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

ALPHA FETOPROTEIN A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R E FERENCES J...

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ALPHA

FETOPROTEIN 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., 1960Alpha Fetoprotein: 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: 0-497-00048-2 1. Alpha Fetoprotein-Popular works. I. Title.

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

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

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Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this book which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which produce publications on alpha fetoprotein. 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 ALPHA FETOPROTEIN ............................................................................... 3 Overview........................................................................................................................................ 3 Federally Funded Research on Alpha Fetoprotein ......................................................................... 3 The National Library of Medicine: PubMed ................................................................................ 18 CHAPTER 2. ALTERNATIVE MEDICINE AND ALPHA FETOPROTEIN ............................................... 29 Overview...................................................................................................................................... 29 National Center for Complementary and Alternative Medicine.................................................. 29 Additional Web Resources ........................................................................................................... 30 General References ....................................................................................................................... 30 CHAPTER 3. PATENTS ON ALPHA FETOPROTEIN............................................................................ 31 Overview...................................................................................................................................... 31 Patents on Alpha Fetoprotein ...................................................................................................... 31 Patent Applications on Alpha Fetoprotein................................................................................... 33 Keeping Current .......................................................................................................................... 34 CHAPTER 4. BOOKS ON ALPHA FETOPROTEIN ............................................................................... 35 Overview...................................................................................................................................... 35 Book Summaries: Federal Agencies.............................................................................................. 35 Chapters on Alpha Fetoprotein .................................................................................................... 36 APPENDIX A. PHYSICIAN RESOURCES ............................................................................................ 39 Overview...................................................................................................................................... 39 NIH Guidelines............................................................................................................................ 39 NIH Databases............................................................................................................................. 41 Other Commercial Databases....................................................................................................... 43 APPENDIX B. PATIENT RESOURCES ................................................................................................. 45 Overview...................................................................................................................................... 45 Patient Guideline Sources............................................................................................................ 45 Finding Associations.................................................................................................................... 47 APPENDIX C. FINDING MEDICAL LIBRARIES .................................................................................. 49 Overview...................................................................................................................................... 49 Preparation................................................................................................................................... 49 Finding a Local Medical Library.................................................................................................. 49 Medical Libraries in the U.S. and Canada ................................................................................... 49 ONLINE GLOSSARIES.................................................................................................................. 55 Online Dictionary Directories ..................................................................................................... 56 ALPHA FETOPROTEIN DICTIONARY ..................................................................................... 57 INDEX ................................................................................................................................................ 91

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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 alpha fetoprotein 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 alpha fetoprotein, 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 alpha fetoprotein, 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 alpha fetoprotein. 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 alpha fetoprotein, 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 alpha fetoprotein. 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 ALPHA FETOPROTEIN Overview In this chapter, we will show you how to locate peer-reviewed references and studies on alpha fetoprotein.

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

Project Title: CARCINOMA

AFP-BASED

IMMUNOTHERAPY

FOR

HEPATOCELLULAR

Principal Investigator & Institution: Ribas, Antoni; Assistant Professor of Medicine and Surg; Medicine; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2007

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

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Summary: (provided by applicant): Hepatocelluar carcinoma (HCC) is a leading cause of cancer death worldwide. There are essentially no effective systemic therapies for this disease and relapses aider local therapies are very common. In previous work we have shown that both the murine and human T cell repertoires can recognize alpha fetoprotein (AFP)-derived peptide epitopes in the context of MHC. In a murine tumor model of genetic immunotherapy, AFP can serve as a tumor rejection antigen. In an extensive mapping of human AFP we have identified 4 immunodominant peptide epitopes in the context of HLA-A2.1. We have initiated a clinical trial testing their safety and immunogenicity. In this proposal, I request support to continue this translational research with two specific aims: AIM 1. AFP IMMUNOTHERAPY CLINICAL TRIALS FOR HCC. (1) AFP Peptide Dendritic Cell Trial. Patients with HCC whose tumors produce AFP and are HLA-A2.1 will be immunized, in a dose-escalation phase I/II trial, with dendritic cells (DC) pulsed with four immunodominant AFP peptides. The main goals are determination of safety and an optimal dose. Trial monitoring includes a careful immunological analysis, using ELISPOT and tetramer assays, to develop biomarkers of effective immunization for further clinical testing of our original hypothesis of the immunogenicity of AFP. (2) AFP-Engineered Dendritic Cell Trial. In this phase I/II trial, patients with AFP+ HCC will be immunized with autologous DC transduced with a recombinant adenovirus vector expressing human AFP. This is the most powerful means of antitumor AFP-based immunization in our preclinical models. Immunological monitoring will include the determination of T cell responses to immunodominant and subdominant epitopes. AIM 2. PRECLINICAL TESTING OF AFP DNA-BASED VACCINES. DNA-based vaccines can generate T cell responses and protective immunity and have clear practical advantages over DC-based vaccines. However, the levels of protection observed thus, far with AFP plasmid or AFP virus alone are inferior to gene-modified DC. I propose to use the same animal models that have allowed the development of the clinical trials in Aim 1 to test promising avenues aimed at enhancing the immune stimulatory ability of DNA-based vaccines. These approaches include the addition of a GM-CSF expression cassette, the use of Sindbis backbones, and/or boosting antigen-specific responses with replication incompetent viral vectors (prime-boost strategy). In summary, I propose a clinically-oriented research program that translates this original work into novel, evidence-based immnunotherapy trials for hepatocellular carcinoma. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: AFRI 1: GENE CLONING AND ITS ROLE IN LIVER REGULATION Principal Investigator & Institution: Spear, Brett T.; Associate Professor; Microbiology Immunology, and Molecular Genetics; University of Kentucky 109 Kinkead Hall Lexington, Ky 40506 Timing: Fiscal Year 2002; Project Start 15-JUL-2002; Project End 30-JUN-2007 Summary: A fundamental goal of biomedical research is to understand the processes that regulate gene expression during development and disease. The mouse alphafetoprotein ATP is particularly well suited for this. AFP is expressed at high levels in the fetal liver but is off in the adult liver. This is due to a 10,000 reduction in transcription during the perinatal period. The AFP gene can be reactivated in the adult liver in response to injury and in hepatocellular carcinomas. These aspects of AFP regulationAFP activation during hepatogenesis, repression at birth, and reactivation in liver cancer and regeneration-have led to considerable interest in the control of this gene. Postnatal AFP repression is regulated in part, by a locus called Alpha-fetoprotein regulator 1 (Afr1). Afr1 was originally identified by differences in AFP levels in different mouse

Studies

5

strains. Thus, unlike a majority of mammalian factors controlling gene expression that have been identified using biochemical approaches, Afr1 was revealed genetically. Of particular interest, Afr1 appears to regulate AFP by a mechanism that couples transcription to post-transcription events. While a connection between these events has been established in the literature, mechanisms that exist to modulate these connections are only beginning to be uncovered. Using tools of contemporary molecular genetics, we propose to identify the Afr1 gene by positional cloning. We can then understand how Afr1 regulates AFP and we are likely to learn more about the transcription/post/transcriptional connections as well as how this may be developmentally regulated to control gene expression. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ANTIESTROTROPHIC MECHANISMS OF ALPHAFETOPROTEIN PEPTIDES Principal Investigator & Institution: Festin, Stephen M.; Biology; Hamilton College Clinton, Ny 13323 Timing: Fiscal Year 2002; Project Start 01-MAY-2002; Project End 30-APR-2005 Summary: (provided by the applicant) Alphafetoprotein (AFP) and synthetic peptide derivatives are potent antiestrotrophic agents with significant potential as a novel class of therapeutic agents against breast cancer. The activity of the full-length protein is localized within an eight amino acid peptide derived from the native human alphafetoprotein elevating this synthetic peptide to a primary target for development. AFP peptide blocks the estrogen-stimulated growth of normal and neoplastic tissues. The anti-oncotic activity of AFP and its derivative peptides is unique to estrogen receptor-containing cells in vivo and in vitro. Until recently, much effort has been invested into the study of the antiestrotrophic activity of AFP fragments and peptides, with the focus on identification of the protein active site, yet very little is known about the cellular mechanism of AFP peptide action. The goal of this project is to discover the fundamental molecular mechanism(s) of AFP peptide activity. To accomplish this goal, it is necessary to identify the components of the cellular machinery involved in AFP action so that we may understand the biochemical and molecular basis of AFP peptide activity. The result of this work is expected to contribute to the development of novel therapeutic targets and will provide valuable information concerning the potential of AFP peptides as agents in the prevention, treatment, and diagnosis of breast cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: COMPLEMENTARY ADENOVIRAL VECTORS FOR TREATMENT OF CANCER Principal Investigator & Institution: Sobol, Robert E.; Magnum Therapeutics 8395 Camino Santa Fe, Ste B San Diego, Ca 921212635 Timing: Fiscal Year 2003; Project Start 07-MAR-2000; Project End 31-AUG-2006 Summary: (provided by applicant) The major goal of this proposal is to determine the therapeutic potential of a replication conditional adenovirus vector, DuaI-AdlL-3. This vector system is composed of two transcomplementing adenoviruses that permit selective replication in the prostate and prostate tumors. It is designed to engender a multimodal therapeutic response by establishing a lytic infection in prostate tumor cells by enhancing the tumoricidal effects of radiation therapy and by enhancing the immune response to endogenous tumor antigens. The genome of one of the viral components, Max-AdlL-3, contains the adenoviral-inverted terminal repeats for replication, the

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Alpha Fetoprotein

adenoviral packaging signal, the E1 genes with E1A under the control of a prostate specific antigen (PSA) promoter, and an IL-3 expression cassette. This vector propagates only in cells that express PSA when the helper adenoviral vector is also present. In animal tumor models, the combination of IL-3 cytokine gene therapy with radiotherapy was synergistic, resulting in enhanced efficacy of local radiotherapy and systemic antitumor immunity. In the preclinical studies of the Phase I SBIR grant we have shown our DuaI-AdlL-3 oncolytic vector system exhibits the oncolytic, immunity enhancing, and radiation-enhancing properties incorporated into the vector. This Phase II proposal will extend this project to clinical application. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: COMPLICATIONS OF CIRRHOSIS IN AMERICAN PATIENTS Principal Investigator & Institution: Marrero, Jorge; Internal Medicine; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2004; Project Start 01-APR-2004; Project End 31-MAR-2009 Summary: (provided by applicant): Hepatocellular carcinoma (HCC) is a tumor with the most rapid increase in incidence in the United States and this trend is expected to continue over the next 2 decades. It is a deadly tumor with only about 10% patients eligible for curative intervention transplantation or surgical resection). The incidence and death rates of HCC are equal because current tools for the diagnosis of HCC: alphafetoprotein (AFP) and ultrasound lack sensitivity and specificity. Therefore, strategies to improve the early detection and to identify those at the highest risk are of paramount importance. This proposal is centered on the validation of novel serum markers for the diagnosis of early HCC. Two studies will be conducted: a case-control study and a prospective cohort study. The case-control study will enroll patients presenting with HCC as cases and patients in the cirrhosis cohort study, who have not developed HCC as controls. Early HCC includes stage I and II HCC according to UNOS TNM system. Preliminary studies showed that des-gamma carboxyprothrombin (DCP), alone or in combination with a novel Golgi Protein-73 (GP73) are more sensitive and specific in the diagnosis of HCC but very few patients with early HCC were included. In this proposal, I will determine if DCP, GP73, and other novel serum markers identified through proteomics, alone or in combination will be more sensitive and specific than AFP in the diagnosis of early HCC. The prospective cohort study will enroll patients with cirrhosis and no HCC followed every 6 months for up to 54 months to determine if DCP, GP73 and other serum markers can lead to the diagnosis of HCC earlier. Demographics, medical history, tobacco and alcohol use, and laboratory data will be obtained to examine risk factors associated with HCC development. My career goal is to be an independently successful clinical investigator focused on early detection of HCC. I recognize that to achieve my goal, additional didactic training and experience in design and conduct of clinical studies under the guidance of accomplished mentors will be crucial. The K23 award will provide the protected time that is critical to my success. During the funding period, I will pursue additional courses in statistics and epidemiology. I will supervise the conduct of the proposed research and meet with my mentors and advisors regularly. Completing this proposal will allow me to achieve my career goal and to contribute to an improve outcome of patients with HCC. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: ELECTROMOBILITY FOCUSING FOR SEPARATION OF PROTEINS Principal Investigator & Institution: Lee, Milton L.; H. Tracy Hall Professor; Chemistry and Biochemistry; Brigham Young University A-261 Asb Provo, Ut 846021231

Studies

7

Timing: Fiscal Year 2003; Project Start 01-FEB-2003; Project End 31-JAN-2007 Summary: (provided by applicant): The protein distribution in the blood can indicate the overall state or condition of the human body. Therefore, determination of the proteins in blood samples can serve as a powerful diagnostic tool for early detection of disease states, such as cancer. Unfortunately, there is no analytical method available today to provide rapid high resolution profiles of proteins present in complex mixtures such as blood. The overall objective of this proposal is to develop a new method called electromobility focusing (EMF) for separating, concentrating, and identifying proteins in complex mixtures with unsurpassed resolution. The physical description of the device for EMF is a channel containing a buffer solution along which a high voltage is applied, similar to capillary electrophoresis, except that the electric field intensity along the column is not linear, but is a continuous gradient. Proteins can be separated and focused with exceptionally high resolution in the channel by applying a pressure-induced liquid flow counter to the electrophoretic migration direction of the proteins. The resulting forces acting on the proteins concentrate them into narrow bands at specific positions along the channel in order of their electrophoretic mobilities. The proteins can be mobilized in the separation channel by changing the magnitude of the pressure-induced counter flow or by reducing the applied voltage. The specific objectives of this work include the development of two different device formats for performing EMF: (a) semipreparative and (b) microchip. EMF will be applied to the rapid quantitative detection of five known protein tumor markers in blood serum, including prostate specific antigen, carcinoembryonic antigen, carcinoma-associated antigen 1 25, alphafetoprotein, and humanchorionic gonadotropin. Proposed new tumor marker, thymidine kinase I, will also be studied. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ETIOLOGIC HETEROGENEITY IN PRETERM DELIVERY Principal Investigator & Institution: Holzman, Claudia B.; Professor; Medicine; Michigan State University 301 Administration Bldg East Lansing, Mi 48824 Timing: Fiscal Year 2002; Project Start 01-SEP-1997; Project End 31-JUL-2006 Summary: (provided by applicant): The continued high rates of preterm delivery in the U.S, particularly among African-American women and poor women, suggests that new paradigms are needed to study this complex public health problem. We propose a placental abnormality-based model for studying PTD subtypes which assesses three major pathways to PTD, one predominantly characterized by placental and fetal membrane infection/inflammation, the second by placental and decidual vascular abnormalities, and the third by premature increases in the production of placental CRH without histopathologic abnormalities. Within each pathway we trace early biologic indicators of underlying pathology, and their psychosocial and behavioral antecedents many of which are potential targets for primary and secondary prevention strategies. To test this model we have assembled an unusually diverse, community-based, prospective cohort of 1,403 pregnant women enrolled from 52 prenatal clinics located within 5 Michigan cities. The cohort study, currently funded by NICHD, has a goal of enrolling 2,903 women by the end of the proposed continuation. The cohort is unique in that it includes collection of multiple biologic samples (hair, urine, blood, vaginal fluid), obtains in-depth maternal interviews, 24 hour ambulatory blood pressure measures, salivary cortisol and urinary catecholamine levels (collected AM and PM for 3 consecutive days), a detailed gross and histological examination of delivered placentas, medical record abstraction, assessment of DNA polymorphisms as effect modifiers, and linkage to census data for ecological level social variables. Most importantly, biologic

8

Alpha Fetoprotein

samples are collected in the second trimester, well before onset of labor and earlier than most published prospective studies of PTD. Research into the origins of prematurity has been largely undertaken from either a psychosocial or a biochemical perspective. This comprehensive study aims to unify both approaches into a coherent causal framework based on a foundation of specific placental findings that we hypothesize underlie several routes to PTD. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: FETO-MATERNAL APPLICATIONS

DNA/RNA

TRAFFICKING:BIOLOGY

&

Principal Investigator & Institution: Bianchi, Diana W.; Professor & Chief; New England Medical Center Hospitals 750 Washington St Boston, Ma 021111533 Timing: Fiscal Year 2004; Project Start 01-DEC-2003; Project End 30-NOV-2008 Summary: (provided by applicant): The overall goal of the proposed project is to understand the biology of feto-maternal cell-free DNA and RNA trafficking, and to use the knowledge gained to develop novel prenatal diagnostic applications. The overall hypothesis to be tested is that cell-free fetal DNA and mRNA in the maternal circulation and amniotic fluid originates from specific fetal tissue sources and contains unique fetal gene sequences that can be used for prenatal diagnosis of genetic and developmental disorders. Evidence thus far indicates that significant amounts of cell-free DNA, and to a lesser degree, RNA, circulate within the serum and plasma of pregnant women. These nucleic acids have a short half-life and are cleared within hours of delivery of the fetus or newborn. There is also a significant amount of cell-free fetal DNA and RNA present in the amniotic fluid. Currently, little is known about the tissue of origin of these nucleic acid sequences and how they are produced. Specific aim 1 of the project is to use cellfree fetal DNA in maternal plasma, archived serum samples, and amniotic fluid supernatants as sources of clinical material to develop new clinical tests that could improve existing noninvasive assays to determine the risk of fetal aneuploidy or single gene disorders such as congenital adrenal hyperplasia (CAH). To date clinical applications have focused on detection and quantitation of uniquely fetal sequences as an indication of pregnancy complications. A major limitation has been that many of these analyses have been limited to male fetuses, which carry a Y chromosome. Thus, specific aim 2 is to use uniquely fetal mRNA gene sequences for the identification and quantitation of fetal nucleic acids in maternal plasma, independent of fetal gender. We will examine if increased or decreased gene expression, as measured by circulating mRNA sequences in maternal blood, can be used to noninvasively detect fetal aneuploidy or other complications of pregnancy. In aim 3 we will determine the tissue of origin of the circulating nucleic acids by amplifying specific genes of hematopoietic, placental, and fetal origin. We will also use cell-free mRNA present in amniotic fluid to examine gene expression via microarrays. We will examine differences between fetuses due to gestational age and different pathologies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: FIRST AND SECOND TRIMESTER EVALUATION OF ANEUPLOIDY RISK Principal Investigator & Institution: D'alton, Mary E.; Professor of Obstetrics and Gynecology; Obstetrics and Gynecology; Columbia University Health Sciences Po Box 49 New York, Ny 10032 Timing: Fiscal Year 2001; Project Start 15-JUN-1999; Project End 31-MAY-2005

