medicine : Official Journal of the American Institute of Ultrasound in Medicine. 2002 September; 21(9): 1053-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12216754

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Mutation analysis of Gaucher disease patients from Argentina: high prevalence of the RecNciI mutation. Author(s): Cormand B, Harboe TL, Gort L, Campoy C, Blanco M, Chamoles N, Chabas A, Vilageliu L, Grinberg D. Source: American Journal of Medical Genetics. 1998 December 4; 80(4): 343-51. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9856561

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Mutation analysis of Gaucher disease using dot-blood samples on FTA filter paper. Author(s): Devost NC, Choy FY. Source: American Journal of Medical Genetics. 2000 October 23; 94(5): 417-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11050629

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Mutation analysis of the acid beta-glucosidase gene in a patient with type 3 Gaucher disease and neutralizing antibody to alglucerase. Author(s): Germain DP, Kaneski CR, Brady RO. Source: Mutation Research. 2001 November 1; 483(1-2): 89-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11600137

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Mutation analysis of type II Gaucher disease in five Taiwanese children: identification of two novel mutations. Author(s): Tsai FJ, Lee CC, Wu MC, Lin SP, Lin CY, Tsai CH, Kodama H, Wu JY. Source: Acta Paediatr Taiwan. 2001 July-August; 42(4): 231-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11550412

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Mutation prevalence among 51 unrelated Spanish patients with Gaucher disease: identification of 11 novel mutations. Author(s): Alfonso P, Cenarro A, Perez-Calvo JI, Giralt M, Giraldo P, Pocovi M. Source: Blood Cells, Molecules & Diseases. 2001 September-October; 27(5): 882-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11783951

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Myoclonic epilepsy in Gaucher disease: genotype-phenotype insights from a rare patient subgroup. Author(s): Park JK, Orvisky E, Tayebi N, Kaneski C, Lamarca ME, Stubblefield BK, Martin BM, Schiffmann R, Sidransky E. Source: Pediatric Research. 2003 March; 53(3): 387-95. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12595585

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Myoclonus from selective dentate nucleus degeneration in type 3 Gaucher disease. Author(s): Verghese J, Goldberg RF, Desnick RJ, Grace ME, Goldman JE, Lee SC, Dickson DW, Rapin I. Source: Archives of Neurology. 2000 March; 57(3): 389-95. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10714667

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Myoclonus in Gaucher disease. Author(s): Frei KP, Schiffmann R. Source: Adv Neurol. 2002; 89: 41-8. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11968465

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Near-total splenectomy for massive splenomegaly due to Gaucher disease: a new surgical approach. Author(s): Morgenstern L, Phillips EH, Fermelia D, Weinstein IM. Source: The Mount Sinai Journal of Medicine, New York. 1986 September; 53(7): 501-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3491301

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Neonatal cholestasis and infantile Gaucher disease: a case report. Author(s): Barbier C, Devisme L, Dobbelaere D, Noizet O, Nelken B, Gottrand F. Source: Acta Paediatrica (Oslo, Norway : 1992). 2002; 91(12): 1399-401. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12578302

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Neurological outcome of a patient with Gaucher disease type III treated by enzymatic replacement therapy. Author(s): Dobbelaere D, Sukno S, Defoort-Dhellemmes S, Lamblin MD, Largilliere C. Source: Journal of Inherited Metabolic Disease. 1998 February; 21(1): 74-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9501273

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Neuronopathic and non-neuronopathic presentation of Gaucher disease in patients with the third most common mutation (D409H) in Spain. Author(s): Chabas A, Cormand B, Balcells S, Gonzalez-Duarte R, Casanova C, Colomer J, Vilageliu L, Grinberg D. Source: Journal of Inherited Metabolic Disease. 1996; 19(6): 798-800. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8982958

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Neuronopathic juvenile glucosylceramidosis due to sap-C deficiency: clinical course, neuropathology and brain lipid composition in this Gaucher disease variant. Author(s): Pampols T, Pineda M, Giros ML, Ferrer I, Cusi V, Chabas A, Sanmarti FX, Vanier MT, Christomanou H. Source: Acta Neuropathologica. 1999 January; 97(1): 91-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9930900

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Neuropathology of the Norrbottnian type of Gaucher disease. Morphological and biochemical studies. Author(s): Conradi NG, Sourander P, Nilsson O, Svennerholm L, Erikson A. Source: Acta Neuropathologica. 1984; 65(2): 99-109. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6524300

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New directions in the treatment of Gaucher disease. Author(s): Futerman AH, Sussman JL, Horowitz M, Silman I, Zimran A. Source: Trends in Pharmacological Sciences. 2004 March; 25(3): 147-51. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15019270

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New Gaucher disease mutations in exon 10: a novel L444R mutation produces a new NciI site the same as L444P. Author(s): Uchiyama A, Tomatsu S, Kondo N, Suzuki Y, Shimozawa N, Fukuda S, Sukegawa K, Taki N, Inamori H, Orii T. Source: Human Molecular Genetics. 1994 July; 3(7): 1183-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7981693

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New insights into the origin of the Gaucher disease-causing mutation N370S: extended haplotype analysis using the 5GC3.2, 5470 G/A, and ITG6.2 polymorphisms. Author(s): Rodriguez-Mari A, Diaz-Font A, Chabas A, Pastores GM, Grinberg D, Vilageliu L. Source: Blood Cells, Molecules & Diseases. 2001 September-October; 27(5): 950-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11783960

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New perspectives in type 2 Gaucher disease. Author(s): Sidransky E. Source: Adv Pediatr. 1997; 44: 73-107. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9265968

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Non-existence of a tight association between a 444leucine to proline mutation and phenotypes of Gaucher disease: high frequency of a NciI polymorphism in the nonneuronopathic form. Author(s): Masuno M, Tomatsu S, Sukegawa K, Orii T. Source: Human Genetics. 1990 January; 84(2): 203-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1967589

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Non-neuropathic Gaucher disease presenting in infancy. Author(s): Hodson P, Goldblatt J, Beighton P. Source: Archives of Disease in Childhood. 1979 September; 54(9): 707-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=518109

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Non-pseudogene-derived complex acid beta-glucosidase mutations causing mild type 1 and severe type 2 Gaucher disease. Author(s): Grace ME, Ashton-Prolla P, Pastores GM, Soni A, Desnick RJ. Source: The Journal of Clinical Investigation. 1999 March; 103(6): 817-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10079102

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Norrbottnian type of Gaucher disease--clinical, biochemical and molecular biology aspects: successful treatment with bone marrow transplantation. Author(s): Svennerholm L, Erikson A, Groth CG, Ringden O, Mansson JE. Source: Developmental Neuroscience. 1991; 13(4-5): 345-51. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1817041

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Novel insertion mutation in a non-Jewish Caucasian type 1 Gaucher disease patient. Author(s): Choy FY, Humphries ML, Ferreira P. Source: American Journal of Medical Genetics. 1997 January 20; 68(2): 211-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9028460

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Novel point mutation (W184R) in neonatal type 2 Gaucher disease. Author(s): Choy FY, Wong K, Vallance HD, Baldwin V. Source: Pediatric and Developmental Pathology : the Official Journal of the Society for Pediatric Pathology and the Paediatric Pathology Society. 2000 March-April; 3(2): 180-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10679038

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N-terminal amino-acid sequence of a sphingolipid activator protein missing in a new human Gaucher disease variant. Author(s): Christomanou H, Kleinschmidt T, Braunitzer G. Source: Biol Chem Hoppe Seyler. 1987 September; 368(9): 1193-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3675870

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Obstetric aspects of Gaucher disease. Author(s): Goldblatt J, Beighton P. Source: British Journal of Obstetrics and Gynaecology. 1985 February; 92(2): 145-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3871632

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Occurrence of Parkinson's syndrome in type I Gaucher disease. Author(s): Neudorfer O, Giladi N, Elstein D, Abrahamov A, Turezkite T, Aghai E, Reches A, Bembi B, Zimran A. Source: Qjm : Monthly Journal of the Association of Physicians. 1996 September; 89(9): 691-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8917744

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Ocular motor abnormalities in Gaucher disease. Author(s): Harris CM, Taylor DS, Vellodi A. Source: Neuropediatrics. 1999 December; 30(6): 289-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10706022

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Ocular movements in lipid storage disease. Reports of juvenile Gaucher disease and the ophthalmoplegic lipidosis. Author(s): Sanders MD, Lake BD. Source: Birth Defects Orig Artic Ser. 1976; 12(3): 535-42. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=953203

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Oculomotor apraxia: the presenting sign of Gaucher disease. Author(s): Gross-Tsur V, Har-Even Y, Gutman I, Amir N. Source: Pediatric Neurology. 1989 March-April; 5(2): 128-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2712947

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Oculomotor deficits in Gaucher disease. Author(s): Stowens DW, Chu FC, Cogan DG, Barranger JA. Source: Prog Clin Biol Res. 1982; 95: 143-7. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7122632

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Oligosaccharide excretion in adult Gaucher disease. Author(s): de Jong JG, Aerts JM, van Weely S, Hollak CE, van Pelt J, van Woerkom LM, Liebrand-van Sambeek ML, Wevers RA. Source: Journal of Inherited Metabolic Disease. 1998 February; 21(1): 49-59. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9501269

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On the age of the most prevalent Gaucher disease-causing mutation, N370S. Author(s): Diaz A, Montfort M, Cormand B, Zeng B, Pastores GM, Chabas A, Vilageliu L, Grinberg D. Source: American Journal of Human Genetics. 2000 June; 66(6): 2014-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10801390

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Operative technique and results of subtotal splenectomy for Gaucher disease. Author(s): Guzzetta PC, Connors RH, Fink J, Barranger JA. Source: Surg Gynecol Obstet. 1987 April; 164(4): 359-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3563849

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Orthotopic liver transplantation in the treatment of complications of type 1 Gaucher disease. Author(s): Carlson DE, Busuttil RW, Giudici TA, Barranger JA. Source: Transplantation. 1990 June; 49(6): 1192-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2360260

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Osteomyelitis in Gaucher disease. Author(s): Bell RS, Mankin HJ, Doppelt SH. Source: The Journal of Bone and Joint Surgery. American Volume. 1986 December; 68(9): 1380-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3782210

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Outcome of partial splenectomy for type I Gaucher disease. Author(s): Zimran A, Elstein D, Schiffmann R, Abrahamov A, Goldberg M, Bar-Maor JA, Brady RO, Guzzetta PC, Barton NW. Source: The Journal of Pediatrics. 1995 April; 126(4): 596-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7699540

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Outcome of total hip arthroplasty in patients with Gaucher disease. Author(s): Lebel E, Itzchaki M, Hadas-Halpern I, Zimran A, Elstein D. Source: The Journal of Arthroplasty. 2001 January; 16(1): 7-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11172263

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Pathologic gene expression in Gaucher disease: up-regulation of cysteine proteinases including osteoclastic cathepsin K. Author(s): Moran MT, Schofield JP, Hayman AR, Shi GP, Young E, Cox TM. Source: Blood. 2000 September 1; 96(5): 1969-78. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10961902

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Pathologic quiz case. A 14-year-old boy with splenomegaly. Pathologic diagnosis: Gaucher disease. Author(s): Khan SB, Alkan S, Pooley R. Source: Archives of Pathology & Laboratory Medicine. 2000 August; 124(8): 1239-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10923094

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Pathological bone fractures preceded by sustained hypercalcaemia in type 1 Gaucher disease. Author(s): Byrne CD, Bermann L, Constant C, Cox TM. Source: Journal of Inherited Metabolic Disease. 1997 September; 20(5): 709-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9323569

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Pediatric non-neuronopathic Gaucher disease: presentation, diagnosis and assessment. Consensus statements. Author(s): Grabowski GA, Andria G, Baldellou A, Campbell PE, Charrow J, Cohen IJ, Harris CM, Kaplan P, Mengel E, Pocovi M, Vellodi A. Source: European Journal of Pediatrics. 2004 February; 163(2): 58-66. Epub 2003 December 16. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14677061

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Perinatal-lethal Gaucher disease. Author(s): Mignot C, Gelot A, Bessieres B, Daffos F, Voyer M, Menez F, Fallet Bianco C, Odent S, Le Duff D, Loget P, Fargier P, Costil J, Josset P, Roume J, Vanier MT, Maire I, Billette de Villemeur T. Source: American Journal of Medical Genetics. 2003 July 30; 120A(3): 338-44. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12838552

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Phenotypic continuum in neuronopathic Gaucher disease: an intermediate phenotype between type 2 and type 3. Author(s): Goker-Alpan O, Schiffmann R, Park JK, Stubblefield BK, Tayebi N, Sidransky E. Source: The Journal of Pediatrics. 2003 August; 143(2): 273-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12970647

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Plasma chitotriosidase activity in Gaucher disease patients who have been treated either by bone marrow transplantation or by enzyme replacement therapy with alglucerase. Author(s): Young E, Chatterton C, Vellodi A, Winchester B. Source: Journal of Inherited Metabolic Disease. 1997 August; 20(4): 595-602. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9266398

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Plasma tumor necrosis factor-a (TNF-a) levels in Gaucher disease. Author(s): Michelakakis H, Spanou C, Kondyli A, Dimitriou E, Van Weely S, Hollak CE, Van Oers MH, Aerts JM. Source: Biochimica Et Biophysica Acta. 1996 December 16; 1317(3): 219-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8988238

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Platelet function abnormalities in Gaucher disease patients. Author(s): Gillis S, Hyam E, Abrahamov A, Elstein D, Zimran A. Source: American Journal of Hematology. 1999 June; 61(2): 103-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10367788

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Polymorphisms in glucosylceramide (glucocerebroside) synthase and the Gaucher disease phenotype. Author(s): Beutler E, West C. Source: Isr Med Assoc J. 2002 November; 4(11): 986-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12489486

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Pregnancy in Gaucher disease. Author(s): Sakarelou N, Kosmaidou Z, Mesogitis S, Dimitriou E, Michelakakis H. Source: European Journal of Obstetrics, Gynecology, and Reproductive Biology. 1999 March; 83(1): 113-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10221620

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Preretinal white dots in adult-type Gaucher disease. Author(s): Wollstein G, Elstein D, Strassman I, Seelenfreund M, Zylbermann R, Zimran A. Source: Retina (Philadelphia, Pa.). 1999; 19(6): 570-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10606464

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Protein, glucose and energy metabolism in Gaucher disease type I. Author(s): Bodamer OA, Vellodi A. Source: Journal of Inherited Metabolic Disease. 2000 February; 23(1): 86-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10682313

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Pseudo-osteomyelitic crisis upon presentation of Gaucher disease. Author(s): Weisstein JS, Steinbach LS, Diamond CA, Huang SJ, O'Donnell RJ. Source: Skeletal Radiology. 2001 July; 30(7): 407-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11499783

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Pulmonary hypertension developing after alglucerase therapy in two patients with type 1 Gaucher disease complicated by the hepatopulmonary syndrome. Author(s): Dawson A, Elias DJ, Rubenson D, Bartz SH, Garver PR, Kay AC, Bloor CM, Beutler E. Source: Annals of Internal Medicine. 1996 December 1; 125(11): 901-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8967670

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Pulmonary hypertension in two patients with type I Gaucher disease while on alglucerase therapy. Author(s): Harats D, Pauzner R, Elstein D, Many A, Klutstein MW, Kramer MR, Farfel Z, Zimran A. Source: Acta Haematologica. 1997; 98(1): 47-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9210915

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Pulmonary involvement in type 1 Gaucher disease: functional and exercise findings in patients with and without clinical interstitial lung disease. Author(s): Miller A, Brown LK, Pastores GM, Desnick RJ. Source: Clinical Genetics. 2003 May; 63(5): 368-76. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12752568

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Pulmonary manifestations of Gaucher disease: an increased risk for L444P homozygotes? Author(s): Santamaria F, Parenti G, Guidi G, Filocamo M, Strisciuglio P, Grillo G, Farina V, Sarnelli P, Rizzolo MG, Rotondo A, Andria G. Source: American Journal of Respiratory and Critical Care Medicine. 1998 March; 157(3 Pt 1): 985-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9517621

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Quality of life assessment in adults with type 1 Gaucher disease. Author(s): Masek BJ, Sims KB, Bove CM, Korson MS, Short P, Norman DK. Source: Quality of Life Research : an International Journal of Quality of Life Aspects of Treatment, Care and Rehabilitation. 1999 May; 8(3): 263-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10472157

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Quantification of bone involvement in Gaucher disease: MR imaging bone marrow burden score as an alternative to Dixon quantitative chemical shift MR imaging-initial experience. Author(s): Maas M, van Kuijk C, Stoker J, Hollak CE, Akkerman EM, Aerts JF, den Heeten GJ. Source: Radiology. 2003 November; 229(2): 554-61. Epub 2003 October 02. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14526090

