FANCONI ANEMIA A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R E FERENCES
J AMES N. P ARKER , M.D. AND P HILIP M. P ARKER , P H .D., E DITORS
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ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright 2004 by ICON Group International, Inc. Copyright 2004 by ICON Group International, Inc. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without written permission from the publisher. Printed in the United States of America. Last digit indicates print number: 10 9 8 7 6 4 5 3 2 1
Publisher, Health Care: Philip Parker, Ph.D. Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher's note: The ideas, procedures, and suggestions contained in this book are not intended for the diagnosis or treatment of a health problem. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960Fanconi Anemia: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References / James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary, and index. ISBN: 0-497-00432-1 1. Fanconi Anemia-Popular works. I. Title.
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Disclaimer This publication is not intended to be used for the diagnosis or treatment of a health problem. It is sold with the understanding that the publisher, editors, and authors are not engaging in the rendering of medical, psychological, financial, legal, or other professional services. References to any entity, product, service, or source of information that may be contained in this publication should not be considered an endorsement, either direct or implied, by the publisher, editors, or authors. ICON Group International, Inc., the editors, and the authors are not responsible for the content of any Web pages or publications referenced in this publication.
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Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this book which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which produce publications on Fanconi anemia. Books in this series draw from various agencies and institutions associated with the United States Department of Health and Human Services, and in particular, the Office of the Secretary of Health and Human Services (OS), the Administration for Children and Families (ACF), the Administration on Aging (AOA), the Agency for Healthcare Research and Quality (AHRQ), the Agency for Toxic Substances and Disease Registry (ATSDR), the Centers for Disease Control and Prevention (CDC), the Food and Drug Administration (FDA), the Healthcare Financing Administration (HCFA), the Health Resources and Services Administration (HRSA), the Indian Health Service (IHS), the institutions of the National Institutes of Health (NIH), the Program Support Center (PSC), and the Substance Abuse and Mental Health Services Administration (SAMHSA). In addition to these sources, information gathered from the National Library of Medicine, the United States Patent Office, the European Union, and their related organizations has been invaluable in the creation of this book. Some of the work represented was financially supported by the Research and Development Committee at INSEAD. This support is gratefully acknowledged. Finally, special thanks are owed to Tiffany Freeman for her excellent editorial support.
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About the Editors James N. Parker, M.D. Dr. James N. Parker received his Bachelor of Science degree in Psychobiology from the University of California, Riverside and his M.D. from the University of California, San Diego. In addition to authoring numerous research publications, he has lectured at various academic institutions. Dr. Parker is the medical editor for health books by ICON Health Publications. Philip M. Parker, Ph.D. Philip M. Parker is the Eli Lilly Chair Professor of Innovation, Business and Society at INSEAD (Fontainebleau, France and Singapore). Dr. Parker has also been Professor at the University of California, San Diego and has taught courses at Harvard University, the Hong Kong University of Science and Technology, the Massachusetts Institute of Technology, Stanford University, and UCLA. Dr. Parker is the associate editor for ICON Health Publications.
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About ICON Health Publications To discover more about ICON Health Publications, simply check with your preferred online booksellers, including Barnes&Noble.com and Amazon.com which currently carry all of our titles. Or, feel free to contact us directly for bulk purchases or institutional discounts: ICON Group International, Inc. 4370 La Jolla Village Drive, Fourth Floor San Diego, CA 92122 USA Fax: 858-546-4341 Web site: www.icongrouponline.com/health
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Table of Contents FORWARD .......................................................................................................................................... 1 CHAPTER 1. STUDIES ON FANCONI ANEMIA .................................................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Fanconi Anemia ............................................................................ 4 E-Journals: PubMed Central ....................................................................................................... 24 The National Library of Medicine: PubMed ................................................................................ 26 CHAPTER 2. NUTRITION AND FANCONI ANEMIA .......................................................................... 73 Overview...................................................................................................................................... 73 Finding Nutrition Studies on Fanconi Anemia........................................................................... 73 Federal Resources on Nutrition ................................................................................................... 75 Additional Web Resources ........................................................................................................... 75 CHAPTER 3. ALTERNATIVE MEDICINE AND FANCONI ANEMIA .................................................... 77 Overview...................................................................................................................................... 77 National Center for Complementary and Alternative Medicine.................................................. 77 Additional Web Resources ........................................................................................................... 78 General References ....................................................................................................................... 79 CHAPTER 4. DISSERTATIONS ON FANCONI ANEMIA...................................................................... 81 Overview...................................................................................................................................... 81 Dissertations on Fanconi Anemia................................................................................................ 81 Keeping Current .......................................................................................................................... 81 CHAPTER 5. PATENTS ON FANCONI ANEMIA ................................................................................ 83 Overview...................................................................................................................................... 83 Patents on Fanconi Anemia ......................................................................................................... 83 Patent Applications on Fanconi Anemia ..................................................................................... 84 Keeping Current .......................................................................................................................... 85 CHAPTER 6. PERIODICALS AND NEWS ON FANCONI ANEMIA ...................................................... 87 Overview...................................................................................................................................... 87 News Services and Press Releases................................................................................................ 87 Academic Periodicals covering Fanconi Anemia ......................................................................... 88 APPENDIX A. PHYSICIAN RESOURCES ............................................................................................ 93 Overview...................................................................................................................................... 93 NIH Guidelines............................................................................................................................ 93 NIH Databases............................................................................................................................. 95 Other Commercial Databases....................................................................................................... 97 APPENDIX B. PATIENT RESOURCES ................................................................................................. 99 Overview...................................................................................................................................... 99 Patient Guideline Sources............................................................................................................ 99 Associations and Fanconi Anemia ............................................................................................. 102 Finding Associations.................................................................................................................. 102 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 105 Overview.................................................................................................................................... 105 Preparation................................................................................................................................. 105 Finding a Local Medical Library................................................................................................ 105 Medical Libraries in the U.S. and Canada ................................................................................. 105 ONLINE GLOSSARIES................................................................................................................ 111 Online Dictionary Directories ................................................................................................... 111 FANCONI ANEMIA DICTIONARY ......................................................................................... 113
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INDEX .............................................................................................................................................. 157
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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 Fanconi anemia is indexed in search engines, such as www.google.com or others, a non-systematic approach to Internet research can be not only time consuming, but also incomplete. This book was created for medical professionals, students, and members of the general public who want to know as much as possible about Fanconi anemia, using the most advanced research tools available and spending the least amount of time doing so. In addition to offering a structured and comprehensive bibliography, the pages that follow will tell you where and how to find reliable information covering virtually all topics related to Fanconi anemia, from the essentials to the most advanced areas of research. Public, academic, government, and peer-reviewed research studies are emphasized. Various abstracts are reproduced to give you some of the latest official information available to date on Fanconi anemia. Abundant guidance is given on how to obtain free-of-charge primary research results via the Internet. While this book focuses on the field of medicine, when some sources provide access to non-medical information relating to Fanconi anemia, these are noted in the text. E-book and electronic versions of this book are fully interactive with each of the Internet sites mentioned (clicking on a hyperlink automatically opens your browser to the site indicated). If you are using the hard copy version of this book, you can access a cited Web site by typing the provided Web address directly into your Internet browser. You may find it useful to refer to synonyms or related terms when accessing these Internet databases. NOTE: At the time of publication, the Web addresses were functional. However, some links may fail due to URL address changes, which is a common occurrence on the Internet. For readers unfamiliar with the Internet, detailed instructions are offered on how to access electronic resources. For readers unfamiliar with medical terminology, a comprehensive glossary is provided. For readers without access to Internet resources, a directory of medical libraries, that have or can locate references cited here, is given. We hope these resources will prove useful to the widest possible audience seeking information on Fanconi anemia. The Editors
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From the NIH, National Cancer Institute (NCI): http://www.cancer.gov/cancerinfo/ten-things-to-know.
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CHAPTER 1. STUDIES ON FANCONI ANEMIA Overview In this chapter, we will show you how to locate peer-reviewed references and studies on Fanconi anemia.
The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and Fanconi anemia, you will need to use the advanced search options. First, go to http://chid.nih.gov/index.html. From there, select the “Detailed Search” option (or go directly to that page with the following hyperlink: http://chid.nih.gov/detail/detail.html). The trick in extracting studies is found in the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Journal Article.” At the top of the search form, select the number of records you would like to see (we recommend 100) and check the box to display “whole records.” We recommend that you type “Fanconi anemia” (or synonyms) into the “For these words:” box. Consider using the option “anywhere in record” to make your search as broad as possible. If you want to limit the search to only a particular field, such as the title of the journal, then select this option in the “Search in these fields” drop box. The following is what you can expect from this type of search: •
Orofacial Manifestations in the Primary Immunodeficiency Disorders Source: Oral Surgery, Oral Medicine, Oral Pathology. 78(1): 4-13. July 1994. Summary: In the past decade, much attention has been given to the many oral manifestations of HIV infection. Though overall much less common, the primary or genetically determined immunodeficiencies have been and are increasingly recognized, yet the oral aspects of these disorders have been given little attention in the oral pathology and medical literature. This review article details the oral aspects of wellcharacterized, primary immunodeficiencies. The authors note that, as with HIV-related disease, oral candidal infection and oral ulceration are relatively common features, and periodontal disease can occur, particularly when there are granulocyte defects. Disorders covered include severe combined immunodeficiency disorders (SCID), Xlinked agammaglobulinemia, common variable immunodeficiency (CVID), selective IgA
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deficiency, other humoral deficiencies, Wiskott-Aldrich syndrome (WAS), ataxia telangiectasia (AT), DiGeorge syndrome, congenital disorders associated with immunodeficiency (Bloom syndrome, Fanconi anemia, Down syndrome, Chediak Higashi syndrome, acrodermatitis enteropathica, hyper IgE syndrome, chronic mucocutaneous candidiasis, and thymoma with immunodeficiency), complement component deficiencies, deficiencies of complement regulatory proteins, reduced leukocyte numbers, and defective phagocyte function. 6 tables. 139 references. (AA-M).
Federally Funded Research on Fanconi Anemia The U.S. Government supports a variety of research studies relating to Fanconi anemia. These studies are tracked by the Office of Extramural Research at the National Institutes of Health.2 CRISP (Computerized Retrieval of Information on Scientific Projects) is a searchable database of federally funded biomedical research projects conducted at universities, hospitals, and other institutions. Search the CRISP Web site at http://crisp.cit.nih.gov/crisp/crisp_query.generate_screen. You will have the option to perform targeted searches by various criteria, including geography, date, and topics related to Fanconi anemia. For most of the studies, the agencies reporting into CRISP provide summaries or abstracts. As opposed to clinical trial research using patients, many federally funded studies use animals or simulated models to explore Fanconi anemia. The following is typical of the type of information found when searching the CRISP database for Fanconi anemia: •
Project Title: CLINICAL APPLICATIONS OF A NOVEL FANCONI ANEMIA ASSAY Principal Investigator & Institution: Shimamura, Akiko; Dana-Farber Cancer Institute 44 Binney St Boston, Ma 02115 Timing: Fiscal Year 2002; Project Start 05-JUL-2002; Project End 31-MAY-2007 Summary: Congenital bone marrow failure syndromes are characterized by abnormal hematopoietic cell growth, differentiation, and survival. Bone marrow transplant is the only available curative treatment, but is associated with significant side effects and limited by donor availability. The development of new therapeutic modalities calls for investigators with: 1. Expertise in bone marrow failure syndromes, 2. An understanding of the clinical implications of new molecular discoveries, 3. Experience in the design and implementation of clinical trials. Dr. Shimamura is a pediatric hematologist/oncologist with a molecular background in signal transduction and apoptosis. The proposed training program is designed to allow her to develop expertise in bone marrow failure syndromes and to gain experience in the design and implementation of patient-oriented research. Her long-term goal is to become an independent investigatory applying our understanding of molecular mechanisms of bone marrow failure to solve clinical problems. Dr. Shimamura will pursue her career development under the co- mentorship of Dr. Alan D'Andrea and Dr. David Nathan. Dr. D'Andrea's studies have uncovered a novel Fanconi anemia (FA) biochemical pathway. She proposes to study the clinical
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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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applications of these findings as follows: 1. Investigate the FANCD activation assay as a new functional screen for the FA pathway, 2. Screen for pharmacological agents that augment FANCD activation, and 3. Assess the effect of FA gene replacement therapy on the restoration of FANCD activity as part of the on-going Dana-Farber/Children's Hospital FA gene therapy project directed by Dr. Nathan. Dr. Shimamura has assembled a committee of expert advisors and collaborators to assist her in this project. Her project will be supported by several local core facilities and programs including the Fanconi Anemia Center, the Harvard Vector Laboratory, the Cell Manipulation and Gene Transfer Laboratories, the Clinical Gene Therapy Program, and the General Clinical Research Center at Children's Hospital. To complete her training, she will attend a bone marrow failure clinic at Children's Hospital, build a bone marrow failure repository for future independent studies, and complete course work on clinical research design, implementation and analysis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: COMPUTATIONAL ANALYSIS OF HUMAN 'AT-RISK' DNA MOTIFS Principal Investigator & Institution: Stenger, Judith E.; Assistant Professor; Medicine; Duke University Durham, Nc 27710 Timing: Fiscal Year 2002; Project Start 01-JUN-2001; Project End 31-MAY-2004 Summary: (Taken from the Candidate's Abstract) At-Risk DNA Motifs (ARMS), which include repetitive elements such as Alu sequences, homonucleotide runs and triplet repeats, are potentially unstable segments of the human genome. ARMS are a factor in genetic susceptibility to disease, requiring particular combinations of genetic backgrounds and environmental triggers to express a disease phenotype. While some of the mechanisms are understood, it is not clear under what circumstances repetitive DNA elements mediate pathological mutagenesis. Although a high burden of these sequences is generally tolerated in humans, they can have an enormous impact on health by contributing to diseases that have devastating effects on afflicted individuals. For example, Alus have been linked to numerous diseases including Fanconi anemia, alphazerothalassemia, leukemia, hypertension, neurofibromatosis, breast, and colon cancers. Trinucleotide repeat expansions have been linked with Kennedy's Disease, Huntington's Disease, myotonic muscular dystrophy, and Friedreich ataxia. The long term objective of this proposal is to gain insight into the genetic factors that mitigate gene rearrangement in hopes of predicting when the presence of a repetitive element truly constitutes a threat to the health of an individual. The hypothesis is that the characterization of ARMS according to all possible attributes (i.e. size of repeats, separation distances between repeats, orientation, sequence similarity between repeats, nucleotide base constitution and proximity and/or containment of mutagenic and/or toxicological agent targets, DNA processive or other enzymatic target sites) can reveal largely excluded situations that can be viewed as unstable. It is also postulated that a multidimensional database of repetitive sequences characterized according to the aforementioned attributes can be used to predict repetitive elements that are most prone to mutation, ARMS, while increasing our understanding of the interactions between these genetic elements and their environment. The approach is to use a combination of computational biology and molecular genomic analysis to locate and analyze ARMS. The specific aims of this proposal are to: 1) characterize available data according to the conceivable relevant attributes of size, distance, orientation, degree of homology, base constitution and containment of known target sequences. 2) To test the hypothesis by computationally identifying loci that have already known to contain ARMS linked to a
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mutation resulting in disease, and then to identify specific genes that may be at-risk for mutation and experimentally testing them using molecular biological approaches. 3) To set up an interactive on-line database and program server so that the scientific community can use the information and apply it to drive experimental research. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CORE--CYTOGENETICS Principal Investigator & Institution: Olson, Susan B.; Oregon Health & Science University Portland, or 972393098 Timing: Fiscal Year 2002 Summary: The Cytogenetics Core is of major significance to the success of Projects 1,2, 3 and the Core C Repository. Its expertise draws on 32 years of experience of the Research and Clinical Cytogenetics Laboratories at Oregon Health Sciences University. These laboratories are recognized internationally for the highest standards of academic cytogenetics excellence. Together, they have a staff of 14 technologists and research associates studying approximately 2,500 blood, bone marrow, solid tumor, amniotic fluid, chorionic villus and other solid tissue samples annually. Through their early efforts of test development, and more recently as the Cytogenetics Core for the current program project grant, these combined laboratories have become a national resource for Fanconi anemia testing. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: CORE--FANCONI ANEMIA CELL REPOSITORY Principal Investigator & Institution: Grompe, Markus Cp.; Professor; Oregon Health & Science University Portland, or 972393098 Timing: Fiscal Year 2002 Summary: The OHSU Fanconi Anemia Cell Repository (Core C) serves as a local, national and internal source of cell lines for research on Fanconi Anemia. In addition, it provides information regarding complementation groups and/or mutations to A patients and their families. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CORRECTION OF CONGENITAL DISEASES BY STEM CELL THERAPY Principal Investigator & Institution: Nathan, David G.; President Emeritus; Dana-Farber Cancer Institute 44 Binney St Boston, Ma 02115 Timing: Fiscal Year 2002 Summary: Gene replacement therapy of congenital bone marrow disorders is a long sought treatment goal and a great challenge to experimental hematology. In this project we focus on gene replacement for Fanconi Anemia and Diamond Blackfan Anemia. Both diseases require successful gene insertion and function in hematopoietic stem cells (HSC) and their progeny. Successful gene transfer into HSC requires selection of transfected and functioning HSC by the host. This will occur in Fanconi Anemia because HSC lacking the Fanconi gene die in the marrow. In Diamond Blackfan Anemia, the selection occurs at the level of the erythroid progenitor and precursor cells. We will use two classes of retrovirus vectors; moloney leukemia based vectors and HIV based lentivirus vectors. These will be tested in vitro and in two in vivo models; the NOD SCID mouse and in rhesus monkey. We have shown that it is imperative to utilize short
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incubations preferably in cold temperatures in order to protect the HSC from toxicity induced by the procedures themselves. These new incubation conditions will be tested in the experimental models. Appropriate vectors will be produced at very high concentrations in our GMP vector laboratory and the scale up to large human samples will be carried out in our GMP cell manipulation core laboratory. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ANEMIA
CYTOKINE-MEDIATED
PATHOPHYSIOLOGY
IN
FANCONI
Principal Investigator & Institution: Chen, Ming; Pediatrics; Weill Medical College of Cornell Univ New York, Ny 10021 Timing: Fiscal Year 2002; Project Start 21-AUG-2002 Summary: Fanconi anemia (FA) is an autosomal recessive disorder characterized by cellular hypersensitivity to DNA crosslinking agents such as mitomycin C (MMC) and diepoxybutane (DEB) (Auerbach 1993), bone marrow (BM) failure, diverse congenital anomalies, and a marked increased in the incidence of malignancies. Eight complementation groups (FA-A through FA-H) have been identified. The human genes defected in the FA-C, FA- A FA-G groups were recently cloned. Fancc-deficient mice have been created by targeted mutations of the murine Fancc gene. Cells from France -/mice showed hypersensitivity to MMC and DEB. Surprisingly, however, no gross hematologic defects or congenital anomalies were detected, although the homozygous mice showed decreased fertility. Evidence has been collected indicating that certain cytokines are involved in Fanconi anemia. TNF-alpha and IFN-gamma are inhibitory cytokines that can induced deregulated. Progenitor growth and apoptosis in Fancc-/hematopoietic progenitor cells (HPC). FANCC transgene protected HPC FANCC transgene protected HPC from Fas-mediated apoptosis. IL-6, TNF-alpha and IFNgamma, among others, are known to mediate immune-neuro-endocrine interactions. More recently, multiple endocrine abnormalities were discovered in FA patients, including deficiencies in growth hormone, thyroid and gonads function. We hypothesize that the endocrine abnormalities be due to aberrant response to cytokines, particularly TNF-alpha and IFN-gamma, in the endocrine glands. The proposed project will use Fancc-deficient mice and cell lines derived from endocrine glands, along with certain cytokines, to test this hypothesis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DNA REPAIR DEFECT IN FANCONI ANEMIA, GROUP A Principal Investigator & Institution: Lambert, Muriel W.; Professor; Pathology and Lab Medicine; Univ of Med/Dent Nj Newark Newark, Nj 07107 Timing: Fiscal Year 2002; Project Start 01-JUL-1995; Project End 31-MAY-2003 Summary: The goal of this proposal is to delineate the relationship between the FAA and FAC gene products and the DNA repair defect in Fanconi anemia, complementation groups A (FA-A) and C (FA-C). It has been hypothesized that an underlying mechanism for this disorder may involve a DNA repair defect. We have isolated a DNA endonuclease complex from the nuclei of FA-A and FA-C cells and shown that it is defective in ability to incise DNA at sites of interstrand cross- links. Levels of a 230 kDa protein, associated with this complex and which binds to crosslinked DNA, are decreased in FA-A and FA-C cells. This protein has recently been identified as nonerythroid alpha spectrinllsigma* (alphaSpIIsigma*). The deficiency in alphaSpIIsigma* is corrected in FA-A cells transduced with a retroviral vector
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expressing the FAA cDNA, indicating that the FAA gene plays a role in its expression or stability. alphaSpIIsigma* also forms a complex with the FAA and FAC proteins in the nucleus which suggests that this complex may play role in DNA repair. It is possible that alphaSpllsigma* acts as a scaffold to help align or enhance interaction between proteins involved in the repair of interstrand cross-links and proteins that interact with FAA and FAC. The present proposal will address this by first determining the isoform of the alphaSpllsigma* we have identified and producing a recombinant protein that can be used in further studies. Exactly what proteins are associated with the FAA-FACalphaSpllsigma* complex, whether any of these proteins have binding affinity for DNA containing interstrand cross-links, and whether there is a deficiency in any of these proteins in FA-A and FA-C cells will be determined. The role of the FAA and FAC proteins in regulating the expression or stability of alphaSpllsigma* will be assessed as will the role of each of these three proteins in the repair of DNA interstrand cross-links. If alphaSpllsigma* is acting as a scaffolding protein, to help align and allow interactions between these as well as other proteins, this could have far reaching implications in a number of different processes, in addition to DNA repair, which have been associated with this protein, such as signal transduction and cell growth and development. A deficiency in alphaSpllsigma* in FA cells could thus ultimately affect hematopoietic differentiation and development. Isolation and identification of proteins associated with the FAA-FAC- alphaSpllsigma* complex and determination of their interactions with each other, other nuclear proteins, and DNA repair should help elucidate the basis of bone marrow failure and the development of aplastic anemia and leukemia in FA. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DOSE INTENSIFICATION BY GENE TRANSDUCTION IN CANCER Principal Investigator & Institution: Erickson, Leonard C.; Robert Wallace Miller Professor of Oncol; Pediatrics; Indiana Univ-Purdue Univ at Indianapolis 620 Union Drive, Room 618 Indianapolis, in 462025167 Timing: Fiscal Year 2002; Project Start 11-MAY-1998; Project End 28-FEB-2004 Summary: The overall goal of this program is to investigate the role of DNA repair in chemotherapy resistance, particularly resistance to DNA damaging agents. In each project, investigators will seek to exploit molecular technology either to investigate the relationship of DNA repair protein expression to resistance of cells t alkylating agents and chemotherapy- induced oxidative damage, or to effect resistance in cells to chemotherapy in preclinical or clinical studies. Goals specifically include new approaches to the treatment of brain tumors, lymphomas, childhood solid tumors, and the pre-cancerous genetic condition, Fanconi Anemia. Individual projects explore the use of retroviral vectors and transgenic mice to effect resistance to chloroethylnitrosoureas (CENU) and other alkylating agents, such as, streptozotocin, bleomycin and cyclophosphamide. A clinical trial using gene transfer technology in patients with high risk brain tumors is proposed. An additional approach to increasing therapeutic effectiveness involves selective depletion of tumor cell DNA repair capacity, which is developed in this proposal in both pre-clinical and clinical studies. Since the organs of toxicity of intensive chemotherapy with both CENUs and other alkylating agents are the bone marrow and lung, the program also explores the role of DNA repair protein expression in these organs in protection from the cytotoxic actions of several alkylating agents. In addition, oxidative DNA damage due to chemotherapy is studied utilizing cells from patients with Fanconi Anemia as a model. The proposed research plan draws upon a group of experienced and well-funded investigators with diverse but complimentary experience in DNA repair, hematopoiesis, molecular biology, vector
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technology, pharmacology, and lung biology. The program seeks to weave these interests and expertise into a cohesive and interrelated research plan which can produce innovative approaches to the treatment of human cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DYSREGULATION OF HEMATOPOIESIS IN FANCONI ANEMIA Principal Investigator & Institution: Bagby, Grover; Professor; Oregon Health & Science University Portland, or 972393098 Timing: Fiscal Year 2002 Summary: Over the past 4 years we have documented that hypersensitivity to mitotic inhibitory factors accounts, at least in part, for the apoptotic phenotype in FA cells. To date we have focused on elucidating the potential relationship between FANC and elements of the IFN-gamma pathway because of persuasive evidence that this cytokine plays a role in the pathogenesis of acquired aplastic anemia. Regarding the function of the FANC protein, we have made tow discoveries we believe to be of critical importance. First, FAN-C cells constitutively express IFN-dependent genes that induce mitotic arrest and apoptosis in hematopoietic progenitor cells and these mutant cells expresses these genes through signaling pathways that do not involve stat1. Transduction of FAN-C cells fail to phosphorylate stat1 after exposure to IFN-gamma because the normal FANC protein functions as a chaperone to deliver stat1 to the docking sites on the IFN- receptor alpha chain (IFNGR1). These two findings have converged with recently published findings on the anti-apoptotic function of hematopoietic growth factor receptors to lead us to hypothesize that Fanconi antiapoptotic function of hematopoietic growth factor receptors to lead us to hypothesize that Fanconi progenitor cells are apoptotic not only because of hypersensitivity to mitotic inhibitors, but because they cannot properly transduce anti-apoptotic signals through hematopoietic growth factor receptors. The studies described in this proposal are designed to test three hypotheses. First, that proper stat- mediated signal transduction via hematopoietic growth factors involves the delivery by the FANC protein, of stat molecules to specific receptor chains after ligand binding (this hypothesis forms the basis of Aim 1). Second, that the delivery of phosphorylated stat molecules to cognate binding sites on nuclear DNA also depends upon binding of stat-dimers to FANC protein (Aim 2). Third, that a specific stat1-independent signaling pathway governs; (a) the constitutive expression of p21wf1, IRF-1 and ISGF3-gamma in FAN-C cells and (b) same non-stat pathway accounts for the IFN/TNF/TGF sensitivity of FANC cells (Aim 3). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: ENTRANCE INTO THE INTERNATIONAL FANCONI ANEMIA REGISTRY Principal Investigator & Institution: Auerbach, Arleen D.; Rockefeller University New York, Ny 100216399 Timing: Fiscal Year 2002 Summary: Fanconi anemia (FA) is a heterogeneous disease involving multiple organ systems including hematologic, skeletal, renal, neurologic and endocrine. Patients are predisposed to malignancies, particularly acute myelogenous leukemia (AML). Although the genes for two of the eight FA complementation groups, FANCC, FANCA and FANCG, (alias FAC, FAA, FAG) have been cloned, and mutations identified in both of these genes in affected individuals, the precise function of these genes has yet to be
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elucidated. It is the objective of this protocol to define the phenotypic spectrum of this rare syndrome by study of a large number of patients with diverse features. These patients will also provide a source of cells for molecular studies. It is an objective our study to extend our ability to define the FA genotype of all patients and to make genotype-phenotype correlations. This would enable physicians to better predict clinical outcome and aid decision-making regarding major therapeutic modalities for this clinically heterogeneous disorder. Understanding the genetic defect in FA should lead to a better understanding of birth defects and cancer predisposition in general, and the interaction of genetic and epigenetic factors in their pathogenesis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: EVALUATION OF GENETIC THERAPY IN FANC MICE Principal Investigator & Institution: Clapp, David W.; Associate Professor; Indiana Univ-Purdue Univ at Indianapolis 620 Union Drive, Room 618 Indianapolis, in 462025167 Timing: Fiscal Year 2002 Summary: Fanconi Anemia (FA) is an autosomal recessive syndrome characterized by progressive pancytopenia, diverse congenital abnormalities, and increased predisposition to malignancy. The only cure for FA has been HLA-matched bone marrow, and more recently umbilical cord blood, transplantation. The cloning of cDNAs for FA by functional complementation has opened up the possibility for correction of the disease by gene therapy. Our hypothesis is that hematopoietic stem and progenitor cells present in cord blood and bone marrow of patients with FA can be efficiently and stably transduced with retroviral- and adeno associated virus (AAV)- vectors containing the FA complementation C gene with correction of the growth patterns of these cells, and the enhanced sensitivity of FA cells to chromosome-breakage and kill by drugs. To this end the following aims are proposed: 1) Construct high titer retroviral- and AAVvectors containing the FA complementation C gene. 2) Compare vectors for high efficiency stable transduction of stem and progenitor cells in normal cord blood and later in normal bone marrow cells using first relatively unseparated cells present in a low-density fraction, then more highly purified cells. These comparisons will then be done in marrow and cord blood cells from patients with complementation C-FA to see if their growth characteristics, chromosomal fragility, and hypersensitivity to drugs can be corrected. 3) Evaluate stable integration of genes into the earliest subsets of hematopoietic stem/progenitor cells and compare this with integration into later more mature subsets of the cells by using a variety of in vitro and in vivo assays. In vitro assays include those for LTC-IC, HPP-CFC, CFU-GEMM, BFU-E and CFU-GM. Replating capacity of single HPP-CFC- and CFU-GEMM-colonies into secondary and subsequent plates will be used as an estimate of self-renewal capacity, and gene integration of sequentially replated colonies determined. For in vivo analysis of stable integration we will use human cell-inoculated SCID mice. 4) Compare stable gene integration, using retroviral and AAV- vectors pre- and post-cryopreservation of cord blood and before and after expansion of the stem and progenitor cells of these tissues sources. The information obtained could lead to a gene therapy approach to cure the FA syndrome by autologous stem/progenitor cell transplantation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: FAC IN STEM CELL FUNCTION AND OXYGEN SENSITIVITY Principal Investigator & Institution: Haneline, Laura S.; Pediatrics; Indiana Univ-Purdue Univ at Indianapolis 620 Union Drive, Room 618 Indianapolis, in 462025167
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Timing: Fiscal Year 2002; Project Start 13-AUG-1999; Project End 31-JUL-2004 Summary: Fanconi anemia (FA) is a complex, autosomal recessive disorder characterized by bone marrow (BM) failure, increased incidence of malignancies, and hypersensitivity to bifunctional alkylating agents such as mitomycin C (MMC). There are eight complementation types of FA that have overlapping phenotypes inferring the existence of eight genes in a common biochemical pathway. It is clear that the hematopoietic progenitor compartment is affected by loss of Fanconi anemia complementation type C protein (FAC). However, no direct studies have been conducted evaluate whether the hematopoietic stem cell (HSC) compartment is similarly affected due to difficulties in assessing HSC function in the human system. The development of a murine model containing a homozygous disruption in the murine homologue (Fac) of FAC allows comprehensive evaluation of this question. Using this murine model, we showed that Fac -/- hematopoietic progenitors were hypersensitive to MMC, similar to FA patients. These data suggest that Fac -/- mice will be a good model system to study FA. Several lines of evidence suggest that FA proteins may have a role in maintaining normal oxidative metabolism. In addition, the recent observation in COS cells that FAC modulates NADPH:cytochrome p450 reductase (RED) activity, an important enzyme that generates oxygen radicals and activates several drugs such as MMC supports this hypothesis. The goals of this application are: 1) to determine whether loss of Fac affects HSC function, 2) to determine if Fac -/- hematopoietic cells have an increased sensitivity to oxidative stress, and 3) to evaluate whether overexpression of RED induces a hypersensitivity to oxidative stresss in Fac +/+ cells. These data will provide important information in elucidating the pathogenesis of BM failure and carcinogenesis in FA as well as investigate a distinct function of Fac in normal oxidative metabolism that could provide potential implications for modifying current treatment protocols for FA patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: FANCONI ANEMIA Principal Investigator & Institution: D'andrea, Alan D.; Professor; Dana-Farber Cancer Institute 44 Binney St Boston, Ma 02115 Timing: Fiscal Year 2002 Summary: Fanconi Anemia (FA) is an autosomal recessive cancer susceptibility disorder characterized by multiple congenital abnormalities, progressive bone marrow failure, and cellular sensitivity to DNA crosslinking agents. FA is characterized by hematopoietic stem cell dysfunction, and the treatment of choice for the disease is an allogeneic bone marrow transplant. Since most FA patients do not have a suitable donor, FA is also a candidate disease for gene therapy. The purpose of the current project is to focus on various of the basic biology of FA related to our ongoing gene therapy trials. The specific aims for the five year study period are (1) To develop and characterize a mouse model for Fanconi Anemia Complementation Group G (FANCG knock-out mouse). Our recent studies demonstrate that FA-G patients have more severe disease than FA-A patients. Therefore, a mouse model for FA-G may demonstrate distinct pathology, compared to the previously describe FA- C mouse. The subaims of this section are to generate a colony of FANCG (-/-, -/+, and +/+) mice, to characterize the hematopoietic system in the FANCG knock-out mouse, to characterize the stem cell population in FANCG knock-out, and to perform competitive repopulation studies, comparing the relative engraftment of FANCG (-/-) cells versus FANCG (+/+) cells. In specific aim 2, we will further develop murine models for Fanconi Anemia Gene Therapy in order to compare the transduction of bone marrow cells from FANCC,