Studies

9

Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENETIC IMMUNOTHERAPY FOR HEPATOCELLULAR CANCER Principal Investigator & Institution: Economou, James S.; Surgery; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2002; Project Start 01-APR-1998; Project End 31-MAR-2005 Summary: (Applicant's Abstract) Hepatocellular carcinoma (HCC) is a leading cause of cancer death globally and there are essentially no effective systemic therapies for this disease. In the previous grant period, we made several novel observations about the immunobiology of this malignancy. Both the murine and human T cell repertoires can recognize alpha fetoprotein (AFP), an oncofetal protein produced by a majority of HCC. In a murine tumor model of genetic immunotherapy, AFP can serve as a tumor rejection antigen. We have performed extensive epitope mapping of hAFP and have identified 4 immunodominant and as many as 10 subdominant peptide epitopes in the context of HLA-A2.1. Finally, we have initiated an AFP peptide trial in patients with HCC and are able to detect T cell responses to these immunodominant peptide epitopes. In this competitive renewal, we request support to continue this translational research program with three specific aims: Aim 1. AFP Peptide Clinical Trial. In this phase I/II trial, AFP/A2.1-positive HCC patients are immunized with four immunodominant AFP peptides [hAFP137-145, hAFP158-166, hAFP325-334 and hAFP542-550] emulsified in incomplete Freund's adjuvant. Peripheral T cell responses will be measured by ELISPOT and tetramer assays. This study will allow us to determine if AFP-derived peptides are immunogenic in vivo. Aim 2. AFP-Engineered Dendritic Cell Trial. In this phase I/II trial, patients will be immunized with autologous dendritic cells (DC) transduced with a recombinant adenovirus vector expressing human AFP. T cell responses to immunodominant and subdominant epitopes will be measured. In this clinical trial, we will determine whether tumor antigen-engineered DC can generate polyclonal responses in vivo. Aim 3. Construction and Preclinical Testing of AFP DNA Vaccines. Plasmid-based DNA vaccines are capable of generating strong T cell responses and protective immunity. We propose to modify our first generation AFP DNA vaccine to improve these responses and test them in both protection and hepatocarcinogenesis models. In summary, we propose a largely clinically-directed research program that translates this original work into novel, evidence-based immunotherapy trials for hepatocellular carcinoma. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: GLYCOCONJUGATE-INDUCED TOLERANCE IN NATURAL KILLER CELLS Principal Investigator & Institution: Clark, Gary F.; Physiol Biochem & Pharmacology; Eastern Virginia Medical School Norfolk, Va 23507 Timing: Fiscal Year 2002; Project Start 01-APR-1999; Project End 31-MAR-2005 Summary: (Adapted from applicant's abstract) The human fetus is well-tolerated in utero regardless of its genetic composition, an accommodation the applicant refers to as fetomaternal tolerance (FMT). The induction of FMT is thought to be the result of suppression of potential allogeneic responses in the uterus and decidua. The major immune cell type in the uterus that could mediate rejection is the natural killer (NK) cell, suggesting that this cell type must be tolerized to the developing human in utero. Decidual NK (dNK) cells express morphological characteristics consistent with an

10

Alpha Fetoprotein

activated phenotype but nonetheless are tolerant of fetal cytotrophoblasts. The predominant model for the induction of tolerance suggests that dNK cells do not respond to cytotrophoblasts because they express the restricted polymorphism major histocompatibility antigen designated HLA-G on their surface. The applicant proposes another paradigm, in which glycoconjugate- induced tolerance in the NK cell response is responsible for inducing FMT. In this model, glycoproteins such as embryonic alpha fetoprotein (AFP) and decidual glycodelin-A use their oligosaccharides to bind the carbohydrate recognition domains of specific killer cell activation and inhibition receptors (KARs and KIRs) expressed on the surface of dNK cells. This interaction induces the expression of the activated NK cell phenotype that is highly tolerant to fetal cells expressing the appropriate glycoconjugate signals such as HLA-G. The primary goal of this study is to carry out experiments complementing preliminary studies in support of this glycoconjugate-based model. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GLYPICAN-3: A NOVEL MARKER FOR HEPATOCELLULAR CARCINOMA Principal Investigator & Institution: Filmus, Jorge E.; Sunnybrook & Women's Coll Hlth Scis Ctr S132 Toronto, on M4n 3M5 Timing: Fiscal Year 2003; Project Start 01-JUN-2003; Project End 31-MAY-2005 Summary: (provided by applicant): Human hepatocellular carcinoma (HCC) is usually asymptomatic at early stages. As a result, HCC is generally at an advanced stage when discovered, and the therapeutic options very limited. HCC is associated with chronic liver injury, primarily chronic viral hepatitis and alcoholic liver disease. The risk of developing HCC is 50 - 100 fold greater in individuals with chronic hepatitis B virus infection than in non-infected individuals, and the incidence of HCC in cirrhotic carriers of hepatitis C virus (HCV) may be as high as 5% per year. In principle, therefore, screening protocols are justified for chronic HBV carriers and cirrhotic HCV patients. The only molecular marker that has been widely used for the diagnosis and detection of HCC is alfafetoprotein (AFP). However, AFP expression is significantly increased in a considerable number of patients with non-malignant chronic liver diseases. Thus, more specific markers for HCC are required. Results recently obtained in this laboratory have shown that a protein called glypican-3 (GPC3) can be detected in most HCC tissue sections but it is undetectable in normal liver or benign liver disease. In addition, examination of a limited number of patients has shown that whereas GPC3 is undetectable in the serum of healthy individuals, its levels are significantly elevated in a large proportion of HCC patients. These results suggest, therefore, that GPC3 could be a better marker than AFP for the diagnosis and detection of HCC. The main goal of this study is to test this hypothesis. To this end, serum GPC3 and AFP will be measured in a cohort of 100 patients with HCC, and in patients with benign liver disease. The specificity and sensitivity of both markers will then be compared. GPC3 levels will also be assessed in 50 additional tissue sections from HCC patients, and a similar number of sections from various benign liver diseases. Another objective of this project is to investigate whether GPC3 could be used as a marker of tumor burden in experimental cancer. If this is the case this study will provide a tool that will simplify the search of novel treatments for HCC, and may open the possibility of using GPC3 measurement for the follow-up of HCC patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: IDENTIFICATION OF SERUM GLYCOSYLATION MARKERS OF HCC Principal Investigator & Institution: Mehta, Anand S.; Associate Professor; Biochem & Molecular Pharmacol; Thomas Jefferson University Office of Research Administration Philadelphia, Pa 191075587 Timing: Fiscal Year 2002; Project Start 01-MAY-2002; Project End 31-MAR-2004 Summary: (provided by applicant): Infection with hepatitis B virus (HBV) (and/or hepatitis C virus) is the major etiology of hepatocellular cancer (HCC). In the United States, chronic hepatitis B and C account for about 30%- 40% of HCC and, worldwide, more than 350 million people are chronically infected with either HBV or HCV. Alteration in the oligosaccharides associated with glycoproteins and glycolipids is one of the many molecular changes that accompany malignant transformations. However, accurate and reliable detection and quantification of oligosaccharides has been technically very difficult or time consuming. It is well established that in HCC there is an elevation in the amount of fucosylated oligosaccharides associated with a-fetal protein (AFP). The increase of a l-6-fucosylated glycans is due, in part, to an abnormal secretion system and other proteins have been shown to be aberrantly glycosylated. However, no systematic analysis has been carried out to identify all the proteins that have an increase in fucosylation. Our hypothesis is that by combining our high throughput oligosaccharide sequencing methodology with our laboratory's proteome expertise, we will be able to use lectin extraction methods to purify and identify fucosylated glycoproteins from HCC sera. Hence, proof of principle experiments will be carried out in the R21 phase using cultured liver cells to demonstrate the utility of the technology; while in the R33 phase the technology will be evaluated in a pilot study using sera obtained from woodchuck, a well established animal model of HBV induced HCC. It is anticipated that this methodology will allow the identification of an array of molecules that show increased fucosylation in HCC. These proteins may be then further evaluated as members of a fucose index to act as a surrogate marker for HCC progression. Obviously the technology would be applicable to any cancer system where oligosaccharide changes are associated with development to neoplasia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: IN REGULATION

VITRO

RECONSTITUTION

OF

ALPHA

FETOPROTEIN

Principal Investigator & Institution: Barton, Michelle C.; Associate Professor; Biochem and Molecular Biology; University of Texas Md Anderson Can Ctr Cancer Center Houston, Tx 77030 Timing: Fiscal Year 2003; Project Start 01-AUG-1997; Project End 31-MAY-2004 Summary: These investigations focus on the regulation of alpha-fetoprotein (AFP) gene expression as a tumor-associated gene switch. During liver regeneration, hepatocarcinoma or germinal tumor generation, AFP transcription is specifically activated. Though widely applied as a diagnostic marker, the regulatory control mechanisms involved in tumorigenic expression of AFP remain largely undetermined, as does the importance of this reactivation for prognostic and therapeutic value. The specific aims of these proposed studies are as follows: Specific Aim 1: To determine the DNA domain(s) that mediates aberrant reactivation of AFP gene expression by: a) construction of a series of AFP deletion and hybrid gene insertion templates, and b) employing these templates in cell culture and transcription systems that reconstitute adult liver repression and hepatoma activation of AFP expression in vitro. Specific Aim

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Alpha Fetoprotein

2: To model the stagewise progression of tumorigenesis by activating AFP gene expression within synthetic nuclei. We will undertake this by: a) assembly of chromatin templates that are repressed for AFP transcription in the presence of normal, adult liver extracts or purified, trans-acting factors; and, b) initiating in vitro, remodeling of the repressed AFP gene templates by presentation of cellular extracts or purified transactivators from AFP expressing sources during semi-conservative DNA replication. c) Activation of chromatin-assembled templates will be determined by subsequent in vitro transcription analysis. Specific Aim 3: To employ identified DNA target elements and model assay systems in order to initiate isolation and identification of the protein factors present in hepatic cells and hepatoma cell cultures that confer the dramatic switch in regulated AFP gene expression between normal adult and tumorigenic liver cells. These studies will test the hypotheses that 1) an identified developmental repressor domain is a likely target for inappropriate activation during tumorigenesis and 2) that DNA replication plays an active role in remodeling DNA-protein interactions with dramatic repercussions for AFP gene expression. The long-term goal of our studies is to understand the initiation and progression of tumorigenesis at a molecular level. In pursuing this goal, we will develop an in vitro model of tumorigenic activation of the mouse AFP gene that reconstitutes many properties of the nuclear environment and regulation while remaining biochemically accessible. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: LONG DISTANCE CONTROL OF LIVER GENE EXPRESSION Principal Investigator & Institution: Locker, Joseph D.; Professor; Pathology; Yeshiva University 500 W 185Th St New York, Ny 10033 Timing: Fiscal Year 2003; Project Start 01-JUL-1996; Project End 30-NOV-2007 Summary: (provided by applicant): Alpha-Fetoprotein (AFP) and Albumin (AIb) are closely related serum proteins, encoded by a coordinately regulated chromosomal locus. AFP is developmentally regulated, expressed in fetal liver, silenced at birth, but reactivated in liver cancer. AIb characterizes hepatocyte specification and its expression persists throughout life. Investigators have long understood that the mechanisms that regulate the AIb-AFP locus will define the normal, fetal, and neoplastic hepatocyte phenotype. Both genes are primarily regulated by distant enhancers, while AFP silencing is mediated by promoter controls. Previous experiments have demonstrated that each promoter interacts with enhancers through a different mechanism. In the Alb promoter, HNF1 is the critical enhancer-activating factor. Aim 1 experiments will define the specific HNF1 domains that mediate this interaction and the cofactors that these domains recruit. Further studies will characterize undefined elements in the rest of the promoter, especially "architectural" factors that facilitate enhancer activation. Aim 2 will focus on the AFP promoter, facilitated by use of a synthetic promoter designed for easy modification. The silencer will be localized; its binding factors and mechanism will be characterized. The potential roles of 6 new transcription factors will also be assessed. These were identified by their coregulation with AFP in microarray studies. Aim 3 will integrate the entire locus into a novel cell transfection system to study enhancers and promoters in their proper chromosomal relationships. The entire 70-kb locus has been slightly modified to clone it into a set of easily manipulated plasmids that can be joined together or experimentally changed. These have been placed into a recombining plasmid that will insert constructs into human HCC cell lines. Cre-mediated site-specific recombination will incorporate a single gene copy into a specific chromosomal location. The system will be used to define the relationships of individual enhancers and

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promoters, a set of new regulatory elements identified in sequence analysis, and specific transcriptional mechanisms. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: NOVEL STRATEGIES TO CAPTURE AND ASSAY LIVER STEM CELLS Principal Investigator & Institution: Faris, Ronald A.; Rhode Island Hospital (Providence, Ri) Providence, Ri 029034923 Timing: Fiscal Year 2002; Project Start 17-JUN-1996; Project End 31-MAR-2005 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: DELIVERY

PLACENTAL

VASCULAR

COMPROMISE

AND

PRETERM

Principal Investigator & Institution: Thorp, John M.; Professor; Obstetrics and Gynecology; University of North Carolina Chapel Hill Aob 104 Airport Drive Cb#1350 Chapel Hill, Nc 27599 Timing: Fiscal Year 2002; Project Start 01-SEP-2001; Project End 31-AUG-2006 Summary: (provided by applicant): There is substantial interest in determining the etiology of preterm delivery (PTD). Despite much effort, the cause remains elusive and effective prevention measures do not exist. Uteroplacental vascular compromise (UPVC) via inflammation, thrombosis, or atherosis is a biologically plausible cause of preterm delivery, albeit not adequately explored. We propose to test his hypothesis by conducting a prospective, epidemiologic study of UPVC and by integrating information about known risk factors for PTD. Placental histopathologic examination and morphometric analysis of the basal plate will be done to assess compromise of placental vessels. We will explore novel, possible antecedents of such compromise, dyslipidemia and insulin resistance, using nuclear magnetic resonance analysis of lipid subclasses and fasting insulin-glucose ratios. Given the inaccessibility of the uteroplacental vasculature in ongoing gestations at midpregnancy, we will utilize non-invasive measures of UPVC, Doppler velocimetry of the uterine artery, and maternal serum alpha fetoprotein to indirectly evaluate vascular function. In addition, we will carefully evaluate tobacco and cocaine use, nutrition, and changes in vaginal microflora within our cohort. The data will enable us to thoroughly assess whether UPVC constitutes a distinct etiologic pathway for PTD and help to identify modifiable risk factors. We will utilize cohort and case-cohort techniques, refined in our present research, to answer these questions. Blood, urine and vaginal fluid are collected twice between 15 and 20 weeks and between 24 and 29 weeks gestation. Hair will be collected after delivery. All subjects will complete two telephone interviews and two self administered questionnaires regarding various behaviors, dietary intake, physical activity, and psychosocial stressors. Placentas will be collected at the time of delivery and histopathologic analysis will be completed by an experienced perinatal pathologist for cases and a non-case subgroup. Nuclear magnetic resonance measurement of lipoprotein subclasses will be done to assess dyslipidemia. Insulin glucose ratios will be measured from fasting blood samples. We expect to enroll a cohort of 1800 women with 250 preterm deliveries and a randomly selected non-case subgroup (n=500). We will analyze the relationship between UPVC and PTD using logistic regression. Given 1) the size of the study, 2) thorough histopathologic assessment of the placenta, 3) extensive questionnaire data, 4) biologic markers of exposure to bacterial vaginosis, insulin resistance, dyslipidemia, and cocaine

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Alpha Fetoprotein

use, and 5) the careful assessment of potential confounding factors, this study promises to markedly advance our knowledge of the potential role of UPVC in the etiology of PTD. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PREGNANCY CANCER RISK

HORMONAL

PROFILE/BIOMARKER

BREAST

Principal Investigator & Institution: Akhmedkhanov, Arslan A.; Assistant Professor; Obstetrics and Gynecology; New York University School of Medicine 550 1St Ave New York, Ny 10016 Timing: Fiscal Year 2002; Project Start 03-JUL-2002; Project End 30-JUN-2005 Summary: (provided by applicant): A large body of epidemiological evidence indicates that an early first full-term pregnancy (before age 25) confers a lasting protection against breast cancer in the mother. Protection increases with decreasing age at pregnancy and is by and large independent of parity. Long-term protective effect of early full-term pregnancy could arise through pregnancy-related hormonal changes causing proliferation and full differentiation of mammary glandular epithelium in preparation for lactation. Fully differentiated mammary glandular cells are less susceptible to neoplastic transformation, while the vast majority of breast carcinomas arise from undifferentiated glandular cells. Experimental evidence revealed that specific hormones, such as human chorionic gonadotropin (hCG), relaxin (RLX) and alpha-fetoprotein (AFP), may play a role in breast tissue differentiation, and may be responsible for the protective effect of pregnancy on breast cancer risk. Recent data demonstrate that compared to Caucasian women in the US, Asian women had significantly higher second and third trimester levels of hormones affecting breast proliferation, such as estradiol (E2), estriol (E3), prolactin (PRL), and growth hormone (GH). These data support the hypothesis that women at low risk of breast cancer may have a specific hormonal profile during their pregnancies than women at high risk of breast cancer. We propose to expand these observations in a cross-sectional study by comparing pregnancy hormone levels affecting breast differentiation (hCG, RLX, AFP) and proliferation (E2, E3, PRL, GH) in women at high risk (Caucasian and African-American women in New York), intermediate risk (Latina immigrants in New York) and low risk (Asian immigrants in New York) of breast cancer. If the study hypothesis is confirmed, hormonal profile during pregnancy can be used for determination of a woman?s risk of breast cancer later in life. Moreover, specific hormone(s) or its analogues responsible for protective effect of pregnancy against breast cancer could be used for development of novel strategies for primary chemoprevention of breast cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: RETINOIC HEPATOMA

ACID RECEPTOR, ALPHA-FETOPROTEIN,

AND

Principal Investigator & Institution: Wan, Yu-Jui Y.; Professor; Harbor-Ucla Research & Educ Inst 1124 W Carson St Torrance, Ca 905022052 Timing: Fiscal Year 2002; Project Start 15-AUG-1991; Project End 31-MAR-2004 Summary: Retinoids regulate essentially all important biological processes including liver development, and these processes are largely regulated by complex transcription networks. In the liver, we have identified a gene, the alpha-fetoprotein (AFP) gene, that can be up- and down-regulated by retinoic acid (RA). AFL represents an important marker for hepatocyte differentiation, maturation, and carcinogenesis. One function of

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AFP is to regulate the concentration of retinoids. Thus, it is possible that RA and AFP might regulate each other in order to balance each other's effects. The goals of this project are to explore the molecular mechanisms involved in RA-mediated AFP gene regulation and to understand the actions of RA and the roles of RA receptors in differentiation and antiproliferation of hepatoma cells. The first specific aim is to characterize a complex DNA element containing one inverted and three direct repeats of GGGTCA-like sequence, which is responsible for the up-regulation of the AFP gene in McA-RH8994 hepatoma cells. Gel-shift assay, transient transfection CAT assay, and mutagenesis study will be employed to analyze the importance of individual repeats in trans-activation of the AFP gene. The possibility of other co-factors involved in upregulating the AFP gene also will be examined. The roles of RA receptors in this positive regulatory pathway will be analyzed using retinoic acid receptor (RAR) and retinoid x receptor (RXR) selective ligands, transient co-transfection with RA receptor expression plasmids, and gel mobility shift assay with specific anti-RAR and -RXR antibodies. RA also appears to play a role in the post-natal down-regulation of AFP, and Hep3B cells can be used as a model system to study this down- regulation. The motif responsible for down-regulation of the AFP gene by RA will be identified and characterized in Hep3B cells. Since down- regulation of the AFP gene is associated with regulation of the RAR and RXR genes in Hep3B cells, the roles RA receptors and other trans-acting factors involved in the negative regulatory pathway will be examined as well. In addition, because the RARbeta gene has been suggested to be a tumor suppressor gene, the roles of RARbeta in differentiation, antiproliferation, and apoptosis of hepatoma cells will be studied by restoration of RARbeta in RARbeta negative hepatoma cells and by inactivation of RARbeta in RARbeta positive hepatoma cell lines. The results obtained from this proposal will enhance our understanding in the actions of RA on hepatocyte differentiation and antiproliferation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SUPPRESSION OF HEPATOMA CELL GROWTH BY CELECOXIB Principal Investigator & Institution: Hu, Ke-Qin; Medicine; University of California Irvine Irvine, Ca 926977600 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-AUG-2005 Summary: (provided by applicant): Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide, accounting for approximately six percent of all human cancers and one million deaths annually. The rising incidence, limited treatment, and poor prognosis of HCC emphasize an urgent need to explore innovative strategies for effective chemoprevention of this disease. Overexpression of cyclooxygenase-2 (COX-2) has been associated with hepatocarcinogenesis. Celecoxib, a selective COX-2 inhibitor, suppresses growth of colon cancer and other malignancies and has recently been approved by FDA for chemoprevention of colon cancer. Even though our previous in vitro studies have indicated a potent inhibitory effect of celecoxib on growth of human HCC cells, such effect has never been tested in vivo. In response to PAR 02-176, we propose to determine the in vivo effect and mechanisms of celecoxib on growth of human HCC xenografts in nude mice. Two different human HCC cell lines, COX-2 expressing HuH7 and COX-2 non-expressing PLC/PRF/5, will be subcutaneously inoculated into nude mice to create HCC xenografts. Either celecoxib or control vehicle will be administered to these mice by gavage feeding. This model will be used to investigate our two specific aims: (1) To determine the in vivo effects of celecoxib on growth of COX-2 expressing HuH7 and COX-2 non-expressing PLC/PRF/5 HCC xenografts. (2) To examine the in vivo mechanisms of celecoxib-induced growth