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Quantitative chemical shift imaging of vertebral bone marrow in patients with Gaucher disease. Author(s): Johnson LA, Hoppel BE, Gerard EL, Miller SP, Doppelt SH, Zirzow GC, Rosenthal DI, Dambrosia JM, Hill SC, Brady RO, et al. Source: Radiology. 1992 February; 182(2): 451-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1732964

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Quantitative imaging of Gaucher disease. Author(s): Rosenthal DI, Barton NW, McKusick KA, Rosen BR, Hill SC, Castronovo FP, Brady RO, Doppelt SH, Mankin HJ. Source: Radiology. 1992 December; 185(3): 841-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1438773

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Rapid genetic testing for Gaucher disease by reverse hybridization. Author(s): Halsall DJ, Kriegshauser G, Moritz A, Elsey TS, Oberkanins C. Source: Annals of Clinical Biochemistry. 2003 July; 40(Pt 4): 419-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12880546

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Rare compound heterozygosity for IVS2 +1G>A and R170P in an Italian patient with Gaucher disease type 1. Author(s): Concolino D, Mussari A, Filocamo M, Strisciuglio P. Source: Clinical Genetics. 2003 September; 64(3): 261-2. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12919144

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Rebound hepatosplenomegaly in type 1 Gaucher disease. Author(s): Toth J, Erdos M, Marodi L. Source: European Journal of Haematology. 2003 February; 70(2): 125-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12581195

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Reciprocal and nonreciprocal recombination at the glucocerebrosidase gene region: implications for complexity in Gaucher disease. Author(s): Tayebi N, Stubblefield BK, Park JK, Orvisky E, Walker JM, LaMarca ME, Sidransky E. Source: American Journal of Human Genetics. 2003 March; 72(3): 519-34. Epub 2003 February 13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12587096

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Recommendations for diagnosis, evaluation, and monitoring of patients with Gaucher disease. Author(s): Elstein D, Abrahamov A, Hadas-Halpern I, Zimran A. Source: Archives of Internal Medicine. 1999 June 14; 159(11): 1254-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10371236

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Recurrence of the D409H mutation in Spanish Gaucher disease patients: description of a new homozygous patient and haplotype analysis. Author(s): Chabas A, Gort L, Montfort M, Castello F, Dominguez MC, Grinberg D, Vilageliu L. Source: Journal of Medical Genetics. 1998 September; 35(9): 775-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9733040

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Remaining problems in the management of patients with Gaucher disease. Author(s): Erikson A. Source: Journal of Inherited Metabolic Disease. 2001; 24 Suppl 2: 122-6; Discussion 87-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11758672

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Repeat abdominal ultrasound evaluation of 100 patients with type I Gaucher disease treated with enzyme replacement therapy for up to 7 years. Author(s): Patlas M, Hadas-Halpern I, Abrahamov A, Zimran A, Elstein D. Source: The Hematology Journal : the Official Journal of the European Haematology Association / Eha. 2002; 3(1): 17-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11960391

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Retroviral transfer of the glucocerebrosidase gene into CD34+ cells from patients with Gaucher disease: in vivo detection of transduced cells without myeloablation. Author(s): Dunbar CE, Kohn DB, Schiffmann R, Barton NW, Nolta JA, Esplin JA, Pensiero M, Long Z, Lockey C, Emmons RV, Csik S, Leitman S, Krebs CB, Carter C, Brady RO, Karlsson S. Source: Human Gene Therapy. 1998 November 20; 9(17): 2629-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9853529

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Routine magnetic resonance imaging of the spine in children with Gaucher disease: does it help therapeutic management? Author(s): Olsen E OE, McHugh K, Vellodi A. Source: Pediatric Radiology. 2003 November; 33(11): 782-5. Epub 2003 September 05. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12961047

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Severe type II Gaucher disease with ichthyosis, arthrogryposis and neuronal apoptosis: molecular and pathological analyses. Author(s): Finn LS, Zhang M, Chen SH, Scott CR. Source: American Journal of Medical Genetics. 2000 March 20; 91(3): 222-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10756347

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Skeletal aspects of Gaucher disease: a review. Author(s): Wenstrup RJ, Roca-Espiau M, Weinreb NJ, Bembi B. Source: The British Journal of Radiology. 2002; 75 Suppl 1: A2-12. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12036828

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Skeletal manifestations in Gaucher disease: presentation and treatment. Author(s): Lebel E, Itzchaki M, Elstein D, Hadas-Halpern I, Abrahamov A, Zimran A. Source: Isr Med Assoc J. 1999 December; 1(4): 267-71. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10731360

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Somatic mosaicism in a patient with Gaucher disease type 2: implication for genetic counseling and therapeutic decision-making. Author(s): Filocamo M, Bonuccelli G, Mazzotti R, Corsolini F, Stroppiano M, Regis S, Gatti R. Source: Blood Cells, Molecules & Diseases. 2000 December; 26(6): 611-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11358352

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Somatosensory evoked potentials as a marker of disease burden in type 3 Gaucher disease. Author(s): Garvey MA, Toro C, Goldstein S, Altarescu G, Wiggs EA, Hallett M, Schiffmann R. Source: Neurology. 2001 February 13; 56(3): 391-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11171908

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Spectrum of abdominal sonographic findings in 103 pediatric patients with Gaucher disease. Author(s): Patlas M, Hadas-Halpern I, Abrahamov A, Elstein D, Zimran A. Source: European Radiology. 2002 February; 12(2): 397-400. Epub 2001 September 07. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11870441

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Splenic lymphoma arising in a patient with Gaucher disease. A case report and review of the literature. Author(s): Bertram HC, Eldibany M, Padgett J, Dragon LH. Source: Archives of Pathology & Laboratory Medicine. 2003 May; 127(5): E242-5. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12708922

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Subarachnoid anesthesia in a patient with type I Gaucher disease. Author(s): Garcia Collada JC, Pereda Marin RM, Martinez AI, Miralles Serrano EM, Pacheco Lopez JF. Source: Acta Anaesthesiologica Scandinavica. 2003 January; 47(1): 106-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12492809

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Substrate reduction therapy: clinical evaluation in type 1 Gaucher disease. Author(s): Moyses C. Source: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences. 2003 May 29; 358(1433): 955-60. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12803929

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Substrate reduction therapy: miglustat as a remedy for symptomatic patients with Gaucher disease type 1. Author(s): Pastores GM, Barnett NL. Source: Expert Opinion on Investigational Drugs. 2003 February; 12(2): 273-81. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12556220

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Tc-99m sestamibi bone marrow scintigraphy in Gaucher disease. Author(s): Aharoni D, Krausz Y, Elstein D, Hadas-Halpern I, Zimran A. Source: Clinical Nuclear Medicine. 2002 July; 27(7): 503-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12072778

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The 1604A (R496H) mutation in Gaucher disease: genotype/phenotype correlation. Author(s): Brautbar A, Elstein D, Abrahamov A, Zeigler M, Chicco G, Beutler E, Scott CR, Zimran A. Source: Blood Cells, Molecules & Diseases. 2003 September-October; 31(2): 187-9; Discussion 190-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12972024

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The E326K mutation and Gaucher disease: mutation or polymorphism? Author(s): Park JK, Tayebi N, Stubblefield BK, LaMarca ME, MacKenzie JJ, Stone DL, Sidransky E. Source: Clinical Genetics. 2002 January; 61(1): 32-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11903352

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The identification of eight novel glucocerebrosidase (GBA) mutations in patients with Gaucher disease. Author(s): Orvisky E, Park JK, Parker A, Walker JM, Martin BM, Stubblefield BK, Uyama E, Tayebi N, Sidransky E. Source: Human Mutation. 2002 April; 19(4): 458-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11933202

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The interleukin-6 promoter polymorphism in Gaucher disease: a new modifier gene? Author(s): Altarescu G, Phillips M, Foldes AJ, Elstein D, Zimran A, Mates M. Source: Qjm : Monthly Journal of the Association of Physicians. 2003 August; 96(8): 5758. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12897342

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The role of the iminosugar N-butyldeoxynojirimycin (miglustat) in the management of type I (non-neuronopathic) Gaucher disease: a position statement. Author(s): Cox TM, Aerts JM, Andria G, Beck M, Belmatoug N, Bembi B, Chertkoff R, Vom Dahl S, Elstein D, Erikson A, Giralt M, Heitner R, Hollak C, Hrebicek M, Lewis S, Mehta A, Pastores GM, Rolfs A, Miranda MC, Zimran A; Advisory Council to the European Working Group on Gaucher Disease. Source: Journal of Inherited Metabolic Disease. 2003; 26(6): 513-26. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14605497

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Three Gaucher-disease-producing mutations in a patient with Gaucher disease: mechanism and diagnostic implications. Author(s): Beutler E, Liebman H, Gelbart T, Stefanski E. Source: Acta Haematologica. 2000; 104(2-3): 103-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11154983

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Thrombocytosis associated with enzyme replacement therapy in Gaucher disease. Author(s): Dweck A, Blickstein D, Elstein D, Zimran A. Source: Acta Haematologica. 2002; 108(2): 94-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12187028

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Type I Gaucher disease in children with and without enzyme therapy. Author(s): Dweck A, Abrahamov A, Hadas-Halpern I, Bdolach-Avram T, Zimran A, Elstein D. Source: Pediatric Hematology and Oncology. 2002 September; 19(6): 389-97. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12186361

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Type II Gaucher disease: compound heterozygote with RecNciI and L444P mutations. Author(s): Lee YS, Poh LK, Ida H, Loke KY. Source: Journal of Tropical Pediatrics. 2001 April; 47(2): 115-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11336129

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Uncoupling of blood flow and oxygen metabolism in the cerebellum in type 3 Gaucher disease. Author(s): Yoshikawa H, Fueki N, Sasaki M, Sakuragawa N. Source: Brain & Development. 1991 May; 13(3): 190-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1928613

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Unsuccessful chimeraplast strategy for the correction of a mutation causing Gaucher disease. Author(s): Diaz-Font A, Cormand B, Chabas A, Vilageliu L, Grinberg D. Source: Blood Cells, Molecules & Diseases. 2003 September-October; 31(2): 183-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12972023

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Use of activators and inhibitors to define the properties of the active site of normal and Gaucher disease lysosomal beta-glucosidase. Author(s): Gatt S, Dinur T, Osiecki K, Desnick RJ, Grabowski GA. Source: Enzyme. 1985; 33(2): 109-19. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3924590

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Use of enzyme replacement therapy for Gaucher disease during pregnancy. Author(s): Elstein D, Granovsky-Grisaru S, Rabinowitz R, Kanai R, Abrahamov A, Zimran A. Source: American Journal of Obstetrics and Gynecology. 1997 December; 177(6): 1509-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9423759

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Use of various diagnostic methods in a patient with Gaucher disease type I. Author(s): Farahati J, Trenn G, John-Mikolajewski V, Zander C, Pastores GM, Sciuk J, Reiners C. Source: Clinical Nuclear Medicine. 1996 August; 21(8): 619-25. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8853914

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Variant Gaucher disease characterized by dysmorphic features, absence of cardiovascular involvement, laryngospasm, and compound heterozygosity for a novel mutation (D409H/C16S). Author(s): Bodamer OA, Church HJ, Cooper A, Wraith JE, Scott CR, Scaglia F. Source: American Journal of Medical Genetics. 2002 May 15; 109(4): 328-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11992489

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Vertebra disc ratio as a parameter for bone marrow involvement and its application in Gaucher disease. Author(s): Vlieger EJ, Maas M, Akkerman EM, Hollak CE, Den Heeten GJ. Source: Journal of Computer Assisted Tomography. 2002 September-October; 26(5): 8438. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12439326

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Viral infections and phenotypic heterogeneity in Gaucher disease. Author(s): Pines G, Morag A, Elstein D, Abrahamov A, Zimran A. Source: Blood Cells, Molecules & Diseases. 2001 March-April; 27(2): 358-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11259156

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Wandering spleen in a young girl with Gaucher disease. Author(s): Dweck A, Abrahamov A, Hadas-Halpern I, Zimran A, Elstein D. Source: Isr Med Assoc J. 2001 August; 3(8): 623-4. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11519393

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X-ray structure of human acid-beta-glucosidase, the defective enzyme in Gaucher disease. Author(s): Dvir H, Harel M, McCarthy AA, Toker L, Silman I, Futerman AH, Sussman JL. Source: Embo Reports. 2003 July; 4(7): 704-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12792654

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Y418C: a novel mutation in exon 9 of the glucocerebrosidase gene of a patient with Gaucher disease creates a new Bgl I site. Author(s): Tuteja R, Tuteja N, Lilliu F, Bembi B, Galanello R, Cao A, Baralle FE. Source: Human Genetics. 1994 September; 94(3): 314-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8076951

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CHAPTER 2. NUTRITION AND GAUCHER DISEASE Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and Gaucher disease.

Finding Nutrition Studies on Gaucher Disease 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 “Gaucher disease” (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 “Gaucher disease” (or a synonym): •

Adult Gaucher disease in association with primary malignant bone tumors. Author(s): Department of Orthopedic Surgery, Eberhard-Karls-Universitat, HoppeSeyler-Strasse 3, 72076 Tubingen, Germany. [email protected] Source: Bohm, P Kunz, W Horny, H P Einsele, H Cancer. 2001 February 1; 91(3): 457-62 0008-543X

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Coagulation abnormalities in type 1 Gaucher disease are due to low-grade activation and can be partly restored by enzyme supplementation therapy. Author(s): Department of Internal Medicine and Haematology, Academic Medical Centre, Amsterdam, The Netherlands. Source: Hollak, C E Levi, M Berends, F Aerts, J M van Oers, M H Br-J-Haematol. 1997 March; 96(3): 470-6 0007-1048

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Complete restoration of glucocerebrosidase deficiency in Gaucher fibroblasts using a bicistronic MDR retrovirus and a new selection strategy. Author(s): Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, Md 20892, USA. Source: Aran, J M Licht, T Gottesman, M M Pastan, I Hum-Gene-Ther. 1996 November 10; 7(17): 2165-75 1043-0342

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In vitro accumulation of glucocerebroside in neuroblastoma cells: a model for study of Gaucher disease pathobiology. Author(s): Division of Medical Genetics, Shriver Center for Mental Retardation, Waltham, Massachusetts, USA. Source: Prence, E M Chaturvedi, P Newburg, D S J-Neurosci-Res. 1996 February 1; 43(3): 365-71 0360-4012

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Phosphatidylcholine synthesis is elevated in neuronal models of Gaucher disease due to direct activation of CTP:phosphocholine cytidylyltransferase by glucosylceramide. Author(s): Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel. Source: Bodennec, J Pelled, D Riebeling, C Trajkovic, S Futerman, A H FASEB-J. 2002 November; 16(13): 1814-6 1530-6860

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 GAUCHER DISEASE Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to Gaucher disease. 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 Gaucher disease 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 “Gaucher disease” (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 Gaucher disease: •

Adult Gaucher disease in association with primary malignant bone tumors. Author(s): Bohm P, Kunz W, Horny HP, Einsele H. Source: Cancer. 2001 February 1; 91(3): 457-62. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11169926

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Association of Hodgkin disease and Gaucher disease. Author(s): Sharer LR, Barondess JA, Silver RT, Gray GF. Source: Arch Pathol. 1974 December; 98(6): 376-8. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4418365

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Characterization of the cytoplasmic inclusion bodies of the spleens from patients with adult form Gaucher's disease. Author(s): Ebato H, Abe T, Yamakawa T, Nagashima K.

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Source: Journal of Biochemistry. 1980 December; 88(6): 1765-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6257671 •

Collaborative research. Author(s): Graham OC, Harnett NE, Harrison E, Considine E. Source: The Journal of Neuroscience Nursing : Journal of the American Association of Neuroscience Nurses. 1994 April; 26(2): 121-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8077774

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Complete restoration of glucocerebrosidase deficiency in Gaucher fibroblasts using a bicistronic MDR retrovirus and a new selection strategy. Author(s): Aran JM, Licht T, Gottesman MM, Pastan I. Source: Human Gene Therapy. 1996 November 10; 7(17): 2165-75. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8934230

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Creating the costliest orphan. The Orphan Drug Act in the development of Ceredase. Author(s): Goldman DP, Clarke AE, Garber AM. Source: International Journal of Technology Assessment in Health Care. 1992 Fall; 8(4): 583-97. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1464480

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Deterioration of the auditory brainstem response in children with type 3 Gaucher disease. Author(s): Campbell PE, Harris CM, Vellodi A. Source: Neurology. 2004 July 27; 63(2): 385-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15277647

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Gaucher's disease. Author(s): Lewis S. Source: Journal of the Royal Society of Medicine. 1992 November; 85(11): 714. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1474570

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Leukocyte sonicates as a source for both enzyme assay and DNA amplification for mutational analysis of certain lysosomal disorders. Author(s): Louie E, Rafi MA, Wenger DA. Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. 1991 May 31; 199(1): 7-15. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1682071

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Non-Hodgkin's lymphoma associated with Gaucher's disease. Author(s): Perales M, Cervantes F, Cobo F, Montserrat E.