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FANCA, and FANCG knockout mouse models with either pMMP (murine) retroviral vectors or lentiviral vectors. A significant strength of this specific aim will be our ability to assay infection efficiency of transduced bone marrow, by using PCR of cDNA integrations and immunofluorescence of expressed heterologous FA proteins. In specific aim 3, we will systematically compare cell lines and primary cells derived from patients from all nine complementation groups of FA for distinct cellular abnormalities. This aim will be closely aligned with our new Fanconi Anemia Diagnostic and Clinical Center at the DFCI, which has provided us with the opportunity to collect and subtype cell lines from many FA patients. We will compare the ionizing radiation (IR) sensitivity and bleomycin sensitivity of all FA complementation groups, and will examine these cell lines for defects in Non-Homologous End joining (NHEJ) and Homologous Recombination (HR). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: FANCONI ANEMIA GENE PATHWAY IN RADIATION RESPONSES Principal Investigator & Institution: Thompson, Lawrence H.; Senior Scientist; Biology & Biotechnology Res; University of Calif-Lawrnc Lvrmr Nat Lab Lawrence Livermore National Lab Livermore, Ca 945509234 Timing: Fiscal Year 2002; Project Start 24-JAN-2001; Project End 31-DEC-2004 Summary: The project's objective is to understand the molecular regulatory processes cells use to minimize genetic damage and genetic instability associated with reactive oxygen species (ROS) arising from endogenous processes or ionizing radiation (IR). This goal is addressed through studies of FANCG/XRCC9, the gene that is defective in. group G of the cancer-prone disorder Fanconi anemia (FA). Because FancG protein confers IR resistance in hamster cells, the human homolog is expected to participate in IR responses in human cells. Historically, a link between the FA genes and radiation responses has been unclear, with some studies suggesting that the primary defect in FA lies in removing DNA interstrand crosslinks. The general hypothesis to be tested is that the FANCG protein, as a member of a multiprotein complex, protects mammalian cells against endogenous and IR-generated oxidative damage and maintains genomic integrity by coordinating homeostasis processes that include regulation of ROS levels, apoptosis, and cell cycle progression. The proposed studies will provide a highly quantitative characterization of FANCG protein's contribution to biochemical and cellular endpoints associated with both normal cell proliferation and responses to IR exposure. Isogenic pairs of mutant and FANCG-complemented cells will be derived in both hamster CHO cells and human lymphoblasts. These pairs will be analyzed with respect to chromosomal aberrations, cell survival, hprt gene mutations, apoptosis, ROS, and cell cycle parameters with and without IR exposure. The FANCG-complemented FA-G lymphoblasts will be used to examine gene and protein regulation during the cell cycle as well as the subcellular localization of the protein with and without IR damage. Three proteins that are candidate interactors with FANCG from preliminary studies will be evaluated for possible involvement in the FA pathway. Finally, already identified high-frequency human allelic variants of FANCG in the US population will be evaluated for degree of dysfunction. The results of these studies will lead to more specific models of the nature of the FA protein "pathway" and its quantitative contributions to multiple biological effects associated with IR-mediated oxidative damage. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: FANCONI ANEMIA--ROLE OF THE C PROTEIN Principal Investigator & Institution: Hoatlin, Maureen E.; Medicine; Oregon Health & Science University Portland, or 972393098 Timing: Fiscal Year 2002; Project Start 01-MAY-1997; Project End 31-MAR-2004 Summary: Fanconi anemia (FA) is a cancer susceptibility syndrome associated with developmental abnormalities and bone marrow failure. Because of the unique cellular hypersensitivity to DNA crosslinking agents FA is considered to be a DNA repair disorder. The first (of at least eight) of the known FA complementation group genes, FANCC, was cloned more than seven years ago. Despite substantial efforts to discover the function of the FANCC protein, and functions of the proteins encoded by the other more recently cloned FA genes (FANCA and FANCG), the basic defect is still unknown. We used a yeast two hybrid screen to identify a new POZ-zinc finger protein (termed FAZF) which interacts with FANCC. We recently showed that FAZF is a transcriptional repressor similar to the promyelocytic zinc finger protein (PLZF). PLZF represses transcription of target genes by recruitment of histone deacetylase through the SMRTmSin3-HDAC co-repressor complex and tethering the complex to specific DNA target sequences. The FANCC/FAZF interaction is intriguing because it suggests that the FANCC protein may be interacting with components of the histone deacetylase complex. We propose to investigate FAZF and its relationship to FA by: (1) Analyzing FAZF/FANCC interaction in response to DNA damage, determine if FAZF is an FA complementing protein, compare the expression of FAZF and FANCC in primary hematopoietic cells (2) Analyze the consequences of enforced expression of FAZF, identify FAZF's binding partners, determine if FAZF is phosphorylated in response to DNA damage (3) Produce and examine the phenotype of FAZF nullizygous mice. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: FUNCTIONAL ANALYSIS OF THE PROTOTYPE MLL FUSION PARTNERS AF4 AND AF9 Principal Investigator & Institution: Domer, Peter; University of Chicago 5801 S Ellis Ave Chicago, Il 60637 Timing: Fiscal Year 2002 Summary: The 11q23 gene MLL (Mixed Lineage Leukemia) is involved in a number of acute leukemia associated interchromosomal translocations. In all of the translocations characterized at a molecular level MLL has formed a chimerical gene encoding an in frame fusion transcript with a partner gene. The diseases seen with these translocations include Acute Leukemia in patients who have been treated with topoisomerase II inhibitor chemotherapy (secondary leukemia). In this work we will study the role the partner gene plays in leukemogenesis and the mechanism which generates the MLL/11q23 translocations. As a prototypic MLL fusion partner we will study the 4q21 MLL fusion partner AF4. We have already cloned the murine homologue of AF4 and preliminarily shown it to be a nuclear protein. In the studies proposed here we will determine the normal biochemical function of murine AF4 and its structure-function relationships. To do this we will generate antibodies to the murine AF4 protein and confirm its subcellular localization, identify proteins it interacts with, and determine its phosphorylation status. We will analyze the structure-function relations which determine the AF4 protein's subcellular localization and stability. We will also determine if murine AF4 binds nucleic acids in a sequence specific manner. In order to gain insight into the mechanism of translocation, we have cloned the der(11) breakpoints from four patients with MLL/11q23 secondary acute myelogenous
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leukemia and one with MLL/11q23 secondary acute lymphoblastic leukemia. In the work proposed in this application we will determine if specific proteins interact with the DNA sequences from these breakpoints. To understand the topoisomerase II-induced DNA rearrangements of lymphoblastoid cell lines derived from patients with Bloom's syndrome, Fanconi Anemia, Atazia Telangiectasia, Xeroderma Pigmentosum, Cockayne's Syndrome, and MLL/11q23 secondary leukemia. From this work we should gain insight both into the mechanisms of leukemogenesis and MLL translocations. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENE EXPRESSION PHENOTYPE IN AUTOSOMAL RECESSIVE DISEASE Principal Investigator & Institution: Cheung, Vivian G.; Assistant Professor; Children's Hospital of Philadelphia 34Th St and Civic Ctr Blvd Philadelphia, Pa 191044399 Timing: Fiscal Year 2004; Project Start 01-MAY-2004; Project End 30-APR-2008 Summary: (provided by applicant): Autosomal recessive diseases are by definition those where only individuals with two mutated copies of the disease genes are affected. However, even in these diseases, there is often some manifestation in the heterozygous carriers. While there are usually no marked phenotypes in carriers, they often have subtle phenotypes that are minor differences from non-carriers. Most autosomal recessive diseases are rare but carriers are not. All individuals are carriers of several deleterious mutations. These mutations are likely to contribute significantly to the wide variation in phenotype among us, from disease susceptibility to variation in response to stress. In this project, we will study the carriers of radiosensitivity syndromes in order to understand the individual variation in response to radiation. We will focus on the gene expression profiles of heterozygous carriers of four radiosensitivity syndromes: Ataxia Telangiectasia, Nijmegen Breakage Syndrome, Bloom Syndrome and Fanconi Anemia. Physical examination and standard biochemical tests do not reliably detect the subtle phenotypes in these carriers. Our previous work (Watts et al, 2002) establishes that heterozygous carriers of Ataxia Telangiectasia have a "gene expression phenotype." In this project, we will extend and determine whether carriers of other radiosensitivity syndromes also have expression phenotypes at baseline and in response to ionizing radiation. The specific aims are: 1) Identify the expression phenotype of carriers of Ataxia Telangiectasia, Bloom Syndrome, Nijmegen Breakage Syndrome and Fanconi Anemia at baseline; 2) Characterize the expression phenotype of carriers of Ataxia Telangiectasia, Bloom Syndrome, Nijmegen Breakage Syndrome and Fanconi Anemia in response to ionizing radiation (IR). The results from this study will have important implications for understanding the basis of variation in radiation response. The approach can also be broadened to study the contribution of heterozygosity of recessive diseases to the complex genetic architecture of human diseases and traits. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GENE REPLACEMENT THERAPY IN HEMATOPOIETIC STEM CELLS Principal Investigator & Institution: Dinauer, Mary C.; Professor; Pediatrics; Indiana Univ-Purdue Univ at Indianapolis 620 Union Drive, Room 618 Indianapolis, in 462025167 Timing: Fiscal Year 2002; Project Start 01-DEC-1994; Project End 28-FEB-2005 Summary: (Adapted from the applicant's abstract) The overall goal of this program is to develop a strong experimental foundation for the correction of inherited disease of bone
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marrow-derived cells by genetic modification of hematopoietic stem cells. Current objectives are focused on the use of recombinant retroviral, lentiviral, and adenoassociated virus (AAV) vectors to achieve efficient transfer of functional genes into primitive hematopoietic stem cells while maintaining their maximal hematopoietic potential. The specific aims are to 1) examine the relationship between cell cycle, fibronectin-mediated adhesion, and cytokine regulators on hematopoietic cell function and viral transduction; 2) determine whether recombinant viral vectors derived from AAV and lentivirus can be used for efficient and stable gene transfer in murine and human hematopoietic cells; 3) identify optimal strategies using viral-mediated gene transfer to correct the phenotype in two inherited blood disorders, X-linked chronic granulomatous disease (X-CGD) and Fanconi anemia group C (FanC); and 4) evaluate non- ablative conditioning regimens and selection of transduced cells using maker proteins or drug resistance genes. Experimental approaches include the use of in vitro culture systems, NOD/SCID mouse-human xenografts, and murine models of X-CGD and FanC previously generated by gene targeting approaches. The implementation of these aims will be shared among 4 projects and 3 core units. This proposal draws from a group of investigators with diverse but complementary experience in stem cell biology, retrovirus-, lentivirus-, and AAV-mediated gene transfer, molecular genetics, virology, bone marrow transplantation, and neonatology. Achievement of these goals will permit the translation of this basic work to the development of clinical protocols for effective viral-mediated gene transfer of genetic blood diseases. On a broader level, these studies should provide insight into the biologic behavior of hematopoietic stem cells and the ability to manipulate them ex vivo. GANT=P01HL31992-17 PROPOSED PROGRAM (Adapted from Applicant's Abstract) The long-term objectives of this Program Project application are to evaluate basic mechanisms and develop new treatments for acute lung injury. High concentrations of oxygen and septic lung injury are the primary models that will be evaluated. The proposed program consists of four projects and three core units. Project 1 will evaluate the efficacy of small molecular weight catalytic antioxidants in the treatment of both hyperoxic and LPS + sepsis-initiated lung injury. This project will also develop new antioxidant mimetics and explore their relationships with the antioxidant properties of heme oxygenase (HO). Project 2 will test the hypothesis that activation of extrinsic coagulation and disordered fibrin turnover are central elements in hyperoxic and septic lung injury. The efficacy of specific blockade of the initiating steps of extrinsic coagulation in reducing inflammation and acute lung injury will be tested using two new anticoagulant drugs that block tissue factor (TF) function and do not cause bleeding. Project 3 will evaluate the regulation and function of the extracellular superoxide dismutase (EC-SOD) in acute lung injury and determine the impact of cleavage of the C-terminal "heparin binding" domain of this enzyme in determining its distribution and function. Project 4 will evaluate control of metabolic pathways and upregulation of lung cell glycolysis in modulating responses to acute injury. This project will test the hypothesis that adaptation to oxidant stress in the lung requires elevated expression of hexokinase (HK), a rate limiting step in glycolysis in the lung. The overall rationale for the Program Project is to use an interdisciplinary approach to define the cellular pathways and cellular adaptive responses involved in acute lung injury and to test new strategies for pharmacologic therapy that can be extended to the treatment of humans with ARDS and sepsis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENE THERAPY FOR PATIENTS WITH FANCONI ANEMIA Principal Investigator & Institution: Kiem, Hans-Peter; Member; University of Washington Grant & Contract Services Seattle, Wa 98105
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Timing: Fiscal Year 2002 Summary: Gene therapy for patients with Fanconi anemia. The overall goal of this project is to develop gene therapy for patients with Fanconi Anemia (FA). FA is an autosomal recessive syndrome which is characterized by congenital abnormalities, predisposition to malignancy and bone marrow failure. Current treatment options for patients with FA include supportive care, growth factor treatment with G-CSF, and hematopoietic stem cell transplantation for patients with HLA-matched siblings; transplantation from unrelated donors has been less successful in a number of different protocols are currently being studied. Gene therapy has also been described, however, gene transfer efficiency has been low and the detection of genetically modified cells in patients has only been transient. Thus, this project will incorporate a number of recently developed technologies to improve CD34+ peripheral blood stem cell (PBSC) mobilization and transduction. Specifically we propose to 1) study mobilization with a combination of G-CSF and SCF to improve CD34+ mobilization in patients with FA, 2) evaluate hematopoietic stem ell gene transfer efficiency using fibronectin assisted transduction in patients with FA, 3) develop improved retroviral packaging cells and vectors for gene transfer into hematopoietic repopulating cells, 4) evaluate novel transduction conditions, vectors and multiple infusions of transduced CD34+ cells in future gene therapy protocols for patients with FA. Other advances from other projects of this RFA and from ongoing stem cell transduction studies in our baboon model will be incorporated into future gene therapy protocols for patients with FA. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENE TRANSFER OF HEMATOPOIETIC STEM CELLS Principal Investigator & Institution: Walsh, Christopher E.; Associate Professor; Medicine; University of North Carolina Chapel Hill Aob 104 Airport Drive Cb#1350 Chapel Hill, Nc 27599 Timing: Fiscal Year 2002; Project Start 01-AUG-2001; Project End 10-NOV-2002 Summary: adapted from applicant's abstract): In order for efficient gene transfer of hematopoietic stem cells to be achieved we believe that the testing of new vectors and better defined stem cell populations are required. We have chosen Fanconi anemia (FA) as a model disease to facilitate improved gene transfer protocols of hematopoietic cells. FA is a rare autosomal recessive disorder characterized principally by bone marrow failure and the development of leukemia. The hematologic manifestations of FA are due to a disorder of stem cell function. The functions of the FANC proteins (FANC complementation groups A-H) are not understood but all FANC cells exhibit hypersensitivity to DNA crosslinkers and suggest a role in maintaining DNA stability. Although we demonstrated that a selective growth advantage exists in gene-corrected FA hematopoietic cells in a knockout model, the corrected stem cell population requires further characterization. Here we propose to identify and test gene transfer on isolated fractions of primitive hematopoietic stem cells based on physiologic rather than immunologic methods from both mouse and human. This purification scheme isolates the previously described novel side population fraction (SP) in both mouse and human hematopoietic cells. Our strategy is to isolate and transduce Fanconi anemia complementation group A (FANCA) and C (FANCC) knockout mice primitive stem cells. Recipient animals will be examined for their response to DNA damaging agents and cytokines and their ability to reconstitute hematopoiesis following gene transfer using moloney-murine retroviral and HIV, equine and feline-base lentiviral vectors. Isolation of human CD34+, CD34+/CD38- and SP fractions from FA patients will be tested for transduction by retroviral vectors using the NOD/scid immunodeficient
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mouse system. Currently we have an ongoing trial for FANCA patients. Information obtained from the planned studies will provide a better understanding of abnormal hematopoiesis in FA and better define therapeutic strategies important for designing future human clinical trials. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GROWTH FAILURE IN FANCONI ANEMIA Principal Investigator & Institution: Wajnrajch, Michael; Weill Medical College of Cornell Univ New York, Ny 10021 Timing: Fiscal Year 2002 Summary: Children with Fanconi anemia (FA) are being studied hormonally to determine the cause of their growth failure. Aspects of endocrine and somatic abnormality are being related to accumulated data regarding the mutations responsible for FA. Two papers relating to this protocol have been accepted for publication in peerreviewed journals. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ISOLATION OF THE FANCONI ANEMIA NUCLEAR PROTEIN COMPLEX Principal Investigator & Institution: Kupfer, Gary M.; Microbiology; University of Virginia Charlottesville Box 400195 Charlottesville, Va 22904 Timing: Fiscal Year 2002; Project Start 10-SEP-2000; Project End 31-AUG-2004 Summary: Fanconi anemia (FA) is a genetic disease with defects in development and hematopoiesis and propensity to cancer, indicating a vital and basic cell biology process at work. The hallmark of FA is genomic instability, evidenced by gross chromosomal breakage and DNA alkylating agent hypersensitivity, which correlates strongly with cancer predilection in general. Studies of FA are important in several ways. First, FA biology is involved across a spectrum of scientific disciplines, including hematology, oncology, and development. Second, since the known FA proteins are found only in mammalian cells and have no previously described protein domain, their study will yield the description of a novel pathway which promotes the maintenance of gnomic stability. Third, work on other proteins derived from rare cancer susceptibility syndromes have proved to have wide applicability in science in general and cancer in particular, such as Li-Fraumeni syndrome (p53), xeroderma pigmentosum (DNA nucleotide excision repair), and ataxia telangiectasia (P13 kinase). Fourth, basic work on FA has already led to clinical use of reagents for diagnosis and genetic counseling, and gene therapy trials are currently underway for treatment of FA. This work focuses on FA protein interactions. Preliminary data have shown that two FA proteins FANCA (Fanconi anemia complementation group A) and FANCC interact in a 500 kD nuclear complex, an interaction that is absent in 7 of the 8 FA complementation groups. Within the nucleus the data reveal that these proteins localize to the DNA and nuclear matrixcontaining fractions and have an appearance that parallels that of other nuclear matrix proteins. Evidence is also presented for inducible localization to chromatin and for direct DNA binding on gel shift assay. The efforts in this proposal will be driven by and will directly test two hypotheses: l) that the FA nuclear complex functions as a multimeric complex whose isolation will yield additional binding partners which will enable us to clone FA complementation group genes, and 2) that the FA proteins are associated with the nuclear matrix and with DNA in a cell cycle-regulated, complementation group-dependent, and drug-inducible fashion and interact with DNA
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either directly or indirectly. First, the FA protein complex will be characterized with respect to size and inducibility. Second, The complex will be isolated and analyzed by mass spectroscopy in order to identify novel and known associated proteins. Third, the subcellular localization of the FA proteins and their interaction with DNA will be investigated in a number of ways, including those which can lead to further new protein isolation. Identification of new proteins and elucidation of FA pathway mechanisms will help uncover a new realm of cancer biology and directly provide clinical applicability. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MOLECULAR ANALYSIS OF FANCONI'S ANEMIA C PROTEIN Principal Investigator & Institution: Plon, Sharon E.; Assistant Professor; Molecular and Human Genetics; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2002; Project Start 01-JUL-1995; Project End 30-JUN-2004 Summary: The long term goals of this project are to elucidate both the 'logic' and molecules involved in the genomic stability of hematopoietic cells through studies of Fanconi anemia (FA). Three FA genes have now been cloned, and the investigator is poised to ask precise questions about the organization and function of their protein products. Although the cellular phenotype of FA implicates these proteins in drugsensitive pathways as "gatekeepers" of genomic stability, their molecular functions remain incompletely understood. FANCC has a role in cellular detoxification by virtue of its interaction with NADPH cytochrome P-450 reductase (RED) and regulation of a pre-DNA damage step. FANCA is homologous to peroxidases, interacts with FANCG, and functions in the nucleus. Using cell culture yeast and mouse models, the investigator proposes to test the hypothesis that cytoplasmic FANCC-RED and nuclear FANCA-FANCG complexes perform detoxification functions in their respective cellular compartments. Thus, the investigator will (I) characterize the expression patterns of FA gene products during mouse embryogenesis, including hematopoietic and germ cell development, by in situ and biochemical strategies; (II) determine the oligomeric structure and regulation of FA proteins; (III) use genetic strategies to IocaIize the function of FA proteins to pre- or post-DNA damage steps, and, in this context, test the function of the FANCA peroxidase domain; and (IV) isolate genes that regulate the FANCC-RED pathway, and characterize the relationship of this pathway to that regulated by FANCA-FANCG. Our combined genetic, cellular and biochemical approaches should result in a comprehensive view of the regulation and function of FA gene products. Aside from improving our understanding of fundamental mechanisms of cellular detoxification and chromosomal stability relevant to hematopoiesis, the manipulation of drug-sensitive pathways controlled by FA genes will provide novel translational opportunities for chemosensitization of leukemias or solid tumors to bifunctional cross-linkers. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MOLECULAR GENETICS OF FANCONI ANEMIA Principal Investigator & Institution: Moses, Robb E.; Professor and Chair; Molecular and Medical Genetics; Oregon Health & Science University Portland, or 972393098 Timing: Fiscal Year 2002; Project Start 01-JUL-1994; Project End 30-JUN-2004 Summary: Fanconi anemia (FA) is an autosomal recessive disease which manifests increased risk of leukemia, regressive bone marrow failure, skeletal abnormalities, altered skin pigmentation and developmental delay. Therefore FA presents alterations in growth and development with anemia, and is an autosomal recessive disease with
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increased risk of cancer. There are eight complementation groups identified, indicating the involvement of multiple genes in the disease. This Program Project will use a molecular genetic approach to define the genetic elements causing Fanconi anemia and the function of the gene products in order to improve diagnosis and treatment. The concept of this project is to take a multi-disciplinary approach to the definition of the causes of Fanconi anemia at the molecular and cellular level. The clinical disciplines represented by the Investigators include medicine, pediatrics, medical genetics, hematology and oncology. The scientific areas of the investigations include molecular hematology, molecular genetics, mouse genetics, gene therapy, stem cell biology and DNA repair. The proposed project will have three investigative components and three core components: Project 1 will participate in cloning the FA-D group gene and analyze the function of the FA-D protein. Pathogenesis of FA as a result of crosslink repair defects will be tested in mouse models. Project 2 will participate in cloning FA-D and will build mouse models deficient in FA-D and FA-A gene products. Project3 will asess the apoptotic cytokine response defects in FA and define the molecular hematological defects in the mouse models. The Cytogenetics Core will test chromosome breakage in new Fanconi anemia cell line candidates and help map candidate Fanconi anemia genes. The Fanconi Anemia Cell Repository will identify Fanconi anemia cell lines for complementation testing and establish permanent cell lines for investigators as well as provide diagnostic procedures for FA patients and their providers. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NUCLEOPHOSMIN IN FANCONI'S ANEMIA-EVOLVED LEUKEMIA Principal Investigator & Institution: Pang, Qishen; Children's Hospital Med Ctr (Cincinnati) 3333 Burnet Ave Cincinnati, Oh 452293039 Timing: Fiscal Year 2004; Project Start 09-JUL-2004; Project End 30-JUN-2009 Summary: (provided by applicant): Most cancer cells share two abnormalities: uncontrolled proliferation and suppressed apoptosis. A direct relationship has been shown between the expression level of nucleophosmin (NPM) and a variety of human cancers including leukemia evolved from Fanconi anemia (FA), a genetic disorder associated with bone marrow failure, clonal proliferation of hematopoietic cells, and transformation to acute leukemia. This suggests a potential role of NPM in cancer development. We identified NPM as a novel cellular inhibitor of the pro-apoptotic protein kinase PKR, and demonstrated that NPM regulates PKR activity and suppresses apoptosis induced by mitogenic inhibitors and therapeutic agents in hematopoietic cells of FA. Our preliminary studies also indicated that NPM is a component of the so-called FA-PKR complex, which functions as a signaling intermediate in cellular responses to apoptotic and survival signals. We hypothesize that NPM suppresses apoptosis and promotes proliferation through inhibiting the pro-apoptotic kinase PKR and accelerating cell-cycle progression and that leukemic evolution in FA and other cancerprone bone marrow diseases may require increased expression of NPM to maintain survival and proliferation. The long term goals of our study are to utilize FA as an experimental system to examine the role of NPM in hematopoiesis and leukemic evolution. We plan to build on our preliminary characterizations of NPM-PKR interaction and NPM deregulation during FA disease progression to explore in molecular details the biochemical and functional alterations of NPM in the context of NPM expression, NPM-PKR interaction, the integrity of the FA-PKR complex, PKR activity, and apoptosis in BM cells from normal donors and FA patients at different stages of disease progression. We will also investigate whether regulation of PKR by NPM and the FA-PKR protein complex are linked mechanistically in these primary BM
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cells. We will employ three unique FA cell lines derived from FA patients at different stages of the disease progression to study the mechanism by which NPM promotes proliferation and suppresses apoptosis. To study the role of NPM in clonal proliferation, we will determine effects of NPM expression on proliferation and differentiation of FA evolved leukemic cells and hematopoietic stem/progenitor cells of FA mice. The proposed study will be of fundamental importance in understanding the evolution of bone marrow failure syndromes such as Fanconi anemia to clonal hematologic diseases such as myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). In addition, study of biological consequences of NPM alterations in the context of PKR suppression during FA disease progression may provide rationale for exploiting this molecule for detection and prevention of certain cancers including FA-evolved leukemia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: STEM CELL TRANSPLANTATION: BASIC/CLINICAL RESEARCH Principal Investigator & Institution: Storb, Rainer F.; Member and Professor/ Program Head; Fred Hutchinson Cancer Research Center Box 19024, 1100 Fairview Ave N Seattle, Wa 98109 Timing: Fiscal Year 2002; Project Start 01-JUL-1985; Project End 31-JUL-2006 Summary: The competitive grant renewal proposes an integrated program of basic and clinical research to improve the short- and long-term efficacy of allogeneic hematopoietic stem cell transplantation (HSCT). Human candidate diseases for HSCT include patients with acquired (e.g aplastic anemia, autoimmune disease) and genetic (e.g. T-cell deficiency diseases, red blood cell disorders) non-malignant diseases, myelodysplastic syndromes (e.g. T-cell deficiency diseases, red blood cell disorders) non- malignant diseases, myelodysplastic syndromes (MDS), and myeloproliferative disorders. Efforts are focused firstly on the application of non-myeloablative HSCT regimens. The novel aspect of our approach of non-myeloablative HSCT is the use of optimized post-grafting immunosuppression not only to control graft-versus-host disease but also host-versus-graft reactions. This way, the need for toxic pre-transplant therapy has been largely eliminated. Initial emphasis is on HLA-matched related and unrelated transplants. A preclinical canine model focuses on the development of nonmyeloablative HSCT strategies for less well matched recipients and on the us of targeted radiation therapy using monoclonal antibodies labeled with alpha-emitting radionuclides. Secondly, for patients with genetic diseases who do not have marrow donors, a project on gene therapy explores optimal gene transfer strategies in a preclinical canine model with ultimate application in human patients with Fanconi anemia. Another laboratory project is aimed at identifying critical cellular components needed to facilitate engraftment in the non-myeloablative setting, particularly when the underlying disease, e.g. MDS, or other conditions, e.g. ABO incompatibilities, pose unique obstacles to this form of therapy. The research studies are supported by five core units which provide sample acquisition and analysis, study design, data processing, statistical analyses, clinical support including that for multi-center studies, long- term follow-up, management of chronic graft-versus-host disease, and grant administration. The principles derived from the proposed studies will make it possible to provide more effective treatment to a greater number of patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: STRUCTURAL STUDIES OF DNA REPAIR PROTEINS Principal Investigator & Institution: Ellenberger, Tom E.; Professor; Biological Chem & Molecular Pharm; Harvard University (Medical School) Medical School Campus Boston, Ma 02115 Timing: Fiscal Year 2003; Project Start 01-MAY-1995; Project End 31-DEC-2006 Summary: (provided by applicant): The first step of the base excision repair (BER) pathway of DNA damage is the recognition and excision of damaged bases by lesionspecific N-glycosylases. The glycosylases that remove alkylation-damaged bases from DNA have an unusually broad catalytic specificity to counteract the promiscuous alkylation of DNA bases by a variety of metabolites and environmental toxins. X-ray structures of these enzymes are being determined complexed to alkylated DNA substrates. Their broad catalytic specificities are not fully explained by the available crystal structures. Catalytic specificity might be manifested during the steps of the reaction, before or after binding of a flipped out nucleotide substrate in the catalytic pocket. For example, alkylated bases might be more easily flipped out of the DNA helix than normal bases, resulting in more exposure of alkylated bases for binding to the enzyme. We are measuring the kinetic and thermodynamic parameters of DNA binding, nucleotide flipping, cleavage of the glycosylic bond, and product release for alkylated and undamaged DNA substrates, in order identify the selectivity determining steps of the reaction that have not been captured in the crystal structures. BER is functionally linked to other DNA repair and recombination processes, which together maintain the chemical and structural integrity of the genome. We are interested in the physical interactions between the damage sensors and the proteins that transmit signals causing the cessation of cell growth and coordination of different DNA repair processes. We have begun crystallographic studies of proteins that are defective in Fanconi Anemia (FA) patients. Cells from FA patients are very sensitive to DNA crosslinking agents, exhibiting severe cytogenetic anomalies after exposure to psoralen or mitomycin C. Available evidence suggests the FANC proteins function in a damage response pathway. They are not homologous to proteins of known function and their structures are likely to provide important clues about this signaling pathway and about the repair of DNA interstrand crosslinks. The silent information regulators (SIR proteins) of yeast form a protein complex that has histone deacetylase activity that is required for transcriptional silencing. The SIR proteins have less well characterized roles in the joining of nonhomolgous DNA ends and DNA repair. Interactions of the yeast Sir2p, Sir3p, and Sir4p proteins with one another and with histone proteins are being studied biochemically and crystallographically. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: TESTING MOLECULAR MODELS OF SPECTRIN FLEXIBILITY Principal Investigator & Institution: Macdonald, Ruby I.; Biochem/Molecular & Cell Biol; Northwestern University 633 Clark Street Evanston, Il 602081110 Timing: Fiscal Year 2002; Project Start 01-JAN-1998; Project End 30-JUN-2005 Summary: (provided by applicant): The long-term objective of this proposal is to understand the molecular basis of flexibility of the ubiquitous cytoskeletal protein, spectrin, and its relatives, alpha-actinin and dystrophin. Continuing the previously successful strategy of determining the X-ray crystal structure of two connected repeating units of chicken brain alpha-spectrin, which led to the proposal of two of the first molecular models of spectrin flexibility, a follow-up investigation is proposed to critically test those models. The strengths of X-ray crystallography, fluorescence and
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nuclear magnetic resonance (NMR) spectroscopy will be exploited to address the following important questions about the models: 1) Is the conformation of a linker region coordinated with that of an adjacent linker region in a three repeat fragment? 2) Are linker regions predicted to be a random coil by secondary structure prediction methods nonhelical (which, if true, could suggest yet a third model of spectrin flexibility and also offer the possibility of studying mutations correlated with hereditary elliptocytosis)? 3) How does the absence of the nearly invariant tryptophan affect the conformation of the linker region and flexibility of two connected repeats? 4) Is conformational rearrangement of one of the previously determined structures-a key feature of one of the models--due to the phasing or to the sequence of the construct? To answer these crucial questions concerning models of spectrin flexibility, 3 structures will be determined by X-ray crystallography, 2 will be studied by fluorescence energy transfer and 10 will be analyzed by NMR. These three approaches will complement each other as the X-ray crystal structures will provide atomic distances for interpretation of energy transfer data and vector orientations for interpretation of NMR data, and energy transfer and NMR data will provide dynamic information about the crystal structures. The cloned spectrin fragments will also be characterized by their circular dichroism and fluorescence spectra, by their stabilities to urea and thermal denaturation and by their molecular weights on analytical ultracentrifugation. Proposed critical testing of molecular models of spectrin flexibility will contribute fundamental knowledge likely to advance understanding of conditions such as hereditary elliptocytosis and spherocytosis, muscular dystrophy, hydrops fetalis and Fanconi anemia, in all of which spectrin or spectrin-related proteins are abnormal or reduced in amount. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: THE RISK OF CANCER IN FANCONI ANEMIA HETEROZYGOTES Principal Investigator & Institution: Berwick, Marianne; Professor and Chief; SloanKettering Institute for Cancer Res New York, Ny 100216007 Timing: Fiscal Year 2002; Project Start 01-APR-2001; Project End 31-MAR-2005 Summary: Fanconi anemia (FA) homozygotes have an increased cancer predisposition. In addition to the extraordinarily high frequency of AML in FA patients (actuarial risk of 52 percent for the development of MDS and/or AML by 40 years of age), FA patients exhibit malignancies of a variety of organ systems, most commonly gastrointestinal and gynecologic. The high incidence of nonhematologic malignancy in FA patients is especially striking because of the predicted early death from hematologic causes associated with the syndrome. Thus patients are unusually young when they develop cancer, and the incidence of malignancy probably would be considerably higher if patients had a longer life expectancy. There is evidence that heterozygote carriers of homozygous recessive familial cancer syndromes, such as Fanconi anemia, ataxia telangiectasia and xeroderma pigmentosum, are at increased risk for cancer. It is now possible to ascertain the carrier status by means of molecular tests rather than impute carrier status through probabilities, and thus it may be possible to arrive at a definitive answer to the role of heterozygosity among Fanconi anemia carriers. This study will directly address the etiology of cancer that involves the role of Fanconi anemia heterozygosity. The major aim of this retrospective cohort study will be to evaluate whether FA heterozygotes are at increased risk for developing cancer. In order to address this aim this study will use the extensive resources of the International Fanconi Anemia Registry at Rockefeller University. The sample will consist of 758 Fanconi anemia heterozygote grandparents of FA probands and 758 grandparents who do not carry an FA allele. Risk factor information will be obtained by questionnaire, blood will
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be collected for DNA analysis, and diagnostic pathology information will be collected using a systematic approach. Analyses will be undertaken to evaluate the role of Fanconi anemia heterozygosity for cancer. If carriers are found to be at increased risk, this information can be used to target individuals for cancer prevention strategies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: THE UW/FHCRC PROGRAM OF EXCELLENCE IN GENE THERAPY Principal Investigator & Institution: Stamatoyannopoulos, George; Professor of Medicine and Genetics; Medicine; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2002; Project Start 28-SEP-2000; Project End 31-AUG-2005 Summary: The UW/FHCRC Program of Excellence in Gene Therapy. The goal of this application from a Program of Excellence in Gene Therapy is to combine the resources of two Institutions, the University of Washington (UW) and the Fred Hutchinson Cancer Research Center (FHCRC), to advance gene therapy in two areas of interest of NHLBIstem cell gene therapy of hematological disorders and gene therapy of two common inherited lung diseases. The program puts together an outstanding group of gene therapy investigators and utilizes several resources of the two Institutions. The PEGT is composed of six projects, four core units, a training program and a Coordinating and Date Core Unit. Two projects propose preclinical studies on new therapy strategies. Four projects plan critical trials. Project 1 focuses on the development of new gene therapy approaches for hemophilia A and alpha-1 anti-trypsin deficiency. The objective of Project 2 is to develop gene targeting methods that can be used to correct genes in cells capable of reconstituting the hemopoietic system. Project 3 is a clinical project on gene therapy of Cystic Fibrosis Project 4 clinical studies on a novel inducible suicide gene based on the induction of apoptosis through oligimerization of the human Fas protein. Project 5 proposes preclinical and clinical studies of gene therapy of sickle cell disease and beta thalassemia. Project 6 is a clinical trial in patients with Fanconi anemia. Four core units support the research of the projects. Core A is a clinical core. Core B is a hemopoietic Cell Procurement and Processing Resource. Core Unit C is a primate stem cell transplantation core. Core D is the administrative core unit of the PEGT. The Hemopoietic Cell Procurement and Processing Core Unit and the Primate Transplantation Core Unit are proposed as core facilities for all the PEGT and NHLBI investigators. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: TRANSPOSON-MEDIATED GENE THERAPY FOR FANCONI ANEMIA Principal Investigator & Institution: Hackett, Perry B.; Professor; Discovery Genomics, Inc. 614 Mckinley Pl Ne Minneapolis, Mn 55413 Timing: Fiscal Year 2004; Project Start 01-APR-2004; Project End 30-SEP-2004 Summary: (provided by applicant): Fanconi anemia (FA) is an inherited recessive disorder caused by deficiency of one of several (up to 9) proteins involved in the regulation of DNA repair. Patients exhibit birth defects, suffer from bone marrow failure early in life, and are prone to develop cancers including leukemia and solid tumors. The only effective treatment for FA is allogeneic bone marrow transplant, but many patients lack a matched donor. We propose the treatment of FA by introduction and expression the FANC gene by combining the cell-loading technology of MaxCyte, Inc., with the DNA integrating technology of Discovery Genomics, Inc. (DGI). In Specific Aim 1, we
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will first test the combination of these two technologies by using reporter genes to ascertain long-term gene transfer and expression in cultured hematopoietic cells. DGI will assemble transposons designed for introduction and expression of red fluorescent protein (dsRed). MaxCyte will then use its electroporation technology for high efficiency loading of the transposon DNA into several different hematopoietic cell lines (Jurkat, KB, K562) along with a source of transposase which mediates transposition from the newly-introduced plasmid DNA into chromosomal DNA. Gene expression will be assayed over time by flow cytometry, and molecular analyses (PCR, Southern blot) will be conducted for analysis of transposition into chromosomal targets. In Aim 2, DGI will assemble transposons designed for expression of the human FANC-C and FANC-A genes. MaxCyte will then load these transposons into lymphoblastoid cell lines established from patients with Fanconi anemia type C or A, respectively, testing these cell populations for reduced sensitivity to the DNA damaging agent mitomycin C as well as for transposition by molecular genetic analysis. These Phase 1 studies will provide the basis for further preclinical development of the combined cell loading and DNA integrating technologies targeting hematopoietic stem cells (HSC) in Phase 2. These studies will be ground-breaking in that long-term expression of genes after nonviral introduction into HSC has yet to be reported, and will require the efficient cell loading and integrating capacities provided by our combined technologies. Initial development cell loading / DNA integration approach is proposed here for Fanconi anemia, subsequently providing the technical basis for treatment of other inherited (immunodeficiencies, hemoglobinopathies) or acquired (AIDS) diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
E-Journals: PubMed Central3 PubMed Central (PMC) is a digital archive of life sciences journal literature developed and managed by the National Center for Biotechnology Information (NCBI) at the U.S. National Library of Medicine (NLM).4 Access to this growing archive of e-journals is free and unrestricted.5 To search, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Pmc, and type “Fanconi anemia” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for Fanconi anemia in the PubMed Central database: •
A Multiprotein Nuclear Complex Connects Fanconi Anemia and Bloom Syndrome. by Meetei AR, Sechi S, Wallisch M, Yang D, Young MK, Joenje H, Hoatlin ME, Wang W.; 2003 May 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=164758
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A physical complex of the Fanconi anemia proteins FANCG /XRCC9 and FANCA. by Waisfisz Q, de Winter JP, Kruyt FA, de Groot J, van der Weel L, Dijkmans LM, Zhi Y, Arwert F, Scheper RJ, Youssoufian H, Hoatlin ME, Joenje H.; 1999 Aug 31; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=17886
3 4
Adapted from the National Library of Medicine: http://www.pubmedcentral.nih.gov/about/intro.html.
With PubMed Central, NCBI is taking the lead in preservation and maintenance of open access to electronic literature, just as NLM has done for decades with printed biomedical literature. PubMed Central aims to become a world-class library of the digital age. 5 The value of PubMed Central, in addition to its role as an archive, lies in the availability of data from diverse sources stored in a common format in a single repository. Many journals already have online publishing operations, and there is a growing tendency to publish material online only, to the exclusion of print.