16

Alpha Fetoprotein

inhibition of these HCC xenografts. The size of HCC xenografts and level of plasma alpha fetoprotein will be used as primary end points to assess the effect of celecoxib on growth of HCC xenografis. COX-2 catalytic activity, alteration of cell cycle progression and apoptosis will be tested for celecoxib-mediated mechanisms. The results of these experiments will provide important information on degree and mechanisms of celecoxibmediated growth inhibition of HCC xenografis in vivo, which is an essential step for future clinical trials to test celecoxib as a clinical agent for HCC chemoprevention. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SYNTHETIC PEPTIDES FROM AFP PREVENT BREAST CANCER Principal Investigator & Institution: Andersen, Thomas T.; Ctr for Cardiovascular Scis; Albany Medical College of Union Univ Albany, Ny 12208 Timing: Fiscal Year 2003; Project Start 13-JUN-2003; Project End 31-MAY-2007 Summary: (provided by applicant): Alpha-fetoprotein (AFP), a protein produced by the fetal liver, is one of the agents of pregnancy that affords significant reduction in risk of acquiring breast cancer to women who experience term pregnancy. AFP stops the growth of estrogen-dependent human breast cancer xenografts. It is non-toxic, and its mechanism of action is different from that of agents currently used in the clinic to treat breast cancer. We have designed a novel cyclic synthetic peptide, AFPep, which mimics the anti-oncotic active site of AFP. AFPep inhibits the growth of T47D breast cancer cells in culture and inhibits the growth of MCF-7 human breast cancer growing as xenografts in mice. AFPep has a novel mechanism (i.e., is different from tamoxifen and does not bind to the estrogen receptor), and it blocks tamoxifen-stimulated uterine growth. Proofof-principle data exist to suggest that AFPep can prevent breast cancer in a rat model. The Iong-term objective of the research program is to develop AFPep (or peptidomimetic analogs of AFPep) for use in the treatment and prevention of breast cancer in women. The hypothesis of this proposal is that administration of AFPep (or peptidomimetic analogs) in combination with tamoxifen to carcinogen (NMU) treated rats will augment cancer chemoprevention efficacy and reduce host toxicity compared to that of tamoxifen alone. The specific aims are: 1.) To compare the ability of AFPep, and that of tamoxifen, to prevent NMU-induced breast cancer in the rat model; 2.) To develop orally active analogs of AFPep (peptidomimetics) and test prevention capability in the rat model; and 3.) To assess safety of the peptide and analogs by obtaining preliminary toxicity measurements. The research design is to use a well-documented assay in which carcinogen-induced rats are treated with vehicle, AFPep, tamoxifen, or AFPep plus tamoxifen. Endpoints will include tumor latency (increased time to first tumors) and tumor burden (decreased incidence) for efficacy, and decreased uterotrophic response to tamoxifen for host toxicity. Health related aspects of the proposal include the observation that there is need for additional agents, with novel mechanisms of action, for the prevention of estrogen-receptor positive breast cancer. The need is emphasized by the observation that currently used chemopreventives for breast cancer are not without adverse side effects. AFPep has the potential to be used in combination with tamoxifen or as a stand-alone preventive agent. Its development and introduction to the clinic could prevent as many as 50,000 cases of breast cancer every year. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: TRANSCRIPTIONAL REGULATION OF STEROL 12-ALPHAHYDROLASE Principal Investigator & Institution: Gil, Gregorio; Associate Professor; Virginia Commonwealth University Richmond, Va 232980568 Timing: Fiscal Year 2002; Project Start 01-JUL-2002; Project End 30-JUN-2007 Summary: (provided by applicant): The most important pathway for the catabolism and excretion of cholesterol in mammals is the formation of bile acids. Improper regulation of this pathway has widespread implications because the rate of elimination of cholesterol is a very important factor in diseases such as atherosclerosis, gallstone disease, and some lipid storage diseases. Two enzymes play major regulatory roles in bile acid synthesis, cholesterol 7alpha-hydroxylase, the rate-limiting enzyme in the classic pathway, and sterol 12alpha-hydroxylase, the specific enzyme for cholic acid synthesis. Bile acids exert negative feedback regulation of their own synthesis by regulating the activity of these two enzymes. This regulation occurs at the level of the transcription of the genes. The applicant's laboratory has recently shown that alpha1fetoprotein transcription factor (FTF) is crucial for the expression and the bile acidmediated regulation of both 7alpha-and 12alpha-hydroxylase. This regulation functions through the interaction of FTF with the small heterodimer partner 1 (SHP). The Principal Investigators laboratory has also unveiled molecular details of how SHP and FTF interact, and has characterized the role of HNF-4 in the activation and regulation of 12alpha-hydroxylase expression. Additionally, they have discovered that sterol regulatory element binding protein 1 and 2 (SREBP-1 and-2) exert opposite effects on the 12alpha-hydroxylase promoter, which was highly unexpected. Understanding the molecular mechanisms regulating bile acid biosynthesis and its control will require knowledge of how SHP, a nuclear receptor co-factor that suppresses not only FTF activity but also many other nuclear receptors, specifically suppresses bile acidregulated genes but not other genes that are activated by HNF-4, ER, RXR, TR, etc., and that are not regulated by bile acids. It will also require an understanding of the molecular mechanisms and function of the SREBP-2 mediated suppression of 12alphahydroxylase. To achieve this goal, the following specific aims will be pursued: 1) Characterization of the FTF/HNF-4 site within the 12alpha-hydroxylase promoter involved in the bile acid-mediated regulation of its transcription. 2) Elucidation of the molecular mechanisms y which the FTF/SHP pathway specifically regulates 12alphahydroxylase transcription. 3) Characterization of the molecular mechanisms involved in the SREBP-2- mediated suppression of the 12alpha-hydroxylase promoter. 4) Characterization of the significance and physiological role of the SREBP-2-mediated suppression of 2alpha-hydroxylase expression. These studies should provide an understanding of the molecular mechanisms involved in the regulation of bile acid synthesis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: VIRAL INDUCED HCC?

ANTIGEN

GLYCOSYLATION--MARKER

FOR

HBV

Principal Investigator & Institution: Block, Timothy M.; Professor and Director; Biochem & Molecular Pharmacol; Thomas Jefferson University Office of Research Administration Philadelphia, Pa 191075587 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2004 Summary: (provided by applicant): In this exploratory program we propose to test the hypothesis that oligosaccharides associated with serum proteins can accurately serve as

18

Alpha Fetoprotein

biomarkers. Oligosaccharide profiles of hepatitis B surface antigens (HBsAg), purified from patient sera of different clinical populations, will be generated using novel HPLC sequencing technology that can reproducibly quantitate greater than 0.1 percent of an individual oligosaccharide in a glycan pool. Our sample population will consist of patients at risk for, or diagnosed with, hepatocellular carcinoma (HCC). The data generated will allow HBsAg oligosaccharides to be compared between different patient populations and the potential diagnostic value to be assessed. Alteration in the oligosaccharides associated with glycoproteins is one of the many molecular changes that accompany malignant transformations. In the case of HCC, an increase in fucosylation of secreted liver proteins is a common alteration. This increase in fucosylation has been postulated as a marker for HCC, however, the proteins of interest that show this alteration are typically found in low abundance (e.g. alpha fetoprotein). Our hypothesis is that, in cases where infection with hepatitis B virus (HBV) leads to the development of HCC, the viral glycoproteins (present up to mg/ml concentration) themselves may display aberrant oligosaccharides that could serve as early detection markers for HCC. Infection with HBV is the major etiology of HCC and, although HCC is a less common cancer in the USA, recent studies have shown that the incidence of HCC is rising both in the USA and worldwide. In addition, HCC is one of the most aggressive malignancies with prognosis being poor due to the late diagnosis. With the paucity of organ donors for liver transplantation and the small number of treatable patients (due to, in part, late diagnosis), early diagnosis will allow intervention at an earlier stage. We expect that this pilot study will firstly generate preliminary data to support the stated hypothesis; secondly, the study will allow the feasibility of a larger study to be determined, and thirdly, the parameters required to design a larger study to determine the value of oligosaccharide structures as potential markers of disease status will be obtained. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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

3

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 22-year-old man with a liver mass and markedly elevated serum alpha fetoprotein. Author(s): McCormick SE, Sjogren MH, Goodman ZD. Source: Seminars in Liver Disease. 1994 November; 14(4): 395-403. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7531871

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A microcomputer data base system for maternal serum alpha fetoprotein screening programmed in BASIC. Author(s): Keel BA, Durfee KK, Cho S. Source: Journal of Perinatal Medicine. 1989; 17(3): 221-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2478690

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A simple two-step purification of human and monkey alpha fetoprotein from amniotic fluid and serum. Author(s): Leal JA, Keel BA. Source: Journal of Medical Primatology. 1991; 20(1): 35-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1711120

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Abnormal maternal serum alpha fetoprotein and pregnancy outcome. Author(s): Zarzour SJ, Gabert HA, Diket AL, St Amant M, Miller JM Jr. Source: The Journal of Maternal-Fetal Medicine. 1998 November-December; 7(6): 304-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9848697

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Alpha fetoprotein and acetylcholinesterase levels in twins discordant for neural tube defects: dependence on type of fetal membranes. Author(s): Schnatterly PT, Hogge WA. Source: American Journal of Medical Genetics. 1989 January; 32(1): 146-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2468285

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Alpha fetoprotein as marker for a case of orbital yolk sac tumour. Author(s): Yih JP, Sullivan P, Taylor D. Source: The British Journal of Ophthalmology. 1995 August; 79(8): 787-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7547794

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Alpha fetoprotein inhibits aggregation of human platelets. Author(s): Czokalo M, Tomasiak M. Source: Haematologia. 1989; 22(1): 11-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2468586

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Alpha fetoprotein levels in newborn infants with reference to sex, gestational age and birth weight. Author(s): Bansal V, Kumari K, Dixit A, Sahib MK. Source: Indian J Exp Biol. 1989 July; 27(7): 666-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2483717

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alpha Fetoprotein producing early gastric cancer with liver metastasis: report of three cases. Author(s): Chang YC, Nagasue N, Abe S, Kohno H, Kumar DD, Nakamura T. Source: Gut. 1991 May; 32(5): 542-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1710199

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Alpha fetoprotein-producing acinar cell carcinoma of the pancreas showing multiple lines of differentiation. Author(s): Shinagawa T, Tadokoro M, Maeyama S, Maeda C, Yamaguchi S, Morohoshi T, Ishikawa E. Source: Virchows Archiv : an International Journal of Pathology. 1995; 426(4): 419-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7541276

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Amniotic fluid alpha fetoprotein (AFAFP) and maternal serum alpha fetoprotein (MSAFP) in abdominal pregnancies: correlation with extent and site of placental implantation and clinical implications. Author(s): Shumway JB, Greenspoon JS, Khouzami AN, Platt LD, Blakemore KJ. Source: The Journal of Maternal-Fetal Medicine. 1996 May-June; 5(3): 120-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8796780

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An economic appraisal of screening for Down's syndrome in pregnancy using maternal age and serum alpha fetoprotein concentration. Author(s): Gill M, Murday V, Slack J. Source: Social Science & Medicine (1982). 1987; 24(9): 725-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2440113

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Antitumor activity of alpha fetoprotein and epidermal growth factor conjugates in vitro and in vivo. Author(s): Lutsenko SV, Feldman NB, Finakova GV, Gukasova NV, Petukhov SP, Posypanova GA, Skryabin KG, Severin SE. Source: Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine. 2000 November-December; 21(6): 367-74. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11006577

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Assay precision of serum alpha fetoprotein in antenatal screening for neural tube defects and Down's syndrome. Author(s): Wald NJ, Hackshaw AK, George LM. Source: Journal of Medical Screening. 2000; 7(2): 74-7. Erratum In: J Med Screen 2000; 7(3): 168. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11002446

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Attempts to suppress experimental allergic encephalomyelitis in rats with alpha fetoprotein. Author(s): Kikukawa A, Peterson BS, Deutsch HF. Source: Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine. 1988; 9(2-3): 84-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2456601

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Characteristics of women who refuse an offer of prenatal diagnosis: data from the California maternal serum alpha fetoprotein blood test experience. Author(s): Press N, Browner CH. Source: American Journal of Medical Genetics. 1998 August 6; 78(5): 433-45. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9714010

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Characterization of human alpha fetoprotein charge microheterogeneity during fetal development. Author(s): Keel BA, Harms RL, Leal JA, Cho S. Source: Molecular Reproduction and Development. 1990 December; 27(4): 281-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1702295

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Clinical value of imaging using antibody to alpha fetoprotein in germ cell tumours. Author(s): Hitchins RN, Begent RH, Green AJ, Searle F, van Heyningen V, Bagshawe KD. Source: Nuklearmedizin. 1989 February; 28(1): 29-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2469059

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Combined alpha fetoprotein testing and ultrasonography as a screening test for primary liver cancer. Author(s): Zhang B, Yang B. Source: Journal of Medical Screening. 1999; 6(2): 108-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10444731

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Congenital cystic adenomatoid malformation of the lung and alpha fetoprotein. Author(s): Journel H, Le Guern H, Le Goff JL. Source: Clinical Genetics. 1988 November; 34(5): 344. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2465855

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Development of an inexpensive and rapid two site microenzyme linked immunosorbent assay kit for human alpha fetoprotein. Author(s): Bansal V, Kumari K, Sahib MK. Source: Indian J Exp Biol. 1989 October; 27(10): 907-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2483953

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Diagnostic value of maternal serum alpha fetoprotein for predicting pregnancy outcome in high risk pregnancies: an epidemiological perspective. Author(s): Pandey J, Talib VH, Loganey D, Yadav S. Source: Indian J Pathol Microbiol. 1993 April; 36(2): 104-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7506236

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Down syndrome and low maternal serum alpha fetoprotein. Author(s): Jacobs S, Giles W. Source: The Australian & New Zealand Journal of Obstetrics & Gynaecology. 1990 November; 30(4): 335-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1707270

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Elevated serum alpha fetoprotein and normal liquor alpha fetoprotein values in association with an abdominal pregnancy. Author(s): Jackson S, Hollingworth T, Macpherson M. Source: The Australian & New Zealand Journal of Obstetrics & Gynaecology. 1993 May; 33(2): 214-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7692840

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Elevated serum alpha fetoprotein levels in postmenopausal women with primary breast carcinoma. Author(s): Sarcione EJ, Biddle W. Source: Disease Markers. 1987 June; 5(2): 75-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2458881

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Epithelial tumor markers: oncofetal antigens (carcinoembryonic antigen, alpha fetoprotein) and epithelial membrane antigen. Author(s): Kloppel G, Caselitz J. Source: Curr Top Pathol. 1987; 77: 103-32. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2448086

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Expanded maternal serum alpha fetoprotein screening. Author(s): Williamson R. Source: Iowa Med. 1994 September; 84(9): 397-400. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7525508

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Expression of S-100 protein, epithelial membrane antigen, carcinoembryonic antigen and alpha fetoprotein in normal salivary glands and primary salivary gland tumors. Author(s): Gunhan O, Evren G, Demiriz M, Can C, Celasun B, Finci R. Source: J Nihon Univ Sch Dent. 1992 December; 34(4): 240-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1283754

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Failure of normalisation of alpha fetoprotein concentration after successful treatment of teratoma. Author(s): Pandha HS, Wasan HS, Harrington K, Waxman J. Source: Bmj (Clinical Research Ed.). 1995 August 12; 311(7002): 434-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7543786

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Fatty acids and squalene carried by alpha fetoprotein, and fetal and adult serum albumin from chicken. Comparison with these from mammals. Author(s): Copado MA, Ruiz-Gutierrez V, Rodriguez-Burgos A. Source: Journal of Protein Chemistry. 1999 May; 18(4): 413-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10449039

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First trimester biochemical screening for trisomy 21: the role of free beta hCG, alpha fetoprotein and pregnancy associated plasma protein A. Author(s): Spencer K, Aitken DA, Crossley JA, McCaw G, Berry E, Anderson R, Connor JM, Macri JN. Source: Annals of Clinical Biochemistry. 1994 September; 31 ( Pt 5): 447-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7530437

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Genetic evolution of alpha fetoprotein producing gastric cancer. Author(s): Fujii H, Ichikawa K, Takagaki T, Nakanishi Y, Ikegami M, Hirose S, Shimoda T. Source: Journal of Clinical Pathology. 2003 December; 56(12): 942-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14645355

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Hepatic hemangioendothelioma of infancy associated with elevated alpha fetoprotein and catecholamine by-products. Author(s): Seo IS, Min KW, Mirkin LD. Source: Pediatr Pathol. 1988; 8(6): 625-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2469076

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Human alpha fetoprotein enhances epidermal growth factor proliferative activity upon porcine granulosa cells in monolayer culture. Author(s): Leal JA, May JV, Keel BA. Source: Endocrinology. 1990 January; 126(1): 669-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1688414

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Identification of a balanced translocation carrier by spouse's low maternal serum alpha fetoprotein associated with an aneuploid fetus. Author(s): Byrne-Essif K, Hoyme HE. Source: Journal of Medical Genetics. 1990 November; 27(11): 728. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1703578

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Impact of a regional screening programme using maternal serum alpha fetoprotein (AFP) and human chorionic gonadotrophin (hCG) on the birth incidence of Down's syndrome in the west of Scotland. Author(s): Crossley JA, Aitken DA, Berry E, Connor JM. Source: Journal of Medical Screening. 1994 July; 1(3): 180-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8790513

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Impact of preoperative serum carcinoembryonic antigen, CA 19-9 and alpha fetoprotein levels in gastric cancer patients. Author(s): Nakajima K, Ochiai T, Suzuki T, Shimada H, Hayashi H, Yasumoto A, Takeda A, Hishikawa E, Isono K. Source: Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine. 1998; 19(6): 464-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9817974

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Increased maternal serum alpha fetoprotein in congenital hypothyroidism. Author(s): Ben-Neriah Z, Yagel S, Zelikoviz B, Bach G. Source: Lancet. 1991 February 16; 337(8738): 437. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1704087

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Influence of exposure to tobacco smoke on serum alpha fetoprotein levels of women in midtrimester pregnancy. Author(s): Mathai M, Skinner A, Lawton K, Weindling M. Source: The Indian Journal of Medical Research. 1992 October; 96: 279-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1281137

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Interaction of human alpha fetoprotein with bilirubin. Author(s): Bansal V, Kumari K, Dixit A, Sahib MK. Source: Indian J Exp Biol. 1990 July; 28(7): 697-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1703124

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Is low serum alpha fetoprotein a sensitive marker for diaphragmatic hernia? Author(s): Tam PK, Angeleri EM. Source: Archives of Disease in Childhood. 1990 August; 65(8): 912-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1698045

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Lectin affinity electrophoresis in a yolk sac tumour in the vagina with yolk sac tumour-type glycoform of alpha fetoprotein. Author(s): Yamamoto R, Taketa K, Ebina Y, Cho Y, Hareyama H, Sakuragi N, Makinoda S, Kobayashi K, Nishi S, Fujimoto S. Source: Journal of Clinical Pathology. 1997 October; 50(10): 856-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9462270

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Limb-body-wall complex: another cause for elevated maternal serum alpha fetoprotein. Author(s): Gorczyca DP, Lindfors KK, McGahan JP, Hanson FW. Source: Journal of Clinical Ultrasound : Jcu. 1990 March-April; 18(3): 198-201. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1690220

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Logistic regression generated probability estimates for trisomy 21 outcomes from serum alpha fetoprotein and beta human chorionic gonadotrophin: simplification with increased specificity. Author(s): Evans MI, Chick L, O'Brien JE, Dvorin E, Johnson MP, Krivchenia E, Sokol RJ. Source: The Journal of Maternal-Fetal Medicine. 1996 January-February; 5(1): 1-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8796757