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Source: Leukemia & Lymphoma. 1998 November; 31(5-6): 609-12. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9922052 •

Plasma chitotriosidase activity in patients with beta-thalassemia. Author(s): Barone R, Di Gregorio F, Romeo MA, Schiliro G, Pavone L. Source: Blood Cells, Molecules & Diseases. 1999 February; 25(1): 1-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10349508

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Sphingomyelinase in normal human spleens and in spleens from subjects with Niemann-Pick disease. Author(s): Schneider PB, Kennedy EP. Source: Journal of Lipid Research. 1967 May; 8(3): 202-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4962590

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/

•

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

•

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

•

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

•

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

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

•

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

•

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

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.

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This Web site provides a general overview of various topics and can lead to a number of general sources.

65

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

Patents on Gaucher Disease By performing a patent search focusing on Gaucher disease, 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. 8Adapted

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

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The following is an example of the type of information that you can expect to obtain from a patent search on Gaucher disease: •

Assay for a new Gaucher disease mutation Inventor(s): Beutler; Ernest (La Jolla, CA), Sorge; Joseph A. (Rancho Santa Fe, CA) Assignee(s): The Scripps Research Institute (La Jolla, CA) Patent Number: 5,234,811 Date filed: September 27, 1991 Abstract: A method for detecting a new Gaucher disease mutation in an allele in a human having an insertion mutation of a guanine nucleotide adjacent to nucleotide position 57 in the normal glucocerebrosidase gene exon 2 is provided. Identification of the mutation is accomplished by first amplifying, with a polymerase chain reaction (PCR) primer, a region of human genomic DNA containing nucleotide positions 57 and 58 of glucocerebrosidase gene exon 2 followed by detection of the mutation. Excerpt(s): The present invention relates to a method for detecting a Gaucher disease allele in a human having an insertion mutation of a guanine nucleotide adjacent to nucleotide position 57 in the normal glucocerebrosidase gene exon 2. Gaucher disease is an autosomal recessive disorder caused by a deficiency of glucocerebrosidase, the enzyme that is required for the lysosomal degradation of lipids containing covalently bound sugars (glycolipids). Brady et al., J. Biol. Chem., 240:39-43 (1965). In the absence of glucocerebrosidase, the extremely insoluble glucosylceramide (glucocerebroside) accumulates. The gene for glucocerebrosidase is located on chromosome-1 in the region of q21. See, Shafit-Zagardo et al., Am. J. Hum Genet., 33:564-575 (1981); Ginns et al., Proc. Natl. Acad. Sci., U.S.A., 82:7101-7105 (1985). The fact that a number of different mutations caused Gaucher disease was inferred from clinical observations (Beutler, Genetic Diseases Among Ashkenazi Jews, eds. Boudman et al., Raven Press, NY, pp. 157-169 (1979)) and from differences in the kinetic properties of the residual enzyme in different patients with the disorder. Grabowski et al., Am J. Hum. Genet., 37:499-510 (1985). However, real understanding of the genetics of this disease has had to await the cloning and sequencing of the cDNA (Sorge et al., Proc. Natl. Acad. Sci., U.S.A., 82:72897293 (1985) and Tsuji et al., N. Engl. J. Med., 316:570-621 (1987)) and of the gene (Horowitz et al., Genomics, 4:87-96 (1989)). Analysis of mutations is complicated by the existence of a pseudogene which is approximately 16 kilobases (Kb) downstream from the glucocerebrosidase gene. Zimran et al., J. Clin. Invest., 86:1137-1141 (1990). The pseudogene is about 95% homologous to the functional gene. It is transcribed (Sorge et al., J. Clin. Invest., 86:1137-1141 (1990)), but cannot be translated into glucocerebrosidase because of numerous deletions of coding sequences. Web site: http://www.delphion.com/details?pn=US05234811__

•

Gene therapy for Gaucher disease using retroviral vectors Inventor(s): Bahnson; Alfred B. (Pittsburgh, PA), Barranger; John A. (Gibsonia, PA), Robbins; Paul (Pittsburgh, PA) Assignee(s): University of Pittsburgh (Pittsburgh, PA) Patent Number: 5,911,983 Date filed: June 6, 1995

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Abstract: The present invention relates to gene therapy for Gaucher disease using retroviral vectors which express the glucocerebrosidase gene. Methods are provided for transduction of autologous hematopoietic stem cells (e.g., human CD34+ cells) with these vectors and for transplantation of the transduced cells into a Gaucher disease patient to provide therapeutically effective levels of glucocerebrosidase activity. The invention also provides for retroviral vectors that express the glucocerebrosidase gene, and for human hematopoietic cells that contain the retroviral vector. Excerpt(s): Gaucher disease is the name given to a group of lysosomal storage disorders caused by mutations in the gene that codes for an enzyme called glucocerebrosidase ("GC"). Gaucher disease is caused by deficiency of GC as reported by Patrick, A. D., Biochem. J. 97:17C (1965) and Brady, R. O., et al., Biochem. Biophys. Res. Commun. 18:221 (1965). All of the mutations in the gene alter the structure and function of the enzyme which lead to an accumulation of the undegraded glycolipid substrate glucosylceramide, also called glucocerebroside, in cells of the reticuloendothelial system. Each particular mutation of the human GC gene leads to a clinical disease collectively known as Gaucher disease. These disorders are usually classified into three types; type 1 (non-neuronopathic), type 2 (acute neuronopathic) and type 3 (subacute neuronopathic), the type depending on the presence and severity of neurologic involvement. Gaucher disease is the most prevalent Jewish genetic disease and the most common lysosomal storage disease. Human GC cDNA was first cloned as described by Ginns, E. I., et al., Biochem. Biophys. Res. Commun. 123:574 (1984). Subsequent characterizations of other GC cDNA clones by, for example, Sorge, J., et al., Proc. Nat. Acad. Sci. USA 82:7289 (1985) and Tsuji, S., et al., J. Biol. Chem. 261:50 (1986), have led to the elucidation of the complete nucleotide sequence of human GC. As reported by Ginns, E. I., et al., Proc. Nat. Acad. Sci. USA 82:7101 (1985), the GC gene was localized to human chromosome lq21 by in situ hybridization. Tsuji, S., et al., New Enql. J. Med. 316:570 (1987), have shown that the GC gene comprises 11 exons and 10 introns spanning approximately 7 Kb. While more than twenty mutations in the human GC gene are known, only two are common. See, Tsuji, S., et al., Proc. Natl. Acad. Sci. USA 85:2349 (1988). The two common mutations account for approximately 70% of the mutant alleles, as reported by Firon, N., et al., Am. J. Hum. Genet. 46:527 (1990). Mutant GC genes code for aberrant proteins that are either catalytically altered or unstable and rapidly disappear from the cell. Web site: http://www.delphion.com/details?pn=US05911983__ •

Products and methods for Gaucher disease therapy Inventor(s): Callahan; John W. (Mississauga, CA), Clarke; Joe T. R. (Toronto, CA), Mahuran; Don J. (Toronto, CA) Assignee(s): HSC Research & Development Limited Partnership (CA) Patent Number: 6,696,272 Date filed: June 2, 2000 Abstract: The invention relates to products and methods for medical treatment of Gaucher disease and, in particular, an improved Gcc DNA for insertion into any applicable expression vector for gene therapy treatment. The invention includes an isolated Gcc DNA molecule, wherein nucleic acid molecules have been modified at cryptic splice sites to prevent or decrease splicing of mRNA produced from the DNA molecule, while preserving the ability of the DNA to express functional Gcc polypeptides.

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Excerpt(s): The invention relates to products and methods for medical treatment of Gaucher disease and, in particular, nucleic acid molecules, polypeptides and vectors for polypeptide or gene therapy treatment. Gaucher disease is a lysosomal storage disease caused by the deficiency of functional glucocerebrosidase (Gcc) enzyme. Gcc is present in all cell types. The defective enzyme cannot break down a fatty substance, glucocerebroside, which is an important component of cell membranes. The fat accumulates in macrophages (which are known as the "Gaucher cells"). The fat-laden macrophages are found typically in the liver, spleen, bone marrow and lungs. The amount of the enzyme deficiency varies from person to person as do the symptoms. Some patients may show no clinical symptoms, while others may die from the disease. The symptoms of the disease and mutant forms of Gcc that cause Gaucher disease are described, for example, in U.S. Pat. No. 5,266,459 (Beutler) and U.S. Pat. No. 5,234,811 (Beutler and Sorge). There are therapies for Gaucher disease. Ceredase is a form of the Gcc enzyme from placenta that is able to metabolize the fat in Gaucher cells. The enzyme restores normal function to a Gaucher cell. The amount of enzyme used in treatment varies. As much as 30-60 units per kilogram of bodyweight (U/kg/bw) may be given every other week. Positive results have been reported with 2.3 U/kg/bw given three times a week. Lower doses, such as 1-5 U/kg/bw twice weekly, have also been used with success, but this is less frequent. The intarcellular half life of the enzyme is up to 60 hours. A large number of placentas are needed to make sufficient Ceredase, so this form of therapy is very expensive. It has been almost completely replaced by treatment with a recombinant form of the enzyme, Cerezyme but this therapy is also expensive. Cerezyme is dispensed as a powder whereas Ceredase comes as a liquid. Sterile water must be added to the Cerezyme bottle to dissolve the powder. The shelf life of the drugs is short (<3 months), and splitting doses is cumbersome and wasteful. Allergic reactions to Ceredase are common, but rarely life-threatening. Adverse reactions to Cerezyme appear to be less common, but experience with the drug is still very limited. Web site: http://www.delphion.com/details?pn=US06696272__

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

Method for enhancing mutant enzyme activity in Gaucher disease Inventor(s): Asano, Naoki; (Ishikawa, JP), Desnick, Robert J.; (New York, NY), Fan, JianQiang; (New York, NY), Ishii, Satoshi; (Oita, JP) Correspondence: Darby & Darby P.C.; Post Office Box 5257; New York; NY; 10150-5257; US Patent Application Number: 20030119874 Date filed: November 26, 2002 Abstract: Method for enhancing in a mammalian cell the activity of an enzyme associated with Gaucher Disease by administering a competitive inhibitor of glucocerebrosidase in an amount effective to enhance the activity of the enzyme.

9

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

Patents 69

Preferred compounds for use in the method are imino sugars and related compounds. In particular, C8-12-alkyl derivatives of N-alkyl-deoxynojirimycin, isofagomine compounds, and calystegine compoiunds are effective to enhance glucocerebrosidase activity. Excerpt(s): This is a continuation of application Ser. No. 09/948,348, filed Sep. 7, 2001, which is a continuation of application Ser. No. 09/604,053, filed Jun. 26, 2000, which is a continuation-in-part of application Ser. No. 08,087,80, filed Jun. 1, 1998, now U.S. Pat. No. 6,274,597. Each of these prior references in hereby incorporated herein by reference. This invention relates to a method of enhancing mutant enzyme activities in lysosomal storage disorders by administration of competitive inhibitors of the enzymes, in particular, imino sugars and related compounds. Proteins are synthesized in the cytoplasm, and the newly synthesized proteins are secreted into the lumen of the endoplasmic reticulum (ER) in a largely unfolded state. In general, protein folding is an event governed by a principle of self assembly. The tendency of proteins to fold into their native (active) conformation is contained in their amino acid sequences (1). In vitro, the primary structure folds into secondary structres of.alpha.-helices and.beta.-sheets coupled with hydrophobic collapse in the formation of biologically active tertiarystructure which also gains increased conformational stability. However, the folding of protein in vivo is rather complicated, because the combination of ambient temperature and high protein concentration stimulates the process of aggregation, in which amino acids normally buried in the hydrophobic core interact with their neighbors non-specifically. To avoid this problem, protein folding is usually facilitated by a special group of proteins called molecular chaperones which prevent nascent polypeptide chains from aggregating, and bind to protein so that the protein refolds in the active state (2). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Methods of enhancing lysosomal storage disease therapy by modulation of cell surface receptor density Inventor(s): Cheng, Seng H.; (Wellesley, MA), Zhu, Yunxiang; (Wayland, MA) Correspondence: Hamilton, Brook, Smith & Reynolds, P.C.; 530 Virginia Road; P.O. Box 9133; Concord; MA; 01742-9133; US Patent Application Number: 20040029779 Date filed: April 4, 2003 Abstract: Methods of modulating uptake of extracellular lysosomal enzymes by administering a pharmaceutical agent and methods of treating a lysosomal storage disease (such as Gaucher disease, Pompe disease, Fabry disease or Niemann-Pick disease) or enhancing enzyme replacement therapy or gene therapy, comprising administering a pharmaceutical agent such as dexamethasone, glucose or insulin, are provided. Excerpt(s): This application claims the benefit of U.S. Provisional Application No. 60/370,747 filed Apr. 5, 2002. The entire teachings of the above application are incorporated herein by reference. Lysosomal storage diseases are a group of rare genetic disorders comprising more than forty individual diseases. Currently, a promising treatment for these diseases is enzyme replacement therapy (ERT). Gene therapy, which employs a depot expression strategy where high-level expression of lysosomal enzymes in one organ can be secreted into the blood stream and carried to other organs for

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uptake, is another promising option. One of the major issues with ERT treatment for lysosomal storage diseases is that the infused lysosomal enzymes are rapidly removed from the blood stream by the liver, either through carbohydrate-binding receptors or non-specifically. For substrate deprivation and small molecule therapies, ERT, gene therapy, and combinations thereof, more efficient uptake of lysosomal enzymes circulating in the blood stream by target cells and/or organs would be desirable. It has now been found that the uptake of extracellular lysosomal enzymes by cells can be increased by up-regulating the cell surface expression and density of carbohydrate binding receptors. For example, up-regulation of the mannose receptor on macrophage cells by a glucocorticosteroid such as dexamethasone, for example, increases the target organ uptake of glucocerebrosidase for the treatment of Gaucher disease (see, e.g., Examples 1 and 2). Furthermore, the dexamethasone-induced increase in glucocerebrosidase uptake is selective for macrophage cells, which are the cells most severely affected by Gaucher disease. Likewise, up-regulation of the mannose 6phosphate/IGF-II receptor (M6P/IGF-II) by insulin/glucose on muscle cell surfaces increases target organ uptake of acid alpha-glucosidase which is needed for the treatment of Pompe's disease (see, e.g., Examples 3 and 4). Based on these discoveries, methods of treating lysosomal storage diseases are contemplated herein. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Methods of screening for inhibitors of phospholipid synthesis related to glycolipidstorage diseases Inventor(s): Bodennec, Jacques; (Lesneven, FR), Futerman, Anthony H.; (Rehovot, IL), Pelled, Dori; (Rehovot, IL), Riebeling, Christian; (Gutersloh, DE), Trajkovic, Selena; (Belgrade, YU) Correspondence: Winston & Strawn; Patent Department; 1400 L Street, N.W.; Washington; DC; 20005-3502; US Patent Application Number: 20040137531 Date filed: January 15, 2003 Abstract: The present invention discloses methods of screening for identification of compounds that inhibit novel targets in the enzymatic pathway of phospholipid synthesis that are related to glycolipid storage diseases, and use of the compounds for treating patients affected with glycolipid storage diseases, particularly Gaucher disease. Specifically, the compounds of the present invention are intended to inhibit the accumulation of phosphatidylcholine (PC), wherein PC accumulation is increased due to the activation of CTP:phosphocholine cytidylyltransferase (CCT) upon glucosylceramide (GlcCer) accumulation. Excerpt(s): The present invention relates in general to the field of glycolipid storage diseases, more particularly to methods of screening for drugs for the treatment of glycolipid storage diseases, specifically for compounds that inhibit deleterious phospholipid synthesis. In humans, a number of inherited disorders occur in lysosomal sphingolipid catabolism (commonly known as "sphingolipidoses"). For example, an inherited deficiency of the lysosomal sphingomyelinase underlies Niemann-Pick disease, and defective activity of the lysosomal ceramidase causes Farber disease. The most frequently encountered disorder of sphingolipid catabolism is Gaucher disease (Barranger J A and Ginns E I.1989. Glucosylceramide lipidoses: Gaucher's disease. In: The Metabolic Basis of Inherited Diseases. C R Scriver, A L Beaudent, W S Sly & D Valle, Eds. McGraw-Hill Inc. New York, 1677-1698). The metabolic basis of this disorder is a