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Abnormal response to DNA crosslinking agents of Fanconi anemia fibroblasts can be corrected by transfection with normal human DNA. by Diatloff-Zito C, Papadopoulo D, Averbeck D, Moustacchi E.; 1986 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=386647
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Analysis of baseline and cisplatin-inducible gene expression in Fanconi anemia cells using oligonucleotide-based microarrays. by Waisfisz Q, Miyazato A, de Winter JP, Liu JM, Joenje H.; 2002; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=138804
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Functional Activity of the Fanconi Anemia Protein FAA Requires FAC Binding and Nuclear Localization. by Naf D, Kupfer GM, Suliman A, Lambert K, D'Andrea AD.; 1998 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=109181
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Hypomutability in Fanconi anemia cells is associated with increased deletion frequency at the HPRT locus. by Papadopoulo D, Guillouf C, Mohrenweiser H, Moustacchi E.; 1990 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=54960
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Irreversible repression of DNA synthesis in Fanconi anemia cells is alleviated by the product of a novel cyclin-related gene. by Digweed M, Gunthert U, Schneider R, Seyschab H, Friedl R, Sperling K.; 1995 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=231958
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Localization of Fanconi anemia C protein to the cytoplasm of mammalian cells. by Youssoufian H.; 1994 Aug 16; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=44527
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Molecular and genealogical evidence for a founder effect in Fanconi anemia families of the Afrikaner population of South Africa. by Tipping AJ, Pearson T, Morgan NV, Gibson RA, Kuyt LP, Havenga C, Gluckman E, Joenje H, de Ravel T, Jansen S, Mathew CG.; 2001 May 8; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=33282
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Phenotypic correction of Fanconi anemia in human hematopoietic cells with a recombinant adeno-associated virus vector. by Walsh CE, Nienhuis AW, Samulski RJ, Brown MG, Miller JL, Young NS, Liu JM.; 1994 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=295276
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Repression of Fanconi anemia gene (FACC) expression inhibits growth of hematopoietic progenitor cells. by Segal GM, Magenis RE, Brown M, Keeble W, Smith TD, Heinrich MC, Bagby GC Jr.; 1994 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=296166
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Sequence variation in the Fanconi anemia gene FAA. by Levran O, Erlich T, Magdalena N, Gregory JJ, Batish SD, Verlander PC, Auerbach AD.; 1997 Nov 25; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=24261
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The Fanconi anemia pathway requires FAA phosphorylation and FAA /FAC nuclear accumulation. by Yamashita T, Kupfer GM, Naf D, Suliman A, Joenje H, Asano S, D'Andrea AD.; 1998 Oct 27; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=23717
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The Fanconi anemia polypeptide FACC is localized to the cytoplasm. by Yamashita T, Barber DL, Zhu Y, Wu N, D'Andrea AD.; 1994 Jul 5; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=44273
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The Fanconi Anemia Protein FANCC Binds to and Facilitates the Activation of STAT1 by Gamma Interferon and Hematopoietic Growth Factors. by Pang Q, Fagerlie S, Christianson TA, Keeble W, Faulkner G, Diaz J, Rathbun RK, Bagby GC.; 2000 Jul 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=85895
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The Molecular Mechanism Underlying Formation of Deletions in Fanconi Anemia Cells May Involve a Site-Specific Recombination. by Laquerbe A, Moustacchi E, Fuscoe JC, Papadopoulo D.; 1995 Jan 31; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=42714
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Transfection of normal human and Chinese hamster DNA corrects diepoxybutaneinduced chromosomal hypersensitivity of Fanconi anemia fibroblasts. by Shaham M, Adler B, Ganguly S, Chaganti RS.; 1987 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=298961
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 Fanconi anemia, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “Fanconi anemia” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for Fanconi anemia (hyperlinks lead to article summaries): •
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A 20-year perspective on the International Fanconi Anemia Registry (IFAR). Author(s): Kutler DI, Singh B, Satagopan J, Batish SD, Berwick M, Giampietro PF, Hanenberg H, Auerbach AD. Source: Blood. 2003 February 15; 101(4): 1249-56. Epub 2002 September 26. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12393516
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 46, XY, dup (1) (q21q32), add(11) (q23) karyotype in a case of Fanconi anemia. Author(s): Babu Rao V, Kerketta L, Ghosh K, Mohanty D. Source: Leukemia Research. 2001 April; 25(4): 347-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11248332
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A cytoplasmic serine protein kinase binds and may regulate the Fanconi anemia protein FANCA. Author(s): Yagasaki H, Adachi D, Oda T, Garcia-Higuera I, Tetteh N, D'Andrea AD, Futaki M, Asano S, Yamashita T. Source: Blood. 2001 December 15; 98(13): 3650-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11739169
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A damage-recognition protein which binds to DNA containing interstrand cross-links is absent or defective in Fanconi anemia, complementation group A, cells. Author(s): Hang B, Yeung AT, Lambert MW. Source: Nucleic Acids Research. 1993 September 11; 21(18): 4187-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8414972
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A deficiency in a 230 kDa DNA repair protein in fanconi anemia complementation group A cells is corrected by the FANCA cDNA. Author(s): Brois DW, McMahon LW, Ramos NI, Anglin LM, Walsh CE, Lambert MW. Source: Carcinogenesis. 1999 September; 20(9): 1845-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10469633
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A DNA double strand break repair defect in Fanconi anemia fibroblasts. Author(s): Donahue SL, Campbell C. Source: The Journal of Biological Chemistry. 2002 November 29; 277(48): 46243-7. Epub 2002 October 01. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12361951
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A functionally active retrovirus vector for gene therapy in Fanconi anemia group C. Author(s): Walsh CE, Grompe M, Vanin E, Buchwald M, Young NS, Nienhuis AW, Liu JM. Source: Blood. 1994 July 15; 84(2): 453-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7517716
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A heterozygous frameshift mutation in the Fanconi anemia C gene in familial T-ALL and secondary malignancy. Author(s): Rischewski JR, Clausen H, Leber V, Niemeyer C, Ritter J, Schindler D, Schneppenheim R. Source: Klinische Padiatrie. 2000 July-August; 212(4): 174-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10994546
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A Leu554-to-Pro substitution completely abolishes the functional complementing activity of the Fanconi anemia (FACC) protein. Author(s): Gavish H, dos Santos CC, Buchwald M. Source: Human Molecular Genetics. 1993 February; 2(2): 123-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8499901
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A locus for Fanconi anemia on 16q determined by homozygosity mapping. Author(s): Gschwend M, Levran O, Kruglyak L, Ranade K, Verlander PC, Shen S, Faure S, Weissenbach J, Altay C, Lander ES, Auerbach AD, Botstein D. Source: American Journal of Human Genetics. 1996 August; 59(2): 377-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8755924
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A multiprotein nuclear complex connects Fanconi anemia and Bloom syndrome. Author(s): Meetei AR, Sechi S, Wallisch M, Yang D, Young MK, Joenje H, Hoatlin ME, Wang W. Source: Molecular and Cellular Biology. 2003 May; 23(10): 3417-26. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12724401
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A novel BTB/POZ transcriptional repressor protein interacts with the Fanconi anemia group C protein and PLZF. Author(s): Hoatlin ME, Zhi Y, Ball H, Silvey K, Melnick A, Stone S, Arai S, Hawe N, Owen G, Zelent A, Licht JD. Source: Blood. 1999 December 1; 94(11): 3737-47. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10572087
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A novel diagnostic screen for defects in the Fanconi anemia pathway. Author(s): Shimamura A, de Oca RM, Svenson JL, Haining N, Moreau LA, Nathan DG, D'Andrea AD. Source: Blood. 2002 December 15; 100(13): 4649-54. Epub 2002 August 29. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12393398
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A novel, membrane receptor-based retroviral vector for Fanconi anemia group C gene therapy. Author(s): Machl AW, Planitzer S, Kubbies M. Source: Gene Therapy. 1997 April; 4(4): 339-45. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9176520
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A patient-derived mutant form of the Fanconi anemia protein, FANCA, is defective in nuclear accumulation. Author(s): Kupfer G, Naf D, Garcia-Higuera I, Wasik J, Cheng A, Yamashita T, Tipping A, Morgan N, Mathew CG, D'Andrea AD. Source: Experimental Hematology. 1999 April; 27(4): 587-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10210316
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A physical complex of the Fanconi anemia proteins FANCG/XRCC9 and FANCA. Author(s): Waisfisz Q, de Winter JP, Kruyt FA, de Groot J, van der Weel L, Dijkmans LM, Zhi Y, Arwert F, Scheper RJ, Youssoufian H, Hoatlin ME, Joenje H. Source: Proceedings of the National Academy of Sciences of the United States of America. 1999 August 31; 96(18): 10320-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10468606
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A Rad50-dependent pathway of DNA repair is deficient in Fanconi anemia fibroblasts. Author(s): Donahue SL, Campbell C. Source: Nucleic Acids Research. 2004 June 15; 32(10): 3248-57. Print 2004. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15199173
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Abnormal lymphokine production: a novel feature of the genetic disease Fanconi anemia. II. In vitro and in vivo spontaneous overproduction of tumor necrosis factor alpha. Author(s): Rosselli F, Sanceau J, Gluckman E, Wietzerbin J, Moustacchi E. Source: Blood. 1994 March 1; 83(5): 1216-25. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8118026
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Abnormal microsomal detoxification implicated in Fanconi anemia group C by interaction of the FAC protein with NADPH cytochrome P450 reductase. Author(s): Kruyt FA, Hoshino T, Liu JM, Joseph P, Jaiswal AK, Youssoufian H. Source: Blood. 1998 November 1; 92(9): 3050-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9787138
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Accelerated telomere shortening in Fanconi anemia fibroblasts--a longitudinal study. Author(s): Adelfalk C, Lorenz M, Serra V, von Zglinicki T, Hirsch-Kauffmann M, Schweiger M. Source: Febs Letters. 2001 September 28; 506(1): 22-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11591364
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Allogeneic bone marrow transplantation in Fanconi anemia from Turkey: a report of four cases. Author(s): Tezcan I, Tuncer M, Uckan D, Cetin M, Alikasifoglu M, Ersoy F, Altay C. Source: Pediatric Transplantation. 1998 August; 2(3): 236-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10084749
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Allogeneic bone marrow transplantation in Fanconi anemia. Author(s): Gluckman E. Source: Bone Marrow Transplantation. 1996 November; 18 Suppl 2: 140-4. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8932816
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An atypical case of Fanconi anemia in elderly sibs. Author(s): Kwee ML, van der Kleij JM, van Essen AJ, Begeer JH, Joenje H, Arwert F, ten Kate LP. Source: American Journal of Medical Genetics. 1997 January 31; 68(3): 362-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9024573
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An oxidative mechanism of interferon induced priming of the Fas pathway in Fanconi anemia cells. Author(s): Pearl-Yafe M, Halperin D, Halevy A, Kalir H, Bielorai B, Fabian I. Source: Biochemical Pharmacology. 2003 March 1; 65(5): 833-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12628494
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Analysis of 133 meioses places the genes for nevoid basal cell carcinoma (Gorlin) syndrome and Fanconi anemia group C in a 2.6-cM interval and contributes to the fine map of 9q22.3. Author(s): Farndon PA, Morris DJ, Hardy C, McConville CM, Weissenbach J, Kilpatrick MW, Reis A. Source: Genomics. 1994 September 15; 23(2): 486-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7835901
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Analysis of 65 Turkish patients with congenital aplastic anemia (Fanconi anemia and non-Fanconi anemia): Hacettepe experience. Author(s): Altay C, Alikasifoglu M, Kara A, Tuncbilek E, Ozbek N, Schroeder-Kurth TM. Source: Clinical Genetics. 1997 May; 51(5): 296-302. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9212176
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Apoptosis is not involved in the hypersensitivity of Fanconi anemia cells to mitomycin C. Author(s): Rey JP, Scott R, Muller H. Source: Cancer Genetics and Cytogenetics. 1994 July 1; 75(1): 67-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8039168
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Arrest of S-phase progression is impaired in Fanconi anemia cells. Author(s): Sala-Trepat M, Rouillard D, Escarceller M, Laquerbe A, Moustacchi E, Papadopoulo D. Source: Experimental Cell Research. 2000 November 1; 260(2): 208-15. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11035915
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Association of complementation group and mutation type with clinical outcome in fanconi anemia. European Fanconi Anemia Research Group. Author(s): Faivre L, Guardiola P, Lewis C, Dokal I, Ebell W, Zatterale A, Altay C, Poole J, Stones D, Kwee ML, van Weel-Sipman M, Havenga C, Morgan N, de Winter J, Digweed M, Savoia A, Pronk J, de Ravel T, Jansen S, Joenje H, Gluckman E, Mathew CG. Source: Blood. 2000 December 15; 96(13): 4064-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11110674
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Atypical PFAPA syndrome (periodic fever, aphthous stomatitis, pharyngitis, adenitis) in a young girl with Fanconi anemia. Author(s): Scimeca PG, James-Herry AG, Weinblatt ME. Source: Journal of Pediatric Hematology/Oncology : Official Journal of the American Society of Pediatric Hematology/Oncology. 1996 May; 18(2): 159-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8846129
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Biallelic inactivation of BRCA2 in Fanconi anemia. Author(s): Howlett NG, Taniguchi T, Olson S, Cox B, Waisfisz Q, De Die-Smulders C, Persky N, Grompe M, Joenje H, Pals G, Ikeda H, Fox EA, D'Andrea AD. Source: Science. 2002 July 26; 297(5581): 606-9. Epub 2002 June 13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12065746
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Body proportions in Fanconi anemia heterozygotes. Author(s): Mohan S, Lakshminarayanan P, Sowmya P, Venkatadesikalu M, Pushpa V. Source: Indian J Pediatr. 2000 November; 67(11): 797-801. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11216377
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Bone marrow cultures in children with Fanconi anemia and the TAR syndrome. Author(s): Lui VK, Ragab AH, Findley HS, Frauen BJ. Source: The Journal of Pediatrics. 1977 December; 91(6): 952-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=925829
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Bone marrow transplantation for Fanconi anemia using low-dose cyclophosphamide/thoracoabdominal irradiation as conditioning regimen: chimerism study by the polymerase chain reaction. Author(s): Socie G, Gluckman E, Raynal B, Petit T, Landman J, Devergie A, Brison O. Source: Blood. 1993 October 1; 82(7): 2249-56. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8400273
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Bone marrow transplantation for Fanconi anemia. Author(s): Gluckman E, Auerbach AD, Horowitz MM, Sobocinski KA, Ash RC, Bortin MM, Butturini A, Camitta BM, Champlin RE, Friedrich W, et al. Source: Blood. 1995 October 1; 86(7): 2856-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7670120
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Bone marrow transplantation for Fanconi anemia. Author(s): Gluckman E, Berger R, Dutreix J. Source: Semin Hematol. 1984 January; 21(1): 20-6. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6367053
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Bone marrow transplantation for Fanconi anemia. Adjustment of the dose of cyclophosphamide for preconditioning. Author(s): Yabe M, Yabe H, Matsuda M, Hinohara T, Oh Y, Hattori K, Ishikawa K, Ohshima T, Yamamoto H, Kato S. Source: Am J Pediatr Hematol Oncol. 1993 November; 15(4): 377-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8214359
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Bone marrow transplantation for patients with Fanconi anemia: a study of 24 cases from a single institution. Author(s): Zanis-Neto J, Ribeiro RC, Medeiros C, Andrade RJ, Ogasawara V, Hush M, Magdalena N, Friedrich ML, Bitencourt MA, Bonfim C, et al. Source: Bone Marrow Transplantation. 1995 February; 15(2): 293-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7773221
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Bone marrow transplantation for patients with Fanconi anemia: reduced doses of cyclophosphamide without irradiation as conditioning. Author(s): Medeiros C, Zanis-Neto J, Pasquini R. Source: Bone Marrow Transplantation. 1999 October; 24(8): 849-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10516695
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Bone marrow transplantation from matched siblings in patients with fanconi anemia utilizing low-dose cyclophosphamide, thoracoabdominal radiation and antithymocyte globulin. Author(s): Ayas M, Solh H, Mustafa MM, Al-Mahr M, Al-Fawaz I, Al-Jefri A, Shalaby L, Al-Nasser A, Al-Sedairy R. Source: Bone Marrow Transplantation. 2001 January; 27(2): 139-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11281382
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Bone marrow transplantation in Fanconi anemia using matched sibling donors. Author(s): Kohli-Kumar M, Morris C, DeLaat C, Sambrano J, Masterson M, Mueller R, Shahidi NT, Yanik G, Desantes K, Friedman DJ, et al. Source: Blood. 1994 September 15; 84(6): 2050-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8081006
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Bone marrow transplantation in patients with Fanconi anemia: experience with cyclophosphamide and total body irradiation conditioning regimen. Author(s): Solh H, Rao K, Martins da Cunha AM, Padmos A, Sackey K, Ernst P, Spence D, Clink H. Source: Pediatric Hematology and Oncology. 1997 January-February; 14(1): 67-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9021815
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BRCA1 interacts directly with the Fanconi anemia protein FANCA. Author(s): Folias A, Matkovic M, Bruun D, Reid S, Hejna J, Grompe M, D'Andrea A, Moses R. Source: Human Molecular Genetics. 2002 October 1; 11(21): 2591-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12354784
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Breaks at telomeres and TRF2-independent end fusions in Fanconi anemia. Author(s): Callen E, Samper E, Ramirez MJ, Creus A, Marcos R, Ortega JJ, Olive T, Badell I, Blasco MA, Surralles J. Source: Human Molecular Genetics. 2002 February 15; 11(4): 439-44. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11854176
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Breast cancer and Fanconi anemia: what are the connections? Author(s): Zdzienicka MZ, Arwert F. Source: Trends in Molecular Medicine. 2002 October; 8(10): 458-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12383764
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Cancer in Fanconi anemia, 1927-2001. Author(s): Alter BP. Source: Cancer. 2003 January 15; 97(2): 425-40. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12518367
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Cancer in Fanconi anemia. Author(s): Alter BP, Greene MH, Velazquez I, Rosenberg PS. Source: Blood. 2003 March 1; 101(5): 2072. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12584146
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Cancer incidence in persons with Fanconi anemia. Author(s): Rosenberg PS, Greene MH, Alter BP. Source: Blood. 2003 February 1; 101(3): 822-6. Epub 2002 September 05. Erratum In: Blood. 2003 March 15; 101(6): 2136. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12393424
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Carboxy terminal region of the Fanconi anemia protein, FANCG/XRCC9, is required for functional activity. Author(s): Kuang Y, Garcia-Higuera I, Moran A, Mondoux M, Digweed M, D'Andrea AD. Source: Blood. 2000 September 1; 96(5): 1625-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10961856
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Cellular function of the Fanconi anemia pathway. Author(s): D'Andrea AD. Source: Nature Medicine. 2001 December; 7(12): 1259-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11726938
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Characterization of Fanconi anemia fibroblasts in terms of clonogenic survival and DNA damage assessed by the Comet assay. Author(s): Djuzenova CS, Flentje M. Source: Medical Science Monitor : International Medical Journal of Experimental and Clinical Research. 2002 October; 8(10): Br421-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12388916
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Characterization of regions functional in the nuclear localization of the Fanconi anemia group A protein. Author(s): Lightfoot J, Alon N, Bosnoyan-Collins L, Buchwald M. Source: Human Molecular Genetics. 1999 June; 8(6): 1007-15. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10332032
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Chromosomal instability of fanconi anemia cells is not the consequence of a defective repair activity of the ribosomal protein S3. Author(s): Ramirez MH, Ruppitsch W, Hirsch-Kauffmann M, Schweiger M. Source: Biochemical and Biophysical Research Communications. 1999 October 22; 264(2): 518-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10529395
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Cisplatin triggers apoptotic or nonapoptotic cell death in Fanconi anemia lymphoblasts in a concentration-dependent manner. Author(s): Ferrer M, Izeboud T, Ferreira CG, Span SW, Giaccone G, Kruyt FA. Source: Experimental Cell Research. 2003 June 10; 286(2): 381-95. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12749865
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Clonal chromosomal aberrations in bone marrow cells of Fanconi anemia patients: gains of the chromosomal segment 3q26q29 as an adverse risk factor. Author(s): Tonnies H, Huber S, Kuhl JS, Gerlach A, Ebell W, Neitzel H. Source: Blood. 2003 May 15; 101(10): 3872-4. Epub 2003 January 02. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12511406
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Cloning and analysis of the mouse Fanconi anemia group A cDNA and an overlapping penta zinc finger cDNA. Author(s): Wong JC, Alon N, Norga K, Kruyt FA, Youssoufian H, Buchwald M. Source: Genomics. 2000 August 1; 67(3): 273-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10936049
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Cloning and characterization of murine fanconi anemia group A gene: Fanca protein is expressed in lymphoid tissues, testis, and ovary. Author(s): van de Vrugt HJ, Cheng NC, de Vries Y, Rooimans MA, de Groot J, Scheper RJ, Zhi Y, Hoatlin ME, Joenje H, Arwert F. Source: Mammalian Genome : Official Journal of the International Mammalian Genome Society. 2000 April; 11(4): 326-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10754110
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Coexistence of sickle cell trait and fanconi anemia in a child. Author(s): Yarali N, Fisgin T, Duru F, Kara A. Source: Pediatric Hematology and Oncology. 2002 June; 19(4): 283-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12051597
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Complementation analysis in Fanconi anemia: assignment of the reference FA-H patient to group A. Author(s): Joenje H, Levitus M, Waisfisz Q, D'Andrea A, Garcia-Higuera I, Pearson T, van Berkel CG, Rooimans MA, Morgan N, Mathew CG, Arwert F. Source: American Journal of Human Genetics. 2000 September; 67(3): 759-62. Epub 2000 August 08. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10936108
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Connecting Fanconi anemia to BRCA1. Author(s): Joenje H, Arwert F. Source: Nature Medicine. 2001 April; 7(4): 406-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11283658
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Constitutive elevation of serum alpha-fetoprotein in Fanconi anemia. Author(s): Cassinat B, Guardiola P, Chevret S, Schlageter MH, Toubert ME, Rain JD, Gluckman E. Source: Blood. 2000 August 1; 96(3): 859-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10910897
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Convergence of the fanconi anemia and ataxia telangiectasia signaling pathways. Author(s): Taniguchi T, Garcia-Higuera I, Xu B, Andreassen PR, Gregory RC, Kim ST, Lane WS, Kastan MB, D'Andrea AD. Source: Cell. 2002 May 17; 109(4): 459-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12086603
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Correction of cross-linker sensitivity of Fanconi anemia group F cells by CD33mediated protein transfer. Author(s): Holmes RK, Harutyunyan K, Shah M, Joenje H, Youssoufian H. Source: Blood. 2001 December 15; 98(13): 3817-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11739191
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Current knowledge on the pathophysiology of Fanconi anemia: from genes to phenotypes. Author(s): Yamashita T, Nakahata T. Source: International Journal of Hematology. 2001 July; 74(1): 33-41. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11530803
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Cytogenetic sensitivity of three Fanconi anemia heterozygotes to bleomycin and ionizing radiation. Author(s): Barquinero JF, Barrios L, Ribas M, Egozcue J, Caballin MR. Source: Cancer Genetics and Cytogenetics. 2001 January 1; 124(1): 80-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11165327
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Cytoplasmic localization of a functionally active Fanconi anemia group A-green fluorescent protein chimera in human 293 cells. Author(s): Kruyt FA, Waisfisz Q, Dijkmans LM, Hermsen MA, Youssoufian H, Arwert F, Joenje H. Source: Blood. 1997 November 1; 90(9): 3288-95. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9345010
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Damage-resistant DNA synthesis in Fanconi anemia cells treated with a DNA crosslinking agent. Author(s): Centurion SA, Kuo HR, Lambert WC. Source: Experimental Cell Research. 2000 November 1; 260(2): 216-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11035916
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DEB test for Fanconi anemia detection in patients with atypical phenotypes. Author(s): Esmer C, Sanchez S, Ramos S, Molina B, Frias S, Carnevale A. Source: American Journal of Medical Genetics. 2004 January 1; 124A(1): 35-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14679584
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Deficient DNA end joining activity in extracts from fanconi anemia fibroblasts. Author(s): Lundberg R, Mavinakere M, Campbell C. Source: The Journal of Biological Chemistry. 2001 March 23; 276(12): 9543-9. Epub 2000 December 21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11124945
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Deficient regulation of DNA double-strand break repair in Fanconi anemia fibroblasts. Author(s): Donahue SL, Lundberg R, Saplis R, Campbell C. Source: The Journal of Biological Chemistry. 2003 August 8; 278(32): 29487-95. Epub 2003 May 14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12748186
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Deletion and reduced expression of the Fanconi anemia FANCA gene in sporadic acute myeloid leukemia. Author(s): Tischkowitz MD, Morgan NV, Grimwade D, Eddy C, Ball S, Vorechovsky I, Langabeer S, Stoger R, Hodgson SV, Mathew CG. Source: Leukemia : Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2004 March; 18(3): 420-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14749703
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Deregulated apoptosis is a hallmark of the Fanconi anemia syndrome. Author(s): Ridet A, Guillouf C, Duchaud E, Cundari E, Fiore M, Moustacchi E, Rosselli F. Source: Cancer Research. 1997 May 1; 57(9): 1722-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9135015
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Detection of monosomy 7 in bone marrow by fluorescence in situ hybridization. A study of Fanconi anemia patients and review of the literature. Author(s): Thurston VC, Ceperich TM, Vance GH, Heerema NA. Source: Cancer Genetics and Cytogenetics. 1999 March; 109(2): 154-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10087952
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Developmental expression of the Fac gene correlates with congenital defects in Fanconi anemia patients. Author(s): Krasnoshtein F, Buchwald M. Source: Human Molecular Genetics. 1996 January; 5(1): 85-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8789444
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Diabetes mellitus in ataxia-telangiectasia, Fanconi anemia, xeroderma pigmentosum, common variable immune deficiency, and severe combined immune deficiency families. Author(s): Morrell D, Chase CL, Kupper LL, Swift M. Source: Diabetes. 1986 February; 35(2): 143-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3943665
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Diagnosis of Fanconi anemia in patients without congenital malformations: an international Fanconi Anemia Registry Study. Author(s): Giampietro PF, Verlander PC, Davis JG, Auerbach AD. Source: American Journal of Medical Genetics. 1997 January 10; 68(1): 58-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8986277
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Differential diagnosis of Fanconi anemia by nitrogen mustard and diepoxybutane. Author(s): Deviren A, Yalman N, Hacihanefioglu S. Source: Annals of Hematology. 2003 April; 82(4): 223-7. Epub 2003 March 01. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12707724
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Differentiation of Fanconi anemia from aplastic anemia by chromosomal breakage test. Author(s): Hou JW, Wang TR. Source: Zhonghua Min Guo Xiao Er Ke Yi Xue Hui Za Zhi. 1997 March-April; 38(2): 1216. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9151465
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Differentiation of Fanconi anemia from idiopathic aplastic anemia by induced chromosomal breakage study using mitomycin-C (MMC). Author(s): Talwar R, Choudhry VP, Kucheria K. Source: Indian Pediatrics. 2004 May; 41(5): 473-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15181297
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Disease model: Fanconi anemia. Author(s): Wong JC, Buchwald M. Source: Trends in Molecular Medicine. 2002 March; 8(3): 139-42. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11879775
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Disruption of the Fanconi anemia-BRCA pathway in cisplatin-sensitive ovarian tumors. Author(s): Taniguchi T, Tischkowitz M, Ameziane N, Hodgson SV, Mathew CG, Joenje H, Mok SC, D'Andrea AD. Source: Nature Medicine. 2003 May; 9(5): 568-74. Epub 2003 April 07. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12692539
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DNA cross-linker-induced G2/M arrest in group C Fanconi anemia lymphoblasts reflects normal checkpoint function. Author(s): Heinrich MC, Hoatlin ME, Zigler AJ, Silvey KV, Bakke AC, Keeble WW, Zhi Y, Reifsteck CA, Grompe M, Brown MG, Magenis RE, Olson SB, Bagby GC. Source: Blood. 1998 January 1; 91(1): 275-87. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9414295
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DNA interstrand cross-linking, repair, and SCE mechanism in human cells in special reference to Fanconi anemia. Author(s): Fujiwara Y, Kano Y, Yamamoto Y. Source: Basic Life Sci. 1984; 29 Pt B: 787-800. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6442145
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DNA semi-conservative synthesis in normal and Fanconi anemia fibroblasts following treatment with 8-methoxypsoralen and near ultraviolet light or with X-rays. Author(s): Moustacchi E, Diatloff-Zito C. Source: Human Genetics. 1985; 70(3): 236-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4018790
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Drug sensitivity spectra in Fanconi anemia lymphoblastoid cell lines of defined complementation groups. Author(s): Carreau M, Alon N, Bosnoyan-Collins L, Joenje H, Buchwald M. Source: Mutation Research. 1999 September 13; 435(1): 103-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10526221
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Effect of caffeine in Fanconi anemia. I. Restoration of a normal duration of G2 phase. Author(s): Sabatier L, Dutrillaux B. Source: Human Genetics. 1988 July; 79(3): 242-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3402996
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Effect of hydroxyurea and normal plasma on DNA synthesis in lymphocytes from Fanconi anemia patients. Author(s): Frias S, Gomez L, Molina B, Rojas E, Ostrosky-Wegman P, Carnevale A. Source: Mutation Research. 1996 October 25; 357(1-2): 115-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8876687
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Effect of mitomycin C and bromodeoxyuridine on Fanconi anemia lymphocytes. Author(s): Frias S, Mendoza S, Molina B, Carnevale A. Source: Annales De Genetique. 1991; 34(2): 104-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1746878
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Effect of oxidants and antioxidants on chromosomal breakage in Fanconi anemia lymphocytes. Author(s): Dallapiccola B, Porfirio B, Mokini V, Alimena G, Isacchi G, Gandini E. Source: Human Genetics. 1985; 69(1): 62-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3967890
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Effect of procarbazine and cyclophosphamide on chromosome breakage in Fanconi anemia cells: relevance to bone marrow transplantation. Author(s): Auerbach AD, Adler B, O'Reilly RJ, Kirkpatrick D, Chaganti RS. Source: Cancer Genetics and Cytogenetics. 1983 May; 9(1): 25-36. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6340822
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Elevated homologous recombination activity in fanconi anemia fibroblasts. Author(s): Thyagarajan B, Campbell C. Source: The Journal of Biological Chemistry. 1997 September 12; 272(37): 23328-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9287344
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Endogenous blockage and delay of the chromosome cycle despite normal recruitment and growth phase explain poor proliferation and frequent edomitosis in Fanconi anemia cells. Author(s): Kubbies M, Schindler D, Hoehn H, Schinzel A, Rabinovitch PS. Source: American Journal of Human Genetics. 1985 September; 37(5): 1022-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4050789
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Engraftment of hematopoietic progenitor cells transduced with the Fanconi anemia group C gene (FANCC). Author(s): Liu JM, Kim S, Read EJ, Futaki M, Dokal I, Carter CS, Leitman SF, Pensiero M, Young NS, Walsh CE. Source: Human Gene Therapy. 1999 September 20; 10(14): 2337-46. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10515453
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Episphalosomic syndrome : a MCA syndrome ressembling Fanconi anemia, with increased baseline level of chromosome breaks but no hypersensivity to clastogens. Author(s): Verloes A, Jamar M, Dideberg V, Herens C. Source: Annales De Genetique. 2001 April-June; 44(2): 59-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11522241
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Evaluation of Fanconi Anemia genes in familial breast cancer predisposition. Author(s): Seal S, Barfoot R, Jayatilake H, Smith P, Renwick A, Bascombe L, McGuffog L, Evans DG, Eccles D, Easton DF, Stratton MR, Rahman N; Breast Cancer Susceptibility Collaboration. Source: Cancer Research. 2003 December 15; 63(24): 8596-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14695169
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Evaluation of granulocyte-macrophage colony-stimulating factor for treatment of pancytopenia in children with fanconi anemia. Author(s): Guinan EC, Lopez KD, Huhn RD, Felser JM, Nathan DG. Source: The Journal of Pediatrics. 1994 January; 124(1): 144-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8283365
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Evaluation of growth and hormonal status in patients referred to the International Fanconi Anemia Registry. Author(s): Wajnrajch MP, Gertner JM, Huma Z, Popovic J, Lin K, Verlander PC, Batish SD, Giampietro PF, Davis JG, New MI, Auerbach AD. Source: Pediatrics. 2001 April; 107(4): 744-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11335753
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Evidence for at least eight Fanconi anemia genes. Author(s): Joenje H, Oostra AB, Wijker M, di Summa FM, van Berkel CG, Rooimans MA, Ebell W, van Weel M, Pronk JC, Buchwald M, Arwert F. Source: American Journal of Human Genetics. 1997 October; 61(4): 940-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9382107
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Evolutionary clues to the molecular function of fanconi anemia genes. Author(s): Blom E, van de Vrugt HJ, de Winter JP, Arwert F, Joenje H. Source: Acta Haematologica. 2002; 108(4): 231-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12432219
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Exon 6 skipping in the Fanconi anemia C gene associated with a nonsense/missense mutation (775C-->T) in exon 5: the first example of a nonsense mutation in one exon causing skipping of another downstream. Author(s): Lo Ten Foe JR, Kruyt FA, Zweekhorst MB, Pals G, Gibson RA, Mathew CG, Joenje H, Arwert F. Source: Human Mutation. 1998; Suppl 1: S25-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9452030
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Expression of hHR21sp gene by peripheral blood and hematopoietic cells of normal subjects and Fanconi anemia patients. Author(s): Deng Y, Li S, Li X, Magali T. Source: Chinese Medical Journal. 2001 December; 114(12): 1295-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11793857
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Expression of the Fanconi anemia gene FAC in human cell lines: lack of effect of oxygen tension. Author(s): Joenje H, Youssoufian H, Kruyt FA, dos Santos CC, Wevrick R, Buchwald M. Source: Blood Cells, Molecules & Diseases. 1995; 21(3): 182-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8673470
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Expression of the Fanconi anemia group A gene (Fanca) during mouse embryogenesis. Author(s): Abu-Issa R, Eichele G, Youssoufian H. Source: Blood. 1999 July 15; 94(2): 818-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10397750
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Expression of the Fanconi anemia group C gene in hematopoietic cells is not influenced by oxidative stress, cross-linking agents, radiation, heat, or mitotic inhibitory factors. Author(s): Tower PA, Christianson TA, Peters ST, Ostroski ML, Hoatlin ME, Zigler AJ, Heinrich MC, Rathbun RK, Keeble W, Faulkner GR, Bagby GC Jr. Source: Experimental Hematology. 1998 January; 26(1): 19-26. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9430510
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Extracutaneous Sweet syndrome involving the gastrointestinal tract in a patient with Fanconi anemia. Author(s): McDermott MB, Corbally MT, O'Marcaigh AS. Source: Journal of Pediatric Hematology/Oncology : Official Journal of the American Society of Pediatric Hematology/Oncology. 2001 January; 23(1): 59-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11196274
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Fanconi anemia A due to a novel frameshift mutation in hotspot motifs: lack of FANCA protein. Author(s): Balta G, de Winter JP, Kayserili H, Pronk JC, Joenje H. Source: Human Mutation. 2000 June; 15(6): 578. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10862090
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Fanconi anemia and breast cancer: what's the connection? Author(s): Youssoufian H. Source: Nature Genetics. 2001 April; 27(4): 352-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11279508
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Fanconi anemia and DNA repair. Author(s): Grompe M, D'Andrea A. Source: Human Molecular Genetics. 2001 October 1; 10(20): 2253-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11673408
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Fanconi anemia and primary cataracts: first case. Author(s): Merriman M, Mora J, McGaughran J. Source: Ophthalmic Genetics. 2002 December; 23(4): 253-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12567268
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Fanconi anemia associated with increased nuchal translucency detected by firsttrimester ultrasound. Author(s): Tercanli S, Miny P, Siebert MS, Hosli I, Surbek DV, Holzgreve W. Source: Ultrasound in Obstetrics & Gynecology : the Official Journal of the International Society of Ultrasound in Obstetrics and Gynecology. 2001 February; 17(2): 160-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11320987
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Fanconi anemia C gene product regulates expression of genes involved in differentiation and inflammation. Author(s): Zanier R, Briot D, Dugas du Villard JA, Sarasin A, Rosselli F. Source: Oncogene. 2004 June 24; 23(29): 5004-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15077170
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Fanconi anemia complementation group A cells are hypersensitive to chromium(VI)induced toxicity. Author(s): Vilcheck SK, O'Brien TJ, Pritchard DE, Ha L, Ceryak S, Fornsaglio JL, Patierno SR. Source: Environmental Health Perspectives. 2002 October; 110 Suppl 5: 773-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12426130
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Fanconi anemia group C protein prevents apoptosis in hematopoietic cells through redox regulation of GSTP1. Author(s): Cumming RC, Lightfoot J, Beard K, Youssoufian H, O'Brien PJ, Buchwald M. Source: Nature Medicine. 2001 July; 7(7): 814-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11433346
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Fanconi anemia lymphocytes: effect of DL-alpha-tocopherol (Vitamin E) on chromatid breaks and on G2 repair efficiency. Author(s): Pincheira J, Bravo M, Santos MJ, de la Torre C, Lopez-Saez JF. Source: Mutation Research. 2001 January 5; 461(4): 265-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11104902
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Fanconi anemia protein complex is a novel target of the IKK signalsome. Author(s): Otsuki T, Young DB, Sasaki DT, Pando MP, Li J, Manning A, Hoekstra M, Hoatlin ME, Mercurio F, Liu JM. Source: Journal of Cellular Biochemistry. 2002; 86(4): 613-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12210728
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Fanconi anemia protein complex: mapping protein interactions in the yeast 2- and 3hybrid systems. Author(s): Gordon SM, Buchwald M. Source: Blood. 2003 July 1; 102(1): 136-41. Epub 2003 March 20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12649160
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Fanconi anemia protein, FANCA, associates with BRG1, a component of the human SWI/SNF complex. Author(s): Otsuki T, Furukawa Y, Ikeda K, Endo H, Yamashita T, Shinohara A, Iwamatsu A, Ozawa K, Liu JM. Source: Human Molecular Genetics. 2001 November 1; 10(23): 2651-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11726552
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Fanconi anemia protein, FANCG, is a phosphoprotein and is upregulated with FANCA after TNF-alpha treatment. Author(s): Futaki M, Watanabe S, Kajigaya S, Liu JM. Source: Biochemical and Biophysical Research Communications. 2001 February 23; 281(2): 347-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11181053
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Fanconi anemia proteins localize to chromatin and the nuclear matrix in a DNA damage- and cell cycle-regulated manner. Author(s): Qiao F, Moss A, Kupfer GM. Source: The Journal of Biological Chemistry. 2001 June 29; 276(26): 23391-6. Epub 2001 April 10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11297559
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Fanconi anemia. a statistical evaluation of cytogenetic results obtained from South African families. Author(s): Pearson T, Jansen S, Havenga C, Stones DK, Joubert G. Source: Cancer Genetics and Cytogenetics. 2001 April 1; 126(1): 52-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11343779
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Fanconi anemia: join the club! Author(s): de Boer J. Source: Trends in Cell Biology. 2001 May; 11(5): 190. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11316592
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Function of the Fanconi anemia pathway in Fanconi anemia complementation group F and D1 cells. Author(s): Siddique MA, Nakanishi K, Taniguchi T, Grompe M, D'Andrea AD. Source: Experimental Hematology. 2001 December; 29(12): 1448-55. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11750104
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Functional analysis of patient-derived mutations in the Fanconi anemia gene, FANCG/XRCC9. Author(s): Nakanishi K, Moran A, Hays T, Kuang Y, Fox E, Garneau D, de Oca RM, Grompe M, D'Andrea AD. Source: Experimental Hematology. 2001 July; 29(7): 842-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11438206
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Functional analysis of the putative peroxidase domain of FANCA, the Fanconi anemia complementation group A protein. Author(s): Ren J, Youssoufian H. Source: Molecular Genetics and Metabolism. 2001 January; 72(1): 54-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11161829
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Functional correction of fanconi anemia group C hematopoietic cells by the use of a novel lentiviral vector. Author(s): Yamada K, Olsen JC, Patel M, Rao KW, Walsh CE. Source: Molecular Therapy : the Journal of the American Society of Gene Therapy. 2001 April; 3(4): 485-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11319908
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Gene therapy for fanconi anemia. Author(s): Croop JM. Source: Curr Hematol Rep. 2003 July; 2(4): 335-40. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12901331
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Genetic basis of Fanconi anemia. Author(s): Bagby GC Jr. Source: Current Opinion in Hematology. 2003 January; 10(1): 68-76. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12483114
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Genetic reversion in an acute myelogenous leukemia cell line from a Fanconi anemia patient with biallelic mutations in BRCA2. Author(s): Ikeda H, Matsushita M, Waisfisz Q, Kinoshita A, Oostra AB, Nieuwint AW, De Winter JP, Hoatlin ME, Kawai Y, Sasaki MS, D'Andrea AD, Kawakami Y, Joenje H. Source: Cancer Research. 2003 May 15; 63(10): 2688-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12750298
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Genomic instability in Down syndrome and Fanconi anemia assessed by micronucleus analysis and single-cell gel electrophoresis. Author(s): Maluf SW, Erdtmann B. Source: Cancer Genetics and Cytogenetics. 2001 January 1; 124(1): 71-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11165325
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Germline mutations in BRCA2: shared genetic susceptibility to breast cancer, early onset leukemia, and Fanconi anemia. Author(s): Wagner JE, Tolar J, Levran O, Scholl T, Deffenbaugh A, Satagopan J, BenPorat L, Mah K, Batish SD, Kutler DI, MacMillan ML, Hanenberg H, Auerbach AD. Source: Blood. 2004 April 15; 103(8): 3226-9. Epub 2004 January 08. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15070707
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Growth of cultured cells from patients with Fanconi anemia. Author(s): Elmore E, Swift M. Source: Journal of Cellular Physiology. 1975 December; 87(2): 229-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1214005
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Hematologic abnormalities in Fanconi anemia. Author(s): Alter BP. Source: Blood. 1995 February 15; 85(4): 1148-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7849307
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Hematologic abnormalities in Fanconi anemia: an International Fanconi Anemia Registry study. Author(s): Butturini A, Gale RP, Verlander PC, Adler-Brecher B, Gillio AP, Auerbach AD. Source: Blood. 1994 September 1; 84(5): 1650-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8068955
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Hematopoietic progenitor cel harvest and functionality in Fanconi anemia patients. Author(s): Larghero J, Marolleau JP, Soulier J, Filion A, Rocha V, Benbunan M, Gluckman E. Source: Blood. 2002 October 15; 100(8): 3051. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12382645
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Hepatic adenoma in Fanconi anemia treated with oxymetholone. Author(s): Mulvihill JJ, Ridolfi RL, Schultz FR, Borzy MS, Haughton PB. Source: The Journal of Pediatrics. 1975 July; 87(1): 122-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=168333
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Heterogeneity in Fanconi anemia: evidence for 2 new genetic subtypes. Author(s): Levitus M, Rooimans MA, Steltenpool J, Cool NF, Oostra AB, Mathew CG, Hoatlin ME, Waisfisz Q, Arwert F, de Winter JP, Joenje H. Source: Blood. 2004 April 1; 103(7): 2498-503. Epub 2003 November 20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14630800
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Heterogeneous activation of the Fanconi anemia pathway by patient-derived FANCA mutants. Author(s): Adachi D, Oda T, Yagasaki H, Nakasato K, Taniguchi T, D'Andrea AD, Asano S, Yamashita T. Source: Human Molecular Genetics. 2002 December 1; 11(25): 3125-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12444097
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Heterozygous manifestations in four autosomal recessive human cancer-prone syndromes: ataxia telangiectasia, xeroderma pigmentosum, Fanconi anemia, and Bloom syndrome. Author(s): Heim RA, Lench NJ, Swift M. Source: Mutation Research. 1992 December 1; 284(1): 25-36. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1279391
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High incidence of head and neck squamous cell carcinoma in patients with Fanconi anemia. Author(s): Kutler DI, Auerbach AD, Satagopan J, Giampietro PF, Batish SD, Huvos AG, Goberdhan A, Shah JP, Singh B. Source: Archives of Otolaryngology--Head & Neck Surgery. 2003 January; 129(1): 10612. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12525204
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HPRT gene expression differs in mutants derived from normal and Fanconi anemia cells: analysis of spontaneous and psoralen-photoinduced mutants. Author(s): Guillouf C, Moustacchi E, Papadopoulo D. Source: Somatic Cell and Molecular Genetics. 1991 November; 17(6): 591-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1685031
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Human alpha spectrin II and the Fanconi anemia proteins FANCA and FANCC interact to form a nuclear complex. Author(s): McMahon LW, Walsh CE, Lambert MW. Source: The Journal of Biological Chemistry. 1999 November 12; 274(46): 32904-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10551855
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Human papillomavirus DNA and p53 polymorphisms in squamous cell carcinomas from Fanconi anemia patients. Author(s): Kutler DI, Wreesmann VB, Goberdhan A, Ben-Porat L, Satagopan J, Ngai I, Huvos AG, Giampietro P, Levran O, Pujara K, Diotti R, Carlson D, Huryn LA, Auerbach AD, Singh B. Source: Journal of the National Cancer Institute. 2003 November 19; 95(22): 1718-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14625263
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Hydrocephalus in Fanconi anemia. Author(s): Alter BP. Source: American Journal of Medical Genetics. 1993 March 15; 45(6): 785. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8456865
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Hypergonadotropic hypogonadism in a boy with Fanconi anemia with growth hormone deficiency and pituitary stalk interruption. Author(s): Massa GG, Heinrichs C, Vamos E, Van Vliet G. Source: The Journal of Pediatrics. 2002 February; 140(2): 277. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11865289
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Hypersensitivity to oxygen is a uniform and secondary defect in Fanconi anemia cells. Author(s): Saito H, Hammond AT, Moses RE. Source: Mutation Research. 1993 October; 294(3): 255-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7692265
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Hypomutability in Fanconi anemia cells is associated with increased deletion frequency at the HPRT locus. Author(s): Papadopoulo D, Guillouf C, Mohrenweiser H, Moustacchi E. Source: Proceedings of the National Academy of Sciences of the United States of America. 1990 November; 87(21): 8383-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2236046
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Identification of cytosolic proteins that bind to the Fanconi anemia complementation group C polypeptide in vitro. Evidence for a multimeric complex. Author(s): Youssoufian H, Auerbach AD, Verlander PC, Steimle V, Mach B. Source: The Journal of Biological Chemistry. 1995 April 28; 270(17): 9876-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7730370