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Markedly elevated serum alpha fetoprotein is an indicator of extrauterine pregnancy. Author(s): Kaur M, Verma IC, Mittal S. Source: American Journal of Medical Genetics. 1997 March 3; 69(1): 112-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9066895

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Maternal serum alpha fetoprotein concentration and fetal sex. Author(s): Petrikovsky B. Source: Prenatal Diagnosis. 1989 June; 9(6): 449-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2474809

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Maternal serum alpha fetoprotein concentrations in mid trimester in hepatitis B surface antigen positive and negative subjects. Author(s): Kitau MJ, Grint P, Heath R, Chard T. Source: Journal of Clinical Pathology. 1987 November; 40(11): 1360-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2447128

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Maternal serum alpha fetoprotein screening project. Author(s): O'Brien WF. Source: J Fla Med Assoc. 1987 May; 74(5): 333-5. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2440976

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Maternal serum alpha fetoprotein testing: some public policy considerations. Author(s): Kasper AS. Source: Women & Health. 1981 Spring-Summer; 6(1-2): 147-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11650640

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Meningitis carcinomatosa originating from an alpha fetoprotein-producing gastric cancer. Author(s): Tsujikawa T, Tsukamoto H, Itoh A, Andoh A, Sasaki M, Koyama S, Fujiyama Y, Bamba T. Source: Intern Med. 2000 March; 39(3): 223-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10772124

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Ovarian Sertoli-Leydig cell tumour with raised serum alpha fetoprotein. A case report. Author(s): Tiltman A, Dehaeck K, Soeters R, Goldberg G, Levin W. Source: Virchows Arch a Pathol Anat Histopathol. 1986; 410(2): 107-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2432721

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Plasma alpha fetoprotein reference ranges in infancy: effect of prematurity. Author(s): Blair JI, Carachi R, Gupta R, Sim FG, McAllister EJ, Weston R. Source: Archives of Disease in Childhood. 1987 April; 62(4): 362-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2439023

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Prediction of fetal alcohol syndrome by maternal alpha fetoprotein, human placental lactogen and pregnancy specific beta 1-glycoprotein. Author(s): Halmesmaki E, Autti I, Granstrom ML, Heikinheimo M, Raivio KO, Ylikorkala O. Source: Alcohol and Alcoholism (Oxford, Oxfordshire). 1987; Suppl 1: 473-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2447904

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Purified human alpha fetoprotein inhibits growth factor-stimulated estradiol production by porcine granulosa cells in monolayer culture. Author(s): Keel BA, Eddy KB, Cho S, Gangrade BK, May JV. Source: Endocrinology. 1992 June; 130(6): 3715-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1375908

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Second trimester maternal serum screening using alpha fetoprotein, free beta human chorionic gonadotropin and maternal age specific risk: result of chromosomal abnormalities detected in screen positive for Down syndrome in an Asian population. Author(s): Chao AS, Chung CL, Wu CD, Chang SD, Cheng PJ, Lin YT, Soong YK. Source: Acta Obstetricia Et Gynecologica Scandinavica. 1999 May; 78(5): 393-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10326883

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Serum alpha fetoprotein in 714 mentally retarded carriers of hepatitis B surface antigen. Author(s): Lohiya G, Lohiya S, Fischer T, Nguyen H, Vuu T, Humerez R. Source: European Journal of Epidemiology. 1988 June; 4(2): 181-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2456944

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Study of serum prealbumin and serum alpha fetoprotein in cases of fulminant hepatic failure. Author(s): Jain SK, Rohatgi A, Raman KK, Sharma VK. Source: J Assoc Physicians India. 1995 July; 43(7): 462-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8713217

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T cell responses to HLA-A*0201-restricted peptides derived from human alpha fetoprotein. Author(s): Butterfield LH, Meng WS, Koh A, Vollmer CM, Ribas A, Dissette VB, Faull K, Glaspy JA, McBride WH, Economou JS. Source: Journal of Immunology (Baltimore, Md. : 1950). 2001 April 15; 166(8): 5300-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11290817

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The role of umbilical cord alpha fetoprotein as a screening tool for neonatal hyperbilirubinemia. Author(s): Riskin A, David M, Peskin B, Tamir A, Vafsi O, Leibovitz Z, Riskin-Mashiah S, Israel N, Merksamer R, Bader D. Source: American Journal of Perinatology. 2004 February; 21(2): 93-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15017473

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Type III congenital cystic adenomatoid malformation of the lung: another cause of elevated alpha fetoprotein? Author(s): Petit P, Bossens M, Thomas D, Moerman P, Fryns JP, Van den Berghe H. Source: Clinical Genetics. 1987 September; 32(3): 172-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2441912

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Ultrasound scanning in women with raised serum alpha fetoprotein: short term psychological effect. Author(s): Tsoi MM, Hunter M, Pearce M, Chudleigh P, Campbell S. Source: Journal of Psychosomatic Research. 1987; 31(1): 35-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2434650

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Unexplained elevated midtrimester maternal serum levels of alpha fetoprotein, human chorionic gonadotropin, or low unconjugated estriol: recurrence risk and association with adverse perinatal outcome. Author(s): Wax JR, Lopes AM, Benn PA, Lerer T, Steinfeld JD, Ingardia CJ. Source: The Journal of Maternal-Fetal Medicine. 2000 May-June; 9(3): 161-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10914623

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

Endodermal sinus tumor of the ovary and alpha fetoprotein: a case report. Author(s): Thomas JH, Panoussopoulos DG, Jewell WR. Source: Journal of Surgical Oncology. 1977; 9(5): 431-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=73632

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Is ectopic production of human chorionic gonadotrophin (hCG) or alpha fetoprotein (AFP) by tumours a marker of chemosensitivity? Author(s): Crawford SM, Ledermann JA, Turkie W, Rustin GJ, Begent RH, Newlands ES, Bagshawe KD. Source: Eur J Cancer Clin Oncol. 1986 December; 22(12): 1483-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2439342

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Unresectable alpha fetoprotein-producing gastric cancer successfully treated with irinotecan and mitomycin C after S-1 failure. Author(s): Hirao K, Hirasaki S, Tsuzuki T, Kajiwara T, Hyodo I. Source: Intern Med. 2004 February; 43(2): 106-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15005251

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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CHAPTER 3. PATENTS ON ALPHA FETOPROTEIN 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.4 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 “alpha fetoprotein” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on alpha fetoprotein, we have not necessarily excluded nonmedical patents in this bibliography.

Patents on Alpha Fetoprotein By performing a patent search focusing on alpha fetoprotein, 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. 4Adapted from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.

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Alpha Fetoprotein

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

Composition and method for detecting cancer with technetium labeled antibody fragments Inventor(s): Burchiel; Scott W. (Albuquerque, NM), Crockford; David R. (Haverhill, MA), Rhodes; Buck A. (Albuquerque, NM) Assignee(s): Nuc-Med, Inc. (Albuquerque, NM), University Patents, Inc. (Norwalk, CT) Patent Number: 4,478,815 Date filed: June 2, 1981 Abstract: F(ab').sub.2 or Fab fragments of antibodies to: (a) human chorionic gonadotropin (hCG), hCG alpha subunit, hCG beta subunit, or an hCG-like material; or (b) other tumor specific or tumor associated molecules, to include carcinoembryonic antigen (CEA), alpha fetoprotein (AFP), human melanoma associated antigens, human sarcoma associated antigens or other antigens, are radiolabeled with technetium-99m (Tc-99m). When the F(ab').sub.2 or Fab fragments of antibody to such tumor associated antigens are injected intravenously into a patient, the radiolabeled composition accumulates at tumor sites. The accumulation of the cancer seeking radiopharmaceutical at tumor sites permits detection by external gamma scintigraphy. Thus, the composition is useful in the monitoring, localization and detection of cancer in the body.In an alternative composition, a double antibody approach to tumor localization using radiolabeled F(ab').sub.2 or Fab fragments is utilized. In this approach, a tumor specific antibody in the form of IgG, F(ab').sub.2 or Fab is first administered to a patient intravenously. Following a sufficient period of time, a second antibody in the form of F(ab').sub.2 or Fab is administered. The second antibody is radiolabeled with Tc-99m and has the property that it is reactive with the first antibody. This double antibody method has the advantage over a single antibody approach in that smaller tumors can be localized and detected and that the total amount of radioactive trace localized at the cancer site is increased. Excerpt(s): This invention relates to compositions and methods capable of detecting cancer cells or malignant tumors in humans. More particularly, this invention relates to compositions radio-labeled with Tc-99m which, when administered to a human, will accumulate at tumor sites producing a) human chorionic gonadotropin (hCG), hCG alpha subunit, hCG beta subunit or an hCG-like material or b) any other tumor associated antigen to which an antibody molecule can be prepared to include carcinoembryonic antigen (CEA) or the like. The use of compositions which emit radiation at levels which can be detected after administration to the human body are well known. These compositions are utilized to visualize and/or monitor the functioning of various parts of the body or are used diagnostically to determine the absence or presence of particular tissue damage or disease. In one particular aspect of the prior art, radiolabeled antibodies are utilized to detect tumors having associated therewith carcinoembryonic antigen (CEA). As disclosed in U.S. Pats. Nos. 3,663,684, 3,867,363 and 3,927,193, I.sup.131 or I.sup.125 labeled antibodies to CEA are utilized to detect tumors which produce or are associated with CEA. Recently, it has been found that neoplastic tissues produce and/or express on their surface chorionic gonadotropin, chorionic gonadotropin-like material, compounds similar to and/or identical to the alpha-chain or beta-chain of chorionic gonadotropin or mixtures thereof, specifically to the degree where it is considered a more general marker than either carcinoembryonic antigen (CEA) or alphafetoprotein (AFP), (Acevedo et al., "Detection and Prevention of

Patents 33

Cancer", Part 2, Vol. I, H. E. Nieburgs (ED) Marcel Dekker, Inc., New York, 1978, pp. 937-979). The positive identification of chorionic gonadotropin in a heterogenous group of cancer cells and its non-detection in non-cancer cells in vitro has suggested to these authors that the compound is a common antigen (common denominator) of every cell with oncogenic properties. Web site: http://www.delphion.com/details?pn=US04478815__

Patent Applications on Alpha Fetoprotein As of December 2000, U.S. patent applications are open to public viewing.5 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 alpha fetoprotein: •

Method and compositions for treating hepatocellular cancer Inventor(s): Butterfield, Lisa H.; (Long Beach, CA), Economou, James S.; (Pacific Palisades, CA), Ribas Bruguera, Antoni; (Los Angeles, CA) Correspondence: David A. Farah, M.D.; Sheldon & Mak; 9th Floor; 225 South Lake Avenue; Pasadena; CA; 91101; US Patent Application Number: 20030143237 Date filed: August 7, 2002 Abstract: A method for preventing or for treating cancer in a mammal, where the cancer cells express at least a part of an alpha fetoprotein molecule at the cell surface. The method comprises creating an immune response in the mammal to at least part of the amino acid sequence of an alpha fetoprotein molecule, where the immune response comprises activating alpha fetoprotein peptide specific T lymphocytes against the cancer cells, and where the part of the alpha fetoprotein molecule is selected from the group consisting of residues 137-145 of SEQ ID NO:2, and residues 325-334 of SEQ ID NO:2 and a combination of the preceeding. Excerpt(s): The present application claims the benefit of U.S. Patent Application No. 60/339,690, filed Dec. 12, 2001; and the present application is a continuation of U.S. patent application Ser. No. 09/781,844, filed Feb. 12, 2001, which claims the benefit of U.S. Provisional Patent Application No. 60/181,966, filed Feb. 10, 2000; and the present application is a continuation of PCT Patent Application PCT/US01/04539, filed Feb. 12, 2001, which is a continuation-in-part of U.S. patent application Ser. No. 09/662,505, filed Sep. 14, 2000 and U.S. patent application Ser. No. 09/660,252, filed Sep. 12, 2000, which are divisional applications of U.S. patent application Ser. No. 09/373,913, filed Aug. 12, 1999, which is a continuation of PCT/US98/02753, filed Feb. 13, 1998, which claims the benefit of U.S. Patent Application No. 60/038,375, filed Feb. 13, 1997; and the contents of all of which are incorporated by reference herein in their entirety. Primary liver cancer is a major cause of cancer deaths worldwide. Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, having a global incidence of approximately 1.2 million cases per year. In some areas of the world, such as Southeast Asia and Subsahara Africa, hepatocellular carcinoma is one of the most common types of malignancies. The high frequency of the disease appears to be related to the high incidence of viral

5

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

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Alpha Fetoprotein

hepatitis in these regions. Curative therapy of hepatocellular carcinoma is currently limited to individuals with nonmetastatic disease and involves surgical resection of the tumor with or without liver transplantation. Even surgical resection and transplantation, however, do not cure most tumors because of recurrence after resection. Chemotherapeutic approaches to treatment have been largely ineffective. 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 alpha fetoprotein, 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 “alpha fetoprotein” (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 alpha fetoprotein. You can also use this procedure to view pending patent applications concerning alpha fetoprotein. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.

35

CHAPTER 4. BOOKS ON ALPHA FETOPROTEIN Overview This chapter provides bibliographic book references relating to alpha fetoprotein. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on alpha fetoprotein include the Combined Health Information Database and the National Library of Medicine. Your local medical library also may have these titles available for loan.

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

Medical Management of Pregnancy Complicated by Diabetes. 3rd ed Source: Alexandria, VA: American Diabetes Association. 2000. 176 p. Contact: Available from American Diabetes Association (ADA). Order Fulfillment Department, P.O. Box 930850, Atlanta, GA 31193-0850. (800) 232-6733. Fax (770) 4429742. Website: www.diabetes.org. PRICE: $39.95 plus shipping and handling. ISBN: 1580400132. Summary: This book, which is part of the American Diabetes Association's Clinical Education Series, provides health professionals with protocols that have resulted in healthy infants in pregnancies complicated by type 1, type 2, or gestational diabetes. The first section focuses on prepregnancy counseling and management of women with preexisting diabetes or previous gestational diabetes. The next section discusses contraceptive methods, including oral contraceptives, the norplant system, barrier

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Alpha Fetoprotein

methods, intrauterine devices, the rhythm method, and permanent sterilization. This is followed by a section that examines the psychological impact of diabetes and pregnancy. Topics include the response to pregnancy in women with preexisting diabetes, the response to a diagnosis of gestational diabetes, long term adaptation, personality types and individualizing treatment, pregnancy crises, and the importance of a team approach and a support system. The fourth section focuses on blood glucose monitoring. Topics include glycosylated hemoglobin measurements in pregnancy for women with preexisting or gestational diabetes, self monitoring of blood glucose and urine ketones, and medical tests to evaluate maternal status in women with preexisting or gestational diabetes. The next section offers guidelines for managing morning sickness with dietary remedies, insulin adjustments, and medical management. The sixth section discusses nutritional management during pregnancy in women with preexisting diabetes. Topics include patient responsibility; the nutrient needs of pregnancy; diet and eating habits; vitamin and mineral supplementation; calorie level; weight gain; meal planning; recordkeeping; use of sodium, caffeine, and artificial sweeteners; the management of hypoglycemia; and postpartum nutritional management. Section seven focuses on the use of insulin during pregnancy in women with preexisting diabetes. Topics include metabolic alterations during normal gestation, therapeutic insulin use, dosage adjustment, insulin during labor and delivery, postpartum insulin requirements, and oral hypoglycemic agents. The next section describes diagnostic tests and methods of fetal surveillance, including ultrasonography, alpha fetoprotein testing, genetic testing, fetal monitoring, and amniocentesis. The ninth section discusses gestational diabetes, focusing on epidemiology, screening, diagnosis, nutritional management, insulin therapy, exercise, and obstetric management. Section ten addresses the issue of neonatal care of infants of women with diabetes. Topics include perinatal mortality and morbidity, resuscitation, nursery care, and long term followup. The final section discusses postpartum followup of women with gestational diabetes. The book includes an index and resources for health care professionals. 3 figures. 39 tables. Numerous references.

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

37

APPENDICES

39

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 Institute6: •

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

6

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

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Alpha Fetoprotein

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

Physician Resources

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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.7 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:8 •

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

7 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). 8 See http://www.nlm.nih.gov/databases/databases.html.

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•

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

•

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

The NLM Gateway9 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.10 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “alpha fetoprotein” (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 13767 233 479 9 49 14537

HSTAT11 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.12 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.13 Simply search by “alpha fetoprotein” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

9

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

10

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). 11 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 12 13

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

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

Physician Resources

43

Coffee Break: Tutorials for Biologists14 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.15 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.16 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/.

14 Adapted 15

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. 16 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 alpha fetoprotein 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 alpha fetoprotein. 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 alpha fetoprotein. 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 “alpha fetoprotein”:

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Alpha Fetoprotein

Birth Defects http://www.nlm.nih.gov/medlineplus/birthdefects.html Hepatitis B http://www.nlm.nih.gov/medlineplus/hepatitisb.html Hepatitis C http://www.nlm.nih.gov/medlineplus/hepatitisc.html High Risk Pregnancy http://www.nlm.nih.gov/medlineplus/highriskpregnancy.html Liver Cancer http://www.nlm.nih.gov/medlineplus/livercancer.html Prenatal Testing http://www.nlm.nih.gov/medlineplus/prenataltesting.html Testicular Cancer http://www.nlm.nih.gov/medlineplus/testicularcancer.html You may also choose to use the search utility provided by MEDLINEplus at the following Web address: http://www.nlm.nih.gov/medlineplus/. Simply type a keyword into the search box and click “Search.” This utility is similar to the NIH search utility, with the exception that it only includes materials that are linked within the MEDLINEplus system (mostly patient-oriented information). It also has the disadvantage of generating unstructured results. We recommend, therefore, that you use this method only if you have a very targeted search. The Combined Health Information Database (CHID) CHID Online is a reference tool that maintains a database directory of thousands of journal articles and patient education guidelines on alpha fetoprotein. CHID offers summaries that describe the guidelines available, including contact information and pricing. CHID’s general Web site is http://chid.nih.gov/. To search this database, go to http://chid.nih.gov/detail/detail.html. In particular, you can use the advanced search options to look up pamphlets, reports, brochures, and information kits. The following was recently posted in this archive: •

Maternal serum alpha fetoprotein screening test Source: San Diego, CA: San Diego- Imperial Counties Developmental Services. n.d. 4 pp. Contact: Available from James O. Cleveland, Ed. D., San Diego- Imperial Counties Developmental Services, 4355 Ruffin Road, Suite 205, San Diego, CA 92123. Telephone: (619) 576-2813 / fax: 619-576-2873. Summary: This booklet provides a brief explanation of the maternal serum alpha fetoprotein screening test and explains what the results of the test may may indicate. It is available in English, Spanish, Laotian, and Vietnamese. [Funded by the Maternal and Child Health Bureau].

•

Maternal serum alpha fetoprotein testing Source: New York, NY: Beth Israel Medical Center and New York State Department of Health. n.d. 1 p.

Patient Resources

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Contact: Available from Beth Israel Medical Center, Division of Medical Genetics, First Avenue and 16th Street, New York, NY 10003. Telephone: (212) 420-4179. Summary: This pamphlet describes facts about maternal serum alpha fetoprotein testing in Chinese. 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 alpha fetoprotein. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html. Additional Web Sources A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •

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

•

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

•

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

•

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

•

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

•

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

•

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

Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to alpha fetoprotein. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with alpha fetoprotein. 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 alpha fetoprotein. 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.