Patents 71

deficiency in activity of the catabolic beta-glucosidase enzyme, glucocerebrosidase (E.C.3.2.1.45), which catalyzes the hydrolysis of glucosylceramide (glucocerebroside) to glucose and ceramide. In patients with Gaucher disease glucosylceramide (GlcCer) accumulates in tubular aggregates, in particular in lysosomes of macrophages. The lipid-laden macrophages have a typical morphology and are usually referred to as "Gaucher cells". In the course of clinical manifestation of Gaucher disease the abnormal macrophages may accumulate in large quantities in various body locations, such as the bone marrow compartment, spleen, liver, kidney, and lungs. The most pronounced clinical symptoms associated with Gaucher disease are progressive splenomegaly, hepatomegaly, and skeletal deterioration. Most Gaucher disease patients do not develop neurological complications. The common non-neuronopathic form of the disease is called Type 1 Gaucher disease. In very severe cases of Gaucher disease characteristic neurological abnormalities may also occur, resulting in lethal complications at infantile (Type 2) or juvenile (Type 3) stages of development. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Products and methods for Gaucher disease therpy Inventor(s): Callahan, John W.; (Mississauga, CA), Clarke, Joe T.R.; (Toronto, CA), Mahuran, Don J.; (Toronto, CA) Correspondence: Synnestvedt & Lechner, Llp; 2600 Aramark Tower; 1101 Market Street; Philadelphia; PA; 191072950 Patent Application Number: 20040082535 Date filed: November 12, 2003 Abstract: The invention relates to products and methods for medical treatment of Gaucher disease and, in particular, an improved Gcc DNA for insertion into any applicable expression vector for gene therapy treatment. The invention includes an isolated Gcc DNA molecule, wherein nucleic acid molecules have been modified at cryptic splice sites to prevent or decrease splicing of mRNA produced from the DNA molecule, while preserving the ability of the DNA to express functional Gcc polypeptides. Excerpt(s): The invention relates to products and methods for medical treatment of Gaucher disease and, in particular, nucleic acid molecules, polypeptides and vectors for polypeptide or gene therapy treatment. Gaucher disease is a lysosomal storage disease caused by the deficiency of functional glucocerebrosidase (Gcc) enzyme. Gcc is present in all cell types. The defective enzyme cannot break down a fatty substance, glucocerebroside, which is an important component of cell membranes. The fat accumulates in macrophages (which are known as the "Gaucher cells"). The fat-laden macrophages are found typically in the liver, spleen, bone marrow and lungs. The amount of the enzyme deficiency varies from person to person as do the symptoms. Some patients may show no clinical symptoms, while others may die from the disease. The symptoms of the disease and mutant forms of Gcc that cause Gaucher disease are described, for example, in U.S. Pat. No. 5,266,459 (Beutler) and U.S. Pat. No. 5,234,811 (Beutler and Sorge). There are therapies for Gaucher disease. Ceredase is a form of the Gcc enzyme from placenta that is able to metabolize the fat in Gaucher cells. The enzyme restores normal function to a Gaucher cell. The amount of enzyme used in treatment varies. As much as 30-60 units per kilogram of bodyweight (U/kg/bw) may be given every other week. Positive results have been reported with 2.3 U/kg/bw given three times a week. Lower doses, such as 1-5 U/kg/bw twice weekly, have also been

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used with success, but this is less frequent. The intarcellular half life of the enzyme is up to 60 hours. A large number of placentas are needed to make sufficient Ceredase, so this form of therapy is very expensive. It has been almost completely replaced by treatment with a recombinant form of the enzyme, Cerezyme but this therapy is also expensive. Cerezyme is dispensed as a powder whereas Ceredase comes as a liquid. Sterile water must be added to the Cerezyme bottle to dissolve the powder. The shelf life of the drugs is short (<3 months), and splitting doses is cumbersome and wasteful. Allergic reactions to Ceredase are common, but rarely life-threatening. Adverse reactions to Cerezyme appear to be less common, but experience with the drug is still very limited. 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 Gaucher disease, 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 “Gaucher disease” (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 Gaucher disease. You can also use this procedure to view pending patent applications concerning Gaucher disease. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.

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CHAPTER 5. BOOKS ON GAUCHER DISEASE Overview This chapter provides bibliographic book references relating to Gaucher disease. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on Gaucher disease include the Combined Health Information Database and the National Library of Medicine. Your local medical library also may have these titles available for loan.

Book Summaries: Federal Agencies The Combined Health Information Database collects various book abstracts from a variety of healthcare institutions and federal agencies. To access these summaries, go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. You will need to use the “Detailed Search” option. To find book summaries, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer. For the format option, select “Monograph/Book.” Now type “Gaucher disease” (or synonyms) into the “For these words:” box. You should check back periodically with this database which is updated every three months. The following is a typical result when searching for books on Gaucher disease: •

Liver Disorders Sourcebook Source: Detroit, MI: Omnigraphics. 2000. 591 p. Contact: Available from Omnigraphics, Inc. 615 Griswold, Detroit, MI 48226. (800) 2341340. Fax (800) 875-1340. PRICE: $78.00 plus shipping and handling. ISBN: 0780802403. Summary: This Sourcebook provides basic health care information about liver functions, guidelines for liver health, and tests that assess liver distress. The book also presents the symptoms, treatments, and preventive measures available for liver cancer; hepatitis A, B, C, D and E; genetically based liver diseases; and other liver diseases. The liver transplantation process is explained. Specific topics include strategies for protecting the liver, risk factors, common laboratory tests in liver disease, liver biopsy, cancer tumor markers, cirrhosis (scarring of the liver), infectious agents and parasites, pregnancy and the liver, jaundice in the healthy newborn, the liver's response to drugs, alcohol and the

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liver, acetaminophen, herbs and alternative medicine, galactosemia, Gaucher disease, hereditary hemochromatosis, Niemann-Pick disease, Wilson's disease, biliary atresia, cystic disease of the liver, fatty liver, gallstones, primary biliary cirrhosis, primary sclerosing cholangitis, organ donation, and the bioartificial liver. A glossary, a directory of organizations and support groups with up to date contact information (including websites and email addresses), a listing of transplant centers, and a subject index conclude the volume.

Chapters on Gaucher Disease In order to find chapters that specifically relate to Gaucher disease, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and Gaucher disease 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 “Gaucher disease” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on Gaucher disease: •

Inborn Errors of Metabolism Source: in Thoene, J.G., ed. Physicians' Guide to Rare Diseases. 2nd ed. Montvale, NJ: Dowden Publishing Company. 1995. p. 167-248. Contact: Available from Dowden Publishing Company, Inc. 110 Summit Avenue, Montvale, NJ 07645. (201) 391-9100. Fax (201) 391-2778. PRICE: $97.50 plus shipping and handling. ISBN: 0962871613. Summary: This chapter, from a physicians' guidebook to rare diseases, discusses inborn errors of metabolism. The book's intent is to help doctors and their patients identify rare disorders and find treatments and support groups. After an introductory section, this chapter covers more than ninety disorders, including the following, which relate to the digestive system: Andersen disease; Fabry disease; Forbes disease; fructose intolerance; galactosemia; Gaucher disease; Menkes disease; phenylketonuria; porphyria; Refsum syndrome; Sandhoff disease; Tangier disease; vitamin E deficiency; von Gierke disease; Wilson disease; and Zellwinger syndrome. For each disorder, the author includes a description, synonyms, and information about signs and symptoms, etiology, epidemiology, related disorders, standard and investigational treatments, and support groups and additional resources. A brief reference list for each disorder is also included.

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

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

Europe's CPMP recommends approval of Oxford Glyco's Gaucher disease drug Source: Reuters Industry Breifing Date: July 26, 2002

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•

Oxford Glyco contracts Teva to tap Gaucher disease market in Israel Source: Reuters Industry Breifing Date: November 20, 2001

•

Oxford Glyco's Gaucher disease drug performs well in studies Source: Reuters Industry Breifing Date: September 24, 2001

•

Oxford GlycoSciences files Gaucher disease treatment for European approval Source: Reuters Industry Breifing Date: July 12, 2001

•

Subset Of Patients Treated For Gaucher Disease At Risk For Pulmonary Hypertension Source: Reuters Medical News Date: December 03, 1996 The NIH

Within MEDLINEplus, the NIH has made an agreement with the New York Times Syndicate, the AP News Service, and Reuters to deliver news that can be browsed by the public. Search news releases at http://www.nlm.nih.gov/medlineplus/alphanews_a.html. MEDLINEplus allows you to browse across an alphabetical index. Or you can search by date at the following Web page: http://www.nlm.nih.gov/medlineplus/newsbydate.html. Often, news items are indexed by MEDLINEplus within its search engine. Business Wire Business Wire is similar to PR Newswire. To access this archive, simply go to http://www.businesswire.com/. You can scan the news by industry category or company name. Market Wire Market Wire is more focused on technology than the other wires. To browse the latest press releases by topic, such as alternative medicine, biotechnology, fitness, healthcare, legal, nutrition, and pharmaceuticals, access Market Wire’s Medical/Health channel at http://www.marketwire.com/mw/release_index?channel=MedicalHealth. Or simply go to Market Wire’s home page at http://www.marketwire.com/mw/home, type “Gaucher disease” (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 “Gaucher disease” (or synonyms). If you know the name of a company that is relevant to

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Gaucher disease, 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 “Gaucher disease” (or synonyms).

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

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CHAPTER 7. RESEARCHING MEDICATIONS Overview While a number of hard copy or CD-ROM resources are available for researching medications, a more flexible method is to use Internet-based databases. Broadly speaking, there are two sources of information on approved medications: public sources and private sources. We will emphasize free-to-use public sources.

U.S. Pharmacopeia Because of historical investments by various organizations and the emergence of the Internet, it has become rather simple to learn about the medications recommended for Gaucher disease. 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 Gaucher disease 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 “Gaucher disease” (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 Gaucher disease: •

Alendronate disodium (trade name: Fosamax) http://www.rarediseases.org/nord/search/nodd_full?code=1082

•

Alendronate disodium (trade name: Fosamax) http://www.rarediseases.org/nord/search/nodd_full?code=1112

•

Alendronate disodium (trade name: Fosamax) http://www.rarediseases.org/nord/search/nodd_full?code=1143

•

Recombinant retroviral vectorglucocerebrosidase http://www.rarediseases.org/nord/search/nodd_full?code=383

•

Retroviral vector, R-GC and GC gene 1750 http://www.rarediseases.org/nord/search/nodd_full?code=894

•

1,5-(Butylimino)-1,5 dideoxy, D-glucitol http://www.rarediseases.org/nord/search/nodd_full?code=917

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

85

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

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

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

10

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

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•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

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

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

11

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

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•

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

•

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

The NLM Gateway13 The NLM (National Library of Medicine) Gateway is a Web-based system that lets users search simultaneously in multiple retrieval systems at the U.S. National Library of Medicine (NLM). It allows users of NLM services to initiate searches from one Web interface, providing one-stop searching for many of NLM’s information resources or databases.14 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “Gaucher disease” (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 2679 19 256 1 41 2996

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

13

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

14

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

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

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

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

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

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

•

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

18 Adapted 19

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

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

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

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Cardiomyopathy http://www.nlm.nih.gov/medlineplus/cardiomyopathy.html Gaucher's Disease http://www.nlm.nih.gov/medlineplus/gauchersdisease.html Genetic Brain Disorders http://www.nlm.nih.gov/medlineplus/geneticbraindisorders.html Leukodystrophies http://www.nlm.nih.gov/medlineplus/leukodystrophies.html Metabolic Disorders http://www.nlm.nih.gov/medlineplus/metabolicdisorders.html Syringomyelia http://www.nlm.nih.gov/medlineplus/syringomyelia.html Tay-Sachs Disease http://www.nlm.nih.gov/medlineplus/taysachsdisease.html You may also choose to use the search utility provided by MEDLINEplus at the following Web address: http://www.nlm.nih.gov/medlineplus/. Simply type a keyword into the search box and click “Search.” This utility is similar to the NIH search utility, with the exception that it only includes materials that are linked within the MEDLINEplus system (mostly patient-oriented information). It also has the disadvantage of generating unstructured results. We recommend, therefore, that you use this method only if you have a very targeted search. The NIH Search Utility The NIH search utility allows you to search for documents on over 100 selected Web sites that comprise the NIH-WEB-SPACE. Each of these servers is “crawled” and indexed on an ongoing basis. Your search will produce a list of various documents, all of which will relate in some way to Gaucher disease. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html. Additional Web Sources A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •

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

•

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

•

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

•

Med Help International: http://www.medhelp.org/HealthTopics/A.html

Patient Resources

•

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

•

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

•

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

93

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

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option “Organization Resource Sheet.” Type “Gaucher disease” (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 “Gaucher disease” (or a synonym) into the search box, and click “Submit Query.”

95

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

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

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

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

21

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

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

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

•

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

•

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

•

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

•

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

•

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

•

California: Gateway Health Library (Sutter Gould Medical Foundation)

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

22

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

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•

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

•

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Finding Medical Libraries

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

•

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/

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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). The NIH suggests the following Web sites in the ADAM Medical Encyclopedia when searching for information on Gaucher disease: •

Basic Guidelines for Gaucher Disease Gaucher disease Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000564.htm

•

Signs & Symptoms for Gaucher Disease Anemia Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000560.htm Ataxia Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003198.htm Bruising Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003235.htm Early satiety Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003127.htm

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Hepatomegaly Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003275.htm Paralysis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003190.htm Seizures Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003200.htm Splenomegaly Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003276.htm •

Diagnostics and Tests for Gaucher Disease Biopsy of the spleen Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003416.htm Bone marrow aspiration Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003658.htm CT Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003330.htm X-ray Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003337.htm X-ray of the skeleton Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003381.htm

•

Surgery and Procedures for Gaucher Disease Splenectomy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002944.htm

•

Background Topics for Gaucher Disease Central nervous system Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002311.htm

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

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

•

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

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•

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

•

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

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GAUCHER DISEASE DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. Abdomen: That portion of the body that lies between the thorax and the pelvis. [NIH] Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Aberrant: Wandering or deviating from the usual or normal course. [EU] Acetaminophen: Analgesic antipyretic derivative of acetanilide. It has weak antiinflammatory properties and is used as a common analgesic, but may cause liver, blood cell, and kidney damage. [NIH] Acid Phosphatase: An enzyme that catalyzes the conversion of an orthophosphoric monoester and water to an alcohol and orthophosphate. EC 3.1.3.2. [NIH] Adaptability: Ability to develop some form of tolerance to conditions extremely different from those under which a living organism evolved. [NIH] Adrenal Glands: Paired glands situated in the retroperitoneal tissues at the superior pole of each kidney. [NIH] Adrenoleukodystrophy: A chromosome X-linked disease. [NIH] Adverse Effect: An unwanted side effect of treatment. [NIH] Aerobic: In biochemistry, reactions that need oxygen to happen or happen when oxygen is present. [NIH] 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] Albumin: 1. Any protein that is soluble in water and moderately concentrated salt solutions and is coagulable by heat. 2. Serum albumin; the major plasma protein (approximately 60 per cent of the total), which is responsible for much of the plasma colloidal osmotic pressure and serves as a transport protein carrying large organic anions, such as fatty acids, bilirubin, and many drugs, and also carrying certain hormones, such as cortisol and thyroxine, when their specific binding globulins are saturated. Albumin is synthesized in the liver. Low serum levels occur in protein malnutrition, active inflammation and serious hepatic and renal disease. [EU] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alleles: Mutually exclusive forms of the same gene, occupying the same locus on

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homologous chromosomes, and governing the same biochemical and developmental process. [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] Alveolar Process: The thickest and spongiest part of the maxilla and mandible hollowed out into deep cavities for the teeth. [NIH] Amino acid: Any organic compound containing an amino (-NH2 and a carboxyl (- COOH) group. The 20 a-amino acids listed in the accompanying table are the amino acids from which proteins are synthesized by formation of peptide bonds during ribosomal translation of messenger RNA; all except glycine, which is not optically active, have the L configuration. Other amino acids occurring in proteins, such as hydroxyproline in collagen, are formed by posttranslational enzymatic modification of amino acids residues in polypeptide chains. There are also several important amino acids, such as the neurotransmitter y-aminobutyric acid, that have no relation to proteins. Abbreviated AA. [EU] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Amplification: The production of additional copies of a chromosomal DNA sequence, found as either intrachromosomal or extrachromosomal DNA. [NIH] Ampulla: A sac-like enlargement of a canal or duct. [NIH] Amyloidosis: A group of diseases in which protein is deposited in specific organs (localized amyloidosis) or throughout the body (systemic amyloidosis). Amyloidosis may be either primary (with no known cause) or secondary (caused by another disease, including some types of cancer). Generally, primary amyloidosis affects the nerves, skin, tongue, joints, heart, and liver; secondary amyloidosis often affects the spleen, kidneys, liver, and adrenal glands. [NIH] Analgesic: An agent that alleviates pain without causing loss of consciousness. [EU] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [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] Angiography: Radiography of blood vessels after injection of a contrast medium. [NIH] Angioma: A tumor composed of lymphatic or blood vessels. [NIH] Animal model: An animal with a disease either the same as or like a disease in humans. Animal models are used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis. [NIH] Ankle: That part of the lower limb directly above the foot. [NIH] Annealing: The spontaneous alignment of two single DNA strands to form a double helix. [NIH]