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Immortalization of four new Fanconi anemia fibroblast cell lines by an improved procedure. Author(s): Jakobs PM, Sahaayaruban P, Saito H, Reifsteck C, Olson S, Joenje H, Moses RE, Grompe M. Source: Somatic Cell and Molecular Genetics. 1996 March; 22(2): 151-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8782494
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Impaired DNA damage-induced nuclear Rad51 foci formation uniquely characterizes Fanconi anemia group D1. Author(s): Godthelp BC, Artwert F, Joenje H, Zdzienicka MZ. Source: Oncogene. 2002 July 25; 21(32): 5002-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12118380
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In vitro hypersensitivity to oxygen of Fanconi anemia (FA) cells is linked to ex vivo evidence for oxidative stress in FA homozygotes and heterozygotes. Author(s): Pagano G, Korkina LG, Degan P, Del Principe D, Lindau-Shepard B, Zatterale A, Franceschi C. Source: Blood. 1997 February 1; 89(3): 1111-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9028345
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In vitro phenotypic correction of hematopoietic progenitors from Fanconi anemia group A knockout mice. Author(s): Rio P, Segovia JC, Hanenberg H, Casado JA, Martinez J, Gottsche K, Cheng NC, Van de Vrugt HJ, Arwert F, Joenje H, Bueren JA. Source: Blood. 2002 September 15; 100(6): 2032-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12200363
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Inactivation of the Fanconi anemia group C gene augments interferon-gammainduced apoptotic responses in hematopoietic cells. Author(s): Rathbun RK, Faulkner GR, Ostroski MH, Christianson TA, Hughes G, Jones G, Cahn R, Maziarz R, Royle G, Keeble W, Heinrich MC, Grompe M, Tower PA, Bagby GC. Source: Blood. 1997 August 1; 90(3): 974-85. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9242526
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Index of suspicion. Case 2. Aplastic anemia (Fanconi anemia). Author(s): McQuilkin P. Source: Pediatrics in Review / American Academy of Pediatrics. 1995 September; 16(9): 349, 350-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7567711
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Induction of Fanconi anemia cellular phenotype in human 293 cells by overexpression of a mutant FAC allele. Author(s): Youssoufian H, Li Y, Martin ME, Buchwald M. Source: The Journal of Clinical Investigation. 1996 February 15; 97(4): 957-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8613549
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Interaction of the Fanconi anemia proteins and BRCA1 in a common pathway. Author(s): Garcia-Higuera I, Taniguchi T, Ganesan S, Meyn MS, Timmers C, Hejna J, Grompe M, D'Andrea AD. Source: Molecular Cell. 2001 February; 7(2): 249-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11239454
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Interferon-gamma-induced apoptotic responses of Fanconi anemia group C hematopoietic progenitor cells involve caspase 8-dependent activation of caspase 3 family members. Author(s): Rathbun RK, Christianson TA, Faulkner GR, Jones G, Keeble W, O'Dwyer M, Bagby GC. Source: Blood. 2000 December 15; 96(13): 4204-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11110692
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Intermediate-dose busulfan and cyclophosphamide as a conditioning regimen for bone marrow transplantation in a case of Fanconi anemia in myelodysplastic transformation. Author(s): Maschan AA, Kryzanovskii OI, Yourlova MI, Skorobogatova EV, Pashanov ED, Potapova YE, Timonova LA, Bogatcheva NY, Samochatova EV, Roumjantzev AG. Source: Bone Marrow Transplantation. 1997 February; 19(4): 385-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9051250
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Intermethod discordance for alpha-fetoprotein measurements in Fanconi anemia. Author(s): Cassinat B, Darsin D, Guardiola P, Toubert ME, Rain JD, Gluckman E, Schlageter MH. Source: Clinical Chemistry. 2001 August; 47(8): 1405-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11468229
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Interstitial lung disease in an adult with Fanconi anemia: clues to the pathogenesis. Author(s): Rubinstein WS, Wenger SL, Hoffman RM, Auerbach AD, Mulvihill JJ. Source: American Journal of Medical Genetics. 1997 March 31; 69(3): 315-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9096763
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Intracellular localization of the Fanconi anemia complementation group A protein. Author(s): Walsh CE, Yountz MR, Simpson DA. Source: Biochemical and Biophysical Research Communications. 1999 June 16; 259(3): 594-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10364463
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Investigation of Fanconi anemia protein interactions by yeast two-hybrid analysis. Author(s): Huber PA, Medhurst AL, Youssoufian H, Mathew CG. Source: Biochemical and Biophysical Research Communications. 2000 February 5; 268(1): 73-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10652215
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Involvement of the Fanconi anemia protein FA-C in repair processes of oxidative DNA damages. Author(s): Lackinger D, Ruppitsch W, Ramirez MH, Hirsch-Kauffmann M, Schweiger M. Source: Febs Letters. 1998 November 27; 440(1-2): 103-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9862435
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Irreversible repression of DNA synthesis in Fanconi anemia cells is alleviated by the product of a novel cyclin-related gene. Author(s): Digweed M, Gunthert U, Schneider R, Seyschab H, Friedl R, Sperling K. Source: Molecular and Cellular Biology. 1995 January; 15(1): 305-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7799938
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Is Fanconi anemia caused by a defect in the processing of DNA damage? Author(s): Buchwald M, Moustacchi E. Source: Mutation Research. 1998 August 7; 408(2): 75-90. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9739810
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Isolated glycerol kinase deficiency and Fanconi anemia. Author(s): Sjarif DR, Revesz T, de Koning TJ, Duran M, Beemer FA, Poll-The BT. Source: American Journal of Medical Genetics. 2001 March 1; 99(2): 159-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11241478
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Isolation of a cDNA representing the Fanconi anemia complementation group E gene. Author(s): de Winter JP, Leveille F, van Berkel CG, Rooimans MA, van Der Weel L, Steltenpool J, Demuth I, Morgan NV, Alon N, Bosnoyan-Collins L, Lightfoot J, Leegwater PA, Waisfisz Q, Komatsu K, Arwert F, Pronk JC, Mathew CG, Digweed M, Buchwald M, Joenje H. Source: American Journal of Human Genetics. 2000 November; 67(5): 1306-8. Epub 2000 September 19. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11001585
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Jun N-terminal kinase activity and early growth-response factor-1 gene expression are down-regulated in Fanconi anemia group A lymphoblasts. Author(s): Pipaon C, Casado JA, Bueren JA, Fernandez-Luna JL. Source: Blood. 2004 January 1; 103(1): 128-32. Epub 2003 September 04. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12958075
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Karyotype evolution in the bone marrow of a patient with Fanconi anemia: breakpoints in clonal anomalies of this disease. Author(s): Huret JL, Tanzer J, Guilhot F, Frocrain-Herchkovitch C, Savage JR. Source: Cytogenetics and Cell Genetics. 1988; 48(4): 224-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3248378
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Klippel-Feil anomaly in Fanconi anemia. Author(s): McGaughran J. Source: Clinical Dysmorphology. 2003 July; 12(3): 197. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14564161
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Letter: Fanconi anemia: simultaneous onset of symptoms in two siblings. Author(s): Jones R. Source: The Journal of Pediatrics. 1976 January; 88(1): 152. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1245921
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Letter: Growth hormone deficiency and Fanconi anemia. Author(s): Clarke WL, Weldon VV. Source: The Journal of Pediatrics. 1975 May; 86(5): 814-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1133668
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Leukemia and preleukemia in Fanconi anemia patients. A review of the literature and report of the International Fanconi Anemia Registry. Author(s): Auerbach AD, Allen RG. Source: Cancer Genetics and Cytogenetics. 1991 January; 51(1): 1-12. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1984836
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Light scatter and DNA accessibility to propidium iodide of ataxia telangiectasia and fanconi anemia cells. Author(s): Djuzenova CS, Flentje M. Source: Biochemical and Biophysical Research Communications. 2001 August 17; 286(2): 365-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11500046
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Localization of Fanconi anemia C protein to the cytoplasm of mammalian cells. Author(s): Youssoufian H. Source: Proceedings of the National Academy of Sciences of the United States of America. 1994 August 16; 91(17): 7975-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8058745
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Localization of the Fanconi anemia complementation group D gene to a 200-kb region on chromosome 3p25.3. Author(s): Hejna JA, Timmers CD, Reifsteck C, Bruun DA, Lucas LW, Jakobs PM, TothFejel S, Unsworth N, Clemens SL, Garcia DK, Naylor SL, Thayer MJ, Olson SB, Grompe M, Moses RE. Source: American Journal of Human Genetics. 2000 May; 66(5): 1540-51. Epub 2000 April 12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10762542
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Long-term bone marrow culture in persons with Fanconi anemia and bone marrow failure. Author(s): Butturini A, Gale RP. Source: Blood. 1994 January 15; 83(2): 336-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8286733
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Loss of the Fanconi anemia group C protein activity results in an inability to activate caspase-3 after ionizing radiation. Author(s): Guillouf C, Vit JP, Rosselli F. Source: Biochimie. 2000 January; 82(1): 51-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10717387
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Low risk of graft-versus-host disease with transplantation of CD34 selected peripheral blood progenitor cells from alternative donors for Fanconi anemia. Author(s): Boyer MW, Gross TG, Loechelt B, Leemhuis T, Filipovich A, Harris RE. Source: Journal of Pediatric Hematology/Oncology : Official Journal of the American Society of Pediatric Hematology/Oncology. 2003 November; 25(11): 890-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14608200
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Lymphoblastic lymphoma and excessive toxicity from chemotherapy: an unusual presentation for Fanconi anemia. Author(s): Goldsby RE, Perkins SL, Virshup DM, Brothman AR, Bruggers CS. Source: Journal of Pediatric Hematology/Oncology : Official Journal of the American Society of Pediatric Hematology/Oncology. 1999 May-June; 21(3): 240-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10363859
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Malignancies after marrow transplantation for aplastic anemia and fanconi anemia: a joint Seattle and Paris analysis of results in 700 patients. Author(s): Deeg HJ, Socie G, Schoch G, Henry-Amar M, Witherspoon RP, Devergie A, Sullivan KM, Gluckman E, Storb R. Source: Blood. 1996 January 1; 87(1): 386-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8547667
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Medulloblastoma as a first presentation of fanconi anemia. Author(s): Tischkowitz MD, Chisholm J, Gaze M, Michalski A, Rosser EM. Source: Journal of Pediatric Hematology/Oncology : Official Journal of the American Society of Pediatric Hematology/Oncology. 2004 January; 26(1): 52-5. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14707715
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Mice with a targeted disruption of the Fanconi anemia homolog Fanca. Author(s): Cheng NC, van de Vrugt HJ, van der Valk MA, Oostra AB, Krimpenfort P, de Vries Y, Joenje H, Berns A, Arwert F. Source: Human Molecular Genetics. 2000 July 22; 9(12): 1805-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10915769
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Mitochondrial alterations in fanconi anemia fibroblasts following ultraviolet A or psoralen photoactivation. Author(s): Rousset S, Nocentini S, Rouillard D, Baroche C, Moustacchi E. Source: Photochemistry and Photobiology. 2002 February; 75(2): 159-66. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11883604
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Mitomycin C chromosome stress test to identify hypersensitivity to bifunctional alkylating agents in patients with Fanconi anemia or aplastic anemia. Author(s): Kuffel DG, Lindor NM, Litzow MR, Zinsmeister AR, Dewald GW. Source: Mayo Clinic Proceedings. 1997 June; 72(6): 579-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9179145
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MLL-CBP fusion transcript in a therapy-related acute myeloid leukemia with the t(11;16)(q23;p13) which developed in an acute lymphoblastic leukemia patient with Fanconi anemia. Author(s): Sugita K, Taki T, Hayashi Y, Shimaoka H, Kumazaki H, Inoue H, Konno Y, Taniwaki M, Kurosawa H, Eguchi M. Source: Genes, Chromosomes & Cancer. 2000 March; 27(3): 264-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10679915
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Mobilization and collection of peripheral blood CD34+ cells from patients with Fanconi anemia. Author(s): Croop JM, Cooper R, Fernandez C, Graves V, Kreissman S, Hanenberg H, Smith FO, Williams DA. Source: Blood. 2001 November 15; 98(10): 2917-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11698271
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Modulation of the spontaneous G2 phase blockage in Fanconi anemia cells by caffeine: differences from cells arrested by X-irradiation. Author(s): Seyschab H, Bretzel G, Friedl R, Schindler D, Sun Y, Hoehn H. Source: Mutation Research. 1994 July 16; 308(2): 149-57. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7518042
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Molecular and genealogical evidence for a founder effect in Fanconi anemia families of the Afrikaner population of South Africa. Author(s): Tipping AJ, Pearson T, Morgan NV, Gibson RA, Kuyt LP, Havenga C, Gluckman E, Joenje H, de Ravel T, Jansen S, Mathew CG. Source: Proceedings of the National Academy of Sciences of the United States of America. 2001 May 8; 98(10): 5734-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11344308
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Molecular biology of Fanconi anemia. Author(s): Kupfer GM, Naf D, D'Andrea AD. Source: Hematology/Oncology Clinics of North America. 1997 December; 11(6): 104560. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9443045
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Molecular biology of Fanconi anemia: implications for diagnosis and therapy. Author(s): D'Andrea AD, Grompe M. Source: Blood. 1997 September 1; 90(5): 1725-36. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9292505
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Molecular characterization of three novel Fanconi anemia mutations in Israeli Arabs. Author(s): Tamary H, Dgany O, Toledano H, Shalev Z, Krasnov T, Shalmon L, Schechter T, Bercovich D, Attias D, Laor R, Koren A, Yaniv I. Source: European Journal of Haematology. 2004 May; 72(5): 330-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15059067
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Molecular insights into Fanconi anemia. Author(s): Sparkes RS. Source: The Journal of Clinical Investigation. 1996 February 15; 97(4): 897-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8613540
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Molecular pathogenesis of fanconi anemia. Author(s): Taniguchi T, Dandrea AD. Source: International Journal of Hematology. 2002 February; 75(2): 123-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11939257
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Molecular spectra of HPRT deletion mutations in circulating T-lymphocytes in Fanconi anemia patients. Author(s): Laquerbe A, Sala-Trepat M, Vives C, Escarceller M, Papadopoulo D. Source: Mutation Research. 1999 December 17; 431(2): 341-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10635999
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Multifocal osteosarcoma in a patient with Fanconi anemia. Author(s): Levinson S, Vincent KA. Source: Journal of Pediatric Hematology/Oncology : Official Journal of the American Society of Pediatric Hematology/Oncology. 1997 May-June; 19(3): 251-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9201150
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Mutagenic processing of psoralen monoadducts differ in normal and Fanconi anemia cells. Author(s): Guillouf C, Laquerbe A, Moustacchi E, Papadopoulo D. Source: Mutagenesis. 1993 July; 8(4): 355-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8377656
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Mutation analysis of the Fanconi anemia gene FACC. Author(s): Verlander PC, Lin JD, Udono MU, Zhang Q, Gibson RA, Mathew CG, Auerbach AD. Source: American Journal of Human Genetics. 1994 April; 54(4): 595-601. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8128956
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Mutations of the Fanconi anemia group A gene (FAA) in Italian patients. Author(s): Savino M, Ianzano L, Strippoli P, Ramenghi U, Arslanian A, Bagnara GP, Joenje H, Zelante L, Savoia A. Source: American Journal of Human Genetics. 1997 December; 61(6): 1246-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9399890
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MxA overexpression reveals a common genetic link in four Fanconi anemia complementation groups. Author(s): Li Y, Youssoufian H. Source: The Journal of Clinical Investigation. 1997 December 1; 100(11): 2873-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9389754
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New recessive syndrome characterized by increased chromosomal breakage and several findings which overlap with Fanconi anemia. Author(s): Giampietro PF, Auerbach AD, Elias ER, Gutman A, Zellers NJ, Davis JG. Source: American Journal of Medical Genetics. 1998 June 16; 78(1): 70-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9637428
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Normal expression of the Fanconi anemia proteins FAA and FAC and sensitivity to mitomycin C in two patients with Seckel syndrome. Author(s): Abou-Zahr F, Bejjani B, Kruyt FA, Kurg R, Bacino C, Shapira SK, Youssoufian H. Source: American Journal of Medical Genetics. 1999 April 23; 83(5): 388-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10232749
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Novel frameshift mutation (1806insA) in exon 14 of the Fanconi anemia C gene, FAC. Author(s): Lo Ten Foe JR, Rooimans MA, Joenje H, Arwert F. Source: Human Mutation. 1996; 7(3): 264-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8829660
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Novel mutations and polymorphisms in the Fanconi anemia group C gene. Author(s): Gibson RA, Morgan NV, Goldstein LH, Pearson IC, Kesterton IP, Foot NJ, Jansen S, Havenga C, Pearson T, de Ravel TJ, Cohn RJ, Marques IM, Dokal I, Roberts I, Marsh J, Ball S, Milner RD, Llerena JC Jr, Samochatova E, Mohan SP, Vasudevan P, Birjandi F, Hajianpour A, Murer-Orlando M, Mathew CG. Source: Human Mutation. 1996; 8(2): 140-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8844212
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Novel mutations of the FANCG gene causing alternative splicing in Japanese Fanconi anemia. Author(s): Yamada T, Tachibana A, Shimizu T, Mugishima H, Okubo M, Sasaki MS. Source: Journal of Human Genetics. 2000; 45(3): 159-66. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10807541
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Nuclear localization of the Fanconi anemia protein FANCC is required for functional activity. Author(s): Garcia-Higuera I, D'Andrea AD. Source: Blood. 1999 June 1; 93(11): 4025-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10383195
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Nuclease modification in Chinese hamster cells hypersensitive to DNA cross-linking agents--a model for Fanconi anemia. Author(s): Sakaguchi K, Zdzienicka MZ, Harris PV, Boyd JB. Source: Mutation Research. 1992 June; 274(1): 11-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1375328
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Otologic manifestations of Fanconi anemia. Author(s): Santos F, Selesnick SH, Glasgold RA. Source: Otology & Neurotology : Official Publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology. 2002 November; 23(6): 873-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12438849
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Outcome of 69 allogeneic stem cell transplantations for Fanconi anemia using HLAmatched unrelated donors: a study on behalf of the European Group for Blood and Marrow Transplantation. Author(s): Guardiola P, Pasquini R, Dokal I, Ortega JJ, van Weel-Sipman M, Marsh JC, Ball SE, Locatelli F, Vermylen C, Skinner R, Ljungman P, Miniero R, Shaw PJ, Souillet G, Michallet M, Bekassy AN, Krivan G, Di Bartolomeo P, Heilmann C, Zanesco L, Cahn JY, Arcese W, Bacigalupo A, Gluckman E. Source: Blood. 2000 January 15; 95(2): 422-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10627445
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Overexpressed thioredoxin compensates Fanconi anemia related chromosomal instability. Author(s): Kontou M, Adelfalk C, Ramirez MH, Ruppitsch W, Hirsch-Kauffmann M, Schweiger M. Source: Oncogene. 2002 April 4; 21(15): 2406-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11948424
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Overexpression of the fanconi anemia group C gene (FAC) protects hematopoietic progenitors from death induced by Fas-mediated apoptosis. Author(s): Wang J, Otsuki T, Youssoufian H, Foe JL, Kim S, Devetten M, Yu J, Li Y, Dunn D, Liu JM. Source: Cancer Research. 1998 August 15; 58(16): 3538-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9721856
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Overexpression of thioredoxin in Fanconi anemia fibroblasts prevents the cytotoxic and DNA damaging effect of mitomycin C and diepoxybutane. Author(s): Ruppitsch W, Meisslitzer C, Hirsch-Kauffmann M, Schweiger M. Source: Febs Letters. 1998 January 23; 422(1): 99-102. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9475178
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Oxidant hypersensitivity of Fanconi anemia type C-deficient cells is dependent on a redox-regulated apoptotic pathway. Author(s): Saadatzadeh MR, Bijangi-Vishehsaraei K, Hong P, Bergmann H, Haneline LS. Source: The Journal of Biological Chemistry. 2004 April 16; 279(16): 16805-12. Epub 2004 February 05. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14764578
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Oxidative stress-related mechanisms are associated with xenobiotics exerting excess toxicity to Fanconi anemia cells. Author(s): Pagano G, Manini P, Bagchi D. Source: Environmental Health Perspectives. 2003 November; 111(14): 1699-703. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14594617
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p53 activates Fanconi anemia group C gene expression. Author(s): Liebetrau W, Budde A, Savoia A, Grummt F, Hoehn H. Source: Human Molecular Genetics. 1997 February; 6(2): 277-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9063748
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p53-dependent pathway of radio-induced apoptosis is altered in Fanconi anemia. Author(s): Rosselli F, Ridet A, Soussi T, Duchaud E, Alapetite C, Moustacchi E. Source: Oncogene. 1995 January 5; 10(1): 9-17. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7824283
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Paroxysmal nocturnal hemoglobinuria arising from Fanconi anemia. Author(s): Wainwright L, Brodsky RA, Erasmus LK, Poyiadjis S, Naidu G, MacKinnon D. Source: Journal of Pediatric Hematology/Oncology : Official Journal of the American Society of Pediatric Hematology/Oncology. 2003 February; 25(2): 167-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12571472
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Partial complementation of the Fanconi anemia defect upon transfection by heterologous DNA. Phenotypic dissociation of chromosomal and cellular hypersensitivity to DNA cross-linking agents. Author(s): Diatloff-Zito C, Rosselli F, Heddle J, Moustacchi E. Source: Human Genetics. 1990 December; 86(2): 151-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2265827
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Partial correction of chromosome instability in Fanconi anemia by desferrioxamine. Author(s): Poot M, Hoehn H. Source: Human Genetics. 1990 May; 84(6): 581-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2338346
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Phenotypic consequences of mutations in the Fanconi anemia FAC gene: an International Fanconi Anemia Registry study. Author(s): Gillio AP, Verlander PC, Batish SD, Giampietro PF, Auerbach AD. Source: Blood. 1997 July 1; 90(1): 105-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9207444
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Phenotypic correction of Fanconi anemia group C knockout mice. Author(s): Gush KA, Fu KL, Grompe M, Walsh CE. Source: Blood. 2000 January 15; 95(2): 700-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10627482
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Phenotypic correction of Fanconi anemia in human hematopoietic cells with a recombinant adeno-associated virus vector. Author(s): Walsh CE, Nienhuis AW, Samulski RJ, Brown MG, Miller JL, Young NS, Liu JM. Source: The Journal of Clinical Investigation. 1994 October; 94(4): 1440-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7929819
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Phenotypic correction of primary Fanconi anemia T cells with retroviral vectors as a diagnostic tool. Author(s): Hanenberg H, Batish SD, Pollok KE, Vieten L, Verlander PC, Leurs C, Cooper RJ, Gottsche K, Haneline L, Clapp DW, Lobitz S, Williams DA, Auerbach AD. Source: Experimental Hematology. 2002 May; 30(5): 410-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12031647
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Phosphorylation of Fanconi anemia protein, FANCA, is regulated by Akt kinase. Author(s): Otsuki T, Nagashima T, Komatsu N, Kirito K, Furukawa Y, Kobayashi Si S, Liu JM, Ozawa K. Source: Biochemical and Biophysical Research Communications. 2002 March 1; 291(3): 628-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11855836
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Plasma/serum levels of flt3 ligand are low in normal individuals and highly elevated in patients with Fanconi anemia and acquired aplastic anemia. Author(s): Lyman SD, Seaberg M, Hanna R, Zappone J, Brasel K, Abkowitz JL, Prchal JT, Schultz JC, Shahidi NT. Source: Blood. 1995 December 1; 86(11): 4091-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7492765
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Positional cloning of a novel Fanconi anemia gene, FANCD2. Author(s): Timmers C, Taniguchi T, Hejna J, Reifsteck C, Lucas L, Bruun D, Thayer M, Cox B, Olson S, D'Andrea AD, Moses R, Grompe M. Source: Molecular Cell. 2001 February; 7(2): 241-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11239453
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Preclinical protocol for in vivo selection of hematopoietic stem cells corrected by gene therapy in Fanconi anemia group C. Author(s): Noll M, Bateman RL, D'Andrea AD, Grompe M. Source: Molecular Therapy : the Journal of the American Society of Gene Therapy. 2001 January; 3(1): 14-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11162306
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Preimplantation diagnosis for Fanconi anemia combined with HLA matching. Author(s): Verlinsky Y, Rechitsky S, Schoolcraft W, Strom C, Kuliev A. Source: Jama : the Journal of the American Medical Association. 2001 June 27; 285(24): 3130-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11427142
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Prenatal identification of potential donors for umbilical cord blood transplantation for Fanconi anemia. Author(s): Auerbach AD, Liu Q, Ghosh R, Pollack MS, Douglas GW, Broxmeyer HE. Source: Transfusion. 1990 October; 30(8): 682-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2219253
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Prolonged administration of granulocyte colony-stimulating factor (filgrastim) to patients with Fanconi anemia: a pilot study. Author(s): Rackoff WR, Orazi A, Robinson CA, Cooper RJ, Alter BP, Freedman MH, Harris RE, Williams DA. Source: Blood. 1996 September 1; 88(5): 1588-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8781414
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Promoter hypermethylation of FANCF: disruption of Fanconi Anemia-BRCA pathway in cervical cancer. Author(s): Narayan G, Arias-Pulido H, Nandula SV, Basso K, Sugirtharaj DD, Vargas H, Mansukhani M, Villella J, Meyer L, Schneider A, Gissmann L, Durst M, Pothuri B, Murty VV. Source: Cancer Research. 2004 May 1; 64(9): 2994-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15126331
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Prompt and durable hematopoietic reconstitution by unrelated cord blood transplantation in a child with Fanconi anemia. Author(s): Yoshimasu T, Tanaka R, Suenobu S, Yagasaki H, Yoshino H, Ueda T, Hisakawa H, Ishii T, Mitsui T, Ebihara Y, Manabe A, Iseki T, Maekawa T, Nakahata T, Asano S, Tsuji K. Source: Bone Marrow Transplantation. 2001 April; 27(7): 767-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11360120
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Prospects for nutritional interventions in the clinical management of Fanconi anemia. Author(s): Pagano G, Korkina LG. Source: Cancer Causes & Control : Ccc. 2000 December; 11(10): 881-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11142522
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Protein replacement by receptor-mediated endocytosis corrects the sensitivity of Fanconi anemia group C cells to mitomycin C. Author(s): Youssoufian H, Kruyt FA, Li X. Source: Blood. 1999 January 1; 93(1): 363-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9864182
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Radiosensitivity in Fanconi anemia: application to the conditioning for bone marrow transplantation. Author(s): Gluckman E. Source: Radiotherapy and Oncology : Journal of the European Society for Therapeutic Radiology and Oncology. 1990; 18 Suppl 1: 88-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2247653
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Re: Human papillomavirus DNA and p53 polymorphisms in squamous cell carcinomas from Fanconi anemia patients. Author(s): van Zeeburg HJ, Snijders PJ, Joenje H, Brakenhoff RH. Source: Journal of the National Cancer Institute. 2004 June 16; 96(12): 968; Author Reply 968-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15199119
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Reactivation of psoralen-reacted plasmid DNA in Fanconi anemia, xeroderma pigmentosum, and normal human fibroblast cells. Author(s): Sun Y, Moses RE. Source: Somatic Cell and Molecular Genetics. 1991 May; 17(3): 229-38. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2047939
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Reduced toxicity and prompt engraftment after minimal conditioning of a patient with Fanconi anemia undergoing hematopoietic stem cell transplantation from an HLA-matched unrelated donor. Author(s): Kurre P, Pulsipher M, Woolfrey A, Maris M, Sandmaier B, Kiem HP, Storb R. Source: Journal of Pediatric Hematology/Oncology : Official Journal of the American Society of Pediatric Hematology/Oncology. 2003 July; 25(7): 581-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12847331
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Reduced uptake and incorporation of 3H-thymidine in Fanconi anemia fibroblasts. Author(s): Shoyab M, Gunnell M, Lubiniecki AS. Source: Human Genetics. 1981; 57(3): 296-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7250972
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Reduction of toxicity of marrow transplantation in children with Fanconi anemia. Author(s): Harris RE. Source: Journal of Pediatric Hematology/Oncology : Official Journal of the American Society of Pediatric Hematology/Oncology. 1999 May-June; 21(3): 175-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10363847
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Refractory pancreatitis associated with graft-versus-host disease in Fanconi anemia. Author(s): Yamamoto M, Hiraumi Y, Ichimura N, Ohtsuki F, Nakagawa M, Ohtsuka Y, Tsujino Y, Tanaka A, Kamiya T, Wada H. Source: American Journal of Hematology. 1996 August; 52(4): 329-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8701959
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Regulated binding of the Fanconi anemia proteins, FANCA and FANCC. Author(s): Garcia-Higuera I, D'Andrea AD. Source: Blood. 1999 February 15; 93(4): 1430-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10075454
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Regulation of the Fanconi anemia group C protein through proteolytic modification. Author(s): Brodeur I, Goulet I, Tremblay CS, Charbonneau C, Delisle MC, Godin C, Huard C, Khandjian EW, Buchwald M, Levesque G, Carreau M. Source: The Journal of Biological Chemistry. 2004 February 6; 279(6): 4713-20. Epub 2003 November 18. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14625294
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Regulation of the Fanconi anemia pathway by monoubiquitination. Author(s): Gregory RC, Taniguchi T, D'Andrea AD. Source: Seminars in Cancer Biology. 2003 February; 13(1): 77-82. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12507559
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Rejection of the second allogeneic graft in a child with Fanconi anemia reversed by antilymphocyte globulin and donor lymphocyte infusion. Author(s): Abdelkefi A, Ben Othman T, Ladeb S, Torjman L, Ben Abdeladhim A. Source: The Hematology Journal : the Official Journal of the European Haematology Association / Eha. 2003; 4(6): 452-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14671621
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Repair kinetics of genomic interstrand DNA cross-links: evidence for DNA doublestrand break-dependent activation of the Fanconi anemia/BRCA pathway. Author(s): Rothfuss A, Grompe M. Source: Molecular and Cellular Biology. 2004 January; 24(1): 123-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14673148
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Repression of Fanconi anemia gene (FACC) expression inhibits growth of hematopoietic progenitor cells. Author(s): Segal GM, Magenis RE, Brown M, Keeble W, Smith TD, Heinrich MC, Bagby GC Jr. Source: The Journal of Clinical Investigation. 1994 August; 94(2): 846-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7518843
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Resistance to mitomycin C requires direct interaction between the Fanconi anemia proteins FANCA and FANCG in the nucleus through an arginine-rich domain. Author(s): Kruyt FA, Abou-Zahr F, Mok H, Youssoufian H. Source: The Journal of Biological Chemistry. 1999 November 26; 274(48): 34212-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10567393
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Response to X-irradiation of Fanconi anemia homozygous and heterozygous cells assessed by the single-cell gel electrophoresis (comet) assay. Author(s): Djuzenova CS, Rothfuss A, Oppitz U, Spelt G, Schindler D, Hoehn H, Flentje M. Source: Laboratory Investigation; a Journal of Technical Methods and Pathology. 2001 February; 81(2): 185-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11232640
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Responses of Fanconi anemia fibroblasts to adenine and purine analogues. Author(s): Frazelle JH, Harris JS, Swift M. Source: Mutation Research. 1981 February; 80(2): 373-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6163077
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Retroviral gene transfer for the assignment of Fanconi anemia (FA) patients to a FA complementation group. Author(s): Fu KL, Thuss PC, Fujino T, Digweed M, Liu JM, Walsh CE. Source: Human Genetics. 1998 February; 102(2): 166-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9521584
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Retroviral mediated gene transfer of the Fanconi anemia complementation group C gene to hematopoietic progenitors of group C patients. Author(s): Liu JM, Young NS, Walsh CE, Cottler-Fox M, Carter C, Dunbar C, Barrett AJ, Emmons R. Source: Human Gene Therapy. 1997 September 20; 8(14): 1715-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9322874
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Reverse mosaicism in Fanconi anemia: natural gene therapy via molecular selfcorrection. Author(s): Gross M, Hanenberg H, Lobitz S, Friedl R, Herterich S, Dietrich R, Gruhn B, Schindler D, Hoehn H. Source: Cytogenetic and Genome Research. 2002; 98(2-3): 126-35. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12697994
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Screening Fanconi anemia lymphoid cell lines of non-A, C, D2, E, F, G subtypes for defects in BRCA2/FANCD1. Author(s): Popp H, Kalb R, Fischer A, Lobitz S, Kokemohr I, Hanenberg H, Schindler D. Source: Cytogenetic and Genome Research. 2003; 103(1-2): 54-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15004464
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Screening strategies for a highly polymorphic gene: DHPLC analysis of the Fanconi anemia group A gene. Author(s): Rischewski J, Schneppenheim R. Source: Journal of Biochemical and Biophysical Methods. 2001 January 30; 47(1-2): 53-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11179761
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Segregation analysis with uncertain ascertainment: application to Fanconi anemia. Author(s): Rogatko A, Auerbach AD. Source: American Journal of Human Genetics. 1988 June; 42(6): 889-97. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3369448
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Selective pressure as an essential force in molecular evolution of myeloid leukemic clones: a view from the window of Fanconi anemia. Author(s): Lensch MW, Rathbun RK, Olson SB, Jones GR, Bagby GC Jr. Source: Leukemia : Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 1999 November; 13(11): 1784-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10557053
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Sequence variation in the Fanconi anemia gene FAA. Author(s): Levran O, Erlich T, Magdalena N, Gregory JJ, Batish SD, Verlander PC, Auerbach AD. Source: Proceedings of the National Academy of Sciences of the United States of America. 1997 November 25; 94(24): 13051-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9371798
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SNX5, a new member of the sorting nexin family, binds to the Fanconi anemia complementation group A protein. Author(s): Otsuki T, Kajigaya S, Ozawa K, Liu JM. Source: Biochemical and Biophysical Research Communications. 1999 November 30; 265(3): 630-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10600472
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Somatic mosaicism in Fanconi anemia: evidence of genotypic reversion in lymphohematopoietic stem cells. Author(s): Gregory JJ Jr, Wagner JE, Verlander PC, Levran O, Batish SD, Eide CR, Steffenhagen A, Hirsch B, Auerbach AD. Source: Proceedings of the National Academy of Sciences of the United States of America. 2001 February 27; 98(5): 2532-7. Epub 2001 Feb 13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11226273
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Somatic mosaicism in Fanconi anemia: molecular basis and clinical significance. Author(s): Lo Ten Foe JR, Kwee ML, Rooimans MA, Oostra AB, Veerman AJ, van Weel M, Pauli RM, Shahidi NT, Dokal I, Roberts I, Altay C, Gluckman E, Gibson RA, Mathew CG, Arwert F, Joenje H. Source: European Journal of Human Genetics : Ejhg. 1997 May-June; 5(3): 137-48. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9272737
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Somatic segregation and Fanconi anemia. Author(s): Berger R, Bussel A, Schenmetzler C. Source: Clinical Genetics. 1977 June; 11(6): 409-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=880740
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Specific cellular defects in patients with Fanconi anemia. Author(s): Weksberg R, Buchwald M, Sargent P, Thompson MW, Siminovitch L. Source: Journal of Cellular Physiology. 1979 November; 101(2): 311-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=511954
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Spectrum of sequence variation in the FANCG gene: an International Fanconi Anemia Registry (IFAR) study. Author(s): Auerbach AD, Greenbaum J, Pujara K, Batish SD, Bitencourt MA, Kokemohr I, Schneider H, Lobitzc S, Pasquini R, Giampietro PF, Hanenberg H, Levran O; International Fanconi Anemia Registry. Source: Human Mutation. 2003 February; 21(2): 158-68. Erratum In: Hum Mutat. 2003 September; 22(3): 255. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12552564
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S-phase-specific interaction of the Fanconi anemia protein, FANCD2, with BRCA1 and RAD51. Author(s): Taniguchi T, Garcia-Higuera I, Andreassen PR, Gregory RC, Grompe M, D'Andrea AD. Source: Blood. 2002 October 1; 100(7): 2414-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12239151
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Spontaneous 6-thioguanine-resistant lymphocytes in Fanconi anemia patients and their heterozygous parents. Author(s): Vijayalaxmi, Wunder E, Schroeder TM. Source: Human Genetics. 1985; 70(3): 264-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4018791
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Squamous cell carcinoma of the tongue in a child with Fanconi anemia: a case report and review of the literature. Author(s): Somers GR, Tabrizi SN, Tiedemann K, Chow CW, Garland SM, Venter DJ. Source: Pediatric Pathology & Laboratory Medicine : Journal of the Society for Pediatric Pathology, Affiliated with the International Paediatric Pathology Association. 1995 JulyAugust; 15(4): 597-607. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8597846
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Studies of gene transfer and reversion to mitomycin C resistance in Fanconi anemia cells. Author(s): Buchwald M, Ng J, Clarke C, Duckworth-Rysiecki G. Source: Mutation Research. 1987 September; 184(2): 153-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3114627
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Studies of malformation syndromes of man XLVII: disappearance of spermatogonia in the Fanconi anemia syndrome. Author(s): Bargman GJ, Shahidi NT, Gilbert EF, Opitz JM. Source: European Journal of Pediatrics. 1977 July 1; 125(3): 163-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=267584
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Successful allogeneic bone marrow transplantation in a case with myelodysplastic syndrome which developed following Fanconi anemia. Author(s): Ikushima S, Hibi S, Todo S, Sawada T, Matsumoto Y, Iwami H, Tsunamoto K, Kasubuchi Y, Yabe M, Kato S, et al. Source: Bone Marrow Transplantation. 1995 October; 16(4): 621-4. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8528182
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Successful allogeneic bone marrow transplantation in a child affected by Fanconi anemia. Author(s): Locatelli F, Bonetti F, Pedrazzoli P, Bongiorno M, Gibardi A, Prete L, Cirincione S, Vitale V, Barra S, Nespoli L, et al. Source: Bone Marrow Transplantation. 1991; 7 Suppl 3: 128-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1855075
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Successful double bone marrow and renal transplantation in a patient with Fanconi anemia. Author(s): Miano M, Ginevri F, Nocera A, Dallorso S, Fontana I, Perfumo F, Dini G, Dufour C. Source: Blood. 2002 May 1; 99(9): 3482-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12001906
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Successful haploidentical bone marrow transplantation in Fanconi anemia. Author(s): Elhasid R, Ben Arush MW, Katz T, Gan Y, Shechter Y, Sami I, Postovsky S, Reisner Y, Rowe JM. Source: Bone Marrow Transplantation. 2000 December; 26(11): 1221-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11149735
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Targeted disruption of the murine Fanconi anemia gene, Fancg/Xrcc9. Author(s): Yang Y, Kuang Y, De Oca RM, Hays T, Moreau L, Lu N, Seed B, D'Andrea AD. Source: Blood. 2001 December 1; 98(12): 3435-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11719385
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The 4N cell cycle delay in Fanconi anemia reflects growth arrest in late S phase. Author(s): Akkari YM, Bateman RL, Reifsteck CA, D'Andrea AD, Olson SB, Grompe M. Source: Molecular Genetics and Metabolism. 2001 December; 74(4): 403-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11749045
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The anti-apoptotic function of Hsp70 in the interferon-inducible double-stranded RNA-dependent protein kinase-mediated death signaling pathway requires the Fanconi anemia protein, FANCC. Author(s): Pang Q, Christianson TA, Keeble W, Koretsky T, Bagby GC. Source: The Journal of Biological Chemistry. 2002 December 20; 277(51): 49638-43. Epub 2002 October 22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12397061
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The cellular control enzyme polyADP ribosyl transferase is eliminated in cultured Fanconi anemia fibroblasts at confluency. Author(s): Ramirez MH, Adelfalk C, Kontou M, Hirsch-Kauffmann M, Schweiger M. Source: Biological Chemistry. 2003 January; 384(1): 169-74. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12674511
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The Drosophila S3 multifunctional DNA repair/ribosomal protein protects Fanconi anemia cells against oxidative DNA damaging agents. Author(s): Kelley MR, Tritt R, Xu Y, New S, Freie B, Clapp DW, Deutsch WA. Source: Mutation Research. 2001 March 7; 485(2): 107-19. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11182542
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The effects of the Fanconi anemia zinc finger (FAZF) on cell cycle, apoptosis, and proliferation are differentiation stage-specific. Author(s): Dai MS, Chevallier N, Stone S, Heinrich MC, McConnell M, Reuter T, Broxmeyer HE, Licht JD, Lu L, Hoatlin ME. Source: The Journal of Biological Chemistry. 2002 July 19; 277(29): 26327-34. Epub 2002 May 01. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11986317
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The FANCG Fanconi anemia protein interacts with CYP2E1: possible role in protection against oxidative DNA damage. Author(s): Futaki M, Igarashi T, Watanabe S, Kajigaya S, Tatsuguchi A, Wang J, Liu JM. Source: Carcinogenesis. 2002 January; 23(1): 67-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11756225
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The Fanconi anemia cell line HSC536N is not sensitive to interferon-gamma and does not cleave PARP in response to FAS-mediated cell killing. Author(s): Rutherford TR, Myatt NE, Gibson FM, Clarke AA. Source: Blood. 2002 April 1; 99(7): 2627-8; Author Reply 2629-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11926188
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The Fanconi anemia complementation group C gene product: structural evidence of multifunctionality. Author(s): Pang Q, Christianson TA, Keeble W, Diaz J, Faulkner GR, Reifsteck C, Olson S, Bagby GC. Source: Blood. 2001 September 1; 98(5): 1392-401. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11520787
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The Fanconi anemia core complex forms four complexes of different sizes in different subcellular compartments. Author(s): Thomashevski A, High AA, Drozd M, Shabanowitz J, Hunt DF, Grant PA, Kupfer GM. Source: The Journal of Biological Chemistry. 2004 June 18; 279(25): 26201-9. Epub 2004 April 13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15082718
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The Fanconi anemia group C gene product: signaling functions in hematopoietic cells. Author(s): Fagerlie S, Lensch MW, Pang Q, Bagby GC Jr. Source: Experimental Hematology. 2001 December; 29(12): 1371-81. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11750095
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The Fanconi anemia protein FANCF forms a nuclear complex with FANCA, FANCC and FANCG. Author(s): de Winter JP, van der Weel L, de Groot J, Stone S, Waisfisz Q, Arwert F, Scheper RJ, Kruyt FA, Hoatlin ME, Joenje H. Source: Human Molecular Genetics. 2000 November 1; 9(18): 2665-74. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11063725
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The Fanconi anemia protein, FANCE, promotes the nuclear accumulation of FANCC. Author(s): Taniguchi T, D'Andrea AD. Source: Blood. 2002 October 1; 100(7): 2457-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12239156
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The fanconi anemia proteins FANCA and FANCG stabilize each other and promote the nuclear accumulation of the Fanconi anemia complex. Author(s): Garcia-Higuera I, Kuang Y, Denham J, D'Andrea AD. Source: Blood. 2000 November 1; 96(9): 3224-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11050007
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The molecular biology of Fanconi anemia. Author(s): Tamary H, Bar-Yam R, Zemach M, Dgany O, Shalmon L, Yaniv I. Source: Isr Med Assoc J. 2002 October; 4(10): 819-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12389351
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The p38 pathway partially mediates caspase-3 activation induced by reactive oxygen species in Fanconi anemia C cells. Author(s): Pearl-Yafe M, Halperin D, Scheuerman O, Fabian I. Source: Biochemical Pharmacology. 2004 February 1; 67(3): 539-46. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15037205
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•
TNF-alpha and IFN-gamma are overexpressed in the bone marrow of Fanconi anemia patients and TNF-alpha suppresses erythropoiesis in vitro. Author(s): Dufour C, Corcione A, Svahn J, Haupt R, Poggi V, Beka'ssy AN, Scime R, Pistorio A, Pistoia V. Source: Blood. 2003 September 15; 102(6): 2053-9. Epub 2003 May 15. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12750172
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Triplication of 1q in Fanconi anemia. Author(s): Ferro MT, Vazquez-Mazariego Y, Ramiro S, Sanchez-Hombre MC, Villalon C, Garcia-Sagredo JM, Ulibarrena C, Sastre JL, Roman CS. Source: Cancer Genetics and Cytogenetics. 2001 May; 127(1): 38-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11408063
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Two common founder mutations of the fanconi anemia group G gene FANCG/XRCC9 in the Japanese population. Author(s): Yagasaki H, Oda T, Adachi D, Nakajima T, Nakahata T, Asano S, Yamashita T. Source: Human Mutation. 2003 May; 21(5): 555. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12673805
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Two different karyotypes with 1q abnormalities in a patient with Fanconi anemia. Author(s): Oliveira NI, Ribeiro EM, Raimondi SC, Bittencourt MA, Pasquini R, Cavalli IJ. Source: Leukemia Research. 2002 November; 26(11): 1047-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12363475
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Ultrastructure of Fanconi anemia fibroblasts. Author(s): Willingale-Theune J, Schweiger M, Hirsch-Kauffmann M, Meek AE, PaulinLevasseur M, Traub P. Source: Journal of Cell Science. 1989 August; 93 ( Pt 4): 651-65. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2691519
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Unrelated cord blood transplantation in a Fanconi anemia patient using fludarabinebased conditioning. Author(s): de Medeiros CR, Silva LM, Pasquini R. Source: Bone Marrow Transplantation. 2001 July; 28(1): 110-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11498756
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Unrelated donor bone marrow transplantation for Fanconi anemia. Author(s): Davies SM, Khan S, Wagner JE, Arthur DC, Auerbach AD, Ramsay NK, Weisdorf DJ. Source: Bone Marrow Transplantation. 1996 January; 17(1): 43-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8673053
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Unrelated peripheral blood stem cell transplantation for Fanconi anemia. Author(s): Massumoto C, Moraes JR, Moraes ME, Macedo MC, Medeiros R, Chamone D, Dulley F. Source: Bone Marrow Transplantation. 1997 February; 19(3): 299-300. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9028563
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VACTERL with hydrocephalus in twins due to Fanconi anemia (FA): mutation in the FAC gene. Author(s): Cox PM, Gibson RA, Morgan N, Brueton LA. Source: American Journal of Medical Genetics. 1997 January 10; 68(1): 86-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8986283
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VACTERL with hydrocephalus: one end of the Fanconi anemia spectrum of anomalies? Author(s): Porteous ME, Cross I, Burn J. Source: American Journal of Medical Genetics. 1992 August 1; 43(6): 1032-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1415330
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Wiskott-Aldrich syndrome in a family with Fanconi anemia. Author(s): Rohrer J, Ribeiro RC, Auerbach AD, Mirro B, Conley ME. Source: The Journal of Pediatrics. 1996 July; 129(1): 50-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8757562
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Yeast two-hybrid screens imply involvement of Fanconi anemia proteins in transcription regulation, cell signaling, oxidative metabolism, and cellular transport. Author(s): Reuter TY, Medhurst AL, Waisfisz Q, Zhi Y, Herterich S, Hoehn H, Gross HJ, Joenje H, Hoatlin ME, Mathew CG, Huber PA. Source: Experimental Cell Research. 2003 October 1; 289(2): 211-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14499622
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CHAPTER 2. NUTRITION AND FANCONI ANEMIA Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and Fanconi anemia.