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Alpha Fetoprotein

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 “alpha fetoprotein” (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 “alpha fetoprotein”. 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 “alpha fetoprotein” (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 “alpha fetoprotein” (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.17

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

17

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)18: •

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

•

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

•

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

•

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

•

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

•

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

•

California: Gateway Health Library (Sutter Gould Medical Foundation)

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

18

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

Finding Medical Libraries

51

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

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•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

Finding Medical Libraries

53

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

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•

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

•

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

•

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

•

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

55

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

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

•

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

•

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

•

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

•

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

•

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

•

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

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

Basic Guidelines for Alpha Fetoprotein Alpha fetoprotein Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003573.htm

•

Signs & Symptoms for Alpha Fetoprotein Fainting Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003092.htm

•

Diagnostics and Tests for Alpha Fetoprotein Albumin Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003480.htm Amniocentesis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003921.htm Blood pressure Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003398.htm

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Venipuncture Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003423.htm •

Nutrition for Alpha Fetoprotein Protein Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002467.htm

•

Background Topics for Alpha Fetoprotein Adolescent test or procedure preparation Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002054.htm Bleeding Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000045.htm Infant test or procedure preparation Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002055.htm Preschooler test or procedure preparation Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002057.htm Schoolage test or procedure preparation Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002058.htm Testes Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002334.htm Toddler test or procedure preparation Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002056.htm

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

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

•

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

•

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

57

ALPHA FETOPROTEIN DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] 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] Accommodation: Adjustment, especially that of the eye for various distances. [EU] Acetaminophen: Analgesic antipyretic derivative of acetanilide. It has weak antiinflammatory properties and is used as a common analgesic, but may cause liver, blood cell, and kidney damage. [NIH] Acetylcholine: A neurotransmitter. Acetylcholine in vertebrates is the major transmitter at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. It is generally not used as an administered drug because it is broken down very rapidly by cholinesterases, but it is useful in some ophthalmological applications. [NIH] Acetylcholinesterase: An enzyme that catalyzes the hydrolysis of acetylcholine to choline and acetate. In the CNS, this enzyme plays a role in the function of peripheral neuromuscular junctions. EC 3.1.1.7. [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] Adenocarcinoma: A malignant epithelial tumor with a glandular organization. [NIH] Adenosine: A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. [NIH] Adenovirus: A group of viruses that cause respiratory tract and eye infections. Adenoviruses used in gene therapy are altered to carry a specific tumor-fighting gene. [NIH] Adjustment: The dynamic process wherein the thoughts, feelings, behavior, and biophysiological mechanisms of the individual continually change to adjust to the environment. [NIH] Adjuvant: A substance which aids another, such as an auxiliary remedy; in immunology, nonspecific stimulator (e.g., BCG vaccine) of the immune response. [EU] Adrenal Cortex: The outer layer of the adrenal gland. It secretes mineralocorticoids, androgens, and glucocorticoids. [NIH] Adrenal Medulla: The inner part of the adrenal gland; it synthesizes, stores and releases

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catecholamines. [NIH] Adverse Effect: An unwanted side effect of treatment. [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] Agonist: In anatomy, a prime mover. In pharmacology, a drug that has affinity for and stimulates physiologic activity at cell receptors normally stimulated by naturally occurring substances. [EU] Albumin: 1. Any protein that is soluble in water and moderately concentrated salt solutions and is coagulable by heat. 2. Serum albumin; the major plasma protein (approximately 60 per cent of the total), which is responsible for much of the plasma colloidal osmotic pressure and serves as a transport protein carrying large organic anions, such as fatty acids, bilirubin, and many drugs, and also carrying certain hormones, such as cortisol and thyroxine, when their specific binding globulins are saturated. Albumin is synthesized in the liver. Low serum levels occur in protein malnutrition, active inflammation and serious hepatic and renal disease. [EU] 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] Allantois: An embryonic diverticulum of the hindgut of reptiles, birds, and mammals; in man its blood vessels give rise to those of the umbilical cord. [NIH] Allogeneic: Taken from different individuals of the same species. [NIH] Allografts: A graft of tissue obtained from the body of another animal of the same species but with genotype differing from that of the recipient; tissue graft from a donor of one genotype to a host of another genotype with host and donor being members of the same species. [NIH] 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-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,

Dictionary 59

magnet therapy, spiritual healing, and meditation. [NIH] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Amino Acid Substitution: The naturally occurring or experimentally induced replacement of one or more amino acids in a protein with another. If a functionally equivalent amino acid is substituted, the protein may retain wild-type activity. Substitution may also diminish or eliminate protein function. Experimentally induced substitution is often used to study enzyme activities and binding site properties. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amniocentesis: Percutaneous transabdominal puncture of the uterus during pregnancy to obtain amniotic fluid. It is commonly used for fetal karyotype determination in order to diagnose abnormal fetal conditions. [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] Amphetamines: Analogs or derivatives of amphetamine. Many are sympathomimetics and central nervous system stimulators causing excitation, vasopression, bronchodilation, and to varying degrees, anorexia, analepsis, nasal decongestion, and some smooth muscle relaxation. [NIH] Anaerobic: 1. Lacking molecular oxygen. 2. Growing, living, or occurring in the absence of molecular oxygen; pertaining to an anaerobe. [EU] Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Analogous: Resembling or similar in some respects, as in function or appearance, but not in origin or development;. [EU] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Aneuploidy: The chromosomal constitution of cells which deviate from the normal by the addition or subtraction of chromosomes or chromosome pairs. In a normally diploid cell the loss of a chromosome pair is termed nullisomy (symbol: 2N-2), the loss of a single chromosome is monosomy (symbol: 2N-1), the addition of a chromosome pair is tetrasomy (symbol: 2N+2), the addition of a single chromosome is trisomy (symbol: 2N+1). [NIH] Animal model: An animal with a disease either the same as or like a disease in humans. Animal models are used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis. [NIH] 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

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Alpha Fetoprotein

supplies) or to production of a specific antibiotic substance (e. g. penicillin). [NIH] 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-presenting cell: APC. A cell that shows antigen on its surface to other cells of the immune system. This is an important part of an immune response. [NIH] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Anti-Inflammatory Agents: Substances that reduce or suppress inflammation. [NIH] Antineoplastic: Inhibiting or preventing the development of neoplasms, checking the maturation and proliferation of malignant cells. [EU] Antiviral: Destroying viruses or suppressing their replication. [EU] Anus: The opening of the rectum to the outside of the body. [NIH] Apolipoproteins: The protein components of lipoproteins which remain after the lipids to which the proteins are bound have been removed. They play an important role in lipid transport and metabolism. [NIH] Apoptosis: One of the two mechanisms by which cell death occurs (the other being the pathological process of necrosis). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA (DNA fragmentation) at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. [NIH] Aqueous: Having to do with water. [NIH] Arteries: The vessels carrying blood away from the heart. [NIH] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Artery: Vessel-carrying blood from the heart to various parts of the body. [NIH] Aspiration: The act of inhaling. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the

Dictionary 61

biological or pharmacological potency of a drug. [EU] Asymptomatic: Having no signs or symptoms of disease. [NIH] Autologous: Taken from an individual's own tissues, cells, or DNA. [NIH] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Bacterial Physiology: Physiological processes and activities of bacteria. [NIH] Base: In chemistry, the nonacid part of a salt; a substance that combines with acids to form salts; a substance that dissociates to give hydroxide ions in aqueous solutions; a substance whose molecule or ion can combine with a proton (hydrogen ion); a substance capable of donating a pair of electrons (to an acid) for the formation of a coordinate covalent bond. [EU] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]

Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Bile Acids: Acids made by the liver that work with bile to break down fats. [NIH] Bile Acids and Salts: Steroid acids and salts. The primary bile acids are derived from cholesterol in the liver and usually conjugated with glycine or taurine. The secondary bile acids are further modified by bacteria in the intestine. They play an important role in the digestion and absorption of fat. They have also been used pharmacologically, especially in the treatment of gallstones. [NIH] Bilirubin: A bile pigment that is a degradation product of heme. [NIH] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biomarkers: Substances sometimes found in an increased amount in the blood, other body fluids, or tissues and that may suggest the presence of some types of cancer. Biomarkers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and GI tract cancers), and PSA (prostate cancer). Also called tumor markers. [NIH] Biosynthesis: The building up of a chemical compound in the physiologic processes of a living organism. [EU] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Bladder: The organ that stores urine. [NIH] Blastocyst: The mammalian embryo in the post-morula stage in which a fluid-filled cavity, enclosed primarily by trophoblast, contains an inner cell mass which becomes the embryonic disc. [NIH] Blood Glucose: Glucose in blood. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH]

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Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Body Fluids: Liquid components of living organisms. [NIH] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bowel: The long tube-shaped organ in the abdomen that completes the process of digestion. There is both a small and a large bowel. Also called the intestine. [NIH] Brachytherapy: A collective term for interstitial, intracavity, and surface radiotherapy. It uses small sealed or partly-sealed sources that may be placed on or near the body surface or within a natural body cavity or implanted directly into the tissues. [NIH] Bradykinin: A nonapeptide messenger that is enzymatically produced from kallidin in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from mast cells during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter. [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 many enzymatic processes. [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] 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] Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen are usually in the proportion to form water, (CH2O)n. The most important carbohydrates are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, polyand heterosaccharides. [EU] Carbon Dioxide: A colorless, odorless gas that can be formed by the body and is necessary for the respiration cycle of plants and animals. [NIH] Carcinoembryonic Antigen: A glycoprotein that is secreted into the luminal surface of the

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epithelia in the gastrointestinal tract. It is found in the feces and pancreaticobiliary secretions and is used to monitor the respone to colon cancer treatment. [NIH] Carcinogen: Any substance that causes cancer. [NIH] Carcinogenesis: The process by which normal cells are transformed into cancer cells. [NIH] Carcinogenic: Producing carcinoma. [EU] Carcinoma: Cancer that begins in the skin or in tissues that line or cover internal organs. [NIH]

Cardiac: Having to do with the heart. [NIH] Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes. [NIH] Case report: A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin). [NIH] Catabolism: Any destructive metabolic process by which organisms convert substances into excreted compounds. [EU] Catecholamine: A group of chemical substances manufactured by the adrenal medulla and secreted during physiological stress. [NIH] Causal: Pertaining to a cause; directed against a cause. [EU] Celecoxib: A drug that reduces pain. Celecoxib belongs to the family of drugs called nonsteroidal anti-inflammatory agents. It is being studied for cancer prevention. [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] 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] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Chemoprevention: The use of drugs, vitamins, or other agents to try to reduce the risk of, or delay the development or recurrence of, cancer. [NIH] Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. [NIH] Cholesterol Esters: Fatty acid esters of cholesterol which constitute about two-thirds of the cholesterol in the plasma. The accumulation of cholesterol esters in the arterial intima is a characteristic feature of atherosclerosis. [NIH] Cholic Acid: A major primary bile acid produced in the liver and usually conjugated with glycine or taurine. It facilitates fat absorption and cholesterol excretion. [NIH] Choline: A basic constituent of lecithin that is found in many plants and animal organs. It is important as a precursor of acetylcholine, as a methyl donor in various metabolic processes, and in lipid metabolism. [NIH] Chorion: The outermost extraembryonic membrane. [NIH] Chromatin: The material of chromosomes. It is a complex of DNA, histones, and nonhistone

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proteins (chromosomal proteins, non-histone) found within the nucleus of a cell. [NIH] Chromosomal: Pertaining to chromosomes. [EU] Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chylomicrons: A class of lipoproteins that carry dietary cholesterol and triglycerides from the small intestines to the tissues. [NIH] Cirrhosis: A type of chronic, progressive liver disease. [NIH] Clear cell carcinoma: A rare type of tumor of the female genital tract in which the inside of the cells looks clear when viewed under a microscope. [NIH] Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH] Coagulation: 1. The process of clot formation. 2. In colloid chemistry, the solidification of a sol into a gelatinous mass; an alteration of a disperse phase or of a dissolved solid which causes the separation of the system into a liquid phase and an insoluble mass called the clot or curd. Coagulation is usually irreversible. 3. In surgery, the disruption of tissue by physical means to form an amorphous residuum, as in electrocoagulation and photocoagulation. [EU] Coca: Any of several South American shrubs of the Erythroxylon genus (and family) that yield cocaine; the leaves are chewed with alum for CNS stimulation. [NIH] Cocaine: An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake. [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] 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

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to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Conception: The onset of pregnancy, marked by implantation of the blastocyst; the formation of a viable zygote. [EU] Confounding: Extraneous variables resulting in outcome effects that obscure or exaggerate the "true" effect of an intervention. [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] Consciousness: Sense of awareness of self and of the environment. [NIH] Contraceptive: An agent that diminishes the likelihood of or prevents conception. [EU] 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] Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [EU] Cortisol: A steroid hormone secreted by the adrenal cortex as part of the body's response to stress. [NIH] Crossing-over: The exchange of corresponding segments between chromatids of homologous chromosomes during meiosia, forming a chiasma. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Cyanosis: A bluish or purplish discoloration of the skin and mucous membranes due to an increase in the amount of deoxygenated hemoglobin in the blood or a structural defect in the

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hemoglobin molecule. [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] Cytokine: Small but highly potent protein that modulates the activity of many cell types, 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] Cytotoxic: Cell-killing. [NIH] Decidua: The epithelial lining of the endometrium that is formed before the fertilized ovum reaches the uterus. The fertilized ovum embeds in the decidua. If the ovum is not fertilized, the decidua is shed during menstruation. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other neurons. [NIH] Dendritic: 1. Branched like a tree. 2. Pertaining to or possessing dendrites. [EU] Dendritic cell: A special type of antigen-presenting cell (APC) that activates T lymphocytes. [NIH]

DES: Diethylstilbestrol. A synthetic hormone that was prescribed from the early 1940s until 1971 to help women with complications of pregnancy. DES has been linked to an increased risk of clear cell carcinoma of the vagina in daughters of women who used DES. DES may also increase the risk of breast cancer in women who used DES. [NIH] Diabetes Mellitus: A heterogeneous group of disorders that share glucose intolerance in common. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Digestive tract: The organs through which food passes when food is eaten. These organs are the mouth, esophagus, stomach, small and large intestines, and rectum. [NIH] 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] 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] Diuresis: Increased excretion of urine. [EU] Dopamine: An endogenous catecholamine and prominent neurotransmitter in several

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systems of the brain. In the synthesis of catecholamines from tyrosine, it is the immediate precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of dopaminergic receptor subtypes mediate its action. Dopamine is used pharmacologically for its direct (beta adrenergic agonist) and indirect (adrenergic releasing) sympathomimetic effects including its actions as an inotropic agent and as a renal vasodilator. [NIH] Drug Tolerance: Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from drug resistance wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from maximum tolerated dose and no-observed-adverse-effect level. [NIH] Duct: A tube through which body fluids pass. [NIH] Duodenum: The first part of the small intestine. [NIH] Dyslipidemia: Disorders in the lipoprotein metabolism; classified as hypercholesterolemia, hypertriglyceridemia, combined hyperlipidemia, and low levels of high-density lipoprotein (HDL) cholesterol. All of the dyslipidemias can be primary or secondary. Both elevated levels of low-density lipoprotein (LDL) cholesterol and low levels of HDL cholesterol predispose to premature atherosclerosis. [NIH] Ectopic: Pertaining to or characterized by ectopia. [EU] 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] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electrons: Stable elementary particles having the smallest known negative charge, present in all elements; also called negatrons. Positively charged electrons are called positrons. The numbers, energies and arrangement of electrons around atomic nuclei determine the chemical identities of elements. Beams of electrons are called cathode rays or beta rays, the latter being a high-energy biproduct of nuclear decay. [NIH] 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] Embryo Transfer: Removal of a mammalian embryo from one environment and replacement in the same or a new environment. The embryo is usually in the pre-nidation phase, i.e., a blastocyst. The process includes embryo or blastocyst transplantation or transfer after in vitro fertilization and transfer of the inner cell mass of the blastocyst. It is not used for transfer of differentiated embryonic tissue, e.g., germ layer cells. [NIH] Encephalitis: Inflammation of the brain due to infection, autoimmune processes, toxins, and other conditions. Viral infections (see encephalitis, viral) are a relatively frequent cause of this condition. [NIH] Encephalocele: Cerebral tissue herniation through a congenital or acquired defect in the skull. The majority of congenital encephaloceles occur in the occipital or frontal regions. Clinical features include a protuberant mass that may be pulsatile. The quantity and location of protruding neural tissue determines the type and degree of neurologic deficit. Visual defects, psychomotor developmental delay, and persistent motor deficits frequently occur. [NIH]

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Encephalomyelitis: A general term indicating inflammation of the brain and spinal cord, often used to indicate an infectious process, but also applicable to a variety of autoimmune and toxic-metabolic conditions. There is significant overlap regarding the usage of this term and encephalitis in the literature. [NIH] Endoderm: The inner of the three germ layers of the embryo. [NIH] Endogenous: Produced inside an organism or cell. The opposite is external (exogenous) production. [NIH] Endometrium: The layer of tissue that lines the uterus. [NIH] Enhancer: Transcriptional element in the virus genome. [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]

Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. [NIH] Epidemiological: Relating to, or involving epidemiology. [EU] Epidermal: Pertaining to or resembling epidermis. Called also epidermic or epidermoid. [EU] Epidermal Growth Factor: A 6 kD polypeptide growth factor initially discovered in mouse submaxillary glands. Human epidermal growth factor was originally isolated from urine based on its ability to inhibit gastric secretion and called urogastrone. epidermal growth factor exerts a wide variety of biological effects including the promotion of proliferation and differentiation of mesenchymal and epithelial cells. [NIH] Epidermis: Nonvascular layer of the skin. It is made up, from within outward, of five layers: 1) basal layer (stratum basale epidermidis); 2) spinous layer (stratum spinosum epidermidis); 3) granular layer (stratum granulosum epidermidis); 4) clear layer (stratum lucidum epidermidis); and 5) horny layer (stratum corneum epidermidis). [NIH] Epigastric: Having to do with the upper middle area of the abdomen. [NIH] Epithelial: Refers to the cells that line the internal and external surfaces of the body. [NIH] Epithelial Cells: Cells that line the inner and outer surfaces of the body. [NIH] Epithelium: One or more layers of epithelial cells, supported by the basal lamina, which covers the inner or outer surfaces of the body. [NIH] Epitope: A molecule or portion of a molecule capable of binding to the combining site of an antibody. For every given antigenic determinant, the body can construct a variety of antibody-combining sites, some of which fit almost perfectly, and others which barely fit. [NIH]

Epitope Mapping: Methods used for studying the interactions of antibodies with specific regions of protein antigens. Important applications of epitope mapping are found within the area of immunochemistry. [NIH] Escalation: Progressive use of more harmful drugs. [NIH] Estradiol: The most potent mammalian estrogenic hormone. It is produced in the ovary, placenta, testis, and possibly the adrenal cortex. [NIH] Estriol: (16 alpha,17 beta)-Estra-1,3,5(10)-triene-3,16,17-triol. A metabolite of estradiol and usually the predominant estrogenic metabolite in urine. During pregnancy, large amounts of estriol are produced by the placenta. It has also been obtained from plant sources. The 16 beta-isomer has also been isolated from the urine of pregnant women. [NIH]

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Estrogen: One of the two female sex hormones. [NIH] Estrogen receptor: ER. Protein found on some cancer cells to which estrogen will attach. [NIH]