Dictionary 107

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] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Antipyretic: An agent that relieves or reduces fever. Called also antifebrile, antithermic and febrifuge. [EU] Apoptosis: One of the two mechanisms by which cell death occurs (the other being the pathological process of necrosis). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA (DNA fragmentation) at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. [NIH] Apraxia: Loss of ability to perform purposeful movements, in the absence of paralysis or sensory disturbance, caused by lesions in the cortex. [NIH] Aqueous: Having to do with water. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [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] Artery: Vessel-carrying blood from the heart to various parts of the body. [NIH] Arthroplasty: Surgical reconstruction of a joint to relieve pain or restore motion. [NIH] Aspiration: The act of inhaling. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Asymptomatic: Having no signs or symptoms of disease. [NIH]

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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] Atypical: Irregular; not conformable to the type; in microbiology, applied specifically to strains of unusual type. [EU] Auditory: Pertaining to the sense of hearing. [EU] Autologous: Taken from an individual's own tissues, cells, or DNA. [NIH] 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] Beta-Glucosidase: An enzyme that catalyzes the hydrolysis of terminal non-reducing residues in beta-D-glucosides with release of beta-glucose. EC 3.2.1.21. [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] Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Bile Acids: Acids made by the liver that work with bile to break down fats. [NIH] Bile duct: A tube through which bile passes in and out of the liver. [NIH] Bile Pigments: Pigments that give a characteristic color to bile including: bilirubin, biliverdine, and bilicyanin. [NIH] Biliary: Having to do with the liver, bile ducts, and/or gallbladder. [NIH] Biliary Atresia: Atresia of the biliary tract, most commonly of the extrahepatic bile ducts. [NIH]

Biliary Tract: The gallbladder and its ducts. [NIH] Bilirubin: A bile pigment that is a degradation product of heme. [NIH] Binding Sites: The reactive parts of a macromolecule that directly participate in its specific combination with another molecule. [NIH] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biological therapy: Treatment to stimulate or restore the ability of the immune system to fight infection and disease. Also used to lessen side effects that may be caused by some

Dictionary 109

cancer treatments. Also known as immunotherapy, biotherapy, or biological response modifier (BRM) therapy. [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] Biotransformation: The chemical alteration of an exogenous substance by or in a biological system. The alteration may inactivate the compound or it may result in the production of an active metabolite of an inactive parent compound. The alteration may be either nonsynthetic (oxidation-reduction, hydrolysis) or synthetic (glucuronide formation, sulfate conjugation, acetylation, methylation). This also includes metabolic detoxication and clearance. [NIH] Bladder: The organ that stores urine. [NIH] Blastocyst: The mammalian embryo in the post-morula stage in which a fluid-filled cavity, enclosed primarily by trophoblast, contains an inner cell mass which becomes the embryonic disc. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Blot: To transfer DNA, RNA, or proteins to an immobilizing matrix such as nitrocellulose. [NIH]

Body Fluids: Liquid components of living organisms. [NIH] Bone Density: The amount of mineral per square centimeter of bone. This is the definition used in clinical practice. Actual bone density would be expressed in grams per milliliter. It is most frequently measured by photon absorptiometry or x-ray computed tomography. [NIH] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bone Marrow Transplantation: The transference of bone marrow from one human or animal to another. [NIH] Bone scan: A technique to create images of bones on a computer screen or on film. A small amount of radioactive material is injected into a blood vessel and travels through the bloodstream; it collects in the bones and is detected by a scanner. [NIH] Bowel: The long tube-shaped organ in the abdomen that completes the process of digestion. There is both a small and a large bowel. Also called the intestine. [NIH] Bowel Movement: Body wastes passed through the rectum and anus. [NIH] Brain Neoplasms: Neoplasms of the intracranial components of the central nervous system,

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including the cerebral hemispheres, basal ganglia, hypothalamus, thalamus, brain stem, and cerebellum. Brain neoplasms are subdivided into primary (originating from brain tissue) and secondary (i.e., metastatic) forms. Primary neoplasms are subdivided into benign and malignant forms. In general, brain tumors may also be classified by age of onset, histologic type, or presenting location in the brain. [NIH] Brain Stem: The part of the brain that connects the cerebral hemispheres with the spinal cord. It consists of the mesencephalon, pons, and medulla oblongata. [NIH] Brucella: A genus of gram-negative, aerobic bacteria that causes brucellosis. Its cells are nonmotile coccobacilli and are animal parasites and pathogens. The bacterium is transmissible to humans through contact with infected dairy products or tissue. [NIH] Brucellosis: Infection caused by bacteria of the genus Brucella mainly involving the reticuloendothelial system. This condition is characterized by fever, weakness, malaise, and weight loss. [NIH] Buccal: Pertaining to or directed toward the cheek. In dental anatomy, used to refer to the buccal surface of a tooth. [EU] Bulbar: Pertaining to a bulb; pertaining to or involving the medulla oblongata, as bulbar paralysis. [EU] Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen are usually in the proportion to form water, (CH2O)n. The most important carbohydrates are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, polyand heterosaccharides. [EU] Carbon Dioxide: A colorless, odorless gas that can be formed by the body and is necessary for the respiration cycle of plants and animals. [NIH] Carcinogenic: Producing carcinoma. [EU] 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] Cardiac catheterization: A procedure in which a thin, hollow tube is inserted into a blood vessel. The tube is then advanced through the vessel into the heart, enabling a physician to study the heart and its pumping activity. [NIH] Cardiomyopathy: A general diagnostic term designating primary myocardial disease, often of obscure or unknown etiology. [EU] Cardiopulmonary: Having to do with the heart and lungs. [NIH] Cardiovascular: Having to do with the heart and blood vessels. [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] Catabolism: Any destructive metabolic process by which organisms convert substances into excreted compounds. [EU] Catheterization: Use or insertion of a tubular device into a duct, blood vessel, hollow organ, or body cavity for injecting or withdrawing fluids for diagnostic or therapeutic purposes. It differs from intubation in that the tube here is used to restore or maintain patency in obstructions. [NIH] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH]

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Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell Division: The fission of a cell. [NIH] Cell membrane: Cell membrane = plasma membrane. The structure enveloping a cell, enclosing the cytoplasm, and forming a selective permeability barrier; it consists of lipids, proteins, and some carbohydrates, the lipids thought to form a bilayer in which integral proteins are embedded to varying degrees. [EU] Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Central Nervous System Infections: Pathogenic infections of the brain, spinal cord, and meninges. DNA virus infections; RNA virus infections; bacterial infections; mycoplasma infections; Spirochaetales infections; fungal infections; protozoan infections; helminthiasis; and prion diseases may involve the central nervous system as a primary or secondary process. [NIH] 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] 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] Cerebrospinal: Pertaining to the brain and spinal cord. [EU] Cerebrospinal fluid: CSF. The fluid flowing around the brain and spinal cord. Cerebrospinal fluid is produced in the ventricles in the brain. [NIH] Cerebrum: The largest part of the brain. It is divided into two hemispheres, or halves, called the cerebral hemispheres. The cerebrum controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. [NIH] Chaperonins: A class of sequence-related molecular chaperones found in bacteria, mitochondria, and plastids. Chaperonins are abundant constitutive proteins that increase in amount after stresses such as heat shock, bacterial infection of macrophages, and an increase in the cellular content of unfolded proteins. Bacterial chaperonins are major immunogens in human bacterial infections because of their accumulation during the stress of infection. Two members of this class of chaperones are chaperonin 10 and chaperonin 60. [NIH] Cholestasis: Impairment of biliary flow at any level from the hepatocyte to Vater's ampulla. [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] Cirrhosis: A type of chronic, progressive liver disease. [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]

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Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] 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] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [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] Collapse: 1. A state of extreme prostration and depression, with failure of circulation. 2. Abnormal falling in of the walls of any part of organ. [EU] Colloidal: Of the nature of a colloid. [EU] Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such

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as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Computed tomography: CT scan. A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized tomography and computerized axial tomography (CAT) scan. [NIH] Computerized axial tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called CAT scan, computed tomography (CT scan), or computerized tomography. [NIH] Conception: The onset of pregnancy, marked by implantation of the blastocyst; the formation of a viable zygote. [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] Continuum: An area over which the vegetation or animal population is of constantly changing composition so that homogeneous, separate communities cannot be distinguished. [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] Contrast medium: A substance that is introduced into or around a structure and, because of the difference in absorption of x-rays by the contrast medium and the surrounding tissues, allows radiographic visualization of the structure. [EU] Coordination: Muscular or motor regulation or the harmonious cooperation of muscles or groups of muscles, in a complex action or series of actions. [NIH] Corneum: The superficial layer of the epidermis containing keratinized cells. [NIH] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [EU] Cortical: Pertaining to or of the nature of a cortex or bark. [EU] Cortices: The outer layer of an organ; used especially of the cerebrum and cerebellum. [NIH] Cortisol: A steroid hormone secreted by the adrenal cortex as part of the body's response to stress. [NIH] Cortisone: A natural steroid hormone produced in the adrenal gland. It can also be made in the laboratory. Cortisone reduces swelling and can suppress immune responses. [NIH] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU]

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Craniocerebral Trauma: Traumatic injuries involving the cranium and intracranial structures (i.e., brain; cranial nerves; meninges; and other structures). Injuries may be classified by whether or not the skull is penetrated (i.e., penetrating vs. nonpenetrating) or whether there is an associated hemorrhage. [NIH] Crossing-over: The exchange of corresponding segments between chromatids of homologous chromosomes during meiosia, forming a chiasma. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Cutaneous: Having to do with the skin. [NIH] 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]

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] Dairy Products: Raw and processed or manufactured milk and milk-derived products. These are usually from cows (bovine) but are also from goats, sheep, reindeer, and water buffalo. [NIH] Decidua: The epithelial lining of the endometrium that is formed before the fertilized ovum reaches the uterus. The fertilized ovum embeds in the decidua. If the ovum is not fertilized, the decidua is shed during menstruation. [NIH] 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] Denaturation: Rupture of the hydrogen bonds by heating a DNA solution and then cooling it rapidly causes the two complementary strands to separate. [NIH] Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other neurons. [NIH] Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] Deprivation: Loss or absence of parts, organs, powers, or things that are needed. [EU] 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] Dexamethasone: (11 beta,16 alpha)-9-Fluoro-11,17,21-trihydroxy-16-methylpregna-1,4diene-3,20-dione. An anti-inflammatory glucocorticoid used either in the free alcohol or esterified form in treatment of conditions that respond generally to cortisone. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Diastolic: Of or pertaining to the diastole. [EU] Differential Threshold: The smallest difference which can be discriminated between two stimuli or one which is barely above the threshold. [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

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movements. The digestive system includes the salivary glands, mouth, esophagus, stomach, liver, pancreas, gallbladder, small and large intestines, and rectum. [NIH] Dilation: A process by which the pupil is temporarily enlarged with special eye drops (mydriatic); allows the eye care specialist to better view the inside of the eye. [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] Discrete: Made up of separate parts or characterized by lesions which do not become blended; not running together; separate. [NIH] Dissociation: 1. The act of separating or state of being separated. 2. The separation of a molecule into two or more fragments (atoms, molecules, ions, or free radicals) produced by the absorption of light or thermal energy or by solvation. 3. In psychology, a defense mechanism in which a group of mental processes are segregated from the rest of a person's mental activity in order to avoid emotional distress, as in the dissociative disorders (q.v.), or in which an idea or object is segregated from its emotional significance; in the first sense it is roughly equivalent to splitting, in the second, to isolation. 4. A defect of mental integration in which one or more groups of mental processes become separated off from normal consciousness and, thus separated, function as a unitary whole. [EU] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Duct: A tube through which body fluids pass. [NIH] Dysostosis: Defective bone formation. [NIH] Echocardiography: Ultrasonic recording of the size, motion, and composition of the heart and surrounding tissues. The standard approach is transthoracic. [NIH] Edema: Excessive amount of watery fluid accumulated in the intercellular spaces, most commonly present in subcutaneous tissue. [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] 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] Electrophoresis: An electrochemical process in which macromolecules or colloidal particles with a net electric charge migrate in a solution under the influence of an electric current. [NIH]

Empiric: Empirical; depending upon experience or observation alone, without using scientific method or theory. [EU] Encapsulated: Confined to a specific, localized area and surrounded by a thin layer of tissue. [NIH]

Endonucleases: Enzymes that catalyze the hydrolysis of the internal bonds and thereby the formation of polynucleotides or oligonucleotides from ribo- or deoxyribonucleotide chains. EC 3.1.-. [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]

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Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] 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] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]

Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH] Evoked Potentials: The electric response evoked in the central nervous system by stimulation of sensory receptors or some point on the sensory pathway leading from the receptor to the cortex. The evoked stimulus can be auditory, somatosensory, or visual, although other modalities have been reported. Event-related potentials is sometimes used synonymously with evoked potentials but is often associated with the execution of a motor, cognitive, or psychophysiological task, as well as with the response to a stimulus. [NIH] Exogenous: Developed or originating outside the organism, as exogenous disease. [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] 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] Extraction: The process or act of pulling or drawing out. [EU] Extravasation: A discharge or escape, as of blood, from a vessel into the tissues. [EU] Facial: Of or pertaining to the face. [EU] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Fat: Total lipids including phospholipids. [NIH] Fatty Liver: The buildup of fat in liver cells. The most common cause is alcoholism. Other causes include obesity, diabetes, and pregnancy. Also called steatosis. [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] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [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] Fold: A plication or doubling of various parts of the body. [NIH]

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Fossa: A cavity, depression, or pit. [NIH] Fructose Intolerance: An autosomal recessive fructose metabolism disorder due to deficient fructose-1-phosphate aldolase (EC 2.1.2.13) activity, resulting in accumulation of fructose-1phosphate. The accumulated fructose-1-phosphate inhibits glycogenolysis and gluconeogenesis, causing severe hypoglycemia following ingestion of fructose. Prolonged fructose ingestion in infants leads ultimately to hepatic failure and death. Patients develop a strong distaste for sweet food, and avoid a chronic course of the disease by remaining on a fructose- and sucrose-free diet. [NIH] Galactosemia: Buildup of galactose in the blood. Caused by lack of one of the enzymes needed to break down galactose into glucose. [NIH] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] Gastric: Having to do with the stomach. [NIH] 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 Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Gene Therapy: The introduction of new genes into cells for the purpose of treating disease by restoring or adding gene expression. Techniques include insertion of retroviral vectors, transfection, homologous recombination, and injection of new genes into the nuclei of single cell embryos. The entire gene therapy process may consist of multiple steps. The new genes may be introduced into proliferating cells in vivo (e.g., bone marrow) or in vitro (e.g., fibroblast cultures) and the modified cells transferred to the site where the gene expression is required. Gene therapy may be particularly useful for treating enzyme deficiency diseases, hemoglobinopathies, and leukemias and may also prove useful in restoring drug sensitivity, particularly for leukemia. [NIH] 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] Genetic testing: Analyzing DNA to look for a genetic alteration that may indicate an increased risk for developing a specific disease or disorder. [NIH] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Gestation: The period of development of the young in viviparous animals, from the time of

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fertilization of the ovum until birth. [EU] Glucocorticoid: A compound that belongs to the family of compounds called corticosteroids (steroids). Glucocorticoids affect metabolism and have anti-inflammatory and immunosuppressive effects. They may be naturally produced (hormones) or synthetic (drugs). [NIH] Gluconeogenesis: The process by which glucose is formed from a non-carbohydrate source. [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]

Glycine: A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter. [NIH] Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Grade: The grade of a tumor depends on how abnormal the cancer cells look under a microscope and how quickly the tumor is likely to grow and spread. Grading systems are different for each type of cancer. [NIH] Gram-negative: Losing the stain or decolorized by alcohol in Gram's method of staining, a primary characteristic of bacteria having a cell wall composed of a thin layer of peptidoglycan covered by an outer membrane of lipoprotein and lipopolysaccharide. [EU] 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] Guanine: One of the four DNA bases. [NIH] Haptens: Small antigenic determinants capable of eliciting an immune response only when coupled to a carrier. Haptens bind to antibodies but by themselves cannot elicit an antibody response. [NIH] Headache: Pain in the cranial region that may occur as an isolated and benign symptom or as a manifestation of a wide variety of conditions including subarachnoid hemorrhage; craniocerebral trauma; central nervous system infections; intracranial hypertension; and other disorders. In general, recurrent headaches that are not associated with a primary disease process are referred to as headache disorders (e.g., migraine). [NIH] Heat-Shock Proteins: Proteins which are synthesized in eukaryotic organisms and bacteria in response to hyperthermia and other environmental stresses. They increase thermal tolerance and perform functions essential to cell survival under these conditions. [NIH] Heat-Shock Proteins 90: A class of molecular chaperones whose members act in the mechanism of signal transduction by steroid receptors. [NIH] Hematoma: An extravasation of blood localized in an organ, space, or tissue. [NIH] Hematopoietic Stem Cells: Progenitor cells from which all blood cells derive. [NIH] Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. [NIH] Hemochromatosis: A disease that occurs when the body absorbs too much iron. The body