Finding Nutrition Studies on Fanconi Anemia The National Institutes of Health’s Office of Dietary Supplements (ODS) offers a searchable bibliographic database called the IBIDS (International Bibliographic Information on Dietary Supplements; National Institutes of Health, Building 31, Room 1B29, 31 Center Drive, MSC 2086, Bethesda, Maryland 20892-2086, Tel: 301-435-2920, Fax: 301-480-1845, E-mail:
[email protected]). The IBIDS contains over 460,000 scientific citations and summaries about dietary supplements and nutrition as well as references to published international, scientific literature on dietary supplements such as vitamins, minerals, and botanicals.7 The IBIDS includes references and citations to both human and animal research studies. As a service of the ODS, access to the IBIDS database is available free of charge at the following Web address: http://ods.od.nih.gov/databases/ibids.html. After entering the search area, you have three choices: (1) IBIDS Consumer Database, (2) Full IBIDS Database, or (3) Peer Reviewed Citations Only. Now that you have selected a database, click on the “Advanced” tab. An advanced search allows you to retrieve up to 100 fully explained references in a comprehensive format. Type “Fanconi anemia” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.
7 Adapted from http://ods.od.nih.gov. IBIDS is produced by the Office of Dietary Supplements (ODS) at the National Institutes of Health to assist the public, healthcare providers, educators, and researchers in locating credible, scientific information on dietary supplements. IBIDS was developed and will be maintained through an interagency partnership with the Food and Nutrition Information Center of the National Agricultural Library, U.S. Department of Agriculture.
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The following information is typical of that found when using the “Full IBIDS Database” to search for “Fanconi anemia” (or a synonym): •
An oxidative mechanism of interferon induced priming of the Fas pathway in Fanconi anemia cells. Author(s): Department of Cell Biology and Histology, Sackler Faculty of Medicine, TelAviv University, Israel. Source: Pearl Yafe, M Halperin, D Halevy, A Kalir, H Bielorai, B Fabian, I BiochemPharmacol. 2003 March 1; 65(5): 833-42 0006-2952
•
Cell cycle defect in connection with oxygen and iron sensitivity in Fanconi anemia lymphoblastoid cells. Author(s): Department of Human Genetics, University of Wurzburg, Germany. Source: Poot, M Gross, O Epe, B Pflaum, M Hoehn, H Exp-Cell-Res. 1996 February 1; 222(2): 262-8 0014-4827
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Comparative study of Fanconi anemia in children of different ethnic origin in South Africa. Author(s): Department of Paediatrics, University of the Witwatersrand, Johannesburg, South Africa. Source: Macdougall, L G Rosendorff, J Poole, J E Cohn, R J McElligott, S E Am-J-MedGenet. 1994 September 1; 52(3): 279-84 0148-7299
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Comparison of the effects of DNA topoisomerase inhibitors on lymphoblasts from normal and Fanconi anemia donors. Author(s): URA 1292 du CNRS, Institut Curie-Biologie, Paris, France. Source: Rosselli, F Duchaud, E Averbeck, D Moustacchi, E Mutat-Res. 1994 December; 325(4): 137-44 0027-5107
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DNA cross-linker-induced G2/M arrest in group C Fanconi anemia lymphoblasts reflects normal checkpoint function. Author(s): Division of Hematology and Medical Oncology, Department of Medicine, Oregon Health Sciences University, Portland, OR, USA. Source: Heinrich, M C Hoatlin, M E Zigler, A J Silvey, K V Bakke, A C Keeble, W W Zhi, Y Reifsteck, C A Grompe, M Brown, M G Magenis, R E Olson, S B Bagby, G C Blood. 1998 January 1; 91(1): 275-87 0006-4971
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Expression of the Fanconi anemia gene FAC in human cell lines: lack of effect of oxygen tension. Author(s): Department of Human Genetics, Free University, Amsterdam, The Netherlands. Source: Joenje, H Youssoufian, H Kruyt, F A dos Santos, C C Wevrick, R Buchwald, M Blood-Cells-Mol-Dis. 1995; 21(3): 182-91 1079-9796
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Modulation of the spontaneous G2 phase blockage in Fanconi anemia cells by caffeine: differences from cells arrested by X-irradiation. Author(s): Department of Human Genetics, University of Wurzburg, Germany. Source: Seyschab, H Bretzel, G Friedl, R Schindler, D Sun, Y Hoehn, H Mutat-Res. 1994 July 16; 308(2): 149-57 0027-5107
•
Release of active oxygen radicals by leukocytes of Fanconi anemia patients. Author(s): Russian Institute of Hematology for Children, Moscow. Source: Korkina, L G Samochatova, E V Maschan, A A Suslova, T B Cheremisina, Z P Afanas'ev, I B J-Leukoc-Biol. 1992 September; 52(3): 357-62 0741-5400
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Federal Resources on Nutrition In addition to the IBIDS, the United States Department of Health and Human Services (HHS) and the United States Department of Agriculture (USDA) provide many sources of information on general nutrition and health. Recommended resources include: •
healthfinder®, HHS’s gateway to health information, including diet and nutrition: http://www.healthfinder.gov/scripts/SearchContext.asp?topic=238&page=0
•
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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WebMDHealth: http://my.webmd.com/nutrition
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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html
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The following is a specific Web list relating to Fanconi anemia; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: •
Minerals Potassium Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10086,00.html
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CHAPTER 3. ALTERNATIVE MEDICINE AND FANCONI ANEMIA Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to Fanconi anemia. At the conclusion of this chapter, we will provide additional sources.
National Center for Complementary and Alternative Medicine The National Center for Complementary and Alternative Medicine (NCCAM) of the National Institutes of Health (http://nccam.nih.gov/) has created a link to the National Library of Medicine’s databases to facilitate research for articles that specifically relate to Fanconi anemia and complementary medicine. To search the database, go to the following Web site: http://www.nlm.nih.gov/nccam/camonpubmed.html. Select “CAM on PubMed.” Enter “Fanconi anemia” (or synonyms) into the search box. Click “Go.” The following references provide information on particular aspects of complementary and alternative medicine that are related to Fanconi anemia: •
Cell cycle effects of the DNA topoisomerase inhibitors camptothecin and m-AMSA in lymphoblastoid cell lines from patients with Fanconi anemia. Author(s): Poot M, Epe B, Hoehn H. Source: Mutation Research. 1992 November 16; 270(2): 185-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1383735
•
Comparison of the effects of DNA topoisomerase inhibitors on lymphoblasts from normal and Fanconi anemia donors. Author(s): Rosselli F, Duchaud E, Averbeck D, Moustacchi E. Source: Mutation Research. 1994 December; 325(4): 137-44. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7527905
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Fanconi anemia cells have a normal gene structure for topoisomerase I. Author(s): Saito H, Grompe M, Neeley TL, Jakobs PM, Moses RE. Source: Human Genetics. 1994 May; 93(5): 583-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8168839
•
Mechanism of inhibitory effects of chelating drugs on lipid peroxidation in rat brain homogenates. Author(s): Kozlov AB, Ostrachovitch EA, Afanas'ev IB. Source: Biochemical Pharmacology. 1994 March 2; 47(5): 795-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8135855
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Oxidative stress in rheumatoid arthritis leukocytes: suppression by rutin and other antioxidants and chelators. Author(s): Ostrakhovitch EA, Afanas'ev IB. Source: Biochemical Pharmacology. 2001 September 15; 62(6): 743-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11551519
•
Release of active oxygen radicals by leukocytes of Fanconi anemia patients. Author(s): Korkina LG, Samochatova EV, Maschan AA, Suslova TB, Cheremisina ZP, Afanas'ev IB. Source: Journal of Leukocyte Biology. 1992 September; 52(3): 357-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1326022
•
Unexpected complications after bone marrow transplantation in transfusiondependent children. Author(s): Saunders EF, Olivieri N, Freedman MH. Source: Bone Marrow Transplantation. 1993; 12 Suppl 1: 88-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8374573
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/
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drkoop.com: http://www.drkoop.com/InteractiveMedicine/IndexC.html
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Family Village: http://www.familyvillage.wisc.edu/med_altn.htm
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Google: http://directory.google.com/Top/Health/Alternative/
•
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/
•
HealthGate: http://www.tnp.com/
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WebMDHealth: 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. This Web site provides a general overview of various topics and can lead to a number of general sources.
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CHAPTER 4. DISSERTATIONS ON FANCONI ANEMIA Overview In this chapter, we will give you a bibliography on recent dissertations relating to Fanconi anemia. We will also provide you with information on how to use the Internet to stay current on dissertations. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical dissertations that use the generic term “Fanconi anemia” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on Fanconi anemia, we have not necessarily excluded non-medical dissertations in this bibliography.
Dissertations on Fanconi Anemia ProQuest Digital Dissertations, the largest archive of academic dissertations available, is located at the following Web address: http://wwwlib.umi.com/dissertations. From this archive, we have compiled the following list covering dissertations devoted to Fanconi anemia. You will see that the information provided includes the dissertation’s title, its author, and the institution with which the author is associated. The following covers recent dissertations found when using this search procedure: •
Defective DNA double-strand break repair activity in Fanconi anemia fibroblasts by Donahue, Sarah Louise, PhD from University of Minnesota, 2003, 157 pages http://wwwlib.umi.com/dissertations/fullcit/3076318
Keeping Current Ask the medical librarian at your library if it has full and unlimited access to the ProQuest Digital Dissertations database. From the library, you should be able to do more complete searches via http://wwwlib.umi.com/dissertations.
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CHAPTER 5. PATENTS ON FANCONI ANEMIA Overview Patents can be physical innovations (e.g. chemicals, pharmaceuticals, medical equipment) or processes (e.g. treatments or diagnostic procedures). The United States Patent and Trademark Office defines a patent as a grant of a property right to the inventor, issued by the Patent and Trademark Office.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 “Fanconi anemia” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on Fanconi anemia, we have not necessarily excluded nonmedical patents in this bibliography.
Patents on Fanconi Anemia By performing a patent search focusing on Fanconi anemia, you can obtain information such as the title of the invention, the names of the inventor(s), the assignee(s) or the company that owns or controls the patent, a short abstract that summarizes the patent, and a few excerpts from the description of the patent. The abstract of a patent tends to be more technical in nature, while the description is often written for the public. Full patent descriptions contain much more information than is presented here (e.g. claims, references, figures, diagrams, etc.). We will tell you how to obtain this information later in the chapter. The following is an 8Adapted
from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.
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example of the type of information that you can expect to obtain from a patent search on Fanconi anemia: •
cDNA for fanconi anemia complementation group A Inventor(s): Joenje; Hans (Lelystad, NL), Lo Ten Foe; Jerome R. (An Almere, NL) Assignee(s): Fanconi Anemia Research Fund, Inc. (Eugene, OR) Patent Number: 5,952,190 Date filed: October 4, 1996 Abstract: A cDNA molecule corresponding to the gene for human Fanconi anemia of complementation group A is disclosed. Also disclosed is the theoretical amino acid sequence of the FA-A protein. Methods of using these biological materials in the diagnosis and treatment of Fanconi anemia are presented. Excerpt(s): The present invention relates to the cloning and sequencing of the human cDNA molecule corresponding to the gene for Fanconi Anemia of complementation group A (FA-A). The present invention also relates to methods of screening for and detection of FA-A carriers, FA-A disease diagnosis, prenatal FA-A screening and diagnosis, and gene therapy utilizing recombinant DNA technologies. Fanconi Anemia (FA) is a rare and usually fatal human disorder characterized by progressive bone marrow failure, increased risk of malignancy and multiple congenital abnormalities mostly associated with developmental hypoplasia. It affects approximately one in 300,000 individuals (Swift, 1971). The disorder may be associated with a variety of overt congenital somatic anomalies, such as hypoplasia or other malformations of the kidney, cutaneous hyperpigmentation, and bony abnormalities, particularly hypoplastic or absent thumbs and radii (Glanz and Fraser, 1982). However, these clinical manifestations of FA are extremely variable, both in type and severity, and so diagnosis of the disease on this basis alone is difficult and unreliable. Web site: http://www.delphion.com/details?pn=US05952190__
Patent Applications on Fanconi Anemia 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 Fanconi anemia: •
Methods and compositions for the diagnosis of cancer susceptibilities and defective DNA repair mechanisms and treatment thereof Inventor(s): D'Andrea, Alan D.; (Winchester, MA), Grompe, Markus; (Portland, OR), Taniguchi, Toshiyasu; (Boston, MA), Timmers, Cynthia; (Columbus, OH) Correspondence: Bromberg & Sunstein Llp; 125 Summer Street; Boston; MA; 02110-1618; US Patent Application Number: 20030093819 Date filed: November 2, 2001
9
This has been a common practice outside the United States prior to December 2000.
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Abstract: Methods and compositions for the diagnosis of cancer susceptibilities, defective DNA repair mechanisms and treatments thereof are provided. Among sequences provided here, the FANCD2 gene has been identified, mapped on the 3p chromosome, cloned into recombinant vectors, used to prepare recombinant cells and sequenced. The FANCD2 gene sequence provides probes and primers for screening patients in genetic based tests and for diagnosing Fanconi anemia and cancer. It has also been possible to target the FANCD2 gene in vivo for preparing experimental mouse models for use in screening new therapeutic agents for treating conditions involving defective DNA repair. Vectors are described for use in gene therapy. The FANCD2 polypeptide has been sequenced and has been shown to exist in two isoforms identified as FANCD2-S and the mono-ubiquinated FANCD-L form. Antibodies including polyclonal and monoclonal antibodies have been prepared that distinguish the two isoforms and have been used in diagnostic tests to determine whether a subject has an intact FA pathway. The FANCD2 has been localized to the nucleus and is associated with BRCA 1 foci. Excerpt(s): This application gains priority from provisional application 60/245,756 filed Nov. 3, 2000, the application being incorporated by reference herein. The present invention relates to the diagnosis of cancer susceptibilities in subjects having a defect in the FANCD2 gene and the determination of suitable treatment protocols for those subjects who have developed cancer. Animal models with defects in the FANCD2 gene can be used to screen for therapeutic agents. The cloned FA proteins encode orphan proteins with no sequence similarity to each other or to other proteins in GenBank and no functional domains are apparent in the protein sequence. Little is known regarding the cellular or biochemical function of these proteins. 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 Fanconi anemia, you can access the U.S. Patent Office archive via the Internet at the following Web address: http://www.uspto.gov/patft/index.html. You will see two broad options: (1) Issued Patent, and (2) Published Applications. To see a list of issued patents, perform the following steps: Under “Issued Patents,” click “Quick Search.” Then, type “Fanconi anemia” (or synonyms) into the “Term 1” box. After clicking on the search button, scroll down to see the various patents which have been granted to date on Fanconi anemia. You can also use this procedure to view pending patent applications concerning Fanconi anemia. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.
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CHAPTER 6. PERIODICALS AND NEWS ON FANCONI ANEMIA Overview In this chapter, we suggest a number of news sources and present various periodicals that cover Fanconi anemia.
News Services and Press Releases One of the simplest ways of tracking press releases on Fanconi anemia is to search the news wires. In the following sample of sources, we will briefly describe how to access each service. These services only post recent news intended for public viewing. PR Newswire To access the PR Newswire archive, simply go to http://www.prnewswire.com/. Select your country. Type “Fanconi anemia” (or synonyms) into the search box. You will automatically receive information on relevant news releases posted within the last 30 days. The search results are shown by order of relevance. Reuters Health The Reuters’ Medical News and Health eLine databases can be very useful in exploring news archives relating to Fanconi anemia. While some of the listed articles are free to view, others are available for purchase for a nominal fee. To access this archive, go to http://www.reutershealth.com/en/index.html and search by “Fanconi anemia” (or synonyms).
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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 “Fanconi anemia” (or synonyms) into the search box, and click on “Search News.” As this service is technology oriented, you may wish to use it when searching for press releases covering diagnostic procedures or tests. Search Engines Medical news is also available in the news sections of commercial Internet search engines. See the health news page at Yahoo (http://dir.yahoo.com/Health/News_and_Media/), or you can use this Web site’s general news search page at http://news.yahoo.com/. Type in “Fanconi anemia” (or synonyms). If you know the name of a company that is relevant to Fanconi anemia, you can go to any stock trading Web site (such as http://www.etrade.com/) and search for the company name there. News items across various news sources are reported on indicated hyperlinks. Google offers a similar service at http://news.google.com/. BBC Covering news from a more European perspective, the British Broadcasting Corporation (BBC) allows the public free access to their news archive located at http://www.bbc.co.uk/. Search by “Fanconi anemia” (or synonyms).
Academic Periodicals covering Fanconi Anemia Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to Fanconi anemia. In addition
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to these sources, you can search for articles covering Fanconi anemia that have been published by any of the periodicals listed in previous chapters. To find the latest studies published, go to http://www.ncbi.nlm.nih.gov/pubmed, type the name of the periodical into the search box, and click “Go.” If you want complete details about the historical contents of a journal, you can also visit the following Web site: http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi. Here, type in the name of the journal or its abbreviation, and you will receive an index of published articles. At http://locatorplus.gov/, you can retrieve more indexing information on medical periodicals (e.g. the name of the publisher). Select the button “Search LOCATORplus.” Then type in the name of the journal and select the advanced search option “Journal Title Search.”
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APPENDICES
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APPENDIX A. PHYSICIAN RESOURCES Overview In this chapter, we focus on databases and Internet-based guidelines and information resources created or written for a professional audience.
NIH Guidelines Commonly referred to as “clinical” or “professional” guidelines, the National Institutes of Health publish physician guidelines for the most common diseases. Publications are available at the following by relevant Institute10: •
Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm
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National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/news/facts/
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National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html
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National Cancer Institute (NCI); guidelines available at http://www.cancer.gov/cancerinfo/list.aspx?viewid=5f35036e-5497-4d86-8c2c714a9f7c8d25
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National Eye Institute (NEI); guidelines available at http://www.nei.nih.gov/order/index.htm
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National Heart, Lung, and Blood Institute (NHLBI); guidelines available at http://www.nhlbi.nih.gov/guidelines/index.htm
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National Human Genome Research Institute (NHGRI); research available at http://www.genome.gov/page.cfm?pageID=10000375
•
National Institute on Aging (NIA); guidelines available at http://www.nia.nih.gov/health/
10
These publications are typically written by one or more of the various NIH Institutes.
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•
National Institute on Alcohol Abuse and Alcoholism (NIAAA); guidelines available at http://www.niaaa.nih.gov/publications/publications.htm
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National Institute of Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/
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National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm
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National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm
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National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/
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National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/
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National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm
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National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html
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National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm
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National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/practitioners/index.cfm
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National Institute of Neurological Disorders and Stroke (NINDS); neurological disorder information pages available at http://www.ninds.nih.gov/health_and_medical/disorder_index.htm
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National Institute of Nursing Research (NINR); publications on selected illnesses at http://www.nih.gov/ninr/news-info/publications.html
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National Institute of Biomedical Imaging and Bioengineering; general information at http://grants.nih.gov/grants/becon/becon_info.htm
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Center for Information Technology (CIT); referrals to other agencies based on keyword searches available at http://kb.nih.gov/www_query_main.asp
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National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/
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National Center for Research Resources (NCRR); various information directories available at http://www.ncrr.nih.gov/publications.asp
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Office of Rare Diseases; various fact sheets available at http://rarediseases.info.nih.gov/html/resources/rep_pubs.html
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Centers for Disease Control and Prevention; various fact sheets on infectious diseases available at http://www.cdc.gov/publications.htm
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NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.11 Physician-oriented resources provide a wide variety of information related to the biomedical and health sciences, both past and present. The format of these resources varies. Searchable databases, bibliographic citations, full-text articles (when available), archival collections, and images are all available. The following are referenced by the National Library of Medicine:12 •
Bioethics: Access to published literature on the ethical, legal, and public policy issues surrounding healthcare and biomedical research. This information is provided in conjunction with the Kennedy Institute of Ethics located at Georgetown University, Washington, D.C.: http://www.nlm.nih.gov/databases/databases_bioethics.html
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HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html
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NLM Online Exhibitions: Describes “Exhibitions in the History of Medicine”: http://www.nlm.nih.gov/exhibition/exhibition.html. Additional resources for historical scholarship in medicine: http://www.nlm.nih.gov/hmd/hmd.html
•
Biotechnology Information: Access to public databases. The National Center for Biotechnology Information conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information for the better understanding of molecular processes affecting human health and disease: http://www.ncbi.nlm.nih.gov/
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Population Information: The National Library of Medicine provides access to worldwide coverage of population, family planning, and related health issues, including family planning technology and programs, fertility, and population law and policy: http://www.nlm.nih.gov/databases/databases_population.html
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Cancer Information: Access to cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html
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Profiles in Science: Offering the archival collections of prominent twentieth-century biomedical scientists to the public through modern digital technology: http://www.profiles.nlm.nih.gov/
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Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html
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Clinical Alerts: Reports the release of findings from the NIH-funded clinical trials where such release could significantly affect morbidity and mortality: http://www.nlm.nih.gov/databases/alerts/clinical_alerts.html
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Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html
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MEDLINE: Bibliographic database covering the fields of medicine, nursing, dentistry, veterinary medicine, the healthcare system, and the pre-clinical sciences: http://www.nlm.nih.gov/databases/databases_medline.html
11
Remember, for the general public, the National Library of Medicine recommends the databases referenced in MEDLINEplus (http://medlineplus.gov/ or http://www.nlm.nih.gov/medlineplus/databases.html). 12 See http://www.nlm.nih.gov/databases/databases.html.
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Toxicology and Environmental Health Information (TOXNET): Databases covering toxicology and environmental health: http://sis.nlm.nih.gov/Tox/ToxMain.html
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Visible Human Interface: Anatomically detailed, three-dimensional representations of normal male and female human bodies: http://www.nlm.nih.gov/research/visible/visible_human.html
The NLM 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 “Fanconi anemia” (or synonyms) into the search box and click “Search.” The results will be presented in a tabular form, indicating the number of references in each database category. Results Summary Category Journal Articles Books / Periodicals / Audio Visual Consumer Health Meeting Abstracts Other Collections Total
Items Found 2190 17 315 1 69 2592
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 “Fanconi anemia” (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 Fanconi anemia can appear at any moment and be published by a number of sources, the best approach to finding guidelines is to systematically scan the Internet-based services that post them.
Patient Guideline Sources The remainder of this chapter directs you to sources which either publish or can help you find additional guidelines on topics related to Fanconi anemia. Due to space limitations, these sources are listed in a concise manner. Do not hesitate to consult the following sources by either using the Internet hyperlink provided, or, in cases where the contact information is provided, contacting the publisher or author directly. The National Institutes of Health The NIH gateway to patients is located at http://health.nih.gov/. From this site, you can search across various sources and institutes, a number of which are summarized below. Topic Pages: MEDLINEplus The National Library of Medicine has created a vast and patient-oriented healthcare information portal called MEDLINEplus. Within this Internet-based system are “health topic pages” which list links to available materials relevant to Fanconi anemia. To access this system, log on to http://www.nlm.nih.gov/medlineplus/healthtopics.html. From there you can either search using the alphabetical index or browse by broad topic areas. Recently, MEDLINEplus listed the following when searched for “Fanconi anemia”:
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Anemia http://www.nlm.nih.gov/medlineplus/anemia.html Blood and Blood Disorders http://www.nlm.nih.gov/medlineplus/bloodandblooddisorders.html Bone Marrow Diseases http://www.nlm.nih.gov/medlineplus/bonemarrowdiseases.html Bone Marrow Transplantation http://www.nlm.nih.gov/medlineplus/bonemarrowtransplantation.html Lymphoma http://www.nlm.nih.gov/medlineplus/lymphoma.html Sickle Cell Anemia http://www.nlm.nih.gov/medlineplus/sicklecellanemia.html Stem Cells and Stem Cell Transplantation http://www.nlm.nih.gov/medlineplus/stemcellsandstemcelltransplantation.html You may also choose to use the search utility provided by MEDLINEplus at the following Web address: http://www.nlm.nih.gov/medlineplus/. Simply type a keyword into the search box and click “Search.” This utility is similar to the NIH search utility, with the exception that it only includes materials that are linked within the MEDLINEplus system (mostly patient-oriented information). It also has the disadvantage of generating unstructured results. We recommend, therefore, that you use this method only if you have a very targeted search. Healthfinder™ Healthfinder™ is sponsored by the U.S. Department of Health and Human Services and offers links to hundreds of other sites that contain healthcare information. This Web site is located at http://www.healthfinder.gov. Again, keyword searches can be used to find guidelines. The following was recently found in this database: •
How is Fanconi Anemia Related to Leukemia and Other Cancers Summary: This document discusses Fanconi anemia patients' risks of developing leukemia and other related cancers. Source: Fanconi Anemia Research Fund, Inc. http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=4636
•
How Is Fanconi Anemia Treated? Summary: A discussion of the types of therapies used in the treatment of Fanconi anemia and who benefits from which, and the risks involved. Source: Fanconi Anemia Research Fund, Inc. http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=4635
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What Is Fanconi Anemia And How Is It Diagnosed? Summary: This consumer health information fact sheet contains basic information about Fanconi anemia including history, description of the disease and its symptoms and treatment. Source: Fanconi Anemia Research Fund, Inc. http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=4634 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 Fanconi anemia. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html. PEDBASE Similar to NORD, PEDBASE covers relatively rare disorders, limited mainly to pediatric conditions. PEDBASE was designed by Dr. Alan Gandy. To access the database, which is more oriented to researchers than patients, you can view the current list of health topics covered at the following Web site: http://www.icondata.com/health/pedbase/pedlynx.htm. Additional Web Sources A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •
AOL: http://search.aol.com/cat.adp?id=168&layer=&from=subcats
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Family Village: http://www.familyvillage.wisc.edu/specific.htm
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Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/
•
Med Help International: http://www.medhelp.org/HealthTopics/A.html
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Open Directory Project: http://dmoz.org/Health/Conditions_and_Diseases/
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Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/
•
WebMDHealth: http://my.webmd.com/health_topics
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Associations and Fanconi Anemia The following is a list of associations that provide information on and resources relating to Fanconi anemia: •
Canadian Fanconi Anemia Research Fund Telephone: 416-489-6393 Fax: 416-489-6393 Email:
[email protected] Web Site: http://www.fanconicanada.org Background: The Canadian Fanconi Anemia Research Fund (CFARF) is a not-for-profit voluntary organization dedicated to raising awareness of the disease in the public arena. Fanconi s Anemia is an inherited condition that leads to a deficiency of certain blood cells that are produced by the bone marrow. Established in 1994, CFARF promotes and supports research on Fanconi s Anemia, provides information and support to affected Canadian families, and gathers information regarding Fanconi s Anemia, bone marrow failure, cancer treatment, and new medications that may assist individuals with the disorder.
•
Fanconi Anemia Research Fund, Inc Telephone: (541) 687-4658 Toll-free: (800) 828-4891 Fax: (541) 687-0548 Email:
[email protected] Web Site: http://www.fanconi.org/ Background: The Fanconi Anemia Research Fund is a non-profit organization that raises funds for medical research into Fanconi anemia, an inherited condition that leads to a deficiency of certain blood cells that are produced by the bone marrow. Established in 1989, the organization supports numerous investigators who are working on various approaches to gene identification and therapy. The Fanconi Anemia Research Fund sponsors an annual international Fanconi Anemia Research Symposium to stimulate scientific progress and collaborative research among scientists. Additionally, the Fund develops and maintains a communication network that supplies information and support to affected families and their physicians. Educational materials include the 'FA Handbook', 'Standards for Clinical Care' and twice yearly Family Newsletters and a Science Letter. The Fund also moderates an electronic list serve for FA patients and their parents.
Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to Fanconi anemia. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with Fanconi anemia.
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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 Fanconi anemia. For more information, see the NHIC’s Web site at http://www.health.gov/NHIC/ or contact an information specialist by calling 1-800-336-4797. Directory of Health Organizations The Directory of Health Organizations, provided by the National Library of Medicine Specialized Information Services, is a comprehensive source of information on associations. The Directory of Health Organizations database can be accessed via the Internet at http://www.sis.nlm.nih.gov/Dir/DirMain.html. It is composed of two parts: DIRLINE and Health Hotlines. The DIRLINE database comprises some 10,000 records of organizations, research centers, and government institutes and associations that primarily focus on health and biomedicine. To access DIRLINE directly, go to the following Web site: http://dirline.nlm.nih.gov/. Simply type in “Fanconi anemia” (or a synonym), and you will receive information on all relevant organizations listed in the database. Health Hotlines directs you to toll-free numbers to over 300 organizations. You can access this database directly at http://www.sis.nlm.nih.gov/hotlines/. On this page, you are given the option to search by keyword or by browsing the subject list. When you have received 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 “Fanconi anemia”. Type the following hyperlink into your Web browser: http://chid.nih.gov/detail/detail.html. To find associations, use the drop boxes at the bottom of the search page where “You may refine your search by.” For publication date, select “All Years.” Then, select your preferred language and the format option “Organization Resource Sheet.” Type “Fanconi anemia” (or synonyms) into the “For these words:” box. You should check back periodically with this database since it is updated every three months. The National Organization for Rare Disorders, Inc. The National Organization for Rare Disorders, Inc. has prepared a Web site that provides, at no charge, lists of associations organized by health topic. You can access this database at the following Web site: http://www.rarediseases.org/search/orgsearch.html. Type “Fanconi anemia” (or a synonym) into the search box, and click “Submit Query.”
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APPENDIX C. FINDING MEDICAL LIBRARIES Overview In this Appendix, we show you how to quickly find a medical library in your area.