Exocrine: Secreting outwardly, via a duct. [EU] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] External-beam radiation: Radiation therapy that uses a machine to aim high-energy rays at the cancer. Also called external radiation. [NIH] Extracellular: Outside a cell or cells. [EU] Extraction: The process or act of pulling or drawing out. [EU] Eye Infections: Infection, moderate to severe, caused by bacteria, fungi, or viruses, which occurs either on the external surface of the eye or intraocularly with probable inflammation, visual impairment, or blindness. [NIH] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Fat: Total lipids including phospholipids. [NIH] Feces: The excrement discharged from the intestines, consisting of bacteria, cells exfoliated from the intestines, secretions, chiefly of the liver, and a small amount of food residue. [EU] Fertilization in Vitro: Fertilization of an egg outside the body when the egg is normally fertilized in the body. [NIH] Fetal Alcohol Syndrome: A disorder occurring in children born to alcoholic women who continue to drink heavily during pregnancy. Common abnormalities are growth deficiency (prenatal and postnatal), altered morphogenesis, mental deficiency, and characteristic facies - small eyes and flattened nasal bridge. Fine motor dysfunction and tremulousness are observed in the newborn. [NIH] Fetal Membranes: Thin layers of tissue which surround the embryo or fetus and provide for its nutrition, respiration, excretion and protection; they are the yolk sac, allantois, amnion, and chorion. [NIH] Fetal Monitoring: Physiologic or biochemical monitoring of the fetus. It is usually done during labor and may be performed in conjunction with the monitoring of uterine activity. It may also be performed prenatally as when the mother is undergoing surgery. [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] Fibrinogen: Plasma glycoprotein clotted by thrombin, composed of a dimer of three nonidentical pairs of polypeptide chains (alpha, beta, gamma) held together by disulfide bonds. Fibrinogen clotting is a sol-gel change involving complex molecular arrangements: whereas fibrinogen is cleaved by thrombin to form polypeptides A and B, the proteolytic action of other enzymes yields different fibrinogen degradation products. [NIH] Fold: A plication or doubling of various parts of the body. [NIH] Forearm: The part between the elbow and the wrist. [NIH] Fucose: Deoxysugar. [NIH] Fulminant Hepatic Failure: Liver failure that occurs suddenly in a previously healthy person. The most common causes of FHF are acute hepatitis, acetaminophen overdose, and liver damage from prescription drugs. [NIH]

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Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Gamma Rays: Very powerful and penetrating, high-energy electromagnetic radiation of shorter wavelength than that of x-rays. They are emitted by a decaying nucleus, usually between 0.01 and 10 MeV. They are also called nuclear x-rays. [NIH] Gastric: Having to do with the stomach. [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] Gavage: Feeding by a tube passed into the stomach; called also tube feeding. [NIH] Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]

Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Gene Therapy: The introduction of new genes into cells for the purpose of treating disease by restoring or adding gene expression. Techniques include insertion of retroviral vectors, transfection, homologous recombination, and injection of new genes into the nuclei of single cell embryos. The entire gene therapy process may consist of multiple steps. The new genes may be introduced into proliferating cells in vivo (e.g., bone marrow) or in vitro (e.g., fibroblast cultures) and the modified cells transferred to the site where the gene expression is required. Gene therapy may be particularly useful for treating enzyme deficiency diseases, hemoglobinopathies, and leukemias and may also prove useful in restoring drug sensitivity, particularly for leukemia. [NIH] Gene-modified: Cells that have been altered to contain different genetic material than they originally contained. [NIH] Genetic Code: The specifications for how information, stored in nucleic acid sequence (base sequence), is translated into protein sequence (amino acid sequence). The start, stop, and order of amino acids of a protein is specified by consecutive triplets of nucleotides called codons (codon). [NIH] Genetic Engineering: Directed modification of the gene complement of a living organism by such techniques as altering the DNA, substituting genetic material by means of a virus, transplanting whole nuclei, transplanting cell hybrids, etc. [NIH] 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] Gestation: The period of development of the young in viviparous animals, from the time of fertilization of the ovum until birth. [EU] Gestational: Psychosis attributable to or occurring during pregnancy. [NIH] Gestational Age: Age of the conceptus. In humans, this may be assessed by medical history, physical examination, early immunologic pregnancy tests, radiography, ultrasonography, and amniotic fluid analysis. [NIH]

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Gland: An organ that produces and releases one or more substances for use in the body. Some glands produce fluids that affect tissues or organs. Others produce hormones or participate in blood production. [NIH] Glucose: D-Glucose. A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. [NIH] Glycine: A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter. [NIH] Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Glycosidic: Formed by elimination of water between the anomeric hydroxyl of one sugar and a hydroxyl of another sugar molecule. [NIH] Gonadotropin: The water-soluble follicle stimulating substance, by some believed to originate in chorionic tissue, obtained from the serum of pregnant mares. It is used to supplement the action of estrogens. [NIH] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Gp120: 120-kD HIV envelope glycoprotein which is involved in the binding of the virus to its membrane receptor, the CD4 molecule, found on the surface of certain cells in the body. [NIH]

Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to replace diseased or injured tissue removed from another part of the body. [NIH] Graft Rejection: An immune response with both cellular and humoral components, directed against an allogeneic transplant, whose tissue antigens are not compatible with those of the recipient. [NIH] Grafting: The operation of transfer of tissue from one site to another. [NIH] Granulosa Cells: Cells of the membrana granulosa lining the vesicular ovarian follicle which become luteal cells after ovulation. [NIH] Gravidity: Pregnancy; the condition of being pregnant, without regard to the outcome. [EU] Half-Life: The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity. [NIH] 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] 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]

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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] Hepatic: Refers to the liver. [NIH] Hepatitis: Inflammation of the liver and liver disease involving degenerative or necrotic alterations of hepatocytes. [NIH] Hepatocellular: Pertaining to or affecting liver cells. [EU] Hepatocellular carcinoma: A type of adenocarcinoma, the most common type of liver tumor. [NIH] Hepatocyte: A liver cell. [NIH] Hepatoma: A liver tumor. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Hernia: Protrusion of a loop or knuckle of an organ or tissue through an abnormal opening. [NIH]

Heterodimer: Zippered pair of nonidentical proteins. [NIH] Heterogeneity: The property of one or more samples or populations which implies that they are not identical in respect of some or all of their parameters, e. g. heterogeneity of variance. [NIH]

Heterogenic: Derived from a different source or species. Also called heterogenous. [NIH] Heterogenous: Derived from a different source or species. Also called heterogenic. [NIH] Histocompatibility: The degree of antigenic similarity between the tissues of different individuals, which determines the acceptance or rejection of allografts. [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] Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] Hormonal: Pertaining to or of the nature of a hormone. [EU] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [NIH] Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H, atomic number 1, and atomic weight 1. It exists, under normal conditions, as a colorless, odorless, tasteless, diatomic gas. Hydrogen ions are protons. Besides the common H1 isotope, hydrogen exists as the stable isotope deuterium and the unstable, radioactive isotope tritium. [NIH] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hydrophobic: Not readily absorbing water, or being adversely affected by water, as a

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hydrophobic colloid. [EU] Hyperbilirubinemia: Pathologic process consisting of an abnormal increase in the amount of bilirubin in the circulating blood, which may result in jaundice. [NIH] Hypercholesterolemia: Abnormally high levels of cholesterol in the blood. [NIH] Hyperlipidemia: An excess of lipids in the blood. [NIH] Hyperplasia: An increase in the number of cells in a tissue or organ, not due to tumor formation. It differs from hypertrophy, which is an increase in bulk without an increase in the number of cells. [NIH] Hypertriglyceridemia: Condition of elevated triglyceride concentration in the blood; an inherited form occurs in familial hyperlipoproteinemia IIb and hyperlipoproteinemia type IV. It has been linked to higher risk of heart disease and arteriosclerosis. [NIH] Hypertrophy: General increase in bulk of a part or organ, not due to tumor formation, nor to an increase in the number of cells. [NIH] Hypoglycemia: Abnormally low blood sugar [NIH] Hypoglycemic: An orally active drug that produces a fall in blood glucose concentration. [NIH]

Hypoglycemic Agents: Agents which lower the blood glucose level. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]

Immune Sera: Serum that contains antibodies. It is obtained from an animal that has been immunized either by antigen injection or infection with microorganisms containing the antigen. [NIH] Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] Immunity: Nonsusceptibility to the invasive or pathogenic microorganisms or to the toxic effect of antigenic substances. [NIH]

effects

of

foreign

Immunization: Deliberate stimulation of the host's immune response. Active immunization involves administration of antigens or immunologic adjuvants. Passive immunization involves administration of immune sera or lymphocytes or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow). [NIH] Immunochemistry: Field of chemistry that pertains to immunological phenomena and the study of chemical reactions related to antigen stimulation of tissues. It includes physicochemical interactions between antigens and antibodies. [NIH] Immunogenic: Producing immunity; evoking an immune response. [EU] Immunoglobulins: Glycoproteins present in the blood (antibodies) and in other tissue. They are classified by structure and activity into five classes (IgA, IgD, IgE, IgG, IgM). [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] Immunosuppressive: Describes the ability to lower immune system responses. [NIH] Immunosuppressive therapy: Therapy used to decrease the body's immune response, such as drugs given to prevent transplant rejection. [NIH] Immunotherapy: Manipulation of the host's immune system in treatment of disease. It

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includes both active and passive immunization as well as immunosuppressive therapy to prevent graft rejection. [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] Implantation: The insertion or grafting into the body of biological, living, inert, or radioactive material. [EU] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incision: A cut made in the body during surgery. [NIH] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] Infancy: The period of complete dependency prior to the acquisition of competence in walking, talking, and self-feeding. [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] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose. It is also an important regulator of protein and lipid metabolism. Insulin is used as a drug to control insulin-dependent diabetes mellitus. [NIH] Insulin-dependent diabetes mellitus: A disease characterized by high levels of blood glucose resulting from defects in insulin secretion, insulin action, or both. Autoimmune, genetic, and environmental factors are involved in the development of type I diabetes. [NIH] 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] Intestinal: Having to do with the intestines. [NIH] Intestinal Mucosa: The surface lining of the intestines where the cells absorb nutrients. [NIH] Intestines: The section of the alimentary canal from the stomach to the anus. It includes the large intestine and small intestine. [NIH] Intracellular: Inside a cell. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques.

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[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] Irinotecan: An anticancer drug that belongs to a family of anticancer drugs called topoisomerase inhibitors. It is a camptothecin analogue. Also called CPT 11. [NIH] Jaundice: A clinical manifestation of hyperbilirubinemia, consisting of deposition of bile pigments in the skin, resulting in a yellowish staining of the skin and mucous membranes. [NIH]

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] Lactation: The period of the secretion of milk. [EU] Latency: The period of apparent inactivity between the time when a stimulus is presented and the moment a response occurs. [NIH] Lectin: A complex molecule that has both protein and sugars. Lectins are able to bind to the outside of a cell and cause biochemical changes in it. Lectins are made by both animals and plants. [NIH] Lesion: An area of abnormal tissue change. [NIH] Leukemia: Cancer of blood-forming tissue. [NIH] Ligament: A band of fibrous tissue that connects bones or cartilages, serving to support and strengthen joints. [EU] Ligands: A RNA simulation method developed by the MIT. [NIH] Linkage: The tendency of two or more genes in the same chromosome to remain together from one generation to the next more frequently than expected according to the law of independent assortment. [NIH] Lipid: Fat. [NIH] Lipoprotein: Any of the lipid-protein complexes in which lipids are transported in the blood; lipoprotein particles consist of a spherical hydrophobic core of triglycerides or cholesterol esters surrounded by an amphipathic monolayer of phospholipids, cholesterol, and apolipoproteins; the four principal classes are high-density, low-density, and very-lowdensity lipoproteins and chylomicrons. [EU] Liquor: 1. A liquid, especially an aqueous solution containing a medicinal substance. 2. A general term used in anatomical nomenclature for certain fluids of the body. [EU] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Liver cancer: A disease in which malignant (cancer) cells are found in the tissues of the liver. [NIH]

Liver Regeneration: Repair or renewal of hepatic tissue. [NIH] Liver Transplantation: The transference of a part of or an entire liver from one human or animal to another. [NIH] Localization: The process of determining or marking the location or site of a lesion or

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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] Loop: A wire usually of platinum bent at one end into a small loop (usually 4 mm inside diameter) and used in transferring microorganisms. [NIH] Low-density lipoprotein: Lipoprotein that contains most of the cholesterol in the blood. LDL carries cholesterol to the tissues of the body, including the arteries. A high level of LDL increases the risk of heart disease. LDL typically contains 60 to 70 percent of the total serum cholesterol and both are directly correlated with CHD risk. [NIH] Lutein Cells: The cells of the corpus luteum which are derived from the granulosa cells and the theca cells of the Graafian follicle. [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] Lymphocytes: White blood cells formed in the body's lymphoid tissue. The nucleus is round or ovoid with coarse, irregularly clumped chromatin while the cytoplasm is typically pale blue with azurophilic (if any) granules. Most lymphocytes can be classified as either T or B (with subpopulations of each); those with characteristics of neither major class are called null cells. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Lytic: 1. Pertaining to lysis or to a lysin. 2. Producing lysis. [EU] 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] Malignant tumor: A tumor capable of metastasizing. [NIH] Mammary: Pertaining to the mamma, or breast. [EU] 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] 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] Melanoma: A form of skin cancer that arises in melanocytes, the cells that produce pigment. Melanoma usually begins in a mole. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Menopause: Permanent cessation of menstruation. [NIH] Menstruation: The normal physiologic discharge through the vagina of blood and mucosal tissues from the nonpregnant uterus. [NIH] Mental: Pertaining to the mind; psychic. 2. (L. mentum chin) pertaining to the chin. [EU] Mental deficiency: A condition of arrested or incomplete development of mind from inherent causes or induced by disease or injury. [NIH]

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Mental Health: The state wherein the person is well adjusted. [NIH] Mentors: Senior professionals who provide guidance, direction and support to those persons desirous of improvement in academic positions, administrative positions or other career development situations. [NIH] Mesenchymal: Refers to cells that develop into connective tissue, blood vessels, and lymphatic tissue. [NIH] Mesoderm: The middle germ layer of the embryo. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] Metastasis: The spread of cancer from one part of the body to another. Tumors formed from cells that have spread are called "secondary tumors" and contain cells that are like those in the original (primary) tumor. The plural is metastases. [NIH] Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [NIH] 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] Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [NIH] Mitomycin: An antineoplastic antibiotic produced by Streptomyces caespitosus. It acts as a bi- or trifunctional alkylating agent causing cross-linking of DNA and inhibition of DNA synthesis. [NIH] Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH] Mobility: Capability of movement, of being moved, or of flowing freely. [EU] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] 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] 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] Morphogenesis: The development of the form of an organ, part of the body, or organism. [NIH]

Morphological: Relating to the configuration or the structure of live organs. [NIH] Mucosa: A mucous membrane, or tunica mucosa. [EU]

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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] Mutagenesis: Process of generating genetic mutations. It may occur spontaneously or be induced by mutagens. [NIH] Mutagens: Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes. [NIH] Necrosis: A pathological process caused by the progressive degradative action of enzymes that is generally associated with severe cellular trauma. It is characterized by mitochondrial swelling, nuclear flocculation, uncontrolled cell lysis, and ultimately cell death. [NIH] Neonatal: Pertaining to the first four weeks after birth. [EU] Neoplasia: Abnormal and uncontrolled cell growth. [NIH] Neoplasm: A new growth of benign or malignant tissue. [NIH] Networks: Pertaining to a nerve or to the nerves, a meshlike structure of interlocking fibers or strands. [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] Neural tube defects: These defects include problems stemming from fetal development of the spinal cord, spine, brain, and skull, and include birth defects such as spina bifida, anencephaly, and encephalocele. Neural tube defects occur early in pregnancy at about 4 to 6 weeks, usually before a woman knows she is pregnant. Many babies with neural tube defects have difficulty walking and with bladder and bowel control. [NIH] Neuromuscular: Pertaining to muscles and nerves. [EU] Neuromuscular Junction: The synapse between a neuron and a muscle. [NIH] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] 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] Nonmetastatic: Cancer that has not spread from the primary (original) site to other sites in the body. [NIH] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the information (genetic code) for the transfer of genetic information from one generation to the next. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Oligosaccharides: Carbohydrates consisting of between two and ten monosaccharides

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connected by either an alpha- or beta-glycosidic link. They are found throughout nature in both the free and bound form. [NIH] Oncogenic: Chemical, viral, radioactive or other agent that causes cancer; carcinogenic. [NIH] Oncolysis: The destruction of or disposal by absorption of any neoplastic cells. [NIH] Oncolytic: Pertaining to, characterized by, or causing oncolysis (= the lysis or destruction of tumour cells). [EU] Oncotic: Pertaining to, caused by, or marked by swelling. [EU] 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] Orbit: One of the two cavities in the skull which contains an eyeball. Each eye is located in a bony socket or orbit. [NIH] Orbital: Pertaining to the orbit (= the bony cavity that contains the eyeball). [EU] Osmotic: Pertaining to or of the nature of osmosis (= the passage of pure solvent from a solution of lesser to one of greater solute concentration when the two solutions are separated by a membrane which selectively prevents the passage of solute molecules, but is permeable to the solvent). [EU] Ovarian Follicle: Spheroidal cell aggregation in the ovary containing an ovum. It consists of an external fibro-vascular coat, an internal coat of nucleated cells, and a transparent, albuminous fluid in which the ovum is suspended. [NIH] Ovaries: The pair of female reproductive glands in which the ova, or eggs, are formed. The ovaries are located in the pelvis, one on each side of the uterus. [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] Overdose: An accidental or deliberate dose of a medication or street drug that is in excess of what is normally used. [NIH] Ovulation: The discharge of a secondary oocyte from a ruptured graafian follicle. [NIH] Ovum: A female germ cell extruded from the ovary at ovulation. [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]

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] Parity: The number of offspring a female has borne. It is contrasted with gravidity, which refers to the number of pregnancies, regardless of outcome. [NIH] Parturition: The act or process of given birth to a child. [EU] 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]

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Alpha Fetoprotein

Pathologic Processes: The abnormal mechanisms and forms involved in the dysfunctions of tissues and organs. [NIH] Pathologies: The study of abnormality, especially the study of diseases. [NIH] Pathologist: A doctor who identifies diseases by studying cells and tissues under a microscope. [NIH] Patient Education: The teaching or training of patients concerning their own health needs. [NIH]

Pelvic: Pertaining to the pelvis. [EU] Pelvis: The lower part of the abdomen, located between the hip bones. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Peptide T: N-(N-(N(2)-(N-(N-(N-(N-D-Alanyl L-seryl)-L-threonyl)-L-threonyl) L-threonyl)L-asparaginyl)-L-tyrosyl) L-threonine. Octapeptide sharing sequence homology with HIV envelope protein gp120. It is potentially useful as antiviral agent in AIDS therapy. The core pentapeptide sequence, TTNYT, consisting of amino acids 4-8 in peptide T, is the HIV envelope sequence required for attachment to the CD4 receptor. [NIH] Perinatal: Pertaining to or occurring in the period shortly before and after birth; variously defined as beginning with completion of the twentieth to twenty-eighth week of gestation and ending 7 to 28 days after birth. [EU] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of yeasts. [NIH] Phospholipids: Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides; glycerophospholipids) or sphingosine (sphingolipids). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system. [NIH] Physical Examination: Systematic and thorough inspection of the patient for physical signs of disease or abnormality. [NIH] Physiologic: Having to do with the functions of the body. When used in the phrase "physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH]

Pigment: A substance that gives color to tissue. Pigments are responsible for the color of skin, eyes, and hair. [NIH] Pilot study: The initial study examining a new method or treatment. [NIH] Placenta: A highly vascular fetal organ through which the fetus absorbs oxygen and other nutrients and excretes carbon dioxide and other wastes. It begins to form about the eighth day of gestation when the blastocyst adheres to the decidua. [NIH] 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]

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Plasma cells: A type of white blood cell that produces antibodies. [NIH] Plasma protein: One of the hundreds of different proteins present in blood plasma, including carrier proteins ( such albumin, transferrin, and haptoglobin), fibrinogen and other coagulation factors, complement components, immunoglobulins, enzyme inhibitors, precursors of substances such as angiotension and bradykinin, and many other types of proteins. [EU] 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] 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] Polymorphism: The occurrence together of two or more distinct forms in the same population. [NIH] Polypeptide: A peptide which on hydrolysis yields more than two amino acids; called tripeptides, tetrapeptides, etc. according to the number of amino acids contained. [EU] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] Posterior: Situated in back of, or in the back part of, or affecting the back or dorsal surface of the body. In lower animals, it refers to the caudal end of the body. [EU] Postmenopausal: Refers to the time after menopause. Menopause is the time in a woman's life when menstrual periods stop permanently; also called "change of life." [NIH] Postnatal: Occurring after birth, with reference to the newborn. [EU] 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] Pregnancy Complications: The co-occurrence of pregnancy and a disease. The disease may precede or follow conception and it may or may not have a deleterious effect on the pregnant woman or fetus. [NIH] Pregnancy Outcome: Results of conception and ensuing pregnancy, including live birth, stillbirth, spontaneous abortion, induced abortion. The outcome may follow natural or artificial insemination or any of the various reproduction techniques, such as embryo transfer or fertilization in vitro. [NIH] Pregnancy Tests: Tests to determine whether or not an individual is pregnant. [NIH] Prenatal: Existing or occurring before birth, with reference to the fetus. [EU] Prenatal Diagnosis: Determination of the nature of a pathological condition or disease in the postimplantation embryo, fetus, or pregnant female before birth. [NIH] Preoperative: Preceding an operation. [EU] Progesterone: Pregn-4-ene-3,20-dione. The principal progestational hormone of the body,