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stores the excess iron in the liver, pancreas, and other organs. May cause cirrhosis of the liver. Also called iron overload disease. [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] Hemoglobinopathies: A group of inherited disorders characterized by structural alterations within the hemoglobin molecule. [NIH] Hemolytic: A disease that affects the blood and blood vessels. It destroys red blood cells, cells that cause the blood to clot, and the lining of blood vessels. HUS is often caused by the Escherichia coli bacterium in contaminated food. People with HUS may develop acute renal failure. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hemostasis: The process which spontaneously arrests the flow of blood from vessels carrying blood under pressure. It is accomplished by contraction of the vessels, adhesion and aggregation of formed blood elements, and the process of blood or plasma coagulation. [NIH]

Hepatic: Refers to the liver. [NIH] Hepatitis: Inflammation of the liver and liver disease involving degenerative or necrotic alterations of hepatocytes. [NIH] Hepatocyte: A liver cell. [NIH] Hepatomegaly: Enlargement of the liver. [NIH] Hepatopulmonary Syndrome: A syndrome consisting of the triad of liver dysfunction, pulmonary vascular dilatation, and abnormal arterial oxygenation in the absence of detectable intrinsic disease of the lung and heart. [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] 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] Homogeneous: Consisting of or composed of similar elements or ingredients; of a uniform quality throughout. [EU] 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] 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

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intestine. [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] Hydrocephalus: Excessive accumulation of cerebrospinal fluid within the cranium which may be associated with dilation of cerebral ventricles, intracranial hypertension; headache; lethargy; urinary incontinence; and ataxia (and in infants macrocephaly). This condition may be caused by obstruction of cerebrospinal fluid pathways due to neurologic abnormalities, intracranial hemorrhages; central nervous system infections; brain neoplasms; craniocerebral trauma; and other conditions. Impaired resorption of cerebrospinal fluid from the arachnoid villi results in a communicating form of hydrocephalus. Hydrocephalus ex-vacuo refers to ventricular dilation that occurs as a result of brain substance loss from cerebral infarction and other conditions. [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] Hydrolases: Any member of the class of enzymes that catalyze the cleavage of the substrate and the addition of water to the resulting molecules, e.g., esterases, glycosidases (glycoside hydrolases), lipases, nucleotidases, peptidases (peptide hydrolases), and phosphatases (phosphoric monoester hydrolases). EC 3. [NIH] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hydrophobic: Not readily absorbing water, or being adversely affected by water, as a hydrophobic colloid. [EU] Hydroxyproline: A hydroxylated form of the imino acid proline. A deficiency in ascorbic acid can result in impaired hydroxyproline formation. [NIH] Hyperbilirubinemia: Pathologic process consisting of an abnormal increase in the amount of bilirubin in the circulating blood, which may result in jaundice. [NIH] Hyperlipidemia: An excess of lipids in the blood. [NIH] Hypersplenism: Condition characterized by splenomegaly, some reduction in the number of circulating blood cells in the presence of a normal or hyperactive bone marrow, and the potential for reversal by splenectomy. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [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] Hypoglycemia: Abnormally low blood sugar [NIH] Hypokinesia: Slow or diminished movement of body musculature. It may be associated with basal ganglia diseases; mental disorders; prolonged inactivity due to illness; experimental protocols used to evaluate the physiologic effects of immobility; and other conditions. [NIH] Ichthyosis: Any of several generalized skin disorders characterized by dryness, roughness, and scaliness, due to hypertrophy of the stratum corneum epidermis. Most are genetic, but some are acquired, developing in association with other systemic disease or genetic

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syndrome. [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] Immunology: The study of the body's immune system. [NIH] In situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU] In Situ Hybridization: A technique that localizes specific nucleic acid sequences within intact chromosomes, eukaryotic cells, or bacterial cells through the use of specific nucleic acid-labeled probes. [NIH] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incontinence: Inability to control the flow of urine from the bladder (urinary incontinence) or the escape of stool from the rectum (fecal incontinence). [NIH] Infancy: The period of complete dependency prior to the acquisition of competence in walking, talking, and self-feeding. [NIH] Infantile: Pertaining to an infant or to infancy. [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]

Infectious Mononucleosis: A common, acute infection usually caused by the Epstein-Barr virus (Human herpesvirus 4). There is an increase in mononuclear white blood cells and other atypical lymphocytes, generalized lymphadenopathy, splenomegaly, and occasionally hepatomegaly with hepatitis. [NIH] 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] Infusion: A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion. [NIH] Ingestion: Taking into the body by mouth [NIH] Innervation: 1. The distribution or supply of nerves to a part. 2. The supply of nervous energy or of nerve stimulus sent to a part. [EU] Insight: The capacity to understand one's own motives, to be aware of one's own psychodynamics, to appreciate the meaning of symbolic behavior. [NIH] 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

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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] Interleukin-6: Factor that stimulates the growth and differentiation of human B-cells and is also a growth factor for hybridomas and plasmacytomas. It is produced by many different cells including T-cells, monocytes, and fibroblasts. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intestines: The section of the alimentary canal from the stomach to the anus. It includes the large intestine and small intestine. [NIH] Intoxication: Poisoning, the state of being poisoned. [EU] Intracellular: Inside a cell. [NIH] Intracranial Hemorrhages: Bleeding within the intracranial cavity, including hemorrhages in the brain and within the cranial epidural, subdural, and subarachnoid spaces. [NIH] Intracranial Hypertension: Increased pressure within the cranial vault. This may result from several conditions, including hydrocephalus; brain edema; intracranial masses; severe systemic hypertension; pseudotumor cerebri; and other disorders. [NIH] Intraperitoneal: IP. Within the peritoneal cavity (the area that contains the abdominal organs). [NIH] Intrathecal: Describes the fluid-filled space between the thin layers of tissue that cover the brain and spinal cord. Drugs can be injected into the fluid or a sample of the fluid can be removed for testing. [NIH] Intravenous: IV. Into a vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Introns: Non-coding, intervening sequences of DNA that are transcribed, but are removed from within the primary gene transcript and rapidly degraded during maturation of messenger RNA. Most genes in the nuclei of eukaryotes contain introns, as do mitochondrial and chloroplast genes. [NIH] 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]

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] 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] Isoenzyme: Different forms of an enzyme, usually occurring in different tissues. The isoenzymes of a particular enzyme catalyze the same reaction but they differ in some of their properties. [NIH] Isozymes: The multiple forms of a single enzyme. [NIH] Jaundice: A clinical manifestation of hyperbilirubinemia, consisting of deposition of bile pigments in the skin, resulting in a yellowish staining of the skin and mucous membranes. [NIH]

Kb: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [NIH]

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Kinetic: Pertaining to or producing motion. [EU] 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] Lethal: Deadly, fatal. [EU] Lethargy: Abnormal drowsiness or stupor; a condition of indifference. [EU] Leukemia: Cancer of blood-forming tissue. [NIH] Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [NIH] Linkage: The tendency of two or more genes in the same chromosome to remain together from one generation to the next more frequently than expected according to the law of independent assortment. [NIH] Linkage Disequilibrium: Nonrandom association of linked genes. This is the tendency of the alleles of two separate but already linked loci to be found together more frequently than would be expected by chance alone. [NIH] Lipid: Fat. [NIH] Liposomal: A drug preparation that contains the active drug in very tiny fat particles. This fat-encapsulated drug is absorbed better, and its distribution to the tumor site is improved. [NIH]

Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Liver cancer: A disease in which malignant (cancer) cells are found in the tissues of the liver. [NIH]

Liver scan: An image of the liver created on a computer screen or on film. A radioactive substance is injected into a blood vessel and travels through the bloodstream. It collects in the liver, especially in abnormal areas, and can be detected by the scanner. [NIH] Liver Transplantation: The transference of a part of or an entire liver from one human or animal to another. [NIH] Localized: Cancer which has not metastasized yet. [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] Lymphocytes: White blood cells formed in the body's lymphoid tissue. The nucleus is round or ovoid with coarse, irregularly clumped chromatin while the cytoplasm is typically pale blue with azurophilic (if any) granules. Most lymphocytes can be classified as either T or B (with subpopulations of each); those with characteristics of neither major class are called null cells. [NIH]

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Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue. [NIH] Lysosomal Storage Diseases: Inborn errors of metabolism characterized by defects in specific lysosomal hydrolases and resulting in intracellular accumulation of unmetabolized substrates. [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] Magnetic Resonance Imaging: Non-invasive method of demonstrating internal anatomy based on the principle that atomic nuclei in a strong magnetic field absorb pulses of radiofrequency energy and emit them as radiowaves which can be reconstructed into computerized images. The concept includes proton spin tomographic techniques. [NIH] 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]

Mandible: The largest and strongest bone of the face constituting the lower jaw. It supports the lower teeth. [NIH] Mannosidosis: Inborn error of metabolism marked by a defect in alpha-mannosidase activity that results in lysosomal accumulation of mannose-rich substrates. Virtually all patients have psychomotor retardation, facial coarsening, and some degree of dysostosis multiplex. It is thought to be an autosomal recessive disorder. [NIH] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] MI: Myocardial infarction. Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] 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] Milliliter: A measure of volume for a liquid. A milliliter is approximately 950-times smaller than a quart and 30-times smaller than a fluid ounce. A milliliter of liquid and a cubic centimeter (cc) of liquid are the same. [NIH] Mitochondrial Swelling: Increase in volume of mitochondria due to an influx of fluid; it occurs in hypotonic solutions due to osmotic pressure and in isotonic solutions as a result of altered permeability of the membranes of respiring mitochondria. [NIH] Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH] 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]

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Molecular Chaperones: A family of cellular proteins that mediate the correct assembly or disassembly of other polypeptides, and in some cases their assembly into oligomeric structures, but which are not components of those final structures. It is believed that chaperone proteins assist polypeptides to self-assemble by inhibiting alternative assembly pathways that produce nonfunctional structures. Some classes of molecular chaperones are the nucleoplasmins, the chaperonins, the heat-shock proteins 70, and the heat-shock proteins 90. [NIH] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] Monocyte: A type of white blood cell. [NIH] Mononuclear: A cell with one nucleus. [NIH] Morphology: The science of the form and structure of organisms (plants, animals, and other forms of life). [NIH] Mosaicism: The occurrence in an individual of two or more cell populations of different chromosomal constitutions, derived from a single zygote, as opposed to chimerism in which the different cell populations are derived from more than one zygote. [NIH] Mucosa: A mucous membrane, or tunica mucosa. [EU] Mutagenesis: Process of generating genetic mutations. It may occur spontaneously or be induced by mutagens. [NIH] Mutagens: Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes. [NIH] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myoclonus: Involuntary shock-like contractions, irregular in rhythm and amplitude, followed by relaxation, of a muscle or a group of muscles. This condition may be a feature of some central nervous systems diseases (e.g., epilepsy, myoclonic). Nocturnal myoclonus may represent a normal physiologic event or occur as the principal feature of the nocturnal myoclonus syndrome. (From Adams et al., Principles of Neurology, 6th ed, pp102-3). [NIH] Necrosis: A pathological process caused by the progressive degradative action of enzymes that is generally associated with severe cellular trauma. It is characterized by mitochondrial swelling, nuclear flocculation, uncontrolled cell lysis, and ultimately cell death. [NIH] Neonatal: Pertaining to the first four weeks after birth. [EU] Neoplastic: Pertaining to or like a neoplasm (= any new and abnormal growth); pertaining to neoplasia (= the formation of a neoplasm). [EU] Nephrosis: Descriptive histopathologic term for renal disease without an inflammatory component. [NIH] Nephrotic: Pertaining to, resembling, or caused by nephrosis. [EU] Nephrotic Syndrome: Clinical association of heavy proteinuria, hypoalbuminemia, and generalized edema. [NIH] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH]

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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] Neuromuscular: Pertaining to muscles and nerves. [EU] Neuromuscular Junction: The synapse between a neuron and a muscle. [NIH] Neuronal: Pertaining to a neuron or neurons (= conducting cells of the nervous system). [EU] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] Neurotransmitter: Any of a group of substances that are released on excitation from the axon terminal of a presynaptic neuron of the central or peripheral nervous system and travel across the synaptic cleft to either excite or inhibit the target cell. Among the many substances that have the properties of a neurotransmitter are acetylcholine, norepinephrine, epinephrine, dopamine, glycine, y-aminobutyrate, glutamic acid, substance P, enkephalins, endorphins, and serotonin. [EU] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the information (genetic code) for the transfer of genetic information from one generation to the next. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Ocular: 1. Of, pertaining to, or affecting the eye. 2. Eyepiece. [EU] Opacity: Degree of density (area most dense taken for reading). [NIH] Ophthalmoplegia: Paralysis of one or more of the ocular muscles due to disorders of the eye muscles, neuromuscular junction, supporting soft tissue, tendons, or innervation to the muscles. [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] Orthopaedic: Pertaining to the correction of deformities of the musculoskeletal system; pertaining to orthopaedics. [EU] Osmotic: Pertaining to or of the nature of osmosis (= the passage of pure solvent from a solution of lesser to one of greater solute concentration when the two solutions are separated by a membrane which selectively prevents the passage of solute molecules, but is permeable to the solvent). [EU] Osteomyelitis: Inflammation of bone caused by a pyogenic organism. It may remain localized or may spread through the bone to involve the marrow, cortex, cancellous tissue, and periosteum. [EU] Oxygenation: The process of supplying, treating, or mixing with oxygen. No:1245 oxygenation the process of supplying, treating, or mixing with oxygen. [EU] Paediatric: Of or relating to the care and medical treatment of children; belonging to or

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concerned with paediatrics. [EU] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Pancytopenia: Deficiency of all three cell elements of the blood, erythrocytes, leukocytes and platelets. [NIH] Paralysis: Loss of ability to move all or part of the body. [NIH] Parkinsonism: A group of neurological disorders characterized by hypokinesia, tremor, and muscular rigidity. [EU] Particle: A tiny mass of material. [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] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Perinatal: Pertaining to or occurring in the period shortly before and after birth; variously defined as beginning with completion of the twentieth to twenty-eighth week of gestation and ending 7 to 28 days after birth. [EU] Peripheral blood: Blood circulating throughout the body. [NIH] Peritoneal: Having to do with the peritoneum (the tissue that lines the abdominal wall and covers most of the organs in the abdomen). [NIH] Peritoneal Cavity: The space enclosed by the peritoneum. It is divided into two portions, the greater sac and the lesser sac or omental bursa, which lies behind the stomach. The two sacs are connected by the foramen of Winslow, or epiploic foramen. [NIH] Peritoneum: Endothelial lining of the abdominal cavity, the parietal peritoneum covering the inside of the abdominal wall and the visceral peritoneum covering the bowel, the mesentery, and certain of the organs. The portion that covers the bowel becomes the serosal layer of the bowel wall. [NIH] PH: The symbol relating the hydrogen ion (H+) concentration or activity of a solution to that of a given standard solution. Numerically the pH is approximately equal to the negative logarithm of H+ concentration expressed in molarity. pH 7 is neutral; above it alkalinity increases and below it acidity increases. [EU] 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]

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Phospholipids: Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides; glycerophospholipids) or sphingosine (sphingolipids). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system. [NIH] Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. [NIH] Physiologic: Having to do with the functions of the body. When used in the phrase "physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH]

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] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] Plasma protein: One of the hundreds of different proteins present in blood plasma, including carrier proteins ( such albumin, transferrin, and haptoglobin), fibrinogen and other coagulation factors, complement components, immunoglobulins, enzyme inhibitors, precursors of substances such as angiotension and bradykinin, and many other types of proteins. [EU] Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Pneumonia: Inflammation of the lungs. [NIH] Point Mutation: A mutation caused by the substitution of one nucleotide for another. This results in the DNA molecule having a change in a single base pair. [NIH] Polymerase: An enzyme which catalyses the synthesis of DNA using a single DNA strand as a template. The polymerase copies the template in the 5'-3'direction provided that sufficient quantities of free nucleotides, dATP and dTTP are present. [NIH] Polymerase Chain Reaction: In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships. [NIH] 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

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tripeptides, tetrapeptides, etc. according to the number of amino acids contained. [EU] Porphyria: A group of disorders characterized by the excessive production of porphyrins or their precursors that arises from abnormalities in the regulation of the porphyrin-heme pathway. The porphyrias are usually divided into three broad groups, erythropoietic, hepatic, and erythrohepatic, according to the major sites of abnormal porphyrin synthesis. [NIH]