Preparation Your local public library and medical libraries have interlibrary loan programs with the National Library of Medicine (NLM), one of the largest medical collections in the world. According to the NLM, most of the literature in the general and historical collections of the National Library of Medicine is available on interlibrary loan to any library. If you would like to access NLM medical literature, then visit a library in your area that can request the publications for you.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
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California: Kris Kelly Health Information Center (St. Joseph Health System, Humboldt), http://www.humboldt1.com/~kkhic/index.html
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California: Community Health Library of Los Gatos, http://www.healthlib.org/orgresources.html
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California: Consumer Health Program and Services (CHIPS) (County of Los Angeles Public Library, Los Angeles County Harbor-UCLA Medical Center Library) - Carson, CA, http://www.colapublib.org/services/chips.html
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California: Gateway Health Library (Sutter Gould Medical Foundation)
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California: Health Library (Stanford University Medical Center), http://wwwmed.stanford.edu/healthlibrary/
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California: Patient Education Resource Center - Health Information and Resources (University of California, San Francisco), http://sfghdean.ucsf.edu/barnett/PERC/default.asp
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California: Redwood Health Library (Petaluma Health Care District), http://www.phcd.org/rdwdlib.html
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California: Los Gatos PlaneTree Health Library, http://planetreesanjose.org/
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California: Sutter Resource Library (Sutter Hospitals Foundation, Sacramento), http://suttermedicalcenter.org/library/
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California: Health Sciences Libraries (University of California, Davis), http://www.lib.ucdavis.edu/healthsci/
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California: ValleyCare Health Library & Ryan Comer Cancer Resource Center (ValleyCare Health System, Pleasanton), http://gaelnet.stmarysca.edu/other.libs/gbal/east/vchl.html
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California: Washington Community Health Resource Library (Fremont), http://www.healthlibrary.org/
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Colorado: William V. Gervasini Memorial Library (Exempla Healthcare), http://www.saintjosephdenver.org/yourhealth/libraries/
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Connecticut: Hartford Hospital Health Science Libraries (Hartford Hospital), http://www.harthosp.org/library/
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Connecticut: Healthnet: Connecticut Consumer Health Information Center (University of Connecticut Health Center, Lyman Maynard Stowe Library), http://library.uchc.edu/departm/hnet/
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Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.
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Connecticut: Waterbury Hospital Health Center Library (Waterbury Hospital, Waterbury), http://www.waterburyhospital.com/library/consumer.shtml
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Delaware: Consumer Health Library (Christiana Care Health System, Eugene du Pont Preventive Medicine & Rehabilitation Institute, Wilmington), http://www.christianacare.org/health_guide/health_guide_pmri_health_info.cfm
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Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine, Wilmington), http://www.delamed.org/chls.html
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Georgia: Family Resource Library (Medical College of Georgia, Augusta), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm
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Georgia: Health Resource Center (Medical Center of Central Georgia, Macon), http://www.mccg.org/hrc/hrchome.asp
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Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library, Honolulu), http://hml.org/CHIS/
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Idaho: DeArmond Consumer Health Library (Kootenai Medical Center, Coeur d’Alene), http://www.nicon.org/DeArmond/index.htm
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Illinois: Health Learning Center of Northwestern Memorial Hospital (Chicago), http://www.nmh.org/health_info/hlc.html
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Illinois: Medical Library (OSF Saint Francis Medical Center, Peoria), http://www.osfsaintfrancis.org/general/library/
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Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital, Lexington), http://www.centralbap.com/education/community/library.cfm
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Kentucky: University of Kentucky - Health Information Library (Chandler Medical Center, Lexington), http://www.mc.uky.edu/PatientEd/
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Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation, New Orleans), http://www.ochsner.org/library/
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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)
•
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/
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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/
•
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/
•
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/
•
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
111
ONLINE GLOSSARIES The Internet provides access to a number of free-to-use medical dictionaries. The National Library of Medicine has compiled the following list of online dictionaries: •
ADAM Medical Encyclopedia (A.D.A.M., Inc.), comprehensive medical reference: http://www.nlm.nih.gov/medlineplus/encyclopedia.html
•
MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp
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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/
•
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 Fanconi anemia: •
Basic Guidelines for Fanconi Anemia Fanconi's syndrome - acquired Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000334.htm
•
Diagnostics and Tests for Fanconi Anemia CBC Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003642.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
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MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html
•
Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/
•
Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine
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FANCONI ANEMIA DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. Aberrant: Wandering or deviating from the usual or normal course. [EU] Acceptor: A substance which, while normally not oxidized by oxygen or reduced by hydrogen, can be oxidized or reduced in presence of a substance which is itself undergoing oxidation or reduction. [NIH] Acrodermatitis: Inflammation involving the skin of the extremities, especially the hands and feet. Several forms are known, some idiopathic and some hereditary. The infantile form is called Gianotti-Crosti syndrome. [NIH] Actin: Essential component of the cell skeleton. [NIH] Actinin: A protein factor that regulates the length of R-actin. It is chemically similar, but immunochemically distinguishable from actin. [NIH] Acute leukemia: A rapidly progressing cancer of the blood-forming tissue (bone marrow). [NIH]
Acute lymphoblastic leukemia: ALL. A quickly progressing disease in which too many immature white blood cells called lymphoblasts are found in the blood and bone marrow. Also called acute lymphocytic leukemia. [NIH] Acute lymphocytic leukemia: ALL. A quickly progressing disease in which too many immature white blood cells called lymphoblasts are found in the blood and bone marrow. Also called acute lymphoblastic leukemia. [NIH] Acute myelogenous leukemia: AML. A quickly progressing disease in which too many immature blood-forming cells are found in the blood and bone marrow. Also called acute myeloid leukemia or acute nonlymphocytic leukemia. [NIH] Acute myeloid leukemia: AML. A quickly progressing disease in which too many immature blood-forming cells are found in the blood and bone marrow. Also called acute myelogenous leukemia or acute nonlymphocytic leukemia. [NIH] Acute nonlymphocytic leukemia: A quickly progressing disease in which too many immature blood-forming cells are found in the blood and bone marrow. Also called acute myeloid leukemia or acute myelogenous leukemia. [NIH] Adaptability: Ability to develop some form of tolerance to conditions extremely different from those under which a living organism evolved. [NIH] Adaptation: 1. The adjustment of an organism to its environment, or the process by which it enhances such fitness. 2. The normal ability of the eye to adjust itself to variations in the intensity of light; the adjustment to such variations. 3. The decline in the frequency of firing of a neuron, particularly of a receptor, under conditions of constant stimulation. 4. In dentistry, (a) the proper fitting of a denture, (b) the degree of proximity and interlocking of restorative material to a tooth preparation, (c) the exact adjustment of bands to teeth. 5. In microbiology, the adjustment of bacterial physiology to a new environment. [EU] Adenine: A purine base and a fundamental unit of adenine nucleotides. [NIH] Adenitis: Inflammation of a gland. [EU] Adenoma: A benign epithelial tumor with a glandular organization. [NIH]
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Adenosine: A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. [NIH] Adjustment: The dynamic process wherein the thoughts, feelings, behavior, and biophysiological mechanisms of the individual continually change to adjust to the environment. [NIH] Adolescence: The period of life beginning with the appearance of secondary sex characteristics and terminating with the cessation of somatic growth. The years usually referred to as adolescence lie between 13 and 18 years of age. [NIH] Adverse Effect: An unwanted side effect of treatment. [NIH] Aerobic: In biochemistry, reactions that need oxygen to happen or happen when oxygen is present. [NIH] Aerobic Metabolism: A chemical process in which oxygen is used to make energy from carbohydrates (sugars). Also known as aerobic respiration, oxidative metabolism, or cell respiration. [NIH] Aerobic Respiration: A chemical process in which oxygen is used to make energy from carbohydrates (sugars). Also known as oxidative metabolism, cell respiration, or aerobic metabolism. [NIH] Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among simple, uniform antigenic determinants such as haptens. Expressed as the association constant (K litres mole -1), which, owing to the heterogeneity of affinities in a population of antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU] Agammaglobulinemia: An immunologic deficiency state characterized by an extremely low level of generally all classes of gamma-globulin in the blood. [NIH] Alertness: A state of readiness to detect and respond to certain specified small changes occurring at random intervals in the environment. [NIH] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alkaloid: A member of a large group of chemicals that are made by plants and have nitrogen in them. Some alkaloids have been shown to work against cancer. [NIH] Alkylating Agents: Highly reactive chemicals that introduce alkyl radicals into biologically active molecules and thereby prevent their proper functioning. Many are used as antineoplastic agents, but most are very toxic, with carcinogenic, mutagenic, teratogenic, and immunosuppressant actions. They have also been used as components in poison gases. [NIH]
Alkylation: The covalent bonding of an alkyl group to an organic compound. It can occur by a simple addition reaction or by substitution of another functional group. [NIH] Alleles: Mutually exclusive forms of the same gene, occupying the same locus on homologous chromosomes, and governing the same biochemical and developmental process. [NIH]
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Allogeneic: Taken from different individuals of the same species. [NIH] Allogeneic bone marrow transplantation: A procedure in which a person receives stem cells, the cells from which all blood cells develop, from a compatible, though not genetically identical, donor. [NIH] Alopecia: Absence of hair from areas where it is normally present. [NIH] Alpha Particles: Positively charged particles composed of two protons and two neutrons, i.e., helium nuclei, emitted during disintegration of very heavy isotopes; a beam of alpha particles or an alpha ray has very strong ionizing power, but weak penetrability. [NIH] Alpha-1: A protein with the property of inactivating proteolytic enzymes such as leucocyte collagenase and elastase. [NIH] Alpha-fetoprotein: AFP. A protein normally produced by a developing fetus. AFP levels are usually undetectable in the blood of healthy nonpregnant adults. An elevated level of AFP suggests the presence of either a primary liver cancer or germ cell tumor. [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] Alternative Splicing: A process whereby multiple protein isoforms are generated from a single gene. Alternative splicing involves the splicing together of nonconsecutive exons during the processing of some, but not all, transcripts of the gene. Thus a particular exon may be connected to any one of several alternative exons to form messenger RNA. The alternative forms produce proteins in which one part is common while the other part is different. [NIH] Amino acid: Any organic compound containing an amino (-NH2 and a carboxyl (- COOH) group. The 20 a-amino acids listed in the accompanying table are the amino acids from which proteins are synthesized by formation of peptide bonds during ribosomal translation of messenger RNA; all except glycine, which is not optically active, have the L configuration. Other amino acids occurring in proteins, such as hydroxyproline in collagen, are formed by posttranslational enzymatic modification of amino acids residues in polypeptide chains. There are also several important amino acids, such as the neurotransmitter y-aminobutyric acid, that have no relation to proteins. Abbreviated AA. [EU] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Ammonia: A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. [NIH] Amnion: The extraembryonic membrane which contains the embryo and amniotic fluid. [NIH]
Amniotic Fluid: Amniotic cavity fluid which is produced by the amnion and fetal lungs and kidneys. [NIH] Amplification: The production of additional copies of a chromosomal DNA sequence, found as either intrachromosomal or extrachromosomal DNA. [NIH] Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Anal: Having to do with the anus, which is the posterior opening of the large bowel. [NIH]
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Analog: In chemistry, a substance that is similar, but not identical, to another. [NIH] Analogous: Resembling or similar in some respects, as in function or appearance, but not in origin or development;. [EU] Anaphylatoxins: The family of peptides C3a, C4a, C5a, and C5a des-arginine produced in the serum during complement activation. They produce smooth muscle contraction, mast cell histamine release, affect platelet aggregation, and act as mediators of the local inflammatory process. The order of anaphylatoxin activity from strongest to weakest is C5a, C3a, C4a, and C5a des-arginine. The latter is the so-called "classical" anaphylatoxin but shows no spasmogenic activity though it contains some chemotactic ability. [NIH] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis. [NIH] Annealing: The spontaneous alignment of two single DNA strands to form a double helix. [NIH]
Anomalies: Birth defects; abnormalities. [NIH] Antagonism: Interference with, or inhibition of, the growth of a living organism by another living organism, due either to creation of unfavorable conditions (e. g. exhaustion of food supplies) or to production of a specific antibiotic substance (e. g. penicillin). [NIH] 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] Antigen-Antibody Complex: The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes immune complex diseases. [NIH] Antimetabolite: A chemical that is very similar to one required in a normal biochemical reaction in cells. Antimetabolites can stop or slow down the reaction. [NIH] Antineoplastic: Inhibiting or preventing the development of neoplasms, checking the maturation and proliferation of malignant cells. [EU]
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Antineoplastic Agents: Substances that inhibit or prevent the proliferation of neoplasms. [NIH]
Antioxidant: A substance that prevents damage caused by free radicals. Free radicals are highly reactive chemicals that often contain oxygen. They are produced when molecules are split to give products that have unpaired electrons. This process is called oxidation. [NIH] Antithymocyte globulin: A protein used to reduce the risk of or to treat graft-versus-host disease. [NIH] Antiviral: Destroying viruses or suppressing their replication. [EU] Anus: The opening of the rectum to the outside of the body. [NIH] Aphthous Stomatitis: Inflammation of the mucous membrane of the mouth. [NIH] Aplastic anemia: A condition in which the bone marrow is unable to produce blood cells. [NIH]
Apoptosis: One of the two mechanisms by which cell death occurs (the other being the pathological process of necrosis). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA (DNA fragmentation) at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. [NIH] Applicability: A list of the commodities to which the candidate method can be applied as presented or with minor modifications. [NIH] Aqueous: Having to do with water. [NIH] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Asymptomatic: Having no signs or symptoms of disease. [NIH] Ataxia: Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharnyx, larnyx, and other structures. 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] Autodigestion: Autolysis; a condition found in disease of the stomach: the stomach wall is digested by the gastric juice. [NIH] Autoimmune disease: A condition in which the body recognizes its own tissues as foreign and directs an immune response against them. [NIH] Autologous: Taken from an individual's own tissues, cells, or DNA. [NIH] Autologous bone marrow transplantation: A procedure in which bone marrow is removed from a person, stored, and then given back to the person after intensive treatment. [NIH] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls,
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multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Bacterial Infections: Infections by bacteria, general or unspecified. [NIH] Bacterial Physiology: Physiological processes and activities of bacteria. [NIH] Bacteriophage: A virus whose host is a bacterial cell; A virus that exclusively infects bacteria. It generally has a protein coat surrounding the genome (DNA or RNA). One of the coliphages most extensively studied is the lambda phage, which is also one of the most important. [NIH] Basal cell carcinoma: A type of skin cancer that arises from the basal cells, small round cells found in the lower part (or base) of the epidermis, the outer layer of the skin. [NIH] Basal cells: Small, round cells found in the lower part (or base) of the epidermis, the outer layer of the skin. [NIH] Basal Ganglia: Large subcortical nuclear masses derived from the telencephalon and located in the basal regions of the cerebral hemispheres. [NIH] Basal Ganglia Diseases: Diseases of the basal ganglia including the putamen; globus pallidus; claustrum; amygdala; and caudate nucleus. Dyskinesias (most notably involuntary movements and alterations of the rate of movement) represent the primary clinical manifestations of these disorders. Common etiologies include cerebrovascular disease; neurodegenerative diseases; and craniocerebral trauma. [NIH] Base Sequence: The sequence of purines and pyrimidines in nucleic acids and polynucleotides. It is also called nucleotide or nucleoside sequence. [NIH] Basophils: Granular leukocytes characterized by a relatively pale-staining, lobate nucleus and cytoplasm containing coarse dark-staining granules of variable size and stainable by basic dyes. [NIH] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]
Biliary: Having to do with the liver, bile ducts, and/or gallbladder. [NIH] Biliary Tract: The gallbladder and its ducts. [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] Biochemical reactions: In living cells, chemical reactions that help sustain life and allow cells to grow. [NIH] Biosynthesis: The building up of a chemical compound in the physiologic processes of a living organism. [EU] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Bleomycin: A complex of related glycopeptide antibiotics from Streptomyces verticillus consisting of bleomycin A2 and B2. It inhibits DNA metabolism and is used as an antineoplastic, especially for solid tumors. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber.
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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]
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 Cells: Cells contained in the bone marrow including fat cells, stromal cells, megakaryocytes, and the immediate precursors of most blood cells. [NIH] Bone Marrow Transplantation: The transference of bone marrow from one human or animal to another. [NIH] Brachytherapy: A collective term for interstitial, intracavity, and surface radiotherapy. It uses small sealed or partly-sealed sources that may be placed on or near the body surface or within a natural body cavity or implanted directly into the tissues. [NIH] Brain Neoplasms: Neoplasms of the intracranial components of the central nervous system, 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] Bromodeoxyuridine: A nucleoside that substitutes for thymidine in DNA and thus acts as an antimetabolite. It causes breaks in chromosomes and has been proposed as an antiviral and antineoplastic agent. It has been given orphan drug status for use in the treatment of primary brain tumors. [NIH] Buffers: A chemical system that functions to control the levels of specific ions in solution. When the level of hydrogen ion in solution is controlled the system is called a pH buffer. [NIH]
Busulfan: An anticancer drug that belongs to the family of drugs called alkylating agents. [NIH]
Caffeine: A methylxanthine naturally occurring in some beverages and also used as a pharmacological agent. Caffeine's most notable pharmacological effect is as a central nervous system stimulant, increasing alertness and producing agitation. It also relaxes smooth muscle, stimulates cardiac muscle, stimulates diuresis, and appears to be useful in the treatment of some types of headache. Several cellular actions of caffeine have been observed, but it is not entirely clear how each contributes to its pharmacological profile. Among the most important are inhibition of cyclic nucleotide phosphodiesterases, antagonism of adenosine receptors, and modulation of intracellular calcium handling. [NIH] Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in
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many enzymatic processes. [NIH] Callus: A callosity or hard, thick skin; the bone-like reparative substance that is formed round the edges and fragments of broken bone. [NIH] Camptothecin: An alkaloid isolated from the stem wood of the Chinese tree, Camptotheca acuminata. This compound selectively inhibits the nuclear enzyme DNA topoisomerase. Several semisynthetic analogs of camptothecin have demonstrated antitumor activity. [NIH] Candidiasis: Infection with a fungus of the genus Candida. It is usually a superficial infection of the moist cutaneous areas of the body, and is generally caused by C. albicans; it most commonly involves the skin (dermatocandidiasis), oral mucous membranes (thrush, def. 1), respiratory tract (bronchocandidiasis), and vagina (vaginitis). Rarely there is a systemic infection or endocarditis. Called also moniliasis, candidosis, oidiomycosis, and formerly blastodendriosis. [EU] Candidosis: An infection caused by an opportunistic yeasts that tends to proliferate and become pathologic when the environment is favorable and the host resistance is weakened. [NIH]
Capillary: Any one of the minute vessels that connect the arterioles and venules, forming a network in nearly all parts of the body. Their walls act as semipermeable membranes for the interchange of various substances, including fluids, between the blood and tissue fluid; called also vas capillare. [EU] Capillary Fragility: The lack of resistance, or susceptibility, of capillaries to damage or disruption under conditions of increased stress. [NIH] 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] Carcinogenesis: The process by which normal cells are transformed into cancer cells. [NIH] Carcinogenic: Producing carcinoma. [EU] Carcinogens: Substances that increase the risk of neoplasms in humans or animals. Both genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism, are included. [NIH] Carcinoma: Cancer that begins in the skin or in tissues that line or cover internal organs. [NIH]
Cardiac: Having to do with the heart. [NIH] Case report: A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin). [NIH] Caspase: Enzyme released by the cell at a crucial stage in apoptosis in order to shred all cellular proteins. [NIH] Cataracts: In medicine, an opacity of the crystalline lens of the eye obstructing partially or totally its transmission of light. [NIH] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Cell Cycle: The complex series of phenomena, occurring between the end of one cell division and the end of the next, by which cellular material is divided between daughter 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 proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH] Cell Respiration: The metabolic process of all living cells (animal and plant) in which oxygen is used to provide a source of energy for the cell. [NIH] Cell Size: The physical dimensions of a cell. It refers mainly to changes in dimensions correlated with physiological or pathological changes in cells. [NIH] Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. [NIH] Cell Transplantation: Transference of cells within an individual, between individuals of the same species, or between individuals of different species. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] 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] Centrifugation: A method of separating organelles or large molecules that relies upon differential sedimentation through a preformed density gradient under the influence of a gravitational field generated in a centrifuge. [NIH] Cerebellar: Pertaining to the cerebellum. [EU] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebral Cortex: The thin layer of gray matter on the surface of the cerebral hemisphere that develops from the telencephalon and folds into gyri. It reaches its highest development in man and is responsible for intellectual faculties and higher mental functions. [NIH] 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] Cervical: Relating to the neck, or to the neck of any organ or structure. Cervical lymph nodes are located in the neck; cervical cancer refers to cancer of the uterine cervix, which is the lower, narrow end (the "neck") of the uterus. [NIH] Cervix: The lower, narrow end of the uterus that forms a canal between the uterus and vagina. [NIH] Chemotactic Factors: Chemical substances that attract or repel cells or organisms. The concept denotes especially those factors released as a result of tissue injury, invasion, or immunologic activity, that attract leukocytes, macrophages, or other cells to the site of infection or insult. [NIH] Chemotherapy: Treatment with anticancer drugs. [NIH] 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] Chromium: A trace element that plays a role in glucose metabolism. It has the atomic
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symbol Cr, atomic number 24, and atomic weight 52. According to the Fourth Annual Report on Carcinogens (NTP85-002,1985), chromium and some of its compounds have been listed as known carcinogens. [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] Chromosome Breakage: A type of chromosomal aberration which may result from spontaneous or induced breakage. Alkylating agents, various types of irradiation, and chemical mutagens have been found to cause induced chromosomal breakage. Breakage can induce base pair translocations, deletions, or chromatid breakage. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Cisplatin: An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle. [NIH] Cleave: A double-stranded cut in DNA with a restriction endonuclease. [NIH] Clinical Medicine: The study and practice of medicine by direct examination of the patient. [NIH]
Clinical Protocols: Precise and detailed plans for the study of a medical or biomedical problem and/or plans for a regimen of therapy. [NIH] Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] Clone: The term "clone" has acquired a new meaning. It is applied specifically to the bits of inserted foreign DNA in the hybrid molecules of the population. Each inserted segment originally resided in the DNA of a complex genome amid millions of other DNA segment. [NIH]
Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH] 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] Colloidal: Of the nature of a colloid. [EU] Colon: The long, coiled, tubelike organ that removes water from digested food. The remaining material, solid waste called stool, moves through the colon to the rectum and leaves the body through the anus. [NIH] Colony-Stimulating Factors: Glycoproteins found in a subfraction of normal mammalian plasma and urine. They stimulate the proliferation of bone marrow cells in agar cultures and the formation of colonies of granulocytes and/or macrophages. The factors include interleukin-3 (IL-3), granulocyte colony-stimulating factor (G-CSF), macrophage colony-
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stimulating factor (M-CSF), and granulocyte-macrophage colony-stimulating factor (GMCSF). [NIH] Common Variable Immunodeficiency: Heterogeneous group of immunodeficiency syndromes characterized by hypogammaglobulinemia of most isotypes, variable B-cell defects, and the presence of recurrent bacterial infections. [NIH] Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementation: The production of a wild-type phenotype when two different mutations are combined in a diploid or a heterokaryon and tested in trans-configuration. [NIH] Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Conjugated: Acting or operating as if joined; simultaneous. [EU] 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]
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Consciousness: Sense of awareness of self and of the environment. [NIH] Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] Coordination: Muscular or motor regulation or the harmonious cooperation of muscles or groups of muscles, in a complex action or series of actions. [NIH] 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] 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] Cryofixation: Fixation of a tissue by localized cooling at very low temperature. [NIH] Cryopreservation: Preservation of cells, tissues, organs, or embryos by freezing. In histological preparations, cryopreservation or cryofixation is used to maintain the existing form, structure, and chemical composition of all the constituent elements of the specimens. [NIH]
Cultured cells: Animal or human cells that are grown in the laboratory. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Cutaneous: Having to do with the skin. [NIH] Cyclic: Pertaining to or occurring in a cycle or cycles; the term is applied to chemical compounds that contain a ring of atoms in the nucleus. [EU] Cyclin: Molecule that regulates the cell cycle. [NIH] Cyclophosphamide: Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the liver to form the active aldophosphamide. It is used in the treatment of lymphomas, leukemias, etc. Its side effect, alopecia, has been made use of in defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer. [NIH] Cytochrome: Any electron transfer hemoprotein having a mode of action in which the transfer of a single electron is effected by a reversible valence change of the central iron atom of the heme prosthetic group between the +2 and +3 oxidation states; classified as cytochromes a in which the heme contains a formyl side chain, cytochromes b, which contain protoheme or a closely similar heme that is not covalently bound to the protein, cytochromes c in which protoheme or other heme is covalently bound to the protein, and cytochromes d in which the iron-tetrapyrrole has fewer conjugated double bonds than the hemes have. Well-known cytochromes have been numbered consecutively within groups and are designated by subscripts (beginning with no subscript), e.g. cytochromes c, c1, C2, . New cytochromes are named according to the wavelength in nanometres of the absorption maximum of the a-band of the iron (II) form in pyridine, e.g., c-555. [EU] Cytogenetics: A branch of genetics which deals with the cytological and molecular behavior of genes and chromosomes during cell division. [NIH] Cytokine: Small but highly potent protein that modulates the activity of many cell types,
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including T and B cells. [NIH] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a continuous aqueous solution (cytosol) and the organelles and inclusions suspended in it (phaneroplasm), and is the site of most of the chemical activities of the cell. [EU] Cytoskeletal Proteins: Major constituent of the cytoskeleton found in the cytoplasm of eukaryotic cells. They form a flexible framework for the cell, provide attachment points for organelles and formed bodies, and make communication between parts of the cell possible. [NIH]
Cytotoxic: Cell-killing. [NIH] Cytotoxicity: Quality of being capable of producing a specific toxic action upon cells of special organs. [NIH] Deamination: The removal of an amino group (NH2) from a chemical compound. [NIH] 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] Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] Desensitization: The prevention or reduction of immediate hypersensitivity reactions by administration of graded doses of allergen; called also hyposensitization and immunotherapy. [EU] Detoxification: Treatment designed to free an addict from his drug habit. [EU] Diagnostic procedure: A method used to identify a disease. [NIH] Diastolic: Of or pertaining to the diastole. [EU] Digestive tract: The organs through which food passes when food is eaten. These organs are the mouth, esophagus, stomach, small and large intestines, and rectum. [NIH] Dihydrotestosterone: Anabolic agent. [NIH] Dihydroxy: AMPA/Kainate antagonist. [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] Disease Susceptibility: A constitution or condition of the body which makes the tissues react in special ways to certain extrinsic stimuli and thus tends to make the individual more than usually susceptible to certain diseases. [NIH] Dissociation: 1. The act of separating or state of being separated. 2. The separation of a molecule into two or more fragments (atoms, molecules, ions, or free radicals) produced by the absorption of light or thermal energy or by solvation. 3. In psychology, a defense mechanism in which a group of mental processes are segregated from the rest of a person's mental activity in order to avoid emotional distress, as in the dissociative disorders (q.v.), or in which an idea or object is segregated from its emotional significance; in the first sense it is roughly equivalent to splitting, in the second, to isolation. 4. A defect of mental integration in which one or more groups of mental processes become separated off from normal consciousness and, thus separated, function as a unitary whole. [EU] Dissociative Disorders: Sudden temporary alterations in the normally integrative functions
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of consciousness. [NIH] Diuresis: Increased excretion of urine. [EU] Drive: A state of internal activity of an organism that is a necessary condition before a given stimulus will elicit a class of responses; e.g., a certain level of hunger (drive) must be present before food will elicit an eating response. [NIH] Drug Resistance: Diminished or failed response of an organism, disease or tissue to the intended effectiveness of a chemical or drug. It should be differentiated from drug tolerance which is the progressive diminution of the susceptibility of a human or animal to the effects of a drug, as a result of continued administration. [NIH] Drug Tolerance: Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from drug resistance wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from maximum tolerated dose and no-observed-adverse-effect level. [NIH] Dystrophin: A muscle protein localized in surface membranes which is the product of the Duchenne/Becker muscular dystrophy gene. Individuals with Duchenne muscular dystrophy usually lack dystrophin completely while those with Becker muscular dystrophy have dystrophin of an altered size. It shares features with other cytoskeletal proteins such as spectrin and alpha-actinin but the precise function of dystrophin is not clear. One possible role might be to preserve the integrity and alignment of the plasma membrane to the myofibrils during muscle contraction and relaxation. MW 400 kDa. [NIH] Dystrophy: Any disorder arising from defective or faulty nutrition, especially the muscular dystrophies. [EU] Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [NIH] Efficacy: The extent to which a specific intervention, procedure, regimen, or service produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is based on the results of a randomized control trial. [NIH] Elective: Subject to the choice or decision of the patient or physician; applied to procedures that are advantageous to the patient but not urgent. [EU] Electrons: Stable elementary particles having the smallest known negative charge, present in all elements; also called negatrons. Positively charged electrons are called positrons. The numbers, energies and arrangement of electrons around atomic nuclei determine the chemical identities of elements. Beams of electrons are called cathode rays or beta rays, the latter being a high-energy biproduct of nuclear decay. [NIH] 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]
Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Embryogenesis: The process of embryo or embryoid formation, whether by sexual (zygotic) or asexual means. In asexual embryogenesis embryoids arise directly from the explant or on intermediary callus tissue. In some cases they arise from individual cells (somatic cell embryoge). [NIH] Emollient: Softening or soothing; called also malactic. [EU] Endemic: Present or usually prevalent in a population or geographical area at all times; said of a disease or agent. Called also endemial. [EU]
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Endocarditis: Exudative and proliferative inflammatory alterations of the endocardium, characterized by the presence of vegetations on the surface of the endocardium or in the endocardium itself, and most commonly involving a heart valve, but sometimes affecting the inner lining of the cardiac chambers or the endocardium elsewhere. It may occur as a primary disorder or as a complication of or in association with another disease. [EU] Endocrine Glands: Ductless glands that secrete substances which are released directly into the circulation and which influence metabolism and other body functions. [NIH] Endocytosis: Cellular uptake of extracellular materials within membrane-limited vacuoles or microvesicles. Endosomes play a central role in endocytosis. [NIH] Endogenous: Produced inside an organism or cell. The opposite is external (exogenous) production. [NIH] Endotoxins: Toxins closely associated with the living cytoplasm or cell wall of certain microorganisms, which do not readily diffuse into the culture medium, but are released upon lysis of the cells. [NIH] Enteropeptidase: A specialized proteolytic enzyme secreted by intestinal cells. It converts trypsinogen into its active form trypsin by removing the N-terminal peptide. EC 3.4.21.9. [NIH]
Environmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health. [NIH]
Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Eosinophil: A polymorphonuclear leucocyte with large eosinophilic granules in its cytoplasm, which plays a role in hypersensitivity reactions. [NIH] Epidemic: Occurring suddenly in numbers clearly in excess of normal expectancy; said especially of infectious diseases but applied also to any disease, injury, or other healthrelated event occurring in such outbreaks. [EU] Epidermis: Nonvascular layer of the skin. It is made up, from within outward, of five layers: 1) basal layer (stratum basale epidermidis); 2) spinous layer (stratum spinosum epidermidis); 3) granular layer (stratum granulosum epidermidis); 4) clear layer (stratum lucidum epidermidis); and 5) horny layer (stratum corneum epidermidis). [NIH] Epidermoid carcinoma: A type of cancer in which the cells are flat and look like fish scales. Also called squamous cell carcinoma. [NIH] Epithelial: Refers to the cells that line the internal and external surfaces of the body. [NIH] Epithelium: One or more layers of epithelial cells, supported by the basal lamina, which covers the inner or outer surfaces of the body. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Erythropoiesis: The production of erythrocytes. [EU] Ethidium: A trypanocidal agent and possible antiviral agent that is widely used in experimental cell biology and biochemistry. Ethidium has several experimentally useful properties including binding to nucleic acids, noncompetitive inhibition of nicotinic acetylcholine receptors, and fluorescence among others. It is most commonly used as the bromide. [NIH] Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH]
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Excisional: The surgical procedure of removing a tumor by cutting it out. The biopsy is then examined under a microscope. [NIH] Excitation: An act of irritation or stimulation or of responding to a stimulus; the addition of energy, as the excitation of a molecule by absorption of photons. [EU] 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] External-beam radiation: Radiation therapy that uses a machine to aim high-energy rays at the cancer. Also called external radiation. [NIH] Extracellular: Outside a cell or cells. [EU] Extracellular Matrix: A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. [NIH] 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] Fetoprotein: Transabdominal aspiration of fluid from the amniotic sac with a view to detecting increases of alpha-fetoprotein in maternal blood during pregnancy, as this is an important indicator of open neural tube defects in the fetus. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [NIH] Fibronectin: An adhesive glycoprotein. One form circulates in plasma, acting as an opsonin; another is a cell-surface protein which mediates cellular adhesive interactions. [NIH] Filgrastim: A colony-stimulating factor that stimulates the production of neutrophils (a type of white blood cell). It is a cytokine that belongs to the family of drugs called hematopoietic (blood-forming) agents. Also called granulocyte colony-stimulating factor (G-CSF). [NIH] Flow Cytometry: Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake. [NIH] Fludarabine: An anticancer drug that belongs to the family of drugs called antimetabolites. [NIH]
Fluorescence: The property of emitting radiation while being irradiated. The radiation emitted is usually of longer wavelength than that incident or absorbed, e.g., a substance can be irradiated with invisible radiation and emit visible light. X-ray fluorescence is used in diagnosis. [NIH] Fluorescent Dyes: Dyes that emit light when exposed to light. The wave length of the emitted light is usually longer than that of the incident light. Fluorochromes are substances