82

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secreted by the corpus luteum, adrenal cortex, and placenta. Its chief function is to prepare the uterus for the reception and development of the fertilized ovum. It acts as an antiovulatory agent when administered on days 5-25 of the menstrual cycle. [NIH] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Prolactin: Pituitary lactogenic hormone. A polypeptide hormone with a molecular weight of about 23,000. It is essential in the induction of lactation in mammals at parturition and is synergistic with estrogen. The hormone also brings about the release of progesterone from lutein cells, which renders the uterine mucosa suited for the embedding of the ovum should fertilization occur. [NIH] Promoter: A chemical substance that increases the activity of a carcinogenic process. [NIH] Prospective Studies: Observation of a population for a sufficient number of persons over a sufficient number of years to generate incidence or mortality rates subsequent to the selection of the study group. [NIH] Prostate: A gland in males that surrounds the neck of the bladder and the urethra. It secretes a substance that liquifies coagulated semen. It is situated in the pelvic cavity behind the lower part of the pubic symphysis, above the deep layer of the triangular ligament, and rests upon the rectum. [NIH] Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation. [NIH] Protein Conformation: The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. Quaternary protein structure describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain). [NIH] Protein S: The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] Proteome: The protein complement of an organism coded for by its genome. [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] Public Health: Branch of medicine concerned with the prevention and control of disease and disability, and the promotion of physical and mental health of the population on the international, national, state, or municipal level. [NIH] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] Pulmonary: Relating to the lungs. [NIH] Pulmonary Artery: The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs. [NIH] Pulse: The rhythmical expansion and contraction of an artery produced by waves of pressure caused by the ejection of blood from the left ventricle of the heart as it contracts. [NIH]

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Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radiation 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] Radiography: Examination of any part of the body for diagnostic purposes by means of roentgen rays, recording the image on a sensitized surface (such as photographic film). [NIH] Radioimmunotherapy: Radiotherapy where cytotoxic radionuclides are linked to antibodies in order to deliver toxins directly to tumor targets. Therapy with targeted radiation rather than antibody-targeted toxins (immunotoxins) has the advantage that adjacent tumor cells, which lack the appropriate antigenic determinants, can be destroyed by radiation cross-fire. Radioimmunotherapy is sometimes called targeted radiotherapy, but this latter term can also refer to radionuclides linked to non-immune molecules (radiotherapy). [NIH] Radiolabeled: Any compound that has been joined with a radioactive substance. [NIH] Radiopharmaceutical: Any medicinal product which, when ready for use, contains one or more radionuclides (radioactive isotopes) included for a medicinal purpose. [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] Reactivation: The restoration of activity to something that has been inactivated. [EU] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Recombination: The formation of new combinations of genes as a result of segregation in crosses between genetically different parents; also the rearrangement of linked genes due to crossing-over. [NIH] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Recurrence: The return of a sign, symptom, or disease after a remission. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [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]

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Alpha Fetoprotein

Relaxin: Hormone produced by the ovaries during pregnancy that loosens ligaments that hold the hip bones together. [NIH] Remission: A decrease in or disappearance of signs and symptoms of cancer. In partial remission, some, but not all, signs and symptoms of cancer have disappeared. In complete remission, all signs and symptoms of cancer have disappeared, although there still may be cancer in the body. [NIH] Repressor: Any of the specific allosteric protein molecules, products of regulator genes, which bind to the operator of operons and prevent RNA polymerase from proceeding into the operon to transcribe messenger RNA. [NIH] Research Design: A plan for collecting and utilizing data so that desired information can be obtained with sufficient precision or so that an hypothesis can be tested properly. [NIH] Resection: Removal of tissue or part or all of an organ by surgery. [NIH] Respiration: The act of breathing with the lungs, consisting of inspiration, or the taking into the lungs of the ambient air, and of expiration, or the expelling of the modified air which contains more carbon dioxide than the air taken in (Blakiston's Gould Medical Dictionary, 4th ed.). This does not include tissue respiration (= oxygen consumption) or cell respiration (= cell respiration). [NIH] Resuscitation: The restoration to life or consciousness of one apparently dead; it includes such measures as artificial respiration and cardiac massage. [EU] Retinoid: Vitamin A or a vitamin A-like compound. [NIH] Retroviral vector: RNA from a virus that is used to insert genetic material into cells. [NIH] Rhythm Method: A contraceptive method whereby abstinence is practiced a few days before and after the estimated day of ovulation. [NIH] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Saliva: The clear, viscous fluid secreted by the salivary glands and mucous glands of the mouth. It contains mucins, water, organic salts, and ptylin. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [NIH] Sarcoma: A connective tissue neoplasm formed by proliferation of mesodermal cells; it is usually highly malignant. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Secondary tumor: Cancer that has spread from the organ in which it first appeared to another organ. For example, breast cancer cells may spread (metastasize) to the lungs and cause the growth of a new tumor. When this happens, the disease is called metastatic breast cancer, and the tumor in the lungs is called a secondary tumor. Also called secondary cancer. [NIH] Secretion: 1. The process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. Any substance produced by secretion. [EU] Segregation: The separation in meiotic cell division of homologous chromosome pairs and their contained allelomorphic gene pairs. [NIH] Selective estrogen receptor modulator: SERM. A drug that acts like estrogen on some tissues, but blocks the effect of estrogen on other tissues. Tamoxifen and raloxifene are SERMs. [NIH]

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Semen: The thick, yellowish-white, viscid fluid secretion of male reproductive organs discharged upon ejaculation. In addition to reproductive organ secretions, it contains spermatozoa and their nutrient plasma. [NIH] Sequence Analysis: A multistage process that includes the determination of a sequence (protein, carbohydrate, etc.), its fragmentation and analysis, and the interpretation of the resulting sequence information. [NIH] Sequence Homology: The degree of similarity between sequences. Studies of amino acid and nucleotide sequences provide useful information about the genetic relatedness of certain species. [NIH] Sequencing: The determination of the order of nucleotides in a DNA or RNA chain. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Serum Albumin: A major plasma protein that serves in maintaining the plasma colloidal osmotic pressure and transporting large organic anions. [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] Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]

Sodium: An element that is a member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23. With a valence of 1, it has a strong affinity for oxygen and other nonmetallic elements. Sodium provides the chief cation of the extracellular body fluids. Its salts are the most widely used in medicine. (From Dorland, 27th ed) Physiologically the sodium ion plays a major role in blood pressure regulation, maintenance of fluid volume, and electrolyte balance. [NIH] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Specificity: Degree of selectivity shown by an antibody with respect to the number and types of antigens with which the antibody combines, as well as with respect to the rates and the extents of these reactions. [NIH] Sperm: The fecundating fluid of the male. [NIH] Spina bifida: A defect in development of the vertebral column in which there is a central deficiency of the vertebral lamina. [NIH] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] Spontaneous Abortion: The non-induced birth of an embryo or of fetus prior to the stage of viability at about 20 weeks of gestation. [NIH] Sterilization: The destroying of all forms of life, especially microorganisms, by heat,

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Alpha Fetoprotein

chemical, or other means. [NIH] Steroid: A group name for lipids that contain a hydrogenated cyclopentanoperhydrophenanthrene ring system. Some of the substances included in this group are progesterone, adrenocortical hormones, the gonadal hormones, cardiac aglycones, bile acids, sterols (such as cholesterol), toad poisons, saponins, and some of the carcinogenic hydrocarbons. [EU] Stillbirth: The birth of a dead fetus or baby. [NIH] Stimulant: 1. Producing stimulation; especially producing stimulation by causing tension on muscle fibre through the nervous tissue. 2. An agent or remedy that produces stimulation. [EU]

Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Stool: The waste matter discharged in a bowel movement; feces. [NIH] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] Subacute: Somewhat acute; between acute and chronic. [EU] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] Submaxillary: Four to six lymph glands, located between the lower jaw and the submandibular salivary gland. [NIH] Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of pain, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses. [NIH]

Supplementation: Adding nutrients to the diet. [NIH] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Symphysis: A secondary cartilaginous joint. [NIH] Synergistic: Acting together; enhancing the effect of another force or agent. [EU] Systemic: Affecting the entire body. [NIH] Tamoxifen: A first generation selective estrogen receptor modulator (SERM). It acts as an agonist for bone tissue and cholesterol metabolism but is an estrogen antagonist in mammary and uterine. [NIH] Taurine: 2-Aminoethanesulfonic acid. A conditionally essential nutrient, important during mammalian development. It is present in milk but is isolated mostly from ox bile and strongly conjugates bile acids. [NIH] Technetium: The first artificially produced element and a radioactive fission product of uranium. The stablest isotope has a mass number 99 and is used diagnostically as a radioactive imaging agent. Technetium has the atomic symbol Tc, atomic number 43, and atomic weight 98.91. [NIH] Teratoma: A type of germ cell tumor that may contain several different types of tissue, such as hair, muscle, and bone. Teratomas occur most often in the ovaries in women, the testicles

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in men, and the tailbone in children. Not all teratomas are malignant. [NIH] Testicles: The two egg-shaped glands found inside the scrotum. They produce sperm and male hormones. Also called testes. [NIH] Testis: Either of the paired male reproductive glands that produce the male germ cells and the male hormones. [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] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] Thrombocytes: Blood cells that help prevent bleeding by causing blood clots to form. Also called platelets. [NIH] 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] Thymidine: A chemical compound found in DNA. Also used as treatment for mucositis. [NIH]

Thymidine Kinase: An enzyme that catalyzes the conversion of ATP and thymidine to ADP and thymidine 5'-phosphate. Deoxyuridine can also act as an acceptor and dGTP as a donor. (From Enzyme Nomenclature, 1992) EC 2.7.1.21. [NIH] Thymus: An organ that is part of the lymphatic system, in which T lymphocytes grow and multiply. The thymus is in the chest behind the breastbone. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tolerance: 1. The ability to endure unusually large doses of a drug or toxin. 2. Acquired drug tolerance; a decreasing response to repeated constant doses of a drug or the need for increasing doses to maintain a constant response. [EU] 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 usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxin: A poison; frequently used to refer specifically to a protein produced by some higher plants, certain animals, and pathogenic bacteria, which is highly toxic for other living organisms. Such substances are differentiated from the simple chemical poisons and the vegetable alkaloids by their high molecular weight and antigenicity. [EU] Trans-Activators: Diffusible gene products that act on homologous or heterologous molecules of viral or cellular DNA to regulate the expression of proteins. [NIH] Transcription Factors: Endogenous substances, usually proteins, which are effective in the

88

Alpha Fetoprotein

initiation, stimulation, or termination of the genetic transcription process. [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Transfer Factor: Factor derived from leukocyte lysates of immune donors which can transfer both local and systemic cellular immunity to nonimmune recipients. [NIH] 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] Trisomy: The possession of a third chromosome of any one type in an otherwise diploid cell. [NIH]

Tumor marker: A substance sometimes found in an increased amount in the blood, other body fluids, or tissues and which may mean that a certain type of cancer is in the body. Examples of tumor markers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and gastrointestinal tract cancers), and PSA (prostate cancer). Also called biomarker. [NIH] Tumor model: A type of animal model which can be used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Tumor suppressor gene: Genes in the body that can suppress or block the development of cancer. [NIH] Tumorigenic: Chemical, viral, radioactive or other agent that causes cancer; carcinogenic. [NIH]

Tumour: 1. Swelling, one of the cardinal signs of inflammations; morbid enlargement. 2. A new growth of tissue in which the multiplication of cells is uncontrolled and progressive; called also neoplasm. [EU] Ultrasonography: The visualization of deep structures of the body by recording the reflections of echoes of pulses of ultrasonic waves directed into the tissues. Use of ultrasound for imaging or diagnostic purposes employs frequencies ranging from 1.6 to 10 megahertz. [NIH] 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] Uranium: A radioactive element of the actinide series of metals. It has an atomic symbol U, atomic number 92, and atomic weight 238.03. U-235 is used as the fissionable fuel in nuclear weapons and as fuel in nuclear power reactors. [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]

Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] Urine: Fluid containing water and waste products. Urine is made by the kidneys, stored in the bladder, and leaves the body through the urethra. [NIH] 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]

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Vaccine: A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. [NIH] Vagina: The muscular canal extending from the uterus to the exterior of the body. Also called the birth canal. [NIH] Vaginal: Of or having to do with the vagina, the birth canal. [NIH] Vaginosis: A condition caused by the overgrowth of anaerobic bacteria (e. g., Gardnerella vaginalis), resulting in vaginal irritation and discharge. [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Vesicular: 1. Composed of or relating to small, saclike bodies. 2. Pertaining to or made up of vesicles on the skin. [EU] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Viral Hepatitis: Hepatitis caused by a virus. Five different viruses (A, B, C, D, and E) most commonly cause this form of hepatitis. Other rare viruses may also cause hepatitis. [NIH] 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] Vitamin A: A substance used in cancer prevention; it belongs to the family of drugs called retinoids. [NIH] Vitelline Membrane: The plasma membrane of the egg. [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]

Womb: A hollow, thick-walled, muscular organ in which the impregnated ovum is developed into a child. [NIH] Xenograft: The cells of one species transplanted to another species. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH]

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Alpha Fetoprotein

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] Yolk Sac: An embryonic membrane formed from endoderm and mesoderm. In reptiles and birds it incorporates the yolk into the digestive tract for nourishing the embryo. In placental mammals its nutritional function is vestigial; however, it is the source of most of the intestinal mucosa and the site of formation of the germ cells. It is sometimes called the vitelline sac, which should not be confused with the vitelline membrane of the egg. [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]

91

INDEX A Abdominal, 20, 22, 57, 79 Aberrant, 11, 18, 57 Acceptor, 57, 79, 87 Accommodation, 9, 57 Acetaminophen, 57, 69 Acetylcholine, 57, 63 Acetylcholinesterase, 19, 57 Adaptation, 36, 57 Adenocarcinoma, 57, 72 Adenosine, 57, 62 Adenovirus, 4, 5, 9, 57 Adjustment, 36, 57 Adjuvant, 9, 57 Adrenal Cortex, 57, 65, 68, 82 Adrenal Medulla, 57, 63 Adverse Effect, 58, 85 Affinity, 25, 58, 85 Agonist, 58, 67, 86 Albumin, 12, 55, 58, 81 Alertness, 58, 62 Algorithms, 58, 61 Alkaloid, 58, 62, 64 Allantois, 58, 69 Allogeneic, 9, 58, 71 Allografts, 58, 72 Alpha Particles, 58, 83 Alpha-fetoprotein, 4, 6, 7, 11, 14, 16, 58, 69 Alternative medicine, 58 Amino Acid Sequence, 33, 59, 60, 70 Amino Acid Substitution, 59, 72 Amino Acids, 59, 70, 80, 81, 82 Amniocentesis, 36, 55, 59 Amnion, 59, 69 Amniotic Fluid, 8, 19, 59, 70 Amphetamines, 59, 64 Anaerobic, 59, 89 Anaesthesia, 59, 74 Analogous, 59, 88 Anatomical, 59, 75 Aneuploidy, 8, 59 Animal model, 4, 11, 59, 88 Anions, 58, 59, 75, 85 Antagonism, 59, 62 Antibiotic, 60, 77 Antibodies, 15, 32, 60, 68, 71, 73, 81, 83 Antibody, 21, 32, 58, 60, 64, 68, 71, 72, 73, 74, 77, 83, 85

Anticoagulant, 60, 82 Antigen, 4, 6, 7, 9, 10, 22, 23, 25, 27, 32, 58, 60, 65, 66, 72, 73, 74 Antigen-presenting cell, 60, 66 Anti-inflammatory, 57, 60, 63 Anti-Inflammatory Agents, 60, 63 Antineoplastic, 60, 77 Antiviral, 60, 80 Anus, 60, 64, 74 Apolipoproteins, 60, 75 Apoptosis, 15, 16, 60 Aqueous, 60, 61, 66, 75 Arteries, 60, 61, 62, 76, 88 Arterioles, 60, 62 Artery, 13, 60, 82, 88 Aspiration, 60, 69 Assay, 12, 15, 16, 21, 22, 60 Asymptomatic, 10, 61 Autologous, 4, 9, 61 B Bacteria, 60, 61, 69, 77, 81, 87, 89 Bacterial Physiology, 57, 61 Base, 19, 61, 70, 75 Benign, 10, 61, 71, 78, 83 Bile, 17, 61, 63, 70, 75, 86 Bile Acids, 17, 61, 86 Bile Acids and Salts, 61 Bilirubin, 24, 58, 61, 73 Biochemical, 5, 8, 23, 61, 69, 75 Biomarkers, 4, 18, 61 Biosynthesis, 17, 61 Biotechnology, 18, 41, 61 Bladder, 61, 78, 82, 88 Blastocyst, 61, 65, 67, 80 Blood Glucose, 36, 61, 71, 73, 74 Blood pressure, 7, 55, 61, 77, 85 Blood vessel, 58, 61, 62, 77, 85, 87, 89 Body Fluids, 61, 62, 67, 85, 88 Bone Marrow, 62, 70, 73, 76 Bowel, 62, 78, 86 Brachytherapy, 62, 74, 83 Bradykinin, 62, 81 C Caffeine, 36, 62 Calcium, 62, 64 Camptothecin, 62, 75 Capillary, 7, 62, 89 Carbohydrate, 10, 62, 81, 85

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Alpha Fetoprotein

Carbon Dioxide, 62, 80, 84 Carcinoembryonic Antigen, 7, 22, 23, 24, 32, 62 Carcinogen, 16, 63 Carcinogenesis, 14, 63 Carcinogenic, 63, 74, 79, 82, 86, 88 Carcinoma, 4, 7, 9, 20, 22, 33, 63 Cardiac, 62, 63, 84, 86 Carrier Proteins, 63, 81 Case report, 26, 29, 63 Catabolism, 17, 63 Catecholamine, 7, 23, 63, 66 Causal, 8, 63 Celecoxib, 15, 63 Cell Cycle, 16, 63 Cell Death, 60, 63, 78 Cell Division, 61, 63, 77, 80, 84 Central Nervous System, 57, 59, 62, 63, 64, 71 Chemoprevention, 14, 15, 16, 63 Cholesterol, 17, 61, 63, 64, 67, 73, 75, 76, 86 Cholesterol Esters, 63, 75 Cholic Acid, 17, 63 Choline, 57, 63 Chorion, 63, 69 Chromatin, 12, 60, 63, 76 Chromosomal, 12, 26, 59, 64, 72, 81 Chromosome, 8, 59, 64, 75, 77, 84, 88 Chronic, 10, 11, 64, 74, 86 Chylomicrons, 64, 75 Cirrhosis, 6, 64 Clear cell carcinoma, 64, 66 Clinical trial, 3, 4, 9, 16, 41, 64, 83 Cloning, 5, 61, 64 Coagulation, 62, 64, 81, 87 Coca, 64 Cocaine, 13, 64 Colloidal, 58, 64, 67, 85 Colon, 15, 63, 64 Complement, 64, 65, 70, 75, 81 Complementary and alternative medicine, 29, 30, 65 Complementary medicine, 29, 65 Computational Biology, 41, 65 Conception, 65, 69, 81 Confounding, 14, 65 Conjugated, 61, 63, 65 Connective Tissue, 62, 65, 77, 84 Consciousness, 65, 66, 84 Contraceptive, 35, 65, 84 Contraindications, ii, 65 Cortex, 65