Porphyrins: A group of compounds containing the porphin structure, four pyrrole rings connected by methine bridges in a cyclic configuration to which a variety of side chains are attached. The nature of the side chain is indicated by a prefix, as uroporphyrin, hematoporphyrin, etc. The porphyrins, in combination with iron, form the heme component in biologically significant compounds such as hemoglobin and myoglobin. [NIH] Posterior: Situated in back of, or in the back part of, or affecting the back or dorsal surface of the body. In lower animals, it refers to the caudal end of the body. [EU] Postnatal: Occurring after birth, with reference to the newborn. [EU] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] Primary Biliary Cirrhosis: A chronic liver disease. Slowly destroys the bile ducts in the liver. This prevents release of bile. Long-term irritation of the liver may cause scarring and cirrhosis in later stages of the disease. [NIH] Primary Sclerosing Cholangitis: Irritation, scarring, and narrowing of the bile ducts inside and outside the liver. Bile builds up in the liver and may damage its cells. Many people with this condition also have ulcerative colitis. [NIH] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Proline: A non-essential amino acid that is synthesized from glutamic acid. It is an essential component of collagen and is important for proper functioning of joints and tendons. [NIH] Promoter: A chemical substance that increases the activity of a carcinogenic process. [NIH] 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] Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation. [NIH] Protein Conformation: The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the

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peptide chain. Quaternary protein structure describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain). [NIH] Protein Folding: A rapid biochemical reaction involved in the formation of proteins. It begins even before a protein has been completely synthesized and proceeds through discrete intermediates (primary, secondary, and tertiary structures) before the final structure (quaternary structure) is developed. [NIH] Protein S: The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] Proteinuria: The presence of protein in the urine, indicating that the kidneys are not working properly. [NIH] Psychoactive: Those drugs which alter sensation, mood, consciousness or other psychological or behavioral functions. [NIH] 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 Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] Publishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing. [NIH]

Pulmonary: Relating to the lungs. [NIH] Pulmonary hypertension: Abnormally high blood pressure in the arteries of the lungs. [NIH] Pyogenic: Producing pus; pyopoietic (= liquid inflammation product made up of cells and a thin fluid called liquor puris). [EU] Pyruvate Kinase: ATP:pyruvate 2-O-phosphotransferase. A phosphotransferase that catalyzes reversibly the phosphorylation of pyruvate to phosphoenolpyruvate in the presence of ATP. It has four isozymes (L, R, M1, and M2). Deficiency of the enzyme results in hemolytic anemia. EC 2.7.1.40. [NIH] Quaternary: 1. Fourth in order. 2. Containing four elements or groups. [EU] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radioactive: Giving off radiation. [NIH] Radiography: Examination of any part of the body for diagnostic purposes by means of roentgen rays, recording the image on a sensitized surface (such as photographic film). [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] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU]

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Recombination: The formation of new combinations of genes as a result of segregation in crosses between genetically different parents; also the rearrangement of linked genes due to crossing-over. [NIH] Rectum: The last 8 to 10 inches of the large intestine. [NIH] 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] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Resorption: The loss of substance through physiologic or pathologic means, such as loss of dentin and cementum of a tooth, or of the alveolar process of the mandible or maxilla. [EU] Restriction Mapping: Use of restriction endonucleases to analyze and generate a physical map of genomes, genes, or other segments of DNA. [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] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Sacroiliac Joint: The immovable joint formed by the lateral surfaces of the sacrum and ilium. [NIH] Saliva: The clear, viscous fluid secreted by the salivary glands and mucous glands of the mouth. It contains mucins, water, organic salts, and ptylin. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [NIH] Scans: Pictures of structures inside the body. Scans often used in diagnosing, staging, and monitoring disease include liver scans, bone scans, and computed tomography (CT) or computerized axial tomography (CAT) scans and magnetic resonance imaging (MRI) scans. In liver scanning and bone scanning, radioactive substances that are injected into the bloodstream collect in these organs. A scanner that detects the radiation is used to create pictures. In CT scanning, an x-ray machine linked to a computer is used to produce detailed pictures of organs inside the body. MRI scans use a large magnet connected to a computer to create pictures of areas inside the body. [NIH] Schizoid: Having qualities resembling those found in greater degree in schizophrenics; a person of schizoid personality. [NIH] Schizophrenia: A mental disorder characterized by a special type of disintegration of the personality. [NIH] Schizotypal Personality Disorder: A personality disorder in which there are oddities of thought (magical thinking, paranoid ideation, suspiciousness), perception (illusions, depersonalization), speech (digressive, vague, overelaborate), and behavior (inappropriate affect in social interactions, frequently social isolation) that are not severe enough to characterize schizophrenia. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Segregation: The separation in meiotic cell division of homologous chromosome pairs and their contained allelomorphic gene pairs. [NIH]

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Sequencing: The determination of the order of nucleotides in a DNA or RNA chain. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] 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]

Shunt: A surgically created diversion of fluid (e.g., blood or cerebrospinal fluid) from one area of the body to another area of the body. [NIH] Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the one sought to be benefited by its administration. [EU] Signs and Symptoms: Clinical manifestations that can be either objective when observed by a physician, or subjective when perceived by the patient. [NIH] 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 many of their internal organs. The skeletons of vertebrates are made of bone and/or cartilage. [NIH] Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [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] 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] 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] Splenomegaly: Enlargement of the spleen. [NIH] Staging: Performing exams and tests to learn the extent of the cancer within the body,

Dictionary 133

especially whether the disease has spread from the original site to other parts of the body. [NIH]

Steatosis: Fatty degeneration. [EU] 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] Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Strand: DNA normally exists in the bacterial nucleus in a helix, in which two strands are coiled together. [NIH] Subacute: Somewhat acute; between acute and chronic. [EU] Subcapsular: Situated below a capsule. [EU] Substrate: A substance upon which an enzyme acts. [EU] Supplementation: Adding nutrients to the diet. [NIH] Support group: A group of people with similar disease who meet to discuss how better to cope with their cancer and treatment. [NIH] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] Systemic: Affecting the entire body. [NIH] Systemic disease: Disease that affects the whole body. [NIH] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] Taurine: 2-Aminoethanesulfonic acid. A conditionally essential nutrient, important during mammalian development. It is present in milk but is isolated mostly from ox bile and strongly conjugates bile acids. [NIH] Tetracycline: An antibiotic originally produced by Streptomyces viridifaciens, but used mostly in synthetic form. It is an inhibitor of aminoacyl-tRNA binding during protein synthesis. [NIH] 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] Thermal: Pertaining to or characterized by heat. [EU] 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] Thrombomodulin: A cell surface glycoprotein of endothelial cells that binds thrombin and

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serves as a cofactor in the activation of protein C and its regulation of blood coagulation. [NIH]

Thrombophilia: A disorder of hemostasis in which there is a tendency for the occurrence of thrombosis. [NIH] Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thyroxine: An amino acid of the thyroid gland which exerts a stimulating effect on thyroid metabolism. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tomography: Imaging methods that result in sharp images of objects located on a chosen plane and blurred images located above or below the plane. [NIH] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicokinetics: Study of the absorption, distribution, metabolism, and excretion of test substances. [NIH] 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] 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] 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] Translation: The process whereby the genetic information present in the linear sequence of ribonucleotides in mRNA is converted into a corresponding sequence of amino acids in a protein. It occurs on the ribosome and is unidirectional. [NIH] 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] Tremor: Cyclical movement of a body part that can represent either a physiologic process or a manifestation of disease. Intention or action tremor, a common manifestation of cerebellar diseases, is aggravated by movement. In contrast, resting tremor is maximal when there is no attempt at voluntary movement, and occurs as a relatively frequent manifestation of Parkinson disease. [NIH] Triad: Trivalent. [NIH] Trisomy: The possession of a third chromosome of any one type in an otherwise diploid cell. [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

Dictionary 135

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] Ulcerative colitis: Chronic inflammation of the colon that produces ulcers in its lining. This condition is marked by abdominal pain, cramps, and loose discharges of pus, blood, and mucus from the bowel. [NIH] Ultrasonography: The visualization of deep structures of the body by recording the reflections of echoes of pulses of ultrasonic waves directed into the tissues. Use of ultrasound for imaging or diagnostic purposes employs frequencies ranging from 1.6 to 10 megahertz. [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]

Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] 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] Vaccines: Suspensions of killed or attenuated microorganisms (bacteria, viruses, fungi, protozoa, or rickettsiae), antigenic proteins derived from them, or synthetic constructs, administered for the prevention, amelioration, or treatment of infectious and other diseases. [NIH]

Vagina: The muscular canal extending from the uterus to the exterior of the body. Also called the birth canal. [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venous: Of or pertaining to the veins. [EU] Ventricles: Fluid-filled cavities in the heart or brain. [NIH] Ventricular: Pertaining to a ventricle. [EU] Vertebral: Of or pertaining to a vertebra. [EU] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Villi: The tiny, fingerlike projections on the surface of the small intestine. Villi help absorb nutrients. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] 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] Visceral: , from viscus a viscus) pertaining to a viscus. [EU] Vitro: Descriptive of an event or enzyme reaction under experimental investigation

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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] White blood cell: A type of cell in the immune system that helps the body fight infection and disease. White blood cells include lymphocytes, granulocytes, macrophages, and others. [NIH]

Withdrawal: 1. A pathological retreat from interpersonal contact and social involvement, as may occur in schizophrenia, depression, or schizoid avoidant and schizotypal personality disorders. 2. (DSM III-R) A substance-specific organic brain syndrome that follows the cessation of use or reduction in intake of a psychoactive substance that had been regularly used to induce a state of intoxication. [EU] Xenograft: The cells of one species transplanted to another species. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH] Yeasts: A general term for single-celled rounded fungi that reproduce by budding. Brewers' and bakers' yeasts are Saccharomyces cerevisiae; therapeutic dried yeast is dried yeast. [NIH] 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]

137

INDEX A Abdomen, 105, 109, 123, 127, 132, 133 Abdominal, 50, 51, 105, 122, 127, 135 Aberrant, 67, 105 Acetaminophen, 74, 105 Acid Phosphatase, 14, 105 Adaptability, 105, 111 Adrenal Glands, 105, 106 Adrenoleukodystrophy, 15, 105 Adverse Effect, 105, 132 Aerobic, 105, 110 Affinity, 32, 105 Albumin, 4, 105, 128 Algorithms, 105, 109 Alleles, 12, 29, 33, 67, 105, 119, 123 Alternative medicine, 74, 76, 106 Alveolar Process, 106, 131 Amino acid, 69, 106, 107, 114, 116, 117, 118, 127, 128, 129, 130, 134 Amino Acid Sequence, 69, 106, 107, 116, 117 Amplification, 62, 106 Ampulla, 106, 111 Amyloidosis, 10, 12, 106 Analgesic, 105, 106 Anemia, 101, 106, 108, 130, 133 Anesthesia, 51, 106 Angiography, 26, 106 Angioma, 37, 106 Animal model, 4, 6, 106 Anions, 105, 106, 122 Ankle, 35, 106 Annealing, 106, 128 Antibacterial, 107, 132 Antibiotic, 107, 132, 133 Antibodies, 24, 107, 118, 120, 128 Antibody, 39, 40, 105, 107, 112, 118, 119, 121, 132 Anticoagulant, 30, 107, 129 Antigen, 105, 107, 112, 119, 121 Anti-inflammatory, 105, 107, 114, 118 Antipyretic, 105, 107 Apoptosis, 50, 107 Apraxia, 44, 107 Aqueous, 107, 114 Arterial, 107, 119, 120, 130, 133 Arteries, 107, 109, 113, 124, 130 Arteriovenous, 28, 107

Arteriovenous Fistula, 28, 107 Artery, 107, 109, 113 Arthroplasty, 45, 107 Aspiration, 102, 107 Assay, 19, 20, 26, 62, 66, 107 Asymptomatic, 8, 13, 107, 108 Ataxia, 101, 108, 120 Atypical, 108, 121 Auditory, 62, 108, 116 Autologous, 67, 108 Autopsy, 12, 24, 108 B Bacteria, 107, 108, 110, 111, 118, 124, 132, 134, 135 Bacteriophage, 108, 134 Bacterium, 108, 110, 119 Beta-Glucosidase, 19, 24, 25, 31, 32, 33, 36, 40, 43, 54, 55, 71, 108 Beta-Thalassemia, 63, 108 Bile, 108, 117, 122, 123, 129, 133 Bile Acids, 108, 133 Bile duct, 108, 129 Bile Pigments, 108, 122 Biliary, 74, 108, 111 Biliary Atresia, 74, 108 Biliary Tract, 108 Bilirubin, 105, 108, 120 Binding Sites, 32, 108 Biochemical, 7, 13, 14, 18, 19, 23, 24, 42, 43, 106, 108, 130 Biological therapy, 108, 118 Biopsy, 73, 102, 109 Biotechnology, 9, 10, 76, 87, 109 Biotransformation, 109 Bladder, 109, 121, 129, 135 Blastocyst, 109, 113, 128 Blood pressure, 109, 120, 130 Blood vessel, 106, 109, 110, 119, 123, 132, 134, 135 Blot, 33, 109 Body Fluids, 109, 115, 135 Bone Density, 16, 109 Bone Marrow, 7, 12, 14, 19, 21, 35, 37, 38, 43, 46, 48, 49, 52, 54, 68, 71, 109, 117, 120, 123 Bone Marrow Transplantation, 7, 12, 37, 43, 46, 109 Bone scan, 16, 109, 131

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Bowel, 109, 114, 127, 135 Bowel Movement, 109, 115 Brain Neoplasms, 109, 120 Brain Stem, 110, 111 Brucella, 27, 110 Brucellosis, 110 Buccal, 110, 123 Bulbar, 36, 110 C Carbohydrate, 10, 70, 110, 118 Carbon Dioxide, 110, 128 Carcinogenic, 110, 129 Carcinoma, 30, 110 Cardiac, 25, 110, 125 Cardiac catheterization, 25, 110 Cardiomyopathy, 92, 110 Cardiopulmonary, 10, 110 Cardiovascular, 16, 54, 110 Case report, 12, 27, 41, 51, 110 Catabolism, 70, 110 Catheterization, 110 Cell Death, 107, 111, 125 Cell Division, 108, 111, 118, 124, 128, 131 Cell membrane, 68, 71, 111, 128 Cell Survival, 30, 111, 118 Central Nervous System, 15, 109, 111, 116, 117, 118, 120, 125 Central Nervous System Infections, 111, 118, 120 Ceramide, 71, 111 Cerebellum, 53, 110, 111, 113 Cerebral, 108, 110, 111, 120, 130 Cerebrospinal, 29, 30, 111, 120, 132 Cerebrospinal fluid, 29, 30, 111, 120, 132 Cerebrum, 111, 113 Chaperonins, 111, 125 Cholestasis, 41, 111 Chromatin, 107, 111, 123 Chromosomal, 106, 111, 125, 131 Chromosome, 34, 40, 66, 67, 105, 111, 119, 123, 131, 134 Chronic, 26, 111, 117, 121, 129, 133, 135 Cirrhosis, 73, 111, 119, 129 Clear cell carcinoma, 111, 114 Clinical trial, 4, 6, 7, 87, 112, 130 Cloning, 66, 109, 112 Cofactor, 112, 130, 134 Collagen, 106, 112, 116, 129 Collapse, 69, 112 Colloidal, 105, 112, 115 Complement, 112, 117, 128

Complementary and alternative medicine, 61, 63, 112 Complementary medicine, 61, 112 Computational Biology, 87, 113 Computed tomography, 109, 113, 131 Computerized axial tomography, 113, 131 Conception, 113, 116 Connective Tissue, 109, 112, 113, 116, 117 Continuum, 46, 113 Contraindications, ii, 113 Contrast medium, 106, 113 Coordination, 111, 113 Corneum, 113, 116, 120 Coronary, 113, 124 Coronary Thrombosis, 113, 124 Cortex, 107, 108, 113, 116, 126 Cortical, 3, 113 Cortices, 3, 113 Cortisol, 105, 113 Cortisone, 113, 114 Cranial, 111, 113, 114, 118, 122 Craniocerebral Trauma, 114, 118, 120 Crossing-over, 114, 131 Curative, 114, 133 Cutaneous, 114, 123 Cysteine, 45, 114 Cystine, 114 Cytoplasm, 69, 107, 111, 114, 123 D Dairy Products, 110, 114 Decidua, 114, 128 Degenerative, 114, 119 Deletion, 31, 33, 107, 114 Denaturation, 114, 128 Dendrites, 114, 126 Density, 15, 69, 70, 109, 114, 126 Deprivation, 70, 114 DES, 12, 114 Dexamethasone, 69, 70, 114 Diagnostic procedure, 65, 76, 114 Diastolic, 114, 120 Differential Threshold, 7, 114 Digestion, 108, 109, 114, 123, 133 Digestive system, 74, 114 Dilation, 115, 120 Diploid, 115, 128, 134 Direct, iii, 58, 115, 131 Discrete, 115, 130 Dissociation, 105, 115, 122 Drug Interactions, 80, 115 Duct, 106, 110, 115, 131 Dysostosis, 115, 124