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that cause fluorescence in other substances, i.e., dyes used to mark or label other compounds with fluorescent tags. They are used as markers in biochemistry and immunology. [NIH] Founder Effect: The principle that when a small subgroup of a larger population establishes itself as a separate and isolated entity, its gene pool carries only a fraction of the genetic diversity of the parental population. This may result in an increased frequency of certain diseases in the subgroup, especially those diseases known to be autosomal recessive. [NIH] Frameshift: A type of mutation which causes out-of-phase transcription of the base sequence; such mutations arise from the addition or delection of nucleotide(s) in numbers other than 3 or multiples of 3. [NIH] Frameshift Mutation: A type of mutation in which a number of nucleotides not divisible by three is deleted from or inserted into a coding sequence, thereby causing an alteration in the reading frame of the entire sequence downstream of the mutation. These mutations may be induced by certain types of mutagens or may occur spontaneously. [NIH] Free Radicals: Highly reactive molecules with an unsatisfied electron valence pair. Free radicals are produced in both normal and pathological processes. They are proven or suspected agents of tissue damage in a wide variety of circumstances including radiation, damage from environment chemicals, and aging. Natural and pharmacological prevention of free radical damage is being actively investigated. [NIH] Fungus: A general term used to denote a group of eukaryotic protists, including mushrooms, yeasts, rusts, moulds, smuts, etc., which are characterized by the absence of chlorophyll and by the presence of a rigid cell wall composed of chitin, mannans, and sometimes cellulose. They are usually of simple morphological form or show some reversible cellular specialization, such as the formation of pseudoparenchymatous tissue in the fruiting body of a mushroom. The dimorphic fungi grow, according to environmental conditions, as moulds or yeasts. [EU] Gamma Rays: Very powerful and penetrating, high-energy electromagnetic radiation of shorter wavelength than that of x-rays. They are emitted by a decaying nucleus, usually between 0.01 and 10 MeV. They are also called nuclear x-rays. [NIH] Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [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 Rearrangement: The ordered rearrangement of gene regions by DNA recombination such as that which occurs normally during development. [NIH] Gene Targeting: The integration of exogenous DNA into the genome of an organism at sites where its expression can be suitably controlled. This integration occurs as a result of homologous recombination. [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
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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] Germ Cells: The reproductive cells in multicellular organisms. [NIH] Gland: An organ that produces and releases one or more substances for use in the body. Some glands produce fluids that affect tissues or organs. Others produce hormones or participate in blood production. [NIH] Glucokinase: A group of enzymes that catalyzes the conversion of ATP and D-glucose to ADP and D-glucose 6-phosphate. They are found in invertebrates and microorganisms and are highly specific for glucose. (Enzyme Nomenclature, 1992) EC 2.7.1.2. [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] Glucuronic Acid: Derivatives of uronic acid found throughout the plant and animal kingdoms. They detoxify drugs and toxins by conjugating with them to form glucuronides in the liver which are more water-soluble metabolites that can be easily eliminated from the body. [NIH] Glycerol: A trihydroxy sugar alcohol that is an intermediate in carbohydrate and lipid metabolism. It is used as a solvent, emollient, pharmaceutical agent, and sweetening agent. [NIH]
Glycerol Kinase: An enzyme that catalyzes the formation of glycerol 3-phosphate from ATP and glycerol. Dihydroxyacetone and L-glyceraldehyde can also act as acceptors; UTP and, in the case of the yeast enzyme, ITP and GTP can act as donors. It provides a way for glycerol derived from fats or glycerides to enter the glycolytic pathway. EC 2.7.1.30. [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] Glycolysis: The pathway by which glucose is catabolized into two molecules of pyruvic acid with the generation of ATP. [NIH] Glycoprotein: A protein that has sugar molecules attached to it. [NIH]
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Gonads: The gamete-producing glands, ovary or testis. [NIH] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to replace diseased or injured tissue removed from another part of the body. [NIH] Grafting: The operation of transfer of tissue from one site to another. [NIH] Graft-versus-host disease: GVHD. A reaction of donated bone marrow or peripheral stem cells against a person's tissue. [NIH] Granulocyte: A type of white blood cell that fights bacterial infection. Neutrophils, eosinophils, and basophils are granulocytes. [NIH] Granulocyte Colony-Stimulating Factor: A glycoprotein of MW 25 kDa containing internal disulfide bonds. It induces the survival, proliferation, and differentiation of neutrophilic granulocyte precursor cells and functionally activates mature blood neutrophils. Among the family of colony-stimulating factors, G-CSF is the most potent inducer of terminal differentiation to granulocytes and macrophages of leukemic myeloid cell lines. [NIH] Granulocyte-Macrophage Colony-Stimulating Factor: An acidic glycoprotein of MW 23 kDa with internal disulfide bonds. The protein is produced in response to a number of inflammatory mediators by mesenchymal cells present in the hemopoietic environment and at peripheral sites of inflammation. GM-CSF is able to stimulate the production of neutrophilic granulocytes, macrophages, and mixed granulocyte-macrophage colonies from bone marrow cells and can stimulate the formation of eosinophil colonies from fetal liver progenitor cells. GM-CSF can also stimulate some functional activities in mature granulocytes and macrophages. [NIH] 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] 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] Hematologic Diseases: Disorders of the blood and blood forming tissues. [NIH] Hematologist: A doctor who specializes in treating diseases of the blood. [NIH] Hematology: A subspecialty of internal medicine concerned with morphology, physiology, and pathology of the blood and blood-forming tissues. [NIH] Hematopoiesis: The development and formation of various types of blood cells. [NIH] Hematopoietic growth factors: A group of proteins that cause blood cells to grow and mature. [NIH] Hematopoietic Stem Cell Transplantation: The transference of stem cells from one animal or human to another (allogeneic), or within the same individual (autologous). The source for the stem cells may be the bone marrow or peripheral blood. Stem cell transplantation has been used as an alternative to autologous bone marrow transplantation in the treatment of a variety of neoplasms. [NIH]
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Hematopoietic Stem Cells: Progenitor cells from which all blood cells derive. [NIH] Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. [NIH] Hemoglobin: One of the fractions of glycosylated hemoglobin A1c. Glycosylated hemoglobin is formed when linkages of glucose and related monosaccharides bind to hemoglobin A and its concentration represents the average blood glucose level over the previous several weeks. HbA1c levels are used as a measure of long-term control of plasma glucose (normal, 4 to 6 percent). In controlled diabetes mellitus, the concentration of glycosylated hemoglobin A is within the normal range, but in uncontrolled cases the level may be 3 to 4 times the normal conentration. Generally, complications are substantially lower among patients with Hb levels of 7 percent or less than in patients with HbA1c levels of 9 percent or more. [NIH] Hemoglobin M: A group of abnormal hemoglobins in which amino acid substitutions take place in either the alpha or beta chains but near the heme iron. This results in facilitated oxidation of the hemoglobin to yield excess methemoglobin which leads to cyanosis. [NIH] Hemoglobinopathies: A group of inherited disorders characterized by structural alterations within the hemoglobin molecule. [NIH] Hemoglobinuria: The presence of free hemoglobin in the urine. [NIH] Hemolytic: A disease that affects the blood and blood vessels. It destroys red blood cells, cells that cause the blood to clot, and the lining of blood vessels. HUS is often caused by the Escherichia coli bacterium in contaminated food. People with HUS may develop acute renal failure. [NIH] Hemophilia: Refers to a group of hereditary disorders in which affected individuals fail to make enough of certain proteins needed to form blood clots. [NIH] Heparin: Heparinic acid. A highly acidic mucopolysaccharide formed of equal parts of sulfated D-glucosamine and D-glucuronic acid with sulfaminic bridges. The molecular weight ranges from six to twenty thousand. Heparin occurs in and is obtained from liver, lung, mast cells, etc., of vertebrates. Its function is unknown, but it is used to prevent blood clotting in vivo and vitro, in the form of many different salts. [NIH] 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] Hexokinase: An enzyme that catalyzes the conversion of ATP and a D-hexose to ADP and a D-hexose 6-phosphate. D-Glucose, D-mannose, D-fructose, sorbitol, and D-glucosamine can act as acceptors; ITP and dATP can act as donors. The liver isoenzyme has sometimes been called glucokinase. (From Enzyme Nomenclature, 1992) EC 2.7.1.1. [NIH] Histone Deacetylase: Hydrolyzes N-acetyl groups on histones. [NIH] Histones: Small chromosomal proteins (approx 12-20 kD) possessing an open, unfolded structure and attached to the DNA in cell nuclei by ionic linkages. Classification into the various types (designated histone I, histone II, etc.) is based on the relative amounts of arginine and lysine in each. [NIH]
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Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable. [NIH] Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] Homozygotes: An individual having a homozygous gene pair. [NIH] Hormonal: Pertaining to or of the nature of a hormone. [EU] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Humoral: Of, relating to, proceeding from, or involving a bodily humour - now often used of endocrine factors as opposed to neural or somatic. [EU] Humour: 1. A normal functioning fluid or semifluid of the body (as the blood, lymph or bile) especially of vertebrates. 2. A secretion that is itself an excitant of activity (as certain hormones). [EU] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [NIH] 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] Hydrogen Peroxide: A strong oxidizing agent used in aqueous solution as a ripening agent, bleach, and topical anti-infective. It is relatively unstable and solutions deteriorate over time unless stabilized by the addition of acetanilide or similar organic materials. [NIH] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hydrops Fetalis: Edema of the entire body due to abnormal accumulation of serous fluid in the tissues, associated with severe anemia and occurring in fetal erythroblastosis. [NIH] Hydroxyproline: A hydroxylated form of the imino acid proline. A deficiency in ascorbic acid can result in impaired hydroxyproline formation. [NIH] Hydroxyurea: An antineoplastic agent that inhibits DNA synthesis through the inhibition of ribonucleoside diphosphate reductase. [NIH] Hyperpigmentation: Excessive pigmentation of the skin, usually as a result of increased melanization of the epidermis rather than as a result of an increased number of melanocytes. Etiology is varied and the condition may arise from exposure to light, chemicals or other substances, or from a primary metabolic imbalance. [NIH] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions
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upon subsequent exposure to that particular antigen. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hypogammaglobulinemia: The most common primary immunodeficiency in which antibody production is deficient. [NIH] Hypogonadism: Condition resulting from or characterized by abnormally decreased functional activity of the gonads, with retardation of growth and sexual development. [NIH] Hypoplasia: Incomplete development or underdevelopment of an organ or tissue. [EU] Idiopathic: Describes a disease of unknown cause. [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] Immunodeficiency: The decreased ability of the body to fight infection and disease. [NIH] Immunodeficiency syndrome: The inability of the body to produce an immune response. [NIH]
Immunofluorescence: A technique for identifying molecules present on the surfaces of cells or in tissues using a highly fluorescent substance coupled to a specific antibody. [NIH] Immunoglobulin: A protein that acts as an antibody. [NIH] Immunologic: The ability of the antibody-forming system to recall a previous experience with an antigen and to respond to a second exposure with the prompt production of large amounts of antibody. [NIH] Immunology: The study of the body's immune system. [NIH] Immunosuppressant: An agent capable of suppressing immune responses. [EU] Immunosuppression: Deliberate prevention or diminution of the host's immune response. It may be nonspecific as in the administration of immunosuppressive agents (drugs or radiation) or by lymphocyte depletion or may be specific as in desensitization or the simultaneous administration of antigen and immunosuppressive drugs. [NIH] Immunosuppressive: Describes the ability to lower immune system responses. [NIH] Immunosuppressive Agents: Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of suppressor T-cell populations or by inhibiting the activation of helper cells. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of interleukins and other cytokines are emerging. [NIH] Implant radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called [NIH] In situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU] In 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)
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or the escape of stool from the rectum (fecal incontinence). [NIH] Incubation: The development of an infectious disease from the entrance of the pathogen to the appearance of clinical symptoms. [EU] Incubation period: The period of time likely to elapse between exposure to the agent of the disease and the onset of clinical symptoms. [NIH] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] 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]
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] Inorganic: Pertaining to substances not of organic origin. [EU] Insecticides: Pesticides designed to control insects that are harmful to man. The insects may be directly harmful, as those acting as disease vectors, or indirectly harmful, as destroyers of crops, food products, or textile fabrics. [NIH] Insight: The capacity to understand one's own motives, to be aware of one's own psychodynamics, to appreciate the meaning of symbolic behavior. [NIH] Interferon: A biological response modifier (a substance that can improve the body's natural response to disease). Interferons interfere with the division of cancer cells and can slow tumor growth. There are several types of interferons, including interferon-alpha, -beta, and gamma. These substances are normally produced by the body. They are also made in the laboratory for use in treating cancer and other diseases. [NIH] Interferon-alpha: One of the type I interferons produced by peripheral blood leukocytes or lymphoblastoid cells when exposed to live or inactivated virus, double-stranded RNA, or bacterial products. It is the major interferon produced by virus-induced leukocyte cultures and, in addition to its pronounced antiviral activity, it causes activation of NK cells. [NIH] Internal radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called brachytherapy, implant radiation, or interstitial radiation therapy. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intestines: The section of the alimentary canal from the stomach to the anus. It includes the large intestine and small intestine. [NIH]
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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] Intravenous: IV. Into a vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [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] Ionizing: Radiation comprising charged particles, e. g. electrons, protons, alpha-particles, etc., having sufficient kinetic energy to produce ionization by collision. [NIH] Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as cations; those with a negative charge are anions. [NIH] Irradiation: The use of high-energy radiation from x-rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Irradiation is also called radiation therapy, radiotherapy, and x-ray therapy. [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] Karyotype: The characteristic chromosome complement of an individual, race, or species as defined by their number, size, shape, etc. [NIH] Kb: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [NIH] Kinetic: Pertaining to or producing motion. [EU] Labile: 1. Gliding; moving from point to point over the surface; unstable; fluctuating. 2. Chemically unstable. [EU] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH] Lens: The transparent, double convex (outward curve on both sides) structure suspended between the aqueous and vitreous; helps to focus light on the retina. [NIH] Lentivirus: A genus of the family Retroviridae consisting of non-oncogenic retroviruses that produce multi-organ diseases characterized by long incubation periods and persistent infection. Lentiviruses are unique in that they contain open reading frames (ORFs) between the pol and env genes and in the 3' env region. Five serogroups are recognized, reflecting the mammalian hosts with which they are associated. HIV-1 is the type species. [NIH] Lesion: An area of abnormal tissue change. [NIH] Lethargy: Abnormal drowsiness or stupor; a condition of indifference. [EU] Leucocyte: All the white cells of the blood and their precursors (myeloid cell series,
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lymphoid cell series) but commonly used to indicate granulocytes exclusive of lymphocytes. [NIH]
Leukemia: Cancer of blood-forming tissue. [NIH] Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [NIH] Life Expectancy: A figure representing the number of years, based on known statistics, to which any person of a given age may reasonably expect to live. [NIH] Lipid: Fat. [NIH] Lipid Peroxidation: Peroxidase catalyzed oxidation of lipids using hydrogen peroxide as an electron acceptor. [NIH] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Liver cancer: A disease in which malignant (cancer) cells are found in the tissues of the liver. [NIH]
Localization: The process of determining or marking the location or site of a lesion or disease. May also refer to the process of keeping a lesion or disease in a specific location or site. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Longitudinal study: Also referred to as a "cohort study" or "prospective study"; the analytic method of epidemiologic study in which subsets of a defined population can be identified who are, have been, or in the future may be exposed or not exposed, or exposed in different degrees, to a factor or factors hypothesized to influence the probability of occurrence of a given disease or other outcome. The main feature of this type of study is to observe large numbers of subjects over an extended time, with comparisons of incidence rates in groups that differ in exposure levels. [NIH] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Lymph node: A rounded mass of lymphatic tissue that is surrounded by a capsule of connective tissue. Also known as a lymph gland. Lymph nodes are spread out along lymphatic vessels and contain many lymphocytes, which filter the lymphatic fluid (lymph). [NIH]
Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] Lymphatic system: The tissues and organs that produce, store, and carry white blood cells that fight infection and other diseases. This system includes the bone marrow, spleen, thymus, lymph nodes and a network of thin tubes that carry lymph and white blood cells. These tubes branch, like blood vessels, into all the tissues of the body. [NIH] Lymphoblasts: Interferon produced predominantly by leucocyte cells. [NIH] Lymphocyte: A white blood cell. Lymphocytes have a number of roles in the immune system, including the production of antibodies and other substances that fight infection and diseases. [NIH] Lymphocyte Depletion: Immunosuppression by reduction of circulating lymphocytes or by T-cell depletion of bone marrow. The former may be accomplished in vivo by thoracic duct drainage or administration of antilymphocyte serum. The latter is performed ex vivo on bone marrow before its transplantation. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in
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which lymphocytes develop. [NIH] Lymphokine: A soluble protein produced by some types of white blood cell that stimulates other white blood cells to kill foreign invaders. [NIH] Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue. [NIH] Lysine: An essential amino acid. It is often added to animal feed. [NIH] Macrophage: A type of white blood cell that surrounds and kills microorganisms, removes dead cells, and stimulates the action of other immune system cells. [NIH] Malformation: A morphologic developmental process. [EU]
defect
resulting
from
an
intrinsically
abnormal
Malignancy: A cancerous tumor that can invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Mechlorethamine: A vesicant and necrotizing irritant destructive to mucous membranes. It was formerly used as a war gas. The hydrochloride is used as an antineoplastic in Hodgkin's disease and lymphomas. It causes severe gastrointestinal and bone marrow damage. [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] Megakaryocytes: Very large bone marrow cells which release mature blood platelets. [NIH] Melanocytes: Epidermal dendritic pigment cells which control long-term morphological color changes by alteration in their number or in the amount of pigment they produce and store in the pigment containing organelles called melanosomes. Melanophores are larger cells which do not exist in mammals. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors. [NIH] Mental: Pertaining to the mind; psychic. 2. (L. mentum chin) pertaining to the chin. [EU] Mental Processes: Conceptual functions or thinking in all its forms. [NIH] Mercury: A silver metallic element that exists as a liquid at room temperature. It has the atomic symbol Hg (from hydrargyrum, liquid silver), atomic number 80, and atomic weight 200.59. Mercury is used in many industrial applications and its salts have been employed therapeutically as purgatives, antisyphilitics, disinfectants, and astringents. It can be absorbed through the skin and mucous membranes which leads to mercury poisoning. Because of its toxicity, the clinical use of mercury and mercurials is diminishing. [NIH] Mesenchymal: Refers to cells that develop into connective tissue, blood vessels, and lymphatic tissue. [NIH] MI: Myocardial infarction. Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and
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viruses. [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] Microsomal: Of or pertaining to microsomes : vesicular fragments of endoplasmic reticulum formed after disruption and centrifugation of cells. [EU] Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH] Mitotic: Cell resulting from mitosis. [NIH] Mitotic inhibitors: Drugs that kill cancer cells by interfering with cell division (mitostis). [NIH]
Mobilization: The process of making a fixed part or stored substance mobile, as by separating a part from surrounding structures to make it accessible for an operative procedure or by causing release into the circulation for body use of a substance stored in the body. [EU] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecular Evolution: Multiple rounds of selection, amplification, and mutation leading to molecules with the desired properties. [NIH] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] Monitor: An apparatus which automatically records such physiological signs as respiration, pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH] Monoclonal: An antibody produced by culturing a single type of cell. It therefore consists of a single species of immunoglobulin molecules. [NIH] Monoclonal antibodies: Laboratory-produced substances that can locate and bind to cancer cells wherever they are in the body. Many monoclonal antibodies are used in cancer detection or therapy; each one recognizes a different protein on certain cancer cells. Monoclonal antibodies can be used alone, or they can be used to deliver drugs, toxins, or radioactive material directly to a tumor. [NIH] Monocytes: Large, phagocytic mononuclear leukocytes produced in the vertebrate bone marrow and released into the blood; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles. [NIH] Mononuclear: A cell with one nucleus. [NIH] Monosomy: The condition in which one chromosome of a pair is missing. In a normally diploid cell it is represented symbolically as 2N-1. [NIH] 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]
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Mucocutaneous: Pertaining to or affecting the mucous membrane and the skin. [EU] Mucositis: A complication of some cancer therapies in which the lining of the digestive system becomes inflamed. Often seen as sores in the mouth. [NIH] Muscle Contraction: A process leading to shortening and/or development of tension in muscle tissue. Muscle contraction occurs by a sliding filament mechanism whereby actin filaments slide inward among the myosin filaments. [NIH] Muscular Dystrophies: A general term for a group of inherited disorders which are characterized by progressive degeneration of skeletal muscles. [NIH] Mutagenesis: Process of generating genetic mutations. It may occur spontaneously or be induced by mutagens. [NIH] Mutagenic: Inducing genetic mutation. [EU] 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] Myelodysplastic syndrome: Disease in which the bone marrow does not function normally. Also called preleukemia or smoldering leukemia. [NIH] Myelogenous: Produced by, or originating in, the bone marrow. [NIH] Myeloproliferative Disorders: Disorders in which one or more stimuli cause proliferation of hemopoietically active tissue or of tissue which has embryonic hemopoietic potential. [NIH] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myofibrils: Highly organized bundles of actin, myosin, and other proteins in the cytoplasm of skeletal and cardiac muscle cells that contract by a sliding filament mechanism. [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] Neonatology: A subspecialty of pediatrics concerned with the newborn infant. [NIH] Neoplasms: New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms. [NIH] Neoplastic: Pertaining to or like a neoplasm (= any new and abnormal growth); pertaining to neoplasia (= the formation of a neoplasm). [EU] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU] Neurologic: Having to do with nerves or 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]
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Neutrons: Electrically neutral elementary particles found in all atomic nuclei except light hydrogen; the mass is equal to that of the proton and electron combined and they are unstable when isolated from the nucleus, undergoing beta decay. Slow, thermal, epithermal, and fast neutrons refer to the energy levels with which the neutrons are ejected from heavier nuclei during their decay. [NIH] Neutrophils: Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes. [NIH] Niacin: Water-soluble vitamin of the B complex occurring in various animal and plant tissues. Required by the body for the formation of coenzymes NAD and NADP. Has pellagra-curative, vasodilating, and antilipemic properties. [NIH] Nitrogen: An element with the atomic symbol N, atomic number 7, and atomic weight 14. Nitrogen exists as a diatomic gas and makes up about 78% of the earth's atmosphere by volume. It is a constituent of proteins and nucleic acids and found in all living cells. [NIH] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] Nuclear Matrix: The fibrogranular network of residual structural elements within which are immersed both chromatin and ribonucleoproteins. It extends throughout the nuclear interior from the nucleolus to the nuclear pore complexes along the nuclear periphery. [NIH] Nuclear Pore: An opening through the nuclear envelope formed by the nuclear pore complex which transports nuclear proteins or RNA into or out of the cell nucleus and which, under some conditions, acts as an ion channel. [NIH] Nuclear Proteins: Proteins found in the nucleus of a cell. Do not confuse with nucleoproteins which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus. [NIH] Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the information (genetic code) for the transfer of genetic information from one generation to the next. [NIH] Nucleolus: A small dense body (sub organelle) within the nucleus of eukaryotic cells, visible by phase contrast and interference microscopy in live cells throughout interphase. Contains RNA and protein and is the site of synthesis of ribosomal RNA. [NIH] Nucleoproteins: Proteins conjugated with nucleic acids. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Oncogenic: Chemical, viral, radioactive or other agent that causes cancer; carcinogenic. [NIH] Oncologist: A doctor who specializes in treating cancer. Some oncologists specialize in a particular type of cancer treatment. For example, a radiation oncologist specializes in treating cancer with radiation. [NIH] Oncology: The study of cancer. [NIH] On-line: A sexually-reproducing population derived from a common parentage. [NIH] Opacity: Degree of density (area most dense taken for reading). [NIH] Open Reading Frames: Reading frames where successive nucleotide triplets can be read as
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codons specifying amino acids and where the sequence of these triplets is not interrupted by stop codons. [NIH] Operon: The genetic unit consisting of a feedback system under the control of an operator gene, in which a structural gene transcribes its message in the form of mRNA upon blockade of a repressor produced by a regulator gene. Included here is the attenuator site of bacterial operons where transcription termination is regulated. [NIH] Oral Manifestations: Disorders of the mouth attendant upon non-oral disease or injury. [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] Osteogenic sarcoma: A malignant tumor of the bone. Also called osteosarcoma. [NIH] Osteosarcoma: A cancer of the bone that affects primarily children and adolescents. Also called osteogenic sarcoma. [NIH] Ovary: Either of the paired glands in the female that produce the female germ cells and secrete some of the female sex hormones. [NIH] Oxidants: Oxidizing agents or electron-accepting molecules in chemical reactions in which electrons are transferred from one molecule to another (oxidation-reduction). In vivo, it appears that phagocyte-generated oxidants function as tumor promoters or cocarcinogens rather than as complete carcinogens perhaps because of the high levels of endogenous antioxidant defenses. It is also thought that oxidative damage in joints may trigger the autoimmune response that characterizes the persistence of the rheumatoid disease process. [NIH]
Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]
Oxidation-Reduction: A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471). [NIH] Oxidative metabolism: A chemical process in which oxygen is used to make energy from carbohydrates (sugars). Also known as aerobic respiration, cell respiration, or aerobic metabolism. [NIH] Oxidative Stress: A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi). [NIH] Oxygenase: Enzyme which breaks down heme, the iron-containing oxygen-carrying constituent of the red blood cells. [NIH] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Pancreatic: Having to do with the pancreas. [NIH]
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Pancreatitis: Acute or chronic inflammation of the pancreas, which may be asymptomatic or symptomatic, and which is due to autodigestion of a pancreatic tissue by its own enzymes. It is caused most often by alcoholism or biliary tract disease; less commonly it may be associated with hyperlipaemia, hyperparathyroidism, abdominal trauma (accidental or operative injury), vasculitis, or uraemia. [EU] Pancytopenia: Deficiency of all three cell elements of the blood, erythrocytes, leukocytes and platelets. [NIH] Papillomavirus: A genus of Papovaviridae causing proliferation of the epithelium, which may lead to malignancy. A wide range of animals are infected including humans, chimpanzees, cattle, rabbits, dogs, and horses. [NIH] Particle: A tiny mass of material. [EU] Pathogen: Any disease-producing microorganism. [EU] Pathogenesis: The cellular events and reactions that occur in the development of disease. [NIH]
Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Pathologic Processes: The abnormal mechanisms and forms involved in the dysfunctions of tissues and organs. [NIH] Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Pediatrics: A medical specialty concerned with maintaining health and providing medical care to children from birth to adolescence. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Periodontal disease: Disease involving the supporting structures of the teeth (as the gums and periodontal membranes). [NIH] Periodontal disease: Disease involving the supporting structures of the teeth (as the gums and periodontal membranes). [NIH] Peripheral blood: Blood circulating throughout the body. [NIH] Peripheral stem cells: Immature cells found circulating in the bloodstream. New blood cells develop from peripheral stem cells. [NIH] Peroxidase: A hemeprotein from leukocytes. Deficiency of this enzyme leads to a hereditary disorder coupled with disseminated moniliasis. It catalyzes the conversion of a donor and peroxide to an oxidized donor and water. EC 1.11.1.7. [NIH] Peroxide: Chemical compound which contains an atom group with two oxygen atoms tied to each other. [NIH] Phagocyte: An immune system cell that can surround and kill microorganisms and remove dead cells. Phagocytes include macrophages. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Pharyngitis: Inflammation of the throat. [NIH] Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of yeasts. [NIH] Phosphorus: A non-metallic element that is found in the blood, muscles, nevers, bones, and teeth, and is a component of adenosine triphosphate (ATP; the primary energy source for
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the body's cells.) [NIH] Phosphorylate: Attached to a phosphate group. [NIH] Phosphorylated: Attached to a phosphate group. [NIH] Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. [NIH] Photosensitivity: An abnormal cutaneous response involving the interaction between photosensitizing substances and sunlight or filtered or artificial light at wavelengths of 280400 mm. There are two main types : photoallergy and photoxicity. [EU] Physiologic: Having to do with the functions of the body. When used in the phrase "physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH]
Physiology: The science that deals with the life processes and functions of organismus, their cells, tissues, and organs. [NIH] Pigmentation: Coloration or discoloration of a part by a pigment. [NIH] Pilot study: The initial study examining a new method or treatment. [NIH] Placenta: A highly vascular fetal organ through which the fetus absorbs oxygen and other nutrients and excretes carbon dioxide and other wastes. It begins to form about the eighth day of gestation when the blastocyst adheres to the decidua. [NIH] 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] Plasmid: An autonomously replicating, extra-chromosomal DNA molecule found in many bacteria. Plasmids are widely used as carriers of cloned genes. [NIH] Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Platinum: Platinum. A heavy, soft, whitish metal, resembling tin, atomic number 78, atomic weight 195.09, symbol Pt. (From Dorland, 28th ed) It is used in manufacturing equipment for laboratory and industrial use. It occurs as a black powder (platinum black) and as a spongy substance (spongy platinum) and may have been known in Pliny's time as "alutiae". [NIH]
Pneumonia: Inflammation of the lungs. [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
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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] Polypeptide: A peptide which on hydrolysis yields more than two amino acids; called tripeptides, tetrapeptides, etc. according to the number of amino acids contained. [EU] 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] Preclinical: Before a disease becomes clinically recognizable. [EU] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Predisposition: A latent susceptibility to disease which may be activated under certain conditions, as by stress. [EU] Prednisone: A synthetic anti-inflammatory glucocorticoid derived from cortisone. It is biologically inert and converted to prednisolone in the liver. [NIH] Preleukemia: Conditions in which the abnormalities in the peripheral blood or bone marrow represent the early manifestations of acute leukemia, but in which the changes are not of sufficient magnitude or specificity to permit a diagnosis of acute leukemia by the usual clinical criteria. [NIH] Prenatal: Existing or occurring before birth, with reference to the fetus. [EU] Procarbazine: An antineoplastic agent used primarily in combination with mechlorethamine, vincristine, and prednisone (the MOPP protocol) in the treatment of Hodgkin's disease. [NIH] Progeny: The offspring produced in any generation. [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] Prone: Having the front portion of the body downwards. [NIH] Propidium: Quaternary ammonium analog of ethidium; an intercalating dye with a specific affinity to certain forms of DNA and, used as diiodide, to separate them in density gradients; also forms fluorescent complexes with cholinesterase which it inhibits. [NIH] Prospective study: An epidemiologic study in which a group of individuals (a cohort), all free of a particular disease and varying in their exposure to a possible risk factor, is followed over a specific amount of time to determine the incidence rates of the disease in the exposed and unexposed groups. [NIH] 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]
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Protein Conformation: The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. Quaternary protein structure describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain). [NIH] Protein Isoforms: Different forms of a protein that may be produced from different genes, or from the same gene by alternative splicing. [NIH] Protein S: The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] Proteolytic: 1. Pertaining to, characterized by, or promoting proteolysis. 2. An enzyme that promotes proteolysis (= the splitting of proteins by hydrolysis of the peptide bonds with formation of smaller polypeptides). [EU] Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or vaccine dosages, length of study, routes of administration, who may participate, and other aspects of trial design. [NIH] Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] Psoralen: A substance that binds to the DNA in cells and stops them from multiplying. It is being studied in the treatment of graft-versus-host disease and is used in the treatment of psoriasis and vitiligo. [NIH] Psoriasis: A common genetically determined, chronic, inflammatory skin disease characterized by rounded erythematous, dry, scaling patches. The lesions have a predilection for nails, scalp, genitalia, extensor surfaces, and the lumbosacral region. Accelerated epidermopoiesis is considered to be the fundamental pathologic feature in psoriasis. [NIH] Psychology: The science dealing with the study of mental processes and behavior in man and animals. [NIH] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] Publishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing. [NIH]
Purines: A series of heterocyclic compounds that are variously substituted in nature and are known also as purine bases. They include adenine and guanine, constituents of nucleic acids, as well as many alkaloids such as caffeine and theophylline. Uric acid is the metabolic end product of purine metabolism. [NIH] Pyrimidines: A family of 6-membered heterocyclic compounds occurring in nature in a wide variety of forms. They include several nucleic acid constituents (cytosine, thymine, and uracil) and form the basic structure of the barbiturates. [NIH] Quality of Life: A generic concept reflecting concern with the modification and enhancement of life attributes, e.g., physical, political, moral and social environment. [NIH] Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not
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sufficiently so as to achieve the status of a taxon. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radiation oncologist: A doctor who specializes in using radiation to treat cancer. [NIH] Radiation therapy: The use of high-energy radiation from x-rays, gamma rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body in the area near cancer cells (internal radiation therapy, implant radiation, or brachytherapy). Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Also called radiotherapy. [NIH] Radioactive: Giving off radiation. [NIH] Radiolabeled: Any compound that has been joined with a radioactive substance. [NIH] Radiotherapy: The use of ionizing radiation to treat malignant neoplasms and other benign conditions. The most common forms of ionizing radiation used as therapy are x-rays, gamma rays, and electrons. A special form of radiotherapy, targeted radiotherapy, links a cytotoxic radionuclide to a molecule that targets the tumor. When this molecule is an antibody or other immunologic molecule, the technique is called radioimmunotherapy. [NIH] Randomized: Describes an experiment or clinical trial in which animal or human subjects are assigned by chance to separate groups that compare different treatments. [NIH] Reactive Oxygen Species: Reactive intermediate oxygen species including both radicals and non-radicals. These substances are constantly formed in the human body and have been shown to kill bacteria and inactivate proteins, and have been implicated in a number of diseases. Scientific data exist that link the reactive oxygen species produced by inflammatory phagocytes to cancer development. [NIH] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Recombination: The formation of new combinations of genes as a result of segregation in crosses between genetically different parents; also the rearrangement of linked genes due to crossing-over. [NIH] Reconstitution: 1. A type of regeneration in which a new organ forms by the rearrangement of tissues rather than from new formation at an injured surface. 2. The restoration to original form of a substance previously altered for preservation and storage, as the restoration to a liquid state of blood serum or plasma that has been dried and stored. [EU] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Red blood cells: RBCs. Cells that carry oxygen to all parts of the body. Also called erythrocytes. [NIH] Red Nucleus: A pinkish-yellow portion of the midbrain situated in the rostral mesencephalic tegmentum. It receives a large projection from the contralateral half of the cerebellum via the superior cerebellar peduncle and a projection from the ipsilateral motor cortex. [NIH] Reductase: Enzyme converting testosterone to dihydrotestosterone. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH]