Cortisol, 7, 58, 65 Crossing-over, 65, 83 Curative, 6, 34, 65 Cyanosis, 65, 72 Cyclic, 16, 62, 66 Cytokine, 6, 66 Cytoplasm, 60, 66, 76 Cytotoxic, 66, 83 D Decidua, 9, 66, 80 Degenerative, 66, 72 Deletion, 11, 60, 66 Dendrites, 66, 78 Dendritic, 4, 9, 66, 76 Dendritic cell, 4, 9, 66 DES, 6, 66 Diabetes Mellitus, 66, 71 Diagnostic procedure, 31, 66 Digestion, 61, 62, 66, 75, 86 Digestive tract, 66, 85, 90 Diploid, 59, 66, 77, 80, 88 Direct, iii, 15, 66, 67, 83 Dissociation, 58, 66 Diuresis, 62, 66 Dopamine, 64, 66 Drug Tolerance, 67, 87 Duct, 67, 69, 84 Duodenum, 61, 67, 86 Dyslipidemia, 13, 67 E Ectopic, 29, 67 Efficacy, 6, 16, 67 Electrolyte, 67, 85 Electrons, 61, 67, 75, 79, 83 Electrophoresis, 7, 25, 67 Embryo, 59, 61, 67, 68, 69, 74, 77, 81, 85, 88, 90 Embryo Transfer, 67, 81 Encephalitis, 67, 68 Encephalocele, 67, 78 Encephalomyelitis, 21, 68 Endoderm, 68, 90 Endogenous, 5, 66, 68, 87 Endometrium, 66, 68 Enhancer, 12, 68 Environmental Health, 40, 42, 68 Enzyme, 17, 57, 59, 62, 68, 70, 81, 87, 89, 90 Enzyme Inhibitors, 68, 81 Epidemiological, 14, 22, 68 Epidermal, 20, 23, 68, 76 Epidermal Growth Factor, 20, 23, 68 Epidermis, 68

93

Epigastric, 68, 79 Epithelial, 22, 23, 57, 66, 68 Epithelial Cells, 68 Epithelium, 14, 68 Epitope, 9, 68 Epitope Mapping, 9, 68 Escalation, 4, 68 Estradiol, 14, 26, 68 Estriol, 14, 28, 68 Estrogen, 5, 16, 69, 82, 84, 86 Estrogen receptor, 5, 16, 69 Exocrine, 69, 79 Exogenous, 68, 69 External-beam radiation, 69, 83 Extracellular, 65, 69, 85 Extraction, 11, 69 Eye Infections, 57, 69 F Family Planning, 41, 69 Fat, 61, 62, 63, 69, 75 Feces, 63, 69, 86 Fertilization in Vitro, 69, 81 Fetal Alcohol Syndrome, 26, 69 Fetal Membranes, 19, 69 Fetal Monitoring, 36, 69 Fetoprotein, 4, 9, 10, 12, 13, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 32, 33, 36, 46, 47, 55, 69 Fetus, 8, 9, 24, 58, 69, 80, 81, 85, 86, 88 Fibrinogen, 69, 81, 87 Fold, 10, 69 Forearm, 61, 69 Fucose, 11, 69 Fulminant Hepatic Failure, 27, 69 G Gallbladder, 57, 70 Gamma Rays, 70, 83 Gastric, 20, 23, 24, 26, 30, 68, 70 Gastrin, 70, 72 Gastrointestinal, 62, 63, 70, 86, 88 Gastrointestinal tract, 63, 70, 88 Gavage, 15, 70 Gene, 4, 6, 8, 11, 12, 14, 57, 61, 70, 79, 84, 87 Gene Expression, 4, 8, 11, 70 Gene Therapy, 6, 57, 70 Gene-modified, 4, 70 Genetic Code, 70, 78 Genetic Engineering, 61, 64, 70 Genetic testing, 36, 70 Genetics, 4, 5, 19, 21, 24, 25, 27, 47, 70 Genotype, 58, 70, 80

Germ Cells, 70, 79, 87, 90 Gestation, 13, 36, 70, 80, 85 Gestational, 8, 20, 35, 70 Gestational Age, 8, 20, 70 Gland, 23, 57, 71, 79, 82, 84, 86 Glucose, 13, 36, 61, 66, 71, 74 Glycine, 61, 63, 71 Glycoprotein, 26, 62, 69, 71, 87 Glycosidic, 71, 79 Gonadotropin, 7, 14, 26, 28, 32, 71 Governing Board, 71, 81 Gp120, 71, 80 Graft, 58, 71, 74 Graft Rejection, 71, 74 Grafting, 71, 74 Granulosa Cells, 23, 26, 71, 76 Gravidity, 71, 79 H Half-Life, 8, 71 Haptens, 58, 71 Headache, 62, 71 Hemoglobin, 36, 65, 71, 72 Hemoglobin M, 36, 66, 72 Hemoglobinopathies, 70, 72 Hepatic, 12, 23, 58, 72, 75 Hepatitis, 10, 11, 18, 25, 27, 46, 69, 72, 89 Hepatocellular, 4, 6, 9, 10, 11, 15, 18, 33, 72 Hepatocellular carcinoma, 4, 6, 9, 10, 15, 18, 33, 72 Hepatocyte, 12, 14, 72 Hepatoma, 11, 15, 72 Heredity, 70, 72 Hernia, 24, 72 Heterodimer, 17, 72 Heterogeneity, 58, 72 Heterogenic, 72 Heterogenous, 33, 72 Histocompatibility, 10, 72 Histones, 63, 72 Homologous, 65, 70, 72, 84, 87 Hormonal, 14, 72 Hormone, 14, 65, 66, 68, 70, 72, 74, 81, 82, 84 Hybrid, 11, 72 Hydrogen, 57, 61, 62, 72, 77, 78, 79, 82 Hydrolysis, 57, 72, 81 Hydrophobic, 72, 75 Hyperbilirubinemia, 27, 73, 75 Hypercholesterolemia, 67, 73 Hyperlipidemia, 67, 73 Hyperplasia, 8, 73 Hypertriglyceridemia, 67, 73

94

Alpha Fetoprotein

Hypertrophy, 73 Hypoglycemia, 36, 73 Hypoglycemic, 36, 73 Hypoglycemic Agents, 36, 73 I Immune response, 5, 33, 57, 60, 71, 73, 86, 89 Immune Sera, 73 Immune system, 60, 73, 89 Immunity, 4, 6, 9, 73, 88 Immunization, 4, 73, 74 Immunochemistry, 68, 73 Immunogenic, 9, 73 Immunoglobulins, 73, 81 Immunologic, 70, 73, 83 Immunology, 4, 27, 57, 58, 73 Immunosuppressive, 73, 74 Immunosuppressive therapy, 73, 74 Immunotherapy, 4, 9, 73 Implant radiation, 74, 83 Implantation, 20, 65, 74 In vitro, 5, 11, 15, 20, 33, 67, 70, 74 In vivo, 5, 9, 15, 20, 70, 74 Incision, 74 Induction, 9, 74, 82 Infancy, 23, 26, 74 Infection, 5, 7, 10, 11, 18, 67, 69, 73, 74, 76, 86, 89 Inflammation, 7, 13, 58, 60, 67, 68, 69, 72, 74, 81 Initiation, 12, 74, 88 Insulin, 13, 36, 74 Insulin-dependent diabetes mellitus, 74 Internal radiation, 74, 83 Intestinal, 74, 90 Intestinal Mucosa, 74, 90 Intestines, 57, 66, 69, 70, 74 Intracellular, 62, 74 Intrinsic, 58, 74 Invasive, 13, 73, 74 Ionizing, 58, 75, 83 Ions, 61, 66, 67, 72, 75 Irinotecan, 30, 75 J Jaundice, 73, 75 K Karyotype, 59, 75 Kb, 12, 40, 75 L Lactation, 14, 75, 82 Latency, 16, 75 Lectin, 11, 25, 75

Lesion, 75 Leukemia, 70, 75 Ligament, 75, 82 Ligands, 15, 75 Linkage, 7, 75 Lipid, 13, 17, 60, 63, 74, 75 Lipoprotein, 13, 67, 75, 76 Liquor, 22, 75 Liver, 4, 10, 11, 12, 14, 16, 18, 19, 20, 21, 33, 46, 57, 58, 61, 63, 64, 69, 70, 72, 75 Liver cancer, 4, 12, 21, 33, 58, 75 Liver Regeneration, 11, 75 Liver Transplantation, 18, 34, 75 Localization, 32, 75 Localized, 5, 12, 32, 74, 76, 80 Loop, 72, 76 Low-density lipoprotein, 67, 75, 76 Lutein Cells, 76, 82 Lymphatic, 74, 76, 77, 87 Lymphocytes, 33, 60, 66, 73, 76, 87, 89 Lymphoid, 60, 76 Lytic, 5, 76 M Malformation, 21, 27, 76 Malignancy, 9, 76 Malignant, 10, 11, 18, 32, 57, 60, 75, 76, 78, 83, 84, 87 Malignant tumor, 32, 76 Mammary, 14, 76, 86 Mediate, 9, 12, 67, 76 MEDLINE, 41, 76 Melanocytes, 76 Melanoma, 32, 76 Membrane, 7, 22, 23, 59, 63, 65, 71, 76, 77, 79, 80, 88, 89, 90 Menopause, 76, 81 Menstruation, 66, 76 Mental, iv, 3, 40, 42, 66, 69, 76, 77, 82 Mental deficiency, 69, 76 Mental Health, iv, 3, 40, 42, 77, 82 Mentors, 6, 77 Mesenchymal, 68, 77 Mesoderm, 77, 90 Metabolite, 68, 77 Metastasis, 20, 77 Microbe, 77, 87 Microbiology, 4, 57, 77 Microorganism, 77, 89 Migration, 7, 77 Mitomycin, 30, 77 Mitosis, 60, 77 Mobility, 15, 77

95

Modification, 12, 70, 77 Molecular, 4, 5, 10, 11, 12, 15, 17, 18, 21, 41, 43, 59, 61, 65, 69, 77, 82, 87 Molecule, 32, 33, 60, 61, 65, 66, 68, 71, 72, 75, 77, 79, 81, 83, 89 Monitor, 32, 63, 77, 78 Monoclonal, 77, 83 Monosomy, 59, 77 Morphogenesis, 69, 77 Morphological, 9, 67, 76, 77 Mucosa, 77, 82 Mucositis, 78, 87 Mutagenesis, 15, 78 Mutagens, 78 N Necrosis, 60, 78 Neonatal, 27, 36, 78 Neoplasia, 11, 78 Neoplasm, 78, 84, 88 Networks, 14, 78 Neural, 19, 21, 67, 69, 78 Neural tube defects, 19, 21, 69, 78 Neuromuscular, 57, 78 Neuromuscular Junction, 57, 78 Neurons, 64, 66, 78 Neutrons, 58, 78, 83 Nonmetastatic, 34, 78 Nuclear, 12, 13, 17, 62, 67, 70, 78, 88 Nuclei, 12, 58, 67, 70, 72, 77, 78, 82 Nucleic acid, 8, 70, 78 Nucleus, 60, 64, 66, 70, 76, 78, 82 O Oligosaccharides, 10, 11, 17, 78 Oncogenic, 33, 79 Oncolysis, 79 Oncolytic, 6, 79 Oncotic, 5, 16, 79 Operon, 79, 84 Orbit, 79 Orbital, 19, 79 Osmotic, 58, 79, 85 Ovarian Follicle, 71, 79 Ovaries, 79, 84, 86 Ovary, 29, 68, 79 Overdose, 69, 79 Ovulation, 71, 79, 84 Ovum, 66, 70, 79, 82, 89 Oxidation, 57, 72, 79 P Pancreas, 20, 57, 61, 74, 79, 88 Parity, 14, 79 Parturition, 79, 82

Pathologic, 60, 73, 79, 80 Pathologic Processes, 60, 80 Pathologies, 8, 80 Pathologist, 13, 80 Patient Education, 46, 50, 52, 56, 80 Pelvic, 80, 82 Pelvis, 79, 80, 88 Peptide, 4, 5, 9, 16, 33, 80, 81, 82 Peptide T, 5, 9, 80 Perinatal, 4, 13, 19, 28, 36, 80 Pharmacologic, 71, 80, 87 Phenotype, 10, 12, 80 Phospholipids, 69, 75, 80 Physical Examination, 70, 80 Physiologic, 58, 61, 69, 71, 76, 80, 83 Pigment, 61, 76, 80 Pilot study, 11, 18, 80 Placenta, 13, 68, 80, 82, 88 Plants, 58, 62, 63, 64, 71, 75, 80, 87 Plasma, 8, 16, 23, 26, 58, 60, 63, 69, 71, 80, 81, 85, 89 Plasma cells, 60, 81 Plasma protein, 23, 58, 81, 85 Plasmid, 4, 9, 12, 81, 89 Platelets, 19, 81, 87 Pneumonia, 65, 81 Polymerase, 81, 84 Polymorphism, 10, 81 Polypeptide, 59, 68, 69, 81, 82, 90 Polysaccharide, 60, 81 Posterior, 79, 81 Postmenopausal, 22, 81 Postnatal, 4, 69, 81 Practice Guidelines, 42, 81 Preclinical, 4, 6, 9, 81 Pregnancy Complications, 8, 81 Pregnancy Outcome, 19, 22, 81 Pregnancy Tests, 70, 81 Prenatal, 7, 8, 21, 25, 46, 67, 69, 81 Prenatal Diagnosis, 8, 21, 25, 81 Preoperative, 24, 81 Progesterone, 81, 82, 86 Progression, 11, 12, 16, 59, 82, 88 Progressive, 64, 67, 68, 78, 82, 88 Prolactin, 14, 82 Promoter, 6, 12, 17, 82 Prospective Studies, 8, 82 Prostate, 5, 7, 61, 82, 88 Protein C, 10, 23, 58, 59, 60, 75, 82 Protein Conformation, 59, 82 Protein S, 61, 70, 82

96

Alpha Fetoprotein

Proteins, 7, 11, 12, 17, 59, 60, 63, 64, 72, 77, 80, 81, 82, 85, 87, 89 Proteome, 11, 82 Protons, 58, 72, 75, 82, 83 Public Health, 7, 42, 82 Public Policy, 26, 41, 82 Pulmonary, 61, 82 Pulmonary Artery, 61, 82 Pulse, 77, 82 R Race, 75, 77, 83 Radiation, 5, 32, 69, 70, 74, 75, 83, 89 Radiation therapy, 5, 69, 74, 83 Radioactive, 32, 71, 72, 74, 78, 79, 83, 86, 88 Radiography, 70, 83 Radioimmunotherapy, 83 Radiolabeled, 32, 83 Radiopharmaceutical, 32, 83 Radiotherapy, 6, 62, 83 Randomized, 67, 83 Reactivation, 4, 11, 83 Receptor, 15, 16, 17, 57, 60, 67, 71, 80, 83 Recombinant, 4, 9, 83, 89 Recombination, 12, 70, 83 Rectum, 60, 64, 66, 82, 83 Recurrence, 28, 34, 63, 83 Refer, 1, 64, 76, 78, 83, 87 Regeneration, 4, 83 Regimen, 67, 83 Relaxin, 14, 84 Remission, 83, 84 Repressor, 12, 79, 84 Research Design, 16, 84 Resection, 6, 34, 84 Respiration, 62, 69, 77, 84 Resuscitation, 36, 84 Retinoid, 15, 84 Retroviral vector, 70, 84 Rhythm Method, 36, 84 Risk factor, 6, 13, 84 S Saliva, 84 Salivary, 7, 23, 84, 86 Salivary glands, 23, 84 Sarcoma, 32, 84 Screening, 10, 19, 20, 21, 22, 23, 24, 25, 26, 27, 36, 46, 64, 84 Secondary tumor, 77, 84 Secretion, 11, 68, 74, 75, 84, 85 Segregation, 83, 84

Selective estrogen receptor modulator, 84, 86 Semen, 82, 85 Sequence Analysis, 13, 85 Sequence Homology, 80, 85 Sequencing, 11, 18, 85 Serum, 6, 7, 8, 10, 12, 13, 17, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 46, 47, 58, 64, 71, 73, 76, 85 Serum Albumin, 23, 85 Side effect, 16, 58, 85, 87 Skull, 67, 78, 79, 85 Small intestine, 64, 67, 72, 74, 85 Smooth muscle, 59, 62, 85, 86 Sodium, 36, 85 Specialist, 47, 85 Species, 58, 72, 75, 77, 83, 85, 88, 89 Specificity, 6, 10, 25, 58, 85 Sperm, 64, 85, 87 Spina bifida, 78, 85 Spinal cord, 63, 68, 78, 85 Spontaneous Abortion, 81, 85 Sterilization, 36, 85 Steroid, 61, 65, 86 Stillbirth, 81, 86 Stimulant, 62, 86 Stimulus, 75, 86 Stomach, 57, 66, 70, 72, 74, 85, 86 Stool, 64, 86 Stress, 63, 65, 86 Subacute, 74, 86 Subclinical, 74, 86 Submaxillary, 68, 86 Substance P, 77, 84, 86 Supplementation, 36, 86 Suppression, 9, 17, 86 Symphysis, 82, 86 Synergistic, 6, 82, 86 Systemic, 4, 6, 9, 61, 74, 83, 86, 88 T Tamoxifen, 16, 84, 86 Taurine, 61, 63, 86 Technetium, 32, 86 Teratoma, 23, 86 Testicles, 86, 87 Testis, 68, 87 Threonine, 80, 87 Thrombin, 69, 82, 87 Thrombocytes, 81, 87 Thrombomodulin, 82, 87 Thrombosis, 13, 82, 87 Thymidine, 7, 87

97

Thymidine Kinase, 7, 87 Thymus, 73, 76, 87 Tolerance, 9, 87 Tooth Preparation, 57, 87 Topoisomerase inhibitors, 75, 87 Toxic, iv, 16, 68, 73, 87 Toxicity, 16, 87 Toxicology, 42, 87 Toxin, 87 Trans-Activators, 12, 87 Transcription Factors, 12, 87 Transfection, 12, 15, 61, 70, 88 Transfer Factor, 73, 88 Translational, 4, 9, 88 Translocation, 24, 88 Transplantation, 6, 34, 67, 73, 88 Trisomy, 23, 25, 59, 88 Tumor marker, 7, 22, 61, 88 Tumor model, 4, 6, 9, 88 Tumor suppressor gene, 15, 88 Tumorigenic, 11, 88 Tumour, 19, 20, 21, 24, 25, 26, 79, 88 U Ultrasonography, 21, 36, 70, 88 Umbilical Arteries, 88 Umbilical Cord, 27, 58, 88 Uranium, 86, 88 Urethra, 82, 88 Urinary, 7, 88 Urine, 7, 13, 36, 61, 66, 68, 88 Uterus, 9, 59, 66, 68, 76, 79, 82, 88, 89

V Vaccine, 9, 57, 89 Vagina, 25, 66, 76, 89 Vaginal, 7, 13, 89 Vaginosis, 13, 89 Vascular, 7, 13, 74, 79, 80, 89 Vector, 4, 5, 9, 89 Vein, 78, 88, 89 Venules, 62, 89 Vesicular, 71, 89 Veterinary Medicine, 41, 89 Viral, 4, 5, 10, 18, 33, 67, 79, 87, 88, 89 Viral Hepatitis, 10, 34, 89 Viral vector, 4, 89 Virulence, 87, 89 Virus, 4, 10, 11, 18, 68, 70, 71, 84, 89 Vitamin A, 36, 84, 89 Vitelline Membrane, 89, 90 Vitro, 12, 89 Vivo, 9, 15, 89 W White blood cell, 60, 76, 81, 89 Womb, 88, 89 X Xenograft, 59, 88, 89 X-ray, 70, 78, 83, 89 Y Yeasts, 80, 90 Yolk Sac, 19, 25, 69, 90 Z Zymogen, 82, 90

98

Alpha Fetoprotein

99

100

Alpha Fetoprotein

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