139

E Echocardiography, 25, 115 Edema, 115, 122, 125 Efficacy, 10, 18, 23, 24, 115 Electrons, 115, 122, 130 Electrophoresis, 21, 115 Empiric, 7, 115 Encapsulated, 115, 123 Endonucleases, 115, 131 Environmental Health, 86, 88, 115 Enzymatic, 7, 9, 41, 70, 106, 112, 116, 128 Epidermis, 113, 116, 120 Erythrocytes, 106, 109, 116, 127 Esophagus, 115, 116, 133 Eukaryotic Cells, 116, 121, 126 Evoked Potentials, 51, 116 Exogenous, 109, 116 Exon, 31, 42, 55, 66, 116 Extracellular, 69, 70, 113, 116 Extracellular Matrix, 113, 116 Extraction, 12, 116 Extravasation, 116, 118 F Facial, 116, 124 Family Planning, 7, 87, 116 Fat, 68, 71, 109, 111, 116, 123, 132 Fatty Liver, 74, 116 Fetus, 26, 116, 128 Fibroblasts, 9, 21, 33, 58, 62, 116, 122 Fibrosis, 16, 116 Fluorescence, 9, 20, 25, 116 Fold, 69, 116 Fossa, 111, 117 Fructose Intolerance, 74, 117 G Galactosemia, 74, 117 Gallbladder, 105, 108, 115, 117 Ganglia, 108, 110, 117, 120, 125 Gastric, 12, 117 Gastrointestinal, 117, 135 Gastrointestinal tract, 117, 135 Gene Expression, 45, 117 Gene Therapy, 5, 6, 8, 20, 39, 50, 62, 67, 68, 69, 70, 71, 117 Genetic Code, 117, 126 Genetic Counseling, 20, 51, 117 Genetic Engineering, 109, 112, 117 Genetic testing, 49, 117, 128 Genotype, 7, 8, 18, 25, 29, 41, 52, 117, 127 Gestation, 117, 127, 128 Glucocorticoid, 114, 118 Gluconeogenesis, 117, 118

Glucose, 32, 47, 69, 70, 71, 108, 117, 118, 119, 121, 122 Glutamic Acid, 118, 126, 129 Glycine, 106, 118, 126 Glycoprotein, 118, 133, 135 Governing Board, 118, 129 Grade, 58, 118 Gram-negative, 110, 118 Growth factors, 35, 118 Guanine, 66, 118 H Haptens, 105, 118 Headache, 118, 120 Heat-Shock Proteins, 118, 125 Heat-Shock Proteins 90, 118, 125 Hematoma, 32, 34, 118 Hematopoietic Stem Cells, 4, 6, 67, 118 Heme, 108, 118, 129 Hemochromatosis, 74, 118 Hemoglobin, 106, 108, 116, 118, 119, 129, 133 Hemoglobinopathies, 117, 119 Hemolytic, 119, 130, 133 Hemorrhage, 36, 114, 118, 119 Hemostasis, 119, 134 Hepatic, 40, 105, 117, 119, 129 Hepatitis, 73, 119, 121 Hepatocyte, 111, 119 Hepatomegaly, 71, 102, 119, 121 Hepatopulmonary Syndrome, 48, 119 Hereditary, 74, 119, 133 Heredity, 117, 119 Heterogeneity, 10, 31, 54, 105, 119 Heterozygote, 53, 119 Homogeneous, 113, 119 Homologous, 66, 106, 114, 117, 119, 131 Homozygotes, 8, 17, 36, 48, 119 Hormone, 113, 114, 119, 121 Hybridomas, 120, 122 Hydrocephalus, 16, 120, 122 Hydrogen, 110, 114, 120, 125, 127 Hydrolases, 120, 124 Hydrolysis, 71, 108, 109, 115, 120, 128 Hydrophobic, 69, 120 Hydroxyproline, 106, 112, 120 Hyperbilirubinemia, 120, 122 Hyperlipidemia, 7, 120 Hypersplenism, 36, 120 Hypertension, 76, 120, 122 Hypertrophy, 120 Hypoglycemia, 117, 120 Hypokinesia, 120, 127

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I Ichthyosis, 50, 120 Immune response, 107, 113, 118, 121, 135 Immune system, 108, 121, 124, 136 Immunology, 105, 121 In situ, 67, 121 In Situ Hybridization, 67, 121 In vitro, 8, 25, 58, 69, 117, 121, 128 In vivo, 8, 20, 28, 50, 69, 117, 121 Incontinence, 120, 121 Infancy, 7, 43, 121 Infantile, 36, 41, 71, 121 Infarction, 113, 120, 121, 124 Infection, 108, 110, 111, 121, 123, 136 Infectious Mononucleosis, 39, 121 Inflammation, 105, 107, 116, 119, 121, 126, 128, 130, 135 Infusion, 6, 121 Ingestion, 117, 121 Innervation, 121, 126 Insight, 9, 121 Insulin, 35, 69, 70, 121, 122 Insulin-dependent diabetes mellitus, 122 Interleukin-6, 52, 122 Interstitial, 48, 122 Intestines, 105, 117, 122 Intoxication, 122, 136 Intracellular, 121, 122, 124 Intracranial Hemorrhages, 120, 122 Intracranial Hypertension, 118, 120, 122 Intraperitoneal, 4, 122 Intrathecal, 6, 122 Intravenous, 4, 32, 121, 122 Intrinsic, 105, 119, 122 Introns, 67, 122 Invasive, 122, 124 Ionization, 12, 122 Ions, 115, 120, 122 Isoenzyme, 12, 122 Isozymes, 122, 130 J Jaundice, 73, 120, 122 K Kb, 66, 67, 86, 122 Kinetic, 66, 123 L Large Intestine, 115, 122, 123, 131 Lethal, 4, 36, 71, 123 Lethargy, 120, 123 Leukemia, 63, 117, 123 Leukocytes, 109, 123, 127, 135 Linkage, 9, 37, 123

Linkage Disequilibrium, 9, 123 Lipid, 42, 44, 63, 71, 121, 123 Liposomal, 8, 123 Liver, 4, 11, 13, 15, 37, 45, 68, 70, 71, 73, 105, 106, 108, 111, 115, 116, 117, 119, 123, 129, 131 Liver cancer, 73, 123 Liver scan, 123, 131 Liver Transplantation, 45, 73, 123 Localized, 67, 106, 115, 118, 121, 123, 126, 128 Lupus, 30, 123 Lymph, 121, 123 Lymphadenopathy, 121, 123 Lymphatic, 106, 121, 123, 132 Lymphatic system, 123, 132 Lymphocytes, 107, 120, 121, 123, 124, 132, 136 Lymphoid, 13, 107, 123, 124 Lymphoma, 51, 62, 63, 124 Lysosomal Storage Diseases, 70, 124 M Macrophage, 8, 22, 70, 124 Magnetic Resonance Imaging, 50, 124, 131 Malignant, 58, 61, 110, 123, 124 Malnutrition, 105, 124 Mandible, 106, 124, 131 Mannosidosis, 15, 124 Mediate, 124, 125 MEDLINE, 87, 124 Membrane, 8, 111, 112, 116, 118, 124, 125, 126, 128 Meninges, 111, 114, 124 MI, 73, 102, 124 Microorganism, 112, 124, 136 Milliliter, 109, 124 Mitochondrial Swelling, 124, 125 Mitosis, 107, 124 Modification, 106, 117, 124 Molecular Chaperones, 69, 111, 118, 125 Molecule, 67, 70, 71, 107, 108, 112, 115, 119, 120, 125, 128, 130, 134, 135 Monocyte, 8, 125 Mononuclear, 121, 125, 135 Morphology, 71, 125 Mosaicism, 51, 125 Mucosa, 123, 125 Mutagenesis, 10, 39, 125 Mutagens, 125 Myocardium, 124, 125 Myoclonus, 36, 41, 125

141

N Necrosis, 13, 107, 121, 124, 125 Neonatal, 41, 43, 125 Neoplastic, 120, 124, 125 Nephrosis, 125 Nephrotic, 28, 125 Nephrotic Syndrome, 28, 125 Nerve, 106, 108, 114, 121, 125, 126, 133 Nervous System, 102, 111, 125, 126 Neuroblastoma, 58, 126 Neurologic, 33, 67, 120, 126 Neuromuscular, 126 Neuromuscular Junction, 126 Neuronal, 6, 50, 58, 126 Neurons, 6, 114, 117, 126 Neurotransmitter, 106, 118, 126 Nuclear, 31, 52, 54, 115, 116, 125, 126 Nuclei, 115, 117, 122, 124, 126 Nucleic acid, 67, 68, 71, 117, 121, 125, 126 Nucleus, 41, 107, 108, 111, 114, 116, 123, 125, 126, 133 O Ocular, 44, 126 Opacity, 114, 126 Ophthalmoplegia, 16, 126 Organelles, 114, 126 Orthopaedic, 35, 126 Osmotic, 105, 124, 126 Osteomyelitis, 36, 45, 126 Oxygenation, 119, 126 P Paediatric, 22, 29, 43, 126 Palliative, 127, 133 Pancreas, 105, 115, 119, 121, 127, 135 Pancytopenia, 8, 35, 127 Paralysis, 102, 107, 110, 126, 127 Parkinsonism, 27, 28, 127 Particle, 127, 134 Pathogenesis, 4, 29, 127 Pathologic, 45, 46, 107, 109, 113, 120, 127, 131 Pathologic Processes, 107, 127 Pathophysiology, 8, 127 Peptide, 106, 120, 127, 128, 130 Perinatal, 36, 46, 127 Peripheral blood, 4, 5, 127 Peritoneal, 12, 122, 127 Peritoneal Cavity, 122, 127 Peritoneum, 127 PH, 9, 109, 127 Pharmacokinetic, 127 Pharmacologic, 106, 127, 134

Phenotype, 5, 7, 8, 18, 25, 29, 41, 46, 47, 52, 127 Phospholipids, 116, 128 Phosphorylation, 128, 130 Physiologic, 4, 120, 125, 128, 130, 131, 134 Placenta, 68, 71, 128 Plants, 110, 118, 125, 128 Plasma, 19, 46, 47, 63, 105, 107, 111, 119, 128 Plasma cells, 107, 128 Plasma protein, 105, 128 Platelets, 127, 128 Pneumonia, 113, 128 Point Mutation, 8, 10, 11, 39, 43, 128 Polymerase, 66, 128 Polymerase Chain Reaction, 66, 128 Polymorphic, 8, 37, 128 Polymorphism, 37, 43, 52, 128 Polypeptide, 68, 69, 71, 106, 112, 128, 130, 133, 136 Porphyria, 74, 129 Porphyrins, 129 Posterior, 108, 111, 127, 129 Postnatal, 129, 133 Practice Guidelines, 88, 129 Precursor, 116, 129 Prevalence, 31, 40, 41, 129 Primary Biliary Cirrhosis, 74, 129 Primary Sclerosing Cholangitis, 74, 129 Progression, 106, 129 Progressive, 71, 111, 125, 129 Proline, 43, 112, 120, 129 Promoter, 52, 129 Prostate, 129, 135 Protein C, 69, 105, 106, 108, 129 Protein Conformation, 106, 129 Protein Folding, 69, 130 Protein S, 69, 109, 117, 130, 133 Proteins, 21, 67, 69, 106, 107, 109, 111, 112, 118, 125, 127, 128, 130, 132, 135 Proteinuria, 125, 130 Psychoactive, 130, 136 Psychomotor, 124, 130 Puberty, 7, 20, 130 Public Policy, 87, 130 Publishing, 9, 74, 130 Pulmonary, 7, 11, 25, 28, 48, 76, 109, 119, 130 Pulmonary hypertension, 25, 48, 130 Pyogenic, 126, 130 Pyruvate Kinase, 37, 130

142

Gaucher Disease

Q Quaternary, 129, 130 R Radiation, 116, 130, 131, 136 Radioactive, 109, 120, 122, 123, 126, 130, 131 Radiography, 3, 106, 130 Randomized, 115, 130 Receptor, 69, 70, 107, 116, 130 Recombinant, 7, 10, 24, 68, 72, 81, 130, 135 Recombination, 11, 49, 117, 131 Rectum, 109, 115, 121, 123, 129, 131 Refer, 1, 110, 112, 131 Refraction, 131, 132 Regimen, 38, 115, 131 Resorption, 3, 120, 131 Restriction Mapping, 10, 131 Retroviral vector, 5, 6, 20, 39, 66, 67, 81, 117, 131 Retrovirus, 58, 62, 131 Risk factor, 73, 131 S Sacroiliac Joint, 13, 131 Saliva, 131 Salivary, 19, 115, 131 Salivary glands, 115, 131 Scans, 131 Schizoid, 131, 136 Schizophrenia, 131, 136 Schizotypal Personality Disorder, 131, 136 Screening, 10, 13, 16, 25, 70, 112, 131 Segregation, 131 Sequencing, 66, 128, 132 Serum, 12, 16, 105, 112, 132, 135 Sex Characteristics, 130, 132 Shock, 111, 125, 132, 134 Shunt, 31, 132 Side effect, 79, 81, 105, 108, 132, 134 Signs and Symptoms, 74, 132 Skeletal, 13, 15, 26, 34, 38, 47, 51, 71, 132 Skeleton, 102, 132 Soft tissue, 109, 126, 132 Specialist, 93, 115, 132 Species, 124, 132, 134, 136 Specificity, 105, 132 Spectrum, 7, 51, 132 Sperm, 111, 132 Spinal cord, 110, 111, 122, 124, 125, 132 Spleen, 4, 11, 13, 15, 21, 26, 37, 54, 68, 71, 102, 106, 123, 132 Splenectomy, 20, 41, 45, 102, 120, 132

Splenomegaly, 35, 36, 39, 41, 46, 71, 102, 120, 121, 132 Staging, 131, 132 Steatosis, 116, 133 Stem Cells, 5, 133 Stimulus, 116, 121, 133 Stomach, 105, 115, 116, 117, 119, 122, 127, 132, 133 Strand, 128, 133 Subacute, 14, 67, 121, 133 Subcapsular, 32, 133 Substrate, 8, 21, 27, 52, 67, 70, 120, 133 Supplementation, 21, 30, 58, 133 Support group, 74, 133 Suppression, 18, 37, 133 Symptomatic, 9, 52, 133 Systemic, 106, 109, 120, 121, 122, 133 Systemic disease, 120, 133 Systolic, 120, 133 T Taurine, 19, 133 Tetracycline, 8, 133 Thalassemia, 108, 133 Therapeutics, 80, 133 Thermal, 115, 118, 128, 133 Threshold, 114, 120, 133 Thrombin, 129, 133 Thrombomodulin, 129, 133 Thrombophilia, 35, 134 Thrombosis, 130, 134 Thyroxine, 105, 134 Tissue, 8, 15, 31, 107, 109, 110, 113, 115, 116, 118, 122, 123, 124, 125, 126, 127, 132, 134 Tomography, 39, 54, 113, 134 Toxic, iv, 134 Toxicity, 115, 134 Toxicokinetics, 134 Toxicology, 88, 134 Transcriptase, 131, 134 Transduction, 67, 118, 134 Transfection, 109, 117, 134 Translation, 106, 134 Transplantation, 5, 6, 15, 37, 45, 67, 134 Trauma, 125, 134 Tremor, 127, 134 Triad, 119, 134 Trisomy, 26, 134 Tuberculosis, 123, 134 Tumor marker, 73, 134 Tumor Necrosis Factor, 47, 135

143

U Ulcerative colitis, 129, 135 Ultrasonography, 11, 26, 135 Urethra, 129, 135 Urinary, 120, 121, 135 Urine, 19, 109, 121, 130, 135 V Vaccines, 135 Vagina, 114, 135 Vascular, 13, 119, 121, 128, 135 Vector, 6, 67, 71, 134, 135 Vein, 107, 122, 126, 135 Venous, 107, 130, 135 Ventricles, 111, 120, 135 Ventricular, 120, 135 Vertebral, 49, 135 Veterinary Medicine, 87, 135 Villi, 120, 135

Viral, 54, 131, 134, 135 Virus, 6, 13, 39, 108, 111, 117, 121, 131, 134, 135 Visceral, 14, 16, 19, 127, 135 Vitro, 135 Vivo, 6, 8, 136 W White blood cell, 107, 121, 123, 124, 125, 128, 136 Withdrawal, 23, 136 X Xenograft, 106, 136 X-ray, 55, 102, 109, 113, 116, 126, 131, 136 Y Yeasts, 127, 136 Z Zygote, 113, 125, 136 Zymogen, 129, 136

144

Gaucher Disease