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Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH] Regeneration: The natural renewal of a structure, as of a lost tissue or part. [EU] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Repopulation: The replacement of functional cells, usually by proliferation, following or during irradiation. [NIH] Repressor: Any of the specific allosteric protein molecules, products of regulator genes, which bind to the operator of operons and prevent RNA polymerase from proceeding into the operon to transcribe messenger RNA. [NIH] 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] Retrospective: Looking back at events that have already taken place. [NIH] Retroviral vector: RNA from a virus that is used to insert genetic material into cells. [NIH] Retrovirus: A member of a group of RNA viruses, the RNA of which is copied during viral replication into DNA by reverse transcriptase. The viral DNA is then able to be integrated into the host chromosomal DNA. [NIH] Reversion: A return to the original condition, e. g. the reappearance of the normal or wild type in previously mutated cells, tissues, or organisms. [NIH] Rheumatism: A group of disorders marked by inflammation or pain in the connective tissue structures of the body. These structures include bone, cartilage, and fat. [NIH] Rheumatoid: Resembling rheumatism. [EU] Rheumatoid arthritis: A form of arthritis, the cause of which is unknown, although infection, hypersensitivity, hormone imbalance and psychologic stress have been suggested as possible causes. [NIH] Ribonucleoside Diphosphate Reductase: An enzyme of the oxidoreductase class that catalyzes the formation of 2'-deoxyribonucleotides from the corresponding ribonucleotides using NADPH as the ultimate electron donor. The deoxyribonucleoside diphosphates are used in DNA synthesis. (From Dorland, 27th ed) EC 1.17.4.1. [NIH] Ribosome: A granule of protein and RNA, synthesized in the nucleolus and found in the cytoplasm of cells. Ribosomes are the main sites of protein synthesis. Messenger RNA attaches to them and there receives molecules of transfer RNA bearing amino acids. [NIH] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Rutin: 3-((6-O-(6-Deoxy-alpha-L-mannopyranosyl)-beta-D-glucopyranosyl)oxy)-2-(3,4dihydroxyphenyl)-5,7-dihydroxy-4H-1-benzopyran-4-one. Found in many plants, including buckwheat, tobacco, forsythia, hydrangea, pansies, etc. It has been used therapeutically to decrease capillary fragility. [NIH] Scatter: The extent to which relative success and failure are divergently manifested in qualitatively different tests. [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] Semisynthetic: Produced by chemical manipulation of naturally occurring substances. [EU] Sepsis: The presence of bacteria in the bloodstream. [NIH]
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Septic: Produced by or due to decomposition by microorganisms; putrefactive. [EU] Sequencing: The determination of the order of nucleotides in a DNA or RNA chain. [NIH] Serine: A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from glycine or threonine. It is involved in the biosynthesis of purines, pyrimidines, and other amino acids. [NIH] Serotonin: A biochemical messenger and regulator, synthesized from the essential amino acid L-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (receptors, serotonin) explain the broad physiological actions and distribution of this biochemical mediator. [NIH] Serous: Having to do with serum, the clear liquid part of blood. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Sickle Cell Trait: The condition of being heterozygous for hemoglobin S. [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] 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] Skin Pigmentation: Coloration of the skin. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Smoldering leukemia: Disease in which the bone marrow does not function normally. Also called preleukemia or myelodysplastic syndrome. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]
Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] Solid tumor: Cancer of body tissues other than blood, bone marrow, or the lymphatic system. [NIH] Solvent: 1. Dissolving; effecting a solution. 2. A liquid that dissolves or that is capable of dissolving; the component of a solution that is present in greater amount. [EU] Soma: The body as distinct from the mind; all the body tissue except the germ cells; all the axial body. [NIH] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] Sorbitol: A polyhydric alcohol with about half the sweetness of sucrose. Sorbitol occurs naturally and is also produced synthetically from glucose. It was formerly used as a diuretic and may still be used as a laxative and in irrigating solutions for some surgical procedures. It is also used in many manufacturing processes, as a pharmaceutical aid, and in several research applications. [NIH] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH]
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Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Specificity: Degree of selectivity shown by an antibody with respect to the number and types of antigens with which the antibody combines, as well as with respect to the rates and the extents of these reactions. [NIH] Spectrin: A high molecular weight (220-250 kDa) water-soluble protein which can be extracted from erythrocyte ghosts in low ionic strength buffers. The protein contains no lipids or carbohydrates, is the predominant species of peripheral erythrocyte membrane proteins, and exists as a fibrous coating on the inner, cytoplasmic surface of the membrane. [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] Spherocytes: Small, abnormal spherical red blood cells with more than the normal amount of hemoglobin. [NIH] Spherocytosis: A condition in which there are abnormally thick, almost spherical, red blood cells or spherocytes in the blood. [NIH] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [EU] Squamous: Scaly, or platelike. [EU] Squamous cell carcinoma: Cancer that begins in squamous cells, which are thin, flat cells resembling fish scales. Squamous cells are found in the tissue that forms the surface of the skin, the lining of the hollow organs of the body, and the passages of the respiratory and digestive tracts. Also called epidermoid carcinoma. [NIH] Squamous cell carcinoma: Cancer that begins in squamous cells, which are thin, flat cells resembling fish scales. Squamous cells are found in the tissue that forms the surface of the skin, the lining of the hollow organs of the body, and the passages of the respiratory and digestive tracts. Also called epidermoid carcinoma. [NIH] Squamous cells: Flat cells that look like fish scales under a microscope. These cells cover internal and external surfaces of the body. [NIH] Stem cell transplantation: A method of replacing immature blood-forming cells that were destroyed by cancer treatment. The stem cells are given to the person after treatment to help the bone marrow recover and continue producing healthy blood cells. [NIH] Stem Cells: Relatively undifferentiated cells of the same lineage (family type) that retain the ability to divide and cycle throughout postnatal life to provide cells that can become specialized and take the place of those that die or are lost. [NIH] Sterility: 1. The inability to produce offspring, i.e., the inability to conceive (female s.) or to induce conception (male s.). 2. The state of being aseptic, or free from microorganisms. [EU] Stimulant: 1. Producing stimulation; especially producing stimulation by causing tension on muscle fibre through the nervous tissue. 2. An agent or remedy that produces stimulation. [EU]
Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other
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excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Stool: The waste matter discharged in a bowel movement; feces. [NIH] Strand: DNA normally exists in the bacterial nucleus in a helix, in which two strands are coiled together. [NIH] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] Stromal: Large, veil-like cell in the bone marrow. [NIH] Stromal Cells: Connective tissue cells of an organ found in the loose connective tissue. These are most often associated with the uterine mucosa and the ovary as well as the hematopoietic system and elsewhere. [NIH] Subacute: Somewhat acute; between acute and chronic. [EU] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of pain, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses. [NIH]
Substrate: A substance upon which an enzyme acts. [EU] Superoxide: Derivative of molecular oxygen that can damage cells. [NIH] Superoxide Dismutase: An oxidoreductase that catalyzes the reaction between superoxide anions and hydrogen to yield molecular oxygen and hydrogen peroxide. The enzyme protects the cell against dangerous levels of superoxide. EC 1.15.1.1. [NIH] Supportive care: Treatment given to prevent, control, or relieve complications and side effects and to improve the comfort and quality of life of people who have cancer. [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] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] Telangiectasia: The permanent enlargement of blood vessels, causing redness in the skin or mucous membranes. [NIH] Telomere: A terminal section of a chromosome which has a specialized structure and which is involved in chromosomal replication and stability. Its length is believed to be a few hundred base pairs. [NIH] Teratogenic: Tending to produce anomalies of formation, or teratism (= anomaly of formation or development : condition of a monster). [EU] Testis: Either of the paired male reproductive glands that produce the male germ cells and the male hormones. [NIH] Testosterone: A hormone that promotes the development and maintenance of male sex characteristics. [NIH]
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Thalamic: Cell that reaches the lateral nucleus of amygdala. [NIH] Thalamic Diseases: Disorders of the centrally located thalamus, which integrates a wide range of cortical and subcortical information. Manifestations include sensory loss, movement disorders; ataxia, pain syndromes, visual disorders, a variety of neuropsychological conditions, and coma. Relatively common etiologies include cerebrovascular disorders; craniocerebral trauma; brain neoplasms; brain hypoxia; intracranial hemorrhages; and infectious processes. [NIH] Thalassemia: A group of hereditary hemolytic anemias in which there is decreased synthesis of one or more hemoglobin polypeptide chains. There are several genetic types with clinical pictures ranging from barely detectable hematologic abnormality to severe and fatal anemia. [NIH] Thermal: Pertaining to or characterized by heat. [EU] Thioguanine: An antineoplastic compound which also has antimetabolite action. The drug is used in the therapy of acute leukemia. [NIH] Thioredoxin: A hydrogen-carrying protein that participates in a variety of biochemical reactions including ribonucleotide reduction. Thioredoxin is oxidized from a dithiol to a disulfide during ribonucleotide reduction. The disulfide form is then reduced by NADPH in a reaction catalyzed by thioredoxin reductase. [NIH] Threonine: An essential amino acid occurring naturally in the L-form, which is the active form. It is found in eggs, milk, gelatin, and other proteins. [NIH] Threshold: For a specified sensory modality (e. g. light, sound, vibration), the lowest level (absolute threshold) or smallest difference (difference threshold, difference limen) or intensity of the stimulus discernible in prescribed conditions of stimulation. [NIH] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] Thrombomodulin: A cell surface glycoprotein of endothelial cells that binds thrombin and serves as a cofactor in the activation of protein C and its regulation of blood coagulation. [NIH]
Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thrush: A disease due to infection with species of fungi of the genus Candida. [NIH] Thymidine: A chemical compound found in DNA. Also used as treatment for mucositis. [NIH]
Thymoma: A tumor of the thymus, an organ that is part of the lymphatic system and is located in the chest, behind the breastbone. [NIH] Thymus: An organ that is part of the lymphatic system, in which T lymphocytes grow and multiply. The thymus is in the chest behind the breastbone. [NIH] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tooth Preparation: Procedures carried out with regard to the teeth or tooth structures preparatory to specified dental therapeutic and surgical measures. [NIH] Topoisomerase inhibitors: A family of anticancer drugs. The topoisomerase enzymes are responsible for the arrangement and rearrangement of DNA in the cell and for cell growth and replication. Inhibiting these enzymes may kill cancer cells or stop their growth. [NIH] Toxic: Having to do with poison or something harmful to the body. Toxic substances
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usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxins: Specific, characterizable, poisonous chemicals, often proteins, with specific biological properties, including immunogenicity, produced by microbes, higher plants, or animals. [NIH] Trace element: Substance or element essential to plant or animal life, but present in extremely small amounts. [NIH] Trachea: The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi. [NIH] Transcriptase: An enzyme which catalyses the synthesis of a complementary mRNA molecule from a DNA template in the presence of a mixture of the four ribonucleotides (ATP, UTP, GTP and CTP). [NIH] Transduction: The transfer of genes from one cell to another by means of a viral (in the case of bacteria, a bacteriophage) vector or a vector which is similar to a virus particle (pseudovirion). [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Transfusion: The infusion of components of blood or whole blood into the bloodstream. The blood may be donated from another person, or it may have been taken from the person earlier and stored until needed. [NIH] Translation: The process whereby the genetic information present in the linear sequence of ribonucleotides in mRNA is converted into a corresponding sequence of amino acids in a protein. It occurs on the ribosome and is unidirectional. [NIH] Translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Translocation: The movement of material in solution inside the body of the plant. [NIH] Transplantation: Transference of a tissue or organ, alive or dead, within an individual, between individuals of the same species, or between individuals of different species. [NIH] Transposase: An enzyme that binds to single-stranded DNA. It is thought to recognize the repetitive ends of a transposon and to participate in the cleavage of the recipient site into which the new transposon copy inserts. EC 2.7.7.-. [NIH] Transposons: Discrete genetic elements capable of inserting, in a non-permuted fashion, into the chromosomes of many bacteria. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Trypsin: A serine endopeptidase that is formed from trypsinogen in the pancreas. It is converted into its active form by enteropeptidase in the small intestine. It catalyzes hydrolysis of the carboxyl group of either arginine or lysine. EC 3.4.21.4. [NIH] Tryptophan: An essential amino acid that is necessary for normal growth in infants and for nitrogen balance in adults. It is a precursor serotonin and niacin. [NIH] Tumor Necrosis Factor: Serum glycoprotein produced by activated macrophages and other mammalian mononuclear leukocytes which has necrotizing activity against tumor cell lines
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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] Ulcer: A localized necrotic lesion of the skin or a mucous surface. [NIH] Ulceration: 1. The formation or development of an ulcer. 2. An ulcer. [EU] Umbilical Arteries: Either of a pair of arteries originating from the internal iliac artery and passing through the umbilical cord to carry blood from the fetus to the placenta. [NIH] Umbilical Cord: The flexible structure, giving passage to the umbilical arteries and vein, which connects the embryo or fetus to the placenta. [NIH] Umbilical cord blood: Blood from the placenta (afterbirth) that contains high concentrations of stem cells needed to produce new blood cells. [NIH] Umbilical cord blood transplantation: The injection of umbilical cord blood to restore an individual's own blood production system suppressed by anticancer drugs, radiation therapy, or both. It is being studied in the treatment of cancer and severe blood disorders such as aplastic anemia. Cord blood contains high concentrations of stem cells needed to produce new blood cells. [NIH] Uraemia: 1. An excess in the blood of urea, creatinine, and other nitrogenous end products of protein and amino acids metabolism; more correctly referred to as azotemia. 2. In current usage the entire constellation of signs and symptoms of chronic renal failure, including nausea, vomiting anorexia, a metallic taste in the mouth, a uraemic odour of the breath, pruritus, uraemic frost on the skin, neuromuscular disorders, pain and twitching in the muscles, hypertension, edema, mental confusion, and acid-base and electrolyte imbalances. [EU]
Urea: A compound (CO(NH2)2), formed in the liver from ammonia produced by the deamination of amino acids. It is the principal end product of protein catabolism and constitutes about one half of the total urinary solids. [NIH] 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] Uterus: The small, hollow, pear-shaped organ in a woman's pelvis. This is the organ in which a fetus develops. Also called the womb. [NIH] 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]
Vacuoles: Any spaces or cavities within a cell. They may function in digestion, storage, secretion, or excretion. [NIH] Vagina: The muscular canal extending from the uterus to the exterior of the body. Also called the birth canal. [NIH] Vaginitis: Inflammation of the vagina characterized by pain and a purulent discharge. [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vasculitis: Inflammation of a blood vessel. [NIH] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venous: Of or pertaining to the veins. [EU]
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Ventricles: Fluid-filled cavities in the heart or brain. [NIH] Ventricular: Pertaining to a ventricle. [EU] Vesicular: 1. Composed of or relating to small, saclike bodies. 2. Pertaining to or made up of vesicles on the skin. [EU] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Villi: The tiny, fingerlike projections on the surface of the small intestine. Villi help absorb nutrients. [NIH] Villus: Cell found in the lining of the small intestine. [NIH] Vincristine: An anticancer drug that belongs to the family of plant drugs called vinca alkaloids. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Viral vector: A type of virus used in cancer therapy. The virus is changed in the laboratory and cannot cause disease. Viral vectors produce tumor antigens (proteins found on a tumor cell) and can stimulate an antitumor immune response in the body. Viral vectors may also be used to carry genes that can change cancer cells back to normal cells. [NIH] Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [NIH] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH] Viscera: Any of the large interior organs in any one of the three great cavities of the body, especially in the abdomen. [NIH] Vitiligo: A disorder consisting of areas of macular depigmentation, commonly on extensor aspects of extremities, on the face or neck, and in skin folds. Age of onset is often in young adulthood and the condition tends to progress gradually with lesions enlarging and extending until a quiescent state is reached. [NIH] Vitro: Descriptive of an event or enzyme reaction under experimental investigation occurring outside a living organism. Parts of an organism or microorganism are used together with artificial substrates and/or conditions. [NIH] Vivo: Outside of or removed from the body of a living organism. [NIH] White blood cell: A type of cell in the immune system that helps the body fight infection and disease. White blood cells include lymphocytes, granulocytes, macrophages, and others. [NIH]
Windpipe: A rigid tube, 10 cm long, extending from the cricoid cartilage to the upper border of the fifth thoracic vertebra. [NIH] Xenobiotics: Chemical substances that are foreign to the biological system. They include naturally occurring compounds, drugs, environmental agents, carcinogens, insecticides, etc. [NIH]
Xeroderma Pigmentosum: A rare, pigmentary, and atrophic autosomal recessive disease affecting all races. It is manifested as an extreme photosensitivity to ultraviolet light as the result of a deficiency in the enzyme that permits excisional repair of ultraviolet-damaged DNA. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH]
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X-ray therapy: The use of high-energy radiation from x-rays to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. X-ray therapy is also called radiation therapy, radiotherapy, and irradiation. [NIH] Yeasts: A general term for single-celled rounded fungi that reproduce by budding. Brewers' and bakers' yeasts are Saccharomyces cerevisiae; therapeutic dried yeast is dried yeast. [NIH] Zygote: The fertilized ovum. [NIH] Zymogen: Inactive form of an enzyme which can then be converted to the active form, usually by excision of a polypeptide, e. g. trypsinogen is the zymogen of trypsin. [NIH]
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INDEX A Aberrant, 7, 113 Acceptor, 113, 137, 142 Acrodermatitis, 4, 113 Actin, 113, 140 Actinin, 21, 113, 126 Acute leukemia, 13, 19, 113, 145, 152 Acute lymphoblastic leukemia, 14, 54, 113 Acute lymphocytic leukemia, 113 Acute myelogenous leukemia, 9, 14, 45, 113 Acute myeloid leukemia, 20, 37, 54, 113 Acute nonlymphocytic leukemia, 113 Adaptability, 113, 121 Adaptation, 15, 113 Adenine, 64, 113, 114, 146 Adenitis, 31, 113 Adenoma, 46, 113 Adenosine, 114, 119, 143 Adjustment, 32, 113, 114 Adolescence, 114, 143 Adverse Effect, 114, 149 Aerobic, 114, 142 Aerobic Metabolism, 114, 142 Aerobic Respiration, 114, 142 Affinity, 8, 114, 145 Agammaglobulinemia, 3, 114 Alertness, 114, 119 Algorithms, 114, 118 Alkaloid, 114, 120 Alkylating Agents, 8, 11, 54, 114, 119 Alkylation, 21, 114 Alleles, 114, 132 Allogeneic, 11, 20, 23, 30, 58, 63, 67, 68, 115, 131 Allogeneic bone marrow transplantation, 30, 67, 68, 115 Alopecia, 115, 124 Alpha Particles, 115, 147 Alpha-1, 23, 115 Alpha-fetoprotein, 36, 50, 115, 128 Alternative medicine, 88, 115 Alternative Splicing, 57, 115, 146 Amino Acid Sequence, 84, 115, 116, 128, 130 Ammonia, 115, 154 Amnion, 115 Amniotic Fluid, 6, 115
Amplification, 115, 139 Anaesthesia, 115, 135 Anal, 115, 137 Analog, 116, 145 Analogous, 116, 153 Anaphylatoxins, 116, 123 Anions, 116, 136, 151 Annealing, 116, 144 Anomalies, 7, 21, 52, 72, 84, 116, 151 Antagonism, 116, 119 Antibacterial, 116, 150 Antibiotic, 116, 150 Antibodies, 13, 85, 116, 131, 137, 139, 144 Antibody, 114, 116, 123, 131, 133, 134, 135, 136, 139, 147, 150, 156 Anticoagulant, 15, 116, 145 Antigen, 114, 116, 123, 133, 134, 135 Antigen-Antibody Complex, 116, 123 Antimetabolite, 116, 119, 152 Antineoplastic, 114, 116, 117, 118, 119, 124, 133, 138, 145, 152 Antineoplastic Agents, 114, 117 Antioxidant, 15, 117, 142 Antithymocyte globulin, 33, 117 Antiviral, 117, 119, 127, 135 Anus, 115, 117, 122, 135 Aphthous Stomatitis, 31, 117 Aplastic anemia, 8, 9, 20, 30, 38, 49, 53, 54, 60, 117, 154 Apoptosis, 4, 7, 9, 12, 19, 23, 30, 37, 43, 58, 59, 69, 117, 120 Applicability, 17, 117 Aqueous, 117, 125, 133, 136 Arginine, 64, 116, 117, 132, 153 Arterial, 117, 134, 146, 151 Arteries, 117, 119, 124, 138, 154 Assay, 5, 12, 17, 34, 64, 117 Asymptomatic, 117, 143 Ataxia, 4, 5, 14, 17, 22, 36, 38, 47, 52, 117, 133, 152 Atypical, 30, 31, 37, 117 Autodigestion, 117, 143 Autoimmune disease, 20, 117 Autologous, 10, 117, 131 Autologous bone marrow transplantation, 117, 131
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B Bacteria, 116, 117, 118, 138, 139, 144, 147, 148, 150, 153, 154 Bacterial Infections, 118, 121, 123 Bacterial Physiology, 113, 118 Bacteriophage, 118, 153 Basal cell carcinoma, 30, 118 Basal cells, 118 Basal Ganglia, 117, 118, 119 Basal Ganglia Diseases, 117, 118 Base Sequence, 118, 129, 130 Basophils, 118, 131, 137 Benign, 113, 118, 119, 131, 140, 147 Biliary, 118, 143 Biliary Tract, 118, 143 Binding Sites, 9, 118 Biochemical, 4, 11, 12, 13, 14, 18, 19, 30, 34, 44, 50, 51, 52, 60, 65, 66, 70, 78, 85, 114, 116, 118, 128, 149, 152 Biochemical reactions, 118, 152 Biosynthesis, 118, 149 Biotechnology, 12, 24, 26, 88, 95, 118 Bleomycin, 8, 12, 36, 118 Blood pressure, 118, 134, 139 Blood vessel, 118, 119, 132, 137, 138, 149, 151, 152, 154 Blot, 24, 119 Bone Marrow Cells, 10, 11, 35, 119, 122, 131, 138 Bone Marrow Transplantation, 15, 30, 32, 33, 40, 50, 61, 62, 67, 68, 71, 72, 78, 100, 119 Brachytherapy, 119, 135, 136, 147, 156 Brain Neoplasms, 119, 133, 152 Bromodeoxyuridine, 40, 119 Buffers, 119, 150 Busulfan, 50, 119 C Caffeine, 39, 55, 74, 119, 146 Calcium, 119, 123 Callus, 120, 126 Camptothecin, 77, 120 Candidiasis, 4, 120 Candidosis, 120 Capillary, 120, 148 Capillary Fragility, 120, 148 Carbohydrate, 120, 130 Carcinogenesis, 11, 27, 69, 120 Carcinogenic, 114, 120, 141 Carcinogens, 120, 122, 142, 155 Carcinoma, 120 Cardiac, 119, 120, 127, 140
Case report, 67, 120 Caspase, 50, 53, 70, 120 Cataracts, 43, 120 Cell Cycle, 12, 15, 17, 44, 68, 69, 120, 122, 124 Cell Death, 35, 117, 121, 140 Cell Division, 118, 120, 121, 124, 131, 139, 144, 148 Cell proliferation, 12, 121 Cell Respiration, 114, 121, 142 Cell Size, 121, 128 Cell Survival, 12, 121, 131 Cell Transplantation, 10, 100, 121 Central Nervous System, 119, 121, 131, 133, 149 Central Nervous System Infections, 121, 131, 133 Centrifugation, 121, 139 Cerebellar, 117, 121, 147 Cerebral, 117, 118, 119, 121, 133 Cerebral Cortex, 117, 121 Cerebrospinal, 121, 133 Cerebrospinal fluid, 121, 133 Cervical, 61, 121 Cervix, 121 Chemotactic Factors, 121, 123 Chemotherapy, 8, 13, 53, 121 Chromatin, 17, 44, 117, 121, 141 Chromium, 43, 121 Chromosomal, 10, 12, 17, 18, 24, 26, 34, 35, 38, 40, 56, 58, 59, 115, 121, 122, 132, 139, 144, 148, 151 Chromosome, 10, 19, 40, 53, 54, 59, 85, 122, 132, 136, 139, 148, 151 Chromosome Breakage, 19, 40, 122 Chronic, 4, 15, 20, 122, 135, 143, 146, 151, 154 Cisplatin, 25, 35, 39, 122 Cleave, 69, 122 Clinical Medicine, 122, 145 Clinical Protocols, 15, 122 Clinical trial, 4, 8, 17, 23, 95, 122, 146, 147 Clone, 17, 122 Cloning, 10, 19, 35, 60, 84, 118, 122 Cofactor, 122, 146, 152 Collagen, 115, 122, 128 Colloidal, 122, 126 Colon, 5, 122 Colony-Stimulating Factors, 122, 131 Common Variable Immunodeficiency, 3, 123 Complement, 4, 22, 116, 123, 130, 136
159
Complementary and alternative medicine, 77, 79, 123 Complementary medicine, 77, 123 Computational Biology, 5, 95, 123 Conjugated, 123, 124, 141 Connective Tissue, 119, 122, 123, 137, 138, 148, 151 Consciousness, 124, 125, 126 Contraindications, ii, 124 Coordination, 21, 124 Coronary, 124, 138 Coronary Thrombosis, 124, 138 Craniocerebral Trauma, 118, 124, 131, 133, 152 Crossing-over, 124, 147 Cryofixation, 124 Cryopreservation, 10, 124 Cultured cells, 46, 124 Curative, 4, 124, 141 Cutaneous, 84, 120, 124, 144 Cyclic, 119, 124 Cyclin, 25, 51, 124 Cyclophosphamide, 8, 32, 33, 40, 50, 124 Cytochrome, 11, 18, 29, 124 Cytogenetics, 6, 19, 30, 36, 37, 40, 44, 46, 52, 71, 124 Cytokine, 9, 15, 19, 124, 128 Cytoplasm, 25, 26, 52, 117, 118, 125, 127, 139, 140, 141, 148 Cytoskeletal Proteins, 125, 126 Cytotoxic, 8, 58, 125, 134, 147 Cytotoxicity, 122, 125 D Deamination, 125, 154 Deletion, 25, 37, 48, 56, 117, 125 Denaturation, 22, 125, 144 Density, 10, 121, 125, 128, 141, 145 Desensitization, 125, 134 Detoxification, 18, 29, 125 Diagnostic procedure, 19, 83, 88, 125 Diastolic, 125, 134 Digestive tract, 125, 149, 150 Dihydrotestosterone, 125, 147 Dihydroxy, 125, 148 Dilation, 125, 133 Diploid, 123, 125, 139, 144 Direct, iii, 11, 17, 19, 64, 122, 125, 147 Disease Susceptibility, 14, 125 Dissociation, 59, 114, 125, 136 Dissociative Disorders, 125 Diuresis, 119, 126 Drive, ii, vi, 6, 8, 10, 14, 16, 73, 126
Drug Resistance, 15, 126 Drug Tolerance, 126 Dystrophin, 21, 126 Dystrophy, 5, 22, 126 E Effector, 123, 126 Efficacy, 15, 20, 126 Elective, 65, 126 Electrons, 117, 126, 136, 142, 147 Electrophoresis, 46, 64, 126 Embryo, 115, 126, 135, 154 Embryogenesis, 18, 42, 126 Emollient, 126, 130 Endemic, 126, 150 Endocarditis, 120, 127 Endocrine Glands, 7, 127 Endocytosis, 62, 127 Endogenous, 12, 40, 127, 142 Endotoxins, 123, 127 Enteropeptidase, 127, 153 Environmental Health, 43, 59, 94, 96, 127 Enzymatic, 5, 115, 120, 123, 127, 144 Eosinophil, 127, 131 Epidemic, 127, 150 Epidermis, 118, 127, 133 Epidermoid carcinoma, 127, 150 Epithelial, 113, 127 Epithelium, 127, 143 Erythrocytes, 116, 119, 127, 143, 147 Erythropoiesis, 71, 127 Ethidium, 127, 145 Eukaryotic Cells, 125, 127, 134, 141, 142 Excisional, 128, 155 Excitation, 128, 140 Exogenous, 127, 128, 129 Exon, 41, 57, 115, 128 External-beam radiation, 128, 136, 147, 156 Extracellular, 15, 123, 127, 128 Extracellular Matrix, 123, 128 F Family Planning, 95, 128 Fat, 119, 128, 137, 148, 149 Fetoprotein, 128 Fetus, 115, 128, 144, 145, 154 Fibroblasts, 25, 26, 27, 29, 34, 37, 39, 40, 54, 58, 62, 64, 69, 71, 81, 128 Fibronectin, 15, 16, 128 Filgrastim, 61, 128 Flow Cytometry, 24, 128 Fludarabine, 71, 128 Fluorescence, 21, 37, 127, 128, 129
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Fanconi Anemia
Fluorescent Dyes, 128 Founder Effect, 25, 55, 129 Frameshift, 27, 42, 57, 129 Frameshift Mutation, 27, 42, 57, 129 Free Radicals, 117, 125, 129 Fungus, 120, 129 G Gamma Rays, 129, 147 Gas, 115, 129, 133, 138, 141 Gastrin, 129, 133 Gastrointestinal, 22, 42, 129, 138, 149, 151 Gastrointestinal tract, 42, 129, 149 Gene Expression, 14, 25, 47, 51, 59, 129 Gene Rearrangement, 5, 129 Gene Targeting, 15, 23, 129 Gene Therapy, 5, 10, 11, 16, 17, 19, 20, 23, 27, 28, 40, 45, 61, 64, 65, 84, 85, 129 Genetic Code, 130, 141 Genetic Counseling, 17, 130 Genetic Engineering, 118, 122, 130 Genetic testing, 130, 145 Genotype, 10, 130, 143 Germ Cells, 130, 142, 149, 151 Gland, 113, 130, 137, 142, 150, 152 Glucokinase, 130, 132 Glucose, 121, 130, 132, 149 Glucuronic Acid, 130, 132 Glycerol, 51, 130 Glycerol Kinase, 51, 130 Glycine, 115, 130, 140, 149 Glycolysis, 15, 130 Glycoprotein, 128, 130, 131, 152, 153 Gonads, 7, 131, 134 Governing Board, 131, 145 Graft, 20, 53, 63, 117, 131, 146 Grafting, 20, 131 Graft-versus-host disease, 20, 53, 63, 117, 131, 146 Granulocyte, 3, 41, 61, 122, 128, 131 Granulocyte Colony-Stimulating Factor, 61, 122, 128, 131 Granulocyte-Macrophage ColonyStimulating Factor, 41, 123, 131 Growth factors, 131 H Haptens, 114, 131 Headache, 119, 131, 133 Hematologic Diseases, 20, 131 Hematologist, 4, 131 Hematology, 6, 17, 19, 29, 31, 33, 35, 36, 38, 42, 45, 53, 54, 55, 56, 59, 60, 62, 63, 70, 74, 131
Hematopoiesis, 8, 16, 17, 18, 19, 131 Hematopoietic growth factors, 9, 131 Hematopoietic Stem Cell Transplantation, 16, 20, 62, 131 Hematopoietic Stem Cells, 6, 15, 16, 24, 61, 132 Heme, 15, 124, 132, 142 Hemoglobin, 116, 127, 132, 149, 150, 152 Hemoglobin M, 132 Hemoglobinopathies, 24, 130, 132 Hemoglobinuria, 59, 132 Hemolytic, 132, 152 Hemophilia, 23, 132 Heparin, 15, 132 Hereditary, 22, 113, 132, 143, 152 Heredity, 129, 130, 132 Heterogeneity, 47, 114, 132 Heterozygote, 22, 132 Hexokinase, 15, 132 Histone Deacetylase, 13, 21, 132 Histones, 121, 132 Homeostasis, 12, 133 Homologous, 12, 18, 21, 40, 114, 124, 129, 132, 133, 148 Homozygotes, 22, 49, 133 Hormonal, 41, 133 Hormone, 7, 48, 52, 129, 133, 138, 148, 151, 152 Humoral, 4, 133 Humour, 133 Hybrid, 13, 44, 51, 72, 122, 133 Hydrocephalus, 48, 72, 133, 136 Hydrogen, 113, 119, 120, 125, 133, 137, 139, 141, 142, 146, 151, 152 Hydrogen Peroxide, 133, 137, 151 Hydrolysis, 122, 133, 145, 146, 153 Hydrops Fetalis, 22, 133 Hydroxyproline, 115, 122, 133 Hydroxyurea, 39, 133 Hyperpigmentation, 84, 133 Hypersensitivity, 7, 9, 10, 11, 13, 16, 17, 26, 30, 48, 49, 54, 58, 59, 125, 127, 133, 148 Hypertension, 5, 134, 136, 154 Hypogammaglobulinemia, 123, 134 Hypogonadism, 48, 134 Hypoplasia, 84, 134 I Idiopathic, 38, 113, 134 Immune response, 116, 117, 131, 134, 151, 155 Immune system, 134, 137, 138, 143, 155 Immunodeficiency, 3, 123, 134
161
Immunodeficiency syndrome, 123, 134 Immunofluorescence, 12, 134 Immunoglobulin, 116, 134, 139 Immunologic, 16, 114, 121, 134, 147 Immunology, 114, 129, 134 Immunosuppressant, 114, 134 Immunosuppression, 20, 134, 137 Immunosuppressive, 124, 134 Immunosuppressive Agents, 134 Implant radiation, 134, 135, 136, 147, 156 In situ, 18, 37, 134 In Situ Hybridization, 37, 134 In vitro, 6, 10, 15, 29, 48, 49, 71, 130, 134, 144 In vivo, 6, 10, 29, 61, 85, 130, 132, 134, 137, 142 Incontinence, 133, 134 Incubation, 7, 135, 136 Incubation period, 135, 136 Induction, 23, 49, 135 Infantile, 113, 135 Infarction, 124, 133, 135, 138 Infection, 3, 12, 120, 121, 131, 134, 135, 136, 137, 148, 151, 152, 155 Inflammation, 15, 43, 113, 117, 131, 135, 143, 144, 148, 154 Infusion, 63, 135, 153 Inorganic, 122, 135 Insecticides, 135, 155 Insight, 5, 13, 15, 135 Interferon, 26, 30, 49, 50, 68, 69, 74, 135, 137 Interferon-alpha, 135 Internal radiation, 135, 136, 147, 156 Interstitial, 50, 119, 135, 136, 156 Intestines, 125, 129, 135 Intracellular, 50, 119, 135, 136, 138 Intracranial Hemorrhages, 133, 136, 152 Intracranial Hypertension, 131, 133, 136 Intravenous, 135, 136 Intrinsic, 114, 136 Ionization, 136 Ionizing, 12, 14, 36, 53, 115, 136, 147 Ions, 119, 125, 133, 136 Irradiation, 32, 33, 55, 64, 74, 122, 136, 148, 156 Isoenzyme, 132, 136 K Karyotype, 27, 52, 136 Kb, 53, 94, 136 Kinetic, 21, 136
L Labile, 123, 136 Latent, 136, 145 Lens, 120, 136 Lentivirus, 6, 15, 136 Lesion, 21, 136, 137, 154 Lethargy, 133, 136 Leucocyte, 115, 127, 136, 137 Leukemia, 5, 6, 8, 13, 16, 18, 19, 23, 27, 37, 46, 52, 65, 71, 100, 130, 137, 145 Leukocytes, 74, 78, 118, 119, 121, 135, 137, 139, 141, 143, 153 Life Expectancy, 22, 137 Lipid, 78, 130, 137, 142 Lipid Peroxidation, 78, 137, 142 Liver, 115, 118, 124, 130, 131, 132, 137, 145, 154 Liver cancer, 115, 137 Localization, 12, 13, 17, 25, 34, 36, 50, 52, 53, 57, 137 Localized, 26, 85, 124, 126, 135, 137, 144, 154 Longitudinal study, 29, 137 Lymph, 121, 133, 137 Lymph node, 121, 137 Lymphatic, 135, 137, 138, 149, 152 Lymphatic system, 137, 149, 152 Lymphoblasts, 12, 35, 39, 51, 74, 77, 113, 137 Lymphocyte, 63, 116, 134, 137 Lymphocyte Depletion, 134, 137 Lymphoid, 35, 65, 116, 137, 138 Lymphokine, 29, 138 Lymphoma, 53, 100, 138 Lysine, 132, 138, 153 M Macrophage, 122, 131, 138 Malformation, 67, 138 Malignancy, 10, 16, 22, 27, 84, 138, 143 Malignant, 20, 116, 119, 137, 138, 140, 142, 147 Mechlorethamine, 138, 145 Mediate, 5, 7, 138 MEDLINE, 95, 138 Megakaryocytes, 119, 138 Melanocytes, 133, 138 Membrane, 28, 115, 117, 123, 126, 127, 128, 138, 140, 142, 150, 153 Membrane Proteins, 138, 150 Mental, iv, 4, 94, 96, 121, 125, 138, 146, 154 Mental Processes, 125, 138, 146 Mercury, 128, 138
162
Fanconi Anemia
Mesenchymal, 131, 138 MI, 41, 50, 112, 138 Microbe, 138, 153 Microbiology, 17, 113, 117, 138 Microorganism, 122, 139, 143, 155 Microsomal, 29, 139 Mitosis, 117, 139 Mitotic, 9, 42, 139 Mitotic inhibitors, 9, 139 Mobilization, 16, 54, 139 Modification, 15, 57, 63, 115, 130, 139, 146 Molecular Evolution, 65, 139 Molecule, 20, 84, 116, 118, 123, 124, 125, 126, 128, 133, 139, 142, 144, 147, 153, 154 Monitor, 34, 139, 141 Monoclonal, 20, 85, 136, 139, 147, 156 Monoclonal antibodies, 20, 85, 139 Monocytes, 137, 139 Mononuclear, 139, 153 Monosomy, 37, 139 Morphology, 131, 139 Mosaicism, 65, 66, 139 Mucocutaneous, 4, 140 Mucositis, 140, 152 Muscle Contraction, 126, 140 Muscular Dystrophies, 126, 140 Mutagenesis, 5, 56, 140 Mutagenic, 5, 56, 114, 140 Mutagens, 122, 129, 140 Myelodysplastic syndrome, 20, 67, 140, 149 Myelogenous, 140 Myeloproliferative Disorders, 20, 140 Myocardium, 138, 140 Myofibrils, 126, 140 N Necrosis, 117, 135, 138, 140 Neonatology, 15, 140 Neoplasms, 116, 117, 119, 120, 131, 140, 147 Neoplastic, 138, 140 Nerve, 117, 140, 150 Nervous System, 121, 140, 151 Neural, 128, 133, 140 Neurologic, 9, 133, 140 Neurotransmitter, 114, 115, 130, 140, 151 Neutrons, 115, 136, 141, 147 Neutrophils, 128, 131, 137, 141 Niacin, 141, 153 Nitrogen, 38, 114, 124, 141, 153 Nuclear Matrix, 17, 44, 141 Nuclear Pore, 141
Nuclear Proteins, 8, 141 Nuclei, 7, 115, 126, 129, 130, 132, 139, 141, 146 Nucleic acid, 13, 118, 127, 130, 134, 140, 141, 146 Nucleolus, 141, 148 Nucleoproteins, 141 Nucleus, 8, 17, 18, 64, 85, 117, 118, 121, 124, 125, 127, 129, 139, 141, 146, 151, 152 O Oncogenic, 136, 141 Oncologist, 4, 141 Oncology, 17, 19, 31, 33, 35, 42, 53, 54, 55, 56, 59, 62, 63, 74, 141 On-line, 6, 111, 141 Opacity, 120, 125, 141 Open Reading Frames, 136, 141 Operon, 142, 148 Oral Manifestations, 3, 142 Organelles, 121, 125, 138, 139, 142 Osteogenic sarcoma, 142 Osteosarcoma, 56, 142 Ovary, 35, 131, 142, 151 Oxidants, 40, 142 Oxidation, 113, 117, 124, 132, 137, 142 Oxidation-Reduction, 142 Oxidative metabolism, 11, 72, 114, 142 Oxidative Stress, 11, 42, 49, 142 Oxygenase, 15, 142 P Pancreas, 142, 143, 153 Pancreatic, 142, 143 Pancreatitis, 63, 143 Pancytopenia, 10, 41, 143 Papillomavirus, 48, 62, 143 Particle, 143, 153 Pathogen, 135, 143 Pathogenesis, 9, 10, 11, 19, 50, 55, 143 Pathologic, 117, 120, 124, 133, 143, 146, 148 Pathologic Processes, 117, 143 Pathophysiology, 36, 143 Pediatrics, 7, 8, 10, 14, 19, 31, 38, 41, 46, 48, 49, 52, 67, 72, 140, 143 Peptide, 115, 127, 143, 145, 146 Periodontal disease, 3, 143 Peripheral blood, 16, 42, 53, 54, 72, 131, 135, 143, 145 Peripheral stem cells, 131, 143 Peroxidase, 18, 45, 137, 143 Peroxide, 143 Phagocyte, 4, 142, 143 Pharmacologic, 15, 143, 153
163
Pharyngitis, 31, 143 Phenotype, 5, 9, 10, 13, 14, 15, 18, 49, 123, 143 Phosphorus, 119, 143, 144 Phosphorylate, 9, 144 Phosphorylated, 9, 13, 144 Phosphorylation, 13, 26, 60, 144 Photosensitivity, 144, 155 Physiologic, 16, 118, 144, 147, 148 Physiology, 46, 66, 131, 144 Pigmentation, 133, 144 Pilot study, 61, 144 Placenta, 144, 154 Plants, 114, 130, 139, 144, 148, 153 Plasma, 39, 60, 116, 122, 126, 128, 132, 144, 147 Plasma cells, 116, 144 Plasmid, 24, 62, 144, 154 Platelets, 138, 143, 144, 149 Platinum, 122, 144 Pneumonia, 124, 144 Polymerase, 32, 144, 148 Polymerase Chain Reaction, 32, 144 Polymorphic, 65, 145 Polypeptide, 26, 48, 85, 115, 122, 145, 146, 152, 156 Posterior, 115, 117, 142, 145 Postnatal, 145, 150 Practice Guidelines, 96, 145 Preclinical, 8, 20, 23, 24, 61, 145 Precursor, 6, 124, 126, 127, 131, 145, 153 Predisposition, 10, 16, 22, 41, 145 Prednisone, 145 Preleukemia, 52, 140, 145, 149 Prenatal, 61, 84, 126, 145 Procarbazine, 40, 145 Progeny, 6, 145 Progression, 12, 19, 31, 145 Progressive, 10, 11, 84, 126, 140, 145 Prone, 5, 12, 19, 23, 47, 145 Propidium, 52, 145 Prospective study, 137, 145 Protein C, 12, 18, 19, 21, 36, 44, 115, 118, 145, 146, 150, 154 Protein Conformation, 115, 146 Protein Isoforms, 115, 146 Protein S, 85, 118, 130, 146, 148 Proteins, 4, 8, 11, 12, 13, 15, 16, 17, 18, 21, 22, 23, 24, 29, 44, 47, 48, 50, 57, 63, 64, 70, 72, 85, 115, 116, 119, 120, 121, 122, 123, 131, 132, 138, 139, 140, 141, 143, 144, 146, 147, 149, 152, 153, 154, 155
Proteolytic, 63, 115, 123, 127, 146 Protocol, 10, 17, 61, 145, 146 Protons, 115, 133, 136, 146, 147 Psoralen, 21, 47, 54, 56, 62, 146 Psoriasis, 146 Psychology, 125, 146 Public Policy, 95, 146 Publishing, 24, 146 Purines, 118, 146, 149 Pyrimidines, 118, 146, 149 Q Quality of Life, 146, 151 R Race, 136, 146 Radiation, 12, 14, 20, 33, 36, 42, 53, 128, 129, 134, 135, 136, 141, 147, 154, 155, 156 Radiation oncologist, 141, 147 Radiation therapy, 20, 128, 135, 136, 147, 154, 156 Radioactive, 133, 134, 135, 136, 139, 141, 147, 156 Radiolabeled, 136, 147, 156 Radiotherapy, 62, 119, 136, 147, 156 Randomized, 126, 147 Reactive Oxygen Species, 12, 70, 147 Receptor, 9, 28, 62, 113, 116, 147, 149 Recombinant, 8, 15, 25, 60, 84, 85, 147, 154 Recombination, 12, 21, 26, 40, 129, 147 Reconstitution, 61, 147 Rectum, 117, 122, 125, 129, 135, 147 Red blood cells, 127, 132, 142, 147, 150 Red Nucleus, 117, 147 Reductase, 11, 18, 29, 147, 152 Refer, 1, 123, 137, 141, 147 Refraction, 148, 150 Regeneration, 147, 148 Regimen, 32, 33, 50, 122, 126, 148 Repopulation, 11, 148 Repressor, 13, 28, 142, 148 Resorption, 133, 148 Retrospective, 22, 148 Retroviral vector, 7, 8, 12, 16, 28, 60, 129, 148 Retrovirus, 6, 15, 27, 148 Reversion, 45, 66, 67, 148 Rheumatism, 148 Rheumatoid, 78, 142, 148 Rheumatoid arthritis, 78, 148 Ribonucleoside Diphosphate Reductase, 133, 148 Ribosome, 148, 153 Risk factor, 22, 35, 145, 148
164
Fanconi Anemia
Rutin, 78, 148 S Scatter, 52, 148 Screening, 65, 84, 85, 122, 148 Segregation, 65, 66, 147, 148 Semisynthetic, 120, 148 Sepsis, 15, 148 Septic, 15, 149 Sequencing, 84, 145, 149 Serine, 27, 149, 153 Serotonin, 140, 149, 153 Serous, 133, 149 Serum, 36, 60, 116, 123, 137, 147, 149, 153 Sickle Cell Trait, 35, 149 Side effect, 4, 114, 124, 149, 151, 153 Skeletal, 9, 18, 140, 149 Skeleton, 113, 149 Skin Pigmentation, 18, 149 Small intestine, 133, 135, 149, 153, 155 Smoldering leukemia, 140, 149 Smooth muscle, 116, 119, 149, 151 Soft tissue, 119, 149 Solid tumor, 6, 8, 18, 23, 118, 149 Solvent, 130, 149 Soma, 149 Somatic, 17, 47, 48, 62, 66, 84, 114, 126, 133, 139, 149 Sorbitol, 132, 149 Specialist, 103, 125, 149 Species, 115, 121, 133, 136, 139, 146, 147, 150, 152, 153, 155 Specificity, 21, 114, 145, 150 Spectrin, 21, 47, 126, 150 Spectrum, 10, 17, 66, 72, 150 Sperm, 122, 150 Spherocytes, 150 Spherocytosis, 22, 150 Sporadic, 37, 150 Squamous, 47, 48, 62, 67, 127, 150 Squamous cell carcinoma, 47, 48, 62, 67, 127, 150 Squamous cells, 150 Stem cell transplantation, 23, 58, 72, 131, 150 Stem Cells, 15, 16, 66, 100, 115, 131, 143, 150, 154 Sterility, 124, 150 Stimulant, 119, 150 Stimulus, 126, 128, 150, 152 Stomach, 117, 125, 129, 133, 135, 149, 151 Stool, 122, 135, 151 Strand, 27, 37, 63, 81, 144, 151
Stress, 14, 15, 54, 59, 78, 120, 142, 145, 148, 151 Stromal, 119, 151 Stromal Cells, 119, 151 Subacute, 135, 151 Subclinical, 135, 151 Substance P, 147, 151 Substrate, 21, 151 Superoxide, 15, 151 Superoxide Dismutase, 15, 151 Supportive care, 16, 151 Suppression, 20, 78, 151 Symptomatic, 143, 151 Systemic, 119, 120, 135, 136, 147, 151, 156 Systolic, 134, 151 T Telangiectasia, 4, 14, 17, 22, 36, 38, 47, 52, 151 Telomere, 29, 151 Teratogenic, 114, 151 Testis, 35, 131, 151 Testosterone, 147, 151 Thalamic, 117, 152 Thalamic Diseases, 117, 152 Thalassemia, 23, 152 Thermal, 22, 125, 141, 144, 152 Thioguanine, 67, 152 Thioredoxin, 58, 152 Threonine, 149, 152 Threshold, 134, 152 Thrombin, 145, 152 Thrombomodulin, 145, 152 Thrombosis, 146, 152 Thrush, 120, 152 Thymidine, 62, 119, 152 Thymoma, 4, 152 Thymus, 137, 152 Thyroid, 7, 152 Tooth Preparation, 113, 152 Topoisomerase inhibitors, 74, 77, 152 Toxic, iv, 20, 114, 125, 152, 153 Toxicity, 7, 8, 43, 53, 59, 62, 63, 138, 153 Toxicology, 96, 153 Toxins, 21, 116, 127, 130, 135, 139, 153 Trace element, 121, 153 Trachea, 152, 153 Transcriptase, 148, 153 Transduction, 4, 8, 9, 10, 11, 15, 16, 153 Transfection, 25, 26, 59, 118, 129, 153 Transfusion, 61, 78, 153 Translation, 15, 115, 153 Translational, 18, 153
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Translocation, 13, 153 Transplantation, 10, 16, 23, 30, 32, 33, 53, 58, 61, 63, 68, 71, 137, 153 Transposase, 24, 153 Transposons, 24, 153 Trauma, 140, 143, 153 Trypsin, 23, 127, 153, 156 Tryptophan, 22, 122, 149, 153 Tumor Necrosis Factor, 29, 153 U Ulcer, 154 Ulceration, 3, 154 Umbilical Arteries, 154 Umbilical Cord, 10, 61, 154 Umbilical cord blood, 10, 61, 154 Umbilical cord blood transplantation, 61, 154 Uraemia, 143, 154 Urea, 22, 154 Urinary, 133, 134, 154 Urine, 122, 126, 132, 134, 154 Uterus, 121, 154 V Vaccines, 154, 155 Vacuoles, 127, 142, 154 Vagina, 120, 121, 154 Vaginitis, 120, 154 Vascular, 135, 144, 154 Vasculitis, 143, 154 Vector, 5, 7, 8, 22, 25, 27, 45, 60, 153, 154 Vein, 136, 141, 154 Venous, 146, 154
Ventricles, 121, 133, 155 Ventricular, 133, 155 Vesicular, 139, 155 Veterinary Medicine, 95, 155 Villi, 133, 155 Villus, 6, 155 Vincristine, 145, 155 Viral, 15, 24, 141, 148, 153, 155 Viral vector, 15, 155 Virulence, 153, 155 Virus, 10, 15, 25, 60, 118, 121, 130, 135, 148, 153, 155 Viscera, 149, 155 Vitiligo, 146, 155 Vitro, 10, 132, 155 Vivo, 10, 15, 49, 137, 155 W White blood cell, 113, 116, 128, 131, 137, 138, 144, 155 Windpipe, 152, 155 X Xenobiotics, 59, 155 Xeroderma Pigmentosum, 14, 17, 22, 38, 47, 62, 155 X-ray, 21, 39, 128, 129, 136, 141, 147, 155, 156 X-ray therapy, 136, 156 Y Yeasts, 120, 129, 143, 156 Z Zygote, 139, 156 Zymogen, 145, 156
166
Fanconi Anemia
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168
Fanconi Anemia
